Datasets:

common-pile
/

oercommons

Dataset card Data Studio Files Files and versions Community

Split (1)

train · 9.34k rows

id stringlengths 54 56	text stringlengths 0 1.34M	source stringclasses 1 value	added stringdate 2025-03-18 00:34:10 2025-03-18 00:39:48	created stringlengths 3 51 ⌀	metadata dict
https://oercommons.org/courseware/lesson/15143/overview	Overview of the Circulatory System Overview By the end of this section, you will be able to: - Describe an open and closed circulatory system - Describe interstitial fluid and hemolymph - Compare and contrast the organization and evolution of the vertebrate circulatory system. In all animals, except a few simple types, the circulatory system is used to transport nutrients and gases through the body. Simple diffusion allows some water, nutrient, waste, and gas exchange into primitive animals that are only a few cell layers thick; however, bulk flow is the only method by which the entire body of larger more complex organisms is accessed. Circulatory System Architecture The circulatory system is effectively a network of cylindrical vessels: the arteries, veins, and capillaries that emanate from a pump, the heart. In all vertebrate organisms, as well as some invertebrates, this is a closed-loop system, in which the blood is not free in a cavity. In a closed circulatory system, blood is contained inside blood vessels and circulates unidirectionally from the heart around the systemic circulatory route, then returns to the heart again, as illustrated in Figurea. As opposed to a closed system, arthropods—including insects, crustaceans, and most mollusks—have an open circulatory system, as illustrated in Figureb. In an open circulatory system, the blood is not enclosed in the blood vessels but is pumped into a cavity called a hemocoel and is called hemolymph because the blood mixes with the interstitial fluid. As the heart beats and the animal moves, the hemolymph circulates around the organs within the body cavity and then reenters the hearts through openings called ostia. This movement allows for gas and nutrient exchange. An open circulatory system does not use as much energy as a closed system to operate or to maintain; however, there is a trade-off with the amount of blood that can be moved to metabolically active organs and tissues that require high levels of oxygen. In fact, one reason that insects with wing spans of up to two feet wide (70 cm) are not around today is probably because they were outcompeted by the arrival of birds 150 million years ago. Birds, having a closed circulatory system, are thought to have moved more agilely, allowing them to get food faster and possibly to prey on the insects. Circulatory System Variation in Animals The circulatory system varies from simple systems in invertebrates to more complex systems in vertebrates. The simplest animals, such as the sponges (Porifera) and rotifers (Rotifera), do not need a circulatory system because diffusion allows adequate exchange of water, nutrients, and waste, as well as dissolved gases, as shown in Figurea. Organisms that are more complex but still only have two layers of cells in their body plan, such as jellies (Cnidaria) and comb jellies (Ctenophora) also use diffusion through their epidermis and internally through the gastrovascular compartment. Both their internal and external tissues are bathed in an aqueous environment and exchange fluids by diffusion on both sides, as illustrated in Figureb. Exchange of fluids is assisted by the pulsing of the jellyfish body. For more complex organisms, diffusion is not efficient for cycling gases, nutrients, and waste effectively through the body; therefore, more complex circulatory systems evolved. Most arthropods and many mollusks have open circulatory systems. In an open system, an elongated beating heart pushes the hemolymph through the body and muscle contractions help to move fluids. The larger more complex crustaceans, including lobsters, have developed arterial-like vessels to push blood through their bodies, and the most active mollusks, such as squids, have evolved a closed circulatory system and are able to move rapidly to catch prey. Closed circulatory systems are a characteristic of vertebrates; however, there are significant differences in the structure of the heart and the circulation of blood between the different vertebrate groups due to adaptation during evolution and associated differences in anatomy. Figure illustrates the basic circulatory systems of some vertebrates: fish, amphibians, reptiles, and mammals. As illustrated in Figurea Fish have a single circuit for blood flow and a two-chambered heart that has only a single atrium and a single ventricle. The atrium collects blood that has returned from the body and the ventricle pumps the blood to the gills where gas exchange occurs and the blood is re-oxygenated; this is called gill circulation. The blood then continues through the rest of the body before arriving back at the atrium; this is called systemic circulation. This unidirectional flow of blood produces a gradient of oxygenated to deoxygenated blood around the fish’s systemic circuit. The result is a limit in the amount of oxygen that can reach some of the organs and tissues of the body, reducing the overall metabolic capacity of fish. In amphibians, reptiles, birds, and mammals, blood flow is directed in two circuits: one through the lungs and back to the heart, which is called pulmonary circulation, and the other throughout the rest of the body and its organs including the brain (systemic circulation). In amphibians, gas exchange also occurs through the skin during pulmonary circulation and is referred to as pulmocutaneous circulation. As shown in Figureb, amphibians have a three-chambered heart that has two atria and one ventricle rather than the two-chambered heart of fish. The two atria (superior heart chambers) receive blood from the two different circuits (the lungs and the systems), and then there is some mixing of the blood in the heart’s ventricle (inferior heart chamber), which reduces the efficiency of oxygenation. The advantage to this arrangement is that high pressure in the vessels pushes blood to the lungs and body. The mixing is mitigated by a ridge within the ventricle that diverts oxygen-rich blood through the systemic circulatory system and deoxygenated blood to the pulmocutaneous circuit. For this reason, amphibians are often described as having double circulation. Most reptiles also have a three-chambered heart similar to the amphibian heart that directs blood to the pulmonary and systemic circuits, as shown in Figurec. The ventricle is divided more effectively by a partial septum, which results in less mixing of oxygenated and deoxygenated blood. Some reptiles (alligators and crocodiles) are the most primitive animals to exhibit a four-chambered heart. Crocodilians have a unique circulatory mechanism where the heart shunts blood from the lungs toward the stomach and other organs during long periods of submergence, for instance, while the animal waits for prey or stays underwater waiting for prey to rot. One adaptation includes two main arteries that leave the same part of the heart: one takes blood to the lungs and the other provides an alternate route to the stomach and other parts of the body. Two other adaptations include a hole in the heart between the two ventricles, called the foramen of Panizza, which allows blood to move from one side of the heart to the other, and specialized connective tissue that slows the blood flow to the lungs. Together these adaptations have made crocodiles and alligators one of the most evolutionarily successful animal groups on earth. In mammals and birds, the heart is also divided into four chambers: two atria and two ventricles, as illustrated in Figured. The oxygenated blood is separated from the deoxygenated blood, which improves the efficiency of double circulation and is probably required for the warm-blooded lifestyle of mammals and birds. The four-chambered heart of birds and mammals evolved independently from a three-chambered heart. The independent evolution of the same or a similar biological trait is referred to as convergent evolution. Section Summary In most animals, the circulatory system is used to transport blood through the body. Some primitive animals use diffusion for the exchange of water, nutrients, and gases. However, complex organisms use the circulatory system to carry gases, nutrients, and waste through the body. Circulatory systems may be open (mixed with the interstitial fluid) or closed (separated from the interstitial fluid). Closed circulatory systems are a characteristic of vertebrates; however, there are significant differences in the structure of the heart and the circulation of blood between the different vertebrate groups due to adaptions during evolution and associated differences in anatomy. Fish have a two-chambered heart with unidirectional circulation. Amphibians have a three-chambered heart, which has some mixing of the blood, and they have double circulation. Most non-avian reptiles have a three-chambered heart, but have little mixing of the blood; they have double circulation. Mammals and birds have a four-chambered heart with no mixing of the blood and double circulation. Review Questions Why are open circulatory systems advantageous to some animals? - They use less metabolic energy. - They help the animal move faster. - They do not need a heart. - They help large insects develop. Hint: A Some animals use diffusion instead of a circulatory system. Examples include: - birds and jellyfish - flatworms and arthropods - mollusks and jellyfish - None of the above Hint: D Blood flow that is directed through the lungs and back to the heart is called ________. - unidirectional circulation - gill circulation - pulmonary circulation - pulmocutaneous circulation Hint: C Free Response Describe a closed circulatory system. Hint: A closed circulatory system is a closed-loop system, in which blood is not free in a cavity. Blood is separate from the bodily interstitial fluid and contained within blood vessels. In this type of system, blood circulates unidirectionally from the heart around the systemic circulatory route, and then returns to the heart. Describe systemic circulation. Hint: Systemic circulation flows through the systems of the body. The blood flows away from the heart to the brain, liver, kidneys, stomach, and other organs, the limbs, and the muscles of the body; it then returns to the heart.	oercommons	2025-03-18T00:36:08.222940	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15143/overview", "title": "Biology, Animal Structure and Function", "author": null }
https://oercommons.org/courseware/lesson/15144/overview	Components of the Blood Overview By the end of this section, you will be able to: - List the basic components of the blood - Compare red and white blood cells - Describe blood plasma and serum Hemoglobin is responsible for distributing oxygen, and to a lesser extent, carbon dioxide, throughout the circulatory systems of humans, vertebrates, and many invertebrates. The blood is more than the proteins, though. Blood is actually a term used to describe the liquid that moves through the vessels and includes plasma (the liquid portion, which contains water, proteins, salts, lipids, and glucose) and the cells (red and white cells) and cell fragments called platelets. Blood plasma is actually the dominant component of blood and contains the water, proteins, electrolytes, lipids, and glucose. The cells are responsible for carrying the gases (red cells) and immune the response (white). The platelets are responsible for blood clotting. Interstitial fluid that surrounds cells is separate from the blood, but in hemolymph, they are combined. In humans, cellular components make up approximately 45 percent of the blood and the liquid plasma 55 percent. Blood is 20 percent of a person’s extracellular fluid and eight percent of weight. The Role of Blood in the Body Blood, like the human blood illustrated in Figure is important for regulation of the body’s systems and homeostasis. Blood helps maintain homeostasis by stabilizing pH, temperature, osmotic pressure, and by eliminating excess heat. Blood supports growth by distributing nutrients and hormones, and by removing waste. Blood plays a protective role by transporting clotting factors and platelets to prevent blood loss and transporting the disease-fighting agents or white blood cells to sites of infection. Red Blood Cells Red blood cells, or erythrocytes (erythro- = “red”; -cyte = “cell”), are specialized cells that circulate through the body delivering oxygen to cells; they are formed from stem cells in the bone marrow. In mammals, red blood cells are small biconcave cells that at maturity do not contain a nucleus or mitochondria and are only 7–8 µm in size. In birds and non-avian reptiles, a nucleus is still maintained in red blood cells. The red coloring of blood comes from the iron-containing protein hemoglobin, illustrated in Figurea. The principal job of this protein is to carry oxygen, but it also transports carbon dioxide as well. Hemoglobin is packed into red blood cells at a rate of about 250 million molecules of hemoglobin per cell. Each hemoglobin molecule binds four oxygen molecules so that each red blood cell carries one billion molecules of oxygen. There are approximately 25 trillion red blood cells in the five liters of blood in the human body, which could carry up to 25 sextillion (25 × 1021) molecules of oxygen in the body at any time. In mammals, the lack of organelles in erythrocytes leaves more room for the hemoglobin molecules, and the lack of mitochondria also prevents use of the oxygen for metabolic respiration. Only mammals have anucleated red blood cells, and some mammals (camels, for instance) even have nucleated red blood cells. The advantage of nucleated red blood cells is that these cells can undergo mitosis. Anucleated red blood cells metabolize anaerobically (without oxygen), making use of a primitive metabolic pathway to produce ATP and increase the efficiency of oxygen transport. Not all organisms use hemoglobin as the method of oxygen transport. Invertebrates that utilize hemolymph rather than blood use different pigments to bind to the oxygen. These pigments use copper or iron to the oxygen. Invertebrates have a variety of other respiratory pigments. Hemocyanin, a blue-green, copper-containing protein, illustrated in Figureb is found in mollusks, crustaceans, and some of the arthropods. Chlorocruorin, a green-colored, iron-containing pigment is found in four families of polychaete tubeworms. Hemerythrin, a red, iron-containing protein is found in some polychaete worms and annelids and is illustrated in Figurec. Despite the name, hemerythrin does not contain a heme group and its oxygen-carrying capacity is poor compared to hemoglobin. The small size and large surface area of red blood cells allows for rapid diffusion of oxygen and carbon dioxide across the plasma membrane. In the lungs, carbon dioxide is released and oxygen is taken in by the blood. In the tissues, oxygen is released from the blood and carbon dioxide is bound for transport back to the lungs. Studies have found that hemoglobin also binds nitrous oxide (NO). NO is a vasodilator that relaxes the blood vessels and capillaries and may help with gas exchange and the passage of red blood cells through narrow vessels. Nitroglycerin, a heart medication for angina and heart attacks, is converted to NO to help relax the blood vessels and increase oxygen flow through the body. A characteristic of red blood cells is their glycolipid and glycoprotein coating; these are lipids and proteins that have carbohydrate molecules attached. In humans, the surface glycoproteins and glycolipids on red blood cells vary between individuals, producing the different blood types, such as A, B, and O. Red blood cells have an average life span of 120 days, at which time they are broken down and recycled in the liver and spleen by phagocytic macrophages, a type of white blood cell. White Blood Cells White blood cells, also called leukocytes (leuko = white), make up approximately one percent by volume of the cells in blood. The role of white blood cells is very different than that of red blood cells: they are primarily involved in the immune response to identify and target pathogens, such as invading bacteria, viruses, and other foreign organisms. White blood cells are formed continually; some only live for hours or days, but some live for years. The morphology of white blood cells differs significantly from red blood cells. They have nuclei and do not contain hemoglobin. The different types of white blood cells are identified by their microscopic appearance after histologic staining, and each has a different specialized function. The two main groups, both illustrated in Figure are the granulocytes, which include the neutrophils, eosinophils, and basophils, and the agranulocytes, which include the monocytes and lymphocytes. Granulocytes contain granules in their cytoplasm; the agranulocytes are so named because of the lack of granules in their cytoplasm. Some leukocytes become macrophages that either stay at the same site or move through the blood stream and gather at sites of infection or inflammation where they are attracted by chemical signals from foreign particles and damaged cells. Lymphocytes are the primary cells of the immune system and include B cells, T cells, and natural killer cells. B cells destroy bacteria and inactivate their toxins. They also produce antibodies. T cells attack viruses, fungi, some bacteria, transplanted cells, and cancer cells. T cells attack viruses by releasing toxins that kill the viruses. Natural killer cells attack a variety of infectious microbes and certain tumor cells. One reason that HIV poses significant management challenges is because the virus directly targets T cells by gaining entry through a receptor. Once inside the cell, HIV then multiplies using the T cell’s own genetic machinery. After the HIV virus replicates, it is transmitted directly from the infected T cell to macrophages. The presence of HIV can remain unrecognized for an extensive period of time before full disease symptoms develop. Platelets and Coagulation Factors Blood must clot to heal wounds and prevent excess blood loss. Small cell fragments called platelets (thrombocytes) are attracted to the wound site where they adhere by extending many projections and releasing their contents. These contents activate other platelets and also interact with other coagulation factors, which convert fibrinogen, a water-soluble protein present in blood serum into fibrin (a non-water soluble protein), causing the blood to clot. Many of the clotting factors require vitamin K to work, and vitamin K deficiency can lead to problems with blood clotting. Many platelets converge and stick together at the wound site forming a platelet plug (also called a fibrin clot), as illustrated in Figureb. The plug or clot lasts for a number of days and stops the loss of blood. Platelets are formed from the disintegration of larger cells called megakaryocytes, like that shown in Figurea. For each megakaryocyte, 2000–3000 platelets are formed with 150,000 to 400,000 platelets present in each cubic millimeter of blood. Each platelet is disc shaped and 2–4 μm in diameter. They contain many small vesicles but do not contain a nucleus. Plasma and Serum The liquid component of blood is called plasma, and it is separated by spinning or centrifuging the blood at high rotations (3000 rpm or higher). The blood cells and platelets are separated by centrifugal forces to the bottom of a specimen tube. The upper liquid layer, the plasma, consists of 90 percent water along with various substances required for maintaining the body’s pH, osmotic load, and for protecting the body. The plasma also contains the coagulation factors and antibodies. The plasma component of blood without the coagulation factors is called the serum. Serum is similar to interstitial fluid in which the correct composition of key ions acting as electrolytes is essential for normal functioning of muscles and nerves. Other components in the serum include proteins that assist with maintaining pH and osmotic balance while giving viscosity to the blood. The serum also contains antibodies, specialized proteins that are important for defense against viruses and bacteria. Lipids, including cholesterol, are also transported in the serum, along with various other substances including nutrients, hormones, metabolic waste, plus external substances, such as, drugs, viruses, and bacteria. Human serum albumin is the most abundant protein in human blood plasma and is synthesized in the liver. Albumin, which constitutes about half of the blood serum protein, transports hormones and fatty acids, buffers pH, and maintains osmotic pressures. Immunoglobin is a protein antibody produced in the mucosal lining and plays an important role in antibody mediated immunity. Evolution Connection Blood Types Related to Proteins on the Surface of the Red Blood Cells Red blood cells are coated in antigens made of glycolipids and glycoproteins. The composition of these molecules is determined by genetics, which have evolved over time. In humans, the different surface antigens are grouped into 24 different blood groups with more than 100 different antigens on each red blood cell. The two most well known blood groups are the ABO, shown in Figure, and Rh systems. The surface antigens in the ABO blood group are glycolipids, called antigen A and antigen B. People with blood type A have antigen A, those with blood type B have antigen B, those with blood type AB have both antigens, and people with blood type O have neither antigen. Antibodies called agglutinougens are found in the blood plasma and react with the A or B antigens, if the two are mixed. When type A and type B blood are combined, agglutination (clumping) of the blood occurs because of antibodies in the plasma that bind with the opposing antigen; this causes clots that coagulate in the kidney causing kidney failure. Type O blood has neither A or B antigens, and therefore, type O blood can be given to all blood types. Type O negative blood is the universal donor. Type AB positive blood is the universal acceptor because it has both A and B antigen. The ABO blood groups were discovered in 1900 and 1901 by Karl Landsteiner at the University of Vienna. The Rh blood group was first discovered in Rhesus monkeys. Most people have the Rh antigen (Rh+) and do not have anti-Rh antibodies in their blood. The few people who do not have the Rh antigen and are Rh– can develop anti-Rh antibodies if exposed to Rh+ blood. This can happen after a blood transfusion or after an Rh– woman has an Rh+ baby. The first exposure does not usually cause a reaction; however, at the second exposure, enough antibodies have built up in the blood to produce a reaction that causes agglutination and breakdown of red blood cells. An injection can prevent this reaction. Link to Learning Play a blood typing game on the Nobel Prize website to solidify your understanding of blood types. Section Summary Specific components of the blood include red blood cells, white blood cells, platelets, and the plasma, which contains coagulation factors and serum. Blood is important for regulation of the body’s pH, temperature, osmotic pressure, the circulation of nutrients and removal of waste, the distribution of hormones from endocrine glands, and the elimination of excess heat; it also contains components for blood clotting. Red blood cells are specialized cells that contain hemoglobin and circulate through the body delivering oxygen to cells. White blood cells are involved in the immune response to identify and target invading bacteria, viruses, and other foreign organisms; they also recycle waste components, such as old red blood cells. Platelets and blood clotting factors cause the change of the soluble protein fibrinogen to the insoluble protein fibrin at a wound site forming a plug. Plasma consists of 90 percent water along with various substances, such as coagulation factors and antibodies. The serum is the plasma component of the blood without the coagulation factors. Review Questions White blood cells: - can be classified as granulocytes or agranulocytes - defend the body against bacteria and viruses - are also called leucocytes - All of the above Hint: D Platelet plug formation occurs at which point? - when large megakaryocytes break up into thousands of smaller fragments - when platelets are dispersed through the blood stream - when platelets are attracted to a site of blood vessel damage - none of the above Hint: C In humans, the plasma comprises what percentage of the blood? - 45 percent - 55 percent - 25 percent - 90 percent Hint: B The red blood cells of birds differ from mammalian red blood cells because: - they are white and have nuclei - they do not have nuclei - they have nuclei - they fight disease Hint: C Free Response Describe the cause of different blood type groups. Hint: Red blood cells are coated with proteins called antigens made of glycolipids and glycoproteins. When type A and type B blood are mixed, the blood agglutinates because of antibodies in the plasma that bind with the opposing antigen. Type O blood has no antigens. The Rh blood group has either the Rh antigen (Rh+) or no Rh antigen (Rh–). List some of the functions of blood in the body. Hint: Blood is important for regulation of the body’s pH, temperature, and osmotic pressure, the circulation of nutrients and removal of wastes, the distribution of hormones from endocrine glands, the elimination of excess heat; it also contains components for the clotting of blood to prevent blood loss. Blood also transports clotting factors and disease-fighting agents. How does the lymphatic system work with blood flow? Hint: Lymph capillaries take fluid from the blood to the lymph nodes. The lymph nodes filter the lymph by percolation through connective tissue filled with white blood cells. The white blood cells remove infectious agents, such as bacteria and viruses, to clean the lymph before it returns to the bloodstream.	oercommons	2025-03-18T00:36:08.255602	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15144/overview", "title": "Biology, Animal Structure and Function", "author": null }
https://oercommons.org/courseware/lesson/15145/overview	Mammalian Heart and Blood Vessels Overview By the end of this section, you will be able to: - Describe the structure of the heart and explain how cardiac muscle is different from other muscles - Describe the cardiac cycle - Explain the structure of arteries, veins, and capillaries, and how blood flows through the body The heart is a complex muscle that pumps blood through the three divisions of the circulatory system: the coronary (vessels that serve the heart), pulmonary (heart and lungs), and systemic (systems of the body), as shown in Figure. Coronary circulation intrinsic to the heart takes blood directly from the main artery (aorta) coming from the heart. For pulmonary and systemic circulation, the heart has to pump blood to the lungs or the rest of the body, respectively. In vertebrates, the lungs are relatively close to the heart in the thoracic cavity. The shorter distance to pump means that the muscle wall on the right side of the heart is not as thick as the left side which must have enough pressure to pump blood all the way to your big toe. Art Connection Which of the following statements about the circulatory system is false? - Blood in the pulmonary vein is deoxygenated. - Blood in the inferior vena cava is deoxygenated. - Blood in the pulmonary artery is deoxygenated. - Blood in the aorta is oxygenated. Structure of the Heart The heart muscle is asymmetrical as a result of the distance blood must travel in the pulmonary and systemic circuits. Since the right side of the heart sends blood to the pulmonary circuit it is smaller than the left side which must send blood out to the whole body in the systemic circuit, as shown in Figure. In humans, the heart is about the size of a clenched fist; it is divided into four chambers: two atria and two ventricles. There is one atrium and one ventricle on the right side and one atrium and one ventricle on the left side. The atria are the chambers that receive blood, and the ventricles are the chambers that pump blood. The right atrium receives deoxygenated blood from the superior vena cava, which drains blood from the jugular vein that comes from the brain and from the veins that come from the arms, as well as from the inferior vena cava which drains blood from the veins that come from the lower organs and the legs. In addition, the right atrium receives blood from the coronary sinus which drains deoxygenated blood from the heart itself. This deoxygenated blood then passes to the right ventricle through the atrioventricular valve or the tricuspid valve, a flap of connective tissue that opens in only one direction to prevent the backflow of blood. The valve separating the chambers on the left side of the heart valve is called the biscuspid or mitral valve. After it is filled, the right ventricle pumps the blood through the pulmonary arteries, by-passing the semilunar valve (or pulmonic valve) to the lungs for re-oxygenation. After blood passes through the pulmonary arteries, the right semilunar valves close preventing the blood from flowing backwards into the right ventricle. The left atrium then receives the oxygen-rich blood from the lungs via the pulmonary veins. This blood passes through the bicuspid valve or mitral valve (the atrioventricular valve on the left side of the heart) to the left ventricle where the blood is pumped out through aorta, the major artery of the body, taking oxygenated blood to the organs and muscles of the body. Once blood is pumped out of the left ventricle and into the aorta, the aortic semilunar valve (or aortic valve) closes preventing blood from flowing backward into the left ventricle. This pattern of pumping is referred to as double circulation and is found in all mammals. Art Connection Which of the following statements about the heart is false? - The mitral valve separates the left ventricle from the left atrium. - Blood travels through the bicuspid valve to the left atrium. - Both the aortic and the pulmonary valves are semilunar valves. - The mitral valve is an atrioventricular valve. The heart is composed of three layers; the epicardium, the myocardium, and the endocardium, illustrated in Figure. The inner wall of the heart has a lining called the endocardium. The myocardium consists of the heart muscle cells that make up the middle layer and the bulk of the heart wall. The outer layer of cells is called the epicardium, of which the second layer is a membranous layered structure called the pericardium that surrounds and protects the heart; it allows enough room for vigorous pumping but also keeps the heart in place to reduce friction between the heart and other structures. The heart has its own blood vessels that supply the heart muscle with blood. The coronary arteries branch from the aorta and surround the outer surface of the heart like a crown. They diverge into capillaries where the heart muscle is supplied with oxygen before converging again into the coronary veins to take the deoxygenated blood back to the right atrium where the blood will be re-oxygenated through the pulmonary circuit. The heart muscle will die without a steady supply of blood. Atherosclerosis is the blockage of an artery by the buildup of fatty plaques. Because of the size (narrow) of the coronary arteries and their function in serving the heart itself, atherosclerosis can be deadly in these arteries. The slowdown of blood flow and subsequent oxygen deprivation that results from atherosclerosis causes severe pain, known as angina, and complete blockage of the arteries will cause myocardial infarction: the death of cardiac muscle tissue, commonly known as a heart attack. The Cardiac Cycle The main purpose of the heart is to pump blood through the body; it does so in a repeating sequence called the cardiac cycle. The cardiac cycle is the coordination of the filling and emptying of the heart of blood by electrical signals that cause the heart muscles to contract and relax. The human heart beats over 100,000 times per day. In each cardiac cycle, the heart contracts (systole), pushing out the blood and pumping it through the body; this is followed by a relaxation phase (diastole), where the heart fills with blood, as illustrated in Figure. The atria contract at the same time, forcing blood through the atrioventricular valves into the ventricles. Closing of the atrioventricular valves produces a monosyllabic “lup” sound. Following a brief delay, the ventricles contract at the same time forcing blood through the semilunar valves into the aorta and the artery transporting blood to the lungs (via the pulmonary artery). Closing of the semilunar valves produces a monosyllabic “dup” sound. The pumping of the heart is a function of the cardiac muscle cells, or cardiomyocytes, that make up the heart muscle. Cardiomyocytes, shown in Figure, are distinctive muscle cells that are striated like skeletal muscle but pump rhythmically and involuntarily like smooth muscle; they are connected by intercalated disks exclusive to cardiac muscle. They are self-stimulated for a period of time and isolated cardiomyocytes will beat if given the correct balance of nutrients and electrolytes. The autonomous beating of cardiac muscle cells is regulated by the heart’s internal pacemaker that uses electrical signals to time the beating of the heart. The electrical signals and mechanical actions, illustrated in Figure, are intimately intertwined. The internal pacemaker starts at the sinoatrial (SA) node, which is located near the wall of the right atrium. Electrical charges spontaneously pulse from the SA node causing the two atria to contract in unison. The pulse reaches a second node, called the atrioventricular (AV) node, between the right atrium and right ventricle where it pauses for approximately 0.1 second before spreading to the walls of the ventricles. From the AV node, the electrical impulse enters the bundle of His, then to the left and right bundle branches extending through the interventricular septum. Finally, the Purkinje fibers conduct the impulse from the apex of the heart up the ventricular myocardium, and then the ventricles contract. This pause allows the atria to empty completely into the ventricles before the ventricles pump out the blood. The electrical impulses in the heart produce electrical currents that flow through the body and can be measured on the skin using electrodes. This information can be observed as an electrocardiogram (ECG)—a recording of the electrical impulses of the cardiac muscle. Link to Learning Visit this site to see the heart’s “pacemaker” in action. Arteries, Veins, and Capillaries The blood from the heart is carried through the body by a complex network of blood vessels (Figure). Arteries take blood away from the heart. The main artery is the aorta that branches into major arteries that take blood to different limbs and organs. These major arteries include the carotid artery that takes blood to the brain, the brachial arteries that take blood to the arms, and the thoracic artery that takes blood to the thorax and then into the hepatic, renal, and gastric arteries for the liver, kidney, and stomach, respectively. The iliac artery takes blood to the lower limbs. The major arteries diverge into minor arteries, and then smaller vessels called arterioles, to reach more deeply into the muscles and organs of the body. Arterioles diverge into capillary beds. Capillary beds contain a large number (10 to 100) of capillaries that branch among the cells and tissues of the body. Capillaries are narrow-diameter tubes that can fit red blood cells through in single file and are the sites for the exchange of nutrients, waste, and oxygen with tissues at the cellular level. Fluid also crosses into the interstitial space from the capillaries. The capillaries converge again into venules that connect to minor veins that finally connect to major veins that take blood high in carbon dioxide back to the heart. Veins are blood vessels that bring blood back to the heart. The major veins drain blood from the same organs and limbs that the major arteries supply. Fluid is also brought back to the heart via the lymphatic system. The structure of the different types of blood vessels reflects their function or layers. There are three distinct layers, or tunics, that form the walls of blood vessels (Figure). The first tunic is a smooth, inner lining of endothelial cells that are in contact with the red blood cells. The endothelial tunic is continuous with the endocardium of the heart. In capillaries, this single layer of cells is the location of diffusion of oxygen and carbon dioxide between the endothelial cells and red blood cells, as well as the exchange site via endocytosis and exocytosis. The movement of materials at the site of capillaries is regulated by vasoconstriction, narrowing of the blood vessels, and vasodilation, widening of the blood vessels; this is important in the overall regulation of blood pressure. Veins and arteries both have two further tunics that surround the endothelium: the middle tunic is composed of smooth muscle and the outermost layer is connective tissue (collagen and elastic fibers). The elastic connective tissue stretches and supports the blood vessels, and the smooth muscle layer helps regulate blood flow by altering vascular resistance through vasoconstriction and vasodilation. The arteries have thicker smooth muscle and connective tissue than the veins to accommodate the higher pressure and speed of freshly pumped blood. The veins are thinner walled as the pressure and rate of flow are much lower. In addition, veins are structurally different than arteries in that veins have valves to prevent the backflow of blood. Because veins have to work against gravity to get blood back to the heart, contraction of skeletal muscle assists with the flow of blood back to the heart. Section Summary The heart muscle pumps blood through three divisions of the circulatory system: coronary, pulmonary, and systemic. There is one atrium and one ventricle on the right side and one atrium and one ventricle on the left side. The pumping of the heart is a function of cardiomyocytes, distinctive muscle cells that are striated like skeletal muscle but pump rhythmically and involuntarily like smooth muscle. The internal pacemaker starts at the sinoatrial node, which is located near the wall of the right atrium. Electrical charges pulse from the SA node causing the two atria to contract in unison; then the pulse reaches the atrioventricular node between the right atrium and right ventricle. A pause in the electric signal allows the atria to empty completely into the ventricles before the ventricles pump out the blood. The blood from the heart is carried through the body by a complex network of blood vessels; arteries take blood away from the heart, and veins bring blood back to the heart. Art Connections Figure Which of the following statements about the heart is false? - The mitral valve separates the left ventricle from the left atrium. - Blood travels through the bicuspid valve to the left atrium. - Both the aortic and the pulmonary valves are semilunar valves. - The mitral valve is an atrioventricular valve. Hint: Figure B Review Questions The heart’s internal pacemaker beats by: - an internal implant that sends an electrical impulse through the heart - the excitation of cardiac muscle cells at the sinoatrial node followed by the atrioventricular node - the excitation of cardiac muscle cells at the atrioventricular node followed by the sinoatrial node - the action of the sinus Hint: B During the systolic phase of the cardiac cycle, the heart is ________. - contracting - relaxing - contracting and relaxing - filling with blood Hint: A Cardiomyocytes are similar to skeletal muscle because: - they beat involuntarily - they are used for weight lifting - they pulse rhythmically - they are striated Hint: D How do arteries differ from veins? - Arteries have thicker smooth muscle layers to accommodate the changes in pressure from the heart. - Arteries carry blood. - Arteries have thinner smooth muscle layers and valves and move blood by the action of skeletal muscle. - Arteries are thin walled and are used for gas exchange. Hint: A Free Response Describe the cardiac cycle. Hint: The heart receives an electrical signal from the sinoatrial node triggering the cardiac muscle cells in the atria to contract. The signal pauses at the atrioventricular node before spreading to the walls of the ventricles so the blood is pumped through the body. This is the systolic phase. The heart then relaxes in the diastole and fills again with blood. What happens in capillaries? Hint: The capillaries basically exchange materials with their surroundings. Their walls are very thin and are made of one or two layers of cells, where gases, nutrients, and waste are diffused. They are distributed as beds, complex networks that link arteries as well as veins.	oercommons	2025-03-18T00:36:08.291194	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15145/overview", "title": "Biology, Animal Structure and Function", "author": null }
https://oercommons.org/courseware/lesson/15146/overview	Blood Flow and Blood Pressure Regulation Overview By the end of this section, you will be able to: - Describe the system of blood flow through the body - Describe how blood pressure is regulated Blood pressure (BP) is the pressure exerted by blood on the walls of a blood vessel that helps to push blood through the body. Systolic blood pressure measures the amount of pressure that blood exerts on vessels while the heart is beating. The optimal systolic blood pressure is 120 mmHg. Diastolic blood pressure measures the pressure in the vessels between heartbeats. The optimal diastolic blood pressure is 80 mmHg. Many factors can affect blood pressure, such as hormones, stress, exercise, eating, sitting, and standing. Blood flow through the body is regulated by the size of blood vessels, by the action of smooth muscle, by one-way valves, and by the fluid pressure of the blood itself. How Blood Flows Through the Body Blood is pushed through the body by the action of the pumping heart. With each rhythmic pump, blood is pushed under high pressure and velocity away from the heart, initially along the main artery, the aorta. In the aorta, the blood travels at 30 cm/sec. As blood moves into the arteries, arterioles, and ultimately to the capillary beds, the rate of movement slows dramatically to about 0.026 cm/sec, one-thousand times slower than the rate of movement in the aorta. While the diameter of each individual arteriole and capillary is far narrower than the diameter of the aorta, and according to the law of continuity, fluid should travel faster through a narrower diameter tube, the rate is actually slower due to the overall diameter of all the combined capillaries being far greater than the diameter of the individual aorta. The slow rate of travel through the capillary beds, which reach almost every cell in the body, assists with gas and nutrient exchange and also promotes the diffusion of fluid into the interstitial space. After the blood has passed through the capillary beds to the venules, veins, and finally to the main venae cavae, the rate of flow increases again but is still much slower than the initial rate in the aorta. Blood primarily moves in the veins by the rhythmic movement of smooth muscle in the vessel wall and by the action of the skeletal muscle as the body moves. Because most veins must move blood against the pull of gravity, blood is prevented from flowing backward in the veins by one-way valves. Because skeletal muscle contraction aids in venous blood flow, it is important to get up and move frequently after long periods of sitting so that blood will not pool in the extremities. Blood flow through the capillary beds is regulated depending on the body’s needs and is directed by nerve and hormone signals. For example, after a large meal, most of the blood is diverted to the stomach by vasodilation of vessels of the digestive system and vasoconstriction of other vessels. During exercise, blood is diverted to the skeletal muscles through vasodilation while blood to the digestive system would be lessened through vasoconstriction. The blood entering some capillary beds is controlled by small muscles, called precapillary sphincters, illustrated in Figure. If the sphincters are open, the blood will flow into the associated branches of the capillary blood. If all of the sphincters are closed, then the blood will flow directly from the arteriole to the venule through the thoroughfare channel (see Figure). These muscles allow the body to precisely control when capillary beds receive blood flow. At any given moment only about 5-10% of our capillary beds actually have blood flowing through them. Art Connection Varicose veins are veins that become enlarged because the valves no longer close properly, allowing blood to flow backward. Varicose veins are often most prominent on the legs. Why do you think this is the case? Link to Learning See the circulatory system’s blood flow. Proteins and other large solutes cannot leave the capillaries. The loss of the watery plasma creates a hyperosmotic solution within the capillaries, especially near the venules. This causes about 85% of the plasma that leaves the capillaries to eventually diffuses back into the capillaries near the venules. The remaining 15% of blood plasma drains out from the interstitial fluid into nearby lymphatic vessels (Figure). The fluid in the lymph is similar in composition to the interstitial fluid. The lymph fluid passes through lymph nodes before it returns to the heart via the vena cava. Lymph nodes are specialized organs that filter the lymph by percolation through a maze of connective tissue filled with white blood cells. The white blood cells remove infectious agents, such as bacteria and viruses, to clean the lymph before it returns to the bloodstream. After it is cleaned, the lymph returns to the heart by the action of smooth muscle pumping, skeletal muscle action, and one-way valves joining the returning blood near the junction of the venae cavae entering the right atrium of the heart. Evolution Connection Vertebrate Diversity in Blood Circulation Blood circulation has evolved differently in vertebrates and may show variation in different animals for the required amount of pressure, organ and vessel location, and organ size. Animals with longs necks and those that live in cold environments have distinct blood pressure adaptations. Long necked animals, such as giraffes, need to pump blood upward from the heart against gravity. The blood pressure required from the pumping of the left ventricle would be equivalent to 250 mm Hg (mm Hg = millimeters of mercury, a unit of pressure) to reach the height of a giraffe’s head, which is 2.5 meters higher than the heart. However, if checks and balances were not in place, this blood pressure would damage the giraffe’s brain, particularly if it was bending down to drink. These checks and balances include valves and feedback mechanisms that reduce the rate of cardiac output. Long-necked dinosaurs such as the sauropods had to pump blood even higher, up to ten meters above the heart. This would have required a blood pressure of more than 600 mm Hg, which could only have been achieved by an enormous heart. Evidence for such an enormous heart does not exist and mechanisms to reduce the blood pressure required include the slowing of metabolism as these animals grew larger. It is likely that they did not routinely feed on tree tops but grazed on the ground. Living in cold water, whales need to maintain the temperature in their blood. This is achieved by the veins and arteries being close together so that heat exchange can occur. This mechanism is called a countercurrent heat exchanger. The blood vessels and the whole body are also protected by thick layers of blubber to prevent heat loss. In land animals that live in cold environments, thick fur and hibernation are used to retain heat and slow metabolism. Blood Pressure The pressure of the blood flow in the body is produced by the hydrostatic pressure of the fluid (blood) against the walls of the blood vessels. Fluid will move from areas of high to low hydrostatic pressures. In the arteries, the hydrostatic pressure near the heart is very high and blood flows to the arterioles where the rate of flow is slowed by the narrow openings of the arterioles. During systole, when new blood is entering the arteries, the artery walls stretch to accommodate the increase of pressure of the extra blood; during diastole, the walls return to normal because of their elastic properties. The blood pressure of the systole phase and the diastole phase, graphed in Figure, gives the two pressure readings for blood pressure. For example, 120/80 indicates a reading of 120 mm Hg during the systole and 80 mm Hg during diastole. Throughout the cardiac cycle, the blood continues to empty into the arterioles at a relatively even rate. This resistance to blood flow is called peripheral resistance. Blood Pressure Regulation Cardiac output is the volume of blood pumped by the heart in one minute. It is calculated by multiplying the number of heart contractions that occur per minute (heart rate) times the stroke volume (the volume of blood pumped into the aorta per contraction of the left ventricle). Therefore, cardiac output can be increased by increasing heart rate, as when exercising. However, cardiac output can also be increased by increasing stroke volume, such as if the heart contracts with greater strength. Stroke volume can also be increased by speeding blood circulation through the body so that more blood enters the heart between contractions. During heavy exertion, the blood vessels relax and increase in diameter, offsetting the increased heart rate and ensuring adequate oxygenated blood gets to the muscles. Stress triggers a decrease in the diameter of the blood vessels, consequently increasing blood pressure. These changes can also be caused by nerve signals or hormones, and even standing up or lying down can have a great effect on blood pressure. Section Summary Blood primarily moves through the body by the rhythmic movement of smooth muscle in the vessel wall and by the action of the skeletal muscle as the body moves. Blood is prevented from flowing backward in the veins by one-way valves. Blood flow through the capillary beds is controlled by precapillary sphincters to increase and decrease flow depending on the body’s needs and is directed by nerve and hormone signals. Lymph vessels take fluid that has leaked out of the blood to the lymph nodes where it is cleaned before returning to the heart. During systole, blood enters the arteries, and the artery walls stretch to accommodate the extra blood. During diastole, the artery walls return to normal. The blood pressure of the systole phase and the diastole phase gives the two pressure readings for blood pressure. Art Connections Figure Varicose veins are veins that become enlarged because the valves no longer close properly, allowing blood to flow backward. Varicose veins are often most prominent on the legs. Why do you think this is the case? Hint: Figure Blood in the legs is farthest away from the heart and has to flow up to reach it. Review Questions High blood pressure would be a result of ________. - a high cardiac output and high peripheral resistance - a high cardiac output and low peripheral resistance - a low cardiac output and high peripheral resistance - a low cardiac output and low peripheral resistance Hint: A Free Response How does blood pressure change during heavy exercise? Hint: The heart rate increases, which increases the hydrostatic pressure against the artery walls. At the same time, the arterioles dilate in response to the increased exercise, which reduces peripheral resistance.	oercommons	2025-03-18T00:36:08.317060	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15146/overview", "title": "Biology, Animal Structure and Function", "author": null }
https://oercommons.org/courseware/lesson/15147/overview	Introduction The daily intake recommendation for human water consumption is eight to ten glasses of water. In order to achieve a healthy balance, the human body should excrete the eight to ten glasses of water every day. This occurs via the processes of urination, defecation, sweating and, to a small extent, respiration. The organs and tissues of the human body are soaked in fluids that are maintained at constant temperature, pH, and solute concentration, all crucial elements of homeostasis. The solutes in body fluids are mainly mineral salts and sugars, and osmotic regulation is the process by which the mineral salts and water are kept in balance. Osmotic homeostasis is maintained despite the influence of external factors like temperature, diet, and weather conditions.	oercommons	2025-03-18T00:36:08.334674	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15147/overview", "title": "Biology, Animal Structure and Function", "author": null }
https://oercommons.org/courseware/lesson/15148/overview	Osmoregulation and Osmotic Balance Overview By the end of this section, you will be able to: - Define osmosis and explain its role within molecules - Explain why osmoregulation and osmotic balance are important body functions - Describe active transport mechanisms - Explain osmolarity and the way in which it is measured - Describe osmoregulators or osmoconformers and how these tools allow animals to adapt to different environments Osmosis is the diffusion of water across a membrane in response to osmotic pressure caused by an imbalance of molecules on either side of the membrane. Osmoregulation is the process of maintenance of salt and water balance (osmotic balance) across membranes within the body’s fluids, which are composed of water, plus electrolytes and non-electrolytes. An electrolyte is a solute that dissociates into ions when dissolved in water. A non-electrolyte, in contrast, doesn’t dissociate into ions during water dissolution. Both electrolytes and non-electrolytes contribute to the osmotic balance. The body’s fluids include blood plasma, the cytosol within cells, and interstitial fluid, the fluid that exists in the spaces between cells and tissues of the body. The membranes of the body (such as the pleural, serous, and cell membranes) are semi-permeable membranes. Semi-permeable membranes are permeable (or permissive) to certain types of solutes and water. Solutions on two sides of a semi-permeable membrane tend to equalize in solute concentration by movement of solutes and/or water across the membrane. As seen in Figure, a cell placed in water tends to swell due to gain of water from the hypotonic or “low salt” environment. A cell placed in a solution with higher salt concentration, on the other hand, tends to make the membrane shrivel up due to loss of water into the hypertonic or “high salt” environment. Isotonic cells have an equal concentration of solutes inside and outside the cell; this equalizes the osmotic pressure on either side of the cell membrane which is a semi-permeable membrane. The body does not exist in isolation. There is a constant input of water and electrolytes into the system. While osmoregulation is achieved across membranes within the body, excess electrolytes and wastes are transported to the kidneys and excreted, helping to maintain osmotic balance. Need for Osmoregulation Biological systems constantly interact and exchange water and nutrients with the environment by way of consumption of food and water and through excretion in the form of sweat, urine, and feces. Without a mechanism to regulate osmotic pressure, or when a disease damages this mechanism, there is a tendency to accumulate toxic waste and water, which can have dire consequences. Mammalian systems have evolved to regulate not only the overall osmotic pressure across membranes, but also specific concentrations of important electrolytes in the three major fluid compartments: blood plasma, extracellular fluid, and intracellular fluid. Since osmotic pressure is regulated by the movement of water across membranes, the volume of the fluid compartments can also change temporarily. Because blood plasma is one of the fluid components, osmotic pressures have a direct bearing on blood pressure. Transport of Electrolytes across Cell Membranes Electrolytes, such as sodium chloride, ionize in water, meaning that they dissociate into their component ions. In water, sodium chloride (NaCl), dissociates into the sodium ion (Na+) and the chloride ion (Cl–). The most important ions, whose concentrations are very closely regulated in body fluids, are the cations sodium (Na+), potassium (K+), calcium (Ca+2), magnesium (Mg+2), and the anions chloride (Cl-), carbonate (CO3-2), bicarbonate (HCO3-), and phosphate(PO3-). Electrolytes are lost from the body during urination and perspiration. For this reason, athletes are encouraged to replace electrolytes and fluids during periods of increased activity and perspiration. Osmotic pressure is influenced by the concentration of solutes in a solution. It is directly proportional to the number of solute atoms or molecules and not dependent on the size of the solute molecules. Because electrolytes dissociate into their component ions, they, in essence, add more solute particles into the solution and have a greater effect on osmotic pressure, per mass than compounds that do not dissociate in water, such as glucose. Water can pass through membranes by passive diffusion. If electrolyte ions could passively diffuse across membranes, it would be impossible to maintain specific concentrations of ions in each fluid compartment therefore they require special mechanisms to cross the semi-permeable membranes in the body. This movement can be accomplished by facilitated diffusion and active transport. Facilitated diffusion requires protein-based channels for moving the solute. Active transport requires energy in the form of ATP conversion, carrier proteins, or pumps in order to move ions against the concentration gradient. Concept of Osmolality and Milliequivalent In order to calculate osmotic pressure, it is necessary to understand how solute concentrations are measured. The unit for measuring solutes is the mole. One mole is defined as the gram molecular weight of the solute. For example, the molecular weight of sodium chloride is 58.44. Thus, one mole of sodium chloride weighs 58.44 grams. The molarity of a solution is the number of moles of solute per liter of solution. The molality of a solution is the number of moles of solute per kilogram of solvent. If the solvent is water, one kilogram of water is equal to one liter of water. While molarity and molality are used to express the concentration of solutions, electrolyte concentrations are usually expressed in terms of milliequivalents per liter (mEq/L): the mEq/L is equal to the ion concentration (in millimoles) multiplied by the number of electrical charges on the ion. The unit of milliequivalent takes into consideration the ions present in the solution (since electrolytes form ions in aqueous solutions) and the charge on the ions. Thus, for ions that have a charge of one, one milliequivalent is equal to one millimole. For ions that have a charge of two (like calcium), one milliequivalent is equal to 0.5 millimoles. Another unit for the expression of electrolyte concentration is the milliosmole (mOsm), which is the number of milliequivalents of solute per kilogram of solvent. Body fluids are usually maintained within the range of 280 to 300 mOsm. Osmoregulators and Osmoconformers Persons lost at sea without any fresh water to drink are at risk of severe dehydration because the human body cannot adapt to drinking seawater, which is hypertonic in comparison to body fluids. Organisms such as goldfish that can tolerate only a relatively narrow range of salinity are referred to as stenohaline. About 90 percent of all bony fish are restricted to either freshwater or seawater. They are incapable of osmotic regulation in the opposite environment. It is possible, however, for a few fishes like salmon to spend part of their life in fresh water and part in sea water. Organisms like the salmon and molly that can tolerate a relatively wide range of salinity are referred to as euryhaline organisms. This is possible because some fish have evolved osmoregulatory mechanisms to survive in all kinds of aquatic environments. When they live in fresh water, their bodies tend to take up water because the environment is relatively hypotonic, as illustrated in Figurea. In such hypotonic environments, these fish do not drink much water. Instead, they pass a lot of very dilute urine, and they achieve electrolyte balance by active transport of salts through the gills. When they move to a hypertonic marine environment, these fish start drinking sea water; they excrete the excess salts through their gills and their urine, as illustrated in Figureb. Most marine invertebrates, on the other hand, may be isotonic with sea water (osmoconformers). Their body fluid concentrations conform to changes in seawater concentration. Cartilaginous fishes’ salt composition of the blood is similar to bony fishes; however, the blood of sharks contains the organic compounds urea and trimethylamine oxide (TMAO). This does not mean that their electrolyte composition is similar to that of sea water. They achieve isotonicity with the sea by storing large concentrations of urea. These animals that secrete urea are called ureotelic animals. TMAO stabilizes proteins in the presence of high urea levels, preventing the disruption of peptide bonds that would occur in other animals exposed to similar levels of urea. Sharks are cartilaginous fish with a rectal gland to secrete salt and assist in osmoregulation. Career Connection Dialysis TechnicianDialysis is a medical process of removing wastes and excess water from the blood by diffusion and ultrafiltration. When kidney function fails, dialysis must be done to artificially rid the body of wastes. This is a vital process to keep patients alive. In some cases, the patients undergo artificial dialysis until they are eligible for a kidney transplant. In others who are not candidates for kidney transplants, dialysis is a life-long necessity. Dialysis technicians typically work in hospitals and clinics. While some roles in this field include equipment development and maintenance, most dialysis technicians work in direct patient care. Their on-the-job duties, which typically occur under the direct supervision of a registered nurse, focus on providing dialysis treatments. This can include reviewing patient history and current condition, assessing and responding to patient needs before and during treatment, and monitoring the dialysis process. Treatment may include taking and reporting a patient’s vital signs and preparing solutions and equipment to ensure accurate and sterile procedures. Section Summary Solute concentrations across a semi-permeable membranes influence the movement of water and solutes across the membrane. It is the number of solute molecules and not the molecular size that is important in osmosis. Osmoregulation and osmotic balance are important bodily functions, resulting in water and salt balance. Not all solutes can pass through a semi-permeable membrane. Osmosis is the movement of water across the membrane. Osmosis occurs to equalize the number of solute molecules across a semi-permeable membrane by the movement of water to the side of higher solute concentration. Facilitated diffusion utilizes protein channels to move solute molecules from areas of higher to lower concentration while active transport mechanisms are required to move solutes against concentration gradients. Osmolarity is measured in units of milliequivalents or milliosmoles, both of which take into consideration the number of solute particles and the charge on them. Fish that live in fresh water or saltwater adapt by being osmoregulators or osmoconformers. Review Questions When a dehydrated human patient needs to be given fluids intravenously, he or she is given: - water, which is hypotonic with respect to body fluids - saline at a concentration that is isotonic with respect to body fluids - glucose because it is a non-electrolyte - blood Hint: B The sodium ion is at the highest concentration in: - intracellular fluid - extracellular fluid - blood plasma - none of the above Hint: B Cells in a hypertonic solution tend to: - shrink due to water loss - swell due to water gain - stay the same size due to water moving into and out of the cell at the same rate - none of the above Hint: A Free Response Why is excretion important in order to achieve osmotic balance? Hint: Excretion allows an organism to rid itself of waste molecules that could be toxic if allowed to accumulate. It also allows the organism to keep the amount of water and dissolved solutes in balance. Why do electrolyte ions move across membranes by active transport? Hint: Electrolyte ions often require special mechanisms to cross the semi-permeable membranes in the body. Active transport is the movement against a concentration gradient.	oercommons	2025-03-18T00:36:08.362123	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15148/overview", "title": "Biology, Animal Structure and Function", "author": null }
https://oercommons.org/courseware/lesson/15149/overview	The Kidneys and Osmoregulatory Organs Overview By the end of this section, you will be able to: - Explain how the kidneys serve as the main osmoregulatory organs in mammalian systems - Describe the structure of the kidneys and the functions of the parts of the kidney - Describe how the nephron is the functional unit of the kidney and explain how it actively filters blood and generates urine - Detail the three steps in the formation of urine: glomerular filtration, tubular reabsorption, and tubular secretion Although the kidneys are the major osmoregulatory organ, the skin and lungs also play a role in the process. Water and electrolytes are lost through sweat glands in the skin, which helps moisturize and cool the skin surface, while the lungs expel a small amount of water in the form of mucous secretions and via evaporation of water vapor. Kidneys: The Main Osmoregulatory Organ The kidneys, illustrated in Figure, are a pair of bean-shaped structures that are located just below and posterior to the liver in the peritoneal cavity. The adrenal glands sit on top of each kidney and are also called the suprarenal glands. Kidneys filter blood and purify it. All the blood in the human body is filtered many times a day by the kidneys; these organs use up almost 25 percent of the oxygen absorbed through the lungs to perform this function. Oxygen allows the kidney cells to efficiently manufacture chemical energy in the form of ATP through aerobic respiration. The filtrate coming out of the kidneys is called urine. Kidney Structure Externally, the kidneys are surrounded by three layers, illustrated in Figure. The outermost layer is a tough connective tissue layer called the renal fascia. The second layer is called the perirenal fat capsule, which helps anchor the kidneys in place. The third and innermost layer is the renal capsule. Internally, the kidney has three regions—an outer cortex, a medulla in the middle, and the renal pelvis in the region called the hilum of the kidney. The hilum is the concave part of the bean-shape where blood vessels and nerves enter and exit the kidney; it is also the point of exit for the ureters. The renal cortex is granular due to the presence of nephrons—the functional unit of the kidney. The medulla consists of multiple pyramidal tissue masses, called the renal pyramids. In between the pyramids are spaces called renal columns through which the blood vessels pass. The tips of the pyramids, called renal papillae, point toward the renal pelvis. There are, on average, eight renal pyramids in each kidney. The renal pyramids along with the adjoining cortical region are called the lobes of the kidney. The renal pelvis leads to the ureter on the outside of the kidney. On the inside of the kidney, the renal pelvis branches out into two or three extensions called the major calyces, which further branch into the minor calyces. The ureters are urine-bearing tubes that exit the kidney and empty into the urinary bladder. Art Connection Which of the following statements about the kidney is false? - The renal pelvis drains into the ureter. - The renal pyramids are in the medulla. - The cortex covers the capsule. - Nephrons are in the renal cortex. Because the kidney filters blood, its network of blood vessels is an important component of its structure and function. The arteries, veins, and nerves that supply the kidney enter and exit at the renal hilum. Renal blood supply starts with the branching of the aorta into the renal arteries (which are each named based on the region of the kidney they pass through) and ends with the exiting of the renal veins to join the inferior vena cava. The renal arteries split into several segmental arteries upon entering the kidneys. Each segmental artery splits further into several interlobar arteries and enters the renal columns, which supply the renal lobes. The interlobar arteries split at the junction of the renal cortex and medulla to form the arcuate arteries. The arcuate “bow shaped” arteries form arcs along the base of the medullary pyramids. Cortical radiate arteries, as the name suggests, radiate out from the arcuate arteries. The cortical radiate arteries branch into numerous afferent arterioles, and then enter the capillaries supplying the nephrons. Veins trace the path of the arteries and have similar names, except there are no segmental veins. As mentioned previously, the functional unit of the kidney is the nephron, illustrated in Figure. Each kidney is made up of over one million nephrons that dot the renal cortex, giving it a granular appearance when sectioned sagittally. There are two types of nephrons—cortical nephrons (85 percent), which are deep in the renal cortex, and juxtamedullary nephrons (15 percent), which lie in the renal cortex close to the renal medulla. A nephron consists of three parts—a renal corpuscle, a renal tubule, and the associated capillary network, which originates from the cortical radiate arteries. Art Connection Which of the following statements about the nephron is false? - The collecting duct empties into the distal convoluted tubule. - The Bowman’s capsule surrounds the glomerulus. - The loop of Henle is between the proximal and distal convoluted tubules. - The loop of Henle empties into the distal convoluted tubule. Renal Corpuscle The renal corpuscle, located in the renal cortex, is made up of a network of capillaries known as the glomerulus and the capsule, a cup-shaped chamber that surrounds it, called the glomerular or Bowman's capsule. Renal Tubule The renal tubule is a long and convoluted structure that emerges from the glomerulus and can be divided into three parts based on function. The first part is called the proximal convoluted tubule (PCT) due to its proximity to the glomerulus; it stays in the renal cortex. The second part is called the loop of Henle, or nephritic loop, because it forms a loop (with descending and ascending limbs) that goes through the renal medulla. The third part of the renal tubule is called the distal convoluted tubule (DCT) and this part is also restricted to the renal cortex. The DCT, which is the last part of the nephron, connects and empties its contents into collecting ducts that line the medullary pyramids. The collecting ducts amass contents from multiple nephrons and fuse together as they enter the papillae of the renal medulla. Capillary Network within the Nephron The capillary network that originates from the renal arteries supplies the nephron with blood that needs to be filtered. The branch that enters the glomerulus is called the afferent arteriole. The branch that exits the glomerulus is called the efferent arteriole. Within the glomerulus, the network of capillaries is called the glomerular capillary bed. Once the efferent arteriole exits the glomerulus, it forms the peritubular capillary network, which surrounds and interacts with parts of the renal tubule. In cortical nephrons, the peritubular capillary network surrounds the PCT and DCT. In juxtamedullary nephrons, the peritubular capillary network forms a network around the loop of Henle and is called the vasa recta. Link to Learning Go to this website to see another coronal section of the kidney and to explore an animation of the workings of nephrons. Kidney Function and Physiology Kidneys filter blood in a three-step process. First, the nephrons filter blood that runs through the capillary network in the glomerulus. Almost all solutes, except for proteins, are filtered out into the glomerulus by a process called glomerular filtration. Second, the filtrate is collected in the renal tubules. Most of the solutes get reabsorbed in the PCT by a process called tubular reabsorption. In the loop of Henle, the filtrate continues to exchange solutes and water with the renal medulla and the peritubular capillary network. Water is also reabsorbed during this step. Then, additional solutes and wastes are secreted into the kidney tubules during tubular secretion, which is, in essence, the opposite process to tubular reabsorption. The collecting ducts collect filtrate coming from the nephrons and fuse in the medullary papillae. From here, the papillae deliver the filtrate, now called urine, into the minor calyces that eventually connect to the ureters through the renal pelvis. This entire process is illustrated in Figure. Glomerular Filtration Glomerular filtration filters out most of the solutes due to high blood pressure and specialized membranes in the afferent arteriole. The blood pressure in the glomerulus is maintained independent of factors that affect systemic blood pressure. The “leaky” connections between the endothelial cells of the glomerular capillary network allow solutes to pass through easily. All solutes in the glomerular capillaries, except for macromolecules like proteins, pass through by passive diffusion. There is no energy requirement at this stage of the filtration process. Glomerular filtration rate (GFR) is the volume of glomerular filtrate formed per minute by the kidneys. GFR is regulated by multiple mechanisms and is an important indicator of kidney function. Link to Learning To learn more about the vascular system of kidneys, click through this review and the steps of blood flow. Tubular Reabsorption and Secretion Tubular reabsorption occurs in the PCT part of the renal tubule. Almost all nutrients are reabsorbed, and this occurs either by passive or active transport. Reabsorption of water and some key electrolytes are regulated and can be influenced by hormones. Sodium (Na+) is the most abundant ion and most of it is reabsorbed by active transport and then transported to the peritubular capillaries. Because Na+ is actively transported out of the tubule, water follows it to even out the osmotic pressure. Water is also independently reabsorbed into the peritubular capillaries due to the presence of aquaporins, or water channels, in the PCT. This occurs due to the low blood pressure and high osmotic pressure in the peritubular capillaries. However, every solute has a transport maximum and the excess is not reabsorbed. In the loop of Henle, the permeability of the membrane changes. The descending limb is permeable to water, not solutes; the opposite is true for the ascending limb. Additionally, the loop of Henle invades the renal medulla, which is naturally high in salt concentration and tends to absorb water from the renal tubule and concentrate the filtrate. The osmotic gradient increases as it moves deeper into the medulla. Because two sides of the loop of Henle perform opposing functions, as illustrated in Figure, it acts as a countercurrent multiplier. The vasa recta around it acts as the countercurrent exchanger. Art Connection Loop diuretics are drugs sometimes used to treat hypertension. These drugs inhibit the reabsorption of Na+ and Cl- ions by the ascending limb of the loop of Henle. A side effect is that they increase urination. Why do you think this is the case? By the time the filtrate reaches the DCT, most of the urine and solutes have been reabsorbed. If the body requires additional water, all of it can be reabsorbed at this point. Further reabsorption is controlled by hormones, which will be discussed in a later section. Excretion of wastes occurs due to lack of reabsorption combined with tubular secretion. Undesirable products like metabolic wastes, urea, uric acid, and certain drugs, are excreted by tubular secretion. Most of the tubular secretion happens in the DCT, but some occurs in the early part of the collecting duct. Kidneys also maintain an acid-base balance by secreting excess H+ ions. Although parts of the renal tubules are named proximal and distal, in a cross-section of the kidney, the tubules are placed close together and in contact with each other and the glomerulus. This allows for exchange of chemical messengers between the different cell types. For example, the DCT ascending limb of the loop of Henle has masses of cells called macula densa, which are in contact with cells of the afferent arterioles called juxtaglomerular cells. Together, the macula densa and juxtaglomerular cells form the juxtaglomerular complex (JGC). The JGC is an endocrine structure that secretes the enzyme renin and the hormone erythropoietin. When hormones trigger the macula densa cells in the DCT due to variations in blood volume, blood pressure, or electrolyte balance, these cells can immediately communicate the problem to the capillaries in the afferent and efferent arterioles, which can constrict or relax to change the glomerular filtration rate of the kidneys. Career Connection NephrologistA nephrologist studies and deals with diseases of the kidneys—both those that cause kidney failure (such as diabetes) and the conditions that are produced by kidney disease (such as hypertension). Blood pressure, blood volume, and changes in electrolyte balance come under the purview of a nephrologist. Nephrologists usually work with other physicians who refer patients to them or consult with them about specific diagnoses and treatment plans. Patients are usually referred to a nephrologist for symptoms such as blood or protein in the urine, very high blood pressure, kidney stones, or renal failure. Nephrology is a subspecialty of internal medicine. To become a nephrologist, medical school is followed by additional training to become certified in internal medicine. An additional two or more years is spent specifically studying kidney disorders and their accompanying effects on the body. Section Summary The kidneys are the main osmoregulatory organs in mammalian systems; they function to filter blood and maintain the osmolarity of body fluids at 300 mOsm. They are surrounded by three layers and are made up internally of three distinct regions—the cortex, medulla, and pelvis. The blood vessels that transport blood into and out of the kidneys arise from and merge with the aorta and inferior vena cava, respectively. The renal arteries branch out from the aorta and enter the kidney where they further divide into segmental, interlobar, arcuate, and cortical radiate arteries. The nephron is the functional unit of the kidney, which actively filters blood and generates urine. The nephron is made up of the renal corpuscle and renal tubule. Cortical nephrons are found in the renal cortex, while juxtamedullary nephrons are found in the renal cortex close to the renal medulla. The nephron filters and exchanges water and solutes with two sets of blood vessels and the tissue fluid in the kidneys. There are three steps in the formation of urine: glomerular filtration, which occurs in the glomerulus; tubular reabsorption, which occurs in the renal tubules; and tubular secretion, which also occurs in the renal tubules. Art Connections Figure Which of the following statements about the nephron is false? - The collecting duct empties into the distal convoluted tubule. - The Bowman’s capsule surrounds the glomerulus. - The loop of Henle is between the proximal and distal convoluted tubules. - The loop of Henle empties into the distal convoluted tubule. Hint: Figure A Figure Loop diuretics are drugs sometimes used to treat hypertension. These drugs inhibit the reabsorption of Na+ and Cl- ions by the ascending limb of the loop of Henle. A side effect is that they increase urination. Why do you think this is the case? Hint: Figure Loop diuretics decrease the excretion of salt into the renal medulla, thereby reducing its osmolality. As a result, less water is excreted into the medulla by the descending limb, and more water is excreted as urine. Review Questions The macula densa is/are: - present in the renal medulla. - dense tissue present in the outer layer of the kidney. - cells present in the DCT and collecting tubules. - present in blood capillaries. Hint: C The osmolarity of body fluids is maintained at ________. - 100 mOsm - 300 mOsm - 1000 mOsm - it is not constantly maintained Hint: B The gland located at the top of the kidney is the ________ gland. - adrenal - pituitary - thyroid - thymus Hint: A Free Response Why are the loop of Henle and vasa recta important for the formation of concentrated urine? Hint: The loop of Henle is part of the renal tubule that loops into the renal medulla. In the loop of Henle, the filtrate exchanges solutes and water with the renal medulla and the vasa recta (the peritubular capillary network). The vasa recta acts as the countercurrent exchanger. The kidneys maintain the osmolality of the rest of the body at a constant 300 mOsm by concentrating the filtrate as it passes through the loop of Henle. Describe the structure of the kidney. Hint: Externally, the kidneys are surrounded by three layers. The outermost layer is a tough connective tissue layer called the renal fascia. The second layer is called the perirenal fat capsule, which helps anchor the kidneys in place. The third and innermost layer is the renal capsule. Internally, the kidney has three regions—an outer cortex, a medulla in the middle, and the renal pelvis in the region called the hilum of the kidney, which is the concave part of the “bean” shape.	oercommons	2025-03-18T00:36:08.400328	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15149/overview", "title": "Biology, Animal Structure and Function", "author": null }
https://oercommons.org/courseware/lesson/15150/overview	Excretion Systems Overview By the end of this section, you will be able to: - Explain how vacuoles, present in microorganisms, work to excrete waste - Describe the way in which flame cells and nephridia in worms perform excretory functions and maintain osmotic balance - Explain how insects use Malpighian tubules to excrete wastes and maintain osmotic balance Microorganisms and invertebrate animals use more primitive and simple mechanisms to get rid of their metabolic wastes than the mammalian system of kidney and urinary function. Three excretory systems evolved in organisms before complex kidneys: vacuoles, flame cells, and Malpighian tubules. Contractile Vacuoles in Microorganisms The most fundamental feature of life is the presence of a cell. In other words, a cell is the simplest functional unit of a life. Bacteria are unicellular, prokaryotic organisms that have some of the least complex life processes in place; however, prokaryotes such as bacteria do not contain membrane-bound vacuoles. The cells of microorganisms like bacteria, protozoa, and fungi are bound by cell membranes and use them to interact with the environment. Some cells, including some leucocytes in humans, are able to engulf food by endocytosis—the formation of vesicles by involution of the cell membrane within the cells. The same vesicles are able to interact and exchange metabolites with the intracellular environment. In some unicellular eukaryotic organisms such as the amoeba, shown in Figure, cellular wastes and excess water are excreted by exocytosis, when the contractile vacuoles merge with the cell membrane and expel wastes into the environment. Contractile vacuoles (CV) should not be confused with vacuoles, which store food or water. Flame Cells of Planaria and Nephridia of Worms As multi-cellular systems evolved to have organ systems that divided the metabolic needs of the body, individual organs evolved to perform the excretory function. Planaria are flatworms that live in fresh water. Their excretory system consists of two tubules connected to a highly branched duct system. The cells in the tubules are called flame cells (or protonephridia) because they have a cluster of cilia that looks like a flickering flame when viewed under the microscope, as illustrated in Figurea. The cilia propel waste matter down the tubules and out of the body through excretory pores that open on the body surface; cilia also draw water from the interstitial fluid, allowing for filtration. Any valuable metabolites are recovered by reabsorption. Flame cells are found in flatworms, including parasitic tapeworms and free-living planaria. They also maintain the organism’s osmotic balance. Earthworms (annelids) have slightly more evolved excretory structures called nephridia, illustrated in Figureb. A pair of nephridia is present on each segment of the earthworm. They are similar to flame cells in that they have a tubule with cilia. Excretion occurs through a pore called the nephridiopore. They are more evolved than the flame cells in that they have a system for tubular reabsorption by a capillary network before excretion. Malpighian Tubules of Insects Malpighian tubules are found lining the gut of some species of arthropods, such as the bee illustrated in Figure. They are usually found in pairs and the number of tubules varies with the species of insect. Malpighian tubules are convoluted, which increases their surface area, and they are lined with microvilli for reabsorption and maintenance of osmotic balance. Malpighian tubules work cooperatively with specialized glands in the wall of the rectum. Body fluids are not filtered as in the case of nephridia; urine is produced by tubular secretion mechanisms by the cells lining the Malpighian tubules that are bathed in hemolymph (a mixture of blood and interstitial fluid that is found in insects and other arthropods as well as most mollusks). Metabolic wastes like uric acid freely diffuse into the tubules. There are exchange pumps lining the tubules, which actively transport H+ ions into the cell and K+ or Na+ ions out; water passively follows to form urine. The secretion of ions alters the osmotic pressure which draws water, electrolytes, and nitrogenous waste (uric acid) into the tubules. Water and electrolytes are reabsorbed when these organisms are faced with low-water environments, and uric acid is excreted as a thick paste or powder. Not dissolving wastes in water helps these organisms to conserve water; this is especially important for life in dry environments. Link to Learning See a dissected cockroach, including a close-up look at its Malpighian tubules. Section Summary Many systems have evolved for excreting wastes that are simpler than the kidney and urinary systems of vertebrate animals. The simplest system is that of contractile vacuoles present in microorganisms. Flame cells and nephridia in worms perform excretory functions and maintain osmotic balance. Some insects have evolved Malpighian tubules to excrete wastes and maintain osmotic balance. Review Questions Active transport of K+ in Malpighian tubules ensures that: - water follows K+ to make urine - osmotic balance is maintained between waste matter and bodily fluids - both a and b - neither a nor b Hint: C Contractile vacuoles in microorganisms: - exclusively perform an excretory function - can perform many functions, one of which is excretion of metabolic wastes - originate from the cell membrane - both b and c Hint: D Flame cells are primitive excretory organs found in ________. - arthropods - annelids - mammals - flatworms Hint: D Free Response Why might specialized organs have evolved for excretion of wastes? Hint: The removal of wastes, which could otherwise be toxic to an organism, is extremely important for survival. Having organs that specialize in this process and that operate separately from other organs provides a measure of safety for the organism. Explain two different excretory systems other than the kidneys. Hint: (1) Microorganisms engulf food by endocytosis—the formation of vacuoles by involution of the cell membrane within the cells. The same vacuoles interact and exchange metabolites with the intracellular environment. Cellular wastes are excreted by exocytosis when the vacuoles merge with the cell membrane and excrete wastes into the environment. (2) Flatworms have an excretory system that consists of two tubules. The cells in the tubules are called flame cells; they have a cluster of cilia that propel waste matter down the tubules and out of the body. (3) Annelids have nephridia which have a tubule with cilia. Excretion occurs through a pore called the nephridiopore. Annelids have a system for tubular reabsorption by a capillary network before excretion. (4) Malpighian tubules are found in some species of arthropods. They are usually found in pairs, and the number of tubules varies with the species of insect. Malpighian tubules are convoluted, which increases their surface area, and they are lined with microvilli for reabsorption and maintenance of osmotic balance. Metabolic wastes like uric acid freely diffuse into the tubules. Potassium ion pumps line the tubules, which actively transport out K+ ions, and water follows to form urine. Water and electrolytes are reabsorbed when these organisms are faced with low-water environments, and uric acid is excreted as a thick paste or powder. By not dissolving wastes in water, these organisms conserve water.	oercommons	2025-03-18T00:36:08.426280	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15150/overview", "title": "Biology, Animal Structure and Function", "author": null }
https://oercommons.org/courseware/lesson/15151/overview	Nitrogenous Wastes Overview By the end of this section, you will be able to: - Compare and contrast the way in which aquatic animals and terrestrial animals can eliminate toxic ammonia from their systems - Compare the major byproduct of ammonia metabolism in vertebrate animals to that of birds, insects, and reptiles Of the four major macromolecules in biological systems, both proteins and nucleic acids contain nitrogen. During the catabolism, or breakdown, of nitrogen-containing macromolecules, carbon, hydrogen, and oxygen are extracted and stored in the form of carbohydrates and fats. Excess nitrogen is excreted from the body. Nitrogenous wastes tend to form toxic ammonia, which raises the pH of body fluids. The formation of ammonia itself requires energy in the form of ATP and large quantities of water to dilute it out of a biological system. Animals that live in aquatic environments tend to release ammonia into the water. Animals that excrete ammonia are said to be ammonotelic. Terrestrial organisms have evolved other mechanisms to excrete nitrogenous wastes. The animals must detoxify ammonia by converting it into a relatively nontoxic form such as urea or uric acid. Mammals, including humans, produce urea, whereas reptiles and many terrestrial invertebrates produce uric acid. Animals that secrete urea as the primary nitrogenous waste material are called ureotelic animals. Nitrogenous Waste in Terrestrial Animals: The Urea Cycle The urea cycle is the primary mechanism by which mammals convert ammonia to urea. Urea is made in the liver and excreted in urine. The overall chemical reaction by which ammonia is converted to urea is 2 NH3 (ammonia) + CO2 + 3 ATP + H2O → H2N-CO-NH2 (urea) + 2 ADP + 4 Pi + AMP. The urea cycle utilizes five intermediate steps, catalyzed by five different enzymes, to convert ammonia to urea, as shown in Figure. The amino acid L-ornithine gets converted into different intermediates before being regenerated at the end of the urea cycle. Hence, the urea cycle is also referred to as the ornithine cycle. The enzyme ornithine transcarbamylase catalyzes a key step in the urea cycle and its deficiency can lead to accumulation of toxic levels of ammonia in the body. The first two reactions occur in the mitochondria and the last three reactions occur in the cytosol. Urea concentration in the blood, called blood urea nitrogen or BUN, is used as an indicator of kidney function. Evolution Connection Excretion of Nitrogenous WasteThe theory of evolution proposes that life started in an aquatic environment. It is not surprising to see that biochemical pathways like the urea cycle evolved to adapt to a changing environment when terrestrial life forms evolved. Arid conditions probably led to the evolution of the uric acid pathway as a means of conserving water. Nitrogenous Waste in Birds and Reptiles: Uric Acid Birds, reptiles, and most terrestrial arthropods convert toxic ammonia to uric acid or the closely related compound guanine (guano) instead of urea. Mammals also form some uric acid during breakdown of nucleic acids. Uric acid is a compound similar to purines found in nucleic acids. It is water insoluble and tends to form a white paste or powder; it is excreted by birds, insects, and reptiles. Conversion of ammonia to uric acid requires more energy and is much more complex than conversion of ammonia to urea Figure. Everyday Connection GoutMammals use uric acid crystals as an antioxidant in their cells. However, too much uric acid tends to form kidney stones and may also cause a painful condition called gout, where uric acid crystals accumulate in the joints, as illustrated in Figure. Food choices that reduce the amount of nitrogenous bases in the diet help reduce the risk of gout. For example, tea, coffee, and chocolate have purine-like compounds, called xanthines, and should be avoided by people with gout and kidney stones. Section Summary Ammonia is the waste produced by metabolism of nitrogen-containing compounds like proteins and nucleic acids. While aquatic animals can easily excrete ammonia into their watery surroundings, terrestrial animals have evolved special mechanisms to eliminate the toxic ammonia from their systems. Urea is the major byproduct of ammonia metabolism in vertebrate animals. Uric acid is the major byproduct of ammonia metabolism in birds, terrestrial arthropods, and reptiles. Review Questions BUN is ________. - blood urea nitrogen - blood uric acid nitrogen - an indicator of blood volume - an indicator of blood pressure Hint: A Human beings accumulate ________ before excreting nitrogenous waste. - nitrogen - ammonia - urea - uric acid Hint: C Free Response In terms of evolution, why might the urea cycle have evolved in organisms? Hint: It is believed that the urea cycle evolved to adapt to a changing environment when terrestrial life forms evolved. Arid conditions probably led to the evolution of the uric acid pathway as a means of conserving water. Compare and contrast the formation of urea and uric acid. Hint: The urea cycle is the primary mechanism by which mammals convert ammonia to urea. Urea is made in the liver and excreted in urine. The urea cycle utilizes five intermediate steps, catalyzed by five different enzymes, to convert ammonia to urea. Birds, reptiles, and insects, on the other hand, convert toxic ammonia to uric acid instead of urea. Conversion of ammonia to uric acid requires more energy and is much more complex than conversion of ammonia to urea.	oercommons	2025-03-18T00:36:08.448794	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15151/overview", "title": "Biology, Animal Structure and Function", "author": null }
https://oercommons.org/courseware/lesson/15152/overview	Hormonal Control of Osmoregulatory Functions Overview By the end of this section, you will be able to: - Explain how hormonal cues help the kidneys synchronize the osmotic needs of the body - Describe how hormones like epinephrine, norepinephrine, renin-angiotensin, aldosterone, anti-diuretic hormone, and atrial natriuretic peptide help regulate waste elimination, maintain correct osmolarity, and perform other osmoregulatory functions While the kidneys operate to maintain osmotic balance and blood pressure in the body, they also act in concert with hormones. Hormones are small molecules that act as messengers within the body. Hormones are typically secreted from one cell and travel in the bloodstream to affect a target cell in another portion of the body. Different regions of the nephron bear specialized cells that have receptors to respond to chemical messengers and hormones. Table summarizes the hormones that control the osmoregulatory functions. \| Hormones That Affect Osmoregulation \| \|\| \|---\|---\|---\| \| Hormone \| Where produced \| Function \| \| Epinephrine and Norepinephrine \| Adrenal medulla \| Can decrease kidney function temporarily by vasoconstriction \| \| Renin \| Kidney nephrons \| Increases blood pressure by acting on angiotensinogen \| \| Angiotensin \| Liver \| Angiotensin II affects multiple processes and increases blood pressure \| \| Aldosterone \| Adrenal cortex \| Prevents loss of sodium and water \| \| Anti-diuretic hormone (vasopressin) \| Hypothalamus (stored in the posterior pituitary) \| Prevents water loss \| \| Atrial natriuretic peptide \| Heart atrium \| Decreases blood pressure by acting as a vasodilator and increasing glomerular filtration rate; decreases sodium reabsorption in kidneys \| Epinephrine and Norepinephrine Epinephrine and norepinephrine are released by the adrenal medulla and nervous system respectively. They are the flight/fight hormones that are released when the body is under extreme stress. During stress, much of the body’s energy is used to combat imminent danger. Kidney function is halted temporarily by epinephrine and norepinephrine. These hormones function by acting directly on the smooth muscles of blood vessels to constrict them. Once the afferent arterioles are constricted, blood flow into the nephrons stops. These hormones go one step further and trigger the renin-angiotensin-aldosterone system. Renin-Angiotensin-Aldosterone The renin-angiotensin-aldosterone system, illustrated in Figure proceeds through several steps to produce angiotensin II, which acts to stabilize blood pressure and volume. Renin (secreted by a part of the juxtaglomerular complex) is produced by the granular cells of the afferent and efferent arterioles. Thus, the kidneys control blood pressure and volume directly. Renin acts on angiotensinogen, which is made in the liver and converts it to angiotensin I. Angiotensin converting enzyme (ACE) converts angiotensin I to angiotensin II. Angiotensin II raises blood pressure by constricting blood vessels. It also triggers the release of the mineralocorticoid aldosterone from the adrenal cortex, which in turn stimulates the renal tubules to reabsorb more sodium. Angiotensin II also triggers the release of anti-diuretic hormone (ADH) from the hypothalamus, leading to water retention in the kidneys. It acts directly on the nephrons and decreases glomerular filtration rate. Medically, blood pressure can be controlled by drugs that inhibit ACE (called ACE inhibitors). Mineralocorticoids Mineralocorticoids are hormones synthesized by the adrenal cortex that affect osmotic balance. Aldosterone is a mineralocorticoid that regulates sodium levels in the blood. Almost all of the sodium in the blood is reclaimed by the renal tubules under the influence of aldosterone. Because sodium is always reabsorbed by active transport and water follows sodium to maintain osmotic balance, aldosterone manages not only sodium levels but also the water levels in body fluids. In contrast, the aldosterone also stimulates potassium secretion concurrently with sodium reabsorption. In contrast, absence of aldosterone means that no sodium gets reabsorbed in the renal tubules and all of it gets excreted in the urine. In addition, the daily dietary potassium load is not secreted and the retention of K+ can cause a dangerous increase in plasma K+ concentration. Patients who have Addison's disease have a failing adrenal cortex and cannot produce aldosterone. They lose sodium in their urine constantly, and if the supply is not replenished, the consequences can be fatal. Antidiurectic Hormone As previously discussed, antidiuretic hormone or ADH (also called vasopressin), as the name suggests, helps the body conserve water when body fluid volume, especially that of blood, is low. It is formed by the hypothalamus and is stored and released from the posterior pituitary. It acts by inserting aquaporins in the collecting ducts and promotes reabsorption of water. ADH also acts as a vasoconstrictor and increases blood pressure during hemorrhaging. Atrial Natriuretic Peptide Hormone The atrial natriuretic peptide (ANP) lowers blood pressure by acting as a vasodilator. It is released by cells in the atrium of the heart in response to high blood pressure and in patients with sleep apnea. ANP affects salt release, and because water passively follows salt to maintain osmotic balance, it also has a diuretic effect. ANP also prevents sodium reabsorption by the renal tubules, decreasing water reabsorption (thus acting as a diuretic) and lowering blood pressure. Its actions suppress the actions of aldosterone, ADH, and renin. Section Summary Hormonal cues help the kidneys synchronize the osmotic needs of the body. Hormones like epinephrine, norepinephrine, renin-angiotensin, aldosterone, anti-diuretic hormone, and atrial natriuretic peptide help regulate the needs of the body as well as the communication between the different organ systems. Review Questions Renin is made by ________. - granular cells of the juxtaglomerular apparatus - the kidneys - the nephrons - All of the above. Hint: A Patients with Addison's disease ________. - retain water - retain salts - lose salts and water - have too much aldosterone Hint: C Which hormone elicits the “fight or flight” response? - epinephrine - mineralcorticoids - anti-diuretic hormone - thyroxine Hint: A Free Response Describe how hormones regulate blood pressure, blood volume, and kidney function. Hint: Hormones are small molecules that act as messengers within the body. Different regions of the nephron bear specialized cells, which have receptors to respond to chemical messengers and hormones. The hormones carry messages to the kidney. These hormonal cues help the kidneys synchronize the osmotic needs of the body. Hormones like epinephrine, norepinephrine, renin-angiotensin, aldosterone, anti-diuretic hormone, and atrial natriuretic peptide help regulate the needs of the body as well as the communication between the different organ systems. How does the renin-angiotensin-aldosterone mechanism function? Why is it controlled by the kidneys? Hint: The renin-angiotensin-aldosterone system acts through several steps to produce angiotensin II, which acts to stabilize blood pressure and volume. Thus, the kidneys control blood pressure and volume directly. Renin acts on angiotensinogen, which is made in the liver and converts it to angiotensin I. ACE (angiotensin converting enzyme) converts angiotensin I to angiotensin II. Angiotensin II raises blood pressure by constricting blood vessels. It triggers the release of aldosterone from the adrenal cortex, which in turn stimulates the renal tubules to reabsorb more sodium. Angiotensin II also triggers the release of anti-diuretic hormone from the hypothalamus, which leads to water retention. It acts directly on the nephrons and decreases GFR.	oercommons	2025-03-18T00:36:08.476138	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15152/overview", "title": "Biology, Animal Structure and Function", "author": null }
https://oercommons.org/courseware/lesson/15153/overview	Introduction The environment consists of numerous pathogens, which are agents, usually microorganisms, that cause diseases in their hosts. A host is the organism that is invaded and often harmed by a pathogen. Pathogens include bacteria, protists, fungi and other infectious organisms. We are constantly exposed to pathogens in food and water, on surfaces, and in the air. Mammalian immune systems evolved for protection from such pathogens; they are composed of an extremely diverse array of specialized cells and soluble molecules that coordinate a rapid and flexible defense system capable of providing protection from a majority of these disease agents. Components of the immune system constantly search the body for signs of pathogens. When pathogens are found, immune factors are mobilized to the site of an infection. The immune factors identify the nature of the pathogen, strengthen the corresponding cells and molecules to combat it efficiently, and then halt the immune response after the infection is cleared to avoid unnecessary host cell damage. The immune system can remember pathogens to which it has been exposed to create a more efficient response upon re-exposure. This memory can last several decades. Features of the immune system, such as pathogen identification, specific response, amplification, retreat, and remembrance are essential for survival against pathogens. The immune response can be classified as either innate or active. The innate immune response is always present and attempts to defend against all pathogens rather than focusing on specific ones. Conversely, the adaptive immune response stores information about past infections and mounts pathogen-specific defenses.	oercommons	2025-03-18T00:36:08.492736	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15153/overview", "title": "Biology, Animal Structure and Function", "author": null }
https://oercommons.org/courseware/lesson/15154/overview	Innate Immune Response Overview By the end of this section, you will be able to: - Describe physical and chemical immune barriers - Explain immediate and induced innate immune responses - Discuss natural killer cells - Describe major histocompatibility class I molecules - Summarize how the proteins in a complement system function to destroy extracellular pathogens The immune system comprises both innate and adaptive immune responses. Innate immunity occurs naturally because of genetic factors or physiology; it is not induced by infection or vaccination but works to reduce the workload for the adaptive immune response. Both the innate and adaptive levels of the immune response involve secreted proteins, receptor-mediated signaling, and intricate cell-to-cell communication. The innate immune system developed early in animal evolution, roughly a billion years ago, as an essential response to infection. Innate immunity has a limited number of specific targets: any pathogenic threat triggers a consistent sequence of events that can identify the type of pathogen and either clear the infection independently or mobilize a highly specialized adaptive immune response. For example, tears and mucus secretions contain microbicidal factors. Physical and Chemical Barriers Before any immune factors are triggered, the skin functions as a continuous, impassable barrier to potentially infectious pathogens. Pathogens are killed or inactivated on the skin by desiccation (drying out) and by the skin’s acidity. In addition, beneficial microorganisms that coexist on the skin compete with invading pathogens, preventing infection. Regions of the body that are not protected by skin (such as the eyes and mucus membranes) have alternative methods of defense, such as tears and mucus secretions that trap and rinse away pathogens, and cilia in the nasal passages and respiratory tract that push the mucus with the pathogens out of the body. Throughout the body are other defenses, such as the low pH of the stomach (which inhibits the growth of pathogens), blood proteins that bind and disrupt bacterial cell membranes, and the process of urination (which flushes pathogens from the urinary tract). Despite these barriers, pathogens may enter the body through skin abrasions or punctures, or by collecting on mucosal surfaces in large numbers that overcome the mucus or cilia. Some pathogens have evolved specific mechanisms that allow them to overcome physical and chemical barriers. When pathogens do enter the body, the innate immune system responds with inflammation, pathogen engulfment, and secretion of immune factors and proteins. Pathogen Recognition An infection may be intracellular or extracellular, depending on the pathogen. All viruses infect cells and replicate within those cells (intracellularly), whereas bacteria and other parasites may replicate intracellularly or extracellularly, depending on the species. The innate immune system must respond accordingly: by identifying the extracellular pathogen and/or by identifying host cells that have already been infected. When a pathogen enters the body, cells in the blood and lymph detect the specific pathogen-associated molecular patterns (PAMPs) on the pathogen’s surface. PAMPs are carbohydrate, polypeptide, and nucleic acid “signatures” that are expressed by viruses, bacteria, and parasites but which differ from molecules on host cells. The immune system has specific cells, described in Figure and shown in Figure, with receptors that recognize these PAMPs. A macrophage is a large phagocytic cell that engulfs foreign particles and pathogens. Macrophages recognize PAMPs via complementary pattern recognition receptors (PRRs). PRRs are molecules on macrophages and dendritic cells which are in contact with the external environment. A monocyte is a type of white blood cell that circulates in the blood and lymph and differentiates into macrophages after it moves into infected tissue. Dendritic cells bind molecular signatures of pathogens and promote pathogen engulfment and destruction. Toll-like receptors (TLRs) are a type of PRR that recognizes molecules that are shared by pathogens but distinguishable from host molecules). TLRs are present in invertebrates as well as vertebrates, and appear to be one of the most ancient components of the immune system. TLRs have also been identified in the mammalian nervous system. Cytokine Release Effect The binding of PRRs with PAMPs triggers the release of cytokines, which signal that a pathogen is present and needs to be destroyed along with any infected cells. A cytokine is a chemical messenger that regulates cell differentiation (form and function), proliferation (production), and gene expression to affect immune responses. At least 40 types of cytokines exist in humans that differ in terms of the cell type that produces them, the cell type that responds to them, and the changes they produce. One type cytokine, interferon, is illustrated in Figure. One subclass of cytokines is the interleukin (IL), so named because they mediate interactions between leukocytes (white blood cells). Interleukins are involved in bridging the innate and adaptive immune responses. In addition to being released from cells after PAMP recognition, cytokines are released by the infected cells which bind to nearby uninfected cells and induce those cells to release cytokines, which results in a cytokine burst. A second class of early-acting cytokines is interferons, which are released by infected cells as a warning to nearby uninfected cells. One of the functions of an interferon is to inhibit viral replication. They also have other important functions, such as tumor surveillance. Interferons work by signaling neighboring uninfected cells to destroy RNA and reduce protein synthesis, signaling neighboring infected cells to undergo apoptosis (programmed cell death), and activating immune cells. In response to interferons, uninfected cells alter their gene expression, which increases the cells’ resistance to infection. One effect of interferon-induced gene expression is a sharply reduced cellular protein synthesis. Virally infected cells produce more viruses by synthesizing large quantities of viral proteins. Thus, by reducing protein synthesis, a cell becomes resistant to viral infection. Phagocytosis and Inflammation The first cytokines to be produced are pro-inflammatory; that is, they encourage inflammation, the localized redness, swelling, heat, and pain that result from the movement of leukocytes and fluid through increasingly permeable capillaries to a site of infection. The population of leukocytes that arrives at an infection site depends on the nature of the infecting pathogen. Both macrophages and dendritic cells engulf pathogens and cellular debris through phagocytosis. A neutrophil is also a phagocytic leukocyte that engulfs and digests pathogens. Neutrophils, shown in Figure, are the most abundant leukocytes of the immune system. Neutrophils have a nucleus with two to five lobes, and they contain organelles, called lysosomes, that digest engulfed pathogens. An eosinophil is a leukocyte that works with other eosinophils to surround a parasite; it is involved in the allergic response and in protection against helminthes (parasitic worms). Neutrophils and eosinophils are particularly important leukocytes that engulf large pathogens, such as bacteria and fungi. A mast cell is a leukocyte that produces inflammatory molecules, such as histamine, in response to large pathogens. A basophil is a leukocyte that, like a neutrophil, releases chemicals to stimulate the inflammatory response as illustrated in Figure. Basophils are also involved in allergy and hypersensitivity responses and induce specific types of inflammatory responses. Eosinophils and basophils produce additional inflammatory mediators to recruit more leukocytes. A hypersensitive immune response to harmless antigens, such as in pollen, often involves the release of histamine by basophils and mast cells. Cytokines also send feedback to cells of the nervous system to bring about the overall symptoms of feeling sick, which include lethargy, muscle pain, and nausea. These effects may have evolved because the symptoms encourage the individual to rest and prevent them from spreading the infection to others. Cytokines also increase the core body temperature, causing a fever, which causes the liver to withhold iron from the blood. Without iron, certain pathogens, such as some bacteria, are unable to replicate; this is called nutritional immunity. Link to Learning Watch this 23-second stop-motion video showing a neutrophil that searches for and engulfs fungus spores during an elapsed time of about 79 minutes. Natural Killer Cells Lymphocytes are leukocytes that are histologically identifiable by their large, darkly staining nuclei; they are small cells with very little cytoplasm, as shown in Figure. Infected cells are identified and destroyed by natural killer (NK) cells, lymphocytes that can kill cells infected with viruses or tumor cells (abnormal cells that uncontrollably divide and invade other tissue). T cells and B cells of the adaptive immune system also are classified as lymphocytes. T cells are lymphocytes that mature in the thymus gland, and B cells are lymphocytes that mature in the bone marrow. NK cells identify intracellular infections, especially from viruses, by the altered expression of major histocompatibility class (MHC) I molecules on the surface of infected cells. MHC I molecules are proteins on the surfaces of all nucleated cells, thus they are scarce on red blood cells and platelets which are non-nucleated. The function of MHC I molecules is to display fragments of proteins from the infectious agents within the cell to T-cells; healthy cells will be ignored, while “non-self” or foreign proteins will be attacked by the immune system. MHC II molecules are found mainly on cells containing antigens (“non-self proteins”) and on lymphocytes. MHC II molecules interact with helper T-cells to trigger the appropriate immune response, which may include the inflammatory response. An infected cell (or a tumor cell) is usually incapable of synthesizing and displaying MHC I molecules appropriately. The metabolic resources of cells infected by some viruses produce proteins that interfere with MHC I processing and/or trafficking to the cell surface. The reduced MHC I on host cells varies from virus to virus and results from active inhibitors being produced by the viruses. This process can deplete host MHC I molecules on the cell surface, which NK cells detect as “unhealthy” or “abnormal” while searching for cellular MHC I molecules. Similarly, the dramatically altered gene expression of tumor cells leads to expression of extremely deformed or absent MHC I molecules that also signal “unhealthy” or “abnormal.” NK cells are always active; an interaction with normal, intact MHC I molecules on a healthy cell disables the killing sequence, and the NK cell moves on. After the NK cell detects an infected or tumor cell, its cytoplasm secretes granules comprised of perforin, a destructive protein that creates a pore in the target cell. Granzymes are released along with the perforin in the immunological synapse. A granzyme is a protease that digests cellular proteins and induces the target cell to undergo programmed cell death, or apoptosis. Phagocytic cells then digest the cell debris left behind. NK cells are constantly patrolling the body and are an effective mechanism for controlling potential infections and preventing cancer progression. Complement An array of approximately 20 types of soluble proteins, called a complement system, functions to destroy extracellular pathogens. Cells of the liver and macrophages synthesize complement proteins continuously; these proteins are abundant in the blood serum and are capable of responding immediately to infecting microorganisms. The complement system is so named because it is complementary to the antibody response of the adaptive immune system. Complement proteins bind to the surfaces of microorganisms and are particularly attracted to pathogens that are already bound by antibodies. Binding of complement proteins occurs in a specific and highly regulated sequence, with each successive protein being activated by cleavage and/or structural changes induced upon binding of the preceding protein(s). After the first few complement proteins bind, a cascade of sequential binding events follows in which the pathogen rapidly becomes coated in complement proteins. Complement proteins perform several functions. The proteins serve as a marker to indicate the presence of a pathogen to phagocytic cells, such as macrophages and B cells, and enhance engulfment; this process is called opsonization. Certain complement proteins can combine to form attack complexes that open pores in microbial cell membranes. These structures destroy pathogens by causing their contents to leak, as illustrated in Figure. Section Summary The innate immune system serves as a first responder to pathogenic threats that bypass natural physical and chemical barriers of the body. Using a combination of cellular and molecular attacks, the innate immune system identifies the nature of a pathogen and responds with inflammation, phagocytosis, cytokine release, destruction by NK cells, and/or a complement system. When innate mechanisms are insufficient to clear an infection, the adaptive immune response is informed and mobilized. Review Questions Which of the following is a barrier against pathogens provided by the skin? - high pH - mucus - tears - desiccation Hint: D Although interferons have several effects, they are particularly useful against infections with which type of pathogen? - bacteria - viruses - fungi - helminths Hint: B Which organelle do phagocytes use to digest engulfed particles? - lysosome - nucleus - endoplasmic reticulum - mitochondria Hint: A Which innate immune system component uses MHC I molecules directly in its defense strategy? - macrophages - neutrophils - NK cells - interferon Hint: C Free Response Different MHC I molecules between donor and recipient cells can lead to rejection of a transplanted organ or tissue. Suggest a reason for this. Hint: If the MHC I molecules expressed on donor cells differ from the MHC I molecules expressed on recipient cells, NK cells may identify the donor cells as “non-self” and produce perforin and granzymes to induce the donor cells to undergo apoptosis, which would destroy the transplanted organ. If a series of genetic mutations prevented some, but not all, of the complement proteins from binding antibodies or pathogens, would the entire complement system be compromised? Hint: The entire complement system would probably be affected even when only a few members were mutated such that they could no longer bind. Because the complement involves the binding of activated proteins in a specific sequence, when one or more proteins in the sequence are absent, the subsequent proteins would be incapable of binding to elicit the complement’s pathogen-destructive effects.	oercommons	2025-03-18T00:36:08.524375	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15154/overview", "title": "Biology, Animal Structure and Function", "author": null }
https://oercommons.org/courseware/lesson/15155/overview	Adaptive Immune Response Overview By the end of this section, you will be able to: - Explain adaptive immunity - Compare and contrast adaptive and innate immunity - Describe cell-mediated immune response and humoral immune response - Describe immune tolerance The adaptive, or acquired, immune response takes days or even weeks to become established—much longer than the innate response; however, adaptive immunity is more specific to pathogens and has memory. Adaptive immunity is an immunity that occurs after exposure to an antigen either from a pathogen or a vaccination. This part of the immune system is activated when the innate immune response is insufficient to control an infection. In fact, without information from the innate immune system, the adaptive response could not be mobilized. There are two types of adaptive responses: the cell-mediated immune response, which is carried out by T cells, and the humoral immune response, which is controlled by activated B cells and antibodies. Activated T cells and B cells that are specific to molecular structures on the pathogen proliferate and attack the invading pathogen. Their attack can kill pathogens directly or secrete antibodies that enhance the phagocytosis of pathogens and disrupt the infection. Adaptive immunity also involves a memory to provide the host with long-term protection from reinfection with the same type of pathogen; on re-exposure, this memory will facilitate an efficient and quick response. Antigen-presenting Cells Unlike NK cells of the innate immune system, B cells (B lymphocytes) are a type of white blood cell that gives rise to antibodies, whereas T cells (T lymphocytes) are a type of white blood cell that plays an important role in the immune response. T cells are a key component in the cell-mediated response—the specific immune response that utilizes T cells to neutralize cells that have been infected with viruses and certain bacteria. There are three types of T cells: cytotoxic, helper, and suppressor T cells. Cytotoxic T cells destroy virus-infected cells in the cell-mediated immune response, and helper T cells play a part in activating both the antibody and the cell-mediated immune responses. Suppressor T cells deactivate T cells and B cells when needed, and thus prevent the immune response from becoming too intense. An antigen is a foreign or “non-self” macromolecule that reacts with cells of the immune system. Not all antigens will provoke a response. For instance, individuals produce innumerable “self” antigens and are constantly exposed to harmless foreign antigens, such as food proteins, pollen, or dust components. The suppression of immune responses to harmless macromolecules is highly regulated and typically prevents processes that could be damaging to the host, known as tolerance. The innate immune system contains cells that detect potentially harmful antigens, and then inform the adaptive immune response about the presence of these antigens. An antigen-presenting cell (APC) is an immune cell that detects, engulfs, and informs the adaptive immune response about an infection. When a pathogen is detected, these APCs will phagocytose the pathogen and digest it to form many different fragments of the antigen. Antigen fragments will then be transported to the surface of the APC, where they will serve as an indicator to other immune cells. Dendritic cells are immune cells that process antigen material; they are present in the skin (Langerhans cells) and the lining of the nose, lungs, stomach, and intestines. Sometimes a dendritic cell presents on the surface of other cells to induce an immune response, thus functioning as an antigen-presenting cell. Macrophages also function as APCs. Before activation and differentiation, B cells can also function as APCs. After phagocytosis by APCs, the phagocytic vesicle fuses with an intracellular lysosome forming phagolysosome. Within the phagolysosome, the components are broken down into fragments; the fragments are then loaded onto MHC class I or MHC class II molecules and are transported to the cell surface for antigen presentation, as illustrated in Figure. Note that T lymphocytes cannot properly respond to the antigen unless it is processed and embedded in an MHC II molecule. APCs express MHC on their surfaces, and when combined with a foreign antigen, these complexes signal a “non-self” invader. Once the fragment of antigen is embedded in the MHC II molecule, the immune cell can respond. Helper T- cells are one of the main lymphocytes that respond to antigen-presenting cells. Recall that all other nucleated cells of the body expressed MHC I molecules, which signal “healthy” or “normal.” Link to Learning This animation from Rockefeller University shows how dendritic cells act as sentinels in the body's immune system. T and B Lymphocytes Lymphocytes in human circulating blood are approximately 80 to 90 percent T cells, shown in Figure, and 10 to 20 percent B cells. Recall that the T cells are involved in the cell-mediated immune response, whereas B cells are part of the humoral immune response. T cells encompass a heterogeneous population of cells with extremely diverse functions. Some T cells respond to APCs of the innate immune system, and indirectly induce immune responses by releasing cytokines. Other T cells stimulate B cells to prepare their own response. Another population of T cells detects APC signals and directly kills the infected cells. Other T cells are involved in suppressing inappropriate immune reactions to harmless or “self” antigens. T and B cells exhibit a common theme of recognition/binding of specific antigens via a complementary receptor, followed by activation and self-amplification/maturation to specifically bind to the particular antigen of the infecting pathogen. T and B lymphocytes are also similar in that each cell only expresses one type of antigen receptor. Any individual may possess a population of T and B cells that together express a near limitless variety of antigen receptors that are capable of recognizing virtually any infecting pathogen. T and B cells are activated when they recognize small components of antigens, called epitopes, presented by APCs, illustrated in Figure. Note that recognition occurs at a specific epitope rather than on the entire antigen; for this reason, epitopes are known as “antigenic determinants.” In the absence of information from APCs, T and B cells remain inactive, or naïve, and are unable to prepare an immune response. The requirement for information from the APCs of innate immunity to trigger B cell or T cell activation illustrates the essential nature of the innate immune response to the functioning of the entire immune system. Naïve T cells can express one of two different molecules, CD4 or CD8, on their surface, as shown in Figure, and are accordingly classified as CD4+ or CD8+ cells. These molecules are important because they regulate how a T cell will interact with and respond to an APC. Naïve CD4+ cells bind APCs via their antigen-embedded MHC II molecules and are stimulated to become helper T (TH) lymphocytes, cells that go on to stimulate B cells (or cytotoxic T cells) directly or secrete cytokines to inform more and various target cells about the pathogenic threat. In contrast, CD8+ cells engage antigen-embedded MHC I molecules on APCs and are stimulated to become cytotoxic T lymphocytes (CTLs), which directly kill infected cells by apoptosis and emit cytokines to amplify the immune response. The two populations of T cells have different mechanisms of immune protection, but both bind MHC molecules via their antigen receptors called T cell receptors (TCRs). The CD4 or CD8 surface molecules differentiate whether the TCR will engage an MHC II or an MHC I molecule. Because they assist in binding specificity, the CD4 and CD8 molecules are described as coreceptors. Art Connection Which of the following statements about T cells is false? - Helper T cells release cytokines while cytotoxic T cells kill the infected cell. - Helper T cells are CD4+, while cytotoxic T cells are CD8+. - MHC II is a receptor found on most body cells, while MHC I is a receptor found on immune cells only. - The T cell receptor is found on both CD4+ and CD8+ T cells. Consider the innumerable possible antigens that an individual will be exposed to during a lifetime. The mammalian adaptive immune system is adept in responding appropriately to each antigen. Mammals have an enormous diversity of T cell populations, resulting from the diversity of TCRs. Each TCR consists of two polypeptide chains that span the T cell membrane, as illustrated in Figure; the chains are linked by a disulfide bridge. Each polypeptide chain is comprised of a constant domain and a variable domain: a domain, in this sense, is a specific region of a protein that may be regulatory or structural. The intracellular domain is involved in intracellular signaling. A single T cell will express thousands of identical copies of one specific TCR variant on its cell surface. The specificity of the adaptive immune system occurs because it synthesizes millions of different T cell populations, each expressing a TCR that differs in its variable domain. This TCR diversity is achieved by the mutation and recombination of genes that encode these receptors in stem cell precursors of T cells. The binding between an antigen-displaying MHC molecule and a complementary TCR “match” indicates that the adaptive immune system needs to activate and produce that specific T cell because its structure is appropriate to recognize and destroy the invading pathogen. Helper T Lymphocytes The TH lymphocytes function indirectly to identify potential pathogens for other cells of the immune system. These cells are important for extracellular infections, such as those caused by certain bacteria, helminths, and protozoa. TH lymphocytes recognize specific antigens displayed in the MHC II complexes of APCs. There are two major populations of TH cells: TH1 and TH2. TH1 cells secrete cytokines to enhance the activities of macrophages and other T cells. TH1 cells activate the action of cyotoxic T cells, as well as macrophages. TH2 cells stimulate naïve B cells to destroy foreign invaders via antibody secretion. Whether a TH1 or a TH2 immune response develops depends on the specific types of cytokines secreted by cells of the innate immune system, which in turn depends on the nature of the invading pathogen. The TH1-mediated response involves macrophages and is associated with inflammation. Recall the frontline defenses of macrophages involved in the innate immune response. Some intracellular bacteria, such as Mycobacterium tuberculosis, have evolved to multiply in macrophages after they have been engulfed. These pathogens evade attempts by macrophages to destroy and digest the pathogen. When M. tuberculosis infection occurs, macrophages can stimulate naïve T cells to become TH1 cells. These stimulated T cells secrete specific cytokines that send feedback to the macrophage to stimulate its digestive capabilities and allow it to destroy the colonizing M. tuberculosis. In the same manner, TH1-activated macrophages also become better suited to ingest and kill tumor cells. In summary; TH1 responses are directed toward intracellular invaders while TH2 responses are aimed at those that are extracellular. B Lymphocytes When stimulated by the TH2 pathway, naïve B cells differentiate into antibody-secreting plasma cells. A plasma cell is an immune cell that secrets antibodies; these cells arise from B cells that were stimulated by antigens. Similar to T cells, naïve B cells initially are coated in thousands of B cell receptors (BCRs), which are membrane-bound forms of Ig (immunoglobulin, or an antibody). The B cell receptor has two heavy chains and two light chains connected by disulfide linkages. Each chain has a constant and a variable region; the latter is involved in antigen binding. Two other membrane proteins, Ig alpha and Ig beta, are involved in signaling. The receptors of any particular B cell, as shown in Figure are all the same, but the hundreds of millions of different B cells in an individual have distinct recognition domains that contribute to extensive diversity in the types of molecular structures to which they can bind. In this state, B cells function as APCs. They bind and engulf foreign antigens via their BCRs and then display processed antigens in the context of MHC II molecules to TH2 cells. When a TH2 cell detects that a B cell is bound to a relevant antigen, it secretes specific cytokines that induce the B cell to proliferate rapidly, which makes thousands of identical (clonal) copies of it, and then it synthesizes and secretes antibodies with the same antigen recognition pattern as the BCRs. The activation of B cells corresponding to one specific BCR variant and the dramatic proliferation of that variant is known as clonal selection. This phenomenon drastically, but briefly, changes the proportions of BCR variants expressed by the immune system, and shifts the balance toward BCRs specific to the infecting pathogen. T and B cells differ in one fundamental way: whereas T cells bind antigens that have been digested and embedded in MHC molecules by APCs, B cells function as APCs that bind intact antigens that have not been processed. Although T and B cells both react with molecules that are termed “antigens,” these lymphocytes actually respond to very different types of molecules. B cells must be able to bind intact antigens because they secrete antibodies that must recognize the pathogen directly, rather than digested remnants of the pathogen. Bacterial carbohydrate and lipid molecules can activate B cells independently from the T cells. Cytotoxic T Lymphocytes CTLs, a subclass of T cells, function to clear infections directly. The cell-mediated part of the adaptive immune system consists of CTLs that attack and destroy infected cells. CTLs are particularly important in protecting against viral infections; this is because viruses replicate within cells where they are shielded from extracellular contact with circulating antibodies. When APCs phagocytize pathogens and present MHC I-embedded antigens to naïve CD8+ T cells that express complementary TCRs, the CD8+ T cells become activated to proliferate according to clonal selection. These resulting CTLs then identify non-APCs displaying the same MHC I-embedded antigens (for example, viral proteins)—for example, the CTLs identify infected host cells. Intracellularly, infected cells typically die after the infecting pathogen replicates to a sufficient concentration and lyses the cell, as many viruses do. CTLs attempt to identify and destroy infected cells before the pathogen can replicate and escape, thereby halting the progression of intracellular infections. CTLs also support NK lymphocytes to destroy early cancers. Cytokines secreted by the TH1 response that stimulates macrophages also stimulate CTLs and enhance their ability to identify and destroy infected cells and tumors. CTLs sense MHC I-embedded antigens by directly interacting with infected cells via their TCRs. Binding of TCRs with antigens activates CTLs to release perforin and granzyme, degradative enzymes that will induce apoptosis of the infected cell. Recall that this is a similar destruction mechanism to that used by NK cells. In this process, the CTL does not become infected and is not harmed by the secretion of perforin and granzymes. In fact, the functions of NK cells and CTLs are complementary and maximize the removal of infected cells, as illustrated in Figure. If the NK cell cannot identify the “missing self” pattern of down-regulated MHC I molecules, then the CTL can identify it by the complex of MHC I with foreign antigens, which signals “altered self.” Similarly, if the CTL cannot detect antigen-embedded MHC I because the receptors are depleted from the cell surface, NK cells will destroy the cell instead. CTLs also emit cytokines, such as interferons, that alter surface protein expression in other infected cells, such that the infected cells can be easily identified and destroyed. Moreover, these interferons can also prevent virally infected cells from releasing virus particles. Art Connection Based on what you know about MHC receptors, why do you think an organ transplanted from an incompatible donor to a recipient will be rejected? Plasma cells and CTLs are collectively called effector cells: they represent differentiated versions of their naïve counterparts, and they are involved in bringing about the immune defense of killing pathogens and infected host cells. Mucosal Surfaces and Immune Tolerance The innate and adaptive immune responses discussed thus far comprise the systemic immune system (affecting the whole body), which is distinct from the mucosal immune system. Mucosal immunity is formed by mucosa-associated lymphoid tissue, which functions independently of the systemic immune system, and which has its own innate and adaptive components. Mucosa-associated lymphoid tissue (MALT), illustrated in Figure, is a collection of lymphatic tissue that combines with epithelial tissue lining the mucosa throughout the body. This tissue functions as the immune barrier and response in areas of the body with direct contact to the external environment. The systemic and mucosal immune systems use many of the same cell types. Foreign particles that make their way to MALT are taken up by absorptive epithelial cells called M cells and delivered to APCs located directly below the mucosal tissue. M cells function in the transport described, and are located in the Peyer’s patch, a lymphoid nodule. APCs of the mucosal immune system are primarily dendritic cells, with B cells and macrophages having minor roles. Processed antigens displayed on APCs are detected by T cells in the MALT and at various mucosal induction sites, such as the tonsils, adenoids, appendix, or the mesenteric lymph nodes of the intestine. Activated T cells then migrate through the lymphatic system and into the circulatory system to mucosal sites of infection. MALT is a crucial component of a functional immune system because mucosal surfaces, such as the nasal passages, are the first tissues onto which inhaled or ingested pathogens are deposited. The mucosal tissue includes the mouth, pharynx, and esophagus, and the gastrointestinal, respiratory, and urogenital tracts. The immune system has to be regulated to prevent wasteful, unnecessary responses to harmless substances, and more importantly so that it does not attack “self.” The acquired ability to prevent an unnecessary or harmful immune response to a detected foreign substance known not to cause disease is described as immune tolerance. Immune tolerance is crucial for maintaining mucosal homeostasis given the tremendous number of foreign substances (such as food proteins) that APCs of the oral cavity, pharynx, and gastrointestinal mucosa encounter. Immune tolerance is brought about by specialized APCs in the liver, lymph nodes, small intestine, and lung that present harmless antigens to an exceptionally diverse population of regulatory T (Treg) cells, specialized lymphocytes that suppress local inflammation and inhibit the secretion of stimulatory immune factors. The combined result of Treg cells is to prevent immunologic activation and inflammation in undesired tissue compartments and to allow the immune system to focus on pathogens instead. In addition to promoting immune tolerance of harmless antigens, other subsets of Treg cells are involved in the prevention of the autoimmune response, which is an inappropriate immune response to host cells or self-antigens. Another Treg class suppresses immune responses to harmful pathogens after the infection has cleared to minimize host cell damage induced by inflammation and cell lysis. Immunological Memory The adaptive immune system possesses a memory component that allows for an efficient and dramatic response upon reinvasion of the same pathogen. Memory is handled by the adaptive immune system with little reliance on cues from the innate response. During the adaptive immune response to a pathogen that has not been encountered before, called a primary response, plasma cells secreting antibodies and differentiated T cells increase, then plateau over time. As B and T cells mature into effector cells, a subset of the naïve populations differentiates into B and T memory cells with the same antigen specificities, as illustrated in Figure. A memory cell is an antigen-specific B or T lymphocyte that does not differentiate into effector cells during the primary immune response, but that can immediately become effector cells upon re-exposure to the same pathogen. During the primary immune response, memory cells do not respond to antigens and do not contribute to host defenses. As the infection is cleared and pathogenic stimuli subside, the effectors are no longer needed, and they undergo apoptosis. In contrast, the memory cells persist in the circulation. Art Connection The Rh antigen is found on Rh-positive red blood cells. An Rh-negative female can usually carry an Rh-positive fetus to term without difficulty. However, if she has a second Rh-positive fetus, her body may launch an immune attack that causes hemolytic disease of the newborn. Why do you think hemolytic disease is only a problem during the second or subsequent pregnancies? If the pathogen is never encountered again during the individual’s lifetime, B and T memory cells will circulate for a few years or even several decades and will gradually die off, having never functioned as effector cells. However, if the host is re-exposed to the same pathogen type, circulating memory cells will immediately differentiate into plasma cells and CTLs without input from APCs or TH cells. One reason the adaptive immune response is delayed is because it takes time for naïve B and T cells with the appropriate antigen specificities to be identified and activated. Upon reinfection, this step is skipped, and the result is a more rapid production of immune defenses. Memory B cells that differentiate into plasma cells output tens to hundreds-fold greater antibody amounts than were secreted during the primary response, as the graph in Figure illustrates. This rapid and dramatic antibody response may stop the infection before it can even become established, and the individual may not realize they had been exposed. Vaccination is based on the knowledge that exposure to noninfectious antigens, derived from known pathogens, generates a mild primary immune response. The immune response to vaccination may not be perceived by the host as illness but still confers immune memory. When exposed to the corresponding pathogen to which an individual was vaccinated, the reaction is similar to a secondary exposure. Because each reinfection generates more memory cells and increased resistance to the pathogen, and because some memory cells die, certain vaccine courses involve one or more booster vaccinations to mimic repeat exposures: for instance, tetanus boosters are necessary every ten years because the memory cells only live that long. Mucosal Immune Memory A subset of T and B cells of the mucosal immune system differentiates into memory cells just as in the systemic immune system. Upon reinvasion of the same pathogen type, a pronounced immune response occurs at the mucosal site where the original pathogen deposited, but a collective defense is also organized within interconnected or adjacent mucosal tissue. For instance, the immune memory of an infection in the oral cavity would also elicit a response in the pharynx if the oral cavity was exposed to the same pathogen. Career Connection VaccinologistVaccination (or immunization) involves the delivery, usually by injection as shown in Figure, of noninfectious antigen(s) derived from known pathogens. Other components, called adjuvants, are delivered in parallel to help stimulate the immune response. Immunological memory is the reason vaccines work. Ideally, the effect of vaccination is to elicit immunological memory, and thus resistance to specific pathogens without the individual having to experience an infection. Vaccinologists are involved in the process of vaccine development from the initial idea to the availability of the completed vaccine. This process can take decades, can cost millions of dollars, and can involve many obstacles along the way. For instance, injected vaccines stimulate the systemic immune system, eliciting humoral and cell-mediated immunity, but have little effect on the mucosal response, which presents a challenge because many pathogens are deposited and replicate in mucosal compartments, and the injection does not provide the most efficient immune memory for these disease agents. For this reason, vaccinologists are actively involved in developing new vaccines that are applied via intranasal, aerosol, oral, or transcutaneous (absorbed through the skin) delivery methods. Importantly, mucosal-administered vaccines elicit both mucosal and systemic immunity and produce the same level of disease resistance as injected vaccines. Currently, a version of intranasal influenza vaccine is available, and the polio and typhoid vaccines can be administered orally, as shown in Figure. Similarly, the measles and rubella vaccines are being adapted to aerosol delivery using inhalation devices. Eventually, transgenic plants may be engineered to produce vaccine antigens that can be eaten to confer disease resistance. Other vaccines may be adapted to rectal or vaginal application to elicit immune responses in rectal, genitourinary, or reproductive mucosa. Finally, vaccine antigens may be adapted to transdermal application in which the skin is lightly scraped and microneedles are used to pierce the outermost layer. In addition to mobilizing the mucosal immune response, this new generation of vaccines may end the anxiety associated with injections and, in turn, improve patient participation. Primary Centers of the Immune System Although the immune system is characterized by circulating cells throughout the body, the regulation, maturation, and intercommunication of immune factors occur at specific sites. The blood circulates immune cells, proteins, and other factors through the body. Approximately 0.1 percent of all cells in the blood are leukocytes, which encompass monocytes (the precursor of macrophages) and lymphocytes. The majority of cells in the blood are erythrocytes (red blood cells). Lymph is a watery fluid that bathes tissues and organs with protective white blood cells and does not contain erythrocytes. Cells of the immune system can travel between the distinct lymphatic and blood circulatory systems, which are separated by interstitial space, by a process called extravasation (passing through to surrounding tissue). The cells of the immune system originate from hematopoietic stem cells in the bone marrow. Cytokines stimulate these stem cells to differentiate into immune cells. B cell maturation occurs in the bone marrow, whereas naïve T cells transit from the bone marrow to the thymus for maturation. In the thymus, immature T cells that express TCRs complementary to self-antigens are destroyed. This process helps prevent autoimmune responses. On maturation, T and B lymphocytes circulate to various destinations. Lymph nodes scattered throughout the body, as illustrated in Figure, house large populations of T and B cells, dendritic cells, and macrophages. Lymph gathers antigens as it drains from tissues. These antigens then are filtered through lymph nodes before the lymph is returned to circulation. APCs in the lymph nodes capture and process antigens and inform nearby lymphocytes about potential pathogens. The spleen houses B and T cells, macrophages, dendritic cells, and NK cells. The spleen, shown in Figure, is the site where APCs that have trapped foreign particles in the blood can communicate with lymphocytes. Antibodies are synthesized and secreted by activated plasma cells in the spleen, and the spleen filters foreign substances and antibody-complexed pathogens from the blood. Functionally, the spleen is to the blood as lymph nodes are to the lymph. Section Summary The adaptive immune response is a slower-acting, longer-lasting, and more specific response than the innate response. However, the adaptive response requires information from the innate immune system to function. APCs display antigens via MHC molecules to complementary naïve T cells. In response, the T cells differentiate and proliferate, becoming TH cells or CTLs. TH cells stimulate B cells that have engulfed and presented pathogen-derived antigens. B cells differentiate into plasma cells that secrete antibodies, whereas CTLs induce apoptosis in intracellularly infected or cancerous cells. Memory cells persist after a primary exposure to a pathogen. If re-exposure occurs, memory cells differentiate into effector cells without input from the innate immune system. The mucosal immune system is largely independent from the systemic immune system but functions in a parallel fashion to protect the extensive mucosal surfaces of the body. Art Connections Figure Which of the following statements about T cells is false? - Helper T cells release cytokines while cytotoxic T cells kill the infected cell. - Helper T cells are CD4+, while cytotoxic T cells are CD8+. - MHC II is a receptor found on most body cells, while MHC I is a receptor found on immune cells only. - The T cell receptor is found on both CD4+ and CD8+ T cells. Hint: Figure C Figure Based on what you know about MHC receptors, why do you think an organ transplanted from an incompatible donor to a recipient will be rejected? Hint: Figure MHC receptors differ from person to person. Thus, MHC receptors on an incompatible donor are considered “non-self” and are rejected by the immune system. Figure The Rh antigen is found on Rh-positive red blood cells. An Rh-negative female can usually carry an Rh-positive fetus to term without difficulty. However, if she has a second Rh-positive fetus, her body may launch an immune attack that causes hemolytic disease of the newborn. Why do you think hemolytic disease is only a problem during the second or subsequent pregnancies? Hint: Figure If the blood of the mother and fetus mixes, memory cells that recognize the Rh antigen can form late in the first pregnancy. During subsequent pregnancies, these memory cells launch an immune attack on the fetal blood cells. Injection of anti-Rh antibody during the first pregnancy prevents the immune response from occurring. Review Questions Which of the following is both a phagocyte and an antigen-presenting cell? - NK cell - eosinophil - neutrophil - macrophage Hint: D Which immune cells bind MHC molecules on APCs via CD8 coreceptors on their cell surfaces? - TH cells - CTLs - mast cells - basophils Hint: B What “self” pattern is identified by NK cells? - altered self - missing self - normal self - non-self Hint: B The acquired ability to prevent an unnecessary or destructive immune reaction to a harmless foreign particle, such as a food protein, is called ________. - the TH2 response - allergy - immune tolerance - autoimmunity Hint: C A memory B cell can differentiate upon re-exposure to a pathogen of which cell type? - CTL - naïve B cell - memory T cell - plasma cell Hint: D Foreign particles circulating in the blood are filtered by the ________. - spleen - lymph nodes - MALT - lymph Hint: A Free Response Explain the difference between an epitope and an antigen. Hint: An antigen is a molecule that reacts with some component of the immune response (antibody, B cell receptor, T cell receptor). An epitope is the region on the antigen through which binding with the immune component actually occurs. What is a naïve B or T cell? Hint: A naïve T or B cell is one that has not been activated by binding to the appropriate epitope. Naïve T and B cells cannot produce responses. How does the TH1 response differ from the TH2 response? Hint: The TH1 response involves the secretion of cytokines to stimulate macrophages and CTLs and improve their destruction of intracellular pathogens and tumor cells. It is associated with inflammation. The TH2 response is involved in the stimulation of B cells into plasma cells that synthesize and secrete antibodies. In mammalian adaptive immune systems, T cell receptors are extraordinarily diverse. What function of the immune system results from this diversity, and how is this diversity achieved? Hint: The diversity of TCRs allows the immune system to have millions of different T cells, and thereby to be specific in distinguishing antigens. This diversity arises from mutation and recombination in the genes that encode the variable regions of TCRs. How do B and T cells differ with respect to antigens that they bind? Hint: T cells bind antigens that have been digested and embedded in MHC molecules by APCs. In contrast, B cells function themselves as APCs to bind intact, unprocessed antigens. Why is the immune response after reinfection much faster than the adaptive immune response after the initial infection? Hint: Upon reinfection, the memory cells will immediately differentiate into plasma cells and CTLs without input from APCs or TH cells. In contrast, the adaptive immune response to the initial infection requires time for naïve B and T cells with the appropriate antigen specificities to be identified and activated.	oercommons	2025-03-18T00:36:08.575368	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15155/overview", "title": "Biology, Animal Structure and Function", "author": null }
https://oercommons.org/courseware/lesson/15156/overview	Antibodies Overview By the end of this section, you will be able to: - Explain cross-reactivity - Describe the structure and function of antibodies - Discuss antibody production An antibody, also known as an immunoglobulin (Ig), is a protein that is produced by plasma cells after stimulation by an antigen. Antibodies are the functional basis of humoral immunity. Antibodies occur in the blood, in gastric and mucus secretions, and in breast milk. Antibodies in these bodily fluids can bind pathogens and mark them for destruction by phagocytes before they can infect cells. Antibody Structure An antibody molecule is comprised of four polypeptides: two identical heavy chains (large peptide units) that are partially bound to each other in a “Y” formation, which are flanked by two identical light chains (small peptide units), as illustrated in Figure. Bonds between the cysteine amino acids in the antibody molecule attach the polypeptides to each other. The areas where the antigen is recognized on the antibody are variable domains and the antibody base is composed of constant domains. In germ-line B cells, the variable region of the light chain gene has 40 variable (V) and five joining (J) segments. An enzyme called DNA recombinase randomly excises most of these segments out of the gene, and splices one V segment to one J segment. During RNA processing, all but one V and J segment are spliced out. Recombination and splicing may result in over 106 possible VJ combinations. As a result, each differentiated B cell in the human body typically has a unique variable chain. The constant domain, which does not bind antibody, is the same for all antibodies. Similar to TCRs and BCRs, antibody diversity is produced by the mutation and recombination of approximately 300 different gene segments encoding the light and heavy chain variable domains in precursor cells that are destined to become B cells. The variable domains from the heavy and light chains interact to form the binding site through which an antibody can bind a specific epitope on an antigen. The numbers of repeated constant domains in Ig classes are the same for all antibodies corresponding to a specific class. Antibodies are structurally similar to the extracellular component of the BCRs, and B cell maturation to plasma cells can be visualized in simple terms as the cell acquires the ability to secrete the extracellular portion of its BCR in large quantities. Antibody Classes Antibodies can be divided into five classes—IgM, IgG, IgA, IgD, IgE—based on their physiochemical, structural, and immunological properties. IgGs, which make up about 80 percent of all antibodies, have heavy chains that consist of one variable domain and three identical constant domains. IgA and IgD also have three constant domains per heavy chain, whereas IgM and IgE each have four constant domains per heavy chain. The variable domain determines binding specificity and the constant domain of the heavy chain determines the immunological mechanism of action of the corresponding antibody class. It is possible for two antibodies to have the same binding specificities but be in different classes and, therefore, to be involved in different functions. After an adaptive defense is produced against a pathogen, typically plasma cells first secrete IgM into the blood. BCRs on naïve B cells are of the IgM class and occasionally IgD class. IgM molecules make up approximately ten percent of all antibodies. Prior to antibody secretion, plasma cells assemble IgM molecules into pentamers (five individual antibodies) linked by a joining (J) chain, as shown in Figure. The pentamer arrangement means that these macromolecules can bind ten identical antigens. However, IgM molecules released early in the adaptive immune response do not bind to antigens as stably as IgGs, which are one of the possible types of antibodies secreted in large quantities upon re-exposure to the same pathogen. Figure summarizes the properties of immunoglobulins and illustrates their basic structures. IgAs populate the saliva, tears, breast milk, and mucus secretions of the gastrointestinal, respiratory, and genitourinary tracts. Collectively, these bodily fluids coat and protect the extensive mucosa (4000 square feet in humans). The total number of IgA molecules in these bodily secretions is greater than the number of IgG molecules in the blood serum. A small amount of IgA is also secreted into the serum in monomeric form. Conversely, some IgM is secreted into bodily fluids of the mucosa. Similar to IgM, IgA molecules are secreted as polymeric structures linked with a J chain. However, IgAs are secreted mostly as dimeric molecules, not pentamers. IgE is present in the serum in small quantities and is best characterized in its role as an allergy mediator. IgD is also present in small quantities. Similar to IgM, BCRs of the IgD class are found on the surface of naïve B cells. This class supports antigen recognition and maturation of B cells to plasma cells. Antibody Functions Differentiated plasma cells are crucial players in the humoral response, and the antibodies they secrete are particularly significant against extracellular pathogens and toxins. Antibodies circulate freely and act independently of plasma cells. Antibodies can be transferred from one individual to another to temporarily protect against infectious disease. For instance, a person who has recently produced a successful immune response against a particular disease agent can donate blood to a nonimmune recipient and confer temporary immunity through antibodies in the donor’s blood serum. This phenomenon is called passive immunity; it also occurs naturally during breastfeeding, which makes breastfed infants highly resistant to infections during the first few months of life. Antibodies coat extracellular pathogens and neutralize them, as illustrated in Figure, by blocking key sites on the pathogen that enhance their infectivity (such as receptors that “dock” pathogens on host cells). Antibody neutralization can prevent pathogens from entering and infecting host cells, as opposed to the CTL-mediated approach of killing cells that are already infected to prevent progression of an established infection. The neutralized antibody-coated pathogens can then be filtered by the spleen and eliminated in urine or feces. Antibodies also mark pathogens for destruction by phagocytic cells, such as macrophages or neutrophils, because phagocytic cells are highly attracted to macromolecules complexed with antibodies. Phagocytic enhancement by antibodies is called opsonization. In a process called complement fixation, IgM and IgG in serum bind to antigens and provide docking sites onto which sequential complement proteins can bind. The combination of antibodies and complement enhances opsonization even further and promotes rapid clearing of pathogens. Affinity, Avidity, and Cross Reactivity Not all antibodies bind with the same strength, specificity, and stability. In fact, antibodies exhibit different affinities (attraction) depending on the molecular complementarity between antigen and antibody molecules, as illustrated in Figure. An antibody with a higher affinity for a particular antigen would bind more strongly and stably, and thus would be expected to present a more challenging defense against the pathogen corresponding to the specific antigen. The term avidity describes binding by antibody classes that are secreted as joined, multivalent structures (such as IgM and IgA). Although avidity measures the strength of binding, just as affinity does, the avidity is not simply the sum of the affinities of the antibodies in a multimeric structure. The avidity depends on the number of identical binding sites on the antigen being detected, as well as other physical and chemical factors. Typically, multimeric antibodies, such as pentameric IgM, are classified as having lower affinity than monomeric antibodies, but high avidity. Essentially, the fact that multimeric antibodies can bind many antigens simultaneously balances their slightly lower binding strength for each antibody/antigen interaction. Antibodies secreted after binding to one epitope on an antigen may exhibit cross reactivity for the same or similar epitopes on different antigens. Because an epitope corresponds to such a small region (the surface area of about four to six amino acids), it is possible for different macromolecules to exhibit the same molecular identities and orientations over short regions. Cross reactivity describes when an antibody binds not to the antigen that elicited its synthesis and secretion, but to a different antigen. Cross reactivity can be beneficial if an individual develops immunity to several related pathogens despite having only been exposed to or vaccinated against one of them. For instance, antibody cross reactivity may occur against the similar surface structures of various Gram-negative bacteria. Conversely, antibodies raised against pathogenic molecular components that resemble self molecules may incorrectly mark host cells for destruction and cause autoimmune damage. Patients who develop systemic lupus erythematosus (SLE) commonly exhibit antibodies that react with their own DNA. These antibodies may have been initially raised against the nucleic acid of microorganisms but later cross-reacted with self-antigens. This phenomenon is also called molecular mimicry. Antibodies of the Mucosal Immune System Antibodies synthesized by the mucosal immune system include IgA and IgM. Activated B cells differentiate into mucosal plasma cells that synthesize and secrete dimeric IgA, and to a lesser extent, pentameric IgM. Secreted IgA is abundant in tears, saliva, breast milk, and in secretions of the gastrointestinal and respiratory tracts. Antibody secretion results in a local humoral response at epithelial surfaces and prevents infection of the mucosa by binding and neutralizing pathogens. Section Summary Antibodies (immunoglobulins) are the molecules secreted from plasma cells that mediate the humoral immune response. There are five antibody classes; an antibody's class determines its mechanism of action and production site but does not control its binding specificity. Antibodies bind antigens via variable domains and can either neutralize pathogens or mark them for phagocytosis or activate the complement cascade. Review Questions The structure of an antibody is similar to the extracellular component of which receptor? - MHC I - MHC II - BCR - none of the above Hint: C The first antibody class to appear in the serum in response to a newly encountered pathogen is ________. - IgM - IgA - IgG - IgE Hint: A What is the most abundant antibody class detected in the serum upon reexposure to a pathogen or in reaction to a vaccine? - IgM - IgA - IgG - IgE Hint: C Breastfed infants typically are resistant to disease because of ________. - active immunity - passive immunity - immune tolerance - immune memory Hint: B Free Response What are the benefits and costs of antibody cross reactivity? Hint: Cross reactivity of antibodies can be beneficial when it allows an individual's immune system to respond to an array of similar pathogens after being exposed to just one of them. A potential cost of cross reactivity is an antibody response to parts of the body (self) in addition to the appropriate antigen.	oercommons	2025-03-18T00:36:08.605235	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15156/overview", "title": "Biology, Animal Structure and Function", "author": null }
https://oercommons.org/courseware/lesson/15157/overview	Disruptions in the Immune System Overview By the end of this section, you will be able to: - Describe hypersensitivity - Define autoimmunity A functioning immune system is essential for survival, but even the sophisticated cellular and molecular defenses of the mammalian immune response can be defeated by pathogens at virtually every step. In the competition between immune protection and pathogen evasion, pathogens have the advantage of more rapid evolution because of their shorter generation time and other characteristics. For instance, Streptococcus pneumoniae (bacterium that cause pneumonia and meningitis) surrounds itself with a capsule that inhibits phagocytes from engulfing it and displaying antigens to the adaptive immune system. Staphylococcus aureus (bacterium that can cause skin infections, abscesses, and meningitis) synthesizes a toxin called leukocidin that kills phagocytes after they engulf the bacterium. Other pathogens can also hinder the adaptive immune system. HIV infects TH cells via their CD4 surface molecules, gradually depleting the number of TH cells in the body; this inhibits the adaptive immune system’s capacity to generate sufficient responses to infection or tumors. As a result, HIV-infected individuals often suffer from infections that would not cause illness in people with healthy immune systems but which can cause devastating illness to immune-compromised individuals. Maladaptive responses of immune cells and molecules themselves can also disrupt the proper functioning of the entire system, leading to host cell damage that could become fatal. Immunodeficiency Failures, insufficiencies, or delays at any level of the immune response can allow pathogens or tumor cells to gain a foothold and replicate or proliferate to high enough levels that the immune system becomes overwhelmed. Immunodeficiency is the failure, insufficiency, or delay in the response of the immune system, which may be acquired or inherited. Immunodeficiency can be acquired as a result of infection with certain pathogens (such as HIV), chemical exposure (including certain medical treatments), malnutrition, or possibly by extreme stress. For instance, radiation exposure can destroy populations of lymphocytes and elevate an individual’s susceptibility to infections and cancer. Dozens of genetic disorders result in immunodeficiencies, including Severe Combined Immunodeficiency (SCID), Bare lymphocyte syndrome, and MHC II deficiencies. Rarely, primary immunodeficiencies that are present from birth may occur. Neutropenia is one form in which the immune system produces a below-average number of neutrophils, the body’s most abundant phagocytes. As a result, bacterial infections may go unrestricted in the blood, causing serious complications. Hypersensitivities Maladaptive immune responses toward harmless foreign substances or self antigens that occur after tissue sensitization are termed hypersensitivities. The types of hypersensitivities include immediate, delayed, and autoimmunity. A large proportion of the population is affected by one or more types of hypersensitivity. Allergies The immune reaction that results from immediate hypersensitivities in which an antibody-mediated immune response occurs within minutes of exposure to a harmless antigen is called an allergy. In the United States, 20 percent of the population exhibits symptoms of allergy or asthma, whereas 55 percent test positive against one or more allergens. Upon initial exposure to a potential allergen, an allergic individual synthesizes antibodies of the IgE class via the typical process of APCs presenting processed antigen to TH cells that stimulate B cells to produce IgE. This class of antibodies also mediates the immune response to parasitic worms. The constant domain of the IgE molecules interact with mast cells embedded in connective tissues. This process primes, or sensitizes, the tissue. Upon subsequent exposure to the same allergen, IgE molecules on mast cells bind the antigen via their variable domains and stimulate the mast cell to release the modified amino acids histamine and serotonin; these chemical mediators then recruit eosinophils which mediate allergic responses. Figure shows an example of an allergic response to ragweed pollen. The effects of an allergic reaction range from mild symptoms like sneezing and itchy, watery eyes to more severe or even life-threatening reactions involving intensely itchy welts or hives, airway contraction with severe respiratory distress, and plummeting blood pressure. This extreme reaction is known as anaphylactic shock. If not treated with epinephrine to counter the blood pressure and breathing effects, this condition can be fatal. Delayed hypersensitivity is a cell-mediated immune response that takes approximately one to two days after secondary exposure for a maximal reaction to be observed. This type of hypersensitivity involves the TH1 cytokine-mediated inflammatory response and may manifest as local tissue lesions or contact dermatitis (rash or skin irritation). Delayed hypersensitivity occurs in some individuals in response to contact with certain types of jewelry or cosmetics. Delayed hypersensitivity facilitates the immune response to poison ivy and is also the reason why the skin test for tuberculosis results in a small region of inflammation on individuals who were previously exposed to Mycobacterium tuberculosis. That is also why cortisone is used to treat such responses: it will inhibit cytokine production. Autoimmunity Autoimmunity is a type of hypersensitivity to self antigens that affects approximately five percent of the population. Most types of autoimmunity involve the humoral immune response. Antibodies that inappropriately mark self components as foreign are termed autoantibodies. In patients with the autoimmune disease myasthenia gravis, muscle cell receptors that induce contraction in response to acetylcholine are targeted by antibodies. The result is muscle weakness that may include marked difficultly with fine and/or gross motor functions. In systemic lupus erythematosus, a diffuse autoantibody response to the individual’s own DNA and proteins results in various systemic diseases. As illustrated in Figure, systemic lupus erythematosus may affect the heart, joints, lungs, skin, kidneys, central nervous system, or other tissues, causing tissue damage via antibody binding, complement recruitment, lysis, and inflammation. Autoimmunity can develop with time, and its causes may be rooted in molecular mimicry. Antibodies and TCRs may bind self antigens that are structurally similar to pathogen antigens, which the immune receptors first raised. As an example, infection with Streptococcus pyogenes (bacterium that causes strep throat) may generate antibodies or T cells that react with heart muscle, which has a similar structure to the surface of S. pyogenes. These antibodies can damage heart muscle with autoimmune attacks, leading to rheumatic fever. Insulin-dependent (Type 1) diabetes mellitus arises from a destructive inflammatory TH1 response against insulin-producing cells of the pancreas. Patients with this autoimmunity must be injected with insulin that originates from other sources. Section Summary Immune disruptions may involve insufficient immune responses or inappropriate immune targets. Immunodeficiency increases an individual's susceptibility to infections and cancers. Hypersensitivities are misdirected responses either to harmless foreign particles, as in the case of allergies, or to host factors, as in the case of autoimmunity. Reactions to self components may be the result of molecular mimicry. Review Questions Allergy to pollen is classified as: - an autoimmune reaction - immunodeficiency - delayed hypersensitivity - immediate hypersensitivity Hint: D A potential cause of acquired autoimmunity is ________. - tissue hypersensitivity - molecular mimicry - histamine release - radiation exposure Hint: B Autoantibodies are probably involved in: - reactions to poison ivy - pollen allergies - systemic lupus erythematosus - HIV/AIDS Hint: C Which of the following diseases is not due to autoimmunity? - rheumatic fever - systemic lupus erythematosus - diabetes mellitus - HIV/AIDS Hint: D	oercommons	2025-03-18T00:36:08.629319	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15157/overview", "title": "Biology, Animal Structure and Function", "author": null }
https://oercommons.org/courseware/lesson/15158/overview	Introduction Animal reproduction is necessary for the survival of a species. In the animal kingdom, there are innumerable ways that species reproduce. Asexual reproduction produces genetically identical organisms (clones), whereas in sexual reproduction, the genetic material of two individuals combines to produce offspring that are genetically different from their parents. During sexual reproduction the male gamete (sperm) may be placed inside the female’s body for internal fertilization, or the sperm and eggs may be released into the environment for external fertilization. Seahorses, like the one shown in Figure, provide an example of the latter. Following a mating dance, the female lays eggs in the male seahorse’s abdominal brood pouch where they are fertilized. The eggs hatch and the offspring develop in the pouch for several weeks.	oercommons	2025-03-18T00:36:08.646181	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15158/overview", "title": "Biology, Animal Structure and Function", "author": null }
https://oercommons.org/courseware/lesson/15159/overview	Reproduction Methods Overview By the end of this section, you will be able to: - Describe advantages and disadvantages of asexual and sexual reproduction - Discuss asexual reproduction methods - Discuss sexual reproduction methods Animals produce offspring through asexual and/or sexual reproduction. Both methods have advantages and disadvantages. Asexual reproduction produces offspring that are genetically identical to the parent because the offspring are all clones of the original parent. A single individual can produce offspring asexually and large numbers of offspring can be produced quickly. In a stable or predictable environment, asexual reproduction is an effective means of reproduction because all the offspring will be adapted to that environment. In an unstable or unpredictable environment asexually-reproducing species may be at a disadvantage because all the offspring are genetically identical and may not have the genetic variation to survive in new or different conditions. On the other hand, the rapid rates of asexual reproduction may allow for a speedy response to environmental changes if individuals have mutations. An additional advantage of asexual reproduction is that colonization of new habitats may be easier when an individual does not need to find a mate to reproduce. During sexual reproduction the genetic material of two individuals is combined to produce genetically diverse offspring that differ from their parents. The genetic diversity of sexually produced offspring is thought to give species a better chance of surviving in an unpredictable or changing environment. Species that reproduce sexually must maintain two different types of individuals, males and females, which can limit the ability to colonize new habitats as both sexes must be present. Asexual Reproduction Asexual reproduction occurs in prokaryotic microorganisms (bacteria) and in some eukaryotic single-celled and multi-celled organisms. There are a number of ways that animals reproduce asexually. Fission Fission, also called binary fission, occurs in prokaryotic microorganisms and in some invertebrate, multi-celled organisms. After a period of growth, an organism splits into two separate organisms. Some unicellular eukaryotic organisms undergo binary fission by mitosis. In other organisms, part of the individual separates and forms a second individual. This process occurs, for example, in many asteroid echinoderms through splitting of the central disk. Some sea anemones and some coral polyps (Figure) also reproduce through fission. Budding Budding is a form of asexual reproduction that results from the outgrowth of a part of a cell or body region leading to a separation from the original organism into two individuals. Budding occurs commonly in some invertebrate animals such as corals and hydras. In hydras, a bud forms that develops into an adult and breaks away from the main body, as illustrated in Figure, whereas in coral budding, the bud does not detach and multiplies as part of a new colony. Link to Learning Watch a video of a hydra budding. Fragmentation Fragmentation is the breaking of the body into two parts with subsequent regeneration. If the animal is capable of fragmentation, and the part is big enough, a separate individual will regrow. For example, in many sea stars, asexual reproduction is accomplished by fragmentation. Figure illustrates a sea star for which an arm of the individual is broken off and regenerates a new sea star. Fisheries workers have been known to try to kill the sea stars eating their clam or oyster beds by cutting them in half and throwing them back into the ocean. Unfortunately for the workers, the two parts can each regenerate a new half, resulting in twice as many sea stars to prey upon the oysters and clams. Fragmentation also occurs in annelid worms, turbellarians, and poriferans. Note that in fragmentation, there is generally a noticeable difference in the size of the individuals, whereas in fission, two individuals of approximate size are formed. Parthenogenesis Parthenogenesis is a form of asexual reproduction where an egg develops into a complete individual without being fertilized. The resulting offspring can be either haploid or diploid, depending on the process and the species. Parthenogenesis occurs in invertebrates such as water flees, rotifers, aphids, stick insects, some ants, wasps, and bees. Bees use parthenogenesis to produce haploid males (drones). If eggs are fertilized, diploid females develop, and if the fertilized eggs are fed special diet (so called royal jelly), a queen is produced. Some vertebrate animals—such as certain reptiles, amphibians, and fish—also reproduce through parthenogenesis. Although more common in plants, parthenogenesis has been observed in animal species that were segregated by sex in terrestrial or marine zoos. Two female Komodo dragons, a hammerhead shark, and a blacktop shark have produced parthenogenic young when the females have been isolated from males. Sexual Reproduction Sexual reproduction is the combination of (usually haploid) reproductive cells from two individuals to form a third (usually diploid) unique offspring. Sexual reproduction produces offspring with novel combinations of genes. This can be an adaptive advantage in unstable or unpredictable environments. As humans, we are used to thinking of animals as having two separate sexes—male and female—determined at conception. However, in the animal kingdom, there are many variations on this theme. Hermaphroditism Hermaphroditism occurs in animals where one individual has both male and female reproductive parts. Invertebrates such as earthworms, slugs, tapeworms and snails, shown in Figure, are often hermaphroditic. Hermaphrodites may self-fertilize or may mate with another of their species, fertilizing each other and both producing offspring. Self fertilization is common in animals that have limited mobility or are not motile, such as barnacles and clams. Sex Determination Mammalian sex determination is determined genetically by the presence of X and Y chromosomes. Individuals homozygous for X (XX) are female and heterozygous individuals (XY) are male. The presence of a Y chromosome causes the development of male characteristics and its absence results in female characteristics. The XY system is also found in some insects and plants. Avian sex determination is dependent on the presence of Z and W chromosomes. Homozygous for Z (ZZ) results in a male and heterozygous (ZW) results in a female. The W appears to be essential in determining the sex of the individual, similar to the Y chromosome in mammals. Some fish, crustaceans, insects (such as butterflies and moths), and reptiles use this system. The sex of some species is not determined by genetics but by some aspect of the environment. Sex determination in some crocodiles and turtles, for example, is often dependent on the temperature during critical periods of egg development. This is referred to as environmental sex determination, or more specifically as temperature-dependent sex determination. In many turtles, cooler temperatures during egg incubation produce males and warm temperatures produce females. In some crocodiles, moderate temperatures produce males and both warm and cool temperatures produce females. In some species, sex is both genetic- and temperature-dependent. Individuals of some species change their sex during their lives, alternating between male and female. If the individual is female first, it is termed protogyny or “first female,” if it is male first, its termed protandry or “first male.” Oysters, for example, are born male, grow, and become female and lay eggs; some oyster species change sex multiple times. Section Summary Reproduction may be asexual when one individual produces genetically identical offspring, or sexual when the genetic material from two individuals is combined to produce genetically diverse offspring. Asexual reproduction occurs through fission, budding, and fragmentation. Sexual reproduction may mean the joining of sperm and eggs within animals’ bodies or it may mean the release of sperm and eggs into the environment. An individual may be one sex, or both; it may start out as one sex and switch during its life, or it may stay male or female. Review Questions Which form of reproduction is thought to be best in a stable environment? - asexual - sexual - budding - parthenogenesis Hint: A Which form of reproduction can result from damage to the original animal? - asexual - fragmentation - budding - parthenogenesis Hint: B Which form of reproduction is useful to an animal with little mobility that reproduces sexually? - fission - budding - parthenogenesis - hermaphroditism Hint: D Genetically unique individuals are produced through ________. - sexual reproduction - parthenogenesis - budding - fragmentation Hint: A Free Response Why is sexual reproduction useful if only half the animals can produce offspring and two separate cells must be combined to form a third? Hint: Sexual reproduction produces a new combination of genes in the offspring that may better enable them to survive changes in the environment and assist in the survival of the species. What determines which sex will result in offspring of birds and mammals? Hint: The presence of the W chromosome in birds determines femaleness and the presence of the Y chromosome in mammals determines maleness. The absence of those chromosomes and the homogeneity of the offspring (ZZ or XX) leads to the development of the other sex.	oercommons	2025-03-18T00:36:08.673440	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15159/overview", "title": "Biology, Animal Structure and Function", "author": null }
https://oercommons.org/courseware/lesson/15160/overview	Fertilization Overview By the end of this section, you will be able to: - Discuss internal and external methods of fertilization - Describe the methods used by animals for development of offspring during gestation - Describe the anatomical adaptions that occurred in animals to facilitate reproduction Sexual reproduction starts with the combination of a sperm and an egg in a process called fertilization. This can occur either inside (internal fertilization) or outside (external fertilization) the body of the female. Humans provide an example of the former whereas seahorse reproduction is an example of the latter. External Fertilization External fertilization usually occurs in aquatic environments where both eggs and sperm are released into the water. After the sperm reaches the egg, fertilization takes place. Most external fertilization happens during the process of spawning where one or several females release their eggs and the male(s) release sperm in the same area, at the same time. The release of the reproductive material may be triggered by water temperature or the length of daylight. Nearly all fish spawn, as do crustaceans (such as crabs and shrimp), mollusks (such as oysters), squid, and echinoderms (such as sea urchins and sea cucumbers). Figure shows salmon spawning in a shallow stream. Frogs, like those shown in Figure, corals, molluscs, and sea cucumbers also spawn. Pairs of fish that are not broadcast spawners may exhibit courtship behavior. This allows the female to select a particular male. The trigger for egg and sperm release (spawning) causes the egg and sperm to be placed in a small area, enhancing the possibility of fertilization. External fertilization in an aquatic environment protects the eggs from drying out. Broadcast spawning can result in a greater mixture of the genes within a group, leading to higher genetic diversity and a greater chance of species survival in a hostile environment. For sessile aquatic organisms like sponges, broadcast spawning is the only mechanism for fertilization and colonization of new environments. The presence of the fertilized eggs and developing young in the water provides opportunities for predation resulting in a loss of offspring. Therefore, millions of eggs must be produced by individuals, and the offspring produced through this method must mature rapidly. The survival rate of eggs produced through broadcast spawning is low. Internal Fertilization Internal fertilization occurs most often in land-based animals, although some aquatic animals also use this method. There are three ways that offspring are produced following internal fertilization. In oviparity, fertilized eggs are laid outside the female’s body and develop there, receiving nourishment from the yolk that is a part of the egg. This occurs in most bony fish, many reptiles, some cartilaginous fish, most amphibians, two mammals, and all birds. Reptiles and insects produce leathery eggs, while birds and turtles produce eggs with high concentrations of calcium carbonate in the shell, making them hard. Chicken eggs are an example of this second type. In ovoviparity, fertilized eggs are retained in the female, but the embryo obtains its nourishment from the egg’s yolk and the young are fully developed when they are hatched. This occurs in some bony fish (like the guppy Lebistes reticulatus), some sharks, some lizards, some snakes (such as the garter snake Thamnophis sirtalis), some vipers, and some invertebrate animals (like the Madagascar hissing cockroach Gromphadorhina portentosa). In viviparity the young develop within the female, receiving nourishment from the mother’s blood through a placenta. The offspring develops in the female and is born alive. This occurs in most mammals, some cartilaginous fish, and a few reptiles. Internal fertilization has the advantage of protecting the fertilized egg from dehydration on land. The embryo is isolated within the female, which limits predation on the young. Internal fertilization enhances the fertilization of eggs by a specific male. Fewer offspring are produced through this method, but their survival rate is higher than that for external fertilization. The Evolution of Reproduction Once multicellular organisms evolved and developed specialized cells, some also developed tissues and organs with specialized functions. An early development in reproduction occurred in the Annelids. These organisms produce sperm and eggs from undifferentiated cells in their coelom and store them in that cavity. When the coelom becomes filled, the cells are released through an excretory opening or by the body splitting open. Reproductive organs evolved with the development of gonads that produce sperm and eggs. These cells went through meiosis, an adaption of mitosis, which reduced the number of chromosomes in each reproductive cell by half, while increasing the number of cells through cell division. Complete reproductive systems were developed in insects, with separate sexes. Sperm are made in testes and then travel through coiled tubes to the epididymis for storage. Eggs mature in the ovary. When they are released from the ovary, they travel to the uterine tubes for fertilization. Some insects have a specialized sac, called a spermatheca, which stores sperm for later use, sometimes up to a year. Fertilization can be timed with environmental or food conditions that are optimal for offspring survival. Vertebrates have similar structures, with a few differences. Non-mammals, such as birds and reptiles, have a common body opening, called a cloaca, for the digestive, excretory and reproductive systems. Coupling between birds usually involves positioning the cloaca openings opposite each other for transfer of sperm. Mammals have separate openings for the systems in the female and a uterus for support of developing offspring. The uterus has two chambers in species that produce large numbers of offspring at a time, while species that produce one offspring, such as primates, have a single uterus. Sperm transfer from the male to the female during reproduction ranges from releasing the sperm into the watery environment for external fertilization, to the joining of cloaca in birds, to the development of a penis for direct delivery into the female’s vagina in mammals. Section Summary Sexual reproduction starts with the combination of a sperm and an egg in a process called fertilization. This can occur either outside the bodies or inside the female. Both methods have advantages and disadvantages. Once fertilized, the eggs can develop inside the female or outside. If the egg develops outside the body, it usually has a protective covering over it. Animal anatomy evolved various ways to fertilize, hold, or expel the egg. The method of fertilization varies among animals. Some species release the egg and sperm into the environment, some species retain the egg and receive the sperm into the female body and then expel the developing embryo covered with shell, while still other species retain the developing offspring through the gestation period. Review Questions External fertilization occurs in which type of environment? - aquatic - forested - savanna - steppe Hint: A Which term applies to egg development within the female with nourishment derived from a yolk? - oviparity - viviparity - ovoviparity - ovovoparity Hint: C Which term applies to egg development outside the female with nourishment derived from a yolk? - oviparity - viviparity - ovoviparity - ovovoparity Hint: A Free Response What are the advantages and disadvantages of external and internal forms of fertilization? Hint: External fertilization can create large numbers of offspring without requiring specialized delivery or reproductive support organs. Offspring develop and mature quickly compared to internally fertilizing species. A disadvantage is that the offspring are out in the environment and predation can account for large loss of offspring. The embryos are susceptible to changes in the environment, which further depletes their numbers. Internally fertilizing species control their environment and protect their offspring from predators but must have specialized organs to complete these tasks and usually produce fewer embryos. Why would paired external fertilization be preferable to group spawning? Hint: Paired external fertilization allows the female to select the male for mating. It also has a greater chance of fertilization taking place, whereas spawning just puts a large number of sperm and eggs together and random interactions result in the fertilization.	oercommons	2025-03-18T00:36:08.698306	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15160/overview", "title": "Biology, Animal Structure and Function", "author": null }
https://oercommons.org/courseware/lesson/15161/overview	Human Reproductive Anatomy and Gametogenesis Overview By the end of this section, you will be able to: - Describe human male and female reproductive anatomies - Discuss the human sexual response - Describe spermatogenesis and oogenesis and discuss their differences and similarities As animals became more complex, specific organs and organ systems developed to support specific functions for the organism. The reproductive structures that evolved in land animals allow males and females to mate, fertilize internally, and support the growth and development of offspring. Human Reproductive Anatomy The reproductive tissues of male and female humans develop similarly in utero until a low level of the hormone testosterone is released from male gonads. Testosterone causes the undeveloped tissues to differentiate into male sexual organs. When testosterone is absent, the tissues develop into female sexual tissues. Primitive gonads become testes or ovaries. Tissues that produce a penis in males produce a clitoris in females. The tissue that will become the scrotum in a male becomes the labia in a female; that is, they are homologous structures. Male Reproductive Anatomy In the male reproductive system, the scrotum houses the testicles or testes (singular: testis), including providing passage for blood vessels, nerves, and muscles related to testicular function. The testes are a pair of male reproductive organs that produce sperm and some reproductive hormones. Each testis is approximately 2.5 by 3.8 cm (1.5 by 1 in) in size and divided into wedge-shaped lobules by connective tissue called septa. Coiled in each wedge are seminiferous tubules that produce sperm. Sperm are immobile at body temperature; therefore, the scrotum and penis are external to the body, as illustrated in Figure so that a proper temperature is maintained for motility. In land mammals, the pair of testes must be suspended outside the body at about 2° C lower than body temperature to produce viable sperm. Infertility can occur in land mammals when the testes do not descend through the abdominal cavity during fetal development. Art Connection Which of the following statements about the male reproductive system is false? - The vas deferens carries sperm from the testes to the penis. - Sperm mature in seminiferous tubules in the testes. - Both the prostate and the bulbourethral glands produce components of the semen. - The prostate gland is located in the testes. Sperm mature in seminiferous tubules that are coiled inside the testes, as illustrated in Figure. The walls of the seminiferous tubules are made up of the developing sperm cells, with the least developed sperm at the periphery of the tubule and the fully developed sperm in the lumen. The sperm cells are mixed with “nursemaid” cells called Sertoli cells which protect the germ cells and promote their development. Other cells mixed in the wall of the tubules are the interstitial cells of Leydig. These cells produce high levels of testosterone once the male reaches adolescence. When the sperm have developed flagella and are nearly mature, they leave the testicles and enter the epididymis, shown in Figure. This structure resembles a comma and lies along the top and posterior portion of the testes; it is the site of sperm maturation. The sperm leave the epididymis and enter the vas deferens (or ductus deferens), which carries the sperm, behind the bladder, and forms the ejaculatory duct with the duct from the seminal vesicles. During a vasectomy, a section of the vas deferens is removed, preventing sperm from being passed out of the body during ejaculation and preventing fertilization. Semen is a mixture of sperm and spermatic duct secretions (about 10 percent of the total) and fluids from accessory glands that contribute most of the semen’s volume. Sperm are haploid cells, consisting of a flagellum as a tail, a neck that contains the cell’s energy-producing mitochondria, and a head that contains the genetic material. Figure shows a micrograph of human sperm as well as a diagram of the parts of the sperm. An acrosome is found at the top of the head of the sperm. This structure contains lysosomal enzymes that can digest the protective coverings that surround the egg to help the sperm penetrate and fertilize the egg. An ejaculate will contain from two to five milliliters of fluid with from 50–120 million sperm per milliliter. The bulk of the semen comes from the accessory glands associated with the male reproductive system. These are the seminal vesicles, the prostate gland, and the bulbourethral gland, all of which are illustrated in Figure. The seminal vesicles are a pair of glands that lie along the posterior border of the urinary bladder. The glands make a solution that is thick, yellowish, and alkaline. As sperm are only motile in an alkaline environment, a basic pH is important to reverse the acidity of the vaginal environment. The solution also contains mucus, fructose (a sperm mitochondrial nutrient), a coagulating enzyme, ascorbic acid, and local-acting hormones called prostaglandins. The seminal vesicle glands account for 60 percent of the bulk of semen. The penis, illustrated in Figure, is an organ that drains urine from the renal bladder and functions as a copulatory organ during intercourse. The penis contains three tubes of erectile tissue running through the length of the organ. These consist of a pair of tubes on the dorsal side, called the corpus cavernosum, and a single tube of tissue on the ventral side, called the corpus spongiosum. This tissue will become engorged with blood, becoming erect and hard, in preparation for intercourse. The organ is inserted into the vagina culminating with an ejaculation. During intercourse, the smooth muscle sphincters at the opening to the renal bladder close and prevent urine from entering the penis. An orgasm is a two-stage process: first, glands and accessory organs connected to the testes contract, then semen (containing sperm) is expelled through the urethra during ejaculation. After intercourse, the blood drains from the erectile tissue and the penis becomes flaccid. The walnut-shaped prostate gland surrounds the urethra, the connection to the urinary bladder. It has a series of short ducts that directly connect to the urethra. The gland is a mixture of smooth muscle and glandular tissue. The muscle provides much of the force needed for ejaculation to occur. The glandular tissue makes a thin, milky fluid that contains citrate (a nutrient), enzymes, and prostate specific antigen (PSA). PSA is a proteolytic enzyme that helps to liquefy the ejaculate several minutes after release from the male. Prostate gland secretions account for about 30 percent of the bulk of semen. The bulbourethral gland, or Cowper’s gland, releases its secretion prior to the release of the bulk of the semen. It neutralizes any acid residue in the urethra left over from urine. This usually accounts for a couple of drops of fluid in the total ejaculate and may contain a few sperm. Withdrawal of the penis from the vagina before ejaculation to prevent pregnancy may not work if sperm are present in the bulbourethral gland secretions. The location and functions of the male reproductive organs are summarized in Table. \| Male Reproductive Anatomy \| \|\| \|---\|---\|---\| \| Organ \| Location \| Function \| \| Scrotum \| External \| Carry and support testes \| \| Penis \| External \| Deliver urine, copulating organ \| \| Testes \| Internal \| Produce sperm and male hormones \| \| Seminal Vesicles \| Internal \| Contribute to semen production \| \| Prostate Gland \| Internal \| Contribute to semen production \| \| Bulbourethral Glands \| Internal \| Clean urethra at ejaculation \| Female Reproductive Anatomy A number of reproductive structures are exterior to the female’s body. These include the breasts and the vulva, which consists of the mons pubis, clitoris, labia majora, labia minora, and the vestibular glands, all illustrated in Figure. The location and functions of the female reproductive organs are summarized in Table. The vulva is an area associated with the vestibule which includes the structures found in the inguinal (groin) area of women. The mons pubis is a round, fatty area that overlies the pubic symphysis. The clitoris is a structure with erectile tissue that contains a large number of sensory nerves and serves as a source of stimulation during intercourse. The labia majora are a pair of elongated folds of tissue that run posterior from the mons pubis and enclose the other components of the vulva. The labia majora derive from the same tissue that produces the scrotum in a male. The labia minora are thin folds of tissue centrally located within the labia majora. These labia protect the openings to the vagina and urethra. The mons pubis and the anterior portion of the labia majora become covered with hair during adolescence; the labia minora is hairless. The greater vestibular glands are found at the sides of the vaginal opening and provide lubrication during intercourse. \| Female Reproductive Anatomy \| \|\| \|---\|---\|---\| \| Organ \| Location \| Function \| \| Clitoris \| External \| Sensory organ \| \| Mons pubis \| External \| Fatty area overlying pubic bone \| \| Labia majora \| External \| Covers labia minora \| \| Labia minora \| External \| Covers vestibule \| \| Greater vestibular glands \| External \| Secrete mucus; lubricate vagina \| \| Breast \| External \| Produce and deliver milk \| \| Ovaries \| Internal \| Carry and develop eggs \| \| Oviducts (Fallopian tubes) \| Internal \| Transport egg to uterus \| \| Uterus \| Internal \| Support developing embryo \| \| Vagina \| Internal \| Common tube for intercourse, birth canal, passing menstrual flow \| The breasts consist of mammary glands and fat. The size of the breast is determined by the amount of fat deposited behind the gland. Each gland consists of 15 to 25 lobes that have ducts that empty at the nipple and that supply the nursing child with nutrient- and antibody-rich milk to aid development and protect the child. Internal female reproductive structures include ovaries, oviducts, the uterus, and the vagina, shown in Figure. The pair of ovaries is held in place in the abdominal cavity by a system of ligaments. Ovaries consist of a medulla and cortex: the medulla contains nerves and blood vessels to supply the cortex with nutrients and remove waste. The outer layers of cells of the cortex are the functional parts of the ovaries. The cortex is made up of follicular cells that surround eggs that develop during fetal development in utero. During the menstrual period, a batch of follicular cells develops and prepares the eggs for release. At ovulation, one follicle ruptures and one egg is released, as illustrated in Figurea. The oviducts, or fallopian tubes, extend from the uterus in the lower abdominal cavity to the ovaries, but they are not in contact with the ovaries. The lateral ends of the oviducts flare out into a trumpet-like structure and have a fringe of finger-like projections called fimbriae, illustrated in Figureb. When an egg is released at ovulation, the fimbrae help the non-motile egg enter into the tube and passage to the uterus. The walls of the oviducts are ciliated and are made up mostly of smooth muscle. The cilia beat toward the middle, and the smooth muscle contracts in the same direction, moving the egg toward the uterus. Fertilization usually takes place within the oviducts and the developing embryo is moved toward the uterus for development. It usually takes the egg or embryo a week to travel through the oviduct. Sterilization in women is called a tubal ligation; it is analogous to a vasectomy in males in that the oviducts are severed and sealed. The uterus is a structure about the size of a woman’s fist. This is lined with an endometrium rich in blood vessels and mucus glands. The uterus supports the developing embryo and fetus during gestation. The thickest portion of the wall of the uterus is made of smooth muscle. Contractions of the smooth muscle in the uterus aid in passing the baby through the vagina during labor. A portion of the lining of the uterus sloughs off during each menstrual period, and then builds up again in preparation for an implantation. Part of the uterus, called the cervix, protrudes into the top of the vagina. The cervix functions as the birth canal. The vagina is a muscular tube that serves several purposes. It allows menstrual flow to leave the body. It is the receptacle for the penis during intercourse and the vessel for the delivery of offspring. It is lined by stratified squamous epithelial cells to protect the underlying tissue. Sexual Response during Intercourse The sexual response in humans is both psychological and physiological. Both sexes experience sexual arousal through psychological and physical stimulation. There are four phases of the sexual response. During phase one, called excitement, vasodilation leads to vasocongestion in erectile tissues in both men and women. The nipples, clitoris, labia, and penis engorge with blood and become enlarged. Vaginal secretions are released to lubricate the vagina to facilitate intercourse. During the second phase, called the plateau, stimulation continues, the outer third of the vaginal wall enlarges with blood, and breathing and heart rate increase. During phase three, or orgasm, rhythmic, involuntary contractions of muscles occur in both sexes. In the male, the reproductive accessory glands and tubules constrict placing semen in the urethra, then the urethra contracts expelling the semen through the penis. In women, the uterus and vaginal muscles contract in waves that may last slightly less than a second each. During phase four, or resolution, the processes described in the first three phases reverse themselves and return to their normal state. Men experience a refractory period in which they cannot maintain an erection or ejaculate for a period of time ranging from minutes to hours. Gametogenesis (Spermatogenesis and Oogenesis) Gametogenesis, the production of sperm and eggs, takes place through the process of meiosis. During meiosis, two cell divisions separate the paired chromosomes in the nucleus and then separate the chromatids that were made during an earlier stage of the cell’s life cycle. Meiosis produces haploid cells with half of each pair of chromosomes normally found in diploid cells. The production of sperm is called spermatogenesis and the production of eggs is called oogenesis. Spermatogenesis Spermatogenesis, illustrated in Figure, occurs in the wall of the seminiferous tubules (Figure), with stem cells at the periphery of the tube and the spermatozoa at the lumen of the tube. Immediately under the capsule of the tubule are diploid, undifferentiated cells. These stem cells, called spermatogonia (singular: spermatagonium), go through mitosis with one offspring going on to differentiate into a sperm cell and the other giving rise to the next generation of sperm. Meiosis starts with a cell called a primary spermatocyte. At the end of the first meiotic division, a haploid cell is produced called a secondary spermatocyte. This cell is haploid and must go through another meiotic cell division. The cell produced at the end of meiosis is called a spermatid and when it reaches the lumen of the tubule and grows a flagellum, it is called a sperm cell. Four sperm result from each primary spermatocyte that goes through meiosis. Stem cells are deposited during gestation and are present at birth through the beginning of adolescence, but in an inactive state. During adolescence, gonadotropic hormones from the anterior pituitary cause the activation of these cells and the production of viable sperm. This continues into old age. Link to Learning Visit this site to see the process of spermatogenesis. Oogenesis Oogenesis, illustrated in Figure, occurs in the outermost layers of the ovaries. As with sperm production, oogenesis starts with a germ cell, called an oogonium (plural: oogonia), but this cell undergoes mitosis to increase in number, eventually resulting in up to about one to two million cells in the embryo. The cell starting meiosis is called a primary oocyte, as shown in Figure. This cell will start the first meiotic division and be arrested in its progress in the first prophase stage. At the time of birth, all future eggs are in the prophase stage. At adolescence, anterior pituitary hormones cause the development of a number of follicles in an ovary. This results in the primary oocyte finishing the first meiotic division. The cell divides unequally, with most of the cellular material and organelles going to one cell, called a secondary oocyte, and only one set of chromosomes and a small amount of cytoplasm going to the other cell. This second cell is called a polar body and usually dies. A secondary meiotic arrest occurs, this time at the metaphase II stage. At ovulation, this secondary oocyte will be released and travel toward the uterus through the oviduct. If the secondary oocyte is fertilized, the cell continues through the meiosis II, producing a second polar body and a fertilized egg containing all 46 chromosomes of a human being, half of them coming from the sperm. Egg production begins before birth, is arrested during meiosis until puberty, and then individual cells continue through at each menstrual cycle. One egg is produced from each meiotic process, with the extra chromosomes and chromatids going into polar bodies that degenerate and are reabsorbed by the body. Section Summary As animals became more complex, specific organs and organ systems developed to support specific functions for the organism. The reproductive structures that evolved in land animals allow males and females to mate, fertilize internally, and support the growth and development of offspring. Processes developed to produce reproductive cells that had exactly half the number of chromosomes of each parent so that new combinations would have the appropriate amount of genetic material. Gametogenesis, the production of sperm (spermatogenesis) and eggs (oogenesis), takes place through the process of meiosis. Figure Which of the following statements about the male reproductive system is false? - The vas deferens carries sperm from the testes to the penis. - Sperm mature in seminiferous tubules in the testes. - Both the prostate and the bulbourethral glands produce components of the semen. - The prostate gland is located in the testes. Hint: Figure D Review Questions Sperm are produced in the ________. - scrotum - seminal vesicles - seminiferous tubules - prostate gland Hint: C Most of the bulk of semen is made by the ________. - scrotum - seminal vesicles - seminiferous tubules - prostate gland Hint: C Which of the following cells in spermatogenesis is diploid? - primary spermatocyte - secondary spermatocyte - spermatid - sperm Hint: A Which female organ has the same embryonic origin as the penis? - clitoris - labia majora - greater vestibular glands - vagina Hint: A Which female organ has an endometrial lining that will support a developing baby? - labia minora - breast - ovaries - uterus Hint: D How many eggs are produced as a result of one meiotic series of cell divisions? - one - two - three - four Hint: A Free Response Describe the phases of the human sexual response. Hint: In phase one (excitement), vasodilation leads to vasocongestion and enlargement of erectile tissues. Vaginal secretions are released to lubricate the vagina during intercourse. In phase two (plateau), stimulation continues, the outer third of the vaginal wall enlarges with blood, and breathing and heart rate increase. In phase three (orgasm), rhythmic, involuntary contractions of muscles occur. In the male, reproductive accessory glands and tubules constrict, depositing semen in the urethra; then, the urethra contracts, expelling the semen through the penis. In women, the uterus and vaginal muscles contract in waves that may last slightly less than a second each. In phase four (resolution), the processes listed in the first three phases reverse themselves and return to their normal state. Men experience a refractory period in which they cannot maintain an erection or ejaculate for a period of time ranging from minutes to hours. Women do not experience a refractory period. Compare spermatogenesis and oogenesis as to timing of the processes and the number and type of cells finally produced. Hint: Stem cells are laid down in the male during gestation and lie dormant until adolescence. Stem cells in the female increase to one to two million and enter the first meiotic division and are arrested in prophase. At adolescence, spermatogenesis begins and continues until death, producing the maximum number of sperm with each meiotic division. Oogenesis continues again at adolescence in batches of oogonia with each menstrual cycle. These oogonia finish the first meiotic division, producing a primary oocyte with most of the cytoplasm and its contents, and a second cell called a polar body containing 23 chromosomes. The second meiotic division results in a secondary oocyte and a second oocyte. At ovulation, a mature haploid egg is released. If this egg is fertilized, it finishes the second meiotic division, including the chromosomes donated by the sperm in the finished cell. This is a diploid, fertilized egg.	oercommons	2025-03-18T00:36:08.739696	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15161/overview", "title": "Biology, Animal Structure and Function", "author": null }
https://oercommons.org/courseware/lesson/15162/overview	Hormonal Control of Human Reproduction Overview By the end of this chapter, you will be able to: - Describe the roles of male and female reproductive hormones - Discuss the interplay of the ovarian and menstrual cycles - Describe the process of menopause The human male and female reproductive cycles are controlled by the interaction of hormones from the hypothalamus and anterior pituitary with hormones from reproductive tissues and organs. In both sexes, the hypothalamus monitors and causes the release of hormones from the pituitary gland. When the reproductive hormone is required, the hypothalamus sends a gonadotropin-releasing hormone (GnRH) to the anterior pituitary. This causes the release of follicle stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary into the blood. Note that the body must reach puberty in order for the adrenals to release the hormones that must be present for GnRH to be produced. Although FSH and LH are named after their functions in female reproduction, they are produced in both sexes and play important roles in controlling reproduction. Other hormones have specific functions in the male and female reproductive systems. Male Hormones At the onset of puberty, the hypothalamus causes the release of FSH and LH into the male system for the first time. FSH enters the testes and stimulates the Sertoli cells to begin facilitating spermatogenesis using negative feedback, as illustrated in Figure. LH also enters the testes and stimulates the interstitial cells of Leydig to make and release testosterone into the testes and the blood. Testosterone, the hormone responsible for the secondary sexual characteristics that develop in the male during adolescence, stimulates spermatogenesis. These secondary sex characteristics include a deepening of the voice, the growth of facial, axillary, and pubic hair, and the beginnings of the sex drive. A negative feedback system occurs in the male with rising levels of testosterone acting on the hypothalamus and anterior pituitary to inhibit the release of GnRH, FSH, and LH. The Sertoli cells produce the hormone inhibin, which is released into the blood when the sperm count is too high. This inhibits the release of GnRH and FSH, which will cause spermatogenesis to slow down. If the sperm count reaches 20 million/ml, the Sertoli cells cease the release of inhibin, and the sperm count increases. Female Hormones The control of reproduction in females is more complex. As with the male, the anterior pituitary hormones cause the release of the hormones FSH and LH. In addition, estrogens and progesterone are released from the developing follicles. Estrogen is the reproductive hormone in females that assists in endometrial regrowth, ovulation, and calcium absorption; it is also responsible for the secondary sexual characteristics of females. These include breast development, flaring of the hips, and a shorter period necessary for bone maturation. Progesterone assists in endometrial re-growth and inhibition of FSH and LH release. In females, FSH stimulates development of egg cells, called ova, which develop in structures called follicles. Follicle cells produce the hormone inhibin, which inhibits FSH production. LH also plays a role in the development of ova, induction of ovulation, and stimulation of estradiol and progesterone production by the ovaries. Estradiol and progesterone are steroid hormones that prepare the body for pregnancy. Estradiol produces secondary sex characteristics in females, while both estradiol and progesterone regulate the menstrual cycle. The Ovarian Cycle and the Menstrual Cycle The ovarian cycle governs the preparation of endocrine tissues and release of eggs, while the menstrual cycle governs the preparation and maintenance of the uterine lining. These cycles occur concurrently and are coordinated over a 22–32 day cycle, with an average length of 28 days. The first half of the ovarian cycle is the follicular phase shown in Figure. Slowly rising levels of FSH and LH cause the growth of follicles on the surface of the ovary. This process prepares the egg for ovulation. As the follicles grow, they begin releasing estrogens and a low level of progesterone. Progesterone maintains the endometrium to help ensure pregnancy. The trip through the fallopian tube takes about seven days. At this stage of development, called the morula, there are 30-60 cells. If pregnancy implantation does not occur, the lining is sloughed off. After about five days, estrogen levels rise and the menstrual cycle enters the proliferative phase. The endometrium begins to regrow, replacing the blood vessels and glands that deteriorated during the end of the last cycle. Art Connection Which of the following statements about hormone regulation of the female reproductive cycle is false? - LH and FSH are produced in the pituitary, and estradiol and progesterone are produced in the ovaries. - Estradiol and progesterone secreted from the corpus luteum cause the endometrium to thicken. - Both progesterone and estradiol are produced by the follicles. - Secretion of GnRH by the hypothalamus is inhibited by low levels of estradiol but stimulated by high levels of estradiol. Just prior to the middle of the cycle (approximately day 14), the high level of estrogen causes FSH and especially LH to rise rapidly, then fall. The spike in LH causes ovulation: the most mature follicle, like that shown in Figure, ruptures and releases its egg. The follicles that did not rupture degenerate and their eggs are lost. The level of estrogen decreases when the extra follicles degenerate. Following ovulation, the ovarian cycle enters its luteal phase, illustrated in Figure and the menstrual cycle enters its secretory phase, both of which run from about day 15 to 28. The luteal and secretory phases refer to changes in the ruptured follicle. The cells in the follicle undergo physical changes and produce a structure called a corpus luteum. The corpus luteum produces estrogen and progesterone. The progesterone facilitates the regrowth of the uterine lining and inhibits the release of further FSH and LH. The uterus is being prepared to accept a fertilized egg, should it occur during this cycle. The inhibition of FSH and LH prevents any further eggs and follicles from developing, while the progesterone is elevated. The level of estrogen produced by the corpus luteum increases to a steady level for the next few days. If no fertilized egg is implanted into the uterus, the corpus luteum degenerates and the levels of estrogen and progesterone decrease. The endometrium begins to degenerate as the progesterone levels drop, initiating the next menstrual cycle. The decrease in progesterone also allows the hypothalamus to send GnRH to the anterior pituitary, releasing FSH and LH and starting the cycles again. Figure visually compares the ovarian and uterine cycles as well as the commensurate hormone levels. Art Connection Which of the following statements about the menstrual cycle is false? - Progesterone levels rise during the luteal phase of the ovarian cycle and the secretory phase of the uterine cycle. - Menstruation occurs just after LH and FSH levels peak. - Menstruation occurs after progesterone levels drop. - Estrogen levels rise before ovulation, while progesterone levels rise after. Menopause As women approach their mid-40s to mid-50s, their ovaries begin to lose their sensitivity to FSH and LH. Menstrual periods become less frequent and finally cease; this is menopause. There are still eggs and potential follicles on the ovaries, but without the stimulation of FSH and LH, they will not produce a viable egg to be released. The outcome of this is the inability to have children. The side effects of menopause include hot flashes, heavy sweating (especially at night), headaches, some hair loss, muscle pain, vaginal dryness, insomnia, depression, weight gain, and mood swings. Estrogen is involved in calcium metabolism and, without it, blood levels of calcium decrease. To replenish the blood, calcium is lost from bone which may decrease the bone density and lead to osteoporosis. Supplementation of estrogen in the form of hormone replacement therapy (HRT) can prevent bone loss, but the therapy can have negative side effects. While HRT is thought to give some protection from colon cancer, osteoporosis, heart disease, macular degeneration, and possibly depression, its negative side effects include increased risk of: stroke or heart attack, blood clots, breast cancer, ovarian cancer, endometrial cancer, gall bladder disease, and possibly dementia. Career Connection Reproductive Endocrinologist A reproductive endocrinologist is a physician who treats a variety of hormonal disorders related to reproduction and infertility in both men and women. The disorders include menstrual problems, infertility, pregnancy loss, sexual dysfunction, and menopause. Doctors may use fertility drugs, surgery, or assisted reproductive techniques (ART) in their therapy. ART involves the use of procedures to manipulate the egg or sperm to facilitate reproduction, such as in vitro fertilization. Reproductive endocrinologists undergo extensive medical training, first in a four-year residency in obstetrics and gynecology, then in a three-year fellowship in reproductive endocrinology. To be board certified in this area, the physician must pass written and oral exams in both areas. Section Summary The male and female reproductive cycles are controlled by hormones released from the hypothalamus and anterior pituitary as well as hormones from reproductive tissues and organs. The hypothalamus monitors the need for the FSH and LH hormones made and released from the anterior pituitary. FSH and LH affect reproductive structures to cause the formation of sperm and the preparation of eggs for release and possible fertilization. In the male, FSH and LH stimulate Sertoli cells and interstitial cells of Leydig in the testes to facilitate sperm production. The Leydig cells produce testosterone, which also is responsible for the secondary sexual characteristics of males. In females, FSH and LH cause estrogen and progesterone to be produced. They regulate the female reproductive system which is divided into the ovarian cycle and the menstrual cycle. Menopause occurs when the ovaries lose their sensitivity to FSH and LH and the female reproductive cycles slow to a stop. Art Connections Figure Which of the following statements about hormone regulation of the female reproductive cycle is false? - LH and FSH are produced in the pituitary, and estradiol and progesterone are produced in the ovaries. - Estradiol and progesterone secreted from the corpus luteum cause the endometrium to thicken. - Both progesterone and estradiol are produced by the follicles. - Secretion of GnRH by the hypothalamus is inhibited by low levels of estradiol but stimulated by high levels of estradiol. Hint: Figure C Figure Which of the following statements about the menstrual cycle is false? - Progesterone levels rise during the luteal phase of the ovarian cycle and the secretory phase of the uterine cycle. - Menstruation occurs just after LH and FSH levels peak. - Menstruation occurs after progesterone levels drop. - Estrogen levels rise before ovulation, while progesterone levels rise after. Hint: Figure B Review Questions Which hormone causes Leydig cells to make testosterone? - FSH - LH - inhibin - estrogen Hint: A Which hormone causes FSH and LH to be released? - testosterone - estrogen - GnRH - progesterone Hint: C Which hormone signals ovulation? - FSH - LH - inhibin - estrogen Hint: B Which hormone causes the re-growth of the endometrial lining of the uterus? - testosterone - estrogen - GnRH - progesterone Hint: D Free Response If male reproductive pathways are not cyclical, how are they controlled? Hint: Negative feedback in the male system is supplied through two hormones: inhibin and testosterone. Inhibin is produced by Sertoli cells when the sperm count exceeds set limits. The hormone inhibits GnRH and FSH, decreasing the activity of the Sertoli cells. Increased levels of testosterone affect the release of both GnRH and LH, decreasing the activity of the Leydig cells, resulting in decreased testosterone and sperm production. Describe the events in the ovarian cycle leading up to ovulation. Hint: Low levels of progesterone allow the hypothalamus to send GnRH to the anterior pituitary and cause the release of FSH and LH. FSH stimulates follicles on the ovary to grow and prepare the eggs for ovulation. As the follicles increase in size, they begin to release estrogen and a low level of progesterone into the blood. The level of estrogen rises to a peak, causing a spike in the concentration of LH. This causes the most mature follicle to rupture and ovulation occurs.	oercommons	2025-03-18T00:36:08.773852	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15162/overview", "title": "Biology, Animal Structure and Function", "author": null }
https://oercommons.org/courseware/lesson/15163/overview	Human Pregnancy and Birth Overview By the end of this section, you will be able to: - Explain fetal development during the three trimesters of gestation - Describe labor and delivery - Compare the efficacy and duration of various types of contraception - Discuss causes of infertility and the therapeutic options available Pregnancy begins with the fertilization of an egg and continues through to the birth of the individual. The length of time of gestation varies among animals, but is very similar among the great apes: human gestation is 266 days, while chimpanzee gestation is 237 days, a gorilla’s is 257 days, and orangutan gestation is 260 days long. The fox has a 57-day gestation. Dogs and cats have similar gestations averaging 60 days. The longest gestation for a land mammal is an African elephant at 640 days. The longest gestations among marine mammals are the beluga and sperm whales at 460 days. Human Gestation Twenty-four hours before fertilization, the egg has finished meiosis and becomes a mature oocyte. When fertilized (at conception) the egg becomes known as a zygote. The zygote travels through the oviduct to the uterus (Figure). The developing embryo must implant into the wall of the uterus within seven days, or it will deteriorate and die. The outer layers of the zygote (blastocyst) grow into the endometrium by digesting the endometrial cells, and wound healing of the endometrium closes up the blastocyst into the tissue. Another layer of the blastocyst, the chorion, begins releasing a hormone called human beta chorionic gonadotropin (β-HCG) which makes its way to the corpus luteum and keeps that structure active. This ensures adequate levels of progesterone that will maintain the endometrium of the uterus for the support of the developing embryo. Pregnancy tests determine the level of β-HCG in urine or serum. If the hormone is present, the test is positive. The gestation period is divided into three equal periods or trimesters. During the first two to four weeks of the first trimester, nutrition and waste are handled by the endometrial lining through diffusion. As the trimester progresses, the outer layer of the embryo begins to merge with the endometrium, and the placenta forms. This organ takes over the nutrient and waste requirements of the embryo and fetus, with the mother’s blood passing nutrients to the placenta and removing waste from it. Chemicals from the fetus, such as bilirubin, are processed by the mother’s liver for elimination. Some of the mother’s immunoglobulins will pass through the placenta, providing passive immunity against some potential infections. Internal organs and body structures begin to develop during the first trimester. By five weeks, limb buds, eyes, the heart, and liver have been basically formed. By eight weeks, the term fetus applies, and the body is essentially formed, as shown in Figure. The individual is about five centimeters (two inches) in length and many of the organs, such as the lungs and liver, are not yet functioning. Exposure to any toxins is especially dangerous during the first trimester, as all of the body’s organs and structures are going through initial development. Anything that affects that development can have a severe effect on the fetus’ survival. During the second trimester, the fetus grows to about 30 cm (12 inches), as shown in Figure. It becomes active and the mother usually feels the first movements. All organs and structures continue to develop. The placenta has taken over the functions of nutrition and waste and the production of estrogen and progesterone from the corpus luteum, which has degenerated. The placenta will continue functioning up through the delivery of the baby. During the third trimester, the fetus grows to 3 to 4 kg (6 ½ -8 ½ lbs.) and about 50 cm (19-20 inches) long, as illustrated in Figure. This is the period of the most rapid growth during the pregnancy. Organ development continues to birth (and some systems, such as the nervous system and liver, continue to develop after birth). The mother will be at her most uncomfortable during this trimester. She may urinate frequently due to pressure on the bladder from the fetus. There may also be intestinal blockage and circulatory problems, especially in her legs. Clots may form in her legs due to pressure from the fetus on returning veins as they enter the abdominal cavity. Link to Learning Visit this site to see the stages of human fetal development. Labor and Birth Labor is the physical efforts of expulsion of the fetus and the placenta from the uterus during birth (parturition). Toward the end of the third trimester, estrogen causes receptors on the uterine wall to develop and bind the hormone oxytocin. At this time, the baby reorients, facing forward and down with the back or crown of the head engaging the cervix (uterine opening). This causes the cervix to stretch and nerve impulses are sent to the hypothalamus, which signals for the release of oxytocin from the posterior pituitary. The oxytocin causes the smooth muscle in the uterine wall to contract. At the same time, the placenta releases prostaglandins into the uterus, increasing the contractions. A positive feedback relay occurs between the uterus, hypothalamus, and the posterior pituitary to assure an adequate supply of oxytocin. As more smooth muscle cells are recruited, the contractions increase in intensity and force. There are three stages to labor. During stage one, the cervix thins and dilates. This is necessary for the baby and placenta to be expelled during birth. The cervix will eventually dilate to about 10 cm. During stage two, the baby is expelled from the uterus. The uterus contracts and the mother pushes as she compresses her abdominal muscles to aid the delivery. The last stage is the passage of the placenta after the baby has been born and the organ has completely disengaged from the uterine wall. If labor should stop before stage two is reached, synthetic oxytocin, known as Pitocin, can be administered to restart and maintain labor. An alternative to labor and delivery is the surgical delivery of the baby through a procedure called a Caesarian section. This is major abdominal surgery and can lead to post-surgical complications for the mother, but in some cases it may be the only way to safely deliver the baby. The mother’s mammary glands go through changes during the third trimester to prepare for lactation and breastfeeding. When the baby begins suckling at the breast, signals are sent to the hypothalamus causing the release of prolactin from the anterior pituitary. Prolactin causes the mammary glands to produce milk. Oxytocin is also released, promoting the release of the milk. The milk contains nutrients for the baby’s development and growth as well as immunoglobulins to protect the child from bacterial and viral infections. Contraception and Birth Control The prevention of a pregnancy comes under the terms contraception or birth control. Strictly speaking, contraception refers to preventing the sperm and egg from joining. Both terms are, however, frequently used interchangeably. \| Contraceptive Methods \| \|\| \|---\|---\|---\| \| Method \| Examples \| Failure Rate in Typical Use Over 12 Months \| \| Barrier \| male condom, female condom, sponge, cervical cap, diaphragm, spermicides \| 15 to 24% \| \| Hormonal \| oral, patch, vaginal ring \| 8% \| \| injection \| 3% \| \| \| implant \| less than 1% \| \| \| Other \| natural family planning \| 12 to 25% \| \| withdrawal \| 27% \| \| \| sterilization \| less than 1% \| Table lists common methods of contraception. The failure rates listed are not the ideal rates that could be realized, but the typical rates that occur. A failure rate is the number of pregnancies resulting from the method’s use over a twelve-month period. Barrier methods, such as condoms, cervical caps, and diaphragms, block sperm from entering the uterus, preventing fertilization. Spermicides are chemicals that are placed in the vagina that kill sperm. Sponges, which are saturated with spermicides, are placed in the vagina at the cervical opening. Combinations of spermicidal chemicals and barrier methods achieve lower failure rates than do the methods when used separately. Nearly a quarter of the couples using barrier methods, natural family planning, or withdrawal can expect a failure of the method. Natural family planning is based on the monitoring of the menstrual cycle and having intercourse only during times when the egg is not available. A woman’s body temperature may rise a degree Celsius at ovulation and the cervical mucus may increase in volume and become more pliable. These changes give a general indication of when intercourse is more or less likely to result in fertilization. Withdrawal involves the removal of the penis from the vagina during intercourse, before ejaculation occurs. This is a risky method with a high failure rate due to the possible presence of sperm in the bulbourethral gland’s secretion, which may enter the vagina prior to removing the penis. Hormonal methods use synthetic progesterone (sometimes in combination with estrogen), to inhibit the hypothalamus from releasing FSH or LH, and thus prevent an egg from being available for fertilization. The method of administering the hormone affects failure rate. The most reliable method, with a failure rate of less than 1 percent, is the implantation of the hormone under the skin. The same rate can be achieved through the sterilization procedures of vasectomy in the man or of tubal ligation in the woman, or by using an intrauterine device (IUD). IUDs are inserted into the uterus and establish an inflammatory condition that prevents fertilized eggs from implanting into the uterine wall. Compliance with the contraceptive method is a strong contributor to the success or failure rate of any particular method. The only method that is completely effective at preventing conception is abstinence. The choice of contraceptive method depends on the goals of the woman or couple. Tubal ligation and vasectomy are considered permanent prevention, while other methods are reversible and provide short-term contraception. Termination of an existing pregnancy can be spontaneous or voluntary. Spontaneous termination is a miscarriage and usually occurs very early in the pregnancy, usually within the first few weeks. This occurs when the fetus cannot develop properly and the gestation is naturally terminated. Voluntary termination of a pregnancy is an abortion. Laws regulating abortion vary between states and tend to view fetal viability as the criteria for allowing or preventing the procedure. Infertility Infertility is the inability to conceive a child or carry a child to birth. About 75 percent of causes of infertility can be identified; these include diseases, such as sexually transmitted diseases that can cause scarring of the reproductive tubes in either men or women, or developmental problems frequently related to abnormal hormone levels in one of the individuals. Inadequate nutrition, especially starvation, can delay menstruation. Stress can also lead to infertility. Short-term stress can affect hormone levels, while long-term stress can delay puberty and cause less frequent menstrual cycles. Other factors that affect fertility include toxins (such as cadmium), tobacco smoking, marijuana use, gonadal injuries, and aging. If infertility is identified, several assisted reproductive technologies (ART) are available to aid conception. A common type of ART is in vitro fertilization (IVF) where an egg and sperm are combined outside the body and then placed in the uterus. Eggs are obtained from the woman after extensive hormonal treatments that prepare mature eggs for fertilization and prepare the uterus for implantation of the fertilized egg. Sperm are obtained from the man and they are combined with the eggs and supported through several cell divisions to ensure viability of the zygotes. When the embryos have reached the eight-cell stage, one or more is implanted into the woman’s uterus. If fertilization is not accomplished by simple IVF, a procedure that injects the sperm into an egg can be used. This is called intracytoplasmic sperm injection (ICSI) and is shown in Figure. IVF procedures produce a surplus of fertilized eggs and embryos that can be frozen and stored for future use. The procedures can also result in multiple births. Section Summary Human pregnancy begins with fertilization of an egg and proceeds through the three trimesters of gestation. The labor process has three stages (contractions, delivery of the fetus, expulsion of the placenta), each propelled by hormones. The first trimester lays down the basic structures of the body, including the limb buds, heart, eyes, and the liver. The second trimester continues the development of all of the organs and systems. The third trimester exhibits the greatest growth of the fetus and culminates in labor and delivery. Prevention of a pregnancy can be accomplished through a variety of methods including barriers, hormones, or other means. Assisted reproductive technologies may help individuals who have infertility problems. Review Questions Nutrient and waste requirements for the developing fetus are handled during the first few weeks by: - the placenta - diffusion through the endometrium - the chorion - the blastocyst Hint: B Progesterone is made during the third trimester by the: - placenta - endometrial lining - chorion - corpus luteum Hint: A Which contraceptive method is 100 percent effective at preventing pregnancy? - condom - oral hormonal methods - sterilization - abstinence Hint: D Which type of short term contraceptive method is generally more effective than others? - barrier - hormonal - natural family planning - withdrawal Hint: B Which hormone is primarily responsible for the contractions during labor? - oxytocin - estrogen - β-HCG - progesterone Hint: A Major organs begin to develop during which part of human gestation? - fertilization - first trimester - second trimester - third trimester Hint: B Free Response Describe the major developments during each trimester of human gestation. Hint: The first trimester lays down the basic structures of the body, including the limb buds, heart, eyes, and the liver. The second trimester continues the development of all of the organs and systems established during the first trimester. The placenta takes over the production of estrogen and high levels of progesterone and handles the nutrient and waste requirements of the fetus. The third trimester exhibits the greatest growth of the fetus, culminating in labor and delivery. Describe the stages of labor. Hint: Stage one of labor results in the thinning of the cervix and the dilation of the cervical opening. Stage two delivers the baby, and stage three delivers the placenta.	oercommons	2025-03-18T00:36:08.809517	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15163/overview", "title": "Biology, Animal Structure and Function", "author": null }
https://oercommons.org/courseware/lesson/15164/overview	Fertilization and Early Embryonic Development Overview By the end of this section, you will be able to: - Discuss how fertilization occurs - Explain how the embryo forms from the zygote - Discuss the role of cleavage and gastrulation in animal development The process in which an organism develops from a single-celled zygote to a multi-cellular organism is complex and well-regulated. The early stages of embryonic development are also crucial for ensuring the fitness of the organism. Fertilization Fertilization, pictured in Figurea is the process in which gametes (an egg and sperm) fuse to form a zygote. The egg and sperm each contain one set of chromosomes. To ensure that the offspring has only one complete diploid set of chromosomes, only one sperm must fuse with one egg. In mammals, the egg is protected by a layer of extracellular matrix consisting mainly of glycoproteins called the zona pellucida. When a sperm binds to the zona pellucida, a series of biochemical events, called the acrosomal reactions, take place. In placental mammals, the acrosome contains digestive enzymes that initiate the degradation of the glycoprotein matrix protecting the egg and allowing the sperm plasma membrane to fuse with the egg plasma membrane, as illustrated in Figureb. The fusion of these two membranes creates an opening through which the sperm nucleus is transferred into the ovum. The nuclear membranes of the egg and sperm break down and the two haploid genomes condense to form a diploid genome. To ensure that no more than one sperm fertilizes the egg, once the acrosomal reactions take place at one location of the egg membrane, the egg releases proteins in other locations to prevent other sperm from fusing with the egg. If this mechanism fails, multiple sperm can fuse with the egg, resulting in polyspermy. The resulting embryo is not genetically viable and dies within a few days. Cleavage and Blastula Stage The development of multi-cellular organisms begins from a single-celled zygote, which undergoes rapid cell division to form the blastula. The rapid, multiple rounds of cell division are termed cleavage. Cleavage is illustrated in (Figurea). After the cleavage has produced over 100 cells, the embryo is called a blastula. The blastula is usually a spherical layer of cells (the blastoderm) surrounding a fluid-filled or yolk-filled cavity (the blastocoel). Mammals at this stage form a structure called the blastocyst, characterized by an inner cell mass that is distinct from the surrounding blastula, shown in Figureb. During cleavage, the cells divide without an increase in mass; that is, one large single-celled zygote divides into multiple smaller cells. Each cell within the blastula is called a blastomere. Cleavage can take place in two ways: holoblastic (total) cleavage or meroblastic (partial) cleavage. The type of cleavage depends on the amount of yolk in the eggs. In placental mammals (including humans) where nourishment is provided by the mother’s body, the eggs have a very small amount of yolk and undergo holoblastic cleavage. Other species, such as birds, with a lot of yolk in the egg to nourish the embryo during development, undergo meroblastic cleavage. In mammals, the blastula forms the blastocyst in the next stage of development. Here the cells in the blastula arrange themselves in two layers: the inner cell mass, and an outer layer called the trophoblast. The inner cell mass is also known as the embryoblast and this mass of cells will go on to form the embryo. At this stage of development, illustrated in Figure the inner cell mass consists of embryonic stem cells that will differentiate into the different cell types needed by the organism. The trophoblast will contribute to the placenta and nourish the embryo. Link to Learning Visit the Virtual Human Embryo project at the Endowment for Human Development site to step through an interactive that shows the stages of embryo development, including micrographs and rotating 3-D images. Gastrulation The typical blastula is a ball of cells. The next stage in embryonic development is the formation of the body plan. The cells in the blastula rearrange themselves spatially to form three layers of cells. This process is called gastrulation. During gastrulation, the blastula folds upon itself to form the three layers of cells. Each of these layers is called a germ layer and each germ layer differentiates into different organ systems. The three germs layers, shown in Figure, are the endoderm, the ectoderm, and the mesoderm. The ectoderm gives rise to the nervous system and the epidermis. The mesoderm gives rise to the muscle cells and connective tissue in the body. The endoderm gives rise to columnar cells found in the digestive system and many internal organs. Everyday Connection Are Designer Babies in Our Future? If you could prevent your child from getting a devastating genetic disease, would you do it? Would you select the sex of your child or select for their attractiveness, strength, or intelligence? How far would you go to maximize the possibility of resistance to disease? The genetic engineering of a human child, the production of "designer babies" with desirable phenotypic characteristics, was once a topic restricted to science fiction. This is the case no longer: science fiction is now overlapping into science fact. Many phenotypic choices for offspring are already available, with many more likely to be possible in the not too distant future. Which traits should be selected and how they should be selected are topics of much debate within the worldwide medical community. The ethical and moral line is not always clear or agreed upon, and some fear that modern reproductive technologies could lead to a new form of eugenics. Eugenics is the use of information and technology from a variety of sources to improve the genetic makeup of the human race. The goal of creating genetically superior humans was quite prevalent (although controversial) in several countries during the early 20th century, but fell into disrepute when Nazi Germany developed an extensive eugenics program in the 1930's and 40's. As part of their program, the Nazis forcibly sterilized hundreds of thousands of the so-called "unfit" and killed tens of thousands of institutionally disabled people as part of a systematic program to develop a genetically superior race of Germans known as Aryans. Ever since, eugenic ideas have not been as publicly expressed, but there are still those who promote them. Efforts have been made in the past to control traits in human children using donated sperm from men with desired traits. In fact, eugenicist Robert Klark Graham established a sperm bank in 1980 that included samples exclusively from donors with high IQs. The "genius" sperm bank failed to capture the public's imagination and the operation closed in 1999. In more recent times, the procedure known as prenatal genetic diagnosis (PGD) has been developed. PGD involves the screening of human embryos as part of the process of in vitro fertilization, during which embryos are conceived and grown outside the mother's body for some period of time before they are implanted. The term PGD usually refers to both the diagnosis, selection, and the implantation of the selected embryos. In the least controversial use of PGD, embryos are tested for the presence of alleles which cause genetic diseases such as sickle cell disease, muscular dystrophy, and hemophilia, in which a single disease-causing allele or pair of alleles has been identified. By excluding embryos containing these alleles from implantation into the mother, the disease is prevented, and the unused embryos are either donated to science or discarded. There are relatively few in the worldwide medical community that question the ethics of this type of procedure, which allows individuals scared to have children because of the alleles they carry to do so successfully. The major limitation to this procedure is its expense. Not usually covered by medical insurance and thus out of reach financially for most couples, only a very small percentage of all live births use such complicated methodologies. Yet, even in cases like these where the ethical issues may seem to be clear-cut, not everyone agrees with the morality of these types of procedures. For example, to those who take the position that human life begins at conception, the discarding of unused embryos, a necessary result of PGD, is unacceptable under any circumstances. A murkier ethical situation is found in the selection of a child's sex, which is easily performed by PGD. Currently, countries such as Great Britain have banned the selection of a child's sex for reasons other than preventing sex-linked diseases. Other countries allow the procedure for "family balancing", based on the desire of some parents to have at least one child of each sex. Still others, including the United States, have taken a scattershot approach to regulating these practices, essentially leaving it to the individual practicing physician to decide which practices are acceptable and which are not. Even murkier are rare instances of disabled parents, such as those with deafness or dwarfism, who select embryos via PGD to ensure that they share their disability. These parents usually cite many positive aspects of their disabilities and associated culture as reasons for their choice, which they see as their moral right. To others, to purposely cause a disability in a child violates the basic medical principle of Primum non nocere, "first, do no harm." This procedure, although not illegal in most countries, demonstrates the complexity of ethical issues associated with choosing genetic traits in offspring. Where could this process lead? Will this technology become more affordable and how should it be used? With the ability of technology to progress rapidly and unpredictably, a lack of definitive guidelines for the use of reproductive technologies before they arise might make it difficult for legislators to keep pace once they are in fact realized, assuming the process needs any government regulation at all. Other bioethicists argue that we should only deal with technologies that exist now, and not in some uncertain future. They argue that these types of procedures will always be expensive and rare, so the fears of eugenics and "master" races are unfounded and overstated. The debate continues. Section Summary The early stages of embryonic development begin with fertilization. The process of fertilization is tightly controlled to ensure that only one sperm fuses with one egg. After fertilization, the zygote undergoes cleavage to form the blastula. The blastula, which in some species is a hollow ball of cells, undergoes a process called gastrulation, in which the three germ layers form. The ectoderm gives rise to the nervous system and the epidermal skin cells, the mesoderm gives rise to the muscle cells and connective tissue in the body, and the endoderm gives rise to columnar cells and internal organs. Review Questions Which of the following is false? - The endoderm, mesoderm, ectoderm are germ layers. - The trophoblast is a germ layer. - The inner cell mass is a source of embryonic stem cells. - The blastula is often a hollow ball of cells. Hint: B During cleavage, the mass of cells: - increases - decreases - doubles with every cell division - does not change significantly Hint: D Free Response What do you think would happen if multiple sperm fused with one egg? Hint: Multiple sperm can fuse with the egg, resulting in polyspermy. The resulting embryo is not genetically viable and dies within a few days. Why do mammalian eggs have a small concentration of yolk, while bird and reptile eggs have a large concentration of yolk? Hint: Mammalian eggs do not need a lot of yolk because the developing fetus obtains nutrients from the mother. Other species, in which the fetus develops outside of the mother’s body, such as occurs with birds, require a lot of yolk in the egg to nourish the embryo during development.	oercommons	2025-03-18T00:36:08.836752	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15164/overview", "title": "Biology, Animal Structure and Function", "author": null }
https://oercommons.org/courseware/lesson/15165/overview	Organogenesis and Vertebrate Formation Overview By the end of this section, you will be able to: - Describe the process of organogenesis - Identify the anatomical axes formed in vertebrates Gastrulation leads to the formation of the three germ layers that give rise, during further development, to the different organs in the animal body. This process is called organogenesis. Organogenesis is characterized by rapid and precise movements of the cells within the embryo. Organogenesis Organs form from the germ layers through the process of differentiation. During differentiation, the embryonic stem cells express specific sets of genes which will determine their ultimate cell type. For example, some cells in the ectoderm will express the genes specific to skin cells. As a result, these cells will differentiate into epidermal cells. The process of differentiation is regulated by cellular signaling cascades. Scientists study organogenesis extensively in the lab in fruit flies (Drosophila) and the nematode Caenorhabditis elegans. Drosophila have segments along their bodies, and the patterning associated with the segment formation has allowed scientists to study which genes play important roles in organogenesis along the length of the embryo at different time points. The nematode C.elegans has roughly 1000 somatic cells and scientists have studied the fate of each of these cells during their development in the nematode life cycle. There is little variation in patterns of cell lineage between individuals, unlike in mammals where cell development from the embryo is dependent on cellular cues. In vertebrates, one of the primary steps during organogenesis is the formation of the neural system. The ectoderm forms epithelial cells and tissues, and neuronal tissues. During the formation of the neural system, special signaling molecules called growth factors signal some cells at the edge of the ectoderm to become epidermis cells. The remaining cells in the center form the neural plate. If the signaling by growth factors were disrupted, then the entire ectoderm would differentiate into neural tissue. The neural plate undergoes a series of cell movements where it rolls up and forms a tube called the neural tube, as illustrated in Figure. In further development, the neural tube will give rise to the brain and the spinal cord. The mesoderm that lies on either side of the vertebrate neural tube will develop into the various connective tissues of the animal body. A spatial pattern of gene expression reorganizes the mesoderm into groups of cells called somites with spaces between them. The somites, illustrated in Figure will further develop into the ribs, lungs, and segmental (spine) muscle. The mesoderm also forms a structure called the notochord, which is rod-shaped and forms the central axis of the animal body. Vertebrate Axis Formation Even as the germ layers form, the ball of cells still retains its spherical shape. However, animal bodies have lateral-medial (left-right), dorsal-ventral (back-belly), and anterior-posterior (head-feet) axes, illustrated in Figure. How are these established? In one of the most seminal experiments ever to be carried out in developmental biology, Spemann and Mangold took dorsal cells from one embryo and transplanted them into the belly region of another embryo. They found that the transplanted embryo now had two notochords: one at the dorsal site from the original cells and another at the transplanted site. This suggested that the dorsal cells were genetically programmed to form the notochord and define the axis. Since then, researchers have identified many genes that are responsible for axis formation. Mutations in these genes leads to the loss of symmetry required for organism development. Animal bodies have externally visible symmetry. However, the internal organs are not symmetric. For example, the heart is on the left side and the liver on the right. The formation of the central left-right axis is an important process during development. This internal asymmetry is established very early during development and involves many genes. Research is still ongoing to fully understand the developmental implications of these genes. Section Summary Organogenesis is the formation of organs from the germ layers. Each germ layer gives rise to specific tissue types. The first stage is the formation of the neural system in the ectoderm. The mesoderm gives rise to somites and the notochord. Formation of vertebrate axis is another important developmental stage. Review Questions Which of the following gives rise to the skin cells? - ectoderm - endoderm - mesoderm - none of the above Hint: A The ribs form from the ________. - notochord - neural plate - neural tube - somites Hint: D Free Response Explain how the different germ layers give rise to different tissue types. Hint: Organs form from the germ layers through the process of differentiation. During differentiation, the embryonic stem cells express a specific set of genes that will determine their ultimate fate as a cell type. For example, some cells in the ectoderm will express the genes specific to skin cells. As a result, these cells will differentiate into epidermal cells. The process of differentiation is regulated by cellular signaling cascades. Explain the role of axis formation in development. Hint: Animal bodies have lateral-medial (left-right), dorsal-ventral (back-belly), and anterior-posterior (head-feet) axes. The dorsal cells are genetically programmed to form the notochord and define the axis. There are many genes responsible for axis formation. Mutations in these genes lead to the loss of symmetry required for organism development.	oercommons	2025-03-18T00:36:08.859892	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15165/overview", "title": "Biology, Animal Structure and Function", "author": null }
https://oercommons.org/courseware/lesson/120377/overview	Classroom Rules IRIS Iris Center Organize the Physical Classroom Teacher Establishes Routines Classroom Management Overview This is a template for an inquiry project in a senior level early childhood course. Purpose of the Project The purpose of this project is to explore the critical elements of classroom arrangement that contribute to effective teaching and learning environments for early childhood learners. We will examine why rules, routines, arrangement, and designing effective classrooms, impact how we aim to highlight how thoughtfully arranged classrooms can foster positive behavior and enhance student engagement. This project will investigate the importance of establishing clear rules and predictable routines, which provide students with a sense of security and structure. Furthermore, we will discuss how the physical arrangement of furniture and resources can support diverse learning styles and encourage collaboration among students. Ultimately, our goal is to design classrooms that not only meet educational needs but also create welcoming and inclusive spaces that promote academic success and social development. Sections in this course: Rules Routines Arrangement Designing effective classrooms Rules Introduction: In a classroom, teachers are required to create rules and routines for their students. The students are then expected to abide by these rules and follow the routines. Rules and routines help the teacher support their students by getting them ready to engage and clear the way for learning. Rules are a set of instructions that tell the students what they are allowed to do or not do inside the classroom. Routines are a sequence of actions that are performed as a part of regular procedure. Rules and routines provide the students with expectations from their teacher. The students know that if they follow the rules and routines they will be successful in achieving their goals. Why are rules important: Having rules implemented into your classroom is so important because it creates a positive learning environment for your students. Rules also create clear expectations for your students and ultimately improve their academic performance. Rules teach our students to be responsible,respectful, and have self discipline. Rules are also used to help the teacher maintain classroom routines and expectations. How to establish rules: When establishing rules inside the classroom, you should always focus on what the students are expected to do rather than what they shouldn’t do. You should also be sure to include the students when creating the rules for your classroom. Once you have established the rules for your classroom, it is imperative that you display them in the classroom where your students can always see them. After creating your classroom rules, as the teacher you should explain and enforce consequences if rules are not followed. In order for students to know what exactly is expected of them you should model the type of behavior that is expected. Throughout the school year you should revisit your classroom rules. Routines Having routines in the classroom is just as important as how you arrange, regulate your rules, and how you design your classroom. Your classroom routines are how you run your classroom, that is your rules, classroom management, and also your transitions and whatever curricular schedule your school has you on. Why should you have routines in your classroom? Your routines are the roots of your classroom. You can break it down and think of it this way: Your principal gives you your daily schedule during in service, this is going to be the base of your day. Once you have your daily schedule you then have to set all of your transitions, this is when the transition will take place, how they’re going to know they will be transitioning and what they’re transitioning to. Once you’ve decided on your transitions you have to decide your method for classroom management.These two things will come to play on the first day of school where you will be deciding your classroom rules with your class. -Laying out the groundwork in your class is so important. If you’re transitions aren’t strong your class will have no stability and if you have weak classroom management your class will lack structure. You need both of these things and both are crucial when you come to making your class rules and implementing them throughout the year. Arrangement Classroom arrangement can be important in so many ways, it is a learning environment for a well-organized classroom that supports a positive learning environment. It allows students to focus better on their tasks and enhances their engagement. Students should also have easy access to materials and resources easily. This is especially important for students with different needs. An arranged classroom helps teachers manage behavior more effectively. Clear sightlines and organized spaces can reduce distractions and maintain a conducive atmosphere for learning. Lastly, safety is very important in a classroom. We have to have clear pathways and emergency exits, ensuring that students can exit quickly in case of an emergency. A thoughtful classroom arrangement not only supports academic success but also fosters a safe and collaborative learning environment. Designing Effective Classrooms Some main things teachers need to focus on when designing their classrooms to be effective for the students: Focus on teacher Visibility Collaboration Inclusive environment Adaptability Supports digital learning Comfort Individual needs Accessibility Safety and navigation	oercommons	2025-03-18T00:36:08.890795	Kayli Deremo	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/120377/overview", "title": "Classroom Management", "author": "Brooke Garza" }
https://oercommons.org/courseware/lesson/112072/overview	OER Fellowship Planning Template Overview OER Fellows are invited to remix this OER Fellowship Planning Template to articulate a) a plan to assess your institution's current state of OER awareness and implementation b) your goals for OER adoption and use, and their targeted success indicators; c) a plan for building and engaging your OER Coalition, Programs, and Partnerships; d) a plan for the development and roll out of campus-level policies, guidelines, and resolutions in support of OER; d) an OER outreach and advocacy plan; and e) a plan for building capacity of your OER initiative. Introduction OER Fellows are invited to remix this OER Fellowship Planning Template to a) a plan to assess your institution's current state of OER awareness and implementation b) your goals for OER adoption and use, and their targeted success indicators; c) a plan for building and engaging your OER Coalition, Programs, and Partnerships; d) a plan for the development and roll out of campus-level policies, guidelines, and resolutions in support of OER; e) an OER outreach and advocacy plan; and f) a plan for building capacity of your OER initiative. When remixing, please give your remix a new title that includes your institution's name and feel free to customize the images and sections to best fit your needs. You can also download this template to your computer by clicking on the cloud with an arrow icon on the upper right of this page or import it into google classroom. Analyzing the OER Landscape Gaining a deeper understanding of the OER landscape in your state, region, institution, and department can greatly help inform your OER initiative. This process might involve informal information gathering or more formal research. One approach is to adapt questions used in the statewide OER landscape studies for use at a specific institution. Because the landscape surveys are openly licensed, campuses are free to draw on the questions and methods used in those surveys to analyze the landscape of OER at their institutions. Applicable questions from the surveys that can be translated to local contexts include: What OER definitions, policies (including open licensing), programs, and courses are already in place? Are course markings being implemented? What individuals, offices, and roles, if any, lead OER efforts on campus? To what extent does internal and/or external collaboration support OER work? What OER enablers (such as professional development and funding) and barriers exist on campus? How does your campus collect data to assess the effectiveness and impact of OER? These questions could be distributed as questionnaires to library staff, administrators, or faculty at an institution informally, if a more formal research approach is not an option. Using campus listservs, putting flyers in faculty mailboxes, or other ways of reaching out directly to potential respondents will yield some information regarding OER awareness and initiatives. In addition, conversations with individuals across the institution, asking questions related to OER and how folks think about it, will provide a sense of the level of awareness on campus. Here is a sample survey that was created by OER Leads at Del Mar College OER (Open Educational Resources) Survey The purpose of this survey is to gain a snapshot of the extent DMC makes use of OER materials 1. Please list the course(s) whereby OER are utilized within your department (e.g. CHEM 1406, BIO 1308, etc.) Note: Don't be concerned if you don't capture every course. 2. To the best of your knowledge, for those who make use of OER, what type of material is it? - Textbook - Online homework portal - YouTube videos - Other 3. In general for those faculty who don't use OER, what are the primary reasons for this? - A suitable OER is not available - Faculty have not been made aware of current repository of OER in their respective disciplines (otherwise they may use such) - Content of course material changes frequently and OER lags behind - Other 4. OPTIONAL: Feel free to offer additional comments with respect to OER Share your plan below to assess your institution's current OER awareness and implementation. Our plan for informal information gathering: Our plan for formal research: OER Goals & Success Indicators OER Goals Articulating your reasons for dedicating people's time and resources to support OER adoption and use is an important place to start. There is not a one-size-fits-all OER goal; institutions are all different, and each institution must consider its unique size, mission, and culture. OER goals can be tied to larger strategic plan goals, such as student recruitment, equitable outcomes in access, retention, and attainment, and/or cost savings. Other important considerations include the needs of student populations and communities, library and instructional design staffing, and resources and budgets. If institutional or system goals are not in place, developing SMART goals can be helpful in narrowing down the focus of an OER Program. SMART stands for specific, measurable, achievable, relevant, and time-bound. For example, the strategic plan for the Austin Community College District (ACCD) includes goals toward achieving equity and access, persistence and engagement, and completion and transition to employment/transfer. In ACCD's 2020-21 Student Success Report, OER initiatives are mentioned as key to supporting the goal of persistence and engagement. Compton College’s OER Initiative goal is to convert 85-100% of course offerings to rely on OER materials by 2035; ultimately, reducing the cost of course materials for students. Share your SMART goals below: OER Goal 1 OER Goal 2 OER Goal 3 OER Success Indicators After setting attainable and realistic goals for establishing OER programs and ensuring their sustainability, developing metrics for success and collecting data using the metrics is an essential next step. The OER Success Indicators Worksheet, which includes a broad list of possible success indicators that can be a helpful starting point to identify and brainstorm additional metrics to track. Review the list of indicators and identify any that you would like to track and brainstorm additional metrics to track below. OER Success Indicators Partnership Growth - Number or new or expanded partnerships - Diversity in the types of partnerships built - Number of individuals adopting the project at the state, district, or school level - Additional partnership growth metrics: Increased Awareness & Reach - Number of tweets about an initiative/project - Number of references in external publications - Number speaking engagements about the project - Number of collections or websites that host/refer to the project or resources - Additional increased awareness and reach metrics: Growth in an OER Collection - Number of new resources added - Number of derivative resources added - Number of user-generated tags added - Number of reviews or ratings added - Additional growth in an OER collection metrics: Impact on Teaching & Learning - Data showing changes in students’ length of time on the resources in the online environment - Percent of educators reporting changes in practice as a result of the OER intervention - Percent reporting changes in student engagement - Improved student test performance - Faculty and staff trained in OER - Faculty course adoptions, remixes, and creations - Faculty and student perceptions of OER - Additional impact on teaching and learning metrics: Cost & Other Efficiencies - Data showing decrease in student spending on course materials - Percent of educators reporting efficiencies gained from using OER - Additional cost and other efficiencies metrics: Additional Success Indicators: Building & Engaging Our OER Coalition, Programs, and Partnerships OER Coalition Once you have clear OER goals and success indicators, you will want to connect with collaborators who can contribute their expertise to help you grow your OER initiative. Before reaching out to your larger campus community, it is helpful to explore if there are any Champions and Early Adopters that are currently using OER, any existing partnerships with OER projects or providers, and any OER priorities, initiatives, policies, programs already in place. Below are a few suggested collaborators you can reach out to and their areas of expertise. Share which collaborators you will be engaging with for your OER initiative and what you will be asking them to contribute below. Campus Role \| Goals and Areas of Interest and Expertise \| Librarians \| Affordable learning, copyright, faculty development, discovery, and curation \| Faculty Adopters \| Equitable student success, equitable student access, academic freedom, course enrollments, engaging curriculum that is locally and culturally relevant, supporting social justice through open pedagogy, high-quality textbooks, readings, and ancillary materials \| Instructional Designers \| Course design, copyright permissions, accessibility \| Administrators \| Retention rates, student feedback, enrollments, equitable student success \| Student Leaders \| Cost savings, quality of curriculum, student engagement in courses, accessibility, equitable access to materials, relevant materials, belonging \| Our OER Coalition Collaborators include: \| Campus Role: \| Goals & Areas of Interest / Expertise \| Additional questions to consider while building and engaging with your OER Coalition include: Who should be included in OER efforts (a committee, taskforce, council, etc.)? How will we train and empower leaders? What leadership messaging needs to be in place that conveys that cross-institution partnerships are a priority on campus? What resources will help to empower those directly advancing open educational resources, so they are able to connect and build effective partnerships in their offices? How might students be engaged in partnerships to help share information and advocate for OER? What are the benefits of student involvement – both to students and the institution? How might academic and student affairs units (e.g., student support services like tutoring, math and writing centers, academic departments, advising, counseling, online and continuing education, instructional design, faculty senate, library, finance and budgeting) be engaged as experts and trusted advocates? What internal or external partners can offer skills or resources to support this work? OER Programs There are important supports available for institutions to develop plans for their OER programs, including participating in training academies, connecting with collaborators, and leveraging best practices. Establishing foundational knowledge on open educational resources and practices, and having a central place for institutions to collaborate, curate, and share resources help build a solid foundation to advance OER programs. The OER Program supports we will leverage include: 1. 2. 3. 4. 5. OER Partnerships Establishing or joining a consortium or less formal partnership across multiple campuses or institutions can help newer OER initiatives benefit from the work of others who are further along the path in their OER programs. Additionally, partners can take advantage of open licensing to create shared resources that can be developed and maintained by faculty across institutions. Such multi-institution relationships are important for both developing and mature OER programs to provide community support, share information and experience, and provide faculty collaborations around content creation, adaptation, and implementation. The Partnerships we plan to build and engage with include: 1. 2. 3. Developing Policies, Guidelines & Resolutions in Support of OER OER policies, guidelines, and resolutions can strengthen an institution’s existing initiatives and lay a foundation for long-term success. The range of options for policies is significant – they can serve to codify responsibilities, allocate resources, or provide a tacit demonstration of administrative support for the overarching purpose of the initiative. Examples exist not only at the campus and institutional levels, but also at the system, state, federal, and international levels. OER Policy Examples - States that have enacted OER-related policies available here SPARC's OER State Policy Tracker - In 2018, Houston Community College adopted the following policy: “Programs must... evaluate the best available open educational resources (OER) when reviewing books for a particular course. If any OER receives a similar score to another commercial textbook that is adopted by the program, the OER must also be adopted. An unlimited number of OER may be approved for adoption. In addition, it is strongly recommended that the Program Committee adopt minimum guidelines for the use of OER or any other free or online materials that have not been evaluated or approved as a textbook. Meeting minutes should note where no OER are available.” - Austin Community College recently updated the ACC policy on copyright ownership to support and encourage the use of Creative Commons licenses when possible. ACC makes it clear that “[c]reators should use the most appropriate license for their work.” - DOERS3 has developed a Tenure and Promotion Matrix and guidelines for institutions looking to make open publishing part of tenure and promotion. Which policies will you develop to support your OER initiative? OER Course Markings - Open License Policies - College Affordability Policies, Initiatives, and Resolutions - OER Outreach & Advocacy Plan Campuswide OER Advocacy Tips Focus on the Why - Focus on the problem that OER can solve for your stakeholders. For administrators, this might be textbook costs; for teachers, it might be lack of quality content. Maintain Objectivity - Listen and maintain your position of why. Being aware of the barriers to change will better equip you to relate to their challenges. Engage the Engaged - At the early stages of change, spend much of your effort on those who are listening. These are the early adopters, and they align with your “why.” Reinforce the Change - Keep your early adopters engaged through reinforcement strategies. Seek their feedback, showcase their work, and know what they are doing next. A helpful resource to show the impacts of OER adoption in Higher Education is this summary of empirical research by the OpenEd Group https://openedgroup.org/review OER Advocacy Steps 1. Tap Into Core Advocacy Skills - Successful OER advocacy requires a range of skills, knowledge, and interests, including the following: - Passion about the concept of open - Clarity on the economic and pedagogical benefits of OER - Insight into how the policy environment may constrain or enable OER use - Understanding of the pros and cons of different open licensing arrangements - Access to practical examples of OER used to illustrate key points - Up-to-date knowledge of the arguments for and against the use of OER - Ability to engage audiences effectively - Capacity to leverage students, administrators, teachers, and librarians and other staff as advocacy partners 2. Understand Your Policy Context - Before embarking on your advocacy effort, it is important to review the following policies that might impact the adoption of OER at your institution. - Intellectual property policies and employment contracts – These address how works created by staff within the scope of employment may be shared with or used by others. Under the United States Copyright Act, the author of the work is generally the owner of the copyright. However, if a work is created within the scope of the author’s employment, the employer holds the copyright unless there is an agreement to the contrary. Check your institution's intellectual property policies and employment contracts, or contact your library and/or intellectual property office for information on faculty and staff rights as creators and sharers of educational materials. - Human resource policy guidelines – These outline whether the creation of certain kinds of work (e.g., learning resources) constitutes part of the job description for faculty and staff, and what the implications are for remuneration and promotion purposes. It is important for OER creators and remixers to understand if their work will be funded and if it could be applied to tenure or promotion opportunities, for example. - Technology policy guidelines – These address access to and use of appropriate technology and technical support, as well as provision for version control and the storage systems for the institution’s educational resources. This impacts your OER work in concrete ways, providing clear strategies and guidelines for how to publish OER, how to manage remixes and versioning, and it can ensure that OER is discovered by those interested. - Materials development and quality assurance policy guidelines – These help ensure appropriate selection, development, quality assurance, and copyright clearance of works that may be shared. This category also encompasses library collection development policies and guidelines, and whether those policies explicitly support OER and open access as part of collection building. - Textbook and instructional materials adoption, ordering, and approval policies – These policies and practices are usually set by a college/university or instructional division and govern who can make decisions about textbook adoption, how adoptions are approved, and what criteria are used to approve textbook adoptions. 3. Understand the Barriers to OER Adoption Understanding the barriers to OER and why your stakeholders may be resistant to its adoption will help you to better tailor your advocacy strategy to specific audiences. Barreirs may include: - Gaps in technical skills to identify OER - Content curation and developemnent costs - Instructor training costs - Skepticism around OER quality - Lack of time, incentives, knowledge to work with OER - Lack of curatorial and collaborative workflows to support OER - Misalignment between open licensing and campus copyright guidlines - Lack of knowledge about intellectual propery rights and open licensing 4. Tailor Your Message - Sharing your passion and reason for being an OER champion is powerful, but what about your audience? Before presenting any change initiative, consider who is in the room and what is in it for them. 5. Formative Evaluation of your OER Program - A sustainable OER program involves not just a one-time evaluation of outcomes but an iterative process of formative evaluation and improvement to the program based on research findings and progress towards those success indicators. 6. Identify Your High-Impact Engagement Strategies - Below are some engagement strategies that have been identified by OER implementation project leads and that are encouraged for exploration. - Formal Presentation: Securing a time slot with one stakeholder group can allow you to focus on their interests and change their perspective on OER. Speaking the language of those in the audience is a stepping stone to cultural change. - Informal Sharing: Sharing your personal story is a great way to declare yourself as an OER champion in your community and can draw engagement and interest from people in a way that educating and informing may not. - Call to Action: Providing a clear “next step” when sharing information, presenting, or communicating via modeling or social media can drive interested parties to become implementers rather than consumers. - Modeling: The “unknown” of change can be the biggest barrier. Modeling the outcomes of change and helping people observe what the end state will or can be is a way to alleviate change-related apprehension. - Social Media: Consider blogging, tweeting, and posting on listservs as important tools for advocacy and outreach. A way to start is to read and comment on relevant blogs and to follow other educators who are writers and influencers on OER. Outreach Communication Planning: Identify your target audience and outreach goals - Content of your outreach – What do you want to share? Be sure to clearly communicate the value add for your intended audience, as well as any relevant links, images, resources, videos, etc. Outreach method – How will you share? (social media, blog, website, listservs, presentation, etc.) Outcome and impact – What action do you hope others will take as a result of your outreach? Upcoming Outreach Opportunities OERizona February 28-March 1 Open Ed Week March 4-8, 2024 Faculty Working Sessions for English, Math, Biology, and Psychology Courses March 29 (reach out to Megan C for more information) Open Ed Virtual Conference October 8-10, 2024 Open Ed Global Conference (dates TBD) Fall 2024 OER Fundamentals Academy (dates TBD) Spring 2025 OER Fellowship (dates TBD) OER Capacity Building There are various opportunities to explore to build capacity for your OER initiative. Identify which options you will prioritize below: OER Funding - Institutional Funding - - State Funded OER Grants - - Federal Grants - - Philanthropic Grants - Professional Learning Opportunities - OER Academies & Fellowship Program OER Conferences	oercommons	2025-03-18T00:36:08.932856	Joanna Schimizzi	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/112072/overview", "title": "OER Fellowship Planning Template", "author": "Megan Simmons" }
https://oercommons.org/courseware/lesson/64064/overview	Education Standards Keeping Students Learning (pdf) Keeping Students Learning - Tips for Online and Offline Learning Overview Suggestions to help keep students updated and engaged when learning remotely. Tips for Online and Offline Learning Tips for Online Learning Motivate the students to manage their own learning. Write a message specific to your class and situation such as: Online learning offers you more flexibility as a student, but it also requires more of your focus and commitment to learn. It is easy to procrastinate or rush your work because there is no one directly guiding you. Keep in mind that you are in the driver’s seat of your learning. Teachers and others are here to help, but your success is ultimately up to you.Keep the technology manageable. Many platforms offer all sorts of options that can sound great for virtual learning, but they don’t all work smoothly and not in every situation. Focus on the technology you know for the backbone of your material such as shared documents (Google, SharePoint, Padlet, etc.) Then, venture into live web conferencing and other apps. - Analyze your current lessons and units to determine what is most important and what is manageable for online learning. Design what you assign with the “end user”, your students, in mind. Picture them in their home setting trying to work the assignment through. - Break up or “chunk” the learning activities and vary them. - Give clear expectations, timelines, instructions. In person, we can get feedback instantly and adjust our message. Online, we need to clearly state these. We should also check for understanding through a question, free write, or even a phone call. - Include fun activities and give students a stretch break. - Set guidelines for discussion rooms and monitor them. - If you have access to Zoom or other webinar platforms, record your session and make it available to students so they can review it. - Use screenshots to show students exactly what is meant. The Snipping Tool on PCs or shift-command-3 or 4 for Macs work well. Not Teaching Virtually? Tips for Keeping Students Learning Regular emails to students (or parents/guardians) to encourage and keep in touch. Include a message with encouragement to keep reading, writing, and learning at home. Email or send activities to do at home. - For teachers with smaller number of students, phone call to check in and see how they are doing. - For students who have online access, give directions for getting a library card and accessing online resources appropriate for their age. - If students have online access, use a streaming access such as Facebook to do read alouds. - Include activities that keep the students physically active. Encourage outdoor time. Attribution Image by Gerd Altmann from Pixabay License Except where otherwise noted, this work by the Office of Superintendent of Public Instruction is licensed under a Creative Commons Attribution License. All logos and trademarks are property of their respective owners.	oercommons	2025-03-18T00:36:08.964206	Career and Technical Education	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/64064/overview", "title": "Keeping Students Learning - Tips for Online and Offline Learning", "author": "Business and Communication" }
https://oercommons.org/courseware/lesson/104138/overview	CREDIT CARS: COSTS, RESPONSIBILITY, AND CONSEQUENCES Overview "Future Ready: Financial Literacy" is an educational resource that explores credit cards, emphasizing the importance of understanding their costs and potential hazards. Learners will develop rational thinking and decision-making skills through a cost-benefit analysis. The content focuses on financial responsibility, highlighting the benefits of wise money management and the costs of irresponsibility. The resource equips individuals with essential knowledge to make informed financial choices and maintain a healthy credit score. WHAT ARE CREDIT CARDS? Future Ready FINANCIAL LITERACY Learning about credit cards, their potential costs and hazards of using them What are credit cards? Photo by AVery Evans on Unsplash LEARNING OBJECTIVES Describe rational thinking and behavior Demonstrate the process of making decisions using a cost-benefit analysis. Identify ways to be a financially responsible individual. Give examples of the benefits of financial responsibility. Give examples of the costs of financial irresponsibility. THE TRUE COST OF USING A CREDIT CARD Credit cards allow you to borrow money from the issuer to buy things, but it's important to remember that if you don't pay back what you borrow each month, you'll have to pay extra money in the form of interest and other fees [1]. So, it's important to be careful when using credit cards and make sure to understand the rules and conditions of the card agreement, so you don't end up with a lot of debt that costs you more money in the long run. THE BOTTOM LINE: Carrying a large balance on your credit card can result in paying a significant amount of interest, especially if the interest rate is high. This is why it's important to keep your balances low and make timely payments to avoid paying more in interest and to maintain a good credit score. VOCABULARY ARP the annual percentage of interest a borrower pays to the lender credit history a person’s individual history of paying bills HOW CAN YOU BORROW MONEY WISELY? To make smart choices when borrowing money, follow these steps: Read and understand the loan details and what it's for. Read and understand the loan details and pick the best one. Read and understand the loan details, like the interest rate and how you have to pay it back. Check if you can afford the monthly payments and the overall cost. Keep track of your loan and make payments on time. By doing these things, you'll be able to borrow money smartly and handle it well BENEFITS TO BEING FINANCIALLY RESPONSIBLE Handling your cash wisely has tons of perks. For instance, if you're in college, you won't need to ask your parents for dough if you're good with your money. This gives you more freedom and independence. After college, you won't have to worry about paying off student loans, a car, or credit cards, giving you the ability to do what you want. Earning more money is just one benefit. Other benefits include: earning more money having good credit having more opportunities gaining independence being prepared for an emergency THINKING CAREFULLY Walk through the thinking process for understanding credit cards and being financially responsible. Being careless with your money can also have consequences. Say you move into an apartment without considering if you can afford it. If you can't make rent, you might have to move back in with your folks. But, you'll owe the apartment company big bucks because you broke your lease. And, it can also hurt your credit score, making it tough to rent a place again for a while. Let’s take a look at a couple of scenarios that demonstrate the importance of becoming financially literate. Simon wants to get a credit card and he gets a form from his bank. He starts reading and sees some confusing terms like "annual percentage rate" and "transaction fee." He doesn't know what those mean and wants more info before deciding if it's the right card for him. What can Simon do? He needs to learn more about money. He can read a book about finances, Google the terms, take a class, call the credit card company, or ask someone who knows a lot about it. Even a bank worker could be a great help. If Simon understands more about money, he can figure out what important financial information means. Let's take a look at another example. Robin got her credit card bill and was shocked to see she owed $100 even though she didn't buy anything and her balance was $0. She called the credit card company and found out it was her annual fee. She realized she read the terms, but didn't understand she'd have to pay a fee every year. What should Robin have done? Before getting the credit card, she should have learned more about it. She should have found a credit card with no annual fee. Knowing more about money would have saved her money in this situation. Lastly, take a look at this final scenario. Anna wanted some new earrings but didn't have enough money. She used her credit card instead. When the bill came, she couldn't pay it all so she only paid part. The next month, the same thing happened. By the third month, she finally paid for the earrings but ended up paying an extra - $22.50 in interest. Paying more money is just one cost of irresponsibility. Other consequences of irresponsibility include: paying more money in fees, penalties, and interest; earning less money in interest; being dependent on others. NOW IT’S YOUR TURN. Use what you have learned to answer the question. Select the items from the following list that are included in financial literacy. using a credit card to make a purchase applying for a credit card selecting a college deciding to rent an apartment paying taxes opening a checking account CHOOSE THE RIGHT ANSWER. Answer the question below. Then read why each answer is correct or incorrect. Let’s say you decide you want to buy a new iPad or tablet that costs $300 but you haent’ had time to savvy up enough to buy it with cash. Your parents cosign the application, so you were able to get a credit card in your name. If the credit card company charges you 18% interest, and you only have to make a minimum payment of $15 a month, how long will it take you to pay off in full? Check to see if you chose the right answer. It sounds great, right? You just got a brand new tablet, didn’t have to spend any cash out of your pocket, and will only have to pay $15 a month. What a deal! Hold on a minute. At $15 a month and with an 18% interest rate, it will take you 24 months to pay off the balance in full. That means you will have paid $359 for the tablet ($300 for the original cost, plus $59 in interest). And if you happen to accidentally miss a payment, your interest rate will probably go up and you’ll be charged a late fee, maybe $25 or more. Does it still seem like a good deal? Now imagine that you only make the minimum monthly payment and continue to use your credit card for everyday purchases like lunch, clothes, and video games. Pretty soon you rack up a $3,000 balance. With an 18% interest rate - and even if you make no more purchases - it will take you nearly 22 years to pay off your credit card debt. If you were 18 when you make your first purchase, you will be 40 when you finally pay it off. You also will have paid $4,100 in interest charges during that time, well over the amount you originally spent. WHY IT MATTERS: Pay off your credit card balance in full each month by the due date. That way you won’t have to pay interest and you’ll never get hit with a late fee NOW IT’S YOUR TURN. To do well on questions about a text, follow these tips: Be a detective and gather information from the text, title, date, and author's background. Be an active reader and ask questions as you go. Stop and reread things you don't understand. Trust your first answer, but double check by looking back at the text to make sure it's right. Think about what the author is saying, the conclusions they make, the arguments they give, and the details they use to support those arguments. Find specific examples in the text that relate to the question. Which of the following is an example of financial irresponsibility? organizing financial documents spending your entire paycheck finding a new job before quitting your current job paying car payments on time Which of the following is an example of financial responsibility? spending money before you have earned it making impulse buys at the grocery store having medical insurance borrowing from your brother to make a car payment 2 more WRITING THE BEST ANSWER POSSIBLE Study the model below. It’s a good example of a written answer. Linda and her husband would like to buy a house soon. She continuously pays bills late. How do her actions affect her and others? Continuously paying bills late can have a negative impact on Lisa's credit score, which can make it more difficult and expensive for her to get a loan or a mortgage to buy a house. It can also affect her relationship with creditors and result in late fees or legal actions. Additionally, her actions may affect her husband's credit score as well if they plan to apply for a loan together. Late payments can also harm her reputation and credibility with utility companies, landlords, and other service providers. Overall, paying bills late can have far-reaching consequences for Lisa's financial well-being and her ability to achieve her goals. NOW IT’S YOUR TURN. Answer the question. Use what you have learned from the model. Do you already demonstrate some ways of showing financial responsibility? In the text box below, write a brief statement about 3-5 ways you already show financial responsibility. Also mention 3-4 areas you would like to start working on. GET READY FOR YOUR FUTURE! As you answer the questions below, remember to: Read each question carefully and consider your answer options. Take as much time as you need to complete these questions. When you finish, check your answers. 🤔Remember: Being financially responsible doesn't just affect you. It can also affect your family, neighbors, and even the world. For example, if you got a car loan and asked your parents to help you by signing for it, but then you kept missing payments, it would not only hurt your credit score, but also your parents' because they co-signed the loan. Answer each question. Read the following two descriptions. Decide who has better financial habits and attitudes. Lindsay doesn't feel that she will ever get her credit card paid off. After seeing her new bill, she tosses it aside so she doesn't have to think about it. Hillary receives a few bills in the mail. She takes out a piece of paper and starts figuring out a plan to pay these bills. Financial literacy includes information about income, banking, loans, and credit cards. True False Read the following actions and decide if they are responsible or irresponsible. checking my credit score: paying a credit card bill one day late: listing expenses in a budget: making decisions without all of the information: purchasing something because it is on sale: writing some goals: researching what a mutual fund is: making financial decisions without discussing it with your spouse: finding a savings account with a great interest rate: looking for the cheapest price for an item: Choose all that apply. A financially responsible person _____. has a budget pays bills on time spends less than they make sets goals pays for everything with a credit card saves their money List three or four effects of financial irresponsibility. REFERENCES, ATTRIBUTION, AND LICENSE References “Credit Card Glossary” by Bank of America CashOnHand - Credit Cards - Brandon - English \| CC BY-NC-ND Credit Card Analysis by Stuart Boersma \| CC BY-NC-SA Cards, Cars, and Currency Curriculum Unit by Federal Reserve Bank of St. Louis \| CC BY-NC-ND Attribution Lesson by Benjamin Troutman, Griffin Bay School, San Juan Island School District Portions of content adapted from Credit Card Comparison Activity by Lexi Shafer \| CC BY-NC Credit Card Terms and Comparison Activity by Rebecca Kingsley \| CC BY-NC Credit Cards and Credit Scores by Lois Hixson \| CC BY-NC-SA License Except where otherwise noted, Future Ready Financial Literacy Learning about Credit Cars, Their Potential Costs and Hazards of Using Them by San Juan Island School District is available under a Creative Commons Attribution 4.0 International License. All logos and trademarks are the property of their respective owners. Sections used under the fair use doctrine (17 U.S.C. § 107) are marked.	oercommons	2025-03-18T00:36:08.994878	Mathematics	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/104138/overview", "title": "CREDIT CARS: COSTS, RESPONSIBILITY, AND CONSEQUENCES", "author": "Finance" }
https://oercommons.org/courseware/lesson/104139/overview	MASTERING FINANCIAL LITERACY: BUDGETING AND STRATEGIES Overview "Future Ready: Financial Literacy" is an educational resource that focuses on teaching essential money management skills. Participants will learn about budgets, financial risks, and strategies to effectively manage their finances. The course covers important concepts such as budgeting, net worth, financial goals, insurance, and saving and investing. By following the provided guidelines and tips, learners will develop a solid understanding of how to manage money in a healthy and responsible way, paving the path towards a financially secure future. HOW DO YOU MANAGE YOUR MONEY? Future Ready FINANCIAL LITERACY Learning about budgets, financial risks, and strategies to manage them How do you manage money? Photo by Kenny Eliason on Unsplash LEARNING OBJECTIVES Understand important money words that will help you understand how to manage your money. Break down the parts of a plan for your money: a list of what you own and owe, what you want to save for, a spending plan, how you'll protect yourself, and a plan for growing your money. Make a plan for keeping your money organized and easy to manage. Understand the concept of a budget and how it helps you keep track of your money, plan for expenses, and achieve your financial goals. MANAGING MONEY IN A HEALTHY WAY When people hear the word "budget", they often think of having to give up things they want and being tight with money. But if you plan ahead and decide how much money you want to save and give, it can actually be very fulfilling. With a good plan, you might be able to save up enough money to do something really fun with your friends, like go on an amazing vacation! In this assignment, you'll learn how to manage your money and create a budget that works for you. VOCABULARY budget A careful plan for how much money you will spend and what you will buy with it net worth A list of what you own and owe financial goals What you want to save for insurance Something you buy to protect yourself in case something bad happens, like a fire or a flood. If that happens, the insurance company will give you money to help pay for what was damaged or destroyed. saving and investing A plan for growing your money net income The money you earn from your work or that you receive from investments after taxes HOW DO YOU MANAGE MONEY? Different financial experts have different ideas on managing money, but there are a few common tips they all agree on. Figure out why you're spending too much and avoid those reasons, like being bored, sad, or feeling pressure from others. Keep track of everything you spend because little purchases can add up quickly. Make a budget by setting goals that are specific, measurable, achievable, important, and have a deadline. Don’t get into debt or use credit cards too much in order to make smart money decisions and handle your finances well. THINKING CAREFULLY Walk through the thinking process for understanding budgeting, financial risks, and strategies to manage them. Here are 7 guidelines that will help you plan a working budget: Determine your income: Make a list of all sources of income, including salary, investments, and any other sources of money that you regularly receive. Identify your expenses: Make a list of all your monthly expenses, including rent or mortgage payments, utilities, food, transportation, entertainment, and other bills. The amount of money you have, minus the amount you owe is your net worth. Prioritize your expenses: Decide which expenses are most important, such as housing and food, and allocate your money accordingly. Track your spending: Keep a record of how much money you spend and on what, so you can see where your money is going and identify areas where you may be overspending. Set aside money for emergencies: It's important to have a reserve of money for unexpected expenses, such as car repairs or medical bills. Plan for long-term goals: Think about your future financial goals, such as buying a house, saving for retirement, or going to college, and make a plan for how to save for these expenses. Review and adjust your budget regularly: Your expenses and income may change over time, so it's important to review your budget regularly and make adjustments as needed to ensure you are staying on track. YOUR TURN Use what you have learned to answer the questions. Net worth is the amount you have, plus the amount you owe. True False A budget is a _____. A plan for spending money A list of expenses A way to save money All of the above Answer: A. A plan for spending money CHOOSING THE RIGHT ANSWER. Read the following and answer the question below. Then read why each answer is correct or incorrect. Managing your money wisely involves making a plan to spend your money on the things you need and want, while also saving for future goals. This plan is called a budget. To make a budget, you add up all the money you make in a month and subtract the money you save, give to charity, and spend on bills and other expenses. There are different ways to make a budget, like using envelopes for different categories of expenses or using computer programs or apps, like Mint, Personal Capital, YNAB, Every Dollar, and Goodbudget. The important thing is to find a method that works best for you. By creating a budget and sticking to it, you can make smart choices with your money and reach your financial goals. Why is a budget important? It helps you keep track of your wants It helps them make smart choices with their money It helps you spend your money freely A plan to spend as much money as possible on long-term purchases and goals. Check to see if you chose the right answer. A budget helps you to plan and manage your spending and saving, allowing you to make informed decisions with your money. It helps you prioritize your needs and wants, while also saving for future goals, and ensures that you don't overspend or run out of money before the end of the month. So, the correct answer is B: "It helps them make smart choices with their money". The other options are incorrect because a budget doesn't necessarily help you spend your money freely (Choice C) or on long-term purchases and goals (Choice D) without any plan or consideration. It also doesn't only help you keep track of your wants (Choice A), but rather helps you to balance your wants and needs with your financial goals. NOW IT’S YOUR TURN. When you're answering the following questions, follow these tips to make sure you get them right: Pay attention and read everything closely. If you don't understand something, ask yourself questions or read it again. Trust your gut, but double-check your answer by looking back at the text. Find specific examples from the text that can help you answer the question. Think about what the writer is saying and why they're saying it. This can help you understand their main ideas and conclusions. What is the first step in creating a budget? Identifying your expenses Prioritizing your expenses Determining your income Tracking your spending Why is it important to track your spending? To see where your money is going To identify areas where you may be overspending To make adjustments to your budget All of the above What is the importance of setting aside money for emergencies? To have money for unexpected expenses To pay off debt To save for long-term goals To buy luxury items Which of the following is a common tip agreed upon by financial experts to manage money? Spend money when you feel bored or sad. Don't keep track of your spending. Make a budget with specific goals. Get into debt and use credit cards excessively. WRITING THE BEST ANSWER POSSIBLE Study the model below. It’s a good example of a written answer. HOW TO START BUDGETING To start budgeting, you need to keep track of your expenses for one month. Think about where your money goes. Do you pay for your own lunches or your portion of the family's cell phone bill? Do you go to the movies often? Do you buy clothes or makeup regularly? Keep track of everything you spend money on for a week or two if you have trouble remembering. Next, figure out how much money you make each month, including allowance, payment for chores, and money from jobs after taxes or selling things (that is, your net income). Don't include occasional gifts or rewards that you only get once or twice a year. Add everything up to find your net monthly income. Then, put your spending into categories like food, clothing, transportation, and entertainment. Add up how much you spend in each category, and include any money you save or donate to charity. Make sure to calculate everything on a monthly basis. Describe how you would create a system to organize your financial information in two to three sentences. To keep track of my money, I would create a plan using a computer program that shows how much money I earn and spend each month, and I will make it look nice with colors and pictures. I will also learn more about important money ideas like saving and investing so that I can be smarter with my money in the future. The student's answer summarizes how to organize finances in a clear and concise way, including using a computer program and educating themselves. However, they could provide more detail on categorizing expenses (eg, food, clothes) and tracking progress over time (eg, weekly expense tracking). NOW IT’S YOUR TURN. Read the following and answer the question. Use what you have learned from the model. BUDGETING 101: CREATING A PLAN THAT FITS YOUR LIFE AND GOALS Creating a budget is easy once you know how much money you make and how much you spend each month. First, list all your income in one column and your expenses in another. It's important to remember your financial goals, like having enough money to cover living expenses for a few months. You should also have a stash of money for unexpected emergencies. After listing all your expenses, including savings and donations, subtract that from your total income. If you have money left over, that's great! You have a balanced budget. But if you spend more than you make, you'll need to adjust your expenses until you have a balanced budget. What's a good budget to follow? Some people use the 50-30-20 Rule if they have a family or live on their own. That means you should spend half of your income on things you need, like food, clothes, and housing, 30% on things you want, and 20% on savings. But if you live with your parents, it's good to save around 10-40% of your income and have a 10% emergency fund. This leaves the rest of your money for fun things like shopping, eating out, and activities. Everyone manages their money differently. It's crucial to create a budget that suits your specific situation to make the best financial decisions. In two to three sentences, how can budgeting help achieve long-term financial goals? GET READY FOR YOUR FUTURE! To ace the following questions, remember these steps: Read carefully and don't skip anything. If you're confused, stop and ask yourself questions or go back and read it again. Go with your first guess, but make sure it's right by checking the text. Look for specific parts of the text that can help you answer the question. Think about what the writer is trying to say and why they're saying it. This will help you understand their big picture and main points. Which of the following is NOT part of a plan for your money? What you own and owe What you want to save for A spending plan A plan for investing in stocks What is net worth? The money you earn from your work or investments after taxes A careful plan for how much money you will spend and what you will buy with it A list of what you own and owe What you want to save for What is insurance? A plan for growing your money How you'll protect yourself A list of what you own and owe What you want to save for What is the purpose of making a budget? To figure out why you're spending too much To keep track of everything you spend To allocate your money for your most important expenses All of the above What is one of the guidelines for planning a working budget? Determine your income Track your spending Set aside money for emergencies All of the above Which of the following is NOT a common tip for managing money? Keep track of everything you spend Figure out why you're spending too much Use credit cards as often as you can Make a budget What are the five parts of a plan for your money? How can you make sure you're not overspending on little purchases? Why is it important to set aside money for emergencies? Explain the concept of budgeting and how it helps you manage your money. Provide at least three examples of how you can make a budget and why each method might work well for certain individuals or situations. Financial Stability and Budgeting Having financial instability can cause many problems, like breaking up families and causing arguments. Money is very important to people and affects everything we do, like politics and wars. It's important to have financial stability because it gives us freedom and peace, and helps us reach our dreams. You don't have to be rich to be financially stable, you just need to manage your money well. Creating a budget can help you do that by separating your needs, like food and car payments, from your wants, like going out with friends. If you spend more than you earn, that's a problem, so you should try to cut back on some things. Making goals and tracking your expenses can help you stick to your budget and save money. If you're disciplined with your money, it can even help you make more money in the future. So, if you want to be financially stable and achieve your dreams, you should start by creating a budget. REFERENCES, ATTRIBUTION, AND LICENSE References Butler, Tamsen. The Complete Guide to Personal Finance for Teenagers and College Students. Atlantic Publishing Group, 2016, p. 79. Pant, Paula. "The 50/30/20 Rule of Thumb for Budgeting." Balance, December 21, 2018. https://www.thebalance.com/the-50-30-20-rule-of-thumb-453922. Attribution Lesson by Benjamin Troutman, Griffin Bay School, San Juan Island School District Portions of content adapted from Budgeting Compass Points Activity by Lexi Shafer \| CC BY-NC Weekly Budget Journal Templete for Financial Literacy by Heather LaGoy \| CC BY-NC-SA Foundations for College Success, Financial Literacy, Readings by Forrest Lane and Heather F. Adair \| CC BY License Except where otherwise noted, Future Ready Financial Literacy Learning about Budgets, Financial Risks, and Strategies to Manage Them by San Juan Island School District is available under a Creative Commons Attribution 4.0 International License. All logos and trademarks are the property of their respective owners. Sections used under the fair use doctrine (17 U.S.C. § 107) are marked.	oercommons	2025-03-18T00:36:09.026844	Mathematics	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/104139/overview", "title": "MASTERING FINANCIAL LITERACY: BUDGETING AND STRATEGIES", "author": "Finance" }
https://oercommons.org/courseware/lesson/115797/overview	Fundamentals of Pharmacy Calculations Overview This text is used as the required textbook for a 1 credit hour Pharmacy Calculations course at SIUE School of Pharmacy. It was written specifically for our course. We have shared it here in case you may find all or parts it useful for your needs. This textbook is provided as is under the Creative Commons BY license. Anyone may copy, display, and/or distribute the book with appropriate citation of the creators. No warranty, express or implied, is granted. Disclaimer: The purpose of this textbook is to develop quantitative competence for pharmacy practice. Nothing in the textbook is intended, nor should it be inferred, as medical advice or opinion. Healthcare professionals are solely responsible for their application of the information contained herein. Introduction to the Text This text is used as the required textbook for a 1 credit hour Pharmacy Calculations course at SIUE School of Pharmacy. It was written specifically for our course. We have shared it here in case you may find all or parts it useful for your needs. This textbook is provided as is under the Creative Commons BY license. Anyone may copy, display, and/or distribute the book with appropriate citation of the creators. No warranty, express or implied, is granted. Disclaimer: The purpose of this textbook is to develop quantitative competence for pharmacy practice. Nothing in the textbook is intended, nor should it be inferred, as medical advice or opinion. Healthcare professionals are solely responsible for their application of the information contained herein. Module 1: Fundamentals of Calculations Introduction Module 1 will introduce and review several fundamental topics: Measurement definitions and conversion between units; Decimal places, significant digits (figures) and rounding, exemplified with syringes; Institutional time notation; Abbreviations common in pharmacy and medicine; some Institute for Safe Medication Practices guidelines; and Ratio and proportion techniques. Module 1A: Measurement Definitions and Conversions A. Measurement Definitions and Conversions Here we review some basic conversion factors you will likely know at this point in your education. Recall the relationships between the Greek and Latin prefixes milli-, micro-, and kilo-. In this course, you will only use these exact conversions. Take some time to verify your familiarity with these units and conversion factors. Volume • 1 Liter = 1000 mL (milliliters) • 1 mL = 1000 mcL (microliters) • 1 teaspoonful (tsp) = 5 mL • 1 tablespoonful (Tbsp) = 15 mL • 1 fluidounce (fl oz) = 30 mL Mass or Weight • 1 gram = 1000 mg (milligrams) • 1 mg = 1000 mcg (micrograms) • 1 mcg = 1000 ng (nanograms) • 30 grams = 1 ounce Note: This is not an exact conversion - it is an approximate value used in reference to drug products. Do NOT use this conversion for calculating patient body weights. • 16 ounces = 1 pound (may be abbreviated 1 lb or 1 #) • 1000 g = 1 kg (kilogram) • 1 kg = 2.2 pounds Length • 1 inch = 2.54 centimeters • 12 inches = 1 foot • 100 centimeters = 1 meter Time • 60 seconds = 1 minute • 1 hour = 60 minutes • 1 day = 24 hours • 1 week = 7 days • 1 month = 30 days Notational Shorthand • A height listed as X’ Y” implies X feet and Y inches 5’ 10” means 5 feet and 10 inches. Example Problems: 1.1 Pounds and ounces to kilograms: A newborn baby weighs 7 pounds and 5 ounces. How many kilograms does the baby weigh? $7\:lbs\:5 oz\equiv 7\:lbs\;+\;\frac{5\;oz}{16\;\frac{oz}{lb}}=\frac{7.3125\;lbs}{2.2\frac{lb}{kg}}=3.32\;kg$ 1.2 Ounces to grams: A pharmacist dispenses 4 ounces of a steroid cream. How many grams were dispensed? $4\;oz\;\times\;\frac{30\;g}{1\;oz}=120\;g$ 1.3 Volume for dispensing: A patient will receive 1 teaspoonful of antibiotic suspension three times a day for 1 week. How many milliliters should you dispense? $1\;\frac{tsp}{dose}\;\times3\;\frac{doses}{day}\;\times7\;\frac{days}{week}\;\times\;5\;\frac{mL}{tsp}\;=\;105\;\frac{mL}{week}$ 1.4 Pounds to kilograms: $\frac{121\;lbs}{2.2\;\frac{lbs}{kg}}\;=\;55\;kg$ 1.5 Feet and inches to centimeters and meters: A patient is 5’ 7” tall. Calculate the patient’s height in centimeters and meters. $5\text{'}\;7\text{"}\;=\;67\text{"}$ $67\text{"}\;\times\;\frac{2.54\;cm}{1\;inch}\;=\;170.18\;cm\;\times\frac{1\;meter}{100\;cm}\;\simeq \;1.7\;meters$ 1.6 Hours to minutes: A patient’s urine was collected for 24 hours in order to perform a creatinine clearance evaluation. For how many minutes was the sample collected? $24\;hours\;\times\;\frac{60\;min}{1\;hr}\;=\;1440\;minutes$ 1.7 Days and months: You receive a prescription with directions for the patient to take 1 tablet daily. How many tablets should be dispensed to fill a 3-month supply? $1\;\frac{tablet}{day}\;\times\;\frac{30\;days}{1\;month}\;\times\;3\;months\;=\;90\;tablets$ Module 1B: Decimal Places, Significant Digits (Figures), and Rounding Decimal numbers represent a whole number and a fractional part of that number. A typical example is 3.125. This notation represents three and one hundred and twenty-five thousandths. We know you are very familiar with this notation, and it is included here as a prelude to discussing significant digits and rounding. For measurments using a graduated device, calculations should be rounded to match the precision of the device. For example, look at the 5 mL oral syringe. Note that the major markings on the barrel run from one to five milliliters. The minor markings are spaced every 0.2 mL. If a patient’s dosage volume calculation resulted in a value of 3.125 mL, how would you explain to the patient or caregiver how to use this device? An individual cannot accurately withdraw 3.125 mL with this syringe. A decision must be made about using the appropriate number of significant figures. In this case, you should advise the patient to measure 3.2 mL. While the actual calculation answer may be 3.125 mL, there is no practical way to make that measurement. Using 3.2 mL for the volume results in a relative error of 2.4%. If you selected 3 mL, the relative error would be 4%. Pharmacists are practical people. The example above demonstrates that selecting the number of milliliters to use is aided by the size and demarcation of the available measuring device. Different parenteral and oral syringes have various markings that range from 0.01 mL to 1 mL. You will see these devices routinely, and it will help you to memorize the table. \| Size (mL) \| Type (Oral or Parenteral) \| Smallest Division (mL) \| \| 1 \| Oral \| 0.01 \| \| 5 \| Oral \| 0.2 \| \| 10 \| Oral \| 0.2 \| \| 1 \| Parenteral \| 0.01 \| \| 3 \| Parenteral \| 0.1 \| \| 5 \| Parenteral \| 0.2 \| \| 10 \| Parenteral \| 0.2 \| Let’s look at another example where the physical situation helps us to determine a practical volume. Example 1.8: An 81.4 kg patient requires a drug dose of 5 mg/kg. $81.4\;kg\times \frac{5\;mg}{kg}=407\;mg$ Example 1.9: What volume of drug suspension is required if the drug concentration is 100 mg/mL? The calculator answer is: $\frac{407\;mg}{100\;\frac{mg}{mL}}=4.07\;mL$ We do not have a syringe with that degree of accuracy and precision. Based on the available parenteral syringes, you should recommend a dose of 400 mg and a volume of 4 mL. Before ending this section, several more issues about significant figures and rounding decimal places will be addressed. Counting significant digits begins with the farthest digit to the left of the decimal place that is not zero and ends with the digit farthest to the right of the decimal place that is not zero. You may have learned a slightly different definition in physics or chemistry, but this definition will work for pharmacy. Let’s look at some problems. In the above dosing calculation example, the patient weighs 81.4 kg. We could say that the patient’s weight is accurate to 3 significant figures or 1 decimal place. You will develop an understanding of how many significant figures are needed for particular situations. Now let’s look at the dose. Based on 5 mg/kg, the patient would receive 407 mg of the drug. How many significant figures are represented in the dose? The concentration of the drug in the vial is 100 mg/mL. Recall that volume = mass/concentration. The actual calculated volume is 4.07 mL. How many significant figures are represented in the volume? How many significant figures are represented in the volume we can accurately measure? Consider this problem from a recent national exam. The formula for a type of “magic mouthwash” is: \| Diphenhydramine syrup 12.5 mg/5 mL \| 80 mL \| \| Lidocaine oral solution 2% \| 30 mL \| \| Maalox antacid suspension \| 90 mL \| \| Total \| 200 mL \| The patient is instructed to orally swish 1 Tbsp (15 mL) of magic mouthwash (MM) three times a day. Example 1.10: How many milliliters of lidocaine solution will the patient receive with each treatment? $\frac{200\;mL\;MM}{30\;mL\;Lidocaine\;soln}=\frac{15\;mL\;MM}{x\;mL\;lidocaine\;soln}$ $x\;=\frac{15\;mL\;MM\;\times\;30\;mL\;lidocaine\;soln}{200\;mL\;MM}=2.25\;mL\;lidocaine\;soln$ What number would you tell a physician if they were curious about the amount of lidocaine the patient received with each dose? This topical therapy is intended to relieve pain in the oral cavity. The amount of lidocaine received is not so critical to the treatment as to require an answer to 2 decimal places. You could tell the physician that the patient receives approximately 2 mL per dose. Some calculations will require different rounding based, in part, on the needed significant figures and the practical circumstances involved with measurement. Your clinical judgment and decision-making skills will sharpen as you advance through the curriculum. The lectures will contain more guidance on this when specific topics are covered. Example 1.11: How many significant figures are represented in the numbers? a. 14.75 – 4 significant figures b. 2.37 – 3 significant figures c. 12.3 – 3 significant figures d. 18.789 – 5 significant figures e. 0.0205 – 3 significant figures f. 0.00330 – 2 significant figures g. 0.09105 – 4 significant figures Example 1.12: Round the numbers to the indicated decimal places. a. 8.357 (2 decimal places) = 8.36 b. 8.354 (2 decimal places) = 8.35 c. 12.276 (1 decimal place) = 12.3 d. 12.249 (1 decimal place) = 12.2 Example 1.13: Round the numbers to the indicated significant figures. a. 12.0041 (3 significant figures) = 12.0, but we do not write trailing zeros after a decimal point, so 12. (See section 1F: ISMP guidelines) b. 0.693147 (3 significant figures) = 0.693 c. 1.0402 (3 significant figures) = 1.04 Module 1C: Patient Weight and Height Pharmacists typically use patient weights in kilograms with two or three significant digits depending on the weight and age. Some healthcare institutions will only use two significant digits for patients weighing over 20 kg. When using metric units for height, either centimeters or meters, continue to use three significant digits. You will be using height in the equation for Body Surface Area. Let’s look at a range of examples. Example 1.14: Weight and height conversions a) A premature newborn weighs 1 pound and 4 ounces. Convert this weight to kg. There are 16 oz in 1 lb, so 1 lb 4 oz = 1.25 lb. $1.25\;lb\times\;\frac{1\;kg}{2.2\;lb}=0.5681818\;kg$ Use 0.568 kg for calculations. b) An infant weighs 19 pounds and 6 ounces. Use 8.81 kg for calculations. c) A child weighs 48 pounds. Use 21.8 kg. d) A teenager weighs 133 pounds. Use 60.5 kg. e) An adult weighs 189 pounds. Use 85.9 kg. f) An adult weighs 235 pounds. Use 107 kg. g) A child is 3’ 6” tall. Use 107 cm, 1.07 m. h) A teenager is 5’7” tall. Use 170 cm, 1.7 m. i) An adult is 6’3” tall. Use 191 cm, 1.91 m. Module 1D: Institutional Time (24 Hour Time) Institutional or 24-hour time is frequently used in healthcare settings to avoid the common 12-hour AM/PM ambiguity. - Institutional time is a 4-digit number, with the first two digits indicating the hour and the last two representing the minutes. - Midnight is 0000 - Morning times are identical in 12- and 24-hour time systems. - Add 12 to afternoon times to convert 12- to 24-hour time systems. If you would like more information, there are several tutorials available online. For example, https://www.militarytime.us/learn-military-time/ Some examples: \| 12 hour time \| 24 hour time \| \| 12:30 AM \| 0030 \| \| 8:00 AM \| 0800 \| \| 12:35 PM \| 1235 \| \| 2:30 PM \| 1430 \| \| 6:15 PM \| 1815 \| \| 11:05 PM \| 2305 \| Example 1.15: A patient received an IV bolus drug dose at 1800 on February 3 and another at 0445 on February 4. How much time elapsed between the 2 doses? 1800 -> 0000 = 6 hours + 4 hours and 45 minutes = 10 hours and 45 minutes = 10.75 hours Example 1.16: A surgeon ordered morphine 2 mg IV every 6 hours if needed for pain relief. The patient received his previous dose at 1730. What is the earliest time he may receive another dose? 1730 + 6 hours = 2330 Example 1.17: A patient is to receive gentamicin 80 mg in 50 mL of normal saline over 30 minutes every 8 hours. If the first infusion was started at 1500, when should the next 2 doses be started? 1500 + 8 hr = 2300 the same day; 2300 + 8 hr = 0700 the next morning Example 1.18: A patient received 300 mg of a drug by IV infusion starting at 0500. The infusion of 500 mL was completed at 0630. What was the infusion rate in mg/h? What was the solution flow rate in mL/min? The infusion ran from 0500 to 0630 or 1.5 hours. 300 mg/1.5 hr = 200 mg/hr = 5.6 mL/min Example 1.19: A patient is scheduled for surgery at 0730 on January 16. She is ordered to receive 2 doses of pre-operative medications 14 hours and 6 hours before surgery. When should the doses be given? 0730 - 6 hours = 0130 on surgery day (Jan 16) 0730 - 14 hours = 1730 the day before surgery (Jan 15) Module 1E: Common Pharmacy Abbreviations The electronic transmittal of prescriptions has reduced the use of historical Latin abbreviations. The Institute for Safe Medical Practices (ISMP, www.ismp.org) advises against using any abbreviations. However, the organization acknowledges that there are abbreviations that are so commonly used that restricting their use would lead to hardships. We expect you to memorize the abbreviations in the table. Table 2.2. Common Abbreviations used in Pharmacy Abbrev \| Meaning \| \| Abbrev \| Meaning \| Prescription Directions \| \| bid \| two times a day \| \| aa. \| of each \| \| tid \| three times a day \| ad \| up to, to make \| \| qid \| four times a day \| NR \| no refills \| \| q (t) h \| every (t) hours \| q.s. \| a sufficient quantity \| \| prn \| as needed \| q.s. ad \| enough to make \| \| \| \| stat \| immediately \| \| a.c. \| before meals \| ut dict \| as directed \| \| p.c. \| after meals \| \| \| \| q AM \| every morning \| Quantity and Measurement \| \| q PM \| every evening \| \| BSA \| body surface area \| \| q HS \| at bedtime \| m2 \| square meters \| \| \| \| \| \| \| p. o. \| by mouth (orally) \| cc, cm3 \| cubic centimeter, mL \| \| NPO \| nothing by mouth \| tsp \| teaspoonful (5 mL) \| \| \| \| Tbsp \| tablespoonful (15 mL) \| \| a.d. \| right ear \| \| \| \| a.s. \| left ear \| mcg \| microgram \| \| a.u. \| each ear \| ng \| nanogram \| \| \| \| mcL \| microliter \| \| o.d. \| right eye \| \| \| \| o.s. \| left eye \| mEq \| milliequivalent \| \| o.u \| each eye \| mmol \| millimole \| \| \| \| mOsm \| milliosmole \| \| IV \| intravenous \| \| \| \| IM \| intramuscular \| \| \| \| ID \| intradermal \| \| \| \| subQ \| subcutaneous \| Module 1F: Some ISMP Guidelines History has provided many opportunities for learning from our mistakes. Unfortunately, patients have suffered from a lack of exact directions or misinterpreting written instructions. IMSP has developed guidelines, and you must use the following in class. • Whole numbers should be written without a decimal point and without a terminal zero. For example, write 6 mg, not 6.0 mg. The decimal point might be missed, and the dose is interpreted as 60 mg. • A number with a value less than one should be written with a leading zero. For example, write 0.4 mg, not .4 mg. The decimal point might be missed, and the dose is interpreted as 4 mg. • Use whole numbers when possible and not the equivalent decimal fraction. Write 100 mg, not 0.1 g. • Do not use the abbreviation u or U for units. Spell out the word units. The letter U has been misinterpreted to represent zero (0). • Be especially careful about using the letter d when representing dose or day. When the situation may be ambiguous, spell out the intended word. What is the meaning of d when written as mg/kg/d? Is this mg/kg/dose or mg/kg/day? Always put the safety of the patient first in your activities. Consider your safety education to start now. Module 1G: Ratio and Proportion Many numerical problems in pharmacy calculations can be solved using ratios and proportions. A ratio compares two quantities, for example the fraction $\frac{4}{7}$, which can also be written as 4 : 7, means 4 parts of one component and 7 parts of the other. In addition to comparing one component to the other, the ratio can also be interpreted as the amount of one component in relation to the sum of all other components. The proportional relationship is usually written as: $\frac{a}{b}=\frac{c}{d}$ To solve this type of problem, you require three values and solve for the fourth by cross-multiplying and then dividing to isolate the term of interest. Remember to include the units and ensure that like units occupy numerators or denominators. Example 1.20: An injectable product contains 350 mcg of a drug in each 0.9 mL. How many micrograms are contained in 0.4 mL? $\frac{350\;mcg}{0.9\;mL}=\frac{x\;mcg}{0.4\;mL}\\\\$ $x\;mL=\frac{350\;mcg\times0.4\;mL}{0.9\;mL}=155.6\; mcg$ Module 1: Practice Problems - A patient will receive 5 mL PO bid of a medication x 10 days. What volume is required? - A patient will receive 3.5 mL PO tid of a medication x 8 days. What volume is required? - A patient will receive 2.5 mL PO qid of a medication x 7 days. What volume is required? - A child weighs 35#. What is the weight in kg? - A newborn weighs 5# 3oz. What is the weight in kg? - An infant weighs 7# 7oz. What is the weight in kg? - A patient weighs 186#. What is the weight in kg? - A patient is 6’4”. What is their height in cm and m? - A patient is 5’6”. What is their height in cm and m? - A patient is 3’7”. What is their height in cm and m? - A patient is 4’3”. What is their height in cm and m? - If you are paid $56.25 for 1 ½ hours of work, what is your hourly wage? - If you are paid $1075.20 for 42 hours of work, what is your hourly wage? - Risankizumab injection contains the following ingredients in each 0.83 mL dose: Risankizumab 75 mg, succinic acid 0.049 mg, sorbitol 34 mg, polysorbate 20 0.17 mg, and sodium succinate anhydrous 0.53 mg. How many milligrams of each ingredient would be present in 10 mL of the solution. - Prednisone is available in 5 mg tablets. How many tablets would be required to fill an Rx with the directions: Day 1 - take 40 mg one time Day 2 - take 30 mg one time, Day 3 - take 20 mg one time Day 4 - take 10 mg one time Days 5 - 10 - take 5 mg one time per day. - A surgeon ordered morphine 2 mg IV every 6 hours if needed for pain relief. The patient received his previous dose at 2230. What is the earliest time he may receive another dose? - A patient will receive an IV drug over 1 hour every 8 hours. If the first infusion was started at 1000 today, at what times should the subsequent 2 doses be started? - Levothyroxine sodium tablets are available in 12 different dosages, from 25 mcg to 300 mcg. Express that range in milligrams. - A patient is prescribed an antibiotic with the directions: 2 tsp qid x 4 days, then 1 tsp bid x 2 days. How many milliliters will the patient take over the course of therapy? - Each dose from a dry powder inhaler weighs a total of 12.5 mg - see label below. The powder mixture contains fluticasone propionate, salmeteral xinafoate, and lactose. The patient inhales two doses (blisters) a day. How many milligrams of lactose are inhaled in one week? 1.65 grams equals mg. 0.25 grams equals mcg. 0.1 grams equals ng. 0.5 mg = mcg If the contents of 1 vial of angiotensin II injection is diluted to a total of 500 mL with normal saline, what is the drug concentration in nanograms per mL (ng/mL). - Read the volume in each syringe \| A \| B \| C \| \| C \| D \| E \| \| G \| H \| I \| \| J \| K \| L \| Answers: - 100 mL - 84 mL - 70 mL - 15.9 kg - 2.36 kg - 3.38 kg - 84.5 kg - 193 cm, 1.93 m - 168 cm, 1.68 m - 109 cm, 1.09 m - 130 cm, 1.3 m - $37.50/h - $25.60/h - Risankizumab 903.6 mg Succinic acid 0.59 mg Sorbitol 409.6 mg Polysorbate 20 2.05 mg Sodium succinate anh. 6.39 mg - 26 tablets - 0430 - 1800, 0200 tomorrow - 0.025 mg – 0.3 mg - 180 mL - 166.985 mg (or 167 mg) lactose - 1650 mg. 250,000 mcg. 100,000,000 ng. 500 mcg. 5000 ng/mL A. 2.6 mL B. 0.8 mL C. 6.8 mL D. 0.68 mL E. 3.2 mL F. 0.62 mL G. 1.6 mL H. 0.35 mL I. 7.6 mL J. 0.51 mL K. 8.4 mL L. 4.8 mL Module 2: Working with Concentrations This module will introduce and review calculations involving different concentration units used in Pharmacy. Concentration A drug product contains one or more active ingredients mixed with excipients, such as diluents, flavorings, and colors. Different concentration terms are used to express the quantity of any single ingredient in relation to the entire mixture. - A suspension contains 250 mg of amoxicillin in every 5 mL of liquid, or 250 mg/5 mL - Tylenol contains 325 mg of acetaminophen in each tablet, or 325 mg/tablet - A cream contains 1% hydrocortisone - A cough suppressant elixir contains 5% alcohol as an inactive ingredient Pharmacists must work with concentrations to calculate the quantity of product to dispense, the dose a patient should take, and the amount of each ingredient required for compounded formulations. Table 2.1 defines the most common concentration terms used in pharmacy. You will need to know these definitions and be able to convert between them. Table 2.1. Common concentration terms Concentration term \| Definition \| Percent weight in volume (% w/v) \| Grams of component in 100 mL of mixture \| Percent weight in weight (% w/w) \| Grams of component in 100 g of mixture \| Percent volume in volume (% v/v) \| mL of component in 100 mL of mixture \| Molar (M) \| Moles of component in 1L of mixture \| Millimolar (mM) \| Millimoles of component in 1L of mixture \| Ratio strength (1:X) \| 1 gram or mL of component in every X g or mL of mixture \| g/mL, mg/mL, Units/mL, etc. \| The amount of component in a specified amount of mixture \| Module 2A: Percent Strength Percent w/v is commonly used for liquid dosage forms, such as solutions and suspensions. The amount of drug in the mixture is stated as grams (g) per 100 mL of the mixture. Example 2.1: A minoxidil 5% topical solution contains 5 g of the drug in every 100 mL of the product. Concentration does not change with the package size, so $\frac{5\;g}{100\;mL}=\frac{0.05\;g}{1\;mL}=\frac{2.5\;g}{50\;mL}=\frac{10\;g}{200\;mL}=\frac{50\;g}{L}=5\%\;w/v$ Example 2.2: How many milligrams of minoxidil are contained in a 60 mL bottle of 5% minoxidil solution? Solve using dimension analysis: $60\;mL \;solution\times\frac{5\;g\;minoxidil}{100\;mL\;solution}=3\;g \;minoxidil$ Solve using proportionality: $\frac{5\;g\;minoxidil}{100\;mL\;solution}=\frac{x\;g\;minoxidil}{60\;mL\;solution}$ Now solve for x: $(5\;g\;minoxidil)(60\;mL\;solution)=(x\;g\;minoxidil)(100\;mL\;solution)$ $\frac{(5\;g\;minoxidil)(60\;mL\;solution)}{(100\;mL\;solution)}=x\;g\;minoxidil$ $x=3\;g\;minoxidil\;in\;every\;60\;mL\;of\;5\%\;solution $ TIP: Whether you choose to solve problems using the dimension analysis or proportionality method, label all values with a unit (g, mL, etc.) and a name to indicate what the unit refers to. This will help organize your work and reduce errors when performing multi-step calculations. Example 2.3: What volume of 17% w/v solution can be prepared from 10 g of benzalkonium chloride (BC)? $17\%\;BC=\frac{17\;g\;BC}{100\;mL\;solution}$ There is 10 g of BC to make the solution, so the volume of solution to prepare is given by: $\frac{17\;g\;BC}{100\;mL\;}=\frac{10\;g\;BC}{x\;mL},\;x\;=\;58.8\;mL$ Percent w/w is used for semisolids (ointments, creams) and concentrated acids (for example, concentrated hydrochloric acid). It may also be used for powder mixtures. A 10% salicylic acid ointment contains 10 g of salicylic acid in every 100 g of the ointment. The weight of all ingredients, including any liquid ingredients, must be included in the ointment total. Example 2.4: An ointment was prepared according to the formula below. Calculate the percent strength (w/w) of triamcinolone acetonide in the ointment. Triamcinolone acetonide 500 mg Glycerin 12.5 g Hydrophilic petrolatum qs 200 g First, understand what the formula means. Triamcinolone acetonide (TA) is a powder. It is packaged in a jar and weighed out on a balance. This batch of ointment will contain 500 mg of TA. Glycerin is a liquid with a density of 1.25 g/mL. The pharmacist preparing the ointment may either measure out the correct volume of glycerin or weigh it into a tared beaker to obtain the required 12.5 g. Hydrophilic petrolatum (HP) is an ointment base, and the amount required is “qs 200 g”. The abbreviation qs means to add enough HP so the total mixture weighs 200 g. The total weight of the drug, TA, is 500 mg, or 0.5 g, and the total weight of the ointment is 200g. The percent strength of TA, then, can be calculated as: $\frac{0.5\;g\;TA}{200\;g\;ointment}=\frac{x\;g\;TA}{100\;g\;ointment}$ Solving for x, the concentration of the ointment is: $\frac{0.25\;g\;TA}{100\;g\;ointment}\;or\;0.25\%\;w/w$ The concentration of all components in a semi-solid are expressed as w/w, including liquids like glycerin, polysorbate 80, water, etc. The density of a liquid is used to convert between the weight and volume of a material, and it has units of g/mL. Glycerin has a density of 1.25 g/mL, so a 1 mL sample of glycerin weighs 1.25 g. Water has a density of 1 g/mL, so a 1 mL sample of water weighs 1 g. Density values for some common liquids are found in Table 2.2. The symbol for density is d, or the Greek letter rho, 𝜌. Example 2.5: A pharmacist requires 25 g of glycerin. Calculate the volume this represents. $25\;g \;glycerin\times\frac{1\;mL\;glycerin}{1.25\;g\;glycerin}=20\;mL\;glycerin$ Or solving by proportions, $\frac{1\;mL\;glycerin}{1.25\;g\;glycerin}=\frac{x\;mL\;glycerin}{25\;g\;glycerin}$ $x=\frac{1\;mL\;glycerin\;\times\;25\;g\;glycerin}{1.25\;g\;glycerin}=20\;mL\;glycerin$ Example 2.6: Calculate the percent strength of polysorbate 80 (PS80) in the cream formula. PS 80 is a liquid with a density of 1.1 g/mL. Lidocaine 10 g Polysorbate 80 10 mL Cream base 200 g This formula calls for the pharmacist to weigh out 10 g of lidocaine powder, 10 mL of PS80, and 200 g of cream base. The formula states that 200 g of base are needed. However, the total formula weight is not 200 grams but the sum of the three individual component weights. The weight of PS80 must be calculated: $10\;mL \;PS80\times\frac{1.1\;g\;PS80}{1\;mL\;PS80}=11\;g \;PS80 $ The formula's total weight is, then, 10 g (lidocaine) + 11 g (PS80) + 200 g (base)= 221 g. The percent strength of PS80 in the formula is then calculated as: $\frac{11\;g\;PS80}{221\;g\;cream}=\frac{x\;g\;PS80}{100\;g\;cream}$ Solving for x, the PS80 concentration is 4.977 g/100 g of cream, or 4.977% w/w. Applying the rules for significant figures from chapter 1, we should round the answer to 1 decimal place, giving an answer of 5.0. However, we do not write values with trailing zeros after the decimal point, so the proper answer is 5% w/w. Table 2.2. Densities of some common pharmaceutical liquids at room temperature. Liquid \| Density (g/mL) \| Alcohol USP \| 0.81 \| Glycerin \| 1.25 \| Mineral oil USP \| 0.89 \| Polyethylene glycol (PEG) 400 \| 1.03 \| Polysorbate 80 \| 1.1 \| Propylene glycol \| 1.04 \| Water \| 1 \| Values from Merck Index 14th Edition. Example 2.6. How many grams of petrolatum should be added to 35 g of zinc oxide to prepare a 10% zinc oxide ointment? 10% zinc oxide means every 100 g of ointment contains 10 g of zinc oxide. Therefore, for every 10 g of zinc oxide, there is 90 g of petrolatum in the product. A simple solution to this problem then, is: $\frac{10\;g\;Zinc\;oxide}{90\;g\;petrolatum}=\frac{35\;g\;zinc\;oxide}{x\;g\;petrolatum}$ x = 315 g petrolatum We can check the answer by using the result to calculate the concentration. $\frac{35\;g\;zinc\;oxide}{35\;g\;zinc\;oxide\;+\;315\;g\;petrolatum}\times100=10\%$ Concentrated acids are traditionally labeled as percent w/w. Concentrated hydrochloric acid, for example, is available as a 37% w/w solution (37 grams of HCl in every 100 g of solution) with a density of 1.2 g/mL. Concentrated phosphoric acid is a viscous solution with a concentration of 85% w/w (85 g of H3PO4 in every 100 g of solution) and a density of 1.84 g/mL. Example 2.7: How many mL of 85% phosphoric acid solution are required to provide 10 g of phosphoric acid (H3PO4). $10\;g\;H_{3}PO_{4}\times\frac{100\;g\;solution}{85\;g\;H_{3}PO_{4}}\times\frac{1\;mL\;solution}{1.84\;g\;solution}=6.4\;mL\;solution$ 6.4 mL of 85% phosphoric acid solution will provide 10 g of H3PO4. Alternatively, the problem can be solved using 2 proportionalities. First, find how many grams of 85% solution contain 10 g of H3PO4. $\frac{x\;g\;solution}{10\;g\;H_{3}PO_{4}}=\frac{100\;g\;solution}{85\;g\;H_{3}PO_{4}}$ Solving for x, 11.76 g of 85% phosphoric acid solution will provide 10 g of H3PO4. Next, convert 11.76 grams of 85% phosphoric acid to mL using the density: $\frac{11.76\;g\;solution}{x\;mL\;}=\frac{1.84\;g\;solution}{1\;mL}$ x = 6.4 mL of 85% solution. Percent v/v is usually used to express the concentration of a liquid solute in another liquid, such as alcohol (ethanol) or glycerin dissolved in water. Pharmacists sometimes use Alcohol USP as the source of ethanol for preparing solutions. Alcohol USP is a solution of ethanol and water with an ethanol concentration of 95% v/v. Example 2.8: A pharmacist needs to prepare 2 L of 70% v/v alcohol by mixing Alcohol USP and Purified Water. How much Alcohol USP is needed? $2\;L\times\frac{70\;mL\;EtOH}{100\;mL\;soln}\times\frac{1000\;mL}{1\;L}\times\frac{100\;mL\;Alc\;USP}{95\;mL\;EtOH}=1473.7\;mL\;Alc\;USP$ To prepare the solution, the pharmacist should measure out 1,473.7 mL of Alcohol USP and then add enough purified water to make the total volume of 2 L. What does it mean when a concentration is labeled with “%” without specifying w/w, w/v, or v/v? The meaning can be determined by using the definition of concentration and the conventions associated with specific types of mixtures. If they are not specified otherwise, then: - Topical products or semisolids are labeled as % w/w - Concentrated acids are labeled as % w/w - Alcohol solutions are labeled as % v/v - Other liquid mixtures are usually labeled as % w/v if the pure solute is a solid or v/v if the pure solute is a liquid. Most pure drugs are solid at room temperature. - Medicated powders, such as athlete’s foot powder, are labeled as % w/w. Module 2B: Molar and millimolar Some clinical chemistry and drug concentrations are expressed in molar units. Recall that 1 mole is the weight in grams equal to the molecular weight of a substance. Sucrose, or table sugar, has a molecular weight of 342, therefore there are 342 g per mole. Drugs are usually used in small amounts, so the more common unit is the millimole, 1/1000th of a mole, or 0.001 mole. A millimole can be defined as the weight in milligrams equal to the molecular weight of a substance. 1 millimole of sucrose weighs 342 mg. The concentration unit Molar (M) is defined as moles of solute contained in each 1 L of solution. Millimolar (mM) is defined as millimoles of solute contained in each 1 L of solution. These concentration units should be familiar because they are used extensively in chemistry and biology courses. Example 2.9: The concentration of glucose in blood, i.e. the blood glucose level, is used as a control measure for diabetic patients. The normal blood glucose level in a non-diabetic patient is approximately 5.5 mM or 5.5 millimoles of glucose per liter of blood. Glucose levels are also frequently expressed in mg of glucose per deciliter (dL, or 100 mL) of blood. Convert 5.5 mM glucose into mg/dL. Glucose is a solid with a molecular weight of 180 g/mole. Solving by dimension analysis: $\frac{5.5\;mmoL\;glucose}{1000\;mL\;blood}\times\frac{180\;mg\;glucose}{1\;mmol\;glucose}=\frac{0.99\;mg\;glucose\;USP}{mL}\times100=\frac{99\;mg\;glucose}{100\;mL}=\frac{99\;mg\;glucose}{dL}$ Alternatively, the problem can be solved by using two proportions to convert mmol of glucose to mg of glucose and 1 L of blood to 1 dL of blood. First, find the milligrams of glucose represented by 5.5 mmoles. $\frac{5.5\;mmol\;glucose}{x\;mg\;glucose}=\frac{1\;mmol\;glucose}{180\;mg\;glucose}$ x = 990 mg glucose. $5.5\;mM=\frac{990\;mg\;glucose}{1\;L\;blood}\;or\;\;\frac{990\;mg\;glucose}{1000\;mL\;blood}$ Next, convert the concentration to 100 mL (1 dL) in the denominator $\frac{990\;mg\;glucose}{1000\;mL\;blood}=\frac{x\;mg\;glucose}{100\;mL\;blood}$ $x=99\;mg,\;so\;\frac{99\;mg\;glucose}{100\;mL\;blood}\;or\;\frac{99\;mg\;glucose}{dL\;blood}$ Phosphate salts are often used for electrolyte replacement, either orally or by intravenous infusion. Intravenous phosphate supplementation is typically ordered in millimoles of phosphate. In water, salts containing phosphates exists as an equilibrium mixture of the dihydrogen phosphate (1– charge) and the monohydrogen phosphate (2– charge), depending on the pH of the solution. According to the Henderson-Hasselbalch equation, the specific concentration of each anion form is determined by the appropriate phosphoric acid pKa and the surrounding solution pH. $H_{2}{PO_{4}^\;}^{-}\leftrightharpoons\;{HPO_{4}}^{2-}$ Both forms have 1 phosphorus (P) atom per anion, so 1 millimole of H2PO4– provides the same amount of phosphorus as 1 millimole of HPO4–2. The “phosphate concentration” is the total of both ion forms present in the solution. Example 2.10: A solution contains 12.42 g of monobasic sodium phosphate monohydrate (NaH2PO4 · H2O, MW = 138) and 6.39 g of dibasic sodium phosphate anhydrous (Na2HPO4, MW = 142) in a total volume of 45 mL. Calculate the phosphate concentration in mM. Monobasic (P1): $\frac{12.42\;g\;P1}{45\;mL\;soln}\times\frac{1\;mol\;P1}{138\;g\;P1}\times \frac{1000\;mmol\;P1}{mol\;P1}\times\frac{1000\;mL\;soln}{L\;soln}=\frac{2000\;mmol\;P1}{L\;soln}$ Dibasic (P2): $\frac{6.39\;g\;P2}{45\;mL\;soln}\;\times\;\frac{1\;mol\;P2}{142\;g\;P2}\;\times\;\frac{1000\;mmol\;P2}{mol\;P2}\;\times\;\frac{1000\;mL\;soln}{L\;soln}\;=\;\frac{1000\;mmol\;P2}{L\;soln}$ Total phosphate concentration = 2000 mM P1 + 1000 mM P2 = 3000 mM Millimoles and millimolar concentrations are also used to calculate solutions' osmolarity, which is an important patient safety consideration in intravenous drug therapy, intramuscular injections, and ophthalmic, otic and nasal solutions. Module 2C: Ratio Strength Ratio strength is typically used to express the concentration of dilute solutions, i.e., solutions with very low solute concentrations. It is important for pharmacists to understand ratio strength because the drug epinephrine is frequently expressed in terms of ratio strength. Ratio strength is expressed as 1:X, which means the concentration is 1 part of solute in X parts of solution. 1 part is either 1 g for a solid or 1 mL for a liquid. Epinephrine is a solid, so 1 part of epinephrine is 1 g. An aqueous solution is liquid, so 1 part of the solution is 1 mL. A 1:1000 epinephrine solution, then, contains 1 g of epinephrine in every 1000 mL of solution. The units are rarely written with the concentration. Most concentration units express how much solute is contained in a fixed amount of the mixture, e.g., millimoles in 1 L, grams in 1 dL, etc. Ratio strength is the exact opposite, because it expresses the amount of the mixture that contains 1 g or 1 mL of the solute. Ratio strength can be converted to other concentration units by expressing the ratio as a fraction and using dimensional analysis or proportions to solve for the desired unit. Example 2.11: An aqueous solution contains a drug at a concentration of 1:2500. Calculate the percent strength of the solution. 1:2500 means there is 1 g of drug in every 2500 mL of the solution. Percent means grams of drug in every 100 mL of solution. These definitions can be combined as a proportion to solve the problem. $\frac{1\;g\;drug}{2500\;mL\;soln}=\frac{x\;g\;drug}{100\;mL\;solution}$ $x=\frac{1\;g\;drug\;\times\;100\;mL\;soln}{2500\;mL\;soln}=0.04\;g\;drug\;in\;every\;100\;mL=0.04\%$ Example 2.12: A patient with a severe allergy to bee venom requires 300 mcg of epinephrine. What volume of a 1:1000 solution is required? This problem can be solved with proportions, as in the previous example. Alternatively, the dimension analysis approach is: $300\;mcg\;epi\times\frac{1\;g\;epi}{1,000,000\;mcg\;epi}\times\frac{1000\;mL\;soln}{1\;g\;epi}=0.3\;mL\;of\;1:1000\;solution$ Example 2.13: Calculate the concentration of epinephrine 1:1000 in mM units. Epinephrine MW = 183. $\frac{1\;g\;epi}{1000\;mL\;soln}\times\frac{1000\;mL\;soln}{1\;L\;soln}\times \frac{1\;mol\;epi}{183\;g\;epi}\times\frac{1000\;mmoL\;epi}{1\;mol\;epi}=\frac{5.5\;mmol\;epi}{L\;soln}=5.5mM\;epi$ Example 2.14: A solution is prepared by dissolving 1.5 mg of drug in enough water to make 3 L. Calculate the ratio strength of the finished solution. The simplest way to solve this problem is to write the concentration as milliliters of solution divided by grams of solute. We need to convert mg to g and L to mL: $\frac{3\;L\;\times\frac{1000\;mL}{L}}{1.5\;mg\;\times\frac{1\;g}{1000\;mg}}=2,000,000$ The ratio strength of the solution is 1:2,000,000. Module 2D: Units of Activity Some drugs, especially those derived from natural sources, are labeled in terms of “Units of activity.” The most important drug expressed as Units is insulin. Insulin concentration is expressed as U-100, U-200, or U-300, meaning 100 Units/mL, 200 Units/mL, or 300 Units/mL. Insulin Units are treated like mg, mmol, or any other term describing the weight of drug. Patients measure their daily insulin doses in terms of Units, either with pre-filled injector pens or traditional insulin syringes. Heparin, a natural anticoagulant, is available in injectable solutions containing 1000 USP Units/mL, 5000 USP Units/mL, 10,000 USP Units/mL, and 20,000 USP Units/mL. Example 2.15: How many microliters of U-200 insulin is required to provide a dose of 35 Units. $\frac{1\;mL}{200\;Units}=\frac{x\;mL}{35\;Units}$ $x\;mL=0.175\;mL\\\\$ $x=0.175\;mL\times\frac{1000\;mcL}{mL}=175\;mcL$ Safety note: Always spell out and capitalize Unit to avoid medication errors. Module 2E: Reducing and enlarging formulas The amount of a component in a mixture is easily scaled to a larger or smaller amount using proportionalities. Example 2.15: The formula for Urea Compounded Irrigation USP specifies using 10 g of urea and enough sodium chloride irrigation solution to make 50 mL. If you needed to prepare 240 mL instead of 50 mL, the amount of urea required would be easily calculated using the proportion: $\frac{10\;g\;urea}{50\;mL\;irrigation}=\frac{x\;g\;urea}{240\;mL\;irrigation}$ $x=48\;g\;urea$ Example 2.16: Compound Clioquinol Topical Powder USP is a solid mixture containing 4 ingredients. The formula for 1 kg of powder is given. a) Calculate the percent strength of clioquinol in the formula. b) Calculate the amount of lactose needed to prepare 250 g of the product. Ingredient \| Amount \| Clioquinol \| 250 g \| Lactic acid \| 25 g \| Zinc stearate \| 200 g \| Lactose \| 525 g \| (Total) \| 1000 g \| The percent strength should be expressed as % w/w because all of the components are solids. $\frac{250\;g\;clioquinol}{1000\;g\;mixture}=\frac{x\;g\;clioquinol}{100\;g\;mixture}$ x=25, so 25% clioquinol The amount of lactose required for 250 g of the mixture is calculated as: $\frac{525\;g\;lactose}{1000\;g\;mixture}=\frac{x\;g\;lactose}{250\;g\;mixture}$ $x=131.25\;g\;lactose\;in\;250\;g\;of\;mixture $ Example 2.17: A gabapentin cream is compounded according to the formula. a) Calculate the percent strength of glycerin in the cream. b) Calculate the grams and milliliters of glycerin required to prepare 60 g of cream. c) Calculate the ratio strength of methylparaben in the preparation. Ingredient \| Amount \| Gabapentin \| 3.5 g \| Glycerin \| 7.5 mL \| Methylparaben \| 75 mg \| Cream base \| qs 100 g \| The product is a cream, so the concentration should be expressed in % w/w. Glycerin is a liquid with a density of 1.25 (Table 2.2). The concentration of glycerin can be calculated as: $\frac{7.5\;mL\;glycerin\;\times\;\frac{1.25\;g\;glycerin}{1\;mL\;glycerin}}{100\;g\;cream}=\frac{9.375\;g\;glycerin}{100\;g\;cream}=9.4\%\;w/w\;glycerin $ The grams of glycerin required for 60 g of cream may be calculated from the percent strength as: $\frac{9.4\;g\;glycerin}{100\;g\;cream}=\frac{x\;g\;glycerin}{60\;g\;cream}$ $x=5.6\;g\;glycerin$ The milliliters of glycerin for 60 mL of cream is calculated from the original formula: $\frac{7.5\;mL\;glycerin}{100\;g\;cream}=\frac{x\;mL\;glycerin}{60\;g\;cream}$ $x=4.5\;mL$ The formula contains 75 mg or 0.075 g of methylparaben (MP) in 100 g of cream, so the ratio strength of MP is calculated as: $\frac{0.075\;g\;MP}{100\;g\;cream}=\frac{1\;g\;MP}{x\;g\;cream},\;x=1333.3$ $\text{The ratio strength of MP = 1:1333}$. Module 2: Practice Problems 1. Calculate the amount of urea in each 60 gram bottle of 40% urea lotion. 2. A solution contains 250 mg of drug, 15 g of sucrose, 250 mg of methylparaben, and 1 mL of grape flavor in every 8 fluidounces. Calculate the percent strength of the drug in the solution. 3. A pharmacist mixed 60 g of cyclodextrin, 20 mL of glycerin (d = 1.25), 1 gram of drug, and 30 mL of water. Calculate the glycerin concentration in % w/w. 4. Convert each concentration to mg/mL. 25% w/v 1:5,000 w/v 15 mM glucose (MW = 180) 45% v/v alcohol (d = 0.81) 5. Convert each concentration to ratio strength. 0.025% w/v 0.05 mg/mL 0.02 mM (MW = 350) 22.5 mL alcohol in 650 mL of solution 6. An ointment contains 1,500 mcg of triamcinolone acetonide in every 60 g tube. Calculate the percent strength of triamcinolone acetonide. 7. How many milliliters of polysorbate 80 (d=1.1) are required to prepare 350 mL of a 3% w/v solution. 8. Convert each concentration to mM. 25% w/v salicylic acid (MW = 138) 1:3300 w/v epinephrine (MW = 183) 50 mg/mL amoxicillin (MW = 365) 45% v/v alcohol (d = 0.81, MW = 46) 9. A pharmacist mixed 800 mg of drug (MW = 159), 20 mL of propylene glycol (d=1.04), and 40 mL of water, resulting in a final solution volume of 62 mL. A: Calculate the drug's millimolar concentration in the solution. B: Calculate the propylene glycol concentration in % w/w. 10. How many mL of 85% phosphoric acid (d=1.84) should be used to prepare 3 L of 2% w/v phosphoric acid solution? 11. Calculate the millimolar concentration of Sodium Bicarbonate Injection USP. Sodium bicarbonate MW = 84. 12. A veterinary product contains neomycin sulfate 2.5 mg and 0.25 mg of triamcinolone acetonide in every mL of solution. Calculate the percent strength of both drugs. 13. A 1% testosterone transdermal gel product delivers 1.25 g of product per actuation of the metered dose pump. How many milligrams of testosterone is contained in each pump? 14. A 0.1% estradiol transdermal gel contains 0.75 g of gel in each packet. How many micrograms of estradiol are contained in each packet? 15. Chlorhexidine gluconate 4% solution is used as an antibacterial skin cleanser. How many grams of chlorhexidine gluconate are contained in each 16-ounce bottle? 16. An allergen extract contains 100 mcg/mL of honey bee venom. Calculate the concentration in percent strength and ratio strength. 17. Sodium phosphates injection contains 276 mg of monobasic sodium phosphate monohydrate (NaH2PO4•H20, MW = 138) and 268 mg of dibasic sodium phosphate heptahydrate (Na2HPO4•7H20, MW = 268) in every milliliter. Calculate the total millimolar concentration of phosphate in the solution. HINT: Calculate the millimolar concentration of each individual salt, then add the numbers together. 18. A 2020 water analysis for Edwardsville IL, reported one sample contained 570 mcg of copper per liter of water. Convert this concentration to ratio strength. 19. A 2020 water analysis for Edwardsville IL, reported one sample contained 2.9 mcg of lead per liter of water. Convert this concentration to ratio strength. 20. A product contains an allergen extract at a concentration of 1:25,000. How many micrograms of allergen does a patient receive with each 0.3 mL dose? 21. Mannitol is available as a 20% solution in water for injection. What volume of mannitol solution is required to provide a dose of 100 g. 22. A pharmacist mixed 35 g of salicylic acid with 20 mL of polyethylene glycol (PEG) 400 (d=1.03) and 15 g of PEG 8000. Calculate the percent strength of salicylic acid, PEG 400, and PEG 8000 in the mixture. 23. Calculate the molarity of 20% mannitol (MW = 182) in water. 24. Sodium acetate injection contains 328 mg of sodium acetate (MW = 82) in every milliliter of solution. Calculate the millimolar concentration. 25. An injectable supplement contains 75.5 mg of manganese sulfate (MW = 151) in every 0.5 mL. Calculate the manganese sulfate concentration in millimolar, percent strength, and ratio strength. 26. Calcitonin salmon injection is a sterile solution containing 400 USP Units in each 2 mL vial. If a patient is ordered 240 USP Units every 6 hours, how many milliliters of the solution should the patient receive daily? 27. Bleomycin for injection is supplied as a vial containing 15 Units of a sterile powder. A hospital pharmacy reconstitutes each vial by adding 3 mL of sterile water for injection. Calculate the drug concentration in the reconstituted solution. Calculate how many milliliters of the reconstituted solution are required to supply a dose of 18 Units. Calculate how many vials are required to provide the dose. 28. How many milligrams of solute are contained in 25 mL of a 1:30,000 solution? 29. Dextrose monohydrate 50% injection is sometimes used to treat severe hypoglycemia. Calculate the solution's molarity. Dextrose·H2O MW = 198. 30. A solution was prepared by dissolving 12 g of monobasic sodium phosphate (NaH2PO4•H20, MW = 138) and 7.1 g of dibasic sodium phosphate (Na2HPO4•7H20, MW = 268) in water to a total volume of 50 mL. Calculate the phosphate concentration in mM. 31. An injectable solution contains aluminum (atomic wt = 27) as a contaminant at approximately 12.5 mcg/L concentration. Calculate the ratio strength, percent strength, and mM concentration of aluminum in the solution. Answers: 1. 24 g 2. 0.1% 3. 21.6% 4. 250 mg/mL 0.2 mg/mL 2.7 mg/mL 364.5 mg/mL 5. 1:4000 1:20,000 1:142857 1:29 6. 0.0025% 7. 9.5 mL 8. 1,812 mM 1.7 mM 137 mM 7924 mM 9. 81.2 mM 33.8% 10. 38.4 mL 11. 500 mM 12. 0.25% neomycin, 0.025% triamcinolone 13. 12.5 mg testosterone 14. 750 mcg estradiol 15. 19.2 g 16. 0.01% 1:10,000 17. 3000 mM 18. 1:1,754,386 19. 1:344,827,586 20. 12 mcg 21. 500 mL 22. 49.6% salicylic acid, 29.2% PEG400, 21.2% PEG8000 23. 1.1 M 24. 4000 mM 25. 1000 mM, 15.1% w/v, 1:6.6 26. 4.8 mL 27. 5 USP Units/mL 3.6 mL 1.2 vials 28. 0.83 mg 29. 2.5 M 30. 2269 mM 31. 1:80,000,000 0.00000125% 0.00046 mM Module 3: Dilution, Alligation, and Concentration This module introduces some mathematical techniques used to alter product strength, either decreasing the active pharmaceutical ingredient (API) concentration or increasing the (API) concentration. The product's physical form could be a solution or a semi-solid, like an ointment or cream. Diluting a product with an appropriate patient-compatible solvent results in lowering the concentration. We can increase the concentration of, or fortify, a product by adding the API in pure form or by using another product with a higher concentration than the one we are working with. Finally, you will learn about an algebraic technique, alligation, which is unique to pharmacy. The method is useful when solving problems that require mixing two different concentrations to make a third concentration between the two starting values. Brief Review In the last module, you learned about concentrations and the various expressions pharmacists use to represent these concepts and relate them to products. As a reminder, the strength or concentration of a pharmaceutical product represents the amount of the active pharmaceutical ingredient (API) relative to the total amount of the product. Example 3.1: If 120 mL of an oral solution contains 6 grams of the drug, then the concentration of the API is 5%. $\frac{6\;g}{120\;mL}\times100\;= 5\;\text{%}$ If you add an additional 50 mL of solvent to the product, the API amount does not change, but the total content volume increases to 170 mL, thus reducing the strength. This is one example of a dilution. $\frac{6\;g}{120\;mL\;+\;50\;mL}\times100\;\cong 3.5\;\text{%}$ This cartoon from Wikipedia depicts a series of dilutions of the most concentrated solute, on the left, to a more dilute solute, on the right. Source: By Grasso Luigi - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=76044995 A very useful equation commonly used by pharmacists is C1V1 = C2V2. You most likely used this equation in your previous chemistry courses. We will demonstrate this equation with representative problems later in the module. Module 3A: Dilution Process Involving Liquids Dilution is a technique where you add a solvent, most commonly water, to a solute already in solution. The amount of the solute is constant, but the final volume is increased, thus decreasing concentration. The Wikipedia picture demonstrates the important formula, C1 · V1 = C2 · V2, and a pictorial cartoon to help visual learners see the outcome. By Theislikerice - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=69653928 Notice that this equation relates four parameters in an algebraic relationship. You may recall from high school algebra that you need three parameters to uniquely solve an equation that contains four parameters. A key fact to remember is that all units must be consistent. If one volume is in milliliters, the second must be in milliliters, not liters. If one concentration is in percent, the second concentration must be in percent, not mg/mL. Let’s see how you can use this equation in pharmacy practice. Example 3.2: What would be the new percent concentration (v/v) if you took 300 mL of a 12% solution and diluted it with water to a new volume of 400 mL? Let’s use C1 · V1 = C2 · V2. Based on the information in the problem, what values do you know? C1 = 12%. V1 = 300 mL. V2 = 400 mL. Now substitute the values into the equation and solve for the unknown value of C2. $\left(12\text{%}\right)\times\left(300\;mL\right)=\left(x\text{%} \right)\times\left(400\;mL \right)$ $x\text{%}=\frac{12\text{%}\;\times\;300\;mL}{400\;mL}$ $x=9\text{%}$ Example 3.3: How much water would you add to 250 mL of a 15% (v/v) aqueous solution to reduce its concentration to 5%? $\left(15\text{%}\right)\times\left(250\;mL\right)=\left(5\text{%} \right)\times\left(x\;mL \right)$ $x\;{mL}=\frac{15\text{%}\;\times\;250\;mL}{5\text{%}}=750\;mL$ This problem requires further explanation. The answer is easily calculated, but the number needs some further thought. The final volume is 750 mL. You started with 250 mL of solution. Therefore, you need to add 750 – 250 mL = 500 mL of water. Please pay close attention to this type of problem which asks how much solvent must be added to the original solution. Example 3.4: You need to prepare 4 L of a solution with a final API concentration of 0.04%. How many milliliters of an 8% stock solution should you use to make the solution? $\left(0.04\text{%}\right)\times\left(4000\;mL\right)=\left(8\text{%} \right)\times\left(x\;mL \right)$ $x\;{mL}=\frac{0.04\text{%}\;\times\;4000\;mL}{8\text{%}}=20\;mL$ Remember to verify that all units are the same throughout the problem. The initial volume was given as 4 L. I decided to use 4000 mL because the original problem asks for the answer in milliliters. Example 3.5: You have 120 mL of a 5% stock solution. What would be the new concentration if you added an additional 50 mL of water to the solution? I will alter the units to demonstrate that technique. Recall that 5% w/v = 50 mg/mL. $\frac{50\;mg}{mL}\times0.12\;L=\frac{x\;mg}{mL}\times0.17\;L $ $ \\\frac{x\;mg}{mL}=\frac{\frac{50\;mg}{mL}\;\times\;0.12\;L}{0.17\;L}\\\\ $ $x\cong \frac{35.3\;mg}{mL}\cong 3.5\text{%}$ Module 3B: Dilution Process Involving Solids and Semisolids Most people think of solutions when you mention the word dilution, but the same ideas, and equation, C1 · V1 = C2 · V2, apply when you are working with solids and semisolids. When working with powders or ointments, gels, and creams, we usually substitute the letter Q (quantity) for V in the equation, thus C1 · Q1 = C2 · Q2. Example 3.6: How much petrolatum base would you add to 60 g of a 2.5% (w/v) steroid ointment to reduce its concentration to 1.5%? Notice the similarity of this problem with Example 2 in the previous section. $\left(2.5\text{%}\right)\times\left(60\;g\right)=\left(1.5\text{%} \right)\times\left(x\;g \right)$ $x\;g=\frac{2.5\text{%}\;\times\;60\;g}{1.5\text{%}}$ Again, the answer is easily calculated, but the number needs further thought. The final quantity is 100 g. You started with 60 g of ointment. Therefore, you need to add an additional amount of petrolatum equal to 100 – 60 g = 40 g. Recall that this problem asks how much base must be added to the original ointment mass. Eample 3.7: How much carbomer gel should you mix with 15 g of 0.05% clobetasol propionate gel to reduce the concentration to 0.025%? $\left(0.05\text{%}\right)\times\left(15\;g\right)=\left(0.025\text{%} \right)\times\left(x\;g \right)$ $x\;g=\frac{0.05\text{%}\;\times\;15\;g}{0.025\text{%}}$ $x = 30\;g$ The final quantity is 30 g. You need to add 30 – 15 g = 15 g of carbomer gel. Example 3.8: A physician asks you to prepare 8 oz of a cream with a final API concentration of 3%. How many grams of a 10% stock cream should you use to make the product? The problem asks for the answer in grams, so I converted 8 oz to 240 g for the equation. $\left(3\text{%}\right)\times\left(240\;g\right)=\left(10\text{%} \right)\times\left(x\;g \right)$ $x\;g=\frac{3\text{%}\;\times\;240\;g}{10\text{%}}$ $x = 72\;g$ Consider the process where you are adding the active ingredient as a powder to a dosage form that already contains the API in the ointment. Example 3.9: What is the final concentration of tapinarof if you added 1 g of the powder to the contents of a 60 g tube of Vtama® (tapinarof) 1%? In these types of problems, the first task is to determine how much of the API is contained in the starting material. Then you sum the requested amount with the starting mass. Finally, divide by the new total amount of product. $\frac{1\;g\;T}{100\;g\;oint}=\frac{x\;g\;T}{60\;g\;oint} $, $x = 0.6\;g\;tapinarof\;from\;60\;g\;tube$ $\frac{1\;g\;+\;0.6\;g\;T}{1\;+\;60\;g\;oint}=\frac{1.6\;g\;T}{61\;g\;oint}=2.6\text{%}\;after\;adding\;1g\;drug\;powder$ Example 3.10: What is the final concentration of mupiricin if you added 2 g of the powder to the contents of a 22 g tube of Mupiricin ointment 2%? $\frac{2\;g\;M}{100\;g\;oint}=\frac{x\;g\;M}{22\;g\;oint}$, $x = 0.44\;g\;mupiricin$ $\frac{2\;g\;+\;0.44\;g\;M}{2\;g\;+\;22\;g\;oint}=\frac{2.44\;g\;M}{24\;g\;oint}=10.2\text{%}$ Dilution Practice Problems: 1. You have a stock solution of benzalkonium chloride 50% w/v. What is the final concentration if 2 mL of the solution is diluted to a final volume of 85 mL? (2 dp) (50%) x (2 mL)/(85 mL) = C2= 1.18% 2. How much water would you add to 185 mL of a 17.5% v/v aqueous solution to reduce its concentration to 12.5%? (17.5%) x (185 mL)/(12.5%) = V2 = 259 – 185 mL = 74 mL water 3. You need to prepare 2 L of a solution with a final API concentration of 25%. How many milliliters of a 70% stock solution should you use to make the solution? (25%) x (2000 mL/(70%) = V2 = 714 mL 4. You have 150 mL of a 60 mg/mL stock solution. What would be the new concentration if you added an additional 75 mL of water to the solution? (60 mg/mL) x (150 mL)/(225 mL) = 40 mg/mL and C2 = 4% 5. How much cream base should you mix with 45 g of 1% Vtama cream (tapinarof) to reduce the concentration to 0.3%? (1%) x (45 g)/(0.3%) = Q2 = 150 – 45 g = 105 g cream base 6. How many milliliters of Lidocaine 4% should be used to prepare 125 mL of an IV solution containing 4 mg/mL? (4 mg/mL) x (125 mL)/(40 mg/mL) = V2 = 12.5 mL 7. If you add 5 g of azelaic acid powder to 50 grams of an ointment containing 10% azelaic acid, what would be the final concentration in the ointment? 5 g + 5 g/55 g total ointment = 18.2% 8. What would be the final concentration of benzocaine in an ointment if you mixed 3 g of the API powder with 4 ounces of an ointment containing 10% benzocaine? 3 g + 12 g/123 g total ointment = 12.2% Module 3C: Alligation Alligation is an arithmetical technique for solving problems that require mixing two solutions to make a third solution. Words fail to describe the technique. It is much easier to demonstrate and work problems than to explain. The lecture will make the problem easier to understand. Alligation works very well when we must make a dilution that involves two solutions, one at a higher concentration and one at a lower concentration. The target concentration is between the upper and lower concentrations. Consider the common problem in pediatric Parenteral Nutrition solutions. The pharmacy prepared a PN solution with a dextrose concentration of 15%. The physicians want to increase the dextrose concentration to 20%. Do you need to prepare a new solution? No. We can add more dextrose solution to the bag to make the desired concentration. We can use Dextrose 70% (D70) or Dextrose 50% (D50), both base compounding solutions are readily available. Note, you cannot solve this problem using C1 · V1 = C2 · V2 , because there are three concentrations involved. Let’s look at the mechanics of the process using D 70. Example 3.11: Draw two vertical lines. The desired concentration stated in the problem goes in the middle space. The order of the concentrations on the LHS does not matter, but I put the larger concentration of the solution I am going to use (the juice) on the top left and the smaller starting concentration on the lower left. Now perform two diagonal subtractions, always resulting in a positive number. In this example D70 – D20 = 50. D20 – D15 = 5. Note that the difference between D70 and the desired strength, D20, represents the number of parts of D15 to be used. The actual volume of the D15 solution in the bag represents 50 parts. You need 5 parts of D70, so that would be equal to 1/10 the volume in the bag. After the addition, the PN volume will be larger. Example 3.12: How many milliliters of Dextrose 50% must be added to a bag of PN solution containing 150 mL of Dextrose 20% such that after the addition, the new dextrose concentration will equal 25%? There are a total of 30 parts. We know the PN bag that needs to be altered contains 150 mL of D20, and that represents the 25 parts in the calculation. Now we can solve for the 5 parts using ratios. $\frac{25\;parts}{150\;mL}=\frac{5\;parts}{x\;mL},\;x=30\;mL\;D50\;required$ New PN volume = 180 mL. Example 3.13: You need to prepare an ointment with a concentration of 2.5%. You have a 20% ointment that can be diluted with an ointment base that contains no drug. How many grams of each component do you need to make 16 ounces (480 g)? There is a total of 20 parts. The 20 parts represent the prescribed mass of ointment. Now we can solve for either part using ratios. $\frac{20\;parts}{480\;g}=\frac{17.5\;parts}{x\;g},\;x=420\;g\;ointment\;base$ $\frac{20\;parts}{480\;g}=\frac{2.5\;parts}{x\;g},\;x=60\;g\;20\%\;ointment\;base$ Total ointment weight = 420 + 60 = 480 g Example 3.14: How many grams of salicylic acid powder should be added to 60 g of polyethylene glycol ointment base to prepare a product containing 6% w/w of salicylic acid? Note that you are starting with 60 g of base, which contains no drug. That 60 g mass represents the 94 parts obtained from the alligation. Now you can solve for the amounts using ratios. $\frac{94\;parts}{60\;g}=\frac{6\;parts}{x\;g},\;x=3.83\;g\text{ salicylic acid powder}$ You can check your work, 3.83 g/63.83 g x 100 = 6%. Module 3: Practice Problems - What would be the new percent concentration (v/v) if you took 45 mL of a 15% solution and diluted it with water to a new volume of 390 mL? - How much water should you add to 75 mL of a 9% (v/v) aqueous solution to reduce its concentration to 5%? - You need to prepare 2.4 L of a solution with a final API concentration of 0.07%. How many milliliters of an 11% stock solution should you use to make the solution? - You have 85 mL of a 4% stock solution. What would be the new concentration, in mg/mL, if you added an additional 35 mL of water to the solution? - You have a stock solution of benzalkonium chloride 85% w/v. What is the final concentration if 12 mL of the solution is diluted to a final volume of 2250 mL? - How much petrolatum base should you add to 45 g of a 5% (w/v) steroid ointment to reduce its concentration to 2%? - How much ointment base should you mix with 45 g of 0.05% clobetasol propionate gel to reduce the concentration to 0.03%? - A physician asks you to prepare 6 oz of a 4% cream. How many grams of a 10% stock cream should you use to provide the correct amount of the API? - How much water would you add to 165 mL of an 18% v/v aqueous solution to reduce its concentration to 15%? - You need to prepare 1.5 L of a solution with a final API concentration of 0.9%. How many milliliters of a 23.4% stock solution should you use to make the solution? - You have 150 mL of a stock solution with a 40 mg/mL concentration. What would be the new concentration (%w/v) if you added an additional 75 mL of water to the solution? - How much cream base should you mix with 60 g of 1% Vtama cream (tapinarof) to reduce the concentration to 0.6%? - How many milliliters of Dobutamine 1.25% should be used to prepare 100 mL of an IV solution containing 4 mg/mL? - If you add 10 g of salicylic acid powder to 4 ounces of an ointment containing 100 mg/g of the API, what would be the final concentration in the ointment? - What would be the final concentration of benzocaine in an ointment if you added an additional 6 g of the API powder with 8 ounces of an ointment containing 10% benzocaine? - How many milliliters of Dextrose 70% must be added to a 300 mL bag of PN solution containing Dextrose 15% so that after the addition, the new dextrose concentration will be equal to 20%? (whole number) - How many milliliters of Dextrose 50% must be added to a 300 mL bag of PN solution containing Dextrose 15% so that after the addition, the new dextrose concentration will be equal to 20%? (whole number) - How many milliliters of Dextrose 70% must be added to a 180 mL bag of PN solution containing Dextrose 12.5% so that after the addition, the new dextrose concentration will be equal to 17.5%? (whole number) - How many milliliters of Dextrose 50% must be added to a 180 mL bag of PN solution containing Dextrose 12.5% so that after the addition, the new dextrose concentration will be equal to 17.5%? (whole number) - How many milliliters of Dextrose 70% must be added to a 200 mL bag of PN solution containing Dextrose 12.5% so that after the addition, the new dextrose concentration will be equal to 15%? (whole number) - How many milliliters of Dextrose 50% must be added to a 200 mL bag of PN solution containing Dextrose 12.5% so that after the addition, the new dextrose concentration will be equal to 15%? (whole number) - How many milliliters of Dextrose 70% must be added to a 450 mL bag of PN solution containing Dextrose 15% so that after the addition, the new dextrose concentration will be equal to 22.5%? (whole number) - How many milliliters of Dextrose 50% must be added to a 450 mL bag of PN solution containing Dextrose 15% so that after the addition, the new dextrose concentration will be equal to 22.5%? (whole number) - How many milliliters of Dextrose 70% must be added to a 150 mL bag of PN solution containing Dextrose 20% so that after the addition, the new dextrose concentration will be equal to 25%? (whole number) - How many milliliters of Dextrose 50% must be added to a 150 mL bag of PN solution containing Dextrose 20% so that after the addition, the new dextrose concentration will be equal to 25%? (whole number) - How many grams of 1% bexarotene gel and a gel base should be mixed in order to prepare 60 g of bexarotene 0.75%? - In what proportion should 5% and 1% ointments be mixed in order to prepare a 2.5% ointment - You have a 20% solution and an 8% solution. How many milliliters of each should be mixed in order to prepare 4 ounces of a 10% solution? - You have a 90% solution and a 50% solution. How many milliliters of each should be mixed in order to prepare 6 ounces of a 70% solution? Answers: - 1.7% - 60 mL - 15.3 mL - 28.3 mL - 0.45% - 67.5 g - 30 g - 72 g - 33 mL - 57.7 mL - 2.7% - 40 g - 32 mL - 16.9% - 12.2% - 30 mL - 50 mL - 17 mL - 28 mL - 9 mL - 14 mL - 71 mL - 123 mL - 17 mL - 30 mL - 45 g bexarotene gel and 15 g of base - 1.5 parts of 5% and 2.5 parts of 1% - 20% solution = 20 mL, and 8% solution = 100 mL - 90 mL of each solution Module 4: Milliequivalents and Milliosmoles This module will introduce and review calculations involving milliequivalents and milliosmoles and the concentration units mEq/L and mOsm/L. Module 4A: Equivalents and Milliequivalents Equivalents and milliequivalents express the concentration of ionic compounds or salts such as sodium chloride, potassium chloride, or sodium bicarbonate. An equivalent is a unit of mass related to a mole and has the symbol Eq. A milliequivalent is simply one thousandth (1/1000) of an equivalent and has the symbol mEq. The definition of an equivalent is based on the charge of the ions produced when the electrolyte dissolves. Recall that an ionic compound has an equal number of positive and negative charges, so the overall salt charge is zero. Positively charged ions are called cations, and negatively charged ions are called anions. Table 4.1 lists the common ions frequently used in pharmacy and medicine and their charges. The dose of an electrolyte may be ordered in terms of mEq (e.g. potassium chloride 40 mEq by IV infusion over 4 hours) and the concentration of an electrolyte solution may be expressed in mEq/mL or mEq/L (e.g. sodium bicarbonate 50 mEq/L infusion to run at 75 mL/hour). Table 4.1 Common pharmaceutical ions Cations \| Anions \| Sodium (Na+) \| Chloride (Cl–) \| Potassium (K+) \| Sulfate (SO42–) \| Calcium (Ca2+) \| Dihydrogen phosphate ion (H2PO4–) \| Magnesium (Mg2+) \| Acetate (C2H3O2–) \| Lithium (Li+) \| Gluconate (C6H11O7–) \| Iron (Fe2+) \| Bicarbonate (HCO3–) \| \| Carbonate (CO32–) \| An equivalent is the weight, measured in grams, equal to the molecular weight of a substance divided by the total cation or total anion charge in the chemical formula. Ionic charges are always whole numbers of 1 or higher, so the equivalent weight of an electrolyte is less than or equal to its molecular weight. $Equivalent\;weight\left( \frac{g}{Eq}\right)=\frac{Molecular\;weight\;(g)}{Total\;cation\;charges}$ $Milliequivalent\;wt\left( \frac{mg}{mEq} \right)=\frac{Molecular\;weight\;\left( mg \right)}{Total\;cation\;charges}$ Sodium chloride (NaCl) has a molecular weight of 58 g/mole. NaCl contains one mole of Na+ and one mole of Cl– ions. The total cation charge of NaCl is equal to 1, and the total anion charge is equal to 1, so each mole of NaCl represents 1 equivalent of NaCl. The equivalent weight of NaCl, therefore, is (58 g/mole)/(1 Eq/mole) = 58 g/Eq. One millimole of NaCl weighs 58 mg, so the milliequivalent weight of NaCl is 58 mg/mEq. Magnesium sulfate (MgSO4) has molecular weight of 120 g/mole. MgSO4 contains 1 mole of Mg2+ and 1 mole of SO42–. The total cation and anion charges are each 2, so one mole of MgSO4 contains 2 equivalents. The equivalent weight of MgSO4 is therefore (120 g/mole)/(2 Eq/mole) = 60 g/Eq. One millimole of MgSO4 weighs 120 mg, so the milliequivalent weight of MgSO4 is 60 mg/mEq. Lithium carbonate (Li2CO3) has a molecular weight of 74 g/mole. Li2CO3 contains 2 moles of Li+ and 1 mole of CO32–. The total cation and anion charges are each 2, so one mole of Li2CO3 contains 2 equivalents. The equivalent weight of Li2CO3 is therefore (74 g/mole)/(2 Eq/mole) = 37 g/Eq. One milliequivalent of Li2CO3 weighs 74 mg, so the milliequivalent weight is 37 mg. Example 4.1: Lithium carbonate is available as capsules containing 600 mg of Li2CO3 per capsule, so the number of milliequivalents per capsule is: $600\;mg\;Li_{2}CO_{3}\times\frac{1\;mEq\;Li_{2}CO_{3}}{37\;mg\;Li_{2}CO_{3}}=16.2\;mEq\;LiCO_{3}\;per\;capsule$ Clinicians sometimes refer to specific ions individually rather than as neutral salt. For example, Li+ is the pharmacologically active component of Li2CO3. The carbonate ion does not contribute to the pharmacologic effect; it is only a convenient salt-forming ion to deliver Li+. The target concentration of Li+ in blood is approximately 1 mEq/L, stated only in terms of the Li+ cation concentration, without reference to any anion. We have calculated that each 600 mg capsule of Li2CO3 represents 16.2 mEq of Li2CO3, but how many mEq of Li+ are present in each capsule? The mEq number for a salt refers to both the cation and the anion, so 16.2 mEq of Li2CO3 contains 16.2 mEq of Li+ and 16.2 mEq of CO32–. Example 4.2: Human plasma contains approximately 140 mEq of sodium ion per liter. How many grams of NaCl contain the same amount of Na+ as 5 liters of plasma. $5\;L\;plasma\times\frac{140\;mEq\;Na^{+}}{L\;plasma}=700\;mEq\;Na^{+}\;in\;5\;L\;of\;plasma$ Since 1 mEq of NaCl contains 1 mEq of Na+ ion, $700\;mEq\;Na^{+}\times\frac{1\;mEq\;NaCl}{1\;mEq\;Na^{+}}\times\frac{1\;mmol\;NaCl}{1\;mEq\;NaCl}\times\frac{58\;mg\;NaCl}{1\;mmol\;NaCl}\times\frac{1\;g}{1000\;mg}=40.6\;g\;NaCl$ Example 4.3: A solution contains 3.36 g of monobasic potassium phosphate (KH2PO4, MW = 136) and 3.54 g of dibasic potassium phosphate (K2HPO4, MW = 174) in every 15 mL vial. Calculate the potassium ion concentration in mEq/mL. Both phosphate salts contribute potassium ions to the solution, so the problem is solved by calculating the mEq/mL concentration of each salt individually and then adding the numbers together. The chemical formulas show that KH2PO4 has 1 Eq/mol, while K2HPO4 has 2 Eq/mol. $Monobasic:\frac{3.36\;g}{15\;mL}\times\frac{1\;mol}{136\;g}\times\frac{1\;Eq}{mol}\times\frac{1000\;mEq}{Eq}=\frac{1.65\;mEq}{mL}$ $Dibasic:\frac{3.54\;g}{15\;mL}\times\frac{1\;mol}{174\;g}\times\frac{2\;Eq}{mol}\times\frac{1000\;mEq}{Eq}=\frac{2.71\;mEq}{mL}$ $Total:\;1.65+2.71=4.36=4.4\;\frac{mEq\;K^{+}}{mL}$ Example 4.4: A pharmacist added 8 mL of sodium phosphates injection to a 250 mL bag of D5W. What is the phosphate concentration in the bag in mmol/mL and mmol/L? What is the sodium concentration in the bag in mEq/mL and mEq/L? This label shows that sodium phosphates injection contains “3 mM P per mL” and “4 mEq Na+ per mL.” Please note: “3 mM P” is an unusual and confusing abbreviation for 3 mmol/mL of phosphate. In every other context, “mM” means millimoles/L. DO NOT use “mM” as an abbreviation for mmole in this course. D5W contains no sodium or phosphate, so the concentrations are 0 mmol/mL phosphate and 0 mEq/mL Na+. The simplest solution to this problem is the C1 · V1 = C2 · V2 method. Solve for the phosphate concentration: $\left( \frac{3\;mmol}{mL} \right)\left( 8\;mL \right)=\left( \frac{x\;mmol}{mL} \right)\left( 8\;mL\;+\;250\;mL \right)$ $x\;=\;\frac{0.093\;mmol}{mL}\;\times\;\frac{1000\;mL}{1\;L}\;=\;93\;\frac{mmol}{L}$ Solve for the sodium concentration: $\left( \frac{4\;mEq}{mL} \right)\left( 8\;mL \right)=\left( \frac{x\;mEq}{mL} \right)\left( 8\;mL\;+\;250\;mL \right)$ $x\;=\;\frac{0.124\;mEq}{mL}\;\times\;\frac{1000\;mL}{1\;L}\;=\;124\;\frac{mEq}{L}$ After mixing, the bag contains 0.093 mmol/mL or 93 mmol/L of phosphate and 0.124 mEq/mL or 124 mEq/L of sodium ion. Example 4.5: A physician orders potassium chloride 30 mEq/L in 250 mL of D5W. How many mL of potassium chloride injection (2 mEq/mL) must be added to the 250 mL bag of D5W. Notice that the order is written in mEq/L, while the drug vial is labeled as mEq/mL. To use the alligation method, the concentrations must all be expressed in the same units. We will solve this problem in terms of mEq/L. 250 mL of D5W represents 1970 parts, so the proportion to solve the problem is: $\frac{250\;mL}{1970\;parts}=\frac{x\;mL}{30\;parts}$ $\\\\x=\text{3.8 mL of KCl injection should be added to the 250 mL bag of D5W.}$ Module 4B: Osmoles and Milliosmoles Osmolarity is a measure of the osmotic pressure or tonicity of a solution. Recall from biology and physiology courses that water molecules freely diffuse through semi-permeable cell membranes in response to osmotic pressure differences between the intracellular and extracellular solutions. You probably did a lab exercise where you placed a drop of blood on a microscope slide and then watched what happened to the red blood cells when you added different solutions to the slide. A ‘hypotonic’ solution has lower osmolarity than the interior of the blood cells. The solute concentration difference causes water to diffuse into the cells. The cells swell to a larger size and will eventually burst due to the influx of excess water attempting to reduce the solute concentration. This process is called lysis. A ‘hypertonic’ solution has a higher osmolarity than the interior of the cells. Here, the solute concentration difference causes water to diffuse out of the cells, causing their size to decrease. This process is called crenation. Finally, an ‘isotonic’ solution has equal osmolarity to the interior of the cells and does not cause any net change in the cells. Pharmacists must be aware of the osmolarity of the products that are injected or infused into the body, placed into the eye or ear, or inserted into the rectum or vagina to minimize the pain or tissue necrosis effects of hypotonic and hypertonic solutions. One osmole (Osm) is one mole of dissolved ions or molecules. Every dissolved ion or molecule has the same effect on osmotic pressure, irrespective of molecular weight. One milliosmole (mOsm) is one thousandth (1/1000) of an Osmole. To calculate milliosmoles, you must determine how many millimoles of dissolved ions or molecules result when the solid completely dissolves. For non-electrolytes, i.e., those compounds that do not dissociate into ions in solution, one millimole is equal to one milliosmole. Electrolytes dissociate into cations and anions when they dissolve, so the number of milliosmoles (mOsm) is greater than the number of millimoles (mmol) for the same mass of material. The chemical formula of the electrolyte tells you how many ions can be produced when complete dissociation occurs. If your background includes physical chemistry you are aware that complete dissociation does not occur, but that is beyond the scope of this course. However, this concept is often shown on parenteral product labels where the term osmolarity has calculated (calc) appended to the value. See the label below. For the purposes of calculations in this course, we define the normal osmolarity of body fluids as 308 mOsm/L. The terms hypotonic (or hypo-osmolar), hypertonic (hyper-osmolar), and isotonic (iso-osmolar) can be defined quantitatively with respect to the normal physiologic osmolarity of 308 mOsm/L. Hypo-osmolar refers to a solution with total solute concentration less than 308 mOsm/L. Iso-osmolar refers to a solution with total solute concentration equal to 308 mOsm/L. Hyper-osmolar refers to a solution with total solute concentration greater than 308 mOsm/L. The maximum osmolarity that should be infused via a peripheral vein is 600 mOsm/L. Any higher osmolarity must be administered via a central venous catheter which terminates into the inferior vena cava, where the blood flow rate is high enough to quickly dilute the solution to physiologic osmolarity. The formula for sodium chloride is NaCl. One millimole of NaCl dissociates into 1 mmol of Na+ and 1 mmole of Cl– in solution, so one mmol of NaCl produces 2 mOsm of dissolved ions. NaCl, therefore, contains 2 mOsm/mmol. Potassium chloride (KCl) dissociates into 1 mmol of K+ and 1 mmole of Cl– in solution, so KCL also contains 2 mOsm/mmol. Magnesium chloride (MgCl2) dissociates into 1 Mg2+ and 2 Cl–, so MgCl2 has 3 mOsm/mmol. Please note: the “polyatomic ions,” including acetate, sulfate, gluconate, and carbonate, remain intact when they dissolve: Sodium acetate: $NaC_{2}H_{3}O_{2}\;\to \;Na^{+}\;+\;C_{2}H_{3}O_{2}^{\;–}$ Sodium acetate contains 1 mEq/mmol and 2 mOsm/mmol. Potassium sulfate: $K_{2}SO_{4}\;\to \;2K^{+}\;+\;SO_{4}^{\;2–}$ Potassium acetate contains 2 mEq/mmol and 3 mOsm/mmol. Calcium gluconate: $Ca(C_{6}H_{11}O_{7})_{2}\;\to \;Ca^{2+}\;+\;2C_{6}H_{11}O_{7}^{\;–}$ Calcium gluconate contains 2 mEq/mmol and 3 mOsm/mmol. Sodium carbonate: $Na_{2}CO_{3}\;\to \;2Na^{+}\;+\;CO_{3}^{\;2–}$ Sodium carbonate contains 2 mEq/mmol and 3 mOsm/mmol. Please note: “waters of hydration” in a chemical formula are ignored when counting milliosmoles per millimole. Magnesium sulfate is produced in several crystalline forms with different waters of hydration and different molecular weights. However, they all have one Mg2+ and one SO42– per mole, so they all have 2 mOsm/mmol. Table 4.2. Hydrated forms of magnesium sulfate Crystal form \| Formula weight (g/mol) \| mOsm/mmol \| MgSO4 (anhydrous) \| 120 \| 2 \| MgSO4 · H2O \| 138 \| 2 \| MgSO4 · 3 H2O \| 174 \| 2 \| MgSO4 · 5 H2O \| 210 \| 2 \| MgSO4 · 6 H2O \| 228 \| 2 \| MgSO4 · 7 H2O \| 246 \| 2 \| Example 4.6: A solution was prepared by dissolving 15 g of magnesium sulfate heptahydrate (MgSO4 · 7 H2O, MW = 246), 10 g of dextrose monohydrate (C6H12O6 · H2O MW = 198), and 1.8 g of sodium chloride (NaCl, MW = 58) in enough water to make 200 mL. Calculate the osmolarity (mOsm/L) of the solution. There are 3 solutes with different molecular weights and mOsm/mmol values. Calculate the mOsm/L concentration for each solute and add the numbers together. $Mag\;sulf:\;\frac{15\;g\;MS}{200\:mL}\times\frac{1000\;mL}{L}\times\frac{1\;mol\;MS}{246\;g\;MS}\times\frac{2\;Osm}{1\;mol\;MS}\times\frac{1000\;mOsm}{1\;Osm}=610\frac{mOsm}{L}$ $NaCl:\;\frac{1.8\;g\;NaCl}{200\:mL}\times\frac{1000\;mL}{L}\times\frac{1\;mol\;NaCl}{58\;g\;NaCl}\times\frac{2\;Osm\;NaCl}{1\;mol\;NaCl}\times\frac{1000\;mOsm}{1\;Osm}=310\frac{mOsm}{L}$ $Dextrose: \frac{5\;g}{100\;mL}\times \frac{1000\;mL}{L}\times \frac{1\;mol}{198\;g}\times \frac{1\;Osm}{mol}\times \frac{1000\;mOsm}{Osm}=253\frac{mOsm}{L}$ The total solution osmolarity is: 610 + 310 + 253 = 1173 mOsm/L. This solution is very hyperosmolar. The osmolarity of injectable solutions is usually printed on the label. A 10% calcium chloride injection has an osmolarity of 2.04 mOsm/mL. A 0.45% sodium chloride injection, also referred to as half normal saline or ½ NS, has an osmolarity of 154 mOsm/L or 0.154 mOsm/mL. Example 4.7: A patient requires a 2 g dose of calcium chloride in ½ NS by IV infusion. The physician wants the solution to be as close to iso-osmolar as possible. ½ NS is available in bags containing 100, 250, 500, or 1000 mL. Which bag size should be used? To solve the problem, determine the volume of calcium chloride injection needed, then calculate the volume of ½ NS that would produce an iso-osmolar solution. Finally, choose the bag size closest to the calculated volume of ½ NS. $CaCl_{2}\;volume:\:2\;g\;CaCl_{2}\times\frac{100\;mL\;injection}{10\;g\;CaCl_{2}}=20\;mL\;CaCl_{2}\;injection$ Volume of ½ NS to make an iso-osmolar solution (osmolarities expressed as mOsm/mL) The volume of CaCl2 injection is 20 mL, so the proportion to solve for ½ NS volume is: $\frac{0.154\;parts}{20\:mL}=\frac{1.732\;parts}{x\:mL},\:x=224.9\;mL$ Adding 20 mL CaCl2 injection to 225 mL of ½ NS would produce an iso-osmolar solution. The closest available bag size to 225 mL is 250 mL, so the infusion should be prepared with 250 mL of ½ NS. Milliequivalents and milliosmoles are related to each other through millimoles, while millimoles and milligrams are related through molecular weight. These relationships allow conversion between milligrams, millimoles, milliequivalents, and milliosmoles for any substance. Example 4.8: Calculate the osmolarity of a solution containing 30 mEq/L of KCl in water. KCl has 1 mEq/mmol and 2 mOsm/mmol. These conversions can be used individually or combined into the single conversion 1 mEq/2 mOsm to solve the problem. $\frac{30\;mEq\;KCl}{L}\times\frac{1\;mmol\;KCl}{1\:mEq\;KCl}\times\frac{2\;mOsm\;KCl}{1\;mmol\;KCl}=60\frac{mOsm\;KCl}{L}$ $Or,\;\frac{30\;mEq\;KCl}{L}\times\frac{2\;mOsm\;KCl}{1\:mEq\;KCl}=60\frac{mOsm\;KCl}{L}$ Example 4.9: A patient is ordered 60 mmol of potassium phosphates in 250 mL of 0.9% sodium chloride injection, also called normal saline or NS. Would this solution be safe to administer in the peripheral vein? The osmolarity limit for peripheral infusion is 600 mOsm/L. Calculate the solution's osmolarity as ordered and determine whether it is greater than or less than 600 mOsm/L. KPhos injection contains 3 mmol/mL of phosphate and 7.4 mOsm/mL osmolarity. NS contains 308 mOsm/L or 0.308 mOsm/mL osmolarity. Calculate the milliosmoles contributed to the total from each solution, then divide by the total volume in liters. $60\;mmol\;KPhos\times\frac{1\;mL}{3\;mmol\;KPhos}=20\;mL\;of\;injection\times\frac{7.4\;mOsm}{mL}=148\;mOsm$ $\\\\\text{The volume of KPhos injection required is 20 mL, and it contributes 148 mOsm to the mixture.}$ $NS\;mOsm:\:250\;mL\times\frac{0.308\;mOsm}{mL\;NS}=77\;mOsm$ NS 250 mL contributes 250 mL of volume and 77 mOsm. The mixture, therefore, contains 148 + 77 = 225 mOsm in a total volume of 20 + 250 = 270 mL. The osmolarity is then calculated as: $\frac{225\;mOsm}{270\;mL}\times\frac{1000\;mL}{L}=833.3\frac{mOsm}{L}$ The maximum osmolarity for peripheral infusion is 600 mOsm/L, so this order with an osmolarity of 833 mOsm/L should be administered through a central venous catheter. Module 4: Practice Problems - Calculate the mEq/L concentration of a 15% potassium chloride (MW 74.6) solution. - A solution is prepared by dissolving 410 grams of sodium acetate (MW 82) in enough water to make 2.5 liters. Calculate the concentration in mEq/L. - Sodium bicarbonate injection is a sterile solution containing 8.4% sodium bicarbonate (MW 84) in water. A pharmacist added 150 mL of sodium bicarbonate injection to a 1 L bag of sterile water for injection. Calculate the solution concentration in mEq/L. - Calculate the osmolarity of a solution prepared by adding 100 mL of sodium bicarbonate injection (50 mEq/50 mL) to 1000 mL of sterile water for injection. - One liter of solution contains 6 g of sodium chloride (MW 58), 300 mg of potassium chloride (MW 74.6), 200 mg of calcium chloride dihydrate (MW 146), and 3.1 g of sodium lactate (NaC3H5O3, MW 112). Calculate the sodium concentration in mEq/L. Calculate the chloride concentration in mEq/L. - A supplement product contains 1.25 g of calcium gluconate (MW 430) per tablet. How many milliequivalents of calcium does the patient receive if the dose is 2 tablets? - A product contains 17.5 g of sodium sulfate (Na2SO4 MW 142), 3.1 g of potassium sulfate (K2SO4 MW 174), and 1.6 g of magnesium sulfate (MgSO4 MW 120) in 180 mL of solution. Calculate the sulfate concentration in mmol/L and mEq/L. - A product contains 17.5 g of sodium sulfate (Na2SO4 MW 142), 3.1 g of potassium sulfate (K2SO4 MW 174), and 1.6 g of magnesium sulfate (MgSO4 MW 120) in 180 mL of solution. Calculate the solution's osmolarity in mOsm/L. - Calculate the osmolarity of a 3% sodium chloride ophthalmic solution. Is the solution hypo-, iso-, or hyperosmolar? - Calculate the osmolarity of a sterile 10% sodium sulfacetamide (NaC8H10N2O3S; MW 236) ophthalmic solution. Is the solution hypo-, iso-, or hyperosmolar? - Calculate the osmolarity of 25% mannitol injection (non-electrolyte; mw 182). Can this product be safely infused into a peripheral vein? - Calculate the osmolarity of a solution prepared by adding 2 g of calcium chloride dihydrate (MW 147) using 10% calcium chloride dihydrate injection, USP. The injection volume is added to 250 mL of normal saline. Can this product be infused into a peripheral vein? - One liter of a total parenteral nutrition (TPN) solution for newborns has 10% dextrose monohydrate (198 g/mol) and 2.5 % amino acids (along with several additives that do not significantly affect the osmolarity). The source of amino acids is 7% amino acids in water with an osmolarity of 561 mOsm/L. Can the TPN solution be infused into a peripheral vein? - Calculate the osmolarity of an oral colon gavage solution containing: Sodium sulfate 21.5 g (142 g/mole) Sodium chloride 5.53 g (58.5 g/mole) Potassium chloride 2.82 g (74.5 g/mole) Sodium bicarbonate 6.36 g (84 g/mole) PEG 3350 227.1 g (3350 g/mole; non-electrolyte Water qs 4L - Calculate the osmolarity of 20 mmol of sodium phosphates IV added to 250 mL D5W. Is the solution safe to administer via a peripheral vein? - Calculate the osmolarity of 20 mmol of sodium phosphate IV added to 100 mL ½ NS. Is the solution safe to administer via a peripheral vein? - Calculate the osmolarity of calcium gluconate (mw 430) 2 g in 500 mL of sterile water. Is the solution safe to administer via a peripheral vein? - Calculate the volume of ½NS that should be added to 30 mEq of KCl injection solution to produce an iso-osmolar solution. - Calculate the volume of sterile water for injection that should be added to 30 mmol of sodium phosphates to produce an iso-osmolar solution. - Calculate the volume of 50 mM NaCl solution that should be added to 1 gram of calcium chloride dihydrate solution to produce an iso-osmolar solution. Answers: - 2010 mEq/L - 2000 mEq/L - 130 mEq/L - 182 mOsm/L - 131 mEq/L Na+ and 110 mEq/L Cl– - 11.6 mEq Ca2+ - 857.7 mM; 1715 mEq/L - 2500 mOsm/L - 1027 mOsm/L - 848 mOsm/L - 1374 mOsm/L; osmolarity too high for peripheral vein - 437 mOsm/L; okay to give by peripheral vein - 704 mOsm/L; osmolarity too high for peripheral vein - 235 mOsm/L - 427 mOsm/L; okay to give by peripheral vein - 582 mOsm/L; okay to give by peripheral vein - 28 mOsm/L; osmolarity may be too low for peripheral vein - 360 mL - 217 mL - 83 mL Module 5: Dose Calculation and Dose Checking We believe pharmacists should be responsible for verifying the right drug and appropriate dose of their patient’s prescribed medication. As you advance through the curriculum, you will learn how to apply the knowledge gained from your coursework to the correct selection of the pharmacologic agent. And it is probably clear that one dose cannot be appropriate for all patients. You will learn to use guidelines and dosing recommendation references. Those references often suggest dosing based on body weight, body surface area, estimated renal function using creatinine clearance, or liver function. Ethically, we are bound to consult with physicians when experience informs us that the drug or dose may be incorrect. This module will provide practice in calculating correct amounts based on different dosing recommendations. Module 5A: Patient-Specific Dosing (mg/kg) Many drugs used in pediatrics are dosed according to body weight (kilograms) or body surface area (m2). In this section, we will focus on mg/kg dosing. Typical calculations involve checking a prescribed dose. Example 5.1: A patient weighs 44 pounds. Recall that to convert patient weight to kilograms, divide the weight in pounds by 2.2. The physician orders Amoxicillin 250 mg PO tid, targeting 30 – 45 mg/kg/day. What is the mg/kg value per day and dose basis? Is the dose consistent with the guideline? $44\;lb\times \frac{1\;kg}{2.2\;lb}=20\;kg$ $\frac{\frac{750\;mg}{day}}{20\;kg}=37.5\;\text{mg/kg/day}$ $\frac{\frac{250\;mg}{dose}}{20\;kg}=12.5\;\text{mg/kg/dose}$ You can check the medication order and see that the physician’s prescribed dose is consistent with the recommended guidelines. When presented with the drug and dosing schedule, divide the dose by the patient’s weight and compare the answer to the recommendation. Practice problems. 1. A physician orders an IV loading dose of Remdesivir of 75 mg for a 33-pound patient. The recommended dose is 5 mg/kg. Is the dose correct? 75 mg/15 kg = 5 mg/kg. The dose is correct. 2. A physician orders Erythromycin ethylsuccinate 300 mg PO tid for a 50-pound patient. The recommended dose is 40 – 50 mg/kg/day. Is the dose correct? 900 mg/day/22.7 kg = 40 mg/kg/day. The dose is correct. 3. A physician orders Gentamicin sulfate 50 mg IV q 8° for a 22-pound patient. The recommended dose is 7.5 mg/kg/day. Is the dose correct? 150 mg/day/10 kg = 15 mg/kg/day. The dose is too high. Contact the physician. 4. A physician orders Gentamicin sulfate 50 mg IV for a 44-pound patient. The recommended dose is 2.5 mg/kg/dose. Is the dose correct? 50 mg/dose/20 kg = 2.5 mg/kg/dose. The dose is correct. 5. The recommended dose for Bactrim (Sulfamethoxazole 200 mg and Trimethoprim 40 mg per 5 mL) based on the TMP component, is 6 – 12 mg/kg/day. Physician orders 2-teaspoonsful q 12° for a 22-pound child. Is the dose correct? 160 mg TMP/day/10 kg = 16 mg/kg/day. The dose is too high. Contact the physician. Some of you will have the opportunity to “write” the drug orders for some patients. Let’s see how this works. I will also give you the product concentrations so you may practice writing realistic volumes along with the calculated doses. Example 5.2: A full-term newborn starts on Digoxin using the TDD 30 mcg/kg protocol. (TDD = total digitalizing dose). The recommended dosing schedule is ½ the TDD initially, followed by ¼ of the TDD for each subsequent dose at 6- to 8-hour intervals for 2 doses. The newborn weighs 6 pounds and 9 ounces. Digoxin oral solution is available as a 50 mcg/mL product. What dose and volume should you calculate for the two different doses? $6\;lb+\left( 9\;oz\times \frac{1\;lb}{16\;oz} \right)=6.5625\;lb$ $6.5625\;lb\times \frac{1\;kg}{2.2\;lb}=2.98\;kg$ The doses are divided into 15 mcg/kg for the first dose, then 7.5 mcg/kg for two additional doses. The TDD = 30 mcg/kg. $2.98\;kg\times \frac{15\;mg}{kg}=44.7\;mg,\;\text{round to 45 mg}$ $45\;mcg\times \frac{1\;mL}{50\;mcg}=0.9\;mL$ This is the initial dose. The next two doses are administered anywhere from 6 – 12 hours later, depending on the cardiologist's protocol. $2.98\;kg\times \frac{7.5\;mg}{kg}=22.4\;mg,\;\text{round to 22.5 mg}$ $22.5\;mcg\times \frac{1\;mL}{50\;mcg}=0.45\;mL$ The volume of the first dose will be 0.9 mL, and the two subsequent dose volumes will be 0.45 mL. Practice problems. 6. Acetaminophen solution contains 160 mg/5 mL. The recommended children's dose is 10 – 15 mg/kg/dose. What reasonable volume of solution should you recommend for a child who weighs 48 pounds? 21.8 kg x 10 – 15 mg/kg = dosage range 220 mg – 330 mg. 220 mg/160 mg/5 mL = 6.9 mL. 330 mg/160 mg/5 mL = 10.3 mL. A reasonable dose is 240 mg (1.5 teaspoonsful or 7.5 mL) 7. Amoxicillin suspension contains 250 mg/5 mL. The recommended children's dose is 15 mg/kg/dose. What reasonable volume of solution should you recommend for a child who weighs 23 pounds? 10.5 kg x 15 mg/kg/dose = 157.5 mg. 157.5 mg/50 mg/mL = 3.15 mL. A practical, measurable dose is 150 mg or 3 mL. 8. Fer-in-sol solution contains 15 mg/mL of elemental iron (75 mg/mL of ferrous sulfate). A recommended dose for iron deficiency anemia is 2 mg/kg/dose. What reasonable volume of solution should you recommend for a child who weighs 13 pounds? 5.91 kg x 2 mg/kg/dose = 11.8 mg. 11.8 mg/15 mg/mL = 0.79 mL. A reasonable volume with a 1 mL oral syringe is 0.8 mL or 12 mg. 9. Amikacin sulfate injection contains 250 mg/mL. A recommended pediatric dose is 7 mg/kg/dose. What reasonable volume of solution should you recommend for a child who weighs 23 pounds? 10.5 kg x 7 mg/kg/dose = 73.5 mg. 73.5 mg/250 mg/mL = 0.29 mL. A reasonable volume with a 1 mL syringe is 0.3 mL or 75 mg. Module 5B: Body Surface Area Some drugs are dosed based on the patient’s body surface area value, calculated in square meters (m2). Dubois and Dubois published some of the earliest works on BSA determination in 1916. Mosteller published a simplified equation in 1987, which is routinely used today. The equation uses the patient's weight in kg and their height in centimeters. You learned how to do these conversions in Module 1. Now, you finally have the opportunity to use the square root key on your calculator! 😊. Calculate all BSA values to 2 decimal places, for example, 1.62 m2. To calculate the patient’s BSA, use this formula, using the patient’s actual body weight: $BSA\;(m^{2})=\sqrt{\frac{wt\;(kg)\;\times\;ht\;(cm)}{3600}}$ Example 5.3: A patient weighs 21 kg and is 3’ 10” in height. Calculate the BSA. 3’ 10” = 46” = 117 cm. $BSA=\sqrt{\frac{21\;kg\;\times\;117\;cm}{3600}}=\sqrt{0.6825}=0.83\;m^{2}$ These problems require you to calculate the BSA, then multiply the dose given in mg/m2 to obtain the dose. Example 5.4: Calculate the dose of Allopurinol for a patient who weighs 25 kg and is 4’ 2”. The recommended dose is 200 mg/m2. $BSA(m^{2})=\sqrt{\frac{25\;kg\;\times\;127\;cm}{3600}}=\sqrt{0.8819}=0.94\;m^{2}$ $0.94\;m^{2}\times \frac{200\;mg}{m^{2}}=188\;mg$ Example 5.5: Calculate the dose of Methotrexate for a patient who weighs 48 kg and is 5’ 3”. The recommended dose is 12 g/m2. 5’ 3” = 63” = 160 cm $BSA(m^{2})=\sqrt{\frac{48\;kg\;\times\;160\;cm}{3600}}=\sqrt{2.1333}=1.46\;m^{2}$ $1.46\;m^{2}\times \frac{12\;g}{m^{2}}=17.5\;g$ Example 5.6: A physician prescribes hydrocortisone 20 mg for a patient. The recommended dose is 20 – 25 mg/m2/day. Is the dose correct? The patient weighs 22 kg and is 118 cm tall. $BSA(m^{2})=\sqrt{\frac{22\;kg\;\times\;118\;cm}{3600}}=\sqrt{0.7211}=0.85\;m^{2}$ $\frac{20\;mg}{0.85\;m^{2}}=\frac{23.5\;mg}{m^{2}}$ The dose is within the recommended range. Practice problems: 10. Caspofungin is an anti-fungal drug administered IV (over 1 hour) as a 70 mg/m2 loading dose the first day, followed by 50 mg/m2 daily thereafter. Calculate the loading dose and maintenance doses for a patient who weighs 24 kg and is 118 cm tall. 11. Dexamethasone is used in treating many conditions. A typical dosing range is 0.6 – 9 mg/m2/day in 3 or 4 divided doses. It is available as an oral solution containing 0.5 mg/5 mL. Calculate the amount and solution volume for a patient who weighs 18 kg and is 108 cm tall, based on 1.5 mg/m2/day of dexamethasone divided into three doses. What volume of the oral solution (0.5 mg/5 mL) should be taken at each dose? 12. Dronabinol is used for nausea prophylaxis in patients receiving chemotherapy. The National Cancer Institute (NCI) guideline for pediatric patients is 5 mg/m2 PO every 6 – 8 hours before beginning chemotherapy treatment, then 5 mg/m2 PO every 4 – 6 hours for up to 12 hours after the treatment. Calculate the dose for a patient who weighs 23 kg and is 114 cm tall. 13. Acyclovir is used to treat viral infections in children. The dosing guideline can range up to 600 mg/m2 every 6 hours for 10 days. The drug may be administered orally as a 40 mg/mL suspension or by an intermittent IV infusion. Each sterile vial (10 mL) contains acyclovir sodium equivalent to 500 mg of acyclovir. Calculate the dose for a patient who weighs 26 kg and is 125 cm tall. Module 5C: Estimating Body Surface Area Anatomically Several medical researchers devised an estimate of the body surface area based on anatomical regions from 1944 to 1960. These include Berkow, Boyd, Brewer, Chu, Lund, Pulaski, Tennison, and Wallace. These individuals were searching for a rapid way to estimate the areas involved with severe burns. The method is often referred to as the Rule of Nines. While the method has been criticized as selective, it has clinically proven its worth. Further information can be found on Wikipedia pages. One other note, many physicians use the rule of thumb that involves the area of the patient's palm. The patient's palm approximates 1% of the body surface area. The method is called the Rule of Nines because the body can be divided into 11 approximate areas with a common factor of 9% (head (1), arms (2), chest/abdoman (2), back (2), legs (4)) . The table explains the concept better than words. Note that children differ in some key areas. We’ll restrict our problems to adults. Note that in the color cartoon, a distinction is made between front and back. The entire torso represents approximately 36% of the BSA value. Body Part \| Estimated BSA Percentage \| \| Adults \| Children \| \| Left arm \| 9% \| 9% \| Right arm \| 9% \| 9% \| Head & neck \| 9% \| 18% \| Chest \| 9% \| 9% \| Abdomen \| 9% \| 9% \| Back \| 18% \| 18% \| Left leg \| 18% \| 14% \| Right leg \| 18% \| 14% \| Example 5.7: An adult oncology patient had their left leg amputated at the hip because of an osteogenic sarcoma tumor. Chemotherapy treatment includes methotrexate 15 g/m2. The patient’s pre-surgical BSA was 1.7 m2. What dose of methotrexate should be considered? Preoperatively, the patient would have received: $1.7\;m^{2}\times \frac{15\;g}{m^{2}}=25.5\;g$ The loss of the left leg results in an 18% reduction in body surface area, so the chemo dose will also need to be reduced by 18%: 25.5 g × 82% = 20.9 g Example 5.8: A treatment protocol requires the administration of IV fluids at a rate of 2 L per m2 per day. The patient had their right arm removed because of an accident. Before the accident, the patient’s BSA was 1.9 m2. What fluid rate (mL/h) should the patient receive? 2 L/ m2/day × 1.9 m2 = 3.8 L/day The loss of the right arm results in a 9% surface area reduction, so: 3.8 L/day × 0.91 = 3.458 L/day 3.458 L/day ≡ 3458 mL/24 h = 144 mL/h Module 5D: Ideal Body Weight The impact of height and weight on medical conditions has been studied since the early 1900s. Studies from the 1950s used the Metropolitan Life Insurance Company height and weight tables to understand these two variables' influence on health. One outcome of that statistical research was the development of the “ideal” body weight (IBW) for adult women and men. This concept is intimately associated with dosing for certain drugs. Devine (1974), Robinson (1983), and Miller (1983) have developed equations to estimate the IBW. A Google search will give you a good starting point for further reading if you are interested. A good review of the topic is the paper by Pai and Paloucek in the Annals of Pharmacotherapy (2000). As you progress through the curriculum, you will use the concept of IBW for calculating doses and estimating a patient’s creatinine clearance. We will use the Devine equation in this course. For Females: IBW = 45.5 kg + 2.3 kg for each inch in height over 60 inches. For Males: IBW = 50 kg + 2.3 kg for each inch in height over 60 inches. Example 5.9: Calculate the IBW for a female patient who is 5’ 5” tall. 45.5 kg + 2.3 kg × (65 – 60”) = 57 kg Example 5.10: Calculate the IBW for a male patient who is 5’ 11” tall. 50 kg + 2.3 kg × (71 – 60”) = 75.3 kg Module 5E: Adjusted Body Weight Certain drugs, when dosed on the patient’s total body weight, may lead to under or overdoses for patients defined as obese. While somewhat controversial, obesity is usually defined as the patient weighing more than 130% of their ideal body weight. In some therapeutic situations, it may be more appropriate to use the adjusted body weight for patients who are obese. There is a continuing controversy over the use of these formulas in patients. We recommend you follow the guidelines in place at your institution. The adjusted body weight formula can be confusing because it contains 2 words starting with the letter A. The adjusted body weight and the actual body weight are used in the formula, so pay close attention to the calculation. The same equation is used for women and men. Also, note that the adjustment factor can vary from one institution to another. The factor is usually within the range of 0.25 to 0.4. While this factor can vary among institutions and practitioners, for all calculations in this book we will use 0.4 as the adjustment factor. This equation should only be used when the product labeling or institutional policy specifies its use. Adj BW = IBW + 0.4 x (Actual BW – IBW) Example 5.11: Calculate the Adj BW (0.4) for a female patient weighing 194 pounds and 5 feet 4 inches tall. IBW = 45.5 kg + 2.3 kg × (64 – 60”) = 54.7 kg 194 lb = 88.2 kg Adj BW = 54.7 kg + 0.4 × (88.2 – 54.7) = 68.1 kg Module 5F: Creatinine Clearance Many drugs are cleared from the body by renal excretion. Depending on the drug, its clearance may be significant or minor. Reduced kidney function can lead to potentially toxic drug levels if renal excretion is a major clearance route. The kidneys receive about 20% of the cardiac output, which equates to a normal male glomerular filtration rate (GFR) of 90 – 120 mL/minute. Serum creatinine has been used as a marker of renal function for many years. Creatinine is a breakdown product of creatine phosphate resulting from the metabolism of muscle and protein. In 1976, D. W. Cockcroft and M. H. Gault published an equation that attempted to estimate an adult patient’s GFR using serum creatinine values. While the equation has been criticized over the years, (for example, see the National Kidney Foundation website https://www.kidney.org/professionals/KDOQI/gfr_calculatorCoc), the C-G CrCL equation remains useful for many drugs. For most patients and most drugs, it has been demonstrated that the Cockcroft and Gault equation estimates the GFR as well as the MDRD equation. An added benefit to using the C-G equation is related to its long historical use in various drug studies. During your career, it is possible that more accurate estimates of renal function may replace the C-G equation. For completeness, we note that the C-G CrCL overestimates the actual glomerular filtration rate by 10 – 20% due to the active secretion of creatinine by the peritubular capillaries. Now, let’s see the equations. $CrCL_{male}=\frac{(140-age)\;\times \;wt\;(kg)}{72\;\times \;SCr}$ where wt is the lower of ideal or actual body weight and SCr is the patient’s serum creatinine level in mg/dL. $CrCL_{female}=0.85\times \frac{(140-age)\;\times \;wt\;(kg)}{72\;\times \;SCr}$ The units for the CrCL are mL/min. Round the value to the closest whole (integer) number. Please note: The most common question students ask about this equation is which body weight should be used. Calculate ideal body weight and actual body weight in kilograms. Then use the lower of these values in the equation. Please note: The most common error students make when using this equation is forgetting to multiply by 0.85 for female patients. Example 5.12: A male patient is 60 years old, 5’ 6” tall, weighs 145#, with an ideal body weight of 140#. His serum creatinine is 1.2 mg/dL. Calculate his CrCL. $CrCL_{male}=\frac{(140\;-\;60)\;\times\;63.8\;kg}{72\;\times\;1.2}=59\;mL/min$ Example 5.13: A female patient is 45 years old, 5’3” tall, weighs 112#, with an ideal body weight of 115#. Her serum creatinine is 1.6 mg/dL. Calculate her CrCL. $CrCL_{female}=0.85\times \frac{(140\;-\;45)\;\times\;50.9\;kg}{72\;\times\;1.6}=36\;mL/min$ BSA-Adjusted Creatinine Clearance Certain drugs are dosed based on Body Surface Area adjusted Creatinine Clearance. The creatinine clearance calculation is dependent on the patient's muscle mass, so smaller or less muscular patients will have a lower CrCL value than larger more muscular patients, even if both patients have similar kidney function. BSA adjustment is done in an attempt to account for this effect. The formula used to adjust the patient's CrCL for BSA is: $BSA\;adjusted\;CrCL\;(mL/min/1.73\;m^{2})=CrCL (mL/min)\times \frac{1.73}{Patient's\;BSA}\;m^2$ The value 1.73 m2 is used because it has traditionally represented the average adult male BSA value. You may question the validity of using 1.73 m2 in light of the changes to the size of the average man in the U.S. since the factor was introduced. Like the C-G CrCL equation, the argument is made that the equation has proved its worth in clinical situations thereby justifying its continued use. Who knows, you may see a change in the value of that factor during your professional career. In summary, the BSA-adjusted CrCL is used to allow easier comparison of an individual patient's CrCL to the average normal adult. Consider an example. Patient A is 40 year old female patient, 5' tall and 45.5 kg (ideal body weight). Patient B is a 40 year old female, 6' tall and 73.1 kg (ideal body weight). Both patients have serum creatinine of 1.1 mg/dL. Table 5.1. Creatinine Clearance for Example Patients A and B. \| Statistic \| Patient A \| Patient B \| \| Age \| 40 \| 40 \| \| Height (feet) \| 5 \| 6 \| \| Weight (kg) \| 45.5 \| 73.1 \| \| Creatinine Clearance (mL/min) \| 50 \| 79 \| \| BSA (m2) \| 1.39 \| 1.93 \| \| BSA-adjusted CrCL (mL/min/1.73 m2) \| 62 \| 71 \| Patient A has CrCL of 50 mL/min, which would indicate possible minor decrease in kidney function. However, the BSA-adjusted CrCL calculation indicates that the patient's kidney function is actually better than CrCL would suggest. Similarly, Patient B has CrCL of 79 mL/min, which would suggest good kidney function. However, the BSA-adjusted CrCL calculation indicates that the patient's kidney function is not quite as good as CrCL would suggest. Example 5.14: A male patient is 60 years old, 5’ 6” tall, weighs 145#, with an ideal body weight of 140#. His serum creatinine is 1.2 mg/dL. Calculate his BSA-adjusted CrCL. There are a few steps to the calculation: i. Calculate CrCL using the lower of ideal or actual body weight. Actual body weight = 145 lb/2.2 = 65.9 kg Ideal body weight = 50 kg + 2.3 kg (66" - 60") = 63.8 kg. Use ideal body weight for CrCL. $CrCL_{male}=\frac{(140\;-\;60)\;\times\;63.8\;kg}{72\;\times\;1.2}=59\;mL/min$ ii. Calculate BSA using actual body weight $BSA\;(m^{2})=\sqrt{\frac{65.9\;kg\;\times\;168\;cm}{3600}}=1.75\;m^{2}$ This patient's BSA is very close to the normal value of 1.73 m2, so BSA-adjusted CrCL will be very similar to the non-adjusted CrCL value. iii. Calculate the BSA-adjusted CrCL. $59\;mL/min\;\times\;\frac{1.73}{1.75}\;m^2=58\;mL/min/1.73\;m^{2}$ Example 5.15: Calculate the BSA-adjusted CrCL for a 34 year old male, 5'1" tall and 51 kg, with SCr of 0.9 mg/dL. $CrCL=\frac{(140\;-\;34)\;\times\;51\;kg}{72\;\times\;0.9\;mg/dL}=83\;mL/min $ $BSA\;(m^{2})=\sqrt{\frac{51\;kg\;\times\;152\;cm}{3600}}=1.47\;m^{2} $ $BSA-adjusted\;CrCL=83\;mL/min\times \frac{1.73}{1.47}\;m^2=98\;mL/min/1.73\;m^{2}$ In this case, the patient's BSA is smaller than 1.73 m2, so the BSA-adjusted CrCl is larger than the previous example. Example 5.16: Calculate the BSA-adjusted CrCL for the female patient in example 5.13. Recall that the C-G equation uses the lesser value for actual body weight or ideal body weight. The Mosteller equation for BSA uses the patient's actual body weight. $BSA\;(m^{2})=\sqrt{\frac{50.9\;kg\;\times\;160\;cm}{3600}}\;=\;\sqrt{2.26}=1.5\;m^{2} $ $CrCL_{BSA-adj}\;=\;36\;mL/min\;\times\;\frac{1.73}{1.5}\;m^{2}\;=\;42\;mL/min$ Please note: BSA-adjusted CrCL has units of mL/min/1.73 m2. Please note: Only use BSA-adjusted CrCL for patient dose calculations when the guidelines for a particular drug specify that it should be used. As an example, the guideline for a particular drug states that the standard dose for adults with BSA-adjusted CrCL > 70 mL/min/1.73 m2 is 250 mg every 6 hours. For a patient of the same weight, but with BSA-adjusted CrCL of 30 mL/min/1.73 m2 should be administered 250 mg every 12 hours, or 1/2 the daily dose of the patient with normal renal function. Pediatric Estimation of Creatinine Clearance The Cockcroft & Gault equation was developed using data from male patients over 30. In 1976, George Schwartz and a team of researchers published a new equation for estimating the glomerular filtration rate (eGFR) in pediatric patients from one week old to 17 years old. The CG equation was used for patients 18 years and older. Schwartz’s equation was updated in 2009 and is currently considered the best estimate of the GFR in that age range. Similar to the CG equation, the primary assumption is that the renal function is not acutely changing, and the serum creatinine value is constant. The original equation used six terms with multiple exponents. Applying some judicious statistical assumptions resulted in a more concise equation colloquially called the “bedside Schwartz.” The bedside Schwartz equation predicts the estimated GFR with the units mL/min/1.73 m2. $eGFR \left( mL/min/1.73^{2} \right) = 0.413\:\times\:\left( \frac{ht\;\left( cm \right)}{SCr\;\left( mg/dL \right)} \right)$ Example 5.17: Calculate the eGFR for a 6-yo male patient who is 45” tall and has a SCr = 1.5. $eGFR = 0.413\: \times \:\left( \frac{114}{1.5} \right)\:=\: 31\: mL/min/1.73^{2}$ Example 5.18: Calculate the eGFR for a 9-yo female patient who is 52” tall and has a SCr = 1.8. $eGFR = 0.413\: \times \:\left( \frac{132}{1.8} \right)\:=\: 30\: mL/min/1.73^{2}$ Example 5.19: Calculate the eGFR for a 14-yo female patient who is 5 ' 3” tall with a SCr = 0.8. $eGFR = 0.413\: \times \:\left( \frac{160}{0.8} \right)\:=\: 83\: mL/min/1.73^{2}$ Example 5.20: Calculate the eGFR for a 5-yo male patient who is 3' 4” tall with a SCr = 0.7. $eGFR = 0.413\: \times \:\left( \frac{102}{0.7} \right)\:=\: 60\: mL/min/1.73^{2}$ Module 5G: Body Mass Index (BMI) The body mass index was first used in a paper from 1972 in the Journal of Chronic Diseases. The calculation was first proposed in about 1840 to represent a scale useful in comparing different sized people. The application and interpretation of the BMI continues to invoke some controversy in medicine. We will not take a position on the socio-political ramifications of the index. Our task is to focus on the calculation and application of the index in appropriate clinical situations. The calculation is intended to be used in people over 20 years old. Please note, as with BSA-adjusted CrCl, only use BMI in dose calculations when a specific drug guideline tells you to. Please note: BMI can be confusing because it is not used directly to calculate a drug dose. Rather, it is usually used to decide whether to use ideal body weight, actual body weight, or adjusted body weight in the dose calculation. The calculation of the BMI is straightforward. $BMI=\frac{Weight\;(kg)}{(Height\;(m))^{2}}$ This formula is an application of earlier conversion factors. Recall the conversion process for height in feet and inches to meters. $6'4^{"}=76^{"}\times \frac{2.54\;cm}{inch}\times \frac{1\;m}{100\;cm}=1.93\;m$ Example 5.17: Calculate the BMI for a 35 yo patient who weighs 180 pounds and is 5’ 7” tall. $BMI=\frac{180\;lb\;\times\;\frac{1\;kg}{2.2\;lb}}{(67\;inches\;\times\;\frac{2.54\;cm}{inch}\;\times \;\frac{1\;m}{100\;cm})^{2}}\;=\;\frac{81.82\;kg}{\left( 1.7\;m \right)^2}\;=\;28.3\;kg/m^{2}$ Example 5.18: Calculate the BMI for a 22 yo patient who weighs 215 pounds and is 5’ 8” tall. $BMI=\frac{215\;lb\;\times\;\frac{1\;kg}{2.2\;lb}}{(68\;inches\;\times\;\frac{2.54\;cm}{inch}\;\times\; \frac{1\;m}{100\;cm})^{2}}\;=\;\frac{97.7\;kg}{\left( 1.73\;m \right)^2}\;=\;32.6\;kg/m^{2}$ Example 5.18: Calculate the BMI for a 61 yo patient who weighs 165 pounds and is 5’ 4” tall. $BMI\;=\;\frac{\frac{165}{2.2}}{\left( \frac{64\;\times\;2.54}{100} \right)^{2}}\;=\;\frac{75}{\left( 1.63 \right)^{2}}\;=\;28.2$ Module 5: Practice Problems 1. A physician wants to start a 7.3 kg pediatric patient on phenobarbital, 2.5 mg/kg/dose given twice daily. Phenobarbital liquid has a concentration of 20 mg/5 mL. Calculate the volume of solution needed to supply each dose. Where should you place the black line dosage marker on the syringe? 2. A physician wants to start a 4.4 kg pediatric patient on phenobarbital, 2 mg/kg/dose given tid. Phenobarbital liquid has a concentration of 20 mg/5 mL. What volume should you instruct the parents to administer? 3. A patient weighs 13 lbs 14 oz. Calculate the IV dose of sodium ampicillin at 100 mg/kg. Round the dose to the nearest 10 mg. 4. A physician orders 325 mg of acetaminophen PO every 4 – 6 hours as needed for pain relief for a patient weighing 35 pounds. The recommended dosage range is 10 – 15 mg/kg/dose. Is the order correct? If not, what dose should you recommend to the doctor? 5. An anesthesiologist orders fentanyl 0.75 mcg/kg/dose for a 30-pound patient. What amount should be prepared? Fentanyl is available as a 50 mcg/mL solution. What volume of fentanyl should be in the syringe? 6. A physician orders Tobramycin 50 mg IV for a 28-pound patient. The recommended dose is 2.5 mg/kg/dose. Is the dose correct? If not, what dose should you recommend to the doctor? The drug concentration is 40 mg/mL. What volume should be prepared? 7. A 25-pound patient needs ondansetron to treat their nausea and vomiting. The recommended dose is 0.15 mg/kg. The drug concentration is 2 mg/mL. How many milligrams of the drug should you order? What volume should be prepared? 8. Bactrim is a suspension containing Sulfamethoxazole 200 mg and Trimethoprim 40 mg per 5 mL. The recommended daily dose of the TMP component is 6 – 12 mg/kg/day. The product is usually administered twice daily. What dose should be prescribed at 8 mg/kg/day for a 43-pound patient? What volume of suspension is required for each dose? 9. What volume of Augmentin suspension (Amoxicillin/Clavulanate - 600 mg/42.9 mg/5 mL) should be administered per dose based on a 90 mg/kg/day amoxicillin component divided twice daily? The patient weighs 24 pounds. 10. Fer-in-sol solution contains 15 mg/mL of elemental iron (75 mg/mL of ferrous sulfate). A recommended dose for iron deficiency anemia is 2 mg/kg/dose administered three times a day. What reasonable volume of solution per dose should you recommend for a child who weighs 20 pounds? 11. A pediatric patient weighs 20 pounds. A physician orders: Amoxicillin suspension: 250 mg/5 mL Sig: 4 mL PO tid x 7 days The recommended dose for the patient’s condition is 45 mg/kg/day in divided doses, every 8 h. Is the dose correct? If not, what should the amount be? What volume should be administered? 12. A pediatric patient weighs 36 pounds. A physician orders: Azithromycin suspension: 200 mg/5 mL Sig: Day 1: 1 tsp PO, then Days 2 – 5: 1 tsp PO qd x 4 doses The recommended loading dose for the patient’s condition is 12 mg/kg on day 1. Subsequent daily doses are 6 mg/kg. Is the dose correct? If not, what should the amount be? What volume should be administered? 13. A pediatric patient weighs 42 pounds. A physician orders: Ibuprofen suspension: 100 mg/5 mL Sig: 1 tsp PO q 6 – 8 hours up to 5 days for pain relief The recommended dose for the patient’s condition is up to 40 mg/kg/day divided into 3 or 4 doses. Is the dosage correct according to the guidelines? If not, what should the amount be? Which size oral syringe should be provided to the parents? 14. The recommended IV dose of Amikacin is 15 mg/kg administered via an infusion over 1 hour. What dose should a 59-pound patient receive? The amikacin vial contains 250 mg/mL. What volume of the injection should be added to the IV bag? 15. A full-term newborn starts on Digoxin using the TDD 30 mcg/kg protocol. (TDD = total digitalizing dose). The recommended dosing schedule is ½ the TDD initially, followed by ¼ of the TDD for each subsequent dose at 8-hour intervals for 2 doses. The newborn weighs 7 pounds and 5 ounces. Digoxin oral solution is available as a 50 mcg/mL product. What dose and volume should you calculate for the two different doses? 16. A patient is 5’ 11” and weighs 206 pounds. Calculate their BSA. 17. A patient is 5’ 3” and weighs 122 pounds. Calculate their BSA. BSA Dosing Problems Use the drug dosing guidelines below to answer the questions about the patients whose height and weight is provided in the table. Patient \| Sex \| Age \| Ht (cm) \| Wt (kg) \| AS \| M \| 7 \| 115 \| 21 \| CY \| F \| 5 \| 118 \| 22 \| ES \| M \| 4 \| 118 \| 24 \| HT \| F \| 4 \| 108 \| 18 \| IM \| F \| 7 \| 114 \| 23 \| KE \| M \| 3 \| 104 \| 17 \| OS \| M \| 5 \| 101 \| 17 \| PC \| M \| 6 \| 109 \| 21 \| RX \| F \| 6 \| 95 \| 14 \| WL \| F \| 3 \| 91 \| 14 \| Refer to the drug labels for concentration information. Acyclovir can be used to treat viral infections in children. The guideline recommends doses as high as 600 mg/m2 every 6 hours for 10 days. The product is a 40 mg/mL oral suspension and sterile vials containing acyclovir sodium solution equivalent to 50 mg/mL. Allopurinol is used to prevent tumor lysis syndrome associated with certain cancer treatments. It is given as a short IV infusion of 200 mg/m2. Allopurinol is marketed as a sterile vial containing the equivalent of 500 mg of allopurinol (as the sodium salt) that is reconstituted to 30 mL before use, 16.7 mg/mL. Caspofungin is an anti-fungal drug given IV (over 1 hour) as a 70 mg/m2 loading dose the first day, followed by 50 mg/m2 daily thereafter. Dexamethasone is used in treating many conditions. The typical dose is 0.6 – 9 mg/m2/day in 3 or 4 divided doses. It is available as an oral solution containing 0.5 mg/5 mL. Dronabinol is used for nausea prophylaxis in chemotherapy patients. The National Cancer Institute (NCI) guideline for pediatric patients is 5 mg/m2 PO every 6 – 8 hours before beginning chemotherapy treatment, then 5 mg/m2 PO every 4 – 6 hours until 12 hours after the treatment. Hydrocortisone may be used to treat many conditions. For normal replacement therapy, the dosing guideline is 20 – 25 mg/m2/day. For congenital adrenal hyperplasia, the dosing guideline is 30 – 36 mg/m2/day, with 1/3 of the dose administered in the morning and 2/3 in the evening. 18. A physician orders acyclovir 600 mg/m2 for AS. What volume of the oral suspension is required for each dose? 19. CY requires 32 mg/m2/day of hydrocortisone for congenital adrenal hyperplasia. How should you instruct her mother to give the daily dose? 20. WL requires hydrocortisone for the treatment of congenital adrenal hyperplasia. The physician ordered hydrocortisone 12 mg in the morning and 24 mg in the evening daily. Is this dose within the recommended guidelines? 21. According to the dosing guidelines for immunocompromised patients, what is the total dose RX should receive for a 10-day course of acyclovir therapy? 22. PC requires allopurinol 200 mg/m2. The pharmacy prepared an infusion solution by transferring 12.5 mL of the sterile allopurinol solution into a 1L bag of normal saline. Is the correct amount of drug in the bag? What volume should have been added? 23. KE requires allopurinol before his chemotherapy. What volume of the reconstituted allopurinol solution should be added to KE’s infusion solution? 24. OS requires acyclovir 450 mg/m2 by IV infusion. What volume of acyclovir solution is required for each dose? 25. PC requires hydrocortisone replacement therapy. What dose should he receive each day? 26. RX requires caspofungin therapy. Calculate the appropriate dosing regimen. 27. WL is ordered dexamethasone 8.4 mg/m2/day in four divided doses. What volume of the oral solution (0.5 mg/5 mL) should she receive at each dose? 28. AS requires dronabinol per the NCI protocol. What dose should he receive? What volume? 29. CY requires allopurinol 200 mg/m2. What volume of the drug solution should be used to prepare the infusion? 30. A physician orders acyclovir 600 mg/m2 for ES. What volume of the drug solution should be used to prepare the bag for IV infusion? 31. HT requires normal hydrocortisone replacement therapy. What is the normal milligram range for this indication? 32. Calculate the caspofungin dosage regimen for IM. 33. KE has a severe allergic reaction, and his physician orders dexamethasone 2 mg every 6 hours. Is the prescribed amount correct? What is the normal range according to the guidelines? 34. Calculate the dose of dronabinol for OS. What volume should be given? 35. What percent loss in BSA would a patient experience whose right arm was amputated at the elbow. 36. A patient enrolled in an NCI protocol should receive an IV solution at 1.8 L/ m2 over 24 hours. Before their surgery, the patient’s BSA = 1.9 m2. What IV fluid rate should be used for the patient if their left arm has been amputated at the shoulder? 37. A patient with psoriasis has skin involvement over the upper chest area. What percentage of their skin surface area has psoriasis? 38. A patient has received severe 2nd and 3rd degree burns over the front of their two legs in a BBQ grilling accident. What percentage of their BSA has been burned? 39. Calculate the Ideal Body Weight for a female patient who is 5’ 6” tall. 40. Calculate the Adjusted Body Weight for a female patient who is 5’ 6” tall and weighs 210 pounds. Factor = 0.4. 41. A drug is dosed based on the adjusted body weight for obese patients using the factor 0.4. For these patients, the dose is 15 mg/kg. Calculate the dose for a female patient who is 5’ 3” and weighs 155 pounds. 42. A drug is dosed based on the adjusted body weight for obese patients using the factor 0.4. For these patients, the dose is 8 mg/kg. Calculate the dose for a female patient who is 5’ 7” and weighs 183 pounds. 43. Calculate the Ideal Body Weight for a male patient who is 5’ 8” tall. 44. Calculate the Adjusted Body Weight for a male patient who is 5’ 8” tall and weighs 215 pounds. Factor = 0.4. 45. A drug is dosed based on the adjusted body weight for obese patients using the factor 0.4. For these patients, the dose is 6 mg/kg. Calculate the dose for a male patient who is 6’ 5” and weighs 329 pounds. 46. A drug is dosed based on the adjusted body weight for obese patients using the factor 0.4. For these patients, the dose is 5 mg/kg. Calculate the dose for a male patient who is 5’ 10” and weighs 215 pounds. 47. Is this patient considered obese? Female, 5’ 4”, weighs 148 pounds. 48. Is this patient considered obese? Female, 5’ 5”, weighs 165 pounds. 49. Is this patient considered obese? Male, 5’ 9”, weighs 200 pounds. 50. Is this patient considered obese? Male, 5’ 11”, weighs 218 pounds. Problems 51 - 56 use the table from the Famvir® prescribing information, "Penciclovir dose adjustments in patients with renal insufficiency." 51. Male, 29 yo, SCr = 1.1 mg/dL, 6’ 1”, 185 pounds, suppressing genital herpes. 52. Male, 64 yo, SCr = 1.5 mg/dL, 5’ 2”, 120 pounds, treatment of herpes zoster. 53. Male, 75 yo, SCr = 1.3 mg/dL, 5’ 11”, 190 pounds, treatment of herpes zoster. 54. Female, 30 yo, SCr = 2.3 mg/dL, 5’ 0”, 210 pounds, suppressing genital herpes. 55. Female, 69 yo, SCr = 2.2 mg/dL, 5’ 2”, 105 pounds, treatment of herpes zoster. 56. Female, 64 yo, SCr = 2.7 mg/dL, 4’ 10”, 165 lb, suppressing genital herpes. Use Table 4 for problems #57 - 62. The dose calculation for this drug is based on the BSA-corrected CrCL. Calculate the patient's CrCL and BSA as usual, then use the following equation to calculate the BSA-adjusted value. $BSA\;adjusted\;CrCl\;(mL/min/1.73\;m^{2})=CrCl (mL/min)\times \frac{1.73}{Patient's\;BSA}\;m^2$ In the left column, choose the weight closest to the patient’s actual body weight. For example, if the patient weighs 52 kg, use the 50 kg dosing line. For a patient weighing 56 kg, use the 60 kg dosing line. Table 4: Reduced intravenous dosage of Primaxin I.V. in adult patients with impaired renal function and/or body weight < 70 kg 57. Male 75 yo, 4’ 11”, 119 pounds, SCr 1.1 mg/dL, imipenem 1 g/day. 58. Male 52 yo, 5’ 8”, 125 pounds, SCr 0.9 mg/dL, imipenem 1.5 g/day. 59. Male 31 yo, 6’ 4”, 202 pounds, SCr 1.5 mg/dL, imipenem 2 g/day. 60. Female 29 yo, 5’ 11”, 190 pounds, SCr 1 mg/dL, imipenem 1 g/day. 61. Female 63 yo, 5’ 2”, 103 pounds, SCr 2.4 mg/dL, imipenem 1.5 g/day. 62. Female 52 yo, 5’ 4”, 137 lb, SCr 1.6 mg/dL, imipenem 2 g/day. Practice calculating BMI 63. Calculate the BMI for a 47 yo patient who weighs 155 pounds and is 5’ 7” tall. 64. Calculate the BMI for a 28 yo patient who weighs 188 pounds and is 5’ 9” tall. 65. Calculate the BMI for a 22 yo patient who weighs 126 pounds and is 5’ 5” tall. 66. Calculate the BMI for a 36 yo patient who weighs 223 pounds and is 6’ 4” tall. Practice estimating affected BSA 67. A patient (BSA = 1.6 m2) is diagnosed with an osteogenic sarcoma involving the left fibula (lower leg). The oncologists recommended treatment with methotrexate 12 g/m2. Before chemotherapy starts, the patient will have a below-knee amputation. What methotrexate dose should be administered after the surgery? 68. An army veteran (pre-injury BSA = 1.8 m2) has been diagnosed with testicular cancer. The oncologists recommended treatment with dactinomycin 1000 mcg/m2. The patient lost their right arm during his tour of duty. What dactinomycin dose should be administered? What volume of solution is needed? The dactinomycin solution concentration is 500 mcg/mL. 69. A patient (pre-injury BSA = 1.5 m2) assigned to an NCI protocol should receive Lactated Ringer’s solution, 1800 mL/m2/day. The patient has had their left arm and left leg removed. Calculate the hourly fluid rate. 70. A woman comes to your store with a severe rash caused by exposure to poison ivy. Both legs are affected, from just above the knees to her ankles. She was walking on an overgrown woodland path. Estimate the percentage of her BSA affected by the rash. Practice using the "bedside" Schwartz equation Schwartz (bedside) eGFR (mL/min/1.73m2 ) \| Lean Body Weight (kg) q 12 h Dose (mcg) \| \| 5 kg \| 10 kg \| \| 30 \| 10 \| 20 \| 50 \| 12 \| 24 \| 70 \| 14 \| 28 \| 90 \| 16 \| 32 \| The q 12 h drug dose is based on the eGFR and the closest lean body weight. For example, if the patient weighs 7 kg, select the dose from the 5 kg column. If the patient weighs 8 kg, select the dose from the 10 kg column. 71. Calculate the drug dose for a 4.8 kg and 23 inches long baby. The SCr = 0.35 mg/dL. 72. Calculate the drug dose for an 11 kg and 33 inches long baby. The SCr = 1.2 mg/dL. 73. Calculate the drug dose for a 6.3 kg and 24 inches long baby. The SCr = 0.8 mg/dL. 74. Calculate the drug dose for a 9.5 kg and 30 inches long baby. The SCr = 0.35 mg/dL. Answers: 1. 4.6 mL 2. 2.2 mL 3. 630 mg 4. No! 160 – 240 mg 5. 10 mcg (0.2 mL) 6. No! 32 mg (0.8 mL) 7. 1.7 mg (0.8 – 0.85 mL)) 8. 160 mg (10 mL) 9. 4 mL 10. 1.2 mL 11. No! 135 mg (2.7 mL) 12. LD – OK. 100 mg (2.5 mL) 13. 190 mg (9.5 – 10 mL) 14. 400 mg (1.6 mL) 15. TDD = 100 mcg; 50 mcg (1 mL), 25 mcg (0.5 mL) 16. 2.2 m2 17. 1.6 m2 18. 12.3 mL 19. 9 mg AM, 18 mg PM 20. No! The range is 17.7 – 21.2 mg/day. 21. 14.64 g 22. No! ~ 9.6 mL 23. 8.4 mL 24. 6.2 mL 25. 16 – 20 mg/day 26. LD = 42.7 mg, then 30.5 mg/day 27. 12.5 mL 28. 4.1 mg (0.82 mL) 29. 10.2 mL 30. 10.7 mL 31. 14.6 – 18.3 mg 32. LD = 59.5 mg, then 42.5 mg/day 33. No, the dose is high. 0.4 – 6.3 mg/day. 34. 3.5 mg (0.7 mL) 35. ~ 4.5% 36. ~ 130 mL/h 37. ~ 9% 38. ~ 18% 39. 59.3 kg 40. 73.8 kg 41. 59.6 kg, 894 mg 42. 70.2 kg, 562 mg 43. 68.4 kg 44. 80.1 kg 45. 113.3 kg, 680 mg 46. 82.9 kg, 415 mg 47. No. < 130% of IBW 48. Yes. > 130% of IBW 49. No. < 130% of IBW 50. Yes. > 130% of IBW 51. 112 mL/min, 250 mg q12° 52. 38 mL/min, 500 mg q24° 53. 52 mL/min, 500 mg q12° 54. 26 mL/min, 125 mg q12° 55. 18 mL/min, 250 mg q24° 56. 14 mL/min, 125 mg q24° 57. 45 mL/min/1.73 m2, 125 mg q6° 58. 81 mL/min/1.73 m2, 250 mg q6° 59. 68 mL/min/1.73 m2, 500 mg q8° 60. 77 mL/min/1.73 m2, 250 mg q6° 61. 21 mL/min/1.73 m2, 250 mg q12° 62. 37 mL/min/1.73 m2, 250 mg q8° 63. 24.3 64. 27.8 65. 21 66. 27.1 67. 10.9 g. (Approx 9% loss of BSA) 68. 1650 mcg; 3.3 mL. (Approx 9% loss of BSA) 69. 82 mL/hr (Approx 27% loss of BSA) 70. Approx 18% 71. Dose = 14 mcg - q 12 h 72. Dose = 20 mcg - q 12 h 73. Dose = 10 mcg - q 12 h 74. Dose = 32 mcg - q 12 h Module 6: Intravenous Fluids and Drug Therapy This module will introduce and review the types of calculations associated with intravenous fluid therapy and intravenous drug administration. Module 6A: Intravenous Therapy A major component of hospital pharmacy practice involves preparing and assisting patient care staff with the appropriate use of intravenous drug therapy. Intravenous therapy can be given in different ways: - IV bolus injection, where a small volume of drug solution (e.g. up to 10 mL) is quickly introduced into a vein with a syringe. - Intermittent IV infusion, where a moderate volume of drug solution (e.g. 50 – 250 mL) is infused into a vein over a short period (e.g. 30 minutes – 2 hours) and repeated on a regular schedule. Most IV drug therapy in the hospital is administered via intermittent infusion. For example, a patient may receive a 30-minute infusion of ampicillin in 100 mL of normal saline every 8 hours for 5 days. - Continuous infusion, where an LVP solution (e.g. 500 or 1000 mL bag) is infused into a vein at a constant rate for several hours or longer. When one bag of solution empties, it is replaced with another bag. Therapy continues until the physician cancels or modifies the order. Hospitalized patients unable to drink enough are often administered IV maintenance fluids to help maintain circulatory volume. Intravenous fluid administration also plays an important role for patients being treated for dehydration, unusual fluid shifts within the body (third-spacing), or patients with heart and lung dysfunction. A commonly used weight-based dosing guideline is the Holliday-Segar method, which will be explained in the next section. Module 6B: Maintenance Fluid Calculations Everyone needs water and electrolytes to survive. Patients unable to eat and drink require fluids and salts to be administered via the vascular system (parenteral administration). While fluid management can be complex depending on the patient’s condition, this section will only introduce the basics. We will only deal with simple maintenance volume calculations. A reasonable question is how much water and salt is normally needed. The Holliday-Segar method was introduced for pediatric patients, but it has found wide applicability for all ages. The method uses the patient’s weight to calculate the daily fluid volume. Table 6.1. Holliday-Segar maintenance fluid calculation Weight \| Daily Requirement \| 1 – 10 kg \| 100 mL/kg \| 11 – 20 kg \| 1000 mL + 50 mL/kg for each kg > 10 kg \| > 20 kg \| 1500 mL + 20 mL/kg for each kg > 20 kg \| Example 6.1: What is the maintenance fluid requirement for a 2-month-old baby who weighs 5.3 kg? Calculate the hourly IV flow rate. $5.3\;kg\;\times\;100\;\frac{mL}{kg·day}\;=\;530\;\frac{mL}{day}$ $530\;\frac{mL}{day}\;\times\;\frac{1\;day}{24\;hours}\;=\;\frac{530\;mL}{24\;hours}\;=\;22.1\;mL/h\;or\;22\;mL/h$ Example 6.2: What is the maintenance fluid requirement for a 16-month-old toddler who weighs 16.5 kg? Calculate the hourly IV flow rate. $16.5\;kg\;=\;1000\;\frac{mL}{day}\;+\;\left( 50\;\frac{mL}{kg·day}\;\times\;6.5\;kg\right)=\;1325\;\frac{mL}{day}$ $1325\;\frac{mL}{day}\;\times\;\frac{1\;day}{24\;hours}\;=\;\frac{1325\;mL}{24\;hours}\;=\;55\;mL/h$ Example 6.3: What is the maintenance fluid requirement for a 10-year-old child who weighs 33 kg? Calculate the hourly IV flow rate. $33\;kg\;=\;1500\;\frac{mL}{day}\;+\;\left(20\;\frac{mL}{kg·day}\;\times\;13\;kg\right)=\;1760\;\frac{mL}{day}$ $1760\;\frac{mL}{day}\;\times\;\frac{1\;day}{24\;hours}\;=\;\frac{1760\;mL}{24\;hours}\;=\;73\;mL/h$ Depending on a patient’s fluid status or organ condition, a reduction or an increase in the maintenance fluid may be necessary. You may see an order to “run the patient a little dry at ¾ maintenance (75%).” Or, “Let’s run the IV at 1 ¼ maintenance (125%).” In these cases, you calculate the IV flow rate and multiply the hourly rate by the appropriate fraction. Example 6.4: For the 10-year-old child in example 3, calculate the IV flow rate if the physician decides to run the IV rate at 1 ¼ maintenance (125%). $1325\;\frac{mL}{day}\;\times\;\frac{1\;day}{24\;hours}\;=\;\frac{1325\;mL}{24\;hours}\;=\;55\;mL/h\;\times\;1.25\;=\;69\;mL/h$ Example 6.5: For the 16-month-old toddler in example 2, calculate the IV flow rate if the physician decides to run the IV rate at ¾ maintenance (75%). $1760\;\frac{mL}{day}\;\times\;\frac{1\;day}{24\;hours}\;=\;\frac{1760\;mL}{24\;hours}\;=\;73\;mL/h\;\times\;0.75\;=\;55\;mL/h$ Module 6C: Product Selection and Consideration Many drugs are manufactured in ready-to-use IV bags. The only preparation required is for the caregiver to connect the bag to the IV tubing and program the infusion pump to run at the correct flow rate and duration of time. Other drugs are supplied in vials as crystals or lyophilized powders that must be reconstituted before administration. The pharmacist must calculate the correct volume of drug to remove from the vial and inject the drug into the correct IV ‘base fluid.’ The most common base fluids are 0.9% sodium chloride injection (also called normal saline or NS) and dextrose 5% in water (also called D5W). Base fluids are available in IV bags containing 50, 100, 150, 250, 500, or 1000 mL to allow flexibility in drug compounding. It is important for patient safety and, sometimes, drug effectiveness to administer IV drugs at the correct infusion rate. Intermittent infusions are usually ordered to run over a convenient time appropriate to the drug and the patient size, e.g. gentamicin 40 mg in 50 mL NS over 1 hour. Some continuous infusions, especially those used in critical care, are administered at a rate depending on the patient body weight or body surface area. Dobutamine, for example, is used to increase a patient's cardiac output in cases of shock. The prescribing information document states, “The rate of infusion needed to increase cardiac output usually ranged from 2.5 to 15 mcg/kg/min ... On rare occasions, infusion rates up to 40 mcg/kg/min have been required to obtain the desired effect.” See: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=89becb0c-da60-4f43-0a98-29ff7a9eca58. Note that the infusion rate is expressed in terms of drug mass per time. The solution flow rate in mL/hour to achieve a specified mcg/kg/min rate depends on the dobutamine concentration in the solution (mcg/mL) and the patient’s body weight (kg). As mentioned earlier, many critical care drugs are commercially available in standardized concentrations in NS or D5W. However, there are patients where the use of these standardized concentration products may not be useful because of total daily fluid volume restrictions. In those cases, pharmacists frequently prepare small volumes of a base solution with a concentration different from those available using vials of the drug. Module 6D: Overfill in IV bags Manufacturers overfill bags of IV fluids to ensure patients can get the full labeled amount out of the bag. Overfill also helps decrease the effect of water evaporation from the bag during storage. The amount of overfill varies by manufacturer and may vary from batch to batch, so it is impossible to state how much overfill is in any particular bag. For example, a customer service representative for an IV fluid manufacturer stated that their bags of IV fluid labeled as 100 mL contained between 105 and 113 mL at the time of manufacture. Since the volume of the IV bag is unknown, it is impossible to accurately state the drug concentration of a compounded IV solution. The standard of practice is to calculate the drug concentration assuming the bag contains the labeled amount of fluid. If the drug concentration in a solution is critical, the base fluid and drug can be individually added to an empty IV bag. This method will usually result in a more accurate and precise concentration. Example 6.6: A physician orders a patient to receive norepinephrine by IV infusion. The hospital policy is to prepare norepinephrine infusions by adding 16 mcg of norepinephrine injection for every 1 mL of fluid in the bag. Norepinephrine is provided in vials containing 4 mg in every 4 mL. How many mL of norepinephrine injection must be added to a 250 mL bag of NS to prepare the infusion? $ 250\;mL\times \frac{16\;mcg\;Nor}{mL\;infusion}\times \frac{1\;mg\;Nor}{1000\;mcg}\times \frac{4\;mL\;inj}{4\;mg\;Nor}=4\;mL\; Nor\;injection$ Example 6.7: Most adult patients achieve blood pressure control with norepinephrine infusion of 2 – 4 mcg/min. How long will 250 mL of a 16 mcg/mL solution last if the drug is infused at the average rate of 3 mcg/min? $250\;mL\;infusion\times \frac{16\;mcg\;Nor}{mL\;infusion}\times \frac{1\;min}{3\;mcg\;Nor}\times \frac{1\;hr}{60\;min}=22.2\;hr$ NOTE: The norepinephrine concentration is slightly less than 16 mcg/mL (due to bag overfill and not including the added drug volume) but this difference is ignored in clinical settings. Example 6.8: A 95 lb patient was ordered a dobutamine infusion to start at 7.5 mcg/kg/min. The pharmacy sent a bag containing 250 mg of dobutamine in 250 mL of D5W. The nurse set the infusion pump to run at 5.5 mL per hour. Did the nurse enter the correct flow rate? $95\;lb\times \frac{1\;kg}{2.2\;lb}\times \frac{7.5\;mcg\;Dob}{kg\;\times \;min}\times \frac{1\;mg}{1000\;mcg}\times \frac{250\;ml\;soln}{250\;mg\;Dob}\times \frac{60\;min}{hr}=19.4\;mL/hr$ The starting infusion rate of 7.5 mcg/kg/min requires a solution flow rate of 19.4 mL/hr. The nurse did not set the correct flow rate on the pump. Example 6.9: A pharmacist added 50 mL of a 4% drug solution to 250 mL of D5W. What is the flow rate (mL/hr) required to deliver 0.02 mg/kg/min for a 175 lb patient? First, calculate the drug concentration in the infusion solution. $Drug\;concentration=\frac{50\;mL\;soln\;\times\; \frac{4000\;mg\;drug}{100\;mL\;soln}}{250\;mL\;+\;50\;mL}=6.67\;mg/mL\;infusion$ Now, find the flow rate based on the patient's body weight. $175\;lb\times \frac{1\;kg}{2.2\;lb}\times \frac{0.02\;mg}{kg\;\times \;min}\times \frac{1\;mL\;infusion}{6.67\;mg}\times \frac{60\;min}{hr}=14.3\;mL/hr$ Example 6.10: A pharmacist prepared an IV solution by adding 4 mL of a 1 Unit/mL solution to 100 mL of normal saline. The nurse set the infusion pump to run at 2 mL/hr. Calculate the infusion rate in Units/min. $Drug\;concentration=\frac{4\;mL\;\times \;\frac{1\;Unit}{4\;mL}}{100\;mL\;+\;4\;mL}=0.038\;Units/mL\\\\$ $\frac{2\;mL}{hr}\times \frac{0.038\;Units}{mL}\times \frac{1\;hr}{60\;min}=0.0013\;Units/min$ Module 6E: Bag Overfill and Added Drug Volume Considerations We know the pre-filled IV bags must contain an overfill, so we cannot know the true volume in the bag at the start of our compounding procedure. A reasonable question is if we are required to compound a solution with a prescribed drug concentration, thus adding more volume to the bag, how do we know the final concentration? We can consider two scenarios. In one case, the entire contents of the bag are infused into the patient. As long as the entire volume is infused, we can conclude that the patient received the correct dose. For example, the pharmacy prepared a 50 mL bag of NS containing 1 g of ampicillin (total volume injected = 4 mL). What volume is in the bag? 50 mL + 4 mL + overfill > 54 mL If all of the solution is infused, the patient receives the prescribed 1-gram dose. The other case involves setting the infusion pump to deliver 50 mL over ½ or 1 hour. In this scenario, the patient’s dose will be decreased by at least 10%, depending on the overfill volume, since the bag contains over 55 mL. As mentioned in the introduction section, there are times when the patient’s fluid status is critical because of heart or kidney dysfunction, pulmonary gas exchange concerns, edema, etc. In these cases, the medical team carefully keeps track of the daily total fluid volume the patient receives. In these situations, you may decide to use a syringe instead of an IV bag to hold the contents. We administer many drugs as IV infusions in critical care settings, like dopamine, dobutamine, nitroglycerin, adenosine, lidocaine, etc. If the bags are pre-mixed by the manufacturers, we can safely conclude the concentrations are correct since they are required to assay the product before release. If the pharmacy prepares the bag, the contents are rarely, if ever, analyzed. How should you handle that situation? While there are recommended starting doses for these drugs, the IV flow rate is frequently tweaked to target a specific response, like blood pressure or heart rate. The actual starting concentration, while unknown, will be close to that prescribed. You can consider a rule of thumb regarding the amount of the added drug in these critical care infusions. You can ignore the added amount if the volume added to the bag is less than 2% of the labeled volume. For example, adding 1 mL or less to a 50 mL bag or 2 mL or less to a 100 mL bag. If the volume to be added is greater than 2% of the stated bag volume, you might consider initially withdrawing that volume of base solution from the bag before injecting the drug. Let’s consider this case. A patient is prescribed 400 mg of infliximab in NS 500 mL to be infused over 2 hours. Each 100 mg vial of the lyophilized product is reconstituted with 10 mL of sterile water for injection. The pharmacy adds 40 mL of the solution to the bag, which is now very full. The infusion is started and set to run at 250 mL/h. After two hours, the nurse was ready to disconnect the IV and send the patient home. However, there was still over 50 mL in the bag, which contained the valuable life-altering drug. This happened to me (BK). I had to request to allow all of the drug to be infused. Remember, depending on the drug and patient condition, the added volume may be significant or insignificant. Module 6: Practice Problems Note: (IVR = IV Flow Rate) 1. Calculate the daily fluid requirement for a newborn weighing 3.1 kg. Calculate the hourly IVR. 2. Calculate the daily fluid requirement for a 6-month-old baby weighing 8.5 kg. Calculate the hourly IVR. 3. Calculate the daily fluid requirement for a 1-year-old baby weighing 9.7 kg. Calculate the hourly IVR. 4. Calculate the daily fluid requirement for a 1-year-old baby weighing 10.5 kg. Calculate the hourly IVR. 5. Calculate the daily fluid requirement for a 3-year-old child weighing 15.6 kg. Calculate the hourly IVR. 6. Calculate the daily fluid requirement for a 5-year-old child weighing 18.3 kg. Calculate the hourly IVR. 7. Calculate the daily fluid requirement for a 6-year-old child weighing 20.2 kg. Calculate the hourly IVR. 8. Calculate the daily fluid requirement for an 8-year-old child weighing 25.4 kg. Calculate the hourly IVR. 9. Calculate the daily fluid requirement for a 16-year-old teen weighing 60.8 kg. Calculate the hourly IVR. 10. Calculate the daily fluid requirement for a 19-year-old weighing 73 kg. Calculate the hourly IVR. 11. A patient weighs 87 kg. Calculate the hourly flow rate for ¾ maintenance. 12. A patient weighs 61 kg. Calculate the hourly flow rate for 1 ¼ maintenance. 13. A patient weighs 7.6 kg. Calculate the hourly flow rate for ¾ maintenance 14. A patient weighs 31 kg. Calculate the hourly flow rate for 1 ¼ maintenance. 15. What IVR (mL/h) will deliver 5 mcg/kg/min for a 35 lb child? D5W 250 mL Dopamine 600 mg/L 16. What IVR (mL/h) will deliver 3 mcg/kg/min for a 40 lb child? D5W 100 mL Dobutamine 400 mg/L 17. What IVR (mL/h) will deliver 20 mcg/kg/min for a 10 kg child? D5W 250 mL Lidocaine 900 mg/L 18. What IVR (mL/h) will deliver 7.5 mcg/kg/min for a 52 lb child? D5W 500 mL Dobutamine 500 mg/L 19. What IVR (mL/h) will deliver 0.3 mcg/min for a 25 lb child? D5W 50 mL Norepinephrine 100 mg/L 20. For problem #15, how many milliliters of Dopamine HCl injection 40 mg/mL do you need to add to a 250 mL bag to make the requested solution? 21. For problem #16, how many milliliters of Dobutamine HCl injection 12.5 mg/mL do you need to add to a 100 mL bag to make the requested solution? 22. For problem #17, how many milliliters of Lidocaine HCl injection 4% do you need to add to a 250 mL bag to make the requested solution? 23. For problem #18, how many milliliters of Dobutamine HCl injection 12.5 mg/mL do you need to add to a 500 mL bag to make the requested solution? 24. For problem #19, how many milliliters of Norepinephrine bitartrate injection 0.1% do you need to add to a 50 mL bag to make the requested solution? 25. You have three commercially available pre-mixed infusions of Dopamine HCl with concentrations of a) 0.8 mg/mL, b) 1.6 mg/mL, and c) 3.2 mg/mL. What IV infusion rates must the pump be set to deliver the dose in problem #1? 26. You have two commercially available pre-mixed infusions of Lidocaine HCl with concentrations of a) 4 mg/mL and b) 8 mg/mL. What IV infusion rates must the pump be set to deliver the dose in problem #17? 27. You have three commercially available pre-mixed infusions of Dobutamine HCl with concentrations of a) 1 mg/mL, b) 2 mg/mL, and c) 4 mg/mL. What IV infusion rates must the pump be set to deliver the dose in problem #18? 28. What IVR (mL/h) will deliver 0.25 mcg/kg/min to a 6lbs 6oz infant? D5W 250 mL Nitroglycerin 50 mg 29. Nitroglycerin is also available as a pre-mixed solution in D5W: a) 25 mg/250 mL, and b) 100 mg/250 mL. What would be the IVR for those solutions to deliver the same dose in problem #28? 30. Labetalol injection contains 100 mg of labetalol in every 20 mL. If 30 mL of labetalol injection is added to 100 mL of NS, what flow rate (mL/hr) is required to infuse 2 mg of labetalol per minute? 31. Vancomycin is available as 500 mg of solid that is reconstituted with 10 mL of sterile water for injection before use to produce a 50 mg/mL solution. How many mL of the reconstituted solution is required to prepare a vancomycin dose of 1250 mg? 32. Vancomycin must be diluted for infusion to a concentration of 5 mg/mL or less. A patient is ordered a dose of 1750 mg of vancomycin in NS. The pharmacy has bags of 50, 100, 250, and 500 mL NS. Which NS bag(s) should be used for this order? 33. Gentamicin injection is a sterile solution containing 80 mg in every 2 mL. The normal dose of gentamicin for certain infections is 5 mg/kg/day in 3 equal doses. How much gentamicin injection is required for each individual dose for a 46 kg child? 34. If the normal dose of gentamicin for certain infections is 5 mg/kg/day in 3 equal doses, what is the recommended daily dose for a 185 lb patient? 35. A patient is ordered 250 mg of paclitaxel by IV infusion. How much paclitaxel injection (30 mg/5 mL) is required to prepare the infusion? 36. Mesna is administered after ifosfamide to protect the bladder from the excreted metabolite acrolein, which causes hemorrhagic cystitis. The recommended mesna dose is 240 mg/m2 to be administered immediately (0 hours) after, then 4 and 8 hours after each dose of ifosfamide. Mesna injection is a solution containing 1 g in 10 mL. How many total mL of mesna injection are required for 3 doses (0, 4, and 8 hours) for a patient with a BSA of 2.2 m2? 37. Argatroban is a ready-to-use injection containing 50 mg in 50 mL. A patient is ordered argatroban infusion at 180 mcg/minute. Calculate the flow rate in mL/hr. 38. A patient receives 50 mg/50 mL of argatroban at 12.5 mL/hr. Calculate the infusion rate in mcg/min. 39. Aggrastat® injection is a ready-to-use solution containing 12.5 mg in every 250 mL. It is administered as a loading dose by IV bolus injection of 25 mcg/kg, followed immediately by a maintenance infusion of 0.15 mcg/kg/min. Calculate the volume of Aggrastat required for the loading dose and the infusion flow rate for a 145 lb patient. 40. Dexmedetomidine is an anesthetic drug and is supplied as a 200 mcg/2 mL injection. It is recommended to be diluted to 4 mcg/mL for infusion by adding the correct volume of drug solution and normal saline to an empty sterile IV bag. A patient is ordered a 0.6 mcg/kg/hr infusion of dexmedetomidine. How many mL of dexmedetomidine injection and how many mL of NS should be mixed to provide enough solution for 28 hours of therapy for a 196 lb patient? 41. Propofol is marketed as an injectable emulsion containing 200 mg of propofol in every 20 mL. The emulsion is administered without further dilution. What flow rate (mL/hr) should be used to provide 125 mcg/kg/min for a 130 lb patient? 42. Micafungin is an antifungal drug. It is supplied as a sterile solid reconstituted with 5 mL of sterile water for injection to produce a 10 mg/mL solution. The normal dose is 2.5 mg/kg once daily for patients ≥ 30 kg or 3 mg/kg for patients < 30 kg. It should be diluted with D5W to a concentration less than 1.5 mg/mL for infusion. Calculate the volume of reconstituted micafungin to provide the dose for a 55 lb patient. The pharmacy has D5W bags in 50, 100, 250, and 500 mL. Which bag size should be used? 43. Lidocaine infusions over 1 hour can be used to treat pain in certain conditions. The dose is based on the smaller actual or ideal body weight value. Calculate the infusion rate needed to deliver 2 mg/kg for: a) male, 5’ 11”, 174#, and b) female, 5’ 3”, 113#. The IV bag contains 2000 mg Lidocaine HCl in 250 mL of D5W. 44. The manufacturer recommends diluting angiotensin II (Giapreza®, 2.5 mg/1 mL) to a total volume of 500 mL with normal saline. What is the solution concentration in ng/mL? 45. Angiotensin II (Giapreza®, 2.5 mg/1 mL) increases blood pressure in patients with septic shock. A typical infusion conentration is 2.5 mg in a total volume of 500 mL normal saline. What IV infusion rate should be used to deliver 20 ng/kg/min for a 55 kg patient? Answers: 1. 310 mL/day - 13 mL/hr 2. 850 mL/day - 35 mL/hr 3. 970 mL/day - 40 mL/hr 4. 1025 mL/day - 43 mL/hr 5. 1280 mL/day - 53 mL/hr 6. 1415 mL/day - 59 mL/hr 7. 1504 mL/day - 63 mL/hr 8. 1608 mL/day - 57 mL/hr 9. 2316 mL/day - 97 mL/hr 10. 2560 mL/day - 107 mL/hr 11. 89 mL/hr 12. 121 mL/hr 13. 24 mL/hr 14. 90 mL/hr 15. 8 mL/hr 16. 8.2 mL/hr 17. 13.3 mL/hr 18. 21.3 mL/hr 19. 2 mL/hr 20. 3.8 mL 21. 3.2 mL 22. 5.6 mL 23. 20 mL 24. 5 mL 25. a) 6 mL/hr, b) 3 mL/hr, c) 1.5 mL/hr 26. a) 3 mL/hr, b) 1.5 mL/hr 27. a) 10.6 mL/hr, b) 5.3 mL/hr, c) 2.7 mL/hr 28. 0.2 mL/hr 29. a) 0.4 or 0.5 mL/hr, b) 0.1 mL/hr 30. 104 mL/hr 31. 25 mL 32. 500 mL bag 33. 1.9 mL/dose 34. 420 mg/day 35. 41.7 mL 36. 15.8 mL 37. 10.8 mL/hr 38. 208 mcg/min 39. Load - 33 mL; maintenance flow rate = 11.9 mL/hr 40. 15 mL of drug; 360 mL of NS; empty 500 mL bag 41. 44.3 mL/hr 42. 25 kg, 75 mg dose = 7.5 mL, 50 mL bag D5W 43. a) 18.8 mL over 1 h, b) 12.8 mL over 1 h. 44. 5000 ng/mL 45. 13.2 mL/hr Module 7: Applications of Linear Regression in Pharmacy Introduction This module is about linear regression (LR). This will be an introduction to the topic for some. For others, it may be a review of material previously learned. In either case, we will concentrate on the mechanics of LR using the TI-84 Plus CE line of calculators. If you don’t own one, you can check one out from the Dean’s office for use during the semester. You will use a TI-84 Plus CE in PHPS 720 Pharmacokinetics next semester to run some PK programs that I have written to make your life a little easier in that course. In this section, you will use your calculator to find the equation of the best-fitting line to a data set. After the data is entered, the calculator will return values for the slope, y-intercept, and r2. R-squared (r2) measures how well a linear regression model predicts the data set. We will not be concerned with the mathematics of the process. If you are interested, you will find plenty of material online, in YouTube videos, or in a statistics course. Module 7A: What is Linear Regression? What is LR? LR is a method for applying a straight-line model between the explanatory variable (x), and the response variable (y). Recall that the equation for a straight-line is: $y\;=\;mx\;+\;b$ where the response (y) can be predicted by multiplying the variable (x) by the slope of the line and then adding the intercept. Too many words! Let’s look at a picture. The red diamonds are scattered, but the y-value seems to increase as the x-value increases. We could ask, “If we know the value of x can we predict the value of y?” Can we mathematically model that relationship? At the most basic level, this is what LR is about. If we know something about the x-value, can we predict the value of y? Let’s look at another case you will frequently be asked to solve. In this case, a straight line does not predict the plasma concentration values very well. The data points are below the line in the middle of the plot. The values are above the prediction line at either end of the data range. Some of you will recall that when dealing with drug plasma concentrations, the relationship is not linear but exponential. $C_{p}=C_{p,0}\;\times\;\,e^{-kt}$ We can linearize the equation by taking the natural log of both sides. $ln\;C_{p}=ln\;C_{p,0}-kt$ Let’s plot the above pharmacokinetic data on a logarithmic scale for the y-axis Cp values and see what we get. Now, this graph appears to show a linear relationship between the ln Cp value and time. What is a model? A model is a mathematical equation used to predict the value of y if you know x, or predict the value of x if you know y. For instance, is there a relationship between a patient’s height and their weight? How about between a patient’s serum creatinine and their creatinine clearance? Is there a relationship between the size of the drug dose and the patient’s peak plasma level? Is there a relationship between the patient’s plasma level and the time elapsed after the dose? You know these relationships exist based on your classes, but you may not be able to predict the y-value given an x-value because you are unaware of the particular model. Here are the two models you will apply most often during your time in the SoP. 1. Logarithmic, 1st – order model (the rate depends on the value of y): $C_{p}=C_{p,0}\;\times\;\,e^{-kt}$ a) Drug degradation from Solution dosage forms, b) Patient drug plasma levels, and c) Radioisotope counts and concentrations. 2. Linear, 0 – order model (the rate is constant): $C_{t}=C_{0}-kt$ d) Drug degradation from Suspension dosage forms, e) In this course, other examples that are not 1st order. What do you need to memorize? If the problem involves radioactivity, drug plasma levels, or drug degradation in solution, the model is 1st – order. If the problem does not involve a, b, or c, but only drug degradation from a suspension, then the model is 0 – order. Four representative examples are provided. Module 7B: Drug Degradation from Suspension Dosage Forms, 0-order, Linear Model A suspension dosage form degrades according to the 0-order model. The equation that predicts the concentration is the starting concentration, C0, minus the product of the 0-order rate constant and time: $C_{t}=C_{0}-kt$ Here is the data for the amount of drug remaining in a suspension over time. Note that time is the x-variable. The y-variable is the measured amount of drug, expressed as the concentration remaining in the bottle. Time (days since prepared) \| Concentration (mg/mL) \| 0 \| 49.8 \| 20 \| 46.6 \| 30 \| 46.1 \| 45 \| 44.8 \| 60 \| 41.7 \| 90 \| 39.9 \| Let’s take a look at the graph. The graph looks linear, although the data is not perfectly straight. We also know that suspensions degrade via a 0 – order process, so based on that scientific reasoning, we are justified in fitting the data to a straight line. We always see some degree of scatter in the data. This is expected since no man-made measurements are absolute. Now, let’s look at the mechanics of entering the data into your calculator. This module has a recorded lecture for the 707 course. If you use this text in an environment that cannot access the recorded lecture, you will find several videos on YouTube demonstrating how to perform linear regression with the TI family of calculators. Setting up your TI-84 Plus CE calculator (You only need to do this once.) 1. Goal: Verify that the stat diagnostics is turned ON. - Turn on the calculator. - Select mode. - Arrow down to stat diagnostics. - Arrow over to ON - Hit enter. 2. Goal: Clear the data columns of all data and equations. - Hit 2nd mem 3 (Clear all entries) - Hit 2nd mem 4 (Clear all lists) 3. Goal: Enter the data - Select stat - Select 1: Edit… - Enter all the x data (usually time) - Arrow over to L2 - Enter all the y data (usually concentration) 4. Goal: Running the Regression calculation - Select stat - Arrow over to CALC - Tab down to 4, or just enter 4. (LinReg(ax+b) 5. Goal: Verify the correct columns for the regression analysis. - You will see this screen. CRITICAL POINTS - You must specify which columns contain the x and y-values - You must verify that the Xlist is L1 and the Ylist is L2. - In this screenshot my Ylist shows L3 from another problem. - To change the Ylist, arrow down and type 2nd 2 (above the keypad for 2 is L2). Now, arrow down to Calculate and select enter. Let me start off by reminding everyone that we are focusing on the mechanics of performing a linear regression with a calculator. This is NOT a statistics course. We will not be asking questions about the interpretation of r or r2. 6. Goal: Interpreting the results of the regression calculation. • The heading reminds you of the regression type, in this case, linear regression. • Line 1 again reminds you of the model, y = ax + b. • Line 2 is the slope, - 0.111. The minus sign indicates the value of the slope is decreasing with increasing x (time) values. Another fine point to note. While the slope is – 0.111, the value of the rate constant is + 0.111. (The negative sign is accounted for in the model equation.) This is represented in the equation by m. The units for m are y units/x units, in this case, mg/mL/day. • Line 3 is the intercept, 49.339. That is the best statistical estimate of the time 0 concentration value. This is represented in the equation by b. The units for b are the units for y, in this case, mg/mL. The regression intercept is rarely, if ever, the same as the zero time value in the table. • Line 4 is r2, the coefficient of determination. It has a formal statistical definition, but we will not concern ourselves with the meaning. The value is not used in any calculations. It does provide interested researchers with information about the “goodness” of the model fit to the data. •Line 5 is r, the square root of r2 although here it is negative because the regression slope is negative. 7. Goal: Summary and writing the answer to the problem. You need to write down the linear regression equation and be able to use it to solve problems. For this problem, the equation is: $C_{t}=49.34\;mg/mL\;-0.111\;\frac{mg}{mL\;\times\; day}\times t \;(days) $ Here are some typical calculations you will be expected to perform. Example 7.1: Find the time required for the concentration to decrease to 45 mg/mL. $45\;\frac{mg}{mL}=49.34\;\frac{mg}{mL}-0.111\frac{mg}{mL\;\times\;day}\times t$ $\frac{(45\;-\;49.34)\;\frac{mg}{mL}}{-0.111\;\frac{mg}{mL\times day}}=39.1\;days$ Example 7.2: Find the concentration at 25 days. $C_{t=25d}=49.34\;\frac{mg}{mL}\;-0.111\;\frac{mg}{mL\;\times\;day}\times\;25\;days=46.6\;mg/mL $ Module 7C: Drug Degradation from Solution Dosage Forms, 1st-Order, Exponential Model Here is the data for the amount of drug remaining in a solution over time. Note that time is the x-variable. The y-variable is the measured amount of drug, expressed as the concentration remaining in the bottle. Time (days since prepared) \| Concentration (mg/mL) \| 2 \| 15.8 \| 5 \| 7.9 \| 8 \| 4.2 \| 12 \| 1.3 \| Let’s take a look at two graphs. In (a), we observe the data points do not fall on a straight line. Recall that drug degradation in solution occurs via a 1st -order process. For a 1st-order process, a plot of ln C versus time is linear. And that is what is observed in (b). We can start to perform the linear regression analysis, but first, let’s clear the data entry table. - Hit 2nd mem 3 (Clear all entries) - Hit 2nd mem 4 (Clear all lists) Enter the data, as described in the previous section (select stat, then Edit… . Your screen should look like this. Now, as shown here, use the arrow (toggle) keys to move the black insertion bar to the cell containing L3, at the top of the column. Note that the text under the table shows L3 = . We know the relationship between x and y should approximate a straight line when the y data is transformed to its natural log value. The command you use to transform all of the numbers at once is: ln ( then 2nd then L2 then enter The calculator inserts the values of ln(L2) in L3. [Note: you can select the number of digits the calculator displays by using the mode key, and tabbing down to float, then tabbing over to the number of digits you prefer. 2nd quit returns you to your previous screen.] Your screen should look like this: Now that the data is entered into the calculator, the next step is to run the regression, as previously described. Select stat, arrow to CALC, select 4: LinReg(ax+b). CRITICAL POINT In this case, the x-values are in L1 and the y-values are in L3. Tab down to Ylist, type 2nd L3 (L3 is above the key labeled 3, how convenient). Tab down to CALCULATE, then select enter. Here are your linear regression results for the ln transformed data. Results Here is how to interpret your results. • The screen heading reminds you that you performed a linear regression. • The model is y = ax + b. Of course, we think of it as y = mx + b. • The slope = - 0.248. This is the 1st-order degradation rate constant. The sign indicates the slope is negative and the concentration decreases with time. Another fine point to note. While the slope is – 0.248, the value of the rate constant is + 0.248. The negative sign is accounted for in the model equation. The units of k for the 1st order model are reciprocal time. In this case, the time units are days. The value of k is interpreted as 0.248/day or 0.248 d-1. • The y-intercept is 3.302. This is the best-fit value of the solution concentration at time = 0. Note the intercept is a transformed value. Recall that the concentration value at 2 hours was approximately 15 mg/mL. The intercept at time = 0 will be bigger than 15 mg/mL. Since the data was transformed by taking the ln (C), to return the real value, you perform the inverse of ln, raise e to the power b. That is eb, or e3.302 = 27.2 mg/mL. A common error is made when students forget to transform the intercept. • r2 = 0.994. (This represents a “good” fit.) • You can ignore the value of r in this course. Summary You need to correctly write and use the linear regression equation to solve problems. In this case, the equation is: $ln\;C_{t}=ln\;C_{0}-kt$ $ln\;C_{t}=3.302-0.248/day\times t$ Here are some typical calculations you will solve in the course. Example 7.3: Find when the solution concentration was 22.5 mg/mL. ln 22.5 = 3.302 – 0.248 × t 3.114 = 3.302 – 0.248 × t 3.302 – 3.114 = 0.248 × t $t=\frac{3.302\;-\;3.114}{0.248}=0.76\;days\cong 18\;hours$ Example 7.4: What is the expected concentration on day 4? $ln\;C(t=4\;days)=3.302-0.248/day\times 4\; days$ $ln\;C(4\;t=days)=2.31 $ $C(t=4\;d)=e^{2.31}=10.1\;mg/mL$ Here is another way to manipulate this equation that you may find quicker to perform with a calculator. This technique will be emphasized in the Pharmacokinetics course. $C_{smaller}=C_{larger}\;\times\;e^{-kt}$ Example 7.5: Let me redo 7.3, $22.5\;mg/mL=27.2\;mg/mL\times e^{-0.248t} $ $\frac{22.5\;mg/mL}{27.2\;mg/mL}=e^{-0.248t}$ $ln\;(\frac{22.5\;mg/mL}{27.2\;mg/mL})=ln(e^{-0.248t})$ $ln(0.827)\;=\;-0.248\;\times\;t$ $\frac{-0.19}{-0.248}=t=0.77\;days\;=\;18\;hours$ The difference between 7.3, (0.76 days) and 7.5, (0.77 days) is due to using three decimal places and general rounding and truncation errors. This is not significant difference as both answers round to 18 hours. Example 7.6: Let me redo 7.4, $C_{smaller}=27.2\;mg/mL\times e^{-0.248/day\;\times\;4\;days}=10.1\;mg/mL$ I am accustomed to using the exponential form of the equation (7.5 and 7.6). You should choose the form with which you feel most comfortable. Module 7D: Plasma Concentrations after an IV Bolus Dose, 1st-Order, Exponential Model The 1st-order model is used for drug degradation in solution dosage forms, plasma concentrations following an IV bolus dose, and in radioactive decay processes. The mathematics and the regression procedures are the same, so we will go a little quicker through these calculations. Please make sure to solve enough problems so you will feel confident when performing these calculations in practice. Here is data for a patient who received an IV bolus dose of a drug. Note that time is the x-variable. The y-variable is the measured plasma drug concentration. This problem is analogous to those in the previous section. Time (h post dose) \| Concentration (mcg/mL) \| 1 \| 28.1 \| 4 \| 16.2 \| 8 \| 6.8 \| 15 \| 1.9 \| Verify that the columns in your calculator are clear of data. - Hit 2nd mem 3 (Clear all entries) - Hit 2nd mem 4 (Clear all lists) Enter the data, and transform L2 to ln(L2) in column L3. Your screen should look like this. Run the regression, verifying that the Xlist is L1 and the Ylist is L3. Summary You need to correctly write the linear regression equation and use it to solve problems. In this case, the equation is: $ln\;C_{t}=ln\;C_0-kt$ $ln\;C_{t}=3.5265-0.1938/hr\times t\;(hr)$ Example 7.7: a) List the values for k, intercept (ln b) and eb, and r2. 0.1938/h, 3.5265, 34 mcg/mL, and 0.9988. b) At what time post-dose was the Cp = 4 mcg/mL? (Solve for t) $ln\;C_{t}=3.5265-0.1938/hr\times t\;(hr)$ $ln\;(4)=3.5265-0.1938/hr\times t\;(hr) $ $1.3863=3.5265-0.1938/hr\times t\;(hr) $ $\frac{1.3863\;-\;3.5265}{-\;0.1938\;\frac{1}{h}}\;=\;11\;h$ c) When will the Cp = 0.7 mcg/mL? (Solve for t) $ln\;(0.7)=3.5265-0.1938/hr\times t\;(hr)$ $-\;0.3567=3.5265-0.1938/hr\times t\;(hr) $ $\frac{-\;0.3567\;-\;3.5265}{-\;0.1938\;\frac{1}{h}}\;=\;20\;h$ d) What is the expected Cp 24 hours after administering the dose? (Solve for Ct) $ln\;C_{t}=3.5265-0.1938/hr\times 24\;hr$ $ln\;C_{t}=3.5265-4.6512$ $ln\;C_{t}=-\;1.1247$ $e^{ln\;C_t}=e^{-1.1247} $ $C_t\;=\;0.3\;\frac{mcg}{mL} $ Module 7E: Radioactive Isotope Decay, 1st-Order, Exponential Model Radioactive decay occurs via a 1st-order process. The decay constant is usually denoted by the Greek letter, 𝜆. Lambda (𝜆) has units of reciprocal time, time-1, for example: h-1, day-1, week-1, month-1, or year-1. Most clinically useful medical isotopes have a half-life measured in hours to days. Recall half-life = 0.693/𝜆. As is usually the case in pharmacy, time is the x-variable. The y-variable is the radioactivity, often measured in milliCurie or microCurie (mCi or 𝜇Ci). (The unit is named in honor of Marie and Pierre Curie.) Please note: Radioactivity remaining in a sample is often denoted by the letter A (activity). Therefore the general first-order equation is: $A_{t}=A_{0}e^{-\lambda t}$ or $Ln\;A_{t}=Ln\;A_{0}-\lambda t$ The mathematical approach to this example problem is analogous to the problems in sections C and D. Let's perform another regression. A radiopharmaceutical was prepared on day 0. Time (days) \| Activity (mCi) \| 2 \| 800 \| 5 \| 565 \| 10 \| 316 \| 24 \| 62 \| Before starting the regression procedure, verify that the columns are clear of data. - Hit 2nd mem 3 (Clear all entries) - Hit 2nd mem 4 (Clear all lists) Enter the data, and transform L2 to ln(L2) in L3. Your screen should look like this. Run the regression, verifying that the Xlist is L1 and Ylist is L3. $Ln\;A_{t}=Ln\;A_{0}-\lambda t$ $ln\;A_{t}=6.9718-0.1163/day\times t$ Example 7.8: a) List the values for 𝜆, intercept (ln b), eb, and r2. 0.1163/d, 6.9178, 1010 mCi, 0.999. b) At what time post-prep was the Activity = 400 mCi? (Solve for t) $ln\;A_{t}=6.9178-0.1163/day\times t\;(days)$ $ln\;(400)=6.9178-0.1163/day\times t\;(days) $ $5.9915=6.9178-0.1163/day\times t\;(days) $ $\frac{5.9915\;-\;6.9178}{-\;0.1163\;\frac{1}{day}}\;=\;8\;days$ c) What is the expected Activity on day 30? (Solve for Ct) $ln\;A_{t}=6.9178-0.1163/day\times 30\;days$ $ln\;A_{t}=6.9178-3.489$ $ln\;A_{t}=3.4288$ $e^{ln\;A_t}=e^{3.4288} $ $A_t\;=\;30.8\;mCi$ Module 7F: Working with Regression Results, the 0-Order Model The motivation for the next 4 sections is based on our experience helping students use the linear regression results to make valid conclusions and predictions. As mentioned earlier in the Module, the equation that describes the degradation of a drug in a suspension dosage form is: $C_{t}=C_0-kt$ Here Ct is the drug concentration at some time t after the suspension was prepared. C0 is the regression drug concentration at time = 0. You can use this equation to find the time when a sample will be a particular concentration. You can also use the equation to predict the sample concentration at a particular time. The important linear regression parameters are b, the y-intercept (C0 value), and k, the 0-order rate constant (the slope). The units for the zero-order rate constant are Conc × t-1. There are four parameters in the equation. LR returns C0 and k. If you want to predict the concentration at a particular time, past or future, solve the equation for Ct by inserting the desired value of t. If you want to predict when a suspension will be a particular concentration, use that value and solve for t. Below is a screen capture of a regression result for a oral suspension. Let’s examine how to manipulate the equation to extract our desired information. In this case, the rate constant units are mg/mL/days, and the concentration is mg/mL. Example 7.9: a) Write out the correct form of the linear regression equation: $C_{t}=C_0-kt$ b) Enter the calculated regression parameters in their correct places: $C_{t}=99.9\;mg/mL\;-0.61\;mg/mL/day\times t\;(days)$ c) What is the concentration of the suspension after 12 days? $C_{t}=99.9\;mg/mL\;-0.61\;mg/mL/day\times 12\;(days)=92.6\;mg/mL$ d) How long will it take for the concentration to decrease to 90 mg/mL? $\frac{(99.9\;-\;90)\;mg/mL}{0.61\;\frac{mg}{mL\;\times\;days}}=16.2\;days$ So, in summary, the equation has four parameters (or values). You obtain two of the values from the regression procedure. Thus, there are only 2 questions that can be asked. Given a time interval, how much drug is remaining? How long will it take to reach a certain concentration? Let’s look at the other three types. Module 7G: Working with Regression Results, the 1st-Order Model, Solution Degradation Below is a screen capture of a regression result from a solution stability study. Let’s review how to manipulate the equation to extract our desired information. In this case, the rate constant units are days-1, and the concentration is mg/mL. Example 7.10: What is the best estimate of the solution concentration at time = 0? $e^{4.3294}=75.9\;mg/mL$ When will the concentration equal 70 mg/mL? (ln 70 = 4.2485) $ln\;C_{t}=ln\;C_{0}-kt $ 4.2485 = 4.3294 - 0.0067 × t $t=\frac{4.3294\;-\;4.2485}{0.0067/day}=13.3\;days$ What is the expected solution concentration thirty days after preparation? $ln\;C_{t}=4.3294\;-\;0.0067\;1/days\;\times\;30\;days$ $ln\;C_{t}=4.3294\;-\;0.201$ $ln\;C_{t}=4.1284$ $C_{t=30\;days}=e^{4.1284}=62.1\;mg/mL$ Module 7H: Working with Regression Results, the 1st-Order Model, Drug Plasma Concentrations Here is another example of the 1st-order model applied to the interpretation of drug plasma concentrations following an IV bolus dose of a medication. This is a typical problem you will solve in the pharmacokinetics course. Below is a screen capture of a regression result from a patient pharmacokinetic study. In this case, the rate constant units are hours-1, and the concentration is mcg/mL. Example 7.11: What is the best estimate of the solution concentration at time = 0? $e^{2.915}=18.4\;mg/mL$ The next dose should be given when Cp = 3 mcg/mL. (Ln 3 = 1.0986) What time will that occur? $ln\;C_{t}=ln\;C_{0}-kt$ $1.0986=2.9150\;-\;0.3048\;\times\;t$ $t=\frac{2.915-1.0986}{0.3048/hr}=6\;hr \;post\;dose$ What is the expected Cp value three hours after the dose was administered? $ln\;C_{t}=2.9150\;-\;0.3048/h\;\times\;3h$ $ln\;C_{t}=2.9150\;-\;0.9144$ $ln\;C_{t}=2.0006$ $C_{t=3h}=e^{2.0006}=7.4\;mcg/mL$ Module 7I: Working with Regression Results, the 1st-Order Model, Radioactive Isotope Decay Recall that radioactive decay also occurs via a 1st-order process. The decay constant is usually denoted by the Greek letter 𝜆. Lambda (𝜆) has units of reciprocal time, time-1, for example, h-1, day-1, week-1, month-1, or year-1. Most clinically useful medical isotopes have a half-life measured in hours or days. Recall half-life = 0.693/𝜆. The units of radioactivity are often measured in milliCurie or microCurie (mCi or mCi). If you like to arise before dawn, nuclear pharmacy might be your specialty! A calibration study was done for 169Yb. The regression results are shown. Units for 𝜆 are in days-1. Example 7.12: What is the activity at t = 0? $A_{0}=e^{8.962}=7800\;mCi$ When will the activity = 3000 mCi? (Ln 3000 = 8.0064) $Ln\;A_{t}=Ln\;A_{0}-\lambda t$ $8.0064=8.9620\;-\;0.0216\;\times\;t$ $t=\frac{8.9620\;-\;8.0064}{0.0216/day}=44.2\;days\;after\;preparation$ Module 7: Practice Problems 1. Data for a drug suspension stability study are shown. Time (months) \| Conc (mg/mL) \| 0 \| 100.0 \| 12 \| 94.1 \| 24 \| 86 \| 36 \| 81.4 \| 48 \| 69.5 \| Calculate the equation of the regression line and r2. Find the time required for the drug concentration to decrease to 40 mg/mL. Find the concentration at 18 months. 2. The stability of an extemporaneously prepared drug suspension was studied. Time (months) \| Conc (mg/mL) \| 3 \| 46.8 \| 6 \| 44.4 \| 12 \| 40.5 \| 24 \| 24.5 \| \| \| Calculate the equation of the regression line and r2. Find the time required for the drug concentration to decrease to 30 mg/mL. Find the initial concentration and the concentration at 4 months. 3. The stability of an experimental drug suspension was studied. Time (months) \| Conc (mg/mL) \| 15 \| 13 \| 40 \| 7.8 \| 60 \| 5.0 \| 85 \| 0.3 \| Calculate the equation of the regression line and r2. Find the time required for the drug concentration to decrease to 5 mg/mL. Find the initial concentration and the concentration at 48 months. 4. The stability of a drug suspension was studied. Time (months) \| Conc (mg/mL) \| 1 \| 247.6 \| 4 \| 240.4 \| 12 \| 221.9 \| 30 \| 196.6 \| Calculate the equation of the regression line and r2. Find the time required for the drug concentration to decrease to 225 mg/mL. Find the initial concentration and the concentration at 36 months. 5. A small-scale clinical study evaluated the utility of predicting a diabetic patient’s average serum glucose (y) based on their Hgb A1c values (x). These data are expected to follow a linear model. A1c (%) \| Ave Glucose (mg/dL) \| 4.7 \| 85 \| 5.2 \| 96 \| 5.7 \| 126 \| 6.4 \| 125 \| 6.8 \| 140 \| 6.9 \| 161 \| 7.5 \| 175 \| 7.7 \| 163 \| 7.9 \| 174 \| 8.2 \| 193 \| Calculate the equation of the regression line and r2. If a patient had an A1c value = 7, what would their average serum glucose have been? If a patient had an average serum glucose value = 150, what would be their % A1c? 6. The stability of a drug suspension was studied. Time (months) \| Conc (mg/mL) \| 3 \| 0.982 \| 6 \| 0.973 \| 12 \| 0.951 \| 24 \| 0.858 \| Calculate the equation of the regression line and r2. Find the time required for the drug concentration to decrease to 0.8 mg/mL. Find the initial concentration and the concentration at 18 months. 7. A group of pediatric specialists conjecture they can predict the 50th percentile weight for patients between 3 and 30 months. These data are expected to follow a linear model. Age (months) \| 50th percentile Weight (kg) \| 3 \| 6 \| 12 \| 10.2 \| 30 \| 13.7 \| Calculate the equation of the regression line and r2. A patient is 18 months old. Predict their weight. A patient weighs 12 kg. Predict their age. 8. The stability of a commercial drug suspension was studied. Time (months) \| Conc (mg/mL) \| 12 \| 48 \| 24 \| 42 \| 36 \| 40 \| 48 \| 33 \| \| \| Calculate the equation of the regression line and r2. Find the time required for the drug concentration to decrease to 25 mg/mL. Find the initial concentration and the concentration at 6 months. 9. A small-scale clinical study evaluated the relationship between diabetic patients' BMI (y) and Hgb A1c values (x). These data are expected to follow a linear model. A1c (%) \| Ave BMI (kg/m2) \| 5.7 \| 25.3 \| 5.8 \| 26.2 \| 5.9 \| 27.1 \| 6.0 \| 28.4 \| 6.1 \| 29.6 \| 6.2 \| 30.7 \| 6.3 \| 27 \| 6.4 \| 35.1 \| Calculate the equation of the regression line and r2. If a patient had an A1c value = 6, what is the best estimate of their BMI? If a patient had a BMI = 32, what is the best estimate of their A1c value? 10. A small-scale clinical study evaluated the relationship between diabetic patients' Waist-to-Hip ratio (y) (WHR) and Hgb A1c values (x). These data are expected to follow a linear model. A1c (%) \| Waist/Hip \| 5.7 \| 0.84 \| 5.8 \| 0.85 \| 5.9 \| 0.84 \| 6.0 \| 0.88 \| 6.1 \| 0.98 \| 6.2 \| 0.93 \| 6.3 \| 0.88 \| 6.4 \| 0.89 \| Calculate the equation of the regression line and r2. If a patient had an A1c value = 6.1, what is the best estimate of their WHR? If a patient had a WHR = 0.9, what is the best estimate of their A1c value? 11. Data from a drug solution stability study are shown. Time (months) \| Conc (mg/mL) \| 3 \| 10.39 \| 12 \| 9.78 \| 24 \| 9.65 \| 36 \| 9.34 \| Calculate the equation of the regression line and r2. Find t90, the time required for the conc to decrease to 90% of the starting conc. Find the time required for the drug concentration to decrease to 8 mg/mL. Find the concentration at 15 months. 12. Data from a drug solution stability study are shown. Time (days) \| Conc (mg/mL) \| 2 \| 50 \| 14 \| 49 \| 20 \| 43 \| 30 \| 41.3 \| Calculate the equation of the regression line and r2. Find t90, the time required for the conc to decrease to 90% of the starting conc. Find the time required for the drug concentration to decrease to 40 mg/mL. Find the concentration at 25 days. 13. Data from a drug solution stability study are shown. Time (days) \| Conc (mg/mL) \| 7 \| 24.3 \| 14 \| 23.4 \| 21 \| 20.5 \| 28 \| 19.1 \| Calculate the equation of the regression line and r2. Find t90, the time required for the conc to decrease to 90% of the starting conc. Find the time required for the drug concentration to decrease to 15 mg/mL. Find the concentration at 35 days. 14. Data from a drug solution stability study are shown. Time (days) \| Conc (mg/mL) \| 10 \| 59.1 \| 20 \| 57.1 \| 25 \| 56.1 \| 30 \| 55.5 \| Calculate the equation of the regression line and r2. Find the time = 0 concentration. Find the time required for the drug concentration to decrease to 55 mg/mL. Find the predicted concentration at 25 days. 15. Data from a drug solution stability study are shown. Time (days) \| Conc (mg/mL) \| 3 \| 11.9 \| 7 \| 11.5 \| 12 \| 10.1 \| 15 \| 9.9 \| Calculate the equation of the regression line and r2. Find the time = 0 concentration. Find the time required for the drug concentration to decrease to 9 mg/mL. Find the predicted concentration at 10 days. 16. Data from a drug solution stability study are shown. Time (days) \| Conc (mg/mL) \| 2 \| 4.7 \| 5 \| 4.1 \| 10 \| 3.4 \| 15 \| 2.9 \| Calculate the equation of the regression line and r2. Find the time = 0 concentration. Find the time required for the drug concentration to decrease to 4.5 mg/mL. Find the predicted concentration at 6 days. 17. A hospital pharmacist formulated a pediatric extemporaneous solution. Samples were sent to SIUE for analysis. The data from the stability study are shown. Time (days) \| Conc (mg/mL) \| 2 \| 28.3 \| 5 \| 17.1 \| 9 \| 7.8 \| 12 \| 5.0 \| Calculate the equation of the regression line and r2. Find the time = 0 concentration. Find the time required for the drug concentration to decrease to 10 mg/mL. Find the predicted concentration at 10 days. 18. A drug solution stability study was conducted at an elevated temperature, 32 °C. The results are shown. Time (days) \| Conc (mg/mL) \| 2 \| 96.5 \| 4 \| 92.2 \| 10 \| 81.4 \| 16 \| 75.5 \| Calculate the equation of the regression line and r2. Find the time = 0 concentration. Find the time needed for the drug concentration to decrease to 90 mg/mL. Find the predicted concentration at 15 days. 19. An oral drug solution product has the stability data below. Time (months) \| Conc (mg/mL) \| 6 \| 44.6 \| 12 \| 39.7 \| 24 \| 32.5 \| 48 \| 21.3 \| Calculate the equation of the regression line and r2. Find the time = 0 concentration. Find the time needed for the drug concentration to decrease to 40 mg/mL. Find the predicted concentration at 3 months. 20. Once opened, an injectable solution has a short half-life. The results of a stability study are shown. Time (hours) \| Conc (mcg/mL) \| 0.5 \| 7.1 \| 1.5 \| 6.6 \| 5 \| 4.6 \| 10 \| 2.8 \| Calculate the equation of the regression line and r2. Find the time = 0 concentration. Find t90, the time required for the conc to decrease to 90% of the starting conc. 21. Patient plasma concentration data is shown. Time (h post dose) \| Conc (mcg/mL) \| 1 \| 29.5 \| 5 \| 13.6 \| 11 \| 5.1 \| Calculate the equation of the regression line and r2. Find the concentration at time = 0 h. Calculate the drug’s half-life for this patient. (t0.5 = 0.693/ke) When will the Cp = 10 mcg/mL? 22. Patient plasma concentration data is shown. Time (h post dose) \| Conc (mcg/mL) \| 2 \| 8.6 \| 8 \| 2.9 \| 12 \| 1.4 \| Calculate the equation of the regression line and r2. Find the concentration at time = 0 h. Calculate the drug’s half-life for this patient. (t0.5 = 0.693/ke) When will the Cp = 1 mcg/mL? 23. Patient plasma concentration data is shown. Time (h post dose) \| Conc (mg/L) \| 2 \| 74 \| 6 \| 67.2 \| 20 \| 16.3 \| Calculate the equation of the regression line and r2. Find the concentration at time = 0 h. Calculate the drug’s half-life for this patient. (t0.5 = 0.693/ke) When will the Cp = 0.7 mg/L? 24. Patient plasma concentration data is shown. Time (h post dose) \| Conc (mg/L) \| 2 \| 16.8 \| 12 \| 11 \| 20 \| 5.6 \| 36 \| 4.4 \| Calculate the equation of the regression line and r2. Find the concentration at time = 0 h. Calculate the drug’s half-life for this patient. (t0.5 = 0.693/ke) Calculate the Cp @ 48 h. 25. Patient plasma concentration data is shown. Time (h post dose) \| Conc (mg/L) \| 0.5 \| 211.8 \| 6 \| 94.1 \| 10 \| 31.9 \| 16 \| 16.6 \| Calculate the equation of the regression line and r2. Find the concentration at time = 0 h. Calculate the drug’s half-life for this patient. (t0.5 = 0.693/ke) Calculate the Cp @ 12 h. 26. Patient plasma concentration data is shown. Time (h post dose) \| Conc (mcg/mL) \| 1 \| 33 \| 6 \| 12.6 \| 10.5 \| 8.8 \| Calculate the equation of the regression line and r2. Find the concentration at time = 0. Calculate the drug’s half-life for this patient. (t0.5 = 0.693/ke) When will the Cp = 4 mcg/mL? 27. Patient plasma concentration data is shown. Time (h post dose) \| Conc (mcg/mL) \| 3 \| 9 \| 8 \| 7.2 \| 16 \| 4.4 \| Calculate the equation of the regression line and r2. Find the concentration at time = 0 h. Calculate the drug’s half-life for this patient. (t0.5 = 0.693/ke) When will the Cp = 2 mcg/mL? 28. Patient plasma concentration data is shown. Time (h post dose) \| Conc (mcg/mL) \| 2 \| 12.6 \| 7.5 \| 3.1 \| 10 \| 1.7 \| Calculate the equation of the regression line and r2. Find the concentration at time = 0 h. Calculate the drug’s half-life for this patient. (t0.5 = 0.693/ke) When will the Cp = 1 mcg/mL? 29. Patient plasma concentration data is shown. Time (h post dose) \| Conc (mcg/mL) \| 4 \| 25.9 \| 9 \| 7.9 \| 12.5 \| 2.9 \| Calculate the equation of the regression line and r2. Find the concentration at time = 0 h. Calculate the drug’s half-life for this patient. (t0.5 = 0.693/ke) When will the Cp = 1.5 mcg/mL? 30. Patient plasma concentration data is shown. Time (h post dose) \| Conc (mcg/mL) \| 4 \| 15.6 \| 8.5 \| 4.4 \| 12 \| 0.9 \| Calculate the equation of the regression line and r2. Find the concentration at time = 0 h. Calculate the drug’s half-life for this patient. (t0.5 = 0.693/ke) When will the Cp = 2 mcg/mL? 31. A solution contains 60 mCi of a radiopharmaceutical five hours after preparation. At 10 hours, the sample contains 25 mCi. Calculate 𝜆 and t½. 32. The data from an analysis of a radioisotope is shown. Time (days) \| Activity (mCi) \| 2 \| 1000 \| 6 \| 358 \| 12 \| 77 \| Calculate 𝜆 and t ½. Find r2. Determine the activity on Day 0, when the isotope was prepared. 33. The data from an analysis of a radioisotope is shown. The isotope was prepared on Day 0. Time (days) \| Activity (mCi) \| 2 \| 143 \| 6 \| 129 \| 12 \| 111 \| Calculate 𝜆 and t ½. Determine the activity on Day 0, when the isotope was prepared. 34. The data from an analysis of a radioisotope is shown. The isotope was prepared on Day 0. Time (days) \| Activity (mCi) \| 3 \| 101 \| 9 \| 26 \| 15 \| 6.6 \| Calculate 𝜆 and t ½. Determine the activity on Day 0, when the isotope was prepared. 35. The data from an analysis of a radioisotope is shown. The isotope was prepared on Day 0. Time (h) \| Activity (mCi) \| 1.5 \| 55 \| 4 \| 48 \| 8 \| 39 \| Calculate 𝜆 and t ½. Determine the activity on Day 0, when the isotope was prepared. 36. The data from an analysis of a radioisotope is shown. The isotope was prepared on Day 0. Time (h) \| Activity (mCi) \| 2 \| 79 \| 5 \| 56 \| 10 \| 32 \| Calculate 𝜆 and t ½. Determine the activity on Day 0, when the isotope was prepared. 37. The data from an analysis of a radioisotope is shown. The isotope was prepared on Day 0. Time (h) \| Activity (mCi) \| 1 \| 342 \| 4 \| 110 \| 16 \| 1.2 \| Calculate 𝜆 and t ½. Determine the activity on Day 0, when the isotope was prepared. 38. The data from an analysis of a radioisotope is shown. The isotope was prepared on Day 0. Time (days) \| Activity (mCi) \| 1 \| 9 \| 7 \| 5 \| 14 \| 2 \| Calculate 𝜆 and t ½. Determine the activity on Day 0, when the isotope was prepared. 39. The data from an analysis of a radioisotope is shown. The isotope was prepared on Day 0. Time (days) \| Activity (mCi) \| 5 \| 31 \| 17 \| 24 \| 40 \| 15 \| Calculate 𝜆 and t ½. Determine the activity on Day 0, when the isotope was prepared. 40. The data from an analysis of a radioisotope is shown. The isotope was prepared on Day 0. Time (days) \| Activity (mCi) \| 1 \| 71 \| 20 \| 28 \| 35 \| 14 \| Calculate 𝜆 and t ½. Determine the activity on Day 0, when the isotope was prepared. 41. The regression parameters for a drug suspension stability study are shown. The rate constant units are mg/mL/day. a) What is the calculated concentration at time = 0? b) When will the concentration = 40 mg/mL? c) What is the expected concentration after 15 days? 42. The regression parameters for a drug suspension stability study are shown. The rate constant units are mg/mL/month. a) What is the calculated concentration at time = 0? b) When will the concentration = 110 mg/mL? c) What is the expected concentration after 105 days? 43. The regression parameters for a drug solution stability study are shown. The rate constant units are 1/month. The concentration units are mg/mL. a) What is the calculated concentration at time = 0? b) When will the concentration = 11 mg/mL? c) What is the expected concentration after 180 days? 44. The regression parameters for a drug solution stability study are shown. The rate constant units are 1/day. The concentration units are mg/mL. a) What is the calculated concentration at time = 0? b) When will the concentration = 36 mg/mL? c) What is the expected concentration after 40 days? 45. A patient received an IV bolus drug dose. The regression parameters are shown. The rate constant units are 1/hour. The concentration units are mcg/mL. a) What is the calculated concentration at time = 0? b) When will the concentration = 9 mcg/mL? c) What is the expected concentration after 18 hours? 46. A patient received an IV bolus drug dose. The regression parameters are shown. The rate constant units are 1/hour. The concentration units are mg/L. a) What is the calculated concentration at time = 0? b) When will the concentration = 6 mg/L? c) What is the expected concentration after 7 hours? 47. The regression parameters for a radiopharmaceutical product are shown. The rate constant units are 1/hour. a) What is the calculated activity (mCi) at time = 0? b) How many hours after preparation will the activity (mCi) = 50? c) What is the expected activity 12 hours after preparation? 48. The regression parameters for a radiopharmaceutical product are shown. The rate constant units are 1/days. a) What is the calculated activity (mCi) at time = 0? b) How many hours after preparation will the activity (mCi) = 10? c) What is the expected activity 30 hours after preparation? Answers 1. C = 100.94 mg/mL – 0.614 mg/mL/month · t; r2 = 0.979; 99.251 months to reach 40 mg/mL; 89.888 mg/mL at 18 months. 2. C = 51.07 mg/mL – 1.0684 mg/mL/month · t; r2 = 0.976; 19.721 months to reach 30 mg/mL; C0 = 51.07 mg/mL; 46.796 mg/mL at 4 months. 3. C = 15.44 mg/mL – 0.178 mg/mL/month · t; r2 = 0.996; 58.652 months to reach 5 mg/mL; C0 = 15.44 mg/mL; 6.896 mg/mL at 48 months. 4. C = 246.986 mg/mL – 1.732 mg/mL/month · t; r2 = 0.983; 12.694 months to reach 225 mg/mL; C0 = 246.986 mg/mL; 184.634 mg/mL at 36 months. 5. Ave Glu = - 51.09 mg/dL + 29.09% · A1c; r2 = 0.9443; %A1c = 6.9. 6. C = 1.0087 mg/mL – 0.00602 mg/mL/month · t; r2 = 0.966; 34.668 months to reach 0.8 mg/mL; C0 = 1.0087 mg/mL; 0.9 mg/mL at 18 months. 7. Wt @ 50th % = 0.272 kg/month × age (months) + 5.9 kg; 18 months old = 10.8 kg; 12 kg = 22.4 months of age. 8. C = 52.5 mg/mL – 0.392 mg/mL/month · t; r2 = 0.9625; 70.15 months to reach 25 mg/mL; C0 = 52.5 mg/mL; 50.1 mg/mL at 6 months. 9. Ave BMI (kg/m2) = - 32.26 (kg/ m2) + 10.07 kg/m2/% · A1c %; r2 = 0.6164; BMI = 28.16 kg/m2; A1c = 6.4%. 10. WHR = 0.1036 1/% · A1c % + 0.2596; r2 = 0.2596; WHR = 0.89; A1c = 6.2%. 11. Ln C = 2.336 – 0.0029 · t, r2 = 0.8957; (90% of C0 = 9.31 mg/mL) t90 = 36.2 months; 88.5 months; 9.9 mg/mL. 12. Ln C = 3.9442 – 0.0074 · t, r2 = 0.8457; (90% of C0 = 46.47 mg/mL) t90 = 14.2 days; 34.4 days; 42.9 mg/mL. 13. Ln C = 3.2920 – 0.0122 · t, r2 = 0.9608; (90% of C0 = 24.21 mg/mL) t90 = 8.6 days; 47.9 days; 17.6 mg/mL. 14. Ln C = 4.1101 – 0.0032 · t, r2 = 0.9926; C0 = 60.9 mg/mL; 31.8 days; 56.2 mg/mL. 15. Ln C = 2.5373 – 0.0169 · t, r2 = 0.9526; C0 = 12.6 mg/mL; 19.9 days; 10.6 mg/mL. 16. Ln C = 1.6071 – 0.0369 · t, r2 = 0.9950; C0 = 5 mg/mL; 2.9 days; 4 mg/mL. 17. Ln C = 3.6969 – 0.1765 · t, r2 = 0.9975; C0 = 40.3 mg/mL; 7.9 days; 6.9 mg/mL. 18. Ln C = 4.5957 – 0.0177 · t, r2 = 0.9844; C0 = 99.1 mg/mL; 5.4 days; 76 mg/mL. 19. Ln C = 3.8982 – 0.0175 · t, r2 = 0.9998; C0 = 49.3 mg/mL; 11.9 months; 46.8 mg/mL. 20. Ln C = 2.0219 – 0.0991 · t, r2 = 0.9994; C0 = 7.6 mcg/mL; (90% of C0 = 6.84 mcg/mL) t90 = 1.1 hours. 21. Ln C = 3.5304 – 0.1746 · t, r2 = 0.9978; C0 = 34.1 mcg/mL; t ½ = 4 h; C = 10 @ 7 h post-dose. 22. Ln C = 2.5153 – 0.1815 · t, r2 = 0.9999; C0 = 12.4 mcg/mL; t ½ = 3.8 h; C = 1 @ 13.9 h post-dose. 23. Ln C = 4.5939 – 0.0885 · t, r2 = 0.9758; C0 = 98.9 mg/L; t ½ = 7.8 h; C = 0.7 @ 55.9 h post-dose. 24. Ln C = 2.8184 – 0.0407 · t, r2 = 0.9051; C0 = 16.8 mg/L; t ½ = 17 h; C @ 48 h post-dose = 2.4 mg/L. 25. Ln C = 5.4297 – 0.1707 · t, r2 = 0.9741; C0 = 228 mg/L; t ½ = 4.1 h; C @ 12 h post-dose = 29.4 mg/L. 26. Ln C = 3.5523 – 0.1401 · t, r2 = 0.9491; C0 = 34.9 mg/L; t ½ = 4.9 h; C = 4 @ 15.5 h post-dose. 27. Ln C = 2.3852 – 0.0557 · t, r2 = 0.9934; C0 = 10.9 mg/L; t ½ = 12.4 h; C = 2 @ 30.4 h post-dose. 28. Ln C = 3.031 – 0.2511 · t, r2 = 0.9998; C0 = 20.7 mg/L; t ½ = 2.8 h; C = 1 @ 12.1 h post-dose. 29. Ln C = 4.3064 – 0.2562 · t, r2 = 0.9972; C0 = 74.2 mg/L; t ½ = 2.7 h; C = 1.5 @ 15.2 h post-dose. 30. Ln C = 4.2579 – 0.3531 · t, r2 = 0.9814; C0 = 70.7 mg/L; t ½ = 2 h; C = 2 @ 10.1 h post-dose. 31. 𝜆 = 0.175 h-1, t ½ = 4 h. 32. 𝜆 = 0.2564 h-1, t ½ = 2.7 days. r2 = 0.9999. C0 = 1668 mCi. 33. 𝜆 = 0.025 d-1, t ½ = 27.4 days. C0 = 150 mCi. 34. 𝜆 = 0.2273 d-1, t ½ = 3.05 days. C0 = 200 mCi. 35. 𝜆 = 0.0528 h-1, t ½ = 13.1 h. C0 = 59 mCi. 36. 𝜆 = 0.1129 h-1, t ½ = 6.1 h. C0 = 99 mCi. 37. 𝜆 = 0.3767 h-1, t ½ = 1.8 h. C0 = 498 mCi. 38. 𝜆 = 0.1161 d-1, t ½ = 6 d. C0 = 11 mCi. 39. 𝜆 = 0.0207 d-1, t ½ = 33.5 d. C0 = 34 mCi. 40. 𝜆 = 0.0478 d-1, t ½ = 14.5 d. C0 = 74 mCi. 41. 49.7 mg/mL, 59.7 days, 47.3 mg/mL. 42. 118.6 mg/mL, 10.2 months, 115.7 mg/mL. 43. 12.2 mg/mL, 23.9 months, 11.9 mg/mL. 44. 40 mg/mL, 27.7 days, 34.4 mg/mL. 45. 20.1 mcg/mL, 7.9 hours post-dose, 3.3 mcg/mL. 46. 45.1 mg/L, 5.8 hours post-dose, 4 mg/L. 47. 98 mCi, 6 hours, 26 mCi. 48. 19.4 mCi, 14.7 hours, 5 mCi. Module 8: Standardized Dosing Protocols This module will demonstrate some examples for calculating patient-specific doses according to institutional protocols and patient lab data. Standard protocols are established by medical societies or hospital committees as a guide for initiating and/or adjusting treatment with a particular drug based on the patient’s weight, kidney function, or other lab test results. They are intended to ensure appropriate personalized drug therapy for patients. It is probably easiest to understand with an example, so let’s jump into the first protocol. Note: Every hospital or institution is free to set their own drug therapy guidelines. These examples are intended to give experience and confidence in implementing treatment protocols. They are not intended as instructions for patient care. You must follow the treatment protocols in use at the institution where you practice. Module 8A: Amikacin Amikacin is an aminoglycoside antibiotic that is administered by IV infusion to treat infections with sensitive strains of Gram-negative bacteria. The dose and frequency of amikacin administration must be chosen appropriately to achieve effective therapy without causing excessive toxicity. If the dose is too low or not given frequently enough, then the amikacin concentration in the patient’s blood and tissues will be too low to cure the infection. If the dose is too high or given too frequently, then the drug concentration will build up in the patient’s blood and tissues to a potentially toxic level. An example protocol is shown below. Table 8.1 Amikacin Protocol \| \|\| CrCl > 60 mL/min \| CrCl 40 – 60 mL/min \| CrCl 20 – 40 mL/min \| 5 – 7.5 mg/kg q8h \| 5 – 7.5 mg/kg* q12h \| 5 – 7.5 mg/kg* q24h \| Use IBW if BMI < 40 kg/m2 \| The normal dose is 5 to 7.5 mg of amikacin per kg of body weight, and the dose is to be administered either every 8 hours, 12 hours, or 24 hours depending on the patient’s creatinine clearance. Body Mass Index (BMI) is used to determine which weight to use in the calculation. For patients with BMI < 40, the dose is calculated using the lower of actual body weight or ideal body weight (IBW). For patients with BMI ≥ 40, the dose is calculated using adjusted body weight (ABW), ABW = IBW + 0.4(Actual wt - IBW) Recall the equation for calculating BMI is the patient’s actual body weight in kg divided by the square of their height in meters. BMI therefore has units of kg/m2. Do not forget to square the patient height. $BMI=\frac{Pt\;actual\;wt\;(kg))}{(Pt\;height\;(m))^{2}}$ IBW and ABW are calculated as you learned in Module 5. Once the correct dose has been determined, the frequency of administration is based on the patient’s creatinine clearance, as you learned in Module 5. Remember to use the lower of ideal or actual body weight when calculating creatinine clearance. Let’s walk through an example. Example 8.1: A physician orders amikacin 7 mg/kg for a 35 year old female patient (165 lb and 5’7”). The patient’s serum creatinine is 1.5 mg/dL. Calculate the appropriate amikacin dose in mg and the correct frequency. Amikacin is supplied in sterile vials containing 500 mg in every 2 mL of solution. Calculate how many milliliters of the drug solution are required to prepare each dose of the drug for this patient. First calculate BMI to determine which weight to use in the dose calculation. $BMI=\frac{165\;lb\times \frac{1\;kg}{2.2\;lb}}{(67\;in\times \frac{2.54\;cm}{in}\times \frac{1\;m}{100\;cm})^{2}}=\frac{25.9\;kg}{m^{2}}$ BMI < 40, so calculate dose using the lower of actual body weight or ideal body weight. $Actual\;weight=165\;lb\times \frac{1\;kg}{2.2\;lb}=75\;kg$ $IBW=45.5\;kg +2.3\;kg(67"-60")=61.6\;kg$ Use IBW to calculate the dose. $Dose=61.6\;kg\times \frac{7\;mg}{kg}=431.2\;mg$ The calculated dose is 431.2 mg, so round this to a reasonable practical dose of 430 mg. Next calculate creatinine clearance to determine the frequency of administration. Remember to use the 0.85 factor for a female and IBW because it is lower than actual body weight. $CrCl=\frac{0.85\;\times \;(140-35)\;\times \;61.6\;kg}{72\;\times \;1.5}=50.9\;mL/min,\text{round to 51}\; mL/min$ 51 mL/min falls between 40 and 60 mL/min, so the appropriate frequency of administration according to Table 8.1 is every 12 hours. An appropriate dosage regimen for this patient, according to the prescriber’s order of 7 mg/kg, is 430 mg every 12 hours. The volume of amikacin solution required for each infusion is calculated as: $430\;mg\times \frac{2\;mL}{500\;mg}=1.7\;mL$ Module 8B: Vancomycin AUC:MIC Ratio Vancomycin is another antibiotic that is administered by IV infusion. Similar to amikacin, the dose and frequency must be chosen to ensure effective therapy while minimizing toxicity. The AUC:mic ratio, or ratio of vancomycin area under the curve (AUC) to minimum inhibitory concentration of the drug for the infecting bacterium can be used to calculate the optimal vancomycin dose. MIC is reported by the microbiology lab, while AUC is estimated from the patient’s creatinine clearance. Vancomycin is primarily eliminated from the body by urinary excretion, so the patient’s kidney function is a major factor in determining the dose. The vancomycin dose is calculated to target AUC as a chosen multiple of MIC, typically 400 or 450. The vancomycin dose is calculated using the equation $\text{Vancomycin daily dose} (\frac{mg}{24\;hr})=0.045\times CrCl\times MIC\times target\;multiple$ Calculate CrCl using the lower of IBW or actual body weight as usual. The factor 0.045 is a unit conversion factor so that the result gives an answer in mg of vancomycin. We note here that some physicians advocate for using the actual body weight when estimating the CrCl for use in this vancomycin calculation. As we have mentioned previously, this text is not offering medical or therapeutic advice. When in practice adhere to the standards in use at your facility. NOTE 1: The daily dose is rounded up to the nearest 250 mg (250, 500, 750, 1000, 1250, 1500, 1750, 2000, etc.)) If the calculated value is 2050 mg per day, then the daily dose should be rounded up to 2250 mg per day. (You will learn more about vancomycin dosing in Pharmacokinetics and Integrated Therapeutics courses.) NOTE 2: The equation calculates the required daily dose of vancomycin, and vancomycin is typically administered every 12 hours. Each individual dose is ½ of the daily dose. Example 8.2: A 60 yo female patient (5’5”, 145 lb, SCr = 0.9 mg/dL) has an infection the physician would like to treat with vancomycin. The MIC for the organism is 1.2 mcg/mL. Calculate the daily dose to target 400 × MIC. The patients actual body weight is 145 lb or 65.9 kg. $IBW=45.5\;kg +2.3\;kg\times\;(65"-60")=57\;kg$ Calculate CrCl using 57 kg. $CrCl=\frac{0.85\;\times \;(140-60)\;\times \;57\;kg}{72\;\times \;0.9}=59.8\;mL/min,\text{round to 60}\; mL/min$ $\text{Daily dose (mg per 24 hours)}=0.045\times 60\times 1.2\times \;400=1296\;mg/24\;hr$ The calculated daily dose of 1296 mg is rounded up to the nearest multiple of 250 mg, or 1500 mg day. Since vancomycin in given every 12 hours, each individual dose is 750 mg. This patient should receive 750 mg every 12 hours. Module 8C: Intravenous Phosphate Supplementation Phosphate is an important plasma electrolyte. Patients with low phosphate levels may require supplements to prevent the negative health effects. Phosphate supplements should be given orally if the patient is able to take it. Many institutions have treatment guidelines to ensure safe intravenous phosphate supplementation when the oral route is not sufficient. Intravenous phosphate supplement products include Sodium Phosphates Injection and Potassium Phosphates Injection. Both products are highly concentrated, containing 3 mmoles of phosphate per mL or 3 moles per liter. Sodium phosphates contains 4 mEq/mL of Na+ and potassium phosphates contains 4.4 mEq/mL of K+. Sodium and potassium are also important electrolytes, and their concentrations must be maintained at a healthy level when administering phosphate supplements. The normal sodium level in plasma is approximately 140 mEq/L, and excess sodium is excreted in the urine. A patient with normal kidney function will excrete any excess sodium that is administered as sodium phosphate supplementation. The normal potassium level in plasma is approximately 3.5 – 5 mEq/L. A patient can experience serious adverse effects if their potassium level falls too low below 3.5 mEq/L or is elevated above 5 mEq/L. For an adult patient, an intravenous dose of 40 mEq of K+ is expected to raise the plasma potassium level by approximately 0.5 mEq/L. Pharmacists must be aware of the patient’s potassium status and the amount of potassium in an order for potassium phosphates infusion to avoid raising the patient’s potassium level above 5 mEq/L. If a patient receives an order for phosphates infusion and their phosphate level is normal, the best choice for phosphate supplementation would be sodium phosphates. If the patient requires both potassium and phosphate supplementation, then potassium phosphates is the convenient choice. Finally, both sodium and potassium phosphates are highly concentrated solutions with osmolarity of 7 or 7.4 mOsm/mL, or 7000 mOsm/L or 7400 mOsm/L. These products must be diluted in a large enough volume to bring the infusion to an osmolarity less than 600 mOsm/L for peripheral infusion. It is useful to memorize the osmolarity of the common base fluids so that you do not need to calculate them for every problem: - 0.9% Sodium Chloride Injectin (Normal Saline, NS), = 308 mOsm/L - 0.45% Sodium Chloride Injection (1/2 Normal Saline, 1/2 NS) = 154 mOsm/L - 5% Dextrose Injection (D5W) = 252 mOsm/L - Sterile Water for Injection (SWI) has no solutes, so 0 mOsm/L Example 8.3: A patient with Na+ of 138 mEq/L and K+ 4.9 mEq/L is ordered 50 mmoles of potassium phosphates in 250 mL of D5W over 6 hours to supplement their low serum phosphate level. How many mEq of potassium would the patient receive from this solution? How much would this raise the patient’s potassium level? Is this the best choice to treat the patient? If not, what should you recommend. Potassium phosphates contains 3 mmoles phosphate and 4.4 mEq potassium per mL. The potassium dose represented by 50 mmoles of potassium phosphate and the resulting expected increase in blood potassium level is: $50\;mmol\;P\times \frac{4.4\;mEq\;K^{+}}{3\;mmol\;P}=73.3\;mEq\;K^{+}\times \frac{0.5\;mEq/L}{40\;mEq\;K^{+}}=0.9\;mEq/L\;increase$ 50 mmoles of potassium phosphate carries a K+ dose of 73.3 mEq, which would raise the K+ level to approximately 4.9 + 0.9 = 5.8 mEq/L. This is higher than the upper limit of normal K+, so it should be avoided. Recommend for patient safety that the supplement order be changed to sodium phosphates 50 mmoles. Example 8.4: An intravenous phosphate supplement is prepared by adding 20 mL of sodium phosphates injection to 250 mL of D5W. Calculate the osmolarity of the solution. Should this be given via peripheral IV line? The solution is prepared by mixing 20 mL of a 7000 mOsm/L solution with 250 mL of a 252 mOsm/L solution. The mixture osmolarity is calculated (with volumes in liters): $\frac{(0.02L\;\times \;\frac{7000\;mOsm}{L})\;+\;(0.25\;L\;\times \;\frac{252\;mOsm}{L})}{0.02\;+\;0.25\;L}=\frac{752\;mOsm}{L}$ The infusion osmolarity is greater than the recommended limit of 600 mOsm/L for peripheral infusion. The sodium phosphate supplement should be diluted in a larger volume. For example, if 20 mL of sodium phosphates injection was added to 500 mL of D5W the osmolarity would be 511 mOsm/L, which is acceptable for peripheral infusion. If the prescriber does not want to use 500 mL of D5W, the phosphate dose could be prepared in other ways. For example, it could be combined with 435 mL of sterile water for injection in an empty IV bag to give an isoosmolar solution (308 mOsm/L). Module 8D: Cisplatin-Etoposide for Non-Small Cell Lung Cancer Cancer chemotherapy is generally administered according to a standard protocol based on the type of cancer being treated and patient-specific variables. As an example, a protocol for treating non-small cell lung cancer (NSCLC) uses two drugs on a defined schedule: - Cisplatin: 80 mg/m2 by IV infusion on day 1 of cycle, - Etoposide 100 mg/m2/day by IV infusion on days 1, 2, and 3 of cycle. Repeat the cycle every 21 days for 4 cycles. One cycle is 3 days of treatment, with both cisplatin and etoposide on day 1 and only etoposide on days 2 and 3. The patient then waits 18 days to start the next cycle. Cisplatin and etoposide doses are based on the patient’s body surface area. Cisplatin is diluted in 2 L of fluid containing 5% dextrose, ⅓ to ½ normal saline, and 37.5 g of mannitol. Etoposide must be diluted to a concentration of 0.2 to 0.4 mg/mL in D5W or NS and should be infused over 60 minutes. Example 8.5: A 47 year old male patient (5’11” and 198 lb) is ordered cisplatin and etoposide according to the protocol above. Calculate the total amount of cisplatin and etoposide the patient should receive in the first cycle. The cycle represents one dose cisplatin and 3 doses of etoposide. Calculate the dose of each. $BSA=\sqrt{\frac{71\;in\;\times \;\frac{2.54\;cm}{in}\;\times \;198\;lb\;\times \;\frac{1\;kg}{2.2\;lb}}{3600}}=2.12m^{2}$ - Cisplatin dose: 2.12 m2 x 80 mg/m2 = 169.6 mg; round this to 170 mg. - Etoposide dose: 2.12 m2 x 100 mg/m2 = 212 mg; round this to 210 mg. - The total cisplatin for 1 cycle is 170 mg. - The total etoposide for 1 cycle is 3 x 210 mg = 630 mg. Module 8E: Dose Rounding for Biologic Drugs Many institutions have implemented a dose rounding policy for biologic drugs, especially those used to treat cancer. These products tend to be expensive and any leftover partial vials represent significant loss of money. Dose rounding protocols are used to manage the cost of cancer therapy. There are several papers in the pharmacy literature describing how hospital or health system pharmacies have saved millions of dollars per year using this approach. The protocol is generally very simple: if the ordered dose for a patient is within ± 10% of a whole number of the drug vials, then the dose is automatically rounded to the nearest whole vial size. Doses may be rounded up or down within the accepted range. NOTE: Some hospitals may use a different percent of the dose when rounding, e.g., ± 5%. As always, follow the specific instructions at your institution. For the purpose of this course, we will use ± 10%. The procedure for determining the appropriate dose for a patient under a dose rounding protocol is: - Calculate dose according to treatment guideline. - Calculate (dose – 10%) and (dose + 10%). - Determine if whole vial sizes fall within the acceptable dose range. If yes – round dose to the whole vial size. If no – use the dose calculated from treatment guideline. NOTE: There may be more than 1 acceptable answer for a particular problem, depending on the vial sizes for a particular drug. Any combination of full vials to provide the correct dose is acceptable for this course. Example 8.6: Bevacizumab is used treat some cancers and is available in 100 mg and 400 mg vials. A 56 kg patient is ordered bevacizumab 5 mg/kg. Calculate the appropriate dose for this patient. $56\;kg\;\times\;5\;\frac{mg}{kg}=280\;mg$ 280 mg ± 10% spans the range 252 – 308 mg. 300 mg represents 3 full 100 mg vials. The acceptable dose range (252 – 308 mg) contains 300 mg, which represents 3 full 100 mg vials. The dose should be rounded up to 300 mg. The figure shows the available full vial doses from combining 100 mg and/or 400 mg vials. The blue box represents the acceptable dose range of 252-308 mg. The mark for 300 mg (3 x 100 mg vials) is within the acceptable range, so the dose should be rounded to 300 mg. Example 8.7: A 70 kg patient is ordered 5 mg/kg of bevacizumab = 350 mg. 350 mg ± 10% is 315 – 385 mg. No combination of full vials falls within this range. Leave dose at 350 mg. Some drug waste is unavoidable in this case. Module 8: Practice Problems - MM is a 53 y.o. female, 5’3” tall and 130 lb, with serum creatinine of 2.1 mg/dL. MM’s physician orders amikacin 7.5 mg/kg. a. Calculate the correct dose and frequency for MM. Round it to the nearest 10 mg. b. Calculate the volume of drug solution for each dose. Round it to a reasonable number. - RP is a 64 y.o. male, 5’8” tall and 265 lb, with serum creatinine of 1.7 mg/dL. RP’s physician orders amikacin 5 mg/kg. a. Calculate the correct dose and frequency for RP. Round it to the nearest 10 mg. b. Calculate the volume of drug solution for each dose. Round it to a reasonable number. - DH is a 39 y.o. male, 6’ tall and 210 lb, with serum creatinine of 1.4 mg/dL. DH’s physician orders amikacin 6 mg/kg. a. Calculate the correct dose and frequency for DH. Round it to the nearest 10 mg. b. Calculate the volume of drug solution for each dose. Round it to a reasonable number. - A 34 yo male patient (5’8”, 155 lb, SCr = 0.8 mg/dL) has an infection the physician would like to treat with vancomycin. The MIC for the organism is 1.2 mcg/mL. Calculate the daily dose to target 400mic and the volume of drug solution required for each individual dose. - A 45 yo female patient (5’11”, 165 lb, SCr = 1.1 mg/dL) has an infection the physician would like to treat with vancomycin. The MIC for the organism is 1.3 mcg/mL. Calculate the daily dose to target 500mic and the volume of drug solution required for each individual dose. - A 62 yo male patient (5’10”, 150 lb, SCr = 1.4 mg/dL) has an infection the physician would like to treat with vancomycin. The MIC for the organism is 1.4 mcg/mL. Calculate the daily dose to target 450*mic and the volume of drug solution required for each individual dose. - Calculate the volume of vancomycin injection required per dose for each patient according to the protocol. a. CrCl = 25 mL/min, AUC/MIC multiple = 400, MIC = 1.1 mcg/mL. b. CrCl = 35 mL/min, AUC/MIC multiple = 500, MIC = 1.3 mcg/mL. c. CrCl = 45 mL/min, AUC/MIC multiple = 600, MIC = 1.5 mcg/mL. d. CrCl = 55 mL/min, AUC/MIC multiple = 500, MIC = 1.3 mcg/mL. e. CrCl = 75 mL/min, AUC/MIC multiple = 400, MIC = 1.1 mcg/mL. f. CrCl = 90 mL/min, AUC/MIC multiple = 500, MIC = 1.3 mcg/mL. - A patient with Na+ of 138 mEq/L and K+ 4.9 mEq/L is ordered 40 mmoles of potassium phosphates in 250 mL of D5W over 6 hours to supplement their low serum phosphate level. How many mEq of potassium would the patient receive from this solution? Is this the best choice to treat the patient? If not, what would you recommend. - A patient with Na+ of 142 mEq/L and K+ 3.7 mEq/L is ordered 35 mmoles of potassium phosphates in 250 mL of D5W over 6 hours to supplement their low serum phosphate level. How many mL of drug solution is required to fill the order. What is the osmolarity of the solution as ordered. Should it be given by peripheral line? - A patient with Na+ of 148 mEq/L and K+ 4.1 mEq/L is ordered 25 mmoles of potassium phosphates in 250 mL of D5W over 6 hours to supplement their low serum phosphate level. How many mL of drug solution is required to fill the order. How many mEq of potassium would the patient receive from this solution? - A 63 year old female patient, 4’11” and 150 lb, is ordered cisplatin-etoposide. Calculate the cisplatin and etoposide dose for day 1 of the treatment cycle. - Calculate the cisplatin and etoposide dose according to the protocol for a 32 year old male, 6’2” and 195 lb. - A patient is ordered cisplatin 150 mg to be added to 2L of fluid containing 5% dextrose, ½ normal saline, and 37.5 g of mannitol. The 2L of fluid diluent is prepared by mixing the appropriate volumes of sterile water for injection, dextrose 70% injection, sodium chloride 4 mEq/mL injection, and mannitol 20% injection. Recall that normal saline is 140 mEq/L of NaCl. Calculate the volume of each component to prepare the 2L of base fluid. Dose Rounding Problems Bevacizumab is supplied in 100 mg and 400 mg vials and is administered at 5, 10, or 15 mg/kg of body weight. - A physician orders a dose of 10 mg/kg for a 75 kg patient. What dose should the patient receive. - A physician orders a dose of 5 mg/kg for a 52 kg patient. What dose should the patient receive. - A physician orders a dose of 15 mg/kg for a 91 kg patient. What dose should the patient receive. - A physician orders a dose of 10 mg/kg for a 147 kg patient. What dose should the patient receive. Daratumumab is supplied in 100 mg and 400 mg vials. It is administered at 16 mg/kg of body weight. - A physician orders a dose of 16 mg/kg for a 75 kg patient. What dose should the patient receive. - A physician orders a dose of 16 mg/kg for a 52 kg patient. What dose should the patient receive. - A physician orders a dose of 16 mg/kg for a 91 kg patient. What dose should the patient receive. - A physician orders a dose of 16 mg/kg for a 63 kg patient. What dose should the patient receive. Trastuzumab is supplied in 150 mg and 420 mg vials. It is administered at 2, 4, 6, or 8 mg/kg of body weight. - A physician orders a dose of 2 mg/kg for a 75 kg patient. What dose should the patient receive. - A physician orders a dose of 4 mg/kg for a 52 kg patient. What dose should the patient receive. - A physician orders a dose of 6 mg/kg for a 91 kg patient. What dose should the patient receive. - A physician orders a dose of 8 mg/kg for a 82 kg patient. What dose should the patient receive. Answers - 390 mg q24h, 1.6 mL - 450 mg q12h, 1.8 mL - 470 mg q8h, 1.9 mL - 2750 mg/day, 27.5 mL per dose - 2250 mg/day, 22.5 mL per dose - 1500 mg/day, 15 mL per dose - a. 5 mL; b. 12.5 mL; c. 20 mL; d. 17.5 mL; e. 15 mL; f. 27.5 mL. - 58.7 mEq K+ would raise patient level 0.7 mEq/L to 5.6 mEq/L. Sodium phosphate would be a better choice. - 11.7 mL of solution required, infusion osmolarity 567 mOsm/L. Okay for peripheral infusion. - 8.3 mL, 36.7 mEq K+. - (134.4 mg) 135 mg cisplatin and (168 mg) 170 mg etoposide. - (172 mg) 170 mg cisplatin and 215 mg etoposide. - 142.9 mL 70% dextrose, 35 mL NaCl 4 mEq/mL, 187.5 mL mannitol 20%, and 1634.6 mL sterile water for injection. Ordered dose 10 mg/kg x 75 kg = 750 mg ± 10% = 675 – 825 mg. 2 x 400 mg vials = 800 mg or 1 x 400 + 3 x 100 = 700 mgOrdered dose 5 mg/kg x 52 kg = 260 mg ± 10% = 234 – 286 mg. This range does not allow for full vial use. The dose of 260 mg should be used.Ordered dose 15 mg/kg x 91 kg = 1365 mg ± 10% = 1228 – 1502 mg. 3 x 400 mg + 1 x 100 mg = 1300 mg or 3 x 400 mg + 2 x 100 mg = 1400 mg Ordered dose 10 mg/kg x 147 kg = 1470 mg ± 10% = 1323 – 1617 mg. 4 x 400 mg = 1600 mg (fewest vials), or 3 x 400 mg + 2 x 100 mg = 1400 mg, or 3 x 400 mg + 3 x 100 mg = 1500 mg (closest to ordered dose)Ordered dose 16 mg/kg x 75 kg = 1200 mg ± 10% = 1080 – 1320 mg. 3 x 400 mg = 1200 mgOrdered dose 16 mg/kg x 52 kg = 832 mg ± 10% = 748 – 915 mg. 2 x 400 mg = 800 mg (fewest vials and closest to ordered dose)Ordered dose 16 mg/kg x 91 kg = 1456 mg ± 10% = 1310 – 1601 mg. 4 x 400 mg = 1600 mg (fewest vials) or 3 x 400 mg + 3 x 100 mg = 1500 mg (closest to ordered dose)Ordered dose 16 mg/kg x 63 kg = 1008 mg ± 10% = 907 – 1109 mg. 2 x 400 mg + 2 x 100 mg = 1000 mg. (closest to ordered dose and fewest vials)Ordered dose 2 mg/kg x 75 kg = 150 mg ± 10% = 135 – 165 mg. 1 x 150 mg = 150 mgOrdered dose 4 mg/kg x 52 kg = 208 mg ± 10% = 187 – 229 mg. This range does not allow for full vial use. The dose of 208 mg should be used.Ordered dose 6 mg/kg x 91 kg = 546 mg ± 10% = 491 – 601 mg. 1 x 150 mg + 1 x 420 mg = 570 mgOrdered dose 8 mg/kg x 82 kg = 656 mg ± 10% = 590 – 722 mg. 1 x 420 mg + 2 x 150 mg = 720 mg Module 9: Case Based Problems This modele applies concepts from the prior 8 modules to case-based problems with more than one calculated answer. The solution to a particular problem may require calculations obtained from earlier steps. Module 9A: Compound an Oral Suspension for Marshmallow the Cat Example 9.1: Marshmallow, a 3 year old cat that weighs 9 lb 4 oz, is diagnosed with a bacterial infection in her intestines. A veterinarian has prescribed metronidazole at a dose of 8 mg/kg twice a day for 7 days. A compounding pharmacy prepared a suspension containing 50 mg/mL of metronidazole. - How many milligrams of metronidazole does Marshmallow require per dose? - How many milliliters of the suspension are required per dose? $9\;lb\;4\;oz=9.25\;lb\times \frac{1\;kg}{2.2\;lb}\times \frac{8\;mg}{kg}=\frac{33.6\;mg}{dose}$ $\frac{33.6\;mg}{dose}\times \frac{1\;mL}{50\;mg\;MTZ}=0.67\;mL/dose,\;round\;to\;0.7\;mL$ Marshmallow refuses to take the metronidazole suspension, probably due to the bad taste of the drug. The vet then orders metronidazole benzoate suspension because cats tend to find the taste less offensive. Metronidazole benzoate is an ester prodrug of metronidazole with a molecular weight of 275.3 g/mole. The prodrug is hydrolyzed in the body to generate metronidazole, which has molecular weight of 171.2 g/mole. The vet wants Marshmallow to receive the equivalent of 8 mg/kg of metronidazole twice daily for 7 days. Metronidazole benzoate suspension may be compounded using the formula:1 Metronidazole benzoate 8 g Glycerin 10 mL Flavoring agent (optional) qs Simple syrup qs 100 mL - How many milligrams of metronidazole benzoate are required to provide the equivalent of 8 mg/kg of metronidazole? - How many milliliters of metronidazole benzoate suspension are required to provide this dose? We already determined that 8 mg/kg of metronidazole is 33.6 mg. We need to adjust the dose using the molecular weights to account for the drug being delivered as the benzoate ester. $33.6\;mg\;MTZ\times \frac{\frac{275.3\;g\;MTZ Benz}{mole}}{\frac{171.2\;g\;MTZ}{mole}}=54\;mg\;MTZ\;Benz\;per\;dose$ The suspension formula specifies 8 g (8000 mg) of metronidazole benzoate per 100 mL of the suspension, so the volume of suspension required per dose is: $54\;mg\;MTZ\;Benz\times \frac{100\;mL}{8000\;mg\;MTZ\;Benz}=0.68\;mL,\;round\;to\;0.7\;mL$ - How much of the metronidazole benzoate suspension should be dispensed to provide 7 days of therapy? $\frac{0.7\;mL}{dose}\times \frac{2\;doses}{day}\times7\;days =9.8\;mL\;required$ You should dispense more than 10 mL to account for some waste, slight measurement errors, etc. Dispensing 15 mL (approximately 5 mL more than the required volume) should allow 7 full days of therapy at 0.7 mL per dose. Marshmallow’s owner is concerned about giving her metronidazole benzoate because they read that benzoates are toxic to cats. A veterinary medical reference states that benzoate is safe in cats if the exposure is less than 200 mg/kg/day. - How many mg/kg of benzoate will Marshmallow ingest per day at a dose of 0.7 mL of metronidazole benzoate suspension twice a day? Metronidazole molecular weight is 171.2 g/mole while metronidazole benzoate molecular weight is 275.3 g/mole. Therefore, metronidazole benzoate is approximately equivalent to 171.2 g of metronidazole and 104.1 g (275.3 – 171.2) of benzoate per mole. $\frac{2\;doses}{day}\times \frac{54\;mg\;MTZ\;Benz}{dose}\times \frac{104.1\;g\;Benzoate}{275.3\;g\;MTZ\;Benz}=40.8\;mg\;benzoate\;per\;day$ Marshmallow weighs 9¼ lb or 4.2 kg, so benzoate intake per day is $\frac{40.8\;mg}{day}=9.7\;mg/kg/day$ This is much lower than the 200 mg/kg/day limit. According to the guidelines, this dose should be safe. Marshmallow takes the metronidazole benzoate suspension without struggling and, after a followup visit, the vet orders another 7 days supply at the same dose. Marshmallow’s owner finds it inconvenient to measure 0.7 mL per dose and would like the suspension to be compounded so that each dose is given in a larger volume. - What volume of suspension should be dispensed if each dose is 2.5 mL? - How much metronidazole benzoate is required to compound this volume of suspension? - How much glycerin is required if the same proportion is used, i.e. 10 mL of glycerin per 100 mL of suspension? $\frac{2.5\;mL}{dose}\times \frac{2\;doses}{day}\times 7\;days=35\;mL\;for\;7\;days.\;Dispense\;40\;mL$ The amount of metronidazole per dose is 54 mg and it will be delivered in 2.5 mL per dose. The total amount of metronidazole benzoate required to compound 40 mL of suspension is: $40\;mL\times \frac{54\;mg\;MTZ\;Benz}{2.5\;mL}=864\;MTZ\;Benz\;needed$ Glycerin is included in the original published suspension formulation at 10 mL per 100 mL of suspension, so for 40 mL of suspension: $\frac{10\;mL\;glycerin}{100\;mL\;suspension}=\frac{x\;mL\;glycerin}{40\;mL\;suspension}=4\;mL\;glycerin\;needed$ 1U.S. Pharmacist 2023;48(4):71-72. Module 9B: Phenytoin Products for Treating Seizure Disorder Phenytoin is an anticonvulsant drug used to treat some types of seizure disorders. It is available in 5 dosage forms as shown in table 9.1. The different dosage forms have different absorption rates and different potencies, so switching from one dosage form to another must be done carefully. Phenytoin chewable tablets and phenytoin suspension contain phenytoin as the free acid. Extended phenytoin sodium capsules and phenytoin injection contain phenytoin sodium. Each milligram of phenytoin sodium has the equivalent of 0.92 mg of phenytoin free acid, and this difference must be taken into account when switching from phenytoin sodium and phenytoin free acid products. Fosphenytoin sodium is an injectable prodrug of phenytoin and each 1.5 mg of fosphenytoin sodium contains the equivalent of 1 mg of phenytoin sodium. In an effort to reduce errors in dose calculation, fosphenytoin sodium is labeled in terms of phenytoin sodium equivalent (PE) dose, where 1.5 mg of fosphenytoin sodium represents 1 mg PE (1 mg of phenytoin sodium). Phenytoin product equivalencies are summarized as: 1 mg PE = 1 mg phenytoin sodium = 0.92 mg phenytoin Table 9.1 Some Phenytoin Dosage Forms Example 9.2: CJ (10 years old, 45 kg, 4’9” tall) has been healthy, taking no regular medications or over-the-counter products until experiencing a serious seizure. CJ is taken to the hospital and the physician orders a fosphenytoin loading dose of 15 mg PE/kg to be infused at a rate of 2 mg PE/kg/min or 150 mg PE/min, whichever is slower. This hospital dilutes fosphenytoin sodium in the smallest volume of D5W that gives a drug concentration less than 25 mg PE/mL. - Calculate the fosphenytoin loading dose in mg PE for CJ. $45\;kg\times \frac{15\;mg\;PE}{kg}=675\;mg\;PE$ - Calculate the volume of fosphenytoin injection required for the dose (see label in Table 9.1). The hospital pharmacy stocks D5W in 50 mL, 100 mL, 250 mL and 500 mL bags. Calculate which bag should the dose be prepared in. $675\;mg\;PE\times \frac{1\;mL}{50\;mg\;PE}=13.5\;mL\;fosphenytoin\;injection$ $\frac{675\;mg\;PE}{x\;mL}=\frac{25\;mg\;PE}{1\;mL},\;x=\;27\;mL$ If the dose was diluted to a total of 27 mL the concentration would be 25 mg PE/mL. The smallest bag is 50 mL, so 50 mL D5W + 13.5 mL fosphenytoin inj = 63.5 mL. Use the 50 mL bag. - Calculate the required solution flow rate in mL/min. From the calculations above, the drug concentration is 675 mg PE/63.5 mL. The preferred flow rate is 2 mg PE/kg/min. $45\;kg\times \frac{2\;mg\;PE}{kg\;\times\;min}\times\frac{63.5\;mL}{675\;mg\;PE} =8.5\;mL/min$ - How many minutes will it take to infuse the loading dose? $63.5\;mL\times \frac{1\;min}{8.5\;mL}=7.5\;min$ After the loading dose has been administered, the physician orders a maintenance dose of fosphenytoin 4 mg PE/kg by IV infusion every 12 hours at a rate of 2 mg PE/kg/min or 150 mg PE/min, whichever is slower. - Calculate the fosphenytoin maintenance dose in mg PE for CJ. $45\;kg\times \frac{4\;mg\;PE}{kg}=180\;mg\;PE$ - Calculate the volume of fosphenytoin injection required for each maintenance dose. $180\;mg\;PE\times \frac{1\;mL}{50\;mg\;PE}=3.6\;mL\;fosphenytoin\;injection$ - What D5W bag size should be used? $\frac{180\;mg\;PE}{x\;mL}=\frac{25\;mg\;PE}{mL},\;x=7.2\;mL$ If the dose was diluted to a total of 7.2 mL the concentration would be 25 mg PE/mL. The smallest bag is 50 mL, so 50 mL D5W + 3.6 mL fosphenytoin inj = 53.6 mL. Use the 50 mL bag. - Calculate the required solution flow rate in mL/min. $45\;kg\times \frac{2\;mg\;PE}{kg\;\times\;min}\times \frac{53.6\;mL}{180\;mg\;PE}=26.8\;mL/min$ - How many minutes will it take to infuse each maintenance dose? $53.6\;mL\times \frac{1\;min}{26.8\;mL}=2\;min$ When CJ is stabilized and ready for discharge, the physician would like to switch from fosphenytoin to phenytoin chewable tablets for CJ’s outpatient maintenance therapy. - Read the phenytoin product labels. Calculate the dose of phenytoin free acid that is equivalent to each fosphenytoin maintenance dose. $180\;mg\;PE\times \frac{0.92\;mg\;phenytoin}{1\;mg\;PE}=165.6\;mg\;phenytoin$ - The physician orders the phenytoin chewable tablets to be administered twice daily. Calculate how many tablets should CJ take per dose. $165.6\;mg\;phenytoin\times \frac{1\;tab}{50\;mg\;phenytoin}=3.3\;tablets$ It is not practicle to break the chewable tablets to obtain a dose of 3.3 tablets. Suggest to the physician to round the dose up to 3.5 tablets. - Calculate how many tablets should be dispensed for a 90 days’ supply. $90\;days\times \frac{2\;doses}{day}\times \frac{3.5\;tabs}{dose}=630\;tablets$ Module 9C: Gentamicin Extended Interval Dosing Nomogram Gentamicin is an aminoglycoside antibiotic administered by IV infusion for treating infections caused by susceptible strains of Gram-negative bacteria. The dose and frequency of gentamicin administration must be carefully chosen to provide effective therapy while minimizing the risk of toxicity to the kidneys. Gentamicin has traditionally been administered in 3 doses per day. Extended interval dosing is an alternative approach to treat patients with normal renal function and uncomplicated infections. These protocols involve giving a single dose of drug every 1 to 2 days, guided by the plasma concentration of gentamicin after the first dose. Extended interval dosing uses a standard weight-based dose and a nomogram to determine the frequency of administration. SIUE Gentamicin protocol2 - The standard dose of gentamicin is 7 mg/kg. Use actual body weight. For patients whose actual body weight is higher than 1.2 x IBW, use adjusted body weight (factor 0.4): (IBW + 0.4 × (Actual weight - IBW)). - Gentamicin is diluted in 100 mL of D5W and infused over 60 minutes. - Obtain the gentamicin plasma level 6 – 12 hours after the first dose is started. If the dose begins at 0800, order a gentamicin level to be drawn between 1400 and 2000 the same day. - Plot the gentamicin concentration and the blood draw time on the nomogram (Figure 9.1) to determine the appropriate interval for subsequent doses. If the concentration is above the borderline for the Q48h interval, then the patient is not a candidate for extended interval dosing and should be treated according to the traditional approach (not covered here). - Check the gentamicin trough plasma level one time per week. Draw the trough blood sample six hours prior to a dose. The concentration should be less than 1 mcg/mL. If the trough value is higher than 1 mcg/mL, refer to the infectious disease team for dose adjustment (not covered here). Examples (see nomogram below): - A - the blood sample was drawn10 hours after the first dose was started and the gentamicin concentration was 4 mcg/mL. The patient should continue to receive 7 mg/kg at an interval of every 24 hours. - B - the blood sample was drawn 8 hours after the first dose was started and the gentamicin concentration was 8 mcg/mL. The patient should continue to receive 7 mg/kg at an interval of every 36 hours. - C - the blood sample was drawn 11 hours after the first dose was started and the gentamicin concentration was 7 mcg/mL. The patient should continue to receive 7 mg/kg at an interval of every 48 hours. - D - the blood sample was drawn 9.5 hours after the first dose was started and the gentamicin concentration was 12 mcg/mL. The patient should not be treated according to the extended dosing protocol. Figure 9.1 - Gentamicin nomogram Example 9.3: Patient BZ (70 yo male, 210 lb, 5’9”) is prescribed gentamicin 7 mg/kg per the protocol. - What weight should you use to calculate the dose? $Actual\;weight=210\;lb\times \frac{1\;kg}{2.2\;lb}=95.5\;kg$ $IBW=50\;kg\;+\;2.3\;kg(69-60^{"})=70.7\;kg$ $\frac{Actual}{IBW}=\frac{95.5\;kg}{70.7\;kg}=1.35\gt 1.2,\;use\;adjusted\;body\;weight$ $ABW=70.7\;kg\;+\;0.4(95.5-70.7\;kg)=80.6\;kg$ - Calculate the dose in milligrams for BZ. $Dose=80.6\;kg\times\frac{7\;mg}{kg}=564\;mg,\;round\;to\;565\;mg $ - Calculate how many milliliters of the gentamicin injection are required for each dose and the flow rate (mL/min) that should be used to infuse the drug. $565\;mg\;gent\times \frac{1\;mL\;inj}{40\;mg\;gent}=14.1\;mL\;injection \;per\;dose $ The drug is added to 100 mL D5W, so concentration = 565 mg/114.1 mL. The drug is infused over 60 minutes, so flow rate = 114.1 mL/60 min = 1.9 mL/min. - BZ’s first infusion started at 0800 on 1/15/24. A blood sample was drawn at 1830 the same day and the gentamicin level was 5.6 mcg/mL. When (dates and times) should the next 3 doses be administered? The gentamicin level was 5.6 mcg/mL at 10.5 hours after the infusion was started. This point falls into the Q36h section of the nomogram. The next 3 doses should be given at: - Dose 2: 0800 1/15/24 + 36 hours = 2000 1/16/24 - Dose 3: 2000 1/16/24 + 36 hours = 0800 1/18/24 - Dose 4: 0800 1/18/24 + 36 hours = 2000 1/19/24 - The physician wants to check the gentamicin trough level before the 4th dose. When (date and time) should the blood sample be drawn. Troughs are drawn 6 hours prior to a dose. Dose 4 scheduled for 2000 on 1/19/24, so trough should be drawn at 1400 on 1/19/24. 2Based on Stanford Health Care Aminoglycosides Dosing Guidelines (https://med.stanford.edu/content/dam/sm/bugsanddrugs/documents/antimicrobial-dosing-protocols/SHC-Aminoglycoside-Dosing-Guide.pdf) Module 9D: Intravenous Phosphate Supplementation Begin by reviewing the phosphate supplementation examples in Module 8 - Sodium phosphates injection contains 3 mmoles of phosphate and 4 mEq sodium per mL. - Potassium phosphates injection contains 3 mmoles of phosphate and 4.4 mEq potassium per mL. - The plasma potassium level is expected to increase by 0.5 mEq/L for every 40 mEq of potassium administered. - The normal potassium plasma level for this course is 3.5 – 5 mEq/L. (Some institutions or testing labs may have slightly different normal values.) The osmolarity of phosphates infusions must be checked to determine if peripheral infusion is appropriate. The maximum osmolarity for peripheral infusion is 600 mOsm/L. Example 9.4: Patient HP has K+ level of 4.1 mEq/L and requires 45 mmoles of phosphate. The expected K+ level after the dose is less than 5, so this KPhos dose is saf - Calculate the expected potassium level after administering 45 mmoles of potassium phosphates. - Is it safe to administer the dose as potassium phosphates? $45\;mmol\;Phos\times \frac{4.4\;mEq\;K^{+}}{3\;mmol\;Phos}=66\;mEq\;K^{+}\\\\ $ $\frac{4.1\;mEq\;K^{+}}{L}\;+\;66\;mEq\times \frac{0.5\;mEq/L}{40\;mEq\;K^{+}\;dose}=4.9\;mEq\;K^{+}/L\;after\;dose $ The expected K+ level after the dose is less than 5, so this KPhos dose is safe. - What is the minimum volume of D5W that the dose be diluted in (50, 100, 250, 500, or 1000 mL) for peripheral administration, i.e. what volume of D5W will give osmolarity < 600 mOsm/L. $45\;mmol\;KPhos\times \frac{1\;mL}{3\;mmol\;Phos}=15\;mL\;KPhos\;injection$ Find the volume of D5W that will give a final 600 mOsm/L using alligation. The KPhos label shows the injection osmolarity is 7.4 mOsm/mL. Recall D5W osmolarity is 252 mOsm/L or 0.252 mOsm/mL. 600 mOsm/L or 0.6 mOsm/mL is the target value. $\frac{15\;mL}{0.348\;parts}=\frac{x\;mL}{6.4\;parts},\;x=276\text{ mL or larger D5W required. Use 500 mL bag}$ - If HP receives 45 mmoles of potassium phosphates in the smallest appropriate bag for peripheral infusion, what flow rate (mL/hr) should be used to administer the dose over 6 hours. The drug volume is 15 mL and the bag volume is 500 mL = 515 mL total. 515 mL/6 hr = 85.8 or 86 mL/hour Example 9.5: RG has K+ level of 4.8 mEq/L. A physician ordered potassium phosphates 25 mmoles in 250 mL of ½ NS. Is this order safe and appropriate? Determine if any changes are needed, i.e. is the appropriate phosphates salt ordered (final K+ level 5 mEq/L or less) and the osmolarity of the solution 600 mOsm/L or less? If the K+ dose is too high, recommend using the Na Phosphates injection. If the osmolarity is too high, use a larger volume of fluid. $25\;mmol\;Phos\;\times\;\frac{4.4\;mEq\;K^+}{3\;mmol\;Phos}=\;36.7\;mEq\;of\;K^+\;ordered$ $\frac{4.8\;mEq\;K^{+}}{L}\;+\;36.7\;mEq\;\times \frac{0.5\;mEq/L}{40\;mEq\;K^{+}\;dose}=5.3\;mEq\;K^{+}/L\;after\;dose$ This dose is not safe. Recommend sodium phosphates injection. $25\;mmol\;Phos\times \frac{1\;mL}{3\;mmol\;Phos}=8.3\;mL\;NaPhos\;injection$ $Osmolarity=\frac{\left(8.3\;mL\times \frac{7\;mOsm}{mL} \right)+\left(250\;mL\times \frac{0.154\;mOsm}{mL} \right)}{8.3\;+\;250\;mL}\times \frac{1000\;mL}{L}=373\;mOsm/L. $ NaPhos 25 mmol in 250 mL of 1/2 NS is appropriate for administration via a peripheral infusion. Module 9E: Parenteral Nutrition Calculations Stanley Dudrick’s development and introduction of parenteral nutrition (PN) solutions in the 1960s profoundly influenced patient care. From the beginning, Dr. Dudrick insisted that pharmacists be members of the Nutrition Support Team. The American Society for Parenteral and Enteral Nutrition (ASPEN) is a professional organization dedicated to advancing the science and practice of clinical nutrition and metabolism. It publishes detailed information on feeding guidelines for patients receiving parenteral nutrition. If you are interested in clinical nutrition, consider joining this organization. A PN solution typically consists of amino acids, dextrose, fat emulsions, and water. Electrolytes, vitamins, and micronutrients are also used to support normal physiology. The pharmacist typically prepares a PN solution by calculating the component volumes and caloric contributions. You may recall the caloric contributions from biochemistry for dextrose (a monosaccharide carbohydrate), amino acids, and fat. Carbohydrates provide 4 kcal/g, but parenteral solutions use dextrose monohydrate with a caloric value of 3.4 kcal/g. In general, we do not count the calories provided by amino acids since these molecules are used for tissue synthesis and are not intended as an energy source for the nourished patient. If fully metabolized, they would contribute 4 kcal/g. Finally, fat is an essential source of calories and essential fatty acids and has a caloric contribution of 9 kcal/g. Component \| Calories \| Amino Acids \| Not counted, but 4 kcal/g \| Dextrose · H2O \| 3.4 kcal/g \| Fat \| 9 kcal/g \| Several manufacturers offer Amino Acid Solutions (AA). Amino acid product solutions are available in several w/v concentrations. Some brand names include Aminosyn, Plenamine, Prosol, Travasol, and Troph-Amine. There are others. We will not discuss the individual amino acid amounts as they do not directly influence calculation issues. The nutrition team usually refers to amino acids as protein. Dextrose USP injection is available in solutions at 50% and 70% w/v concentrations. Fat emulsions (ILE – intravenous lipid emulsions) are available with several different oil components, and the three commercial concentrations are 10%, 20%, and 30% w/v. Sterile Water for injection (SWFI) makes the final volume after adding electrolytes, vitamins, and minerals. These calculations are identical to the w/v calculations seen in Module 2A. When writing PN orders use 1 decimal place in the percentages for protein, dextrose, and fat. Consider the PN solution order for a hospitalized 180-pound, medically stable patient unable to eat following GI tract surgery. The electrolytes, vitamins, and micronutrients add 65 mL to the total volume. Total daily volume = 2000 mL. The nutrition team wants to provide 20 - 30 kcal/kg/day of energy, not counting the contribution from protein. Amino Acids 3 % Dextrose 19 % Lipids 3 % Your PN compounding supplies include Dextrose 70% injection, an Amino Acid 15% solution, a 20% IV fat emulsion, and sterile water for injection. What volume (mL) of each component is needed to prepare the 2L solution? Dextrose How many grams of Dextrose are in 2000 mL of the PN solution? $\frac{19\;g\;Dextrose}{100\; mL}\;=\frac{X\;g\;Dextrose}{2000\;mL};\;X\;=\;380\;g$ What volume of D70 provides 380 g? $\frac{70\;g\;Dextrose}{100\; mL}\;=\frac{380\;g\;Dextrose}{X\;mL};\;X\;=\;543\;mL$ Amino Acids How many grams of Protein are in 2000 mL? $\frac{3\;g\;Plenamine}{100\; mL}\;=\frac{X\;g\;Plenamine}{2000\;mL};\;X\;=\;60\;g$ What volume of Plenamine 15% provides 60 g? $\frac{15\;g\;Plenamine}{100\; mL}\;=\frac{60\;g\;Plenamine}{X\;mL};\;X\;=\;400\;mL$ Fat How many grams of Fat are in 2000 mL? $\frac{3\;g\;Fat}{100\; mL}\;=\frac{X\;g\;Fat}{2000\;mL};\;X\;=\;60\;g$ What volume of SMOFLipid 20% provides 60 g? $\frac{20\;g\;Fat}{100\; mL}\;=\frac{60\;g\;Fat}{X\;mL};\;X\;=\;300\;mL$ SWFI How much SWFI is needed to qs to 2000 mL? $2000\;mL\;-\;543\;mL\:-\;400\;mL\;-\;300\;mL\;-\;65\;mL\;=\;692\;mL\;water $ Dextrose calories How many kcal are provided by Dextrose when the patient receives the 2000 mL? $380\; g\;\times \;3.4\;\frac{kcal}{g}\;=\;1292\;kcal$ Fat calories How many fat calories are provided by the 2000 mL PN solution per day? Intravenous lipid emulsion (ILE) products use emulsifiers and glycerin in the formulation. The egg phospholipid emulsifiers and glycerin increase the caloric value beyond what you might calculate based on 9 kcal/g of fat. The caloric values per milliliter for several products are summarized in the table. Product \| kcal/mL \| Intralipid 10 % \| 1.1 \| Intralipid 20 % \| 2 \| Intralipid 30 % \| 3 \| Nutrilipid 20 % \| 2 \| Omegaven 10 % \| 1.1 \| SMOFLipid 20 % \| 2 \| $300\; mL\;\times \;2\;\frac{kcal}{mL}\;=\;600\;kcal$ Total Nonprotein Calories An ASPEN guideline suggests providing a total energy (carbohydrate and fat) component of 20 – 30 kcal/kg/day. Does the PN solution attain that target? $1292\;+\;600\;=\;1892\;kcal/day$ $\frac{1892\;kcal/day}{82\;kg}\;=\;23\;kcal/kg/day$ Yes, the formulation meets the target goal. Module 9: Practice Problems 1. Chewbacca needs metronidazole too. Chewbacca is a 17 lb male Maine Coon cat. The veterinarian ordered metronidazole 50 mg/mL suspension, 2 mL PO BID x 10 days for an infection. - The usual dose for this indication in cats is 8 mg/kg BID. Check the dose – if it is not the usual dose, what should you report as the usual dose and volume of 50 mg/mL suspension per dose for Chewbacca when checking with the vet? - Chewbacca’s vet thanks you and accepts your recommendation for the dose. What volume of the drug suspension should be dispensed according to the dosing guideline? (Add about 5 mL extra to allow for some loss during the week of therapy.) - What size of oral syringe should you dispense with the suspension. Your pharmacy compounds metronidazole suspension according to the formula: Metronidazole 5 g Ora Plus® suspending agent 40 mL Flavor concentrate 2.5 mL Purified water qs 100 mL - How many 250 metronidazole tablets should be used to compound the required amount of suspension for Chewbacca? - The flavor concentrate contains fish flavor and 35% v/v propylene glycol in water. - Calculate the percent strength of propylene glycol in the metronidazole suspension. 2. BK (9 years old, 53 kg) is hospitalized for new onset seizures. The physician orders fosphenytoin loading dose and maintenance dose according to the guidelines. - Calculate the recommended loading dose of fosphenytoin for BK - Calculate the recommended flow rate and time required to admininster the loading dose. - Calculate the recommended maintenance dose of fosphenytoin. - Calculate the recommended flow rate and time required to administer the maintenance dose. - Calculate the recommended oral phenytoin dose and the number of infatabs required per dose. - Calculate the number of infatabs that should be dispensed for one month of therapy. Gentamicin Practice Cases 3. Patient IB (38 yo male, 6’1”, 320 lb) is prescribed gentamicin 7 mg/kg per protocol. - Calculate the dose in milligrams for IB. - Calculate how many milliliters of the gentamicin injection are required to prepare each dose and the appropriate flow rate in mL/min. - IB’s first infusion started at 1900 on 2/12/24. A blood sample was drawn at 0630 the next morning and the gentamicin level was 8.8 mcg/mL. When (dates and times) should the next doses be administered? 4. Patient HD (52 yo female, 5’10”, 155 lb) is prescribed gentamicin 7 mg/kg per protocol. - Calculate the dose in milligrams for HD. - Calculate the volume of gentamicin injection required to prepare the dose and the appropriate flow rate in mL/hr. - The first dose infusion was started at 1300 on 2/3/24. What is the window of time (earliest to latest) for the first blood sample to be drawn to determine the gentamicin plasma level according to the protocol. - The first gentamicin plasma level was 3.2 mcg/mL, taken 11 hours after starting the infusion. When should the next dose be administered. Phosphate Practice Cases 5. A 45 year old patient has K+ level of 4.3 mEq/L. The patient is ordered 55 mmol of KPhos to be administered as an isotonic solution by IV infusion over 6 hours. Determine if the order is safe as written. If it is not safe, what should you recommend. The pharmacy will prepare the dose by adding the correct amounts of phosphates injection and sterile water for injection to an empty IV bag. Calculate the volume of sterile water required to make the infusion isotonic. 6. A patient with potassium level of 4.1 mEq/L is ordered 40 mmol of K phos in 250 mL of D5W. Is the order safe and appropriate? If not, recommend an appropriate order. 7. A patient with potassium level of 4.8 mEq/L is ordered 50 mmol of K phos in 250 mL of ½ NS. Is the order safe and appropriate? If not, recommend an appropriate order. 8. A patient with potassium level of 4.6 mEq/L is ordered 30 mmol of K phos to be administered as an isotonic solution in sterile water for injection. Is the order safe and appropriate? If not recommend an appropriate order. Calculate the volume of sterile water required for the final order. 9. A PN solution order is written for a 150-pound, medically stable patient who will use the solution at home after discharge from the hospital. The electrolytes, vitamins, and micronutrients add 90 mL to the total volume. Total daily volume = 1800 mL. Amino Acids 4.1 % Dextrose 20 % Lipids 2.6 % Your PN compounding supplies include Dextrose 50% for injection, an Amino Acids 15%, a 20% IV Fat emulsion, and Sterile Water For Injection. What volume (mL) of each component is needed to prepare 2 L of the solution? How many g/kg/day of amino acids does the patient receive? How many carbohydrate calories are provided by the formula? How many fat calories are provided by the ILE product? How many non-protein kcal/kg/day does the patient receive? How much SWFI is required to make the 1800 mL total volume? 10. Write a PN solution order for a 70 kg patient that provides 1 g/kg/day of amino acids, 0.8 g/kg/day of fat, and 1540 kcal of carbohydrate. Your starting materials are a 10% amino acid solution, a 20% ILE product, Dextrose 70%, and SWFI. The electrolytes, vitamins, and micronutrients add 110 mL to the total volume. The total PN daily volume is 2100 mL. How much SWFI is needed to bring the total volume to 2100 mL? To start, calculate the number of grams needed for each component. Calculate the final concentrations, as in the above problem. You will need to calculate the component volumes to find the required volume of SWFI. 11. A PN solution order is written for a 66-pound, medically stable patient who will use the solution at home after discharge from the hospital. The electrolytes, vitamins, and micronutrients add 50 mL to the total volume. Total daily volume = 1360 mL. Amino Acids 4.4 % Dextrose 19.5 % Lipids 4.4 % Your PN compounding supplies include Dextrose 50% injection, an Amino acid 15% solution, a 20% IV Fat emulsion, and Sterile water for injection. What volume (mL) of each component is needed to prepare the 2 L solution? How many g/kg/day of amino acids does the patient receive? How many carbohydrate calories are provided by the formula? How many fat calories are provided by the ILE product? How many non-protein kcal/kg/day does the patient receive? How much SWFI is required to make the 1360 mL total volume? 12. Write a PN solution order for a 3 kg patient that provides 3 g/kg/day of amino acids, 2.5 g/kg/day of fat, and 176 kcal of carbohydrate. Your starting materials are a 15% amino acid solution, a 30% ILE product, Dextrose 70%, and SWFI. The electrolytes, vitamins, and micronutrients add 41 mL to the total volume. The total PN daily volume is 240 mL. How much SWFI is needed to bring the total volume to 240 mL? To start, calculate the number of grams needed for each component. Calculate the final concentrations, as in the above problem. You will need to calculate the component volumes to find the required volume of SWFI. Follow the advice provided in problem 10. 13. A PN solution order is written for a 55-pound, medically stable patient who is hospitalized and unable to eat. The electrolytes, vitamins, and micronutrients add 60 mL to the total volume. Total daily PN volume = 1200 mL. Amino Acids 4.6 % Dextrose 27 % Lipids 4.4 % Your PN compounding supplies include a 70% dextrose injection, a 15% amino acid solution, a 20% IV Fat emulsion, and Sterile Water for Injection. What volume (mL) of each component is needed to prepare the 2 L solution? How many g/kg/day of amino acids does the patient receive? How many carbohydrate calories are provided by the formula? How many fat calories are provided by the ILE product? How many non-protein kcal/kg/day does the patient receive? How much SWFI is required to make the 1200 mL total volume? 14. Write a PN solution order for a 7 kg patient that provides 2.5 g/kg/day of amino acids, 3 g/kg/day of fat, and 515 kcal of carbohydrate. Your starting materials are a 15% amino acid solution, a 30% ILE product, Dextrose 70%, and SWFI. The electrolytes, vitamins, and micronutrients add 50 mL to the total volume. The total PN daily volume is 630 mL. How much SWFI is needed to bring the total volume to 630 mL? To start, calculate the number of grams needed for each component. Calculate the final concentrations, as in the above problem. You will need to calculate the component volumes to find the required volume of SWFI. Follow the advice provided in problem 10. Answers: Practice Case 1 – Chewbacca the cat - The ordered dose represents 12.9 mg/kg; the dose guideline for Chewbacca is 61.8 mg or 1.2 – 1.3 mL BID. - 1.3 mL BID x 10 days is 26 mL; dispense 30 mL - Dispense a 3 mL (preferred) or 5 mL oral syringe - Six (6) tablets are needed - The propylene glycol concentration is 0.875 or 0.9% v/v Practice Case 2 – Phenytoin - Loading dose 780 mg PE - 15.6 mL fosphenytoin injection required; dose should be diluted in a 50 mL bag of D5W, and infused at 8.7 mL/min, infusion will run for 7.5 minutes - Maintenance dose 210 mg PE (rounded up from 208) - MD should be diluted in 50 mL D5W and infused at 27.1 mL/min, for 2 minutes. - Oral dose 200 mg (rounded up from 191 mg – with MD approval), requires 4 infatabs per dose; dispense 240 tablets for 30 days supply. Practice Cases 3 and 4 - Gentamicin - Calculate 743 mg, round to 745 mg - 18. 6 mL of injection, flow rate 2 mL/min for 118.6 mL - 1900 0630 is 11.5 hours. 8.8 mcg/mL @ 11.5 hours is above the 48 hour line - Protocol is not appropriate for this patient – refer to the infectious disease team - Calculate 494 mg, round to 495 mg - 12.4 mL of injection, 1.9 mL/min to infuse 112.4 mL - Draw 1st level between 6 and 12 hours after starting first dose – so between 1900 2/3 and 0100 2/4 - 3.2 mcg/mL @ 11 hours indicates 24 hr interval, so next dose at 0800 2/4 Practice Cases 5, 6, 7, and 8 - Phosphate Supplementation 5. The K+ level would be 5.3 mEq/L after the dose – recommend 55 mmol Na Phos instead. To produce an isotonic solution, mix 398 mL sterile water + 18.3 mL of NaPhos injection. 6. The K+ level would be 4.8 mEq/L after the dose, so K Phos is appropriate. The osmolarity will be too high (614 mOsm/L) in 250 mL of D5W – recommend 500 mL D5W (438 mOsm/L). 7. The K+ level would be 5.7 mEq/L after the dose – recommend Na Phos. The osmolarity would be 582 mOsm/L in 250 mL of ½ NS, so this volume is appropriate. 8. The K+ level would be 5.2 mEq/L after the dose – recommend Na Phos. The required amount of sterile water is 217 mL. Parenteral Nutrition 9. A PN solution order for a 150-pound, medically stable patient who will use the solution at home after discharge from the hospital. - AA 15% 492 mL D 50% 720 mL ILE 20% 238 mL (Other 90 mL) SEFI 264 mL - Protein ~ 1.1 g/kg/day - Carbs 1224 kcal/day - Fat 476 kcal/day - Calories ~ 25 kcal/kg/day 10. A PN solution for a 70 kg patient. - Amino acids 3.3 % Dextrose 21.6 % Lipids 2.7 % SWFI = 369 mL 11. A PN solution for a 66-pound patient. - AA 15% 400 mL D 50% 529 mL ILE 20% 300 mL (Other 50 mL) SWFI 81 mL - Protein ~ 2 g/kg/day - Carbs 902 kcal/day - Fat 600 kcal/day - Calories ~ 50 kcal/kg/day 12. A PN solution for a 3 kg patient. - Amino acids 3.75 % Dextrose 21.6 % Lipids 3.1 % SWFI = 40 mL 13. A PN solution for a 55-pound patient. - AA 15% 368 mL D 70% 463 mL ILE 20% 264 mL (Other 60 mL) SWFI 45 mL - Protein 2.2 g/kg/day - Carbs 1102 kcal/day - Fat 526 kcal/day - Calories ~ 65 kcal/kg/day 14. A PN solution for a 7 kg patient. - Amino acids 2.8 % Dextrose 24 % Lipids 3.3 % SWFI = 177 mL	oercommons	2025-03-18T00:36:10.069590	Timothy McPherson	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/115797/overview", "title": "Fundamentals of Pharmacy Calculations", "author": "Module" }
https://oercommons.org/courseware/lesson/69346/overview	Albert Bandura: Bobo Doll Experiment APA Code of Ethics APA Cultural Psychology APA Learning and Memory Bio-psychology Bio-psychology Open Stacks Bronfenbrenner Ecological Systems Theory Case Study Examples CaseStudy Salem's Secrets CBT Practice 2 Case Examples Class Activities Cognition, Emotion and Motivation Cognitive Behavioral Case Formulations Confirmation Bias Cultural Perspective Cultural Survey DSM-5 Emotion and Motivation OpenStax Enneagram-personality-test Enneagram Symbol Facebook Reflect Personality Face Recognition Hierarchy of Needs Explained History of Psychology Information Processing Intrinsic Motivation Intrinsic vs. Extrinsic Motivation Introduction to Bio-psychology Is Our Self Related to Personality? Learning Learning and Memory: From Brain to Behavior Little Albert Experiment Lumen Boundless Psychology Lumen Learning Sensation and Perception Memory Motivation and Emotion OpenText Myers Briggs 16Personality Myers Brigss Indicator National Alliance on Mental Illness One Head, Two Brains, Hidden Brain OpenStax Personality OpenStax Psychology Text 2e Optical Illusions Organizational Psychology Motivation Theory Pavlov's Dogs Phenomenological Research Methods for Counseling Psychology Pinel - Touch and Pain Psychological Disorders OpenStax Psychological Facts Psychological Research Research Methods Sensation and Perception Sensation vs. Perception Simple Psychology Abraham Maslow Simple Psychology Social Psychology Social Psychology OpenStax Strengths by Virtue Substance Abuse and Mental Health Services Administration (SAMHSA) Techniques to Enhance Memory and Learning The Focus of Cross-cultural Psychology The Origins of Psychology Timeline History of Psychology # Types of Behavioral Learning Understanding Psychology VIA Character Strengths Survey VIA Classification what-did-you-see-first What is Culture? OpenStax Why Maslow's Hierarchy Matters Introduction to Psychology Overview This course introduces students to the scientific study of the mind and behavior and to the applications of psychological theory to life. Topics include: research methods; biopsychology; lifespan development; memory; learning; social psychology; personality; and psychological health and disorders. This course will establish a foundation for subsequent study in psychology. Resources include: Video, Articles, and Class Activities. Introduction to Psychology This course introduces students to the scientific study of the mind and behavior and to the applications of psychological theory to life. Topics include: research methods; biopsychology; lifespan development; memory; learning; social psychology; personality; and psychological health and disorders. This course will establish a foundation for subsequent study in psychology. History of Psychology Overview: This section will cover the History of Psychology Bio-psychology The human brain is the command center for the human nervous system. It receives signals from the body's sensory organs and outputs information to the muscles. The human brain has the same basic structure as other mammal brains but is larger in relation to body size than any other brains. Facts about the human brain - The human brain is the largest brain of all vertebrates relative to body size. - It weighs about 3.3 lbs. (1.5 kilograms). - The average male has a brain volume of 1,274 cubic centimeters. - The average female brain has a volume of 1,131 cm3. - The brain makes up about 2 percent of a human's body weight. - The cerebrum makes up 85 percent of the brain's weight. - It contains about 86 billion nerve cells (neurons) — the "gray matter." - It contains billions of nerve fibers (axons and dendrites) — the "white matter." - These neurons are connected by trillions of connections, or synapses. Anatomy of the human brain The largest part of the human brain is the cerebrum, which is divided into two hemispheres, according to the Mayfield Clinic. Underneath lies the brainstem, and behind that sits the cerebellum. The outermost layer of the cerebrum is the cerebral cortex, which consists of four lobes: the frontal, parietal, temporal and occipital. [Nervous System: Facts, Functions & Diseases] Like all vertebrate brains, the human brain develops from three sections known as the forebrain, midbrain and hindbrain. Each of these contains fluid-filled cavities called ventricles. The forebrain develops into the cerebrum and underlying structures; the midbrain becomes part of the brainstem; and the hindbrain gives rise to regions of the brainstem and the cerebellum. The cerebral cortex is greatly enlarged in human brains and is considered the seat of complex thought. Visual processing takes place in the occipital lobe, near the back of the skull. The temporal lobe processes sound and language, and includes the hippocampus and amygdala, which play roles in memory and emotion, respectively. The parietal lobe integrates input from different senses and is important for spatial orientation and navigation. The brainstem connects to the spinal cord and consists of the medulla oblongata, pons and midbrain. The primary functions of the brainstem include relaying information between the brain and the body; supplying some of the cranial nerves to the face and head; and performing critical functions in controlling the heart, breathing and consciousness. Between the cerebrum and brainstem lie the thalamus and hypothalamus. The thalamus relays sensory and motor signals to the cortex and is involved in regulating consciousness, sleep and alertness. The hypothalamus connects the nervous system to the endocrine system — where hormones are produced — via the pituitary gland. The cerebellum lies beneath the cerebrum and has important functions in motor control. It plays a role in coordination and balance and may also have some cognitive functions. Humans vs. other animals Overall brain size doesn't correlate with level of intelligence. For instance, the brain of a sperm whale is more than five times heavier than the human brain but humans are considered to be of higher intelligence than sperm whales. The more accurate measure of how intelligent an animal may be is the ratio between the size of the brain and the body size, according to the University of California San Diego's Temporal Dynamics of Learning Center. Among humans, however, brain size doesn't indicate how smart someone is. Some geniuses in their field have smaller- than-average brains, while others larger than average, according to Christof Koch, a neuroscientist and president of the Allen Institute for Brain Science in Seattle. For example, compare the brains of two highly acclaimed writers. The Russian novelist Ivan Turgenev's brain was found to be 2,021 grams, while writer Anatole France's brain weighed only 1,017 grams. Humans have a very high brain-weight-to-body-weight ratio, but so do other animals. The reason why the human's intelligence, in part, is neurons and folds. Humans have more neurons per unit volume than other animals, and the only way to do that with the brain's layered structure is to make folds in the outer layer, or cortex, said Eric Holland, a neurosurgeon and cancer biologist at the Fred Hutchinson Cancer Research Center and the University of Washington. "The more complicated a brain gets, the more gyri and sulci, or wiggly hills and valleys, it has," Holland told Live Science. Other intelligent animals, such as monkeys and dolphins, also have these folds in their cortex, whereas mice have smooth brains, he said. Humans also have the largest frontal lobes of any animal, Holland said. The frontal lobes are associated with higher-level functions such as self-control, planning, logic and abstract thought — basically, "the things that make us particularly human," he said. Left brain vs. right brain The human brain is divided into two hemispheres, the left and right, connected by a bundle of nerve fibers called the corpus callosum. The hemispheres are strongly, though not entirely, symmetrical. The left brain controls all the muscles on the right-hand side of the body and the right brain controls the left side. One hemisphere may be slightly dominant, as with left- or right-handedness. The popular notions about "left brain" and "right brain" qualities are generalizations that are not well supported by evidence. Still, there are some important differences between these areas. The left brain contains regions involved in speech and language (called the Broca's area and Wernicke's area, respectively) and is also associated with mathematical calculation and fact retrieval, Holland said. The right brain plays a role in visual and auditory processing, spatial skills and artistic ability — more instinctive or creative things, Holland said — though these functions involve both hemispheres. "Everyone uses both halves all the time," he said. BRAIN Initiative In April 2013, President Barack Obama announced a scientific grand challenge known as the BRAIN Initiative, short for Brain Research through Advancing Innovative Neurotechnologies. The $100-million-plus effort aimed to develop new technologies that will produce a dynamic picture of the human brain, from the level of individual cells to complex circuits. Like other major science efforts such as the Human Genome Project, although it's expensive, it's usually worth the investment, Holland said. Scientists hope the increased understanding will lead to new ways to treat, cure and prevent brain disorders. The project contains members from several government agencies, including the National Institutes of Health (NIH), the National Science Foundation (NSF) and the Defense Advanced Research Projects Agency (DARPA), as well as private research organizations, including the Allen Institute for Brain Science and the Howard Hughes Medical Institute in Chevy Chase, Maryland. In March 2013, the project's backers outlined their goals in the journal Science. In September 2014, the NIH announced $46 million in BRAIN Initiative grants. Members of industry pledged another $30 million to support the effort, and major foundations and universities also agreed to apply more than $240 million of their own research toward BRAIN Initiative goals. When the project was announced, President Obama convened a commission to evaluate the ethical issues involved in research on the brain. In May 2014, the commission released the first half of its report, calling for ethics to be integrated early and explicitly in neuroscience research. In March 2015, the commission released the second half of the report, which focused on issues of cognitive enhancement, informed consent and using neuroscience in the legal system. The Brain Initiative has achieved several of its goals. As of 2018, the National Institutes of Health (NIH) has "invested more than $559 million in the research of more than 500 scientists," and Congress appropriated "close to $400 million in NIH funding for fiscal year 2018," according to the initiative's website. The research funding facilitated the development of new brain-imaging and brain-mapping tools, and helped create the BRAIN Initiative Cell Census Network — an effort to catalog the brain's "parts' list." Together, these efforts contribute to major advancements in understanding the brain. Additional resources - "Evolution of the brain and Intelligence," by Gerhard Roth and Ursula Dicke, in Trends in Cognitive Sciences (May 2005) - NIH: The BRAIN Initiative - NSF: Understanding the Brain Parts of the human body - Bladder: Facts, Function & Disease - Colon (Large Intestine): Facts, Function & Diseases - Ears: Facts, Function & Disease - Esophagus: Facts, Function & Diseases - How the Human Eye Works - Gallbladder: Function, Problems & Healthy Diet - Human Heart: Anatomy, Function & Facts - Kidneys: Facts, Function & Diseases - Liver: Function, Failure & Disease - Lungs: Facts, Function & Diseases - Nose: Facts, Function & Diseases - Pancreas: Function, Location & Diseases - Small Intestine: Function, Length & Problems - Spleen: Function, Location & Problems - Stomach: Facts, Function & Diseases - The Tongue: Facts, Function & Diseases This article was updated on Sept. 28, 2018, by Live Science contributor Alina Bradford. Research Methods Research Methods: the ways we collect data to answer a research question data collection techniques including how we get respondents, how we ask questions, role of researcher in research and in the respondents/participants lives’, how we analyze the data Research Design: plan for how to answer the research question · Determine which methods are best used for answering the question · Map out how each method will be utilized · Determine limitations of each method for a research project Why do we need a research design? 1. To answer research question systematically/scientifically 2. To control variance: a. Maximize experimental variance (variance of key concepts) b. Minimize extraneous variance (confounding variables, and error) Textbook vs. Real research Academic vs. Applied research Data Collection + Data Analysis = Research Methods and Research Design Quantitative vs. Qualitative Paradigms: Data Collection Methods \| Quantitative: distinct methods Inductive, apriorism hypotheses, Positivism, Durkheim, functionalism, researcher separate from participants \| Qualitative: fluid lines, Deductive, no apriorism hypotheses, Interpretivism, Weber, Symbolic Interactionism, researcher interacts with participants \| \| Experiments: true, quasi \| Observation: participant, non-participant \| \| Surveys: f-to-f, mail, phone \| In-depth interviews: structured, unstructured \| \| Longitudinal: \| Advanced Qualitative Methods: \| \| a. trend: follow 1 variable over timeb. cohort: follow a pop over timec. panel: follow same group over time \| ethnomethodology: study small interactions (moments, situations), look for rules/methods of interaction \| \| phenomenology: study experiences \| \| \| case study, extended case study \| Other data collection methods: historical, document analysis, existing data Dichotomy of Quantitative and Qualitative Methods: Multi-methods: Using more than one research method Evaluation research, applied, action research = use qual + quant research methods Mixed Methods: Usually this works well, but depending on the topic/population, there can be limits: Ex: Doing Grounded Theory with Survey data: really impossible because whomever developed the survey had to have some theory/thoughts to even come up with questions Ex: Ethnography and experiments do not work together Exploratory research often draws on elements of both qual and quant data collection: Can be qualitative or quantitative. Most qualitative research is exploratory. The results of exploratory research often guide additional studies on the topic. · No literature to draw on · Developing a theory/model · Small sample, not representative Rationale Quantitative Research: There is one reality/truth that exists independent of the research. We can know it before observing reality. We can summarize it in words. We can measure it and test it objectively (free from researcher bias, values). “Based on my particular explanation of how the world works, this is what I expect to observe. If I find evidence supporting expectation, then the explanation is correct.” Positivism Quantitative Relationship between theory and method: T+ (theory) RQ+ (research question) M+ (method) T (theory) Rationale Qualitative Research: There is no one reality for a theory (as quantitatively known) to capture. There is no one understanding. Meanings and reality change across people, place and time. Let reality drive understanding (grounded theory). Researcher’s values enhance/shape the study. (Bias) Interpretivism Qualitative Relationship between theory and method: RQ+M+T Which methods you use will influence your research design, research question, researcher, theory, resources, study participants, goals, etc.… Examples of qualitative research questions: 1. Why don’t men go to the doctor when they are sick? 2. How does economic status shape a person’s beliefs and values? 3. How do boys play differently than girls? Examples of quantitative research questions: 1. What is the effect of information seeking on health status? 2. How many women in Pitt County have been raped in their lives? 3. What is the effect of race on women’s career success? Some people only do one method or do only qualitative or quant · Training · Politics · Interest: the types of RQs they ask are best studied with that method · Skills All Research Questions begin with some theory (except grounded theory) Theory: theory shapes concepts, theory determines what is important, previous research leaves holes in understanding: Theory = Symbolic Interaction, Sample RQ = does taking the role of other lower prejudice? Theory= Feminist Theory, Sample RQ = how do men subordinate other men in everyday life? Research Goals Do Quantitative if: · Need to generalize · Need to answer “what” questions, estimate prevalence, incidence of a phenomenon · Need to do research quickly (1 year) Do Qualitative if: · Need to answer how or why questions · If it is a process · If too complicated of a phenomenon to operationalize questions · If you don’t know enough about the phenomenon to develop questions that would reflect the entire the phenomenon · If you think people wouldn’t or couldn’t tell the truth on a survey or experiment · Impossible to reach the people you need to study by survey/experiment · You want to learn about people’s understandings, experiences Developing/writing Research questions Choosing/developing a research question is influenced by researcher, theory, importance of topic to discipline and society Develop research question by: · Reading lit · Talking to people who know about subject · Talking to people who live the subject Start out broad and get narrower as you become familiar with literature and then narrower when you choose your research design Writing Research questions: written clearly, no unnecessary words, no fancy words · Free from ambiguity · Central ideas, key concepts identify · Express relationships btw. Concepts · It is an empirically answerable question · Terminology reflects design: Qualitative = shape, explore / Quant = cause, relationship, influence, affect/effect You will need to refine your research question as you learn more about it from the scientific literature and from experts. With qualitative research: you might refine the question during the study: With quantitative research: you cannot change RQ once data collection has started. So you need to spend a great deal of time upfront nailing down RQs. Your hypotheses can be developed during research, somewhat. Hypotheses in quantitative research: · Conceptual hypotheses follow from research question ex. · The more experiences a person has with taking the role of others, the less prejudice they are. · Operationalized hypothesis follows from conceptual ones after methods are selected: Ex. Respondents who have higher scores on the role taking scale will have lower scores on the prejudice scale than respondents who have lower scores on the role taking scale. · Statistical hypotheses follow from operationalized hyps: mean group 1 < mean group 2 Hypotheses in qualitative research: Do not have hypotheses. You may have expectations. Research Process: How a research project unfolds Quantitative Research Process: impersonal relationship between researcher and study, and between researcher and study participants Theory research question conceptual hypotheses choose methods operationalized hypothesis collect data test data interpret results (support/refute theory) Theory = explanation Theory guides every step in the research process: question, choice of methods, management of concepts Several studies support theory, theory becomes more credible All studies support theory, theory becomes a law (rare in the social sciences) Biases: · Theory determines every part of the research process. Variable selection and msmt. Build a model to test based on theory. Predisposes data to support theory. (Ex. Gender models, measure gender with sex) · Operationalizations error · Variable sociology: build unrealistic “models” and then play god, talk about relationships between variables, differences between variables, · Context free: doesn’t always translate to anything real or meaningful about real life Sections to a Quantitative paper Abstract, Introduction (statement of problem), Lit Review, Methods, Results, Discussion, Conclusion (either summarize paper or review limitations of study) Qualitative Research Process: not a set pattern like quantitative research, process depends on method used Grounded theory: research question choose methods collect data revise research question collect data results (look for patterns) build theory from patterns draw on lit to further develop/validate explanation (Theory is built from data) Ethnography: same as grounded theory or: research question choose methods collect data revise research question collect data results (look for patterns) draw on theory/lit to explain patterns (draw on theory/lit at end rather than at beginning) Phenomenology: research question methods results (No theory) General qualitative: similar to quantitative process: Theory research question choose methods lit review collect data revise research question collect data results (look for patterns, do they support theory) Bias: 1. generalizations poor (“Here is how the world looked when I observed it.”), impossible to do true grounded theory 2. Only micro topics Sections to a Qualitative paper: no 1 format, depends on method, writing personal Ethnography: Abstract* (not always with qual paper), Introduction/Theory/Research Q, Methods, Results/Discussion (These sections are usually combined, explain findings as you present them drawing on theory and lit to explain) Grounded Theory: Abstract, Intro/ Research Q, Methods, Results/Discussion (draw on lit, explain theory that is built from data) General Qualitative: same as quantitative Research Proposal Sections 1. Introduction: make reader care, written plainly,no fancy words statement of problem initial research question hy important: how important to society, discipline 2. Literature Review: Summarize findings of previous or related research explain theory review previous work on research question a. What do we already know: Findings, how studied, concepts, limitations/problems, Identify your narrowed down research question, how your study will be different from previous work, conceptual hypotheses (if quant) only review articles which are directly related to your research question. Exception: there are no other studies on your question (not recommended for thesis) 3. Research Design: · Data collection methods why chose this method · Sampling: who observed/interviewed, unit of analysis · Variables/questions/measurement (interview guide) · Data documentation (video, audio) · Length of data collection · Role of researcher · Operationalized specific hypotheses · Data analysis plans · Statistical hypotheses (*bridge to results in papers) · Potential limitations of methods · Appendices: diagram of research design, survey, interview guide, informed consent, timeline of data collection, statistical model to be tested Learning and Memory Learning and memory are closely related concepts. Learning is the acquisition of skill or knowledge, while memory is the expression of what you’ve acquired. Another difference is the speed with which the two things happen. If you acquire the new skill or knowledge slowly and laboriously, that’s learning. If acquisition occurs instantly, that’s making a memory. The relationship between learning and memory is incredibly close and intertwined. As stated by the American Psychological Association, learning means securing various skills and information, while memory relates to how the mind stores and recalls information. It is almost impossible for an individual to truly learn something without also having the memory to retain what they have learned. In many ways, learning and memory maintain a very interdependent relationship, one that is much more nuanced and complex than it may appear to be on the surface. The Interdependence Of Learning And Memory Learning and memory share quite interesting parallels. First and foremost, both functions exist in and rely upon the brain. Without the brain, both learning and memory would be impossible. While learning can concern events that can take place in the past, present, and future, memory pertains to occurrences that have already passed. In other words, an individual can learn something new at virtually any time. Information, however, can only be mentally processed and stored in memory after learning. The ability to learn relies upon one's memory. Learning requires brain stimulation from the memory just as memory needs functional learning processes to collect and store new information. Everyone has different styles of learning, and sometimes some extra assistance from an educator or a counselor is needed to improve a person's ability to learn and retain information. However, there are things that you can do on your own to help improve these essential cognitive functions. What Is Learning? Learning is an adaptive function by which our nervous system changes in relation to stimuli in the environment, thus changing our behavioral responses and permitting us to function in our environment. The process occurs initially in our nervous system in response to environmental stimuli. Neural pathways can be strengthened, pruned, activated, or rerouted, all of which cause changes in our behavioral responses. Instincts and reflexes are innate behaviors—they occur naturally and do not involve learning. In contrast, learning is a change in behavior or knowledge that results from experience. The field of behavioral psychology focuses largely on measurable behaviors that are learned, rather than trying to understand internal states such as emotions and attitudes. Types of Learning There are three main types of learning: classical conditioning, operant conditioning, and observational learning. Both classical and operant conditioning are forms of associative learning, in which associations are made between events that occur together. Observational learning is just as it sounds: learning by observing others. Classical Conditioning Classical conditioning is a process by which we learn to associate events, or stimuli, that frequently happen together; as a result of this, we learn to anticipate events. Ivan Pavlov conducted a famous study involving dogs in which he trained (or conditioned) the dogs to associate the sound of a bell with the presence of a piece of meat. The conditioning is achieved when the sound of the bell on its own makes the dog salivate in anticipation for the meat. Operant Conditioning Operant conditioning is the learning process by which behaviors are reinforced or punished, thus strengthening or extinguishing a response. Edward Thorndike coined the term “law of effect,” in which behaviors that are followed by consequences that are satisfying to the organism are more likely to be repeated, and behaviors that are followed by unpleasant consequences are less likely to be repeated. B. F. Skinner researched operant conditioning by conducting experiments with rats in what he called a “Skinner box.” Over time, the rats learned that stepping on the lever directly caused the release of food, demonstrating that behavior can be influenced by rewards or punishments. He differentiated between positive and negative reinforcement, and also explored the concept of extinction. Observational Learning Observational learning occurs through observing the behaviors of others and imitating those behaviors—even if there is no reinforcement at the time. Albert Bandura noticed that children often learn through imitating adults, and he tested his theory using his famous Bobo-doll experiment. Through this experiment, Bandura learned that children would attack the Bobo doll after viewing adults hitting the doll. Adapted from: Introduction to Learning \| Boundless Psychology Sensation and Perception Sensation and perception are two separate processes that are very closely related. Sensation is input about the physical world obtained by our sensory receptors, and perception is the process by which the brain selects, organizes, and interprets these sensations. In other words, senses are the physiological basis of perception. Perception of the same senses may vary from one person to another because each person’s brain interprets stimuli differently based on that individual’s learning, memory, emotions, and expectations. The sensitivity of a given sensory system to the relevant stimuli can be expressed as an absolute threshold. Absolute threshold refers to the minimum amount of stimulus energy that must be present for the stimulus to be detected 50% of the time. Another way to think about this is by asking how dim can a light be or how soft can a sound be and still be detected half of the time. The sensitivity of our sensory receptors can be quite amazing. It has been estimated that on a clear night, the most sensitive sensory cells in the back of the eye can detect a candle flame 30 miles away (Okawa & Sampath, 2007). Under quiet conditions, the hair cells (the receptor cells of the inner ear) can detect the tick of a clock 20 feet away (Galanter, 1962). It is also possible for us to get messages that are presented below the threshold for conscious awareness—these are called subliminal messages. A stimulus reaches a physiological threshold when it is strong enough to excite sensory receptors and send nerve impulses to the brain: this is an absolute threshold. A message below that threshold is said to be subliminal: we receive it, but we are not consciously aware of it. Therefore, the message is sensed, but for whatever reason, it has not been selected for processing in working or short-term memory. Over the years there has been a great deal of speculation about the use of subliminal messages in advertising, rock music, and self-help audio programs. Research evidence shows that in laboratory settings, people can process and respond to information outside of awareness. But this does not mean that we obey these messages like zombies; in fact, hidden messages have little effect on behavior outside the laboratory (Kunst-Wilson & Zajonc, 1980; Rensink, 2004; Nelson, 2008; Radel, Sarrazin, Legrain, & Gobancé, 2009; Loersch, Durso, & Petty, 2013). Perception While our sensory receptors are constantly collecting information from the environment, it is ultimately how we interpret that information that affects how we interact with the world. Perception refers to the way sensory information is organized, interpreted, and consciously experienced. Perception involves both bottom-up and top-down processing. Bottom-up processing refers to the fact that perceptions are built from sensory input. On the other hand, how we interpret those sensations is influenced by our available knowledge, our experiences, and our thoughts. This is called top-down processing. Look at the shape in Figure 3 below. Seen alone, your brain engages in bottom-up processing. There are two thick vertical lines and three thin horizontal lines. There is no context to give it a specific meaning, so there is no top-down processing involved. Figure 3. What is this image? Without any context, you must use bottom-up processing. Now, look at the same shape in two different contexts. Surrounded by sequential letters, your brain expects the shape to be a letter and to complete the sequence. In that context, you perceive the lines to form the shape of the letter “B.” Figure 4. With top-down processing, you use context to give meaning to this image. Surrounded by numbers, the same shape now looks like the number “13.” Figure 5. With top-down processing, you use context to give meaning to this image. When given a context, your perception is driven by your cognitive expectations. Now you are processing the shape in a top-down fashion. One way to think of this concept is that sensation is a physical process, whereas perception is psychological. For example, upon walking into a kitchen and smelling the scent of baking cinnamon rolls, the sensation is the scent receptors detecting the odor of cinnamon, but the perception may be “Mmm, this smells like the bread Grandma used to bake when the family gathered for holidays.” Although our perceptions are built from sensations, not all sensations result in perception. In fact, we often don’t perceive stimuli that remain relatively constant over prolonged periods of time. This is known as sensory adaptation. Imagine entering a classroom with an old analog clock. Upon first entering the room, you can hear the ticking of the clock; as you begin to engage in conversation with classmates or listen to your professor greet the class, you are no longer aware of the ticking. The clock is still ticking, and that information is still affecting sensory receptors of the auditory system. The fact that you no longer perceive the sound demonstrates sensory adaptation and shows that while closely associated, sensation and perception are different. Adapted from: Sensation and Perception \| Introduction to Psychology Motivation and Emotion Abraham Maslow’s Hierarchy of Needs The Hierarchy of Needs Maslow contextualized his theory of self-actualization within a hierarchy of needs. The hierarchy represents five needs arranged from lowest to highest, as follows: - Physiological needs: These include needs that keep us alive, such as food, water, shelter, warmth, and sleep. - Safety needs: The need to feel secure, stable, and unafraid. - Love and belongingness needs: The need to belong socially by developing relationships with friends and family. - Esteem needs: The need to feel both (a) self-esteem based on one’s achievements and abilities and (b) recognition and respect from others. - Self-actualization needs: The need to pursue and fulfill one’s unique potentials. When Maslow originally explained the hierarchy in 1943, he stated that higher needs generally won’t be pursued until lower needs are met. However, he added, a need does not have to be completely satisfied for someone to move onto the next need in the hierarchy. Instead, the needs must be partially satisfied, meaning that an individual can pursue all five needs, at least to some extent, at the same time. Maslow included caveats in order to explain why certain individuals might pursue higher needs before lower ones. For example, some people who are especially driven by the desire to express themselves creatively may pursue self-actualization even if their lower needs are unmet. Similarly, individuals who are particularly dedicated to pursuing higher ideals may achieve self-actualization despite adversity that prevents them from meeting their lower needs. Defining Self-Actualization To Maslow, self-actualization is the ability to become the best version of oneself. Maslow stated, “This tendency might be phrased as the desire to become more and more what one is, to become everything that one is capable of becoming.” Of course, we all hold different values, desires, and capacities. As a result, self-actualization will manifest itself differently in different people. One person may self-actualize through artistic expression, while another will do so by becoming a parent, and yet another by inventing new technologies. Maslow believed that, because of the difficulty of fulfilling the four lower needs, very few people would successfully become self-actualized, or would only do so in a limited capacity. He proposed that the people who can successfully self actualize share certain characteristics. He called these people self-actualizers. According to Maslow, self-actualizers share the ability to achieve peak experiences, or moments of joy and transcendence. While anyone can have a peak experience, self-actualizers have them more frequently. In addition, Maslow suggested that self-actualizers tend to be highly creative, autonomous, objective, concerned about humanity, and accepting of themselves and others. Maslow contended that some people are simply not motivated to self-actualize. He made this point by differentiating between deficiency needs, or D-needs, which encompass the four lower needs in his hierarchy, and being needs, or B-needs. Maslow said that D-needs come from external sources, while B-needs come from within the individual. According to Maslow, self-actualizers are more motivated to pursue B-needs than non-self-actualizers. Criticism and Further Study The theory of self-actualization has been criticized for its lack of empirical support and for its suggestion that lower needs must be met before self-actualization is possible. In 1976, Wahba and Bridwell investigated these issues by reviewing a number of studies exploring different parts of the theory. They found only inconsistent support for the theory, and limited support for the proposed progression through Maslow’s hierarchy. However, the idea that some people are more motivated by B-needs than D-needs was supported by their research, lending increased evidence to the idea that some people may be more naturally motivated towards self-actualization than others. A 2011 study by Tay and Diener explored the satisfaction of needs that roughly matched those in Maslow’s hierarchy in 123 countries. They found that the needs were largely universal, but that the fulfillment of one need was not dependent on the fulfillment of another. For example, an individual can benefit from self-actualization even if they have not met their need to belong. However, the study also showed that when most citizens in a society have their basic needs met, more people in that society focus on pursuing a fulfilling and meaningful life. Taken together, the results of this study suggest that self-actualization can be attained before all of the four other needs are met, but that having one's most basic needs met makes self-actualization much more likely. The evidence for Maslow’s theory is not conclusive. Future research involving self-actualizers is needed in order to learn more. Yet given its importance to the history of psychology, the theory of self-actualization will maintain its place in the pantheon of classic psychological theories. Adapted from: Understanding Maslow's Theory of Self-Actualization Personality and Self What Is Personality? From eccentric and introverted to boisterous and bold, the human personality is a complex and colorful thing. Personality refers to a person's distinctive patterns of thinking, feeling, and behaving. It derives from a mix of innate dispositions and inclinations along with environmental factors and experiences. Although personality can change over a lifetime, one's core personality traits tend to remain relatively consistent during adulthood. While there are countless characteristics that combine in an almost infinite number of ways, people have been trying to find a way to classify personalities ever since Hippocrates and the ancient Greeks proposed four basic temperaments. Today, psychologists often describe personality in terms of five basic traits. The so-called Big Five are openness to experience, conscientiousness, extraversion, agreeableness, and neuroticism. A newer model, called HEXACO, incorporates honesty-humility as a sixth key trait. What's My Personality Type? The idea of a personality "type" is fairly widespread. Many people associate a "Type A" personality with a more organized, rigid, competitive, and anxious person, for example. Yet there’s little empirical support for the idea. The personality types supplied by the popular Myers-Briggs Type Indicator have also been challenged by scientists. Psychologists who study personality believe such typologies generally are too simplistic to account for the ways people differ. Instead, there is broad scientific consensus around the Big Five model of trait dimensions, each of which contributes to one's personality and is largely independent of the others. Why Personality Matters Personality psychology—with its different ways of organizing, measuring, and understanding individual differences—can help people better grasp and articulate what they are like and how they compare to others. But the details of personality are relevant to more than just a person's self-image. The tendencies in thinking and behaving that concepts like the Big Five represent are related to a variety of other ways in which people compare to one another. These include differences in personal success, health and well-being, and how people get along with others. Personality also crosses into the realm of mental health: Professionals use a list of personality disorders involving long-term dysfunctional tendencies to diagnose and treat patients. Personality Traits Traits are the building blocks of personality. So what is a trait? In short, it’s a relatively stable way of thinking and behaving that can be used to describe a person and compare and contrast that person with others. Traits can be cast in very broad terms, such as how positively disposed a person generally is toward other people, or in more specific ones, such as how much that person tends to trust other people. These more specific aspects of personality are sometimes referred to as “facets.” Personality traits are usually considered distinct from mental abilities (including general intelligence) that are assessed based on how well one responds to problems or questions. Psychologists have developed a variety of ways to define and organize the span of personality traits. They are often bundled together based on broad personality factors, as in the commonly used Big Five trait taxonomy. But personality can be sliced in many different ways, and some traits are frequently measured and studied by psychologists on their own. Here are some of the scientifically studied groups of personality traits. Importantly, people generally do not simply have these traits or not have them—they can rate high, low, or somewhere in the middle on each one, compared to other people. The Big Five Personality Traits The Big Five traits—usually labeled openness, conscientiousness, extroversion, agreeableness, and neuroticism, or OCEAN for short—are among the most commonly studied in psychology. The five-factor model splits personality into five broad traits that an individual can rate higher or lower on compared to other people, based on the extent to which the person exhibits them. Each of the five personality factors covers a group of narrower personality facets that tend to go together in individuals. For more on the five-factor model, see the Big Five Personality Traits. HEXACO and Honesty-Humility Some personality researchers have proposed a sixth major trait factor, in addition to the Big Five: it’s called honesty-humility and provides the “H” in the HEXACO model. Honesty-humility as a trait concept reflects the degree to which people place themselves ahead of other people, such as by seeking special treatment or manipulating others. Proposed facets include sincerity, fairness, and the avoidance of greed. For more on honesty-humility, see HEXACO. The Dark Triad Three traits, often called the Dark Triad—narcissism, psychopathy, and Machiavellianism—are commonly assessed to investigate the darker, or more antagonistic and self-interested side of human nature. While they represent particular ways of thinking about anti-social thoughts and behavior, they are not necessarily separate from other traits—for instance, it’s easy to see how they share some common ground with the Big Five concept of agreeableness or HEXACO’s honesty-humility. Some people who rate highly on these traits are described as being “a narcissist” or a “psychopath,” but the Dark Triad traits can be thought of in terms of a spectrum: A person can rate low, high, or anywhere in between on each one. Personality disorders, some of which involve Dark Triad-related behavior, are defined differently, using specified cut-offs for diagnosis. For more, see Dark Triad and Personality Disorders Adapted from: Personality Traits Psychological Disorders The term psychological disorder is sometimes used to refer to what is more frequently known as mental disorders or psychiatric disorders. Mental disorders are patterns of behavioral or psychological symptoms that impact multiple areas of life. These disorders create distress for the person experiencing these symptoms. While not a comprehensive list of every mental disorder, the following list includes some of the major categories of disorders described in the Diagnostic and Statistical Manual of Mental Disorders (DSM). The latest edition of the diagnostic manual is the DSM-5 and was released in May of 2013.1 The DSM is one of the most widely used systems for classifying mental disorders and provides standardized diagnostic criteria. Neurodevelopmental disorders are those that are typically diagnosed during infancy, childhood, or adolescence. These psychological disorders include: Intellectual Disability Sometimes called Intellectual Developmental Disorder, this diagnosis was formerly referred to as mental retardation.1 This type of developmental disorder originates prior to the age of 18 and is characterized by limitations in both intellectual functioning and adaptive behaviors. Limitations to intellectual functioning are often identified through the use of IQ tests, with an IQ score under 70 often indicating the presence of a limitation. Adaptive behaviors are those that involve practical, everyday skills such as self-care, social interaction, and living skills. Global Developmental Delay This diagnosis is for developmental disabilities in children who are under the age of five. Such delays relate to cognition, social functioning, speech, language, and motor skills. It is generally seen as a temporary diagnosis applying to kids who are still too young to take standardized IQ tests. Once children reach the age where they are able to take a standardized intelligence test, they may be diagnosed with an intellectual disability. Communication Disorders These disorders are those that impact the ability to use, understand, or detect language and speech. The DSM-5 identifies four different subtypes of communication disorders: language disorder, speech sound disorder, childhood onset fluency disorder (stuttering), and social (pragmatic) communication disorder. Autism Spectrum Disorder This disorder is characterized by persistent deficits in social interaction and communication in multiple life areas as well as restricted and repetitive patterns of behaviors. The DSM specifies that symptoms of autism spectrum disorder must be present during the early developmental period and that these symptoms must cause significant impairment in important areas of life including social and occupational functioning. Attention-Deficit Hyperactivity Disorder (ADHD) ADHD is characterized by a persistent pattern of hyperactivity-impulsivity and/or inattention that interferes with functioning and presents itself in two or more settings such as at home, work, school, and social situations.The DSM-5 specifies that several of the symptoms must have been present prior to the age of 12 and that these symptoms must have a negative impact on social, occupational, or academic functioning. Bipolar and Related Disorders Bipolar disorder is characterized by shifts in mood as well as changes in activity and energy levels. The disorder often involves experiencing shifts between elevated moods and periods of depression. Such elevated moods can be pronounced and are referred to either as mania or hypomania. Mania This mood is characterized by a distinct period of elevated, expansive, or irritable mood accompanied by increased activity and energy. Periods of mania are sometimes marked by feelings of distraction, irritability, and excessive confidence. People experiencing mania are also more prone to engage in activities that might have negative long-term consequences such as gambling and shopping sprees. Depressive Episodes These episodes are characterized by feelings of a depressed or sad mood along with a lack of interest in activities. It may also involve feelings of guilt, fatigue, and irritability. During a depressive period, people with bipolar disorder may lose interest in activities that they previously enjoyed, experience sleeping difficulties, and even have thoughts of suicide. Both manic and depressive episodes can be frightening for both the person experiencing these symptoms as well as family, friends and other loved ones who observe these behaviors and mood shifts. Fortunately, appropriate and effective treatments, which often include both medications and psychotherapy, can help people with bipolar disorder successfully manage their symptoms. Anxiety Disorders Anxiety disorders are those that are characterized by excessive and persistent fear, worry, anxiety and related behavioral disturbances. Fear involves an emotional response to a threat, whether that threat is real or perceived. Anxiety involves the anticipation that a future threat may arise. Types of anxiety disorders include: Generalized Anxiety Disorder (GAD) This disorder is marked by excessive worry about everyday events. While some stress and worry are a normal and even common part of life, GAD involves worry that is so excessive that it interferes with a person's well-being and functioning. Agoraphobia This condition is characterized by a pronounced fear of a wide range of public places. People who experience this disorder often fear that they will suffer a panic attack in a setting where escape might be difficult. Because of this fear, those with agoraphobia often avoid situations that might trigger an anxiety attack. In some cases, this avoidance behavior can reach a point where the individual is unable to even leave their own home. Social Anxiety Disorder Social anxiety disorder is a fairly common psychological disorder that involves an irrational fear of being watched or judged. The anxiety caused by this disorder can have a major impact on an individual's life and make it difficult to function at school, work, and other social settings. Specific Phobias These phobias involve an extreme fear of a specific object or situation in the environment. Some examples of common specific phobias include the fear of spiders, fear of heights, or fear of snakes. The four main types of specific phobias involve natural events (thunder, lightening, tornadoes), medical (medical procedures, dental procedures, medical equipment), animals (dogs, snakes, bugs), and situational (small spaces, leaving home, driving). When confronted by a phobic object or situation, people may experience nausea, trembling, rapid heart rate, and even a fear of dying. Panic Disorder This psychiatric disorder is characterized by panic attacks that often seem to strike out of the blue and for no reason at all. Because of this, people with panic disorder often experience anxiety and preoccupation over the possibility of having another panic attack. People may begin to avoid situations and settings where attacks have occurred in the past or where they might occur in the future. This can create significant impairments in many areas of everyday life and make it difficult to carry out normal routines. Separation Anxiety Disorder This condition is a type of anxiety disorder involving an excessive amount of fear or anxiety related to being separated from attachment figures. People are often familiar with the idea of separation anxiety as it relates to young children's fear of being apart from their parents, but older children and adults can experience it as well. When symptoms become so severe that they interfere with normal functioning, the individual may be diagnosed with separation anxiety disorder. Symptoms involve an extreme fear of being away from the caregiver or attachment figure. The person suffering these symptoms may avoid moving away from home, going to school, or getting married in order to remain in close proximity to the attachment figure. Stress Related Disorder Trauma and stressor-related disorders involve exposure to a stressful or traumatic event.6 These were previously grouped with anxiety disorders but are now considered a distinct category of disorders. Disorders included in this category include: Acute Stress Disorder Acute stress disorder is characterized by the emergence of severe anxiety for up to a one month period after exposure to a traumatic event. Some examples of traumatic events include natural disasters, war, accidents, and witnessing a death. As a result, the individual may experience dissociative symptoms such as a sense of altered reality, an inability to remember important aspects of the event, and vivid flashbacks as if the event were reoccurring. Other symptoms can include reduced emotional responsiveness, distressing memories of the trauma, and difficulty experiencing positive emotions. Adjustment Disorders Adjustment disorders can occur as a response to a sudden change such as divorce, job loss, end of a close relationship, a move, or some other loss or disappointment. This type of psychological disorder can affect both children and adults and is characterized by symptoms such as anxiety, irritability, depressed mood, worry, anger, hopelessness, and feelings of isolation. Post-Traumatic Stress Disorder (PTSD) PTSD can develop after an individual has experienced exposure to actual or threatened death, serious injury, or sexual violence. Symptoms of PTSD include episodes of reliving or re-experiencing the event, avoiding things that remind the individual about the event, feeling on edge, and having negative thoughts. Reactive Attachment Disorder Reactive attachment disorder can result when children do not form normal healthy relationships and attachments with adult caregivers during the first few years of childhood. Symptoms of the disorder include being withdrawn from adult caregivers and social and emotional disturbances that result from patterns of insufficient care and neglect. Dissociative Disorders Dissociative disorders are psychological disorders that involve a dissociation or interruption in aspects of consciousness, including identity and memory.1 Dissociative disorders include: Dissociative Amnesia This disorder involves a temporary loss of memory as a result of dissociation. In many cases, this memory loss, which may last for just a brief period or for many years, is a result of some type of psychological trauma. Dissociative amnesia is much more than simple forgetfulness. Those who experience this disorder may remember some details about events but may have no recall of other details around a circumscribed period of time. Dissociative Identity Disorder Formerly known as multiple personality disorder, dissociative identity disorder involves the presence of two or more different identities or personalities. Each of these personalities has its own way of perceiving and interacting with the environment. People with this disorder experience changes in behavior, memory, perception, emotional response, and consciousness. Depersonalization/Derealization Disorder Depersonalization/derealization disorder is characterized by experiencing a sense of being outside of one's own body (depersonalization) and being disconnected from reality (derealization). People who have this disorder often feel a sense of unreality and an involuntary disconnect from their own memories, feelings, and consciousness. Somatic Symptom Disorders Formerly referred to under the heading of somatoform disorders, this category is now known as somatic symptoms and related disorders.7 Somatic symptom disorders are a class of psychological disorders that involve prominent physical symptoms that may not have a diagnosable physical cause. In contrast to previous ways of conceptualizing these disorders based on the absence of a medical explanation for the physical symptoms, the current diagnosis emphasizes the abnormal thoughts, feelings, and behaviors that occur in response to these symptoms. Disorders included in this category: Somatic Symptom Disorder Somatic symptom disorder involves a preoccupation with physical symptoms that make it difficult to function normally. This preoccupation with symptoms results in emotional distress and difficulty coping with daily life. It is important to note that somatic symptoms do not indicate that individuals are faking their physical pain, fatigue, or other symptoms. In this situation, it is not so much the actual physical symptoms that are disrupting the individual's life as it is the extreme reaction and resulting behaviors. Illness Anxiety Disorder Illness anxiety disorder is characterized by excessive concern about having an undiagnosed medical condition. Those who experience this psychological disorder worry excessively about body functions and sensations are convinced that they have or will get a serious disease, and are not reassured when medical tests come back negative. Conversion Disorder Conversion disorder involves experiencing motor or sensory symptoms that lack a compatible neurological or medical explanation. In many cases, the disorder follows a real physical injury or stressful event which then results in a psychological and emotional response. Factitious Disorder Factitious disorder used to have its own category, is now included under the somatic symptom and related disorders category of the DSM-5. A factitious disorder is when an individual intentionally creates, fakes, or exaggerates symptoms of illness. Munchausen syndrome, in which people feign an illness to attract attention, is one severe form of factitious disorder. Eating Disorders Eating disorders are characterized by obsessive concerns with weight and disruptive eating patterns that negatively impact physical and mental health. Feeding and eating disorders that used to be diagnosed during infancy and childhood have been moved to this category in the DSM-5.⁸ Types of eating disorders include: Anorexia Nervosa Anorexia nervosa is characterized by restricted food consumption that leads to weight loss and a very low body weight. Those who experience this disorder also have a preoccupation and fear of gaining weight as well as a distorted view of their own appearance and behavior. Bulimia Nervosa Bulimia nervosa involves binging and then taking extreme steps to compensate for these binges. These compensatory behaviors might include self-induced vomiting, the abuse of laxatives or diuretics, and excessive exercise. Rumination Disorder Rumination disorder is marked by regurgitating previously chewed or swallowed food in order to either spit it out or re-swallow it. Most of those affected by this disorder are children or adults who also have a developmental delay or intellectual disability. Pica Pica involves craving and consuming non-food substances such as dirt, paint, or soap. The disorder most commonly affects children and those with developmental disabilities. Binge-Eating Disorder Binge-eating disorder was first introduced in the DSM-5 and involves episodes of binge eating where the individual consumes an unusually large amount of over the course of a couple hours. Not only do people overeat, however, they also feel as if they have no control over their eating. Binge eating episodes are sometimes triggered by certain emotions such as feeling happy or anxious, by boredom or following stressful events. Sleep Disorders Sleep disorders involve an interruption in sleep patterns that lead to distress and affects daytime functioning. Examples of sleep disorders include: Narcolepsy Narcolepsy is a condition in which people experience an irrepressible need to sleep. People with narcolepsy may experience a sudden loss of muscle tone. Insomnia Disorder Insomnia disorder involves being unable to get enough sleep to feel rested. While all people experience sleeping difficulties and interruptions at some point, insomnia is considered a disorder when it is accompanied by significant distress or impairment over time. Hypersomnolence Hypersomnolence disorder is characterized by excessive sleepiness despite an adequate main sleep period. People with this condition may fall asleep during the day at inappropriate times such as at work and school. Breathing-Related Sleep Disorders Breathing-related sleep disorders are those that involve breathing anomalies such as sleep apnea that can occur during sleep. These breathing problems can result in brief interruptions in sleep that can lead to other problems including insomnia and daytime sleepiness. Parasomnias Parasomnias involve disorders that feature abnormal behaviors that take place during sleep. Such disorders include sleepwalking, sleep terrors, sleep talking, and sleep eating. Restless Legs Syndrome Restless legs syndrome is a neurological condition that involves having uncomfortable sensations in the legs and an irresistible urge to move the legs in order to relieve the sensations. People with this condition may feel tugging, creeping, burning, and crawling sensations in their legs resulting in an excessive movement which then interferes with sleep. Sleep disorders related to other mental disorders as well as sleep disorders related to general medical conditions have been removed from the DSM-5. The latest edition of the DSM also provides more emphasis on coexisting conditions for each of the sleep-wake disorders. Disruptive Disorders Impulse-control disorders are those that involve an inability to control emotions and behaviors, resulting in harm to oneself or others.1 These problems with emotional and behavioral regulation are characterized by actions that violate the rights of others such as destroying property or physical aggression and/or those that conflict with societal norms, authority figures, and laws. Types of impulse-control disorders include: Kleptomania Kleptomania involves an inability to control the impulse to steal. People who have kleptomania will often steal things that they do not really need or that have no real monetary value. Those with this condition experience escalating tension prior to committing a theft and feel relief and gratification afterwards. Pyromania Pyromania involves a fascination with fire that results in acts of fire-starting that endanger the self and others. People who struggle with pyromania purposefully and deliberately have set fires more than one time. They also experience tension and emotional arousal before setting a fire. Intermittent Explosive Disorder Intermittent explosive disorder is characterized by brief outbursts of anger and violence that are out of proportion for the situation. People with this disorder may erupt into angry outbursts or violent actions in response to everyday annoyances or disappointments. Conduct Disorder Conduct disorder is a condition diagnosed in children and adolescents under the age of 18 who regularly violate social norms and the rights of others. Children with this disorder display aggression toward people and animals, destroy property, steal and deceive, and violate other rules and laws. These behaviors result in significant problems in a child's academic, work, or social functioning. Oppositional Defiant Disorder Oppositional defiant disorder begins prior to the age of 18 and is characterized by defiance, irritability, anger, aggression, and vindictiveness. While all kids behave defiantly sometimes, kids with oppositional defiant disorder refuse to comply with adult requests almost all the time and engage in behaviors to deliberately annoy others. Depressive Disorders Depressive disorders are a type of mood disorder that include a number of conditions. They are all characterized by the presence of sad, empty, or irritable moods accompanied by physical and cognitive symptoms. They differ in terms of duration, timing, or presumed etiology. - Disruptive mood dysregulation disorder: A childhood condition characterized by extreme anger and irritability. Children display frequent and intense outbursts of temper. - Major depressive disorder: A condition characterized by loss of interest in activities and depressed mood which leads to significant impairments in how a person is able to function. - Persistent depressive disorder (dysthymia): This is a type of ongoing, chronic depression that is characterized by other symptoms of depression that, while often less severe, are longer lasting. Diagnosis requires experiencing depressed mood on most days for a period of at least two years. - Other or unspecified depressive disorder: This diagnosis is for cases when symptoms do not meet the criteria for the diagnosis of another depressive disorder, but they still create problems with an individual's life and functioning. - Premenstrual dysphoric disorder: This condition is a form of premenstrual syndrome (PMS) characterized by significant depression, irritability, and anxiety that begins a week or two before menstruation begins. Symptoms usually go away within a few day's following a woman's period. - Substance/medication-induced depressive disorder: This condition occurs when an individual experiences symptoms of a depressive disorder either while using alcohol or other substances or while going through withdrawal from a substance. - Depressive disorder due to another medical condition: This condition is diagnosed when a person's medical history suggests that their depressive symptoms may be the result of a medical condition. Medical conditions that may contribute to or cause depression include diabetes, stroke, Parkinson's disease, autoimmune conditions, chronic pain conditions, cancer, infections and HIV/AIDS. The depressive disorders are all characterized by feelings of sadness and low mood that are persistent and severe enough to affect how a person functions. Common symptoms shared by these disorders include difficulty feeling interested and motivated, lack of interest in previously enjoyed activities, sleep disturbances, and poor concentration. The diagnostic criteria vary for each specific condition. For major depressive disorder, diagnosis requires an individual to experience five or more of the following symptoms over the same two-week period. One of these symptoms must include either depressed mood or loss of interest or pleasure in previously enjoyed activities. Symptoms can include: - Depressed mood for most or all of the day - Decreased or lack of interest in activities the individual previously enjoyed - Significant weight loss or gain, or decreased or increased appetite - Sleep disturbances (insomnia or hypersomnia) - Feelings of slowed physical activity or restlessness - Lack of energy or fatigue that lasts most or all of the day - Feelings of guilt or worthlessness - Difficulty thinking or concentrating - Preoccupation with death or thoughts of suicide If you are having suicidal thoughts, contact the National Suicide Prevention Lifeline at 1-800-273-8255 for support and assistance from a trained counselor. If you or a loved one are in immediate danger, call 911. For more mental health resources, see our National Helpline Database. Treatments for depressive disorders often involve a combination of psychotherapy and medications. Substance-Related Disorders Substance-related disorders are those that involve the use and abuse of different substances such as cocaine, methamphetamine, opiates, and alcohol.1 These disorders may include substance-induced conditions that can result in many associated diagnoses including intoxication, withdrawal, the emergence of psychosis, anxiety, and delirium. Examples of substance-related disorders: - Alcohol-related disorders involve the consumption of alcohol, the most widely used (and frequently overused) drug in the United States. - Cannabis-related disorders include symptoms such as using more than originally intended, feeling unable to stop using the drug, and continuing to use despite adverse effects in one's life. - Inhalant-use disorders involve inhaling fumes from things such as paints or solvents. As with other substance-related disorders, people with this condition experience cravings for the substance and find it difficult to control or stop engaging in the behavior. - Stimulant use disorder involves the use of stimulants such as meth, amphetamines, and cocaine. - Tobacco use disorder is characterized by symptoms such as consuming more tobacco than intended, difficulty cutting back or quitting, cravings, and suffering adverse social consequences as a result of tobacco use Neurocognitive Disorders Neurocognitive disorders are characterized by acquired deficits in cognitive function.1 These disorders do not include those in which impaired cognition was present at birth or early in life. Types of cognitive disorders include: Delirium Delirium is also known as an acute confusional state. This disorder develops over a short period of time—usually a few hours or a few days—and is characterized by disturbances in attention and awareness. Neurocognitive Disorders Major and mild neurocognitive disorders have the primary feature of acquired cognitive decline in one or more areas including memory, attention, language, learning, and perception. These cognitive disorders can be due to medical conditions including Alzheimer's disease, HIV infection, Parkinson's disease, substance/medication use, vascular disease, and others. Schizophrenia Schizophrenia is a chronic psychiatric condition that affects a person’s thinking, feeling, and behavior. It is a complex, long-term condition that affects about one percent of people in the United States. The DSM-5 diagnostic criteria specify that two or more symptoms of schizophrenia must be present for a period of at least one month. One symptom must be one of the following: - Delusions: beliefs that conflict with reality - Hallucinations: seeing or hearing things that aren't really there - Disorganized speech: words do not follow the rules of language and may be impossible to understand The second symptom may be one of the following: - Grossly disorganized or catatonic behavior: confused thinking, bizarre behavior or movements - Negative symptoms: the inability to initiate plans, speak, express emotions, or feel pleasure Diagnosis also requires significant impairments in social or occupational functioning for a period of at least six months. The onset of schizophrenia is usually in the late teens or early 20s, with men usually showing symptoms earlier than women. Earlier signs of the condition that may occur before diagnosis include poor motivation, difficult relationships, and poor school performance. The National Institute of Mental Health suggests that multiple factors may play a role in causing schizophrenia including genetics, brain chemistry, environmental factors, and substance use. Obsessive-Compulsive Disorders Obsessive-compulsive and related disorders is a category of psychiatric conditions that include: - Obsessive-compulsive disorder (OCD) - Body-dysmorphic disorder - Hoarding disorder - Trichotillomania (hair-pulling disorder) - Excoriation disorder (skin picking) - Substance/medication-induced obsessive-compulsive and related disorder - Obsessive-compulsive and related disorder due to another medical condition Each condition in this classification has its own set of diagnostic criteria. Obsessive-Compulsive Disorder The diagnostic criteria in the DSM-5 specify that in order to be diagnosed with obsessive-compulsive disorder, a person must experience obsessions, compulsions, or both. - Obsessions: defined as recurrent, persistent thoughts, impulses, and urges that lead to distress or anxiety - Compulsions: repetitive and excessive behaviors that the individual feels that they must perform. These actions are performed to reduce anxiety or to prevent some dreaded outcome from occurring. Treatments for OCD usually focus on a combination of therapy and medications. Cognitive-behavioral therapy (CBT) or a form of CBT known as exposure and response prevention (ERP) if commonly used. Antidepressants such as clomipramine or fluoxetine may also be prescribed to manage symptoms. Personality Disorders Personality disorders are characterized by an enduring pattern of maladaptive thoughts, feelings, and behaviors that can cause serious detrimental barriers to relationships and other life areas. Types of personality disorders include: Antisocial Personality Disorder Antisocial personality disorder is characterized by a long-standing disregard for rules, social norms, and the rights of others. People with this disorder typically begin displaying symptoms during childhood, have difficulty feeling empathy for others, and lack remorse for their destructive behaviors. Avoidant Personality Disorder Avoidant personality disorder involves severe social inhibition and sensitivity to rejection. Such feelings of insecurity lead to significant problems with the individual's daily life and functioning. Borderline Personality Disorder Borderline personality disorder is associated with symptoms including emotional instability, unstable and intense interpersonal relationships, unstable self-image, and impulsive behaviors. Dependent Personality Disorder Dependent personality disorder involves a chronic pattern of fearing separation and an excessive need to be taken care of. People with this disorder will often engage in behaviors that are designed to produce care-giving actions in others. Histrionic Personality Disorder Histrionic personality disorder is associated with patterns of extreme emotionality and attention-seeking behaviors. People with this condition feel uncomfortable in settings where they are not the center of attention, have rapidly changing emotions, and may engage in socially inappropriate behaviors designed to attract attention from others. Narcissistic Personality Disorder Narcissistic personality disorder is associated with a lasting pattern of exaggerated self-image, self-centeredness, and low empathy. People with this condition tend to be more interested in themselves than with others. Obsessive-Compulsive Personality Disorder Obsessive-compulsive personality disorder is a pervasive pattern of preoccupation with orderliness, perfectionism, inflexibility, and mental and interpersonal control. This is a different condition than obsessive compulsive disorder (OCD). Paranoid Personality Disorder Paranoid personality disorder is characterized by a distrust of others, even family, friends, and romantic partners. People with this disorder perceive others intentions as malevolent, even without any evidence or justification. Schizoid Personality Disorder Schizoid personality disorder involves symptoms that include being detached from social relationships. People with this disorder are directed toward their inner lives and are often indifferent to relationships. They generally display a lack of emotional expression and can appear cold and aloof. Schizotypal Personality Disorder Schizotypal personality disorder features eccentricities in speech, behaviors, appearance, and thought. People with this condition may experience odd beliefs or "magical thinking" and difficulty forming relationships. References: - Regier DA, Kuhl EA, Kupfer DJ. The DSM-5: Classification and criteria changes. World Psychiatry. 2013;12(2):92-8. doi:10.1002/wps.20050 - Swineford LB, Thurm A, Baird G, Wetherby AM, Swedo S. Social (pragmatic) communication disorder: a research review of this new DSM-5 diagnostic category. J Neurodev Disord. 2014;6(1):41. doi:10.1186/1866-1955-6-41 - Kulage KM, Goldberg J, Usseglio J, Romero D, Bain JM, Smaldone AM. How has DSM-5 Affected Autism Diagnosis? A 5-Year Follow-Up Systematic Literature Review and Meta-analysis. J Autism Dev Disord. 2019; doi:10.1007/s10803-019-03967-5 - Ramtekkar UP. DSM-5 Changes in Attention Deficit Hyperactivity Disorder and Autism Spectrum Disorder: Implications for Comorbid Sleep Issues. Children (Basel). 2017;4(8) doi:10.3390/children4080062 - Kupfer DJ. Anxiety and DSM-5. Dialogues Clin Neurosci. 2015;17(3):245-6. - Friedman MJ, Resick PA, Bryant RA, Strain J, Horowitz M, Spiegel D. Classification of trauma and stressor-related disorders in DSM-5. Depress Anxiety. 2011; doi:10.1002/da.20845 - Toussaint A, Hüsing P, Kohlmann S, Löwe B. Detecting DSM-5 somatic symptom disorder: criterion validity of the Patient Health Questionnaire-15 (PHQ-15) and the Somatic Symptom Scale-8 (SSS-8) in combination with the Somatic Symptom Disorder - B Criteria Scale (SSD-12). Psychol Med. 2019;:1-10. doi: 10.1017/S003329171900014X - Attia E, Becker AE, Bryant-waugh R, et al. Feeding and eating disorders in DSM-5. Am J Psychiatry. 2013;170(11):1237-9. doi:10.1176/appi.ajp.2013.13030326 - Seow LSE, Verma SK, Mok YM, et al. Evaluating DSM-5 Insomnia Disorder and the Treatment of Sleep Problems in a Psychiatric Population. J Clin Sleep Med. 2018;14(2):237-244. doi:10.5664/jcsm.6942 - Schmeck K, Schlüter-müller S, Foelsch PA, Doering S. The role of identity in the DSM-5 classification of personality disorders. Child Adolesc Psychiatry Ment Health. 2013;7(1):27. doi:10.1186/1753-2000-7-27 Additional Reading: - American Psychiatric Association. Highlights of changes from DSM-IV-TR to DSM-5; 2013. - American Psychiatry Association. Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington: American Psychiatric Publishing; 2013. - American Psychiatry Association. Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington: American Psychiatric Publishing; 2013. - Kessler, R.C., Chiu, W.T., Demler, O., & Walters, E.E. Prevalence, severity, and comorbidity of twelve-month DSM-IV disorders in the National Comorbidity Survey Replication (NCS-R). Archives of General Psychiatry. 2005; 62(6): 617-27. - National Institute of Mental Health. Panic Disorder: When Fear Overwhelms. 2016. - National Institute of Mental Health. Bipolar disorder; 2016. Adapted from: A List of Psychological Disorders Social Psychology Sociocultural theory is an emerging theory in psychology that looks at the important contributions that society makes to individual development. This theory stresses the interaction between developing people and the culture in which they live. Sociocultural theory also suggests that human learning is largely a social process. Vygotsky and Sociocultural Theory Sociocultural theory grew from the work of seminal psychologist Lev Vygotsky, who believed that parents, caregivers, peers, and the culture at large were responsible for developing higher-order functions. According to Vygotsky, learning has its basis in interacting with other people. Once this has occurred, the information is then integrated on the individual level. Vygotsky was a contemporary of other great thinkers such as Freud, Skinner, and Piaget, but his early death at age 37 and the suppression of his work in Stalinist Russia left him in relative obscurity until fairly recently. As his work became more widely published, his ideas have grown increasingly influential in areas including child development, cognitive psychology, and education. Sociocultural theory focuses not only how adults and peers influence individual learning, but also on how cultural beliefs and attitudes affect how learning takes place. According to Vygotsky, children are born with basic biological constraints on their minds. Each culture, however, provides "tools of intellectual adaptation." These tools allow children to use their abilities in a way that is adaptive to the culture in which they live. For example, while one culture might emphasize memory strategies such as note-taking, another might use tools like reminders or rote memorization. Piaget vs. Vygotsky: Key Differences How does Vygotsky's sociocultural theory differ from Piaget's theory of cognitive development? First, Vygotsky placed a greater emphasis on how social factors influence development. While Piaget's theory stressed how a child's interactions and explorations influenced development, Vygotsky stressed the essential role that social interactions play in cognitive development.1 Another important difference between the two theories is that while Piaget's theory suggests that development is largely universal, Vygotsky asserts that cognitive development can differ between different cultures. The course of development in Western culture, for example, might be different than it is in Eastern culture. In his text, "Social and Personality Development," David R. Shaffer explains that while Piaget believed that cognitive development was fairly universal, Vygotsky believed that each culture presents unique differences. Because cultures can vary so dramatically, Vygotsky's sociocultural theory suggests that both the course and content of intellectual development are not as universal as Piaget believed. Support and Criticism of Piaget's Stage Theory Adapted from:Socio-cultural Theory of Development Cultural Perspectives Cross-cultural psychology is a branch of psychology that looks at how cultural factors influence human behavior. While many aspects of human thought and behavior are universal, cultural differences can lead to often surprising differences in how people think, feel, and act. Some cultures, for example, might stress individualism and the importance of personal autonomy. Other cultures, however, may place a higher value on collectivism and cooperation among members of the group. Such differences can play a powerful role in many aspects of life. Cross-cultural psychology is also emerging as an increasingly important topic as researchers strive to understand both the differences and similarities among people of various cultures throughout the world. The International Association of Cross-Cultural Psychology (IACCP) was established in 1972, and this branch of psychology has continued to grow and develop since that time.1 Today, increasing numbers of psychologists investigate how behavior differs among various cultures throughout the world. Why Cross-Cultural Psychology Is Important After prioritizing European and North American research for many years, Western researchers began to question whether many of the observations and ideas that were once believed to be universal might apply to cultures outside of these areas. Could their findings and assumptions about human psychology be biased based on the sample from which their observations were drawn? Cross-cultural psychologists work to rectify many of the biases that may exist in the current research2 and determine if the phenomena that appear in European and North American cultures also appear in other parts of the world. For example, consider how something such as social cognition might vary from an individualist culture such as the United States versus a collectivist culture such as China. Do people in China rely on the same social cues as people in the U.S. do? What cultural differences might influence how people perceive each other? These are just some of the questions that a cross-cultural psychologist might explore. What Exactly Is Culture? Culture refers to many characteristics of a group of people, including attitudes, behaviors, customs, and values that are transmitted from one generation to the next. Cultures throughout the world share many similarities but are marked by considerable differences. For example, while people of all cultures experience happiness, how this feeling is expressed varies from one culture to the next.3 The goal of cross-cultural psychologists is to look at both universal behaviors and unique behaviors to identify the ways in which culture impacts our behavior, family life, education, social experiences, and other areas.4 Many cross-cultural psychologists choose to focus on one of two approaches: - The etic approach studies culture through an "outsider" perspective, applying one "universal" set of concepts and measurements to all cultures. - The emic approach studies culture using an "insider" perspective, analyzing concepts within the specific context of the observed culture. Some cross-cultural psychologists take a combined emic-etic approach.5 Meanwhile, some cross-cultural psychologists also study something known as ethnocentrism. Ethnocentrism refers to a tendency to use your own culture as the standard by which to judge and evaluate other cultures.6 In other words, taking an ethnocentric point of view means using your understanding of your own culture to gauge what is "normal." This can lead to biases and a tendency to view cultural differences as abnormal or in a negative light. It can also make it difficult to see how your own cultural background influences your behaviors. Cross-cultural psychologists often look at how ethnocentrism influences our behaviors and thoughts, including how we interact with individuals from other cultures.6 Psychologists are also concerned with how ethnocentrism can influence the research process. For example, a study might be criticized for having an ethnocentric bias. Major Topics in Cross-Cultural Psychology - Emotions - Language acquisition - Child development - Personality - Social behavior - Family and social relationships How Cross-Cultural Psychology Differs From Other Branches of Psychology - Many other branches of psychology focus on how parents, friends, and other people impact human behavior, but most do not take into account the powerful impact that culture may have on individual human actions. - Cross-cultural psychology, on the other hand, is focused on studying human behavior in a way that takes the effects of culture into account. - According to Walter J. Lonner, writing for Eye on Psi Chi, cross-cultural psychology can be thought of as a type of research methodology rather than an entirely separate field within psychology.4 Who Should Study Cross-Cultural Psychology? Cross-cultural psychology touches on a wide range of topics, so students with an interest in other psychology topics may choose to also focus on this area of psychology. The following are just a few examples of who may benefit from the study of cross-cultural psychology: - Students interested in learning how child-rearing practices in different cultures impact development. - Teachers, educators, and curriculum designers who create multicultural education lessons and materials can benefit from learning more about how cultural differences impact student learning, achievement, and motivation. - Students interested in social or personality psychology can benefit from learning about how culture impacts social behavior and individual personality. References: - International Association of Cross-Cultural Psychology. About us. - Wang Q. Why should we all be cultural psychologists? Lessons from the study of social cognition. Perspect Psychol Sci. 2016;11(5):583-596. doi:10.1177/1745691616645552 - Mathews G. Happiness, culture, and context. International Journal of Wellbeing. 2012;2(4):299-312. doi:10.5502/ijw.v2.i4.2 - Lonner WJ. On the growth and continuing importance of cross-cultural psychology. Eye on Psi Chi. 2000;4(3):22-26. doi:10.24839/1092-0803.Eye4.3.22 - Cheung FM, van de Vijver FJ, Leong FT. Toward a new approach to the study of personality in culture. Am Psychol. 2011;66(7):593-603. doi:10.1037/a0022389 - Keith KD. Visual illusions and ethnocentrism: Exemplars for teaching cross-cultural concepts. Hist Psychol. 2012;15(2):171-176. doi:10.1037/a0027271 Adapted from: The Focus of Cross-Cultural Psychology	oercommons	2025-03-18T00:36:10.305294	Case Study	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/69346/overview", "title": "Introduction to Psychology", "author": "Assessment" }
https://oercommons.org/courseware/lesson/85991/overview	Generating Speech Topics: Clustering Method Overview This is a great handout to complete in class with your students as an in-class activity or assign as out-of-class work. This handout helps students generate speech topics. Generating Speech Topics: Clustering Method Generating Speech Topics: Clustering Method Having trouble coming up with a speech topic? Everyone does from time to time and it’s completely normal. Generating speech topics can be trying, which is where this handout comes in; it can help you narrow down ideas for your speech topic! Use this handout to brainstorm ideas. Directions: 1. In each square write down 3 - 5 ideas that come to mind for the topic. 2. Review your speech assignment requirements and remove any ideas that may not meet the requirements. 3. Narrow down your ideas once more by removing: any ideas: - Ideas you aren’t interested in. - Ideas that may be too mundane for your audience. - Ideas that may be too overwhelming for your audience with your time limit in mind. 4. Select something you’re interested or passionate about with the available topics and begin collecting your research! \| People \| Places \| Things \| \| Events \| Processes \| Concepts \| \| Natural Phenomena \| Problems \| Plans and Policies \|	oercommons	2025-03-18T00:36:10.332834	09/20/2021	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/85991/overview", "title": "Generating Speech Topics: Clustering Method", "author": "Thalia Bobadilla" }
https://oercommons.org/courseware/lesson/101972/overview	WA.SEL.6-8.1B Washington Social Emotional Learning Standards Grades 6-8 Learning Domain: 1: Self-Awareness Standard: Demonstrates awareness of personal and collective identity encompassing strengths, areas for growth, aspirations, and cultural and linguistic assets. WA.SEL.6-8.1C Washington Social Emotional Learning Standards Grades 6-8 Learning Domain: 1: Self-Awareness Standard: Demonstrates self-awareness and understanding of external influences, e.g., culture, family, school, and community resources and supports. WA.SEL.6-8.2B Washington Social Emotional Learning Standards Grades 6-8 Learning Domain: 2: Self-Management Standard: Demonstrates responsible decision-making and problem-solving skills. WA.SEL.6-8.3B Washington Social Emotional Learning Standards Grades 6-8 Learning Domain: 3: Self-Efficacy Standard: Demonstrates problem-solving skills to engage responsibly in a variety of situations. WA.SEL.6-8.4A Washington Social Emotional Learning Standards Grades 6-8 Learning Domain: 4: Social Awareness Standard: Demonstrates awareness of other people’s emotions, perspectives, cultures, languages, histories, identities, and abilities WA.SEL.6-8.4B Washington Social Emotional Learning Standards Grades 6-8 Learning Domain: 4: Social Awareness Standard: Demonstrates an awareness and respect for similarities and differences among community, cultural and social groups. WA.SEL.6-8.4C Washington Social Emotional Learning Standards Grades 6-8 Learning Domain: 4: Social Awareness Standard: Demonstrates an understanding of the variation within and across cultures. WA.SEL.6-8.5A Washington Social Emotional Learning Standards Grades 6-8 Learning Domain: 5: Social Management Standard: Demonstrates a range of communication and social skills to interact effectively with others WA.SEL.6-8.5C Washington Social Emotional Learning Standards Grades 6-8 Learning Domain: 5: Social Management Standard: Demonstrates the ability to engage in respectful and healthy relationships with individuals of diverse perspectives, cultures, language, history, identity, and ability. WA.SEL.6-8.6A Washington Social Emotional Learning Standards Grades 6-8 Learning Domain: 6: Social Engagement Standard: Demonstrates a sense of school and community responsibility. Learning Domain: Civics Standard: Describe ways in which people benefit from and are challenged by working together, including through government, workplaces, voluntary organizations, and families Learning Domain: Social Studies Skills Standard: Create and use research questions to guide inquiry on an issue or event Learning Domain: Reading for Literature Standard: Determine a theme or central idea of a text and how it is conveyed through particular details; provide a summary of the text distinct from personal opinions or judgments. Learning Domain: Reading for Literature Standard: Describe how a particular story’s or drama’s plot unfolds in a series of episodes as well as how the characters respond or change as the plot moves toward a resolution. Learning Domain: Reading for Literature Standard: Determine the meaning of words and phrases as they are used in a text, including figurative and connotative meanings; analyze the impact of a specific word choice on meaning and tone. Learning Domain: Reading for Literature Standard: Cite textual evidence to support analysis of what the text says explicitly as well as inferences drawn from the text. Learning Domain: Reading for Informational Text Standard: Determine a central idea of a text and how it is conveyed through particular details; provide a summary of the text distinct from personal opinions or judgments. Learning Domain: Reading for Informational Text Standard: Analyze in detail how a key individual, event, or idea is introduced, illustrated, and elaborated in a text (e.g., through examples or anecdotes). Learning Domain: Reading for Informational Text Standard: Determine the meaning of words and phrases as they are used in a text, including figurative, connotative, and technical meanings. Learning Domain: Reading for Informational Text Standard: Cite textual evidence to support analysis of what the text says explicitly as well as inferences drawn from the text. Learning Domain: Writing Standard: Write narratives to develop real or imagined experiences or events using effective technique, relevant descriptive details, and well-structured event sequences. Learning Domain: Writing Standard: Engage and orient the reader by establishing a context and introducing a narrator and/or characters; organize an event sequence that unfolds naturally and logically. Learning Domain: Writing Standard: Use narrative techniques, such as dialogue, pacing, and description, to develop experiences, events, and/or characters. Learning Domain: Writing Standard: Use a variety of transition words, phrases, and clauses to convey sequence and signal shifts from one time frame or setting to another. Learning Domain: Writing Standard: Use precise words and phrases, relevant descriptive details, and sensory language to convey experiences and events. Learning Domain: Writing Standard: Provide a conclusion that follows from the narrated experiences or events. Learning Domain: Writing Standard: Draw evidence from literary or informational texts to support analysis, reflection, and research. Learning Domain: Writing Standard: Apply grade 6 Reading standards to literature (e.g., “Compare and contrast texts in different forms or genres [e.g., stories and poems; historical novels and fantasy stories]in terms of their approaches to similar themes and topics”). Learning Domain: Speaking and Listening Standard: Come to discussions prepared, having read or studied required material; explicitly draw on that preparation by referring to evidence on the topic, text, or issue to probe and reflect on ideas under discussion. Learning Domain: Speaking and Listening Standard: Present claims and findings, sequencing ideas logically and using pertinent descriptions, facts, and details to accentuate main ideas or themes; use appropriate eye contact, adequate volume, and clear pronunciation. Learning Domain: Speaking and Listening Standard: Engage effectively in a range of collaborative discussions (one-on-one, in groups, and teacher-led) with diverse partners on grade 6 topics, texts, and issues, building on others’ ideas and expressing their own clearly. Learning Domain: Reading for Literature Standard: Determine a theme or central idea of a text and analyze its development over the course of the text; provide an objective summary of the text. Learning Domain: Reading for Literature Standard: Analyze how particular elements of a story or drama interact (e.g., how setting shapes the characters or plot). Learning Domain: Reading for Literature Standard: Cite several pieces of textual evidence to support analysis of what the text says explicitly as well as inferences drawn from the text. Learning Domain: Writing Standard: Write narratives to develop real or imagined experiences or events using effective technique, relevant descriptive details, and well-structured event sequences. Learning Domain: Writing Standard: Draw evidence from literary or informational texts to support analysis, reflection, and research. Learning Domain: Speaking and Listening Standard: Analyze the main ideas and supporting details presented in diverse media and formats (e.g., visually, quantitatively, orally) and explain how the ideas clarify a topic, text, or issue under study. Learning Domain: Speaking and Listening Standard: Present claims and findings, emphasizing salient points in a focused, coherent manner with pertinent descriptions, facts, details, and examples; use appropriate eye contact, adequate volume, and clear pronunciation. Learning Domain: Speaking and Listening Standard: Engage effectively in a range of collaborative discussions (one-on-one, in groups, and teacher-led) with diverse partners on grade 7 topics, texts, and issues, building on others’ ideas and expressing their own clearly. Learning Domain: Reading for Literature Standard: Determine a theme or central idea of a text and analyze its development over the course of the text, including its relationship to the characters, setting, and plot; provide an objective summary of the text. Learning Domain: Reading for Literature Standard: Analyze how particular lines of dialogue or incidents in a story or drama propel the action, reveal aspects of a character, or provoke a decision. Learning Domain: Reading for Literature Standard: Cite the textual evidence that most strongly supports an analysis of what the text says explicitly as well as inferences drawn from the text. Learning Domain: Writing Standard: Write narratives to develop real or imagined experiences or events using effective technique, relevant descriptive details, and well-structured event sequences. Learning Domain: Writing Standard: Draw evidence from literary or informational texts to support analysis, reflection, and research. Learning Domain: Speaking and Listening Standard: Present claims and findings, emphasizing salient points in a focused, coherent manner with relevant evidence, sound valid reasoning, and well-chosen details; use appropriate eye contact, adequate volume, and clear pronunciation. Learning Domain: Speaking and Listening Standard: Engage effectively in a range of collaborative discussions (one-on-one, in groups, and teacher-led) with diverse partners on grade 8 topics, texts, and issues, building on others’ ideas and expressing their own clearly. Learning Domain: Reading Literature Standard: Determine a theme or central idea of a text and how it is conveyed through particular details; provide a summary of the text distinct from personal opinions or judgments. Learning Domain: Reading Literature Standard: Describe how a particular story's or drama's plot unfolds in a series of episodes as well as how the characters respond or change as the plot moves toward a resolution. Learning Domain: Reading Literature Standard: Determine the meaning of words and phrases as they are used in a text, including figurative and connotative meanings; analyze the impact of a specific word choice on meaning and tone. Learning Domain: Reading Literature Standard: Cite textual evidence to support analysis of what the text says explicitly as well as inferences drawn from the text. Learning Domain: Reading for Informational Text Standard: Determine a central idea of a text and how it is conveyed through particular details; provide a summary of the text distinct from personal opinions or judgments. Learning Domain: Reading for Informational Text Standard: Analyze in detail how a key individual, event, or idea is introduced, illustrated, and elaborated in a text (e.g., through examples or anecdotes). Learning Domain: Reading for Informational Text Standard: Determine the meaning of words and phrases as they are used in a text, including figurative, connotative, and technical meanings. Learning Domain: Reading for Informational Text Standard: Cite textual evidence to support analysis of what the text says explicitly as well as inferences drawn from the text. Learning Domain: Writing Standard: Write narratives to develop real or imagined experiences or events using effective technique, relevant descriptive details, and well-structured event sequences. Learning Domain: Writing Standard: Engage and orient the reader by establishing a context and introducing a narrator and/or characters; organize an event sequence that unfolds naturally and logically. Learning Domain: Writing Standard: Use narrative techniques, such as dialogue, pacing, and description, to develop experiences, events, and/or characters. Learning Domain: Writing Standard: Use a variety of transition words, phrases, and clauses to convey sequence and signal shifts from one time frame or setting to another. Learning Domain: Writing Standard: Use precise words and phrases, relevant descriptive details, and sensory language to convey experiences and events. Learning Domain: Writing Standard: Provide a conclusion that follows from the narrated experiences or events. Learning Domain: Writing Standard: Draw evidence from literary or informational texts to support analysis, reflection, and research. Learning Domain: Writing Standard: Apply grade 6 Reading standards to literature (e.g., "Compare and contrast texts in different forms or genres [e.g., stories and poems; historical novels and fantasy stories]in terms of their approaches to similar themes and topics"). Learning Domain: Speaking and Listening Standard: Come to discussions prepared, having read or studied required material; explicitly draw on that preparation by referring to evidence on the topic, text, or issue to probe and reflect on ideas under discussion. Learning Domain: Speaking and Listening Standard: Present claims and findings, sequencing ideas logically and using pertinent descriptions, facts, and details to accentuate main ideas or themes; use appropriate eye contact, adequate volume, and clear pronunciation. Learning Domain: Speaking and Listening Standard: Engage effectively in a range of collaborative discussions (one-on-one, in groups, and teacher-led) with diverse partners on grade 6 topics, texts, and issues, building on others�۪ ideas and expressing their own clearly. Learning Domain: Reading Literature Standard: Determine a theme or central idea of a text and analyze its development over the course of the text; provide an objective summary of the text. Learning Domain: Reading Literature Standard: Analyze how particular elements of a story or drama interact (e.g., how setting shapes the characters or plot). Learning Domain: Reading Literature Standard: Cite several pieces of textual evidence to support analysis of what the text says explicitly as well as inferences drawn from the text. Learning Domain: Writing Standard: Write narratives to develop real or imagined experiences or events using effective technique, relevant descriptive details, and well-structured event sequences. Learning Domain: Writing Standard: Draw evidence from literary or informational texts to support analysis, reflection, and research. Learning Domain: Speaking and Listening Standard: Analyze the main ideas and supporting details presented in diverse media and formats (e.g., visually, quantitatively, orally) and explain how the ideas clarify a topic, text, or issue under study. Learning Domain: Speaking and Listening Standard: Present claims and findings, emphasizing salient points in a focused, coherent manner with pertinent descriptions, facts, details, and examples; use appropriate eye contact, adequate volume, and clear pronunciation. Learning Domain: Speaking and Listening Standard: Engage effectively in a range of collaborative discussions (one-on-one, in groups, and teacher-led) with diverse partners on grade 7 topics, texts, and issues, building on others�۪ ideas and expressing their own clearly. Learning Domain: Reading Literature Standard: Determine a theme or central idea of a text and analyze its development over the course of the text, including its relationship to the characters, setting, and plot; provide an objective summary of the text. Learning Domain: Reading Literature Standard: Analyze how particular lines of dialogue or incidents in a story or drama propel the action, reveal aspects of a character, or provoke a decision. Learning Domain: Reading Literature Standard: Cite the textual evidence that most strongly supports an analysis of what the text says explicitly as well as inferences drawn from the text. Learning Domain: Writing Standard: Write narratives to develop real or imagined experiences or events using effective technique, relevant descriptive details, and well-structured event sequences. Learning Domain: Writing Standard: Draw evidence from literary or informational texts to support analysis, reflection, and research. Learning Domain: Speaking and Listening Standard: Present claims and findings, emphasizing salient points in a focused, coherent manner with relevant evidence, sound valid reasoning, and well-chosen details; use appropriate eye contact, adequate volume, and clear pronunciation. Learning Domain: Speaking and Listening Standard: Engage effectively in a range of collaborative discussions (one-on-one, in groups, and teacher-led) with diverse partners on grade 8 topics, texts, and issues, building on others�۪ ideas and expressing their own clearly. Cluster: Key Ideas and Details. Standard: Determine a theme or central idea of a text and how it is conveyed through particular details; provide a summary of the text distinct from personal opinions or judgments. Cluster: Key Ideas and Details. Standard: Describe how a particular story’s or drama’s plot unfolds in a series of episodes as well as how the characters respond or change as the plot moves toward a resolution. Cluster: Craft and Structure. Standard: Determine the meaning of words and phrases as they are used in a text, including figurative and connotative meanings; analyze the impact of a specific word choice on meaning and tone. Cluster: Key Ideas and Details. Standard: Cite textual evidence to support analysis of what the text says explicitly as well as inferences drawn from the text. Cluster: Key Ideas and Details. Standard: Determine a central idea of a text and how it is conveyed through particular details; provide a summary of the text distinct from personal opinions or judgments. Cluster: Key Ideas and Details. Standard: Analyze in detail how a key individual, event, or idea is introduced, illustrated, and elaborated in a text (e.g., through examples or anecdotes). Cluster: Craft and Structure. Standard: Determine the meaning of words and phrases as they are used in a text, including figurative, connotative, and technical meanings. Cluster: Key Ideas and Details. Standard: Cite textual evidence to support analysis of what the text says explicitly as well as inferences drawn from the text. Cluster: Text Types and Purposes. Standard: Write narratives to develop real or imagined experiences or events using effective technique, relevant descriptive details, and well-structured event sequences. Cluster: Text Types and Purposes. Standard: Engage and orient the reader by establishing a context and introducing a narrator and/or characters; organize an event sequence that unfolds naturally and logically. Cluster: Text Types and Purposes. Standard: Use narrative techniques, such as dialogue, pacing, and description, to develop experiences, events, and/or characters. Cluster: Text Types and Purposes. Standard: Use a variety of transition words, phrases, and clauses to convey sequence and signal shifts from one time frame or setting to another. Cluster: Text Types and Purposes. Standard: Use precise words and phrases, relevant descriptive details, and sensory language to convey experiences and events. Cluster: Text Types and Purposes. Standard: Provide a conclusion that follows from the narrated experiences or events. Cluster: Research to Build and Present Knowledge. Standard: Draw evidence from literary or informational texts to support analysis, reflection, and research. Cluster: Research to Build and Present Knowledge. Standard: Apply grade 6 Reading standards to literature (e.g., “Compare and contrast texts in different forms or genres [e.g., stories and poems; historical novels and fantasy stories]in terms of their approaches to similar themes and topics”). Cluster: Comprehension and Collaboration. Standard: Come to discussions prepared, having read or studied required material; explicitly draw on that preparation by referring to evidence on the topic, text, or issue to probe and reflect on ideas under discussion. Cluster: Presentation of Knowledge and Ideas. Standard: Present claims and findings, sequencing ideas logically and using pertinent descriptions, facts, and details to accentuate main ideas or themes; use appropriate eye contact, adequate volume, and clear pronunciation. Cluster: Comprehension and Collaboration. Standard: Engage effectively in a range of collaborative discussions (one-on-one, in groups, and teacher-led) with diverse partners on grade 6 topics, texts, and issues, building on others’ ideas and expressing their own clearly. Cluster: Key Ideas and Details. Standard: Determine a theme or central idea of a text and analyze its development over the course of the text; provide an objective summary of the text. Cluster: Key Ideas and Details. Standard: Analyze how particular elements of a story or drama interact (e.g., how setting shapes the characters or plot). Cluster: Key Ideas and Details. Standard: Cite several pieces of textual evidence to support analysis of what the text says explicitly as well as inferences drawn from the text. Cluster: Text Types and Purposes. Standard: Write narratives to develop real or imagined experiences or events using effective technique, relevant descriptive details, and well-structured event sequences. Cluster: Research to Build and Present Knowledge. Standard: Draw evidence from literary or informational texts to support analysis, reflection, and research. Cluster: Comprehension and Collaboration. Standard: Analyze the main ideas and supporting details presented in diverse media and formats (e.g., visually, quantitatively, orally) and explain how the ideas clarify a topic, text, or issue under study. Cluster: Presentation of Knowledge and Ideas. Standard: Present claims and findings, emphasizing salient points in a focused, coherent manner with pertinent descriptions, facts, details, and examples; use appropriate eye contact, adequate volume, and clear pronunciation. Cluster: Comprehension and Collaboration. Standard: Engage effectively in a range of collaborative discussions (one-on-one, in groups, and teacher-led) with diverse partners on grade 7 topics, texts, and issues, building on others’ ideas and expressing their own clearly. Cluster: Key Ideas and Details. Standard: Determine a theme or central idea of a text and analyze its development over the course of the text, including its relationship to the characters, setting, and plot; provide an objective summary of the text. Cluster: Key Ideas and Details. Standard: Analyze how particular lines of dialogue or incidents in a story or drama propel the action, reveal aspects of a character, or provoke a decision. Cluster: Key Ideas and Details. Standard: Cite the textual evidence that most strongly supports an analysis of what the text says explicitly as well as inferences drawn from the text. Cluster: Text Types and Purposes. Standard: Write narratives to develop real or imagined experiences or events using effective technique, relevant descriptive details, and well-structured event sequences. Cluster: Research to Build and Present Knowledge. Standard: Draw evidence from literary or informational texts to support analysis, reflection, and research. Cluster: Presentation of Knowledge and Ideas. Standard: Present claims and findings, emphasizing salient points in a focused, coherent manner with relevant evidence, sound valid reasoning, and well-chosen details; use appropriate eye contact, adequate volume, and clear pronunciation. Cluster: Comprehension and Collaboration. Standard: Engage effectively in a range of collaborative discussions (one-on-one, in groups, and teacher-led) with diverse partners on grade 8 topics, texts, and issues, building on others’ ideas and expressing their own clearly.	oercommons	2025-03-18T00:36:10.522130	Jerry Price	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/101972/overview", "title": "Animating Civic Action: Middle School Lesson - Empathy", "author": "Lesson Plan" }
https://oercommons.org/courseware/lesson/15340/overview	Introduction Welcome to the story of your life. In this chapter we explore the fascinating tale of how you have grown and developed into the person you are today. We also look at some ideas about who you will grow into tomorrow. Yours is a story of lifespan development (Figure), from the start of life to the end. The process of human growth and development is more obvious in infancy and childhood, yet your development is happening this moment and will continue, minute by minute, for the rest of your life. Who you are today and who you will be in the future depends on a blend of genetics, environment, culture, relationships, and more, as you continue through each phase of life. You have experienced firsthand much of what is discussed in this chapter. Now consider what psychological science has to say about your physical, cognitive, and psychosocial development, from the womb to the tomb. References Ainsworth, M. D. S., & Bell, S. M. (1970). Attachment, exploration, and separation: Illustrated by the behavior of one-year-olds in a strange situation. Child Development, 41, 49–67. Ainsworth, M. D. S., Blehar, M. C., Waters, E., & Wall, S. (1978). Patterns of attachment: A psychological study of the strange situation. Hillsdale, NJ: Erlbaum. American Academy of Pediatrics. (2007). The importance of play in promoting healthy child development and maintaining strong parent-child bonds. Pediatrics, 199(1), 182–191. Amsterdam, B. (1972). Mirror image reactions before age two. Developmental Psychobiology, 5, 297–305. Archer, J. (1992). Ethology and human development. New York, NY: Harvester Wheatsheaf. Arnett, J. (2000). Emerging adulthood: A theory of development from the late teens through the twenties. American Psychologist, 55(5), 469–480. Ashley, S. J., Magnuson, S. I., Omnell, L. M., & Clarren, S. K. (1999). Fetal alcohol syndrome: Changes in craniofacial form with age, cognition, and timing of ethanol exposure in the macaque. Teratology, 59(3), 163–172. Bahr, S. J., & Hoffman, J. P. (2010). Parenting style, religiosity, peers, and adolescent heavy drinking. Journal of Studies on Alcohol and Drugs, 71, 539–543. Baillargeon, R. (2004). Infants’ reasoning about hidden objects: Evidence for event-general and event-specific expectations. Developmental Science, 7(4), 391–424. Baillargeon, R. (1987). Young infants' reasoning about the physical and spatial properties of a hidden object. Cognitive Development, 2(3), 179–200. Baillargeon, R., Li, J., Gertner, Y., & Wu, D. (2011). How do infants reason about physical events. The Wiley-Blackwell handbook of childhood cognitive development, 2, 11–48. Barber, B. K. (1994). Cultural, family, and person contexts of parent-adolescent conflict. Journal of Marriage and the Family, 56, 375–386. Basseches, M. (1984). Dialectical thinking as metasystematic form of cognitive organization. In M. L. Commons, F. A. Richards, & C. Armon (Eds.), Beyond formal operations: Late adolescent and adult cognitive development (pp. 216–238). New York, NY: Praeger. Baumrind, D. (1971). Current patterns of parental authority. Developmental Psychology, 4(1, Pt. 2), 1–103. doi:10.1037/h0030372 Baumrind, D. (1991). The influence of parenting style on adolescent competence and substance use. Journal of Early Adolescence, 11(1), 56–95. Bayley, N., & Oden, M. H. (1955). The maintenance of intellectual ability in gifted adults. Journal of Gerontology, 10, 91–107. Bjorklund, D. F. (1987). A note on neonatal imitation. Developmental Review, 7, 86–92. Blossom, M., & Morgan, J.L. (2006). Does the face say what the mouth says? A study of infants’ sensitivity to visual prosody. In 30th anuual Boston University conference on language development, Somerville, MA. Bogartz, R. S., Shinskey, J. L., & Schilling, T. (2000). Infancy, 1(4), 403–428. Bowlby, J. (1969). Attachment and loss: Attachment (Vol. 1). New York, NY: Basic Books. Bowlby, J. (1988). A secure base: Parent-child attachment and health human development. New York, NY: Basic Books. Brumley, R., Enquidanos, S., Jamison, P., Seitz, R., Morgenstern, N., Saito, S., . . . Gonzalez, J. (2007). Increased satisfaction with care and lower costs: Results of a randomized trial of in-home palliative care. Journal of the American Geriatric Society, 55(7), 993–1000. Brumley, R. D., Enquidanos, S., & Cherin, D. A. (2003). Effectiveness of a home-based palliative care program for end-of-life. Journal of Palliative Medicine, 6(5), 715–724. Callaghan, T. C., Rochat, P., Lillard, A., Claux, M.L., Odden, H., Itakura, S., . . . Singh, S. (2005). Synchrony in the onset of mental-state reasoning. Psychological Science, 16, 378–384. Carel, J-C., Lahlou, N., Roger, M., & Chaussain, J. L. (2004). Precocious puberty and statural growth. Human Reproduction Update, 10(2), 135–147. Carstensen, L. L. (1992). Social and emotional patterns in adulthood: Support for socioemotional selectivity. Psychology and Aging, 7(3), 331–338. Case, R. (1985). Intellectual development: Birth to Adulthood. New York, NY: Academic. Casey, B. J., Tottenham, N., Liston, C., & Durston, S. (2005). Imaging the developing brain: What have we learned about cognitive development? TRENDS in Cognitive Sciences, 19(3), 104–110. Centers for Disease Control and Prevention. (2013). Smoking during pregnancy. Retrieved from http://www.cdc.gov/tobacco/basic_information/health_effects/pregnancy/ Chick, K., Heilman-Houser, R., & Hunter, M. (2002). The impact of child care on gender role development and gender stereotypes. Early Childhood Education Journal, 29(3), 149–154. Chomsky, N. (1957). Syntactic structures. The Hague, Netherlands: Mouton. Clements, R. (2004). An investigation of the status of outdoor play. Contemporary Issues in Early Childhood, 5(1), 68–80. Commons, M. L., & Bresette, L. M. (2006). Illuminating major creative scientific innovators with postformal stages. In C. Hoare (Ed.), Handbook of adult development and learning (pp. 255–280). New York, NY: Oxford University Press. Connor, S. R., Pyenson, B., Fitch, K., Spence, C., & Iwasaki, K. (2007). Comparing hospice and nonhospice patient survival among patients who die within a three-year window. Journal of Pain and Symptom Management, 33(3), 238–246. Courage, M. L., & Howe, M. L. (2002). From infant to child: The dynamics of cognitive change in the second year of life. Psychological Bulletin, 128, 250–277. Curtiss, S. (1981). Dissociations between language and cognition: Cases and implications. Journal of Autism and Developmental Disorders, 11(1), 15–30. Darling, N. (1999). Parenting style and its correlates. Retrieved from ERIC database (EDO-PS-99-3) http://ecap.crc.illinois.edu/eecearchive/digests/1999/darlin99.pdf de Hevia, M. D., & Spelke, E. S. (2010). Number-space mapping in human infants. Psychological Science, 21(5), 653–660. Dennett, D. (1987). The intentional stance. Cambridge, MA: MIT Press. Diamond, A. (2009). The interplay of biology and the environment broadly defined. Developmental Psychology, 45(1), 1–8. Donenberg, G. R., Wilson, H. W., Emerson, E., Bryant, F. B. (2002). Holding the line with a watchful eye: The impact of perceived parental permissiveness and parental monitoring on risky sexual behavior among adolescents in psychiatric care. AIDS Education Prevention, 14(2), 138–157. Dornbusch, S. M., Ritter, P. L., Leiderman, P. H., Roberts, D. F., & Fraleigh, M. J. (1987). The relation of parenting style to adolescent school performance. Child Development, 58(5), 1244–1257. Duncan, G. J., & Magnuson, K. A. (2005). Can family socioeconomic resources account for racial and ethnic test score gaps? The Future of Children, 15(1), 35–54. Erikson, E. H. (1963). Childhood and Society (2nd ed.). New York, NY: Norton. Erikson, E. H. (1968). Identity: Youth and crisis. New York, NY: Norton. Ferrer, M., & Fugate, A. (2003). Helping your school-age child develop a healthy self-concept. Retrieved from http://edis.ifas.ufl.edu/fy570#FOOTNOTE_2 Figdor, E., & Kaeser, L. (1998). Concerns mount over punitive approaches to substance abuse among pregnant women. The Guttmacher Report on Public Policy 1(5), 3–5. Fischer, K. W., Yan, Z., & Stewart, J. (2003). Adult cognitive development: Dynamics in the developmental web. In J. Valsiner & K Connolly (Eds.), Handbook of developmental psychology (pp. 491–516). Thousand Oaks, CA: Sage Publications. Flannery, D. J., Rowe, D. C., & Gulley, B. L. (1993). Impact of pubertal status, timing, and age on adolescent sexual experience and delinquency. Journal of Adolescent Research, 8, 21–40. Freud, S. (1909). Analysis of a phobia in a five-year-old boy. In Collected Papers: Volume 111, Case Histories (1949) (pp. 149–289). Hogarth Press: London. Fromkin, V., Krashen, S., Curtiss, S., Rigler, D., & Rigler, M. (1974). The development of language in Genie: A case of language acquisition beyond the critical period. Brain and Language, 1, 81–107. Galambos, N. L., & Almeida, D. M. (1992). Does parent-adolescent conflict increase in early adolescence? Journal of Marriage and the Family, 54, 737–747. Ganger, J., & Brent, M.R. (2004). Reexamining the vocabulary spurt. Developmental Psychology, 40(4), 621–632. Ge, X., Conger, R. D., & Elder, G. H. (2001). Pubertal transition, stressful life events, and the emergence of gender differences in adolescent depressive symptoms. Developmental Psychology, 37, 404–417. Gervai, J. (2009). Environmental and genetic influences on early attachment. Child and Adolescent Psychiatry and Mental Health, 3, 25. Gesell, A. (1933). Maturation and the patterning of behavior. In C. Murchison (Ed.), A handbook of child psychology (2nd ed., pp. 209–235). Worcester, MA: Clark University Press. Gesell, A. (1939). Biographies of child development. New York, NY: Paul B. Hoeber. Gesell, A. (1940). The first five years of life. New York, NY: Harper. Gesell, A., & Ilg, F. L. (1946). The child from five to ten. New York, NY: Harper. Gilligan, C. (1982). In a different voice: Psychological theory and women's development. Cambridge, MA: Harvard University Press. Gleitman, L.R., & Newport, E. L. (1995). The invention of language by children: Environmental and biological influences on the acquisition of language. In D.N. Osherson , L.R. Gleitman, & M. Liberman (Eds.), An invitation to cognitive science: Language (pp. 1–24). Cambridge, MA: The MIT Press. Gleitman, L. R., & Newport, E. L. (1995). The invention of language by children: Environmental and biological influences on the acquisition of language. In L. R. Gleitman & M. Liberman (Eds.), An invitation to cognitive science, Vol. 1: Language. (2nd ed.) (pp. 1–24). Cambridge, MA: MIT Press. Godkin, M., Krant, M., & Doster, N. (1984). The impact of hospice care on families. International Journal of Psychiatry in Medicine, 13, 153–165. Graber, J. A., Lewinsohn, P. M., Seeley, J. R., & Brooks-Gunn, J. (1997). Is psychopathology associated with the timing of pubertal development? Journal of the Academy of Child and Adolescent Psychiatry, 36, 1768–1776. Hair, E. C., Moore, K. A., Garrett, S. B., Kinukawa, A., Lippman, L., & Michelson, E. (2005). The parent-adolescent relationship scale. In L. Lippman (Ed.), Conceptualizing and Measuring Indicators of Positive Development: What Do Children Need to Fluorish? (pp. 183–202). New York, NY: Kluwer Academic/Plenum Press. Hall, S. S. (2004, May). The good egg. Discover, 30–39. Hall, G. S. (1904). Adolescence. New York, NY: Appleton. Harlow, H. (1958). The nature of love. American Psychologist, 13, 673–685. Harris, J. R. (2009). The nurture assumption: Why children turn out the way they do (2nd ed.). New York, NY: Free Press. Hart, B., & Risley, T. R. (2003). The early catastrophe: The 30 million word gap. American Educator, 27(1), 4–9. Hatch, E. (1983). Psycholinguistics: A second language perspective. Rowley, MA: Newbury House. Hertzog, C., Kramer, A. F., Wilson, R. S., & Lindenberger, U. (2009). Enrichment effects on adult cognitive development. Psychological Science in the Public Interest, 9(1), 1–65. Hood, R. W., Jr., Spilka, B., Hunsberger, B., & Corsuch, R. (1996). The psychology of religion: An empirical approach (2nd ed.). New York, NY: Guilford. Huebler, F. (2005, December 14). International education statistics [Web log post]. Retrieved from http://huebler.blogspot.com/2005/12/age-and-level-of-education-in-nigeria.html Hutchinson, N. (2011). A geographically informed vision of skills development. Geographical Education, 24, 15. Huttenlocher, P. R., & Dabholkar, A. S. (1997). Regional differences in synaptogenesis in human cerebral cortex. Journal of Comparative Neurology, 387(2), 167–178. Iverson, J.M., & Goldin-Meadow, S. (2005). Gesture paves the way for language development. Psychological Science, 16(5), 367–71. Iyengar, S. S., Wells, R. E., & Schwartz, B. (2006). Doing better but feeling worse: Looking for the best job undermines satisfaction. Psychological Science, 17, 143–150. Jos, P. H., Marshall, M. F., & Perlmutter, M. (1995). The Charleston policy on cocaine use during pregnancy: A cautionary tale. The Journal of Law, Medicine & Ethics, 23(2), 120–128. Kaltiala-Heino, R. A., Rimpela, M., Rissanen, A., & Rantanen, P. (2001). Early puberty and early sexual activity are associated with bulimic-type eating pathology in middle adolescence. Journal of Adolescent Health, 28, 346–352. Kaplan, H., & Dove, H. (1987). Infant development among the Aché of Eastern Paraguay. Developmental Psychology, 23, 190–198. Karasik, L. B., Adolph, K. E., Tamis-LeMonda, C. S., & Bornstein, M. H. (2010). WEIRD Walking: Cross-cultural research on motor development. Behavioral & Brain Sciences, 33(2-3), 95–96. Karnik, S., & Kanekar, A. (2012). Childhood obesity: A global public health crisis. International Journal of Preventive Medicine, 3(1), 1–7. Kohlberg, L. (1969). Stage and sequence: The cognitive-developmental approach to socialization. In D. A. Goslin (Ed.), Handbook of socialization theory and research (p. 379). Chicago, IL: Rand McNally. Kolb, B., & Whishaw, I. Q. (2009). Fundamentals of human neuropsychology. New York, NY: Worth. Kübler-Ross, E. (1969). On death and dying. New York, NY: Macmillan. Labouvie-Vief, G., & Diehl, M. (1999). Self and personality development. In J. C. Cavanaugh & S. K. Whitbourne (Eds.), Gerontology: An interdisciplinary perspective (pp. 238–268). New York, NY: Oxford University Press. Larson, E. B., Wang, L., Bowen, J. D., McCormick, W. C., Teri, L., Crane, P., & Kukull, W. (2006). Exercise is associated with reduced risk for incident dementia among persons 65 years of age or older. Annals of Internal Medicine, 144, 73–81. Lee, V. E., & Burkam, D. T. (2002). Inequality at the starting gate: Social background differences in achievement as children begin school. Washington, DC: Economic Policy Institute. Lobo, I. (2008) Environmental influences on gene expression. Nature Education 1(1), 39. Loop, E. (2013). Major milestones in cognitive development in early childhood. Retrieved from http://everydaylife.globalpost.com/major-milestones-cognitive-development-early-childhood-4625.html Maccoby, E. (1980). Social development: Psychological growth and the parent-child relationship. New York, NY: Harcourt Brace Jovanovich. MacFarlane, A. (1978, February). What a baby knows. Human Nature, 74–81. Maier, S. E., & West, J. R. (2001). Drinking patterns and alcohol-related birth defects. Alcohol Research & Health, 25(3), 168–174. Main, M., & Solomon, J. (1990). Procedures for identifying infants as disorganized/disoriented during the Ainsworth Strange Situation. In M. T. Greenberg, D. Cicchetti, & E. M. Cummings (Eds.), Attachment in the Preschool Years (pp. 121–160). Chicago, IL: University of Chicago Press. Markus, H. R., Ryff, C. D., Curan, K., & Palmersheim, K. A. (2004). In their own words: Well-being at midlife among high school-educated and college-educated adults. In O. G. Brim, C. D. Ryff, & R. C. Kessler (Eds.), How healthy are we? A national study of well-being at midlife (pp. 273–319). Chicago, IL: University of Chicago Press. McIntosh, D. N., Silver, R. C., & Wortman, C. B. (1993). Religion’s role in adjustment to a negative life event: Coping with the loss of a child. Journal of Personality and Social Psychology, 65, 812–821. McMillan, S. C., Small, B. J., Weitzner, M., Schonwetter, R., Tittle, M., Moody, L., & Haley, W. E. (2006). Impact of coping skills intervention with family caregivers of hospice patients with cancer. Cancer, 106(1), 214-222. Miklikowska, M., Duriez, B., & Soenens, B. (2011). Family roots of empathy-related characteristics: The role of perceived maternal and paternal need support in adolescence. Developmental Psychology, 47(5), 1342–1352. Mills, M., & Melhuish, E. (1974). Recognition of mother’s voice in early infancy. Nature, 252, 123–124. Mohr, R. D., & Zoghi, C. (2006). Is job enrichment really enriching? (U.S. Bureau of Labor Statistics Working Paper 389). Washington, DC: U.S. Bureau of Labor Statistics. Retrieved from http://www.bls.gov/ore/pdf/ec060010.pdf Moore, K. A., Guzman, L., Hair, E. C., Lippman, L., & Garrett, S. B. (2004). Parent-teen relationships and interactions: Far more positive than not. Child Trends Research Brief, 2004-25. Washington, DC: Child Trends. National Institutes of Health. (2013). What is prenatal care and why is it important? Retrieved from http://www.nichd.nih.gov/health/topics/pregnancy/conditioninfo/Pages/prenatal-care.aspx Nolen-Hoeksema, S., & Larson, J. (1999). Coping with loss. Mahweh, NJ: Erlbaum. Overman, W. H., Bachevalier, J., Turner, M., & Peuster, A. (1992). Object recognition versus object discrimination: Comparison between human infants and infant monkeys. Behavioral Neuroscience, 106, 15–29. Paloutzian, R. F. (1996). Invitation to the psychology of religion. Boston, MA: Allyn & Bacon. Parent, J., Forehand, R., Merchant, M. J., Edwards, M. C., Conners-Burrow, N. A., Long, N., & Jones, D. J. (2011). The relation of harsh and permissive discipline with child disruptive behaviors: Does child gender make a difference in an at-risk sample? Journal of Family Violence, 26, 527–533. Piaget, J. (1954). The construction of reality in the child. New York: Basic Books. Pickens, J. (1994). Full-term and preterm infants’ perception of face-voice synchrony. Infant Behavior and Development, 17, 447–455. Piaget, J. (1930). The child’s conception of the world. New York, NY: Harcourt, Brace & World. Piaget, J. (1932). The moral judgment of the child. New York, NY: Harcourt, Brace & World. Podewils, L. J., Guallar, E., Kuller, L. H., Fried, L. P., Lopez, O. L., Carlson, M., & Lyketsos, C. G. (2005). Physical activity, APOE genotype, and dementia risk: Findings from the Cardiovascular Health Cognition Study. American Journal of Epidemiology, 161, 639–651. Pollack, W., & Shuster, T. (2000). Real boys’ voices. New York, NY: Random House. Rhodes, R. L., Mitchell, S. L., Miller, S. C., Connor, S. R., & Teno, J. M. (2008). Bereaved family members' evaluation of hospice care: What factors influence overall satisfaction with services? Journal of Pain and Symptom Management, 35, 365–371. Risley, T. R., & Hart, B. (2006). Promoting early language development. In N. F. Watt, C. Ayoub, R. H. Bradley, J. E. Puma, & W. A. LeBoeuf (Eds.), The crisis in youth mental health: Early intervention programs and policies (Vol. 4, pp. 83–88). Westport, CT: Praeger. Rothbaum, R., Weisz, J., Pott, M., Miyake, K., & Morelli, G. (2000). Attachment and culture: Security in the United States and Japan. American Psychologist, 55, 1093–1104. Russell, S. T., Crockett, L. J., & Chao, R. (Eds.). (2010). Asian American parenting and parent-adolescent relationships. In R. Levesque (Series Ed.), Advancing responsible adolescent development. New York, NY: Springer. Ryff, C. D., & Singer, B. (2009). Understanding healthy aging: Key components and their integration. In V. L. Bengtson, D. Gans., N. M. Putney, & M. Silverstein. (Eds.), Handbook of theories of aging (2nd ed., pp. 117–144). New York, NY: Springer. Samarel, N. (1991). Caring for life after death. Washington, DC: Hemisphere. Sanson, A., & Rothbart, M. K. (1995). Child temperament and parenting. In M. Bornstein (Ed.), Applied and practical parenting (Vol. 4, pp. 299–321). Mahwah, NJ: Lawrence Erlbaum. Schechter, C., & Byeb, B. (2007). Preliminary evidence for the impact of mixed-income preschools on low-income children’s language growth. Early Childhood Research Quarterly, 22, 137–146. Shamay-Tsoory, S. G., Tomer, R., & Aharon-Peretz, J. (2005). The neuroanatomical basis of understanding sarcasm and its relationship to social cognition. Neuropsychology, 19(3), 288–300. Shanahan, L., McHale, S. M., Osgood, D. W., & Crouter, A. C. (2007). Conflict frequency with mothers and fathers from middle childhood to late adolescence: Within and between family comparisons. Developmental Psychology, 43, 539–550. Siegler, R. S. (2005). Children’s thinking (4th ed). Mahwah, NJ: Erlbaum. Siegler, R. S. (2006). Microgenetic analyses of learning. In D. Kuhn & R. S. Siegler (Eds.), Handbook of child psychology: Cognition, perception, and language (6th ed., Vol. 2). New York: Wiley. Sinnott, J. D. (1998). The development of logic in adulthood: Postformal thought and its applications. New York, NY: Springer. Small, M. F. (1999). Our babies, ourselves: How biology and culture shape the way we parent. New York, NY: Anchor Books. Spelke, E.S., & Cortelyou, A. (1981). Perceptual aspects of social knowing: Looking and listening in infancy. In M.E. Lamb & L.R. Sherrod (Eds.), Infant social cognition: Empirical and theoretical considerations (pp. 61–83). Hillsdale, NJ: Erlbaum. Steinberg, L., & Morris, A. S. (2001). Adolescent development. Annual Review of Psychology, 52, 83–110. Sterns, H. L., & Huyck, M. H. (2001). The role of work in midlife. In M. Lachman (Ed.), The handbook of midlife development (pp. 447–486). New York, NY:Wiley. Steven L. Youngentob, et. al. (2007). Experience-induced fetal plasticity: The effect of gestational ethanol exposure on the behavioral and neurophysiologic olfactory response to ethanol odor in early postnatal and adult rats. Behavioral Neuroscience, 121(6), 1293–1305. Stork, F. C., & Widdowson, D. A. (1974). Learning about linguistics. London, UK: Hutchinson Ltd. Streissguth, A. P., Bookstein, F. L., Barr, H. M., Sampson, P. D., O’Malley, K., & Young, J. K. (2004). Risk factors for adverse life outcomes in fetal alcohol syndrome and fetal alcohol effects. Developmental and Behavioral Pediatrics, 25(4), 228–238. Striegel-Moore, R. H., & Cachelin, F. M. (1999). Body image concerns and disordered eating in adolescent girls: Risk and protective factors. In N. G. Johnson, M. C. Roberts, & J. Worell (Eds.), Beyond appearance: A new look at adolescent girls. Washington, DC: American Psychological Association Tanner, J. M. (1978). Fetus into man: Physical growth from conception to maturity. Cambridge, MA: Harvard University Press. Temel, J. S., Greer, J. A., Muzikansky, A., Gallagher, E. R., Admane, S., Jackson, V. A. . . . Lynch, T. J. (2010). Early palliative care for patients with metastic non-small-cell lung cancer. New England Journal of Medicine, 363, 733–742. Thomas, A. (1984). Temperament research: Where we are, where we are going. Merrill-Palmer Quarterly, 30(2), 103–109. Tran, T. D., & Kelly, S. J. (2003). Critical periods for ethanol-induced cell loss in the hippocampal formation. Neurotoxicology and Teratology, 25(5), 519–528. Umberson, D., Pudrovska, T., & Reczek, C. (2010). Parenthood, childlessness, and well-being: A life course perspective. Journal of Marriage and the Family, 72(3), 612–629. United Nations Educational, Scientific and Cultural Organization. (2013, June). UIS Fact Sheet: Schooling for millions of children jeopardized by reductions in aid. Montreal, Canada: UNESCO Institute for Statistics. Vaillant, G. E. (2002). Aging well. New York, NY: Little Brown & Co. Van der Graaff, J., Branje, S., De Wied, M., Hawk, S., Van Lier, P., & Meeus, W. (2013). Perspective taking and empathetic concern in adolescence: Gender differences in developmental changes. Developmental Psychology, 50(3), 881. van Ijzendoorn, M. H., & Sagi-Schwartz, A. (2008). Cross-cultural patterns of attachment: Universal and contextual dimensions. In J. Cassidy & P. R. Shaver (Eds.), Handbook of attachment. New York, NY: Guilford. Vouloumanos, A., & Werker, J. F. (2004). Tuned to the signal: The privileged status of speech for young infants. Developmental Science, 7, 270–276. WHO Multicentre Growth Reference Study Group. (2006). WHO Child growth standards: Methods and development: Length/height-for-age, weight-for-age, weight-for-length, weight-for-height and body mass index-for-age. Geneva, Switzerland: World Health Organization. Winerman, L. (2011). Closing the achievement gap. Monitor of Psychology, 42(8), 36. Wortman, J. H., & Park, C. L. (2008). Religion and spirituality in adjustment following bereavement: An integrative review. Death Studies	oercommons	2025-03-18T00:36:10.558867	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15340/overview", "title": "Psychology, Lifespan Development", "author": null }
https://oercommons.org/courseware/lesson/15341/overview	What Is Lifespan Development? Overview By the end of this section, you will be able to: - Define and distinguish between the three domains of development: physical, cognitive and psychosocial - Discuss the normative approach to development - Understand the three major issues in development: continuity and discontinuity, one common course of development or many unique courses of development, and nature versus nurture My heart leaps up when I behold A rainbow in the sky: So was it when my life began; So is it now I am a man; So be it when I shall grow old, Or let me die! The Child is father of the Man; I could wish my days to be Bound each to each by natural piety. (Wordsworth, 1802) In this poem, William Wordsworth writes, “the child is father of the man.” What does this seemingly incongruous statement mean, and what does it have to do with lifespan development? Wordsworth might be suggesting that the person he is as an adult depends largely on the experiences he had in childhood. Consider the following questions: To what extent is the adult you are today influenced by the child you once were? To what extent is a child fundamentally different from the adult he grows up to be? These are the types of questions developmental psychologists try to answer, by studying how humans change and grow from conception through childhood, adolescence, adulthood, and death. They view development as a lifelong process that can be studied scientifically across three developmental domains—physical, cognitive, and psychosocial development. Physical development involves growth and changes in the body and brain, the senses, motor skills, and health and wellness. Cognitive development involves learning, attention, memory, language, thinking, reasoning, and creativity. Psychosocial development involves emotions, personality, and social relationships. We refer to these domains throughout the chapter. Research Methods in Developmental Psychology You’ve learned about a variety of research methods used by psychologists. Developmental psychologists use many of these approaches in order to better understand how individuals change mentally and physically over time. These methods include naturalistic observations, case studies, surveys, and experiments, among others. Naturalistic observations involve observing behavior in its natural context. A developmental psychologist might observe how children behave on a playground, at a daycare center, or in the child’s own home. While this research approach provides a glimpse into how children behave in their natural settings, researchers have very little control over the types and/or frequencies of displayed behavior. In a case study, developmental psychologists collect a great deal of information from one individual in order to better understand physical and psychological changes over the lifespan. This particular approach is an excellent way to better understand individuals, who are exceptional in some way, but it is especially prone to researcher bias in interpretation, and it is difficult to generalize conclusions to the larger population. In one classic example of this research method being applied to a study of lifespan development Sigmund Freud analyzed the development of a child known as “Little Hans” (Freud, 1909/1949). Freud’s findings helped inform his theories of psychosexual development in children, which you will learn about later in this chapter. Little Genie, the subject of a case study discussed in the chapter on thinking and intelligence, provides another example of how psychologists examine developmental milestones through detailed research on a single individual. In Genie’s case, her neglectful and abusive upbringing led to her being unable to speak until, at age 13, she was removed from that harmful environment. As she learned to use language, psychologists were able to compare how her language acquisition abilities differed when occurring in her late-stage development compared to the typical acquisition of those skills during the ages of infancy through early childhood (Fromkin, Krashen, Curtiss, Rigler, & Rigler, 1974; Curtiss, 1981). The survey method asks individuals to self-report important information about their thoughts, experiences, and beliefs. This particular method can provide large amounts of information in relatively short amounts of time; however, validity of data collected in this way relies on honest self-reporting, and the data is relatively shallow when compared to the depth of information collected in a case study. Experiments involve significant control over extraneous variables and manipulation of the independent variable. As such, experimental research allows developmental psychologists to make causal statements about certain variables that are important for the developmental process. Because experimental research must occur in a controlled environment, researchers must be cautious about whether behaviors observed in the laboratory translate to an individual’s natural environment. Later in this chapter, you will learn about several experiments in which toddlers and young children observe scenes or actions so that researchers can determine at what age specific cognitive abilities develop. For example, children may observe a quantity of liquid poured from a short, fat glass into a tall, skinny glass. As the experimenters question the children about what occurred, the subjects’ answers help psychologists understand at what age a child begins to comprehend that the volume of liquid remained the same although the shapes of the containers differs. Across these three domains—physical, cognitive, and psychosocial—the normative approach to development is also discussed. This approach asks, “What is normal development?” In the early decades of the 20th century, normative psychologists studied large numbers of children at various ages to determine norms (i.e., average ages) of when most children reach specific developmental milestones in each of the three domains (Gesell, 1933, 1939, 1940; Gesell & Ilg, 1946; Hall, 1904). Although children develop at slightly different rates, we can use these age-related averages as general guidelines to compare children with same-age peers to determine the approximate ages they should reach specific normative events called developmental milestones (e.g., crawling, walking, writing, dressing, naming colors, speaking in sentences, and starting puberty). Not all normative events are universal, meaning they are not experienced by all individuals across all cultures. Biological milestones, such as puberty, tend to be universal, but social milestones, such as the age when children begin formal schooling, are not necessarily universal; instead, they affect most individuals in a particular culture (Gesell & Ilg, 1946). For example, in developed countries children begin school around 5 or 6 years old, but in developing countries, like Nigeria, children often enter school at an advanced age, if at all (Huebler, 2005; United Nations Educational, Scientific, and Cultural Organization [UNESCO], 2013). To better understand the normative approach, imagine two new mothers, Louisa and Kimberly, who are close friends and have children around the same age. Louisa’s daughter is 14 months old, and Kimberly’s son is 12 months old. According to the normative approach, the average age a child starts to walk is 12 months. However, at 14 months Louisa’s daughter still isn’t walking. She tells Kimberly she is worried that something might be wrong with her baby. Kimberly is surprised because her son started walking when he was only 10 months old. Should Louisa be worried? Should she be concerned if her daughter is not walking by 15 months or 18 months? The Centers for Disease Control and Prevention (CDC) describes the developmental milestones for children from 2 months through 5 years old. After reviewing the information, take this quiz to see how well you recall what you’ve learned. If you are a parent with concerns about your child’s development, contact your pediatrician. ISSUES IN DEVELOPMENTAL PSYCHOLOGY There are many different theoretical approaches regarding human development. As we evaluate them in this chapter, recall that developmental psychology focuses on how people change, and keep in mind that all the approaches that we present in this chapter address questions of change: Is the change smooth or uneven (continuous versus discontinuous)? Is this pattern of change the same for everyone, or are there many different patterns of change (one course of development versus many courses)? How do genetics and environment interact to influence development (nature versus nurture)? Is Development Continuous or Discontinuous? Continuous development views development as a cumulative process, gradually improving on existing skills (Figure). With this type of development, there is gradual change. Consider, for example, a child’s physical growth: adding inches to her height year by year. In contrast, theorists who view development as discontinuous believe that development takes place in unique stages: It occurs at specific times or ages. With this type of development, the change is more sudden, such as an infant’s ability to conceive object permanence. Is There One Course of Development or Many? Is development essentially the same, or universal, for all children (i.e., there is one course of development) or does development follow a different course for each child, depending on the child’s specific genetics and environment (i.e., there are many courses of development)? Do people across the world share more similarities or more differences in their development? How much do culture and genetics influence a child’s behavior? Stage theories hold that the sequence of development is universal. For example, in cross-cultural studies of language development, children from around the world reach language milestones in a similar sequence (Gleitman & Newport, 1995). Infants in all cultures coo before they babble. They begin babbling at about the same age and utter their first word around 12 months old. Yet we live in diverse contexts that have a unique effect on each of us. For example, researchers once believed that motor development follows one course for all children regardless of culture. However, child care practices vary by culture, and different practices have been found to accelerate or inhibit achievement of developmental milestones such as sitting, crawling, and walking (Karasik, Adolph, Tamis-LeMonda, & Bornstein, 2010). For instance, let’s look at the Aché society in Paraguay. They spend a significant amount of time foraging in forests. While foraging, Aché mothers carry their young children, rarely putting them down in order to protect them from getting hurt in the forest. Consequently, their children walk much later: They walk around 23–25 months old, in comparison to infants in Western cultures who begin to walk around 12 months old. However, as Aché children become older, they are allowed more freedom to move about, and by about age 9, their motor skills surpass those of U.S. children of the same age: Aché children are able to climb trees up to 25 feet tall and use machetes to chop their way through the forest (Kaplan & Dove, 1987). As you can see, our development is influenced by multiple contexts, so the timing of basic motor functions may vary across cultures. However, the functions themselves are present in all societies (Figure). How Do Nature and Nurture Influence Development? Are we who we are because of nature (biology and genetics), or are we who we are because of nurture (our environment and culture)? This longstanding question is known in psychology as the nature versus nurture debate. It seeks to understand how our personalities and traits are the product of our genetic makeup and biological factors, and how they are shaped by our environment, including our parents, peers, and culture. For instance, why do biological children sometimes act like their parents—is it because of genetics or because of early childhood environment and what the child has learned from the parents? What about children who are adopted—are they more like their biological families or more like their adoptive families? And how can siblings from the same family be so different? We are all born with specific genetic traits inherited from our parents, such as eye color, height, and certain personality traits. Beyond our basic genotype, however, there is a deep interaction between our genes and our environment: Our unique experiences in our environment influence whether and how particular traits are expressed, and at the same time, our genes influence how we interact with our environment (Diamond, 2009; Lobo, 2008). This chapter will show that there is a reciprocal interaction between nature and nurture as they both shape who we become, but the debate continues as to the relative contributions of each. The Achievement Gap: How Does Socioeconomic Status Affect Development? The achievement gap refers to the persistent difference in grades, test scores, and graduation rates that exist among students of different ethnicities, races, and—in certain subjects—sexes (Winerman, 2011). Research suggests that these achievement gaps are strongly influenced by differences in socioeconomic factors that exist among the families of these children. While the researchers acknowledge that programs aimed at reducing such socioeconomic discrepancies would likely aid in equalizing the aptitude and performance of children from different backgrounds, they recognize that such large-scale interventions would be difficult to achieve. Therefore, it is recommended that programs aimed at fostering aptitude and achievement among disadvantaged children may be the best option for dealing with issues related to academic achievement gaps (Duncan & Magnuson, 2005). Low-income children perform significantly more poorly than their middle- and high-income peers on a number of educational variables: They have significantly lower standardized test scores, graduation rates, and college entrance rates, and they have much higher school dropout rates. There have been attempts to correct the achievement gap through state and federal legislation, but what if the problems start before the children even enter school? Psychologists Betty Hart and Todd Risley (2006) spent their careers looking at early language ability and progression of children in various income levels. In one longitudinal study, they found that although all the parents in the study engaged and interacted with their children, middle- and high-income parents interacted with their children differently than low-income parents. After analyzing 1,300 hours of parent-child interactions, the researchers found that middle- and high-income parents talk to their children significantly more, starting when the children are infants. By 3 years old, high-income children knew almost double the number of words known by their low-income counterparts, and they had heard an estimated total of 30 million more words than the low-income counterparts (Hart & Risley, 2003). And the gaps only become more pronounced. Before entering kindergarten, high-income children score 60% higher on achievement tests than their low-income peers (Lee & Burkam, 2002). There are solutions to this problem. At the University of Chicago, experts are working with low-income families, visiting them at their homes, and encouraging them to speak more to their children on a daily and hourly basis. Other experts are designing preschools in which students from diverse economic backgrounds are placed in the same classroom. In this research, low-income children made significant gains in their language development, likely as a result of attending the specialized preschool (Schechter & Byeb, 2007). What other methods or interventions could be used to decrease the achievement gap? What types of activities could be implemented to help the children of your community or a neighboring community? Summary Lifespan development explores how we change and grow from conception to death. This field of psychology is studied by developmental psychologists. They view development as a lifelong process that can be studied scientifically across three developmental domains: physical, cognitive development, and psychosocial. There are several theories of development that focus on the following issues: whether development is continuous or discontinuous, whether development follows one course or many, and the relative influence of nature versus nurture on development. Review Questions The view that development is a cumulative process, gradually adding to the same type of skills is known as ________. - nature - nurture - continuous development - discontinuous development Hint: C Developmental psychologists study human growth and development across three domains. Which of the following is not one of these domains? - cognitive - psychological - physical - psychosocial Hint: B How is lifespan development defined? - The study of how we grow and change from conception to death. - The study of how we grow and change in infancy and childhood. - The study of physical, cognitive, and psychosocial growth in children. - The study of emotions, personality, and social relationships. Hint: A Critical Thinking Questions Describe the nature versus nurture controversy, and give an example of a trait and how it might be influenced by each? Hint: The nature versus nurture controversy seeks to understand whether our personalities and traits are the product of our genetic makeup and biological factors, or whether they are shaped by our environment, which includes such things as our parents, peers, and culture. Today, psychologists agree that both nature and nurture interact to shape who we become, but the debate over the relative contributions of each continues. An example would be a child learning to walk: Nature influences when the physical ability occurs, but culture can influence when a child masters this skill, as in Aché culture. Compare and contrast continuous and discontinuous development. Hint: Continuous development sees our development as a cumulative process: Changes are gradual. On the other hand, discontinuous development sees our development as taking place in specific steps or stages: Changes are sudden. Why should developmental milestones only be used as a general guideline for normal child development? Hint: Children develop at different rates. For example, some children may walk and talk as early as 8 months old, while others may not do so until well after their first birthday. Each child’s unique contexts will influence when he reaches these milestones. Personal Application Questions How are you different today from the person you were at 6 years old? What about at 16 years old? How are you the same as the person you were at those ages? Your 3-year-old daughter is not yet potty trained. Based on what you know about the normative approach, should you be concerned? Why or why not?	oercommons	2025-03-18T00:36:10.592384	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15341/overview", "title": "Psychology, Lifespan Development", "author": null }
https://oercommons.org/courseware/lesson/15342/overview	Lifespan Theories Overview By the end of this section, you will be able to: - Discuss Freud’s theory of psychosexual development - Describe the major tasks of child and adult psychosocial development according to Erikson - Discuss Piaget’s view of cognitive development and apply the stages to understanding childhood cognition - Describe Kohlberg’s theory of moral development There are many theories regarding how babies and children grow and develop into happy, healthy adults. We explore several of these theories in this section. PSYCHOSEXUAL THEORY OF DEVELOPMENT Sigmund Freud (1856–1939) believed that personality develops during early childhood. For Freud, childhood experiences shape our personalities and behavior as adults. Freud viewed development as discontinuous; he believed that each of us must pass through a serious of stages during childhood, and that if we lack proper nurturance and parenting during a stage, we may become stuck, or fixated, in that stage. Freud’s stages are called the stages of psychosexual development. According to Freud, children’s pleasure-seeking urges are focused on a different area of the body, called an erogenous zone, at each of the five stages of development: oral, anal, phallic, latency, and genital. While most of Freud’s ideas have not found support in modern research, we cannot discount the contributions that Freud has made to the field of psychology. Psychologists today dispute Freud's psychosexual stages as a legitimate explanation for how one's personality develops, but what we can take away from Freud’s theory is that personality is shaped, in some part, by experiences we have in childhood. These stages are discussed in detail in the chapter on personality. PSYCHOSOCIAL THEORY OF DEVELOPMENT Erik Erikson (1902–1994) (Figure), another stage theorist, took Freud’s theory and modified it as psychosocial theory. Erikson’s psychosocial development theory emphasizes the social nature of our development rather than its sexual nature. While Freud believed that personality is shaped only in childhood, Erikson proposed that personality development takes place all through the lifespan. Erikson suggested that how we interact with others is what affects our sense of self, or what he called the ego identity. Erikson proposed that we are motivated by a need to achieve competence in certain areas of our lives. According to psychosocial theory, we experience eight stages of development over our lifespan, from infancy through late adulthood. At each stage there is a conflict, or task, that we need to resolve. Successful completion of each developmental task results in a sense of competence and a healthy personality. Failure to master these tasks leads to feelings of inadequacy. According to Erikson (1963), trust is the basis of our development during infancy (birth to 12 months). Therefore, the primary task of this stage is trust versus mistrust. Infants are dependent upon their caregivers, so caregivers who are responsive and sensitive to their infant’s needs help their baby to develop a sense of trust; their baby will see the world as a safe, predictable place. Unresponsive caregivers who do not meet their baby’s needs can engender feelings of anxiety, fear, and mistrust; their baby may see the world as unpredictable. As toddlers (ages 1–3 years) begin to explore their world, they learn that they can control their actions and act on the environment to get results. They begin to show clear preferences for certain elements of the environment, such as food, toys, and clothing. A toddler’s main task is to resolve the issue of autonomy versus shame and doubt, by working to establish independence. This is the “me do it” stage. For example, we might observe a budding sense of autonomy in a 2-year-old child who wants to choose her clothes and dress herself. Although her outfits might not be appropriate for the situation, her input in such basic decisions has an effect on her sense of independence. If denied the opportunity to act on her environment, she may begin to doubt her abilities, which could lead to low self-esteem and feelings of shame. Once children reach the preschool stage (ages 3–6 years), they are capable of initiating activities and asserting control over their world through social interactions and play. According to Erikson, preschool children must resolve the task of initiative versus guilt. By learning to plan and achieve goals while interacting with others, preschool children can master this task. Those who do will develop self-confidence and feel a sense of purpose. Those who are unsuccessful at this stage—with their initiative misfiring or stifled—may develop feelings of guilt. How might over-controlling parents stifle a child’s initiative? During the elementary school stage (ages 6–12), children face the task of industry versus inferiority. Children begin to compare themselves to their peers to see how they measure up. They either develop a sense of pride and accomplishment in their schoolwork, sports, social activities, and family life, or they feel inferior and inadequate when they don’t measure up. What are some things parents and teachers can do to help children develop a sense of competence and a belief in themselves and their abilities? In adolescence (ages 12–18), children face the task of identity versus role confusion. According to Erikson, an adolescent’s main task is developing a sense of self. Adolescents struggle with questions such as “Who am I?” and “What do I want to do with my life?” Along the way, most adolescents try on many different selves to see which ones fit. Adolescents who are successful at this stage have a strong sense of identity and are able to remain true to their beliefs and values in the face of problems and other people’s perspectives. What happens to apathetic adolescents, who do not make a conscious search for identity, or those who are pressured to conform to their parents’ ideas for the future? These teens will have a weak sense of self and experience role confusion. They are unsure of their identity and confused about the future. People in early adulthood (i.e., 20s through early 40s) are concerned with intimacy versus isolation. After we have developed a sense of self in adolescence, we are ready to share our life with others. Erikson said that we must have a strong sense of self before developing intimate relationships with others. Adults who do not develop a positive self-concept in adolescence may experience feelings of loneliness and emotional isolation. When people reach their 40s, they enter the time known as middle adulthood, which extends to the mid-60s. The social task of middle adulthood is generativity versus stagnation. Generativity involves finding your life’s work and contributing to the development of others, through activities such as volunteering, mentoring, and raising children. Those who do not master this task may experience stagnation, having little connection with others and little interest in productivity and self-improvement. From the mid-60s to the end of life, we are in the period of development known as late adulthood. Erikson’s task at this stage is called integrity versus despair. He said that people in late adulthood reflect on their lives and feel either a sense of satisfaction or a sense of failure. People who feel proud of their accomplishments feel a sense of integrity, and they can look back on their lives with few regrets. However, people who are not successful at this stage may feel as if their life has been wasted. They focus on what “would have,” “should have,” and “could have” been. They face the end of their lives with feelings of bitterness, depression, and despair. Table summarizes the stages of Erikson’s theory. \| Stage \| Age (years) \| Developmental Task \| Description \| \|---\|---\|---\|---\| \| 1 \| 0–1 \| Trust vs. mistrust \| Trust (or mistrust) that basic needs, such as nourishment and affection, will be met \| \| 2 \| 1–3 \| Autonomy vs. shame/doubt \| Develop a sense of independence in many tasks \| \| 3 \| 3–6 \| Initiative vs. guilt \| Take initiative on some activities—may develop guilt when unsuccessful or boundaries overstepped \| \| 4 \| 7–11 \| Industry vs. inferiority \| Develop self-confidence in abilities when competent or sense of inferiority when not \| \| 5 \| 12–18 \| Identity vs. confusion \| Experiment with and develop identity and roles \| \| 6 \| 19–29 \| Intimacy vs. isolation \| Establish intimacy and relationships with others \| \| 7 \| 30–64 \| Generativity vs. stagnation \| Contribute to society and be part of a family \| \| 8 \| 65– \| Integrity vs. despair \| Assess and make sense of life and meaning of contributions \| COGNITIVE THEORY OF DEVELOPMENT Jean Piaget (1896–1980) is another stage theorist who studied childhood development (Figure). Instead of approaching development from a psychoanalytical or psychosocial perspective, Piaget focused on children’s cognitive growth. He believed that thinking is a central aspect of development and that children are naturally inquisitive. However, he said that children do not think and reason like adults (Piaget, 1930, 1932). His theory of cognitive development holds that our cognitive abilities develop through specific stages, which exemplifies the discontinuity approach to development. As we progress to a new stage, there is a distinct shift in how we think and reason. Piaget said that children develop schemata to help them understand the world. Schemata are concepts (mental models) that are used to help us categorize and interpret information. By the time children have reached adulthood, they have created schemata for almost everything. When children learn new information, they adjust their schemata through two processes: assimilation and accommodation. First, they assimilate new information or experiences in terms of their current schemata: assimilation is when they take in information that is comparable to what they already know. Accommodation describes when they change their schemata based on new information. This process continues as children interact with their environment. For example, 2-year-old Blake learned the schema for dogs because his family has a Labrador retriever. When Blake sees other dogs in his picture books, he says, “Look mommy, dog!” Thus, he has assimilated them into his schema for dogs. One day, Blake sees a sheep for the first time and says, “Look mommy, dog!” Having a basic schema that a dog is an animal with four legs and fur, Blake thinks all furry, four-legged creatures are dogs. When Blake’s mom tells him that the animal he sees is a sheep, not a dog, Blake must accommodate his schema for dogs to include more information based on his new experiences. Blake’s schema for dog was too broad, since not all furry, four-legged creatures are dogs. He now modifies his schema for dogs and forms a new one for sheep. Like Freud and Erikson, Piaget thought development unfolds in a series of stages approximately associated with age ranges. He proposed a theory of cognitive development that unfolds in four stages: sensorimotor, preoperational, concrete operational, and formal operational (Table). \| Age (years) \| Stage \| Description \| Developmental issues \| \|---\|---\|---\|---\| \| 0–2 \| Sensorimotor \| World experienced through senses and actions \| Object permanence Stranger anxiety \| \| 2–6 \| Preoperational \| Use words and images to represent things, but lack logical reasoning \| Pretend play Egocentrism Language development \| \| 7–11 \| Concrete operational \| Understand concrete events and analogies logically; perform arithmetical operations \| Conservation Mathematical transformations \| \| 12– \| Formal operational \| Formal operations Utilize abstract reasoning \| Abstract logic Moral reasoning \| The first stage is the sensorimotor stage, which lasts from birth to about 2 years old. During this stage, children learn about the world through their senses and motor behavior. Young children put objects in their mouths to see if the items are edible, and once they can grasp objects, they may shake or bang them to see if they make sounds. Between 5 and 8 months old, the child develops object permanence, which is the understanding that even if something is out of sight, it still exists (Bogartz, Shinskey, & Schilling, 2000). According to Piaget, young infants do not remember an object after it has been removed from sight. Piaget studied infants’ reactions when a toy was first shown to an infant and then hidden under a blanket. Infants who had already developed object permanence would reach for the hidden toy, indicating that they knew it still existed, whereas infants who had not developed object permanence would appear confused. Please take a few minutes to view this brief video demonstrating different children’s ability to understand object permanence. In Piaget’s view, around the same time children develop object permanence, they also begin to exhibit stranger anxiety, which is a fear of unfamiliar people. Babies may demonstrate this by crying and turning away from a stranger, by clinging to a caregiver, or by attempting to reach their arms toward familiar faces such as parents. Stranger anxiety results when a child is unable to assimilate the stranger into an existing schema; therefore, she can’t predict what her experience with that stranger will be like, which results in a fear response. Piaget’s second stage is the preoperational stage, which is from approximately 2 to 7 years old. In this stage, children can use symbols to represent words, images, and ideas, which is why children in this stage engage in pretend play. A child’s arms might become airplane wings as he zooms around the room, or a child with a stick might become a brave knight with a sword. Children also begin to use language in the preoperational stage, but they cannot understand adult logic or mentally manipulate information (the term operational refers to logical manipulation of information, so children at this stage are considered to be pre-operational). Children’s logic is based on their own personal knowledge of the world so far, rather than on conventional knowledge. For example, dad gave a slice of pizza to 10-year-old Keiko and another slice to her 3-year-old brother, Kenny. Kenny’s pizza slice was cut into five pieces, so Kenny told his sister that he got more pizza than she did. Children in this stage cannot perform mental operations because they have not developed an understanding of conservation, which is the idea that even if you change the appearance of something, it is still equal in size as long as nothing has been removed or added. This video shows a 4.5-year-old boy in the preoperational stage as he responds to Piaget’s conservation tasks. During this stage, we also expect children to display egocentrism, which means that the child is not able to take the perspective of others. A child at this stage thinks that everyone sees, thinks, and feels just as they do. Let’s look at Kenny and Keiko again. Keiko’s birthday is coming up, so their mom takes Kenny to the toy store to choose a present for his sister. He selects an Iron Man action figure for her, thinking that if he likes the toy, his sister will too. An egocentric child is not able to infer the perspective of other people and instead attributes his own perspective. Piaget developed the Three-Mountain Task to determine the level of egocentrism displayed by children. Children view a 3-dimensional mountain scene from one viewpoint, and are asked what another person at a different viewpoint would see in the same scene. Watch the Three-Mountain Task in action in this short video from the University of Minnesota and the Science Museum of Minnesota. Piaget’s third stage is the concrete operational stage, which occurs from about 7 to 11 years old. In this stage, children can think logically about real (concrete) events; they have a firm grasp on the use of numbers and start to employ memory strategies. They can perform mathematical operations and understand transformations, such as addition is the opposite of subtraction, and multiplication is the opposite of division. In this stage, children also master the concept of conservation: Even if something changes shape, its mass, volume, and number stay the same. For example, if you pour water from a tall, thin glass to a short, fat glass, you still have the same amount of water. Remember Keiko and Kenny and the pizza? How did Keiko know that Kenny was wrong when he said that he had more pizza? Children in the concrete operational stage also understand the principle of reversibility, which means that objects can be changed and then returned back to their original form or condition. Take, for example, water that you poured into the short, fat glass: You can pour water from the fat glass back to the thin glass and still have the same amount (minus a couple of drops). The fourth, and last, stage in Piaget’s theory is the formal operational stage, which is from about age 11 to adulthood. Whereas children in the concrete operational stage are able to think logically only about concrete events, children in the formal operational stage can also deal with abstract ideas and hypothetical situations. Children in this stage can use abstract thinking to problem solve, look at alternative solutions, and test these solutions. In adolescence, a renewed egocentrism occurs. For example, a 15-year-old with a very small pimple on her face might think it is huge and incredibly visible, under the mistaken impression that others must share her perceptions. Beyond Formal Operational Thought As with other major contributors of theories of development, several of Piaget’s ideas have come under criticism based on the results of further research. For example, several contemporary studies support a model of development that is more continuous than Piaget’s discrete stages (Courage & Howe, 2002; Siegler, 2005, 2006). Many others suggest that children reach cognitive milestones earlier than Piaget describes (Baillargeon, 2004; de Hevia & Spelke, 2010). According to Piaget, the highest level of cognitive development is formal operational thought, which develops between 11 and 20 years old. However, many developmental psychologists disagree with Piaget, suggesting a fifth stage of cognitive development, known as the postformal stage (Basseches, 1984; Commons & Bresette, 2006; Sinnott, 1998). In postformal thinking, decisions are made based on situations and circumstances, and logic is integrated with emotion as adults develop principles that depend on contexts. One way that we can see the difference between an adult in postformal thought and an adolescent in formal operations is in terms of how they handle emotionally charged issues. It seems that once we reach adulthood our problem solving abilities change: As we attempt to solve problems, we tend to think more deeply about many areas of our lives, such as relationships, work, and politics (Labouvie-Vief & Diehl, 1999). Because of this, postformal thinkers are able to draw on past experiences to help them solve new problems. Problem-solving strategies using postformal thought vary, depending on the situation. What does this mean? Adults can recognize, for example, that what seems to be an ideal solution to a problem at work involving a disagreement with a colleague may not be the best solution to a disagreement with a significant other. THEORY OF MORAL DEVELOPMENT A major task beginning in childhood and continuing into adolescence is discerning right from wrong. Psychologist Lawrence Kohlberg (1927–1987) extended upon the foundation that Piaget built regarding cognitive development. Kohlberg believed that moral development, like cognitive development, follows a series of stages. To develop this theory, Kohlberg posed moral dilemmas to people of all ages, and then he analyzed their answers to find evidence of their particular stage of moral development. Before reading about the stages, take a minute to consider how you would answer one of Kohlberg's best-known moral dilemmas, commonly known as the Heinz dilemma: In Europe, a woman was near death from a special kind of cancer. There was one drug that the doctors thought might save her. It was a form of radium that a druggist in the same town had recently discovered. The drug was expensive to make, but the druggist was charging ten times what the drug cost him to make. He paid $200 for the radium and charged $2,000 for a small dose of the drug. The sick woman's husband, Heinz, went to everyone he knew to borrow the money, but he could only get together about $1,000, which is half of what it cost. He told the druggist that his wife was dying and asked him to sell it cheaper or let him pay later. But the druggist said: “No, I discovered the drug and I'm going to make money from it.” So Heinz got desperate and broke into the man's store to steal the drug for his wife. Should the husband have done that? (Kohlberg, 1969, p. 379) How would you answer this dilemma? Kohlberg was not interested in whether you answer yes or no to the dilemma: Instead, he was interested in the reasoning behind your answer. After presenting people with this and various other moral dilemmas, Kohlberg reviewed people’s responses and placed them in different stages of moral reasoning (Figure). According to Kohlberg, an individual progresses from the capacity for pre-conventional morality (before age 9) to the capacity for conventional morality (early adolescence), and toward attaining post-conventional morality (once formal operational thought is attained), which only a few fully achieve. Kohlberg placed in the highest stage responses that reflected the reasoning that Heinz should steal the drug because his wife’s life is more important than the pharmacist making money. The value of a human life overrides the pharmacist’s greed. It is important to realize that even those people who have the most sophisticated, post-conventional reasons for some choices may make other choices for the simplest of pre-conventional reasons. Many psychologists agree with Kohlberg's theory of moral development but point out that moral reasoning is very different from moral behavior. Sometimes what we say we would do in a situation is not what we actually do in that situation. In other words, we might “talk the talk,” but not “walk the walk.” How does this theory apply to males and females? Kohlberg (1969) felt that more males than females move past stage four in their moral development. He went on to note that women seem to be deficient in their moral reasoning abilities. These ideas were not well received by Carol Gilligan, a research assistant of Kohlberg, who consequently developed her own ideas of moral development. In her groundbreaking book, In a Different Voice: Psychological Theory and Women’s Development, Gilligan (1982) criticized her former mentor’s theory because it was based only on upper class White men and boys. She argued that women are not deficient in their moral reasoning—she proposed that males and females reason differently. Girls and women focus more on staying connected and the importance of interpersonal relationships. Therefore, in the Heinz dilemma, many girls and women respond that Heinz should not steal the medicine. Their reasoning is that if he steals the medicine, is arrested, and is put in jail, then he and his wife will be separated, and she could die while he is still in prison. Summary There are many theories regarding how babies and children grow and develop into happy, healthy adults. Sigmund Freud suggested that we pass through a series of psychosexual stages in which our energy is focused on certain erogenous zones on the body. Eric Erikson modified Freud’s ideas and suggested a theory of psychosocial development. Erikson said that our social interactions and successful completion of social tasks shape our sense of self. Jean Piaget proposed a theory of cognitive development that explains how children think and reason as they move through various stages. Finally, Lawrence Kohlberg turned his attention to moral development. He said that we pass through three levels of moral thinking that build on our cognitive development. Review Questions The idea that even if something is out of sight, it still exists is called ________. - egocentrism - object permanence - conservation - reversibility Hint: B Which theorist proposed that moral thinking proceeds through a series of stages? - Sigmund Freud - Erik Erikson - John Watson - Lawrence Kohlberg Hint: D According to Erikson’s theory of psychosocial development, what is the main task of the adolescent? - developing autonomy - feeling competent - forming an identity - forming intimate relationships Hint: C Critical Thinking Questions What is the difference between assimilation and accommodation? Provide examples of each. Hint: Assimilation is when we take in information that is comparable to what we already know. Accommodation is when we change our schemata based on new information. An example of assimilation is a child’s schema of “dog” based on the family’s golden retriever being expanded to include two newly adopted golden retrievers. An example of accommodation is that same child’s schema of “dog” being adjusted to exclude other four-legged furry animals such as sheep and foxes. Why was Carol Gilligan critical of Kohlberg’s theory of moral development? Hint: Gilligan criticized Kohlberg because his theory was based on the responses of upper class White men and boys, arguing that it was biased against women. While Kohlberg concluded that women must be deficient in their moral reasoning abilities, Gilligan disagreed, suggesting that female moral reasoning is not deficient, just different. What is egocentrism? Provide an original example. Hint: Egocentrism is the inability to take the perspective of another person. This type of thinking is common in young children in the preoperational stage of cognitive development. An example might be that upon seeing his mother crying, a young child gives her his favorite stuffed animal to make her feel better. Personal Application Questions Explain how you would use your understanding of one of the major developmental theories to deal with each of the difficulties listed below: - Your infant daughter puts everything in her mouth, including the dog's food. - Your eight-year-old son is failing math; all he cares about is baseball. - Your two-year-old daughter refuses to wear the clothes you pick for her every morning, which makes getting dressed a twenty-minute battle. - Your sixty-eight-year-old neighbor is chronically depressed and feels she has wasted her life. - Your 18-year-old daughter has decided not to go to college. Instead she’s moving to Colorado to become a ski instructor. - Your 11-year-old son is the class bully.	oercommons	2025-03-18T00:36:10.637723	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15342/overview", "title": "Psychology, Lifespan Development", "author": null }
https://oercommons.org/courseware/lesson/15343/overview	Stages of Development Overview By the end of this section, you will be able to: - Describe the stages of prenatal development and recognize the importance of prenatal care - Discuss physical, cognitive, and emotional development that occurs from infancy through childhood - Discuss physical, cognitive, and emotional development that occurs during adolescence - Discuss physical, cognitive, and emotional development that occurs in adulthood From the moment we are born until the moment we die, we continue to develop. As discussed at the beginning of this chapter, developmental psychologists often divide our development into three areas: physical development, cognitive development, and psychosocial development. Mirroring Erikson’s stages, lifespan development is divided into different stages that are based on age. We will discuss prenatal, infant, child, adolescent, and adult development. PRENATAL DEVELOPMENT How did you come to be who you are? From beginning as a one-cell structure to your birth, your prenatal development occurred in an orderly and delicate sequence. There are three stages of prenatal development: germinal, embryonic, and fetal. Let’s take a look at what happens to the developing baby in each of these stages. Germinal Stage (Weeks 1–2) In the discussion of biopsychology earlier in the book, you learned about genetics and DNA. A mother and father’s DNA is passed on to the child at the moment of conception. Conception occurs when sperm fertilizes an egg and forms a zygote (Figure). A zygote begins as a one-cell structure that is created when a sperm and egg merge. The genetic makeup and sex of the baby are set at this point. During the first week after conception, the zygote divides and multiplies, going from a one-cell structure to two cells, then four cells, then eight cells, and so on. This process of cell division is called mitosis. Mitosis is a fragile process, and fewer than one-half of all zygotes survive beyond the first two weeks (Hall, 2004). After 5 days of mitosis there are 100 cells, and after 9 months there are billions of cells. As the cells divide, they become more specialized, forming different organs and body parts. In the germinal stage, the mass of cells has yet to attach itself to the lining of the mother’s uterus. Once it does, the next stage begins. Embryonic Stage (Weeks 3–8) After the zygote divides for about 7–10 days and has 150 cells, it travels down the fallopian tubes and implants itself in the lining of the uterus. Upon implantation, this multi-cellular organism is called an embryo. Now blood vessels grow, forming the placenta. The placenta is a structure connected to the uterus that provides nourishment and oxygen from the mother to the developing embryo via the umbilical cord. Basic structures of the embryo start to develop into areas that will become the head, chest, and abdomen. During the embryonic stage, the heart begins to beat and organs form and begin to function. The neural tube forms along the back of the embryo, developing into the spinal cord and brain. Fetal Stage (Weeks 9–40) When the organism is about nine weeks old, the embryo is called a fetus. At this stage, the fetus is about the size of a kidney bean and begins to take on the recognizable form of a human being as the “tail” begins to disappear. From 9–12 weeks, the sex organs begin to differentiate. At about 16 weeks, the fetus is approximately 4.5 inches long. Fingers and toes are fully developed, and fingerprints are visible. By the time the fetus reaches the sixth month of development (24 weeks), it weighs up to 1.4 pounds. Hearing has developed, so the fetus can respond to sounds. The internal organs, such as the lungs, heart, stomach, and intestines, have formed enough that a fetus born prematurely at this point has a chance to survive outside of the mother’s womb. Throughout the fetal stage the brain continues to grow and develop, nearly doubling in size from weeks 16 to 28. Around 36 weeks, the fetus is almost ready for birth. It weighs about 6 pounds and is about 18.5 inches long, and by week 37 all of the fetus’s organ systems are developed enough that it could survive outside the mother’s uterus without many of the risks associated with premature birth. The fetus continues to gain weight and grow in length until approximately 40 weeks. By then, the fetus has very little room to move around and birth becomes imminent. The progression through the stages is shown in Figure. For an amazing look at prenatal development and the process of birth, view the video Life’s Greatest Miracle from Nova and PBS. Prenatal Influences During each prenatal stage, genetic and environmental factors can affect development. The developing fetus is completely dependent on the mother for life. It is important that the mother takes good care of herself and receives prenatal care, which is medical care during pregnancy that monitors the health of both the mother and the fetus (Figure). According to the National Institutes of Health ([NIH], 2013), routine prenatal care is important because it can reduce the risk of complications to the mother and fetus during pregnancy. In fact, women who are trying to become pregnant or who may become pregnant should discuss pregnancy planning with their doctor. They may be advised, for example, to take a vitamin containing folic acid, which helps prevent certain birth defects, or to monitor aspects of their diet or exercise routines. Recall that when the zygote attaches to the wall of the mother’s uterus, the placenta is formed. The placenta provides nourishment and oxygen to the fetus. Most everything the mother ingests, including food, liquid, and even medication, travels through the placenta to the fetus, hence the common phrase “eating for two.” Anything the mother is exposed to in the environment affects the fetus; if the mother is exposed to something harmful, the child can show life-long effects. A teratogen is any environmental agent—biological, chemical, or physical—that causes damage to the developing embryo or fetus. There are different types of teratogens. Alcohol and most drugs cross the placenta and affect the fetus. Alcohol is not safe to drink in any amount during pregnancy. Alcohol use during pregnancy has been found to be the leading preventable cause of mental retardation in children in the United States (Maier & West, 2001). Excessive maternal drinking while pregnant can cause fetal alcohol spectrum disorders with life-long consequences for the child ranging in severity from minor to major (Table). Fetal alcohol spectrum disorders (FASD) are a collection of birth defects associated with heavy consumption of alcohol during pregnancy. Physically, children with FASD may have a small head size and abnormal facial features. Cognitively, these children may have poor judgment, poor impulse control, higher rates of ADHD, learning issues, and lower IQ scores. These developmental problems and delays persist into adulthood (Streissguth et al., 2004). Based on studies conducted on animals, it also has been suggested that a mother’s alcohol consumption during pregnancy may predispose her child to like alcohol (Youngentob et al., 2007). \| Facial Feature \| Potential Effect of Fetal Alcohol Syndrome \| \|---\|---\| \| Head size \| Below-average head circumference \| \| Eyes \| Smaller than average eye opening, skin folds at corners of eyes \| \| Nose \| Low nasal bridge, short nose \| \| Midface \| Smaller than average midface size \| \| Lip and philtrum \| Thin upper lip, indistinct philtrum \| Smoking is also considered a teratogen because nicotine travels through the placenta to the fetus. When the mother smokes, the developing baby experiences a reduction in blood oxygen levels. According to the Centers for Disease Control and Prevention (2013), smoking while pregnant can result in premature birth, low-birth-weight infants, stillbirth, and sudden infant death syndrome (SIDS). Heroin, cocaine, methamphetamine, almost all prescription medicines, and most over-the counter medications are also considered teratogens. Babies born with a heroin addiction need heroin just like an adult addict. The child will need to be gradually weaned from the heroin under medical supervision; otherwise, the child could have seizures and die. Other teratogens include radiation, viruses such as HIV and herpes, and rubella (German measles). Women in the United States are much less likely to be afflicted with rubella because most women received childhood immunizations or vaccinations that protect the body from disease. Each organ of the fetus develops during a specific period in the pregnancy, called the critical or sensitive period (Figure). For example, research with primate models of FASD has demonstrated that the time during which a developing fetus is exposed to alcohol can dramatically affect the appearance of facial characteristics associated with fetal alcohol syndrome. Specifically, this research suggests that alcohol exposure that is limited to day 19 or 20 of gestation can lead to significant facial abnormalities in the offspring (Ashley, Magnuson, Omnell, & Clarren, 1999). Given regions of the brain also show sensitive periods during which they are most susceptible to the teratogenic effects of alcohol (Tran & Kelly, 2003). Should Women Who Use Drugs During Pregnancy Be Arrested and Jailed? As you now know, women who use drugs or alcohol during pregnancy can cause serious lifelong harm to their child. Some people have advocated mandatory screenings for women who are pregnant and have a history of drug abuse, and if the women continue using, to arrest, prosecute, and incarcerate them (Figdor & Kaeser, 1998). This policy was tried in Charleston, South Carolina, as recently as 20 years ago. The policy was called the Interagency Policy on Management of Substance Abuse During Pregnancy, and had disastrous results. The Interagency Policy applied to patients attending the obstetrics clinic at MUSC, which primarily serves patients who are indigent or on Medicaid. It did not apply to private obstetrical patients. The policy required patient education about the harmful effects of substance abuse during pregnancy. . . . [A] statement also warned patients that protection of unborn and newborn children from the harms of illegal drug abuse could involve the Charleston police, the Solicitor of the Ninth Judicial Court, and the Protective Services Division of the Department of Social Services (DSS). (Jos, Marshall, & Perlmutter, 1995, pp. 120–121) This policy seemed to deter women from seeking prenatal care, deterred them from seeking other social services, and was applied solely to low-income women, resulting in lawsuits. The program was canceled after 5 years, during which 42 women were arrested. A federal agency later determined that the program involved human experimentation without the approval and oversight of an institutional review board (IRB). What were the flaws in the program and how would you correct them? What are the ethical implications of charging pregnant women with child abuse? INFANCY THROUGH CHILDHOOD The average newborn weighs approximately 7.5 pounds. Although small, a newborn is not completely helpless because his reflexes and sensory capacities help him interact with the environment from the moment of birth. All healthy babies are born with newborn reflexes: inborn automatic responses to particular forms of stimulation. Reflexes help the newborn survive until it is capable of more complex behaviors—these reflexes are crucial to survival. They are present in babies whose brains are developing normally and usually disappear around 4–5 months old. Let’s take a look at some of these newborn reflexes. The rooting reflex is the newborn’s response to anything that touches her cheek: When you stroke a baby’s cheek, she naturally turns her head in that direction and begins to suck. The sucking reflex is the automatic, unlearned, sucking motions that infants do with their mouths. Several other interesting newborn reflexes can be observed. For instance, if you put your finger into a newborn’s hand, you will witness the grasping reflex, in which a baby automatically grasps anything that touches his palms. The Moro reflex is the newborn’s response when she feels like she is falling. The baby spreads her arms, pulls them back in, and then (usually) cries. How do you think these reflexes promote survival in the first months of life? Take a few minutes to view this brief video clip illustrating several newborn reflexes. What can young infants see, hear, and smell? Newborn infants’ sensory abilities are significant, but their senses are not yet fully developed. Many of a newborn’s innate preferences facilitate interaction with caregivers and other humans. Although vision is their least developed sense, newborns already show a preference for faces. Babies who are just a few days old also prefer human voices, they will listen to voices longer than sounds that do not involve speech (Vouloumanos & Werker, 2004), and they seem to prefer their mother’s voice over a stranger’s voice (Mills & Melhuish, 1974). In an interesting experiment, 3-week-old babies were given pacifiers that played a recording of the infant’s mother’s voice and of a stranger’s voice. When the infants heard their mother’s voice, they sucked more strongly at the pacifier (Mills & Melhuish, 1974). Newborns also have a strong sense of smell. For instance, newborn babies can distinguish the smell of their own mother from that of others. In a study by MacFarlane (1978), 1-week-old babies who were being breastfed were placed between two gauze pads. One gauze pad was from the bra of a nursing mother who was a stranger, and the other gauze pad was from the bra of the infant’s own mother. More than two-thirds of the week-old babies turned toward the gauze pad with their mother’s scent. Physical Development In infancy, toddlerhood, and early childhood, the body’s physical development is rapid (Figure). On average, newborns weigh between 5 and 10 pounds, and a newborn’s weight typically doubles in six months and triples in one year. By 2 years old the weight will have quadrupled, so we can expect that a 2 year old should weigh between 20 and 40 pounds. The average length of a newborn is 19.5 inches, increasing to 29.5 inches by 12 months and 34.4 inches by 2 years old (WHO Multicentre Growth Reference Study Group, 2006). During infancy and childhood, growth does not occur at a steady rate (Carel, Lahlou, Roger, & Chaussain, 2004). Growth slows between 4 and 6 years old: During this time children gain 5–7 pounds and grow about 2–3 inches per year. Once girls reach 8–9 years old, their growth rate outpaces that of boys due to a pubertal growth spurt. This growth spurt continues until around 12 years old, coinciding with the start of the menstrual cycle. By 10 years old, the average girl weighs 88 pounds, and the average boy weighs 85 pounds. We are born with all of the brain cells that we will ever have—about 100–200 billion neurons (nerve cells) whose function is to store and transmit information (Huttenlocher & Dabholkar, 1997). However, the nervous system continues to grow and develop. Each neural pathway forms thousands of new connections during infancy and toddlerhood. This period of rapid neural growth is called blooming. Neural pathways continue to develop through puberty. The blooming period of neural growth is then followed by a period of pruning, where neural connections are reduced. It is thought that pruning causes the brain to function more efficiently, allowing for mastery of more complex skills (Hutchinson, 2011). Blooming occurs during the first few years of life, and pruning continues through childhood and into adolescence in various areas of the brain. The size of our brains increases rapidly. For example, the brain of a 2-year-old is 55% of its adult size, and by 6 years old the brain is about 90% of its adult size (Tanner, 1978). During early childhood (ages 3–6), the frontal lobes grow rapidly. Recalling our discussion of the 4 lobes of the brain earlier in this book, the frontal lobes are associated with planning, reasoning, memory, and impulse control. Therefore, by the time children reach school age, they are developmentally capable of controlling their attention and behavior. Through the elementary school years, the frontal, temporal, occipital, and parietal lobes all grow in size. The brain growth spurts experienced in childhood tend to follow Piaget’s sequence of cognitive development, so that significant changes in neural functioning account for cognitive advances (Kolb & Whishaw, 2009; Overman, Bachevalier, Turner, & Peuster, 1992). Motor development occurs in an orderly sequence as infants move from reflexive reactions (e.g., sucking and rooting) to more advanced motor functioning. For instance, babies first learn to hold their heads up, then to sit with assistance, and then to sit unassisted, followed later by crawling and then walking. Motor skills refer to our ability to move our bodies and manipulate objects. Fine motor skills focus on the muscles in our fingers, toes, and eyes, and enable coordination of small actions (e.g., grasping a toy, writing with a pencil, and using a spoon). Gross motor skills focus on large muscle groups that control our arms and legs and involve larger movements (e.g., balancing, running, and jumping). As motor skills develop, there are certain developmental milestones that young children should achieve (Table). For each milestone there is an average age, as well as a range of ages in which the milestone should be reached. An example of a developmental milestone is sitting. On average, most babies sit alone at 7 months old. Sitting involves both coordination and muscle strength, and 90% of babies achieve this milestone between 5 and 9 months old. In another example, babies on average are able to hold up their head at 6 weeks old, and 90% of babies achieve this between 3 weeks and 4 months old. If a baby is not holding up his head by 4 months old, he is showing a delay. If the child is displaying delays on several milestones, that is reason for concern, and the parent or caregiver should discuss this with the child’s pediatrician. Some developmental delays can be identified and addressed through early intervention. \| Age (years) \| Physical \| Personal/Social \| Language \| Cognitive \| \|---\|---\|---\|---\|---\| \| 2 \| Kicks a ball; walks up and down stairs \| Plays alongside other children; copies adults \| Points to objects when named; puts 2–4 words together in a sentence \| Sorts shapes and colors; follows 2-step instructions \| \| 3 \| Climbs and runs; pedals tricycle \| Takes turns; expresses many emotions; dresses self \| Names familiar things; uses pronouns \| Plays make believe; works toys with parts (levers, handles) \| \| 4 \| Catches balls; uses scissors \| Prefers social play to solo play; knows likes and interests \| Knows songs and rhymes by memory \| Names colors and numbers; begins writing letters \| \| 5 \| Hops and swings; uses fork and spoon \| Distinguishes real from pretend; likes to please friends \| Speaks clearly; uses full sentences \| Counts to 10 or higher; prints some letters and copies basic shapes \| Cognitive Development In addition to rapid physical growth, young children also exhibit significant development of their cognitive abilities. Piaget thought that children’s ability to understand objects—such as learning that a rattle makes a noise when shaken—was a cognitive skill that develops slowly as a child matures and interacts with the environment. Today, developmental psychologists think Piaget was incorrect. Researchers have found that even very young children understand objects and how they work long before they have experience with those objects (Baillargeon, 1987; Baillargeon, Li, Gertner, & Wu, 2011). For example, children as young as 3 months old demonstrated knowledge of the properties of objects that they had only viewed and did not have prior experience with them. In one study, 3-month-old infants were shown a truck rolling down a track and behind a screen. The box, which appeared solid but was actually hollow, was placed next to the track. The truck rolled past the box as would be expected. Then the box was placed on the track to block the path of the truck. When the truck was rolled down the track this time, it continued unimpeded. The infants spent significantly more time looking at this impossible event (Figure). Baillargeon (1987) concluded that they knew solid objects cannot pass through each other. Baillargeon’s findings suggest that very young children have an understanding of objects and how they work, which Piaget (1954) would have said is beyond their cognitive abilities due to their limited experiences in the world. Just as there are physical milestones that we expect children to reach, there are also cognitive milestones. It is helpful to be aware of these milestones as children gain new abilities to think, problem solve, and communicate. For example, infants shake their head “no” around 6–9 months, and they respond to verbal requests to do things like “wave bye-bye” or “blow a kiss” around 9–12 months. Remember Piaget’s ideas about object permanence? We can expect children to grasp the concept that objects continue to exist even when they are not in sight by around 8 months old. Because toddlers (i.e., 12–24 months old) have mastered object permanence, they enjoy games like hide and seek, and they realize that when someone leaves the room they will come back (Loop, 2013). Toddlers also point to pictures in books and look in appropriate places when you ask them to find objects. Preschool-age children (i.e., 3–5 years old) also make steady progress in cognitive development. Not only can they count, name colors, and tell you their name and age, but they can also make some decisions on their own, such as choosing an outfit to wear. Preschool-age children understand basic time concepts and sequencing (e.g., before and after), and they can predict what will happen next in a story. They also begin to enjoy the use of humor in stories. Because they can think symbolically, they enjoy pretend play and inventing elaborate characters and scenarios. One of the most common examples of their cognitive growth is their blossoming curiosity. Preschool-age children love to ask “Why?” An important cognitive change occurs in children this age. Recall that Piaget described 2–3 year olds as egocentric, meaning that they do not have an awareness of others’ points of view. Between 3 and 5 years old, children come to understand that people have thoughts, feelings, and beliefs that are different from their own. This is known as theory-of-mind (TOM). Children can use this skill to tease others, persuade their parents to purchase a candy bar, or understand why a sibling might be angry. When children develop TOM, they can recognize that others have false beliefs (Dennett, 1987; Callaghan et al., 2005). False-belief tasks are useful in determining a child’s acquisition of theory-of-mind (TOM). Take a look at this video clip showing a false-belief task involving a box of crayons. Cognitive skills continue to expand in middle and late childhood (6–11 years old). Thought processes become more logical and organized when dealing with concrete information (Figure). Children at this age understand concepts such as the past, present, and future, giving them the ability to plan and work toward goals. Additionally, they can process complex ideas such as addition and subtraction and cause-and-effect relationships. However, children’s attention spans tend to be very limited until they are around 11 years old. After that point, it begins to improve through adulthood. One well-researched aspect of cognitive development is language acquisition. As mentioned earlier, the order in which children learn language structures is consistent across children and cultures (Hatch, 1983). You’ve also learned that some psychological researchers have proposed that children possess a biological predisposition for language acquisition. Starting before birth, babies begin to develop language and communication skills. At birth, babies apparently recognize their mother’s voice and can discriminate between the language(s) spoken by their mothers and foreign languages, and they show preferences for faces that are moving in synchrony with audible language (Blossom & Morgan, 2006; Pickens, 1994; Spelke & Cortelyou, 1981). Children communicate information through gesturing long before they speak, and there is some evidence that gesture usage predicts subsequent language development (Iverson & Goldin-Meadow, 2005). In terms of producing spoken language, babies begin to coo almost immediately. Cooing is a one-syllable combination of a consonant and a vowel sound (e.g., coo or ba). Interestingly, babies replicate sounds from their own languages. A baby whose parents speak French will coo in a different tone than a baby whose parents speak Spanish or Urdu. After cooing, the baby starts to babble. Babbling begins with repeating a syllable, such as ma-ma, da-da, or ba-ba. When a baby is about 12 months old, we expect her to say her first word for meaning, and to start combining words for meaning at about 18 months. At about 2 years old, a toddler uses between 50 and 200 words; by 3 years old they have a vocabulary of up to 1,000 words and can speak in sentences. During the early childhood years, children's vocabulary increases at a rapid pace. This is sometimes referred to as the “vocabulary spurt” and has been claimed to involve an expansion in vocabulary at a rate of 10–20 new words per week. Recent research may indicate that while some children experience these spurts, it is far from universal (as discussed in Ganger & Brent, 2004). It has been estimated that, 5 year olds understand about 6,000 words, speak 2,000 words, and can define words and question their meanings. They can rhyme and name the days of the week. Seven year olds speak fluently and use slang and clichés (Stork & Widdowson, 1974). What accounts for such dramatic language learning by children? Behaviorist B. F. Skinner thought that we learn language in response to reinforcement or feedback, such as through parental approval or through being understood. For example, when a two-year-old child asks for juice, he might say, “me juice,” to which his mother might respond by giving him a cup of apple juice. Noam Chomsky (1957) criticized Skinner’s theory and proposed that we are all born with an innate capacity to learn language. Chomsky called this mechanism a language acquisition device (LAD). Who is correct? Both Chomsky and Skinner are right. Remember that we are a product of both nature and nurture. Researchers now believe that language acquisition is partially inborn and partially learned through our interactions with our linguistic environment (Gleitman & Newport, 1995; Stork & Widdowson, 1974). Attachment Psychosocial development occurs as children form relationships, interact with others, and understand and manage their feelings. In social and emotional development, forming healthy attachments is very important and is the major social milestone of infancy. Attachment is a long-standing connection or bond with others. Developmental psychologists are interested in how infants reach this milestone. They ask such questions as: How do parent and infant attachment bonds form? How does neglect affect these bonds? What accounts for children’s attachment differences? Researchers Harry Harlow, John Bowlby, and Mary Ainsworth conducted studies designed to answer these questions. In the 1950s, Harlow conducted a series of experiments on monkeys. He separated newborn monkeys from their mothers. Each monkey was presented with two surrogate mothers. One surrogate monkey was made out of wire mesh, and she could dispense milk. The other monkey was softer and made from cloth: This monkey did not dispense milk. Research shows that the monkeys preferred the soft, cuddly cloth monkey, even though she did not provide any nourishment. The baby monkeys spent their time clinging to the cloth monkey and only went to the wire monkey when they needed to be fed. Prior to this study, the medical and scientific communities generally thought that babies become attached to the people who provide their nourishment. However, Harlow (1958) concluded that there was more to the mother-child bond than nourishment. Feelings of comfort and security are the critical components to maternal-infant bonding, which leads to healthy psychosocial development. Harlow’s studies of monkeys were performed before modern ethics guidelines were in place, and today his experiments are widely considered to be unethical and even cruel. Watch this video to see actual footage of Harlow’s monkey studies. Building on the work of Harlow and others, John Bowlby developed the concept of attachment theory. He defined attachment as the affectional bond or tie that an infant forms with the mother (Bowlby, 1969). An infant must form this bond with a primary caregiver in order to have normal social and emotional development. In addition, Bowlby proposed that this attachment bond is very powerful and continues throughout life. He used the concept of secure base to define a healthy attachment between parent and child (1988). A secure base is a parental presence that gives the child a sense of safety as he explores his surroundings. Bowlby said that two things are needed for a healthy attachment: The caregiver must be responsive to the child’s physical, social, and emotional needs; and the caregiver and child must engage in mutually enjoyable interactions (Bowlby, 1969) (Figure). While Bowlby thought attachment was an all-or-nothing process, Mary Ainsworth’s (1970) research showed otherwise. Ainsworth wanted to know if children differ in the ways they bond, and if so, why. To find the answers, she used the Strange Situation procedure to study attachment between mothers and their infants (1970). In the Strange Situation, the mother (or primary caregiver) and the infant (age 12-18 months) are placed in a room together. There are toys in the room, and the caregiver and child spend some time alone in the room. After the child has had time to explore her surroundings, a stranger enters the room. The mother then leaves her baby with the stranger. After a few minutes, she returns to comfort her child. Based on how the infants/toddlers responded to the separation and reunion, Ainsworth identified three types of parent-child attachments: secure, avoidant, and resistant (Ainsworth & Bell, 1970). A fourth style, known as disorganized attachment, was later described (Main & Solomon, 1990). The most common type of attachment—also considered the healthiest—is called secure attachment (Figure). In this type of attachment, the toddler prefers his parent over a stranger. The attachment figure is used as a secure base to explore the environment and is sought out in times of stress. Securely attached children were distressed when their caregivers left the room in the Strange Situation experiment, but when their caregivers returned, the securely attached children were happy to see them. Securely attached children have caregivers who are sensitive and responsive to their needs. With avoidant attachment, the child is unresponsive to the parent, does not use the parent as a secure base, and does not care if the parent leaves. The toddler reacts to the parent the same way she reacts to a stranger. When the parent does return, the child is slow to show a positive reaction. Ainsworth theorized that these children were most likely to have a caregiver who was insensitive and inattentive to their needs (Ainsworth, Blehar, Waters, & Wall, 1978). In cases of resistant attachment, children tend to show clingy behavior, but then they reject the attachment figure’s attempts to interact with them (Ainsworth & Bell, 1970). These children do not explore the toys in the room, as they are too fearful. During separation in the Strange Situation, they became extremely disturbed and angry with the parent. When the parent returns, the children are difficult to comfort. Resistant attachment is the result of the caregivers’ inconsistent level of response to their child. Finally, children with disorganized attachment behaved oddly in the Strange Situation. They freeze, run around the room in an erratic manner, or try to run away when the caregiver returns (Main & Solomon, 1990). This type of attachment is seen most often in kids who have been abused. Research has shown that abuse disrupts a child’s ability to regulate their emotions. While Ainsworth’s research has found support in subsequent studies, it has also met criticism. Some researchers have pointed out that a child’s temperament may have a strong influence on attachment (Gervai, 2009; Harris, 2009), and others have noted that attachment varies from culture to culture, a factor not accounted for in Ainsworth’s research (Rothbaum, Weisz, Pott, Miyake, & Morelli, 2000; van Ijzendoorn & Sagi-Schwartz, 2008). Watch this video to view a clip of the Strange Situation. Try to identify which type of attachment baby Lisa exhibits. Self-Concept Just as attachment is the main psychosocial milestone of infancy, the primary psychosocial milestone of childhood is the development of a positive sense of self. How does self-awareness develop? Infants don’t have a self-concept, which is an understanding of who they are. If you place a baby in front of a mirror, she will reach out to touch her image, thinking it is another baby. However, by about 18 months a toddler will recognize that the person in the mirror is herself. How do we know this? In a well-known experiment, a researcher placed a red dot of paint on children’s noses before putting them in front of a mirror (Amsterdam, 1972). Commonly known as the mirror test, this behavior is demonstrated by humans and a few other species and is considered evidence of self-recognition (Archer, 1992). At 18 months old they would touch their own noses when they saw the paint, surprised to see a spot on their faces. By 24–36 months old children can name and/or point to themselves in pictures, clearly indicating self-recognition. Children from 2–4 years old display a great increase in social behavior once they have established a self-concept. They enjoy playing with other children, but they have difficulty sharing their possessions. Also, through play children explore and come to understand their gender roles and can label themselves as a girl or boy (Chick, Heilman-Houser, & Hunter, 2002). By 4 years old, children can cooperate with other children, share when asked, and separate from parents with little anxiety. Children at this age also exhibit autonomy, initiate tasks, and carry out plans. Success in these areas contributes to a positive sense of self. Once children reach 6 years old, they can identify themselves in terms of group memberships: “I’m a first grader!” School-age children compare themselves to their peers and discover that they are competent in some areas and less so in others (recall Erikson’s task of industry versus inferiority). At this age, children recognize their own personality traits as well as some other traits they would like to have. For example, 10-year-old Layla says, “I’m kind of shy. I wish I could be more talkative like my friend Alexa.” Development of a positive self-concept is important to healthy development. Children with a positive self-concept tend to be more confident, do better in school, act more independently, and are more willing to try new activities (Maccoby, 1980; Ferrer & Fugate, 2003). Formation of a positive self-concept begins in Erikson’s toddlerhood stage, when children establish autonomy and become confident in their abilities. Development of self-concept continues in elementary school, when children compare themselves to others. When the comparison is favorable, children feel a sense of competence and are motivated to work harder and accomplish more. Self-concept is re-evaluated in Erikson’s adolescence stage, as teens form an identity. They internalize the messages they have received regarding their strengths and weaknesses, keeping some messages and rejecting others. Adolescents who have achieved identity formation are capable of contributing positively to society (Erikson, 1968). What can parents do to nurture a healthy self-concept? Diana Baumrind (1971, 1991) thinks parenting style may be a factor. The way we parent is an important factor in a child’s socioemotional growth. Baumrind developed and refined a theory describing four parenting styles: authoritative, authoritarian, permissive, and uninvolved. With the authoritative style, the parent gives reasonable demands and consistent limits, expresses warmth and affection, and listens to the child’s point of view. Parents set rules and explain the reasons behind them. They are also flexible and willing to make exceptions to the rules in certain cases—for example, temporarily relaxing bedtime rules to allow for a nighttime swim during a family vacation. Of the four parenting styles, the authoritative style is the one that is most encouraged in modern American society. American children raised by authoritative parents tend to have high self-esteem and social skills. However, effective parenting styles vary as a function of culture and, as Small (1999) points out, the authoritative style is not necessarily preferred or appropriate in all cultures. In authoritarian style, the parent places high value on conformity and obedience. The parents are often strict, tightly monitor their children, and express little warmth. In contrast to the authoritative style, authoritarian parents probably would not relax bedtime rules during a vacation because they consider the rules to be set, and they expect obedience. This style can create anxious, withdrawn, and unhappy kids. However, it is important to point out that authoritarian parenting is as beneficial as the authoritative style in some ethnic groups (Russell, Crockett, & Chao, 2010). For instance, first-generation Chinese American children raised by authoritarian parents did just as well in school as their peers who were raised by authoritative parents (Russell et al., 2010). For parents who employ the permissive style of parenting, the kids run the show and anything goes. Permissive parents make few demands and rarely use punishment. They tend to be very nurturing and loving, and may play the role of friend rather than parent. In terms of our example of vacation bedtimes, permissive parents might not have bedtime rules at all—instead they allow the child to choose his bedtime whether on vacation or not. Not surprisingly, children raised by permissive parents tend to lack self-discipline, and the permissive parenting style is negatively associated with grades (Dornbusch, Ritter, Leiderman, Roberts, & Fraleigh, 1987). The permissive style may also contribute to other risky behaviors such as alcohol abuse (Bahr & Hoffman, 2010), risky sexual behavior especially among female children (Donenberg, Wilson, Emerson, & Bryant, 2002), and increased display of disruptive behaviors by male children (Parent et al., 2011). However, there are some positive outcomes associated with children raised by permissive parents. They tend to have higher self-esteem, better social skills, and report lower levels of depression (Darling, 1999). With the uninvolved style of parenting, the parents are indifferent, uninvolved, and sometimes referred to as neglectful. They don’t respond to the child’s needs and make relatively few demands. This could be because of severe depression or substance abuse, or other factors such as the parents’ extreme focus on work. These parents may provide for the child’s basic needs, but little else. The children raised in this parenting style are usually emotionally withdrawn, fearful, anxious, perform poorly in school, and are at an increased risk of substance abuse (Darling, 1999). As you can see, parenting styles influence childhood adjustment, but could a child’s temperament likewise influence parenting? Temperament refers to innate traits that influence how one thinks, behaves, and reacts with the environment. Children with easy temperaments demonstrate positive emotions, adapt well to change, and are capable of regulating their emotions. Conversely, children with difficult temperaments demonstrate negative emotions and have difficulty adapting to change and regulating their emotions. Difficult children are much more likely to challenge parents, teachers, and other caregivers (Thomas, 1984). Therefore, it’s possible that easy children (i.e., social, adaptable, and easy to soothe) tend to elicit warm and responsive parenting, while demanding, irritable, withdrawn children evoke irritation in their parents or cause their parents to withdraw (Sanson & Rothbart, 1995). The Importance of Play and Recess According to the American Academy of Pediatrics (2007), unstructured play is an integral part of a child’s development. It builds creativity, problem solving skills, and social relationships. Play also allows children to develop a theory-of-mind as they imaginatively take on the perspective of others. Outdoor play allows children the opportunity to directly experience and sense the world around them. While doing so, they may collect objects that they come across and develop lifelong interests and hobbies. They also benefit from increased exercise, and engaging in outdoor play can actually increase how much they enjoy physical activity. This helps support the development of a healthy heart and brain. Unfortunately, research suggests that today’s children are engaging in less and less outdoor play (Clements, 2004). Perhaps, it is no surprise to learn that lowered levels of physical activity in conjunction with easy access to calorie-dense foods with little nutritional value are contributing to alarming levels of childhood obesity (Karnik & Kanekar, 2012). Despite the adverse consequences associated with reduced play, some children are over scheduled and have little free time to engage in unstructured play. In addition, some schools have taken away recess time for children in a push for students to do better on standardized tests, and many schools commonly use loss of recess as a form of punishment. Do you agree with these practices? Why or why not? ADOLESCENCE Adolescence is a socially constructed concept. In pre-industrial society, children were considered adults when they reached physical maturity, but today we have an extended time between childhood and adulthood called adolescence. Adolescence is the period of development that begins at puberty and ends at emerging adulthood, which is discussed later. In the United States, adolescence is seen as a time to develop independence from parents while remaining connected to them (Figure). The typical age range of adolescence is from 12 to 18 years, and this stage of development also has some predictable physical, cognitive, and psychosocial milestones. Physical Development As noted above, adolescence begins with puberty. While the sequence of physical changes in puberty is predictable, the onset and pace of puberty vary widely. Several physical changes occur during puberty, such as adrenarche and gonadarche, the maturing of the adrenal glands and sex glands, respectively. Also during this time, primary and secondary sexual characteristics develop and mature. Primary sexual characteristics are organs specifically needed for reproduction, like the uterus and ovaries in females and testes in males. Secondary sexual characteristics are physical signs of sexual maturation that do not directly involve sex organs, such as development of breasts and hips in girls, and development of facial hair and a deepened voice in boys. Girls experience menarche, the beginning of menstrual periods, usually around 12–13 years old, and boys experience spermarche, the first ejaculation, around 13–14 years old. During puberty, both sexes experience a rapid increase in height (i.e., growth spurt). For girls this begins between 8 and 13 years old, with adult height reached between 10 and 16 years old. Boys begin their growth spurt slightly later, usually between 10 and 16 years old, and reach their adult height between 13 and 17 years old. Both nature (i.e., genes) and nurture (e.g., nutrition, medications, and medical conditions) can influence height. Because rates of physical development vary so widely among teenagers, puberty can be a source of pride or embarrassment. Early maturing boys tend to be stronger, taller, and more athletic than their later maturing peers. They are usually more popular, confident, and independent, but they are also at a greater risk for substance abuse and early sexual activity (Flannery, Rowe, & Gulley, 1993; Kaltiala-Heino, Rimpela, Rissanen, & Rantanen, 2001). Early maturing girls may be teased or overtly admired, which can cause them to feel self-conscious about their developing bodies. These girls are at a higher risk for depression, substance abuse, and eating disorders (Ge, Conger, & Elder, 2001; Graber, Lewinsohn, Seeley, & Brooks-Gunn, 1997; Striegel-Moore & Cachelin, 1999). Late blooming boys and girls (i.e., they develop more slowly than their peers) may feel self-conscious about their lack of physical development. Negative feelings are particularly a problem for late maturing boys, who are at a higher risk for depression and conflict with parents (Graber et al., 1997) and more likely to be bullied (Pollack & Shuster, 2000). The adolescent brain also remains under development. Up until puberty, brain cells continue to bloom in the frontal region. Adolescents engage in increased risk-taking behaviors and emotional outbursts possibly because the frontal lobes of their brains are still developing (Figure). Recall that this area is responsible for judgment, impulse control, and planning, and it is still maturing into early adulthood (Casey, Tottenham, Liston, & Durston, 2005). According to neuroscientist Jay Giedd in the Frontline video “Inside the Teenage Brain” (2013), “It’s sort of unfair to expect [teens] to have adult levels of organizational skills or decision-making before their brains are finished being built.” Watch this segment on “The Wiring of the Adolescent Brain” to find out more about the developing brain during adolescence. Cognitive Development More complex thinking abilities emerge during adolescence. Some researchers suggest this is due to increases in processing speed and efficiency rather than as the result of an increase in mental capacity—in other words, due to improvements in existing skills rather than development of new ones (Bjorkland, 1987; Case, 1985). During adolescence, teenagers move beyond concrete thinking and become capable of abstract thought. Recall that Piaget refers to this stage as formal operational thought. Teen thinking is also characterized by the ability to consider multiple points of view, imagine hypothetical situations, debate ideas and opinions (e.g., politics, religion, and justice), and form new ideas (Figure). In addition, it’s not uncommon for adolescents to question authority or challenge established societal norms. Cognitive empathy, also known as theory-of-mind (which we discussed earlier with regard to egocentrism), relates to the ability to take the perspective of others and feel concern for others (Shamay-Tsoory, Tomer, & Aharon-Peretz, 2005). Cognitive empathy begins to increase in adolescence and is an important component of social problem solving and conflict avoidance. According to one longitudinal study, levels of cognitive empathy begin rising in girls around 13 years old, and around 15 years old in boys (Van der Graaff et al., 2013). Teens who reported having supportive fathers with whom they could discuss their worries were found to be better able to take the perspective of others (Miklikowska, Duriez, & Soenens, 2011). Psychosocial Development Adolescents continue to refine their sense of self as they relate to others. Erikson referred to the task of the adolescent as one of identity versus role confusion. Thus, in Erikson’s view, an adolescent’s main questions are “Who am I?” and “Who do I want to be?” Some adolescents adopt the values and roles that their parents expect for them. Other teens develop identities that are in opposition to their parents but align with a peer group. This is common as peer relationships become a central focus in adolescents’ lives. As adolescents work to form their identities, they pull away from their parents, and the peer group becomes very important (Shanahan, McHale, Osgood, & Crouter, 2007). Despite spending less time with their parents, most teens report positive feelings toward them (Moore, Guzman, Hair, Lippman, & Garrett, 2004). Warm and healthy parent-child relationships have been associated with positive child outcomes, such as better grades and fewer school behavior problems, in the United States as well as in other countries (Hair et al., 2005). It appears that most teens don’t experience adolescent storm and stress to the degree once famously suggested by G. Stanley Hall, a pioneer in the study of adolescent development. Only small numbers of teens have major conflicts with their parents (Steinberg & Morris, 2001), and most disagreements are minor. For example, in a study of over 1,800 parents of adolescents from various cultural and ethnic groups, Barber (1994) found that conflicts occurred over day-to-day issues such as homework, money, curfews, clothing, chores, and friends. These types of arguments tend to decrease as teens develop (Galambos & Almeida, 1992). Emerging Adulthood The next stage of development is emerging adulthood. This is a relatively newly defined period of lifespan development spanning from 18 years old to the mid-20s, characterized as an in-between time where identity exploration is focused on work and love. When does a person become an adult? There are many ways to answer this question. In the United States, you are legally considered an adult at 18 years old. But other definitions of adulthood vary widely; in sociology, for example, a person may be considered an adult when she becomes self-supporting, chooses a career, gets married, or starts a family. The ages at which we achieve these milestones vary from person to person as well as from culture to culture. For example, in the African country of Malawi, 15-year-old Njemile was married at 14 years old and had her first child at 15 years old. In her culture she is considered an adult. Children in Malawi take on adult responsibilities such as marriage and work (e.g., carrying water, tending babies, and working fields) as early as 10 years old. In stark contrast, independence in Western cultures is taking longer and longer, effectively delaying the onset of adult life. Why is it taking twentysomethings so long to grow up? It seems that emerging adulthood is a product of both Western culture and our current times (Arnett, 2000). People in developed countries are living longer, allowing the freedom to take an extra decade to start a career and family. Changes in the workforce also play a role. For example, 50 years ago, a young adult with a high school diploma could immediately enter the work force and climb the corporate ladder. That is no longer the case. Bachelor’s and even graduate degrees are required more and more often—even for entry-level jobs (Arnett, 2000). In addition, many students are taking longer (five or six years) to complete a college degree as a result of working and going to school at the same time. After graduation, many young adults return to the family home because they have difficulty finding a job. Changing cultural expectations may be the most important reason for the delay in entering adult roles. Young people are spending more time exploring their options, so they are delaying marriage and work as they change majors and jobs multiple times, putting them on a much later timetable than their parents (Arnett, 2000). ADULTHOOD Adulthood begins around 20 years old and has three distinct stages: early, middle, and late. Each stage brings its own set of rewards and challenges. Physical Development By the time we reach early adulthood (20 to early 40s), our physical maturation is complete, although our height and weight may increase slightly. In young adulthood, our physical abilities are at their peak, including muscle strength, reaction time, sensory abilities, and cardiac functioning. Most professional athletes are at the top of their game during this stage. Many women have children in the young adulthood years, so they may see additional weight gain and breast changes. Middle adulthood extends from the 40s to the 60s (Figure). Physical decline is gradual. The skin loses some elasticity, and wrinkles are among the first signs of aging. Visual acuity decreases during this time. Women experience a gradual decline in fertility as they approach the onset of menopause, the end of the menstrual cycle, around 50 years old. Both men and women tend to gain weight: in the abdominal area for men and in the hips and thighs for women. Hair begins to thin and turn gray. Late adulthood is considered to extend from the 60s on. This is the last stage of physical change. The skin continues to lose elasticity, reaction time slows further, and muscle strength diminishes. Smell, taste, hearing, and vision, so sharp in our twenties, decline significantly. The brain may also no longer function at optimal levels, leading to problems like memory loss, dementia, and Alzheimer’s disease in later years. Aging doesn’t mean a person can’t explore new pursuits, learn new skills, and continue to grow. Watch this inspiring story about Neil Unger who is a newbie to the world of skateboarding at 60 years old. Cognitive Development Because we spend so many years in adulthood (more than any other stage), cognitive changes are numerous. In fact, research suggests that adult cognitive development is a complex, ever changing process that may be even more active than cognitive development in infancy and early childhood (Fischer, Yan, & Stewart, 2003). There is good news for the middle age brain. View this brief video to find out what it is. Unlike our physical abilities, which peak in our mid-20s and then begin a slow decline, our cognitive abilities remain steady throughout early and middle adulthood. Our crystalized intelligence (information, skills, and strategies we have gathered through a lifetime of experience) tends to hold steady as we age—it may even improve. For example, adults show relatively stable to increasing scores on intelligence tests until their mid-30s to mid-50s (Bayley & Oden, 1955). However, in late adulthood we begin to experience a decline in another area of our cognitive abilities—fluid intelligence (information processing abilities, reasoning, and memory). These processes become slower. How can we delay the onset of cognitive decline? Mental and physical activity seems to play a part (Figure). Research has found adults who engage in mentally and physically stimulating activities experience less cognitive decline and have a reduced incidence of mild cognitive impairment and dementia (Hertzog, Kramer, Wilson, & Lindenberger, 2009; Larson et al., 2006; Podewils et al., 2005). Psychosocial Development There are many theories about the social and emotional aspects of aging. Some aspects of healthy aging include activities, social connectedness, and the role of a person’s culture. According to many theorists, including George Vaillant (2002), who studied and analyzed over 50 years of data, we need to have and continue to find meaning throughout our lives. For those in early and middle adulthood, meaning is found through work (Sterns & Huyck, 2001) and family life (Markus, Ryff, Curan, & Palmersheim, 2004). These areas relate to the tasks that Erikson referred to as generativity and intimacy. As mentioned previously, adults tend to define themselves by what they do—their careers. Earnings peak during this time, yet job satisfaction is more closely tied to work that involves contact with other people, is interesting, provides opportunities for advancement, and allows some independence (Mohr & Zoghi, 2006) than it is to salary (Iyengar, Wells, & Schwartz, 2006). How might being unemployed or being in a dead-end job challenge adult well-being? Positive relationships with significant others in our adult years have been found to contribute to a state of well-being (Ryff & Singer, 2009). Most adults in the United States identify themselves through their relationships with family—particularly with spouses, children, and parents (Markus et al., 2004). While raising children can be stressful, especially when they are young, research suggests that parents reap the rewards down the road, as adult children tend to have a positive effect on parental well-being (Umberson, Pudrovska, & Reczek, 2010). Having a stable marriage has also been found to contribute to well-being throughout adulthood (Vaillant, 2002). Another aspect of positive aging is believed to be social connectedness and social support. As we get older, socioemotional selectivity theory suggests that our social support and friendships dwindle in number, but remain as close, if not more close than in our earlier years (Carstensen, 1992) (Figure). To learn more, view this video on aging in America. Summary At conception the egg and sperm cell are united to form a zygote, which will begin to divide rapidly. This marks the beginning of the first stage of prenatal development (germinal stage), which lasts about two weeks. Then the zygote implants itself into the lining of the woman’s uterus, marking the beginning of the second stage of prenatal development (embryonic stage), which lasts about six weeks. The embryo begins to develop body and organ structures, and the neural tube forms, which will later become the brain and spinal cord. The third phase of prenatal development (fetal stage) begins at 9 weeks and lasts until birth. The body, brain, and organs grow rapidly during this stage. During all stages of pregnancy it is important that the mother receive prenatal care to reduce health risks to herself and to her developing baby. Newborn infants weigh about 7.5 pounds. Doctors assess a newborn’s reflexes, such as the sucking, rooting, and Moro reflexes. Our physical, cognitive, and psychosocial skills grow and change as we move through developmental stages from infancy through late adulthood. Attachment in infancy is a critical component of healthy development. Parenting styles have been found to have an effect on childhood outcomes of well-being. The transition from adolescence to adulthood can be challenging due to the timing of puberty, and due to the extended amount of time spent in emerging adulthood. Although physical decline begins in middle adulthood, cognitive decline does not begin until later. Activities that keep the body and mind active can help maintain good physical and cognitive health as we age. Social supports through family and friends remain important as we age. Review Questions Which of the following is the correct order of prenatal development? - zygote, fetus, embryo - fetus, embryo zygote - fetus, zygote, embryo - zygote, embryo, fetus Hint: D The time during fetal growth when specific parts or organs develop is known as ________. - critical period - mitosis - conception - pregnancy Hint: A What begins as a single-cell structure that is created when a sperm and egg merge at conception? - embryo - fetus - zygote - infant Hint: C Using scissors to cut out paper shapes is an example of ________. - gross motor skills - fine motor skills - large motor skills - small motor skills Hint: B The child uses the parent as a base from which to explore her world in which attachment style? - secure - insecure avoidant - insecure ambivalent-resistant - disorganized Hint: A The frontal lobes become fully developed ________. - at birth - at the beginning of adolescence - at the end of adolescence - by 25 years old Hint: D Critical Thinking Questions What are some known teratogens, and what kind of damage can they do to the developing fetus? Hint: Alcohol is a teratogen. Excessive drinking can cause mental retardation in children. The child can also have a small head and abnormal facial features, which are characteristic of fetal alcohol syndrome (FAS). Another teratogen is nicotine. Smoking while pregnant can lead to low-birth weight, premature birth, stillbirth, and SIDS. What is prenatal care and why is it important? Hint: Prenatal care is medical care during pregnancy that monitors the health of both the mother and fetus. It’s important to receive prenatal care because it can reduce complications to the mother and fetus during pregnancy. Describe what happens in the embryonic stage of development. Describe what happens in the fetal stage of development. Hint: In the embryonic stage, basic structures of the embryo start to develop into areas that will become the head, chest, and abdomen. The heart begins to beat and organs form and begin to function. The neural tube forms along the back of the embryo, developing into the spinal cord and brain. In the fetal stage, the brain and body continue to develop. Fingers and toes develop along with hearing, and internal organs form. What makes a personal quality part of someone’s personality? Hint: The particular quality or trait must be part of an enduring behavior pattern, so that it is a consistent or predictable quality. Describe some of the newborn reflexes. How might they promote survival? Hint: The sucking reflex is the automatic, unlearned sucking motions that infants do with their mouths. It may help promote survival because this action helps the baby take in nourishment. The rooting reflex is the newborn’s response to anything that touches her cheek. When you stroke a baby’s cheek she will naturally turn her head that way and begin to suck. This may aid survival because it helps the newborn locate a source of food. Compare and contrast the four attachment styles and describe the kinds of childhood outcomes we can expect with each. Hint: With the authoritative style, children are given reasonable demands and consistent limits, warmth and affection are expressed, the parent listens to the child’s point of view, and the child initiates positive standards. Children raised by authoritative parents tend to have high self-esteem and social skills. Another parenting style is authoritarian: The parent places a high value on conformity and obedience. The parents are often strict, tightly monitor their children, and express little warmth. This style can create anxious, withdrawn, and unhappy kids. The third parenting style is permissive: Parents make few demands, rarely use punishment, and give their children free rein. Children raised by permissive parents tend to lack self-discipline, which contributes to poor grades and alcohol abuse. However, they have higher self-esteem, better social skills, and lower levels of depression. The fourth style is the uninvolved parent: They are indifferent, uninvolved, and sometimes called neglectful. The children raised in this parenting style are usually emotionally withdrawn, fearful, anxious, perform poorly in school, and are at an increased risk of substance abuse. What is emerging adulthood and what are some factors that have contributed to this new stage of development? Hint: Emerging adulthood is a relatively new period of lifespan development from 18 years old to the mid-20s, characterized as a transitional time in which identity exploration focuses on work and love. According to Arnett, changing cultural expectations facilitate the delay to full adulthood. People are spending more time exploring their options, so they are delaying marriage and work as they change majors and jobs multiple times, putting them on a much later timetable than their parents. Personal Application Questions Which parenting style describes how you were raised? Provide an example or two to support your answer. Would you describe your experience of puberty as one of pride or embarrassment? Why? Your best friend is a smoker who just found out she is pregnant. What would you tell her about smoking and pregnancy? Imagine you are a nurse working at a clinic that provides prenatal care for pregnant women. Your patient, Anna, has heard that it’s a good idea to play music for her unborn baby, and she wants to know when her baby’s hearing will develop. What will you tell her?	oercommons	2025-03-18T00:36:10.705688	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15343/overview", "title": "Psychology, Lifespan Development", "author": null }
https://oercommons.org/courseware/lesson/15344/overview	Death and Dying Overview By the end of this section, you will be able to: - Discuss hospice care - Describe the five stages of grief - Define living will and DNR Every story has an ending. Death marks the end of your life story (Figure). Our culture and individual backgrounds influence how we view death. In some cultures, death is accepted as a natural part of life and is embraced. In contrast, until about 50 years ago in the United States, a doctor might not inform someone that they were dying, and the majority of deaths occurred in hospitals. In 1967 that reality began to change with Cicely Saunders, who created the first modern hospice in England. The aim of hospice is to help provide a death with dignity and pain management in a humane and comfortable environment, which is usually outside of a hospital setting. In 1974, Florence Wald founded the first hospice in the United States. Today, hospice provides care for 1.65 million Americans and their families. Because of hospice care, many terminally ill people are able to spend their last days at home. Research has indicated that hospice care is beneficial for the patient (Brumley, Enquidanos, & Cherin, 2003; Brumley et al., 2007; Godkin, Krant, & Doster, 1984) and for the patient’s family (Rhodes, Mitchell, Miller, Connor, & Teno, 2008; Godkin et al., 1984). Hospice patients report high levels of satisfaction with hospice care because they are able to remain at home and are not completely dependent on strangers for care (Brumley et al., 2007). In addition, hospice patients tend to live longer than non-hospice patients (Connor, Pyenson, Fitch, Spence, & Iwasaki, 2007; Temel et al., 2010). Family members receive emotional support and are regularly informed of their loved one’s treatment and condition. The family member’s burden of care is also reduced (McMillan et al., 2006). Both the patient and the patient’s family members report increased family support, increased social support, and improved coping while receiving hospice services (Godkin et al., 1984). How do you think you might react if you were diagnosed with a terminal illness like cancer? Elizabeth Kübler-Ross (1969), who worked with the founders of hospice care, described the process of an individual accepting his own death. She proposed five stages of grief: denial, anger, bargaining, depression, and acceptance. Most individuals experience these stages, but the stages may occur in different orders, depending on the individual. In addition, not all people experience all of the stages. It is also important to note that some psychologists believe that the more a dying person fights death, the more likely he is to remain stuck in the denial phase. This could make it difficult for the dying person to face death with dignity. However, other psychologists believe that not facing death until the very end is an adaptive coping mechanism for some people. Whether due to illness or old age, not everyone facing death or the loss of a loved one experiences the negative emotions outlined in the Kübler-Ross model (Nolen-Hoeksema & Larson, 1999). For example, research suggests that people with religious or spiritual beliefs are better able to cope with death because of their hope in an afterlife and because of social support from religious or spiritual associations (Hood, Spilka, Hunsberger, & Corsuch, 1996; McIntosh, Silver, & Wortman, 1993; Paloutzian, 1996; Samarel, 1991; Wortman & Park, 2008). A prominent example of a person creating meaning through death is Randy Pausch, who was a well-loved and respected professor at Carnegie Mellon University. Diagnosed with terminal pancreatic cancer in his mid-40s and given only 3–6 months to live, Pausch focused on living in a fulfilling way in the time he had left. Instead of becoming angry and depressed, he presented his now famous last lecture called “Really Achieving Your Childhood Dreams.” In his moving, yet humorous talk, he shares his insights on seeing the good in others, overcoming obstacles, and experiencing zero gravity, among many other things. Despite his terminal diagnosis, Pausch lived the final year of his life with joy and hope, showing us that our plans for the future still matter, even if we know that we are dying. Really Achieving Your Childhood Dreams is Randy Pausch’s last lecture. Listen to his inspiring talk. Summary Death marks the endpoint of our lifespan. There are many ways that we might react when facing death. Kübler-Ross developed a five-stage model of grief as a way to explain this process. Many people facing death choose hospice care, which allows their last days to be spent at home in a comfortable, supportive environment. Review Questions Who created the very first modern hospice? - Elizabeth Kübler-Ross - Cicely Saunders - Florence Wald - Florence Nightingale Hint: B Which of the following is the order of stages in Kübler-Ross’s five-stage model of grief? - denial, bargaining, anger, depression, acceptance - anger, depression, bargaining, acceptance, denial - denial, anger, bargaining, depression, acceptance - anger, acceptance, denial, depression, bargaining Hint: C Critical Thinking Questions Describe the five stages of grief and provide examples of how a person might react in each stage. Hint: The first stage is denial. The person receives news that he is dying, and either does not take it seriously or tries to escape from the reality of the situation. He might say something like, “Cancer could never happen to me. I take good care of myself. This has to be a mistake.” The next stage is anger. He realizes time is short, and he may not have a chance to accomplish what he wanted in life. “It’s not fair. I promised my grandchildren that we would go to Disney World, and now I’ll never have the chance to take them.” The third stage is bargaining. In this stage, he tries to delay the inevitable by bargaining or pleading for extra time, usually with God, family members, or medical care providers. “God, just give me one more year so I can take that trip with my grandchildren. They’re too young to understand what’s happening and why I can’t take them.” The fourth stage is depression. He becomes sad about his impending death. “I can’t believe this is how I’m going to die. I’m in so much pain. What’s going to become of my family when I’m gone?” The final stage is acceptance. This stage is usually reached in the last few days or weeks before death. He recognizes that death is inevitable. “I need to get everything in order and say all of my good-byes to the people I love.” What is the purpose of hospice care? Hint: Hospice is a program of services that provide medical, social, and spiritual support for dying people and their families. Personal Application Questions Have you ever had to cope with the loss of a loved one? If so, what concepts described in this section provide context that may help you understand your experience and process of grieving? If you were diagnosed with a terminal illness would you choose hospice care or a traditional death in a hospital? Why?	oercommons	2025-03-18T00:36:10.734202	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15344/overview", "title": "Psychology, Lifespan Development", "author": null }
https://oercommons.org/courseware/lesson/125669/overview	Key Message Three: Increasing Challenges Confront Food and Fiber Production in the Southwest Overview Educational Resources and Guiding Questions Aligned with the Regional Key Messages: Each Key Message in this Lesson features three guiding questions to help educators navigate these topics with students. Each guiding question includes example lessons and supporting videos. The lessons were taken from the Climate Literacy and Energy Awareness Network (CLEAN) educational resources database. The videos were selected from reputable sources to support the lessons. Continuing drought and water scarcity will make it more difficult to raise food and fiber in the Southwest without major shifts to new strategies and technologies. Extreme heat events will increase animal stress and reduce crop quality and yield, thereby resulting in widespread economic impacts. Because people in the Southwest have adapted to drought impacts for millennia, incorporating Indigenous Knowledge with technological innovation can offer solutions to protect food security and sovereignty. Guiding Question One What are social and economic barriers to agricultural adaptation in the Southwest? Example Lesson American Farm Bureau Foundation for Agriculture Description: This set of five lessons addresses climate change impacts to agriculture and provides sustainable solutions. Lesson two covers the relationship between agriculture and local, national, and global economies. Lesson five covers the role that agriculture plays in society. Instructional Time: Each lesson takes 60 minutes to complete Grade Level: Ninth through twelfth Supporting Video Unrelenting drought leaves millions who rely on the Colorado River facing an uncertain future PBS NewsHour Description: The Colorado River is a critical resource for the western U.S. But a megadrought, one significantly exacerbated by climate change, is jeopardizing the river's future and threatening to upend how its water is used and longstanding agreements between states. Miles O'Brien reports as part of our coverage on how climate change is creating a "Tipping Point" for the U.S. and around the world. Video Length: 7:21 minutes Guiding Question Two Notes From Our Reviewers The CLEAN collection is hand-picked and rigorously reviewed for scientific accuracy and classroom effectiveness. Teaching Tips - Providing learners with appropriate data sets for this or other regions will help them gain a quantitative handle on the topic of climate change and freshwater resources. - Because of the length of the activity, it could be used as an entire unit on the Colorado River watershed or customized for other watersheds. About the Content - Students research the impact of climate change on the Colorado River Basin by analyzing snowpack data sets and satellite images of land and vegetation. - Some data sets and images are presented to support the activity, source citations are not available. - Comments from expert scientist: Addresses key issues of water quantity across Colorado River Basin and potential impact based on historical changes. - Need to address potential water quality concerns as CRB also serve for drinking water supply. About the Pedagogy - This is a structured, problem-based learning module using the impact of climate change on the water levels in the Colorado River Basin and as a case study. The authentic final assessment asks students to use their research and analysis of data and images to suggest revisions to the 2007 Colorado Basin water allotment agreement. - Activity provides background information and guiding questions for students to work through the data. - Instructors may want to customize this activity for their own area of interest and assessment needs. - This resource engages students in using scientific data. See other data-rich activities Technical Details/Ease of Use - Teacher notes are not included because this is a college-level module and thus assumes the expertise of the professor. However, the four parts of the module are scaffolded enough to enable 11th and 12th grade students to successfully use the module. Related URLs These related sites were noted by our reviewers but have not been reviewed by CLEAN for Part 3 Colorado River District video 'Colorado Water Supply' see http://www.coloradoriverdistrict.org/video-gallery/or https://www.youtube.com/watch?v=bVot9tEG0aw What are the challenges to distributing water equitably between urban and rural communities? Example Lesson Encyclopedia of Earth Description: This activity addresses climate change impacts that affect all states that are part of the Colorado River Basin and are dependent on its water. Students examine available data, the possible consequences of changes to various user groups, and suggest solutions to adapt to these changes. Instructional Time: Activity takes about one to two class periods and homework assignments. Grade Level: Ninth through twelfth Supporting Video The Colorado River: Lifeblood for the American Southwest 9News Description: The Southwest is tipping on the precipice of indecision. For more than 100 years the Colorado River's water has been split between seven states, Native American tribes and Mexico thanks to a compact that experts say was written using flawed data. There was never enough water to go around, and beneath the crushing weight of longer droughts and hotter weather, everyone is caught between the Law of the River and reality. Video Length: 12:12 minutes Guiding Question Three Which new technologies and adaptive practices are likely to support agriculture in the Southwest through the impacts of climate change? Example Lesson Agriculture and Climate Change Learning Lab The Climate Initiative Description: This interactive learning lab will help students learn how climate change is affecting our ability to produce food, what sustainable agriculture looks like, how agriculture looks in different states, how snowpack in places like the Sierra Nevada mountains affects agriculture, and how people are affected by these changes and practices. Students will watch videos, read articles, view maps, and answer questions to broaden their understanding of the connections between agriculture and climate change. Instructional Time: Six classroom periods Grade Level: Seventh through twelfth Supporting Video Kiss the Ground for Schools Big Picture Ranch https://kissthegroundmovie.com/for-schools/ Description: This documentary explores the potential of regenerative agriculture to address climate change and restore ecosystems. Password: schools Video Length: 46:26 minutes	oercommons	2025-03-18T00:36:10.756675	Melinda Newfarmer	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/125669/overview", "title": "National Climate Assessment: The Southwest, Key Messages for the Southwest, Key Message Three: Increasing Challenges Confront Food and Fiber Production in the Southwest", "author": "Lesson Plan" }
https://oercommons.org/courseware/lesson/71613/overview	Experimentation and Innovation: Building the Hale Telescope Overview The primary sources in this project, drawn from the collections at the Rockefeller Archive Center, include correspondence and diagrams that document the process of fabricating what became a 200-inch Pyrex telescope mirror. These sources can be used to strengthen critical reading skills, to support inquiry-based learning exercises, and to expose students to the stories of trial and error that lie behind most scientific or engineering breakthroughs. Students are encouraged to annotate in the margins in order to support the development of document analysis and critical thinking skills. This project contains a suggested exercise that builds on the themes of the primary source documents. Primary Source Project The 200-inch Hale Telescope at Palomar Observatory in California was, in many respects, an ambitious dream, as no manufacturer had successfully fabricated a mirror 200-inches in diameter at that time. The process of making the mirror, however, was lengthy, expensive, and required a lot of experimentation. The primary sources in this project, drawn from the collections at the Rockefeller Archive Center, include correspondence and diagrams that document the process of fabricating what became a 200-inch Pyrex telescope mirror. These sources can be used to strengthen critical reading skills, to support inquiry-based learning exercises, and to expose students to the stories of trial and error that lie behind most scientific or engineering breakthroughs. Students are encouraged to annotate in the margins in order to support the development of document analysis and critical thinking skills. This project contains a suggested exercise that builds on the themes of the primary source documents.	oercommons	2025-03-18T00:36:10.774962	Mathematics	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/71613/overview", "title": "Experimentation and Innovation: Building the Hale Telescope", "author": "Information Science" }
https://oercommons.org/courseware/lesson/56690/overview	Unit 8.1 : Photosynthesis 8.1 Photosynthesis (video) part 1 Overview of photosynthesis video. Part 1 on Lecture for Chapter 8 Openstax Biology 2e Overview of photosynthesis video. Part 1 on Lecture for Chapter 8 Openstax Biology 2e Overview of photosynthesis video. Part 1 on Lecture for Chapter 8 Openstax Biology 2e Overview of photosynthesis video. Part 1 on Lecture for Chapter 8 Openstax Biology 2e	oercommons	2025-03-18T00:36:10.790046	08/05/2019	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/56690/overview", "title": "Unit 8.1 : Photosynthesis", "author": "Urbi Ghosh" }
https://oercommons.org/courseware/lesson/67011/overview	Bio and Cover Letter handout Daily Class Breakdown DRR IDS Dead River Review Style Guide and Handbook for Copyediting DRR Editor Tracking Sheet DRR Student Tracking Sheet drrsubmissionsguidelines DRR Webmaster Tracking Sheet Final Project Assignment Eng 151 Instructor Tracking Sheet missionstatement OER Eng 151 Class Breakdown OER Eng 151 Syllabus OER IDS 102 Syllabus Publication Rights Statement The Dead River Review Rejection letter Rejection Query Reverse Engineering Your Career Time Management for Writers WordPress - Working with DRR Working With and Around Copyrights Workshop Sign Up Sheet MCC Eng 151 Creative Writing and Publishing the Dead River Review IDS Overview This is the complete curriculum for Eng 151 Creative Writing and Publishing course run in the spring at Middlesex Community College as well as the linked IDS course that is resonsible for publishing the Dead River Review, the college's ezine. This includes instructions, PowerPoints, worksheets, and assignments. Instructions for the English 151: Creative Writing and Publishing course at Middlesex Community College Instructions on using this OER Eng 151 Creative Writing and Publishing Course The Creative Writing and Publishing course is intended to give students who are in the Creative Writing Program knowledge and experience in navigating the publishing world from different perspectives. It includes guest speakers, exercises, and opportunities to send their creative work out for consideration at small journals and magazines. Another focus of the course is to introduce the student to different careers possible in the publishing world. From editors, publishers, to writers, the students should understand that though publishing their own writing may not be lucrative in itself, their writing skills can land them jobs in the industry as editors, publishers, and writers. This course is meant to flow seamlessly into the linked course in the OER IDs 101 and 102: Service Seminar where the students will gain experience in editing, publishing, and ezine web building by creating the college’s ezine: The Dead River Review. Many students come to this class without having been published (except perhaps in the Dead River Review) and they often have little idea of how to begin sending their creative work out into the world. They should come from the class with confidence in their ability to get their work into the hands of editors, and they should gain an understanding of how queries, proposals, cover letters, and agents work in the publishing world. Space for guest speakers are in included in the syllabus to provide students with expertise in publishing in journals and magazines (even small ones), editing for magazines, as well as connecting with the local art and writing scene and running a reading series. If you do not have one or more of these experts in your circle, you can find almost all of these within the faculty member pool in the college. Just ask around in the Creative Writing Department, and they should be able to match you up with an appropriate guest to help you complete your syllabus. Book these guests as soon as possible so you can adjust the syllabus accordingly. Another component of this course is workshopping. The students should be familiar with workshopping already but feel free to run the workshops as you see fit. There is a workshop signup sheet provided. The final project is a portfolio that is useful in building the students’ image as a writer and their understanding of what is expected of him or her in the publishing world. It includes some pieces of work that were required earlier in the class like bios and cover letters. Some time to finish the rest of the requirements is built into the course. Good luck and have fun! Eng 151 Syllabus and Day-to-Day Class Breakdown This is an example syllabus for the Eng 151 course and the day-to-day breakdown of what should be covered for each class period. Handouts for the Eng 151 course All of these sheets can be altered to suit the needs of the instructor. The Time Management Worksheet is the first handout besides the syllabus. It helps students organize their time. The Workshop Signup Sheet schedules the students for their respective workshop groups. The Bio and Cover Letter handout shows examples of author bios and cover letters. The Reverse Engineering Your Career worksheet helps students plan their path from college to career. The Final Project Assignment describes the last assignment for the course that has the students create and gather materials they will need for their writing careers. Syllabus and Day-to-Day Class Breakdown for the IDS 101&102 Service Seminar Responsible for Publishing the MCC e-zine the Dead River Review This section contains the syllabus and well as the full day-to-day breakdown for the IDS class that is linked to the Eng 151 course taught at Middlesex Community College. PowerPoint Slides for the DRR IDS These PowerPoints were created to assist the students in learning about the DRR website and Creative Commons. Tracking Sheets for Incoming Submissions These are sheets that can help the instructor and the students keep track of their progress when dealing with submissions. Use some or all as necessary. Dead River Review Guidelines and Email Templates These are documents that give important information about the magazine and its policies. Also included here are the email templates for communicating with the submitters to the magazine. These templates are also available on the google drive.	oercommons	2025-03-18T00:36:10.831060	Visual Arts	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/67011/overview", "title": "MCC Eng 151 Creative Writing and Publishing the Dead River Review IDS", "author": "Literature" }
https://oercommons.org/courseware/lesson/103755/overview	HGTC's Accessibility in OER Implementation Guide Overview In this section, you and your team will engage in a Landscape Analysis to uncover key structures and supports that can guide your work to support Accessibility in OER. You may or may not answer all of these questions, but this is an offering. May 11 - Section One: Landscape Analysis for Accessibility in OER in Local Context (Work on during May 11th implementation) In this section, you and your team will engage in a Landscape Analysis to uncover key structures and supports that can guide your work to support Accessibility in OER. We exnourage to explore some of the questions from each category. You may or may not answer all of these questions, but this is an offering. We ask that you complete Parts One, Two and Six. Part One: Initial Thoughts - What is your team's initial goal for this series? - We have some confusion over what we are expected to produce. - Update: We are developing an Accessibiliity workshop series for faculty -- it will have multiple assessments and activities and will be housed publicly so anyone can use it (therefore making it an OER as well). Part Two: Introductory probing questions: What does accessibility look like in our organization? How do we measure accessibility? We don't have a specific department or person that oversees accessibility, and we don't measure it from an objective perspective. Faculty are asked to make materials and documents accessible, and we provide some training/support (from folks who are self-taught on accessibility), but it is not thoroughly addressed/overseen in the way it should be. What does OER look like in our organization? How do we measure access to OER? We have a better grasp on OER in terms of developing/implementing them, but we don't really measure the accessibility of these materials in many cases... so far, we haven't had many people create their own OERs, so we're using what is already out there, much of which is already accessible -- but it's something we need to be checking for on our end anyway. Part Three: Clarifying questions for accessibility: What is the organizational structure that supports accessibility? Who generates most of the accessibility structures/conversation in our organization? Where do most educators get support with accessibility? What content areas might have the largest gaps in access to accessibility? Part Four: Clarifying questions for OER: What is our organizational structure that supports curricular resources? What is our organizational structure that supports OER? Who generates most of the curricular resources in our organization? Where do most educators get support with curricular resources? What content areas might have the largest gaps in access to curricular resources/OER? Part Five: Clarifying questions for Faculty learning and engagement: What Professional Learning (PL) structures have the best participation rates for our educators? What PL structures have the best "production" rates for our educators? What incentive do we have to offer people for participating in learning and engagement? Who are the educators that would be most creative with accessibility and OER? Who are the educators that would benefit the most from accessibility and OER? Part Six: Final Probing questions: What is our current goal for Accessibility in OER and why is that our goal? We weren't sure initially, but we landed on building an accessibility workshop series for our faculty/staff that demonstrates all these tools and defines accessibility... this will start with the basics of the checker in Word, etc., and build to looking at websites for those who may want to create their own OERs moving forward or may be using websites for instruction. Who have we not yet included while thinking about this work? disability services for the student perspective, additional faculty/staff for support/buy-in, students (understanding their needs) What barriers remain when considering this work? resources, as there is no department for accessibility (or even OER for that matter) at our institution... this is why we're looking for a pre-built, self-paced Accessibility workshop, but we'd like to offer actual training sessions on the topics as well What would genuine change look like for our organization for this work? For accessibility, just a general awareness, buy-in, and effort to make documents and materials accessible for students Section Two: Team Focus (Finish before May 25th to share during Implementation Session Two) Identifying and Describing a Problem of Practice The following questions should help your team ensure that you are focusing your collaboration. What is your Team’s specific goal for this series? You may consider using AEM Quality Indicators for Creating Accessible Materials to help add to or narrow your work. Implementation Goal: Create an accessibility workshop training series to offer internally (and share as public free resource [OER]) What other partners might support this work? Library, Academic Services, faculty, disability services, tutoring center What is your desired timeframe for this work? Possible timeline: create over summer and begin offering during Fall semester (later in semester, October/November + PD in December) How will you include diverse voices and experiences in this work? Reach out to disability services and the tutoring center to get their thoughts/perspective. Survey the faculty as well as the students to get a better idea of what the needs are. Select certain faculty to be representatives for the initiative and loop them in to the conversation. Please create a Focus Question that explains your goal and provides specific topics that you would like feedback on. This is what you will share in your breakout groups for feedback. How should we consider breaking our series into multiple workshops? What topics go first, what can be combined, how much time should we plan for in-person sessions... for the OER version, how many assessments are needed and should anything be given at the end like a certificate? (And if so, who will manage and oversee this?) (Save for during May 25th's session.) What feedback did you receive from another team during the May 25th Implementation Session? We worked with our other HGTC team, so we discussed our projects and how to combine them to make effective change at the college... we also discussed some of the topics and outline for our workshop series. Section Three: Team Work Time and Next Steps (Complete by the end of Implementation Session Three) Sharing and Next Steps What was your redefined goal for this series? It took us a while to determine what we really wanted to do for the project, so we started with no real goal at all and ended up with a solid project of a way we can share accessibility internally and also as an OER. What does your team want to celebrate? We're proud of the libguide we put together for now and are glad we chose the libguide format -- we originally planned to do it here in OER Commons but found the libguide easier to navigate and use since we were already familiar with it... and our librarians are whizzes when it comes to updating them, etc., so it works really well for us internally but also allows us to share it publicly. What did your team accomplish? If you have links to resources, please include them here. Accessibility Workshop (LibGuide) It only has resources right now, but once we figure out the full outline for our workshop series, we'll reorganize and add it here -- the idea is to have separate modules/tabs for each topic and create an assessment of some kind for each. We'd like to have it built so there's a self-paced aspect but also some activities for when we have our in-person workshops (and we will have an "instructor's manual" of sorts to share with facilitators of these workshops so they have guidance on what to do any how). What are your team’s next steps? As a starting point, we want to offer a "crash course" Accessibility Workshop at our next required professional development day.... starting to expose faculty to some of the basics is the goal with this, and that way, when we introduce an entire workshop series, it (hopefully) won't be so overwhelming.	oercommons	2025-03-18T00:36:10.858833	Richard Moniz	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/103755/overview", "title": "HGTC's Accessibility in OER Implementation Guide", "author": "Alicia Ramberg" }
https://oercommons.org/courseware/lesson/89659/overview	Outlining 101 - The Basics Overview This simple guide to outlining addresses first steps, required elements, and common pitfalls in writing that make outlining an essential step. Outlining 101 - The Basics Outlining 101 – The Basics As a general rule…ALWAYS OUTLINE! It may seem like extra work, however, the small amount of time you spend preparing to write saves a significant amount of time on the revising and editing portion of your writing. As a second general rule...start simple A basic outline captures the essential elements of an essay while also guiding its structure and flow (not to mention keeps you from making errors in repetition and/or missing information). An outline does not have to be overly formal but there are some guiding elements you must be certain to include. I. Intro Give an idea of what the essay will be about. The first sentence should grab your reader and let them know that there is something worth reading here. The first paragraph includes your THESIS STATEMENT, usually at the end of the paragraph and typically one sentence (it can be more if your essay is longer or more complex). This statement presents your topic being discussed, your position on the topic, and the relevant information that will be presented throughout the essay. It should also generate a position from which you can build your points (it should not be a statement of fact). II. Body A. Idea, Position, Concept 1 Each paragraph should tie into your thesis but present ideas and supporting evidence The facts or details you present within each body section should support the topic sentence of the idea, position, or concept and also relate specifically to the overall thesis of your essay. There is no required number but you need enough to substantially support your idea without too many that they should be separated into another idea. Follow the arrows… \| independent of other paragraph information. This requires a TOPIC SENTENCE to feature at the introduction of this new idea. Each time you have a sub-idea within an idea section, begin a new paragraph (but not a new idea). TRANSITION SENTENCES are critical here so your reader can see the logical flow of information between idea subsections and then from one idea to the next big idea. Transition sentences can come at the end of one paragraph or as the first sentence of the next. - Fact or Detail - Fact or Detail - Fact or Detail B. Idea, Position, Concept 2 Make certain you do not repeat information. That is the purpose of outlining. If it seems like your ideas are too closely related or too much information overlaps, rethink what you want to emphasize. Particularly with research, if too many of your sources are too similar, you will not have enough material for a substantial essay (every Body section will sound the same). ideas. This idea will also have 1-4 facts and details listed that support the 2nd idea and relate to the overall thesis. Intro-Thesis \| C. Idea, Position, Concept 3 This is just a basic, general outline. As you get into longer essays, add additional sections under each idea (i.e. 1, 2, 3, a, b, c etc. to maintain the flow of your essay and to separate sections and ideas). III. Conclusion There should be no new information in the conclusion. However, the conclusion is not just a regurgitation of the introduction. The conclusion should summarize what you wanted the reader to discover/learn/understand in your essay. You are letting the reader know that you have supported your thesis statement and they should now applaud and want to read more of what you write! Some sound writing guidelines: - Avoid “this” and “that.” These are generic and unspecific terms. They will also curb your writing (make essays shorter). As an example: In looking at enrollment for freshmen in college, 50% of students have a remedial course. This is a staggering percentage. Instead, be specific and explain your position with clarity: In looking at enrollment for freshmen in college, 50% of students have a remedial course. Fifty percent is half of an incoming freshman class and is a staggering percentage. Result-more description and detail, less ambiguity as to what “this” is. This gives your argument strength. You have now indicated your stance on the issue and positioned yourself to provide the reader with factual evidence in support of your position. - “Very” is the most overused word in writing! Instead of very, nouns or verbs can be significant, considerable, outstanding, overlooked, consequential, etc. Make an impact with your language. Feel free to take liberal advantage of a dictionary/thesaurus app on your phone! (I will send out “word of the day” emails if there are very many verys!) - Cite properly and ask why. Any time you use a source or piece of material (and there is a whole separate conversation on what to use versus what not to use), make certain you give appropriate citations and ALWAYS ASK YOURSELF WHY…why did you include a particular piece of information from someone else? Why did you think it was critical? Why is it important to your overall thesis or to the reader? - You will get much more out of (and into) your essays if you constantly ask yourself “why.” This applies to cited material as well as your own idea development. If it is not relevant to you, it will not be relevant to your reader. On the other hand, if it is relevant to you, it gives you the opportunity to expand on it and develop the relevance-strengthening your position and the essay’s complexity.	oercommons	2025-03-18T00:36:10.889616	01/31/2022	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/89659/overview", "title": "Outlining 101 - The Basics", "author": "Emily Lawrence" }
https://oercommons.org/courseware/lesson/80766/overview	Writing the Evaluation Essay Overview This is a Google doc with multiple steps and resources to walk students through the writing process for an Evaluation Essay Writing the Evaluation Essay Evaluation Essay - In this tutorial, you will walk through instruction and writing steps that will lead you to an Evaluation Essay. Please make a copy of this document (File>Make Copy) and complete all of the steps below: \| Evaluation Essay Requirements: Evaluate a movie or film3 pages, double spaced (750 words)MLA FormatSee your course and fill in your due dates \| \| \| Prewriting Check (Week 6) \| Due Date: \| \| Draft Due to Peer Editing Form (Week 7) \| Due Dates (there are 2 due dates): \| \| Final Draft (Week 8) \| Due Date: \| Grading Sometimes it’s nice to know how your paper will be graded before you start writing. Here are the key features of a well-written paper about a film of your choosing. From Norton Field Guide chapter 16 \| A Concise Description of the subject. You should include just enough information to let readers who may not be familiar with your subject understand what it is; the goal is to evaluate, not summarize. Depending on your topic and medium, some of this information may be in visual or audio form. Describe the main plot points of a movie, only providing what readers need to understand the context of your evaluation \| \| Clearly Defined Criteria. You need to determine clear criteria as the basis for your judgment. In reviews or other evaluations written for a broad audience, you can integrate the criteria into the discussion as reasons for your assessment. In more formal evaluations, you may need to announce your criteria explicitly. For instance, you could evaluate a film based on stars’ performances, the complexity of their characters, and the film’s coherence. There are lots of other criteria to choose from, depending on your film choice. \| \| A knowledgeable discussion of the subject. To evaluate something credibly, you need to show that you know it yourself and that you understand its context. Cite many examples showing your knowledge of the film. Some evaluations require that you research what other authoritative sources have said about your subject. You are welcome to refer to other film reviews to show you have researched other views, but your review should be your own \| \| A balanced and fair assessment. An evaluation is centered on a judgment. You can point out both its weaknesses and strengths. It is important that any judgment be balanced and fair. Seldom is something all good or all bad. A fair evaluation need not be all positive or all negative; it may acknowledge both strengths and weaknesses. For example, a movie’s soundtrack may be wonderful while the plot is not. \| \| Well-supported reasons. You need to argue for your judgment, providing reasons and evidence that might include visual and audio as well as verbal material. Support your reasons with several specific examples from the film. \| Step 1: Choosing a Topic For this assignment, you will choose a film you have watched that was meaningful enough to evaluate. It can be one that was meaningful because it changed your perspective, for instance. You are also welcome to choose a film that was critically acclaimed, but you have objections to. Choose something that strikes you as a film worth analyzing and discussing. \| \| What film are you going to evaluate in this essay? Make sure it is one that is accessible to you (you own it, you have checked it out from the library, it’s available through a subscription like Netflix, Amazon Prime, Disney Plus, etc.) You will need to watch it and take detailed notes so that you have specifics, dialogue, etc. to include. \| \| What film will you evaluate? \| \| Paste the film’s citation in MLA format in the box below. Here is a resource that describes how to cite Films or Movies \| \| Paste your MLA citation here. You will need it later when you write your paper \| Step 2: Generating Ideas and Text \| In the columns below you will generate text. Much of it may be used later as you draft your paper, but don’t worry about that now. Use these exercises to help you get your ideas down. \| \| \| Explore what you already know. Freewrite to answer the following questions: What do you know about this subject? What are your initial or gut feelings, and why do you feel as you do? How does this film reflect or affect your basic values or beliefs? How have others evaluated subjects like this? \| \| \| Identify criteria. Make a list of criteria you think should be used to evaluate your film. Think about which criteria will likely be important to your audience. \| \| \| Evaluate your subject. Study your film closely to determine to what extent it meets each of your criteria. You may want to list your criteria and take notes related to each one as you watch the film. You may develop a rating scale for each criterion to help stay focused on it. Come up with a tentative judgment. Choose 3-4 criteria to discuss in your essay. \| \| \| Compare your subject with others. Often, evaluating something involves comparing and contrasting it with similar things. We judge movies in comparison with other movies we’ve seen in a similar genre. \| \| \| State your judgment as a tentative thesis statement. Your thesis statement should be one that addresses both pros and cons. “Hawaii Five-O is fun to watch despite its stilted dialogue” “Of the five sport utility vehicles tested, the Toyota 4 Runner emerged as the best in comfort, power, and durability, though not in styling or cargo capacity.” Both of these examples offer a judgment but qualify it according to the writer’s criteria. Experiment with thesis statements and highlight one you want to use. \| \| \| Anticipate other opinions. I think Will Ferrell is a comic genius whose movies are first-rate. You think Will Ferrell is a terrible actor who makes awful movies. How can I write a review of his latest film that you will at least consider? One way is by acknowledging other opinions--and refuting those opinions as best I can. I may not persuade you to see Ferrell’s next film, but I can at least demonstrate that by certain criteria he should be appreciated. You may need to research how others have evaluated your subject. \| \| \| Identify and support your reasons. Write out all the reasons you can think of that will convince your audience to accept your judgment. Review your list to identify the most convincing or important reasons. Then review how well your subject meets your criteria and decide how best to support your reasons; through examples, authoritative opinions, statistics, visual or audio evidence, or something else. \| Step 3: Organization of the Evaluation Essay \| Below are two different options for organizing your essay. Choose one of them (don’t be afraid to choose something other than chronological!). Click on the image and use the down arrow to open the drawing and fill in the boxes with elements from your story to help you outline your organization \| \| Once you have completed Steps 1-3, submit a link to your copy of this document to your teacher as your Prewriting Check \| Step 4- Draft Use this MLA formatted writing template linked HERE to draft out your 3 page (750 word) essay by making a copy and adding your own information. Add a link to your paper in the box below. Make sure it is set so that “Anyone with a link CAN COMMENT” Do this by clicking SHARE in the top right corner. Then click “change” under the “get link” box, and use the down arrow to change so that anyone at MHA can edit. \| link to paper: \| Step 5: Get Feedback \| Submit your draft to paperrater.com. Use feedback to polish your essay. Here is a TUTORIAL for paperrater.com \| \| What feedback did you get from paperrater.com? Paste it in this box: \| Step 6- Peer Editing Go back to the course and submit your draft for peer editing. You will post your own draft, then edit two of your peers’ drafts. Read the directions carefully in the Peer Editing Forum. Step 7: Final Paper Once you have revised your draft, you will submit your final draft to your teacher in the course. You may also paste the draft below. Make sure it is shared so that anyone from MHA with a link can edit: \| Paste in Link: \| Link to the Evaluation Essay Google Doc Make a copy using File>Make a Copy	oercommons	2025-03-18T00:36:10.955971	Unit of Study	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/80766/overview", "title": "Writing the Evaluation Essay", "author": "Module" }
https://oercommons.org/courseware/lesson/116150/overview	Using Credit Cards Lesson Money Matters: Using Credit Cards with Care Overview During this lesson, the student(s) will: • Understand the risks of credit cards and how interest rates can increase your credit card balance. • Learn about credit records and the importance of good credit. • Explain why it’s important to pay credit card bills in full and on time. Lesson Plan See attachment for lesson plan and handouts.	oercommons	2025-03-18T00:36:10.974630	05/17/2024	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/116150/overview", "title": "Money Matters: Using Credit Cards with Care", "author": "Aujalee Moore" }
https://oercommons.org/courseware/lesson/101241/overview	30 year-old female with menorrhagia case study Overview An immunohematology teaching case with questions. For use or adaption with teaching/examination resources for transfusion medicine, immunohematology, and blood banking. Case Study Question Can use multiple choice or write open ended questions to resolve the case. Detailed solutions for the published questions are below. - From the results above what can be determined about the patient’s blood type? A: a The patient’s front and back type both indicate that the patient’s cells have the A and D antigens present with anti-B antibodies present in the plasma. This correlates with a type A Pos and matches the patient’s historical type. - Based on the patient’s condition, type and antibody screen results, which of the following would be the next best step for this patient? A: b. The patient appears to have an previously unknown alloantibody. Best practices indicate that at minimum, performance of an antibody panel, potential need to test selected cells, antigen typing, and a complete crossmatch through AHG will delay availability of crossmatched blood for transfusion 45-90 minutes or more than is expected for a patient without unexpected antibodies. Early communication of this expected delay can allow for best patient care as evaluated by the care team at the patient bedside and the patient blood management team. - Based on the results of the panel which of the following is most likely? A: a. The panel pattern of reactivity matches up with a single antibody with anti-c specificity, with all other clinically significant antibodies able to be ruled out. The autocontrol or testing of patient plasma with patient cells at the bottom of the panel indicate that the patient has an alloantibody and not an autoantibody. The rule of three is met for an anti-c antibody with three reactive and three non-reactive cells. - What is the likely specificity of the alloantibody in the patient’s plasma? A: b. The panel indicates an anti-c antibody. - Approximately how many units will you need to antigen-type to find 1 compatible unit for this patient? A: b. The c antigen is present in approximately 80% of donors, therefore, antigen testing 5 random ABO compatible units should yield at least 1 c-negative unit. - Which of the following strategies could best aid in identifying compatible blood? A: b. The c antigen is present in approximately 98% of donors of African decent and r’ or ry genes are extremely rare in any type making Rh-negative donors unlikely to be c-negative. While use of patient plasma to screen for rare antigens can be useful when anti-sera is scarce or expensive causing need to conserve the antisera, monoclonal anti-c antisera is generally readily available commercially and FDA cleared for donor testing. Additionally, anti-C is typically an IgG antibody therefore, the units would need to be screened at AHG phase as IS testing is expected to yield false negative results. The father is unlikely to be a match (see below). - Based on the patient history given which of the following is most likely? A: c. The mother was likely immunized to the c antigen though transfusion or pregnancy since her last record 4 years ago indicated a negative antibody screen. It is likely that the father of the child was the source of the c gene inherited and expressed by the child and the mother was likely immunized to the c antigen through fetomaternal hemorrhage. Blood Bank Case Study: 30 year-old bleeding female of child-bearing potential[1] A 26 year-old female patient, Candi Cameroon was typed as Type A positive with a negative antibody screen during an uncomplicated pregnancy four years ago. Today she is admitted for shortness of breath, fatigue, and menorrhagia. The patient’s hemoglobin is 6.5 and hematocrit of 21%. The physician orders 1 unit of RBCs for STAT transfusion. The patient’s initial blood typing, antibody screen and panel are included in the attached document. [1] Disclaimer: This case is fictitious and for teaching and learning purposes only. Resemblance to any real patient is coincidental.	oercommons	2025-03-18T00:36:10.999062	Marianne Downes	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/101241/overview", "title": "30 year-old female with menorrhagia case study", "author": "Homework/Assignment" }
https://oercommons.org/courseware/lesson/102255/overview	CHAPTER 2: COMMUNICATION AND THE SELF Overview Introduction to Communication textbook. Learning Objectives After reading this chapter you should be able to: • Define self-concept and discuss how we develop our self-concept and how it impacts interpersonal communication. • Define self-esteem and discuss how we develop self esteem and how it impacts interpersonal communication . • Discuss how social norms, family, culture, and media influence self-perception. • Define self-presentation and discuss common impression management skills and how it impacts interpersonal communication . 2.1 SELF-CONCEPT, SELF-ESTEEM AND SELF-EFFICACY Just as our perception of others affects how we communicate, so does our perception or view of ourselves. But what influences how we see ourselves? How much of our self is a product of our own making and how much of it is constructed based on how others react to us? How do we present ourselves to others in ways that maintain our sense of self or challenge how others see us? We will begin to answer these questions in this section as we explore self-concept, self-esteem, and self presentation. Self-concept refers to the overall idea of who a person thinks he or she is. If I said, “Tell me who you are,” your answers would be clues as to how you see yourself, your self-concept. Each person has an overall self-concept that might be encapsulated in a short list of overarching characteristics that he or she finds important physical characteristics, personality traits, roles/ relationships, skills, talents, beliefs etc. But each person’s self concept is also influenced by context, meaning we think differently about ourselves depending on the situation we are in. In some situations, personal characteristics, such as our abilities, personality, and other distinguishing features, will best describe who we are. You might consider yourself laid back, traditional, funny, open-minded, or driven, or you might label yourself a leader or a thrill-seeker. In other situations, our self-concept may be tied to a group or cultural membership. For example, you might consider yourself a member of the drama club or a member of the track team. Our self-concept is also formed through our interactions with others and their reactions to us. The concept of the looking glass self explains that we see ourselves reflected in other people’s reactions to us and then form our self-concept based on how we believe other people see us. This reflective process of building our self-concept is based on what other people have actually said, such as “You’re a good listener,” and other people’s actions, such as coming to you for advice. These thoughts evoke emotional responses that feed into our self concept. For example, you may think, “I’m glad that people can count on me to listen to their problems.” We also develop our self-concept through comparisons to other people. Social comparison theory states that we describe and evaluate ourselves in terms of how we compare to other people. Social comparisons are based on two dimensions: superiority/ inferiority and similarity /difference. In terms of superiority and inferiority, we evaluate characteristics like attractiveness, intelligence, athletic ability, and so on. For example, you may judge yourself to be more intelligent than your brother or less athletic than your best friend, and these judgments are incorporated into your self-concept. This process of comparison and evaluation isn’t necessarily a bad thing, but it can have negative consequences if our reference group isn’t appropriate. Reference groups are the groups we use for social comparison, and they typically change based on what we are evaluating. In terms of athletic ability, many people choose unreasonable reference groups with which to engage in social comparison. If a person wants to get into better shape and starts an exercise routine, they may be discouraged by the difficulty of keeping up with an aerobics instructor or running partner and judge themselves as inferior. This kind of comparison could negatively affect a person’s self concept. If instead, this person used a reference group made up of people who have only recently started a fitness program but have shown progress, could help maintain a more accurate and hopefully positive self-concept. We also engage in social comparison based on similarity and difference. Since self-concept is context-specific, similarity may be desirable in some situations and difference more desirable in others. Factors like age and personality may influence whether or not we want to fit in or stand out. Although we compare ourselves to others throughout our lives, adolescent and teen years usually bring new pressure to be similar to or different from particular reference groups. Think of all the cliques in high school and how people voluntarily and involuntarily broke off into groups based on popularity, interest, culture, or grade level. Some kids in your high school probably wanted to fit in with and be similar to other people in the marching band but be different from the football players. Conversely, athletes were probably more apt to compare themselves, in terms of similar athletic ability, to other athletes rather than kids in show choir. But social comparison can be complicated by perceptual influences. As we learned earlier, we organize information based on similarity and difference, but these patterns don’t always hold true. Even though students involved in athletics and students involved in arts may seem very different, a dancer or singer may also be very athletic, perhaps even more so than a member of the football team. There are positive and negative consequences of social comparison. We generally want to know where we fall in terms of ability and performance as compared to others, but what people do with this information and how it affects self-concept varies. Not all people feel they need to be at the top of the list, but some won’t stop until they break a record score or set a new school record in a track-and-field event. Some people strive to be first chair in the clarinet section of the orchestra, while another person may be content to be second chair. The education system promotes social comparison through grades and rewards such as honor rolls and dean’s lists. Although education and privacy laws prevent a teacher from displaying each student’s grade on a test or paper for the whole class to see, teachers do typically report the aggregate grades, meaning the total number of As, Bs, Cs, and so on. This doesn’t violate anyone’s privacy rights, but it allows students to see where they fell in the distribution. This type of social comparison can be used as motivation. The student who was one of only three out of twenty-three to get a D on the exam knows that most of her classmates are performing better than she is, which may lead her to think, “If they can do it, I can do it.” But social comparison that isn’t reasoned can have negative effects and result in negative thoughts like “Look at how bad I did. I’m not as smart as my classmates.” These negative thoughts can lead to negative behaviors, because we try to maintain internal consistency, meaning we act in ways that match up with our self-concept. So if the student begins to question her academic abilities and then incorporates an assessment of herself as a “bad student” into her self-concept, she may then behave in ways consistent with that, which is only going to worsen her academic performance. Additionally, a student might be comforted to learn that he isn’t the only person who got a D and then not feel the need to try to improve, since he has company. You can see in this example that evaluations we place on our self-concept can lead to cycles of thinking and acting. These cycles relate to self-esteem and self-efficacy, which are components of our self concept. Student studying https://unsplash.com/photos/ ddwbTn5HDdQ Self-Esteem Self-esteem refers to the judgments and evaluations we make about our self-concept. While self-concept is a broad description of the self, self-esteem is more specifically an evaluation of the self. If I again prompted you to “Tell me who you are,” and then asked you to evaluate (label as good/bad, positive/negative, desirable/undesirable) each of the things you listed about yourself, I would get clues about your self-esteem. Like self-concept, self-esteem has general and specific elements. Generally, some people are more likely to evaluate themselves positively while others are more likely to evaluate themselves negatively. More specifically, our self-esteem varies across our life span and across contexts. How we judge ourselves affects our communication and our behaviors, but not every negative or positive judgment carries the same weight. The negative evaluation of a trait that isn’t very important for our self-concept will likely not result in a loss of self-esteem. For example, I am not very good at drawing. While I appreciate drawing as an art form, I don’t consider drawing ability to be a very big part of my self-concept. If someone critiqued my drawing ability, my self-esteem wouldn’t take a big hit. I do consider myself a good teacher, however, and I have spent and continue to spend considerable time and effort on improving my knowledge of teaching and my teaching skills. If someone critiqued my teaching knowledge and/or abilities, my self-esteem would definitely be hurt. This doesn’t mean that we can’t be evaluated on something we find important. Even though teaching is very important to my self concept, I am regularly evaluated on it. Periodically I am evaluated by my students, my dean, and my colleagues. Most of that feedback is in the form of praise and constructive criticism, (which can still be difficult to receive), but when taken in the spirit of self-improvement, it is valuable and may even enhance our self-concept and self-esteem. In fact, in professional contexts, people with higher self-esteem are more likely to work harder based on negative feedback, are less negatively affected by work stress, are able to handle workplace conflict better, and are better able to work independently and solve problems. Self-esteem isn’t the only factor that contributes to our self-concept; perceptions about our competence also play a role in developing our sense of self. Self-Efficacy refers to the judgments people make about their ability to perform a task within a specific context. Let’s look at an example: Toni did a good job on her first college speech. During a meeting with her professor, Toni indicates that she is confident going into the next speech and thinks she will do well. This skill-based assessment is an indication that Toni has a high level of self efficacy related to public speaking. If she does well on the speech, the praise from her classmates and professor will reinforce her self-efficacy and lead her to positively evaluate her speaking skills, which will contribute to her high self-esteem. By the end of the class, Toni likely thinks of herself as a good public speaker, which may then become an important part of her self-concept. Throughout these points of connection, it’s important to remember that self-perception affects how we communicate, behave, and perceive other things. Toni’s increased feeling of self-efficacy may give her more confidence in her delivery, which will likely result in positive feedback that reinforces her self-perception. She may start to perceive her professor more positively since they share an interest in public speaking, and she may begin to notice other people’s speaking skills more during class presentations and public lectures. Over time, she may even start to think about changing her major to communication or pursuing career options that incorporate public speaking, which would further integrate being “a good public speaker” into her self-concept. You can hopefully see that these interconnections can create powerful positive or negative cycles. While some of this process is under our control, much of it is also shaped by the people in our lives. The verbal and nonverbal feedback we get from people affect our feelings of self-efficacy and our self-esteem. As we saw in Toni’s example, being given positive feedback can increase our self-efficacy, which may make us more likely to engage in a similar task in the future. Obviously, negative feedback can lead to decreased self-efficacy and a declining interest in engaging with the activity again. In general, people adjust their expectations about their abilities based on feedback they get from others. Positive feedback tends to make people raise their expectations for themselves and negative feedback does the opposite, which ultimately affects behaviors and creates the cycle. When feedback from others is different from how we view ourselves, additional cycles may develop that impact self-esteem and self concept. 2.2 SELF-DISCREPANCY THEORY 2.2 SELF-DISCREPANCY THEORY Self-discrepancy theory states that people have beliefs about and expectations for their actual and potential selves that do not always match up with what they actually experience. To understand this theory, we have to understand the different “selves” that make up our self-concept, which are the actual, ideal, and ought selves. The actual self consists of the attributes that you or someone else believes you actually possess. The ideal self consists of the attributes that you or someone else would like you to possess. The ought self consists of the attributes you or someone else believes you should possess. These different selves can conflict with each other in various combinations. Discrepancies between the actual and ideal/ought selves can be motivating in some ways and prompt people to act for self improvement. For example, if your ought self should volunteer more for the local animal shelter, then your actual self may be more inclined to do so. Discrepancies between the ideal and ought selves can be especially stressful. For example, many professional women who are also mothers have an ideal view of self that includes professional success and advancement. They may also have an ought self that includes a sense of duty and obligation to be a full-time mother. The actual self may be someone who does okay at both but doesn’t quite live up to the expectations of either. These discrepancies do not just create cognitive unease—they also lead to emotional, behavioral, and communicative changes. When we compare the actual self to the expectations of ourselves and others, we can see particular patterns of emotional and behavioral effects. When our actual self doesn’t match up with our own ideals of self, we are not obtaining our own desires and hopes, which can lead to feelings of dejection including disappointment, dissatisfaction, and frustration. For example, if your ideal self has no credit card debt and your actual self does, you may be frustrated with your lack of financial discipline and be motivated to stick to your budget and pay off your credit card bills. When our actual self doesn’t match up with other people’s ideals for us, we may not be obtaining significant others’ desires and hopes, which can lead to feelings of dejection including shame, embarrassment, and concern for losing the affection or approval of others. For example, if a significant other sees you as an “A” student and you get a 2.8 GPA your first year of college, then you may be embarrassed to share your grades with that person. When our actual self doesn’t match up with what we think other people think we should obtain, we are not living up to the ought self that we think others have constructed for us, which can lead to feelings of agitation, feeling threatened, and fearing potential punishment. For example, if your parents think you should follow in their footsteps and take over the family business, but your actual self wants to go into the military, then you may be unsure of what to do and fear being isolated from the family. Finally, when our actual self doesn’t match up with what we think we should obtain, we are not meeting what we see as our duties or obligations, which can lead to feelings of agitation including guilt, weakness, and a feeling that we have fallen short of our moral standard. For example, if your ought self should volunteer more for the local animal shelter, then your actual self may be more inclined to do so due to the guilt of reading about the increasing number of animals being housed at the facility. The following is a review of the four potential discrepancies between selves: ➢ Actual vs. own ideals. We have an overall feeling that we are not obtaining our desires and hopes, which leads to feelings of disappointment, dissatisfaction, and frustration. ➢ Actual vs. others’ ideals. We have an overall feeling that we are not obtaining significant others’ desires and hopes for us, which leads to feelings of shame and embarrassment. ➢ Actual vs. others’ ought. We have an overall feeling that we are not meeting what others see as our duties and obligations, which leads to feelings of agitation including fear of potential punishment. ➢ Actual vs. own ought. We have an overall feeling that we are not meeting our duties and obligations, which can lead to a feeling that we have fallen short of our own moral standards. Influences on the Self We have already learned that other people influence our self concept and self- esteem. While interactions we have with individuals and groups are definitely important to consider, we must also note the influence that larger, more systemic forces have on our self-perception. Social and family influences, culture, and the media all play a role in shaping who we think we are and how we feel about ourselves. Although these are powerful socializing forces, there are ways to maintain some control over our self-perception, our view of ourselves. Adult reading to baby https://unsplash.com/photos/ 2FcAFcIHpas Social and Family Influences Various forces help socialize us into our respective social and cultural groups and play a powerful role in presenting us with options about who we can be. While we may like to think that our self-perception starts with a blank canvas, our perceptions are limited by our experiences and various social and cultural contexts. Parents and peers shape our self-perceptions in positive and negative ways. The feedback that we get from significant others, which includes close family, can lead to positive views of self. “ASCENSION by WILLPOWER STUDIOS (WILLIAM ISMAEL) + Carrie Mae Rose” by WILLPOWER STUDIOS is licensed under CC BY 2.0 The theory of symbolic interactionism poses that the self is a product of the messages it has encountered over past interactions. Many of these interactions and messages come from our social influences (at school, work and beyond) as well as our family and friends. There are cultural differences in the amount of praise and positive feedback that teachers and parents give their children. For example, teachers give less positive reinforcement in Japanese and Taiwanese classrooms than do teachers in US classrooms. Chinese and Kenyan parents do not regularly praise their children because they fear it may make them too individualistic, rude, or arrogant. So the phenomenon of overpraising isn’t universal, and the debate over its potential effects is not resolved. Research has also found that communication patterns develop between parents and children that are common to many verbally and physically abusive relationships. Such patterns have negative effects on a child’s self-efficacy and self-esteem. Attributions are links we make to identify the cause of a behavior. In the case of aggressive or abusive parents, they are not as able to distinguish between mistakes and intentional behaviors, often seeing honest mistakes as intended and reacting negatively to the child. Such parents also communicate generally negative evaluations to their child by saying, for example, “You can’t do anything right!” or “You’re a bad girl.” When children do exhibit positive behaviors, abusive parents are more likely to use external attributions (causes outside of the child) that diminish the achievement of the child by saying, for example, “You only won because the other team was off their game.” In general, abusive parents have unpredictable reactions to their children’s positive and negative behavior, which creates an uncertain and often scary climate for a child that can lead to lower self-esteem and erratic or aggressive behavior. The cycles of praise and blame are just two examples of how the family as a socializing force can influence our self-perceptions. “Bunches of Carrots” by Scott 97006 is licensed under CC BY 2.0 Motivation is the underlying force that drives us to do things. Sometimes we are intrinsically motivated, meaning we want to do something for the love of doing it or the resulting internal satisfaction. Other times we are extrinsically motivated, meaning we do something to receive a reward or avoid punishment. If you put effort into completing a short documentary for a class because you love film-making and editing, you have been largely motivated by intrinsic forces. If you complete the documentary because you want an “A” and know that if you fail your parents will not give you money for your spring break trip, then you are motivated by extrinsic factors. Both can, of course, effectively motivate us. Praise is a form of extrinsic reward, and if there is an actual reward associated with the praise, like money or special recognition, some people speculate that intrinsic motivation will suffer. But what’s so good about intrinsic motivation? Intrinsic motivation is more substantial and long-lasting than extrinsic motivation and can lead to the development of a work ethic and a sense of pride in one’s abilities. Intrinsic motivation can move people to accomplish great things over long periods of time and be happy despite the effort and sacrifices made. Extrinsic motivation dies when the reward stops. Additionally, too much praise can lead people to have a misguided sense of their abilities. College professors who are reluctant to fail students who produce failing work may be setting those students up to be shocked when their supervisor critiques their abilities or output once they get into a professional context. “Culture” by greyshine is licensed under CC BY 2.0 Culture How people perceive themselves varies across cultures. For example, many cultures exhibit a phenomenon known as the self-enhancement bias, meaning that we tend to emphasize our desirable qualities relative to other people. But the degree to which people engage in self-enhancement varies. A review of many studies in this area found that people in Western countries such as the United States were significantly more likely to self-enhance than people in countries such as Japan. Many scholars explain this variation using a common measure of cultural variation that claims people in individualistic cultures are more likely to engage in competition and openly praise accomplishments than people in collectivistic cultures. The difference in self-enhancement has also been tied to economics, with scholars arguing that people in countries with greater income inequality are more likely to view themselves as superior to others or want to be perceived as superior to others (even if they don’t have economic wealth) in order to conform to the country’s values and norms. This holds true because countries with high levels of economic inequality, like the United States, typically value competition and the right to boast about winning or succeeding, while countries with more economic equality, like Japan, have a cultural norm of modesty. Gender differences have been studied but are very often exaggerated beyond the actual variations. Socialization and internalization of societal norms for gender differences account for much more of our perceived differences than do innate or natural differences between genders. These gender norms may be explicitly stated— for example, a mother may say to her son, “Boys don’t play with dolls”—or they may be more implicit, with girls being encouraged to pursue historically feminine professions like teaching or nursing without others actually stating the expectation. Ultimately these norms, which are very common even across cultures, affect self-perception deeply and can make individuals feel dissatisfied with themselves if they don’t fit into the norms. “al jazeera new media” by Paul Keller is licensed under CC BY 2.0 Media The representations we see in the media affect our self-concept. The vast majority of media images include idealized representations of attractiveness. Despite the fact that the images of people we see in glossy magazines and on movie screens are not typically what we see when we look at the people around us in a classroom, at work, or at the grocery store, many of us continue to hold ourselves to an unrealistic standard of beauty and attractiveness. Movies, magazines, television shows, and social media sites are filled with what our society views as ideally beautiful people. Even people who possess society’s more ideal physical characteristics are further enhanced with digital manipulation (filters, photo-editing software). When “regular” people are present in the media, they are typically portrayed as the butt of jokes, villains, or only as background extras. Aside from overall attractiveness, the media also offers narrow representations of acceptable body weight and body types. Researchers have found that only 12 percent of prime-time characters are overweight, which is dramatically less than the national statistics for obesity among the actual US population. Further, an analysis of how weight is discussed on prime-time sitcoms found that larger female characters were often the targets of negative comments and jokes that audience members responded to with laughter. Conversely, positive comments about women’s bodies were related to their thinness. In short, the bigger the character, the more negative the comments, and the thinner the character, the more positive the comments. The same researchers analyzed sitcoms for content regarding male characters’ weight and found that although comments regarding their weight were made, they were fewer in number and not as negative, ultimately supporting the notion that overweight male characters are more accepted in media than overweight female characters. Much more attention has been paid in recent years to the potential negative effects of such narrow media representations. The following “Getting Critical” box explores the role of media in the construction of body image. In terms of self-concept, media representations offer us guidance on what is acceptable or unacceptable and valued or not valued in our society. Mediated messages, in general, reinforce cultural stereotypes related to race, gender, age, sexual orientation, ability, and class. People from historically marginalized groups must look much harder than those in the dominant groups to find positive representations of their identities in media. As a critical thinker, it is important to question media messages and to examine who is included and who is excluded. Advertising, in particular, encourages people to engage in social comparison, regularly communicating to us that we are inferior because we lack a certain product or that we need to change some aspect of our lives to keep up with and be similar to others. For example, for many years advertising targeted at women instilled in them a fear of having a dirty house, selling them products that promised to keep their house clean, make their family happy, and impress their friends and neighbors. Now messages tell us to fear becoming old or unattractive, selling products to keep our skin tight and clear, which will, in turn, make us happy and popular. “Body Image. The subjective concept of one’s physical appearance based on self-observation and the reactions of others.” by Charlotte Astrid is licensed under CC BY 2.0 “Getting Critical” – Body Image and Self-Perception Take a look at any magazine, television show, or movie and you will most likely see people society deems as beautiful. When you look around you in your daily life, there are likely not as many glamorous people. Scholars and media critics have critiqued this discrepancy for decades because it has contributed to many social issues and public health issues ranging from body dysmorphic disorder to eating disorders, to lowered self-esteem. Much of the media is driven by advertising, and the business of media has been to perpetuate a “culture of lack.” This means that we are constantly told, via mediated images, that we lack something. In short, advertisements often tell us we don’t have enough money, enough beauty, or enough material possessions. Over the past few decades, women’s bodies in the media have gotten smaller and thinner, while men’s bodies have gotten bigger and more muscular. At the same time, the US population has become dramatically more obese. As research shows that men and women are becoming more and more dissatisfied with their bodies, which ultimately affects their self-concept and self-esteem, health and beauty product lines proliferate and cosmetic surgeries and other types of enhancements become more and more popular. From young children to older adults, people are becoming more aware of and oftentimes unhappy with their bodies, which results in a variety of self-perception problems. Exercises 1 Reflection Questions 1. How do you think the media influences your self-perception and body image? 2. Describe the typical man that is portrayed in the media. Describe the typical woman that isportrayed in the media. What impressions do these typical bodies make on others? What are the potential positive and negative effects of the way the media portrays the human body? 3. Find an example of an “atypical” body represented in the media (a magazine, TV show, or movie). Is this person presented in a positive, negative, or neutral way? Why do you think this person was chosen? 2.3 SELF-PRESENTATION How we perceive ourselves manifests in how we present ourselves to others. Self- presentation or impression management is the process of strategically concealing or revealing personal information in order to influence others’ perceptions. We engage in this process daily and for different reasons. Although people occasionally intentionally deceive others in the process of self-presentation, in general, we try to make a good impression while still remaining authentic. Since self-presentation helps meet our instrumental, relational, and identity needs, we stand to lose quite a bit if we are caught intentionally misrepresenting ourselves. In May of 2012, Yahoo!’s CEO resigned after it became known that he stated on official documents that he had two college degrees when he actually only had one. In a similar incident, a woman who had long served as the dean of admissions for the prestigious Massachusetts Institute of Technology was dismissed from her position after it was learned that she had only attended one year of college and had falsely indicated she had a bachelor’s and master’s degree. Such incidents clearly show that although people can get away with such false self-presentation for a while, the eventual consequences of being found out are dire. As communicators, we sometimes engage in more subtle forms of inauthentic self presentation. For example, a person may state or imply that they know more about a subject or situation than they actually do in order to seem smart or “in the loop.” During a speech, a speaker works on a polished and competent delivery to distract from a lack of substantive content. These cases of strategic self presentation may not ever be found out, but communicators should still avoid them as they do not live up to the standards of ethical communication. “in which it is determined that the urge to moblog can overpower the instinct for self-preservation” by Tim Pierce is licensed under CC BY 2.0 Consciously and competently engaging in self-presentation can have benefits because we can provide others with a more positive and accurate picture of who we are. People who are skilled at impression management are typically more engaging and confident, which allows others to pick up on more cues from which to form impressions. Being a skilled self-presenter draws on many of the practices used by competent communicators, including becoming a higher self-monitor. When self-presentation skills and self-monitoring skills combine, communicators can simultaneously monitor their own expressions, the reaction of others, and the situational and social context. In general, we strive to present a public image that matches up with our self-concept, but we can also use self-presentation strategies to enhance our self-concept. When we present ourselves in order to evoke a positive evaluative response, we are engaging in self-enhancement. In the pursuit of self enhancement, a person might try to be as appealing as possible in a particular area or with a particular person to gain feedback that will enhance one’s self-esteem. For example, a singer might train and practice for weeks before singing in front of a well respected vocal coach but not invest as much effort in preparing to sing in front of friends. Although positive feedback from friends is beneficial, positive feedback from an experienced singer could enhance a person’s self-concept. Self-enhancement can be productive and achieved competently, or it can be used inappropriately. Using self-enhancement behaviors just to gain the approval of others or out of self-centeredness may lead people to communicate in ways that are perceived as phony or overbearing and end up making an unfavorable impression. “Getting Plugged In” – Self-Presentation Online: Social Media, Digital Trails, and Your Reputation Although social networking has long been a way to keep in touch with friends and colleagues, the advent of social media has made the process of making connections and those all important first impressions much more complex. Just looking at Facebook as an example, we can clearly see that the very acts of constructing a profile, posting status updates, “liking” certain things, and sharing various information via Facebook features and apps is self-presentation. People also form impressions based on the number of friends we have and the photos and posts that other people tag us in. All this information floating around can be difficult to manage. So how do we manage the impressions we make digitally given that there is a permanent record? Research shows that people overall engage in positive and honest self-presentation on Facebook. Since people know how visible the information they post is, they may choose to only reveal things they think will form favorable impressions. But the mediated nature of Facebook also leads some people to disclose more personal information than they might otherwise in such public or semi-public forums. These hyperpersonal disclosures run the risk of forming negative impressions based on who sees them. In general, the ease of digital communication, not just on Facebook, has presented new challenges for our self-control and information management. Sending someone a sexually provocative image used to take some effort before the age of digital cameras, but now “sexting” an explicit photo only takes a few seconds. So people who would have likely not engaged in such behavior before are more tempted to now, and it is the desire to present oneself as desirable or cool that leads people to send photos they may later regret. In fact, new technology in the form of apps is trying to give people a little more control over the exchange of digital information. An iPhone app called “Snapchat” allows users to send photos that will only be visible for a few seconds. Although this isn’t a guaranteed safety net, the demand for such apps is increasing, which illustrates the point that we all now leave digital trails of information that can be useful in terms of our self-presentation but can also create new challenges in terms of managing the information floating around from which others may form impressions of us. Exercises 2 Reflection Questions 1. What impressions do you want people to form of you based on the information they can see on your social media? 2. Have you ever used social media or the Internet to do “research” on a person? What things would you find favorable and unfavorable? 3. Do you have any guidelines you follow regarding what information about yourself you will put online or not? If so, what are they? If not, why? 2.4 IMPROVING SELF-PERCEPTION KEY TAKEAWAYS • Our self-concept is the overall idea of who we think we are. It is developed through our interactions with others and through social comparison that allows us to compare our beliefs and behaviors to others. • Our self-esteem is based on the evaluations and judgments we make about various characteristics of our self-concept. It is developed through an assessment and evaluation of our various skills and abilities, known as self efficacy, and through comparison and evaluation of who we are, who we would like to be, and who we should be (self-discrepancy theory). • Social comparison theory and self-discrepancy theory affect our self-concept and self-esteem because through comparison with others and comparison of our actual, ideal, and ought selves we make judgments about who we are and our self-worth. These judgments then affect how we communicate and behave. • Socializing forces like family, culture, and media affect our self-perception because they give us feedback on who we are. This feedback can be evaluated positively or negatively and can lead to positive or negative patterns that influence our self-perception and then our communication. • Self-presentation refers to the process of strategically concealing and/or revealing personal information in order to influence others’ perceptions. Prosocial self presentation is intended to benefit others and self-serving self-presentation is intended to benefit the self at the expense of others. People also engage in self enhancement, which is a self-presentation strategy by which people intentionally seek out positive evaluations. KEY TERMS KEY TERMS • Self-concept • looking glass self • social comparison theory • self-esteem, self-efficacy • symbolic interactionism • self-discrepancy theory • self-presentation ASSIGNMENT LINKS FOR INSTRUCTORS ASSIGNMENT LINKS FOR INSTRUCTORS The Self-Concept Container https://docs.google.com/document/d/0B07gGjrjXan8NE5lVlpUd2FraDQ/edit Self-Concept Journal Questions https://drive.google.com/file/d/1j9pFEu5KgopL1aC5JK2aoCmVcDIpAiQl/view?usp=sharing HUMAN COMMUNICATION: AN OPEN TEXT 57	oercommons	2025-03-18T00:36:11.035141	Terri Johnson	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/102255/overview", "title": "CHAPTER 2: COMMUNICATION AND THE SELF", "author": "Textbook" }
https://oercommons.org/courseware/lesson/15567/overview	The Declaration of Independence When in the Course of human events, it becomes necessary for one people to dissolve the political bands which have connected them with another, and to assume among the powers of the earth, the separate and equal station to which the Laws of Nature and of Nature's God entitle them, a decent respect to the opinions of mankind requires that they should declare the causes which impel them to the separation. We hold these truths to be self-evident, that all men are created equal, that they are endowed by their Creator with certain unalienable Rights, that among these are Life, Liberty and the pursuit of Happiness. —That to secure these rights, Governments are instituted among Men, deriving their just powers from the consent of the governed, —That whenever any Form of Government becomes destructive of these ends, it is the Right of the People to alter or to abolish it, and to institute new Government, laying its foundation on such principles and organizing its powers in such form, as to them shall seem most likely to effect their Safety and Happiness. Prudence, indeed, will dictate that Governments long established should not be changed for light and transient causes; and accordingly all experience hath shewn, that mankind are more disposed to suffer, while evils are sufferable, than to right themselves by abolishing the forms to which they are accustomed. But when a long train of abuses and usurpations, pursuing invariably the same Object evinces a design to reduce them under absolute Despotism, it is their right, it is their duty, to throw off such Government, and to provide new Guards for their future security. —Such has been the patient sufferance of these Colonies; and such is now the necessity which constrains them to alter their former Systems of Government. The history of the present King of Great Britain is a history of repeated injuries and usurpations, all having in direct object the establishment of an absolute Tyranny over these States. To prove this, let Facts be submitted to a candid world. He has refused his Assent to Laws, the most wholesome and necessary for the public good. He has forbidden his Governors to pass Laws of immediate and pressing importance, unless suspended in their operation till his Assent should be obtained; and when so suspended, he has utterly neglected to attend to them. He has refused to pass other Laws for the accommodation of large districts of people, unless those people would relinquish the right of Representation in the Legislature, a right inestimable to them and formidable to tyrants only. He has called together legislative bodies at places unusual, uncomfortable, and distant from the depository of their public Records, for the sole purpose of fatiguing them into compliance with his measures. He has dissolved Representative Houses repeatedly, for opposing with manly firmness his invasions on the rights of the people. He has refused for a long time, after such dissolutions, to cause others to be elected; whereby the Legislative powers, incapable of Annihilation, have returned to the People at large for their exercise; the State remaining in the mean time exposed to all the dangers of invasion from without, and convulsions within. He has endeavoured to prevent the population of these States; for that purpose obstructing the Laws for Naturalization of Foreigners; refusing to pass others to encourage their migrations hither, and raising the conditions of new Appropriations of Lands. He has obstructed the Administration of Justice, by refusing his Assent to Laws for establishing Judiciary powers. He has made Judges dependent on his Will alone, for the tenure of their offices, and the amount and payment of their salaries. He has erected a multitude of New Offices, and sent hither swarms of Officers to harrass our people, and eat out their substance. He has kept among us, in times of peace, Standing Armies without the Consent of our legislatures. He has affected to render the Military independent of and superior to the Civil power. He has combined with others to subject us to a jurisdiction foreign to our constitution, and unacknowledged by our laws; giving his Assent to their Acts of pretended Legislation: For Quartering large bodies of armed troops among us: For protecting them, by a mock Trial, from punishment for any Murders which they should commit on the Inhabitants of these States: For cutting off our Trade with all parts of the world: For imposing Taxes on us without our Consent: For depriving us in many cases, of the benefits of Trial by Jury: For transporting us beyond Seas to be tried for pretended offences: For abolishing the free System of English Laws in a neighbouring Province, establishing therein an Arbitrary government, and enlarging its Boundaries so as to render it at once an example and fit instrument for introducing the same absolute rule into these Colonies: For taking away our Charters, abolishing our most valuable Laws, and altering fundamentally the Forms of our Governments: For suspending our own Legislatures, and declaring themselves invested with power to legislate for us in all cases whatsoever. He has abdicated Government here, by declaring us out of his Protection and waging War against us. He has plundered our seas, ravaged our Coasts, burnt our towns, and destroyed the lives of our people. He is at this time transporting large Armies of foreign Mercenaries to compleat the works of death, desolation and tyranny, already begun with circumstances of Cruelty & perfidy scarcely paralleled in the most barbarous ages, and totally unworthy the Head of a civilized nation. He has constrained our fellow Citizens taken Captive on the high Seas to bear Arms against their Country, to become the executioners of their friends and Brethren, or to fall themselves by their Hands. He has excited domestic insurrections amongst us, and has endeavoured to bring on the inhabitants of our frontiers, the merciless Indian Savages, whose known rule of warfare, is an undistinguished destruction of all ages, sexes and conditions. In every stage of these Oppressions We have Petitioned for Redress in the most humble terms: Our repeated Petitions have been answered only by repeated injury. A Prince whose character is thus marked by every act which may define a Tyrant, is unfit to be the ruler of a free people. Nor have We been wanting in attentions to our Brittish brethren. We have warned them from time to time of attempts by their legislature to extend an unwarrantable jurisdiction over us. We have reminded them of the circumstances of our emigration and settlement here. We have appealed to their native justice and magnanimity, and we have conjured them by the ties of our common kindred to disavow these usurpations, which, would inevitably interrupt our connections and correspondence. They too have been deaf to the voice of justice and of consanguinity. We must, therefore, acquiesce in the necessity, which denounces our Separation, and hold them, as we hold the rest of mankind, Enemies in War, in Peace Friends. We, therefore, the Representatives of the united States of America, in General Congress, Assembled, appealing to the Supreme Judge of the world for the rectitude of our intentions, do, in the Name, and by Authority of the good People of these Colonies, solemnly publish and declare, That these United Colonies are, and of Right ought to be Free and Independent States; that they are Absolved from all Allegiance to the British Crown, and that all political connection between them and the State of Great Britain, is and ought to be totally dissolved; and that as Free and Independent States, they have full Power to levy War, conclude Peace, contract Alliances, establish Commerce, and to do all other Acts and Things which Independent States may of right do. And for the support of this Declaration, with a firm reliance on the protection of divine Providence, we mutually pledge to each other our Lives, our Fortunes and our sacred Honor. The 56 signatures on the Declaration appear in the positions indicated: Column 1 Georgia: Button Gwinnett Lyman Hall George Walton Column 2 North Carolina: William Hooper Joseph Hewes John Penn South Carolina: Edward Rutledge Thomas Heyward, Jr. Thomas Lynch, Jr. Arthur Middleton Column 3 Massachusetts: John Hancock Maryland: Samuel Chase William Paca Thomas Stone Charles Carroll of Carrollton Virginia: George Wythe Richard Henry Lee Thomas Jefferson Benjamin Harrison Thomas Nelson, Jr. Francis Lightfoot Lee Carter Braxton Column 4 Pennsylvania: Robert Morris Benjamin Rush Benjamin Franklin John Morton George Clymer James Smith George Taylor James Wilson George Ross Delaware: Caesar Rodney George Read Thomas McKean Column 5 New York: William Floyd Philip Livingston Francis Lewis Lewis Morris New Jersey: Richard Stockton John Witherspoon Francis Hopkinson John Hart Abraham Clark Column 6 New Hampshire: Josiah Bartlett William Whipple Massachusetts: Samuel Adams John Adams Robert Treat Paine Elbridge Gerry Rhode Island: Stephen Hopkins William Ellery Connecticut: Roger Sherman Samuel Huntington William Williams Oliver Wolcott New Hampshire: Matthew Thornton	oercommons	2025-03-18T00:36:11.058765	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15567/overview", "title": "U.S. History, The Declaration of Independence", "author": null }
https://oercommons.org/courseware/lesson/15571/overview	Sign in to see your Hubs Sign in to see your Groups Create a standalone learning module, lesson, assignment, assessment or activity Submit OER from the web for review by our librarians Please log in to save materials. Log in or	oercommons	2025-03-18T00:36:11.092665	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15571/overview", "title": "U.S. History, U.S. Topographical Map", "author": null }
https://oercommons.org/courseware/lesson/15573/overview	Further Reading THE PRE-COLUMBIAN WORLD AND EARLY GLOBALIZATION Alchon, Suzanne Austin. 2003. A Pest in the Land: New World Epidemics in a Global Perspective. Albuquerque: University of New Mexico Press. Brown, Kathleen M. 1996. Good Wives, Nasty Wenches, and Anxious Patriarchs: Gender, Race, and Power in Colonial Virginia. Chapel Hill: University of North Carolina Press. Clendinnen, Inga. 1991. Aztecs: An Interpretation. Cambridge: Cambridge University Press. Cook, Harold John. 2007. Matters of Exchange: Commerce, Medicine, and Science in the Dutch Golden Age. New Haven: Yale University Press. Curtin, Philip D. 1990. The Rise and Fall of the Plantation Complex: Essays in Atlantic History. Cambridge: Cambridge University Press. Leon, Portilla Miguel. (1992) 2006. The Broken Spears: The Aztec Account of the Conquest of Mexico. Boston: Beacon Press. Mann, Charles C. 2005. 1491: New Revelations of the Americas Before Columbus. New York: Knopf. —. 2011. 1493: Uncovering the New World Columbus Created. New York: Knopf. Meltzer, David J. 2009. First Peoples in a New World: Colonizing Ice Age America. Berkeley: University of California Press. Niane, Djibril Tamsir. 1965. Sundiata: An Epic of Old Mali. Translated by G. D. Pickett. London: Longmans. Northrup, David. 2013. Africa's Discovery of Europe. Oxford: Oxford University Press. Pagden, Anthony. 1995. Lords of all the World: Ideologies of Empire in Spain, Britain and France c.1500–c.1800. New Haven: Yale University Press. Prescott, William Hickling. 1936. History of the Conquest of Mexico, and History of the Conquest of Peru. New York: Modern Library. Seed, Patricia. 1995. Ceremonies of Possession in Europe’s Conquest of the New World, 1492–1640. Cambridge: Cambridge University Press. Taylor, Alan. 2002. American Colonies. New York: Penguin Books. Thornton, John K. 1992. Africa and Africans in the Making of the Atlantic World, 1400–1680. Cambridge: Cambridge University Press. Wey Gómez, Nicolás. 2008. The Tropics of Empire: Why Columbus Sailed South to the Indies. Cambridge, MA: MIT Press. THE COLONIAL AMERICAS Bailyn, Bernard. 2012. The Barbarous Years: The Peopling of British North America: The Conflict of Civilizations, 1600–1675. New York: Vintage Books. Berlin, Ira. 1998. Many Thousands Gone: The First Two Centuries of Slavery in North America. Cambridge, MA: Belknap Press. Calloway, Colin G. 2011. First Peoples: A Documentary Survey of American Indian History. Fourth edition, Boston: Bedford/St. Martin’s Press. Elliott, J. H. 2006. Empires of the Atlantic World: Britain and Spain in America, 1492–1830. New Haven: Yale University Press. Fischer, David H. 1989. Albion’s Seed: Four British Folkways in America. New York: Oxford University Press. Gaustad, Edwin S. 1982. A Documentary History of Religion in America. Grand Rapids, MI: Eerdmans. Gibson, Charles. 1964. The Aztecs Under Spanish Rule: A History of the Indians of the Valley of Mexico, 1519–1810. Stanford, CA: Stanford University Press. Hatfield, April Lee. 2004. Atlantic Virginia: Intercolonial Relations in the Seventeenth Century. Philadelphia: University of Pennsylvania Press. Liss, Peggy K. 1975. Mexico Under Spain, 1521–1556: Society and the Origins of Nationality. Chicago: University of Chicago Press. Morgan, Edmund S. 1958. The Puritan Dilemma: The Story of John Winthrop. Boston: Little, Brown. Rediker, Marcus. 2007. The Slave Ship: A Human History. New York: Viking Books. Richter, Daniel K. 2001. Facing East from Indian Country: A Native History of Early America. Cambridge, MA: Harvard University Press. Roberts, David. 2004. The Pueblo Revolt: The Secret Rebellion that Drove the Spaniards Out of the Southwest. New York: Simon & Schuster. Spicer, Edward Holland. 1962. Cycles of Conquest: The Impact of Spain, Mexico, and the United States on the Indians of the Southwest, 1533–1960. Tucson: University of Arizona Press. Twinam, Ann. 1982. Miners, Merchants, and Farmers in Colonial Colombia. Austin: University of Texas Press. Weber, David J. 1992. The Spanish Frontier in North America. New Haven: Yale University Press. REFORM, PROTEST, AND REVOLUTION Anderson, Fred. 2005. The War That Made America: A Short History of the French and Indian War. New York: Viking Books. Bailyn, Bernard. 1986. The Peopling of British North America: An Introduction. New York: Knopf Doubleday. Breen, Timothy H. 2004. The Marketplace of Revolution: How Consumer Politics Shaped American Independence. Oxford: Oxford University Press. Butler, Jon. 2000. Becoming America: The Revolution before 1776. Cambridge, MA: Harvard University Press. Calloway, Colin G. 1995. The American Revolution in Indian Country: Crisis and Diversity in Native American Communities. Cambridge: Cambridge University Press. Cook, Don. 1995. The Long Fuse: How England Lost the American Colonies, 1760–1785. New York: Atlantic Monthly Press. Egerton, Douglas R. 2009. Death or Liberty: African Americans and Revolutionary America. Oxford: Oxford University Press. Ellis, Joseph J. 2003. Founding Brothers: The Revolutionary Generation. New York: Random House. Fischer, David Hackett. 2004. Washington’s Crossing. Oxford: Oxford University Press. Fleming, Thomas J. 1997. Liberty! The American Revolution. New York: Viking Books. Holton, Woody. 1999. Forced Founders: Indians, Debtors, Slaves, and the Making of the American Revolution in Virginia. Chapel Hill: University of North Carolina Press. —. 2007. Unruly Americans and the Origins of the Constitution. New York: Hill and Wang. Isaac, Rhys. 1982. The Transformation of Virginia, 1740-1790. Chapel Hill: University of North Carolina Press. Lovejoy, David S. 1972. The Glorious Revolution in America. New York: Harper & Row. McCullough, David. 2005. 1776. New York: Simon & Schuster. Middlekauff, Robert. 1982. The Glorious Cause: The American Revolution, 1763–1789. New York: Oxford University Press. Noll, Mark A. 2003. The Rise of Evangelicalism: The Age of Edwards, Whitefield, and the Wesleys. Downers Grove, IL: InterVarsity Press. Norton, Mary Beth. 1980. Liberty’s Daughters: The Revolutionary Experience of American Women, 1750–1800. Boston: Little, Brown. Olwell, Robert. 1998. Masters, Slaves & Subjects: The Culture of Power in the South Carolina Low Country, 1740–1790. Ithaca, NY: Cornell University Press. Rakove, Jack N. 2010. Revolutionaries: A New History of the Invention of America. Boston: Houghton Mifflin Harcourt. Raphael, Ray. 2001. A People’s History of the American Revolution: How Common People Shaped the Fight for Independence. New York: New Press. Stout, Harry S. 1991. The Divine Dramatist: George Whitefield and the Rise of Modern Evangelicalism. Grand Rapids, MI: Eerdmans. Webb, Stephen Saunders. 1995. Lord Churchill’s Coup: The Anglo-American Empire and the Glorious Revolution Reconsidered. New York: Knopf. Wood, Gordon S. 1992. The Radicalism of the American Revolution. New York: Knopf. Young, Alfred Fabian. 1999. The Shoemaker and the Tea Party: Memory and the American Revolution. Boston: Beacon Press. THE EARLY REPUBLIC Appleby, Joyce Oldham. 2000. Inheriting the Revolution: The First Generation of Americans. Cambridge, MA: Belknap Press. Dubois, Laurent. 2004. Avengers of the New World: The Story of the Haitian Revolution. Cambridge, MA: Belknap Press. Ellis, Joseph J. 1997. American Sphinx: The Character of Thomas Jefferson. New York: Knopf. Ferling, John. 2004. Adams vs. Jefferson: The Tumultuous Election of 1800. New York: Oxford University Press. Hickey, Donald R. 1989. The War of 1812: A Forgotten Conflict. Urbana: University of Illinois Press. Kamensky, Jane. 2008. The Exchange Artist: A Tale of High-Flying Speculation and America’s First Banking Collapse. New York: Viking Books. Langguth, A. J. 2006. Union 1812: The Americans Who Fought the Second War of Independence. New York: Simon & Schuster. Litwack, Leon F. 1961. North of Slavery: The Negro in the Free States, 1790–1860. Chicago: University of Chicago Press. Maier, Pauline. 1997. American Scripture: Making the Declaration of Independence. New York: Knopf. Smith, Jean Edward. 1996. John Marshall: Definer of a Nation. New York: Holt. Taylor, Alan. 2010. The Civil War of 1812: American Citizens, British Subjects, Irish Rebels, & Indian Allies. New York: Vintage Books. INDUSTRIALIZATION AND TRANSFORMATION Blackmar, Elizabeth. 1989. Manhattan for Rent, 1785–1850. Ithaca, NY: Cornell University Press. Howe, Daniel Walker. 2007. What Hath God Wrought: The Transformation of America, 1815–1848. New York: Oxford University Press. Igler, David. 2013. The Great Ocean: Pacific Worlds from Captain Cook to the Gold Rush. Oxford: Oxford University Press. Johnson, Paul E. 1978. A Shopkeeper’s Millennium: Society and Revivals in Rochester, New York, 1815–1837. New York: Hill and Wang. Johnson, Walter. 1999. Soul by Soul: Life Inside the Antebellum Slave Market. Cambridge, MA: Harvard University Press. Marx, Leo. 1964. The Machine in the Garden: Technology and the Pastoral Ideal in America. New York: Oxford University Press. Rees, Jonathan. 2013. Industrialization and the Transformation of American Life: A Brief Introduction. Armonk, NY: M.E. Sharpe. Sandage, Scott A. 2005. Born Losers: A History of Failure in America. Cambridge, MA: Harvard University Press. JACKSONIAN DEMOCRACY Allgor, Catherine. 2000. Parlor Politics: In Which the Ladies of Washington Help Build a City and a Government. Charlottesville: University of Virginia Press. Deloria, Philip Joseph. 1998. Playing Indian. New Haven: Yale University Press. Deyle, Steven. 2005. Carry Me Back: The Domestic Slave Trade in American Life. New York: Oxford University Press. Dippie, Brian W. 1982. The Vanishing American: White Attitudes and U.S. Indian Policy. Middletown, CT: Wesleyan University Press. Feller, Daniel. 1995. The Jacksonian Promise: America, 1815–1840. Baltimore: Johns Hopkins University Press. Marszalek, John F. 1997. The Petticoat Affair: Manners, Mutiny, and Sex in Andrew Jackson’s White House. New York: Free Press. Meacham, Jon. 2008. American Lion: Andrew Jackson in the White House. New York: Random House. Mihm, Stephen. 2007. A Nation of Counterfeiters: Capitalists, Con Men, and the Making of the United States. Cambridge, MA: Harvard University Press. Saxton, Alexander. 1990. The Rise and Fall of the White Republic: Class Politics and Mass Culture in Nineteenth-Century America. London: Verso. Sellers, Charles. 1991. The Market Revolution: Jacksonian America, 1815–1846. New York: Oxford University Press. Steinberg, Theodore. 1991. Nature Incorporated: Industrialization and the Waters of New England. Cambridge: Cambridge University Press. Watson, Harry L. 1990. Liberty and Power: The Politics of Jacksonian America. New York: Hill and Wang. —. 1998. Andrew Jackson vs. Henry Clay: Democracy and Development in Antebellum America. Boston: Bedford/St. Martin’s Press. Wilentz, Sean. 2005. The Rise of American Democracy: Jefferson to Lincoln. New York: Norton. THE ANTEBELLUM SOUTH Berlin, Ira. 2003. Generations of Captivity: A History of African-American Slaves. Cambridge, MA: Belknap Press. Clark, Emily. 2013. The Strange History of the American Quadroon: Free Women of Color in the Revolutionary Atlantic World. Chapel Hill: University of North Carolina Press. Delfino, Susanna, and Michele Gillespie. 2002. Neither Lady nor Slave: Working Women of the Old South. Chapel Hill: University of North Carolina Press. Fox-Genovese, Elizabeth. 1988. Within the Plantation Household: Black and White Women of the Old South. Chapel Hill: University of North Carolina Press. Genovese, Eugene D. 1974. Roll, Jordan, Roll: The World the Slaves Made. New York: Pantheon Books. Hall, Gwendolyn Midlo. 1992. Africans in Colonial Louisiana: The Development of Afro-Creole Culture in the Eighteenth Century. Baton Rouge: Louisiana State University Press. Johnson, Walter. 1999. Soul by Soul: Life Inside the Antebellum Slave Market. Cambridge, MA: Harvard University Press. McCurry, Stephanie. 1995. Masters of Small Worlds: Yeoman Households, Gender Relations, and the Political Culture of the Antebellum South Carolina Low Country. New York: Oxford University Press. Potter, David Morris, and Don E. Fehrenbacher. 1976. The Impending Crisis, 1848–1861. New York: Harper & Row. Rasmussen, Daniel. 2011. American Uprising: The Untold Story of America’s Largest Slave Revolt. New York: HarperCollins. Wyatt-Brown, Bertram. 1982. Southern Honor: Ethics and Behavior in the Old South. New York: Oxford University Press. REFORM AND ABOLITION DuBois, Ellen Carol. 1978. Feminism and Suffrage: The Emergence of an Independent Women’s Movement in America, 1848-1869. Ithaca, NY: Cornell University Press. DuBois, Ellen Carol, and Lynn Dumenil. 2005. Through Women’s Eyes: An American History with Documents. Boston: Bedford/St. Martin’s Press. Heyrman, Christine Leigh. 1997. Southern Cross: The Beginnings of the Bible Belt. New York: Knopf. Mayer, Henry. 1998. All On Fire: William Lloyd Garrison and the Abolition of Slavery. New York: Bedford/St. Martin’s Press. Mintz, Steven. 1995. Moralists and Modernizers: America’s Pre-Civil War Reformers. Baltimore: Johns Hopkins University Press. Rorabaugh, W. J. 1979. The Alcoholic Republic, an American Tradition. New York: Oxford University Press. Stewart, James Brewer. 1976. Holy Warriors: The Abolitionists and American Slavery. New York: Hill and Wang. CIVIL WAR AND RECONSTRUCTION Alcott, Louisa May, and Bessie Zahan Jones. 1960. Hospital Sketches. Cambridge, MA: Harvard University Press. Berlin, Ira, Joseph P. Reidy, and Leslie S. Rowland. 1998. Freedom’s Soldiers: The Black Military Experience in the Civil War. Cambridge: Cambridge University Press. Blight, David W. 2001. Race and Reunion: The Civil War in American Memory. Cambridge, MA: Belknap Press. Catton, Bruce. 1962. Mr. Lincoln’s Army. Garden City, NY: Doubleday. Donald, David Herbert. 1960. Charles Sumner and the Coming of the Civil War. New York: Knopf. Earle, Jonathan Halperin. 2008. John Brown’s Raid on Harpers Ferry: A Brief History with Documents. Boston: Bedford/St. Martin’s Press. Egerton, Douglas R. 2014. The Wars of Reconstruction: The Brief, Violent History of America’s Most Progressive Era. London: Bloomsbury Press. Emberton, Carole. 2013. Beyond Redemption: Race, Violence, and the American South After the Civil War. Chicago: University of Chicago Press. Faust, Drew Gilpin. 2008. This Republic of Suffering: Death and the American Civil War. New York: Knopf. Fehrenbacher, Don E. 1978. The Dred Scott Case, Its Significance in American Law and Politics. New York: Oxford University Press. Foner, Eric. 1970. Free Soil, Free Labor, Free Men: The Ideology of the Republican Party Before the Civil War. New York: Oxford University Press. —. 2006. Forever Free: The Story of Emancipation and Reconstruction. New York: Vintage Books. Gallagher, Gary W. 2011. The Union War. Cambridge, MA: Harvard University Press. —. 2013. Becoming Confederates: Paths to a New National Loyalty. Atlanta: University of Georgia Press. Gienapp, William E. 2002. Abraham Lincoln and Civil War America: A Biography. New York: Oxford University Press. Goodwin, Doris Kearns. 2006. Team of Rivals: The Political Genius of Abraham Lincoln. New York: Simon & Schuster. Guelzo, Allen C. 2013. Gettysburg: The Last Invasion. New York: Knopf Hahn, Steven. 2003. A Nation Under Our Feet: Black Political Struggles in the Rural South, from Slavery to the Great Migration. Cambridge, MA: Belknap Press. Holt, Michael F. 1978. The Political Crisis of the 1850s. New York: Wiley. LaFantasie, Glenn W. 2007. Twilight at Little Round Top: July 2, 1863—The Tide Turns at Gettysburg. New York: Vintage Books. Lemann, Nicholas. 2006. Redemption: The Last Battle of the Civil War. New York: Farrar, Straus & Giroux. Levine, Bruce C., and Eric Foner. 1992. Half Slave and Half Free: The Roots of Civil War. New York: Hill and Wang. Manning, Chanda. 2008. What this Cruel War Was Over: Soldiers, Slavery, and the Civil War. New York: Vintage Books. McPherson, James M. 1994. What They Fought For 1861–1865. Baton Rouge: Louisiana State University Press. Oates, Stephen B. 1970. To Purge This Land with Blood: A Biography of John Brown. New York: Harper & Row. Richardson, Heather Cox. 2001. The Death of Reconstruction: Race, Labor, and Politics in the Post-Civil War North, 1865–1901. Cambridge, MA: Harvard University Press. Stampp, Kenneth M. 1990. America in 1857: A Nation on the Brink. New York: Oxford University Press. Thomas, Emory M. 1991. The Confederacy as a Revolutionary Experience. Columbia: University of South Carolina Press. Vorenberg, Michael. 2001. Final Freedom: The Civil War, the Abolition of Slavery, and the Thirteenth Amendment. Cambridge: Cambridge University Press. Williams, Heather Andrea. 2005. Self-Taught: African American Education in Slavery and Freedom. Chapel Hill: University of North Carolina Press. WESTWARD EXPANSION Brown, Dee. 1970. Bury My Heart at Wounded Knee: An Indian History of the American West. New York: Holt Rinehart Winston. Dando-Collins, Stephen. 2008. Tycoon’s War: How Cornelius Vanderbilt Invaded a Country to Overthrow America’s Most Famous Military Adventurer. Philadelphia: Da Capo Press. Greenberg, Amy S. 2012. A Wicked War: Polk, Clay, Lincoln, and the 1846 U.S. Invasion of Mexico. New York: Knopf. Madley, Benjamin. 2012. “The Genocide of California’s Yana Indians.” In Centuries of Genocide: Essays and Eyewitness Accounts, edited by Samuel Totten and Williams S. Parsons, 16–53. New York: Routledge. Mahon, John K. 1967. History of the Second Seminole War, 1835–1842. Gainesville: University of Florida Press. Neihardt, John G. 1975. Black Elk Speaks: Being the Life Story of a Holy Man of the Oglala Sioux. New York: Pocket Books. Richardson, Heather Cox. 2008. West from Appomattox: The Reconstruction of America After the Civil War. New Haven: Yale University Press. Soluri, John. 2005. Banana Cultures: Agriculture, Consumption, and Environmental Change in Honduras and the United States. Austin: University of Texas Press. Stephanson, Anders. 1995. Manifest Destiny: American Expansionism and the Empire of Right. New York: Hill and Wang. White, Richard. 2011. Railroaded: The Transcontinentals and the Making of Modern America. New York: Norton. FROM THE GILDED AGE TO THE PROGRESSIVE ERA Addams, Jane, and Norah Hamilton. 1910. Twenty Years at Hull-House: With Autobiographical Notes. New York: Macmillan. Bederman, Gail. 1995. Manliness & Civilization: A Cultural History of Gender and Race in the United States, 1880–1917. Chicago: University of Chicago Press. Berg, A. Scott. 2013. Wilson. New York: Simon & Schuster. Boyer, Paul S. 1978. Urban Masses and Moral Order in America, 1820–1920. Cambridge, MA: Harvard University Press. Chauncey, George. 1994. Gay New York: Gender, Urban Culture, and the Makings of the Gay Male World, 1890-1940. New York: Basic Books. Cronon, William. 1991. Nature's Metropolis: Chicago and the Great West. New York: Norton. Dalton, Kathleen. 2002. Theodore Roosevelt: A Strenuous Life. New York: Knopf. Dewey, John. 1915. The School and Society. Chicago: The University of Chicago Press. Du Bois, W. E. B., David W. Blight, and Robert Gooding-Williams. 1997. The Souls of Black Folk. Boston: Bedford Books. Fitzpatrick, Ellen F., Lincoln Steffens, Ida M. Tarbell, and Ray Stannard Baker. 1994. Muckraking: Three Landmark Articles. Boston: Bedford/St. Martin’s Press. Gilmore, Glenda E. 1996. Gender and Jim Crow: Women and the Politics of White Supremacy in North Carolina. Chapel Hill: University of North Carolina Press. Goodwin, Doris Kearns. 2013. The Bully Pulpit: Theodore Roosevelt, William Howard Taft, and the Golden Age of Journalism. New York: Simon & Schuster. Goodwyn, Lawrence. 1976. Democratic Promise: The Populist Moment in America. New York: Oxford University Press. Hershkowitz, Leo. 1977. Tweed’s New York: Another Look. Garden City, NY: Anchor Press. James, William. 1975. Pragmatism. Cambridge, MA: Harvard University Press. Kraditor, Aileen S. 1981. The Ideas of the Woman Suffrage Movement 1890–1920. New York: Norton. Lears, T. J. Jackson. 2009. Rebirth of a Nation: The Making of Modern America, 1877–1920. New York: HarperCollins. Lunardini, Christine A. 1986. From Equal Suffrage to Equal Rights: Alice Paul and the National Woman’s Party, 1910–1928. New York: New York University Press. Matthews, Jean V. 2003. The Rise of the New Woman: The Women’s Movement in America, 1875–1930. Chicago: Dee. Osofsky, Gilbert. 1971. Harlem: The Making of a Ghetto. Negro New York, 1890–1930. New York: Harper & Row. Pegram, Thomas R. 1998. Battling Demon Rum: The Struggle for a Dry America, 1800–1933. Chicago: Dee. Peiss, Kathy Lee. 1986. Cheap Amusements: Working Women and Leisure in Turn-of-the-Century New York. Philadelphia: Temple University Press. Quammen, David. 2008. Charles Darwin On the Origin of Species: The Illustrated Edition. New York: Sterling. Riis, Jacob A. 1971. How the Other Half Lives: Studies Among the Tenements of New York. New York: Dover. Sinclair, Upton. 1971. The Jungle. Cambridge, MA: Bentley. Von Drehle, David. 2003. Triangle: The Fire That Changed America. New York: Atlantic Monthly Press. Washington, Booker T. 1963. Up from Slavery, An Autobiography. Garden City, NY: Doubleday. Wiebe, Robert H. The Search for Order, 1877–1920. New York: Hill and Wang. Woodward, C. Vann. 1957. The Strange Career of Jim Crow. New York: Oxford University Press. IMPERIAL EXPANSION AND THE FIRST WORLD WAR Barry, John M. 2004. The Great Influenza: The Epic Story of the Deadliest Plague in History. New York: Viking Books. Eisenhower, John S. D. 2001. Yanks: The Epic Story of the American Army in World War I. New York: Simon & Schuster. Fromkin, David. 2004. Europe’s Last Summer: Who Started the Great War in 1914? New York: Knopf. Hart, Peter. 2007. Aces Falling: War Above the Trenches, 1918. London: Weidenfeld & Nicolson. Hoganson, Kristin L. 1998. Fighting for American Manhood: How Gender Politics Provoked the Spanish-American and Philippine-American Wars. New Haven: Yale University Press. Kaplan, Amy. 2002. The Anarchy of Empire in the Making of U.S. Culture. Cambridge, MA: Harvard University Press. Kennedy, David M. 1980. Over Here: The First World War and American Society. New York: Oxford University Press. Lengel, Edward G. 2008. To Conquer Hell: The Meuse-Argonne, 1918. New York: Holt. Maier, Charles S. 2006. Among Empires: American Ascendancy and Its Predecessors. Cambridge, MA: Harvard University Press. McCullough, David G. 1977. The Path between the Seas: The Creation of the Panama Canal, 1870–1914. New York: Simon & Schuster. Thomas, Evan. 2010. The War Lovers: Roosevelt, Lodge, Hearst, and the Rush to Empire, 1898. New York: Little, Brown. Tooze, J. Adam. 2014. The Deluge: The Great War and the Remaking of Global Order 1916–1931. New York: Viking Books. Twain, Mark. 2009. Following the Equator A Journey Around the World. Waiheke Island: Floating Press. THE ROARING TWENTIES Allen, Frederick Lewis. 1931. Only Yesterday: An Informal History of the Nineteen-Twenties. New York: Harper & Bros. Bryson, Bill. 2013. One Summer: America, 1927. New York: Anchor Books. Davison M. Douglas. 2005. Jim Crow Moves North: The Battle over Northern School Desegregation, 1865–1954. New York: Cambridge University Press. Moore, Lucy. 2010. Anything Goes: A Biography of the Roaring Twenties. New York: Overlook Press. Robinson, Thomas A., and Lanette R. Ruff. 2011. Out of the Mouths of Babes: Girl Evangelists in the Flapper Era. New York: Oxford University Press. Russell, Francis. 1968. The Shadow of Blooming Grove: Warren G. Harding in His Times. New York: McGraw-Hill. Shlaes, Amity. 2013. Coolidge. New York: Harper. Watts, Steven. 2005. The People’s Tycoon: Henry Ford and the American Century. New York: Knopf. THE GREAT DEPRESSION AND THE NEW DEAL Browder, Laura. 1998. Rousing the Nation Radical Culture in Depression America. Amherst: University of Massachusetts Press. Cohen, Lizabeth. 1990. Making a New Deal: Industrial Workers in Chicago, 1919–1939. Cambridge: Cambridge University Press. Domhoff, G. William, and Michael J. Webber. 2011. Class and Power in the New Deal: Corporate Moderates, Southern Democrats, and the Liberal-Labor Coalition. Stanford, CA: Stanford University Press. Hamby, Alonzo L. 2004. For the Survival of Democracy: Franklin Roosevelt and the World Crisis of the 1930s. New York: Free Press. Hofstadter, Richard. 1955. The Age of Reform: From Bryan to F.D.R. New York: Knopf. Hurt, R. Douglas. 1984. The Dust Bowl: An Agricultural and Social History. Chicago: Nelson-Hall. Katznelson, Ira. 2013. Fear Itself: The New Deal and the Origins of Our Time. New York: Norton. Kennedy, David M. 1999. Freedom from Fear: The American People in Depression and War, 1929–1945. New York: Oxford University Press. Lumley, Darwyn H. 2009. Breaking the Banks in Motor City: The Auto Industry, the 1933 Detroit Banking Crisis and the Start of the New Deal. Jefferson, NC: McFarland. Poppendieck, Janet, and Marion Nestle. 2014. Breadlines Knee-Deep in Wheat: Food Assistance in the Great Depression. Berkeley: University of California Press. Shindo, Charles J. 1997. Dust Bowl Migrants in the American Imagination. Lawrence: University of Kansas Press. Shlaes, Amity. 2007. The Forgotten Man: A New History of the Great Depression. New York: HarperCollins. Smith, Fred C. 2014. Trouble in Goshen: Plain Folk, Roosevelt, Jesus, and Marx in the Great Depression South. Jackson: University Press of Mississippi. Solomon, William. 2002. Literature, Amusement, and Technology in the Great Depression. Cambridge: Cambridge University Press. Terkel, Studs. 1970. Hard Times: An Oral History of the Great Depression. New York: Pantheon Books. WORLD WAR, COLD WAR, AND AMERICAN PROSPERITY Dobrynin, Anatoly. 1995. In Confidence: Moscow’s Ambassador to America’s Six Cold War Presidents. New York: Crown. Doenecke, Justus D., and Mark A. Stoler. 2005. Debating Franklin D. Roosevelt’s Foreign Policies, 1933–1945. Lanham, MD: Rowman & Littlefield. Fischer, Conan. 2003. The Ruhr Crisis, 1923–1924. Oxford: Oxford University Press. Homan, Lynn M., and Thomas Reilly. 2001. Black Knights: The Story of the Tuskegee Airmen. Gretna, LA: Pelican. Kessler-Harris, Alice. 1982. Out to Work: A History of Wage-Earning Women in the United States. New York: Oxford University Press. Mitchell, Greg. 1998. Tricky Dick and the Pink Lady: Richard Nixon vs. Helen Gahagan Douglas—Sexual Politics and the Red Scare, 1950. New York: Random House. O’Sullivan, John. 2006. The President, the Pope, and the Prime Minister: Three Who Changed the World. New York: Regnery. Overy, R. J. 1995. Why the Allies Won. New York: Norton. Robinson, Jo Ann Gibson, and David J. Garrow. 1987. The Montgomery Bus Boycott and the Women Who Started It: The Memoir of Jo Ann Gibson Robinson. Knoxville: University of Tennessee Press. Schweizer, Peter. 2002. Reagan’s War: The Epic Story of His Forty-Year Struggle and Final Triumph over Communism. New York: Doubleday. Sone, Monica Itoi. 1979. Nisei Daughter. Seattle: University of Washington Press. Weinberg, Gerhard L. 1994. A World at Arms: A Global History of World War II. Cambridge: Cambridge University Press. Wyman, David S. 1998. The Abandonment of the Jews: America and the Holocaust 1941–1945. New York: New Press. FROM CAMELOT TO CULTURE WARS Appy, Christian G. 2003. Patriots: The Vietnam War Remembered from All Sides. New York: Viking Books. Branch, Taylor. 1988. Parting the Waters: America in the King Years, 1954–63. New York: Simon & Schuster. Clendinen, Dudley, and Adam Nagourney. 1999. Out for Good: The Struggle to Build a Gay Rights Movement in America. New York: Simon & Schuster. Clinton, Bill. 2004. My Life. New York: Knopf. Cowie, Jefferson. 2010. Stayin’ Alive: The 1970s and the Last Days of the Working Class. New York: New Press. Delpla, Isabelle, Xavier Bougarel, and Jean-Louis Fournel, eds. 2012. Investigating Srebrenica: Institutions, Facts, Responsibilities. New York: Berghahn Books. Dudziak, Mary L. 2000. Cold War Civil Rights: Race and the Image of American Democracy. Princeton, NJ: Princeton University Press. Farber, David R. 1994. The Age of Great Dreams: America in the 1960s. New York: Hill and Wang. Frank, Thomas. 2004. What's the Matter with Kansas? How Conservatives Won the Heart of America. New York: Metropolitan Books. Friedan, Betty. 1963. The Feminine Mystique. New York: Norton. Gitlin, Todd. 1993. The Sixties: Years of Hope, Days of Rage. New York: Bantam Books. Goodwin, Doris Kearns. 1976. Lyndon Johnson and the American Dream. New York: Harper & Row. Karnow, Stanley. 1983. Vietnam, a History. New York: Viking Press. King, Martin Luther. 1986. A Testament of Hope: The Essential Writings of Martin Luther King, Jr. Edited by James Melvin Washington. San Francisco: Harper & Row. Levy, Ariel. 2006. Female Chauvinist Pigs: Women and the Rise of Raunch Culture. New York: Free Press. McCain, John, and Mark Salter. 1999. Faith of My Fathers. New York: Random House. Meriwether, James. 2008. “‘Worth a Lot of Negro Votes:’ Black Voters, Africa, and the 1960 Presidential Campaign.” Journal of American History 95(3): 737–63. Murch, Donna Jean. 2010. Living for the City: Migration, Education, and the Rise of the Black Panther Party in Oakland, California. Chapel Hill: University of North Carolina Press. Schlesinger, Arthur M. 1965. A Thousand Days: John F. Kennedy in the White House. Boston: Houghton Mifflin. Selvin, Joel. 1994. Summer of Love: The Inside Story of LSD, Rock & Roll, Free Love, and High Times in the Wild West. New York: Dutton. Stein, Judith. 2010. Pivotal Decade: How the United States Traded Factories for Finance in the Seventies. New Haven: Yale University Press. Warren Commission. 1964. Report of the Warren Commission on the Assassination of President Kennedy. New York: McGraw-Hill. X, Malcolm. 1992. The Autobiography of Malcolm X. Edited by Alex Haley. New York: One World/Ballantine Books. TWENTY-FIRST-CENTURY PROBLEMS Bravin, Jess. 2013. The Terror Courts: Rough Justice at Guantanamo Bay. New Haven: Yale University Press. Cowen, Tyler. 2001. The Great Stagnation: How America Ate All the Low-Hanging Fruit of Modern History, Got Sick, and Will (Eventually) Feel Better. New York: Dutton. Ehrenreich, Barbara. 2001. Nickel and Dimed: On (Not) Getting by in America. New York: Metropolitan Books. Gerges, Fawaz A. 2011. The Rise and Fall of Al-Qaeda. Oxford: Oxford University Press. Gordon, Joy. 2010. Invisible War: The United States and the Iraq Sanctions. Cambridge, MA: Harvard University Press. John Cannan, 2013. “A Legislative History of the Affordable Care Act: How Legislative Procedure Shapes Legislative History.” Law Library Journal 105(2): 132–73. Keen, D. 2012. Useful Enemies: When Waging Wars Is More Important than Winning Them. New Haven: Yale University Press. Lance, Peter. 2004. 1000 Years for Revenge: International Terrorism and the FBI. New York: Regan Books. Lewis, Michael. 2010. The Big Short: Inside the Doomsday Machine. New York: Norton. Little, Douglas. 2002. American Orientalism: The United States and the Middle East since 1945. Chapel Hill: University of North Carolina Press. Oreskes, Naomi, and Erik M. Conway. 2010. Merchants of Doubt: How a Handful of Scientists Obscured the Truth on Issues from Tobacco Smoke to Global Warming. New York: Bloomsbury Press. Rivoli, Pietra. 2005. The Travels of a T-Shirt in the Global Economy: An Economist Examines the Markets, Power and Politics of World Trade. Hoboken, NJ: Wiley. Simon, Bryant. 2009. Everything but the Coffee: Learning About America from Starbucks. Berkeley: University of California Press. Wright, Lawrence. 2006. The Looming Tower: Al-Qaeda and the Road to 9/11. New York: Knopf.	oercommons	2025-03-18T00:36:11.148720	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15573/overview", "title": "U.S. History, Further Reading", "author": null }
https://oercommons.org/courseware/lesson/87986/overview	Communism and the Man of Steel: The Rise of Joseph Stalin, 1922-1938 Overview Russia under Stalin: 1922-1938 It is ironic that the most iconic Russian of the twentieth century was not Russian by birth. Ioseb Besarionis dze Jughashvili, later known as Joseph Stalin, was born in the Caucasus Mountains of the neighboring country, Georgia. His rise to power in the Bolshevik party was unexpected, and his rule as the Soviet leader surpassed both Lenin’s and his successors in length. During Stalin’s time in office, he enacted numerous changes in domestic policies during the 1930s, oversaw Russian involvement in World War II, and instigated nearly a decade of Cold War tensions between Russia and the United States. Learning Objectives - Identify the key programs developed by Stalin in the 1920s and 1930s. - Evaluate Stalin’s rise to power. - Analyze how Stalin’s policies as leader of the Soviet Union differed from Lenin’s. Key Terms / Key Concepts Joseph Stalin: Secretary General of the Soviet Union from 1922/24 – 1953. Grigori Zinoviev: initially, a political ally of Stalin and member of the troika that helped defeat Trotsky during his attempt to succeed Lenin Lev Kamenev: initially, a political ally of Stalin and member of the troika that helped defeat Trotsky during his attempt to succeed Lenin Nikolai Bukharin: editor of the Bolshevik paper, Pravda, and initial close ally of Stalin First Five-Year Plan: state-dictated economic policy (1928 – 33) that relied heavily on forced labor on collective farms, as well as requisitioning, to meet agricultural quotas Collectivization: policy of the Five-Year Plans in which the state forced peasant farmers to give up individual farms and move onto large, collective farms with industrial machinery for mass agricultural output Gulags: series of hundreds of prison camps through the Soviet Union known for their forced labor and harsh conditions and treatment of prisoners Kazakh: a person from Kazakhstan in Central-Asia Holodomor: artificial famine in Ukraine (1931 – 3) that occurred through Soviet practices and resulted in the deaths of over three million Ukrainians dekulakization: brutal practice of the Russians in which they arrested, executed, or exiled “wealthy” peasant farmers NKVD: the organization responsible for daily police and secret police activities that carried out excessive violence during the Great Purge Great Purge: two-years in which the NKVD, acting under Stalin’s orders, executed over one million people considered “enemies of the state” show trial: a trial where the verdict is already known and the case is carried out for spectacle before a court audience Stalin's Soviet Union in the 1920s Background: Joseph Stalin Joseph Stalin was born to a poor, working-class family near Tbilisi, Georgia in the late 1870s. The only child to survive to adulthood, Stalin’s father reportedly was an abusive alcoholic who took his frustrations out on his wife and son. Years later, historians speculated that the abuse influenced Stalin’s general psyche and actions as head of the Soviet Union. When his father died, Stalin’s mother found the money to send her son to seminary school. Despite his academic talents, Stalin quickly rebelled against the traditional school, learned Russian, and found inspiration through the writing and activities of the Bolsheviks. As a young man, he initially did not measure up to the other Bolsheviks of the 1910s. His counterparts considered him poorly educated, a poor speaker, and overly “Asiatic” in his volatile temper and behavior. Stalin, was, however, valued for his skills as an organizer, as well as for his ruthless treatment of political enemies. Unfortunately for his rivals, Stalin was also a master strategist and knew how to oust his comrades in the pursuit of moving up the political ladder. Scramble for Succession By 1921, it was evident that a successor must be chosen because of Lenin’s failing health. He had suffered two strokes (and would suffer a third before he died in 1924). A handful of prominent Bolshevik leaders vied for the position of successor to Vladimir Lenin; Stalin being one of them. Increasingly, Stalin, who was General Secretary of the Communist Party, tried to press closer to Lenin’s side. In most matters, Stalin idolized Lenin, despite their disagreements. By 1922, he had taken on the role of determining who would be allowed to see Lenin during his convalescence. And yet, the closer Stalin pressed to Lenin, the more Lenin seemed to push him away. A year before his death, Lenin described Stalin as not good for the party because of his excessive crudeness. Privately, he advocated for Leon Trotsky to be his successor. Trotsky was a skilled orator, politician, and intelligent statesman who had been closely involved with Lenin since the days of the October Revolution. The death of Lenin sparked a scramble for succession as leader of the Soviet Union. Leon Trotsky was the favorite choice of Lenin, but he was despised by Stalin and disliked by two other prominent Bolsheviks: Lev Kamenev and Grigori Zinoviev. Together with Stalin, Zinoviev and Kamenev formed a troika (political alliance) where the three acted as the governing head of the Soviet Union to block Trotsky’s ascension to power. Trotsky was forced into exile. Eventually, he made his way to Mexico—only to be murdered by one of Stalin’s henchmen in 1940. Political squabbling continued, and Stalin had no intention of sharing power with Zinoviev and Kamenev. Their troika dissolved following Trotsky’s defeat. Both men lost faith in Stalin. During the Great Purge of 1936, both men would die before a firing squad ordered by their former ally. Complex negotiations and party support instilled Stalin as Lenin’s sole successor and head of the Soviet Union in 1924. He quickly turned his attention to transforming agrarian Russia into a society of steel and industry. Domestic Policies At the time of Stalin’s ascension to power, Russia was still overwhelmingly an agrarian nation. The First World War had shown how technologically inferior Russia was to its Western counterparts. Stalin sought to change that and transform the country overnight. Chief among his goals was the death of the New Economic Policy that Lenin began. Although he would not publicly advocate for the policy’s demise because Lenin had backed it, Stalin would strategically find ways to dissolve the plan that called for a mixed economy (partially state-run, partially capitalist). In its place he would put a program that helped transform Russia, but at the highest human cost. The First Five-Year Plan Under Lenin’s New Economic Program, farmers had been forced to sell grain to the state but could also engage in private sales. A balance of state and private farming had ensued. Stalin sought to erase that in 1928 based on his plan to increase agricultural output to feed the rapidly-increasing urban population who worked in the factories. To achieve this goal, Stalin introduced the First Five-Year Plan. This program eliminated private farming. Farms were merged into large, government-run collective farms across the Soviet Union. Moreover, each farm was required to meet government quotas for grain and meat. Stalin enacted these radical measures by excessive use of force. The “kulaks” (private farmers) emerged again as the public enemy of the Bolshevik regime. A central goal of Stalin’s program was to dekulakize the Soviet Union. Kulaks were vaguely defined as the “more prosperous farmers.” And Stalin waged war on them as part of the Bolshevik philosophy of class struggle. In the 1920s, a “prosperous farmer” could have been a private farmer with a large farm and high production yields. Usually, it meant a farmer who was more prosperous than the neighbor nextdoor. In such cases, a kulak might be classified as a farmer with eight acres, instead of one. Or seven cows instead of one. Once again, Stalin used force to suppress “the enemy.” Kulaks were targeted by the state police for arrest, seizure of property, exile, and in some cases, execution. Across the board, farmers saw wages reduced and higher state quotas emerge. Resistance to such measures were severely punished. Neighbors turned against one another. Class struggle became not only a Bolshevik principle on paper but also daily practice under Stalin. The first year of Stalin’s new program showed that despite the collectivized farms, agrarian shortages still prevailed. To counter this, Stalin continued his war on the kulaks and encouraged the poorest classes to do the same. Requisitioning—the government seizure and redistribution of goods—ruled the day. Across Russia, farmers and Bolsheviks alike targeted the kulaks. Government officials would arrive at their homes and seize grain and farm animals. Often, these kulaks were shot or exiled to one of Stalin’s infamous chain of gulags across Russia. Two ethnic groups suffered especially during Stalin’s First Five-Year Plan: Ukrainians and Kazakhs. Kazakhstan was a Soviet ethnic state in central Asia. Although the Kazakhs were farmers, they were typically nomadic farmers. Unaccustomed to permanent settlement, they knew very little about producing cereal crops, much less vast yields of barley, wheat, and rye. Stalin deployed the Red Army to handle the situation. Kazakh farmers who resisted were shot. Those who did not produce high enough yields were shot. Threats and seizures of farm yields ensued. It is estimated that between 1.3 and1.8 million Kazakhs died during the First Five-Year Plan because of widespread famine, malnutrition, disease, and executions. Ukraine experienced a similar situation. As an ethnic state within the Soviet Union, Ukraine was rich in agrarian resources. Ukrainian farmers prospered, even under the NEP. But unsurprisingly, these prosperous farmers who were considered somewhat distant and lesser cousins of the Russians, were targeted by Stalin for being kulaks and, by extension, “class enemies.” In 1932, the Red Army sealed the border between Ukraine and Russia, prohibiting travel. Then the army moved from one Ukrainian village to another, seizing grain stores and livestock, often indiscriminately murdering the inhabitants. With the kulaks eliminated, the peasants were forced to produce yields that met state quotas. The situation devolved. With the Red Army murdering citizens and seizing crop yields and livestock, the Ukrainian people quickly perished. Those who were not murdered frequently succumbed to malnutrition and starvation as a devastating famine swept through the countryside. The debate about the nature of the famine that swept over Ukraine in the late 1930s remains. It is often called the Holodomor. The name literally translates to “death inflicted by starvation.” Scholars continue to debate and analyze the Great Famine, to determine if Stalin intentionally murdered the Ukrainian people or if the event was an unintentional byproduct of Soviet agricultural practices. Regardless, conservative estimates claim that 3.5 million Ukrainians died between 1932 – 1933; while others suggest the real number of deaths is nearer to 8 million. Still, not everyone approved of Stalin’s measures. His former close ally, Nikolai Bukharin, who edited the Bolshevik paper, the Pravda, strongly opposed Stalin. Russians themselves also opposed the measures of collectivization. By the early 1930s, several thousand people had rallied in opposition to Stalin. In response, Stalin deployed the Red Army, including the artillery, to subdue the population. It would not be the last time this happened; rather it was the start of severe measures against anyone Stalin perceived as opposition. Industrialization Background Under Lenin, the Bolsheviks had encouraged class conflict to such an extent that it severely impacted industry. Workers turned on their employers and businesses and factories shut down. Thus, the party had stepped in and transformed private businesses into state-owned and regulated industries. This produced only marginal economic recovery. And when Stalin took power he understood Russia still lagged a hundred years behind its Western counterparts. Stalin's Industrialization Campaign Stalin’s goal for the Soviet Union was to transform it into an industrialized nation on par with the West. On some levels, he came close to achieving it. In twenty years, Russia had been transformed from an agrarian society into an industrialized one. The quality of Russian-made goods remained, however, exceptionally poor in comparison to Western goods. To finance his industrialization project, Stalin decreed that all profits made from the collectivization process would be used to build factories. Peasants flocked to the city in search of opportunity and work. Heavy industry thrived. Women entered the workforce in droves. In a single decade, women workers comprised nearly forty percent of the Russian workforce. The Russian economy was slowly recovering from years of turmoil. The Great Terror Background: Murder of Sergei Kirov Stalin’s personality had always been described as “harsh,” “brutal,” and “crude” by his Bolshevik comrades. Lenin considered him the most brutal of all comrades and “too crude” for the party’s good. Moreover, Stalin seemed to find the chaos and violence of revolution fascinating. Atop this, Stalin had paranoia that increased enormously over the years. Reportedly, Stalin adopted a paranoia of being assassinated. But a single event in 1934 catapulted his paranoia into his most severe repression of the Russian people. In December 1934, one of Stalin’s discontented citizens walked into the office of Sergei Kirov, a leading Bolshevik politician in Leningrad (St. Petersburg) and a close friend to Stalin. The young man, Leonid Nikolaev, shot Kirov at point-blank range, killing him. For Stalin, the action was far more than the loss of a comrade. It represented a threat on the Bolshevik party, as well as to himself. He responded swiftly. The young assassin was seized and summarily executed. More importantly, Stalin gave the NKVD, head of the police and the secret police, power to arrest and execute enemies of the state freely. Stalin’s Great Purge had begun. The Great Purge Purging Political Rivals Kirov’s death signaled to Stalin that there were enemies within the government, and worse, within his inner circle of comrades. Because Kirov’s assassin had supported Stalin’s old adversary, Grigori Zinoviev, Stalin seized Zinoviev and his partner, Lev Kamenev. He asserted that the two men were behind Kirov’s assassination. Following nearly two years of political maneuvers, Zinoviev and Kamenev were put on a show trial. The court confirmed their guilt and the following morning, the two men who had once worked as Stalin’s allies were executed by firing squad. Next on Stalin’s list of targets was his former friend, Nikolai Bukharin. The two men had split over Stalin’s economic policies. Ever-paranoid, Stalin accused Bukharin of being a spy and of plotting against him. The trumped-up charges worked. Bukharin was imprisoned, put on show trial before the court, and declared guilty. Before his execution, Bukharin wrote a note to Stalin in which he referred to his friend by his old pseudonym, “Koba, why do you need me to die?” In addition to purging his political rivals, Stalin believed that the Bolshevik party should be purged at the local level. For two years, the NKVD arrested and executed alleged enemies of the state. These victims included not only politicians, but also members of the military, members of ethnic groups, and clerics. By the end of 1938, over a million people had been murdered as part of Stalin’s “Great Purge.” Impact Not every measure undertaken by Stalin and the Bolsheviks was murderous and ill-fated, but they were all undertaken with the intent of creating a totalitarian state. In his transformation of the Russian state, Stalin promoted literacy and compulsory education—at state-run schools. In his first decade as head of the Soviet Union, Stalin ensured that his communist party controlled all education, entertainment, media, businesses, and agriculture. Those who resisted were arrested, executed, or exiled. In his quest for complete control of the Soviet Union, Stalin proved he was exactly what his Bolshevik comrades had claimed years ago—the harshest of them all. And he was proud of it. Attributions All images from Wikimedia Commons Service, Robert. A History of Modern Russia: From Nicholas II to Vladimir Putin. Harvard University Press, Cambridge: 2003. 169-234.	oercommons	2025-03-18T00:36:11.192427	Neil Greenwood	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/87986/overview", "title": "Statewide Dual Credit World History, The Catastrophe of the Modern Era: 1919-Present CE, Chapter 13: Post WWI, Communism and the Man of Steel: The Rise of Joseph Stalin, 1922-1938", "author": "Anna McCollum" }
https://oercommons.org/courseware/lesson/88053/overview	Mussolini’s Prewar Territorial Gains Overview Mussolini's Territorial Expansion In a secret speech to the Italian military leadership in January 1925, Mussolini argued that Italy needed to win spazio vitale (vital space). As such, his ultimate goal was to join “the two shores of the Mediterranean and of the Indian Ocean into a single Italian territory.” Thus, Mussolini envisioned Italy would once again be restored as major, global power as it had been in the days of the Roman Empire. Learning Objectives - Identify Mussolini's territorial expansions Key Terms / Key Concepts Albania: small, European country in the Balkans, just north of Greece Ethiopia: country in far eastern Africa spazio vitale: Mussolini's concept of "vital space," and used as justification for Italian conquests The Italians in Ethiopia and Albania In 1935, Mussolini invaded Ethiopia. On the surface, the invasion looked random. Why would Italy set its sites on taking a country in east Africa? There were, however, a few reasons driving Mussolini. Firstly, he recalled the miserable defeat the Italians had suffered against the Ethiopians in the 1896 war. Italy had tried to claim Ethiopia during the "Scramble for Africa," and failed miserably. Secondly, it remained one of the only independent nations in Africa in the 1930s. Almost all of the rest of the continent remained under British, French, and Spanish colonial rule. Lastly, Mussolini hoped to conquer Ethiopia, then follow up his success by conquering other small nations around the Aegean and Mediterranean Seas. In 1936, the Italians invaded Ethiopia. More than 200,000 Italian troops fought in the campaign to conquer Ethiopia. While the Ethiopians tried to resist, they were severely outgunned and lacked radios and other technological advancements. Within a year, the Italians had claimed victory and proclaimed the Italian King, Victor Emmanuel, Emperor. Still, conflict continued between the Ethiopians and Italians until 1939. This proved a resource drain for the Italians, who increasingly relied on their alliance with Nazi Germany to protect them at home. In April 1939, Italy launched an invasion of Albania. Again, the maneuver seemed peculiar. Albania was a small country in the Balkans with very little political sway in global affairs. Why did Mussolini want to seize it? Firstly, because of the country's position on the Adriatic Sea. Albania had several significant ports which could offer the Italians control of the Adriatic. Secondly, Albania had once been part of the Roman Empire. Therefore, Mussolini believed that reclaiming it would also help restore Italian influence. Lastly, Mussolini felt enormous pressure to expand Italian influence following Hitler's successes in annexing Austria. Afraid that Italy was falling behind Germany in terms of its military and political power, Mussolini was determined to conquer territories. Within a few days of the invasion, Albania capitulated to the Italians. The Albanian king was deposed, and the Italian King, Victor Emmanuel, became the king of Albania. Mussolini's plan had worked. Attributions Images courtesy of Wikimedia Commons.	oercommons	2025-03-18T00:36:11.211127	Neil Greenwood	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/88053/overview", "title": "Statewide Dual Credit World History, The Catastrophe of the Modern Era: 1919-Present CE, Chapter 14: The World Afire: World War II, Mussolini’s Prewar Territorial Gains", "author": "Anna McCollum" }
https://oercommons.org/courseware/lesson/96044/overview	A&P 2 OER Lab Manual First Edition Compilation with Practice Included No ISBN v2 with corrected errata PDF File Lab 10--Respiratory Anatomy Lab 11--Respiratory Physiology Simulation Lab 13--Digestive Anatomy Lab 14--Digestive System Physiology Lab 15--Urinary Anatomy Lab 17--Urinalysis Lab 18--Reproductive Anatomy Lab 1--Endocrine Anatomy Lab 2--Endocrine Physiology Simulation Lab 3--Blood Lab 4--The Heart Lab 6--Anatomy of Blood Vessels Lab Materials & Equipment for Julie's A&P 2 OER Lab Manual for OER Commons Practice for Blood Vessel in Models Practice for Digestive Models Labeling Practice for Endocrine Histology Practice for Respiratory and Digestive System Histology v2 Practice for Urinary and Reproductive System Histology Practice Reading Blood Typing Plates Anatomy & Physiology 2 Lab Manual Overview Laboratory manual for undergraduate Anatomy & Physiology 2 Anatomy & Physiology 2 Lab Manual 1st Edition Hello fellow instructors, At the end of the manual, there are "practice documents" developed with RVCC models and course content in mind. Due to formatting requirements of the print on demand service I'm using (Lulu.com), many of the pictures in these practice pages (and some in the lab exercises) are not editable. The individual lab exercises and practice documents are included below; most images in these are editable. If you have any questions, please feel free to email me jrobinson@ccsnh.edu. This lab manual was written for Anatomy & Physiology 2, a 200-level A&P course, at River Valley Community College. The course uses the OpenStax A&P textbook. The manual is intended to complement any text but does derive a good deal of its content from the OpenStax A&P textbook. The PDF file has been flattened and fonts are embedded, so it should be ready for a print-on-demand service. Please note that there is a small error on page 125. The procedural title should say "Procedure for Activity 6.1, Part A: Examining Histology of Blood Vessels", instead of "Procedure for Activity 6.1, Part A: Examining Histology of the Esophagus and Stomach". Updated 1/28/23: The Word document below has all the errata that I know of fixed. This is the link to the errata list: https://docs.google.com/document/d/1A1ssv_oDJyLEF3Mh41Qxt6yPlNMX1q-LssUlSssC0jc/edit?usp=sharing There is a BIG error in the answer key for the digestive and respiratory histology practice due to offsetting of the automatic numbering-sorry! Please be sure to share the corrections with your students. Individual Labs These documents are the individual labs that were compiled into the full lab manual. Attributions for each lab are included at the end of each lab; the compiled manual includes all updated attributions at the end. Please note that there is no lab for cardiovascular physiology because we're using a lab that accompanies our Vernier probes. There are some great virtual labs for cardiovascular physiology here: https://pphys.edugen.wiley.com/index.html Lab Assignments are also included with each lab, so you can assign as many of the activities and follow up questions as you like. Practice Documents These files contain the practice documents (in their original form) that are included in the manual compilation. The practice documents are specific to required content and materials available for students at my college. I'll add more if I create them. I believe one of the few left to create for students is on reproductive and urinary lab models. Instructor Resources I'm not able to load the documents directly to OERCommons. If you would like the instructor resources, please send an email to me (jrobinson@ccsnh.edu) from your verifiable instructor email account, so I can send you the link these documents. The instructor resources are included for instructor accounts only. Equipment & Materials List The equipment and supplies list for each lab was built with RVCC's lab resources in mind. Please be sure to revise as needed for your institution. If you have any questions, please email me (jrobinson@ccsnh.edu).	oercommons	2025-03-18T00:36:11.252147	Activity/Lab	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/96044/overview", "title": "Anatomy & Physiology 2 Lab Manual", "author": "Health, Medicine and Nursing" }
https://oercommons.org/courseware/lesson/88049/overview	Japanese Invasion of Manchuria Overview The Japanese Invasion of Manchuria and the Beginning of World War II When did World War II begin? For the U.S. it began officially in 1941. For Europe in 1939. For Asia, and the world as a whole, it began with the Japanese invasion of Manchuria on 18 September 1931. While this invasion marked the beginning of World War II, for Japan it was another stage in the expansion of the Japanese empire which began with the Meiji Restoration. The Japanese invasion of Manchuria represented a new stage in Japanese expansion, growing out of the control of the Japanese government by chauvanistic nationalists and militarists with a vision of Japanese control over the eastern half of Asia and the Pacific Ocean out through the Hawaiian islands. Along with strategic importance of Manchuria to Japanese imperial ambitions, it also held useful resources for the Japanese economy. Learning Objective - Identify key features of Japanese politics and territorial expansion prior to the outbreak of World War II, including the outbreak of the Second Sino-Japanese War. - Explain why and how the Japanese invasion of Manchuria occurred, and assess the historic significance and impact of this invasion, particularly in World War II. Key Terms / Key Concepts Kwantung Army - Japanese field army that invaded Manchuria in 1931, without the authorization of the Japanese government, an action that reflected the militarization of Japan Manchukuo - puppet state created by the Kwantung Army Manchurian Incident: a staged event engineered by Japanese military personnel as a pretext for the Japanese invasion in 1931 of northeastern China, known as Manchuria League of Nations: an intergovernmental organization founded on January 10, 1920, as a result of the Paris Peace Conference that ended the First World War; the first international organization whose principal mission was to maintain world peace. Its primary goals as stated in its Covenant included preventing wars through collective security and disarmament and settling international disputes through negotiation and arbitration. Japan had been pursuing expansion into Manchuria since the 1890s, defeating China in 1895 and Russia in 1905 in limited wars as part of these efforts. On 18 September 1931 the Japanese force in Manchuria, the Kwantung Army, invaded Manchuria on the pretense of protecting Japanese interests in Manchuria. Manchuria was then under Chinese control, but Japan held certain interests within Manchuria by various treaties. The Kwantung Army had been formed in 1906 as part of the effort to expand the Japanese presence in northeast Asia. Kwantung refers to the territory in Manchuria that Japan took from China in the 1894-5 war. To provide an excuse for invading Manchuria on September 18, members of the Kwantung Army blew up a small section of the South Manchurian Railway, for which the Kwantung Army had responsibility, otherwise known as the Manchurian Incident. The Kwantung Army then carried out a campaign to take control of Manchuria, which ended successfully for the Kwantung Army in February 1932. The Kwantung Army then created the puppet state of Manchukuo to legitimize its conquest, placing the last Chinese emperor, Puyi, on its throne. Along with initiating World War II, this invasion marked the militarists taking control of the Japanese government. The Kwantung Army carried out the conquest of Manchuria without the authorization of the Japanese government. Because of the growing strength of nationalistic and militaristic army and navy officers within the Japanese government during the twenties and early thirties, and because of the constitutional requirement that the army and the navy be represented in the Japanese cabinet, the civilian government not only had to accept the Kwantung Army's invasion of Manchuria, it also had to support the Army's and the Navy's program for expanding the Japanese Army. Tragically, in the classic and literal definition of this word, militarists remained in control of the Japanese government and the Japanese war effort until the detonation of a second atomic bomb over Nagasaki on 9 August 1945, ending Japan's war. Along with marking the beginning of World War II, the Kwantung Army's invasion of Manchuria also contributed to the end of the League of Nations. In response to this invasion the League formed the Lytton Commission, named after the British politician and lord who led it, to investigate. The Commission released its report in October 1932, stating that Japan was the aggressor, the invasion had been wrong, and Manchuria should be returned to China. In March 1933 Japan formally withdrew from the League, further weakening it then already in decline. The Japanese Invasion of China and the Second Sino-Japanese War, 1937-41 By 1937, Japan controlled Manchuria and it was also ready to move deeper into China. The Marco Polo Bridge Incident on 7 July 1937 provoked full-scale war between China and Japan, known as the Second Sino-Japanese War. The Nationalist Party and the Chinese Communists suspended the civil war they were then engaged in so that they could form a nominal alliance against Japan. And the Soviet Union quickly lent support to Chinese troops by providing large amounts of material. Learning Objectives - Identify key features of Japanese politics and territorial expansion prior to the outbreak of World War II, including the outbreak of the Second Sino-Japanese War. - Assess the historic significance and impact of the Second Sino-Japanese War Key Terms / Key Concepts Second Sino-Japanese War: 1937-45 War between China and Japan that was one of the component wars of World War II Chiang Kai-shek: leader of Chinese Nationalist forces in the Second Sino-Japanese War Nanjing Massacre - Japanese mass murder of an estimated 200,000 Chinese in December 1937 through January 1938 after the Japanese capture of that city In August 1937, Generalissimo Chiang Kai-shek deployed his best army to fight about 300,000 Japanese troops in Shanghai, but, after three months of fighting, Shanghai fell. The Japanese continued to push the Chinese forces back, capturing the capital Nanjing in December 1937, where they conducted the Nanjing Massacre. In March 1938, Chinese Nationalist forces won their first victory at Taierzhuang, but then the city of Xuzhou was taken by the Japanese in May. In June 1938, Japan deployed about 350,000 troops to invade Wuhan and captured it in October. The Japanese achieved major military victories, but world opinion at the time—in particular in the United States—condemned Japan, especially after the Panay incident. In 1939, Japanese forces tried to push into the Soviet Far East from Manchuria. They were soundly defeated in the Battle of Khalkhin Gol by a mixed Soviet and Mongolian force led by Georgy Zhukov. This stopped Japanese expansion to the north; meanwhile, Soviet aid to China ended as a result of the signing of the Soviet–Japanese Neutrality Pact at the beginning of its war against Germany. In September 1940, Japan decided to cut China's only land line to the outside world by seizing French Indochina, which was controlled at the time by Vichy France. Japanese forces broke their agreement with the Vichy administration and fighting broke out, ending in a Japanese victory. On 27 September 1940 Japan signed a military alliance with Germany and Italy, becoming one of the three main Axis Powers. The war entered a new phase with the unprecedented defeat of the Japanese at the Battle of Suixian–Zaoyang, 1st Battle of Changsha, Battle of Kunlun Pass, and Battle of Zaoyi. After these victories, Chinese nationalist forces launched a large-scale counter-offensive in early 1940; however, due to its low military-industrial capacity, China was repulsed by the Imperial Japanese Army in late March 1940. In August 1940, Chinese communists launched an offensive in Central China; in retaliation, Japan instituted the "Three Alls Policy" ("Kill all, Burn all, Loot all") in occupied areas to reduce human and material resources for the communists. By 1941 the conflict had become a stalemate. Although Japan had occupied much of northern, central, and coastal China, the Nationalist Government had retreated to the interior with a provisional capital set up at Chungking, while the Chinese communists remained in control of base areas in Shaanxi. In addition, Japanese control of northern and central China was somewhat tenuous, in that Japan was usually able to control railroads and the major cities ("points and lines"), but did not have a major military or administrative presence in the vast Chinese countryside. The Japanese found its aggression against the retreating and regrouping Chinese army was stalled by the mountainous terrain in southwestern China, while the Communists organized widespread guerrilla and saboteur activities in northern and eastern China behind the Japanese front line. Japan sponsored several puppet governments. However, Japanese policies of brutality toward the Chinese population, of not yielding any real power to these regimes, and of supporting several rival governments failed to make any of them a viable alternative to the Nationalist government led by Chiang Kai-shek. Conflicts between Chinese Communist and Nationalist forces vying for territory control behind enemy lines culminated in a major armed clash in January 1941, effectively ending their co-operation. Japanese strategic bombing efforts mostly targeted large Chinese cities, such as Shanghai, Wuhan, and Chongqing, with around 5,000 raids from February 1938 to August 1943 in the latter case. Japan's strategic bombing campaigns devastated Chinese cities extensively, killing 260,000 – 350,934 non-combatants. Attributions Images courtesy of Wikimedia Commons Title Image - Japanese troops entering Tsitsihar, 19 November 1932. Attribution: English: Osaka Mainichi war cameramen日本語: 大阪毎日従軍寫眞班撮影, Public domain, via Wikimedia Commons. Provided by: Wikipedia Commons. Location: https://commons.wikimedia.org/wiki/File:Japanese_troops_entering_Tsitsihar.jpg. License: CC BY-SA: Attribution-ShareAlike Wikipedia "Japanese Invasion of Manchuria" Adapted from https://en.wikipedia.org/wiki/Japanese_invasion_of_Manchuria CC LICENSED CONTENT, SHARED PREVIOUSLY Curation and Revision. Provided by: Wikipedia.com. License: Creative Commons Attribution-ShareAlike License 3.0 CC LICENSED CONTENT, SPECIFIC ATTRIBUTION - Thorne, Christopher. "Viscount Cecil, the Government and the Far Eastern Crisis of 1931." Historical Journal 14, no. 4 (1971): 805–26. http://www.jstor.org/stable/2638108 online]. - [1] - Sun, Fengyun. 《東北抗日聯軍鬥爭史》 - Coogan, Anthony (1994). Northeast China and the Origins of the Anti-Japanese United Front. Modern China, Vol. 20, No. 3 (July 1994), pp. 282-314: Sage Publications. - Matsusaka, Yoshihisa Tak (2003). The Making of Japanese Manchuria, 1904-1932. Harvard University Asia Center. ISBN 978-0-674-01206-6. - Guo, Rugui (2005-07-01). Huang Yuzhang (ed.). 中国抗日战争正面战场作战记 [China's Anti-Japanese War Combat Operations]. Jiangsu People's Publishing House. ISBN 7-214-03034-9. - 中国抗日战争正面战场作战记 [China's Anti-Japanese War Combat Operations]. wehoo.net. Archived from the original on 2011-10-01. - 第二部分：从“九一八”事变到西安事变“九一八”事变和东北沦陷 ["9/18" Emergency and Northeast falls to the enemy]. wehoo.net. Archived from the original on 2011-07-24. - 第二部分：从“九一八”事变到西安事变事变爆发和辽宁吉林的沦陷 [The emergency erupts with Liaoning, Jilin falling to the enemy]. wehoo.net. Archived from the original on 2007-05-27. - "Wehoo.net" 第二部分：从“九一八”事变到西安事变江桥抗战和黑龙江省的失陷 [River bridge defense and Heilongjiang Province falls to the enemy]. wehoo.net.[dead link] - 第二部分：从“九一八”事变到西安事变锦州作战及其失陷 [The Jinzhou battle and its fall to the enemy]. wehoo.net. Archived from the original on 2007-05-27. - 第二部分：从“九一八”事变到西安事变哈尔滨保卫战 [The defense of Harbin]. wehoo.net. Archived from the original on 2011-10-01. - 中国抗日战争正面战场作战记 [China's Anti-Japanese War Combat Operations]. wehoo.net. Archived from the original on 2011-10-01. "Second Sino-Japanese War" Adapted from https://en.wikipedia.org/wiki/Second_Sino-Japanese_War CC LICENSED CONTENT, SHARED PREVIOUSLY Curation and Revision. Provided by: Wikipedia.com. License: Creative Commons Attribution-ShareAlike License 3.0 CC LICENSED CONTENT, SPECIFIC ATTRIBUTION - Bayly, C. A., and T. N. Harper. Forgotten Armies: The Fall of British Asia, 1941–1945. Cambridge, MA: Belknap Press of Harvard University Press, 2005. xxxiii, 555p. ISBN 0-674-01748-X. - Bayly, C. A., T. N. Harper. Forgotten Wars: Freedom and Revolution in Southeast Asia. Cambridge, MA: Belknap Press of Harvard University Press, 2007. xxx, 674p. ISBN 978-0-674-02153-2. - Benesch, Oleg. "Castles and the Militarisation of Urban Society in Imperial Japan," Transactions of the Royal Historical Society, Vol. 28 (Dec. 2018), pp. 107–134. - Buss, Claude A. War And Diplomacy in Eastern Asia (1941) 570pp online free - Duiker, William (1976). The Rise of Nationalism in Vietnam, 1900–1941. Ithaca, New York: Cornell University Press. ISBN 0-8014-0951-9. - Gordon, David M. "The China–Japan War, 1931–1945" Journal of Military History (January 2006). v. 70#1, pp, 137–82. Historiographical overview of major books from the 1970s through 2006 - Guo Rugui, editor-in-chief Huang Yuzhang,中国抗日战争正面战场作战记 China's Anti-Japanese War Combat Operations (Jiangsu People's Publishing House, 2005) ISBN 7-214-03034-9. On line in Chinese: 中国抗战正向战场作战记 - Hastings, Max (2009). Retribution: The Battle for Japan, 1944–45. Vintage Books. ISBN 978-0-307-27536-3. - Förster, Stig; Gessler, Myriam (2005). "The Ultimate Horror: Reflections on Total War and Genocide". In Roger Chickering, Stig Förster and Bernd Greiner, eds., A World at Total War: Global Conflict and the Politics of Destruction, 1937–1945 (pp. 53–68). Cambridge: Cambridge University Press. ISBN 978-0-521-83432-2. - Hsiung, James Chieh; Levine, Steven I., eds. (1992), China's Bitter Victory: The War with Japan, 1937–1945, Armonk, NY: M.E. Sharpe, ISBN 0-87332-708-X. Reprinted: Abingdon, Oxon; New York: Routledge, 2015. Chapters on military, economic, diplomatic aspects of the war. - Huang, Ray (31 January 1994). 從大歷史的角度讀蔣介石日記 (Reading Chiang Kai-shek's Diary from a Macro History Perspective). China Times Publishing Company. ISBN 957-13-0962-1. - Annalee Jacoby and Theodore H. White, Thunder out of China, New York: William Sloane Associates, 1946. Critical account of Chiang's government by Time magazine reporters. - Jowett, Phillip (2005). Rays of the Rising Sun: Japan's Asian Allies 1931–45 Volume 1: China and Manchukuo. Helion and Company Ltd. ISBN 1-874622-21-3. – Book about the Chinese and Mongolians who fought for the Japanese during the war. - Hsu, Long-hsuen; Chang Ming-kai (1972). History of the Sino-Japanese war (1937–1945). Chung Wu Publishers. ASIN B00005W210. - Lary, Diana and Stephen R. Mackinnon, eds. The Scars of War: The Impact of Warfare on Modern China. Vancouver: UBC Press, 2001. 210p. ISBN 0-7748-0840-3. - Laureau, Patrick (June 1993). "Des Français en Chine (2ème partie)" [The French in China]. Avions: Toute l'aéronautique et son histoire (in French) (4): 32–38. ISSN 1243-8650. - MacKinnon, Stephen R., Diana Lary and Ezra F. Vogel, eds. China at War: Regions of China, 1937–1945. Stanford University Press, 2007. xviii, 380p. ISBN 978-0-8047-5509-2. - Macri, Franco David. Clash of Empires in South China: The Allied Nations' Proxy War with Japan, 1935–1941 (2015) online - Mitter, Rana (2013). Forgotten Ally: China's World War II, 1937–1945. HMH. ISBN 978-0-547-84056-7. - Peattie, Mark. Edward Drea, and Hans van de Ven, eds. The Battle for China: Essays on the Military History of the Sino-Japanese War of 1937–1945 (Stanford University Press, 2011); 614 pages - Quigley, Harold S. Far Eastern War 1937 1941 (1942) online free - Steiner, Zara. "Thunder from the East: The Sino-Japanese Conflict and the European Powers, 1933=1938": in Steiner, The Triumph of the Dark: European International History 1933–1939 (2011) pp 474–551. - Stevens, Keith (March 2005). "A token operation: 204 military mission to China, 1941–1945". Asian Affairs. 36 (1): 66–74. doi:10.1080/03068370500039151. S2CID 161326427. - Taylor, Jay (2009). The Generalissimo: Chiang Kai-shek and the struggle for modern China. Cambridge, Massachusetts: Harvard University Press. ISBN 978-0-674-03338-2. - Van de Ven, Hans, Diana Lary, Stephen MacKinnon, eds. Negotiating China's Destiny in World War II (Stanford University Press, 2014) 336 pp. online review - van de Ven, Hans (2017). China at War: Triumph and Tragedy in the Emergence of the New China, 1937–1952. London: Cambridge, MA: Harvard University Press, 2017: Profile Books. ISBN 9781781251942. - Wilson, Dick (1982). When Tigers Fight: The story of the Sino-Japanese War, 1937–1945. New York: Viking Press. ISBN 0-670-76003-X. - Zarrow, Peter (2005). "The War of Resistance, 1937–45". China in War and Revolution 1895–1949. London: Routledge. - China at war, Volume 1, Issue 3. China Information Committee. 1938. p. 66. Retrieved 21 March 2012. Issue 40 of China, a collection of pamphlets. Original from Pennsylvania State University. Digitized 15 September 2009	oercommons	2025-03-18T00:36:11.284526	Neil Greenwood	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/88049/overview", "title": "Statewide Dual Credit World History, The Catastrophe of the Modern Era: 1919-Present CE, Chapter 14: The World Afire: World War II, Japanese Invasion of Manchuria", "author": "Anna McCollum" }
https://oercommons.org/courseware/lesson/84376/overview	OER Cells and Tissues Lab Hyperdoc OER Integumentary System Lab Hyperdoc OER Muscular System 1 Lab Hyperdoc OER Muscular System 2 Lab Hyperdoc OER Nervous System 1 Lab Hyperdoc OER Nervous System 2 Lab Hyperdoc OER Skeletal System 1 Lab Hyperdoc OER Skeletal System 2 Lab Hyperdoc OER Special Senses Lab Hyperdoc Anatomy & Physiology 1 Lab HyperDocs Overview These HyperDocs are intended to be used as standalone lab resources for an online Anatomy & Physiology 1 Lab. Within the Study Activities section at the end of each document, the red, bolded, and capitalized words are meant to be replaced at the instructor's discretion. Fundamentals of Anatomy & Physiology This lab covers the fundamentals of Anatomy and Physiology, including body surface regions, directional terms, planes, body cavities, organ systems, bonds, and molecules. Cells and Tissues This lab covers content related to organic molecules, protein structure, organelle identification and function, and tissues. Nervous System 1 - Neuron, Spinal Cord, and Spinal Nerves This lab covers the divisions of the nervous system, neuron anatomy, meninges, spinal cord anatomy, and spinal nerves. Nervous System 2 - Brain and Crainial Nerves This lab covers nervous system divisions, anatomy of the brain, cerebrospinal fluid, and cranial nerves. Special Senses This lab covers the special senses of vision, hearing, and equilibrium, and focuses on the anatomy of the eye and ear. Skeletal System 1 - Axial Skeleton This lab covers divisions of the skeletal system, and the shapes, surface features, and select bones and bone markings of the axial skeleton. Skeletal System 2 - Appendicular Skeleton This lab covers divisions of the skeletal system, and the shapes, surface features, and select bones and bone markings of the appendicular skeleton. Muscular System 1 - Muscles of the Axial Skeleton This lab covers basic terminology related to muscles and muscle groups, muscle shapes, joint movements, and select muscles of the axial skeleton. Muscular System 2 - Muscles of the Appendicular Skeleton This lab covers select muscles and muscle actions of the appendicular skeleton. Integumentary System This lab covers the regions of the integumentary system, the layers of the epidermis, the layers of the dermis, and the accessory structures of the skin.	oercommons	2025-03-18T00:36:11.318329	07/30/2021	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/84376/overview", "title": "Anatomy & Physiology 1 Lab HyperDocs", "author": "Michael Anderson" }
https://oercommons.org/courseware/lesson/124577/overview	The Adventure of the Cheap Flat The Final Problem The Purloined Letter The Mystery Genre Overview A selection of public domain reading related to the origins and conventions of the mystery genre. Reading 1. Poe, E.A. "The Purloined Letter" 2. Doyle, A.C. "The Final Problem" 3. Christie, A. "The Adventure of the Cheap Flat." 4. Orwell, G. "The Decline of the English Murder."	oercommons	2025-03-18T00:36:11.338629	Wendy Stephens	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/124577/overview", "title": "The Mystery Genre", "author": "Textbook" }
https://oercommons.org/courseware/lesson/56351/overview	An Introduction to the Human Body Introduction Figure 1.1 Blood Pressure A proficiency in anatomy and physiology is fundamental to any career in the health professions. (credit: Bryan Mason/flickr) CHAPTER OBJECTIVES After studying this chapter, you will be able to: - Distinguish between anatomy and physiology, and identify several branches of each - Describe the structure of the body, from simplest to most complex, in terms of the six levels of organization - Identify the functional characteristics of human life - Identify the four requirements for human survival - Define homeostasis and explain its importance to normal human functioning - Use appropriate anatomical terminology to identify key body structures, body regions, and directions in the body - Compare and contrast at least four medical imagining techniques in terms of their function and use in medicine Though you may approach a course in anatomy and physiology strictly as a requirement for your field of study, the knowledge you gain in this course will serve you well in many aspects of your life. An understanding of anatomy and physiology is not only fundamental to any career in the health professions, but it can also benefit your own health. Familiarity with the human body can help you make healthful choices and prompt you to take appropriate action when signs of illness arise. Your knowledge in this field will help you understand news about nutrition, medications, medical devices, and procedures and help you understand genetic or infectious diseases. At some point, everyone will have a problem with some aspect of his or her body and your knowledge can help you to be a better parent, spouse, partner, friend, colleague, or caregiver. This chapter begins with an overview of anatomy and physiology and a preview of the body regions and functions. It then covers the characteristics of life and how the body works to maintain stable conditions. It introduces a set of standard terms for body structures and for planes and positions in the body that will serve as a foundation for more comprehensive information covered later in the text. It ends with examples of medical imaging used to see inside the living body. Overview of Anatomy and Physiology - Compare and contrast anatomy and physiology, including their specializations and methods of study - Discuss the fundamental relationship between anatomy and physiology Human anatomy is the scientific study of the body’s structures. Some of these structures are very small and can only be observed and analyzed with the assistance of a microscope. Other larger structures can readily be seen, manipulated, measured, and weighed. The word “anatomy” comes from a Greek root that means “to cut apart.” Human anatomy was first studied by observing the exterior of the body and observing the wounds of soldiers and other injuries. Later, physicians were allowed to dissect bodies of the dead to augment their knowledge. When a body is dissected, its structures are cut apart in order to observe their physical attributes and their relationships to one another. Dissection is still used in medical schools, anatomy courses, and in pathology labs. In order to observe structures in living people, however, a number of imaging techniques have been developed. These techniques allow clinicians to visualize structures inside the living body such as a cancerous tumor or a fractured bone. Like most scientific disciplines, anatomy has areas of specialization. Gross anatomy is the study of the larger structures of the body, those visible without the aid of magnification (Figure 1.2a). Macro- means “large,” thus, gross anatomy is also referred to as macroscopic anatomy. In contrast, micro- means “small,” and microscopic anatomy is the study of structures that can be observed only with the use of a microscope or other magnification devices (Figure 1.2b). Microscopic anatomy includes cytology, the study of cells and histology, the study of tissues. As the technology of microscopes has advanced, anatomists have been able to observe smaller and smaller structures of the body, from slices of large structures like the heart, to the three-dimensional structures of large molecules in the body. Figure 1.2 Gross and Microscopic Anatomy (a) Gross anatomy considers large structures such as the brain. (b) Microscopic anatomy can deal with the same structures, though at a different scale. This is a micrograph of nerve cells from the brain. LM × 1600. (credit a: “WriterHound”/Wikimedia Commons; credit b: Micrograph provided by the Regents of University of Michigan Medical School © 2012) Anatomists take two general approaches to the study of the body’s structures: regional and systemic. Regional anatomy is the study of the interrelationships of all of the structures in a specific body region, such as the abdomen. Studying regional anatomy helps us appreciate the interrelationships of body structures, such as how muscles, nerves, blood vessels, and other structures work together to serve a particular body region. In contrast, systemic anatomy is the study of the structures that make up a discrete body system—that is, a group of structures that work together to perform a unique body function. For example, a systemic anatomical study of the muscular system would consider all of the skeletal muscles of the body. Whereas anatomy is about structure, physiology is about function. Human physiology is the scientific study of the chemistry and physics of the structures of the body and the ways in which they work together to support the functions of life. Much of the study of physiology centers on the body’s tendency toward homeostasis. Homeostasis is the state of steady internal conditions maintained by living things. The study of physiology certainly includes observation, both with the naked eye and with microscopes, as well as manipulations and measurements. However, current advances in physiology usually depend on carefully designed laboratory experiments that reveal the functions of the many structures and chemical compounds that make up the human body. Like anatomists, physiologists typically specialize in a particular branch of physiology. For example, neurophysiology is the study of the brain, spinal cord, and nerves and how these work together to perform functions as complex and diverse as vision, movement, and thinking. Physiologists may work from the organ level (exploring, for example, what different parts of the brain do) to the molecular level (such as exploring how an electrochemical signal travels along nerves). Form is closely related to function in all living things. For example, the thin flap of your eyelid can snap down to clear away dust particles and almost instantaneously slide back up to allow you to see again. At the microscopic level, the arrangement and function of the nerves and muscles that serve the eyelid allow for its quick action and retreat. At a smaller level of analysis, the function of these nerves and muscles likewise relies on the interactions of specific molecules and ions. Even the three-dimensional structure of certain molecules is essential to their function. Your study of anatomy and physiology will make more sense if you continually relate the form of the structures you are studying to their function. In fact, it can be somewhat frustrating to attempt to study anatomy without an understanding of the physiology that a body structure supports. Imagine, for example, trying to appreciate the unique arrangement of the bones of the human hand if you had no conception of the function of the hand. Fortunately, your understanding of how the human hand manipulates tools—from pens to cell phones—helps you appreciate the unique alignment of the thumb in opposition to the four fingers, making your hand a structure that allows you to pinch and grasp objects and type text messages. Structural Organization of the Human Body By the end of this section, you will be able to:- Describe the structure of the human body in terms of six levels of organization - List the eleven organ systems of the human body and identify at least one organ and one major function of each Before you begin to study the different structures and functions of the human body, it is helpful to consider its basic architecture; that is, how its smallest parts are assembled into larger structures. It is convenient to consider the structures of the body in terms of fundamental levels of organization that increase in complexity: subatomic particles, atoms, molecules, organelles, cells, tissues, organs, organ systems, organisms and biosphere (Figure 1.3). Figure 1.3 Levels of Structural Organization of the Human Body The organization of the body often is discussed in terms of six distinct levels of increasing complexity, from the smallest chemical building blocks to a unique human organism. The Levels of Organization To study the chemical level of organization, scientists consider the simplest building blocks of matter: subatomic particles, atoms and molecules. All matter in the universe is composed of one or more unique pure substances called elements, familiar examples of which are hydrogen, oxygen, carbon, nitrogen, calcium, and iron. The smallest unit of any of these pure substances (elements) is an atom. Atoms are made up of subatomic particles such as the proton, electron and neutron. Two or more atoms combine to form a molecule, such as the water molecules, proteins, and sugars found in living things. Molecules are the chemical building blocks of all body structures. A cell is the smallest independently functioning unit of a living organism. Even bacteria, which are extremely small, independently-living organisms, have a cellular structure. Each bacterium is a single cell. All living structures of human anatomy contain cells, and almost all functions of human physiology are performed in cells or are initiated by cells. A human cell typically consists of flexible membranes that enclose cytoplasm, a water-based cellular fluid together with a variety of tiny functioning units called organelles. In humans, as in all organisms, cells perform all functions of life. A tissue is a group of many similar cells (though sometimes composed of a few related types) that work together to perform a specific function. An organ is an anatomically distinct structure of the body composed of two or more tissue types. Each organ performs one or more specific physiological functions. An organ system is a group of organs that work together to perform major functions or meet physiological needs of the body. This book covers eleven distinct organ systems in the human body (Figure 1.4 and Figure 1.5). Assigning organs to organ systems can be imprecise since organs that “belong” to one system can also have functions integral to another system. In fact, most organs contribute to more than one system. Figure 1.4 Organ Systems of the Human Body Organs that work together are grouped into organ systems. Figure 1.5 Organ Systems of the Human Body (continued) Organs that work together are grouped into organ systems The organism level is the highest level of organization. An organism is a living being that has a cellular structure and that can independently perform all physiologic functions necessary for life. In multicellular organisms, including humans, all cells, tissues, organs, and organ systems of the body work together to maintain the life and health of the organism Functions of Human Life - Explain the importance of organization to the function of the human organism - Distinguish between metabolism, anabolism, and catabolism - Provide at least two examples of human responsiveness and human movement - Compare and contrast growth, differentiation, and reproduction The different organ systems each have different functions and therefore unique roles to perform in physiology. These many functions can be summarized in terms of a few that we might consider definitive of human life: organization, metabolism, responsiveness, movement, development, and reproduction. Organization A human body consists of trillions of cells organized in a way that maintains distinct internal compartments. These compartments keep body cells separated from external environmental threats and keep the cells moist and nourished. They also separate internal body fluids from the countless microorganisms that grow on body surfaces, including the lining of certain passageways that connect to the outer surface of the body. The intestinal tract, for example, is home to more bacterial cells than the total of all human cells in the body, yet these bacteria are outside the body and cannot be allowed to circulate freely inside the body. Cells, for example, have a cell membrane (also referred to as the plasma membrane) that keeps the intracellular environment—the fluids and organelles—separate from the extracellular environment. Blood vessels keep blood inside a closed circulatory system, and nerves and muscles are wrapped in connective tissue sheaths that separate them from surrounding structures. In the chest and abdomen, a variety of internal membranes keep major organs such as the lungs, heart, and kidneys separate from others. The body’s largest organ system is the integumentary system, which includes the skin and its associated structures, such as hair and nails. The surface tissue of skin is a barrier that protects internal structures and fluids from potentially harmful microorganisms and other toxins. Metabolism The first law of thermodynamics holds that energy can neither be created nor destroyed—it can only change form. Your basic function as an organism is to consume (ingest) energy and molecules in the foods you eat, convert some of it into fuel for movement, sustain your body functions, and build and maintain your body structures. There are two types of reactions that accomplish this: anabolism and catabolism. - Anabolism is the process whereby smaller, simpler molecules are combined into larger, more complex substances. Your body can assemble, by utilizing energy, the complex chemicals it needs by combining small molecules derived from the foods you eat - Catabolism is the process by which larger more complex substances are broken down into smaller simpler molecules. Catabolism releases energy. The complex molecules found in foods are broken down so the body can use their parts to assemble the structures and substances needed for life. Taken together, these two processes are called metabolism. Metabolism is the sum of all anabolic and catabolic reactions that take place in the body (Figure 1.6). Both anabolism and catabolism occur simultaneously and continuously to keep you alive. Figure 1.6 Metabolism Anabolic reactions are building reactions, and they consume energy. Catabolic reactions break materials down and release energy. Metabolism includes both anabolic and catabolic reactions. Every cell in your body makes use of a chemical compound, adenosine triphosphate (ATP), to store and release energy. The cell stores energy in the synthesis (anabolism) of ATP, then moves the ATP molecules to the location where energy is needed to fuel cellular activities. Then the ATP is broken down (catabolism) and a controlled amount of energy is released, which is used by the cell to perform a particular job. INTERACTIVE LINK View this animation to learn more about metabolic processes. Which organs of the body likely carry out anabolic processes? What about catabolic processes? Responsiveness Responsiveness is the ability of an organism to adjust to changes in its internal and external environments. An example of responsiveness to external stimuli could include moving toward sources of food and water and away from perceived dangers. Changes in an organism’s internal environment, such as increased body temperature, can cause the responses of sweating and the dilation of blood vessels in the skin in order to decrease body temperature, as shown by the runners in Figure 1.7. Movement Human movement includes not only actions at the joints of the body, but also the motion of individual organs and even individual cells. As you read these words, red and white blood cells are moving throughout your body, muscle cells are contracting and relaxing to maintain your posture and to focus your vision, and glands are secreting chemicals to regulate body functions. Your body is coordinating the action of entire muscle groups to enable you to move air into and out of your lungs, to push blood throughout your body, and to propel the food you have eaten through your digestive tract. Consciously, of course, you contract your skeletal muscles to move the bones of your skeleton to get from one place to another (as the runners are doing in Figure 1.7), and to carry out all of the activities of your daily life. Figure 1.7 Marathon Runners Runners demonstrate two characteristics of living humans—responsiveness and movement. Anatomic structures and physiological processes allow runners to coordinate the action of muscle groups and sweat in response to rising internal body temperature. (credit: Phil Roeder/flickr) Development, growth and reproduction Development is all of the changes the body goes through in life. Development includes the process of differentiation, in which unspecialized cells become specialized in structure and function to perform certain tasks in the body. Development also includes the processes of growth and repair, both of which involve cell differentiation. Growth is the increase in body size. Humans, like all multicellular organisms, grow by increasing the number of existing cells, increasing the amount of non-cellular material around cells (such as mineral deposits in bone), and, within very narrow limits, increasing the size of existing cells. Reproduction is the formation of a new organism from parent organisms. In humans, reproduction is carried out by the male and female reproductive systems. Because death will come to all complex organisms, without reproduction, the line of organisms would end. Requirements for Human Life - Discuss the role of oxygen and nutrients in maintaining human survival - Explain why extreme heat and extreme cold threaten human survival - Explain how the pressure exerted by gases and fluids influences human survival Humans have been adapting to life on Earth for at least the past 200,000 years. Earth and its atmosphere have provided us with air to breathe, water to drink, and food to eat, but these are not the only requirements for survival. Although you may rarely think about it, you also cannot live outside of a certain range of temperature and pressure that the surface of our planet and its atmosphere provides. The next sections explore these four requirements of life. Oxygen Atmospheric air is only about 20 percent oxygen, but that oxygen is a key component of the chemical reactions that keep the body alive, including the reactions that produce ATP. Brain cells are especially sensitive to lack of oxygen because of their requirement for a high-and-steady production of ATP. Brain damage is likely within five minutes without oxygen, and death is likely within ten minutes. Nutrients A nutrient is a substance in foods and beverages that is essential to human survival. The three basic classes of nutrients are water, the energy-yielding and body-building nutrients, and the micronutrients (vitamins and minerals). The most critical nutrient is water. Depending on the environmental temperature and our state of health, we may be able to survive for only a few days without water. The body’s functional chemicals are dissolved and transported in water, and the chemical reactions of life take place in water. Moreover, water is the largest component of cells, blood, and the fluid between cells, and water makes up about 70 percent of an adult’s body mass. Water also helps regulate our internal temperature and cushions, protects, and lubricates joints and many other body structures. The energy-yielding nutrients are primarily carbohydrates and lipids, while proteins mainly supply the amino acids that are the building blocks of the body itself. You ingest these in plant and animal foods and beverages, and the digestive system breaks them down into molecules small enough to be absorbed. The breakdown products of carbohydrates and lipids can then be used in the metabolic processes that convert them to ATP. Although you might feel as if you are starving after missing a single meal, you can survive without consuming the energy-yielding nutrients for at least several weeks. Water and the energy-yielding nutrients are also referred to as macronutrients because the body needs them in large amounts. In contrast, micronutrients are vitamins and minerals. These elements and compounds participate in many essential chemical reactions and processes, such as nerve impulses, and some, such as calcium, also contribute to the body’s structure. Your body can store some of the micronutrients in its tissues, and draw on those reserves if you fail to consume them in your diet for a few days or weeks. Some others micronutrients, such as vitamin C and most of the B vitamins, are water-soluble and cannot be stored, so you need to consume them every day or two. Narrow Range of Temperature You have probably seen news stories about athletes who died of heat stroke, or hikers who died of exposure to cold. Such deaths occur because the chemical reactions upon which the body depends can only take place within a narrow range of body temperature, from just below to just above 37°C (98.6°F). When body temperature rises well above or drops well below normal, certain proteins (enzymes) that facilitate chemical reactions lose their normal structure and their ability to function and the chemical reactions of metabolism cannot proceed. That said, the body can respond effectively to short-term exposure to heat (Figure 1.8) or cold. One of the body’s responses to heat is, of course, sweating. As sweat evaporates from skin, it removes some thermal energy from the body, cooling it. Adequate water (from the extracellular fluid in the body) is necessary to produce sweat, so adequate fluid intake is essential to balance that loss during the sweat response. Not surprisingly, the sweat response is much less effective in a humid environment because the air is already saturated with water. Thus, the sweat on the skin’s surface is not able to evaporate, and internal body temperature can get dangerously high. Figure 1.8 Extreme Heat Humans adapt to some degree to repeated exposure to high temperatures. (credit: McKay Savage/flickr) The body can also respond effectively to short-term exposure to cold. One response to cold is shivering, which is random muscle movement that generates heat. Another response is increased breakdown of stored energy to generate heat. When that energy reserve is depleted, however, and the core temperature begins to drop significantly, red blood cells will lose their ability to give up oxygen, denying the brain of this critical component of ATP production. This lack of oxygen can cause confusion, lethargy, and eventually loss of consciousness and death. The body responds to cold by reducing blood circulation to the extremities, the hands and feet, in order to prevent blood from cooling there and so that the body’s core can stay warm. Even when core body temperature remains stable, however, tissues exposed to severe cold, especially the fingers and toes, can develop frostbite when blood flow to the extremities has been much reduced. This form of tissue damage can be permanent and lead to gangrene, requiring amputation of the affected region. EVERYDAY CONNECTION Controlled Hypothermia As you have learned, the body continuously engages in coordinated physiological processes to maintain a stable temperature. In some cases, however, overriding this system can be useful, or even life-saving. Hypothermia is the clinical term for an abnormally low body temperature (hypo- = “below” or “under”). Controlled hypothermia is clinically induced hypothermia performed in order to reduce the metabolic rate of an organ or of a person’s entire body. Controlled hypothermia often is used, for example, during open-heart surgery because it decreases the metabolic needs of the brain, heart, and other organs, reducing the risk of damage to them. When controlled hypothermia is used clinically, the patient is given medication to prevent shivering. The body is then cooled to 25–32°C (79–89°F). The heart is stopped and an external heart-lung pump maintains circulation to the patient’s body. The heart is cooled further and is maintained at a temperature below 15°C (60°F) for the duration of the surgery. This very cold temperature helps the heart muscle to tolerate its lack of blood supply during the surgery. Some emergency department physicians use controlled hypothermia to reduce damage to the heart in patients who have suffered a cardiac arrest. In the emergency department, the physician induces coma and lowers the patient’s body temperature to approximately 91 degrees. This condition, which is maintained for 24 hours, slows the patient’s metabolic rate. Because the patient’s organs require less blood to function, the heart’s workload is reduced. Narrow Range of Atmospheric Pressure Pressure is a force exerted by a substance that is in contact with another substance. Atmospheric pressure is pressure exerted by the mixture of gases (primarily nitrogen and oxygen) in the Earth’s atmosphere. Although you may not perceive it, atmospheric pressure is constantly pressing down on your body. This pressure keeps gases within your body, such as the gaseous nitrogen in body fluids, dissolved. If you were suddenly ejected from a space ship above Earth’s atmosphere, you would go from a situation of normal pressure to one of very low pressure. The pressure of the nitrogen gas in your blood would be much higher than the pressure of nitrogen in the space surrounding your body. As a result, the nitrogen gas in your blood would expand, forming bubbles that could block blood vessels and even cause cells to break apart. Atmospheric pressure does more than just keep blood gases dissolved. Your ability to breathe—that is, to take in oxygen and release carbon dioxide—also depends upon a precise atmospheric pressure. Altitude sickness occurs in part because the atmosphere at high altitudes exerts less pressure, reducing the exchange of these gases, and causing shortness of breath, confusion, headache, lethargy, and nausea. Mountain climbers carry oxygen to reduce the effects of both low oxygen levels and low barometric pressure at higher altitudes (Figure 1.9). Figure 1.9 Harsh Conditions Climbers on Mount Everest must accommodate extreme cold, low oxygen levels, and low barometric pressure in an environment hostile to human life. (credit: Melanie Ko/flickr) HOMEOSTATIC IMBALANCES Decompression Sickness Decompression sickness (DCS) is a condition in which gases dissolved in the blood or in other body tissues are no longer dissolved following a reduction in pressure on the body. This condition affects underwater divers who surface from a deep dive too quickly, and it can affect pilots flying at high altitudes in planes with unpressurized cabins. Divers often call this condition “the bends,” a reference to joint pain that is a symptom of DCS. In all cases, DCS is brought about by a reduction in barometric pressure. At high altitude, barometric pressure is much less than on Earth’s surface because pressure is produced by the weight of the column of air above the body pressing down on the body. The very great pressures on divers in deep water are likewise from the weight of a column of water pressing down on the body. For divers, DCS occurs at normal barometric pressure (at sea level), but it is brought on by the relatively rapid decrease of pressure as divers rise from the high pressure conditions of deep water to the now low, by comparison, pressure at sea level. Not surprisingly, diving in deep mountain lakes, where barometric pressure at the surface of the lake is less than that at sea level is more likely to result in DCS than diving in water at sea level. In DCS, gases dissolved in the blood (primarily nitrogen) come rapidly out of solution, forming bubbles in the blood and in other body tissues. This occurs because when pressure of a gas over a liquid is decreased, the amount of gas that can remain dissolved in the liquid also is decreased. It is air pressure that keeps your normal blood gases dissolved in the blood. When pressure is reduced, less gas remains dissolved. You have seen this in effect when you open a carbonated drink. Removing the seal of the bottle reduces the pressure of the gas over the liquid. This in turn causes bubbles as dissolved gases (in this case, carbon dioxide) come out of solution in the liquid. The most common symptoms of DCS are pain in the joints, with headache and disturbances of vision occurring in 10 percent to 15 percent of cases. Left untreated, very severe DCS can result in death. Immediate treatment is with pure oxygen. The affected person is then moved into a hyperbaric chamber. A hyperbaric chamber is a reinforced, closed chamber that is pressurized to greater than atmospheric pressure. It treats DCS by repressurizing the body so that pressure can then be removed much more gradually. Because the hyperbaric chamber introduces oxygen to the body at high pressure, it increases the concentration of oxygen in the blood. This has the effect of replacing some of the nitrogen in the blood with oxygen, which is easier to tolerate out of solution. The dynamic pressure of body fluids is also important to human survival. For example, blood pressure, which is the pressure exerted by blood as it flows within blood vessels, must be great enough to enable blood to reach all body tissues, and yet low enough to ensure that the delicate blood vessels can withstand the friction and force of the pulsating flow of pressurized blood. Homeostasis - Discuss the role of homeostasis in healthy functioning - Contrast negative and positive feedback, giving one physiologic example of each mechanism Maintaining homeostasis requires that the body continuously monitor its internal conditions. From body temperature to blood pressure to levels of certain nutrients, each physiological condition has a particular set point. A set point is the physiological value around which the normal range fluctuates. A normal range is the restricted set of values that is optimally healthful and stable. For example, the set point for normal human body temperature is approximately 37°C (98.6°F) Physiological parameters, such as body temperature and blood pressure, tend to fluctuate within a normal range a few degrees above and below that point. Control centers in the brain and other parts of the body monitor and react to deviations from homeostasis using negative feedback. Negative feedback is a mechanism that reverses a deviation from the set point. Therefore, negative feedback maintains body parameters within their normal range. The maintenance of homeostasis by negative feedback goes on throughout the body at all times, and an understanding of negative feedback is thus fundamental to an understanding of human physiology. Negative Feedback A negative feedback system has three basic components (Figure 1.10a). A sensor, also referred to a receptor, is a component of a feedback system that monitors a physiological value. This value is reported to the control center. The control center is the component in a feedback system that compares the value to the normal range. If the value deviates too much from the set point, then the control center activates an effector. An effector is the component in a feedback system that causes a change to reverse the situation and return the value to the normal range. Figure 1.10 Negative Feedback Loop In a negative feedback loop, a stimulus—a deviation from a set point—is resisted through a physiological process that returns the body to homeostasis. (a) A negative feedback loop has four basic parts. (b) Body temperature is regulated by negative feedback. In order to set the system in motion, a stimulus must drive a physiological parameter beyond its normal range (that is, beyond homeostasis). This stimulus is “heard” by a specific sensor. For example, in the control of blood glucose, specific endocrine cells in the pancreas detect excess glucose (the stimulus) in the bloodstream. These pancreatic beta cells respond to the increased level of blood glucose by releasing the hormone insulin into the bloodstream. The insulin signals skeletal muscle fibers, fat cells (adipocytes), and liver cells to take up the excess glucose, removing it from the bloodstream. As glucose concentration in the bloodstream drops, the decrease in concentration—the actual negative feedback—is detected by pancreatic alpha cells, and insulin release stops. This prevents blood sugar levels from continuing to drop below the normal range. Humans have a similar temperature regulation feedback system that works by promoting either heat loss or heat gain (Figure 1.10b). When the brain’s temperature regulation center receives data from the sensors indicating that the body’s temperature exceeds its normal range, it stimulates a cluster of brain cells referred to as the “heat-loss center.” This stimulation has three major effects: - Blood vessels in the skin begin to dilate allowing more blood from the body core to flow to the surface of the skin allowing the heat to radiate into the environment. - As blood flow to the skin increases, sweat glands are activated to increase their output. As the sweat evaporates from the skin surface into the surrounding air, it takes heat with it. - The depth of respiration increases, and a person may breathe through an open mouth instead of through the nasal passageways. This further increases heat loss from the lungs. In contrast, activation of the brain’s heat-gain center by exposure to cold reduces blood flow to the skin, and blood returning from the limbs is diverted into a network of deep veins. This arrangement traps heat closer to the body core and restricts heat loss. If heat loss is severe, the brain triggers an increase in random signals to skeletal muscles, causing them to contract and producing shivering. The muscle contractions of shivering release heat while using up ATP. The brain triggers the thyroid gland in the endocrine system to release thyroid hormone, which increases metabolic activity and heat production in cells throughout the body. The brain also signals the adrenal glands to release epinephrine (adrenaline), a hormone that causes the breakdown of glycogen into glucose, which can be used as an energy source. The breakdown of glycogen into glucose also results in increased metabolism and heat production. INTERACTIVE LINK Water concentration in the body is critical for proper functioning. A person’s body retains very tight control on water levels without conscious control by the person. Watch this video to learn more about water concentration in the body. Which organ has primary control over the amount of water in the body? Positive Feedback Positive feedback intensifies a change in the body’s physiological condition rather than reversing it. A deviation from the normal range results in more change, and the system moves farther away from the normal range. Positive feedback in the body is normal only when there is a definite end point. Childbirth and the body’s response to blood loss are two examples of positive feedback loops that are normal but are activated only when needed. Childbirth at full term is an example of a situation in which the maintenance of the existing body state is not desired. Enormous changes in the mother’s body are required to expel the baby at the end of pregnancy. And the events of childbirth, once begun, must progress rapidly to a conclusion or the life of the mother and the baby are at risk. The extreme muscular work of labor and delivery are the result of a positive feedback system (Figure 1.11). Figure 1.11 Positive Feedback Loop Normal childbirth is driven by a positive feedback loop. A positive feedback loop results in a change in the body’s status, rather than a return to homeostasis. The first contractions of labor (the stimulus) push the baby toward the cervix (the lowest part of the uterus). The cervix contains stretch-sensitive nerve cells that monitor the degree of stretching (the sensors). These nerve cells send messages to the brain, which in turn causes the pituitary gland at the base of the brain to release the hormone oxytocin into the bloodstream. Oxytocin causes stronger contractions of the smooth muscles in of the uterus (the effectors), pushing the baby further down the birth canal. This causes even greater stretching of the cervix. The cycle of stretching, oxytocin release, and increasingly more forceful contractions stops only when the baby is born. At this point, the stretching of the cervix halts, stopping the release of oxytocin. A second example of positive feedback centers on reversing extreme damage to the body. Following a penetrating wound, the most immediate threat is excessive blood loss. Less blood circulating means reduced blood pressure and reduced perfusion (penetration of blood) to the brain and other vital organs. If perfusion is severely reduced, vital organs will shut down and the person will die. The body responds to this potential catastrophe by releasing substances in the injured blood vessel wall that begin the process of blood clotting. As each step of clotting occurs, it stimulates the release of more clotting substances. This accelerates the processes of clotting and sealing off the damaged area. Clotting is contained in a local area based on the tightly controlled availability of clotting proteins. This is an adaptive, life-saving cascade of events. Anatomical Terminology - Demonstrate the anatomical position - Describe the human body using directional and regional terms - Identify three planes most commonly used in the study of anatomy - Distinguish between the posterior (dorsal) and the anterior (ventral) body cavities, identifying their subdivisions and representative organs found in each - Describe serous membrane and explain its function Anatomists and health care providers use terminology that can be bewildering to the uninitiated. However, the purpose of this language is not to confuse, but rather to increase precision and reduce medical errors. For example, is a scar “above the wrist” located on the forearm two or three inches away from the hand? Or is it at the base of the hand? Is it on the palm-side or back-side? By using precise anatomical terminology, we eliminate ambiguity. Anatomical terms derive from ancient Greek and Latin words. Because these languages are no longer used in everyday conversation, the meaning of their words does not change. Anatomical terms are made up of roots, prefixes, and suffixes. The root of a term often refers to an organ, tissue, or condition, whereas the prefix or suffix often describes the root. For example, in the disorder hypertension, the prefix “hyper-” means “high” or “over,” and the root word “tension” refers to pressure, so the word “hypertension” refers to abnormally high blood pressure. Anatomical Position To further increase precision, anatomists standardize the way in which they view the body. Just as maps are normally oriented with north at the top, the standard body “map,” or anatomical position, is that of the body standing upright, with the feet at shoulder width and parallel, toes forward. The upper limbs are held out to each side, and the palms of the hands face forward as illustrated in Figure 1.12. Using this standard position reduces confusion. It does not matter how the body being described is oriented, the terms are used as if it is in anatomical position. For example, a scar in the “anterior (front) carpal (wrist) region” would be present on the palm side of the wrist. The term “anterior” would be used even if the hand were palm down on a table. Figure 1.12 Regions of the Human Body The human body is shown in anatomical position in an (a) anterior view and a (b) posterior view. The regions of the body are labeled in boldface. A body that is lying down is described as either prone or supine. Prone describes a face-down orientation, and supinedescribes a face up orientation. These terms are sometimes used in describing the position of the body during specific physical examinations or surgical procedures. Regional Terms The human body’s numerous regions have specific terms to help increase precision (see Figure 1.12). Notice that the term “brachium” or “arm” is reserved for the “upper arm” and “antebrachium” or “forearm” is used rather than “lower arm.” Similarly, “femur” or “thigh” is correct, and “leg” or “crus” is reserved for the portion of the lower limb between the knee and the ankle. You will be able to describe the body’s regions using the terms from the figure. Directional Terms Certain directional anatomical terms appear throughout this and any other anatomy textbook (Figure 1.13). These terms are essential for describing the relative locations of different body structures. For instance, an anatomist might describe one band of tissue as “inferior to” another or a physician might describe a tumor as “superficial to” a deeper body structure. Commit these terms to memory to avoid confusion when you are studying or describing the locations of particular body parts. - Anterior (or ventral) Describes the front or direction toward the front of the body. The toes are anterior to the foot. - Posterior (or dorsal) Describes the back or direction toward the back of the body. The popliteus is posterior to the patella. - Superior (or cranial) describes a position above or higher than another part of the body proper. The orbits are superior to the oris. - Inferior (or caudal) describes a position below or lower than another part of the body proper; near or toward the tail (in humans, the coccyx, or lowest part of the spinal column). The pelvis is inferior to the abdomen. - Lateral describes the side or direction toward the side of the body. The thumb (pollex) is lateral to the digits. - Medial describes the middle or direction toward the middle of the body. The hallux is the medial toe. - Proximal describes a position in a limb that is nearer to the point of attachment or the trunk of the body. The brachium is proximal to the antebrachium. - Distal describes a position in a limb that is farther from the point of attachment or the trunk of the body. The crus is distal to the femur. - Superficial describes a position closer to the surface of the body. The skin is superficial to the bones. - Deep describes a position farther from the surface of the body. The brain is deep to the skull. Figure 1.13 Directional Terms Applied to the Human Body Paired directional terms are shown as applied to the human body. Body Planes A section is a two-dimensional surface of a three-dimensional structure that has been cut. Modern medical imaging devices enable clinicians to obtain “virtual sections” of living bodies. We call these scans. Body sections and scans can be correctly interpreted, however, only if the viewer understands the plane along which the section was made. A plane is an imaginary two-dimensional surface that passes through the body. There are three planes commonly referred to in anatomy and medicine, as illustrated in Figure 1.14. - The sagittal plane is the plane that divides the body or an organ vertically into right and left sides. If this vertical plane runs directly down the middle of the body, it is called the midsagittal or median plane. If it divides the body into unequal right and left sides, it is called a parasagittal plane or less commonly a longitudinal section. - The frontal plane is the plane that divides the body or an organ into an anterior (front) portion and a posterior (rear) portion. The frontal plane is often referred to as a coronal plane. (“Corona” is Latin for “crown.”) - The transverse plane is the plane that divides the body or organ horizontally into upper and lower portions. Transverse planes produce images referred to as cross sections. Figure 1.14 Planes of the Body The three planes most commonly used in anatomical and medical imaging are the sagittal, frontal (or coronal), and transverse plane. Body Cavities and Serous Membranes The body maintains its internal organization by means of membranes, sheaths, and other structures that separate compartments. The dorsal (posterior) cavity and the ventral (anterior) cavity are the largest body compartments (Figure 1.15). These cavities contain and protect delicate internal organs, and the ventral cavity allows for significant changes in the size and shape of the organs as they perform their functions. The lungs, heart, stomach, and intestines, for example, can expand and contract without distorting other tissues or disrupting the activity of nearby organs. Figure 1.15 Dorsal and Ventral Body Cavities The ventral cavity includes the thoracic and abdominopelvic cavities and their subdivisions. The dorsal cavity includes the cranial and spinal cavities. Subdivisions of the Posterior (Dorsal) and Anterior (Ventral) Cavities The posterior (dorsal) and anterior (ventral) cavities are each subdivided into smaller cavities. In the posterior (dorsal) cavity, the cranial cavity houses the brain, and the spinal cavity (or vertebral cavity) encloses the spinal cord. Just as the brain and spinal cord make up a continuous, uninterrupted structure, the cranial and spinal cavities that house them are also continuous. The brain and spinal cord are protected by the bones of the skull and vertebral column and by cerebrospinal fluid, a colorless fluid produced by the brain, which cushions the brain and spinal cord within the posterior (dorsal) cavity. The anterior (ventral) cavity has two main subdivisions: the thoracic cavity and the abdominopelvic cavity (see Figure 1.15). The thoracic cavity is the more superior subdivision of the anterior cavity, and it is enclosed by the rib cage. The thoracic cavity contains the lungs and the heart, which is located in the mediastinum. The diaphragm forms the floor of the thoracic cavity and separates it from the more inferior abdominopelvic cavity. The abdominopelvic cavity is the largest cavity in the body. Although no membrane physically divides the abdominopelvic cavity, it can be useful to distinguish between the abdominal cavity, the division that houses the digestive organs, and the pelvic cavity, the division that houses the organs of reproduction. Abdominal Regions and Quadrants To promote clear communication, for instance about the location of a patient’s abdominal pain or a suspicious mass, health care providers typically divide up the cavity into either nine regions or four quadrants (Figure 1.16). Figure 1.16 Regions and Quadrants of the Peritoneal Cavity There are (a) nine abdominal regions and (b) four abdominal quadrants in the peritoneal cavity. The more detailed regional approach subdivides the cavity with one horizontal line immediately inferior to the ribs and one immediately superior to the pelvis, and two vertical lines drawn as if dropped from the midpoint of each clavicle (collarbone). There are nine resulting regions. The simpler quadrants approach, which is more commonly used in medicine, subdivides the cavity with one horizontal and one vertical line that intersect at the patient’s umbilicus (navel). Membranes of the Anterior (Ventral) Body Cavity A serous membrane (also referred to a serosa) is one of the thin membranes that cover the walls and organs in the thoracic and abdominopelvic cavities. The parietal layers of the membranes line the walls of the body cavity (pariet- refers to a cavity wall). The visceral layer of the membrane covers the organs (the viscera). Between the parietal and visceral layers is a very thin, fluid-filled serous space, or cavity (Figure 1.17). Figure 1.17 Serous Membrane Serous membrane lines the pericardial cavity and reflects back to cover the heart—much the same way that an underinflated balloon would form two layers surrounding a fist. There are three serous cavities and their associated membranes. The pleura is the serous membrane that encloses the pleural cavity; the pleural cavity surrounds the lungs. The pericardium is the serous membrane that encloses the pericardial cavity; the pericardial cavity surrounds the heart. The peritoneum is the serous membrane that encloses the peritoneal cavity; the peritoneal cavity surrounds several organs in the abdominopelvic cavity. The serous membranes form fluid-filled sacs, or cavities, that are meant to cushion and reduce friction on internal organs when they move, such as when the lungs inflate or the heart beats. Both the parietal and visceral serosa secrete the thin, slippery serous fluid located within the serous cavities. The pleural cavity reduces friction between the lungs and the body wall. Likewise, the pericardial cavity reduces friction between the heart and the wall of the pericardium. The peritoneal cavity reduces friction between the abdominal and pelvic organs and the body wall. Therefore, serous membranes provide additional protection to the viscera they enclose by reducing friction that could lead to inflammation of the organs. Medical Imaging - Discuss the uses and drawbacks of X-ray imaging - Identify four modern medical imaging techniques and how they are used For thousands of years, fear of the dead and legal sanctions limited the ability of anatomists and physicians to study the internal structures of the human body. An inability to control bleeding, infection, and pain made surgeries infrequent, and those that were performed—such as wound suturing, amputations, tooth and tumor removals, skull drilling, and cesarean births—did not greatly advance knowledge about internal anatomy. Theories about the function of the body and about disease were therefore largely based on external observations and imagination. During the fourteenth and fifteenth centuries, however, the detailed anatomical drawings of Italian artist and anatomist Leonardo da Vinci and Flemish anatomist Andreas Vesalius were published, and interest in human anatomy began to increase. Medical schools began to teach anatomy using human dissection; although some resorted to grave robbing to obtain corpses. Laws were eventually passed that enabled students to dissect the corpses of criminals and those who donated their bodies for research. Still, it was not until the late nineteenth century that medical researchers discovered non-surgical methods to look inside the living body. X-Rays German physicist Wilhelm Röntgen (1845–1923) was experimenting with electrical current when he discovered that a mysterious and invisible “ray” would pass through his flesh but leave an outline of his bones on a screen coated with a metal compound. In 1895, Röntgen made the first durable record of the internal parts of a living human: an “X-ray” image (as it came to be called) of his wife’s hand. Scientists around the world quickly began their own experiments with X-rays, and by 1900, X-rays were widely used to detect a variety of injuries and diseases. In 1901, Röntgen was awarded the first Nobel Prize for physics for his work in this field. The X-ray is a form of high energy electromagnetic radiation with a short wavelength capable of penetrating solids and ionizing gases. As they are used in medicine, X-rays are emitted from an X-ray machine and directed toward a specially treated metallic plate placed behind the patient’s body. The beam of radiation results in darkening of the X-ray plate. X-rays are slightly impeded by soft tissues, which show up as gray on the X-ray plate, whereas hard tissues, such as bone, largely block the rays, producing a light-toned “shadow.” Thus, X-rays are best used to visualize hard body structures such as teeth and bones (Figure 1.18). Like many forms of high energy radiation, however, X-rays are capable of damaging cells and initiating changes that can lead to cancer. This danger of excessive exposure to X-rays was not fully appreciated for many years after their widespread use. Figure 1.18 X-Ray of a Hand High energy electromagnetic radiation allows the internal structures of the body, such as bones, to be seen in X-rays like these. (credit: Trace Meek/flickr) Refinements and enhancements of X-ray techniques have continued throughout the twentieth and twenty-first centuries. Although often supplanted by more sophisticated imaging techniques, the X-ray remains a “workhorse” in medical imaging, especially for viewing fractures and for dentistry. The disadvantage of irradiation to the patient and the operator is now attenuated by proper shielding and by limiting exposure. Modern Medical Imaging X-rays can depict a two-dimensional image of a body region, and only from a single angle. In contrast, more recent medical imaging technologies produce data that is integrated and analyzed by computers to produce three-dimensional images or images that reveal aspects of body functioning. Computed Tomography Tomography refers to imaging by sections. Computed tomography (CT) is a noninvasive imaging technique that uses computers to analyze several cross-sectional X-rays in order to reveal minute details about structures in the body (Figure 1.19a). The technique was invented in the 1970s and is based on the principle that, as X-rays pass through the body, they are absorbed or reflected at different levels. In the technique, a patient lies on a motorized platform while a computerized axial tomography (CAT) scanner rotates 360 degrees around the patient, taking X-ray images. A computer combines these images into a two-dimensional view of the scanned area, or “slice.” Figure 1.19 Medical Imaging Techniques (a) The results of a CT scan of the head are shown as successive transverse sections. (b) An MRI machine generates a magnetic field around a patient. (c) PET scans use radiopharmaceuticals to create images of active blood flow and physiologic activity of the organ or organs being targeted. (d) Ultrasound technology is used to monitor pregnancies because it is the least invasive of imaging techniques and uses no electromagnetic radiation. (credit a: Akira Ohgaki/flickr; credit b: “Digital Cate”/flickr; credit c: “Raziel”/Wikimedia Commons; credit d: “Isis”/Wikimedia Commons) Since 1970, the development of more powerful computers and more sophisticated software has made CT scanning routine for many types of diagnostic evaluations. It is especially useful for soft tissue scanning, such as of the brain and the thoracic and abdominal viscera. Its level of detail is so precise that it can allow physicians to measure the size of a mass down to a millimeter. The main disadvantage of CT scanning is that it exposes patients to a dose of radiation many times higher than that of X-rays. In fact, children who undergo CT scans are at increased risk of developing cancer, as are adults who have multiple CT scans. INTERACTIVE LINK A CT or CAT scan relies on a circling scanner that revolves around the patient’s body. Watch this video to learn more about CT and CAT scans. What type of radiation does a CT scanner use? Magnetic Resonance Imaging Magnetic resonance imaging (MRI) is a noninvasive medical imaging technique based on a phenomenon of nuclear physics discovered in the 1930s, in which matter exposed to magnetic fields and radio waves was found to emit radio signals. In 1970, a physician and researcher named Raymond Damadian noticed that malignant (cancerous) tissue gave off different signals than normal body tissue. He applied for a patent for the first MRI scanning device, which was in use clinically by the early 1980s. The early MRI scanners were crude, but advances in digital computing and electronics led to their advancement over any other technique for precise imaging, especially to discover tumors. MRI also has the major advantage of not exposing patients to radiation. Drawbacks of MRI scans include their much higher cost, and patient discomfort with the procedure. The MRI scanner subjects the patient to such powerful electromagnets that the scan room must be shielded. The patient must be enclosed in a metal tube-like device for the duration of the scan (see Figure 1.19b), sometimes as long as thirty minutes, which can be uncomfortable and impractical for ill patients. The device is also so noisy that, even with earplugs, patients can become anxious or even fearful. These problems have been overcome somewhat with the development of “open” MRI scanning, which does not require the patient to be entirely enclosed in the metal tube. Patients with iron-containing metallic implants (internal sutures, some prosthetic devices, and so on) cannot undergo MRI scanning because it can dislodge these implants. Functional MRIs (fMRIs), which detect the concentration of blood flow in certain parts of the body, are increasingly being used to study the activity in parts of the brain during various body activities. This has helped scientists learn more about the locations of different brain functions and more about brain abnormalities and diseases. INTERACTIVE LINK A patient undergoing an MRI is surrounded by a tube-shaped scanner. Watch this video to learn more about MRIs. What is the function of magnets in an MRI? Positron Emission Tomography Positron emission tomography (PET) is a medical imaging technique involving the use of so-called radiopharmaceuticals, substances that emit radiation that is short-lived and therefore relatively safe to administer to the body. Although the first PET scanner was introduced in 1961, it took 15 more years before radiopharmaceuticals were combined with the technique and revolutionized its potential. The main advantage is that PET (see Figure 1.19c) can illustrate physiologic activity—including nutrient metabolism and blood flow—of the organ or organs being targeted, whereas CT and MRI scans can only show static images. PET is widely used to diagnose a multitude of conditions, such as heart disease, the spread of cancer, certain forms of infection, brain abnormalities, bone disease, and thyroid disease. INTERACTIVE LINK PET relies on radioactive substances administered several minutes before the scan. Watch this video to learn more about PET. How is PET used in chemotherapy? Ultrasonography Ultrasonography is an imaging technique that uses the transmission of high-frequency sound waves into the body to generate an echo signal that is converted by a computer into a real-time image of anatomy and physiology (see Figure 1.19d). Ultrasonography is the least invasive of all imaging techniques, and it is therefore used more freely in sensitive situations such as pregnancy. The technology was first developed in the 1940s and 1950s. Ultrasonography is used to study heart function, blood flow in the neck or extremities, certain conditions such as gallbladder disease, and fetal growth and development. The main disadvantages of ultrasonography are that the image quality is heavily operator-dependent and that it is unable to penetrate bone and gas. Key Terms - abdominopelvic cavity - division of the anterior (ventral) cavity that houses the abdominal and pelvic viscera - anabolism - assembly of more complex molecules from simpler molecules - anatomical position - standard reference position used for describing locations and directions on the human body - anatomy - science that studies the form and composition of the body’s structures - anterior - describes the front or direction toward the front of the body; also referred to as ventral - anterior cavity - larger body cavity located anterior to the posterior (dorsal) body cavity; includes the serous membrane-lined pleural cavities for the lungs, pericardial cavity for the heart, and peritoneal cavity for the abdominal and pelvic organs; also referred to as ventral cavity - catabolism - breaking down of more complex molecules into simpler molecules - caudal - describes a position below or lower than another part of the body proper; near or toward the tail (in humans, the coccyx, or lowest part of the spinal column); also referred to as inferior - cell - smallest independently functioning unit of all organisms; in animals, a cell contains cytoplasm, composed of fluid and organelles - computed tomography (CT) - medical imaging technique in which a computer-enhanced cross-sectional X-ray image is obtained - control center - compares values to their normal range; deviations cause the activation of an effector - cranial - describes a position above or higher than another part of the body proper; also referred to as superior - cranial cavity - division of the posterior (dorsal) cavity that houses the brain - deep - describes a position farther from the surface of the body - development - changes an organism goes through during its life - differentiation - process by which unspecialized cells become specialized in structure and function - distal - describes a position farther from the point of attachment or the trunk of the body - dorsal - describes the back or direction toward the back of the body; also referred to as posterior - dorsal cavity - posterior body cavity that houses the brain and spinal cord; also referred to the posterior body cavity - effector - organ that can cause a change in a value - frontal plane - two-dimensional, vertical plane that divides the body or organ into anterior and posterior portions - gross anatomy - study of the larger structures of the body, typically with the unaided eye; also referred to macroscopic anatomy - growth - process of increasing in size - homeostasis - steady state of body systems that living organisms maintain - inferior - describes a position below or lower than another part of the body proper; near or toward the tail (in humans, the coccyx, or lowest part of the spinal column); also referred to as caudal - lateral - describes the side or direction toward the side of the body - magnetic resonance imaging (MRI) - medical imaging technique in which a device generates a magnetic field to obtain detailed sectional images of the internal structures of the body - medial - describes the middle or direction toward the middle of the body - metabolism - sum of all of the body’s chemical reactions - microscopic anatomy - study of very small structures of the body using magnification - negative feedback - homeostatic mechanism that tends to stabilize an upset in the body’s physiological condition by preventing an excessive response to a stimulus, typically as the stimulus is removed - normal range - range of values around the set point that do not cause a reaction by the control center - nutrient - chemical obtained from foods and beverages that is critical to human survival - organ - functionally distinct structure composed of two or more types of tissues - organ system - group of organs that work together to carry out a particular function - organism - living being that has a cellular structure and that can independently perform all physiologic functions necessary for life - pericardium - sac that encloses the heart - peritoneum - serous membrane that lines the abdominopelvic cavity and covers the organs found there - physiology - science that studies the chemistry, biochemistry, and physics of the body’s functions - plane - imaginary two-dimensional surface that passes through the body - pleura - serous membrane that lines the pleural cavity and covers the lungs - positive feedback - mechanism that intensifies a change in the body’s physiological condition in response to a stimulus - positron emission tomography (PET) - medical imaging technique in which radiopharmaceuticals are traced to reveal metabolic and physiological functions in tissues - posterior - describes the back or direction toward the back of the body; also referred to as dorsal - posterior cavity - posterior body cavity that houses the brain and spinal cord; also referred to as dorsal cavity - pressure - force exerted by a substance in contact with another substance - prone - face down - proximal - describes a position nearer to the point of attachment or the trunk of the body - regional anatomy - study of the structures that contribute to specific body regions - renewal - process by which worn-out cells are replaced - reproduction - process by which new organisms are generated - responsiveness - ability of an organisms or a system to adjust to changes in conditions - sagittal plane - two-dimensional, vertical plane that divides the body or organ into right and left sides - section - in anatomy, a single flat surface of a three-dimensional structure that has been cut through - sensor - (also, receptor) reports a monitored physiological value to the control center - serosa - membrane that covers organs and reduces friction; also referred to as serous membrane - serous membrane - membrane that covers organs and reduces friction; also referred to as serosa - set point - ideal value for a physiological parameter; the level or small range within which a physiological parameter such as blood pressure is stable and optimally healthful, that is, within its parameters of homeostasis - spinal cavity - division of the dorsal cavity that houses the spinal cord; also referred to as vertebral cavity - superficial - describes a position nearer to the surface of the body - superior - describes a position above or higher than another part of the body proper; also referred to as cranial - supine - face up - systemic anatomy - study of the structures that contribute to specific body systems - thoracic cavity - division of the anterior (ventral) cavity that houses the heart, lungs, esophagus, and trachea - tissue - group of similar or closely related cells that act together to perform a specific function - transverse plane - two-dimensional, horizontal plane that divides the body or organ into superior and inferior portions - ultrasonography - application of ultrasonic waves to visualize subcutaneous body structures such as tendons and organs - ventral - describes the front or direction toward the front of the body; also referred to as anterior - ventral cavity - larger body cavity located anterior to the posterior (dorsal) body cavity; includes the serous membrane-lined pleural cavities for the lungs, pericardial cavity for the heart, and peritoneal cavity for the abdominal and pelvic organs; also referred to as anterior body cavity - X-ray - form of high energy electromagnetic radiation with a short wavelength capable of penetrating solids and ionizing gases; used in medicine as a diagnostic aid to visualize body structures such as bones Chapter Review 1.1 Overview of Anatomy and Physiology Human anatomy is the scientific study of the body’s structures. In the past, anatomy has primarily been studied via observing injuries, and later by the dissection of anatomical structures of cadavers, but in the past century, computer-assisted imaging techniques have allowed clinicians to look inside the living body. Human physiology is the scientific study of the chemistry and physics of the structures of the body. Physiology explains how the structures of the body work together to maintain life. It is difficult to study structure (anatomy) without knowledge of function (physiology). The two disciplines are typically studied together because form and function are closely related in all living things. 1.2 Structural Organization of the Human Body Life processes of the human body are maintained at several levels of structural organization. These include the chemical, cellular, tissue, organ, organ system, and the organism level. Higher levels of organization are built from lower levels. Therefore, molecules combine to form cells, cells combine to form tissues, tissues combine to form organs, organs combine to form organ systems, and organ systems combine to form organisms. 1.3 Functions of Human Life Most processes that occur in the human body are not consciously controlled. They occur continuously to build, maintain, and sustain life. These processes include: organization, in terms of the maintenance of essential body boundaries; metabolism, including energy transfer via anabolic and catabolic reactions; responsiveness; movement; and growth, differentiation, reproduction, and renewal. 1.4 Requirements for Human Life Humans cannot survive for more than a few minutes without oxygen, for more than several days without water, and for more than several weeks without carbohydrates, lipids, proteins, vitamins, and minerals. Although the body can respond to high temperatures by sweating and to low temperatures by shivering and increased fuel consumption, long-term exposure to extreme heat and cold is not compatible with survival. The body requires a precise atmospheric pressure to maintain its gases in solution and to facilitate respiration—the intake of oxygen and the release of carbon dioxide. Humans also require blood pressure high enough to ensure that blood reaches all body tissues but low enough to avoid damage to blood vessels. 1.5 Homeostasis Homeostasis is the activity of cells throughout the body to maintain the physiological state within a narrow range that is compatible with life. Homeostasis is regulated by negative feedback loops and, much less frequently, by positive feedback loops. Both have the same components of a stimulus, sensor, control center, and effector; however, negative feedback loops work to prevent an excessive response to the stimulus, whereas positive feedback loops intensify the response until an end point is reached. 1.6 Anatomical Terminology Ancient Greek and Latin words are used to build anatomical terms. A standard reference position for mapping the body’s structures is the normal anatomical position. Regions of the body are identified using terms such as “occipital” that are more precise than common words and phrases such as “the back of the head.” Directional terms such as anterior and posterior are essential for accurately describing the relative locations of body structures. Images of the body’s interior commonly align along one of three planes: the sagittal, frontal, or transverse. The body’s organs are organized in one of two main cavities—dorsal (also referred to posterior) and ventral (also referred to anterior)—which are further sub-divided according to the structures present in each area. The serous membranes have two layers—parietal and visceral—surrounding a fluid filled space. Serous membranes cover the lungs (pleural serosa), heart (pericardial serosa), and some abdominopelvic organs (peritoneal serosa). 1.7 Medical Imaging Detailed anatomical drawings of the human body first became available in the fifteenth and sixteenth centuries; however, it was not until the end of the nineteenth century, and the discovery of X-rays, that anatomists and physicians discovered non-surgical methods to look inside a living body. Since then, many other techniques, including CT scans, MRI scans, PET scans, and ultrasonography, have been developed, providing more accurate and detailed views of the form and function of the human body. Interactive Link Questions View this animation to learn more about metabolic processes. What kind of catabolism occurs in the heart? 2.Water concentration in the body is critical for proper functioning. A person’s body retains very tight control on water levels without conscious control by the person. Watch this video to learn more about water concentration in the body. Which organ has primary control over the amount of water in the body? 3.A CT or CAT scan relies on a circling scanner that revolves around the patient’s body. Watch this video to learn more about CT and CAT scans. What type of radiation does a CT scanner use? 4.A patient undergoing an MRI is surrounded by a tube-shaped scanner. Watch this video to learn more about MRIs. What is the function of magnets in an MRI? 5.PET relies on radioactive substances administered several minutes before the scan. Watch this video to learn more about PET. How is PET used in chemotherapy? Review Questions Which of the following specialties might focus on studying all of the structures of the ankle and foot? - microscopic anatomy - muscle anatomy - regional anatomy - systemic anatomy A scientist wants to study how the body uses foods and fluids during a marathon run. This scientist is most likely a(n) ________. - exercise physiologist - microscopic anatomist - regional physiologist - systemic anatomist The smallest independently functioning unit of an organism is a(n) ________. - cell - molecule - organ - tissue A collection of similar tissues that performs a specific function is an ________. - organ - organelle - organism - organ system The body system responsible for structural support and movement is the ________. - cardiovascular system - endocrine system - muscular system - skeletal system Metabolism can be defined as the ________. - adjustment by an organism to external or internal changes - process whereby all unspecialized cells become specialized to perform distinct functions - process whereby new cells are formed to replace worn-out cells - sum of all chemical reactions in an organism Adenosine triphosphate (ATP) is an important molecule because it ________. - is the result of catabolism - release energy in uncontrolled bursts - stores energy for use by body cells - All of the above Cancer cells can be characterized as “generic” cells that perform no specialized body function. Thus cancer cells lack ________. - differentiation - reproduction - responsiveness - both reproduction and responsiveness Humans have the most urgent need for a continuous supply of ________. - food - nitrogen - oxygen - water Which of the following statements about nutrients is true? - All classes of nutrients are essential to human survival. - Because the body cannot store any micronutrients, they need to be consumed nearly every day. - Carbohydrates, lipids, and proteins are micronutrients. - Macronutrients are vitamins and minerals. C.J. is stuck in her car during a bitterly cold blizzard. Her body responds to the cold by ________. - increasing the blood to her hands and feet - becoming lethargic to conserve heat - breaking down stored energy - significantly increasing blood oxygen levels After you eat lunch, nerve cells in your stomach respond to the distension (the stimulus) resulting from the food. They relay this information to ________. - a control center - a set point - effectors - sensors Stimulation of the heat-loss center causes ________. - blood vessels in the skin to constrict - breathing to become slow and shallow - sweat glands to increase their output - All of the above Which of the following is an example of a normal physiologic process that uses a positive feedback loop? - blood pressure regulation - childbirth - regulation of fluid balance - temperature regulation What is the position of the body when it is in the “normal anatomical position?” - The person is prone with upper limbs, including palms, touching sides and lower limbs touching at sides. - The person is standing facing the observer, with upper limbs extended out at a ninety-degree angle from the torso and lower limbs in a wide stance with feet pointing laterally - The person is supine with upper limbs, including palms, touching sides and lower limbs touching at sides. - None of the above To make a banana split, you halve a banana into two long, thin, right and left sides along the ________. - coronal plane - longitudinal plane - midsagittal plane - transverse plane The lumbar region is ________. - inferior to the gluteal region - inferior to the umbilical region - superior to the cervical region - superior to the popliteal region The heart is within the ________. - cranial cavity - mediastinum - posterior (dorsal) cavity - All of the above In 1901, Wilhelm Röntgen was the first person to win the Nobel Prize for physics. For what discovery did he win? - nuclear physics - radiopharmaceuticals - the link between radiation and cancer - X-rays Which of the following imaging techniques would be best to use to study the uptake of nutrients by rapidly multiplying cancer cells? - CT - MRI - PET - ultrasonography Which of the following imaging studies can be used most safely during pregnancy? - CT scans - PET scans - ultrasounds - X-rays What are two major disadvantages of MRI scans? - release of radiation and poor quality images - high cost and the need for shielding from the magnetic signals - can only view metabolically active tissues and inadequate availability of equipment - release of radiation and the need for a patient to be confined to metal tube for up to 30 minutes Critical Thinking Questions Name at least three reasons to study anatomy and physiology. 29.For whom would an appreciation of the structural characteristics of the human heart come more easily: an alien who lands on Earth, abducts a human, and dissects his heart, or an anatomy and physiology student performing a dissection of the heart on her very first day of class? Why? 30.Name the six levels of organization of the human body. 31.The female ovaries and the male testes are a part of which body system? Can these organs be members of more than one organ system? Why or why not? 32.Explain why the smell of smoke when you are sitting at a campfire does not trigger alarm, but the smell of smoke in your residence hall does. 33.Identify three different ways that growth can occur in the human body. 34.When you open a bottle of sparkling water, the carbon dioxide gas in the bottle form bubbles. If the bottle is left open, the water will eventually “go flat.” Explain these phenomena in terms of atmospheric pressure. 35.On his midsummer trek through the desert, Josh ran out of water. Why is this particularly dangerous? 36.Identify the four components of a negative feedback loop and explain what would happen if secretion of a body chemical controlled by a negative feedback system became too great. 37.What regulatory processes would your body use if you were trapped by a blizzard in an unheated, uninsulated cabin in the woods? 38.In which direction would an MRI scanner move to produce sequential images of the body in the frontal plane, and in which direction would an MRI scanner move to produce sequential images of the body in the sagittal plane? 39.If a bullet were to penetrate a lung, which three anterior thoracic body cavities would it enter, and which layer of the serous membrane would it encounter first? 40.Which medical imaging technique is most dangerous to use repeatedly, and why? 41.Explain why ultrasound imaging is the technique of choice for studying fetal growth and development.	oercommons	2025-03-18T00:36:11.421975	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/56351/overview", "title": "Anatomy and Physiology, Levels of Organization", "author": null }
https://oercommons.org/courseware/lesson/56352/overview	The Chemical Level of Organization Introduction Figure 2.1 Human DNA Human DNA is described as a double helix that resembles a molecular spiral staircase. In humans the DNA is organized into 46 chromosomes. CHAPTER OBJECTIVES After studying this chapter, you will be able to: - Describe the fundamental composition of matter - Identify the three subatomic particles - Identify the four most abundant elements in the body - Explain the relationship between an atom’s number of electrons and its relative stability - Distinguish between ionic bonds, covalent bonds, and hydrogen bonds - Explain how energy is invested, stored, and released via chemical reactions, particularly those reactions that are critical to life - Explain the importance of the inorganic compounds that contribute to life, such as water, salts, acids, and bases - Compare and contrast the four important classes of organic (carbon-based) compounds—proteins, carbohydrates, lipids and nucleic acids—according to their composition and functional importance to human life The smallest, most fundamental material components of the human body are basic chemical elements. In fact, chemicals called nucleotide bases are the foundation of the genetic code with the instructions on how to build and maintain the human body from conception through old age. There are about three billion of these base pairs in human DNA. Human chemistry includes organic molecules (carbon-based) and biochemicals (those produced by the body). Human chemistry also includes elements. In fact, life cannot exist without many of the elements that are part of the earth. All of the elements that contribute to chemical reactions, to the transformation of energy, and to electrical activity and muscle contraction—elements that include phosphorus, carbon, sodium, and calcium, to name a few—originated in stars. These elements, in turn, can form both the inorganic and organic chemical compounds important to life, including, for example, water, glucose, and proteins. This chapter begins by examining elements and how the structures of atoms, the basic units of matter, determine the characteristics of elements by the number of protons, neutrons, and electrons in the atoms. The chapter then builds the framework of life from there. Elements and Atoms: The Building Blocks of Matter - Discuss the relationships between matter, mass, elements, compounds, atoms, and subatomic particles - Distinguish between atomic number and mass number - Identify the key distinction between isotopes of the same element - Explain how electrons occupy electron shells and their contribution to an atom’s relative stability The substance of the universe—from a grain of sand to a star—is called matter. Scientists define matter as anything that occupies space and has mass. An object’s mass and its weight are related concepts, but not quite the same. An object’s mass is the amount of matter contained in the object, and the object’s mass is the same whether that object is on Earth or in the zero-gravity environment of outer space. An object’s weight, on the other hand, is its mass as affected by the pull of gravity. Where gravity strongly pulls on an object’s mass its weight is greater than it is where gravity is less strong. An object of a certain mass weighs less on the moon, for example, than it does on Earth because the gravity of the moon is less than that of Earth. In other words, weight is variable, and is influenced by gravity. A piece of cheese that weighs a pound on Earth weighs only a few ounces on the moon. Elements and Compounds All matter in the natural world is composed of one or more of the 92 fundamental substances called elements. An element is a pure substance that is distinguished from all other matter by the fact that it cannot be created or broken down by ordinary chemical means. While your body can assemble many of the chemical compounds needed for life from their constituent elements, it cannot make elements. They must come from the environment. A familiar example of an element that you must take in is calcium (Ca++). Calcium is essential to the human body; it is absorbed and used for a number of processes, including strengthening bones. When you consume dairy products your digestive system breaks down the food into components small enough to cross into the bloodstream. Among these is calcium, which, because it is an element, cannot be broken down further. The elemental calcium in cheese, therefore, is the same as the calcium that forms your bones. Some other elements you might be familiar with are oxygen, sodium, and iron. The elements in the human body are shown in Figure 2.2, beginning with the most abundant: oxygen (O), carbon (C), hydrogen (H), and nitrogen (N). Each element’s name can be replaced by a one- or two-letter symbol; you will become familiar with some of these during this course. All the elements in your body are derived from the foods you eat and the air you breathe. Figure 2.2 Elements of the Human Body The main elements that compose the human body are shown from most abundant to least abundant. In nature, elements rarely occur alone. Instead, they combine to form compounds. A compound is a substance composed of two or more elements joined by chemical bonds. For example, the compound glucose is an important body fuel. It is always composed of the same three elements: carbon, hydrogen, and oxygen. Moreover, the elements that make up any given compound always occur in the same relative amounts. In glucose, there are always six carbon and six oxygen units for every twelve hydrogen units. But what, exactly, are these “units” of elements? Atoms and Subatomic Particles An atom is the smallest quantity of an element that retains the unique properties of that element. In other words, an atom of hydrogen is a unit of hydrogen—the smallest amount of hydrogen that can exist. As you might guess, atoms are almost unfathomably small. The period at the end of this sentence is millions of atoms wide. Atomic Structure and Energy Atoms are made up of even smaller subatomic particles, three types of which are important: the proton, neutron, and electron. The number of positively-charged protons and non-charged (“neutral”) neutrons, gives mass to the atom, and the number of each in the nucleus of the atom determine the element. The number of negatively-charged electrons that “spin” around the nucleus at close to the speed of light equals the number of protons. An electron has about 1/2000th the mass of a proton or neutron. Figure 2.3 shows two models that can help you imagine the structure of an atom—in this case, helium (He). In the planetary model, helium’s two electrons are shown circling the nucleus in a fixed orbit depicted as a ring. Although this model is helpful in visualizing atomic structure, in reality, electrons do not travel in fixed orbits, but whiz around the nucleus erratically in a so-called electron cloud. Figure 2.3 Two Models of Atomic Structure (a) In the planetary model, the electrons of helium are shown in fixed orbits, depicted as rings, at a precise distance from the nucleus, somewhat like planets orbiting the sun. (b) In the electron cloud model, the electrons of carbon are shown in the variety of locations they would have at different distances from the nucleus over time. An atom’s protons and electrons carry electrical charges. Protons, with their positive charge, are designated p+. Electrons, which have a negative charge, are designated e–. An atom’s neutrons have no charge: they are electrically neutral. Just as a magnet sticks to a steel refrigerator because their opposite charges attract, the positively charged protons attract the negatively charged electrons. This mutual attraction gives the atom some structural stability. The attraction by the positively charged nucleus helps keep electrons from straying far. The number of protons and electrons within a neutral atom are equal, thus, the atom’s overall charge is balanced. Atomic Number and Mass Number An atom of carbon is unique to carbon, but a proton of carbon is not. One proton is the same as another, whether it is found in an atom of carbon, sodium (Na), or iron (Fe). The same is true for neutrons and electrons. So, what gives an element its distinctive properties—what makes carbon so different from sodium or iron? The answer is the unique quantity of protons each contains. Carbon by definition is an element whose atoms contain six protons. No other element has exactly six protons in its atoms. Moreover, all atoms of carbon, whether found in your liver or in a lump of coal, contain six protons. Thus, the atomic number, which is the number of protons in the nucleus of the atom, identifies the element. Because an atom usually has the same number of electrons as protons, the atomic number identifies the usual number of electrons as well. In their most common form, many elements also contain the same number of neutrons as protons. The most common form of carbon, for example, has six neutrons as well as six protons, for a total of 12 subatomic particles in its nucleus. An element’s mass number is the sum of the number of protons and neutrons in its nucleus. So the most common form of carbon’s mass number is 12. (Electrons have so little mass that they do not appreciably contribute to the mass of an atom.) Carbon is a relatively light element. Uranium (U), in contrast, has a mass number of 238 and is referred to as a heavy metal. Its atomic number is 92 (it has 92 protons) but it contains 146 neutrons; it has the most mass of all the naturally occurring elements. The periodic table of the elements, shown in Figure 2.4, is a chart identifying the 92 elements found in nature, as well as several larger, unstable elements discovered experimentally. The elements are arranged in order of their atomic number, with hydrogen and helium at the top of the table, and the more massive elements below. The periodic table is a useful device because for each element, it identifies the chemical symbol, the atomic number, and the mass number, while organizing elements according to their propensity to react with other elements. The number of protons and electrons in an element are equal. The number of protons and neutrons may be equal for some elements, but are not equal for all. Figure 2.4 The Periodic Table of the Elements (credit: R.A. Dragoset, A. Musgrove, C.W. Clark, W.C. Martin) INTERACTIVE LINK Visit this website to view the periodic table. In the periodic table of the elements, elements in a single column have the same number of electrons that can participate in a chemical reaction. These electrons are known as “valence electrons.” For example, the elements in the first column all have a single valence electron, an electron that can be “donated” in a chemical reaction with another atom. What is the meaning of a mass number shown in parentheses? Isotopes Although each element has a unique number of protons, it can exist as different isotopes. An isotope is one of the different forms of an element, distinguished from one another by different numbers of neutrons. The standard isotope of carbon is 12C, commonly called carbon twelve. 12C has six protons and six neutrons, for a mass number of twelve. All of the isotopes of carbon have the same number of protons; therefore, 13C has seven neutrons, and 14C has eight neutrons. The different isotopes of an element can also be indicated with the mass number hyphenated (for example, C-12 instead of 12C). Hydrogen has three common isotopes, shown in Figure 2.5. Figure 2.5 Isotopes of Hydrogen Protium, designated 1H, has one proton and no neutrons. It is by far the most abundant isotope of hydrogen in nature. Deuterium, designated 2H, has one proton and one neutron. Tritium, designated 3H, has two neutrons. An isotope that contains more than the usual number of neutrons is referred to as a heavy isotope. An example is 14C. Heavy isotopes tend to be unstable, and unstable isotopes are radioactive. A radioactive isotope is an isotope whose nucleus readily decays, giving off subatomic particles and electromagnetic energy. Different radioactive isotopes (also called radioisotopes) differ in their half-life, the time it takes for half of any size sample of an isotope to decay. For example, the half-life of tritium—a radioisotope of hydrogen—is about 12 years, indicating it takes 12 years for half of the tritium nuclei in a sample to decay. Excessive exposure to radioactive isotopes can damage human cells and even cause cancer and birth defects, but when exposure is controlled, some radioactive isotopes can be useful in medicine. For more information, see the Career Connections. CAREER CONNECTION Interventional Radiologist The controlled use of radioisotopes has advanced medical diagnosis and treatment of disease. Interventional radiologists are physicians who treat disease by using minimally invasive techniques involving radiation. Many conditions that could once only be treated with a lengthy and traumatic operation can now be treated non-surgically, reducing the cost, pain, length of hospital stay, and recovery time for patients. For example, in the past, the only options for a patient with one or more tumors in the liver were surgery and chemotherapy (the administration of drugs to treat cancer). Some liver tumors, however, are difficult to access surgically, and others could require the surgeon to remove too much of the liver. Moreover, chemotherapy is highly toxic to the liver, and certain tumors do not respond well to it anyway. In some such cases, an interventional radiologist can treat the tumors by disrupting their blood supply, which they need if they are to continue to grow. In this procedure, called radioembolization, the radiologist accesses the liver with a fine needle, threaded through one of the patient’s blood vessels. The radiologist then inserts tiny radioactive “seeds” into the blood vessels that supply the tumors. In the days and weeks following the procedure, the radiation emitted from the seeds destroys the vessels and directly kills the tumor cells in the vicinity of the treatment. Radioisotopes emit subatomic particles that can be detected and tracked by imaging technologies. One of the most advanced uses of radioisotopes in medicine is the positron emission tomography (PET) scanner, which detects the activity in the body of a very small injection of radioactive glucose, the simple sugar that cells use for energy. The PET camera reveals to the medical team which of the patient’s tissues are taking up the most glucose. Thus, the most metabolically active tissues show up as bright “hot spots” on the images (Figure 2.6). PET can reveal some cancerous masses because cancer cells consume glucose at a high rate to fuel their rapid reproduction. Figure 2.6 PET Scan PET highlights areas in the body where there is relatively high glucose use, which is characteristic of cancerous tissue. This PET scan shows sites of the spread of a large primary tumor to other sites. The Behavior of Electrons In the human body, atoms do not exist as independent entities. Rather, they are constantly reacting with other atoms to form and to break down more complex substances. To fully understand anatomy and physiology you must grasp how atoms participate in such reactions. The key is understanding the behavior of electrons. Although electrons do not follow rigid orbits a set distance away from the atom’s nucleus, they do tend to stay within certain regions of space called electron shells. An electron shell is a layer of electrons that encircle the nucleus at a distinct energy level. The atoms of the elements found in the human body have from one to five electron shells, and all electron shells hold eight electrons except the first shell, which can only hold two. This configuration of electron shells is the same for all atoms. The precise number of shells depends on the number of electrons in the atom. Hydrogen and helium have just one and two electrons, respectively. If you take a look at the periodic table of the elements, you will notice that hydrogen and helium are placed alone on either sides of the top row; they are the only elements that have just one electron shell (Figure 2.7). A second shell is necessary to hold the electrons in all elements larger than hydrogen and helium. Lithium (Li), whose atomic number is 3, has three electrons. Two of these fill the first electron shell, and the third spills over into a second shell. The second electron shell can accommodate as many as eight electrons. Carbon, with its six electrons, entirely fills its first shell, and half-fills its second. With ten electrons, neon (Ne) entirely fills its two electron shells. Again, a look at the periodic table reveals that all of the elements in the second row, from lithium to neon, have just two electron shells. Atoms with more than ten electrons require more than two shells. These elements occupy the third and subsequent rows of the periodic table. Figure 2.7 Electron Shells Electrons orbit the atomic nucleus at distinct levels of energy called electron shells. (a) With one electron, hydrogen only half-fills its electron shell. Helium also has a single shell, but its two electrons completely fill it. (b) The electrons of carbon completely fill its first electron shell, but only half-fills its second. (c) Neon, an element that does not occur in the body, has 10 electrons, filling both of its electron shells. The factor that most strongly governs the tendency of an atom to participate in chemical reactions is the number of electrons in its valence shell. A valence shell is an atom’s outermost electron shell. If the valence shell is full, the atom is stable; meaning its electrons are unlikely to be pulled away from the nucleus by the electrical charge of other atoms. If the valence shell is not full, the atom is reactive; meaning it will tend to react with other atoms in ways that make the valence shell full. Consider hydrogen, with its one electron only half-filling its valence shell. This single electron is likely to be drawn into relationships with the atoms of other elements, so that hydrogen’s single valence shell can be stabilized. All atoms (except hydrogen and helium with their single electron shells) are most stable when there are exactly eight electrons in their valence shell. This principle is referred to as the octet rule, and it states that an atom will give up, gain, or share electrons with another atom so that it ends up with eight electrons in its own valence shell. For example, oxygen, with six electrons in its valence shell, is likely to react with other atoms in a way that results in the addition of two electrons to oxygen’s valence shell, bringing the number to eight. When two hydrogen atoms each share their single electron with oxygen, covalent bonds are formed, resulting in a molecule of water, H2O. In nature, atoms of one element tend to join with atoms of other elements in characteristic ways. For example, carbon commonly fills its valence shell by linking up with four atoms of hydrogen. In so doing, the two elements form the simplest of organic molecules, methane, which also is one of the most abundant and stable carbon-containing compounds on Earth. As stated above, another example is water; oxygen needs two electrons to fill its valence shell. It commonly interacts with two atoms of hydrogen, forming H2O. Incidentally, the name “hydrogen” reflects its contribution to water (hydro- = “water”; -gen = “maker”). Thus, hydrogen is the “water maker.” Chemical Bonds - Explain the relationship between molecules and compounds - Distinguish between ions, cations, and anions - Identify the key difference between ionic and covalent bonds - Distinguish between nonpolar and polar covalent bonds - Explain how water molecules link via hydrogen bonds Atoms separated by a great distance cannot link; rather, they must come close enough for the electrons in their valence shells to interact. But do atoms ever actually touch one another? Most physicists would say no, because the negatively charged electrons in their valence shells repel one another. No force within the human body—or anywhere in the natural world—is strong enough to overcome this electrical repulsion. So when you read about atoms linking together or colliding, bear in mind that the atoms are not merging in a physical sense. Instead, atoms link by forming a chemical bond. A bond is a weak or strong electrical attraction that holds atoms in the same vicinity. The new grouping is typically more stable—less likely to react again—than its component atoms were when they were separate. A more or less stable grouping of two or more atoms held together by chemical bonds is called a molecule. The bonded atoms may be of the same element, as in the case of H2, which is called molecular hydrogen or hydrogen gas. When a molecule is made up of two or more atoms of different elements, it is called a chemical compound. Thus, a unit of water, or H2O, is a compound, as is a single molecule of the gas methane, or CH4. Three types of chemical bonds are important in human physiology, because they hold together substances that are used by the body for critical aspects of homeostasis, signaling, and energy production, to name just a few important processes. These are ionic bonds, covalent bonds, and hydrogen bonds. Ions and Ionic Bonds Recall that an atom typically has the same number of positively charged protons and negatively charged electrons. As long as this situation remains, the atom is electrically neutral. But when an atom participates in a chemical reaction that results in the donation or acceptance of one or more electrons, the atom will then become positively or negatively charged. This happens frequently for most atoms in order to have a full valence shell, as described previously. This can happen either by gaining electrons to fill a shell that is more than half-full, or by giving away electrons to empty a shell that is less than half-full, thereby leaving the next smaller electron shell as the new, full, valence shell. An atom that has an electrical charge—whether positive or negative—is an ion. INTERACTIVE LINK Visit this website to learn about electrical energy and the attraction/repulsion of charges. What happens to the charged electroscope when a conductor is moved between its plastic sheets, and why? Potassium (K), for instance, is an important element in all body cells. Its atomic number is 19. It has just one electron in its valence shell. This characteristic makes potassium highly likely to participate in chemical reactions in which it donates one electron. (It is easier for potassium to donate one electron than to gain seven electrons.) The loss will cause the positive charge of potassium’s protons to be more influential than the negative charge of potassium’s electrons. In other words, the resulting potassium ion will be slightly positive. A potassium ion is written K+, indicating that it has lost a single electron. A positively charged ion is known as a cation. Now consider fluorine (F), a component of bones and teeth. Its atomic number is nine, and it has seven electrons in its valence shell. Thus, it is highly likely to bond with other atoms in such a way that fluorine accepts one electron (it is easier for fluorine to gain one electron than to donate seven electrons). When it does, its electrons will outnumber its protons by one, and it will have an overall negative charge. The ionized form of fluorine is called fluoride, and is written as F–. A negatively charged ion is known as an anion. Atoms that have more than one electron to donate or accept will end up with stronger positive or negative charges. A cation that has donated two electrons has a net charge of +2. Using magnesium (Mg) as an example, this can be written Mg++ or Mg2+. An anion that has accepted two electrons has a net charge of –2. The ionic form of selenium (Se), for example, is typically written Se2–. The opposite charges of cations and anions exert a moderately strong mutual attraction that keeps the atoms in close proximity forming an ionic bond. An ionic bond is an ongoing, close association between ions of opposite charge. The table salt you sprinkle on your food owes its existence to ionic bonding. As shown in Figure 2.8, sodium commonly donates an electron to chlorine, becoming the cation Na+. When chlorine accepts the electron, it becomes the chloride anion, Cl–. With their opposing charges, these two ions strongly attract each other. Figure 2.8 Ionic Bonding (a) Sodium readily donates the solitary electron in its valence shell to chlorine, which needs only one electron to have a full valence shell. (b) The opposite electrical charges of the resulting sodium cation and chloride anion result in the formation of a bond of attraction called an ionic bond. (c) The attraction of many sodium and chloride ions results in the formation of large groupings called crystals. Water is an essential component of life because it is able to break the ionic bonds in salts to free the ions. In fact, in biological fluids, most individual atoms exist as ions. These dissolved ions produce electrical charges within the body. The behavior of these ions produces the tracings of heart and brain function observed as waves on an electrocardiogram (EKG or ECG) or an electroencephalogram (EEG). The electrical activity that derives from the interactions of the charged ions is why they are also called electrolytes. Covalent Bonds Unlike ionic bonds formed by the attraction between a cation’s positive charge and an anion’s negative charge, molecules formed by a covalent bond share electrons in a mutually stabilizing relationship. Like next-door neighbors whose kids hang out first at one home and then at the other, the atoms do not lose or gain electrons permanently. Instead, the electrons move back and forth between the elements. Because of the close sharing of pairs of electrons (one electron from each of two atoms), covalent bonds are stronger than ionic bonds. Nonpolar Covalent Bonds Figure 2.9 shows several common types of covalent bonds. Notice that the two covalently bonded atoms typically share just one or two electron pairs, though larger sharings are possible. The important concept to take from this is that in covalent bonds, electrons in the outermost valence shell are shared to fill the valence shells of both atoms, ultimately stabilizing both of the atoms involved. In a single covalent bond, a single electron is shared between two atoms, while in a double covalent bond, two pairs of electrons are shared between two atoms. There even are triple covalent bonds, where three atoms are shared. Figure 2.9 Covalent Bonding You can see that the covalent bonds shown in Figure 2.9 are balanced. The sharing of the negative electrons is relatively equal, as is the electrical pull of the positive protons in the nucleus of the atoms involved. This is why covalently bonded molecules that are electrically balanced in this way are described as nonpolar; that is, no region of the molecule is either more positive or more negative than any other. Polar Covalent Bonds Groups of legislators with completely opposite views on a particular issue are often described as “polarized” by news writers. In chemistry, a polar molecule is a molecule that contains regions that have opposite electrical charges. Polar molecules occur when atoms share electrons unequally, in polar covalent bonds. The most familiar example of a polar molecule is water (Figure 2.10). The molecule has three parts: one atom of oxygen, the nucleus of which contains eight protons, and two hydrogen atoms, whose nuclei each contain only one proton. Because every proton exerts an identical positive charge, a nucleus that contains eight protons exerts a charge eight times greater than a nucleus that contains one proton. This means that the negatively charged electrons present in the water molecule are more strongly attracted to the oxygen nucleus than to the hydrogen nuclei. Each hydrogen atom’s single negative electron therefore migrates toward the oxygen atom, making the oxygen end of their bond slightly more negative than the hydrogen end of their bond. Figure 2.10 Polar Covalent Bonds in a Water Molecule What is true for the bonds is true for the water molecule as a whole; that is, the oxygen region has a slightly negative charge and the regions of the hydrogen atoms have a slightly positive charge. These charges are often referred to as “partial charges” because the strength of the charge is less than one full electron, as would occur in an ionic bond. As shown in Figure 2.10, regions of weak polarity are indicated with the Greek letter delta (δ) and a plus (+) or minus (–) sign. Even though a single water molecule is unimaginably tiny, it has mass, and the opposing electrical charges on the molecule pull that mass in such a way that it creates a shape somewhat like a triangular tent (see Figure 2.10b). This dipole, with the positive charges at one end formed by the hydrogen atoms at the “bottom” of the tent and the negative charge at the opposite end (the oxygen atom at the “top” of the tent) makes the charged regions highly likely to interact with charged regions of other polar molecules. For human physiology, the resulting bond is one of the most important formed by water—the hydrogen bond. Hydrogen Bonds A hydrogen bond is formed when a weakly positive hydrogen atom already bonded to one electronegative atom (for example, the oxygen in the water molecule) is attracted to another electronegative atom from another molecule. In other words, hydrogen bonds always include hydrogen that is already part of a polar molecule. The most common example of hydrogen bonding in the natural world occurs between molecules of water. It happens before your eyes whenever two raindrops merge into a larger bead, or a creek spills into a river. Hydrogen bonding occurs because the weakly negative oxygen atom in one water molecule is attracted to the weakly positive hydrogen atoms of two other water molecules (Figure 2.11). Figure 2.11 Hydrogen Bonds between Water Molecules Notice that the bonds occur between the weakly positive charge on the hydrogen atoms and the weakly negative charge on the oxygen atoms. Hydrogen bonds are relatively weak, and therefore are indicated with a dotted (rather than a solid) line. Water molecules also strongly attract other types of charged molecules as well as ions. This explains why “table salt,” for example, actually is a molecule called a “salt” in chemistry, which consists of equal numbers of positively-charged sodium (Na+) and negatively-charged chloride (Cl–), dissolves so readily in water, in this case forming dipole-ion bonds between the water and the electrically-charged ions (electrolytes). Water molecules also repel molecules with nonpolar covalent bonds, like fats, lipids, and oils. You can demonstrate this with a simple kitchen experiment: pour a teaspoon of vegetable oil, a compound formed by nonpolar covalent bonds, into a glass of water. Instead of instantly dissolving in the water, the oil forms a distinct bead because the polar water molecules repel the nonpolar oil. Chemical Reactions - Distinguish between kinetic and potential energy, and between exergonic and endergonic chemical reactions - Identify four forms of energy important in human functioning - Describe the three basic types of chemical reactions - Identify several factors influencing the rate of chemical reactions One characteristic of a living organism is metabolism, which is the sum total of all of the chemical reactions that go on to maintain that organism’s health and life. The bonding processes you have learned thus far are anabolic chemical reactions; that is, they form larger molecules from smaller molecules or atoms. But recall that metabolism can proceed in another direction: in catabolic chemical reactions, bonds between components of larger molecules break, releasing smaller molecules or atoms. Both types of reaction involve exchanges not only of matter, but of energy. The Role of Energy in Chemical Reactions Chemical reactions require a sufficient amount of energy to cause the matter to collide with enough precision and force that old chemical bonds can be broken and new ones formed. In general, kinetic energy is the form of energy powering any type of matter in motion. Imagine you are building a brick wall. The energy it takes to lift and place one brick atop another is kinetic energy—the energy matter possesses because of its motion. Once the wall is in place, it stores potential energy. Potential energy is the energy of position, or the energy matter possesses because of the positioning or structure of its components. If the brick wall collapses, the stored potential energy is released as kinetic energy as the bricks fall. In the human body, potential energy is stored in the bonds between atoms and molecules. Chemical energy is the form of potential energy in which energy is stored in chemical bonds. When those bonds are formed, chemical energy is invested, and when they break, chemical energy is released. Notice that chemical energy, like all energy, is neither created nor destroyed; rather, it is converted from one form to another. When you eat an energy bar before heading out the door for a hike, the honey, nuts, and other foods the bar contains are broken down and rearranged by your body into molecules that your muscle cells convert to kinetic energy. Chemical reactions that release more energy than they absorb are characterized as exergonic. The catabolism of the foods in your energy bar is an example. Some of the chemical energy stored in the bar is absorbed into molecules your body uses for fuel, but some of it is released—for example, as heat. In contrast, chemical reactions that absorb more energy than they release are endergonic. These reactions require energy input, and the resulting molecule stores not only the chemical energy in the original components, but also the energy that fueled the reaction. Because energy is neither created nor destroyed, where does the energy needed for endergonic reactions come from? In many cases, it comes from exergonic reactions. Forms of Energy Important in Human Functioning You have already learned that chemical energy is absorbed, stored, and released by chemical bonds. In addition to chemical energy, mechanical, radiant, and electrical energy are important in human functioning. - Mechanical energy, which is stored in physical systems such as machines, engines, or the human body, directly powers the movement of matter. When you lift a brick into place on a wall, your muscles provide the mechanical energy that moves the brick. - Radiant energy is energy emitted and transmitted as waves rather than matter. These waves vary in length from long radio waves and microwaves to short gamma waves emitted from decaying atomic nuclei. The full spectrum of radiant energy is referred to as the electromagnetic spectrum. The body uses the ultraviolet energy of sunlight to convert a compound in skin cells to vitamin D, which is essential to human functioning. The human eye evolved to see the wavelengths that comprise the colors of the rainbow, from red to violet, so that range in the spectrum is called “visible light.” - Electrical energy, supplied by electrolytes in cells and body fluids, contributes to the voltage changes that help transmit impulses in nerve and muscle cells. Characteristics of Chemical Reactions All chemical reactions begin with a reactant, the general term for the one or more substances that enter into the reaction. Sodium and chloride ions, for example, are the reactants in the production of table salt. The one or more substances produced by a chemical reaction are called the product. In chemical reactions, the components of the reactants—the elements involved and the number of atoms of each—are all present in the product(s). Similarly, there is nothing present in the products that are not present in the reactants. This is because chemical reactions are governed by the law of conservation of mass, which states that matter cannot be created or destroyed in a chemical reaction. Just as you can express mathematical calculations in equations such as 2 + 7 = 9, you can use chemical equations to show how reactants become products. As in math, chemical equations proceed from left to right, but instead of an equal sign, they employ an arrow or arrows indicating the direction in which the chemical reaction proceeds. For example, the chemical reaction in which one atom of nitrogen and three atoms of hydrogen produce ammonia would be written as N + 3H→NH3N + 3H→NH3 NH3→N + 3H.NH3→N + 3H. Notice that, in the first example, a nitrogen (N) atom and three hydrogen (H) atoms bond to form a compound. This anabolic reaction requires energy, which is then stored within the compound’s bonds. Such reactions are referred to as synthesis reactions. A synthesis reaction is a chemical reaction that results in the synthesis (joining) of components that were formerly separate (Figure 2.12a). Again, nitrogen and hydrogen are reactants in a synthesis reaction that yields ammonia as the product. The general equation for a synthesis reaction is A + B→AB.A + B→AB. Figure 2.12 The Three Fundamental Chemical Reactions The atoms and molecules involved in the three fundamental chemical reactions can be imagined as words. In the second example, ammonia is catabolized into its smaller components, and the potential energy that had been stored in its bonds is released. Such reactions are referred to as decomposition reactions. A decomposition reaction is a chemical reaction that breaks down or “de-composes” something larger into its constituent parts (see Figure 2.12b). The general equation for a decomposition reaction is: AB→A+BAB→A+B An exchange reaction is a chemical reaction in which both synthesis and decomposition occur, chemical bonds are both formed and broken, and chemical energy is absorbed, stored, and released (see Figure 2.12c). The simplest form of an exchange reaction might be: A+BC→AB+CA+BC→AB+CAB+CD→AC+BDAB+CD→AC+BD AB+CD→AD+BCAB+CD→AD+BC In theory, any chemical reaction can proceed in either direction under the right conditions. Reactants may synthesize into a product that is later decomposed. Reversibility is also a quality of exchange reactions. For instance, A+BC→AB+CA+BC→AB+C AB+C→A+BCAB+C→A+BC A+BC⇄AB+CA+BC⇄AB+C Factors Influencing the Rate of Chemical Reactions If you pour vinegar into baking soda, the reaction is instantaneous; the concoction will bubble and fizz. But many chemical reactions take time. A variety of factors influence the rate of chemical reactions. This section, however, will consider only the most important in human functioning. Properties of the Reactants If chemical reactions are to occur quickly, the atoms in the reactants have to have easy access to one another. Thus, the greater the surface area of the reactants, the more readily they will interact. When you pop a cube of cheese into your mouth, you chew it before you swallow it. Among other things, chewing increases the surface area of the food so that digestive chemicals can more easily get at it. As a general rule, gases tend to react faster than liquids or solids, again because it takes energy to separate particles of a substance, and gases by definition already have space between their particles. Similarly, the larger the molecule, the greater the number of total bonds, so reactions involving smaller molecules, with fewer total bonds, would be expected to proceed faster. In addition, recall that some elements are more reactive than others. Reactions that involve highly reactive elements like hydrogen proceed more quickly than reactions that involve less reactive elements. Reactions involving stable elements like helium are not likely to happen at all. Temperature Nearly all chemical reactions occur at a faster rate at higher temperatures. Recall that kinetic energy is the energy of matter in motion. The kinetic energy of subatomic particles increases in response to increases in thermal energy. The higher the temperature, the faster the particles move, and the more likely they are to come in contact and react. Concentration and Pressure If just a few people are dancing at a club, they are unlikely to step on each other’s toes. But as more and more people get up to dance—especially if the music is fast—collisions are likely to occur. It is the same with chemical reactions: the more particles present within a given space, the more likely those particles are to bump into one another. This means that chemists can speed up chemical reactions not only by increasing the concentration of particles—the number of particles in the space—but also by decreasing the volume of the space, which would correspondingly increase the pressure. If there were 100 dancers in that club, and the manager abruptly moved the party to a room half the size, the concentration of the dancers would double in the new space, and the likelihood of collisions would increase accordingly. Enzymes and Other Catalysts For two chemicals in nature to react with each other they first have to come into contact, and this occurs through random collisions. Because heat helps increase the kinetic energy of atoms, ions, and molecules, it promotes their collision. But in the body, extremely high heat—such as a very high fever—can damage body cells and be life-threatening. On the other hand, normal body temperature is not high enough to promote the chemical reactions that sustain life. That is where catalysts come in. In chemistry, a catalyst is a substance that increases the rate of a chemical reaction without itself undergoing any change. You can think of a catalyst as a chemical change agent. They help increase the rate and force at which atoms, ions, and molecules collide, thereby increasing the probability that their valence shell electrons will interact. The most important catalysts in the human body are enzymes. An enzyme is a catalyst composed of protein or ribonucleic acid (RNA), both of which will be discussed later in this chapter. Like all catalysts, enzymes work by lowering the level of energy that needs to be invested in a chemical reaction. A chemical reaction’s activation energy is the “threshold” level of energy needed to break the bonds in the reactants. Once those bonds are broken, new arrangements can form. Without an enzyme to act as a catalyst, a much larger investment of energy is needed to ignite a chemical reaction (Figure 2.13). Figure 2.13 Enzymes Enzymes decrease the activation energy required for a given chemical reaction to occur. (a) Without an enzyme, the energy input needed for a reaction to begin is high. (b) With the help of an enzyme, less energy is needed for a reaction to begin. Enzymes are critical to the body’s healthy functioning. They assist, for example, with the breakdown of food and its conversion to energy. In fact, most of the chemical reactions in the body are facilitated by enzymes. Inorganic Compounds Essential to Human Functioning - Compare and contrast inorganic and organic compounds - Identify the properties of water that make it essential to life - Explain the role of salts in body functioning - Distinguish between acids and bases, and explain their role in pH - Discuss the role of buffers in helping the body maintain pH homeostasis The concepts you have learned so far in this chapter govern all forms of matter, and would work as a foundation for geology as well as biology. This section of the chapter narrows the focus to the chemistry of human life; that is, the compounds important for the body’s structure and function. In general, these compounds are either inorganic or organic. - An inorganic compound is a substance that does not contain both carbon and hydrogen. A great many inorganic compounds do contain hydrogen atoms, such as water (H2O) and the hydrochloric acid (HCl) produced by your stomach. In contrast, only a handful of inorganic compounds contain carbon atoms. Carbon dioxide (CO2) is one of the few examples. - An organic compound, then, is a substance that contains both carbon and hydrogen. Organic compounds are synthesized via covalent bonds within living organisms, including the human body. Recall that carbon and hydrogen are the second and third most abundant elements in your body. You will soon discover how these two elements combine in the foods you eat, in the compounds that make up your body structure, and in the chemicals that fuel your functioning. The following section examines the three groups of inorganic compounds essential to life: water, salts, acids, and bases. Organic compounds are covered later in the chapter. Water As much as 70 percent of an adult’s body weight is water. This water is contained both within the cells and between the cells that make up tissues and organs. Its several roles make water indispensable to human functioning. Water as a Lubricant and Cushion Water is a major component of many of the body’s lubricating fluids. Just as oil lubricates the hinge on a door, water in synovial fluid lubricates the actions of body joints, and water in pleural fluid helps the lungs expand and recoil with breathing. Watery fluids help keep food flowing through the digestive tract, and ensure that the movement of adjacent abdominal organs is friction free. Water also protects cells and organs from physical trauma, cushioning the brain within the skull, for example, and protecting the delicate nerve tissue of the eyes. Water cushions a developing fetus in the mother’s womb as well. Water as a Heat Sink A heat sink is a substance or object that absorbs and dissipates heat but does not experience a corresponding increase in temperature. In the body, water absorbs the heat generated by chemical reactions without greatly increasing in temperature. Moreover, when the environmental temperature soars, the water stored in the body helps keep the body cool. This cooling effect happens as warm blood from the body’s core flows to the blood vessels just under the skin and is transferred to the environment. At the same time, sweat glands release warm water in sweat. As the water evaporates into the air, it carries away heat, and then the cooler blood from the periphery circulates back to the body core. Water as a Component of Liquid Mixtures A mixture is a combination of two or more substances, each of which maintains its own chemical identity. In other words, the constituent substances are not chemically bonded into a new, larger chemical compound. The concept is easy to imagine if you think of powdery substances such as flour and sugar; when you stir them together in a bowl, they obviously do not bond to form a new compound. The room air you breathe is a gaseous mixture, containing three discrete elements—nitrogen, oxygen, and argon—and one compound, carbon dioxide. There are three types of liquid mixtures, all of which contain water as a key component. These are solutions, colloids, and suspensions. For cells in the body to survive, they must be kept moist in a water-based liquid called a solution. In chemistry, a liquid solution consists of a solvent that dissolves a substance called a solute. An important characteristic of solutions is that they are homogeneous; that is, the solute molecules are distributed evenly throughout the solution. If you were to stir a teaspoon of sugar into a glass of water, the sugar would dissolve into sugar molecules separated by water molecules. The ratio of sugar to water in the left side of the glass would be the same as the ratio of sugar to water in the right side of the glass. If you were to add more sugar, the ratio of sugar to water would change, but the distribution—provided you had stirred well—would still be even. Water is considered the “universal solvent” and it is believed that life cannot exist without water because of this. Water is certainly the most abundant solvent in the body; essentially all of the body’s chemical reactions occur among compounds dissolved in water. Because water molecules are polar, with regions of positive and negative electrical charge, water readily dissolves ionic compounds and polar covalent compounds. Such compounds are referred to as hydrophilic, or “water-loving.” As mentioned above, sugar dissolves well in water. This is because sugar molecules contain regions of hydrogen-oxygen polar bonds, making it hydrophilic. Nonpolar molecules, which do not readily dissolve in water, are called hydrophobic, or “water-fearing.” Concentrations of Solutes Various mixtures of solutes and water are described in chemistry. The concentration of a given solute is the number of particles of that solute in a given space (oxygen makes up about 21 percent of atmospheric air). In the bloodstream of humans, glucose concentration is usually measured in milligram (mg) per deciliter (dL), and in a healthy adult averages about 100 mg/dL. Another method of measuring the concentration of a solute is by its molarilty—which is moles (M) of the molecules per liter (L). The mole of an element is its atomic weight, while a mole of a compound is the sum of the atomic weights of its components, called the molecular weight. An often-used example is calculating a mole of glucose, with the chemical formula C6H12O6. Using the periodic table, the atomic weight of carbon (C) is 12.011 grams (g), and there are six carbons in glucose, for a total atomic weight of 72.066 g. Doing the same calculations for hydrogen (H) and oxygen (O), the molecular weight equals 180.156g (the “gram molecular weight” of glucose). When water is added to make one liter of solution, you have one mole (1M) of glucose. This is particularly useful in chemistry because of the relationship of moles to “Avogadro’s number.” A mole of any solution has the same number of particles in it: 6.02 × 1023. Many substances in the bloodstream and other tissue of the body are measured in thousandths of a mole, or millimoles (mM). A colloid is a mixture that is somewhat like a heavy solution. The solute particles consist of tiny clumps of molecules large enough to make the liquid mixture opaque (because the particles are large enough to scatter light). Familiar examples of colloids are milk and cream. In the thyroid glands, the thyroid hormone is stored as a thick protein mixture also called a colloid. A suspension is a liquid mixture in which a heavier substance is suspended temporarily in a liquid, but over time, settles out. This separation of particles from a suspension is called sedimentation. An example of sedimentation occurs in the blood test that establishes sedimentation rate, or sed rate. The test measures how quickly red blood cells in a test tube settle out of the watery portion of blood (known as plasma) over a set period of time. Rapid sedimentation of blood cells does not normally happen in the healthy body, but aspects of certain diseases can cause blood cells to clump together, and these heavy clumps of blood cells settle to the bottom of the test tube more quickly than do normal blood cells. The Role of Water in Chemical Reactions Two types of chemical reactions involve the creation or the consumption of water: dehydration synthesis and hydrolysis. - In dehydration synthesis, one reactant gives up an atom of hydrogen and another reactant gives up a hydroxyl group (OH) in the synthesis of a new product. In the formation of their covalent bond, a molecule of water is released as a byproduct (Figure 2.14). This is also sometimes referred to as a condensation reaction. - In hydrolysis, a molecule of water disrupts a compound, breaking its bonds. The water is itself split into H and OH. One portion of the severed compound then bonds with the hydrogen atom, and the other portion bonds with the hydroxyl group. These reactions are reversible, and play an important role in the chemistry of organic compounds (which will be discussed shortly). Figure 2.14 Dehydration Synthesis and Hydrolysis Monomers, the basic units for building larger molecules, form polymers (two or more chemically-bonded monomers). (a) In dehydration synthesis, two monomers are covalently bonded in a reaction in which one gives up a hydroxyl group and the other a hydrogen atom. A molecule of water is released as a byproduct during dehydration reactions. (b) In hydrolysis, the covalent bond between two monomers is split by the addition of a hydrogen atom to one and a hydroxyl group to the other, which requires the contribution of one molecule of water. Salts Recall that salts are formed when ions form ionic bonds. In these reactions, one atom gives up one or more electrons, and thus becomes positively charged, whereas the other accepts one or more electrons and becomes negatively charged. You can now define a salt as a substance that, when dissolved in water, dissociates into ions other than H+ or OH–. This fact is important in distinguishing salts from acids and bases, discussed next. A typical salt, NaCl, dissociates completely in water (Figure 2.15). The positive and negative regions on the water molecule (the hydrogen and oxygen ends respectively) attract the negative chloride and positive sodium ions, pulling them away from each other. Again, whereas nonpolar and polar covalently bonded compounds break apart into molecules in solution, salts dissociate into ions. These ions are electrolytes; they are capable of conducting an electrical current in solution. This property is critical to the function of ions in transmitting nerve impulses and prompting muscle contraction. Figure 2.15 Dissociation of Sodium Chloride in Water Notice that the crystals of sodium chloride dissociate not into molecules of NaCl, but into Na+ cations and Cl–anions, each completely surrounded by water molecules. Many other salts are important in the body. For example, bile salts produced by the liver help break apart dietary fats, and calcium phosphate salts form the mineral portion of teeth and bones. Acids and Bases Acids and bases, like salts, dissociate in water into electrolytes. Acids and bases can very much change the properties of the solutions in which they are dissolved. Acids An acid is a substance that releases hydrogen ions (H+) in solution (Figure 2.16a). Because an atom of hydrogen has just one proton and one electron, a positively charged hydrogen ion is simply a proton. This solitary proton is highly likely to participate in chemical reactions. Strong acids are compounds that release all of their H+ in solution; that is, they ionize completely. Hydrochloric acid (HCl), which is released from cells in the lining of the stomach, is a strong acid because it releases all of its H+ in the stomach’s watery environment. This strong acid aids in digestion and kills ingested microbes. Weak acids do not ionize completely; that is, some of their hydrogen ions remain bonded within a compound in solution. An example of a weak acid is vinegar, or acetic acid; it is called acetate after it gives up a proton. Figure 2.16 Acids and Bases (a) In aqueous solution, an acid dissociates into hydrogen ions (H+) and anions. Nearly every molecule of a strong acid dissociates, producing a high concentration of H+. (b) In aqueous solution, a base dissociates into hydroxyl ions (OH–) and cations. Nearly every molecule of a strong base dissociates, producing a high concentration of OH–. Bases A base is a substance that releases hydroxyl ions (OH–) in solution, or one that accepts H+ already present in solution (see Figure 2.16b). The hydroxyl ions (also known as hydroxide ions) or other basic substances combine with H+ present to form a water molecule, thereby removing H+ and reducing the solution’s acidity. Strong bases release most or all of their hydroxyl ions; weak bases release only some hydroxyl ions or absorb only a few H+. Food mixed with hydrochloric acid from the stomach would burn the small intestine, the next portion of the digestive tract after the stomach, if it were not for the release of bicarbonate (HCO3–), a weak base that attracts H+. Bicarbonate accepts some of the H+ protons, thereby reducing the acidity of the solution. The Concept of pH The relative acidity or alkalinity of a solution can be indicated by its pH. A solution’s pH is the negative, base-10 logarithm of the hydrogen ion (H+) concentration of the solution. As an example, a pH 4 solution has an H+ concentration that is ten times greater than that of a pH 5 solution. That is, a solution with a pH of 4 is ten times more acidic than a solution with a pH of 5. The concept of pH will begin to make more sense when you study the pH scale, like that shown in Figure 2.17. The scale consists of a series of increments ranging from 0 to 14. A solution with a pH of 7 is considered neutral—neither acidic nor basic. Pure water has a pH of 7. The lower the number below 7, the more acidic the solution, or the greater the concentration of H+. The concentration of hydrogen ions at each pH value is 10 times different than the next pH. For instance, a pH value of 4 corresponds to a proton concentration of 10–4 M, or 0.0001M, while a pH value of 5 corresponds to a proton concentration of 10–5 M, or 0.00001M. The higher the number above 7, the more basic (alkaline) the solution, or the lower the concentration of H+. Human urine, for example, is ten times more acidic than pure water, and HCl is 10,000,000 times more acidic than water. Figure 2.17 The pH Scale Buffers The pH of human blood normally ranges from 7.35 to 7.45, although it is typically identified as pH 7.4. At this slightly basic pH, blood can reduce the acidity resulting from the carbon dioxide (CO2) constantly being released into the bloodstream by the trillions of cells in the body. Homeostatic mechanisms (along with exhaling CO2 while breathing) normally keep the pH of blood within this narrow range. This is critical, because fluctuations—either too acidic or too alkaline—can lead to life-threatening disorders. All cells of the body depend on homeostatic regulation of acid–base balance at a pH of approximately 7.4. The body therefore has several mechanisms for this regulation, involving breathing, the excretion of chemicals in urine, and the internal release of chemicals collectively called buffers into body fluids. A buffer is a solution of a weak acid and its conjugate base. A buffer can neutralize small amounts of acids or bases in body fluids. For example, if there is even a slight decrease below 7.35 in the pH of a bodily fluid, the buffer in the fluid—in this case, acting as a weak base—will bind the excess hydrogen ions. In contrast, if pH rises above 7.45, the buffer will act as a weak acid and contribute hydrogen ions. HOMEOSTATIC IMBALANCES Acids and Bases Excessive acidity of the blood and other body fluids is known as acidosis. Common causes of acidosis are situations and disorders that reduce the effectiveness of breathing, especially the person’s ability to exhale fully, which causes a buildup of CO2 (and H+) in the bloodstream. Acidosis can also be caused by metabolic problems that reduce the level or function of buffers that act as bases, or that promote the production of acids. For instance, with severe diarrhea, too much bicarbonate can be lost from the body, allowing acids to build up in body fluids. In people with poorly managed diabetes (ineffective regulation of blood sugar), acids called ketones are produced as a form of body fuel. These can build up in the blood, causing a serious condition called diabetic ketoacidosis. Kidney failure, liver failure, heart failure, cancer, and other disorders also can prompt metabolic acidosis. In contrast, alkalosis is a condition in which the blood and other body fluids are too alkaline (basic). As with acidosis, respiratory disorders are a major cause; however, in respiratory alkalosis, carbon dioxide levels fall too low. Lung disease, aspirin overdose, shock, and ordinary anxiety can cause respiratory alkalosis, which reduces the normal concentration of H+. Metabolic alkalosis often results from prolonged, severe vomiting, which causes a loss of hydrogen and chloride ions (as components of HCl). Medications also can prompt alkalosis. These include diuretics that cause the body to lose potassium ions, as well as antacids when taken in excessive amounts, for instance by someone with persistent heartburn or an ulcer. Organic Compounds Essential to Human Functioning - Identify four types of organic molecules essential to human functioning - Explain the chemistry behind carbon’s affinity for covalently bonding in organic compounds - Provide examples of three types of carbohydrates, and identify the primary functions of carbohydrates in the body - Discuss four types of lipids important in human functioning - Describe the structure of proteins, and discuss their importance to human functioning - Identify the building blocks of nucleic acids, and the roles of DNA, RNA, and ATP in human functioning Organic compounds typically consist of groups of carbon atoms covalently bonded to hydrogen, usually oxygen, and often other elements as well. Created by living things, they are found throughout the world, in soils and seas, commercial products, and every cell of the human body. The four types most important to human structure and function are carbohydrates, lipids, proteins, and nucleotides. Before exploring these compounds, you need to first understand the chemistry of carbon. The Chemistry of Carbon What makes organic compounds ubiquitous is the chemistry of their carbon core. Recall that carbon atoms have four electrons in their valence shell, and that the octet rule dictates that atoms tend to react in such a way as to complete their valence shell with eight electrons. Carbon atoms do not complete their valence shells by donating or accepting four electrons. Instead, they readily share electrons via covalent bonds. Commonly, carbon atoms share with other carbon atoms, often forming a long carbon chain referred to as a carbon skeleton. When they do share, however, they do not share all their electrons exclusively with each other. Rather, carbon atoms tend to share electrons with a variety of other elements, one of which is always hydrogen. Carbon and hydrogen groupings are called hydrocarbons. If you study the figures of organic compounds in the remainder of this chapter, you will see several with chains of hydrocarbons in one region of the compound. Many combinations are possible to fill carbon’s four “vacancies.” Carbon may share electrons with oxygen or nitrogen or other atoms in a particular region of an organic compound. Moreover, the atoms to which carbon atoms bond may also be part of a functional group. A functional group is a group of atoms linked by strong covalent bonds and tending to function in chemical reactions as a single unit. You can think of functional groups as tightly knit “cliques” whose members are unlikely to be parted. Five functional groups are important in human physiology; these are the hydroxyl, carboxyl, amino, methyl and phosphate groups (Table 2.1). Carbon’s affinity for covalent bonding means that many distinct and relatively stable organic molecules nevertheless readily form larger, more complex molecules. Any large molecule is referred to as macromolecule (macro- = “large”), and the organic compounds in this section all fit this description. However, some macromolecules are made up of several “copies” of single units called monomer (mono- = “one”; -mer = “part”). Like beads in a long necklace, these monomers link by covalent bonds to form long polymers (poly- = “many”). There are many examples of monomers and polymers among the organic compounds. Monomers form polymers by engaging in dehydration synthesis (see Figure 2.14). As was noted earlier, this reaction results in the release of a molecule of water. Each monomer contributes: One gives up a hydrogen atom and the other gives up a hydroxyl group. Polymers are split into monomers by hydrolysis (-lysis = “rupture”). The bonds between their monomers are broken, via the donation of a molecule of water, which contributes a hydrogen atom to one monomer and a hydroxyl group to the other. Carbohydrates The term carbohydrate means “hydrated carbon.” Recall that the root hydro- indicates water. A carbohydrate is a molecule composed of carbon, hydrogen, and oxygen; in most carbohydrates, hydrogen and oxygen are found in the same two-to-one relative proportions they have in water. In fact, the chemical formula for a “generic” molecule of carbohydrate is (CH2O)n. Carbohydrates are referred to as saccharides, a word meaning “sugars.” Three forms are important in the body. Monosaccharides are the monomers of carbohydrates. Disaccharides (di- = “two”) are made up of two monomers. Polysaccharides are the polymers, and can consist of hundreds to thousands of monomers. Monosaccharides A monosaccharide is a monomer of carbohydrates. Five monosaccharides are important in the body. Three of these are the hexose sugars, so called because they each contain six atoms of carbon. These are glucose, fructose, and galactose, shown in Figure 2.18a. The remaining monosaccharides are the two pentose sugars, each of which contains five atoms of carbon. They are ribose and deoxyribose, shown in Figure 2.18b. Figure 2.18 Five Important Monosaccharides Disaccharides A disaccharide is a pair of monosaccharides. Disaccharides are formed via dehydration synthesis, and the bond linking them is referred to as a glycosidic bond (glyco- = “sugar”). Three disaccharides (shown in Figure 2.19) are important to humans. These are sucrose, commonly referred to as table sugar; lactose, or milk sugar; and maltose, or malt sugar. As you can tell from their common names, you consume these in your diet; however, your body cannot use them directly. Instead, in the digestive tract, they are split into their component monosaccharides via hydrolysis. Figure 2.19 Three Important Disaccharides All three important disaccharides form by dehydration synthesis. INTERACTIVE LINK Watch this video to observe the formation of a disaccharide. What happens when water encounters a glycosidic bond? Polysaccharides Polysaccharides can contain a few to a thousand or more monosaccharides. Three are important to the body (Figure 2.20): - Starches are polymers of glucose. They occur in long chains called amylose or branched chains called amylopectin, both of which are stored in plant-based foods and are relatively easy to digest. - Glycogen is also a polymer of glucose, but it is stored in the tissues of animals, especially in the muscles and liver. It is not considered a dietary carbohydrate because very little glycogen remains in animal tissues after slaughter; however, the human body stores excess glucose as glycogen, again, in the muscles and liver. - Cellulose, a polysaccharide that is the primary component of the cell wall of green plants, is the component of plant food referred to as “fiber”. In humans, cellulose/fiber is not digestible; however, dietary fiber has many health benefits. It helps you feel full so you eat less, it promotes a healthy digestive tract, and a diet high in fiber is thought to reduce the risk of heart disease and possibly some forms of cancer. Figure 2.20 Three Important Polysaccharides Three important polysaccharides are starches, glycogen, and fiber. Functions of Carbohydrates The body obtains carbohydrates from plant-based foods. Grains, fruits, and legumes and other vegetables provide most of the carbohydrate in the human diet, although lactose is found in dairy products. Although most body cells can break down other organic compounds for fuel, all body cells can use glucose. Moreover, nerve cells (neurons) in the brain, spinal cord, and through the peripheral nervous system, as well as red blood cells, can use only glucose for fuel. In the breakdown of glucose for energy, molecules of adenosine triphosphate, better known as ATP, are produced. Adenosine triphosphate (ATP) is composed of a ribose sugar, an adenine base, and three phosphate groups. ATP releases free energy when its phosphate bonds are broken, and thus supplies ready energy to the cell. More ATP is produced in the presence of oxygen (O2) than in pathways that do not use oxygen. The overall reaction for the conversion of the energy in glucose to energy stored in ATP can be written: C6H12O6 + 6 O2 → 6 CO2 + 6 H2O + ATPC6H12O6 + 6 O2 → 6 CO2 + 6 H2O + ATPIn addition to being a critical fuel source, carbohydrates are present in very small amounts in cells’ structure. For instance, some carbohydrate molecules bind with proteins to produce glycoproteins, and others combine with lipids to produce glycolipids, both of which are found in the membrane that encloses the contents of body cells. Lipids A lipid is one of a highly diverse group of compounds made up mostly of hydrocarbons. The few oxygen atoms they contain are often at the periphery of the molecule. Their nonpolar hydrocarbons make all lipids hydrophobic. In water, lipids do not form a true solution, but they may form an emulsion, which is the term for a mixture of solutions that do not mix well. Triglycerides A triglyceride is one of the most common dietary lipid groups, and the type found most abundantly in body tissues. This compound, which is commonly referred to as a fat, is formed from the synthesis of two types of molecules (Figure 2.21): - A glycerol backbone at the core of triglycerides, consists of three carbon atoms. - Three fatty acids, long chains of hydrocarbons with a carboxyl group and a methyl group at opposite ends, extend from each of the carbons of the glycerol. Figure 2.21 Triglycerides Triglycerides are composed of glycerol attached to three fatty acids via dehydration synthesis. Notice that glycerol gives up a hydrogen atom, and the carboxyl groups on the fatty acids each give up a hydroxyl group. Triglycerides form via dehydration synthesis. Glycerol gives up hydrogen atoms from its hydroxyl groups at each bond, and the carboxyl group on each fatty acid chain gives up a hydroxyl group. A total of three water molecules are thereby released. Fatty acid chains that have no double carbon bonds anywhere along their length and therefore contain the maximum number of hydrogen atoms are called saturated fatty acids. These straight, rigid chains pack tightly together and are solid or semi-solid at room temperature (Figure 2.22a). Butter and lard are examples, as is the fat found on a steak or in your own body. In contrast, fatty acids with one double carbon bond are kinked at that bond (Figure 2.22b). These monounsaturated fatty acids are therefore unable to pack together tightly, and are liquid at room temperature. Polyunsaturated fatty acids contain two or more double carbon bonds, and are also liquid at room temperature. Plant oils such as olive oil typically contain both mono- and polyunsaturated fatty acids. Figure 2.22 Fatty Acid Shapes The level of saturation of a fatty acid affects its shape. (a) Saturated fatty acid chains are straight. (b) Unsaturated fatty acid chains are kinked. Whereas a diet high in saturated fatty acids increases the risk of heart disease, a diet high in unsaturated fatty acids is thought to reduce the risk. This is especially true for the omega-3 unsaturated fatty acids found in cold-water fish such as salmon. These fatty acids have their first double carbon bond at the third hydrocarbon from the methyl group (referred to as the omega end of the molecule). Finally, trans fatty acids found in some processed foods, including some stick and tub margarines, are thought to be even more harmful to the heart and blood vessels than saturated fatty acids. Trans fats are created from unsaturated fatty acids (such as corn oil) when chemically treated to produce partially hydrogenated fats. As a group, triglycerides are a major fuel source for the body. When you are resting or asleep, a majority of the energy used to keep you alive is derived from triglycerides stored in your fat (adipose) tissues. Triglycerides also fuel long, slow physical activity such as gardening or hiking, and contribute a modest percentage of energy for vigorous physical activity. Dietary fat also assists the absorption and transport of the nonpolar fat-soluble vitamins A, D, E, and K. Additionally, stored body fat protects and cushions the body’s bones and internal organs, and acts as insulation to retain body heat. Fatty acids are also components of glycolipids, which are sugar-fat compounds found in the cell membrane. Lipoproteins are compounds in which the hydrophobic triglycerides are packaged in protein envelopes for transport in body fluids. Phospholipids As its name suggests, a phospholipid is a bond between the glycerol component of a lipid and a phosphorous molecule. In fact, phospholipids are similar in structure to triglycerides. However, instead of having three fatty acids, a phospholipid is generated from a diglyceride, a glycerol with just two fatty acid chains (Figure 2.23). The third binding site on the glycerol is taken up by the phosphate group, which in turn is attached to a polar “head” region of the molecule. Recall that triglycerides are nonpolar and hydrophobic. This still holds for the fatty acid portion of a phospholipid compound. However, the head of a phospholipid contains charges on the phosphate groups, as well as on the nitrogen atom. These charges make the phospholipid head hydrophilic. Therefore, phospholipids are said to have hydrophobic tails, containing the neutral fatty acids, and hydrophilic heads, containing the charged phosphate groups and nitrogen atom. Figure 2.23 Other Important Lipids (a) Phospholipids are composed of two fatty acids, glycerol, and a phosphate group. (b) Sterols are ring-shaped lipids. Shown here is cholesterol. (c) Prostaglandins are derived from unsaturated fatty acids. Prostaglandin E2 (PGE2) includes hydroxyl and carboxyl groups. Steroids A steroid compound (referred to as a sterol) has as its foundation a set of four hydrocarbon rings bonded to a variety of other atoms and molecules (see Figure 2.23b). Although both plants and animals synthesize sterols, the type that makes the most important contribution to human structure and function is cholesterol, which is synthesized by the liver in humans and animals and is also present in most animal-based foods. Like other lipids, cholesterol’s hydrocarbons make it hydrophobic; however, it has a polar hydroxyl head that is hydrophilic. Cholesterol is an important component of bile acids, compounds that help emulsify dietary fats. In fact, the word root chole- refers to bile. Cholesterol is also a building block of many hormones, signaling molecules that the body releases to regulate processes at distant sites. Finally, like phospholipids, cholesterol molecules are found in the cell membrane, where their hydrophobic and hydrophilic regions help regulate the flow of substances into and out of the cell. Prostaglandins Like a hormone, a prostaglandin is one of a group of signaling molecules, but prostaglandins are derived from unsaturated fatty acids (see Figure 2.23c). One reason that the omega-3 fatty acids found in fish are beneficial is that they stimulate the production of certain prostaglandins that help regulate aspects of blood pressure and inflammation, and thereby reduce the risk for heart disease. Prostaglandins also sensitize nerves to pain. One class of pain-relieving medications called nonsteroidal anti-inflammatory drugs (NSAIDs) works by reducing the effects of prostaglandins. Proteins You might associate proteins with muscle tissue, but in fact, proteins are critical components of all tissues and organs. A protein is an organic molecule composed of amino acids linked by peptide bonds. Proteins include the keratin in the epidermis of skin that protects underlying tissues, the collagen found in the dermis of skin, in bones, and in the meninges that cover the brain and spinal cord. Proteins are also components of many of the body’s functional chemicals, including digestive enzymes in the digestive tract, antibodies, the neurotransmitters that neurons use to communicate with other cells, and the peptide-based hormones that regulate certain body functions (for instance, growth hormone). While carbohydrates and lipids are composed of hydrocarbons and oxygen, all proteins also contain nitrogen (N), and many contain sulfur (S), in addition to carbon, hydrogen, and oxygen. Microstructure of Proteins Proteins are polymers made up of nitrogen-containing monomers called amino acids. An amino acid is a molecule composed of an amino group and a carboxyl group, together with a variable side chain. Just 20 different amino acids contribute to nearly all of the thousands of different proteins important in human structure and function. Body proteins contain a unique combination of a few dozen to a few hundred of these 20 amino acid monomers. All 20 of these amino acids share a similar structure (Figure 2.24). All consist of a central carbon atom to which the following are bonded: - a hydrogen atom - an alkaline (basic) amino group NH2 (see Table 2.1) - an acidic carboxyl group COOH (see Table 2.1) - a variable group Figure 2.24 Structure of an Amino Acid Notice that all amino acids contain both an acid (the carboxyl group) and a base (the amino group) (amine = “nitrogen-containing”). For this reason, they make excellent buffers, helping the body regulate acid–base balance. What distinguishes the 20 amino acids from one another is their variable group, which is referred to as a side chain or an R-group. This group can vary in size and can be polar or nonpolar, giving each amino acid its unique characteristics. For example, the side chains of two amino acids—cysteine and methionine—contain sulfur. Sulfur does not readily participate in hydrogen bonds, whereas all other amino acids do. This variation influences the way that proteins containing cysteine and methionine are assembled. Amino acids join via dehydration synthesis to form protein polymers (Figure 2.25). The unique bond holding amino acids together is called a peptide bond. A peptide bond is a covalent bond between two amino acids that forms by dehydration synthesis. A peptide, in fact, is a very short chain of amino acids. Strands containing fewer than about 100 amino acids are generally referred to as polypeptides rather than proteins. Figure 2.25 Peptide Bond Different amino acids join together to form peptides, polypeptides, or proteins via dehydration synthesis. The bonds between the amino acids are peptide bonds. The body is able to synthesize most of the amino acids from components of other molecules; however, nine cannot be synthesized and have to be consumed in the diet. These are known as the essential amino acids. Free amino acids available for protein construction are said to reside in the amino acid pool within cells. Structures within cells use these amino acids when assembling proteins. If a particular essential amino acid is not available in sufficient quantities in the amino acid pool, however, synthesis of proteins containing it can slow or even cease. Shape of Proteins Just as a fork cannot be used to eat soup and a spoon cannot be used to spear meat, a protein’s shape is essential to its function. A protein’s shape is determined, most fundamentally, by the sequence of amino acids of which it is made (Figure 2.26a). The sequence is called the primary structure of the protein. Figure 2.26 The Shape of Proteins (a) The primary structure is the sequence of amino acids that make up the polypeptide chain. (b) The secondary structure, which can take the form of an alpha-helix or a beta-pleated sheet, is maintained by hydrogen bonds between amino acids in different regions of the original polypeptide strand. (c) The tertiary structure occurs as a result of further folding and bonding of the secondary structure. (d) The quaternary structure occurs as a result of interactions between two or more tertiary subunits. The example shown here is hemoglobin, a protein in red blood cells which transports oxygen to body tissues. Although some polypeptides exist as linear chains, most are twisted or folded into more complex secondary structures that form when bonding occurs between amino acids with different properties at different regions of the polypeptide. The most common secondary structure is a spiral called an alpha-helix. If you were to take a length of string and simply twist it into a spiral, it would not hold the shape. Similarly, a strand of amino acids could not maintain a stable spiral shape without the help of hydrogen bonds, which create bridges between different regions of the same strand (see Figure 2.26b). Less commonly, a polypeptide chain can form a beta-pleated sheet, in which hydrogen bonds form bridges between different regions of a single polypeptide that has folded back upon itself, or between two or more adjacent polypeptide chains. The secondary structure of proteins further folds into a compact three-dimensional shape, referred to as the protein’s tertiary structure (see Figure 2.26c). In this configuration, amino acids that had been very distant in the primary chain can be brought quite close via hydrogen bonds or, in proteins containing cysteine, via disulfide bonds. A disulfide bond is a covalent bond between sulfur atoms in a polypeptide. Often, two or more separate polypeptides bond to form an even larger protein with a quaternary structure (see Figure 2.26d). The polypeptide subunits forming a quaternary structure can be identical or different. For instance, hemoglobin, the protein found in red blood cells is composed of four tertiary polypeptides, two of which are called alpha chains and two of which are called beta chains. When they are exposed to extreme heat, acids, bases, and certain other substances, proteins will denature. Denaturation is a change in the structure of a molecule through physical or chemical means. Denatured proteins lose their functional shape and are no longer able to carry out their jobs. An everyday example of protein denaturation is the curdling of milk when acidic lemon juice is added. The contribution of the shape of a protein to its function can hardly be exaggerated. For example, the long, slender shape of protein strands that make up muscle tissue is essential to their ability to contract (shorten) and relax (lengthen). As another example, bones contain long threads of a protein called collagen that acts as scaffolding upon which bone minerals are deposited. These elongated proteins, called fibrous proteins, are strong and durable and typically hydrophobic. In contrast, globular proteins are globes or spheres that tend to be highly reactive and are hydrophilic. The hemoglobin proteins packed into red blood cells are an example (see Figure 2.26d); however, globular proteins are abundant throughout the body, playing critical roles in most body functions. Enzymes, introduced earlier as protein catalysts, are examples of this. The next section takes a closer look at the action of enzymes. Proteins Function as Enzymes If you were trying to type a paper, and every time you hit a key on your laptop there was a delay of six or seven minutes before you got a response, you would probably get a new laptop. In a similar way, without enzymes to catalyze chemical reactions, the human body would be nonfunctional. It functions only because enzymes function. Enzymatic reactions—chemical reactions catalyzed by enzymes—begin when substrates bind to the enzyme. A substrate is a reactant in an enzymatic reaction. This occurs on regions of the enzyme known as active sites (Figure 2.27). Any given enzyme catalyzes just one type of chemical reaction. This characteristic, called specificity, is due to the fact that a substrate with a particular shape and electrical charge can bind only to an active site corresponding to that substrate. Due to this jigsaw puzzle-like match between an enzyme and its substrates, enzymes are known for their specificity. In fact, as an enzyme binds to its substrate(s), the enzyme structure changes slightly to find the best fit between the transition state (a structural intermediate between the substrate and product) and the active site, just as a rubber glove molds to a hand inserted into it. This active-site modification in the presence of substrate, along with the simultaneous formation of the transition state, is called induced fit. Overall, there is a specifically matched enzyme for each substrate and, thus, for each chemical reaction; however, there is some flexibility as well. Some enzymes have the ability to act on several different structurally related substrates. Figure 2.27 Steps in an Enzymatic Reaction According to the induced-fit model, the active site of the enzyme undergoes conformational changes upon binding with the substrate.(a) Substrates approach active sites on enzyme. (b) Substrates bind to active sites, producing an enzyme–substrate complex. (c) Changes internal to the enzyme–substrate complex facilitate interaction of the substrates. (d) Products are released and the enzyme returns to its original form, ready to facilitate another enzymatic reaction. Binding of a substrate produces an enzyme–substrate complex. It is likely that enzymes speed up chemical reactions in part because the enzyme–substrate complex undergoes a set of temporary and reversible changes that cause the substrates to be oriented toward each other in an optimal position to facilitate their interaction. This promotes increased reaction speed. The enzyme then releases the product(s), and resumes its original shape. The enzyme is then free to engage in the process again, and will do so as long as substrate remains. Other Functions of Proteins Advertisements for protein bars, powders, and shakes all say that protein is important in building, repairing, and maintaining muscle tissue, but the truth is that proteins contribute to all body tissues, from the skin to the brain cells. Also, certain proteins act as hormones, chemical messengers that help regulate body functions, For example, growth hormone is important for skeletal growth, among other roles. As was noted earlier, the basic and acidic components enable proteins to function as buffers in maintaining acid–base balance, but they also help regulate fluid–electrolyte balance. Proteins attract fluid, and a healthy concentration of proteins in the blood, the cells, and the spaces between cells helps ensure a balance of fluids in these various “compartments.” Moreover, proteins in the cell membrane help to transport electrolytes in and out of the cell, keeping these ions in a healthy balance. Like lipids, proteins can bind with carbohydrates. They can thereby produce glycoproteins or proteoglycans, both of which have many functions in the body. The body can use proteins for energy when carbohydrate and fat intake is inadequate, and stores of glycogen and adipose tissue become depleted. However, since there is no storage site for protein except functional tissues, using protein for energy causes tissue breakdown, and results in body wasting. Nucleotides The fourth type of organic compound important to human structure and function are the nucleotides (Figure 2.28). A nucleotide is one of a class of organic compounds composed of three subunits: - one or more phosphate groups - a pentose sugar: either deoxyribose or ribose - a nitrogen-containing base: adenine, cytosine, guanine, thymine, or uracil Nucleotides can be assembled into nucleic acids (DNA or RNA) or the energy compound adenosine triphosphate. Figure 2.28 Nucleotides (a) The building blocks of all nucleotides are one or more phosphate groups, a pentose sugar, and a nitrogen-containing base. (b) The nitrogen-containing bases of nucleotides. (c) The two pentose sugars of DNA and RNA. Nucleic Acids The nucleic acids differ in their type of pentose sugar. Deoxyribonucleic acid (DNA) is nucleotide that stores genetic information. DNA contains deoxyribose (so-called because it has one less atom of oxygen than ribose) plus one phosphate group and one nitrogen-containing base. The “choices” of base for DNA are adenine, cytosine, guanine, and thymine. Ribonucleic acid (RNA) is a ribose-containing nucleotide that helps manifest the genetic code as protein. RNA contains ribose, one phosphate group, and one nitrogen-containing base, but the “choices” of base for RNA are adenine, cytosine, guanine, and uracil. The nitrogen-containing bases adenine and guanine are classified as purines. A purine is a nitrogen-containing molecule with a double ring structure, which accommodates several nitrogen atoms. The bases cytosine, thymine (found in DNA only) and uracil (found in RNA only) are pyramidines. A pyramidine is a nitrogen-containing base with a single ring structure Bonds formed by dehydration synthesis between the pentose sugar of one nucleic acid monomer and the phosphate group of another form a “backbone,” from which the components’ nitrogen-containing bases protrude. In DNA, two such backbones attach at their protruding bases via hydrogen bonds. These twist to form a shape known as a double helix (Figure 2.29). The sequence of nitrogen-containing bases within a strand of DNA form the genes that act as a molecular code instructing cells in the assembly of amino acids into proteins. Humans have almost 22,000 genes in their DNA, locked up in the 46 chromosomes inside the nucleus of each cell (except red blood cells which lose their nuclei during development). These genes carry the genetic code to build one’s body, and are unique for each individual except identical twins. Figure 2.29 DNA In the DNA double helix, two strands attach via hydrogen bonds between the bases of the component nucleotides. In contrast, RNA consists of a single strand of sugar-phosphate backbone studded with bases. Messenger RNA (mRNA) is created during protein synthesis to carry the genetic instructions from the DNA to the cell’s protein manufacturing plants in the cytoplasm, the ribosomes. Adenosine Triphosphate The nucleotide adenosine triphosphate (ATP), is composed of a ribose sugar, an adenine base, and three phosphate groups (Figure 2.30). ATP is classified as a high energy compound because the two covalent bonds linking its three phosphates store a significant amount of potential energy. In the body, the energy released from these high energy bonds helps fuel the body’s activities, from muscle contraction to the transport of substances in and out of cells to anabolic chemical reactions. Figure 2.30 Structure of Adenosine Triphosphate (ATP) When a phosphate group is cleaved from ATP, the products are adenosine diphosphate (ADP) and inorganic phosphate (Pi). This hydrolysis reaction can be written: ATP + H2O → ADP + Pi + energyATP + H2O → ADP + Pi + energy Removal of a second phosphate leaves adenosine monophosphate (AMP) and two phosphate groups. Again, these reactions also liberate the energy that had been stored in the phosphate-phosphate bonds. They are reversible, too, as when ADP undergoes phosphorylation. Phosphorylation is the addition of a phosphate group to an organic compound, in this case, resulting in ATP. In such cases, the same level of energy that had been released during hydrolysis must be reinvested to power dehydration synthesis. Cells can also transfer a phosphate group from ATP to another organic compound. For example, when glucose first enters a cell, a phosphate group is transferred from ATP, forming glucose phosphate (C6H12O6—P) and ADP. Once glucose is phosphorylated in this way, it can be stored as glycogen or metabolized for immediate energy. Key Terms - acid - compound that releases hydrogen ions (H+) in solution - activation energy - amount of energy greater than the energy contained in the reactants, which must be overcome for a reaction to proceed - adenosine triphosphate (ATP) - nucleotide containing ribose and an adenine base that is essential in energy transfer - amino acid - building block of proteins; characterized by an amino and carboxyl functional groups and a variable side-chain - anion - atom with a negative charge - atom - smallest unit of an element that retains the unique properties of that element - atomic number - number of protons in the nucleus of an atom - base - compound that accepts hydrogen ions (H+) in solution - bond - electrical force linking atoms - buffer - solution containing a weak acid or a weak base that opposes wide fluctuations in the pH of body fluids - carbohydrate - class of organic compounds built from sugars, molecules containing carbon, hydrogen, and oxygen in a 1-2-1 ratio - catalyst - substance that increases the rate of a chemical reaction without itself being changed in the process - cation - atom with a positive charge - chemical energy - form of energy that is absorbed as chemical bonds form, stored as they are maintained, and released as they are broken - colloid - liquid mixture in which the solute particles consist of clumps of molecules large enough to scatter light - compound - substance composed of two or more different elements joined by chemical bonds - concentration - number of particles within a given space - covalent bond - chemical bond in which two atoms share electrons, thereby completing their valence shells - decomposition reaction - type of catabolic reaction in which one or more bonds within a larger molecule are broken, resulting in the release of smaller molecules or atoms - denaturation - change in the structure of a molecule through physical or chemical means - deoxyribonucleic acid (DNA) - deoxyribose-containing nucleotide that stores genetic information - disaccharide - pair of carbohydrate monomers bonded by dehydration synthesis via a glycosidic bond - disulfide bond - covalent bond formed within a polypeptide between sulfide groups of sulfur-containing amino acids, for example, cysteine - electron - subatomic particle having a negative charge and nearly no mass; found orbiting the atom’s nucleus - electron shell - area of space a given distance from an atom’s nucleus in which electrons are grouped - element - substance that cannot be created or broken down by ordinary chemical means - enzyme - protein or RNA that catalyzes chemical reactions - exchange reaction - type of chemical reaction in which bonds are both formed and broken, resulting in the transfer of components - functional group - group of atoms linked by strong covalent bonds that tends to behave as a distinct unit in chemical reactions with other atoms - hydrogen bond - dipole-dipole bond in which a hydrogen atom covalently bonded to an electronegative atom is weakly attracted to a second electronegative atom - inorganic compound - substance that does not contain both carbon and hydrogen - ion - atom with an overall positive or negative charge - ionic bond - attraction between an anion and a cation - isotope - one of the variations of an element in which the number of neutrons differ from each other - kinetic energy - energy that matter possesses because of its motion - lipid - class of nonpolar organic compounds built from hydrocarbons and distinguished by the fact that they are not soluble in water - macromolecule - large molecule formed by covalent bonding - mass number - sum of the number of protons and neutrons in the nucleus of an atom - matter - physical substance; that which occupies space and has mass - molecule - two or more atoms covalently bonded together - monosaccharide - monomer of carbohydrate; also known as a simple sugar - neutron - heavy subatomic particle having no electrical charge and found in the atom’s nucleus - nucleotide - class of organic compounds composed of one or more phosphate groups, a pentose sugar, and a base - organic compound - substance that contains both carbon and hydrogen - peptide bond - covalent bond formed by dehydration synthesis between two amino acids - periodic table of the elements - arrangement of the elements in a table according to their atomic number; elements having similar properties because of their electron arrangements compose columns in the table, while elements having the same number of valence shells compose rows in the table - pH - negative logarithm of the hydrogen ion (H+) concentration of a solution - phospholipid - a lipid compound in which a phosphate group is combined with a diglyceride - phosphorylation - addition of one or more phosphate groups to an organic compound - polar molecule - molecule with regions that have opposite charges resulting from uneven numbers of electrons in the nuclei of the atoms participating in the covalent bond - polysaccharide - compound consisting of more than two carbohydrate monomers bonded by dehydration synthesis via glycosidic bonds - potential energy - stored energy matter possesses because of the positioning or structure of its components - product - one or more substances produced by a chemical reaction - prostaglandin - lipid compound derived from fatty acid chains and important in regulating several body processes - protein - class of organic compounds that are composed of many amino acids linked together by peptide bonds - proton - heavy subatomic particle having a positive charge and found in the atom’s nucleus - purine - nitrogen-containing base with a double ring structure; adenine and guanine - pyrimidine - nitrogen-containing base with a single ring structure; cytosine, thiamine, and uracil - radioactive isotope - unstable, heavy isotope that gives off subatomic particles, or electromagnetic energy, as it decays; also called radioisotopes - reactant - one or more substances that enter into the reaction - ribonucleic acid (RNA) - ribose-containing nucleotide that helps manifest the genetic code as protein - solution - homogeneous liquid mixture in which a solute is dissolved into molecules within a solvent - steroid - (also, sterol) lipid compound composed of four hydrocarbon rings bonded to a variety of other atoms and molecules - substrate - reactant in an enzymatic reaction - suspension - liquid mixture in which particles distributed in the liquid settle out over time - synthesis reaction - type of anabolic reaction in which two or more atoms or molecules bond, resulting in the formation of a larger molecule - triglyceride - lipid compound composed of a glycerol molecule bonded with three fatty acid chains - valence shell - outermost electron shell of an atom Chapter Review 2.1 Elements and Atoms: The Building Blocks of Matter The human body is composed of elements, the most abundant of which are oxygen (O), carbon (C), hydrogen (H) and nitrogen (N). You obtain these elements from the foods you eat and the air you breathe. The smallest unit of an element that retains all of the properties of that element is an atom. But, atoms themselves contain many subatomic particles, the three most important of which are protons, neutrons, and electrons. These particles do not vary in quality from one element to another; rather, what gives an element its distinctive identification is the quantity of its protons, called its atomic number. Protons and neutrons contribute nearly all of an atom’s mass; the number of protons and neutrons is an element’s mass number. Heavier and lighter versions of the same element can occur in nature because these versions have different numbers of neutrons. Different versions of an element are called isotopes. The tendency of an atom to be stable or to react readily with other atoms is largely due to the behavior of the electrons within the atom’s outermost electron shell, called its valence shell. Helium, as well as larger atoms with eight electrons in their valence shell, is unlikely to participate in chemical reactions because they are stable. All other atoms tend to accept, donate, or share electrons in a process that brings the electrons in their valence shell to eight (or in the case of hydrogen, to two). 2.2 Chemical Bonds Each moment of life, atoms of oxygen, carbon, hydrogen, and the other elements of the human body are making and breaking chemical bonds. Ions are charged atoms that form when an atom donates or accepts one or more negatively charged electrons. Cations (ions with a positive charge) are attracted to anions (ions with a negative charge). This attraction is called an ionic bond. In covalent bonds, the participating atoms do not lose or gain electrons, but rather share them. Molecules with nonpolar covalent bonds are electrically balanced, and have a linear three-dimensional shape. Molecules with polar covalent bonds have “poles”—regions of weakly positive and negative charge—and have a triangular three-dimensional shape. An atom of oxygen and two atoms of hydrogen form water molecules by means of polar covalent bonds. Hydrogen bonds link hydrogen atoms already participating in polar covalent bonds to anions or electronegative regions of other polar molecules. Hydrogen bonds link water molecules, resulting in the properties of water that are important to living things. 2.3 Chemical Reactions Chemical reactions, in which chemical bonds are broken and formed, require an initial investment of energy. Kinetic energy, the energy of matter in motion, fuels the collisions of atoms, ions, and molecules that are necessary if their old bonds are to break and new ones to form. All molecules store potential energy, which is released when their bonds are broken. Four forms of energy essential to human functioning are: chemical energy, which is stored and released as chemical bonds are formed and broken; mechanical energy, which directly powers physical activity; radiant energy, emitted as waves such as in sunlight; and electrical energy, the power of moving electrons. Chemical reactions begin with reactants and end with products. Synthesis reactions bond reactants together, a process that requires energy, whereas decomposition reactions break the bonds within a reactant and thereby release energy. In exchange reactions, bonds are both broken and formed, and energy is exchanged. The rate at which chemical reactions occur is influenced by several properties of the reactants: temperature, concentration and pressure, and the presence or absence of a catalyst. An enzyme is a catalytic protein that speeds up chemical reactions in the human body. 2.4 Inorganic Compounds Essential to Human Functioning Inorganic compounds essential to human functioning include water, salts, acids, and bases. These compounds are inorganic; that is, they do not contain both hydrogen and carbon. Water is a lubricant and cushion, a heat sink, a component of liquid mixtures, a byproduct of dehydration synthesis reactions, and a reactant in hydrolysis reactions. Salts are compounds that, when dissolved in water, dissociate into ions other than H+ or OH–. In contrast, acids release H+ in solution, making it more acidic. Bases accept H+, thereby making the solution more alkaline (caustic). The pH of any solution is its relative concentration of H+. A solution with pH 7 is neutral. Solutions with pH below 7 are acids, and solutions with pH above 7 are bases. A change in a single digit on the pH scale (e.g., from 7 to 8) represents a ten-fold increase or decrease in the concentration of H+. In a healthy adult, the pH of blood ranges from 7.35 to 7.45. Homeostatic control mechanisms important for keeping blood in a healthy pH range include chemicals called buffers, weak acids and weak bases released when the pH of blood or other body fluids fluctuates in either direction outside of this normal range. 2.5 Organic Compounds Essential to Human Functioning Organic compounds essential to human functioning include carbohydrates, lipids, proteins, and nucleotides. These compounds are said to be organic because they contain both carbon and hydrogen. Carbon atoms in organic compounds readily share electrons with hydrogen and other atoms, usually oxygen, and sometimes nitrogen. Carbon atoms also may bond with one or more functional groups such as carboxyls, hydroxyls, aminos, or phosphates. Monomers are single units of organic compounds. They bond by dehydration synthesis to form polymers, which can in turn be broken by hydrolysis. Carbohydrate compounds provide essential body fuel. Their structural forms include monosaccharides such as glucose, disaccharides such as lactose, and polysaccharides, including starches (polymers of glucose), glycogen (the storage form of glucose), and fiber. All body cells can use glucose for fuel. It is converted via an oxidation-reduction reaction to ATP. Lipids are hydrophobic compounds that provide body fuel and are important components of many biological compounds. Triglycerides are the most abundant lipid in the body, and are composed of a glycerol backbone attached to three fatty acid chains. Phospholipids are compounds composed of a diglyceride with a phosphate group attached at the molecule’s head. The result is a molecule with polar and nonpolar regions. Steroids are lipids formed of four hydrocarbon rings. The most important is cholesterol. Prostaglandins are signaling molecules derived from unsaturated fatty acids. Proteins are critical components of all body tissues. They are made up of monomers called amino acids, which contain nitrogen, joined by peptide bonds. Protein shape is critical to its function. Most body proteins are globular. An example is enzymes, which catalyze chemical reactions. Nucleotides are compounds with three building blocks: one or more phosphate groups, a pentose sugar, and a nitrogen-containing base. DNA and RNA are nucleic acids that function in protein synthesis. ATP is the body’s fundamental molecule of energy transfer. Removal or addition of phosphates releases or invests energy. Interactive Link Questions Visit this website to view the periodic table. In the periodic table of the elements, elements in a single column have the same number of electrons that can participate in a chemical reaction. These electrons are known as “valence electrons.” For example, the elements in the first column all have a single valence electron—an electron that can be “donated” in a chemical reaction with another atom. What is the meaning of a mass number shown in parentheses? 2.Visit this website to learn about electrical energy and the attraction/repulsion of charges. What happens to the charged electroscope when a conductor is moved between its plastic sheets, and why? 3.Watch this video to observe the formation of a disaccharide. What happens when water encounters a glycosidic bond? Review Questions Together, just four elements make up more than 95 percent of the body’s mass. These include ________. - calcium, magnesium, iron, and carbon - oxygen, calcium, iron, and nitrogen - sodium, chlorine, carbon, and hydrogen - oxygen, carbon, hydrogen, and nitrogen The smallest unit of an element that still retains the distinctive behavior of that element is an ________. - electron - atom - elemental particle - isotope The characteristic that gives an element its distinctive properties is its number of ________. - protons - neutrons - electrons - atoms On the periodic table of the elements, mercury (Hg) has an atomic number of 80 and a mass number of 200.59. It has seven stable isotopes. The most abundant of these probably have ________. - about 80 neutrons each - fewer than 80 neutrons each - more than 80 neutrons each - more electrons than neutrons Nitrogen has an atomic number of seven. How many electron shells does it likely have? - one - two - three - four Which of the following is a molecule, but not a compound? - H2O - 2H - H2 - H+ A molecule of ammonia contains one atom of nitrogen and three atoms of hydrogen. These are linked with ________. - ionic bonds - nonpolar covalent bonds - polar covalent bonds - hydrogen bonds When an atom donates an electron to another atom, it becomes - an ion - an anion - nonpolar - all of the above A substance formed of crystals of equal numbers of cations and anions held together by ionic bonds is called a(n) ________. - noble gas - salt - electrolyte - dipole Which of the following statements about chemical bonds is true? - Covalent bonds are stronger than ionic bonds. - Hydrogen bonds occur between two atoms of hydrogen. - Bonding readily occurs between nonpolar and polar molecules. - A molecule of water is unlikely to bond with an ion. The energy stored in a foot of snow on a steep roof is ________. - potential energy - kinetic energy - radiant energy - activation energy The bonding of calcium, phosphorus, and other elements produces mineral crystals that are found in bone. This is an example of a(n) ________ reaction. - catabolic - synthesis - decomposition - exchange AB→A+BAB→A+B is a general notation for a(n) ________ reaction. - anabolic - endergonic - decomposition - exchange ________ reactions release energy. - Catabolic - Exergonic - Decomposition - Catabolic, exergonic, and decomposition Which of the following combinations of atoms is most likely to result in a chemical reaction? - hydrogen and hydrogen - hydrogen and helium - helium and helium - neon and helium Chewing a bite of bread mixes it with saliva and facilitates its chemical breakdown. This is most likely due to the fact that ________. - the inside of the mouth maintains a very high temperature - chewing stores potential energy - chewing facilitates synthesis reactions - saliva contains enzymes CH4 is methane. This compound is ________. - inorganic - organic - reactive - a crystal Which of the following is most likely to be found evenly distributed in water in a homogeneous solution? - sodium ions and chloride ions - NaCl molecules - salt crystals - red blood cells Jenny mixes up a batch of pancake batter, then stirs in some chocolate chips. As she is waiting for the first few pancakes to cook, she notices the chocolate chips sinking to the bottom of the clear glass mixing bowl. The chocolate-chip batter is an example of a ________. - solvent - solute - solution - suspension A substance dissociates into K+ and Cl– in solution. The substance is a(n) ________. - acid - base - salt - buffer Ty is three years old and as a result of a “stomach bug” has been vomiting for about 24 hours. His blood pH is 7.48. What does this mean? - Ty’s blood is slightly acidic. - Ty’s blood is slightly alkaline. - Ty’s blood is highly acidic. - Ty’s blood is within the normal range C6H12O6 is the chemical formula for a ________. - polymer of carbohydrate - pentose monosaccharide - hexose monosaccharide - all of the above What organic compound do brain cells primarily rely on for fuel? - glucose - glycogen - galactose - glycerol Which of the following is a functional group that is part of a building block of proteins? - phosphate - adenine - amino - ribose A pentose sugar is a part of the monomer used to build which type of macromolecule? - polysaccharides - nucleic acids - phosphorylated glucose - glycogen A phospholipid ________. - has both polar and nonpolar regions - is made up of a triglyceride bonded to a phosphate group - is a building block of ATP - can donate both cations and anions in solution In DNA, nucleotide bonding forms a compound with a characteristic shape known as a(n) ________. - beta chain - pleated sheet - alpha helix - double helix Uracil ________. - contains nitrogen - is a pyrimidine - is found in RNA - all of the above The ability of an enzyme’s active sites to bind only substrates of compatible shape and charge is known as ________. - selectivity - specificity - subjectivity - specialty Critical Thinking Questions The most abundant elements in the foods and beverages you consume are oxygen, carbon, hydrogen, and nitrogen. Why might having these elements in consumables be useful? 34.Oxygen, whose atomic number is eight, has three stable isotopes: 16O, 17O, and 18O. Explain what this means in terms of the number of protons and neutrons. 35.Magnesium is an important element in the human body, especially in bones. Magnesium’s atomic number is 12. Is it stable or reactive? Why? If it were to react with another atom, would it be more likely to accept or to donate one or more electrons? 36.Explain why CH4 is one of the most common molecules found in nature. Are the bonds between the atoms ionic or covalent? 37.In a hurry one day, you merely rinse your lunch dishes with water. As you are drying your salad bowl, you notice that it still has an oily film. Why was the water alone not effective in cleaning the bowl? 38.Could two atoms of oxygen engage in ionic bonding? Why or why not? 39.AB+CD→AD+BEAB+CD→AD+BE Is this a legitimate example of an exchange reaction? Why or why not? 40.When you do a load of laundry, why do you not just drop a bar of soap into the washing machine? In other words, why is laundry detergent sold as a liquid or powder? 41.The pH of lemon juice is 2, and the pH of orange juice is 4. Which of these is more acidic, and by how much? What does this mean? 42.During a party, Eli loses a bet and is forced to drink a bottle of lemon juice. Not long thereafter, he begins complaining of having difficulty breathing, and his friends take him to the local emergency room. There, he is given an intravenous solution of bicarbonate. Why? 43.If the disaccharide maltose is formed from two glucose monosaccharides, which are hexose sugars, how many atoms of carbon, hydrogen, and oxygen does maltose contain and why? 44.Once dietary fats are digested and absorbed, why can they not be released directly into the bloodstream?	oercommons	2025-03-18T00:36:11.534204	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/56352/overview", "title": "Anatomy and Physiology, Levels of Organization", "author": null }
https://oercommons.org/courseware/lesson/56353/overview	The Cellular Level of Organization Introduction Figure 3.1 Fluorescence-stained Cell Undergoing Mitosis A lung cell from a newt, commonly studied for its similarity to human lung cells, is stained with fluorescent dyes. The green stain reveals mitotic spindles, red is the cell membrane and part of the cytoplasm, and the structures that appear light blue are chromosomes. This cell is in anaphase of mitosis. (credit: “Mortadelo2005”/Wikimedia Commons) CHAPTER OBJECTIVES After studying this chapter, you will be able to: - Describe the structure and function of the cell membrane, including its regulation of materials into and out of the cell - Describe the functions of the various cytoplasmic organelles - Explain the structure and contents of the nucleus, as well as the process of DNA replication - Explain the process by which a cell builds proteins using the DNA code - List the stages of the cell cycle in order, including the steps of cell division in somatic cells - Discuss how a cell differentiates and becomes more specialized - List the morphological and physiological characteristics of some representative cell types in the human body You developed from a single fertilized egg cell into the complex organism containing trillions of cells that you see when you look in a mirror. During this developmental process, early, undifferentiated cells differentiate and become specialized in their structure and function. These different cell types form specialized tissues that work in concert to perform all of the functions necessary for the living organism. Cellular and developmental biologists study how the continued division of a single cell leads to such complexity and differentiation. Consider the difference between a structural cell in the skin and a nerve cell. A structural skin cell may be shaped like a flat plate (squamous) and live only for a short time before it is shed and replaced. Packed tightly into rows and sheets, the squamous skin cells provide a protective barrier for the cells and tissues that lie beneath. A nerve cell, on the other hand, may be shaped something like a star, sending out long processes up to a meter in length and may live for the entire lifetime of the organism. With their long winding appendages, nerve cells can communicate with one another and with other types of body cells and send rapid signals that inform the organism about its environment and allow it to interact with that environment. These differences illustrate one very important theme that is consistent at all organizational levels of biology: the form of a structure is optimally suited to perform particular functions assigned to that structure. Keep this theme in mind as you tour the inside of a cell and are introduced to the various types of cells in the body. A primary responsibility of each cell is to contribute to homeostasis. Homeostasis is a term used in biology that refers to a dynamic state of balance within parameters that are compatible with life. For example, living cells require a water-based environment to survive in, and there are various physical (anatomical) and physiological mechanisms that keep all of the trillions of living cells in the human body moist. This is one aspect of homeostasis. When a particular parameter, such as blood pressure or blood oxygen content, moves far enough out of homeostasis (generally becoming too high or too low), illness or disease—and sometimes death—inevitably results. The concept of a cell started with microscopic observations of dead cork tissue by scientist Robert Hooke in 1665. Without realizing their function or importance, Hook coined the term “cell” based on the resemblance of the small subdivisions in the cork to the rooms that monks inhabited, called cells. About ten years later, Antonie van Leeuwenhoek became the first person to observe living and moving cells under a microscope. In the century that followed, the theory that cells represented the basic unit of life would develop. These tiny fluid-filled sacs house components responsible for the thousands of biochemical reactions necessary for an organism to grow and survive. In this chapter, you will learn about the major components and functions of a prototypical, generalized cell and discover some of the different types of cells in the human body. The Cell Membrane - Describe the molecular components that make up the cell membrane - Explain the major features and properties of the cell membrane - Differentiate between materials that can and cannot diffuse through the lipid bilayer - Compare and contrast different types of passive transport with active transport, providing examples of each Despite differences in structure and function, all living cells in multicellular organisms have a surrounding cell membrane. As the outer layer of your skin separates your body from its environment, the cell membrane (also known as the plasma membrane) separates the inner contents of a cell from its exterior environment. This cell membrane provides a protective barrier around the cell and regulates which materials can pass in or out. Structure and Composition of the Cell Membrane The cell membrane is an extremely pliable structure composed primarily of back-to-back phospholipids (a “bilayer”). Cholesterol is also present, which contributes to the fluidity of the membrane, and there are various proteins embedded within the membrane that have a variety of functions. A single phospholipid molecule has a phosphate group on one end, called the “head,” and two side-by-side chains of fatty acids that make up the lipid tails (Figure 3.2). The phosphate group is negatively charged, making the head polar and hydrophilic—or “water loving.” A hydrophilic molecule (or region of a molecule) is one that is attracted to water. The phosphate heads are thus attracted to the water molecules of both the extracellular and intracellular environments. The lipid tails, on the other hand, are uncharged, or nonpolar, and are hydrophobic—or “water fearing.” A hydrophobic molecule (or region of a molecule) repels and is repelled by water. Some lipid tails consist of saturated fatty acids and some contain unsaturated fatty acids. This combination adds to the fluidity of the tails that are constantly in motion. Phospholipids are thus amphipathic molecules. An amphipathic molecule is one that contains both a hydrophilic and a hydrophobic region. In fact, soap works to remove oil and grease stains because it has amphipathic properties. The hydrophilic portion can dissolve in water while the hydrophobic portion can trap grease in micelles that then can be washed away. Figure 3.2 Phospholipid Structure A phospholipid molecule consists of a polar phosphate “head,” which is hydrophilic and a non-polar lipid “tail,” which is hydrophobic. Unsaturated fatty acids result in kinks in the hydrophobic tails. The cell membrane consists of two adjacent layers of phospholipids. The lipid tails of one layer face the lipid tails of the other layer, meeting at the interface of the two layers. The phospholipid heads face outward, one layer exposed to the interior of the cell and one layer exposed to the exterior (Figure 3.3). Because the phosphate groups are polar and hydrophilic, they are attracted to water in the intracellular fluid. Intracellular fluid (ICF) is the fluid interior of the cell. The phosphate groups are also attracted to the extracellular fluid. Extracellular fluid (ECF) is the fluid environment outside the enclosure of the cell membrane. Interstitial fluid (IF) is the term given to extracellular fluid not contained within blood vessels. Because the lipid tails are hydrophobic, they meet in the inner region of the membrane, excluding watery intracellular and extracellular fluid from this space. The cell membrane has many proteins, as well as other lipids (such as cholesterol), that are associated with the phospholipid bilayer. An important feature of the membrane is that it remains fluid; the lipids and proteins in the cell membrane are not rigidly locked in place. Figure 3.3 Phospolipid Bilayer The phospholipid bilayer consists of two adjacent sheets of phospholipids, arranged tail to tail. The hydrophobic tails associate with one another, forming the interior of the membrane. The polar heads contact the fluid inside and outside of the cell. Membrane Proteins The lipid bilayer forms the basis of the cell membrane, but it is peppered throughout with various proteins. Two different types of proteins that are commonly associated with the cell membrane are the integral proteins and peripheral protein (Figure 3.4). As its name suggests, an integral protein is a protein that is embedded in the membrane. A channel protein is an example of an integral protein that selectively allows particular materials, such as certain ions, to pass into or out of the cell. Figure 3.4 Cell Membrane The cell membrane of the cell is a phospholipid bilayer containing many different molecular components, including proteins and cholesterol, some with carbohydrate groups attached. Another important group of integral proteins are cell recognition proteins, which serve to mark a cell’s identity so that it can be recognized by other cells. A receptor is a type of recognition protein that can selectively bind a specific molecule outside the cell, and this binding induces a chemical reaction within the cell. A ligand is the specific molecule that binds to and activates a receptor. Some integral proteins serve dual roles as both a receptor and an ion channel. One example of a receptor-ligand interaction is the receptors on nerve cells that bind neurotransmitters, such as dopamine. When a dopamine molecule binds to a dopamine receptor protein, a channel within the transmembrane protein opens to allow certain ions to flow into the cell. Some integral membrane proteins are glycoproteins. A glycoprotein is a protein that has carbohydrate molecules attached, which extend into the extracellular matrix. The attached carbohydrate tags on glycoproteins aid in cell recognition. The carbohydrates that extend from membrane proteins and even from some membrane lipids collectively form the glycocalyx. The glycocalyx is a fuzzy-appearing coating around the cell formed from glycoproteins and other carbohydrates attached to the cell membrane. The glycocalyx can have various roles. For example, it may have molecules that allow the cell to bind to another cell, it may contain receptors for hormones, or it might have enzymes to break down nutrients. The glycocalyces found in a person’s body are products of that person’s genetic makeup. They give each of the individual’s trillions of cells the “identity” of belonging in the person’s body. This identity is the primary way that a person’s immune defense cells “know” not to attack the person’s own body cells, but it also is the reason organs donated by another person might be rejected. Peripheral proteins are typically found on the inner or outer surface of the lipid bilayer but can also be attached to the internal or external surface of an integral protein. These proteins typically perform a specific function for the cell. Some peripheral proteins on the surface of intestinal cells, for example, act as digestive enzymes to break down nutrients to sizes that can pass through the cells and into the bloodstream. Transport across the Cell Membrane One of the great wonders of the cell membrane is its ability to regulate the concentration of substances inside the cell. These substances include ions such as Ca++, Na+, K+, and Cl–; nutrients including sugars, fatty acids, and amino acids; and waste products, particularly carbon dioxide (CO2), which must leave the cell. The membrane’s lipid bilayer structure provides the first level of control. The phospholipids are tightly packed together, and the membrane has a hydrophobic interior. This structure causes the membrane to be selectively permeable. A membrane that has selective permeability allows only substances meeting certain criteria to pass through it unaided. In the case of the cell membrane, only relatively small, nonpolar materials can move through the lipid bilayer (remember, the lipid tails of the membrane are nonpolar). Some examples of these are other lipids, oxygen and carbon dioxide gases, and alcohol. However, water-soluble materials—like glucose, amino acids, and electrolytes—need some assistance to cross the membrane because they are repelled by the hydrophobic tails of the phospholipid bilayer. All substances that move through the membrane do so by one of two general methods, which are categorized based on whether or not energy is required. Passive transport is the movement of substances across the membrane without the expenditure of cellular energy. In contrast, active transport is the movement of substances across the membrane using energy from adenosine triphosphate (ATP). Passive Transport In order to understand how substances move passively across a cell membrane, it is necessary to understand concentration gradients and diffusion. A concentration gradient is the difference in concentration of a substance across a space. Molecules (or ions) will spread/diffuse from where they are more concentrated to where they are less concentrated until they are equally distributed in that space. (When molecules move in this way, they are said to move down their concentration gradient.) Diffusion is the movement of particles from an area of higher concentration to an area of lower concentration. A couple of common examples will help to illustrate this concept. Imagine being inside a closed bathroom. If a bottle of perfume were sprayed, the scent molecules would naturally diffuse from the spot where they left the bottle to all corners of the bathroom, and this diffusion would go on until no more concentration gradient remains. Another example is a spoonful of sugar placed in a cup of tea. Eventually the sugar will diffuse throughout the tea until no concentration gradient remains. In both cases, if the room is warmer or the tea hotter, diffusion occurs even faster as the molecules are bumping into each other and spreading out faster than at cooler temperatures. Having an internal body temperature around 98.6° F thus also aids in diffusion of particles within the body. INTERACTIVE LINK Visit this link to see diffusion and how it is propelled by the kinetic energy of molecules in solution. How does temperature affect diffusion rate, and why? Whenever a substance exists in greater concentration on one side of a semipermeable membrane, such as the cell membranes, any substance that can move down its concentration gradient across the membrane will do so. Consider substances that can easily diffuse through the lipid bilayer of the cell membrane, such as the gases oxygen (O2) and CO2. O2generally diffuses into cells because it is more concentrated outside of them, and CO2 typically diffuses out of cells because it is more concentrated inside of them. Neither of these examples requires any energy on the part of the cell, and therefore they use passive transport to move across the membrane. Before moving on, you need to review the gases that can diffuse across a cell membrane. Because cells rapidly use up oxygen during metabolism, there is typically a lower concentration of O2 inside the cell than outside. As a result, oxygen will diffuse from the interstitial fluid directly through the lipid bilayer of the membrane and into the cytoplasm within the cell. On the other hand, because cells produce CO2 as a byproduct of metabolism, CO2 concentrations rise within the cytoplasm; therefore, CO2will move from the cell through the lipid bilayer and into the interstitial fluid, where its concentration is lower. This mechanism of molecules moving across a cell membrane from the side where they are more concentrated to the side where they are less concentrated is a form of passive transport called simple diffusion (Figure 3.5). Figure 3.5 Simple Diffusion across the Cell (Plasma) MembraneThe structure of the lipid bilayer allows small, uncharged substances such as oxygen and carbon dioxide, and hydrophobic molecules such as lipids, to pass through the cell membrane, down their concentration gradient, by simple diffusion. Large polar or ionic molecules, which are hydrophilic, cannot easily cross the phospholipid bilayer. Very small polar molecules, such as water, can cross via simple diffusion due to their small size. Charged atoms or molecules of any size cannot cross the cell membrane via simple diffusion as the charges are repelled by the hydrophobic tails in the interior of the phospholipid bilayer. Solutes dissolved in water on either side of the cell membrane will tend to diffuse down their concentration gradients, but because most substances cannot pass freely through the lipid bilayer of the cell membrane, their movement is restricted to protein channels and specialized transport mechanisms in the membrane. Facilitated diffusion is the diffusion process used for those substances that cannot cross the lipid bilayer due to their size, charge, and/or polarity (Figure 3.6). A common example of facilitated diffusion is the movement of glucose into the cell, where it is used to make ATP. Although glucose can be more concentrated outside of a cell, it cannot cross the lipid bilayer via simple diffusion because it is both large and polar. To resolve this, a specialized carrier protein called the glucose transporter will transfer glucose molecules into the cell to facilitate its inward diffusion. Figure 3.6 Facilitated Diffusion (a) Facilitated diffusion of substances crossing the cell (plasma) membrane takes place with the help of proteins such as channel proteins and carrier proteins. Channel proteins are less selective than carrier proteins, and usually mildly discriminate between their cargo based on size and charge. (b) Carrier proteins are more selective, often only allowing one particular type of molecule to cross. As an example, even though sodium ions (Na+) are highly concentrated outside of cells, these electrolytes are charged and cannot pass through the nonpolar lipid bilayer of the membrane. Their diffusion is facilitated by membrane proteins that form sodium channels (or “pores”), so that Na+ ions can move down their concentration gradient from outside the cells to inside the cells. There are many other solutes that must undergo facilitated diffusion to move into a cell, such as amino acids, or to move out of a cell, such as wastes. Because facilitated diffusion is a passive process, it does not require energy expenditure by the cell. Water also can move freely across the cell membrane of all cells, either through protein channels or by slipping between the lipid tails of the membrane itself. Osmosis is the diffusion of water through a semipermeable membrane (Figure 3.7). Figure 3.7 Osmosis Osmosis is the diffusion of water through a semipermeable membrane down its concentration gradient. If a membrane is permeable to water, though not to a solute, water will equalize its own concentration by diffusing to the side of lower water concentration (and thus the side of higher solute concentration). In the beaker on the left, the solution on the right side of the membrane is hypertonic. The movement of water molecules is not itself regulated by cells, so it is important that cells are exposed to an environment in which the concentration of solutes outside of the cells (in the extracellular fluid) is equal to the concentration of solutes inside the cells (in the cytoplasm). Two solutions that have the same concentration of solutes are said to be isotonic (equal tension). When cells and their extracellular environments are isotonic, the concentration of water molecules is the same outside and inside the cells, and the cells maintain their normal shape (and function). Osmosis occurs when there is an imbalance of solutes outside of a cell versus inside the cell. A solution that has a higher concentration of solutes than another solution is said to be hypertonic, and water molecules tend to diffuse into a hypertonic solution (Figure 3.8). Cells in a hypertonic solution will shrivel as water leaves the cell via osmosis. In contrast, a solution that has a lower concentration of solutes than another solution is said to be hypotonic, and water molecules tend to diffuse out of a hypotonic solution. Cells in a hypotonic solution will take on too much water and swell, with the risk of eventually bursting. A critical aspect of homeostasis in living things is to create an internal environment in which all of the body’s cells are in an isotonic solution. Various organ systems, particularly the kidneys, work to maintain this homeostasis. Figure 3.8 Concentration of Solutions A hypertonic solution has a solute concentration higher than another solution. An isotonic solution has a solute concentration equal to another solution. A hypotonic solution has a solute concentration lower than another solution. Another mechanism besides diffusion to passively transport materials between compartments is filtration. Unlike diffusion of a substance from where it is more concentrated to less concentrated, filtration uses a hydrostatic pressure gradient that pushes the fluid—and the solutes within it—from a higher pressure area to a lower pressure area. Filtration is an extremely important process in the body. For example, the circulatory system uses filtration to move plasma and substances across the endothelial lining of capillaries and into surrounding tissues, supplying cells with the nutrients. Filtration pressure in the kidneys provides the mechanism to remove wastes from the bloodstream. Active Transport For all of the transport methods described above, the cell expends no energy. Membrane proteins that aid in the passive transport of substances do so without the use of ATP. During active transport, ATP is required to move a substance across a membrane, often with the help of protein carriers, and usually against its concentration gradient. One of the most common types of active transport involves proteins that serve as pumps. The word “pump” probably conjures up thoughts of using energy to pump up the tire of a bicycle or a basketball. Similarly, energy from ATP is required for these membrane proteins to transport substances—molecules or ions—across the membrane, usually against their concentration gradients (from an area of low concentration to an area of high concentration). The sodium-potassium pump, which is also called Na+/K+ ATPase, transports sodium out of a cell while moving potassium into the cell. The Na+/K+ pump is an important ion pump found in the membranes of many types of cells. These pumps are particularly abundant in nerve cells, which are constantly pumping out sodium ions and pulling in potassium ions to maintain an electrical gradient across their cell membranes. An electrical gradient is a difference in electrical charge across a space. In the case of nerve cells, for example, the electrical gradient exists between the inside and outside of the cell, with the inside being negatively-charged (at around -70 mV) relative to the outside. The negative electrical gradient is maintained because each Na+/K+ pump moves three Na+ ions out of the cell and two K+ ions into the cell for each ATP molecule that is used (Figure 3.9). This process is so important for nerve cells that it accounts for the majority of their ATP usage. Figure 3.9 Sodium-Potassium Pump The sodium-potassium pump is found in many cell (plasma) membranes. Powered by ATP, the pump moves sodium and potassium ions in opposite directions, each against its concentration gradient. In a single cycle of the pump, three sodium ions are extruded from and two potassium ions are imported into the cell. Active transport pumps can also work together with other active or passive transport systems to move substances across the membrane. For example, the sodium-potassium pump maintains a high concentration of sodium ions outside of the cell. Therefore, if the cell needs sodium ions, all it has to do is open a passive sodium channel, as the concentration gradient of the sodium ions will drive them to diffuse into the cell. In this way, the action of an active transport pump (the sodium-potassium pump) powers the passive transport of sodium ions by creating a concentration gradient. When active transport powers the transport of another substance in this way, it is called secondary active transport. Symporters are secondary active transporters that move two substances in the same direction. For example, the sodium-glucose symporter uses sodium ions to “pull” glucose molecules into the cell. Because cells store glucose for energy, glucose is typically at a higher concentration inside of the cell than outside. However, due to the action of the sodium-potassium pump, sodium ions will easily diffuse into the cell when the symporter is opened. The flood of sodium ions through the symporter provides the energy that allows glucose to move through the symporter and into the cell, against its concentration gradient. Conversely, antiporters are secondary active transport systems that transport substances in opposite directions. For example, the sodium-hydrogen ion antiporter uses the energy from the inward flood of sodium ions to move hydrogen ions (H+) out of the cell. The sodium-hydrogen antiporter is used to maintain the pH of the cell's interior. Other forms of active transport do not involve membrane carriers. Endocytosis (bringing “into the cell”) is the process of a cell ingesting material by enveloping it in a portion of its cell membrane, and then pinching off that portion of membrane (Figure 3.10). Once pinched off, the portion of membrane and its contents becomes an independent, intracellular vesicle. A vesicle is a membranous sac—a spherical and hollow organelle bounded by a lipid bilayer membrane. Endocytosis often brings materials into the cell that must to be broken down or digested. Phagocytosis (“cell eating”) is the endocytosis of large particles. Many immune cells engage in phagocytosis of invading pathogens. Like little Pac-men, their job is to patrol body tissues for unwanted matter, such as invading bacterial cells, phagocytize them, and digest them. In contrast to phagocytosis, pinocytosis (“cell drinking”) brings fluid containing dissolved substances into a cell through membrane vesicles. Figure 3.10 Three Forms of Endocytosis Endocytosis is a form of active transport in which a cell envelopes extracellular materials using its cell membrane. (a) In phagocytosis, which is relatively nonselective, the cell takes in a large particle. (b) In pinocytosis, the cell takes in small particles in fluid. (c) In contrast, receptor-mediated endocytosis is quite selective. When external receptors bind a specific ligand, the cell responds by endocytosing the ligand. Phagocytosis and pinocytosis take in large portions of extracellular material, and they are typically not highly selective in the substances they bring in. Cells regulate the endocytosis of specific substances via receptor-mediated endocytosis. Receptor-mediated endocytosis is endocytosis by a portion of the cell membrane that contains many receptors that are specific for a certain substance. Once the surface receptors have bound sufficient amounts of the specific substance (the receptor’s ligand), the cell will endocytose the part of the cell membrane containing the receptor-ligand complexes. Iron, a required component of hemoglobin, is endocytosed by red blood cells in this way. Iron is bound to a protein called transferrin in the blood. Specific transferrin receptors on red blood cell surfaces bind the iron-transferrin molecules, and the cell endocytoses the receptor-ligand complexes. In contrast with endocytosis, exocytosis (taking “out of the cell”) is the process of a cell exporting material using vesicular transport (Figure 3.11). Many cells manufacture substances that must be secreted, like a factory manufacturing a product for export. These substances are typically packaged into membrane-bound vesicles within the cell. When the vesicle membrane fuses with the cell membrane, the vesicle releases it contents into the interstitial fluid. The vesicle membrane then becomes part of the cell membrane. Cells of the stomach and pancreas produce and secrete digestive enzymes through exocytosis (Figure 3.12). Endocrine cells produce and secrete hormones that are sent throughout the body, and certain immune cells produce and secrete large amounts of histamine, a chemical important for immune responses. Figure 3.11 Exocytosis Exocytosis is much like endocytosis in reverse. Material destined for export is packaged into a vesicle inside the cell. The membrane of the vesicle fuses with the cell membrane, and the contents are released into the extracellular space. Figure 3.12 Pancreatic Cells' Enzyme Products The pancreatic acinar cells produce and secrete many enzymes that digest food. The tiny black granules in this electron micrograph are secretory vesicles filled with enzymes that will be exported from the cells via exocytosis. LM × 2900. (Micrograph provided by the Regents of University of Michigan Medical School © 2012) INTERACTIVE LINK View the University of Michigan WebScope to explore the tissue sample in greater detail. DISEASES OF THE... Cell: Cystic Fibrosis Cystic fibrosis (CF) affects approximately 30,000 people in the United States, with about 1,000 new cases reported each year. The genetic disease is most well known for its damage to the lungs, causing breathing difficulties and chronic lung infections, but it also affects the liver, pancreas, and intestines. Only about 50 years ago, the prognosis for children born with CF was very grim—a life expectancy rarely over 10 years. Today, with advances in medical treatment, many CF patients live into their 30s. The symptoms of CF result from a malfunctioning membrane ion channel called the cystic fibrosis transmembrane conductance regulator, or CFTR. In healthy people, the CFTR protein is an integral membrane protein that transports Cl– ions out of the cell. In a person who has CF, the gene for the CFTR is mutated, thus, the cell manufactures a defective channel protein that typically is not incorporated into the membrane, but is instead degraded by the cell. The CFTR requires ATP in order to function, making its Cl– transport a form of active transport. This characteristic puzzled researchers for a long time because the Cl– ions are actually flowing down their concentration gradient when transported out of cells. Active transport generally pumps ions against their concentration gradient, but the CFTR presents an exception to this rule. In normal lung tissue, the movement of Cl– out of the cell maintains a Cl–-rich, negatively charged environment immediately outside of the cell. This is particularly important in the epithelial lining of the respiratory system. Respiratory epithelial cells secrete mucus, which serves to trap dust, bacteria, and other debris. A cilium (plural = cilia) is one of the hair-like appendages found on certain cells. Cilia on the epithelial cells move the mucus and its trapped particles up the airways away from the lungs and toward the outside. In order to be effectively moved upward, the mucus cannot be too viscous; rather it must have a thin, watery consistency. The transport of Cl– and the maintenance of an electronegative environment outside of the cell attract positive ions such as Na+ to the extracellular space. The accumulation of both Cl– and Na+ ions in the extracellular space creates solute-rich mucus, which has a low concentration of water molecules. As a result, through osmosis, water moves from cells and extracellular matrix into the mucus, “thinning” it out. This is how, in a normal respiratory system, the mucus is kept sufficiently watered-down to be propelled out of the respiratory system. If the CFTR channel is absent, Cl– ions are not transported out of the cell in adequate numbers, thus preventing them from drawing positive ions. The absence of ions in the secreted mucus results in the lack of a normal water concentration gradient. Thus, there is no osmotic pressure pulling water into the mucus. The resulting mucus is thick and sticky, and the ciliated epithelia cannot effectively remove it from the respiratory system. Passageways in the lungs become blocked with mucus, along with the debris it carries. Bacterial infections occur more easily because bacterial cells are not effectively carried away from the lungs. The Cytoplasm and Cellular Organelles - Describe the structure and function of the cellular organelles associated with the endomembrane system, including the endoplasmic reticulum, Golgi apparatus, and lysosomes - Describe the structure and function of mitochondria and peroxisomes - Explain the three components of the cytoskeleton, including their composition and functions Now that you have learned that the cell membrane surrounds all cells, you can dive inside of a prototypical human cell to learn about its internal components and their functions. All living cells in multicellular organisms contain an internal cytoplasmic compartment, and a nucleus within the cytoplasm. Cytosol, the jelly-like substance within the cell, provides the fluid medium necessary for biochemical reactions. Eukaryotic cells, including all animal cells, also contain various cellular organelles. An organelle (“little organ”) is one of several different types of membrane-enclosed bodies in the cell, each performing a unique function. Just as the various bodily organs work together in harmony to perform all of a human’s functions, the many different cellular organelles work together to keep the cell healthy and performing all of its important functions. The organelles and cytosol, taken together, compose the cell’s cytoplasm. The nucleus is a cell’s central organelle, which contains the cell’s DNA (Figure 3.13). Figure 3.13 Prototypical Human Cell While this image is not indicative of any one particular human cell, it is a prototypical example of a cell containing the primary organelles and internal structures. Organelles of the Endomembrane System A set of three major organelles together form a system within the cell called the endomembrane system. These organelles work together to perform various cellular jobs, including the task of producing, packaging, and exporting certain cellular products. The organelles of the endomembrane system include the endoplasmic reticulum, Golgi apparatus, and vesicles. Endoplasmic Reticulum The endoplasmic reticulum (ER) is a system of channels that is continuous with the nuclear membrane (or “envelope”) covering the nucleus and composed of the same lipid bilayer material. The ER can be thought of as a series of winding thoroughfares similar to the waterway canals in Venice. The ER provides passages throughout much of the cell that function in transporting, synthesizing, and storing materials. The winding structure of the ER results in a large membranous surface area that supports its many functions (Figure 3.14). Figure 3.14 Endoplasmic Reticulum (ER) (a) The ER is a winding network of thin membranous sacs found in close association with the cell nucleus. The smooth and rough endoplasmic reticula are very different in appearance and function (source: mouse tissue). (b) Rough ER is studded with numerous ribosomes, which are sites of protein synthesis (source: mouse tissue). EM × 110,000. (c) Smooth ER synthesizes phospholipids, steroid hormones, regulates the concentration of cellular Ca++, metabolizes some carbohydrates, and breaks down certain toxins (source: mouse tissue). EM × 110,510. (Micrographs provided by the Regents of University of Michigan Medical School © 2012) Endoplasmic reticulum can exist in two forms: rough ER and smooth ER. These two types of ER perform some very different functions and can be found in very different amounts depending on the type of cell. Rough ER (RER) is so-called because its membrane is dotted with embedded granules—organelles called ribosomes, giving the RER a bumpy appearance. A ribosomeis an organelle that serves as the site of protein synthesis. It is composed of two ribosomal RNA subunits that wrap around mRNA to start the process of translation, followed by protein synthesis. Smooth ER (SER) lacks these ribosomes. One of the main functions of the smooth ER is in the synthesis of lipids. The smooth ER synthesizes phospholipids, the main component of biological membranes, as well as steroid hormones. For this reason, cells that produce large quantities of such hormones, such as those of the female ovaries and male testes, contain large amounts of smooth ER. In addition to lipid synthesis, the smooth ER also sequesters (i.e., stores) and regulates the concentration of cellular Ca++, a function extremely important in cells of the nervous system where Ca++ is the trigger for neurotransmitter release. The smooth ER additionally metabolizes some carbohydrates and performs a detoxification role, breaking down certain toxins. In contrast with the smooth ER, the primary job of the rough ER is the synthesis and modification of proteins destined for the cell membrane or for export from the cell. For this protein synthesis, many ribosomes attach to the ER (giving it the studded appearance of rough ER). Typically, a protein is synthesized within the ribosome and released inside the channel of the rough ER, where sugars can be added to it (by a process called glycosylation) before it is transported within a vesicle to the next stage in the packaging and shipping process: the Golgi apparatus. The Golgi Apparatus The Golgi apparatus is responsible for sorting, modifying, and shipping off the products that come from the rough ER, much like a post-office. The Golgi apparatus looks like stacked flattened discs, almost like stacks of oddly shaped pancakes. Like the ER, these discs are membranous. The Golgi apparatus has two distinct sides, each with a different role. One side of the apparatus receives products in vesicles. These products are sorted through the apparatus, and then they are released from the opposite side after being repackaged into new vesicles. If the product is to be exported from the cell, the vesicle migrates to the cell surface and fuses to the cell membrane, and the cargo is secreted (Figure 3.15). Figure 3.15 Golgi Apparatus (a) The Golgi apparatus manipulates products from the rough ER, and also produces new organelles called lysosomes. Proteins and other products of the ER are sent to the Golgi apparatus, which organizes, modifies, packages, and tags them. Some of these products are transported to other areas of the cell and some are exported from the cell through exocytosis. Enzymatic proteins are packaged as new lysosomes (or packaged and sent for fusion with existing lysosomes). (b) An electron micrograph of the Golgi apparatus. Lysosomes Some of the protein products packaged by the Golgi include digestive enzymes that are meant to remain inside the cell for use in breaking down certain materials. The enzyme-containing vesicles released by the Golgi may form new lysosomes, or fuse with existing, lysosomes. A lysosome is an organelle that contains enzymes that break down and digest unneeded cellular components, such as a damaged organelle. (A lysosome is similar to a wrecking crew that takes down old and unsound buildings in a neighborhood.) Autophagy (“self-eating”) is the process of a cell digesting its own structures. Lysosomes are also important for breaking down foreign material. For example, when certain immune defense cells (white blood cells) phagocytize bacteria, the bacterial cell is transported into a lysosome and digested by the enzymes inside. As one might imagine, such phagocytic defense cells contain large numbers of lysosomes. Under certain circumstances, lysosomes perform a more grand and dire function. In the case of damaged or unhealthy cells, lysosomes can be triggered to open up and release their digestive enzymes into the cytoplasm of the cell, killing the cell. This “self-destruct” mechanism is called autolysis, and makes the process of cell death controlled (a mechanism called “apoptosis”). INTERACTIVE LINK Watch this video to learn about the endomembrane system, which includes the rough and smooth ER and the Golgi body as well as lysosomes and vesicles. What is the primary role of the endomembrane system? Organelles for Energy Production and Detoxification In addition to the jobs performed by the endomembrane system, the cell has many other important functions. Just as you must consume nutrients to provide yourself with energy, so must each of your cells take in nutrients, some of which convert to chemical energy that can be used to power biochemical reactions. Another important function of the cell is detoxification. Humans take in all sorts of toxins from the environment and also produce harmful chemicals as byproducts of cellular processes. Cells called hepatocytes in the liver detoxify many of these toxins. Mitochondria A mitochondrion (plural = mitochondria) is a membranous, bean-shaped organelle that is the “energy transformer” of the cell. Mitochondria consist of an outer lipid bilayer membrane as well as an additional inner lipid bilayer membrane (Figure 3.16). The inner membrane is highly folded into winding structures with a great deal of surface area, called cristae. It is along this inner membrane that a series of proteins, enzymes, and other molecules perform the biochemical reactions of cellular respiration. These reactions convert energy stored in nutrient molecules (such as glucose) into adenosine triphosphate (ATP), which provides usable cellular energy to the cell. Cells use ATP constantly, and so the mitochondria are constantly at work. Oxygen molecules are required during cellular respiration, which is why you must constantly breathe it in. One of the organ systems in the body that uses huge amounts of ATP is the muscular system because ATP is required to sustain muscle contraction. As a result, muscle cells are packed full of mitochondria. Nerve cells also need large quantities of ATP to run their sodium-potassium pumps. Therefore, an individual neuron will be loaded with over a thousand mitochondria. On the other hand, a bone cell, which is not nearly as metabolically-active, might only have a couple hundred mitochondria. Figure 3.16 Mitochondrion The mitochondria are the energy-conversion factories of the cell. (a) A mitochondrion is composed of two separate lipid bilayer membranes. Along the inner membrane are various molecules that work together to produce ATP, the cell’s major energy currency. (b) An electron micrograph of mitochondria. EM × 236,000. (Micrograph provided by the Regents of University of Michigan Medical School © 2012) Peroxisomes Like lysosomes, a peroxisome is a membrane-bound cellular organelle that contains mostly enzymes (Figure 3.17). Peroxisomes perform a couple of different functions, including lipid metabolism and chemical detoxification. In contrast to the digestive enzymes found in lysosomes, the enzymes within peroxisomes serve to transfer hydrogen atoms from various molecules to oxygen, producing hydrogen peroxide (H2O2). In this way, peroxisomes neutralize poisons such as alcohol. In order to appreciate the importance of peroxisomes, it is necessary to understand the concept of reactive oxygen species. Figure 3.17 Peroxisome Peroxisomes are membrane-bound organelles that contain an abundance of enzymes for detoxifying harmful substances and lipid metabolism. Reactive oxygen species (ROS) such as peroxides and free radicals are the highly reactive products of many normal cellular processes, including the mitochondrial reactions that produce ATP and oxygen metabolism. Examples of ROS include the hydroxyl radical OH, H2O2, and superoxide (O−2O2− Peroxisomes, on the other hand, oversee reactions that neutralize free radicals. Peroxisomes produce large amounts of the toxic H2O2 in the process, but peroxisomes contain enzymes that convert H2O2 into water and oxygen. These byproducts are safely released into the cytoplasm. Like miniature sewage treatment plants, peroxisomes neutralize harmful toxins so that they do not wreak havoc in the cells. The liver is the organ primarily responsible for detoxifying the blood before it travels throughout the body, and liver cells contain an exceptionally high number of peroxisomes. Defense mechanisms such as detoxification within the peroxisome and certain cellular antioxidants serve to neutralize many of these molecules. Some vitamins and other substances, found primarily in fruits and vegetables, have antioxidant properties. Antioxidants work by being oxidized themselves, halting the destructive reaction cascades initiated by the free radicals. Sometimes though, ROS accumulate beyond the capacity of such defenses. Oxidative stress is the term used to describe damage to cellular components caused by ROS. Due to their characteristic unpaired electrons, ROS can set off chain reactions where they remove electrons from other molecules, which then become oxidized and reactive, and do the same to other molecules, causing a chain reaction. ROS can cause permanent damage to cellular lipids, proteins, carbohydrates, and nucleic acids. Damaged DNA can lead to genetic mutations and even cancer. A mutation is a change in the nucleotide sequence in a gene within a cell’s DNA, potentially altering the protein coded by that gene. Other diseases believed to be triggered or exacerbated by ROS include Alzheimer’s disease, cardiovascular diseases, diabetes, Parkinson’s disease, arthritis, Huntington’s disease, and schizophrenia, among many others. It is noteworthy that these diseases are largely age-related. Many scientists believe that oxidative stress is a major contributor to the aging process. AGING AND THE... Cell: The Free Radical Theory The free radical theory on aging was originally proposed in the 1950s, and still remains under debate. Generally speaking, the free radical theory of aging suggests that accumulated cellular damage from oxidative stress contributes to the physiological and anatomical effects of aging. There are two significantly different versions of this theory: one states that the aging process itself is a result of oxidative damage, and the other states that oxidative damage causes age-related disease and disorders. The latter version of the theory is more widely accepted than the former. However, many lines of evidence suggest that oxidative damage does contribute to the aging process. Research has shown that reducing oxidative damage can result in a longer lifespan in certain organisms such as yeast, worms, and fruit flies. Conversely, increasing oxidative damage can shorten the lifespan of mice and worms. Interestingly, a manipulation called calorie-restriction (moderately restricting the caloric intake) has been shown to increase life span in some laboratory animals. It is believed that this increase is at least in part due to a reduction of oxidative stress. However, a long-term study of primates with calorie-restriction showed no increase in their lifespan. A great deal of additional research will be required to better understand the link between reactive oxygen species and aging. The Cytoskeleton Much like the bony skeleton structurally supports the human body, the cytoskeleton helps the cells to maintain their structural integrity. The cytoskeleton is a group of fibrous proteins that provide structural support for cells, but this is only one of the functions of the cytoskeleton. Cytoskeletal components are also critical for cell motility, cell reproduction, and transportation of substances within the cell. The cytoskeleton forms a complex thread-like network throughout the cell consisting of three different kinds of protein-based filaments: microfilaments, intermediate filaments, and microtubules (Figure 3.18). The thickest of the three is the microtubule, a structural filament composed of subunits of a protein called tubulin. Microtubules maintain cell shape and structure, help resist compression of the cell, and play a role in positioning the organelles within the cell. Microtubules also make up two types of cellular appendages important for motion: cilia and flagella. Cilia are found on many cells of the body, including the epithelial cells that line the airways of the respiratory system. Cilia move rhythmically; they beat constantly, moving waste materials such as dust, mucus, and bacteria upward through the airways, away from the lungs and toward the mouth. Beating cilia on cells in the female fallopian tubes move egg cells from the ovary towards the uterus. A flagellum (plural = flagella) is an appendage larger than a cilium and specialized for cell locomotion. The only flagellated cell in humans is the sperm cell that must propel itself towards female egg cells. Figure 3.18 The Three Components of the Cytoskeleton The cytoskeleton consists of (a) microtubules, (b) microfilaments, and (c) intermediate filaments. The cytoskeleton plays an important role in maintaining cell shape and structure, promoting cellular movement, and aiding cell division. A very important function of microtubules is to set the paths (somewhat like railroad tracks) along which the genetic material can be pulled (a process requiring ATP) during cell division, so that each new daughter cell receives the appropriate set of chromosomes. Two short, identical microtubule structures called centrioles are found near the nucleus of cells. A centriole can serve as the cellular origin point for microtubules extending outward as cilia or flagella or can assist with the separation of DNA during cell division. Microtubules grow out from the centrioles by adding more tubulin subunits, like adding additional links to a chain. In contrast with microtubules, the microfilament is a thinner type of cytoskeletal filament (see Figure 3.18b). Actin, a protein that forms chains, is the primary component of these microfilaments. Actin fibers, twisted chains of actin filaments, constitute a large component of muscle tissue and, along with the protein myosin, are responsible for muscle contraction. Like microtubules, actin filaments are long chains of single subunits (called actin subunits). In muscle cells, these long actin strands, called thin filaments, are “pulled” by thick filaments of the myosin protein to contract the cell. Actin also has an important role during cell division. When a cell is about to split in half during cell division, actin filaments work with myosin to create a cleavage furrow that eventually splits the cell down the middle, forming two new cells from the original cell. The final cytoskeletal filament is the intermediate filament. As its name would suggest, an intermediate filament is a filament intermediate in thickness between the microtubules and microfilaments (see Figure 3.18c). Intermediate filaments are made up of long fibrous subunits of a protein called keratin that are wound together like the threads that compose a rope. Intermediate filaments, in concert with the microtubules, are important for maintaining cell shape and structure. Unlike the microtubules, which resist compression, intermediate filaments resist tension—the forces that pull apart cells. There are many cases in which cells are prone to tension, such as when epithelial cells of the skin are compressed, tugging them in different directions. Intermediate filaments help anchor organelles together within a cell and also link cells to other cells by forming special cell-to-cell junctions. The Nucleus and DNA Replication - Describe the structure and features of the nuclear membrane - List the contents of the nucleus - Explain the organization of the DNA molecule within the nucleus - Describe the process of DNA replication The nucleus is the largest and most prominent of a cell’s organelles (Figure 3.19). The nucleus is generally considered the control center of the cell because it stores all of the genetic instructions for manufacturing proteins. Interestingly, some cells in the body, such as muscle cells, contain more than one nucleus (Figure 3.20), which is known as multinucleated. Other cells, such as mammalian red blood cells (RBCs), do not contain nuclei at all. RBCs eject their nuclei as they mature, making space for the large numbers of hemoglobin molecules that carry oxygen throughout the body (Figure 3.21). Without nuclei, the life span of RBCs is short, and so the body must produce new ones constantly. Figure 3.19 The Nucleus The nucleus is the control center of the cell. The nucleus of living cells contains the genetic material that determines the entire structure and function of that cell. Figure 3.20 Multinucleate Muscle Cell Unlike cardiac muscle cells and smooth muscle cells, which have a single nucleus, a skeletal muscle cell contains many nuclei, and is referred to as “multinucleated.” These muscle cells are long and fibrous (often referred to as muscle fibers). During development, many smaller cells fuse to form a mature muscle fiber. The nuclei of the fused cells are conserved in the mature cell, thus imparting a multinucleate characteristic to mature muscle cells. LM × 104.3. (Micrograph provided by the Regents of University of Michigan Medical School © 2012) INTERACTIVE LINK View the University of Michigan WebScope to explore the tissue sample in greater detail. Figure 3.21 Red Blood Cell Extruding Its Nucleus Mature red blood cells lack a nucleus. As they mature, erythroblasts extrude their nucleus, making room for more hemoglobin. The two panels here show an erythroblast before and after ejecting its nucleus, respectively. (credit: modification of micrograph provided by the Regents of University of Michigan Medical School © 2012) INTERACTIVE LINK View the University of Michigan WebScope to explore the tissue sample in greater detail. Inside the nucleus lies the blueprint that dictates everything a cell will do and all of the products it will make. This information is stored within DNA. The nucleus sends “commands” to the cell via molecular messengers that translate the information from DNA. Each cell in your body (with the exception of germ cells) contains the complete set of your DNA. When a cell divides, the DNA must be duplicated so that the each new cell receives a full complement of DNA. The following section will explore the structure of the nucleus and its contents, as well as the process of DNA replication. Organization of the Nucleus and Its DNA Like most other cellular organelles, the nucleus is surrounded by a membrane called the nuclear envelope. This membranous covering consists of two adjacent lipid bilayers with a thin fluid space in between them. Spanning these two bilayers are nuclear pores. A nuclear pore is a tiny passageway for the passage of proteins, RNA, and solutes between the nucleus and the cytoplasm. Proteins called pore complexes lining the nuclear pores regulate the passage of materials into and out of the nucleus. Inside the nuclear envelope is a gel-like nucleoplasm with solutes that include the building blocks of nucleic acids. There also can be a dark-staining mass often visible under a simple light microscope, called a nucleolus (plural = nucleoli). The nucleolus is a region of the nucleus that is responsible for manufacturing the RNA necessary for construction of ribosomes. Once synthesized, newly made ribosomal subunits exit the cell’s nucleus through the nuclear pores. The genetic instructions that are used to build and maintain an organism are arranged in an orderly manner in strands of DNA. Within the nucleus are threads of chromatin composed of DNA and associated proteins (Figure 3.22). Along the chromatin threads, the DNA is wrapped around a set of histone proteins. A nucleosome is a single, wrapped DNA-histone complex. Multiple nucleosomes along the entire molecule of DNA appear like a beaded necklace, in which the string is the DNA and the beads are the associated histones. When a cell is in the process of division, the chromatin condenses into chromosomes, so that the DNA can be safely transported to the “daughter cells.” The chromosome is composed of DNA and proteins; it is the condensed form of chromatin. It is estimated that humans have almost 22,000 genes distributed on 46 chromosomes. Figure 3.22 DNA Macrostructure Strands of DNA are wrapped around supporting histones. These proteins are increasingly bundled and condensed into chromatin, which is packed tightly into chromosomes when the cell is ready to divide. DNA Replication In order for an organism to grow, develop, and maintain its health, cells must reproduce themselves by dividing to produce two new daughter cells, each with the full complement of DNA as found in the original cell. Billions of new cells are produced in an adult human every day. Only very few cell types in the body do not divide, including nerve cells, skeletal muscle fibers, and cardiac muscle cells. The division time of different cell types varies. Epithelial cells of the skin and gastrointestinal lining, for instance, divide very frequently to replace those that are constantly being rubbed off of the surface by friction. A DNA molecule is made of two strands that “complement” each other in the sense that the molecules that compose the strands fit together and bind to each other, creating a double-stranded molecule that looks much like a long, twisted ladder. Each side rail of the DNA ladder is composed of alternating sugar and phosphate groups (Figure 3.23). The two sides of the ladder are not identical, but are complementary. These two backbones are bonded to each other across pairs of protruding bases, each bonded pair forming one “rung,” or cross member. The four DNA bases are adenine (A), thymine (T), cytosine (C), and guanine (G). Because of their shape and charge, the two bases that compose a pair always bond together. Adenine always binds with thymine, and cytosine always binds with guanine. The particular sequence of bases along the DNA molecule determines the genetic code. Therefore, if the two complementary strands of DNA were pulled apart, you could infer the order of the bases in one strand from the bases in the other, complementary strand. For example, if one strand has a region with the sequence AGTGCCT, then the sequence of the complementary strand would be TCACGGA. Figure 3.23 Molecular Structure of DNA The DNA double helix is composed of two complementary strands. The strands are bonded together via their nitrogenous base pairs using hydrogen bonds. DNA replication is the copying of DNA that occurs before cell division can take place. After a great deal of debate and experimentation, the general method of DNA replication was deduced in 1958 by two scientists in California, Matthew Meselson and Franklin Stahl. This method is illustrated in Figure 3.24 and described below. Figure 3.24 DNA Replication DNA replication faithfully duplicates the entire genome of the cell. During DNA replication, a number of different enzymes work together to pull apart the two strands so each strand can be used as a template to synthesize new complementary strands. The two new daughter DNA molecules each contain one pre-existing strand and one newly synthesized strand. Thus, DNA replication is said to be “semiconservative.” Stage 1: Initiation. The two complementary strands are separated, much like unzipping a zipper. Special enzymes, including helicase, untwist and separate the two strands of DNA. Stage 2: Elongation. Each strand becomes a template along which a new complementary strand is built. DNA polymerasebrings in the correct bases to complement the template strand, synthesizing a new strand base by base. A DNA polymerase is an enzyme that adds free nucleotides to the end of a chain of DNA, making a new double strand. This growing strand continues to be built until it has fully complemented the template strand. Stage 3: Termination. Once the two original strands are bound to their own, finished, complementary strands, DNA replication is stopped and the two new identical DNA molecules are complete. Each new DNA molecule contains one strand from the original molecule and one newly synthesized strand. The term for this mode of replication is “semiconservative,” because half of the original DNA molecule is conserved in each new DNA molecule. This process continues until the cell’s entire genome, the entire complement of an organism’s DNA, is replicated. As you might imagine, it is very important that DNA replication take place precisely so that new cells in the body contain the exact same genetic material as their parent cells. Mistakes made during DNA replication, such as the accidental addition of an inappropriate nucleotide, have the potential to render a gene dysfunctional or useless. Fortunately, there are mechanisms in place to minimize such mistakes. A DNA proofreading process enlists the help of special enzymes that scan the newly synthesized molecule for mistakes and corrects them. Once the process of DNA replication is complete, the cell is ready to divide. You will explore the process of cell division later in the chapter. INTERACTIVE LINK Watch this video to learn about DNA replication. DNA replication proceeds simultaneously at several sites on the same molecule. What separates the base pair at the start of DNA replication? Protein Synthesis - Explain how the genetic code stored within DNA determines the protein that will form - Describe the process of transcription - Describe the process of translation - Discuss the function of ribosomes It was mentioned earlier that DNA provides a “blueprint” for the cell structure and physiology. This refers to the fact that DNA contains the information necessary for the cell to build one very important type of molecule: the protein. Most structural components of the cell are made up, at least in part, by proteins and virtually all the functions that a cell carries out are completed with the help of proteins. One of the most important classes of proteins is enzymes, which help speed up necessary biochemical reactions that take place inside the cell. Some of these critical biochemical reactions include building larger molecules from smaller components (such as occurs during DNA replication or synthesis of microtubules) and breaking down larger molecules into smaller components (such as when harvesting chemical energy from nutrient molecules). Whatever the cellular process may be, it is almost sure to involve proteins. Just as the cell’s genome describes its full complement of DNA, a cell’s proteome is its full complement of proteins. Protein synthesis begins with genes. A gene is a functional segment of DNA that provides the genetic information necessary to build a protein. Each particular gene provides the code necessary to construct a particular protein. Gene expression, which transforms the information coded in a gene to a final gene product, ultimately dictates the structure and function of a cell by determining which proteins are made. The interpretation of genes works in the following way. Recall that proteins are polymers, or chains, of many amino acid building blocks. The sequence of bases in a gene (that is, its sequence of A, T, C, G nucleotides) translates to an amino acid sequence. A triplet is a section of three DNA bases in a row that codes for a specific amino acid. Similar to the way in which the three-letter code d-o-g signals the image of a dog, the three-letter DNA base code signals the use of a particular amino acid. For example, the DNA triplet CAC (cytosine, adenine, and cytosine) specifies the amino acid valine. Therefore, a gene, which is composed of multiple triplets in a unique sequence, provides the code to build an entire protein, with multiple amino acids in the proper sequence (Figure 3.25). The mechanism by which cells turn the DNA code into a protein product is a two-step process, with an RNA molecule as the intermediate. Figure 3.25 The Genetic Code DNA holds all of the genetic information necessary to build a cell’s proteins. The nucleotide sequence of a gene is ultimately translated into an amino acid sequence of the gene’s corresponding protein. From DNA to RNA: Transcription DNA is housed within the nucleus, and protein synthesis takes place in the cytoplasm, thus there must be some sort of intermediate messenger that leaves the nucleus and manages protein synthesis. This intermediate messenger is messenger RNA (mRNA), a single-stranded nucleic acid that carries a copy of the genetic code for a single gene out of the nucleus and into the cytoplasm where it is used to produce proteins. There are several different types of RNA, each having different functions in the cell. The structure of RNA is similar to DNA with a few small exceptions. For one thing, unlike DNA, most types of RNA, including mRNA, are single-stranded and contain no complementary strand. Second, the ribose sugar in RNA contains an additional oxygen atom compared with DNA. Finally, instead of the base thymine, RNA contains the base uracil. This means that adenine will always pair up with uracil during the protein synthesis process. Gene expression begins with the process called transcription, which is the synthesis of a strand of mRNA that is complementary to the gene of interest. This process is called transcription because the mRNA is like a transcript, or copy, of the gene’s DNA code. Transcription begins in a fashion somewhat like DNA replication, in that a region of DNA unwinds and the two strands separate, however, only that small portion of the DNA will be split apart. The triplets within the gene on this section of the DNA molecule are used as the template to transcribe the complementary strand of RNA (Figure 3.26). A codonis a three-base sequence of mRNA, so-called because they directly encode amino acids. Like DNA replication, there are three stages to transcription: initiation, elongation, and termination. Figure 3.26 Transcription: from DNA to mRNA In the first of the two stages of making protein from DNA, a gene on the DNA molecule is transcribed into a complementary mRNA molecule. Stage 1: Initiation. A region at the beginning of the gene called a promoter—a particular sequence of nucleotides—triggers the start of transcription. Stage 2: Elongation. Transcription starts when RNA polymerase unwinds the DNA segment. One strand, referred to as the coding strand, becomes the template with the genes to be coded. The polymerase then aligns the correct nucleic acid (A, C, G, or U) with its complementary base on the coding strand of DNA. RNA polymerase is an enzyme that adds new nucleotides to a growing strand of RNA. This process builds a strand of mRNA. Stage 3: Termination. When the polymerase has reached the end of the gene, one of three specific triplets (UAA, UAG, or UGA) codes a “stop” signal, which triggers the enzymes to terminate transcription and release the mRNA transcript. Before the mRNA molecule leaves the nucleus and proceeds to protein synthesis, it is modified in a number of ways. For this reason, it is often called a pre-mRNA at this stage. For example, your DNA, and thus complementary mRNA, contains long regions called non-coding regions that do not code for amino acids. Their function is still a mystery, but the process called splicing removes these non-coding regions from the pre-mRNA transcript (Figure 3.27). A spliceosome—a structure composed of various proteins and other molecules—attaches to the mRNA and “splices” or cuts out the non-coding regions. The removed segment of the transcript is called an intron. The remaining exons are pasted together. An exon is a segment of RNA that remains after splicing. Interestingly, some introns that are removed from mRNA are not always non-coding. When different coding regions of mRNA are spliced out, different variations of the protein will eventually result, with differences in structure and function. This process results in a much larger variety of possible proteins and protein functions. When the mRNA transcript is ready, it travels out of the nucleus and into the cytoplasm. Figure 3.27 Splicing DNA In the nucleus, a structure called a spliceosome cuts out introns (noncoding regions) within a pre-mRNA transcript and reconnects the exons. From RNA to Protein: Translation Like translating a book from one language into another, the codons on a strand of mRNA must be translated into the amino acid alphabet of proteins. Translation is the process of synthesizing a chain of amino acids called a polypeptide. Translation requires two major aids: first, a “translator,” the molecule that will conduct the translation, and second, a substrate on which the mRNA strand is translated into a new protein, like the translator’s “desk.” Both of these requirements are fulfilled by other types of RNA. The substrate on which translation takes place is the ribosome. Remember that many of a cell’s ribosomes are found associated with the rough ER, and carry out the synthesis of proteins destined for the Golgi apparatus. Ribosomal RNA (rRNA) is a type of RNA that, together with proteins, composes the structure of the ribosome. Ribosomes exist in the cytoplasm as two distinct components, a small and a large subunit. When an mRNA molecule is ready to be translated, the two subunits come together and attach to the mRNA. The ribosome provides a substrate for translation, bringing together and aligning the mRNA molecule with the molecular “translators” that must decipher its code. The other major requirement for protein synthesis is the translator molecules that physically “read” the mRNA codons. Transfer RNA (tRNA) is a type of RNA that ferries the appropriate corresponding amino acids to the ribosome, and attaches each new amino acid to the last, building the polypeptide chain one-by-one. Thus tRNA transfers specific amino acids from the cytoplasm to a growing polypeptide. The tRNA molecules must be able to recognize the codons on mRNA and match them with the correct amino acid. The tRNA is modified for this function. On one end of its structure is a binding site for a specific amino acid. On the other end is a base sequence that matches the codon specifying its particular amino acid. This sequence of three bases on the tRNA molecule is called an anticodon. For example, a tRNA responsible for shuttling the amino acid glycine contains a binding site for glycine on one end. On the other end it contains an anticodon that complements the glycine codon (GGA is a codon for glycine, and so the tRNAs anticodon would read CCU). Equipped with its particular cargo and matching anticodon, a tRNA molecule can read its recognized mRNA codon and bring the corresponding amino acid to the growing chain (Figure 3.28). Figure 3.28 Translation from RNA to ProteinDuring translation, the mRNA transcript is “read” by a functional complex consisting of the ribosome and tRNA molecules. tRNAs bring the appropriate amino acids in sequence to the growing polypeptide chain by matching their anti-codons with codons on the mRNA strand. Much like the processes of DNA replication and transcription, translation consists of three main stages: initiation, elongation, and termination. Initiation takes place with the binding of a ribosome to an mRNA transcript. The elongation stage involves the recognition of a tRNA anticodon with the next mRNA codon in the sequence. Once the anticodon and codon sequences are bound (remember, they are complementary base pairs), the tRNA presents its amino acid cargo and the growing polypeptide strand is attached to this next amino acid. This attachment takes place with the assistance of various enzymes and requires energy. The tRNA molecule then releases the mRNA strand, the mRNA strand shifts one codon over in the ribosome, and the next appropriate tRNA arrives with its matching anticodon. This process continues until the final codon on the mRNA is reached which provides a “stop” message that signals termination of translation and triggers the release of the complete, newly synthesized protein. Thus, a gene within the DNA molecule is transcribed into mRNA, which is then translated into a protein product (Figure 3.29). Figure 3.29 From DNA to Protein: Transcription through Translation Transcription within the cell nucleus produces an mRNA molecule, which is modified and then sent into the cytoplasm for translation. The transcript is decoded into a protein with the help of a ribosome and tRNA molecules. Commonly, an mRNA transcription will be translated simultaneously by several adjacent ribosomes. This increases the efficiency of protein synthesis. A single ribosome might translate an mRNA molecule in approximately one minute; so multiple ribosomes aboard a single transcript could produce multiple times the number of the same protein in the same minute. A polyribosome is a string of ribosomes translating a single mRNA strand. INTERACTIVE LINK Watch this video to learn about ribosomes. The ribosome binds to the mRNA molecule to start translation of its code into a protein. What happens to the small and large ribosomal subunits at the end of translation? Cell Growth and Division - Describe the stages of the cell cycle - Discuss how the cell cycle is regulated - Describe the implications of losing control over the cell cycle - Describe the stages of mitosis and cytokinesis, in order So far in this chapter, you have read numerous times of the importance and prevalence of cell division. While there are a few cells in the body that do not undergo cell division (such as gametes, red blood cells, most neurons, and some muscle cells), most somatic cells divide regularly. A somatic cell is a general term for a body cell, and all human cells, except for the cells that produce eggs and sperm (which are referred to as germ cells), are somatic cells. Somatic cells contain two copies of each of their chromosomes (one copy received from each parent). A homologous pair of chromosomes is the two copies of a single chromosome found in each somatic cell. The human is a diploid organism, having 23 homologous pairs of chromosomes in each of the somatic cells. The condition of having pairs of chromosomes is known as diploidy. Cells in the body replace themselves over the lifetime of a person. For example, the cells lining the gastrointestinal tract must be frequently replaced when constantly “worn off” by the movement of food through the gut. But what triggers a cell to divide, and how does it prepare for and complete cell division? The cell cycle is the sequence of events in the life of the cell from the moment it is created at the end of a previous cycle of cell division until it then divides itself, generating two new cells. The Cell Cycle One “turn” or cycle of the cell cycle consists of two general phases: interphase, followed by mitosis and cytokinesis. Interphase is the period of the cell cycle during which the cell is not dividing. The majority of cells are in interphase most of the time. Mitosis is the division of genetic material, during which the cell nucleus breaks down and two new, fully functional, nuclei are formed. Cytokinesis divides the cytoplasm into two distinctive cells. Interphase A cell grows and carries out all normal metabolic functions and processes in a period called G1 (Figure 3.30). G1 phase (gap 1 phase) is the first gap, or growth phase in the cell cycle. For cells that will divide again, G1 is followed by replication of the DNA, during the S phase. The S phase (synthesis phase) is period during which a cell replicates its DNA. Figure 3.30 Cell Cycle The two major phases of the cell cycle include mitosis (cell division), and interphase, when the cell grows and performs all of its normal functions. Interphase is further subdivided into G1, S, and G2 phases. After the synthesis phase, the cell proceeds through the G2 phase. The G2 phase is a second gap phase, during which the cell continues to grow and makes the necessary preparations for mitosis. Between G1, S, and G2 phases, cells will vary the most in their duration of the G1 phase. It is here that a cell might spend a couple of hours, or many days. The S phase typically lasts between 8-10 hours and the G2 phase approximately 5 hours. In contrast to these phases, the G0 phase is a resting phase of the cell cycle. Cells that have temporarily stopped dividing and are resting (a common condition) and cells that have permanently ceased dividing (like nerve cells) are said to be in G0. The Structure of Chromosomes Billions of cells in the human body divide every day. During the synthesis phase (S, for DNA synthesis) of interphase, the amount of DNA within the cell precisely doubles. Therefore, after DNA replication but before cell division, each cell actually contains two copies of each chromosome. Each copy of the chromosome is referred to as a sister chromatid and is physically bound to the other copy. The centromere is the structure that attaches one sister chromatid to another. Because a human cell has 46 chromosomes, during this phase, there are 92 chromatids (46 × 2) in the cell. Make sure not to confuse the concept of a pair of chromatids (one chromosome and its exact copy attached during mitosis) and a homologous pair of chromosomes (two paired chromosomes which were inherited separately, one from each parent) (Figure 3.31). Figure 3.31 A Homologous Pair of Chromosomes with their Attached Sister Chromatids The red and blue colors correspond to a homologous pair of chromosomes. Each member of the pair was separately inherited from one parent. Each chromosome in the homologous pair is also bound to an identical sister chromatid, which is produced by DNA replication, and results in the familiar “X” shape. Mitosis and Cytokinesis The mitotic phase of the cell typically takes between 1 and 2 hours. During this phase, a cell undergoes two major processes. First, it completes mitosis, during which the contents of the nucleus are equitably pulled apart and distributed between its two halves. Cytokinesis then occurs, dividing the cytoplasm and cell body into two new cells. Mitosis is divided into four major stages that take place after interphase (Figure 3.32) and in the following order: prophase, metaphase, anaphase, and telophase. The process is then followed by cytokinesis. Figure 3.32 Cell Division: Mitosis Followed by Cytokinesis The stages of cell division oversee the separation of identical genetic material into two new nuclei, followed by the division of the cytoplasm. Prophase is the first phase of mitosis, during which the loosely packed chromatin coils and condenses into visible chromosomes. During prophase, each chromosome becomes visible with its identical partner attached, forming the familiar X-shape of sister chromatids. The nucleolus disappears early during this phase, and the nuclear envelope also disintegrates. A major occurrence during prophase concerns a very important structure that contains the origin site for microtubule growth. Recall the cellular structures called centrioles that serve as origin points from which microtubules extend. These tiny structures also play a very important role during mitosis. A centrosome is a pair of centrioles together. The cell contains two centrosomes side-by-side, which begin to move apart during prophase. As the centrosomes migrate to two different sides of the cell, microtubules begin to extend from each like long fingers from two hands extending toward each other. The mitotic spindle is the structure composed of the centrosomes and their emerging microtubules. Near the end of prophase there is an invasion of the nuclear area by microtubules from the mitotic spindle. The nuclear membrane has disintegrated, and the microtubules attach themselves to the centromeres that adjoin pairs of sister chromatids. The kinetochore is a protein structure on the centromere that is the point of attachment between the mitotic spindle and the sister chromatids. This stage is referred to as late prophase or “prometaphase” to indicate the transition between prophase and metaphase. Metaphase is the second stage of mitosis. During this stage, the sister chromatids, with their attached microtubules, line up along a linear plane in the middle of the cell. A metaphase plate forms between the centrosomes that are now located at either end of the cell. The metaphase plate is the name for the plane through the center of the spindle on which the sister chromatids are positioned. The microtubules are now poised to pull apart the sister chromatids and bring one from each pair to each side of the cell. Anaphase is the third stage of mitosis. Anaphase takes place over a few minutes, when the pairs of sister chromatids are separated from one another, forming individual chromosomes once again. These chromosomes are pulled to opposite ends of the cell by their kinetochores, as the microtubules shorten. Each end of the cell receives one partner from each pair of sister chromatids, ensuring that the two new daughter cells will contain identical genetic material. Telophase is the final stage of mitosis. Telophase is characterized by the formation of two new daughter nuclei at either end of the dividing cell. These newly formed nuclei surround the genetic material, which uncoils such that the chromosomes return to loosely packed chromatin. Nucleoli also reappear within the new nuclei, and the mitotic spindle breaks apart, each new cell receiving its own complement of DNA, organelles, membranes, and centrioles. At this point, the cell is already beginning to split in half as cytokinesis begins. The cleavage furrow is a contractile band made up of microfilaments that forms around the midline of the cell during cytokinesis. (Recall that microfilaments consist of actin.) This contractile band squeezes the two cells apart until they finally separate. Two new cells are now formed. One of these cells (the “stem cell”) enters its own cell cycle; able to grow and divide again at some future time. The other cell transforms into the functional cell of the tissue, typically replacing an “old” cell there. Imagine a cell that completed mitosis but never underwent cytokinesis. In some cases, a cell may divide its genetic material and grow in size, but fail to undergo cytokinesis. This results in larger cells with more than one nucleus. Usually this is an unwanted aberration and can be a sign of cancerous cells. Cell Cycle Control A very elaborate and precise system of regulation controls direct the way cells proceed from one phase to the next in the cell cycle and begin mitosis. The control system involves molecules within the cell as well as external triggers. These internal and external control triggers provide “stop” and “advance” signals for the cell. Precise regulation of the cell cycle is critical for maintaining the health of an organism, and loss of cell cycle control can lead to cancer. Mechanisms of Cell Cycle Control As the cell proceeds through its cycle, each phase involves certain processes that must be completed before the cell should advance to the next phase. A checkpoint is a point in the cell cycle at which the cycle can be signaled to move forward or stopped. At each of these checkpoints, different varieties of molecules provide the stop or go signals, depending on certain conditions within the cell. A cyclin is one of the primary classes of cell cycle control molecules (Figure 3.33). A cyclin-dependent kinase (CDK) is one of a group of molecules that work together with cyclins to determine progression past cell checkpoints. By interacting with many additional molecules, these triggers push the cell cycle forward unless prevented from doing so by “stop” signals, if for some reason the cell is not ready. At the G1 checkpoint, the cell must be ready for DNA synthesis to occur. At the G2 checkpoint the cell must be fully prepared for mitosis. Even during mitosis, a crucial stop and go checkpoint in metaphase ensures that the cell is fully prepared to complete cell division. The metaphase checkpoint ensures that all sister chromatids are properly attached to their respective microtubules and lined up at the metaphase plate before the signal is given to separate them during anaphase. Figure 3.33 Control of the Cell Cycle Cells proceed through the cell cycle under the control of a variety of molecules, such as cyclins and cyclin-dependent kinases. These control molecules determine whether or not the cell is prepared to move into the following stage. The Cell Cycle Out of Control: Implications Most people understand that cancer or tumors are caused by abnormal cells that multiply continuously. If the abnormal cells continue to divide unstopped, they can damage the tissues around them, spread to other parts of the body, and eventually result in death. In healthy cells, the tight regulation mechanisms of the cell cycle prevent this from happening, while failures of cell cycle control can cause unwanted and excessive cell division. Failures of control may be caused by inherited genetic abnormalities that compromise the function of certain “stop” and “go” signals. Environmental insult that damages DNA can also cause dysfunction in those signals. Often, a combination of both genetic predisposition and environmental factors lead to cancer. The process of a cell escaping its normal control system and becoming cancerous may actually happen throughout the body quite frequently. Fortunately, certain cells of the immune system are capable of recognizing cells that have become cancerous and destroying them. However, in certain cases the cancerous cells remain undetected and continue to proliferate. If the resulting tumor does not pose a threat to surrounding tissues, it is said to be benign and can usually be easily removed. If capable of damage, the tumor is considered malignant and the patient is diagnosed with cancer. HOMEOSTATIC IMBALANCES Cancer Arises from Homeostatic Imbalances Cancer is an extremely complex condition, capable of arising from a wide variety of genetic and environmental causes. Typically, mutations or aberrations in a cell’s DNA that compromise normal cell cycle control systems lead to cancerous tumors. Cell cycle control is an example of a homeostatic mechanism that maintains proper cell function and health. While progressing through the phases of the cell cycle, a large variety of intracellular molecules provide stop and go signals to regulate movement forward to the next phase. These signals are maintained in an intricate balance so that the cell only proceeds to the next phase when it is ready. This homeostatic control of the cell cycle can be thought of like a car’s cruise control. Cruise control will continually apply just the right amount of acceleration to maintain a desired speed, unless the driver hits the brakes, in which case the car will slow down. Similarly, the cell includes molecular messengers, such as cyclins, that push the cell forward in its cycle. In addition to cyclins, a class of proteins that are encoded by genes called proto-oncogenes provide important signals that regulate the cell cycle and move it forward. Examples of proto-oncogene products include cell-surface receptors for growth factors, or cell-signaling molecules, two classes of molecules that can promote DNA replication and cell division. In contrast, a second class of genes known as tumor suppressor genes sends stop signals during a cell cycle. For example, certain protein products of tumor suppressor genes signal potential problems with the DNA and thus stop the cell from dividing, while other proteins signal the cell to die if it is damaged beyond repair. Some tumor suppressor proteins also signal a sufficient surrounding cellular density, which indicates that the cell need not presently divide. The latter function is uniquely important in preventing tumor growth: normal cells exhibit a phenomenon called “contact inhibition;” thus, extensive cellular contact with neighboring cells causes a signal that stops further cell division. These two contrasting classes of genes, proto-oncogenes and tumor suppressor genes, are like the accelerator and brake pedal of the cell’s own “cruise control system,” respectively. Under normal conditions, these stop and go signals are maintained in a homeostatic balance. Generally speaking, there are two ways that the cell’s cruise control can lose control: a malfunctioning (overactive) accelerator, or a malfunctioning (underactive) brake. When compromised through a mutation, or otherwise altered, proto-oncogenes can be converted to oncogenes, which produce oncoproteins that push a cell forward in its cycle and stimulate cell division even when it is undesirable to do so. For example, a cell that should be programmed to self-destruct (a process called apoptosis) due to extensive DNA damage might instead be triggered to proliferate by an oncoprotein. On the other hand, a dysfunctional tumor suppressor gene may fail to provide the cell with a necessary stop signal, also resulting in unwanted cell division and proliferation. A delicate homeostatic balance between the many proto-oncogenes and tumor suppressor genes delicately controls the cell cycle and ensures that only healthy cells replicate. Therefore, a disruption of this homeostatic balance can cause aberrant cell division and cancerous growths. INTERACTIVE LINK Visit this link to learn about mitosis. Mitosis results in two identical diploid cells. What structures forms during prophase? Cellular Differentiation - Discuss how the generalized cells of a developing embryo or the stem cells of an adult organism become differentiated into specialized cells - Distinguish between the categories of stem cells How does a complex organism such as a human develop from a single cell—a fertilized egg—into the vast array of cell types such as nerve cells, muscle cells, and epithelial cells that characterize the adult? Throughout development and adulthood, the process of cellular differentiation leads cells to assume their final morphology and physiology. Differentiation is the process by which unspecialized cells become specialized to carry out distinct functions. Stem Cells A stem cell is an unspecialized cell that can divide without limit as needed and can, under specific conditions, differentiate into specialized cells. Stem cells are divided into several categories according to their potential to differentiate. The first embryonic cells that arise from the division of the zygote are the ultimate stem cells; these stems cells are described as totipotent because they have the potential to differentiate into any of the cells needed to enable an organism to grow and develop. The embryonic cells that develop from totipotent stem cells and are precursors to the fundamental tissue layers of the embryo are classified as pluripotent. A pluripotent stem cell is one that has the potential to differentiate into any type of human tissue but cannot support the full development of an organism. These cells then become slightly more specialized, and are referred to as multipotent cells. A multipotent stem cell has the potential to differentiate into different types of cells within a given cell lineage or small number of lineages, such as a red blood cell or white blood cell. Finally, multipotent cells can become further specialized oligopotent cells. An oligopotent stem cell is limited to becoming one of a few different cell types. In contrast, a unipotent cell is fully specialized and can only reproduce to generate more of its own specific cell type. Stem cells are unique in that they can also continually divide and regenerate new stem cells instead of further specializing. There are different stem cells present at different stages of a human’s life. They include the embryonic stem cells of the embryo, fetal stem cells of the fetus, and adult stem cells in the adult. One type of adult stem cell is the epithelial stem cell, which gives rise to the keratinocytes in the multiple layers of epithelial cells in the epidermis of skin. Adult bone marrow has three distinct types of stem cells: hematopoietic stem cells, which give rise to red blood cells, white blood cells, and platelets (Figure 3.34); endothelial stem cells, which give rise to the endothelial cell types that line blood and lymph vessels; and mesenchymal stem cells, which give rise to the different types of muscle cells. Figure 3.34 Hematopoiesis The process of hematopoiesis involves the differentiation of multipotent cells into blood and immune cells. The multipotent hematopoietic stem cells give rise to many different cell types, including the cells of the immune system and red blood cells. Differentiation When a cell differentiates (becomes more specialized), it may undertake major changes in its size, shape, metabolic activity, and overall function. Because all cells in the body, beginning with the fertilized egg, contain the same DNA, how do the different cell types come to be so different? The answer is analogous to a movie script. The different actors in a movie all read from the same script, however, they are each only reading their own part of the script. Similarly, all cells contain the same full complement of DNA, but each type of cell only “reads” the portions of DNA that are relevant to its own function. In biology, this is referred to as the unique genetic expression of each cell. In order for a cell to differentiate into its specialized form and function, it need only manipulate those genes (and thus those proteins) that will be expressed, and not those that will remain silent. The primary mechanism by which genes are turned “on” or “off” is through transcription factors. A transcription factor is one of a class of proteins that bind to specific genes on the DNA molecule and either promote or inhibit their transcription (Figure 3.35). Figure 3.35 Transcription Factors Regulate Gene Expression While each body cell contains the organism’s entire genome, different cells regulate gene expression with the use of various transcription factors. Transcription factors are proteins that affect the binding of RNA polymerase to a particular gene on the DNA molecule. EVERYDAY CONNECTION Stem Cell Research Stem cell research aims to find ways to use stem cells to regenerate and repair cellular damage. Over time, most adult cells undergo the wear and tear of aging and lose their ability to divide and repair themselves. Stem cells do not display a particular morphology or function. Adult stem cells, which exist as a small subset of cells in most tissues, keep dividing and can differentiate into a number of specialized cells generally formed by that tissue. These cells enable the body to renew and repair body tissues. The mechanisms that induce a non-differentiated cell to become a specialized cell are poorly understood. In a laboratory setting, it is possible to induce stem cells to differentiate into specialized cells by changing the physical and chemical conditions of growth. Several sources of stem cells are used experimentally and are classified according to their origin and potential for differentiation. Human embryonic stem cells (hESCs) are extracted from embryos and are pluripotent. The adult stem cells that are present in many organs and differentiated tissues, such as bone marrow and skin, are multipotent, being limited in differentiation to the types of cells found in those tissues. The stem cells isolated from umbilical cord blood are also multipotent, as are cells from deciduous teeth (baby teeth). Researchers have recently developed induced pluripotent stem cells (iPSCs) from mouse and human adult stem cells. These cells are genetically reprogrammed multipotent adult cells that function like embryonic stem cells; they are capable of generating cells characteristic of all three germ layers. Because of their capacity to divide and differentiate into specialized cells, stem cells offer a potential treatment for diseases such as diabetes and heart disease (Figure 3.36). Cell-based therapy refers to treatment in which stem cells induced to differentiate in a growth dish are injected into a patient to repair damaged or destroyed cells or tissues. Many obstacles must be overcome for the application of cell-based therapy. Although embryonic stem cells have a nearly unlimited range of differentiation potential, they are seen as foreign by the patient’s immune system and may trigger rejection. Also, the destruction of embryos to isolate embryonic stem cells raises considerable ethical and legal questions. Figure 3.36 Stem Cells The capacity of stem cells to differentiate into specialized cells make them potentially valuable in therapeutic applications designed to replace damaged cells of different body tissues. In contrast, adult stem cells isolated from a patient are not seen as foreign by the body, but they have a limited range of differentiation. Some individuals bank the cord blood or deciduous teeth of their child, storing away those sources of stem cells for future use, should their child need it. Induced pluripotent stem cells are considered a promising advance in the field because using them avoids the legal, ethical, and immunological pitfalls of embryonic stem cells. Key Terms - active transport - form of transport across the cell membrane that requires input of cellular energy - amphipathic - describes a molecule that exhibits a difference in polarity between its two ends, resulting in a difference in water solubility - anaphase - third stage of mitosis (and meiosis), during which sister chromatids separate into two new nuclear regions of a dividing cell - anticodon - consecutive sequence of three nucleotides on a tRNA molecule that is complementary to a specific codon on an mRNA molecule - autolysis - breakdown of cells by their own enzymatic action - autophagy - lysosomal breakdown of a cell’s own components - cell cycle - life cycle of a single cell, from its birth until its division into two new daughter cells - cell membrane - membrane surrounding all animal cells, composed of a lipid bilayer interspersed with various molecules; also known as plasma membrane - centriole - small, self-replicating organelle that provides the origin for microtubule growth and moves DNA during cell division - centromere - region of attachment for two sister chromatids - centrosome - cellular structure that organizes microtubules during cell division - channel protein - membrane-spanning protein that has an inner pore which allows the passage of one or more substances - checkpoint - progress point in the cell cycle during which certain conditions must be met in order for the cell to proceed to a subsequence phase - chromatin - substance consisting of DNA and associated proteins - chromosome - condensed version of chromatin - cilia - small appendage on certain cells formed by microtubules and modified for movement of materials across the cellular surface - cleavage furrow - contractile ring that forms around a cell during cytokinesis that pinches the cell into two halves - codon - consecutive sequence of three nucleotides on an mRNA molecule that corresponds to a specific amino acid - concentration gradient - difference in the concentration of a substance between two regions - cyclin - one of a group of proteins that function in the progression of the cell cycle - cyclin-dependent kinase (CDK) - one of a group of enzymes associated with cyclins that help them perform their functions - cytokinesis - final stage in cell division, where the cytoplasm divides to form two separate daughter cells - cytoplasm - internal material between the cell membrane and nucleus of a cell, mainly consisting of a water-based fluid called cytosol, within which are all the other organelles and cellular solute and suspended materials - cytoskeleton - “skeleton” of a cell; formed by rod-like proteins that support the cell’s shape and provide, among other functions, locomotive abilities - cytosol - clear, semi-fluid medium of the cytoplasm, made up mostly of water - diffusion - movement of a substance from an area of higher concentration to one of lower concentration - diploid - condition marked by the presence of a double complement of genetic material (two sets of chromosomes, one set inherited from each of two parents) - DNA polymerase - enzyme that functions in adding new nucleotides to a growing strand of DNA during DNA replication - DNA replication - process of duplicating a molecule of DNA - electrical gradient - difference in the electrical charge (potential) between two regions - endocytosis - import of material into the cell by formation of a membrane-bound vesicle - endoplasmic reticulum (ER) - cellular organelle that consists of interconnected membrane-bound tubules, which may or may not be associated with ribosomes (rough type or smooth type, respectively) - exocytosis - export of a substance out of a cell by formation of a membrane-bound vesicle - exon - one of the coding regions of an mRNA molecule that remain after splicing - extracellular fluid (ECF) - fluid exterior to cells; includes the interstitial fluid, blood plasma, and fluid found in other reservoirs in the body - facilitated diffusion - diffusion of a substance with the aid of a membrane protein - flagellum - appendage on certain cells formed by microtubules and modified for movement - G0 phase - phase of the cell cycle, usually entered from the G1 phase; characterized by long or permanent periods where the cell does not move forward into the DNA synthesis phase - G1 phase - first phase of the cell cycle, after a new cell is born - G2 phase - third phase of the cell cycle, after the DNA synthesis phase - gene - functional length of DNA that provides the genetic information necessary to build a protein - gene expression - active interpretation of the information coded in a gene to produce a functional gene product - genome - entire complement of an organism’s DNA; found within virtually every cell - glycocalyx - coating of sugar molecules that surrounds the cell membrane - glycoprotein - protein that has one or more carbohydrates attached - Golgi apparatus - cellular organelle formed by a series of flattened, membrane-bound sacs that functions in protein modification, tagging, packaging, and transport - helicase - enzyme that functions to separate the two DNA strands of a double helix during DNA replication - histone - family of proteins that associate with DNA in the nucleus to form chromatin - homologous - describes two copies of the same chromosome (not identical), one inherited from each parent - hydrophilic - describes a substance or structure attracted to water - hydrophobic - describes a substance or structure repelled by water - hypertonic - describes a solution concentration that is higher than a reference concentration - hypotonic - describes a solution concentration that is lower than a reference concentration - integral protein - membrane-associated protein that spans the entire width of the lipid bilayer - intermediate filament - type of cytoskeletal filament made of keratin, characterized by an intermediate thickness, and playing a role in resisting cellular tension - interphase - entire life cycle of a cell, excluding mitosis - interstitial fluid (IF) - fluid in the small spaces between cells not contained within blood vessels - intracellular fluid (ICF) - fluid in the cytosol of cells - intron - non-coding regions of a pre-mRNA transcript that may be removed during splicing - isotonic - describes a solution concentration that is the same as a reference concentration - kinetochore - region of a centromere where microtubules attach to a pair of sister chromatids - ligand - molecule that binds with specificity to a specific receptor molecule - lysosome - membrane-bound cellular organelle originating from the Golgi apparatus and containing digestive enzymes - messenger RNA (mRNA) - nucleotide molecule that serves as an intermediate in the genetic code between DNA and protein - metaphase - second stage of mitosis (and meiosis), characterized by the linear alignment of sister chromatids in the center of the cell - metaphase plate - linear alignment of sister chromatids in the center of the cell, which takes place during metaphase - microfilament - the thinnest of the cytoskeletal filaments; composed of actin subunits that function in muscle contraction and cellular structural support - microtubule - the thickest of the cytoskeletal filaments, composed of tubulin subunits that function in cellular movement and structural support - mitochondrion - one of the cellular organelles bound by a double lipid bilayer that function primarily in the production of cellular energy (ATP) - mitosis - division of genetic material, during which the cell nucleus breaks down and two new, fully functional, nuclei are formed - mitotic phase - phase of the cell cycle in which a cell undergoes mitosis - mitotic spindle - network of microtubules, originating from centrioles, that arranges and pulls apart chromosomes during mitosis - multipotent - describes the condition of being able to differentiate into different types of cells within a given cell lineage or small number of lineages, such as a red blood cell or white blood cell - mutation - change in the nucleotide sequence in a gene within a cell’s DNA - nuclear envelope - membrane that surrounds the nucleus; consisting of a double lipid-bilayer - nuclear pore - one of the small, protein-lined openings found scattered throughout the nuclear envelope - nucleolus - small region of the nucleus that functions in ribosome synthesis - nucleosome - unit of chromatin consisting of a DNA strand wrapped around histone proteins - nucleus - cell’s central organelle; contains the cell’s DNA - oligopotent - describes the condition of being more specialized than multipotency; the condition of being able to differentiate into one of a few possible cell types - organelle - any of several different types of membrane-enclosed specialized structures in the cell that perform specific functions for the cell - osmosis - diffusion of water molecules down their concentration gradient across a selectively permeable membrane - passive transport - form of transport across the cell membrane that does not require input of cellular energy - peripheral protein - membrane-associated protein that does not span the width of the lipid bilayer, but is attached peripherally to integral proteins, membrane lipids, or other components of the membrane - peroxisome - membrane-bound organelle that contains enzymes primarily responsible for detoxifying harmful substances - phagocytosis - endocytosis of large particles - pinocytosis - endocytosis of fluid - pluripotent - describes the condition of being able to differentiate into a large variety of cell types - polypeptide - chain of amino acids linked by peptide bonds - polyribosome - simultaneous translation of a single mRNA transcript by multiple ribosomes - promoter - region of DNA that signals transcription to begin at that site within the gene - prophase - first stage of mitosis (and meiosis), characterized by breakdown of the nuclear envelope and condensing of the chromatin to form chromosomes - proteome - full complement of proteins produced by a cell (determined by the cell’s specific gene expression) - reactive oxygen species (ROS) - a group of extremely reactive peroxides and oxygen-containing radicals that may contribute to cellular damage - receptor - protein molecule that contains a binding site for another specific molecule (called a ligand) - receptor-mediated endocytosis - endocytosis of ligands attached to membrane-bound receptors - ribosomal RNA (rRNA) - RNA that makes up the subunits of a ribosome - ribosome - cellular organelle that functions in protein synthesis - RNA polymerase - enzyme that unwinds DNA and then adds new nucleotides to a growing strand of RNA for the transcription phase of protein synthesis - S phase - stage of the cell cycle during which DNA replication occurs - selective permeability - feature of any barrier that allows certain substances to cross but excludes others - sister chromatid - one of a pair of identical chromosomes, formed during DNA replication - sodium-potassium pump - (also, Na+/K+ ATP-ase) membrane-embedded protein pump that uses ATP to move Na+ out of a cell and K+ into the cell - somatic cell - all cells of the body excluding gamete cells - spliceosome - complex of enzymes that serves to splice out the introns of a pre-mRNA transcript - splicing - the process of modifying a pre-mRNA transcript by removing certain, typically non-coding, regions - stem cell - cell that is oligo-, multi-, or pleuripotent that has the ability to produce additional stem cells rather than becoming further specialized - telophase - final stage of mitosis (and meiosis), preceding cytokinesis, characterized by the formation of two new daughter nuclei - totipotent - embryonic cells that have the ability to differentiate into any type of cell and organ in the body - transcription - process of producing an mRNA molecule that is complementary to a particular gene of DNA - transcription factor - one of the proteins that regulate the transcription of genes - transfer RNA (tRNA) - molecules of RNA that serve to bring amino acids to a growing polypeptide strand and properly place them into the sequence - translation - process of producing a protein from the nucleotide sequence code of an mRNA transcript - triplet - consecutive sequence of three nucleotides on a DNA molecule that, when transcribed into an mRNA codon, corresponds to a particular amino acid - unipotent - describes the condition of being committed to a single specialized cell type - vesicle - membrane-bound structure that contains materials within or outside of the cell Chapter Review 3.1 The Cell Membrane The cell membrane provides a barrier around the cell, separating its internal components from the extracellular environment. It is composed of a phospholipid bilayer, with hydrophobic internal lipid “tails” and hydrophilic external phosphate “heads.” Various membrane proteins are scattered throughout the bilayer, both inserted within it and attached to it peripherally. The cell membrane is selectively permeable, allowing only a limited number of materials to diffuse through its lipid bilayer. All materials that cross the membrane do so using passive (non energy-requiring) or active (energy-requiring) transport processes. During passive transport, materials move by simple diffusion or by facilitated diffusion through the membrane, down their concentration gradient. Water passes through the membrane in a diffusion process called osmosis. During active transport, energy is expended to assist material movement across the membrane in a direction against their concentration gradient. Active transport may take place with the help of protein pumps or through the use of vesicles. 3.2 The Cytoplasm and Cellular Organelles The internal environmental of a living cell is made up of a fluid, jelly-like substance called cytosol, which consists mainly of water, but also contains various dissolved nutrients and other molecules. The cell contains an array of cellular organelles, each one performing a unique function and helping to maintain the health and activity of the cell. The cytosol and organelles together compose the cell’s cytoplasm. Most organelles are surrounded by a lipid membrane similar to the cell membrane of the cell. The endoplasmic reticulum (ER), Golgi apparatus, and lysosomes share a functional connectivity and are collectively referred to as the endomembrane system. There are two types of ER: smooth and rough. While the smooth ER performs many functions, including lipid synthesis and ion storage, the rough ER is mainly responsible for protein synthesis using its associated ribosomes. The rough ER sends newly made proteins to the Golgi apparatus where they are modified and packaged for delivery to various locations within or outside of the cell. Some of these protein products are enzymes destined to break down unwanted material and are packaged as lysosomes for use inside the cell. Cells also contain mitochondria and peroxisomes, which are the organelles responsible for producing the cell’s energy supply and detoxifying certain chemicals, respectively. Biochemical reactions within mitochondria transform energy-carrying molecules into the usable form of cellular energy known as ATP. Peroxisomes contain enzymes that transform harmful substances such as free radicals into oxygen and water. Cells also contain a miniaturized “skeleton” of protein filaments that extend throughout its interior. Three different kinds of filaments compose this cytoskeleton (in order of increasing thickness): microfilaments, intermediate filaments, and microtubules. Each cytoskeletal component performs unique functions as well as provides a supportive framework for the cell. 3.3 The Nucleus and DNA Replication The nucleus is the command center of the cell, containing the genetic instructions for all of the materials a cell will make (and thus all of its functions it can perform). The nucleus is encased within a membrane of two interconnected lipid bilayers, side-by-side. This nuclear envelope is studded with protein-lined pores that allow materials to be trafficked into and out of the nucleus. The nucleus contains one or more nucleoli, which serve as sites for ribosome synthesis. The nucleus houses the genetic material of the cell: DNA. DNA is normally found as a loosely contained structure called chromatin within the nucleus, where it is wound up and associated with a variety of histone proteins. When a cell is about to divide, the chromatin coils tightly and condenses to form chromosomes. There is a pool of cells constantly dividing within your body. The result is billions of new cells being created each day. Before any cell is ready to divide, it must replicate its DNA so that each new daughter cell will receive an exact copy of the organism’s genome. A variety of enzymes are enlisted during DNA replication. These enzymes unwind the DNA molecule, separate the two strands, and assist with the building of complementary strands along each parent strand. The original DNA strands serve as templates from which the nucleotide sequence of the new strands are determined and synthesized. When replication is completed, two identical DNA molecules exist. Each one contains one original strand and one newly synthesized complementary strand. 3.4 Protein Synthesis DNA stores the information necessary for instructing the cell to perform all of its functions. Cells use the genetic code stored within DNA to build proteins, which ultimately determine the structure and function of the cell. This genetic code lies in the particular sequence of nucleotides that make up each gene along the DNA molecule. To “read” this code, the cell must perform two sequential steps. In the first step, transcription, the DNA code is converted into a RNA code. A molecule of messenger RNA that is complementary to a specific gene is synthesized in a process similar to DNA replication. The molecule of mRNA provides the code to synthesize a protein. In the process of translation, the mRNA attaches to a ribosome. Next, tRNA molecules shuttle the appropriate amino acids to the ribosome, one-by-one, coded by sequential triplet codons on the mRNA, until the protein is fully synthesized. When completed, the mRNA detaches from the ribosome, and the protein is released. Typically, multiple ribosomes attach to a single mRNA molecule at once such that multiple proteins can be manufactured from the mRNA concurrently. 3.5 Cell Growth and Division The life of cell consists of stages that make up the cell cycle. After a cell is born, it passes through an interphase before it is ready to replicate itself and produce daughter cells. This interphase includes two gap phases (G1 and G2), as well as an S phase, during which its DNA is replicated in preparation for cell division. The cell cycle is under precise regulation by chemical messengers both inside and outside the cell that provide “stop” and “go” signals for movement from one phase to the next. Failures of these signals can result in cells that continue to divide uncontrollably, which can lead to cancer. Once a cell has completed interphase and is ready for cell division, it proceeds through four separate stages of mitosis (prophase, metaphase, anaphase, and telophase). Telophase is followed by the division of the cytoplasm (cytokinesis), which generates two daughter cells. This process takes place in all normally dividing cells of the body except for the germ cells that produce eggs and sperm. 3.6 Cellular Differentiation One of the major areas of research in biology is that of how cells specialize to assume their unique structures and functions, since all cells essentially originate from a single fertilized egg. Cell differentiation is the process of cells becoming specialized as they body develops. A stem cell is an unspecialized cell that can divide without limit as needed and can, under specific conditions, differentiate into specialized cells. Stem cells are divided into several categories according to their potential to differentiate. While all somatic cells contain the exact same genome, different cell types only express some of those genes at any given time. These differences in gene expression ultimately dictate a cell’s unique morphological and physiological characteristics. The primary mechanism that determines which genes will be expressed and which ones will not is through the use of different transcription factor proteins, which bind to DNA and promote or hinder the transcription of different genes. Through the action of these transcription factors, cells specialize into one of hundreds of different cell types in the human body. Interactive Link Questions 1. Visit this link to see diffusion and how it is propelled by the kinetic energy of molecules in solution. How does temperature affect diffusion rate, and why? 2.Watch this video to learn about the endomembrane system, which includes the rough and smooth ER and the Golgi body as well as lysosomes and vesicles. What is the primary role of the endomembrane system? 3.Watch this video to learn about DNA replication. DNA replication proceeds simultaneously at several sites on the same molecule. What separates the base pair at the start of DNA replication? 4.Watch this video to learn about ribosomes. The ribosome binds to the mRNA molecule to start translation of its code into a protein. What happens to the small and large ribosomal subunits at the end of translation? 5.Visit this link to learn about mitosis. Mitosis results in two identical diploid cells. What structures form during prophase? Review Questions Because they are embedded within the membrane, ion channels are examples of ________. - receptor proteins - integral proteins - peripheral proteins - glycoproteins The diffusion of substances within a solution tends to move those substances ________ their ________ gradient. - up; electrical - up; electrochemical - down; pressure - down; concentration Ion pumps and phagocytosis are both examples of ________. - endocytosis - passive transport - active transport - facilitated diffusion Choose the answer that best completes the following analogy: Diffusion is to ________ as endocytosis is to ________. - filtration; phagocytosis - osmosis; pinocytosis - solutes; fluid - gradient; chemical energy Choose the term that best completes the following analogy: Cytoplasm is to cytosol as a swimming pool containing chlorine and flotation toys is to ________. - the walls of the pool - the chlorine - the flotation toys - the water The rough ER has its name due to what associated structures? - Golgi apparatus - ribosomes - lysosomes - proteins Which of the following is a function of the rough ER? - production of proteins - detoxification of certain substances - synthesis of steroid hormones - regulation of intracellular calcium concentration Which of the following is a feature common to all three components of the cytoskeleton? - They all serve to scaffold the organelles within the cell. - They are all characterized by roughly the same diameter. - They are all polymers of protein subunits. - They all help the cell resist compression and tension. Which of the following organelles produces large quantities of ATP when both glucose and oxygen are available to the cell? - mitochondria - peroxisomes - lysosomes - ER The nucleus and mitochondria share which of the following features? - protein-lined membrane pores - a double cell membrane - the synthesis of ribosomes - the production of cellular energy Which of the following structures could be found within the nucleolus? - chromatin - histones - ribosomes - nucleosomes Which of the following sequences on a DNA molecule would be complementary to GCTTATAT? - TAGGCGCG - ATCCGCGC - CGAATATA - TGCCTCTC Place the following structures in order from least to most complex organization: chromatin, nucleosome, DNA, chromosome - DNA, nucleosome, chromatin, chromosome - nucleosome, DNA, chromosome, chromatin - DNA, chromatin, nucleosome, chromosome - nucleosome, chromatin, DNA, chromosome Which of the following is part of the elongation step of DNA synthesis? - pulling apart the two DNA strands - attaching complementary nucleotides to the template strand - untwisting the DNA helix - none of the above Which of the following is not a difference between DNA and RNA? - DNA contains thymine whereas RNA contains uracil - DNA contains deoxyribose and RNA contains ribose - DNA contains alternating sugar-phosphate molecules whereas RNA does not contain sugars - RNA is single stranded and DNA is double stranded Transcription and translation take place in the ________ and ________, respectively. - nucleus; cytoplasm - nucleolus; nucleus - nucleolus; cytoplasm - cytoplasm; nucleus How many “letters” of an RNA molecule, in sequence, does it take to provide the code for a single amino acid? - 1 - 2 - 3 - 4 Which of the following is not made out of RNA? - the carriers that shuffle amino acids to a growing polypeptide strand - the ribosome - the messenger molecule that provides the code for protein synthesis - the intron Which of the following phases is characterized by preparation for DNA synthesis? - G0 - G1 - G2 - S A mutation in the gene for a cyclin protein might result in which of the following? - a cell with additional genetic material than normal - cancer - a cell with less genetic material than normal - any of the above What is a primary function of tumor suppressor genes? - stop all cells from dividing - stop certain cells from dividing - help oncogenes produce oncoproteins - allow the cell to skip certain phases of the cell cycle Arrange the following terms in order of increasing specialization: oligopotency, pleuripotency, unipotency, multipotency. - multipotency, pleuripotency, oligopotency, unipotency - pleuripotency, oligopotency, multipotency unipotency - oligopotency, pleuripotency, unipotency, multipotency - pleuripotency, multipotency, oligopotency, unipotency Which type of stem cell gives rise to red and white blood cells? - endothelial - epithelial - hematopoietic - mesenchymal What multipotent stem cells from children sometimes banked by parents? - fetal stem cells - embryonic stem cells - cells from the umbilical cord and from baby teeth - hematopoietic stem cells from red and white blood cells Critical Thinking Questions What materials can easily diffuse through the lipid bilayer, and why? 31.Why is receptor-mediated endocytosis said to be more selective than phagocytosis or pinocytosis? 32.What do osmosis, diffusion, filtration, and the movement of ions away from like charge all have in common? In what way do they differ? 33.Explain why the structure of the ER, mitochondria, and Golgi apparatus assist their respective functions. 34.Compare and contrast lysosomes with peroxisomes: name at least two similarities and one difference. 35.Explain in your own words why DNA replication is said to be “semiconservative”? 36.Why is it important that DNA replication take place before cell division? What would happen if cell division of a body cell took place without DNA replication, or when DNA replication was incomplete? 37.Briefly explain the similarities between transcription and DNA replication. 38.Contrast transcription and translation. Name at least three differences between the two processes. 39.What would happen if anaphase proceeded even though the sister chromatids were not properly attached to their respective microtubules and lined up at the metaphase plate? 40.What are cyclins and cyclin-dependent kinases, and how do they interact? 41.Explain how a transcription factor ultimately determines whether or not a protein will be present in a given cell? 42.Discuss two reasons why the therapeutic use of embryonic stem cells can present a problem.	oercommons	2025-03-18T00:36:11.655186	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/56353/overview", "title": "Anatomy and Physiology, Levels of Organization", "author": null }
https://oercommons.org/courseware/lesson/56354/overview	The Tissue Level of Organization Introduction Figure 4.1 Micrograph of Cervical Tissue This figure is a view of the regular architecture of normal tissue contrasted with the irregular arrangement of cancerous cells. (credit: “Haymanj”/Wikimedia Commons) CHAPTER OBJECTIVES After studying this chapter, you will be able to: - Identify the main tissue types and discuss their roles in the human body - Identify the four types of tissue membranes and the characteristics of each that make them functional - Explain the functions of various epithelial tissues and how their forms enable their functions - Explain the functions of various connective tissues and how their forms enable their functions - Describe the characteristics of muscle tissue and how these enable function - Discuss the characteristics of nervous tissue and how these enable information processing and control of muscular and glandular activities The body contains at least 200 distinct cell types. These cells contain essentially the same internal structures yet they vary enormously in shape and function. The different types of cells are not randomly distributed throughout the body; rather they occur in organized layers, a level of organization referred to as tissue. The micrograph that opens this chapter shows the high degree of organization among different types of cells in the tissue of the cervix. You can also see how that organization breaks down when cancer takes over the regular mitotic functioning of a cell. The variety in shape reflects the many different roles that cells fulfill in your body. The human body starts as a single cell at fertilization. As this fertilized egg divides, it gives rise to trillions of cells, each built from the same blueprint, but organizing into tissues and becoming irreversibly committed to a developmental pathway. Types of Tissues - Identify the four main tissue types - Discuss the functions of each tissue type - Relate the structure of each tissue type to their function - Discuss the embryonic origin of tissue - Identify the three major germ layers - Identify the main types of tissue membranes The term tissue is used to describe a group of cells found together in the body. The cells within a tissue share a common embryonic origin. Microscopic observation reveals that the cells in a tissue share morphological features and are arranged in an orderly pattern that achieves the tissue’s functions. From the evolutionary perspective, tissues appear in more complex organisms. For example, multicellular protists, ancient eukaryotes, do not have cells organized into tissues. Although there are many types of cells in the human body, they are organized into four broad categories of tissues: epithelial, connective, muscle, and nervous. Each of these categories is characterized by specific functions that contribute to the overall health and maintenance of the body. A disruption of the structure is a sign of injury or disease. Such changes can be detected through histology, the microscopic study of tissue appearance, organization, and function. The Four Types of Tissues Epithelial tissue, also referred to as epithelium, refers to the sheets of cells that cover exterior surfaces of the body, lines internal cavities and passageways, and forms certain glands. Connective tissue, as its name implies, binds the cells and organs of the body together and functions in the protection, support, and integration of all parts of the body. Muscle tissue is excitable, responding to stimulation and contracting to provide movement, and occurs as three major types: skeletal (voluntary) muscle, smooth muscle, and cardiac muscle in the heart. Nervous tissue is also excitable, allowing the propagation of electrochemical signals in the form of nerve impulses that communicate between different regions of the body (Figure 4.2). The next level of organization is the organ, where several types of tissues come together to form a working unit. Just as knowing the structure and function of cells helps you in your study of tissues, knowledge of tissues will help you understand how organs function. The epithelial and connective tissues are discussed in detail in this chapter. Muscle and nervous tissues will be discussed only briefly in this chapter. Figure 4.2 Four Types of Tissue: Body The four types of tissues are exemplified in nervous tissue, stratified squamous epithelial tissue, cardiac muscle tissue, and connective tissue in small intestine. Clockwise from nervous tissue, LM × 872, LM × 282, LM × 460, LM × 800. (Micrographs provided by the Regents of University of Michigan Medical School © 2012) Embryonic Origin of Tissues The zygote, or fertilized egg, is a single cell formed by the fusion of an egg and sperm. After fertilization the zygote gives rise to rapid mitotic cycles, generating many cells to form the embryo. The first embryonic cells generated have the ability to differentiate into any type of cell in the body and, as such, are called totipotent, meaning each has the capacity to divide, differentiate, and develop into a new organism. As cell proliferation progresses, three major cell lineages are established within the embryo. As explained in a later chapter, each of these lineages of embryonic cells forms the distinct germ layers from which all the tissues and organs of the human body eventually form. Each germ layer is identified by its relative position: ectoderm (ecto- = “outer”), mesoderm (meso- = “middle”), and endoderm (endo- = “inner”). Figure 4.3 shows the types of tissues and organs associated with the each of the three germ layers. Note that epithelial tissue originates in all three layers, whereas nervous tissue derives primarily from the ectoderm and muscle tissue from mesoderm. Figure 4.3 Embryonic Origin of Tissues and Major Organs INTERACTIVE LINK View this slideshow to learn more about stem cells. How do somatic stem cells differ from embryonic stem cells? Tissue Membranes A tissue membrane is a thin layer or sheet of cells that covers the outside of the body (for example, skin), the organs (for example, pericardium), internal passageways that lead to the exterior of the body (for example, abdominal mesenteries), and the lining of the moveable joint cavities. There are two basic types of tissue membranes: connective tissue and epithelial membranes (Figure 4.4). Figure 4.4 Tissue Membranes The two broad categories of tissue membranes in the body are (1) connective tissue membranes, which include synovial membranes, and (2) epithelial membranes, which include mucous membranes, serous membranes, and the cutaneous membrane, in other words, the skin. Connective Tissue Membranes The connective tissue membrane is formed solely from connective tissue. These membranes encapsulate organs, such as the kidneys, and line our movable joints. A synovial membrane is a type of connective tissue membrane that lines the cavity of a freely movable joint. For example, synovial membranes surround the joints of the shoulder, elbow, and knee. Fibroblasts in the inner layer of the synovial membrane release hyaluronan into the joint cavity. The hyaluronan effectively traps available water to form the synovial fluid, a natural lubricant that enables the bones of a joint to move freely against one another without much friction. This synovial fluid readily exchanges water and nutrients with blood, as do all body fluids. Epithelial Membranes The epithelial membrane is composed of epithelium attached to a layer of connective tissue, for example, your skin. The mucous membrane is also a composite of connective and epithelial tissues. Sometimes called mucosae, these epithelial membranes line the body cavities and hollow passageways that open to the external environment, and include the digestive, respiratory, excretory, and reproductive tracts. Mucous, produced by the epithelial exocrine glands, covers the epithelial layer. The underlying connective tissue, called the lamina propria (literally “own layer”), help support the fragile epithelial layer. A serous membrane is an epithelial membrane composed of mesodermally derived epithelium called the mesothelium that is supported by connective tissue. These membranes line the coelomic cavities of the body, that is, those cavities that do not open to the outside, and they cover the organs located within those cavities. They are essentially membranous bags, with mesothelium lining the inside and connective tissue on the outside. Serous fluid secreted by the cells of the thin squamous mesothelium lubricates the membrane and reduces abrasion and friction between organs. Serous membranes are identified according locations. Three serous membranes line the thoracic cavity; the two pleura that cover the lungs and the pericardium that covers the heart. A fourth, the peritoneum, is the serous membrane in the abdominal cavity that covers abdominal organs and forms double sheets of mesenteries that suspend many of the digestive organs. The skin is an epithelial membrane also called the cutaneous membrane. It is a stratified squamous epithelial membrane resting on top of connective tissue. The apical surface of this membrane is exposed to the external environment and is covered with dead, keratinized cells that help protect the body from desiccation and pathogens. Epithelial Tissue - Explain the structure and function of epithelial tissue - Distinguish between tight junctions, anchoring junctions, and gap junctions - Distinguish between simple epithelia and stratified epithelia, as well as between squamous, cuboidal, and columnar epithelia - Describe the structure and function of endocrine and exocrine glands and their respective secretions Most epithelial tissues are essentially large sheets of cells covering all the surfaces of the body exposed to the outside world and lining the outside of organs. Epithelium also forms much of the glandular tissue of the body. Skin is not the only area of the body exposed to the outside. Other areas include the airways, the digestive tract, as well as the urinary and reproductive systems, all of which are lined by an epithelium. Hollow organs and body cavities that do not connect to the exterior of the body, which includes, blood vessels and serous membranes, are lined by endothelium (plural = endothelia), which is a type of epithelium. Epithelial cells derive from all three major embryonic layers. The epithelia lining the skin, parts of the mouth and nose, and the anus develop from the ectoderm. Cells lining the airways and most of the digestive system originate in the endoderm. The epithelium that lines vessels in the lymphatic and cardiovascular system derives from the mesoderm and is called an endothelium. All epithelia share some important structural and functional features. This tissue is highly cellular, with little or no extracellular material present between cells. Adjoining cells form a specialized intercellular connection between their cell membranes called a cell junction. The epithelial cells exhibit polarity with differences in structure and function between the exposed or apicalfacing surface of the cell and the basal surface close to the underlying body structures. The basal lamina, a mixture of glycoproteins and collagen, provides an attachment site for the epithelium, separating it from underlying connective tissue. The basal lamina attaches to a reticular lamina, which is secreted by the underlying connective tissue, forming a basement membrane that helps hold it all together. Epithelial tissues are nearly completely avascular. For instance, no blood vessels cross the basement membrane to enter the tissue, and nutrients must come by diffusion or absorption from underlying tissues or the surface. Many epithelial tissues are capable of rapidly replacing damaged and dead cells. Sloughing off of damaged or dead cells is a characteristic of surface epithelium and allows our airways and digestive tracts to rapidly replace damaged cells with new cells. Generalized Functions of Epithelial Tissue Epithelial tissues provide the body’s first line of protection from physical, chemical, and biological wear and tear. The cells of an epithelium act as gatekeepers of the body controlling permeability and allowing selective transfer of materials across a physical barrier. All substances that enter the body must cross an epithelium. Some epithelia often include structural features that allow the selective transport of molecules and ions across their cell membranes. Many epithelial cells are capable of secretion and release mucous and specific chemical compounds onto their apical surfaces. The epithelium of the small intestine releases digestive enzymes, for example. Cells lining the respiratory tract secrete mucous that traps incoming microorganisms and particles. A glandular epithelium contains many secretory cells. The Epithelial Cell Epithelial cells are typically characterized by the polarized distribution of organelles and membrane-bound proteins between their basal and apical surfaces. Particular structures found in some epithelial cells are an adaptation to specific functions. Certain organelles are segregated to the basal sides, whereas other organelles and extensions, such as cilia, when present, are on the apical surface. Cilia are microscopic extensions of the apical cell membrane that are supported by microtubules. They beat in unison and move fluids as well as trapped particles. Ciliated epithelium lines the ventricles of the brain where it helps circulate the cerebrospinal fluid. The ciliated epithelium of your airway forms a mucociliary escalator that sweeps particles of dust and pathogens trapped in the secreted mucous toward the throat. It is called an escalator because it continuously pushes mucous with trapped particles upward. In contrast, nasal cilia sweep the mucous blanket down towards your throat. In both cases, the transported materials are usually swallowed, and end up in the acidic environment of your stomach. Cell to Cell Junctions Cells of epithelia are closely connected and are not separated by intracellular material. Three basic types of connections allow varying degrees of interaction between the cells: tight junctions, anchoring junctions, and gap junctions (Figure 4.5). Figure 4.5 Types of Cell Junctions The three basic types of cell-to-cell junctions are tight junctions, gap junctions, and anchoring junctions. At one end of the spectrum is the tight junction, which separates the cells into apical and basal compartments. When two adjacent epithelial cells form a tight junction, there is no extracellular space between them and the movement of substances through the extracellular space between the cells is blocked. This enables the epithelia to act as selective barriers. An anchoring junction includes several types of cell junctions that help stabilize epithelial tissues. Anchoring junctions are common on the lateral and basal surfaces of cells where they provide strong and flexible connections. There are three types of anchoring junctions: desmosomes, hemidesmosomes, and adherens. Desmosomes occur in patches on the membranes of cells. The patches are structural proteins on the inner surface of the cell’s membrane. The adhesion molecule, cadherin, is embedded in these patches and projects through the cell membrane to link with the cadherin molecules of adjacent cells. These connections are especially important in holding cells together. Hemidesmosomes, which look like half a desmosome, link cells to the extracellular matrix, for example, the basal lamina. While similar in appearance to desmosomes, they include the adhesion proteins called integrins rather than cadherins. Adherens junctions use either cadherins or integrins depending on whether they are linking to other cells or matrix. The junctions are characterized by the presence of the contractile protein actin located on the cytoplasmic surface of the cell membrane. The actin can connect isolated patches or form a belt-like structure inside the cell. These junctions influence the shape and folding of the epithelial tissue. In contrast with the tight and anchoring junctions, a gap junction forms an intercellular passageway between the membranes of adjacent cells to facilitate the movement of small molecules and ions between the cytoplasm of adjacent cells. These junctions allow electrical and metabolic coupling of adjacent cells, which coordinates function in large groups of cells. Classification of Epithelial Tissues Epithelial tissues are classified according to the shape of the cells and number of the cell layers formed (Figure 4.6). Cell shapes can be squamous (flattened and thin), cuboidal (boxy, as wide as it is tall), or columnar (rectangular, taller than it is wide). Similarly, the number of cell layers in the tissue can be one—where every cell rests on the basal lamina—which is a simple epithelium, or more than one, which is a stratified epithelium and only the basal layer of cells rests on the basal lamina. Pseudostratified (pseudo- = “false”) describes tissue with a single layer of irregularly shaped cells that give the appearance of more than one layer. Transitional describes a form of specialized stratified epithelium in which the shape of the cells can vary. Figure 4.6 Cells of Epithelial Tissue Simple epithelial tissue is organized as a single layer of cells and stratified epithelial tissue is formed by several layers of cells. Simple Epithelium The shape of the cells in the single cell layer of simple epithelium reflects the functioning of those cells. The cells in simple squamous epithelium have the appearance of thin scales. Squamous cell nuclei tend to be flat, horizontal, and elliptical, mirroring the form of the cell. The endothelium is the epithelial tissue that lines vessels of the lymphatic and cardiovascular system, and it is made up of a single layer of squamous cells. Simple squamous epithelium, because of the thinness of the cell, is present where rapid passage of chemical compounds is observed. The alveoli of lungs where gases diffuse, segments of kidney tubules, and the lining of capillaries are also made of simple squamous epithelial tissue. The mesothelium is a simple squamous epithelium that forms the surface layer of the serous membrane that lines body cavities and internal organs. Its primary function is to provide a smooth and protective surface. Mesothelial cells are squamous epithelial cells that secrete a fluid that lubricates the mesothelium. In simple cuboidal epithelium, the nucleus of the box-like cells appears round and is generally located near the center of the cell. These epithelia are active in the secretion and absorptions of molecules. Simple cuboidal epithelia are observed in the lining of the kidney tubules and in the ducts of glands. In simple columnar epithelium, the nucleus of the tall column-like cells tends to be elongated and located in the basal end of the cells. Like the cuboidal epithelia, this epithelium is active in the absorption and secretion of molecules. Simple columnar epithelium forms the lining of some sections of the digestive system and parts of the female reproductive tract. Ciliated columnar epithelium is composed of simple columnar epithelial cells with cilia on their apical surfaces. These epithelial cells are found in the lining of the fallopian tubes and parts of the respiratory system, where the beating of the cilia helps remove particulate matter. Pseudostratified columnar epithelium is a type of epithelium that appears to be stratified but instead consists of a single layer of irregularly shaped and differently sized columnar cells. In pseudostratified epithelium, nuclei of neighboring cells appear at different levels rather than clustered in the basal end. The arrangement gives the appearance of stratification; but in fact all the cells are in contact with the basal lamina, although some do not reach the apical surface. Pseudostratified columnar epithelium is found in the respiratory tract, where some of these cells have cilia. Both simple and pseudostratified columnar epithelia are heterogeneous epithelia because they include additional types of cells interspersed among the epithelial cells. For example, a goblet cell is a mucous-secreting unicellular “gland” interspersed between the columnar epithelial cells of mucous membranes (Figure 4.7). Figure 4.7 Goblet Cell (a) In the lining of the small intestine, columnar epithelium cells are interspersed with goblet cells. (b) The arrows in this micrograph point to the mucous-secreting goblet cells. LM × 1600. (Micrograph provided by the Regents of University of Michigan Medical School © 2012) INTERACTIVE LINK View the University of Michigan WebScope to explore the tissue sample in greater detail. Stratified Epithelium A stratified epithelium consists of several stacked layers of cells. This epithelium protects against physical and chemical wear and tear. The stratified epithelium is named by the shape of the most apical layer of cells, closest to the free space. Stratified squamous epithelium is the most common type of stratified epithelium in the human body. The apical cells are squamous, whereas the basal layer contains either columnar or cuboidal cells. The top layer may be covered with dead cells filled with keratin. Mammalian skin is an example of this dry, keratinized, stratified squamous epithelium. The lining of the mouth cavity is an example of an unkeratinized, stratified squamous epithelium. Stratified cuboidal epithelium and stratified columnar epithelium can also be found in certain glands and ducts, but are uncommon in the human body. Another kind of stratified epithelium is transitional epithelium, so-called because of the gradual changes in the shapes of the apical cells as the bladder fills with urine. It is found only in the urinary system, specifically the ureters and urinary bladder. When the bladder is empty, this epithelium is convoluted and has cuboidal apical cells with convex, umbrella shaped, apical surfaces. As the bladder fills with urine, this epithelium loses its convolutions and the apical cells transition from cuboidal to squamous. It appears thicker and more multi-layered when the bladder is empty, and more stretched out and less stratified when the bladder is full and distended. Figure 4.8 summarizes the different categories of epithelial cell tissue cells. Figure 4.8 Summary of Epithelial Tissue Cells INTERACTIVE LINK Watch this video to find out more about the anatomy of epithelial tissues. Where in the body would one find non-keratinizing stratified squamous epithelium? Glandular Epithelium A gland is a structure made up of one or more cells modified to synthesize and secrete chemical substances. Most glands consist of groups of epithelial cells. A gland can be classified as an endocrine gland, a ductless gland that releases secretions directly into surrounding tissues and fluids (endo- = “inside”), or an exocrine gland whose secretions leave through a duct that opens directly, or indirectly, to the external environment (exo- = “outside”). Endocrine Glands The secretions of endocrine glands are called hormones. Hormones are released into the interstitial fluid, diffused into the bloodstream, and delivered to targets, in other words, cells that have receptors to bind the hormones. The endocrine system is part of a major regulatory system coordinating the regulation and integration of body responses. A few examples of endocrine glands include the anterior pituitary, thymus, adrenal cortex, and gonads. Exocrine Glands Exocrine glands release their contents through a duct that leads to the epithelial surface. Mucous, sweat, saliva, and breast milk are all examples of secretions from exocrine glands. They are all discharged through tubular ducts. Secretions into the lumen of the gastrointestinal tract, technically outside of the body, are of the exocrine category. Glandular Structure Exocrine glands are classified as either unicellular or multicellular. The unicellular glands are scattered single cells, such as goblet cells, found in the mucous membranes of the small and large intestine. The multicellular exocrine glands known as serous glands develop from simple epithelium to form a secretory surface that secretes directly into an inner cavity. These glands line the internal cavities of the abdomen and chest and release their secretions directly into the cavities. Other multicellular exocrine glands release their contents through a tubular duct. The duct is single in a simple gland but in compound glands is divided into one or more branches (Figure 4.9). In tubular glands, the ducts can be straight or coiled, whereas tubes that form pockets are alveolar (acinar), such as the exocrine portion of the pancreas. Combinations of tubes and pockets are known as tubuloalveolar (tubuloacinar) compound glands. In a branched gland, a duct is connected to more than one secretory group of cells. Figure 4.9 Types of Exocrine Glands Exocrine glands are classified by their structure. Methods and Types of Secretion Exocrine glands can be classified by their mode of secretion and the nature of the substances released, as well as by the structure of the glands and shape of ducts (Figure 4.10). Merocrine secretion is the most common type of exocrine secretion. The secretions are enclosed in vesicles that move to the apical surface of the cell where the contents are released by exocytosis. For example, watery mucous containing the glycoprotein mucin, a lubricant that offers some pathogen protection is a merocrine secretion. The eccrine glands that produce and secrete sweat are another example. Figure 4.10 Modes of Glandular Secretion (a) In merocrine secretion, the cell remains intact. (b) In apocrine secretion, the apical portion of the cell is released, as well. (c) In holocrine secretion, the cell is destroyed as it releases its product and the cell itself becomes part of the secretion. Apocrine secretion accumulates near the apical portion of the cell. That portion of the cell and its secretory contents pinch off from the cell and are released. Apocrine sweat glands in the axillary and genital areas release fatty secretions that local bacteria break down; this causes body odor. Both merocrine and apocrine glands continue to produce and secrete their contents with little damage caused to the cell because the nucleus and golgi regions remain intact after secretion. In contrast, the process of holocrine secretion involves the rupture and destruction of the entire gland cell. The cell accumulates its secretory products and releases them only when it bursts. New gland cells differentiate from cells in the surrounding tissue to replace those lost by secretion. The sebaceous glands that produce the oils on the skin and hair are holocrine glands/cells (Figure 4.11). Figure 4.11 Sebaceous Glands These glands secrete oils that lubricate and protect the skin. They are holocrine glands and they are destroyed after releasing their contents. New glandular cells form to replace the cells that are lost. LM × 400. (Micrograph provided by the Regents of University of Michigan Medical School © 2012) Glands are also named after the products they produce. The serous gland produces watery, blood-plasma-like secretions rich in enzymes such as alpha amylase, whereas the mucous gland releases watery to viscous products rich in the glycoprotein mucin. Both serous and mucous glands are common in the salivary glands of the mouth. Mixed exocrine glands contain both serous and mucous glands and release both types of secretions. Connective Tissue Supports and Protects - Identify and distinguish between the types of connective tissue: proper, supportive, and fluid - Explain the functions of connective tissues As may be obvious from its name, one of the major functions of connective tissue is to connect tissues and organs. Unlike epithelial tissue, which is composed of cells closely packed with little or no extracellular space in between, connective tissue cells are dispersed in a matrix. The matrix usually includes a large amount of extracellular material produced by the connective tissue cells that are embedded within it. The matrix plays a major role in the functioning of this tissue. The major component of the matrix is a ground substance often crisscrossed by protein fibers. This ground substance is usually a fluid, but it can also be mineralized and solid, as in bones. Connective tissues come in a vast variety of forms, yet they typically have in common three characteristic components: cells, large amounts of amorphous ground substance, and protein fibers. The amount and structure of each component correlates with the function of the tissue, from the rigid ground substance in bones supporting the body to the inclusion of specialized cells; for example, a phagocytic cell that engulfs pathogens and also rids tissue of cellular debris. Functions of Connective Tissues Connective tissues perform many functions in the body, but most importantly, they support and connect other tissues; from the connective tissue sheath that surrounds muscle cells, to the tendons that attach muscles to bones, and to the skeleton that supports the positions of the body. Protection is another major function of connective tissue, in the form of fibrous capsules and bones that protect delicate organs and, of course, the skeletal system. Specialized cells in connective tissue defend the body from microorganisms that enter the body. Transport of fluid, nutrients, waste, and chemical messengers is ensured by specialized fluid connective tissues, such as blood and lymph. Adipose cells store surplus energy in the form of fat and contribute to the thermal insulation of the body. Embryonic Connective Tissue All connective tissues derive from the mesodermal layer of the embryo (see Figure 4.3). The first connective tissue to develop in the embryo is mesenchyme, the stem cell line from which all connective tissues are later derived. Clusters of mesenchymal cells are scattered throughout adult tissue and supply the cells needed for replacement and repair after a connective tissue injury. A second type of embryonic connective tissue forms in the umbilical cord, called mucous connective tissue or Wharton’s jelly. This tissue is no longer present after birth, leaving only scattered mesenchymal cells throughout the body. Classification of Connective Tissues The three broad categories of connective tissue are classified according to the characteristics of their ground substance and the types of fibers found within the matrix (Table 4.1). Connective tissue proper includes loose connective tissue and dense connective tissue. Both tissues have a variety of cell types and protein fibers suspended in a viscous ground substance. Dense connective tissue is reinforced by bundles of fibers that provide tensile strength, elasticity, and protection. In loose connective tissue, the fibers are loosely organized, leaving large spaces in between. Supportive connective tissue—bone and cartilage—provide structure and strength to the body and protect soft tissues. A few distinct cell types and densely packed fibers in a matrix characterize these tissues. In bone, the matrix is rigid and described as calcified because of the deposited calcium salts. In fluid connective tissue, in other words, lymph and blood, various specialized cells circulate in a watery fluid containing salts, nutrients, and dissolved proteins. Connective Tissue Proper Fibroblasts are present in all connective tissue proper (Figure 4.12). Fibrocytes, adipocytes, and mesenchymal cells are fixed cells, which means they remain within the connective tissue. Other cells move in and out of the connective tissue in response to chemical signals. Macrophages, mast cells, lymphocytes, plasma cells, and phagocytic cells are found in connective tissue proper but are actually part of the immune system protecting the body. Figure 4.12 Connective Tissue Proper Fibroblasts produce this fibrous tissue. Connective tissue proper includes the fixed cells fibrocytes, adipocytes, and mesenchymal cells. LM × 400. (Micrograph provided by the Regents of University of Michigan Medical School © 2012) Cell Types The most abundant cell in connective tissue proper is the fibroblast. Polysaccharides and proteins secreted by fibroblasts combine with extra-cellular fluids to produce a viscous ground substance that, with embedded fibrous proteins, forms the extra-cellular matrix. As you might expect, a fibrocyte, a less active form of fibroblast, is the second most common cell type in connective tissue proper. Adipocytes are cells that store lipids as droplets that fill most of the cytoplasm. There are two basic types of adipocytes: white and brown. The brown adipocytes store lipids as many droplets, and have high metabolic activity. In contrast, white fat adipocytes store lipids as a single large drop and are metabolically less active. Their effectiveness at storing large amounts of fat is witnessed in obese individuals. The number and type of adipocytes depends on the tissue and location, and vary among individuals in the population. The mesenchymal cell is a multipotent adult stem cell. These cells can differentiate into any type of connective tissue cells needed for repair and healing of damaged tissue. The macrophage cell is a large cell derived from a monocyte, a type of blood cell, which enters the connective tissue matrix from the blood vessels. The macrophage cells are an essential component of the immune system, which is the body’s defense against potential pathogens and degraded host cells. When stimulated, macrophages release cytokines, small proteins that act as chemical messengers. Cytokines recruit other cells of the immune system to infected sites and stimulate their activities. Roaming, or free, macrophages move rapidly by amoeboid movement, engulfing infectious agents and cellular debris. In contrast, fixed macrophages are permanent residents of their tissues. The mast cell, found in connective tissue proper, has many cytoplasmic granules. These granules contain the chemical signals histamine and heparin. When irritated or damaged, mast cells release histamine, an inflammatory mediator, which causes vasodilation and increased blood flow at a site of injury or infection, along with itching, swelling, and redness you recognize as an allergic response. Like blood cells, mast cells are derived from hematopoietic stem cells and are part of the immune system. Connective Tissue Fibers and Ground Substance Three main types of fibers are secreted by fibroblasts: collagen fibers, elastic fibers, and reticular fibers. Collagen fiber is made from fibrous protein subunits linked together to form a long and straight fiber. Collagen fibers, while flexible, have great tensile strength, resist stretching, and give ligaments and tendons their characteristic resilience and strength. These fibers hold connective tissues together, even during the movement of the body. Elastic fiber contains the protein elastin along with lesser amounts of other proteins and glycoproteins. The main property of elastin is that after being stretched or compressed, it will return to its original shape. Elastic fibers are prominent in elastic tissues found in skin and the elastic ligaments of the vertebral column. Reticular fiber is also formed from the same protein subunits as collagen fibers; however, these fibers remain narrow and are arrayed in a branching network. They are found throughout the body, but are most abundant in the reticular tissue of soft organs, such as liver and spleen, where they anchor and provide structural support to the parenchyma (the functional cells, blood vessels, and nerves of the organ). All of these fiber types are embedded in ground substance. Secreted by fibroblasts, ground substance is made of polysaccharides, specifically hyaluronic acid, and proteins. These combine to form a proteoglycan with a protein core and polysaccharide branches. The proteoglycan attracts and traps available moisture forming the clear, viscous, colorless matrix you now know as ground substance. Loose Connective Tissue Loose connective tissue is found between many organs where it acts both to absorb shock and bind tissues together. It allows water, salts, and various nutrients to diffuse through to adjacent or imbedded cells and tissues. Adipose tissue consists mostly of fat storage cells, with little extracellular matrix (Figure 4.13). A large number of capillaries allow rapid storage and mobilization of lipid molecules. White adipose tissue is most abundant. It can appear yellow and owes its color to carotene and related pigments from plant food. White fat contributes mostly to lipid storage and can serve as insulation from cold temperatures and mechanical injuries. White adipose tissue can be found protecting the kidneys and cushioning the back of the eye. Brown adipose tissue is more common in infants, hence the term “baby fat.” In adults, there is a reduced amount of brown fat and it is found mainly in the neck and clavicular regions of the body. The many mitochondria in the cytoplasm of brown adipose tissue help explain its efficiency at metabolizing stored fat. Brown adipose tissue is thermogenic, meaning that as it breaks down fats, it releases metabolic heat, rather than producing adenosine triphosphate (ATP), a key molecule used in metabolism. Figure 4.13 Adipose Tissue This is a loose connective tissue that consists of fat cells with little extracellular matrix. It stores fat for energy and provides insulation. LM × 800. (Micrograph provided by the Regents of University of Michigan Medical School © 2012) Areolar tissue shows little specialization. It contains all the cell types and fibers previously described and is distributed in a random, web-like fashion. It fills the spaces between muscle fibers, surrounds blood and lymph vessels, and supports organs in the abdominal cavity. Areolar tissue underlies most epithelia and represents the connective tissue component of epithelial membranes, which are described further in a later section. Reticular tissue is a mesh-like, supportive framework for soft organs such as lymphatic tissue, the spleen, and the liver (Figure 4.14). Reticular cells produce the reticular fibers that form the network onto which other cells attach. It derives its name from the Latin reticulus, which means “little net.” Figure 4.14 Reticular Tissue This is a loose connective tissue made up of a network of reticular fibers that provides a supportive framework for soft organs. LM × 1600. (Micrograph provided by the Regents of University of Michigan Medical School © 2012) Dense Connective Tissue Dense connective tissue contains more collagen fibers than does loose connective tissue. As a consequence, it displays greater resistance to stretching. There are two major categories of dense connective tissue: regular and irregular. Dense regular connective tissue fibers are parallel to each other, enhancing tensile strength and resistance to stretching in the direction of the fiber orientations. Ligaments and tendons are made of dense regular connective tissue, but in ligaments not all fibers are parallel. Dense regular elastic tissue contains elastin fibers in addition to collagen fibers, which allows the ligament to return to its original length after stretching. The ligaments in the vocal folds and between the vertebrae in the vertebral column are elastic. In dense irregular connective tissue, the direction of fibers is random. This arrangement gives the tissue greater strength in all directions and less strength in one particular direction. In some tissues, fibers crisscross and form a mesh. In other tissues, stretching in several directions is achieved by alternating layers where fibers run in the same orientation in each layer, and it is the layers themselves that are stacked at an angle. The dermis of the skin is an example of dense irregular connective tissue rich in collagen fibers. Dense irregular elastic tissues give arterial walls the strength and the ability to regain original shape after stretching (Figure 4.15). Figure 4.15 Dense Connective Tissue (a) Dense regular connective tissue consists of collagenous fibers packed into parallel bundles. (b) Dense irregular connective tissue consists of collagenous fibers interwoven into a mesh-like network. From top, LM × 1000, LM × 200. (Micrographs provided by the Regents of University of Michigan Medical School © 2012) DISORDERS OF THE... Connective Tissue: Tendinitis Your opponent stands ready as you prepare to hit the serve, but you are confident that you will smash the ball past your opponent. As you toss the ball high in the air, a burning pain shoots across your wrist and you drop the tennis racket. That dull ache in the wrist that you ignored through the summer is now an unbearable pain. The game is over for now. After examining your swollen wrist, the doctor in the emergency room announces that you have developed wrist tendinitis. She recommends icing the tender area, taking non-steroidal anti-inflammatory medication to ease the pain and to reduce swelling, and complete rest for a few weeks. She interrupts your protests that you cannot stop playing. She issues a stern warning about the risk of aggravating the condition and the possibility of surgery. She consoles you by mentioning that well known tennis players such as Venus and Serena Williams and Rafael Nadal have also suffered from tendinitis related injuries. What is tendinitis and how did it happen? Tendinitis is the inflammation of a tendon, the thick band of fibrous connective tissue that attaches a muscle to a bone. The condition causes pain and tenderness in the area around a joint. On rare occasions, a sudden serious injury will cause tendinitis. Most often, the condition results from repetitive motions over time that strain the tendons needed to perform the tasks. Persons whose jobs and hobbies involve performing the same movements over and over again are often at the greatest risk of tendinitis. You hear of tennis and golfer’s elbow, jumper's knee, and swimmer’s shoulder. In all cases, overuse of the joint causes a microtrauma that initiates the inflammatory response. Tendinitis is routinely diagnosed through a clinical examination. In case of severe pain, X-rays can be examined to rule out the possibility of a bone injury. Severe cases of tendinitis can even tear loose a tendon. Surgical repair of a tendon is painful. Connective tissue in the tendon does not have abundant blood supply and heals slowly. While older adults are at risk for tendinitis because the elasticity of tendon tissue decreases with age, active people of all ages can develop tendinitis. Young athletes, dancers, and computer operators; anyone who performs the same movements constantly is at risk for tendinitis. Although repetitive motions are unavoidable in many activities and may lead to tendinitis, precautions can be taken that can lessen the probability of developing tendinitis. For active individuals, stretches before exercising and cross training or changing exercises are recommended. For the passionate athlete, it may be time to take some lessons to improve technique. All of the preventive measures aim to increase the strength of the tendon and decrease the stress put on it. With proper rest and managed care, you will be back on the court to hit that slice-spin serve over the net. INTERACTIVE LINK Watch this animation to learn more about tendonitis, a painful condition caused by swollen or injured tendons. Supportive Connective Tissues Two major forms of supportive connective tissue, cartilage and bone, allow the body to maintain its posture and protect internal organs. Cartilage The distinctive appearance of cartilage is due to polysaccharides called chondroitin sulfates, which bind with ground substance proteins to form proteoglycans. Embedded within the cartilage matrix are chondrocytes, or cartilage cells, and the space they occupy are called lacunae (singular = lacuna). A layer of dense irregular connective tissue, the perichondrium, encapsulates the cartilage. Cartilaginous tissue is avascular, thus all nutrients need to diffuse through the matrix to reach the chondrocytes. This is a factor contributing to the very slow healing of cartilaginous tissues. The three main types of cartilage tissue are hyaline cartilage, fibrocartilage, and elastic cartilage (Figure 4.16). Hyaline cartilage, the most common type of cartilage in the body, consists of short and dispersed collagen fibers and contains large amounts of proteoglycans. Under the microscope, tissue samples appear clear. The surface of hyaline cartilage is smooth. Both strong and flexible, it is found in the rib cage and nose and covers bones where they meet to form moveable joints. It makes up a template of the embryonic skeleton before bone formation. A plate of hyaline cartilage at the ends of bone allows continued growth until adulthood. Fibrocartilage is tough because it has thick bundles of collagen fibers dispersed through its matrix. Menisci in the knee joint and the intervertebral discs are examples of fibrocartilage. Elastic cartilage contains elastic fibers as well as collagen and proteoglycans. This tissue gives rigid support as well as elasticity. Tug gently at your ear lobes, and notice that the lobes return to their initial shape. The external ear contains elastic cartilage. Figure 4.16 Types of Cartilage Cartilage is a connective tissue consisting of collagenous fibers embedded in a firm matrix of chondroitin sulfates. (a) Hyaline cartilage provides support with some flexibility. The example is from dog tissue. (b) Fibrocartilage provides some compressibility and can absorb pressure. (c) Elastic cartilage provides firm but elastic support. From top, LM × 300, LM × 1200, LM × 1016. (Micrographs provided by the Regents of University of Michigan Medical School © 2012) Bone Bone is the hardest connective tissue. It provides protection to internal organs and supports the body. Bone’s rigid extracellular matrix contains mostly collagen fibers embedded in a mineralized ground substance containing hydroxyapatite, a form of calcium phosphate. Both components of the matrix, organic and inorganic, contribute to the unusual properties of bone. Without collagen, bones would be brittle and shatter easily. Without mineral crystals, bones would flex and provide little support. Osteocytes, bone cells like chondrocytes, are located within lacunae. The histology of transverse tissue from long bone shows a typical arrangement of osteocytes in concentric circles around a central canal. Bone is a highly vascularized tissue. Unlike cartilage, bone tissue can recover from injuries in a relatively short time. Cancellous bone looks like a sponge under the microscope and contains empty spaces between trabeculae, or arches of bone proper. It is lighter than compact bone and found in the interior of some bones and at the end of long bones. Compact bone is solid and has greater structural strength. Fluid Connective Tissue Blood and lymph are fluid connective tissues. Cells circulate in a liquid extracellular matrix. The formed elements circulating in blood are all derived from hematopoietic stem cells located in bone marrow (Figure 4.17). Erythrocytes, red blood cells, transport oxygen and some carbon dioxide. Leukocytes, white blood cells, are responsible for defending against potentially harmful microorganisms or molecules. Platelets are cell fragments involved in blood clotting. Some white blood cells have the ability to cross the endothelial layer that lines blood vessels and enter adjacent tissues. Nutrients, salts, and wastes are dissolved in the liquid matrix and transported through the body. Lymph contains a liquid matrix and white blood cells. Lymphatic capillaries are extremely permeable, allowing larger molecules and excess fluid from interstitial spaces to enter the lymphatic vessels. Lymph drains into blood vessels, delivering molecules to the blood that could not otherwise directly enter the bloodstream. In this way, specialized lymphatic capillaries transport absorbed fats away from the intestine and deliver these molecules to the blood. Figure 4.17 Blood: A Fluid Connective Tissue Blood is a fluid connective tissue containing erythrocytes and various types of leukocytes that circulate in a liquid extracellular matrix. LM × 1600. (Micrograph provided by the Regents of University of Michigan Medical School © 2012) INTERACTIVE LINK View the University of Michigan Webscope to explore the tissue sample in greater detail. INTERACTIVE LINK Visit this link to test your connective tissue knowledge with this 10-question quiz. Can you name the 10 tissue types shown in the histology slides? Muscle Tissue and Motion - Identify the three types of muscle tissue - Compare and contrast the functions of each muscle tissue type - Explain how muscle tissue can enable motion Muscle tissue is characterized by properties that allow movement. Muscle cells are excitable; they respond to a stimulus. They are contractile, meaning they can shorten and generate a pulling force. When attached between two movable objects, in other words, bones, contractions of the muscles cause the bones to move. Some muscle movement is voluntary, which means it is under conscious control. For example, a person decides to open a book and read a chapter on anatomy. Other movements are involuntary, meaning they are not under conscious control, such as the contraction of your pupil in bright light. Muscle tissue is classified into three types according to structure and function: skeletal, cardiac, and smooth (Table 4.2). Skeletal muscle is attached to bones and its contraction makes possible locomotion, facial expressions, posture, and other voluntary movements of the body. Forty percent of your body mass is made up of skeletal muscle. Skeletal muscles generate heat as a byproduct of their contraction and thus participate in thermal homeostasis. Shivering is an involuntary contraction of skeletal muscles in response to perceived lower than normal body temperature. The muscle cell, or myocyte, develops from myoblasts derived from the mesoderm. Myocytes and their numbers remain relatively constant throughout life. Skeletal muscle tissue is arranged in bundles surrounded by connective tissue. Under the light microscope, muscle cells appear striated with many nuclei squeezed along the membranes. The striation is due to the regular alternation of the contractile proteins actin and myosin, along with the structural proteins that couple the contractile proteins to connective tissues. The cells are multinucleated as a result of the fusion of the many myoblasts that fuse to form each long muscle fiber. Cardiac muscle forms the contractile walls of the heart. The cells of cardiac muscle, known as cardiomyocytes, also appear striated under the microscope. Unlike skeletal muscle fibers, cardiomyocytes are single cells typically with a single centrally located nucleus. A principal characteristic of cardiomyocytes is that they contract on their own intrinsic rhythms without any external stimulation. Cardiomyocyte attach to one another with specialized cell junctions called intercalated discs. Intercalated discs have both anchoring junctions and gap junctions. Attached cells form long, branching cardiac muscle fibers that are, essentially, a mechanical and electrochemical syncytium allowing the cells to synchronize their actions. The cardiac muscle pumps blood through the body and is under involuntary control. The attachment junctions hold adjacent cells together across the dynamic pressures changes of the cardiac cycle. Smooth muscle tissue contraction is responsible for involuntary movements in the internal organs. It forms the contractile component of the digestive, urinary, and reproductive systems as well as the airways and arteries. Each cell is spindle shaped with a single nucleus and no visible striations (Figure 4.18). Figure 4.18 Muscle Tissue (a) Skeletal muscle cells have prominent striation and nuclei on their periphery. (b) Smooth muscle cells have a single nucleus and no visible striations. (c) Cardiac muscle cells appear striated and have a single nucleus. From top, LM × 1600, LM × 1600, LM × 1600. (Micrographs provided by the Regents of University of Michigan Medical School © 2012) INTERACTIVE LINK Watch this video to learn more about muscle tissue. In looking through a microscope how could you distinguish skeletal muscle tissue from smooth muscle? Nervous Tissue Mediates Perception and Response By the end of this section, you will be able to:- Identify the classes of cells that make up nervous tissue - Discuss how nervous tissue mediates perception and response Nervous tissue is characterized as being excitable and capable of sending and receiving electrochemical signals that provide the body with information. Two main classes of cells make up nervous tissue: the neuron and neuroglia (Figure 4.19). Neurons propagate information via electrochemical impulses, called action potentials, which are biochemically linked to the release of chemical signals. Neuroglia play an essential role in supporting neurons and modulating their information propagation. Figure 4.19 The Neuron The cell body of a neuron, also called the soma, contains the nucleus and mitochondria. The dendrites transfer the nerve impulse to the soma. The axon carries the action potential away to another excitable cell. LM × 1600. (Micrograph provided by the Regents of University of Michigan Medical School © 2012) INTERACTIVE LINK Follow this link to learn more about nervous tissue. What are the main parts of a nerve cell? Neurons display distinctive morphology, well suited to their role as conducting cells, with three main parts. The cell body includes most of the cytoplasm, the organelles, and the nucleus. Dendrites branch off the cell body and appear as thin extensions. A long “tail,” the axon, extends from the neuron body and can be wrapped in an insulating layer known as myelin, which is formed by accessory cells. The synapse is the gap between nerve cells, or between a nerve cell and its target, for example, a muscle or a gland, across which the impulse is transmitted by chemical compounds known as neurotransmitters. Neurons categorized as multipolar neurons have several dendrites and a single prominent axon. Bipolar neurons possess a single dendrite and axon with the cell body, while unipolar neurons have only a single process extending out from the cell body, which divides into a functional dendrite and into a functional axon. When a neuron is sufficiently stimulated, it generates an action potential that propagates down the axon towards the synapse. If enough neurotransmitters are released at the synapse to stimulate the next neuron or target, a response is generated. The second class of neural cells comprises the neuroglia or glial cells, which have been characterized as having a simple support role. The word “glia” comes from the Greek word for glue. Recent research is shedding light on the more complex role of neuroglia in the function of the brain and nervous system. Astrocyte cells, named for their distinctive star shape, are abundant in the central nervous system. The astrocytes have many functions, including regulation of ion concentration in the intercellular space, uptake and/or breakdown of some neurotransmitters, and formation of the blood-brain barrier, the membrane that separates the circulatory system from the brain. Microglia protect the nervous system against infection but are not nervous tissue because they are related to macrophages. Oligodendrocyte cells produce myelin in the central nervous system (brain and spinal cord) while the Schwann cell produces myelin in the peripheral nervous system (Figure 4.20). Figure 4.20 Nervous Tissue Nervous tissue is made up of neurons and neuroglia. The cells of nervous tissue are specialized to transmit and receive impulses. LM × 872. (Micrograph provided by the Regents of University of Michigan Medical School © 2012) Tissue Injury and Aging - Identify the cardinal signs of inflammation - List the body’s response to tissue injury - Explain the process of tissue repair - Discuss the progressive impact of aging on tissue - Describe cancerous mutations’ effect on tissue Tissues of all types are vulnerable to injury and, inevitably, aging. In the former case, understanding how tissues respond to damage can guide strategies to aid repair. In the latter case, understanding the impact of aging can help in the search for ways to diminish its effects. Tissue Injury and Repair Inflammation is the standard, initial response of the body to injury. Whether biological, chemical, physical, or radiation burns, all injuries lead to the same sequence of physiological events. Inflammation limits the extent of injury, partially or fully eliminates the cause of injury, and initiates repair and regeneration of damaged tissue. Necrosis, or accidental cell death, causes inflammation. Apoptosis is programmed cell death, a normal step-by-step process that destroys cells no longer needed by the body. By mechanisms still under investigation, apoptosis does not initiate the inflammatory response. Acute inflammation resolves over time by the healing of tissue. If inflammation persists, it becomes chronic and leads to diseased conditions. Arthritis and tuberculosis are examples of chronic inflammation. The suffix “-itis” denotes inflammation of a specific organ or type, for example, peritonitis is the inflammation of the peritoneum, and meningitis refers to the inflammation of the meninges, the tough membranes that surround the central nervous system The four cardinal signs of inflammation—redness, swelling, pain, and local heat—were first recorded in antiquity. Cornelius Celsus is credited with documenting these signs during the days of the Roman Empire, as early as the first century AD. A fifth sign, loss of function, may also accompany inflammation. Upon tissue injury, damaged cells release inflammatory chemical signals that evoke local vasodilation, the widening of the blood vessels. Increased blood flow results in apparent redness and heat. In response to injury, mast cells present in tissue degranulate, releasing the potent vasodilator histamine. Increased blood flow and inflammatory mediators recruit white blood cells to the site of inflammation. The endothelium lining the local blood vessel becomes “leaky” under the influence of histamine and other inflammatory mediators allowing neutrophils, macrophages, and fluid to move from the blood into the interstitial tissue spaces. The excess liquid in tissue causes swelling, more properly called edema. The swollen tissues squeezing pain receptors cause the sensation of pain. Prostaglandins released from injured cells also activate pain neurons. Non-steroidal anti-inflammatory drugs (NSAIDs) reduce pain because they inhibit the synthesis of prostaglandins. High levels of NSAIDs reduce inflammation. Antihistamines decrease allergies by blocking histamine receptors and as a result the histamine response. After containment of an injury, the tissue repair phase starts with removal of toxins and waste products. Clotting (coagulation) reduces blood loss from damaged blood vessels and forms a network of fibrin proteins that trap blood cells and bind the edges of the wound together. A scab forms when the clot dries, reducing the risk of infection. Sometimes a mixture of dead leukocytes and fluid called pus accumulates in the wound. As healing progresses, fibroblasts from the surrounding connective tissues replace the collagen and extracellular material lost by the injury. Angiogenesis, the growth of new blood vessels, results in vascularization of the new tissue known as granulation tissue. The clot retracts pulling the edges of the wound together, and it slowly dissolves as the tissue is repaired. When a large amount of granulation tissue forms and capillaries disappear, a pale scar is often visible in the healed area. A primary union describes the healing of a wound where the edges are close together. When there is a gaping wound, it takes longer to refill the area with cells and collagen. The process called secondary unionoccurs as the edges of the wound are pulled together by what is called wound contraction. When a wound is more than one quarter of an inch deep, sutures (stitches) are recommended to promote a primary union and avoid the formation of a disfiguring scar. Regeneration is the addition of new cells of the same type as the ones that were injured (Figure 4.21). Figure 4.21 Tissue Healing During wound repair, collagen fibers are laid down randomly by fibroblasts that move into repair the area. INTERACTIVE LINK Watch this video to see a hand heal. Over what period of time do you think these images were taken? Tissue and Aging According to poet Ralph Waldo Emerson, “The surest poison is time.” In fact, biology confirms that many functions of the body decline with age. All the cells, tissues, and organs are affected by senescence, with noticeable variability between individuals owing to different genetic makeup and lifestyles. The outward signs of aging are easily recognizable. The skin and other tissues become thinner and drier, reducing their elasticity, contributing to wrinkles and high blood pressure. Hair turns gray because follicles produce less melanin, the brown pigment of hair and the iris of the eye. The face looks flabby because elastic and collagen fibers decrease in connective tissue and muscle tone is lost. Glasses and hearing aids may become parts of life as the senses slowly deteriorate, all due to reduced elasticity. Overall height decreases as the bones lose calcium and other minerals. With age, fluid decreases in the fibrous cartilage disks intercalated between the vertebrae in the spine. Joints lose cartilage and stiffen. Many tissues, including those in muscles, lose mass through a process called atrophy. Lumps and rigidity become more widespread. As a consequence, the passageways, blood vessels, and airways become more rigid. The brain and spinal cord lose mass. Nerves do not transmit impulses with the same speed and frequency as in the past. Some loss of thought clarity and memory can accompany aging. More severe problems are not necessarily associated with the aging process and may be symptoms of underlying illness. As exterior signs of aging increase, so do the interior signs, which are not as noticeable. The incidence of heart diseases, respiratory syndromes, and type 2 diabetes increases with age, though these are not necessarily age-dependent effects. Wound healing is slower in the elderly, accompanied by a higher frequency of infection as the capacity of the immune system to fend off pathogen declines. Aging is also apparent at the cellular level because all cells experience changes with aging. Telomeres, regions of the chromosomes necessary for cell division, shorten each time cells divide. As they do, cells are less able to divide and regenerate. Because of alterations in cell membranes, transport of oxygen and nutrients into the cell and removal of carbon dioxide and waste products from the cell are not as efficient in the elderly. Cells may begin to function abnormally, which may lead to diseases associated with aging, including arthritis, memory issues, and some cancers. The progressive impact of aging on the body varies considerably among individuals, but Studies indicate, however, that exercise and healthy lifestyle choices can slow down the deterioration of the body that comes with old age. HOMEOSTATIC IMBALANCES Tissues and Cancer Cancer is a generic term for many diseases in which cells escape regulatory signals. Uncontrolled growth, invasion into adjacent tissues, and colonization of other organs, if not treated early enough, are its hallmarks. Health suffers when tumors “rob” blood supply from the “normal” organs. A mutation is defined as a permanent change in the DNA of a cell. Epigenetic modifications, changes that do not affect the code of the DNA but alter how the DNA is decoded, are also known to generate abnormal cells. Alterations in the genetic material may be caused by environmental agents, infectious agents, or errors in the replication of DNA that accumulate with age. Many mutations do not cause any noticeable change in the functions of a cell. However, if the modification affects key proteins that have an impact on the cell’s ability to proliferate in an orderly fashion, the cell starts to divide abnormally. As changes in cells accumulate, they lose their ability to form regular tissues. A tumor, a mass of cells displaying abnormal architecture, forms in the tissue. Many tumors are benign, meaning they do not metastasize nor cause disease. A tumor becomes malignant, or cancerous, when it breaches the confines of its tissue, promotes angiogenesis, attracts the growth of capillaries, and metastasizes to other organs (Figure 4.22). The specific names of cancers reflect the tissue of origin. Cancers derived from epithelial cells are referred to as carcinomas. Cancer in myeloid tissue or blood cells form myelomas. Leukemias are cancers of white blood cells, whereas sarcomas derive from connective tissue. Cells in tumors differ both in structure and function. Some cells, called cancer stem cells, appear to be a subtype of cell responsible for uncontrolled growth. Recent research shows that contrary to what was previously assumed, tumors are not disorganized masses of cells, but have their own structures. Figure 4.22 Development of Cancer Note the change in cell size, nucleus size, and organization in the tissue. INTERACTIVE LINK Watch this video to learn more about tumors. What is a tumor? Cancer treatments vary depending on the disease’s type and stage. Traditional approaches, including surgery, radiation, chemotherapy, and hormonal therapy, aim to remove or kill rapidly dividing cancer cells, but these strategies have their limitations. Depending on a tumor’s location, for example, cancer surgeons may be unable to remove it. Radiation and chemotherapy are difficult, and it is often impossible to target only the cancer cells. The treatments inevitably destroy healthy tissue as well. To address this, researchers are working on pharmaceuticals that can target specific proteins implicated in cancer-associated molecular pathways. Key Terms - adipocytes - lipid storage cells - adipose tissue - specialized areolar tissue rich in stored fat - anchoring junction - mechanically attaches adjacent cells to each other or to the basement membrane - apical - that part of a cell or tissue which, in general, faces an open space - apocrine secretion - release of a substance along with the apical portion of the cell - apoptosis - programmed cell death - areolar tissue - (also, loose connective tissue) a type of connective tissue proper that shows little specialization with cells dispersed in the matrix - astrocyte - star-shaped cell in the central nervous system that regulates ions and uptake and/or breakdown of some neurotransmitters and contributes to the formation of the blood-brain barrier - atrophy - loss of mass and function - basal lamina - thin extracellular layer that lies underneath epithelial cells and separates them from other tissues - basement membrane - in epithelial tissue, a thin layer of fibrous material that anchors the epithelial tissue to the underlying connective tissue; made up of the basal lamina and reticular lamina - cardiac muscle - heart muscle, under involuntary control, composed of striated cells that attach to form fibers, each cell contains a single nucleus, contracts autonomously - cell junction - point of cell-to-cell contact that connects one cell to another in a tissue - chondrocytes - cells of the cartilage - clotting - also called coagulation; complex process by which blood components form a plug to stop bleeding - collagen fiber - flexible fibrous proteins that give connective tissue tensile strength - connective tissue - type of tissue that serves to hold in place, connect, and integrate the body’s organs and systems - connective tissue membrane - connective tissue that encapsulates organs and lines movable joints - connective tissue proper - connective tissue containing a viscous matrix, fibers, and cells. - cutaneous membrane - skin; epithelial tissue made up of a stratified squamous epithelial cells that cover the outside of the body - dense connective tissue - connective tissue proper that contains many fibers that provide both elasticity and protection - ectoderm - outermost embryonic germ layer from which the epidermis and the nervous tissue derive - elastic cartilage - type of cartilage, with elastin as the major protein, characterized by rigid support as well as elasticity - elastic fiber - fibrous protein within connective tissue that contains a high percentage of the protein elastin that allows the fibers to stretch and return to original size - endocrine gland - groups of cells that release chemical signals into the intercellular fluid to be picked up and transported to their target organs by blood - endoderm - innermost embryonic germ layer from which most of the digestive system and lower respiratory system derive - endothelium - tissue that lines vessels of the lymphatic and cardiovascular system, made up of a simple squamous epithelium - epithelial membrane - epithelium attached to a layer of connective tissue - epithelial tissue - type of tissue that serves primarily as a covering or lining of body parts, protecting the body; it also functions in absorption, transport, and secretion - exocrine gland - group of epithelial cells that secrete substances through ducts that open to the skin or to internal body surfaces that lead to the exterior of the body - fibroblast - most abundant cell type in connective tissue, secretes protein fibers and matrix into the extracellular space - fibrocartilage - tough form of cartilage, made of thick bundles of collagen fibers embedded in chondroitin sulfate ground substance - fibrocyte - less active form of fibroblast - fluid connective tissue - specialized cells that circulate in a watery fluid containing salts, nutrients, and dissolved proteins - gap junction - allows cytoplasmic communications to occur between cells - goblet cell - unicellular gland found in columnar epithelium that secretes mucous - ground substance - fluid or semi-fluid portion of the matrix - histamine - chemical compound released by mast cells in response to injury that causes vasodilation and endothelium permeability - histology - microscopic study of tissue architecture, organization, and function - holocrine secretion - release of a substance caused by the rupture of a gland cell, which becomes part of the secretion - hyaline cartilage - most common type of cartilage, smooth and made of short collagen fibers embedded in a chondroitin sulfate ground substance - inflammation - response of tissue to injury - lacunae - (singular = lacuna) small spaces in bone or cartilage tissue that cells occupy - lamina propria - areolar connective tissue underlying a mucous membrane - loose connective tissue - (also, areolar tissue) type of connective tissue proper that shows little specialization with cells dispersed in the matrix - matrix - extracellular material which is produced by the cells embedded in it, containing ground substance and fibers - merocrine secretion - release of a substance from a gland via exocytosis - mesenchymal cell - adult stem cell from which most connective tissue cells are derived - mesenchyme - embryonic tissue from which connective tissue cells derive - mesoderm - middle embryonic germ layer from which connective tissue, muscle tissue, and some epithelial tissue derive - mesothelium - simple squamous epithelial tissue which covers the major body cavities and is the epithelial portion of serous membranes - mucous connective tissue - specialized loose connective tissue present in the umbilical cord - mucous gland - group of cells that secrete mucous, a thick, slippery substance that keeps tissues moist and acts as a lubricant - mucous membrane - tissue membrane that is covered by protective mucous and lines tissue exposed to the outside environment - muscle tissue - type of tissue that is capable of contracting and generating tension in response to stimulation; produces movement. - myelin - layer of lipid inside some neuroglial cells that wraps around the axons of some neurons - myocyte - muscle cells - necrosis - accidental death of cells and tissues - nervous tissue - type of tissue that is capable of sending and receiving impulses through electrochemical signals. - neuroglia - supportive neural cells - neuron - excitable neural cell that transfer nerve impulses - oligodendrocyte - neuroglial cell that produces myelin in the brain - parenchyma - functional cells of a gland or organ, in contrast with the supportive or connective tissue of a gland or organ - primary union - condition of a wound where the wound edges are close enough to be brought together and fastened if necessary, allowing quicker and more thorough healing - pseudostratified columnar epithelium - tissue that consists of a single layer of irregularly shaped and sized cells that give the appearance of multiple layers; found in ducts of certain glands and the upper respiratory tract - reticular fiber - fine fibrous protein, made of collagen subunits, which cross-link to form supporting “nets” within connective tissue - reticular lamina - matrix containing collagen and elastin secreted by connective tissue; a component of the basement membrane - reticular tissue - type of loose connective tissue that provides a supportive framework to soft organs, such as lymphatic tissue, spleen, and the liver - Schwann cell - neuroglial cell that produces myelin in the peripheral nervous system - secondary union - wound healing facilitated by wound contraction - serous gland - group of cells within the serous membrane that secrete a lubricating substance onto the surface - serous membrane - type of tissue membrane that lines body cavities and lubricates them with serous fluid - simple columnar epithelium - tissue that consists of a single layer of column-like cells; promotes secretion and absorption in tissues and organs - simple cuboidal epithelium - tissue that consists of a single layer of cube-shaped cells; promotes secretion and absorption in ducts and tubules - simple squamous epithelium - tissue that consists of a single layer of flat scale-like cells; promotes diffusion and filtration across surface - skeletal muscle - usually attached to bone, under voluntary control, each cell is a fiber that is multinucleated and striated - smooth muscle - under involuntary control, moves internal organs, cells contain a single nucleus, are spindle-shaped, and do not appear striated; each cell is a fiber - stratified columnar epithelium - tissue that consists of two or more layers of column-like cells, contains glands and is found in some ducts - stratified cuboidal epithelium - tissue that consists of two or more layers of cube-shaped cells, found in some ducts - stratified squamous epithelium - tissue that consists of multiple layers of cells with the most apical being flat scale-like cells; protects surfaces from abrasion - striation - alignment of parallel actin and myosin filaments which form a banded pattern - supportive connective tissue - type of connective tissue that provides strength to the body and protects soft tissue - synovial membrane - connective tissue membrane that lines the cavities of freely movable joints, producing synovial fluid for lubrication - tight junction - forms an impermeable barrier between cells - tissue - group of cells that are similar in form and perform related functions - tissue membrane - thin layer or sheet of cells that covers the outside of the body, organs, and internal cavities - totipotent - embryonic cells that have the ability to differentiate into any type of cell and organ in the body - transitional epithelium - form of stratified epithelium found in the urinary tract, characterized by an apical layer of cells that change shape in response to the presence of urine - vasodilation - widening of blood vessels - wound contraction - process whereby the borders of a wound are physically drawn together Chapter Review 4.1 Types of Tissues The human body contains more than 200 types of cells that can all be classified into four types of tissues: epithelial, connective, muscle, and nervous. Epithelial tissues act as coverings controlling the movement of materials across the surface. Connective tissue integrates the various parts of the body and provides support and protection to organs. Muscle tissue allows the body to move. Nervous tissues propagate information. The study of the shape and arrangement of cells in tissue is called histology. All cells and tissues in the body derive from three germ layers in the embryo: the ectoderm, mesoderm, and endoderm. Different types of tissues form membranes that enclose organs, provide a friction-free interaction between organs, and keep organs together. Synovial membranes are connective tissue membranes that protect and line the joints. Epithelial membranes are formed from epithelial tissue attached to a layer of connective tissue. There are three types of epithelial membranes: mucous, which contain glands; serous, which secrete fluid; and cutaneous which makes up the skin. 4.2 Epithelial Tissue In epithelial tissue, cells are closely packed with little or no extracellular matrix except for the basal lamina that separates the epithelium from underlying tissue. The main functions of epithelia are protection from the environment, coverage, secretion and excretion, absorption, and filtration. Cells are bound together by tight junctions that form an impermeable barrier. They can also be connected by gap junctions, which allow free exchange of soluble molecules between cells, and anchoring junctions, which attach cell to cell or cell to matrix. The different types of epithelial tissues are characterized by their cellular shapes and arrangements: squamous, cuboidal, or columnar epithelia. Single cell layers form simple epithelia, whereas stacked cells form stratified epithelia. Very few capillaries penetrate these tissues. Glands are secretory tissues and organs that are derived from epithelial tissues. Exocrine glands release their products through ducts. Endocrine glands secrete hormones directly into the interstitial fluid and blood stream. Glands are classified both according to the type of secretion and by their structure. Merocrine glands secrete products as they are synthesized. Apocrine glands release secretions by pinching off the apical portion of the cell, whereas holocrine gland cells store their secretions until they rupture and release their contents. In this case, the cell becomes part of the secretion. 4.3 Connective Tissue Supports and Protects Connective tissue is a heterogeneous tissue with many cell shapes and tissue architecture. Structurally, all connective tissues contain cells that are embedded in an extracellular matrix stabilized by proteins. The chemical nature and physical layout of the extracellular matrix and proteins vary enormously among tissues, reflecting the variety of functions that connective tissue fulfills in the body. Connective tissues separate and cushion organs, protecting them from shifting or traumatic injury. Connect tissues provide support and assist movement, store and transport energy molecules, protect against infections, and contribute to temperature homeostasis. Many different cells contribute to the formation of connective tissues. They originate in the mesodermal germ layer and differentiate from mesenchyme and hematopoietic tissue in the bone marrow. Fibroblasts are the most abundant and secrete many protein fibers, adipocytes specialize in fat storage, hematopoietic cells from the bone marrow give rise to all the blood cells, chondrocytes form cartilage, and osteocytes form bone. The extracellular matrix contains fluid, proteins, polysaccharide derivatives, and, in the case of bone, mineral crystals. Protein fibers fall into three major groups: collagen fibers that are thick, strong, flexible, and resist stretch; reticular fibers that are thin and form a supportive mesh; and elastin fibers that are thin and elastic. The major types of connective tissue are connective tissue proper, supportive tissue, and fluid tissue. Loose connective tissue proper includes adipose tissue, areolar tissue, and reticular tissue. These serve to hold organs and other tissues in place and, in the case of adipose tissue, isolate and store energy reserves. The matrix is the most abundant feature for loose tissue although adipose tissue does not have much extracellular matrix. Dense connective tissue proper is richer in fibers and may be regular, with fibers oriented in parallel as in ligaments and tendons, or irregular, with fibers oriented in several directions. Organ capsules (collagenous type) and walls of arteries (elastic type) contain dense irregular connective tissue. Cartilage and bone are supportive tissue. Cartilage contains chondrocytes and is somewhat flexible. Hyaline cartilage is smooth and clear, covers joints, and is found in the growing portion of bones. Fibrocartilage is tough because of extra collagen fibers and forms, among other things, the intervertebral discs. Elastic cartilage can stretch and recoil to its original shape because of its high content of elastic fibers. The matrix contains very few blood vessels. Bones are made of a rigid, mineralized matrix containing calcium salts, crystals, and osteocytes lodged in lacunae. Bone tissue is highly vascularized. Cancellous bone is spongy and less solid than compact bone. Fluid tissue, for example blood and lymph, is characterized by a liquid matrix and no supporting fibers. 4.4 Muscle Tissue and Motion The three types of muscle cells are skeletal, cardiac, and smooth. Their morphologies match their specific functions in the body. Skeletal muscle is voluntary and responds to conscious stimuli. The cells are striated and multinucleated appearing as long, unbranched cylinders. Cardiac muscle is involuntary and found only in the heart. Each cell is striated with a single nucleus and they attach to one another to form long fibers. Cells are attached to one another at intercalated disks. The cells are interconnected physically and electrochemically to act as a syncytium. Cardiac muscle cells contract autonomously and involuntarily. Smooth muscle is involuntary. Each cell is a spindle-shaped fiber and contains a single nucleus. No striations are evident because the actin and myosin filaments do not align in the cytoplasm. 4.5 Nervous Tissue Mediates Perception and Response The most prominent cell of the nervous tissue, the neuron, is characterized mainly by its ability to receive stimuli and respond by generating an electrical signal, known as an action potential, which can travel rapidly over great distances in the body. A typical neuron displays a distinctive morphology: a large cell body branches out into short extensions called dendrites, which receive chemical signals from other neurons, and a long tail called an axon, which relays signals away from the cell to other neurons, muscles, or glands. Many axons are wrapped by a myelin sheath, a lipid derivative that acts as an insulator and speeds up the transmission of the action potential. Other cells in the nervous tissue, the neuroglia, include the astrocytes, microglia, oligodendrocytes, and Schwann cells. 4.6 Tissue Injury and Aging Inflammation is the classic response of the body to injury and follows a common sequence of events. The area is red, feels warm to the touch, swells, and is painful. Injured cells, mast cells, and resident macrophages release chemical signals that cause vasodilation and fluid leakage in the surrounding tissue. The repair phase includes blood clotting, followed by regeneration of tissue as fibroblasts deposit collagen. Some tissues regenerate more readily than others. Epithelial and connective tissues replace damaged or dead cells from a supply of adult stem cells. Muscle and nervous tissues undergo either slow regeneration or do not repair at all. Age affects all the tissues and organs of the body. Damaged cells do not regenerate as rapidly as in younger people. Perception of sensation and effectiveness of response are lost in the nervous system. Muscles atrophy, and bones lose mass and become brittle. Collagen decreases in some connective tissue, and joints stiffen. Interactive Link Questions View this slideshow to learn more about stem cells. How do somatic stem cells differ from embryonic stem cells? 2.Watch this video to find out more about the anatomy of epithelial tissues. Where in the body would one find non-keratinizing stratified squamous epithelium? 3.Visit this link to test your connective tissue knowledge with this 10-question quiz. Can you name the 10 tissue types shown in the histology slides? 4.Watch this video to learn more about muscle tissue. In looking through a microscope how could you distinguish skeletal muscle tissue from smooth muscle? 5.Follow this link to learn more about nervous tissue. What are the main parts of a nerve cell? 6.Watch this video to see a hand heal. Over what period of time do you think these images were taken? 7.Watch this video to learn more about tumors. What is a tumor? Review Questions Which of the following is not a type of tissue? - muscle - nervous - embryonic - epithelial The process by which a less specialized cell matures into a more specialized cell is called ________. - differentiation - maturation - modification - specialization Differentiated cells in a developing embryo derive from ________. - endothelium, mesothelium, and epithelium - ectoderm, mesoderm, and endoderm - connective tissue, epithelial tissue, and muscle tissue - epidermis, mesoderm, and endothelium Which of the following lines the body cavities exposed to the external environment? - mesothelium - lamina propria - mesenteries - mucosa In observing epithelial cells under a microscope, the cells are arranged in a single layer and look tall and narrow, and the nucleus is located close to the basal side of the cell. The specimen is what type of epithelial tissue? - columnar - stratified - squamous - transitional Which of the following is the epithelial tissue that lines the interior of blood vessels? - columnar - pseudostratified - simple squamous - transitional Which type of epithelial tissue specializes in moving particles across its surface and is found in airways and lining of the oviduct? - transitional - stratified columnar - pseudostratified ciliated columnar - stratified squamous The ________ exocrine gland stores its secretion until the glandular cell ruptures, whereas the ________ gland releases its apical region and reforms. - holocrine; apocrine - eccrine; endocrine - apocrine; holocrine - eccrine; apocrine Connective tissue is made of which three essential components? - cells, ground substance, and carbohydrate fibers - cells, ground substance, and protein fibers - collagen, ground substance, and protein fibers - matrix, ground substance, and fluid Under the microscope, a tissue specimen shows cells located in spaces scattered in a transparent background. This is probably ________. - loose connective tissue - a tendon - bone - hyaline cartilage Which connective tissue specializes in storage of fat? - tendon - adipose tissue - reticular tissue - dense connective tissue Ligaments connect bones together and withstand a lot of stress. What type of connective tissue should you expect ligaments to contain? - areolar tissue - adipose tissue - dense regular connective tissue - dense irregular connective tissue In adults, new connective tissue cells originate from the ________. - mesoderm - mesenchyme - ectoderm - endoderm In bone, the main cells are ________. - fibroblasts - chondrocytes - lymphocytes - osteocytes Striations, cylindrical cells, and multiple nuclei are observed in ________. - skeletal muscle only - cardiac muscle only - smooth muscle only - skeletal and cardiac muscles The cells of muscles, myocytes, develop from ________. - myoblasts - endoderm - fibrocytes - chondrocytes Skeletal muscle is composed of very hard working cells. Which organelles do you expect to find in abundance in skeletal muscle cell? - nuclei - striations - golgi bodies - mitochondria The cells responsible for the transmission of the nerve impulse are ________. - neurons - oligodendrocytes - astrocytes - microglia The nerve impulse travels down a(n) ________, away from the cell body. - dendrite - axon - microglia - collagen fiber Which of the following central nervous system cells regulate ions, regulate the uptake and/or breakdown of some neurotransmitters, and contribute to the formation of the blood-brain barrier? - microglia - neuroglia - oligodendrocytes - astrocytes Which of the following processes is not a cardinal sign of inflammation? - redness - heat - fever - swelling When a mast cell reacts to an irritation, which of the following chemicals does it release? - collagen - histamine - hyaluronic acid - meylin Atrophy refers to ________. - loss of elasticity - loss of mass - loss of rigidity - loss of permeability Individuals can slow the rate of aging by modifying all of these lifestyle aspects except for ________. - diet - exercise - genetic factors - stress Critical Thinking Questions Identify the four types of tissue in the body, and describe the major functions of each tissue. 33.The zygote is described as totipotent because it ultimately gives rise to all the cells in your body including the highly specialized cells of your nervous system. Describe this transition, discussing the steps and processes that lead to these specialized cells. 34.What is the function of synovial membranes? 35.The structure of a tissue usually is optimized for its function. Describe how the structure of the mucosa and its cells match its function of nutrient absorption. 36.One of the main functions of connective tissue is to integrate organs and organ systems in the body. Discuss how blood fulfills this role. 37.Why does an injury to cartilage, especially hyaline cartilage, heal much more slowly than a bone fracture? 38.You are watching cells in a dish spontaneously contract. They are all contracting at different rates; some fast, some slow. After a while, several cells link up and they begin contracting in synchrony. Discuss what is going on and what type of cells you are looking at. 39.Why does skeletal muscle look striated? 40.Which morphological adaptations of neurons make them suitable for the transmission of nerve impulse? 41.What are the functions of astrocytes? 42.Why is it important to watch for increased redness, swelling and pain after a cut or abrasion has been cleaned and bandaged? 43.Aspirin is a non-steroidal anti-inflammatory drug (NSAID) that inhibits the formation of blood clots and is taken regularly by individuals with a heart condition. Steroids such as cortisol are used to control some autoimmune diseases and severe arthritis by down-regulating the inflammatory response. After reading the role of inflammation in the body’s response to infection, can you predict an undesirable consequence of taking anti-inflammatory drugs on a regular basis? 44.As an individual ages, a constellation of symptoms begins the decline to the point where an individual’s functioning is compromised. Identify and discuss two factors that have a role in factors leading to the compromised situation. 45.Discuss changes that occur in cells as a person ages.	oercommons	2025-03-18T00:36:11.760079	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/56354/overview", "title": "Anatomy and Physiology, Levels of Organization", "author": null }
https://oercommons.org/courseware/lesson/58771/overview	The Digestive System Introduction Figure 23.1 Eating Apples Eating may be one of the simple pleasures in life, but digesting even one apple requires the coordinated work of many organs. (credit: “Aimanness Photography”/Flickr) CHAPTER OBJECTIVES After studying this chapter, you will be able to: - List and describe the functional anatomy of the organs and accessory organs of the digestive system - Discuss the processes and control of ingestion, propulsion, mechanical digestion, chemical digestion, absorption, and defecation - Discuss the roles of the liver, pancreas, and gallbladder in digestion - Compare and contrast the digestion of the three macronutrients The digestive system is continually at work, yet people seldom appreciate the complex tasks it performs in a choreographed biologic symphony. Consider what happens when you eat an apple. Of course, you enjoy the apple’s taste as you chew it, but in the hours that follow, unless something goes amiss and you get a stomachache, you don’t notice that your digestive system is working. You may be taking a walk or studying or sleeping, having forgotten all about the apple, but your stomach and intestines are busy digesting it and absorbing its vitamins and other nutrients. By the time any waste material is excreted, the body has appropriated all it can use from the apple. In short, whether you pay attention or not, the organs of the digestive system perform their specific functions, allowing you to use the food you eat to keep you going. This chapter examines the structure and functions of these organs, and explores the mechanics and chemistry of the digestive processes. Overview of the Digestive System By the end of this section, you will be able to: - Identify the organs of the alimentary canal from proximal to distal, and briefly state their function - Identify the accessory digestive organs and briefly state their function Describe the four fundamental tissue layers of the alimentary canal Contrast the contributions of the enteric and autonomic nervous systems to digestive system functioning - Explain how the peritoneum anchors the digestive organs The function of the digestive system is to break down the foods you eat, release their nutrients, and absorb those nutrients into the body. Although the small intestine is the workhorse of the system, where the majority of digestion occurs, and where most of the released nutrients are absorbed into the blood or lymph, each of the digestive system organs makes a vital contribution to this process (Figure 23.2). Figure 23.2 Components of the Digestive System All digestive organs play integral roles in the life-sustaining process of digestion. As is the case with all body systems, the digestive system does not work in isolation; it functions cooperatively with the other systems of the body. Consider for example, the interrelationship between the digestive and cardiovascular systems. Arteries supply the digestive organs with oxygen and processed nutrients, and veins drain the digestive tract. These intestinal veins, constituting the hepatic portal system, are unique; they do not return blood directly to the heart. Rather, this blood is diverted to the liver where its nutrients are off-loaded for processing before blood completes its circuit back to the heart. At the same time, the digestive system provides nutrients to the heart muscle and vascular tissue to support their functioning. The interrelationship of the digestive and endocrine systems is also critical. Hormones secreted by several endocrine glands, as well as endocrine cells of the pancreas, the stomach, and the small intestine, contribute to the control of digestion and nutrient metabolism. In turn, the digestive system provides the nutrients to fuel endocrine function. Table 23.1 gives a quick glimpse at how these other systems contribute to the functioning of the digestive system. Contribution of Other Body Systems to the Digestive System \| Body system \| Benefits received by the digestive system \| \|---\|---\| \| Cardiovascular \| Blood supplies digestive organs with oxygen and processed nutrients \| \| Endocrine \| Endocrine hormones help regulate secretion in digestive glands and accessory organs \| \| Integumentary \| Skin helps protect digestive organs and synthesizes vitamin D for calcium absorption \| \| Lymphatic \| Mucosa-associated lymphoid tissue and other lymphatic tissue defend against entry of pathogens; lacteals absorb lipids; and lymphatic vessels transport lipids to bloodstream \| \| Muscular \| Skeletal muscles support and protect abdominal organs \| \| Nervous \| Sensory and motor neurons help regulate secretions and muscle contractions in the digestive tract \| \| Respiratory \| Respiratory organs provide oxygen and remove carbon dioxide \| \| Skeletal \| Bones help protect and support digestive organs \| \| Urinary \| Kidneys convert vitamin D into its active form, allowing calcium absorption in the small intestine \| Table 23.1 Digestive System Organs The easiest way to understand the digestive system is to divide its organs into two main categories. The first group is the organs that make up the alimentary canal. Accessory digestive organs comprise the second group and are critical for orchestrating the breakdown of food and the assimilation of its nutrients into the body. Accessory digestive organs, despite their name, are critical to the function of the digestive system. Alimentary Canal Organs Also called the gastrointestinal (GI) tract or gut, the alimentary canal (aliment- = “to nourish”) is a one-way tube about 7.62 meters (25 feet) in length during life and closer to 10.67 meters (35 feet) in length when measured after death, once smooth muscle tone is lost. The main function of the organs of the alimentary canal is to nourish the body. This tube begins at the mouth and terminates at the anus. Between those two points, the canal is modified as the pharynx, esophagus, stomach, and small and large intestines to fit the functional needs of the body. Both the mouth and anus are open to the external environment; thus, food and wastes within the alimentary canal are technically considered to be outside the body. Only through the process of absorption do the nutrients in food enter into and nourish the body’s “inner space.” Accessory Structures Each accessory digestive organ aids in the breakdown of food (Figure 23.3). Within the mouth, the teeth and tongue begin mechanical digestion, whereas the salivary glands begin chemical digestion. Once food products enter the small intestine, the gallbladder, liver, and pancreas release secretions—such as bile and enzymes—essential for digestion to continue. Together, these are called accessory organs because they sprout from the lining cells of the developing gut (mucosa) and augment its function; indeed, you could not live without their vital contributions, and many significant diseases result from their malfunction. Even after development is complete, they maintain a connection to the gut by way of ducts. Histology of the Alimentary Canal Throughout its length, the alimentary tract is composed of the same four tissue layers; the details of their structural arrangements vary to fit their specific functions. Starting from the lumen and moving outwards, these layers are the mucosa, submucosa, muscularis, and serosa, which is continuous with the mesentery (see Figure 23.3). Figure 23.3 Layers of the Alimentary Canal The wall of the alimentary canal has four basic tissue layers: the mucosa, submucosa, muscularis, and serosa. The mucosa is referred to as a mucous membrane, because mucus production is a characteristic feature of gut epithelium. The membrane consists of epithelium, which is in direct contact with ingested food, and the lamina propria, a layer of connective tissue analogous to the dermis. In addition, the mucosa has a thin, smooth muscle layer, called the muscularis mucosa (not to be confused with the muscularis layer, described below). Epithelium—In the mouth, pharynx, esophagus, and anal canal, the epithelium is primarily a non-keratinized, stratified squamous epithelium. In the stomach and intestines, it is a simple columnar epithelium. Notice that the epithelium is in direct contact with the lumen, the space inside the alimentary canal. Interspersed among its epithelial cells are goblet cells, which secrete mucus and fluid into the lumen, and enteroendocrine cells, which secrete hormones into the interstitial spaces between cells. Epithelial cells have a very brief lifespan, averaging from only a couple of days (in the mouth) to about a week (in the gut). This process of rapid renewal helps preserve the health of the alimentary canal, despite the wear and tear resulting from continued contact with foodstuffs. Lamina propria—In addition to loose connective tissue, the lamina propria contains numerous blood and lymphatic vessels that transport nutrients absorbed through the alimentary canal to other parts of the body. The lamina propria also serves an immune function by housing clusters of lymphocytes, making up the mucosa-associated lymphoid tissue (MALT). These lymphocyte clusters are particularly substantial in the distal ileum where they are known as Peyer’s patches. When you consider that the alimentary canal is exposed to foodborne bacteria and other foreign matter, it is not hard to appreciate why the immune system has evolved a means of defending against the pathogens encountered within it. Muscularis mucosa—This thin layer of smooth muscle is in a constant state of tension, pulling the mucosa of the stomach and small intestine into undulating folds. These folds dramatically increase the surface area available for digestion and absorption. As its name implies, the submucosa lies immediately beneath the mucosa. A broad layer of dense connective tissue, it connects the overlying mucosa to the underlying muscularis. It includes blood and lymphatic vessels (which transport absorbed nutrients), and a scattering of submucosal glands that release digestive secretions. Additionally, it serves as a conduit for a dense branching network of nerves, the submucosal plexus, which functions as described below. The third layer of the alimentary canal is the muscularis (also called the muscularis externa). The muscularis in the small intestine is made up of a double layer of smooth muscle: an inner circular layer and an outer longitudinal layer. The contractions of these layers promote mechanical digestion, expose more of the food to digestive chemicals, and move the food along the canal. In the most proximal and distal regions of the alimentary canal, including the mouth, pharynx, anterior part of the esophagus, and external anal sphincter, the muscularis is made up of skeletal muscle, which gives you voluntary control over swallowing and defecation. The basic two-layer structure found in the small intestine is modified in the organs proximal and distal to it. The stomach is equipped for its churning function by the addition of a third layer, the oblique muscle. While the colon has two layers like the small intestine, its longitudinal layer is segregated into three narrow parallel bands, the tenia coli, which make it look like a series of pouches rather than a simple tube. The serosa is the portion of the alimentary canal superficial to the muscularis. Present only in the region of the alimentary canal within the abdominal cavity, it consists of a layer of visceral peritoneum overlying a layer of loose connective tissue. Instead of serosa, the mouth, pharynx, and esophagus have a dense sheath of collagen fibers called the adventitia. These tissues serve to hold the alimentary canal in place near the ventral surface of the vertebral column. Nerve Supply As soon as food enters the mouth, it is detected by receptors that send impulses along the sensory neurons of cranial nerves. Without these nerves, not only would your food be without taste, but you would also be unable to feel either the food or the structures of your mouth, and you would be unable to avoid biting yourself as you chew, an action enabled by the motor branches of cranial nerves. Intrinsic innervation of much of the alimentary canal is provided by the enteric nervous system, which runs from the esophagus to the anus, and contains approximately 100 million motor, sensory, and interneurons (unique to this system compared to all other parts of the peripheral nervous system). These enteric neurons are grouped into two plexuses. The myenteric plexus(plexus of Auerbach) lies in the muscularis layer of the alimentary canal and is responsible for motility, especially the rhythm and force of the contractions of the muscularis. The submucosal plexus (plexus of Meissner) lies in the submucosal layer and is responsible for regulating digestive secretions and reacting to the presence of food (see Figure 23.3). Extrinsic innervations of the alimentary canal are provided by the autonomic nervous system, which includes both sympathetic and parasympathetic nerves. In general, sympathetic activation (the fight-or-flight response) restricts the activity of enteric neurons, thereby decreasing GI secretion and motility. In contrast, parasympathetic activation (the rest-and-digest response) increases GI secretion and motility by stimulating neurons of the enteric nervous system. Blood Supply The blood vessels serving the digestive system have two functions. They transport the protein and carbohydrate nutrients absorbed by mucosal cells after food is digested in the lumen. Lipids are absorbed via lacteals, tiny structures of the lymphatic system. The blood vessels’ second function is to supply the organs of the alimentary canal with the nutrients and oxygen needed to drive their cellular processes. Specifically, the more anterior parts of the alimentary canal are supplied with blood by arteries branching off the aortic arch and thoracic aorta. Below this point, the alimentary canal is supplied with blood by arteries branching from the abdominal aorta. The celiac trunk services the liver, stomach, and duodenum, whereas the superior and inferior mesenteric arteries supply blood to the remaining small and large intestines. The veins that collect nutrient-rich blood from the small intestine (where most absorption occurs) empty into the hepatic portal system. This venous network takes the blood into the liver where the nutrients are either processed or stored for later use. Only then does the blood drained from the alimentary canal viscera circulate back to the heart. To appreciate just how demanding the digestive process is on the cardiovascular system, consider that while you are “resting and digesting,” about one-fourth of the blood pumped with each heartbeat enters arteries serving the intestines. The Peritoneum The digestive organs within the abdominal cavity are held in place by the peritoneum, a broad serous membranous sac made up of squamous epithelial tissue surrounded by connective tissue. It is composed of two different regions: the parietal peritoneum, which lines the abdominal wall, and the visceral peritoneum, which envelopes the abdominal organs (Figure 23.4). The peritoneal cavity is the space bounded by the visceral and parietal peritoneal surfaces. A few milliliters of watery fluid act as a lubricant to minimize friction between the serosal surfaces of the peritoneum. Figure 23.4 The Peritoneum A cross-section of the abdomen shows the relationship between abdominal organs and the peritoneum (darker lines). DISORDERS OF THE... Digestive System: Peritonitis Inflammation of the peritoneum is called peritonitis. Chemical peritonitis can develop any time the wall of the alimentary canal is breached, allowing the contents of the lumen entry into the peritoneal cavity. For example, when an ulcer perforates the stomach wall, gastric juices spill into the peritoneal cavity. Hemorrhagic peritonitis occurs after a ruptured tubal pregnancy or traumatic injury to the liver or spleen fills the peritoneal cavity with blood. Even more severe peritonitis is associated with bacterial infections seen with appendicitis, colonic diverticulitis, and pelvic inflammatory disease (infection of uterine tubes, usually by sexually transmitted bacteria). Peritonitis is life threatening and often results in emergency surgery to correct the underlying problem and intensive antibiotic therapy. When your great grandparents and even your parents were young, the mortality from peritonitis was high. Aggressive surgery, improvements in anesthesia safety, the advance of critical care expertise, and antibiotics have greatly improved the mortality rate from this condition. Even so, the mortality rate still ranges from 30 to 40 percent. The visceral peritoneum includes multiple large folds that envelope various abdominal organs, holding them to the dorsal surface of the body wall. Within these folds are blood vessels, lymphatic vessels, and nerves that innervate the organs with which they are in contact, supplying their adjacent organs. The five major peritoneal folds are described in Table 23.2. Note that during fetal development, certain digestive structures, including the first portion of the small intestine (called the duodenum), the pancreas, and portions of the large intestine (the ascending and descending colon, and the rectum) remain completely or partially posterior to the peritoneum. Thus, the location of these organs is described as retroperitoneal. The Five Major Peritoneal Folds \| Fold \| Description \| \|---\|---\| \| Greater omentum \| Apron-like structure that lies superficial to the small intestine and transverse colon; a site of fat deposition in people who are overweight \| \| Falciform ligament \| Anchors the liver to the anterior abdominal wall and inferior border of the diaphragm \| \| Lesser omentum \| Suspends the stomach from the inferior border of the liver; provides a pathway for structures connecting to the liver \| \| Mesentery \| Vertical band of tissue anterior to the lumbar vertebrae and anchoring all of the small intestine except the initial portion (the duodenum) \| \| Mesocolon \| Attaches two portions of the large intestine (the transverse and sigmoid colon) to the posterior abdominal wall \| Table 23.2 INTERACTIVE LINK By clicking on this link you can watch a short video of what happens to the food you eat, as it passes from your mouth to your intestine. Along the way, note how the food changes consistency and form. How does this change in consistency facilitate your gaining nutrients from food? Digestive System Processes and Regulation - Discuss six fundamental activities of the digestive system, giving an example of each - Compare and contrast the neural and hormonal controls involved in digestion The digestive system uses mechanical and chemical activities to break food down into absorbable substances during its journey through the digestive system. Table 23.3 provides an overview of the basic functions of the digestive organs. INTERACTIVE LINK Visit this site for an overview of digestion of food in different regions of the digestive tract. Note the route of non-fat nutrients from the small intestine to their release as nutrients to the body. Functions of the Digestive Organs \| Organ \| Major functions \| Other functions \| \|---\|---\|---\| \| Mouth \| \| \| \| Pharynx \| \| \| \| Esophagus \| \| \| \| Stomach \| \| \| \| Small intestine \| \| \| \| Accessory organs \| \| \| \| Large intestine \| \| \| Table 23.3 Digestive Processes The processes of digestion include six activities: ingestion, propulsion, mechanical or physical digestion, chemical digestion, absorption, and defecation. The first of these processes, ingestion, refers to the entry of food into the alimentary canal through the mouth. There, the food is chewed and mixed with saliva, which contains enzymes that begin breaking down the carbohydrates in the food plus some lipid digestion via lingual lipase. Chewing increases the surface area of the food and allows an appropriately sized bolus to be produced. Food leaves the mouth when the tongue and pharyngeal muscles propel it into the esophagus. This act of swallowing, the last voluntary act until defecation, is an example of propulsion, which refers to the movement of food through the digestive tract. It includes both the voluntary process of swallowing and the involuntary process of peristalsis. Peristalsis consists of sequential, alternating waves of contraction and relaxation of alimentary wall smooth muscles, which act to propel food along (Figure 23.5). These waves also play a role in mixing food with digestive juices. Peristalsis is so powerful that foods and liquids you swallow enter your stomach even if you are standing on your head. Figure 23.5 Peristalsis Peristalsis moves food through the digestive tract with alternating waves of muscle contraction and relaxation. Digestion includes both mechanical and chemical processes. Mechanical digestion is a purely physical process that does not change the chemical nature of the food. Instead, it makes the food smaller to increase both surface area and mobility. It includes mastication, or chewing, as well as tongue movements that help break food into smaller bits and mix food with saliva. Although there may be a tendency to think that mechanical digestion is limited to the first steps of the digestive process, it occurs after the food leaves the mouth, as well. The mechanical churning of food in the stomach serves to further break it apart and expose more of its surface area to digestive juices, creating an acidic “soup” called chyme. Segmentation, which occurs mainly in the small intestine, consists of localized contractions of circular muscle of the muscularis layer of the alimentary canal. These contractions isolate small sections of the intestine, moving their contents back and forth while continuously subdividing, breaking up, and mixing the contents. By moving food back and forth in the intestinal lumen, segmentation mixes food with digestive juices and facilitates absorption. In chemical digestion, starting in the mouth, digestive secretions break down complex food molecules into their chemical building blocks (for example, proteins into separate amino acids). These secretions vary in composition, but typically contain water, various enzymes, acids, and salts. The process is completed in the small intestine. Food that has been broken down is of no value to the body unless it enters the bloodstream and its nutrients are put to work. This occurs through the process of absorption, which takes place primarily within the small intestine. There, most nutrients are absorbed from the lumen of the alimentary canal into the bloodstream through the epithelial cells that make up the mucosa. Lipids are absorbed into lacteals and are transported via the lymphatic vessels to the bloodstream (the subclavian veins near the heart). The details of these processes will be discussed later. In defecation, the final step in digestion, undigested materials are removed from the body as feces. AGING AND THE... Digestive System: From Appetite Suppression to Constipation Age-related changes in the digestive system begin in the mouth and can affect virtually every aspect of the digestive system. Taste buds become less sensitive, so food isn’t as appetizing as it once was. A slice of pizza is a challenge, not a treat, when you have lost teeth, your gums are diseased, and your salivary glands aren’t producing enough saliva. Swallowing can be difficult, and ingested food moves slowly through the alimentary canal because of reduced strength and tone of muscular tissue. Neurosensory feedback is also dampened, slowing the transmission of messages that stimulate the release of enzymes and hormones. Pathologies that affect the digestive organs—such as hiatal hernia, gastritis, and peptic ulcer disease—can occur at greater frequencies as you age. Problems in the small intestine may include duodenal ulcers, maldigestion, and malabsorption. Problems in the large intestine include hemorrhoids, diverticular disease, and constipation. Conditions that affect the function of accessory organs—and their abilities to deliver pancreatic enzymes and bile to the small intestine—include jaundice, acute pancreatitis, cirrhosis, and gallstones. In some cases, a single organ is in charge of a digestive process. For example, ingestion occurs only in the mouth and defecation only in the anus. However, most digestive processes involve the interaction of several organs and occur gradually as food moves through the alimentary canal (Figure 23.6). Figure 23.6 Digestive Processes The digestive processes are ingestion, propulsion, mechanical digestion, chemical digestion, absorption, and defecation. Some chemical digestion occurs in the mouth. Some absorption can occur in the mouth and stomach, for example, alcohol and aspirin. Regulatory Mechanisms Neural and endocrine regulatory mechanisms work to maintain the optimal conditions in the lumen needed for digestion and absorption. These regulatory mechanisms, which stimulate digestive activity through mechanical and chemical activity, are controlled both extrinsically and intrinsically. Neural Controls The walls of the alimentary canal contain a variety of sensors that help regulate digestive functions. These include mechanoreceptors, chemoreceptors, and osmoreceptors, which are capable of detecting mechanical, chemical, and osmotic stimuli, respectively. For example, these receptors can sense when the presence of food has caused the stomach to expand, whether food particles have been sufficiently broken down, how much liquid is present, and the type of nutrients in the food (lipids, carbohydrates, and/or proteins). Stimulation of these receptors provokes an appropriate reflex that furthers the process of digestion. This may entail sending a message that activates the glands that secrete digestive juices into the lumen, or it may mean the stimulation of muscles within the alimentary canal, thereby activating peristalsis and segmentation that move food along the intestinal tract. The walls of the entire alimentary canal are embedded with nerve plexuses that interact with the central nervous system and other nerve plexuses—either within the same digestive organ or in different ones. These interactions prompt several types of reflexes. Extrinsic nerve plexuses orchestrate long reflexes, which involve the central and autonomic nervous systems and work in response to stimuli from outside the digestive system. Short reflexes, on the other hand, are orchestrated by intrinsic nerve plexuses within the alimentary canal wall. These two plexuses and their connections were introduced earlier as the enteric nervous system. Short reflexes regulate activities in one area of the digestive tract and may coordinate local peristaltic movements and stimulate digestive secretions. For example, the sight, smell, and taste of food initiate long reflexes that begin with a sensory neuron delivering a signal to the medulla oblongata. The response to the signal is to stimulate cells in the stomach to begin secreting digestive juices in preparation for incoming food. In contrast, food that distends the stomach initiates short reflexes that cause cells in the stomach wall to increase their secretion of digestive juices. Hormonal Controls A variety of hormones are involved in the digestive process. The main digestive hormone of the stomach is gastrin, which is secreted in response to the presence of food. Gastrin stimulates the secretion of gastric acid by the parietal cells of the stomach mucosa. Other GI hormones are produced and act upon the gut and its accessory organs. Hormones produced by the duodenum include secretin, which stimulates a watery secretion of bicarbonate by the pancreas; cholecystokinin (CCK), which stimulates the secretion of pancreatic enzymes and bile from the liver and release of bile from the gallbladder; and gastric inhibitory peptide, which inhibits gastric secretion and slows gastric emptying and motility. These GI hormones are secreted by specialized epithelial cells, called endocrinocytes, located in the mucosal epithelium of the stomach and small intestine. These hormones then enter the bloodstream, through which they can reach their target organs. The Mouth, Pharynx, and Esophagus - Describe the structures of the mouth, including its three accessory digestive organs - Group the 32 adult teeth according to name, location, and function - Describe the process of swallowing, including the roles of the tongue, upper esophageal sphincter, and epiglottis - Trace the pathway food follows from ingestion into the mouth through release into the stomach In this section, you will examine the anatomy and functions of the three main organs of the upper alimentary canal—the mouth, pharynx, and esophagus—as well as three associated accessory organs—the tongue, salivary glands, and teeth. The Mouth The cheeks, tongue, and palate frame the mouth, which is also called the oral cavity (or buccal cavity). The structures of the mouth are illustrated in Figure 23.7. At the entrance to the mouth are the lips, or labia (singular = labium). Their outer covering is skin, which transitions to a mucous membrane in the mouth proper. Lips are very vascular with a thin layer of keratin; hence, the reason they are "red." They have a huge representation on the cerebral cortex, which probably explains the human fascination with kissing! The lips cover the orbicularis oris muscle, which regulates what comes in and goes out of the mouth. The labial frenulum is a midline fold of mucous membrane that attaches the inner surface of each lip to the gum. The cheeks make up the oral cavity’s sidewalls. While their outer covering is skin, their inner covering is mucous membrane. This membrane is made up of non-keratinized, stratified squamous epithelium. Between the skin and mucous membranes are connective tissue and buccinator muscles. The next time you eat some food, notice how the buccinator muscles in your cheeks and the orbicularis oris muscle in your lips contract, helping you keep the food from falling out of your mouth. Additionally, notice how these muscles work when you are speaking. The pocket-like part of the mouth that is framed on the inside by the gums and teeth, and on the outside by the cheeks and lips is called the oral vestibule. Moving farther into the mouth, the opening between the oral cavity and throat (oropharynx) is called the fauces (like the kitchen "faucet"). The main open area of the mouth, or oral cavity proper, runs from the gums and teeth to the fauces. When you are chewing, you do not find it difficult to breathe simultaneously. The next time you have food in your mouth, notice how the arched shape of the roof of your mouth allows you to handle both digestion and respiration at the same time. This arch is called the palate. The anterior region of the palate serves as a wall (or septum) between the oral and nasal cavities as well as a rigid shelf against which the tongue can push food. It is created by the maxillary and palatine bones of the skull and, given its bony structure, is known as the hard palate. If you run your tongue along the roof of your mouth, you’ll notice that the hard palate ends in the posterior oral cavity, and the tissue becomes fleshier. This part of the palate, known as the soft palate, is composed mainly of skeletal muscle. You can therefore manipulate, subconsciously, the soft palate—for instance, to yawn, swallow, or sing (see Figure 23.7). Figure 23.7 Mouth The mouth includes the lips, tongue, palate, gums, and teeth. A fleshy bead of tissue called the uvula drops down from the center of the posterior edge of the soft palate. Although some have suggested that the uvula is a vestigial organ, it serves an important purpose. When you swallow, the soft palate and uvula move upward, helping to keep foods and liquid from entering the nasal cavity. Unfortunately, it can also contribute to the sound produced by snoring. Two muscular folds extend downward from the soft palate, on either side of the uvula. Toward the front, the palatoglossal arch lies next to the base of the tongue; behind it, the palatopharyngeal arch forms the superior and lateral margins of the fauces. Between these two arches are the palatine tonsils, clusters of lymphoid tissue that protect the pharynx. The lingual tonsils are located at the base of the tongue. The Tongue Perhaps you have heard it said that the tongue is the strongest muscle in the body. Those who stake this claim cite its strength proportionate to its size. Although it is difficult to quantify the relative strength of different muscles, it remains indisputable that the tongue is a workhorse, facilitating ingestion, mechanical digestion, chemical digestion (lingual lipase), sensation (of taste, texture, and temperature of food), swallowing, and vocalization. The tongue is attached to the mandible, the styloid processes of the temporal bones, and the hyoid bone. The hyoid is unique in that it only distantly/indirectly articulates with other bones. The tongue is positioned over the floor of the oral cavity. A medial septum extends the entire length of the tongue, dividing it into symmetrical halves. Beneath its mucous membrane covering, each half of the tongue is composed of the same number and type of intrinsic and extrinsic skeletal muscles. The intrinsic muscles (those within the tongue) are the longitudinalis inferior, longitudinalis superior, transversus linguae, and verticalis linguae muscles. These allow you to change the size and shape of your tongue, as well as to stick it out, if you wish. Having such a flexible tongue facilitates both swallowing and speech. As you learned in your study of the muscular system, the extrinsic muscles of the tongue are the mylohyoid, hyoglossus, styloglossus, and genioglossus muscles. These muscles originate outside the tongue and insert into connective tissues within the tongue. The mylohyoid is responsible for raising the tongue, the hyoglossus pulls it down and back, the styloglossus pulls it up and back, and the genioglossus pulls it forward. Working in concert, these muscles perform three important digestive functions in the mouth: (1) position food for optimal chewing, (2) gather food into a bolus (rounded mass), and (3) position food so it can be swallowed. The top and sides of the tongue are studded with papillae, extensions of lamina propria of the mucosa, which are covered in stratified squamous epithelium (Figure 23.8). Fungiform papillae, which are mushroom shaped, cover a large area of the tongue; they tend to be larger toward the rear of the tongue and smaller on the tip and sides. In contrast, filiform papillae are long and thin. Fungiform papillae contain taste buds, and filiform papillae have touch receptors that help the tongue move food around in the mouth. The filiform papillae create an abrasive surface that performs mechanically, much like a cat’s rough tongue that is used for grooming. Lingual glands in the lamina propria of the tongue secrete mucus and a watery serous fluid that contains the enzyme lingual lipase, which plays a minor role in breaking down triglycerides but does not begin working until it is activated in the stomach. A fold of mucous membrane on the underside of the tongue, the lingual frenulum, tethers the tongue to the floor of the mouth. People with the congenital anomaly ankyloglossia, also known by the non-medical term “tongue tie,” have a lingual frenulum that is too short or otherwise malformed. Severe ankyloglossia can impair speech and must be corrected with surgery. Figure 23.8 Tongue This superior view of the tongue shows the locations and types of lingual papillae. The Salivary Glands Many small salivary glands are housed within the mucous membranes of the mouth and tongue. These minor exocrine glands are constantly secreting saliva, either directly into the oral cavity or indirectly through ducts, even while you sleep. In fact, an average of 1 to 1.5 liters of saliva is secreted each day. Usually just enough saliva is present to moisten the mouth and teeth. Secretion increases when you eat, because saliva is essential to moisten food and initiate the chemical breakdown of carbohydrates. Small amounts of saliva are also secreted by the labial glands in the lips. In addition, the buccal glands in the cheeks, palatal glands in the palate, and lingual glands in the tongue help ensure that all areas of the mouth are supplied with adequate saliva. The Major Salivary Glands Outside the oral mucosa are three pairs of major salivary glands, which secrete the majority of saliva into ducts that open into the mouth: - The submandibular glands, which are in the floor of the mouth, secrete saliva into the mouth through the submandibular ducts. - The sublingual glands, which lie below the tongue, use the lesser sublingual ducts to secrete saliva into the oral cavity. - The parotid glands lie between the skin and the masseter muscle, near the ears. They secrete saliva into the mouth through the parotid duct, which is located near the second upper molar tooth (Figure 23.9). Saliva Saliva is essentially (98 to 99.5 percent) water. The remaining 4.5 percent is a complex mixture of ions, glycoproteins, enzymes, growth factors, and waste products. Perhaps the most important ingredient in saliva from the perspective of digestion is the enzyme salivary amylase, which initiates the breakdown of carbohydrates. Food does not spend enough time in the mouth to allow all the carbohydrates to break down, but salivary amylase continues acting until it is inactivated by stomach acids. Bicarbonate and phosphate ions function as chemical buffers, maintaining saliva at a pH between 6.35 and 6.85. Salivary mucus helps lubricate food, facilitating movement in the mouth, bolus formation, and swallowing. Saliva contains immunoglobulin A, which prevents microbes from penetrating the epithelium, and lysozyme, which makes saliva antimicrobial. Saliva also contains epidermal growth factor, which might have given rise to the adage “a mother’s kiss can heal a wound.” Each of the major salivary glands secretes a unique formulation of saliva according to its cellular makeup. For example, the parotid glands secrete a watery solution that contains salivary amylase. The submandibular glands have cells similar to those of the parotid glands, as well as mucus-secreting cells. Therefore, saliva secreted by the submandibular glands also contains amylase but in a liquid thickened with mucus. The sublingual glands contain mostly mucous cells, and they secrete the thickest saliva with the least amount of salivary amylase. Figure 23.9 Salivary glands The major salivary glands are located outside the oral mucosa and deliver saliva into the mouth through ducts. HOMEOSTATIC IMBALANCES The Parotid Glands: Mumps Infections of the nasal passages and pharynx can attack any salivary gland. The parotid glands are the usual site of infection with the virus that causes mumps (paramyxovirus). Mumps manifests by enlargement and inflammation of the parotid glands, causing a characteristic swelling between the ears and the jaw. Symptoms include fever and throat pain, which can be severe when swallowing acidic substances such as orange juice. In about one-third of men who are past puberty, mumps also causes testicular inflammation, typically affecting only one testis and rarely resulting in sterility. With the increasing use and effectiveness of mumps vaccines, the incidence of mumps has decreased dramatically. According to the U.S. Centers for Disease Control and Prevention (CDC), the number of mumps cases dropped from more than 150,000 in 1968 to fewer than 1700 in 1993 to only 11 reported cases in 2011. Regulation of Salivation The autonomic nervous system regulates salivation (the secretion of saliva). In the absence of food, parasympathetic stimulation keeps saliva flowing at just the right level for comfort as you speak, swallow, sleep, and generally go about life. Over-salivation can occur, for example, if you are stimulated by the smell of food, but that food is not available for you to eat. Drooling is an extreme instance of the overproduction of saliva. During times of stress, such as before speaking in public, sympathetic stimulation takes over, reducing salivation and producing the symptom of dry mouth often associated with anxiety. When you are dehydrated, salivation is reduced, causing the mouth to feel dry and prompting you to take action to quench your thirst. Salivation can be stimulated by the sight, smell, and taste of food. It can even be stimulated by thinking about food. You might notice whether reading about food and salivation right now has had any effect on your production of saliva. How does the salivation process work while you are eating? Food contains chemicals that stimulate taste receptors on the tongue, which send impulses to the superior and inferior salivatory nuclei in the brain stem. These two nuclei then send back parasympathetic impulses through fibers in the glossopharyngeal and facial nerves, which stimulate salivation. Even after you swallow food, salivation is increased to cleanse the mouth and to water down and neutralize any irritating chemical remnants, such as that hot sauce in your burrito. Most saliva is swallowed along with food and is reabsorbed, so that fluid is not lost. The Teeth The teeth, or dentes (singular = dens), are organs similar to bones that you use to tear, grind, and otherwise mechanically break down food. Types of Teeth During the course of your lifetime, you have two sets of teeth (one set of teeth is a dentition). Your 20 deciduous teeth, or baby teeth, first begin to appear at about 6 months of age. Between approximately age 6 and 12, these teeth are replaced by 32 permanent teeth. Moving from the center of the mouth toward the side, these are as follows (Figure 23.10): - The eight incisors, four top and four bottom, are the sharp front teeth you use for biting into food. - The four cuspids (or canines) flank the incisors and have a pointed edge (cusp) to tear up food. These fang-like teeth are superb for piercing tough or fleshy foods. - Posterior to the cuspids are the eight premolars (or bicuspids), which have an overall flatter shape with two rounded cusps useful for mashing foods. - The most posterior and largest are the 12 molars, which have several pointed cusps used to crush food so it is ready for swallowing. The third members of each set of three molars, top and bottom, are commonly referred to as the wisdom teeth, because their eruption is commonly delayed until early adulthood. It is not uncommon for wisdom teeth to fail to erupt; that is, they remain impacted. In these cases, the teeth are typically removed by orthodontic surgery. Figure 23.10 Permanent and Deciduous Teeth This figure of two human dentitions shows the arrangement of teeth in the maxilla and mandible, and the relationship between the deciduous and permanent teeth. Anatomy of a Tooth The teeth are secured in the alveolar processes (sockets) of the maxilla and the mandible. Gingivae (commonly called the gums) are soft tissues that line the alveolar processes and surround the necks of the teeth. Teeth are also held in their sockets by a connective tissue called the periodontal ligament. The two main parts of a tooth are the crown, which is the portion projecting above the gum line, and the root, which is embedded within the maxilla and mandible. Both parts contain an inner pulp cavity, containing loose connective tissue through which run nerves and blood vessels. The region of the pulp cavity that runs through the root of the tooth is called the root canal. Surrounding the pulp cavity is dentin, a bone-like tissue. In the root of each tooth, the dentin is covered by an even harder bone-like layer called cementum. In the crown of each tooth, the dentin is covered by an outer layer of enamel, the hardest substance in the body (Figure 23.11). Although enamel protects the underlying dentin and pulp cavity, it is still nonetheless susceptible to mechanical and chemical erosion, or what is known as tooth decay. The most common form, dental caries (cavities) develops when colonies of bacteria feeding on sugars in the mouth release acids that cause soft tissue inflammation and degradation of the calcium crystals of the enamel. The digestive functions of the mouth are summarized in Table 23.4. Figure 23.11 The Structure of the Tooth This longitudinal section through a molar in its alveolar socket shows the relationships between enamel, dentin, and pulp. Digestive Functions of the Mouth \| Structure \| Action \| Outcome \| \|---\|---\|---\| \| Lips and cheeks \| Confine food between teeth \| \| \| Salivary glands \| Secrete saliva \| \| \| Tongue’s extrinsic muscles \| Move tongue sideways, and in and out \| \| \| Tongue’s intrinsic muscles \| Change tongue shape \| \| \| Taste buds \| Sense food in mouth and sense taste \| \| \| Lingual glands \| Secrete lingual lipase \| \| \| Teeth \| Shred and crush food \| \| Table 23.4 The Pharynx The pharynx (throat) is involved in both digestion and respiration. It receives food and air from the mouth, and air from the nasal cavities. When food enters the pharynx, involuntary muscle contractions close off the air passageways. A short tube of skeletal muscle lined with a mucous membrane, the pharynx runs from the posterior oral and nasal cavities to the opening of the esophagus and larynx. It has three subdivisions. The most superior, the nasopharynx, is involved only in breathing and speech. The other two subdivisions, the oropharynx and the laryngopharynx, are used for both breathing and digestion. The oropharynx begins inferior to the nasopharynx and is continuous below with the laryngopharynx (Figure 23.12). The inferior border of the laryngopharynx connects to the esophagus, whereas the anterior portion connects to the larynx, allowing air to flow into the bronchial tree. Figure 23.12 Pharynx The pharynx runs from the nostrils to the esophagus and the larynx. Histologically, the wall of the oropharynx is similar to that of the oral cavity. The mucosa includes a stratified squamous epithelium that is endowed with mucus-producing glands. During swallowing, the elevator skeletal muscles of the pharynx contract, raising and expanding the pharynx to receive the bolus of food. Once received, these muscles relax and the constrictor muscles of the pharynx contract, forcing the bolus into the esophagus and initiating peristalsis. Usually during swallowing, the soft palate and uvula rise reflexively to close off the entrance to the nasopharynx. At the same time, the larynx is pulled superiorly and the cartilaginous epiglottis, its most superior structure, folds inferiorly, covering the glottis (the opening to the larynx); this process effectively blocks access to the trachea and bronchi. When the food “goes down the wrong way,” it goes into the trachea. When food enters the trachea, the reaction is to cough, which usually forces the food up and out of the trachea, and back into the pharynx. The Esophagus The esophagus is a muscular tube that connects the pharynx to the stomach. It is approximately 25.4 cm (10 in) in length, located posterior to the trachea, and remains in a collapsed form when not engaged in swallowing. As you can see in Figure 23.13, the esophagus runs a mainly straight route through the mediastinum of the thorax. To enter the abdomen, the esophagus penetrates the diaphragm through an opening called the esophageal hiatus. Passage of Food through the Esophagus The upper esophageal sphincter, which is continuous with the inferior pharyngeal constrictor, controls the movement of food from the pharynx into the esophagus. The upper two-thirds of the esophagus consists of both smooth and skeletal muscle fibers, with the latter fading out in the bottom third of the esophagus. Rhythmic waves of peristalsis, which begin in the upper esophagus, propel the bolus of food toward the stomach. Meanwhile, secretions from the esophageal mucosa lubricate the esophagus and food. Food passes from the esophagus into the stomach at the lower esophageal sphincter (also called the gastroesophageal or cardiac sphincter). Recall that sphincters are muscles that surround tubes and serve as valves, closing the tube when the sphincters contract and opening it when they relax. The lower esophageal sphincter relaxes to let food pass into the stomach, and then contracts to prevent stomach acids from backing up into the esophagus. Surrounding this sphincter is the muscular diaphragm, which helps close off the sphincter when no food is being swallowed. When the lower esophageal sphincter does not completely close, the stomach’s contents can reflux (that is, back up into the esophagus), causing heartburn or gastroesophageal reflux disease (GERD). Figure 23.13 Esophagus The upper esophageal sphincter controls the movement of food from the pharynx to the esophagus. The lower esophageal sphincter controls the movement of food from the esophagus to the stomach. Histology of the Esophagus The mucosa of the esophagus is made up of an epithelial lining that contains non-keratinized, stratified squamous epithelium, with a layer of basal and parabasal cells. This epithelium protects against erosion from food particles. The mucosa’s lamina propria contains mucus-secreting glands. The muscularis layer changes according to location: In the upper third of the esophagus, the muscularis is skeletal muscle. In the middle third, it is both skeletal and smooth muscle. In the lower third, it is smooth muscle. As mentioned previously, the most superficial layer of the esophagus is called the adventitia, not the serosa. In contrast to the stomach and intestines, the loose connective tissue of the adventitia is not covered by a fold of visceral peritoneum. The digestive functions of the esophagus are identified in Table 23.5. Digestive Functions of the Esophagus \| Action \| Outcome \| \|---\|---\| \| Upper esophageal sphincter relaxation \| Allows the bolus to move from the laryngopharynx to the esophagus \| \| Peristalsis \| Propels the bolus through the esophagus \| \| Lower esophageal sphincter relaxation \| Allows the bolus to move from the esophagus into the stomach and prevents chime from entering the esophagus \| \| Mucus secretion \| Lubricates the esophagus, allowing easy passage of the bolus \| Table 23.5 Deglutition Deglutition is another word for swallowing—the movement of food from the mouth to the stomach. The entire process takes about 4 to 8 seconds for solid or semisolid food, and about 1 second for very soft food and liquids. Although this sounds quick and effortless, deglutition is, in fact, a complex process that involves both the skeletal muscle of the tongue and the muscles of the pharynx and esophagus. It is aided by the presence of mucus and saliva. There are three stages in deglutition: the voluntary phase, the pharyngeal phase, and the esophageal phase (Figure 23.14). The autonomic nervous system controls the latter two phases. Figure 23.14 Deglutition Deglutition includes the voluntary phase and two involuntary phases: the pharyngeal phase and the esophageal phase. The Voluntary Phase The voluntary phase of deglutition (also known as the oral or buccal phase) is so called because you can control when you swallow food. In this phase, chewing has been completed and swallowing is set in motion. The tongue moves upward and backward against the palate, pushing the bolus to the back of the oral cavity and into the oropharynx. Other muscles keep the mouth closed and prevent food from falling out. At this point, the two involuntary phases of swallowing begin. The Pharyngeal Phase In the pharyngeal phase, stimulation of receptors in the oropharynx sends impulses to the deglutition center (a collection of neurons that controls swallowing) in the medulla oblongata. Impulses are then sent back to the uvula and soft palate, causing them to move upward and close off the nasopharynx. The laryngeal muscles also constrict to prevent aspiration of food into the trachea. At this point, deglutition apnea takes place, which means that breathing ceases for a very brief time. Contractions of the pharyngeal constrictor muscles move the bolus through the oropharynx and laryngopharynx. Relaxation of the upper esophageal sphincter then allows food to enter the esophagus. The Esophageal Phase The entry of food into the esophagus marks the beginning of the esophageal phase of deglutition and the initiation of peristalsis. As in the previous phase, the complex neuromuscular actions are controlled by the medulla oblongata. Peristalsis propels the bolus through the esophagus and toward the stomach. The circular muscle layer of the muscularis contracts, pinching the esophageal wall and forcing the bolus forward. At the same time, the longitudinal muscle layer of the muscularis also contracts, shortening this area and pushing out its walls to receive the bolus. In this way, a series of contractions keeps moving food toward the stomach. When the bolus nears the stomach, distention of the esophagus initiates a short reflex relaxation of the lower esophageal sphincter that allows the bolus to pass into the stomach. During the esophageal phase, esophageal glands secrete mucus that lubricates the bolus and minimizes friction. INTERACTIVE LINK Watch this animation to see how swallowing is a complex process that involves the nervous system to coordinate the actions of upper respiratory and digestive activities. During which stage of swallowing is there a risk of food entering respiratory pathways and how is this risk blocked? The Stomach - Label on a diagram the four main regions of the stomach, its curvatures, and its sphincter - Identify the four main types of secreting cells in gastric glands, and their important products - Explain why the stomach does not digest itself - Describe the mechanical and chemical digestion of food entering the stomach Although a minimal amount of carbohydrate digestion occurs in the mouth, chemical digestion really gets underway in the stomach. An expansion of the alimentary canal that lies immediately inferior to the esophagus, the stomach links the esophagus to the first part of the small intestine (the duodenum) and is relatively fixed in place at its esophageal and duodenal ends. In between, however, it can be a highly active structure, contracting and continually changing position and size. These contractions provide mechanical assistance to digestion. The empty stomach is only about the size of your fist, but can stretch to hold as much as 4 liters of food and fluid, or more than 75 times its empty volume, and then return to its resting size when empty. Although you might think that the size of a person’s stomach is related to how much food that individual consumes, body weight does not correlate with stomach size. Rather, when you eat greater quantities of food—such as at holiday dinner—you stretch the stomach more than when you eat less. Popular culture tends to refer to the stomach as the location where all digestion takes place. Of course, this is not true. An important function of the stomach is to serve as a temporary holding chamber. You can ingest a meal far more quickly than it can be digested and absorbed by the small intestine. Thus, the stomach holds food and parses only small amounts into the small intestine at a time. Foods are not processed in the order they are eaten; rather, they are mixed together with digestive juices in the stomach until they are converted into chyme, which is released into the small intestine. As you will see in the sections that follow, the stomach plays several important roles in chemical digestion, including the continued digestion of carbohydrates and the initial digestion of proteins and triglycerides. Little if any nutrient absorption occurs in the stomach, with the exception of the negligible amount of nutrients in alcohol. Structure There are four main regions in the stomach: the cardia, fundus, body, and pylorus (Figure 23.15). The cardia (or cardiac region) is the point where the esophagus connects to the stomach and through which food passes into the stomach. Located inferior to the diaphragm, above and to the left of the cardia, is the dome-shaped fundus. Below the fundus is the body, the main part of the stomach. The funnel-shaped pylorus connects the stomach to the duodenum. The wider end of the funnel, the pyloric antrum, connects to the body of the stomach. The narrower end is called the pyloric canal, which connects to the duodenum. The smooth muscle pyloric sphincter is located at this latter point of connection and controls stomach emptying. In the absence of food, the stomach deflates inward, and its mucosa and submucosa fall into a large fold called a ruga. Figure 23.15 Stomach The stomach has four major regions: the cardia, fundus, body, and pylorus. The addition of an inner oblique smooth muscle layer gives the muscularis the ability to vigorously churn and mix food. The convex lateral surface of the stomach is called the greater curvature; the concave medial border is the lesser curvature. The stomach is held in place by the lesser omentum, which extends from the liver to the lesser curvature, and the greater omentum, which runs from the greater curvature to the posterior abdominal wall. Histology The wall of the stomach is made of the same four layers as most of the rest of the alimentary canal, but with adaptations to the mucosa and muscularis for the unique functions of this organ. In addition to the typical circular and longitudinal smooth muscle layers, the muscularis has an inner oblique smooth muscle layer (Figure 23.16). As a result, in addition to moving food through the canal, the stomach can vigorously churn food, mechanically breaking it down into smaller particles. Figure 23.16 Histology of the Stomach The stomach wall is adapted for the functions of the stomach. In the epithelium, gastric pits lead to gastric glands that secrete gastric juice. The gastric glands (one gland is shown enlarged on the right) contain different types of cells that secrete a variety of enzymes, including hydrochloride acid, which activates the protein-digesting enzyme pepsin. The stomach mucosa’s epithelial lining consists only of surface mucus cells, which secrete a protective coat of alkaline mucus. A vast number of gastric pits dot the surface of the epithelium, giving it the appearance of a well-used pincushion, and mark the entry to each gastric gland, which secretes a complex digestive fluid referred to as gastric juice. Although the walls of the gastric pits are made up primarily of mucus cells, the gastric glands are made up of different types of cells. The glands of the cardia and pylorus are composed primarily of mucus-secreting cells. Cells that make up the pyloric antrum secrete mucus and a number of hormones, including the majority of the stimulatory hormone, gastrin. The much larger glands of the fundus and body of the stomach, the site of most chemical digestion, produce most of the gastric secretions. These glands are made up of a variety of secretory cells. These include parietal cells, chief cells, mucous neck cells, and enteroendocrine cells. Parietal cells—Located primarily in the middle region of the gastric glands are parietal cells, which are among the most highly differentiated of the body’s epithelial cells. These relatively large cells produce both hydrochloric acid (HCl) and intrinsic factor. HCl is responsible for the high acidity (pH 1.5 to 3.5) of the stomach contents and is needed to activate the protein-digesting enzyme, pepsin. The acidity also kills much of the bacteria you ingest with food and helps to denature proteins, making them more available for enzymatic digestion. Intrinsic factor is a glycoprotein necessary for the absorption of vitamin B12in the small intestine. Chief cells—Located primarily in the basal regions of gastric glands are chief cells, which secrete pepsinogen, the inactive proenzyme form of pepsin. HCl is necessary for the conversion of pepsinogen to pepsin. Mucous neck cells—Gastric glands in the upper part of the stomach contain mucous neck cells that secrete thin, acidic mucus that is much different from the mucus secreted by the goblet cells of the surface epithelium. The role of this mucus is not currently known. Enteroendocrine cells—Finally, enteroendocrine cells found in the gastric glands secrete various hormones into the interstitial fluid of the lamina propria. These include gastrin, which is released mainly by enteroendocrine G cells. Table 23.6 describes the digestive functions of important hormones secreted by the stomach. INTERACTIVE LINK Watch this animation that depicts the structure of the stomach and how this structure functions in the initiation of protein digestion. This view of the stomach shows the characteristic rugae. What is the function of these rugae? Hormones Secreted by the Stomach \| Hormone \| Production site \| Production stimulus \| Target organ \| Action \| \|---\|---\|---\|---\|---\| \| Gastrin \| Stomach mucosa, mainly G cells of the pyloric antrum \| Presence of peptides and amino acids in stomach \| Stomach \| Increases secretion by gastric glands; promotes gastric emptying \| \| Gastrin \| Stomach mucosa, mainly G cells of the pyloric antrum \| Presence of peptides and amino acids in stomach \| Small intestine \| Promotes intestinal muscle contraction \| \| Gastrin \| Stomach mucosa, mainly G cells of the pyloric antrum \| Presence of peptides and amino acids in stomach \| Ileocecal valve \| Relaxes valve \| \| Gastrin \| Stomach mucosa, mainly G cells of the pyloric antrum \| Presence of peptides and amino acids in stomach \| Large intestine \| Triggers mass movements \| \| Ghrelin \| Stomach mucosa, mainly fundus \| Fasting state (levels increase just prior to meals) \| Hypothalamus \| Regulates food intake, primarily by stimulating hunger and satiety \| \| Histamine \| Stomach mucosa \| Presence of food in the stomach \| Stomach \| Stimulates parietal cells to release HCl \| \| Serotonin \| Stomach mucosa \| Presence of food in the stomach \| Stomach \| Contracts stomach muscle \| \| Somatostatin \| Mucosa of stomach, especially pyloric antrum; also duodenum \| Presence of food in the stomach; sympathetic axon stimulation \| Stomach \| Restricts all gastric secretions, gastric motility, and emptying \| \| Somatostatin \| Mucosa of stomach, especially pyloric antrum; also duodenum \| Presence of food in the stomach; sympathetic axon stimulation \| Pancreas \| Restricts pancreatic secretions \| \| Somatostatin \| Mucosa of stomach, especially pyloric antrum; also duodenum \| Presence of food in the stomach; sympathetic axon stimulation \| Small intestine \| Reduces intestinal absorption by reducing blood flow \| Table 23.6 Gastric Secretion The secretion of gastric juice is controlled by both nerves and hormones. Stimuli in the brain, stomach, and small intestine activate or inhibit gastric juice production. This is why the three phases of gastric secretion are called the cephalic, gastric, and intestinal phases (Figure 23.17). However, once gastric secretion begins, all three phases can occur simultaneously. Figure 23.17 The Three Phases of Gastric Secretion Gastric secretion occurs in three phases: cephalic, gastric, and intestinal. During each phase, the secretion of gastric juice can be stimulated or inhibited. The cephalic phase (reflex phase) of gastric secretion, which is relatively brief, takes place before food enters the stomach. The smell, taste, sight, or thought of food triggers this phase. For example, when you bring a piece of sushi to your lips, impulses from receptors in your taste buds or the nose are relayed to your brain, which returns signals that increase gastric secretion to prepare your stomach for digestion. This enhanced secretion is a conditioned reflex, meaning it occurs only if you like or want a particular food. Depression and loss of appetite can suppress the cephalic reflex. The gastric phase of secretion lasts 3 to 4 hours, and is set in motion by local neural and hormonal mechanisms triggered by the entry of food into the stomach. For example, when your sushi reaches the stomach, it creates distention that activates the stretch receptors. This stimulates parasympathetic neurons to release acetylcholine, which then provokes increased secretion of gastric juice. Partially digested proteins, caffeine, and rising pH stimulate the release of gastrin from enteroendocrine G cells, which in turn induces parietal cells to increase their production of HCl, which is needed to create an acidic environment for the conversion of pepsinogen to pepsin, and protein digestion. Additionally, the release of gastrin activates vigorous smooth muscle contractions. However, it should be noted that the stomach does have a natural means of avoiding excessive acid secretion and potential heartburn. Whenever pH levels drop too low, cells in the stomach react by suspending HCl secretion and increasing mucous secretions. The intestinal phase of gastric secretion has both excitatory and inhibitory elements. The duodenum has a major role in regulating the stomach and its emptying. When partially digested food fills the duodenum, intestinal mucosal cells release a hormone called intestinal (enteric) gastrin, which further excites gastric juice secretion. This stimulatory activity is brief, however, because when the intestine distends with chyme, the enterogastric reflex inhibits secretion. One of the effects of this reflex is to close the pyloric sphincter, which blocks additional chyme from entering the duodenum. The Mucosal Barrier The mucosa of the stomach is exposed to the highly corrosive acidity of gastric juice. Gastric enzymes that can digest protein can also digest the stomach itself. The stomach is protected from self-digestion by the mucosal barrier. This barrier has several components. First, the stomach wall is covered by a thick coating of bicarbonate-rich mucus. This mucus forms a physical barrier, and its bicarbonate ions neutralize acid. Second, the epithelial cells of the stomach's mucosa meet at tight junctions, which block gastric juice from penetrating the underlying tissue layers. Finally, stem cells located where gastric glands join the gastric pits quickly replace damaged epithelial mucosal cells, when the epithelial cells are shed. In fact, the surface epithelium of the stomach is completely replaced every 3 to 6 days. HOMEOSTATIC IMBALANCES Ulcers: When the Mucosal Barrier Breaks Down As effective as the mucosal barrier is, it is not a “fail-safe” mechanism. Sometimes, gastric juice eats away at the superficial lining of the stomach mucosa, creating erosions, which mostly heal on their own. Deeper and larger erosions are called ulcers. Why does the mucosal barrier break down? A number of factors can interfere with its ability to protect the stomach lining. The majority of all ulcers are caused by either excessive intake of non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, or Helicobacter pylori infection. Antacids help relieve symptoms of ulcers such as “burning” pain and indigestion. When ulcers are caused by NSAID use, switching to other classes of pain relievers allows healing. When caused by H. pylori infection, antibiotics are effective. A potential complication of ulcers is perforation: Perforated ulcers create a hole in the stomach wall, resulting in peritonitis (inflammation of the peritoneum). These ulcers must be repaired surgically. Digestive Functions of the Stomach The stomach participates in virtually all the digestive activities with the exception of ingestion and defecation. Although almost all absorption takes place in the small intestine, the stomach does absorb some nonpolar substances, such as alcohol and aspirin. Mechanical Digestion Within a few moments after food enters your stomach, mixing waves begin to occur at intervals of approximately 20 seconds. A mixing wave is a unique type of peristalsis that mixes and softens the food with gastric juices to create chyme. The initial mixing waves are relatively gentle, but these are followed by more intense waves, starting at the body of the stomach and increasing in force as they reach the pylorus. It is fair to say that long before your sushi exits through the pyloric sphincter, it bears little resemblance to the sushi you ate. The pylorus, which holds around 30 mL (1 fluid ounce) of chyme, acts as a filter, permitting only liquids and small food particles to pass through the mostly, but not fully, closed pyloric sphincter. In a process called gastric emptying, rhythmic mixing waves force about 3 mL of chyme at a time through the pyloric sphincter and into the duodenum. Release of a greater amount of chyme at one time would overwhelm the capacity of the small intestine to handle it. The rest of the chyme is pushed back into the body of the stomach, where it continues mixing. This process is repeated when the next mixing waves force more chyme into the duodenum. Gastric emptying is regulated by both the stomach and the duodenum. The presence of chyme in the duodenum activates receptors that inhibit gastric secretion. This prevents additional chyme from being released by the stomach before the duodenum is ready to process it. Chemical Digestion The fundus plays an important role, because it stores both undigested food and gases that are released during the process of chemical digestion. Food may sit in the fundus of the stomach for a while before being mixed with the chyme. While the food is in the fundus, the digestive activities of salivary amylase continue until the food begins mixing with the acidic chyme. Ultimately, mixing waves incorporate this food with the chyme, the acidity of which inactivates salivary amylase and activates lingual lipase. Lingual lipase then begins breaking down triglycerides into free fatty acids, and mono- and diglycerides. The breakdown of protein begins in the stomach through the actions of HCl and the enzyme pepsin. During infancy, gastric glands also produce rennin, an enzyme that helps digest milk protein. Its numerous digestive functions notwithstanding, there is only one stomach function necessary to life: the production of intrinsic factor. The intestinal absorption of vitamin B12, which is necessary for both the production of mature red blood cells and normal neurological functioning, cannot occur without intrinsic factor. People who undergo total gastrectomy (stomach removal)—for life-threatening stomach cancer, for example—can survive with minimal digestive dysfunction if they receive vitamin B12injections. The contents of the stomach are completely emptied into the duodenum within 2 to 4 hours after you eat a meal. Different types of food take different amounts of time to process. Foods heavy in carbohydrates empty fastest, followed by high-protein foods. Meals with a high triglyceride content remain in the stomach the longest. Since enzymes in the small intestine digest fats slowly, food can stay in the stomach for 6 hours or longer when the duodenum is processing fatty chyme. However, note that this is still a fraction of the 24 to 72 hours that full digestion typically takes from start to finish. The Small and Large Intestines - Compare and contrast the location and gross anatomy of the small and large intestines - Identify three main adaptations of the small intestine wall that increase its absorptive capacity - Describe the mechanical and chemical digestion of chyme upon its release into the small intestine - List three features unique to the wall of the large intestine and identify their contributions to its function - Identify the beneficial roles of the bacterial flora in digestive system functioning - Trace the pathway of food waste from its point of entry into the large intestine through its exit from the body as feces The word intestine is derived from a Latin root meaning “internal,” and indeed, the two organs together nearly fill the interior of the abdominal cavity. In addition, called the small and large bowel, or colloquially the “guts,” they constitute the greatest mass and length of the alimentary canal and, with the exception of ingestion, perform all digestive system functions. The Small Intestine Chyme released from the stomach enters the small intestine, which is the primary digestive organ in the body. Not only is this where most digestion occurs, it is also where practically all absorption occurs. The longest part of the alimentary canal, the small intestine is about 3.05 meters (10 feet) long in a living person (but about twice as long in a cadaver due to the loss of muscle tone). Since this makes it about five times longer than the large intestine, you might wonder why it is called “small.” In fact, its name derives from its relatively smaller diameter of only about 2.54 cm (1 in), compared with 7.62 cm (3 in) for the large intestine. As we’ll see shortly, in addition to its length, the folds and projections of the lining of the small intestine work to give it an enormous surface area, which is approximately 200 m2, more than 100 times the surface area of your skin. This large surface area is necessary for complex processes of digestion and absorption that occur within it. Structure The coiled tube of the small intestine is subdivided into three regions. From proximal (at the stomach) to distal, these are the duodenum, jejunum, and ileum (Figure 23.18). The shortest region is the 25.4-cm (10-in) duodenum, which begins at the pyloric sphincter. Just past the pyloric sphincter, it bends posteriorly behind the peritoneum, becoming retroperitoneal, and then makes a C-shaped curve around the head of the pancreas before ascending anteriorly again to return to the peritoneal cavity and join the jejunum. The duodenum can therefore be subdivided into four segments: the superior, descending, horizontal, and ascending duodenum. Of particular interest is the hepatopancreatic ampulla (ampulla of Vater). Located in the duodenal wall, the ampulla marks the transition from the anterior portion of the alimentary canal to the mid-region, and is where the bile duct (through which bile passes from the liver) and the main pancreatic duct (through which pancreatic juice passes from the pancreas) join. This ampulla opens into the duodenum at a tiny volcano-shaped structure called the major duodenal papilla. The hepatopancreatic sphincter (sphincter of Oddi) regulates the flow of both bile and pancreatic juice from the ampulla into the duodenum. Figure 23.18 Small Intestine The three regions of the small intestine are the duodenum, jejunum, and ileum. The jejunum is about 0.9 meters (3 feet) long (in life) and runs from the duodenum to the ileum. Jejunum means “empty” in Latin and supposedly was so named by the ancient Greeks who noticed it was always empty at death. No clear demarcation exists between the jejunum and the final segment of the small intestine, the ileum. The ileum is the longest part of the small intestine, measuring about 1.8 meters (6 feet) in length. It is thicker, more vascular, and has more developed mucosal folds than the jejunum. The ileum joins the cecum, the first portion of the large intestine, at the ileocecal sphincter (or valve). The jejunum and ileum are tethered to the posterior abdominal wall by the mesentery. The large intestine frames these three parts of the small intestine. Parasympathetic nerve fibers from the vagus nerve and sympathetic nerve fibers from the thoracic splanchnic nerve provide extrinsic innervation to the small intestine. The superior mesenteric artery is its main arterial supply. Veins run parallel to the arteries and drain into the superior mesenteric vein. Nutrient-rich blood from the small intestine is then carried to the liver via the hepatic portal vein. Histology The wall of the small intestine is composed of the same four layers typically present in the alimentary system. However, three features of the mucosa and submucosa are unique. These features, which increase the absorptive surface area of the small intestine more than 600-fold, include circular folds, villi, and microvilli (Figure 23.19). These adaptations are most abundant in the proximal two-thirds of the small intestine, where the majority of absorption occurs. Figure 23.19 Histology of the Small Intestine (a) The absorptive surface of the small intestine is vastly enlarged by the presence of circular folds, villi, and microvilli. (b) Micrograph of the circular folds. (c) Micrograph of the villi. (d) Electron micrograph of the microvilli. From left to right, LM x 56, LM x 508, EM x 196,000. (credit b-d: Micrograph provided by the Regents of University of Michigan Medical School © 2012) Circular folds Also called a plica circulare, a circular fold is a deep ridge in the mucosa and submucosa. Beginning near the proximal part of the duodenum and ending near the middle of the ileum, these folds facilitate absorption. Their shape causes the chyme to spiral, rather than move in a straight line, through the small intestine. Spiraling slows the movement of chyme and provides the time needed for nutrients to be fully absorbed. Villi Within the circular folds are small (0.5–1 mm long) hairlike vascularized projections called villi (singular = villus) that give the mucosa a furry texture. There are about 20 to 40 villi per square millimeter, increasing the surface area of the epithelium tremendously. The mucosal epithelium, primarily composed of absorptive cells, covers the villi. In addition to muscle and connective tissue to support its structure, each villus contains a capillary bed composed of one arteriole and one venule, as well as a lymphatic capillary called a lacteal. The breakdown products of carbohydrates and proteins (sugars and amino acids) can enter the bloodstream directly, but lipid breakdown products are absorbed by the lacteals and transported to the bloodstream via the lymphatic system. Microvilli As their name suggests, microvilli (singular = microvillus) are much smaller (1 µm) than villi. They are cylindrical apical surface extensions of the plasma membrane of the mucosa’s epithelial cells, and are supported by microfilaments within those cells. Although their small size makes it difficult to see each microvillus, their combined microscopic appearance suggests a mass of bristles, which is termed the brush border. Fixed to the surface of the microvilli membranes are enzymes that finish digesting carbohydrates and proteins. There are an estimated 200 million microvilli per square millimeter of small intestine, greatly expanding the surface area of the plasma membrane and thus greatly enhancing absorption. Intestinal Glands In addition to the three specialized absorptive features just discussed, the mucosa between the villi is dotted with deep crevices that each lead into a tubular intestinal gland (crypt of Lieberkühn), which is formed by cells that line the crevices (see Figure 23.19). These produce intestinal juice, a slightly alkaline (pH 7.4 to 7.8) mixture of water and mucus. Each day, about 0.95 to 1.9 liters (1 to 2 quarts) are secreted in response to the distention of the small intestine or the irritating effects of chyme on the intestinal mucosa. The submucosa of the duodenum is the only site of the complex mucus-secreting duodenal glands (Brunner’s glands), which produce a bicarbonate-rich alkaline mucus that buffers the acidic chyme as it enters from the stomach. The roles of the cells in the small intestinal mucosa are detailed in Table 23.7. Cells of the Small Intestinal Mucosa \| Cell type \| Location in the mucosa \| Function \| \|---\|---\|---\| \| Absorptive \| Epithelium/intestinal glands \| Digestion and absorption of nutrients in chyme \| \| Goblet \| Epithelium/intestinal glands \| Secretion of mucus \| \| Paneth \| Intestinal glands \| Secretion of the bactericidal enzyme lysozyme; phagocytosis \| \| G cells \| Intestinal glands of duodenum \| Secretion of the hormone intestinal gastrin \| \| I cells \| Intestinal glands of duodenum \| Secretion of the hormone cholecystokinin, which stimulates release of pancreatic juices and bile \| \| K cells \| Intestinal glands \| Secretion of the hormone glucose-dependent insulinotropic peptide, which stimulates the release of insulin \| \| M cells \| Intestinal glands of duodenum and jejunum \| Secretion of the hormone motilin, which accelerates gastric emptying, stimulates intestinal peristalsis, and stimulates the production of pepsin \| \| S cells \| Intestinal glands \| Secretion of the hormone secretin \| Table 23.7 Intestinal MALT The lamina propria of the small intestine mucosa is studded with quite a bit of MALT. In addition to solitary lymphatic nodules, aggregations of intestinal MALT, which are typically referred to as Peyer’s patches, are concentrated in the distal ileum, and serve to keep bacteria from entering the bloodstream. Peyer’s patches are most prominent in young people and become less distinct as you age, which coincides with the general activity of our immune system. INTERACTIVE LINK Watch this animation that depicts the structure of the small intestine, and, in particular, the villi. Epithelial cells continue the digestion and absorption of nutrients and transport these nutrients to the lymphatic and circulatory systems. In the small intestine, the products of food digestion are absorbed by different structures in the villi. Which structure absorbs and transports fats? Mechanical Digestion in the Small Intestine The movement of intestinal smooth muscles includes both segmentation and a form of peristalsis called migrating motility complexes. The kind of peristaltic mixing waves seen in the stomach are not observed here. If you could see into the small intestine when it was going through segmentation, it would look as if the contents were being shoved incrementally back and forth, as the rings of smooth muscle repeatedly contract and then relax. Segmentation in the small intestine does not force chyme through the tract. Instead, it combines the chyme with digestive juices and pushes food particles against the mucosa to be absorbed. The duodenum is where the most rapid segmentation occurs, at a rate of about 12 times per minute. In the ileum, segmentations are only about eight times per minute (Figure 23.20). Figure 23.20 Segmentation Segmentation separates chyme and then pushes it back together, mixing it and providing time for digestion and absorption. When most of the chyme has been absorbed, the small intestinal wall becomes less distended. At this point, the localized segmentation process is replaced by transport movements. The duodenal mucosa secretes the hormone motilin, which initiates peristalsis in the form of a migrating motility complex. These complexes, which begin in the duodenum, force chyme through a short section of the small intestine and then stop. The next contraction begins a little bit farther down than the first, forces chyme a bit farther through the small intestine, then stops. These complexes move slowly down the small intestine, forcing chyme on the way, taking around 90 to 120 minutes to finally reach the end of the ileum. At this point, the process is repeated, starting in the duodenum. The ileocecal valve, a sphincter, is usually in a constricted state, but when motility in the ileum increases, this sphincter relaxes, allowing food residue to enter the first portion of the large intestine, the cecum. Relaxation of the ileocecal sphincter is controlled by both nerves and hormones. First, digestive activity in the stomach provokes the gastroileal reflex, which increases the force of ileal segmentation. Second, the stomach releases the hormone gastrin, which enhances ileal motility, thus relaxing the ileocecal sphincter. After chyme passes through, backward pressure helps close the sphincter, preventing backflow into the ileum. Because of this reflex, your lunch is completely emptied from your stomach and small intestine by the time you eat your dinner. It takes about 3 to 5 hours for all chyme to leave the small intestine. Chemical Digestion in the Small Intestine The digestion of proteins and carbohydrates, which partially occurs in the stomach, is completed in the small intestine with the aid of intestinal and pancreatic juices. Lipids arrive in the intestine largely undigested, so much of the focus here is on lipid digestion, which is facilitated by bile and the enzyme pancreatic lipase. Moreover, intestinal juice combines with pancreatic juice to provide a liquid medium that facilitates absorption. The intestine is also where most water is absorbed, via osmosis. The small intestine’s absorptive cells also synthesize digestive enzymes and then place them in the plasma membranes of the microvilli. This distinguishes the small intestine from the stomach; that is, enzymatic digestion occurs not only in the lumen, but also on the luminal surfaces of the mucosal cells. For optimal chemical digestion, chyme must be delivered from the stomach slowly and in small amounts. This is because chyme from the stomach is typically hypertonic, and if large quantities were forced all at once into the small intestine, the resulting osmotic water loss from the blood into the intestinal lumen would result in potentially life-threatening low blood volume. In addition, continued digestion requires an upward adjustment of the low pH of stomach chyme, along with rigorous mixing of the chyme with bile and pancreatic juices. Both processes take time, so the pumping action of the pylorus must be carefully controlled to prevent the duodenum from being overwhelmed with chyme. DISORDERS OF THE... Small Intestine: Lactose Intolerance Lactose intolerance is a condition characterized by indigestion caused by dairy products. It occurs when the absorptive cells of the small intestine do not produce enough lactase, the enzyme that digests the milk sugar lactose. In most mammals, lactose intolerance increases with age. In contrast, some human populations, most notably Caucasians, are able to maintain the ability to produce lactase as adults. In people with lactose intolerance, the lactose in chyme is not digested. Bacteria in the large intestine ferment the undigested lactose, a process that produces gas. In addition to gas, symptoms include abdominal cramps, bloating, and diarrhea. Symptom severity ranges from mild discomfort to severe pain; however, symptoms resolve once the lactose is eliminated in feces. The hydrogen breath test is used to help diagnose lactose intolerance. Lactose-tolerant people have very little hydrogen in their breath. Those with lactose intolerance exhale hydrogen, which is one of the gases produced by the bacterial fermentation of lactose in the colon. After the hydrogen is absorbed from the intestine, it is transported through blood vessels into the lungs. There are a number of lactose-free dairy products available in grocery stores. In addition, dietary supplements are available. Taken with food, they provide lactase to help digest lactose. The Large Intestine The large intestine is the terminal part of the alimentary canal. The primary function of this organ is to finish absorption of nutrients and water, synthesize certain vitamins, form feces, and eliminate feces from the body. Structure The large intestine runs from the appendix to the anus. It frames the small intestine on three sides. Despite its being about one-half as long as the small intestine, it is called large because it is more than twice the diameter of the small intestine, about 3 inches. Subdivisions The large intestine is subdivided into four main regions: the cecum, the colon, the rectum, and the anus. The ileocecal valve, located at the opening between the ileum and the large intestine, controls the flow of chyme from the small intestine to the large intestine. Cecum The first part of the large intestine is the cecum, a sac-like structure that is suspended inferior to the ileocecal valve. It is about 6 cm (2.4 in) long, receives the contents of the ileum, and continues the absorption of water and salts. The appendix (or vermiform appendix) is a winding tube that attaches to the cecum. Although the 7.6-cm (3-in) long appendix contains lymphoid tissue, suggesting an immunologic function, this organ is generally considered vestigial. However, at least one recent report postulates a survival advantage conferred by the appendix: In diarrheal illness, the appendix may serve as a bacterial reservoir to repopulate the enteric bacteria for those surviving the initial phases of the illness. Moreover, its twisted anatomy provides a haven for the accumulation and multiplication of enteric bacteria. The mesoappendix, the mesentery of the appendix, tethers it to the mesentery of the ileum. Colon The cecum blends seamlessly with the colon. Upon entering the colon, the food residue first travels up the ascending colon on the right side of the abdomen. At the inferior surface of the liver, the colon bends to form the right colic flexure (hepatic flexure) and becomes the transverse colon. The region defined as hindgut begins with the last third of the transverse colon and continues on. Food residue passing through the transverse colon travels across to the left side of the abdomen, where the colon angles sharply immediately inferior to the spleen, at the left colic flexure (splenic flexure). From there, food residue passes through the descending colon, which runs down the left side of the posterior abdominal wall. After entering the pelvis inferiorly, it becomes the s-shaped sigmoid colon, which extends medially to the midline (Figure 23.21). The ascending and descending colon, and the rectum (discussed next) are located in the retroperitoneum. The transverse and sigmoid colon are tethered to the posterior abdominal wall by the mesocolon. Figure 23.21 Large Intestine The large intestine includes the cecum, colon, and rectum. HOMEOSTATIC IMBALANCES Colorectal Cancer Each year, approximately 140,000 Americans are diagnosed with colorectal cancer, and another 49,000 die from it, making it one of the most deadly malignancies. People with a family history of colorectal cancer are at increased risk. Smoking, excessive alcohol consumption, and a diet high in animal fat and protein also increase the risk. Despite popular opinion to the contrary, studies support the conclusion that dietary fiber and calcium do not reduce the risk of colorectal cancer. Colorectal cancer may be signaled by constipation or diarrhea, cramping, abdominal pain, and rectal bleeding. Bleeding from the rectum may be either obvious or occult (hidden in feces). Since most colon cancers arise from benign mucosal growths called polyps, cancer prevention is focused on identifying these polyps. The colonoscopy is both diagnostic and therapeutic. Colonoscopy not only allows identification of precancerous polyps, the procedure also enables them to be removed before they become malignant. Screening for fecal occult blood tests and colonoscopy is recommended for those over 50 years of age. Rectum Food residue leaving the sigmoid colon enters the rectum in the pelvis, near the third sacral vertebra. The final 20.3 cm (8 in) of the alimentary canal, the rectum extends anterior to the sacrum and coccyx. Even though rectum is Latin for “straight,” this structure follows the curved contour of the sacrum and has three lateral bends that create a trio of internal transverse folds called the rectal valves. These valves help separate the feces from gas to prevent the simultaneous passage of feces and gas. Anal Canal Finally, food residue reaches the last part of the large intestine, the anal canal, which is located in the perineum, completely outside of the abdominopelvic cavity. This 3.8–5 cm (1.5–2 in) long structure opens to the exterior of the body at the anus. The anal canal includes two sphincters. The internal anal sphincter is made of smooth muscle, and its contractions are involuntary. The external anal sphincter is made of skeletal muscle, which is under voluntary control. Except when defecating, both usually remain closed. Histology There are several notable differences between the walls of the large and small intestines (Figure 23.22). For example, few enzyme-secreting cells are found in the wall of the large intestine, and there are no circular folds or villi. Other than in the anal canal, the mucosa of the colon is simple columnar epithelium made mostly of enterocytes (absorptive cells) and goblet cells. In addition, the wall of the large intestine has far more intestinal glands, which contain a vast population of enterocytes and goblet cells. These goblet cells secrete mucus that eases the movement of feces and protects the intestine from the effects of the acids and gases produced by enteric bacteria. The enterocytes absorb water and salts as well as vitamins produced by your intestinal bacteria. Figure 23.22 Histology of the large Intestine (a) The histologies of the large intestine and small intestine (not shown) are adapted for the digestive functions of each organ. (b) This micrograph shows the colon’s simple columnar epithelium and goblet cells. LM x 464. (credit b: Micrograph provided by the Regents of University of Michigan Medical School © 2012) Anatomy Three features are unique to the large intestine: teniae coli, haustra, and epiploic appendages (Figure 23.23). The teniae coli are three bands of smooth muscle that make up the longitudinal muscle layer of the muscularis of the large intestine, except at its terminal end. Tonic contractions of the teniae coli bunch up the colon into a succession of pouches called haustra (singular = haustrum), which are responsible for the wrinkled appearance of the colon. Attached to the teniae coli are small, fat-filled sacs of visceral peritoneum called epiploic appendages. The purpose of these is unknown. Although the rectum and anal canal have neither teniae coli nor haustra, they do have well-developed layers of muscularis that create the strong contractions needed for defecation. Figure 23.23 Teniae Coli, Haustra, and Epiploic Appendages The stratified squamous epithelial mucosa of the anal canal connects to the skin on the outside of the anus. This mucosa varies considerably from that of the rest of the colon to accommodate the high level of abrasion as feces pass through. The anal canal’s mucous membrane is organized into longitudinal folds, each called an anal column, which house a grid of arteries and veins. Two superficial venous plexuses are found in the anal canal: one within the anal columns and one at the anus. Depressions between the anal columns, each called an anal sinus, secrete mucus that facilitates defecation. The pectinate line(or dentate line) is a horizontal, jagged band that runs circumferentially just below the level of the anal sinuses, and represents the junction between the hindgut and external skin. The mucosa above this line is fairly insensitive, whereas the area below is very sensitive. The resulting difference in pain threshold is due to the fact that the upper region is innervated by visceral sensory fibers, and the lower region is innervated by somatic sensory fibers. Bacterial Flora Most bacteria that enter the alimentary canal are killed by lysozyme, defensins, HCl, or protein-digesting enzymes. However, trillions of bacteria live within the large intestine and are referred to as the bacterial flora. Most of the more than 700 species of these bacteria are nonpathogenic commensal organisms that cause no harm as long as they stay in the gut lumen. In fact, many facilitate chemical digestion and absorption, and some synthesize certain vitamins, mainly biotin, pantothenic acid, and vitamin K. Some are linked to increased immune response. A refined system prevents these bacteria from crossing the mucosal barrier. First, peptidoglycan, a component of bacterial cell walls, activates the release of chemicals by the mucosa’s epithelial cells, which draft immune cells, especially dendritic cells, into the mucosa. Dendritic cells open the tight junctions between epithelial cells and extend probes into the lumen to evaluate the microbial antigens. The dendritic cells with antigens then travel to neighboring lymphoid follicles in the mucosa where T cells inspect for antigens. This process triggers an IgA-mediated response, if warranted, in the lumen that blocks the commensal organisms from infiltrating the mucosa and setting off a far greater, widespread systematic reaction. Digestive Functions of the Large Intestine The residue of chyme that enters the large intestine contains few nutrients except water, which is reabsorbed as the residue lingers in the large intestine, typically for 12 to 24 hours. Thus, it may not surprise you that the large intestine can be completely removed without significantly affecting digestive functioning. For example, in severe cases of inflammatory bowel disease, the large intestine can be removed by a procedure known as a colectomy. Often, a new fecal pouch can be crafted from the small intestine and sutured to the anus, but if not, an ileostomy can be created by bringing the distal ileum through the abdominal wall, allowing the watery chyme to be collected in a bag-like adhesive appliance. Mechanical Digestion In the large intestine, mechanical digestion begins when chyme moves from the ileum into the cecum, an activity regulated by the ileocecal sphincter. Right after you eat, peristalsis in the ileum forces chyme into the cecum. When the cecum is distended with chyme, contractions of the ileocecal sphincter strengthen. Once chyme enters the cecum, colon movements begin. Mechanical digestion in the large intestine includes a combination of three types of movements. The presence of food residues in the colon stimulates a slow-moving haustral contraction. This type of movement involves sluggish segmentation, primarily in the transverse and descending colons. When a haustrum is distended with chyme, its muscle contracts, pushing the residue into the next haustrum. These contractions occur about every 30 minutes, and each last about 1 minute. These movements also mix the food residue, which helps the large intestine absorb water. The second type of movement is peristalsis, which, in the large intestine, is slower than in the more proximal portions of the alimentary canal. The third type is a mass movement. These strong waves start midway through the transverse colon and quickly force the contents toward the rectum. Mass movements usually occur three or four times per day, either while you eat or immediately afterward. Distension in the stomach and the breakdown products of digestion in the small intestine provoke the gastrocolic reflex, which increases motility, including mass movements, in the colon. Fiber in the diet both softens the stool and increases the power of colonic contractions, optimizing the activities of the colon. Chemical Digestion Although the glands of the large intestine secrete mucus, they do not secrete digestive enzymes. Therefore, chemical digestion in the large intestine occurs exclusively because of bacteria in the lumen of the colon. Through the process of saccharolytic fermentation, bacteria break down some of the remaining carbohydrates. This results in the discharge of hydrogen, carbon dioxide, and methane gases that create flatus (gas) in the colon; flatulence is excessive flatus. Each day, up to 1500 mL of flatus is produced in the colon. More is produced when you eat foods such as beans, which are rich in otherwise indigestible sugars and complex carbohydrates like soluble dietary fiber. Absorption, Feces Formation, and Defecation The small intestine absorbs about 90 percent of the water you ingest (either as liquid or within solid food). The large intestine absorbs most of the remaining water, a process that converts the liquid chyme residue into semisolid feces (“stool”). Feces is composed of undigested food residues, unabsorbed digested substances, millions of bacteria, old epithelial cells from the GI mucosa, inorganic salts, and enough water to let it pass smoothly out of the body. Of every 500 mL (17 ounces) of food residue that enters the cecum each day, about 150 mL (5 ounces) become feces. Feces are eliminated through contractions of the rectal muscles. You help this process by a voluntary procedure called Valsalva’s maneuver, in which you increase intra-abdominal pressure by contracting your diaphragm and abdominal wall muscles, and closing your glottis. The process of defecation begins when mass movements force feces from the colon into the rectum, stretching the rectal wall and provoking the defecation reflex, which eliminates feces from the rectum. This parasympathetic reflex is mediated by the spinal cord. It contracts the sigmoid colon and rectum, relaxes the internal anal sphincter, and initially contracts the external anal sphincter. The presence of feces in the anal canal sends a signal to the brain, which gives you the choice of voluntarily opening the external anal sphincter (defecating) or keeping it temporarily closed. If you decide to delay defecation, it takes a few seconds for the reflex contractions to stop and the rectal walls to relax. The next mass movement will trigger additional defecation reflexes until you defecate. If defecation is delayed for an extended time, additional water is absorbed, making the feces firmer and potentially leading to constipation. On the other hand, if the waste matter moves too quickly through the intestines, not enough water is absorbed, and diarrhea can result. This can be caused by the ingestion of foodborne pathogens. In general, diet, health, and stress determine the frequency of bowel movements. The number of bowel movements varies greatly between individuals, ranging from two or three per day to three or four per week. INTERACTIVE LINK By watching this animation you will see that for the various food groups—proteins, fats, and carbohydrates—digestion begins in different parts of the digestion system, though all end in the same place. Of the three major food classes (carbohydrates, fats, and proteins), which is digested in the mouth, the stomach, and the small intestine? Accessory Organs in Digestion: The Liver, Pancreas, and Gallbladder - State the main digestive roles of the liver, pancreas, and gallbladder - Identify three main features of liver histology that are critical to its function - Discuss the composition and function of bile - Identify the major types of enzymes and buffers present in pancreatic juice Chemical digestion in the small intestine relies on the activities of three accessory digestive organs: the liver, pancreas, and gallbladder (Figure 23.24). The digestive role of the liver is to produce bile and export it to the duodenum. The gallbladder primarily stores, concentrates, and releases bile. The pancreas produces pancreatic juice, which contains digestive enzymes and bicarbonate ions, and delivers it to the duodenum. Figure 23.24 Accessory Organs The liver, pancreas, and gallbladder are considered accessory digestive organs, but their roles in the digestive system are vital. The Liver The liver is the largest gland in the body, weighing about three pounds in an adult. It is also one of the most important organs. In addition to being an accessory digestive organ, it plays a number of roles in metabolism and regulation. The liver lies inferior to the diaphragm in the right upper quadrant of the abdominal cavity and receives protection from the surrounding ribs. The liver is divided into two primary lobes: a large right lobe and a much smaller left lobe. In the right lobe, some anatomists also identify an inferior quadrate lobe and a posterior caudate lobe, which are defined by internal features. The liver is connected to the abdominal wall and diaphragm by five peritoneal folds referred to as ligaments. These are the falciform ligament, the coronary ligament, two lateral ligaments, and the ligamentum teres hepatis. The falciform ligament and ligamentum teres hepatis are actually remnants of the umbilical vein, and separate the right and left lobes anteriorly. The lesser omentum tethers the liver to the lesser curvature of the stomach. The porta hepatis (“gate to the liver”) is where the hepatic artery and hepatic portal vein enter the liver. These two vessels, along with the common hepatic duct, run behind the lateral border of the lesser omentum on the way to their destinations. As shown in Figure 23.25, the hepatic artery delivers oxygenated blood from the heart to the liver. The hepatic portal vein delivers partially deoxygenated blood containing nutrients absorbed from the small intestine and actually supplies more oxygen to the liver than do the much smaller hepatic arteries. In addition to nutrients, drugs and toxins are also absorbed. After processing the bloodborne nutrients and toxins, the liver releases nutrients needed by other cells back into the blood, which drains into the central vein and then through the hepatic vein to the inferior vena cava. With this hepatic portal circulation, all blood from the alimentary canal passes through the liver. This largely explains why the liver is the most common site for the metastasis of cancers that originate in the alimentary canal. Figure 23.25 Microscopic Anatomy of the Liver The liver receives oxygenated blood from the hepatic artery and nutrient-rich deoxygenated blood from the hepatic portal vein. Histology The liver has three main components: hepatocytes, bile canaliculi, and hepatic sinusoids. A hepatocyte is the liver’s main cell type, accounting for around 80 percent of the liver's volume. These cells play a role in a wide variety of secretory, metabolic, and endocrine functions. Plates of hepatocytes called hepatic laminae radiate outward from the portal vein in each hepatic lobule. Between adjacent hepatocytes, grooves in the cell membranes provide room for each bile canaliculus (plural = canaliculi). These small ducts accumulate the bile produced by hepatocytes. From here, bile flows first into bile ductules and then into bile ducts. The bile ducts unite to form the larger right and left hepatic ducts, which themselves merge and exit the liver as the common hepatic duct. This duct then joins with the cystic duct from the gallbladder, forming the common bile duct through which bile flows into the small intestine. A hepatic sinusoid is an open, porous blood space formed by fenestrated capillaries from nutrient-rich hepatic portal veins and oxygen-rich hepatic arteries. Hepatocytes are tightly packed around the fenestrated endothelium of these spaces, giving them easy access to the blood. From their central position, hepatocytes process the nutrients, toxins, and waste materials carried by the blood. Materials such as bilirubin are processed and excreted into the bile canaliculi. Other materials including proteins, lipids, and carbohydrates are processed and secreted into the sinusoids or just stored in the cells until called upon. The hepatic sinusoids combine and send blood to a central vein. Blood then flows through a hepatic vein into the inferior vena cava. This means that blood and bile flow in opposite directions. The hepatic sinusoids also contain star-shaped reticuloendothelial cells(Kupffer cells), phagocytes that remove dead red and white blood cells, bacteria, and other foreign material that enter the sinusoids. The portal triad is a distinctive arrangement around the perimeter of hepatic lobules, consisting of three basic structures: a bile duct, a hepatic artery branch, and a hepatic portal vein branch. Bile Recall that lipids are hydrophobic, that is, they do not dissolve in water. Thus, before they can be digested in the watery environment of the small intestine, large lipid globules must be broken down into smaller lipid globules, a process called emulsification. Bile is a mixture secreted by the liver to accomplish the emulsification of lipids in the small intestine. Hepatocytes secrete about one liter of bile each day. A yellow-brown or yellow-green alkaline solution (pH 7.6 to 8.6), bile is a mixture of water, bile salts, bile pigments, phospholipids (such as lecithin), electrolytes, cholesterol, and triglycerides. The components most critical to emulsification are bile salts and phospholipids, which have a nonpolar (hydrophobic) region as well as a polar (hydrophilic) region. The hydrophobic region interacts with the large lipid molecules, whereas the hydrophilic region interacts with the watery chyme in the intestine. This results in the large lipid globules being pulled apart into many tiny lipid fragments of about 1 µm in diameter. This change dramatically increases the surface area available for lipid-digesting enzyme activity. This is the same way dish soap works on fats mixed with water. Bile salts act as emulsifying agents, so they are also important for the absorption of digested lipids. While most constituents of bile are eliminated in feces, bile salts are reclaimed by the enterohepatic circulation. Once bile salts reach the ileum, they are absorbed and returned to the liver in the hepatic portal blood. The hepatocytes then excrete the bile salts into newly formed bile. Thus, this precious resource is recycled. Bilirubin, the main bile pigment, is a waste product produced when the spleen removes old or damaged red blood cells from the circulation. These breakdown products, including proteins, iron, and toxic bilirubin, are transported to the liver via the splenic vein of the hepatic portal system. In the liver, proteins and iron are recycled, whereas bilirubin is excreted in the bile. It accounts for the green color of bile. Bilirubin is eventually transformed by intestinal bacteria into stercobilin, a brown pigment that gives your stool its characteristic color! In some disease states, bile does not enter the intestine, resulting in white (‘acholic’) stool with a high fat content, since virtually no fats are broken down or absorbed. Hepatocytes work non-stop, but bile production increases when fatty chyme enters the duodenum and stimulates the secretion of the gut hormone secretin. Between meals, bile is produced but conserved. The valve-like hepatopancreatic ampulla closes, allowing bile to divert to the gallbladder, where it is concentrated and stored until the next meal. INTERACTIVE LINK Watch this video to see the structure of the liver and how this structure supports the functions of the liver, including the processing of nutrients, toxins, and wastes. At rest, about 1500 mL of blood per minute flow through the liver. What percentage of this blood flow comes from the hepatic portal system? The Pancreas The soft, oblong, glandular pancreas lies transversely in the retroperitoneum behind the stomach. Its head is nestled into the “c-shaped” curvature of the duodenum with the body extending to the left about 15.2 cm (6 in) and ending as a tapering tail in the hilum of the spleen. It is a curious mix of exocrine (secreting digestive enzymes) and endocrine (releasing hormones into the blood) functions (Figure 23.26). Figure 23.26 Exocrine and Endocrine Pancreas The pancreas has a head, a body, and a tail. It delivers pancreatic juice to the duodenum through the pancreatic duct. The exocrine part of the pancreas arises as little grape-like cell clusters, each called an acinus (plural = acini), located at the terminal ends of pancreatic ducts. These acinar cells secrete enzyme-rich pancreatic juice into tiny merging ducts that form two dominant ducts. The larger duct fuses with the common bile duct (carrying bile from the liver and gallbladder) just before entering the duodenum via a common opening (the hepatopancreatic ampulla). The smooth muscle sphincter of the hepatopancreatic ampulla controls the release of pancreatic juice and bile into the small intestine. The second and smaller pancreatic duct, the accessory duct (duct of Santorini), runs from the pancreas directly into the duodenum, approximately 1 inch above the hepatopancreatic ampulla. When present, it is a persistent remnant of pancreatic development. Scattered through the sea of exocrine acini are small islands of endocrine cells, the islets of Langerhans. These vital cells produce the hormones pancreatic polypeptide, insulin, glucagon, and somatostatin. Pancreatic Juice The pancreas produces over a liter of pancreatic juice each day. Unlike bile, it is clear and composed mostly of water along with some salts, sodium bicarbonate, and several digestive enzymes. Sodium bicarbonate is responsible for the slight alkalinity of pancreatic juice (pH 7.1 to 8.2), which serves to buffer the acidic gastric juice in chyme, inactivate pepsin from the stomach, and create an optimal environment for the activity of pH-sensitive digestive enzymes in the small intestine. Pancreatic enzymes are active in the digestion of sugars, proteins, and fats. The pancreas produces protein-digesting enzymes in their inactive forms. These enzymes are activated in the duodenum. If produced in an active form, they would digest the pancreas (which is exactly what occurs in the disease, pancreatitis). The intestinal brush border enzyme enteropeptidase stimulates the activation of trypsin from trypsinogen of the pancreas, which in turn changes the pancreatic enzymes procarboxypeptidase and chymotrypsinogen into their active forms, carboxypeptidase and chymotrypsin. The enzymes that digest starch (amylase), fat (lipase), and nucleic acids (nuclease) are secreted in their active forms, since they do not attack the pancreas as do the protein-digesting enzymes. Pancreatic Secretion Regulation of pancreatic secretion is the job of hormones and the parasympathetic nervous system. The entry of acidic chyme into the duodenum stimulates the release of secretin, which in turn causes the duct cells to release bicarbonate-rich pancreatic juice. The presence of proteins and fats in the duodenum stimulates the secretion of CCK, which then stimulates the acini to secrete enzyme-rich pancreatic juice and enhances the activity of secretin. Parasympathetic regulation occurs mainly during the cephalic and gastric phases of gastric secretion, when vagal stimulation prompts the secretion of pancreatic juice. Usually, the pancreas secretes just enough bicarbonate to counterbalance the amount of HCl produced in the stomach. Hydrogen ions enter the blood when bicarbonate is secreted by the pancreas. Thus, the acidic blood draining from the pancreas neutralizes the alkaline blood draining from the stomach, maintaining the pH of the venous blood that flows to the liver. The Gallbladder The gallbladder is 8–10 cm (~3–4 in) long and is nested in a shallow area on the posterior aspect of the right lobe of the liver. This muscular sac stores, concentrates, and, when stimulated, propels the bile into the duodenum via the common bile duct. It is divided into three regions. The fundus is the widest portion and tapers medially into the body, which in turn narrows to become the neck. The neck angles slightly superiorly as it approaches the hepatic duct. The cystic duct is 1–2 cm (less than 1 in) long and turns inferiorly as it bridges the neck and hepatic duct. The simple columnar epithelium of the gallbladder mucosa is organized in rugae, similar to those of the stomach. There is no submucosa in the gallbladder wall. The wall’s middle, muscular coat is made of smooth muscle fibers. When these fibers contract, the gallbladder’s contents are ejected through the cystic duct and into the bile duct (Figure 23.27). Visceral peritoneum reflected from the liver capsule holds the gallbladder against the liver and forms the outer coat of the gallbladder. The gallbladder's mucosa absorbs water and ions from bile, concentrating it by up to 10-fold. Figure 23.27 Gallbladder The gallbladder stores and concentrates bile, and releases it into the two-way cystic duct when it is needed by the small intestine. Chemical Digestion and Absorption: A Closer Look - Identify the locations and primary secretions involved in the chemical digestion of carbohydrates, proteins, lipids, and nucleic acids - Compare and contrast absorption of the hydrophilic and hydrophobic nutrients As you have learned, the process of mechanical digestion is relatively simple. It involves the physical breakdown of food but does not alter its chemical makeup. Chemical digestion, on the other hand, is a complex process that reduces food into its chemical building blocks, which are then absorbed to nourish the cells of the body (Figure 23.28). In this section, you will look more closely at the processes of chemical digestion and absorption. Figure 23.28 Digestion and Absorption Digestion begins in the mouth and continues as food travels through the small intestine. Most absorption occurs in the small intestine. Chemical Digestion Large food molecules (for example, proteins, lipids, nucleic acids, and starches) must be broken down into subunits that are small enough to be absorbed by the lining of the alimentary canal. This is accomplished by enzymes through hydrolysis. The many enzymes involved in chemical digestion are summarized in Table 23.8. The Digestive Enzymes \| Enzyme Category \| Enzyme Name \| Source \| Substrate \| Product \| \|---\|---\|---\|---\|---\| \| Salivary Enzymes \| Lingual lipase \| Lingual glands \| Triglycerides \| Free fatty acids, and mono- and diglycerides \| \| Salivary Enzymes \| Salivary amylase \| Salivary glands \| Polysaccharides \| Disaccharides and trisaccharides \| \| Gastric enzymes \| Gastric lipase \| Chief cells \| Triglycerides \| Fatty acids and monoacylglycerides \| \| Gastric enzymes \| Pepsin* \| Chief cells \| Proteins \| Peptides \| \| Brush border enzymes \| α-Dextrinase \| Small intestine \| α-Dextrins \| Glucose \| \| Brush border enzymes \| Enteropeptidase \| Small intestine \| Trypsinogen \| Trypsin \| \| Brush border enzymes \| Lactase \| Small intestine \| Lactose \| Glucose and galactose \| \| Brush border enzymes \| Maltase \| Small intestine \| Maltose \| Glucose \| \| Brush border enzymes \| Nucleosidases and phosphatases \| Small intestine \| Nucleotides \| Phosphates, nitrogenous bases, and pentoses \| \| Brush border enzymes \| Peptidases \| Small intestine \| \| \| \| Brush border enzymes \| Sucrase \| Small intestine \| Sucrose \| Glucose and fructose \| \| Pancreatic enzymes \| Carboxy-peptidase* \| Pancreatic acinar cells \| Amino acids at the carboxyl end of peptides \| Amino acids and peptides \| \| Pancreatic enzymes \| Chymotrypsin* \| Pancreatic acinar cells \| Proteins \| Peptides \| \| Pancreatic enzymes \| Elastase* \| Pancreatic acinar cells \| Proteins \| Peptides \| \| Pancreatic enzymes \| Nucleases \| Pancreatic acinar cells \| \| Nucleotides \| \| Pancreatic enzymes \| Pancreatic amylase \| Pancreatic acinar cells \| Polysaccharides (starches) \| α-Dextrins, disaccharides (maltose), trisaccharides (maltotriose) \| \| Pancreatic enzymes \| Pancreatic lipase \| Pancreatic acinar cells \| Triglycerides that have been emulsified by bile salts \| Fatty acids and monoacylglycerides \| \| Pancreatic enzymes \| Trypsin* \| Pancreatic acinar cells \| Proteins \| Peptides \| Table 23.8 *These enzymes have been activated by other substances. Carbohydrate Digestion The average American diet is about 50 percent carbohydrates, which may be classified according to the number of monomers they contain of simple sugars (monosaccharides and disaccharides) and/or complex sugars (polysaccharides). Glucose, galactose, and fructose are the three monosaccharides that are commonly consumed and are readily absorbed. Your digestive system is also able to break down the disaccharide sucrose (regular table sugar: glucose + fructose), lactose (milk sugar: glucose + galactose), and maltose (grain sugar: glucose + glucose), and the polysaccharides glycogen and starch (chains of monosaccharides). Your bodies do not produce enzymes that can break down most fibrous polysaccharides, such as cellulose. While indigestible polysaccharides do not provide any nutritional value, they do provide dietary fiber, which helps propel food through the alimentary canal. The chemical digestion of starches begins in the mouth and has been reviewed above. In the small intestine, pancreatic amylase does the ‘heavy lifting’ for starch and carbohydrate digestion (Figure 23.29). After amylases break down starch into smaller fragments, the brush border enzyme α-dextrinase starts working on α-dextrin, breaking off one glucose unit at a time. Three brush border enzymes hydrolyze sucrose, lactose, and maltose into monosaccharides. Sucrase splits sucrose into one molecule of fructose and one molecule of glucose; maltase breaks down maltose and maltotriose into two and three glucose molecules, respectively; and lactase breaks down lactose into one molecule of glucose and one molecule of galactose. Insufficient lactase can lead to lactose intolerance. Figure 23.29 Carbohydrate Digestion Flow Chart Carbohydrates are broken down into their monomers in a series of steps. Protein Digestion Proteins are polymers composed of amino acids linked by peptide bonds to form long chains. Digestion reduces them to their constituent amino acids. You usually consume about 15 to 20 percent of your total calorie intake as protein. The digestion of protein starts in the stomach, where HCl and pepsin break proteins into smaller polypeptides, which then travel to the small intestine (Figure 23.30). Chemical digestion in the small intestine is continued by pancreatic enzymes, including chymotrypsin and trypsin, each of which act on specific bonds in amino acid sequences. At the same time, the cells of the brush border secrete enzymes such as aminopeptidase and dipeptidase, which further break down peptide chains. This results in molecules small enough to enter the bloodstream (Figure 23.31). Figure 23.30 Digestion of Protein The digestion of protein begins in the stomach and is completed in the small intestine. Figure 23.31 Digestion of Protein Flow Chart Proteins are successively broken down into their amino acid components. Lipid Digestion A healthy diet limits lipid intake to 35 percent of total calorie intake. The most common dietary lipids are triglycerides, which are made up of a glycerol molecule bound to three fatty acid chains. Small amounts of dietary cholesterol and phospholipids are also consumed. The three lipases responsible for lipid digestion are lingual lipase, gastric lipase, and pancreatic lipase. However, because the pancreas is the only consequential source of lipase, virtually all lipid digestion occurs in the small intestine. Pancreatic lipase breaks down each triglyceride into two free fatty acids and a monoglyceride. The fatty acids include both short-chain (less than 10 to 12 carbons) and long-chain fatty acids. Nucleic Acid Digestion The nucleic acids DNA and RNA are found in most of the foods you eat. Two types of pancreatic nuclease are responsible for their digestion: deoxyribonuclease, which digests DNA, and ribonuclease, which digests RNA. The nucleotides produced by this digestion are further broken down by two intestinal brush border enzymes (nucleosidase and phosphatase) into pentoses, phosphates, and nitrogenous bases, which can be absorbed through the alimentary canal wall. The large food molecules that must be broken down into subunits are summarized Table 23.9 Absorbable Food Substances \| Source \| Substance \| \|---\|---\| \| Carbohydrates \| Monosaccharides: glucose, galactose, and fructose \| \| Proteins \| Single amino acids, dipeptides, and tripeptides \| \| Triglycerides \| Monoacylglycerides, glycerol, and free fatty acids \| \| Nucleic acids \| Pentose sugars, phosphates, and nitrogenous bases \| Table 23.9 Absorption The mechanical and digestive processes have one goal: to convert food into molecules small enough to be absorbed by the epithelial cells of the intestinal villi. The absorptive capacity of the alimentary canal is almost endless. Each day, the alimentary canal processes up to 10 liters of food, liquids, and GI secretions, yet less than one liter enters the large intestine. Almost all ingested food, 80 percent of electrolytes, and 90 percent of water are absorbed in the small intestine. Although the entire small intestine is involved in the absorption of water and lipids, most absorption of carbohydrates and proteins occurs in the jejunum. Notably, bile salts and vitamin B12 are absorbed in the terminal ileum. By the time chyme passes from the ileum into the large intestine, it is essentially indigestible food residue (mainly plant fibers like cellulose), some water, and millions of bacteria (Figure 23.32). Figure 23.32 Digestive Secretions and Absorption of Water Absorption is a complex process, in which nutrients from digested food are harvested. Absorption can occur through five mechanisms: (1) active transport, (2) passive diffusion, (3) facilitated diffusion, (4) co-transport (or secondary active transport), and (5) endocytosis. As you will recall from Chapter 3, active transport refers to the movement of a substance across a cell membrane going from an area of lower concentration to an area of higher concentration (up the concentration gradient). In this type of transport, proteins within the cell membrane act as “pumps,” using cellular energy (ATP) to move the substance. Passive diffusion refers to the movement of substances from an area of higher concentration to an area of lower concentration, while facilitated diffusion refers to the movement of substances from an area of higher to an area of lower concentration using a carrier protein in the cell membrane. Co-transport uses the movement of one molecule through the membrane from higher to lower concentration to power the movement of another from lower to higher. Finally, endocytosis is a transportation process in which the cell membrane engulfs material. It requires energy, generally in the form of ATP. Because the cell’s plasma membrane is made up of hydrophobic phospholipids, water-soluble nutrients must use transport molecules embedded in the membrane to enter cells. Moreover, substances cannot pass between the epithelial cells of the intestinal mucosa because these cells are bound together by tight junctions. Thus, substances can only enter blood capillaries by passing through the apical surfaces of epithelial cells and into the interstitial fluid. Water-soluble nutrients enter the capillary blood in the villi and travel to the liver via the hepatic portal vein. In contrast to the water-soluble nutrients, lipid-soluble nutrients can diffuse through the plasma membrane. Once inside the cell, they are packaged for transport via the base of the cell and then enter the lacteals of the villi to be transported by lymphatic vessels to the systemic circulation via the thoracic duct. The absorption of most nutrients through the mucosa of the intestinal villi requires active transport fueled by ATP. The routes of absorption for each food category are summarized in Table 23.10. Absorption in the Alimentary Canal \| Food \| Breakdown products \| Absorption mechanism \| Entry to bloodstream \| Destination \| \|---\|---\|---\|---\|---\| \| Carbohydrates \| Glucose \| Co-transport with sodium ions \| Capillary blood in villi \| Liver via hepatic portal vein \| \| Carbohydrates \| Galactose \| Co-transport with sodium ions \| Capillary blood in villi \| Liver via hepatic portal vein \| \| Carbohydrates \| Fructose \| Facilitated diffusion \| Capillary blood in villi \| Liver via hepatic portal vein \| \| Protein \| Amino acids \| Co-transport with sodium ions \| Capillary blood in villi \| Liver via hepatic portal vein \| \| Lipids \| Long-chain fatty acids \| Diffusion into intestinal cells, where they are combined with proteins to create chylomicrons \| Lacteals of villi \| Systemic circulation via lymph entering thoracic duct \| \| Lipids \| Monoacylglycerides \| Diffusion into intestinal cells, where they are combined with proteins to create chylomicrons \| Lacteals of villi \| Systemic circulation via lymph entering thoracic duct \| \| Lipids \| Short-chain fatty acids \| Simple diffusion \| Capillary blood in villi \| Liver via hepatic portal vein \| \| Lipids \| Glycerol \| Simple diffusion \| Capillary blood in villi \| Liver via hepatic portal vein \| \| Nucleic Acids \| Nucleic acid digestion products \| Active transport via membrane carriers \| Capillary blood in villi \| Liver via hepatic portal vein \| Table 23.10 Carbohydrate Absorption All carbohydrates are absorbed in the form of monosaccharides. The small intestine is highly efficient at this, absorbing monosaccharides at an estimated rate of 120 grams per hour. All normally digested dietary carbohydrates are absorbed; indigestible fibers are eliminated in the feces. The monosaccharides glucose and galactose are transported into the epithelial cells by common protein carriers via secondary active transport (that is, co-transport with sodium ions). The monosaccharides leave these cells via facilitated diffusion and enter the capillaries through intercellular clefts. The monosaccharide fructose (which is in fruit) is absorbed and transported by facilitated diffusion alone. The monosaccharides combine with the transport proteins immediately after the disaccharides are broken down. Protein Absorption Active transport mechanisms, primarily in the duodenum and jejunum, absorb most proteins as their breakdown products, amino acids. Almost all (95 to 98 percent) protein is digested and absorbed in the small intestine. The type of carrier that transports an amino acid varies. Most carriers are linked to the active transport of sodium. Short chains of two amino acids (dipeptides) or three amino acids (tripeptides) are also transported actively. However, after they enter the absorptive epithelial cells, they are broken down into their amino acids before leaving the cell and entering the capillary blood via diffusion. Lipid Absorption About 95 percent of lipids are absorbed in the small intestine. Bile salts not only speed up lipid digestion, they are also essential to the absorption of the end products of lipid digestion. Short-chain fatty acids are relatively water soluble and can enter the absorptive cells (enterocytes) directly. The small size of short-chain fatty acids enables them to be absorbed by enterocytes via simple diffusion, and then take the same path as monosaccharides and amino acids into the blood capillary of a villus. The large and hydrophobic long-chain fatty acids and monoacylglycerides are not so easily suspended in the watery intestinal chyme. However, bile salts and lecithin resolve this issue by enclosing them in a micelle, which is a tiny sphere with polar (hydrophilic) ends facing the watery environment and hydrophobic tails turned to the interior, creating a receptive environment for the long-chain fatty acids. The core also includes cholesterol and fat-soluble vitamins. Without micelles, lipids would sit on the surface of chyme and never come in contact with the absorptive surfaces of the epithelial cells. Micelles can easily squeeze between microvilli and get very near the luminal cell surface. At this point, lipid substances exit the micelle and are absorbed via simple diffusion. The free fatty acids and monoacylglycerides that enter the epithelial cells are reincorporated into triglycerides. The triglycerides are mixed with phospholipids and cholesterol, and surrounded with a protein coat. This new complex, called a chylomicron, is a water-soluble lipoprotein. After being processed by the Golgi apparatus, chylomicrons are released from the cell (Figure 23.33). Too big to pass through the basement membranes of blood capillaries, chylomicrons instead enter the large pores of lacteals. The lacteals come together to form the lymphatic vessels. The chylomicrons are transported in the lymphatic vessels and empty through the thoracic duct into the subclavian vein of the circulatory system. Once in the bloodstream, the enzyme lipoprotein lipase breaks down the triglycerides of the chylomicrons into free fatty acids and glycerol. These breakdown products then pass through capillary walls to be used for energy by cells or stored in adipose tissue as fat. Liver cells combine the remaining chylomicron remnants with proteins, forming lipoproteins that transport cholesterol in the blood. Figure 23.33 Lipid Absorption Unlike amino acids and simple sugars, lipids are transformed as they are absorbed through epithelial cells. Nucleic Acid Absorption The products of nucleic acid digestion—pentose sugars, nitrogenous bases, and phosphate ions—are transported by carriers across the villus epithelium via active transport. These products then enter the bloodstream. Mineral Absorption The electrolytes absorbed by the small intestine are from both GI secretions and ingested foods. Since electrolytes dissociate into ions in water, most are absorbed via active transport throughout the entire small intestine. During absorption, co-transport mechanisms result in the accumulation of sodium ions inside the cells, whereas anti-port mechanisms reduce the potassium ion concentration inside the cells. To restore the sodium-potassium gradient across the cell membrane, a sodium-potassium pump requiring ATP pumps sodium out and potassium in. In general, all minerals that enter the intestine are absorbed, whether you need them or not. Iron and calcium are exceptions; they are absorbed in the duodenum in amounts that meet the body’s current requirements, as follows: Iron—The ionic iron needed for the production of hemoglobin is absorbed into mucosal cells via active transport. Once inside mucosal cells, ionic iron binds to the protein ferritin, creating iron-ferritin complexes that store iron until needed. When the body has enough iron, most of the stored iron is lost when worn-out epithelial cells slough off. When the body needs iron because, for example, it is lost during acute or chronic bleeding, there is increased uptake of iron from the intestine and accelerated release of iron into the bloodstream. Since women experience significant iron loss during menstruation, they have around four times as many iron transport proteins in their intestinal epithelial cells as do men. Calcium—Blood levels of ionic calcium determine the absorption of dietary calcium. When blood levels of ionic calcium drop, parathyroid hormone (PTH) secreted by the parathyroid glands stimulates the release of calcium ions from bone matrices and increases the reabsorption of calcium by the kidneys. PTH also upregulates the activation of vitamin D in the kidney, which then facilitates intestinal calcium ion absorption. Vitamin Absorption The small intestine absorbs the vitamins that occur naturally in food and supplements. Fat-soluble vitamins (A, D, E, and K) are absorbed along with dietary lipids in micelles via simple diffusion. This is why you are advised to eat some fatty foods when you take fat-soluble vitamin supplements. Most water-soluble vitamins (including most B vitamins and vitamin C) also are absorbed by simple diffusion. An exception is vitamin B12, which is a very large molecule. Intrinsic factor secreted in the stomach binds to vitamin B12, preventing its digestion and creating a complex that binds to mucosal receptors in the terminal ileum, where it is taken up by endocytosis. Water Absorption Each day, about nine liters of fluid enter the small intestine. About 2.3 liters are ingested in foods and beverages, and the rest is from GI secretions. About 90 percent of this water is absorbed in the small intestine. Water absorption is driven by the concentration gradient of the water: The concentration of water is higher in chyme than it is in epithelial cells. Thus, water moves down its concentration gradient from the chyme into cells. As noted earlier, much of the remaining water is then absorbed in the colon. Key Terms - absorption - passage of digested products from the intestinal lumen through mucosal cells and into the bloodstream or lacteals - accessory digestive organ - includes teeth, tongue, salivary glands, gallbladder, liver, and pancreas - accessory duct - (also, duct of Santorini) duct that runs from the pancreas into the duodenum - acinus - cluster of glandular epithelial cells in the pancreas that secretes pancreatic juice in the pancreas - alimentary canal - continuous muscular digestive tube that extends from the mouth to the anus - aminopeptidase - brush border enzyme that acts on proteins - anal canal - final segment of the large intestine - anal column - long fold of mucosa in the anal canal - anal sinus - recess between anal columns - appendix - (vermiform appendix) coiled tube attached to the cecum - ascending colon - first region of the colon - bacterial flora - bacteria in the large intestine - bile - alkaline solution produced by the liver and important for the emulsification of lipids - bile canaliculus - small duct between hepatocytes that collects bile - bilirubin - main bile pigment, which is responsible for the brown color of feces - body - mid-portion of the stomach - bolus - mass of chewed food - brush border - fuzzy appearance of the small intestinal mucosa created by microvilli - cardia - (also, cardiac region) part of the stomach surrounding the cardiac orifice (esophageal hiatus) - cecum - pouch forming the beginning of the large intestine - cementum - bone-like tissue covering the root of a tooth - central vein - vein that receives blood from hepatic sinusoids - cephalic phase - (also, reflex phase) initial phase of gastric secretion that occurs before food enters the stomach - chemical digestion - enzymatic breakdown of food - chief cell - gastric gland cell that secretes pepsinogen - chylomicron - large lipid-transport compound made up of triglycerides, phospholipids, cholesterol, and proteins - chyme - soupy liquid created when food is mixed with digestive juices - circular fold - (also, plica circulare) deep fold in the mucosa and submucosa of the small intestine - colon - part of the large intestine between the cecum and the rectum - common bile duct - structure formed by the union of the common hepatic duct and the gallbladder’s cystic duct - common hepatic duct - duct formed by the merger of the two hepatic ducts - crown - portion of tooth visible superior to the gum line - cuspid - (also, canine) pointed tooth used for tearing and shredding food - cystic duct - duct through which bile drains and enters the gallbladder - deciduous tooth - one of 20 “baby teeth” - defecation - elimination of undigested substances from the body in the form of feces - deglutition - three-stage process of swallowing - dens - tooth - dentin - bone-like tissue immediately deep to the enamel of the crown or cementum of the root of a tooth - dentition - set of teeth - deoxyribonuclease - pancreatic enzyme that digests DNA - descending colon - part of the colon between the transverse colon and the sigmoid colon - dipeptidase - brush border enzyme that acts on proteins - duodenal gland - (also, Brunner’s gland) mucous-secreting gland in the duodenal submucosa - duodenum - first part of the small intestine, which starts at the pyloric sphincter and ends at the jejunum - enamel - covering of the dentin of the crown of a tooth - enteroendocrine cell - gastric gland cell that releases hormones - enterohepatic circulation - recycling mechanism that conserves bile salts - enteropeptidase - intestinal brush-border enzyme that activates trypsinogen to trypsin - epiploic appendage - small sac of fat-filled visceral peritoneum attached to teniae coli - esophagus - muscular tube that runs from the pharynx to the stomach - external anal sphincter - voluntary skeletal muscle sphincter in the anal canal - fauces - opening between the oral cavity and the oropharynx - feces - semisolid waste product of digestion - flatus - gas in the intestine - fundus - dome-shaped region of the stomach above and to the left of the cardia - G cell - gastrin-secreting enteroendocrine cell - gallbladder - accessory digestive organ that stores and concentrates bile - gastric emptying - process by which mixing waves gradually cause the release of chyme into the duodenum - gastric gland - gland in the stomach mucosal epithelium that produces gastric juice - gastric phase - phase of gastric secretion that begins when food enters the stomach - gastric pit - narrow channel formed by the epithelial lining of the stomach mucosa - gastrin - peptide hormone that stimulates secretion of hydrochloric acid and gut motility - gastrocolic reflex - propulsive movement in the colon activated by the presence of food in the stomach - gastroileal reflex - long reflex that increases the strength of segmentation in the ileum - gingiva - gum - haustral contraction - slow segmentation in the large intestine - haustrum - small pouch in the colon created by tonic contractions of teniae coli - hepatic artery - artery that supplies oxygenated blood to the liver - hepatic lobule - hexagonal-shaped structure composed of hepatocytes that radiate outward from a central vein - hepatic portal vein - vein that supplies deoxygenated nutrient-rich blood to the liver - hepatic sinusoid - blood capillaries between rows of hepatocytes that receive blood from the hepatic portal vein and the branches of the hepatic artery - hepatic vein - vein that drains into the inferior vena cava - hepatocytes - major functional cells of the liver - hepatopancreatic ampulla - (also, ampulla of Vater) bulb-like point in the wall of the duodenum where the bile duct and main pancreatic duct unite - hepatopancreatic sphincter - (also, sphincter of Oddi) sphincter regulating the flow of bile and pancreatic juice into the duodenum - hydrochloric acid (HCl) - digestive acid secreted by parietal cells in the stomach - ileocecal sphincter - sphincter located where the small intestine joins with the large intestine - ileum - end of the small intestine between the jejunum and the large intestine - incisor - midline, chisel-shaped tooth used for cutting into food - ingestion - taking food into the GI tract through the mouth - internal anal sphincter - involuntary smooth muscle sphincter in the anal canal - intestinal gland - (also, crypt of Lieberkühn) gland in the small intestinal mucosa that secretes intestinal juice - intestinal juice - mixture of water and mucus that helps absorb nutrients from chyme - intestinal phase - phase of gastric secretion that begins when chyme enters the intestine - intrinsic factor - glycoprotein required for vitamin B12 absorption in the small intestine - jejunum - middle part of the small intestine between the duodenum and the ileum - labial frenulum - midline mucous membrane fold that attaches the inner surface of the lips to the gums - labium - lip - lactase - brush border enzyme that breaks down lactose into glucose and galactose - lacteal - lymphatic capillary in the villi - large intestine - terminal portion of the alimentary canal - laryngopharynx - part of the pharynx that functions in respiration and digestion - left colic flexure - (also, splenic flexure) point where the transverse colon curves below the inferior end of the spleen - lingual frenulum - mucous membrane fold that attaches the bottom of the tongue to the floor of the mouth - lingual lipase - digestive enzyme from glands in the tongue that acts on triglycerides - lipoprotein lipase - enzyme that breaks down triglycerides in chylomicrons into fatty acids and monoglycerides - liver - largest gland in the body whose main digestive function is the production of bile - lower esophageal sphincter - smooth muscle sphincter that regulates food movement from the esophagus to the stomach - main pancreatic duct - (also, duct of Wirsung) duct through which pancreatic juice drains from the pancreas - major duodenal papilla - point at which the hepatopancreatic ampulla opens into the duodenum - maltase - brush border enzyme that breaks down maltose and maltotriose into two and three molecules of glucose, respectively - mass movement - long, slow, peristaltic wave in the large intestine - mastication - chewing - mechanical digestion - chewing, mixing, and segmentation that prepares food for chemical digestion - mesoappendix - mesentery of the appendix - micelle - tiny lipid-transport compound composed of bile salts and phospholipids with a fatty acid and monoacylglyceride core - microvillus - small projection of the plasma membrane of the absorptive cells of the small intestinal mucosa - migrating motility complex - form of peristalsis in the small intestine - mixing wave - unique type of peristalsis that occurs in the stomach - molar - tooth used for crushing and grinding food - motilin - hormone that initiates migrating motility complexes - motility - movement of food through the GI tract - mucosa - innermost lining of the alimentary canal - mucosal barrier - protective barrier that prevents gastric juice from destroying the stomach itself - mucous neck cell - gastric gland cell that secretes a uniquely acidic mucus - muscularis - muscle (skeletal or smooth) layer of the alimentary canal wall - myenteric plexus - (plexus of Auerbach) major nerve supply to alimentary canal wall; controls motility - nucleosidase - brush border enzyme that digests nucleotides - oral cavity - (also, buccal cavity) mouth - oral vestibule - part of the mouth bounded externally by the cheeks and lips, and internally by the gums and teeth - oropharynx - part of the pharynx continuous with the oral cavity that functions in respiration and digestion - palatoglossal arch - muscular fold that extends from the lateral side of the soft palate to the base of the tongue - palatopharyngeal arch - muscular fold that extends from the lateral side of the soft palate to the side of the pharynx - pancreas - accessory digestive organ that secretes pancreatic juice - pancreatic amylase - enzyme secreted by the pancreas that completes the chemical digestion of carbohydrates in the small intestine - pancreatic juice - secretion of the pancreas containing digestive enzymes and bicarbonate - pancreatic lipase - enzyme secreted by the pancreas that participates in lipid digestion - pancreatic nuclease - enzyme secreted by the pancreas that participates in nucleic acid digestion - parietal cell - gastric gland cell that secretes hydrochloric acid and intrinsic factor - parotid gland - one of a pair of major salivary glands located inferior and anterior to the ears - pectinate line - horizontal line that runs like a ring, perpendicular to the inferior margins of the anal sinuses - pepsinogen - inactive form of pepsin - peristalsis - muscular contractions and relaxations that propel food through the GI tract - permanent tooth - one of 32 adult teeth - pharynx - throat - phosphatase - brush border enzyme that digests nucleotides - porta hepatis - “gateway to the liver” where the hepatic artery and hepatic portal vein enter the liver - portal triad - bile duct, hepatic artery branch, and hepatic portal vein branch - premolar - (also, bicuspid) transitional tooth used for mastication, crushing, and grinding food - propulsion - voluntary process of swallowing and the involuntary process of peristalsis that moves food through the digestive tract - pulp cavity - deepest portion of a tooth, containing nerve endings and blood vessels - pyloric antrum - wider, more superior part of the pylorus - pyloric canal - narrow, more inferior part of the pylorus - pyloric sphincter - sphincter that controls stomach emptying - pylorus - lower, funnel-shaped part of the stomach that is continuous with the duodenum - rectal valve - one of three transverse folds in the rectum where feces is separated from flatus - rectum - part of the large intestine between the sigmoid colon and anal canal - reticuloendothelial cell - (also, Kupffer cell) phagocyte in hepatic sinusoids that filters out material from venous blood from the alimentary canal - retroperitoneal - located posterior to the peritoneum - ribonuclease - pancreatic enzyme that digests RNA - right colic flexure - (also, hepatic flexure) point, at the inferior surface of the liver, where the ascending colon turns abruptly to the left - root - portion of a tooth embedded in the alveolar processes beneath the gum line - ruga - fold of alimentary canal mucosa and submucosa in the empty stomach and other organs - saccharolytic fermentation - anaerobic decomposition of carbohydrates - saliva - aqueous solution of proteins and ions secreted into the mouth by the salivary glands - salivary amylase - digestive enzyme in saliva that acts on starch - salivary gland - an exocrine gland that secretes a digestive fluid called saliva - salivation - secretion of saliva - segmentation - alternating contractions and relaxations of non-adjacent segments of the intestine that move food forward and backward, breaking it apart and mixing it with digestive juices - serosa - outermost layer of the alimentary canal wall present in regions within the abdominal cavity - sigmoid colon - end portion of the colon, which terminates at the rectum - small intestine - section of the alimentary canal where most digestion and absorption occurs - soft palate - posterior region of the bottom portion of the nasal cavity that consists of skeletal muscle - stomach - alimentary canal organ that contributes to chemical and mechanical digestion of food from the esophagus before releasing it, as chyme, to the small intestine - sublingual gland - one of a pair of major salivary glands located beneath the tongue - submandibular gland - one of a pair of major salivary glands located in the floor of the mouth - submucosa - layer of dense connective tissue in the alimentary canal wall that binds the overlying mucosa to the underlying muscularis - submucosal plexus - (plexus of Meissner) nerve supply that regulates activity of glands and smooth muscle - sucrase - brush border enzyme that breaks down sucrose into glucose and fructose - tenia coli - one of three smooth muscle bands that make up the longitudinal muscle layer of the muscularis in all of the large intestine except the terminal end - tongue - accessory digestive organ of the mouth, the bulk of which is composed of skeletal muscle - transverse colon - part of the colon between the ascending colon and the descending colon - upper esophageal sphincter - skeletal muscle sphincter that regulates food movement from the pharynx to the esophagus - Valsalva’s maneuver - voluntary contraction of the diaphragm and abdominal wall muscles and closing of the glottis, which increases intra-abdominal pressure and facilitates defecation - villus - projection of the mucosa of the small intestine - voluntary phase - initial phase of deglutition, in which the bolus moves from the mouth to the oropharynx - α-dextrin - breakdown product of starch - α-dextrinase - brush border enzyme that acts on α-dextrins Chapter Review 23.1 Overview of the Digestive System The digestive system includes the organs of the alimentary canal and accessory structures. The alimentary canal forms a continuous tube that is open to the outside environment at both ends. The organs of the alimentary canal are the mouth, pharynx, esophagus, stomach, small intestine, and large intestine. The accessory digestive structures include the teeth, tongue, salivary glands, liver, pancreas, and gallbladder. The wall of the alimentary canal is composed of four basic tissue layers: mucosa, submucosa, muscularis, and serosa. The enteric nervous system provides intrinsic innervation, and the autonomic nervous system provides extrinsic innervation. 23.2 Digestive System Processes and Regulation The digestive system ingests and digests food, absorbs released nutrients, and excretes food components that are indigestible. The six activities involved in this process are ingestion, motility, mechanical digestion, chemical digestion, absorption, and defecation. These processes are regulated by neural and hormonal mechanisms. 23.3 The Mouth, Pharynx, and Esophagus In the mouth, the tongue and the teeth begin mechanical digestion, and saliva begins chemical digestion. The pharynx, which plays roles in breathing and vocalization as well as digestion, runs from the nasal and oral cavities superiorly to the esophagus inferiorly (for digestion) and to the larynx anteriorly (for respiration). During deglutition (swallowing), the soft palate rises to close off the nasopharynx, the larynx elevates, and the epiglottis folds over the glottis. The esophagus includes an upper esophageal sphincter made of skeletal muscle, which regulates the movement of food from the pharynx to the esophagus. It also has a lower esophageal sphincter, made of smooth muscle, which controls the passage of food from the esophagus to the stomach. Cells in the esophageal wall secrete mucus that eases the passage of the food bolus. 23.4 The Stomach The stomach participates in all digestive activities except ingestion and defecation. It vigorously churns food. It secretes gastric juices that break down food and absorbs certain drugs, including aspirin and some alcohol. The stomach begins the digestion of protein and continues the digestion of carbohydrates and fats. It stores food as an acidic liquid called chyme, and releases it gradually into the small intestine through the pyloric sphincter. 23.5 The Small and Large Intestines The three main regions of the small intestine are the duodenum, the jejunum, and the ileum. The small intestine is where digestion is completed and virtually all absorption occurs. These two activities are facilitated by structural adaptations that increase the mucosal surface area by 600-fold, including circular folds, villi, and microvilli. There are around 200 million microvilli per square millimeter of small intestine, which contain brush border enzymes that complete the digestion of carbohydrates and proteins. Combined with pancreatic juice, intestinal juice provides the liquid medium needed to further digest and absorb substances from chyme. The small intestine is also the site of unique mechanical digestive movements. Segmentation moves the chyme back and forth, increasing mixing and opportunities for absorption. Migrating motility complexes propel the residual chyme toward the large intestine. The main regions of the large intestine are the cecum, the colon, and the rectum. The large intestine absorbs water and forms feces, and is responsible for defecation. Bacterial flora break down additional carbohydrate residue, and synthesize certain vitamins. The mucosa of the large intestinal wall is generously endowed with goblet cells, which secrete mucus that eases the passage of feces. The entry of feces into the rectum activates the defecation reflex. 23.6 Accessory Organs in Digestion: The Liver, Pancreas, and Gallbladder Chemical digestion in the small intestine cannot occur without the help of the liver and pancreas. The liver produces bile and delivers it to the common hepatic duct. Bile contains bile salts and phospholipids, which emulsify large lipid globules into tiny lipid droplets, a necessary step in lipid digestion and absorption. The gallbladder stores and concentrates bile, releasing it when it is needed by the small intestine. The pancreas produces the enzyme- and bicarbonate-rich pancreatic juice and delivers it to the small intestine through ducts. Pancreatic juice buffers the acidic gastric juice in chyme, inactivates pepsin from the stomach, and enables the optimal functioning of digestive enzymes in the small intestine. 23.7 Chemical Digestion and Absorption: A Closer Look The small intestine is the site of most chemical digestion and almost all absorption. Chemical digestion breaks large food molecules down into their chemical building blocks, which can then be absorbed through the intestinal wall and into the general circulation. Intestinal brush border enzymes and pancreatic enzymes are responsible for the majority of chemical digestion. The breakdown of fat also requires bile. Most nutrients are absorbed by transport mechanisms at the apical surface of enterocytes. Exceptions include lipids, fat-soluble vitamins, and most water-soluble vitamins. With the help of bile salts and lecithin, the dietary fats are emulsified to form micelles, which can carry the fat particles to the surface of the enterocytes. There, the micelles release their fats to diffuse across the cell membrane. The fats are then reassembled into triglycerides and mixed with other lipids and proteins into chylomicrons that can pass into lacteals. Other absorbed monomers travel from blood capillaries in the villus to the hepatic portal vein and then to the liver. Interactive Link Questions By clicking on this link, you can watch a short video of what happens to the food you eat as it passes from your mouth to your intestine. Along the way, note how the food changes consistency and form. How does this change in consistency facilitate your gaining nutrients from food? 2.Visit this site for an overview of digestion of food in different regions of the digestive tract. Note the route of non-fat nutrients from the small intestine to their release as nutrients to the body. 3.Watch this animation to see how swallowing is a complex process that involves the nervous system to coordinate the actions of upper respiratory and digestive activities. During which stage of swallowing is there a risk of food entering respiratory pathways and how is this risk blocked? 4.Watch this animation that depicts the structure of the stomach and how this structure functions in the initiation of protein digestion. This view of the stomach shows the characteristic rugae. What is the function of these rugae? 5.Watch this animation that depicts the structure of the small intestine, and, in particular, the villi. Epithelial cells continue the digestion and absorption of nutrients and transport these nutrients to the lymphatic and circulatory systems. In the small intestine, the products of food digestion are absorbed by different structures in the villi. Which structure absorbs and transports fats? 6.By watching this animation, you will see that for the various food groups—proteins, fats, and carbohydrates—digestion begins in different parts of the digestion system, though all end in the same place. Of the three major food classes (carbohydrates, fats, and proteins), which is digested in the mouth, the stomach, and the small intestine? 7.Watch this video to see the structure of the liver and how this structure supports the functions of the liver, including the processing of nutrients, toxins, and wastes. At rest, about 1500 mL of blood per minute flow through the liver. What percentage of this blood flow comes from the hepatic portal system? Review Questions Which of these organs is not considered an accessory digestive structure? - mouth - salivary glands - pancreas - liver Which of the following organs is supported by a layer of adventitia rather than serosa? - esophagus - stomach - small intestine - large intestine Which of the following membranes covers the stomach? - falciform ligament - mesocolon - parietal peritoneum - visceral peritoneum Which of these processes occurs in the mouth? - ingestion - mechanical digestion - chemical digestion - all of the above Which of these processes occurs throughout most of the alimentary canal? - ingestion - propulsion - segmentation - absorption Which of the following stimuli activates sensors in the walls of digestive organs? - breakdown products of digestion - distension - pH of chyme - all of the above Which of these statements about reflexes in the GI tract is false? - Short reflexes are provoked by nerves near the GI tract. - Short reflexes are mediated by the enteric nervous system. - Food that distends the stomach initiates long reflexes. - Long reflexes can be provoked by stimuli originating outside the GI tract. Which of these ingredients in saliva is responsible for activating salivary amylase? - mucus - phosphate ions - chloride ions - urea Which of these statements about the pharynx is true? - It extends from the nasal and oral cavities superiorly to the esophagus anteriorly. - The oropharynx is continuous superiorly with the nasopharynx. - The nasopharynx is involved in digestion. - The laryngopharynx is composed partially of cartilage. Which structure is located where the esophagus penetrates the diaphragm? - esophageal hiatus - cardiac orifice - upper esophageal sphincter - lower esophageal sphincter Which phase of deglutition involves contraction of the longitudinal muscle layer of the muscularis? - voluntary phase - buccal phase - pharyngeal phase - esophageal phase Which of these cells secrete hormones? - parietal cells - mucous neck cells - enteroendocrine cells - chief cells Where does the majority of chemical digestion in the stomach occur? - fundus and body - cardia and fundus - body and pylorus - body During gastric emptying, chyme is released into the duodenum through the ________. - esophageal hiatus - pyloric antrum - pyloric canal - pyloric sphincter Parietal cells secrete ________. - gastrin - hydrochloric acid - pepsin - pepsinogen In which part of the alimentary canal does most digestion occur? - stomach - proximal small intestine - distal small intestine - ascending colon Which of these is most associated with villi? - haustra - lacteals - bacterial flora - intestinal glands What is the role of the small intestine’s MALT? - secreting mucus - buffering acidic chyme - activating pepsin - preventing bacteria from entering the bloodstream Which part of the large intestine attaches to the appendix? - cecum - ascending colon - transverse colon - descending colon Which of these statements about bile is true? - About 500 mL is secreted daily. - Its main function is the denaturation of proteins. - It is synthesized in the gallbladder. - Bile salts are recycled. Pancreatic juice ________. - deactivates bile. - is secreted by pancreatic islet cells. - buffers chyme. - is released into the cystic duct. Where does the chemical digestion of starch begin? - mouth - esophagus - stomach - small intestine Which of these is involved in the chemical digestion of protein? - pancreatic amylase - trypsin - sucrase - pancreatic nuclease Where are most fat-digesting enzymes produced? - small intestine - gallbladder - liver - pancreas Which of these nutrients is absorbed mainly in the duodenum? - glucose - iron - sodium - water Critical Thinking Questions Explain how the enteric nervous system supports the digestive system. What might occur that could result in the autonomic nervous system having a negative impact on digestion? 34.What layer of the alimentary canal tissue is capable of helping to protect the body against disease, and through what mechanism? 35.Offer a theory to explain why segmentation occurs and peristalsis slows in the small intestine. 36.It has been several hours since you last ate. Walking past a bakery, you catch a whiff of freshly baked bread. What type of reflex is triggered, and what is the result? 37.The composition of saliva varies from gland to gland. Discuss how saliva produced by the parotid gland differs in action from saliva produced by the sublingual gland. 38.During a hockey game, the puck hits a player in the mouth, knocking out all eight of his most anterior teeth. Which teeth did the player lose and how does this loss affect food ingestion? 39.What prevents swallowed food from entering the airways? 40.Explain the mechanism responsible for gastroesophageal reflux. 41.Describe the three processes involved in the esophageal phase of deglutition. 42.Explain how the stomach is protected from self-digestion and why this is necessary. 43.Describe unique anatomical features that enable the stomach to perform digestive functions. 44.Explain how nutrients absorbed in the small intestine pass into the general circulation. 45.Why is it important that chyme from the stomach is delivered to the small intestine slowly and in small amounts? 46.Describe three of the differences between the walls of the large and small intestines. 47.Why does the pancreas secrete some enzymes in their inactive forms, and where are these enzymes activated? 48.Describe the location of hepatocytes in the liver and how this arrangement enhances their function. 49.Explain the role of bile salts and lecithin in the emulsification of lipids (fats). 50.How is vitamin B12 absorbed?	oercommons	2025-03-18T00:36:11.940772	10/14/2019	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/58771/overview", "title": "Anatomy and Physiology, Energy, Maintenance, and Environmental Exchange, The Digestive System", "author": null }
https://oercommons.org/courseware/lesson/56370/overview	The Muscular System Introduction Figure 11.1 A Body in Motion The muscular system allows us to move, flex and contort our bodies. Practicing yoga, as pictured here, is a good example of the voluntary use of the muscular system. (credit: Dmitry Yanchylenko) CHAPTER OBJECTIVES After studying this chapter, you will be able to: - Describe the actions and roles of agonists and antagonists - Explain the structure and organization of muscle fascicles and their role in generating force - Explain the criteria used to name skeletal muscles - Identify the skeletal muscles and their actions on the skeleton and soft tissues of the body - Identify the origins and insertions of skeletal muscles and the prime movements Think about the things that you do each day—talking, walking, sitting, standing, and running—all of these activities require movement of particular skeletal muscles. Skeletal muscles are even used during sleep. The diaphragm is a sheet of skeletal muscle that has to contract and relax for you to breathe day and night. If you recall from your study of the skeletal system and joints, body movement occurs around the joints in the body. The focus of this chapter is on skeletal muscle organization. The system to name skeletal muscles will be explained; in some cases, the muscle is named by its shape, and in other cases it is named by its location or attachments to the skeleton. If you understand the meaning of the name of the muscle, often it will help you remember its location and/or what it does. This chapter also will describe how skeletal muscles are arranged to accomplish movement, and how other muscles may assist, or be arranged on the skeleton to resist or carry out the opposite movement. The actions of the skeletal muscles will be covered in a regional manner, working from the head down to the toes. Interactions of Skeletal Muscles, Their Fascicle Arrangement, and Their Lever Systems - Compare and contrast agonist and antagonist muscles - Describe how fascicles are arranged within a skeletal muscle - Explain the major events of a skeletal muscle contraction within a muscle in generating force To move the skeleton, the tension created by the contraction of the fibers in most skeletal muscles is transferred to the tendons. The tendons are strong bands of dense, regular connective tissue that connect muscles to bones. The bone connection is why this muscle tissue is called skeletal muscle. Interactions of Skeletal Muscles in the Body To pull on a bone, that is, to change the angle at its synovial joint, which essentially moves the skeleton, a skeletal muscle must also be attached to a fixed part of the skeleton. The moveable end of the muscle that attaches to the bone being pulled is called the muscle’s insertion, and the end of the muscle attached to a fixed (stabilized) bone is called the origin. During forearm flexion—bending the elbow—the brachioradialis assists the brachialis. Although a number of muscles may be involved in an action, the principal muscle involved is called the prime mover, or agonist. To lift a cup, a muscle called the biceps brachii is actually the prime mover; however, because it can be assisted by the brachialis, the brachialis is called a synergist in this action (Figure 11.2). A synergist can also be a fixator that stabilizes the bone that is the attachment for the prime mover’s origin. Figure 11.2 Prime Movers and Synergists The biceps brachii flex the lower arm. The brachoradialis, in the forearm, and brachialis, located deep to the biceps in the upper arm, are both synergists that aid in this motion. A muscle with the opposite action of the prime mover is called an antagonist. Antagonists play two important roles in muscle function: (1) they maintain body or limb position, such as holding the arm out or standing erect; and (2) they control rapid movement, as in shadow boxing without landing a punch or the ability to check the motion of a limb. For example, to extend the knee, a group of four muscles called the quadriceps femoris in the anterior compartment of the thigh are activated (and would be called the agonists of knee extension). However, to flex the knee joint, an opposite or antagonistic set of muscles called the hamstrings is activated. As you can see, these terms would also be reversed for the opposing action. If you consider the first action as the knee bending, the hamstrings would be called the agonists and the quadriceps femoris would then be called the antagonists. See Table 11.1 for a list of some agonists and antagonists. Agonist and Antagonist Skeletal Muscle Pairs \| Agonist \| Antagonist \| Movement \| \|---\|---\|---\| \| Biceps brachii: in the anterior compartment of the arm \| Triceps brachii: in the posterior compartment of the arm \| The biceps brachii flexes the forearm, whereas the triceps brachii extends it. \| \| Hamstrings: group of three muscles in the posterior compartment of the thigh \| Quadriceps femoris: group of four muscles in the anterior compartment of the thigh \| The hamstrings flex the leg, whereas the quadriceps femoris extend it. \| \| Flexor digitorum superficialis and flexor digitorum profundus: in the anterior compartment of the forearm \| Extensor digitorum: in the posterior compartment of the forearm \| The flexor digitorum superficialis and flexor digitorum profundus flex the fingers and the hand at the wrist, whereas the extensor digitorum extends the fingers and the hand at the wrist. \| Table 11.1 There are also skeletal muscles that do not pull against the skeleton for movements. For example, there are the muscles that produce facial expressions. The insertions and origins of facial muscles are in the skin, so that certain individual muscles contract to form a smile or frown, form sounds or words, and raise the eyebrows. There also are skeletal muscles in the tongue, and the external urinary and anal sphincters that allow for voluntary regulation of urination and defecation, respectively. In addition, the diaphragm contracts and relaxes to change the volume of the pleural cavities but it does not move the skeleton to do this. EVERYDAY CONNECTION Exercise and Stretching When exercising, it is important to first warm up the muscles. Stretching pulls on the muscle fibers and it also results in an increased blood flow to the muscles being worked. Without a proper warm-up, it is possible that you may either damage some of the muscle fibers or pull a tendon. A pulled tendon, regardless of location, results in pain, swelling, and diminished function; if it is moderate to severe, the injury could immobilize you for an extended period. Recall the discussion about muscles crossing joints to create movement. Most of the joints you use during exercise are synovial joints, which have synovial fluid in the joint space between two bones. Exercise and stretching may also have a beneficial effect on synovial joints. Synovial fluid is a thin, but viscous film with the consistency of egg whites. When you first get up and start moving, your joints feel stiff for a number of reasons. After proper stretching and warm-up, the synovial fluid may become less viscous, allowing for better joint function. Patterns of Fascicle Organization Skeletal muscle is enclosed in connective tissue scaffolding at three levels. Each muscle fiber (cell) is covered by endomysium and the entire muscle is covered by epimysium. When a group of muscle fibers is “bundled” as a unit within the whole muscle by an additional covering of a connective tissue called perimysium, that bundled group of muscle fibers is called a fascicle. Fascicle arrangement by perimysia is correlated to the force generated by a muscle; it also affects the range of motion of the muscle. Based on the patterns of fascicle arrangement, skeletal muscles can be classified in several ways. What follows are the most common fascicle arrangements. Parallel muscles have fascicles that are arranged in the same direction as the long axis of the muscle (Figure 11.3). The majority of skeletal muscles in the body have this type of organization. Some parallel muscles are flat sheets that expand at the ends to make broad attachments. Other parallel muscles are rotund with tendons at one or both ends. Muscles that seem to be plump have a large mass of tissue located in the middle of the muscle, between the insertion and the origin, which is known as the central body. A more common name for this muscle is belly. When a muscle contracts, the contractile fibers shorten it to an even larger bulge. For example, extend and then flex your biceps brachii muscle; the large, middle section is the belly (Figure 11.4). When a parallel muscle has a central, large belly that is spindle-shaped, meaning it tapers as it extends to its origin and insertion, it sometimes is called fusiform. Figure 11.3 Muscle Shapes and Fiber Alignment The skeletal muscles of the body typically come in seven different general shapes. Figure 11.4 Biceps Brachii Muscle Contraction The large mass at the center of a muscle is called the belly. Tendons emerge from both ends of the belly and connect the muscle to the bones, allowing the skeleton to move. The tendons of the bicep connect to the upper arm and the forearm. (credit: Victoria Garcia) Circular muscles are also called sphincters (see Figure 11.3). When they relax, the sphincters’ concentrically arranged bundles of muscle fibers increase the size of the opening, and when they contract, the size of the opening shrinks to the point of closure. The orbicularis oris muscle is a circular muscle that goes around the mouth. When it contracts, the oral opening becomes smaller, as when puckering the lips for whistling. Another example is the orbicularis oculi, one of which surrounds each eye. Consider, for example, the names of the two orbicularis muscles (orbicularis oris and oribicularis oculi), where part of the first name of both muscles is the same. The first part of orbicularis, orb (orb = “circular”), is a reference to a round or circular structure; it may also make one think of orbit, such as the moon’s path around the earth. The word oris (oris = “oral”) refers to the oral cavity, or the mouth. The word oculi (ocular = “eye”) refers to the eye. There are other muscles throughout the body named by their shape or location. The deltoid is a large, triangular-shaped muscle that covers the shoulder. It is so-named because the Greek letter delta looks like a triangle. The rectus abdomis (rector = “straight”) is the straight muscle in the anterior wall of the abdomen, while the rectus femoris is the straight muscle in the anterior compartment of the thigh. When a muscle has a widespread expansion over a sizable area, but then the fascicles come to a single, common attachment point, the muscle is called convergent. The attachment point for a convergent muscle could be a tendon, an aponeurosis (a flat, broad tendon), or a raphe (a very slender tendon). The large muscle on the chest, the pectoralis major, is an example of a convergent muscle because it converges on the greater tubercle of the humerus via a tendon. The temporalis muscle of the cranium is another. Pennate muscles (penna = “feathers”) blend into a tendon that runs through the central region of the muscle for its whole length, somewhat like the quill of a feather with the muscle arranged similar to the feathers. Due to this design, the muscle fibers in a pennate muscle can only pull at an angle, and as a result, contracting pennate muscles do not move their tendons very far. However, because a pennate muscle generally can hold more muscle fibers within it, it can produce relatively more tension for its size. There are three subtypes of pennate muscles. In a unipennate muscle, the fascicles are located on one side of the tendon. The extensor digitorum of the forearm is an example of a unipennate muscle. A bipennate muscle has fascicles on both sides of the tendon. In some pennate muscles, the muscle fibers wrap around the tendon, sometimes forming individual fascicles in the process. This arrangement is referred to as multipennate. A common example is the deltoid muscle of the shoulder, which covers the shoulder but has a single tendon that inserts on the deltoid tuberosity of the humerus. Because of fascicles, a portion of a multipennate muscle like the deltoid can be stimulated by the nervous system to change the direction of the pull. For example, when the deltoid muscle contracts, the arm abducts (moves away from midline in the sagittal plane), but when only the anterior fascicle is stimulated, the arm will abduct and flex (move anteriorly at the shoulder joint). The Lever System of Muscle and Bone Interactions Skeletal muscles do not work by themselves. Muscles are arranged in pairs based on their functions. For muscles attached to the bones of the skeleton, the connection determines the force, speed, and range of movement. These characteristics depend on each other and can explain the general organization of the muscular and skeletal systems. The skeleton and muscles act together to move the body. Have you ever used the back of a hammer to remove a nail from wood? The handle acts as a lever and the head of the hammer acts as a fulcrum, the fixed point that the force is applied to when you pull back or push down on the handle. The effort applied to this system is the pulling or pushing on the handle to remove the nail, which is the load, or “resistance” to the movement of the handle in the system. Our musculoskeletal system works in a similar manner, with bones being stiff levers and the articular endings of the bones—encased in synovial joints—acting as fulcrums. The load would be an object being lifted or any resistance to a movement (your head is a load when you are lifting it), and the effort, or applied force, comes from contracting skeletal muscle. Naming Skeletal Muscles - Describe the criteria used to name skeletal muscles - Explain how understanding the muscle names helps describe shapes, location, and actions of various muscles The Greeks and Romans conducted the first studies done on the human body in Western culture. The educated class of subsequent societies studied Latin and Greek, and therefore the early pioneers of anatomy continued to apply Latin and Greek terminology or roots when they named the skeletal muscles. The large number of muscles in the body and unfamiliar words can make learning the names of the muscles in the body seem daunting, but understanding the etymology can help. Etymology is the study of how the root of a particular word entered a language and how the use of the word evolved over time. Taking the time to learn the root of the words is crucial to understanding the vocabulary of anatomy and physiology. When you understand the names of muscles it will help you remember where the muscles are located and what they do (Figure 11.5, Figure 11.6, and Table 11.2). Pronunciation of words and terms will take a bit of time to master, but after you have some basic information; the correct names and pronunciations will become easier. Figure 11.5 Overview of the Muscular System On the anterior and posterior views of the muscular system above, superficial muscles (those at the surface) are shown on the right side of the body while deep muscles (those underneath the superficial muscles) are shown on the left half of the body. For the legs, superficial muscles are shown in the anterior view while the posterior view shows both superficial and deep muscles. Figure 11.6 Understanding a Muscle Name from the Latin Mnemonic Device for Latin Roots \| Example \| Latin or Greek Translation \| Mnemonic Device \| \|---\|---\|---\| \| ad \| to; toward \| ADvance toward your goal \| \| ab \| away from \| n/a \| \| sub \| under \| SUBmarines move under water. \| \| ductor \| something that moves \| A conDUCTOR makes a train move. \| \| anti \| against \| If you are antisocial, you are against engaging in social activities. \| \| epi \| on top of \| n/a \| \| apo \| to the side of \| n/a \| \| longissimus \| longest \| “Longissimus” is longer than the word “long.” \| \| longus \| long \| long \| \| brevis \| short \| brief \| \| maximus \| large \| max \| \| medius \| medium \| “Medius” and “medium” both begin with “med.” \| \| minimus \| tiny; little \| mini \| \| rectus \| straight \| To RECTify a situation is to straighten it out. \| \| multi \| many \| If something is MULTIcolored, it has many colors. \| \| uni \| one \| A UNIcorn has one horn. \| \| bi/di \| two \| If a ring is DIcast, it is made of two metals. \| \| tri \| three \| TRIple the amount of money is three times as much. \| \| quad \| four \| QUADruplets are four children born at one birth. \| \| externus \| outside \| EXternal \| \| internus \| inside \| INternal \| Table 11.2 Anatomists name the skeletal muscles according to a number of criteria, each of which describes the muscle in some way. These include naming the muscle after its shape, its size compared to other muscles in the area, its location in the body or the location of its attachments to the skeleton, how many origins it has, or its action. The skeletal muscle’s anatomical location or its relationship to a particular bone often determines its name. For example, the frontalis muscle is located on top of the frontal bone of the skull. Similarly, the shapes of some muscles are very distinctive and the names, such as orbicularis, reflect the shape. For the buttocks, the size of the muscles influences the names: gluteus maximus (largest), gluteus medius (medium), and the gluteus minimus (smallest). Names were given to indicate length—brevis(short), longus (long)—and to identify position relative to the midline: lateralis (to the outside away from the midline), and medialis (toward the midline). The direction of the muscle fibers and fascicles are used to describe muscles relative to the midline, such as the rectus (straight) abdominis, or the oblique (at an angle) muscles of the abdomen. Some muscle names indicate the number of muscles in a group. One example of this is the quadriceps, a group of four muscles located on the anterior (front) thigh. Other muscle names can provide information as to how many origins a particular muscle has, such as the biceps brachii. The prefix bi indicates that the muscle has two origins and tri indicates three origins. The location of a muscle’s attachment can also appear in its name. When the name of a muscle is based on the attachments, the origin is always named first. For instance, the sternocleidomastoid muscle of the neck has a dual origin on the sternum (sterno) and clavicle (cleido), and it inserts on the mastoid process of the temporal bone. The last feature by which to name a muscle is its action. When muscles are named for the movement they produce, one can find action words in their name. Some examples are flexor (decreases the angle at the joint), extensor (increases the angle at the joint), abductor (moves the bone away from the midline), or adductor (moves the bone toward the midline). Axial Muscles of the Head, Neck, and Back - Identify the axial muscles of the face, head, and neck - Identify the movement and function of the face, head, and neck muscles The skeletal muscles are divided into axial (muscles of the trunk and head) and appendicular (muscles of the arms and legs) categories. This system reflects the bones of the skeleton system, which are also arranged in this manner. The axial muscles are grouped based on location, function, or both. Some of the axial muscles may seem to blur the boundaries because they cross over to the appendicular skeleton. The first grouping of the axial muscles you will review includes the muscles of the head and neck, then you will review the muscles of the vertebral column, and finally you will review the oblique and rectus muscles. Muscles That Create Facial Expression The origins of the muscles of facial expression are on the surface of the skull (remember, the origin of a muscle does not move). The insertions of these muscles have fibers intertwined with connective tissue and the dermis of the skin. Because the muscles insert in the skin rather than on bone, when they contract, the skin moves to create facial expression (Figure 11.7). Figure 11.7 Muscles of Facial Expression Many of the muscles of facial expression insert into the skin surrounding the eyelids, nose and mouth, producing facial expressions by moving the skin rather than bones. The orbicularis oris is a circular muscle that moves the lips, and the orbicularis oculi is a circular muscle that closes the eye. The occipitofrontalis muscle moves up the scalp and eyebrows. The muscle has a frontal belly and an occipital (near the occipital bone on the posterior part of the skull) belly. In other words, there is a muscle on the forehead (frontalis) and one on the back of the head (occipitalis), but there is no muscle across the top of the head. Instead, the two bellies are connected by a broad tendon called the epicranial aponeurosis, or galea aponeurosis (galea = “helmet”). The physicians originally studying human anatomy thought the skull looked like an helmet. A large portion of the face is composed of the buccinator muscle, which compresses the cheek. This muscle allows you to whistle, blow, and suck; and it contributes to the action of chewing. There are several small facial muscles, one of which is the corrugator supercilii, which is the prime mover of the eyebrows. Place your finger on your eyebrows at the point of the bridge of the nose. Raise your eyebrows as if you were surprised and lower your eyebrows as if you were frowning. With these movements, you can feel the action of the corrugator supercilli. Additional muscles of facial expression are presented in Figure 11.8. Figure 11.8 Muscles in Facial Expression Muscles That Move the Eyes The movement of the eyeball is under the control of the extrinsic eye muscles, which originate outside the eye and insert onto the outer surface of the white of the eye. These muscles are located inside the eye socket and cannot be seen on any part of the visible eyeball (Figure 11.9 and Table 11.3). If you have ever been to a doctor who held up a finger and asked you to follow it up, down, and to both sides, he or she is checking to make sure your eye muscles are acting in a coordinated pattern. Figure 11.9 Muscles of the Eyes (a) The extrinsic eye muscles originate outside of the eye on the skull. (b) Each muscle inserts onto the eyeball. Muscles of the Eyes \| Movement \| Target \| Target motion direction \| Prime mover \| Origin \| Insertion \| \|---\|---\|---\|---\|---\|---\| \| Moves eyes up and toward nose; rotates eyes from 1 o’clock to 3 o’clock \| Eyeballs \| Superior (elevates); medial (adducts) \| Superior rectus \| Common tendinous ring (ring attaches to optic foramen) \| Superior surface of eyeball \| \| Moves eyes down and toward nose; rotates eyes from 6 o’clock to 3 o’clock \| Eyeballs \| Inferior (depresses); medial (adducts) \| Inferior rectus \| Common tendinous ring (ring attaches to optic foramen) \| Inferior surface of eyeball \| \| Moves eyes away from nose \| Eyeballs \| Lateral (abducts) \| Lateral rectus \| Common tendinous ring (ring attaches to optic foramen) \| Lateral surface of eyeball \| \| Moves eyes toward nose \| Eyeballs \| Medial (adducts) \| Medial rectus \| Common tendinous ring (ring attaches to optic foramen) \| Medial surface of eyeball \| \| Moves eyes up and away from nose; rotates eyeball from 12 o’clock to 9 o’clock \| Eyeballs \| Superior (elevates); lateral (abducts) \| Inferior oblique \| Floor of orbit (maxilla) \| Surface of eyeball between inferior rectus and lateral rectus \| \| Moves eyes down and away from nose; rotates eyeball from 6 o’clock to 9 o’clock \| Eyeballs \| Superior (elevates); lateral (abducts) \| Superior oblique \| Sphenoid bone \| Suface of eyeball between superior rectus and lateral rectus \| \| Opens eyes \| Upper eyelid \| Superior (elevates) \| Levator palpabrae superioris \| Roof of orbit (sphenoid bone) \| Skin of upper eyelids \| \| Closes eyelids \| Eyelid skin \| Compression along superior–inferior axis \| Orbicularis oculi \| Medial bones composing the orbit \| Circumference of orbit \| Table 11.3 Muscles That Move the Lower Jaw In anatomical terminology, chewing is called mastication. Muscles involved in chewing must be able to exert enough pressure to bite through and then chew food before it is swallowed (Figure 11.10 and Table 11.4). The masseter muscle is the main muscle used for chewing because it elevates the mandible (lower jaw) to close the mouth, and it is assisted by the temporalismuscle, which retracts the mandible. You can feel the temporalis move by putting your fingers to your temple as you chew. Figure 11.10 Muscles That Move the Lower Jaw The muscles that move the lower jaw are typically located within the cheek and originate from processes in the skull. This provides the jaw muscles with the large amount of leverage needed for chewing. Muscles of the Lower Jaw \| Movement \| Target \| Target motion direction \| Prime mover \| Origin \| Insertion \| \|---\|---\|---\|---\|---\|---\| \| Closes mouth; aids chewing \| Mandible \| Superior (elevates) \| Masseter \| Maxilla arch; zygomatic arch (for masseter) \| Mandible \| \| Closes mouth; pulls lower jaw in under upper jaw \| Mandible \| Superior (elevates); posterior (retracts) \| Temporalis \| Temporal bone \| Mandible \| \| Opens mouth; pushes lower jaw out under upper jaw; moves lower jaw side-to-side \| Mandible \| Inferior (depresses); posterior (protracts); lateral (abducts); medial (adducts) \| Lateral pterygoid \| Pterygoid process of sphenoid bone \| Mandible \| \| Closes mouth; pushes lower jaw out under upper jaw; moves lower jaw side-to-side \| Mandible \| Superior (elevates); posterior (protracts); lateral (abducts); medial (adducts) \| Medial pterygoid \| Sphenoid bone; maxilla \| Mandible; temporo-mandibular joint \| Table 11.4 Although the masseter and temporalis are responsible for elevating and closing the jaw to break food into digestible pieces, the medial pterygoid and lateral pterygoid muscles provide assistance in chewing and moving food within the mouth. Muscles That Move the Tongue Although the tongue is obviously important for tasting food, it is also necessary for mastication, deglutition (swallowing), and speech (Figure 11.11 and Figure 11.12). Because it is so moveable, the tongue facilitates complex speech patterns and sounds. Figure 11.11 Muscles that Move the Tongue Figure 11.12 Muscles for Tongue Movement, Swallowing, and Speech Tongue muscles can be extrinsic or intrinsic. Extrinsic tongue muscles insert into the tongue from outside origins, and the intrinsic tongue muscles insert into the tongue from origins within it. The extrinsic muscles move the whole tongue in different directions, whereas the intrinsic muscles allow the tongue to change its shape (such as, curling the tongue in a loop or flattening it). The extrinsic muscles all include the word root glossus (glossus = “tongue”), and the muscle names are derived from where the muscle originates. The genioglossus (genio = “chin”) originates on the mandible and allows the tongue to move downward and forward. The styloglossus originates on the styloid bone, and allows upward and backward motion. The palatoglossusoriginates on the soft palate to elevate the back of the tongue, and the hyoglossus originates on the hyoid bone to move the tongue downward and flatten it. EVERYDAY CONNECTION Anesthesia and the Tongue Muscles Before surgery, a patient must be made ready for general anesthesia. The normal homeostatic controls of the body are put “on hold” so that the patient can be prepped for surgery. Control of respiration must be switched from the patient’s homeostatic control to the control of the anesthesiologist. The drugs used for anesthesia relax a majority of the body’s muscles. Among the muscles affected during general anesthesia are those that are necessary for breathing and moving the tongue. Under anesthesia, the tongue can relax and partially or fully block the airway, and the muscles of respiration may not move the diaphragm or chest wall. To avoid possible complications, the safest procedure to use on a patient is called endotracheal intubation. Placing a tube into the trachea allows the doctors to maintain a patient’s (open) airway to the lungs and seal the airway off from the oropharynx. Post-surgery, the anesthesiologist gradually changes the mixture of the gases that keep the patient unconscious, and when the muscles of respiration begin to function, the tube is removed. It still takes about 30 minutes for a patient to wake up, and for breathing muscles to regain control of respiration. After surgery, most people have a sore or scratchy throat for a few days. Muscles of the Anterior Neck The muscles of the anterior neck assist in deglutition (swallowing) and speech by controlling the positions of the larynx (voice box), and the hyoid bone, a horseshoe-shaped bone that functions as a solid foundation on which the tongue can move. The muscles of the neck are categorized according to their position relative to the hyoid bone (Figure 11.13). Suprahyoid musclesare superior to it, and the infrahyoid muscles are located inferiorly. Figure 11.13 Muscles of the Anterior Neck The anterior muscles of the neck facilitate swallowing and speech. The suprahyoid muscles originate from above the hyoid bone in the chin region. The infrahyoid muscles originate below the hyoid bone in the lower neck. The suprahyoid muscles raise the hyoid bone, the floor of the mouth, and the larynx during deglutition. These include the digastric muscle, which has anterior and posterior bellies that work to elevate the hyoid bone and larynx when one swallows; it also depresses the mandible. The stylohyoid muscle moves the hyoid bone posteriorly, elevating the larynx, and the mylohyoidmuscle lifts it and helps press the tongue to the top of the mouth. The geniohyoid depresses the mandible in addition to raising and pulling the hyoid bone anteriorly. The strap-like infrahyoid muscles generally depress the hyoid bone and control the position of the larynx. The omohyoidmuscle, which has superior and inferior bellies, depresses the hyoid bone in conjunction with the sternohyoid and thyrohyoidmuscles. The thyrohyoid muscle also elevates the larynx’s thyroid cartilage, whereas the sternothyroid depresses it to create different tones of voice. Muscles That Move the Head The head, attached to the top of the vertebral column, is balanced, moved, and rotated by the neck muscles (Table 11.5). When these muscles act unilaterally, the head rotates. When they contract bilaterally, the head flexes or extends. The major muscle that laterally flexes and rotates the head is the sternocleidomastoid. In addition, both muscles working together are the flexors of the head. Place your fingers on both sides of the neck and turn your head to the left and to the right. You will feel the movement originate there. This muscle divides the neck into anterior and posterior triangles when viewed from the side (Figure 11.14). Figure 11.14 Posterior and Lateral Views of the Neck The superficial and deep muscles of the neck are responsible for moving the head, cervical vertebrae, and scapulas. Muscles That Move the Head \| Movement \| Target \| Target motion direction \| Prime mover \| Origin \| Insertion \| \|---\|---\|---\|---\|---\|---\| \| Rotates and tilts head to the side; tilts head forward \| Skull; vertebrae \| Individually: rotates head to opposite side; bilaterally: flexion \| Sternocleidomastoid \| Sternum; clavicle \| Temporal bone (mastoid process); occipital bone \| \| Rotates and tilts head backward \| Skull; vertebrae \| Individually: laterally flexes and rotates head to same side; bilaterally: extension \| Semispinalis capitis \| Transverse and articular processes of cervical and thoracic vertebra \| Occipital bone \| \| Rotates and tilts head to the side; tilts head backward \| Skull; vertebrae \| Individually: laterally flexes and rotates head to same side; bilaterally: extension \| Splenius capitis \| Spinous processes of cervical and thoracic vertebra \| Temporal bone (mastoid process); occipital bone \| \| Rotates and tilts head to the side; tilts head backward \| Skull; vertebrae \| Individually: laterally flexes and rotates head to same side; bilaterally: extension \| Longissimus capitis \| Transverse and articular processes of cervical and thoracic vertebra \| Temporal bone (mastoid process) \| Table 11.5 Muscles of the Posterior Neck and the Back The posterior muscles of the neck are primarily concerned with head movements, like extension. The back muscles stabilize and move the vertebral column, and are grouped according to the lengths and direction of the fascicles. The splenius muscles originate at the midline and run laterally and superiorly to their insertions. From the sides and the back of the neck, the splenius capitis inserts onto the head region, and the splenius cervicis extends onto the cervical region. These muscles can extend the head, laterally flex it, and rotate it (Figure 11.15). Figure 11.15 Muscles of the Neck and Back The large, complex muscles of the neck and back move the head, shoulders, and vertebral column. The erector spinae group forms the majority of the muscle mass of the back and it is the primary extensor of the vertebral column. It controls flexion, lateral flexion, and rotation of the vertebral column, and maintains the lumbar curve. The erector spinae comprises the iliocostalis (laterally placed) group, the longissimus (intermediately placed) group, and the spinalis (medially placed) group. The iliocostalis group includes the iliocostalis cervicis, associated with the cervical region; the iliocostalis thoracis, associated with the thoracic region; and the iliocostalis lumborum, associated with the lumbar region. The three muscles of the longissimus group are the longissimus capitis, associated with the head region; the longissimus cervicis, associated with the cervical region; and the longissimus thoracis, associated with the thoracic region. The third group, the spinalis group, comprises the spinalis capitis (head region), the spinalis cervicis (cervical region), and the spinalis thoracis (thoracic region). The transversospinales muscles run from the transverse processes to the spinous processes of the vertebrae. Similar to the erector spinae muscles, the semispinalis muscles in this group are named for the areas of the body with which they are associated. The semispinalis muscles include the semispinalis capitis, the semispinalis cervicis, and the semispinalis thoracis. The multifidus muscle of the lumbar region helps extend and laterally flex the vertebral column. Important in the stabilization of the vertebral column is the segmental muscle group, which includes the interspinales and intertransversarii muscles. These muscles bring together the spinous and transverse processes of each consecutive vertebra. Finally, the scalene muscles work together to flex, laterally flex, and rotate the head. They also contribute to deep inhalation. The scalene muscles include the anterior scalene muscle (anterior to the middle scalene), the middle scalene muscle (the longest, intermediate between the anterior and posterior scalenes), and the posterior scalene muscle (the smallest, posterior to the middle scalene). Axial Muscles of the Abdominal Wall, and Thorax - Identify the intrinsic skeletal muscles of the back and neck, and the skeletal muscles of the abdominal wall and thorax - Identify the movement and function of the intrinsic skeletal muscles of the back and neck, and the skeletal muscles of the abdominal wall and thorax It is a complex job to balance the body on two feet and walk upright. The muscles of the vertebral column, thorax, and abdominal wall extend, flex, and stabilize different parts of the body’s trunk. The deep muscles of the core of the body help maintain posture as well as carry out other functions. The brain sends out electrical impulses to these various muscle groups to control posture by alternate contraction and relaxation. This is necessary so that no single muscle group becomes fatigued too quickly. If any one group fails to function, body posture will be compromised. Muscles of the Abdomen There are four pairs of abdominal muscles that cover the anterior and lateral abdominal region and meet at the anterior midline. These muscles of the anterolateral abdominal wall can be divided into four groups: the external obliques, the internal obliques, the transversus abdominis, and the rectus abdominis (Figure 11.16 and Table 11.6). Figure 11.16 Muscles of the Abdomen (a) The anterior abdominal muscles include the medially located rectus abdominis, which is covered by a sheet of connective tissue called the rectus sheath. On the flanks of the body, medial to the rectus abdominis, the abdominal wall is composed of three layers. The external oblique muscles form the superficial layer, while the internal oblique muscles form the middle layer, and the transverses abdominus forms the deepest layer. (b) The muscles of the lower back move the lumbar spine but also assist in femur movements. Muscles of the Abdomen \| Movement \| Target \| Target motion direction \| Prime mover \| Origin \| Insertion \| \|---\|---\|---\|---\|---\|---\| \| Twisting at waist; also bending to the side \| Vertebral column \| Supination; lateral flexion \| External obliques; internal obliques \| Ribs 5–12; ilium \| Ribs 7–10; linea alba; ilium \| \| Squeezing abdomen during forceful exhalations, defecation, urination, and childbirth \| Abdominal cavity \| Compression \| Transversus abdominus \| Ilium; ribs 5–10 \| Sternum; linea alba; pubis \| \| Sitting up \| Vertebral column \| Flexion \| Rectus abdominis \| Pubis \| Sternum; ribs 5 and 7 \| \| Bending to the side \| Vertebral column \| Lateral flexion \| Quadratus lumborum \| Ilium; ribs 5–10 \| Rib 12; vertebrae L1–L4 \| Table 11.6 There are three flat skeletal muscles in the antero-lateral wall of the abdomen. The external oblique, closest to the surface, extend inferiorly and medially, in the direction of sliding one’s four fingers into pants pockets. Perpendicular to it is the intermediate internal oblique, extending superiorly and medially, the direction the thumbs usually go when the other fingers are in the pants pocket. The deep muscle, the transversus abdominis, is arranged transversely around the abdomen, similar to the front of a belt on a pair of pants. This arrangement of three bands of muscles in different orientations allows various movements and rotations of the trunk. The three layers of muscle also help to protect the internal abdominal organs in an area where there is no bone. The linea alba is a white, fibrous band that is made of the bilateral rectus sheaths that join at the anterior midline of the body. These enclose the rectus abdominis muscles (a pair of long, linear muscles, commonly called the “sit-up” muscles) that originate at the pubic crest and symphysis, and extend the length of the body’s trunk. Each muscle is segmented by three transverse bands of collagen fibers called the tendinous intersections. This results in the look of “six-pack abs,” as each segment hypertrophies on individuals at the gym who do many sit-ups. The posterior abdominal wall is formed by the lumbar vertebrae, parts of the ilia of the hip bones, psoas major and iliacus muscles, and quadratus lumborum muscle. This part of the core plays a key role in stabilizing the rest of the body and maintaining posture. CAREER CONNECTION Physical Therapists Those who have a muscle or joint injury will most likely be sent to a physical therapist (PT) after seeing their regular doctor. PTs have a master’s degree or doctorate, and are highly trained experts in the mechanics of body movements. Many PTs also specialize in sports injuries. If you injured your shoulder while you were kayaking, the first thing a physical therapist would do during your first visit is to assess the functionality of the joint. The range of motion of a particular joint refers to the normal movements the joint performs. The PT will ask you to abduct and adduct, circumduct, and flex and extend the arm. The PT will note the shoulder’s degree of function, and based on the assessment of the injury, will create an appropriate physical therapy plan. The first step in physical therapy will probably be applying a heat pack to the injured site, which acts much like a warm-up to draw blood to the area, to enhance healing. You will be instructed to do a series of exercises to continue the therapy at home, followed by icing, to decrease inflammation and swelling, which will continue for several weeks. When physical therapy is complete, the PT will do an exit exam and send a detailed report on the improved range of motion and return of normal limb function to your doctor. Gradually, as the injury heals, the shoulder will begin to function correctly. A PT works closely with patients to help them get back to their normal level of physical activity. Muscles of the Thorax The muscles of the chest serve to facilitate breathing by changing the size of the thoracic cavity (Table 11.7). When you inhale, your chest rises because the cavity expands. Alternately, when you exhale, your chest falls because the thoracic cavity decreases in size. Muscles of the Thorax \| Movement \| Target \| Target motion direction \| Prime mover \| Origin \| Insertion \| \|---\|---\|---\|---\|---\|---\| \| Inhalation; exhalation \| Thoracic cavity \| Compression; expansion \| Diaphragm \| Sternum; ribs 6–12; lumbar vertebrae \| Central tendon \| \| Inhalation;exhalation \| Ribs \| Elevation (expands thoracic cavity) \| External intercostals \| Rib superior to each intercostal muscle \| Rib inferior to each intercostal muscle \| \| Forced exhalation \| Ribs \| Movement along superior/inferior axis to bring ribs closer together \| Internal intercostals \| Rib inferior to each intercostal muscle \| Rib superior to each intercostal muscle \| Table 11.7 The Diaphragm The change in volume of the thoracic cavity during breathing is due to the alternate contraction and relaxation of the diaphragm(Figure 11.17). It separates the thoracic and abdominal cavities, and is dome-shaped at rest. The superior surface of the diaphragm is convex, creating the elevated floor of the thoracic cavity. The inferior surface is concave, creating the curved roof of the abdominal cavity. Figure 11.17 Muscles of the Diaphragm The diaphragm separates the thoracic and abdominal cavities. Defecating, urination, and even childbirth involve cooperation between the diaphragm and abdominal muscles (this cooperation is referred to as the “Valsalva maneuver”). You hold your breath by a steady contraction of the diaphragm; this stabilizes the volume and pressure of the peritoneal cavity. When the abdominal muscles contract, the pressure cannot push the diaphragm up, so it increases pressure on the intestinal tract (defecation), urinary tract (urination), or reproductive tract (childbirth). The inferior surface of the pericardial sac and the inferior surfaces of the pleural membranes (parietal pleura) fuse onto the central tendon of the diaphragm. To the sides of the tendon are the skeletal muscle portions of the diaphragm, which insert into the tendon while having a number of origins including the xiphoid process of the sternum anteriorly, the inferior six ribs and their cartilages laterally, and the lumbar vertebrae and 12th ribs posteriorly. The diaphragm also includes three openings for the passage of structures between the thorax and the abdomen. The inferior vena cava passes through the caval opening, and the esophagus and attached nerves pass through the esophageal hiatus. The aorta, thoracic duct, and azygous vein pass through the aortic hiatus of the posterior diaphragm. The Intercostal Muscles There are three sets of muscles, called intercostal muscles, which span each of the intercostal spaces. The principal role of the intercostal muscles is to assist in breathing by changing the dimensions of the rib cage (Figure 11.18). Figure 11.18 Intercostal Muscles The external intercostals are located laterally on the sides of the body. The internal intercostals are located medially near the sternum. The innermost intercostals are located deep to both the internal and external intercostals. The 11 pairs of superficial external intercostal muscles aid in inspiration of air during breathing because when they contract, they raise the rib cage, which expands it. The 11 pairs of internal intercostal muscles, just under the externals, are used for expiration because they draw the ribs together to constrict the rib cage. The innermost intercostal muscles are the deepest, and they act as synergists for the action of the internal intercostals. Muscles of the Pelvic Floor and Perineum The pelvic floor is a muscular sheet that defines the inferior portion of the pelvic cavity. The pelvic diaphragm, spanning anteriorly to posteriorly from the pubis to the coccyx, comprises the levator ani and the ischiococcygeus. Its openings include the anal canal and urethra, and the vagina in women. The large levator ani consists of two skeletal muscles, the pubococcygeus and the iliococcygeus (Figure 11.19). The levator ani is considered the most important muscle of the pelvic floor because it supports the pelvic viscera. It resists the pressure produced by contraction of the abdominal muscles so that the pressure is applied to the colon to aid in defecation and to the uterus to aid in childbirth (assisted by the ischiococcygeus, which pulls the coccyx anteriorly). This muscle also creates skeletal muscle sphincters at the urethra and anus. Figure 11.19 Muscles of the Pelvic Floor The pelvic floor muscles support the pelvic organs, resist intra-abdominal pressure, and work as sphincters for the urethra, rectum, and vagina. The perineum is the diamond-shaped space between the pubic symphysis (anteriorly), the coccyx (posteriorly), and the ischial tuberosities (laterally), lying just inferior to the pelvic diaphragm (levator ani and coccygeus). Divided transversely into triangles, the anterior is the urogenital triangle, which includes the external genitals. The posterior is the anal triangle, which contains the anus (Figure 11.20). The perineum is also divided into superficial and deep layers with some of the muscles common to men and women (Figure 11.21). Women also have the compressor urethrae and the sphincter urethrovaginalis, which function to close the vagina. In men, there is the deep transverse perineal muscle that plays a role in ejaculation. Figure 11.20 Muscles of the Perineum The perineum muscles play roles in urination in both sexes, ejaculation in men, and vaginal contraction in women. Figure 11.21 Muscles of the Perineum Common to Men and Women Muscles of the Pectoral Girdle and Upper Limbs - Identify the muscles of the pectoral girdle and upper limbs - Identify the movement and function of the pectoral girdle and upper limbs Muscles of the shoulder and upper limb can be divided into four groups: muscles that stabilize and position the pectoral girdle, muscles that move the arm, muscles that move the forearm, and muscles that move the wrists, hands, and fingers. The pectoral girdle, or shoulder girdle, consists of the lateral ends of the clavicle and scapula, along with the proximal end of the humerus, and the muscles covering these three bones to stabilize the shoulder joint. The girdle creates a base from which the head of the humerus, in its ball-and-socket joint with the glenoid fossa of the scapula, can move the arm in multiple directions. Muscles That Position the Pectoral Girdle Muscles that position the pectoral girdle are located either on the anterior thorax or on the posterior thorax (Figure 11.22 and Table 11.8). The anterior muscles include the subclavius, pectoralis minor, and serratus anterior. The posterior muscles include the trapezius, rhomboid major, and rhomboid minor. When the rhomboids are contracted, your scapula moves medially, which can pull the shoulder and upper limb posteriorly. Figure 11.22 Muscles That Position the Pectoral Girdle The muscles that stabilize the pectoral girdle make it a steady base on which other muscles can move the arm. Note that the pectoralis major and deltoid, which move the humerus, are cut here to show the deeper positioning muscles. Muscles that Position the Pectoral girdle \| Position in the thorax \| Movement \| Target \| Target motion direction \| Prime mover \| Origin \| Insertion \| \|---\|---\|---\|---\|---\|---\|---\| \| Anterior thorax \| Stabilizes clavicle during movement by depressing it \| Clavicle \| Depression \| Subclavius \| First rib \| Inferior surface of clavicle \| \| Anterior thorax \| Rotates shoulder anteriorly (throwing motion); assists with inhalation \| Scapula; ribs \| Scapula: depresses; ribs: elevates \| Pectoralis minor \| Anterior surfaces of certain ribs (2–4 or 3–5) \| Coracoid process of scapula \| \| Anterior thorax \| Moves arm from side of body to front of body; assists with inhalation \| Scapula; ribs \| Scapula: protracts; ribs: elevates \| Serratus anterior \| Muscle slips from certain ribs (1–8 or 1–9) \| Anterior surface of vertebral border of scapula \| \| Posterior thorax \| Elevates shoulders (shrugging); pulls shoulder blades together; tilts head backwards \| Scapula; cervical spine \| Scapula: rotests inferiorly, retracts, elevates, and depresses; spine: extends \| Trapezius \| Skull; vertebral column \| Acromion and spine of scapula; clavicle \| \| Posterior thorax \| Stabilizes scapula during pectoral girdle movement \| Scapula \| Retracts; rotates inferiorly \| Rhomboid major \| Thoracic vertebrae (T2–T5) \| Medial border of scapula \| \| Posterior thorax \| Stabilizes scapula during pectoral girdle movement \| Scapula \| Retracts; rotates inferiorly \| Rhomboid minor \| Cervical and thoracic vertebrae (C7 and T1) \| Medial border of scapula \| Table 11.8 Muscles That Move the Humerus Similar to the muscles that position the pectoral girdle, muscles that cross the shoulder joint and move the humerus bone of the arm include both axial and scapular muscles (Figure 11.23 and Figure 11.24). The two axial muscles are the pectoralis major and the latissimus dorsi. The pectoralis major is thick and fan-shaped, covering much of the superior portion of the anterior thorax. The broad, triangular latissimus dorsi is located on the inferior part of the back, where it inserts into a thick connective tissue shealth called an aponeurosis. Figure 11.23 Muscles That Move the Humerus (a, c) The muscles that move the humerus anteriorly are generally located on the anterior side of the body and originate from the sternum (e.g., pectoralis major) or the anterior side of the scapula (e.g., subscapularis). (b) The muscles that move the humerus superiorly generally originate from the superior surfaces of the scapula and/or the clavicle (e.g., deltoids). The muscles that move the humerus inferiorly generally originate from middle or lower back (e.g., latissiumus dorsi). (d) The muscles that move the humerus posteriorly are generally located on the posterior side of the body and insert into the scapula (e.g., infraspinatus). Figure 11.24 Muscles That Move the Humerus The rest of the shoulder muscles originate on the scapula. The anatomical and ligamental structure of the shoulder joint and the arrangements of the muscles covering it, allows the arm to carry out different types of movements. The deltoid, the thick muscle that creates the rounded lines of the shoulder is the major abductor of the arm, but it also facilitates flexing and medial rotation, as well as extension and lateral rotation. The subscapularis originates on the anterior scapula and medially rotates the arm. Named for their locations, the supraspinatus (superior to the spine of the scapula) and the infraspinatus (inferior to the spine of the scapula) abduct the arm, and laterally rotate the arm, respectively. The thick and flat teres major is inferior to the teres minor and extends the arm, and assists in adduction and medial rotation of it. The long teres minor laterally rotates and extends the arm. Finally, the coracobrachialis flexes and adducts the arm. The tendons of the deep subscapularis, supraspinatus, infraspinatus, and teres minor connect the scapula to the humerus, forming the rotator cuff (musculotendinous cuff), the circle of tendons around the shoulder joint. When baseball pitchers undergo shoulder surgery it is usually on the rotator cuff, which becomes pinched and inflamed, and may tear away from the bone due to the repetitive motion of bring the arm overhead to throw a fast pitch. Muscles That Move the Forearm The forearm, made of the radius and ulna bones, has four main types of action at the hinge of the elbow joint: flexion, extension, pronation, and supination. The forearm flexors include the biceps brachii, brachialis, and brachioradialis. The extensors are the triceps brachii and anconeus. The pronators are the pronator teres and the pronator quadratus, and the supinator is the only one that turns the forearm anteriorly. When the forearm faces anteriorly, it is supinated. When the forearm faces posteriorly, it is pronated. The biceps brachii, brachialis, and brachioradialis flex the forearm. The two-headed biceps brachii crosses the shoulder and elbow joints to flex the forearm, also taking part in supinating the forearm at the radioulnar joints and flexing the arm at the shoulder joint. Deep to the biceps brachii, the brachialis provides additional power in flexing the forearm. Finally, the brachioradialis can flex the forearm quickly or help lift a load slowly. These muscles and their associated blood vessels and nerves form the anterior compartment of the arm (anterior flexor compartment of the arm) (Figure 11.25 and Figure 11.26). Figure 11.25 Muscles That Move the Forearm The muscles originating in the upper arm flex, extend, pronate, and supinate the forearm. The muscles originating in the forearm move the wrists, hands, and fingers. Figure 11.26 Muscles That Move the Forearm Muscles That Move the Wrist, Hand, and Fingers Wrist, hand, and finger movements are facilitated by two groups of muscles. The forearm is the origin of the extrinsic muscles of the hand. The palm is the origin of the intrinsic muscles of the hand. Muscles of the Arm That Move the Wrists, Hands, and Fingers The muscles in the anterior compartment of the forearm (anterior flexor compartment of the forearm) originate on the humerus and insert onto different parts of the hand. These make up the bulk of the forearm. From lateral to medial, the superficial anterior compartment of the forearm includes the flexor carpi radialis, palmaris longus, flexor carpi ulnaris, and flexor digitorum superficialis. The flexor digitorum superficialis flexes the hand as well as the digits at the knuckles, which allows for rapid finger movements, as in typing or playing a musical instrument (see Figure 11.27 and Table 11.9). However, poor ergonomics can irritate the tendons of these muscles as they slide back and forth with the carpal tunnel of the anterior wrist and pinch the median nerve, which also travels through the tunnel, causing Carpal Tunnel Syndrome. The deep anterior compartment produces flexion and bends fingers to make a fist. These are the flexor pollicis longus and the flexor digitorum profundus. The muscles in the superficial posterior compartment of the forearm (superficial posterior extensor compartment of the forearm) originate on the humerus. These are the extensor radialis longus, extensor carpi radialis brevis, extensor digitorum, extensor digiti minimi, and the extensor carpi ulnaris. The muscles of the deep posterior compartment of the forearm (deep posterior extensor compartment of the forearm) originate on the radius and ulna. These include the abductor pollicis longus, extensor pollicis brevis, extensor pollicis longus, and extensor indicis (see Figure 11.27). Figure 11.27 Muscles That Move the Wrist, Hands, and Forearm The tendons of the forearm muscles attach to the wrist and extend into the hand. Fibrous bands called retinacula sheath the tendons at the wrist. The flexor retinaculum extends over the palmar surface of the hand while the extensor retinaculumextends over the dorsal surface of the hand. Intrinsic Muscles of the Hand The intrinsic muscles of the hand both originate and insert within it (Figure 11.28). These muscles allow your fingers to also make precise movements for actions, such as typing or writing. These muscles are divided into three groups. The thenarmuscles are on the radial aspect of the palm. The hypothenar muscles are on the medial aspect of the palm, and the intermediate muscles are midpalmar. The thenar muscles include the abductor pollicis brevis, opponens pollicis, flexor pollicis brevis, and the adductor pollicis. These muscles form the thenar eminence, the rounded contour of the base of the thumb, and all act on the thumb. The movements of the thumb play an integral role in most precise movements of the hand. The hypothenar muscles include the abductor digiti minimi, flexor digiti minimi brevis, and the opponens digiti minimi. These muscles form the hypothenar eminence, the rounded contour of the little finger, and as such, they all act on the little finger. Finally, the intermediate muscles act on all the fingers and include the lumbrical, the palmar interossei, and the dorsal interossei. Figure 11.28 Intrinsic Muscles of the Hand The intrinsic muscles of the hand both originate and insert within the hand. These muscles provide the fine motor control of the fingers by flexing, extending, abducting, and adducting the more distal finger and thumb segments. Intrinsic Muscles of the Hand \| Muscle \| Movement \| Target \| Target motion direction \| Prime mover \| Origin \| Insertion \| \|---\|---\|---\|---\|---\|---\|---\| \| Thenar muscles \| Moves thumb toward body \| Thumb \| Abduction \| Abductor pollicis brevis \| Flexor retinaculum; and nearby carpals \| Lateral base of proximal phalanx of thumb \| \| Thenar muscles \| Moves thumb across palm to touch other fingers \| Thumb \| Opposition \| Opponens pollicis \| Flexor retinaculum; trapezium \| Anterior of first metacarpal \| \| Thenar muscles \| Flexes thumb \| Thumb \| Flexion \| Flexor pollicis brevis \| Flexor retinaculum; trapezium \| Lateral base of proximal phalanx of thumb \| \| Thenar muscles \| Moves thumb away from body \| Thumb \| Adduction \| Adductor pollicis \| Capitate bone; bases of metacarpals 2–4; front of metacarpal 3 \| Medial base of proximal phalanx of thumb \| \| Hypothenar muscles \| Moves little finger toward body \| Little finger \| Abduction \| Abductor digiti minimi \| Pisiform bone \| Medial side of proximal phalanx of little finger \| \| Hypothenar muscles \| Flexes little finger \| Little finger \| Flexion \| Flexor digiti minimi brevis \| Hamate bone; flexor retinaculum \| Medial side of proximal phalanx of little finger \| \| Hypothenar muscles \| Moves little finger across palm to touch thumb \| Little finger \| Opposition \| Opponens digiti minimi \| Hamate bone; flexor retinaculum \| Medial side of fifth metacarpal \| \| Intermediate muscles \| Flexes each finger at metacarpo-phalangeal joints; extends each finger at interphalangeal joints \| Fingers \| Flexion \| Lumbricals \| Palm (lateral sides of tendons in flexor digitorum profundus) \| Fingers 2–5 (lateral edges of extensional expansions on first phalanges) \| \| Intermediate muscles \| Adducts and flexes each finger at metacarpo-phalangeal joints; extends each finger at interphalangeal joints \| Fingers \| Adduction; flexion; extension \| Palmar interossei \| Side of each metacarpal that faces metacarpal 3 (absent from metacarpal 3) \| Extensor expansion on first phalanx of each finger (except finger 3) on side facing finger 3 \| \| Intermediate muscles \| Abducts and flexes the three middle fingers at metacarpo-phalangeal joints; extends the three middle fingers at interphalangeal joints \| Fingers \| Abduction; flexion; extension \| Dorsal interossei \| Sides of metacarpals \| Both sides of finger 3; for each other finger, extensor expansion over first phalanx on side opposite finger 3 \| Table 11.9 Appendicular Muscles of the Pelvic Girdle and Lower Limbs - Identify the appendicular muscles of the pelvic girdle and lower limb - Identify the movement and function of the pelvic girdle and lower limb The appendicular muscles of the lower body position and stabilize the pelvic girdle, which serves as a foundation for the lower limbs. Comparatively, there is much more movement at the pectoral girdle than at the pelvic girdle. There is very little movement of the pelvic girdle because of its connection with the sacrum at the base of the axial skeleton. The pelvic girdle is less range of motion because it was designed to stabilize and support the body. Muscles of the Thigh What would happen if the pelvic girdle, which attaches the lower limbs to the torso, were capable of the same range of motion as the pectoral girdle? For one thing, walking would expend more energy if the heads of the femurs were not secured in the acetabula of the pelvis. The body’s center of gravity is in the area of the pelvis. If the center of gravity were not to remain fixed, standing up would be difficult as well. Therefore, what the leg muscles lack in range of motion and versatility, they make up for in size and power, facilitating the body’s stabilization, posture, and movement. Gluteal Region Muscles That Move the Femur Most muscles that insert on the femur (the thigh bone) and move it, originate on the pelvic girdle. The psoas major and iliacusmake up the iliopsoas group. Some of the largest and most powerful muscles in the body are the gluteal muscles or gluteal group. The gluteus maximus is the largest; deep to the gluteus maximus is the gluteus medius, and deep to the gluteus medius is the gluteus minimus, the smallest of the trio (Figure 11.29 and Figure 11.30). Figure 11.29 Hip and Thigh Muscles The large and powerful muscles of the hip that move the femur generally originate on the pelvic girdle and insert into the femur. The muscles that move the lower leg typically originate on the femur and insert into the bones of the knee joint. The anterior muscles of the femur extend the lower leg but also aid in flexing the thigh. The posterior muscles of the femur flex the lower leg but also aid in extending the thigh. A combination of gluteal and thigh muscles also adduct, abduct, and rotate the thigh and lower leg. Figure 11.30 Gluteal Region Muscles That Move the Femur The tensor fascia latae is a thick, squarish muscle in the superior aspect of the lateral thigh. It acts as a synergist of the gluteus medius and iliopsoas in flexing and abducting the thigh. It also helps stabilize the lateral aspect of the knee by pulling on the iliotibial tract (band), making it taut. Deep to the gluteus maximus, the piriformis, obturator internus, obturator externus, superior gemellus, inferior gemellus, and quadratus femoris laterally rotate the femur at the hip. The adductor longus, adductor brevis, and adductor magnus can both medially and laterally rotate the thigh depending on the placement of the foot. The adductor longus flexes the thigh, whereas the adductor magnus extends it. The pectineusadducts and flexes the femur at the hip as well. The pectineus is located in the femoral triangle, which is formed at the junction between the hip and the leg and also includes the femoral nerve, the femoral artery, the femoral vein, and the deep inguinal lymph nodes. Thigh Muscles That Move the Femur, Tibia, and Fibula Deep fascia in the thigh separates it into medial, anterior, and posterior compartments (see Figure 11.29 and Figure 11.31). The muscles in the medial compartment of the thigh are responsible for adducting the femur at the hip. Along with the adductor longus, adductor brevis, adductor magnus, and pectineus, the strap-like gracilis adducts the thigh in addition to flexing the leg at the knee. Figure 11.31 Thigh Muscles That Move the Femur, Tibia, and Fibula The muscles of the anterior compartment of the thigh flex the thigh and extend the leg. This compartment contains the quadriceps femoris group, which actually comprises four muscles that extend and stabilize the knee. The rectus femoris is on the anterior aspect of the thigh, the vastus lateralis is on the lateral aspect of the thigh, the vastus medialis is on the medial aspect of the thigh, and the vastus intermedius is between the vastus lateralis and vastus medialis and deep to the rectus femoris. The tendon common to all four is the quadriceps tendon (patellar tendon), which inserts into the patella and continues below it as the patellar ligament. The patellar ligament attaches to the tibial tuberosity. In addition to the quadriceps femoris, the sartorius is a band-like muscle that extends from the anterior superior iliac spine to the medial side of the proximal tibia. This versatile muscle flexes the leg at the knee and flexes, abducts, and laterally rotates the leg at the hip. This muscle allows us to sit cross-legged. The posterior compartment of the thigh includes muscles that flex the leg and extend the thigh. The three long muscles on the back of the knee are the hamstring group, which flexes the knee. These are the biceps femoris, semitendinosus, and semimembranosus. The tendons of these muscles form the popliteal fossa, the diamond-shaped space at the back of the knee. Muscles That Move the Feet and Toes Similar to the thigh muscles, the muscles of the leg are divided by deep fascia into compartments, although the leg has three: anterior, lateral, and posterior (Figure 11.32 and Figure 11.33). Figure 11.32 Muscles of the Lower Leg The muscles of the anterior compartment of the lower leg are generally responsible for dorsiflexion, and the muscles of the posterior compartment of the lower leg are generally responsible for plantar flexion. The lateral and medial muscles in both compartments invert, evert, and rotate the foot. Figure 11.33 Muscles That Move the Feet and Toes The muscles in the anterior compartment of the leg: the tibialis anterior, a long and thick muscle on the lateral surface of the tibia, the extensor hallucis longus, deep under it, and the extensor digitorum longus, lateral to it, all contribute to raising the front of the foot when they contract. The fibularis tertius, a small muscle that originates on the anterior surface of the fibula, is associated with the extensor digitorum longus and sometimes fused to it, but is not present in all people. Thick bands of connective tissue called the superior extensor retinaculum (transverse ligament of the ankle) and the inferior extensor retinaculum, hold the tendons of these muscles in place during dorsiflexion. The lateral compartment of the leg includes two muscles: the fibularis longus (peroneus longus) and the fibularis brevis(peroneus brevis). The superficial muscles in the posterior compartment of the leg all insert onto the calcaneal tendon(Achilles tendon), a strong tendon that inserts into the calcaneal bone of the ankle. The muscles in this compartment are large and strong and keep humans upright. The most superficial and visible muscle of the calf is the gastrocnemius. Deep to the gastrocnemius is the wide, flat soleus. The plantaris runs obliquely between the two; some people may have two of these muscles, whereas no plantaris is observed in about seven percent of other cadaver dissections. The plantaris tendon is a desirable substitute for the fascia lata in hernia repair, tendon transplants, and repair of ligaments. There are four deep muscles in the posterior compartment of the leg as well: the popliteus, flexor digitorum longus, flexor hallucis longus, and tibialis posterior. The foot also has intrinsic muscles, which originate and insert within it (similar to the intrinsic muscles of the hand). These muscles primarily provide support for the foot and its arch, and contribute to movements of the toes (Figure 11.34 and Figure 11.35). The principal support for the longitudinal arch of the foot is a deep fascia called plantar aponeurosis, which runs from the calcaneus bone to the toes (inflammation of this tissue is the cause of “plantar fasciitis,” which can affect runners. The intrinsic muscles of the foot consist of two groups. The dorsal group includes only one muscle, the extensor digitorum brevis. The second group is the plantar group, which consists of four layers, starting with the most superficial. Figure 11.34 Intrinsic Muscles of the Foot The muscles along the dorsal side of the foot (a) generally extend the toes while the muscles of the plantar side of the foot (b, c, d) generally flex the toes. The plantar muscles exist in three layers, providing the foot the strength to counterbalance the weight of the body. In this diagram, these three layers are shown from a plantar view beginning with the bottom-most layer just under the plantar skin of the foot (b) and ending with the top-most layer (d) located just inferior to the foot and toe bones. Figure 11.35 Intrinsic Muscles in the Foot Key Terms - abduct - move away from midline in the sagittal plane - abductor - moves the bone away from the midline - abductor digiti minimi - muscle that abducts the little finger - abductor pollicis brevis - muscle that abducts the thumb - abductor pollicis longus - muscle that inserts into the first metacarpal - adductor - moves the bone toward the midline - adductor brevis - muscle that adducts and medially rotates the thigh - adductor longus - muscle that adducts, medially rotates, and flexes the thigh - adductor magnus - muscle with an anterior fascicle that adducts, medially rotates and flexes the thigh, and a posterior fascicle that assists in thigh extension - adductor pollicis - muscle that adducts the thumb - agonist - (also, prime mover) muscle whose contraction is responsible for producing a particular motion - anal triangle - posterior triangle of the perineum that includes the anus - anconeus - small muscle on the lateral posterior elbow that extends the forearm - antagonist - muscle that opposes the action of an agonist - anterior compartment of the arm - (anterior flexor compartment of the arm) the biceps brachii, brachialis, brachioradialis, and their associated blood vessels and nerves - anterior compartment of the forearm - (anterior flexor compartment of the forearm) deep and superficial muscles that originate on the humerus and insert into the hand - anterior compartment of the leg - region that includes muscles that dorsiflex the foot - anterior compartment of the thigh - region that includes muscles that flex the thigh and extend the leg - anterior scalene - a muscle anterior to the middle scalene - appendicular - of the arms and legs - axial - of the trunk and head - belly - bulky central body of a muscle - bi - two - biceps brachii - two-headed muscle that crosses the shoulder and elbow joints to flex the forearm while assisting in supinating it and flexing the arm at the shoulder - biceps femoris - hamstring muscle - bipennate - pennate muscle that has fascicles that are located on both sides of the tendon - brachialis - muscle deep to the biceps brachii that provides power in flexing the forearm. - brachioradialis - muscle that can flex the forearm quickly or help lift a load slowly - brevis - short - buccinator - muscle that compresses the cheek - calcaneal tendon - (also, Achilles tendon) strong tendon that inserts into the calcaneal bone of the ankle - caval opening - opening in the diaphragm that allows the inferior vena cava to pass through; foramen for the vena cava - circular - (also, sphincter) fascicles that are concentrically arranged around an opening - compressor urethrae - deep perineal muscle in women - convergent - fascicles that extend over a broad area and converge on a common attachment site - coracobrachialis - muscle that flexes and adducts the arm - corrugator supercilii - prime mover of the eyebrows - deep anterior compartment - flexor pollicis longus, flexor digitorum profundus, and their associated blood vessels and nerves - deep posterior compartment of the forearm - (deep posterior extensor compartment of the forearm) the abductor pollicis longus, extensor pollicis brevis, extensor pollicis longus, extensor indicis, and their associated blood vessels and nerves - deep transverse perineal - deep perineal muscle in men - deglutition - swallowing - deltoid - shoulder muscle that abducts the arm as well as flexes and medially rotates it, and extends and laterally rotates it - diaphragm - skeletal muscle that separates the thoracic and abdominal cavities and is dome-shaped at rest - digastric - muscle that has anterior and posterior bellies and elevates the hyoid bone and larynx when one swallows; it also depresses the mandible - dorsal group - region that includes the extensor digitorum brevis - dorsal interossei - muscles that abduct and flex the three middle fingers at the metacarpophalangeal joints and extend them at the interphalangeal joints - epicranial aponeurosis - (also, galea aponeurosis) flat broad tendon that connects the frontalis and occipitalis - erector spinae group - large muscle mass of the back; primary extensor of the vertebral column - extensor - muscle that increases the angle at the joint - extensor carpi radialis brevis - muscle that extends and abducts the hand at the wrist - extensor carpi ulnaris - muscle that extends and adducts the hand - extensor digiti minimi - muscle that extends the little finger - extensor digitorum - muscle that extends the hand at the wrist and the phalanges - extensor digitorum brevis - muscle that extends the toes - extensor digitorum longus - muscle that is lateral to the tibialis anterior - extensor hallucis longus - muscle that is partly deep to the tibialis anterior and extensor digitorum longus - extensor indicis - muscle that inserts onto the tendon of the extensor digitorum of the index finger - extensor pollicis brevis - muscle that inserts onto the base of the proximal phalanx of the thumb - extensor pollicis longus - muscle that inserts onto the base of the distal phalanx of the thumb - extensor radialis longus - muscle that extends and abducts the hand at the wrist - extensor retinaculum - band of connective tissue that extends over the dorsal surface of the hand - external intercostal - superficial intercostal muscles that raise the rib cage - external oblique - superficial abdominal muscle with fascicles that extend inferiorly and medially - extrinsic eye muscles - originate outside the eye and insert onto the outer surface of the white of the eye, and create eyeball movement - extrinsic muscles of the hand - muscles that move the wrists, hands, and fingers and originate on the arm - fascicle - muscle fibers bundled by perimysium into a unit - femoral triangle - region formed at the junction between the hip and the leg and includes the pectineus, femoral nerve, femoral artery, femoral vein, and deep inguinal lymph nodes - fibularis brevis - (also, peroneus brevis) muscle that plantar flexes the foot at the ankle and everts it at the intertarsal joints - fibularis longus - (also, peroneus longus) muscle that plantar flexes the foot at the ankle and everts it at the intertarsal joints - fibularis tertius - small muscle that is associated with the extensor digitorum longus - fixator - synergist that assists an agonist by preventing or reducing movement at another joint, thereby stabilizing the origin of the agonist - flexion - movement that decreases the angle of a joint - flexor - muscle that decreases the angle at the joint - flexor carpi radialis - muscle that flexes and abducts the hand at the wrist - flexor carpi ulnaris - muscle that flexes and adducts the hand at the wrist - flexor digiti minimi brevis - muscle that flexes the little finger - flexor digitorum longus - muscle that flexes the four small toes - flexor digitorum profundus - muscle that flexes the phalanges of the fingers and the hand at the wrist - flexor digitorum superficialis - muscle that flexes the hand and the digits - flexor hallucis longus - muscle that flexes the big toe - flexor pollicis brevis - muscle that flexes the thumb - flexor pollicis longus - muscle that flexes the distal phalanx of the thumb - flexor retinaculum - band of connective tissue that extends over the palmar surface of the hand - frontalis - front part of the occipitofrontalis muscle - fusiform - muscle that has fascicles that are spindle-shaped to create large bellies - gastrocnemius - most superficial muscle of the calf - genioglossus - muscle that originates on the mandible and allows the tongue to move downward and forward - geniohyoid - muscle that depresses the mandible, and raises and pulls the hyoid bone anteriorly - gluteal group - muscle group that extends, flexes, rotates, adducts, and abducts the femur - gluteus maximus - largest of the gluteus muscles that extends the femur - gluteus medius - muscle deep to the gluteus maximus that abducts the femur at the hip - gluteus minimus - smallest of the gluteal muscles and deep to the gluteus medius - gracilis - muscle that adducts the thigh and flexes the leg at the knee - hamstring group - three long muscles on the back of the leg - hyoglossus - muscle that originates on the hyoid bone to move the tongue downward and flatten it - hypothenar - group of muscles on the medial aspect of the palm - hypothenar eminence - rounded contour of muscle at the base of the little finger - iliacus - muscle that, along with the psoas major, makes up the iliopsoas - iliococcygeus - muscle that makes up the levator ani along with the pubococcygeus - iliocostalis cervicis - muscle of the iliocostalis group associated with the cervical region - iliocostalis group - laterally placed muscles of the erector spinae - iliocostalis lumborum - muscle of the iliocostalis group associated with the lumbar region - iliocostalis thoracis - muscle of the iliocostalis group associated with the thoracic region - iliopsoas group - muscle group consisting of iliacus and psoas major muscles, that flexes the thigh at the hip, rotates it laterally, and flexes the trunk of the body onto the hip - iliotibial tract - muscle that inserts onto the tibia; made up of the gluteus maximus and connective tissues of the tensor fasciae latae - inferior extensor retinaculum - cruciate ligament of the ankle - inferior gemellus - muscle deep to the gluteus maximus on the lateral surface of the thigh that laterally rotates the femur at the hip - infrahyoid muscles - anterior neck muscles that are attached to, and inferior to the hyoid bone - infraspinatus - muscle that laterally rotates the arm - innermost intercostal - the deepest intercostal muscles that draw the ribs together - insertion - end of a skeletal muscle that is attached to the structure (usually a bone) that is moved when the muscle contracts - intercostal muscles - muscles that span the spaces between the ribs - intermediate - group of midpalmar muscles - internal intercostal - muscles the intermediate intercostal muscles that draw the ribs together - internal oblique - flat, intermediate abdominal muscle with fascicles that run perpendicular to those of the external oblique - intrinsic muscles of the hand - muscles that move the wrists, hands, and fingers and originate in the palm - ischiococcygeus - muscle that assists the levator ani and pulls the coccyx anteriorly - lateral compartment of the leg - region that includes the fibularis (peroneus) longus and the fibularis (peroneus) brevis and their associated blood vessels and nerves - lateral pterygoid - muscle that moves the mandible from side to side - lateralis - to the outside - latissimus dorsi - broad, triangular axial muscle located on the inferior part of the back - levator ani - pelvic muscle that resists intra-abdominal pressure and supports the pelvic viscera - linea alba - white, fibrous band that runs along the midline of the trunk - longissimus capitis - muscle of the longissimus group associated with the head region - longissimus cervicis - muscle of the longissimus group associated with the cervical region - longissimus group - intermediately placed muscles of the erector spinae - longissimus thoracis - muscle of the longissimus group associated with the thoracic region - longus - long - lumbrical - muscle that flexes each finger at the metacarpophalangeal joints and extend each finger at the interphalangeal joints - masseter - main muscle for chewing that elevates the mandible to close the mouth - mastication - chewing - maximus - largest - medial compartment of the thigh - a region that includes the adductor longus, adductor brevis, adductor magnus, pectineus, gracilis, and their associated blood vessels and nerves - medial pterygoid - muscle that moves the mandible from side to side - medialis - to the inside - medius - medium - middle scalene - longest scalene muscle, located between the anterior and posterior scalenes - minimus - smallest - multifidus - muscle of the lumbar region that helps extend and laterally flex the vertebral column - multipennate - pennate muscle that has a tendon branching within it - mylohyoid - muscle that lifts the hyoid bone and helps press the tongue to the top of the mouth - oblique - at an angle - obturator externus - muscle deep to the gluteus maximus on the lateral surface of the thigh that laterally rotates the femur at the hip - obturator internus - muscle deep to the gluteus maximus on the lateral surface of the thigh that laterally rotates the femur at the hip - occipitalis - posterior part of the occipitofrontalis muscle - occipitofrontalis - muscle that makes up the scalp with a frontal belly and an occipital belly - omohyoid - muscle that has superior and inferior bellies and depresses the hyoid bone - opponens digiti minimi - muscle that brings the little finger across the palm to meet the thumb - opponens pollicis - muscle that moves the thumb across the palm to meet another finger - orbicularis oculi - circular muscle that closes the eye - orbicularis oris - circular muscle that moves the lips - origin - end of a skeletal muscle that is attached to another structure (usually a bone) in a fixed position - palatoglossus - muscle that originates on the soft palate to elevate the back of the tongue - palmar interossei - muscles that abduct and flex each finger at the metacarpophalangeal joints and extend each finger at the interphalangeal joints - palmaris longus - muscle that provides weak flexion of the hand at the wrist - parallel - fascicles that extend in the same direction as the long axis of the muscle - patellar ligament - extension of the quadriceps tendon below the patella - pectineus - muscle that abducts and flexes the femur at the hip - pectoral girdle - shoulder girdle, made up of the clavicle and scapula - pectoralis major - thick, fan-shaped axial muscle that covers much of the superior thorax - pectoralis minor - muscle that moves the scapula and assists in inhalation - pelvic diaphragm - muscular sheet that comprises the levator ani and the ischiococcygeus - pelvic girdle - hips, a foundation for the lower limb - pennate - fascicles that are arranged differently based on their angles to the tendon - perineum - diamond-shaped region between the pubic symphysis, coccyx, and ischial tuberosities - piriformis - muscle deep to the gluteus maximus on the lateral surface of the thigh that laterally rotates the femur at the hip - plantar aponeurosis - muscle that supports the longitudinal arch of the foot - plantar group - four-layered group of intrinsic foot muscles - plantaris - muscle that runs obliquely between the gastrocnemius and the soleus - popliteal fossa - diamond-shaped space at the back of the knee - popliteus - muscle that flexes the leg at the knee and creates the floor of the popliteal fossa - posterior compartment of the leg - region that includes the superficial gastrocnemius, soleus, and plantaris, and the deep popliteus, flexor digitorum longus, flexor hallucis longus, and tibialis posterior - posterior compartment of the thigh - region that includes muscles that flex the leg and extend the thigh - posterior scalene - smallest scalene muscle, located posterior to the middle scalene - prime mover - (also, agonist) principle muscle involved in an action - pronator quadratus - pronator that originates on the ulna and inserts on the radius - pronator teres - pronator that originates on the humerus and inserts on the radius - psoas major - muscle that, along with the iliacus, makes up the iliopsoas - pubococcygeus - muscle that makes up the levator ani along with the iliococcygeus - quadratus femoris - muscle deep to the gluteus maximus on the lateral surface of the thigh that laterally rotates the femur at the hip - quadratus lumborum - posterior part of the abdominal wall that helps with posture and stabilization of the body - quadriceps femoris group - four muscles, that extend and stabilize the knee - quadriceps tendon - (also, patellar tendon) tendon common to all four quadriceps muscles, inserts into the patella - rectus - straight - rectus abdominis - long, linear muscle that extends along the middle of the trunk - rectus femoris - quadricep muscle on the anterior aspect of the thigh - rectus sheaths - tissue that makes up the linea alba - retinacula - fibrous bands that sheath the tendons at the wrist - rhomboid major - muscle that attaches the vertebral border of the scapula to the spinous process of the thoracic vertebrae - rhomboid minor - muscle that attaches the vertebral border of the scapula to the spinous process of the thoracic vertebrae - rotator cuff - (also, musculotendinous cuff) the circle of tendons around the shoulder joint - sartorius - band-like muscle that flexes, abducts, and laterally rotates the leg at the hip - scalene muscles - flex, laterally flex, and rotate the head; contribute to deep inhalation - segmental muscle group - interspinales and intertransversarii muscles that bring together the spinous and transverse processes of each consecutive vertebra - semimembranosus - hamstring muscle - semispinalis capitis - transversospinales muscle associated with the head region - semispinalis cervicis - transversospinales muscle associated with the cervical region - semispinalis thoracis - transversospinales muscle associated with the thoracic region - semitendinosus - hamstring muscle - serratus anterior - large and flat muscle that originates on the ribs and inserts onto the scapula - soleus - wide, flat muscle deep to the gastrocnemius - sphincter urethrovaginalis - deep perineal muscle in women - spinalis capitis - muscle of the spinalis group associated with the head region - spinalis cervicis - muscle of the spinalis group associated with the cervical region - spinalis group - medially placed muscles of the erector spinae - spinalis thoracis - muscle of the spinalis group associated with the thoracic region - splenius - posterior neck muscles; includes the splenius capitis and splenius cervicis - splenius capitis - neck muscle that inserts into the head region - splenius cervicis - neck muscle that inserts into the cervical region - sternocleidomastoid - major muscle that laterally flexes and rotates the head - sternohyoid - muscle that depresses the hyoid bone - sternothyroid - muscle that depresses the larynx’s thyroid cartilage - styloglossus - muscle that originates on the styloid bone, and allows upward and backward motion of the tongue - stylohyoid - muscle that elevates the hyoid bone posteriorly - subclavius - muscle that stabilizes the clavicle during movement - subscapularis - muscle that originates on the anterior scapula and medially rotates the arm - superficial anterior compartment of the forearm - flexor carpi radialis, palmaris longus, flexor carpi ulnaris, flexor digitorum superficialis, and their associated blood vessels and nerves - superficial posterior compartment of the forearm - extensor radialis longus, extensor carpi radialis brevis, extensor digitorum, extensor digiti minimi, extensor carpi ulnaris, and their associated blood vessels and nerves - superior extensor retinaculum - transverse ligament of the ankle - superior gemellus - muscle deep to the gluteus maximus on the lateral surface of the thigh that laterally rotates the femur at the hip - supinator - muscle that moves the palm and forearm anteriorly - suprahyoid muscles - neck muscles that are superior to the hyoid bone - supraspinatus - muscle that abducts the arm - synergist - muscle whose contraction helps a prime mover in an action - temporalis - muscle that retracts the mandible - tendinous intersections - three transverse bands of collagen fibers that divide the rectus abdominis into segments - tensor fascia lata - muscle that flexes and abducts the thigh - teres major - muscle that extends the arm and assists in adduction and medial rotation of it - teres minor - muscle that laterally rotates and extends the arm - thenar - group of muscles on the lateral aspect of the palm - thenar eminence - rounded contour of muscle at the base of the thumb - thyrohyoid - muscle that depresses the hyoid bone and elevates the larynx’s thyroid cartilage - tibialis anterior - muscle located on the lateral surface of the tibia - tibialis posterior - muscle that plantar flexes and inverts the foot - transversospinales - muscles that originate at the transverse processes and insert at the spinous processes of the vertebrae - transversus abdominis - deep layer of the abdomen that has fascicles arranged transversely around the abdomen - trapezius - muscle that stabilizes the upper part of the back - tri - three - triceps brachii - three-headed muscle that extends the forearm - unipennate - pennate muscle that has fascicles located on one side of the tendon - urogenital triangle - anterior triangle of the perineum that includes the external genitals - vastus intermedius - quadricep muscle that is between the vastus lateralis and vastus medialis and is deep to the rectus femoris - vastus lateralis - quadricep muscle on the lateral aspect of the thigh - vastus medialis - quadricep muscle on the medial aspect of the thigh Chapter Review 11.1 Interactions of Skeletal Muscles, Their Fascicle Arrangement, and Their Lever Systems Skeletal muscles each have an origin and an insertion. The end of the muscle that attaches to the bone being pulled is called the muscle’s insertion and the end of the muscle attached to a fixed, or stabilized, bone is called the origin. The muscle primarily responsible for a movement is called the prime mover, and muscles that assist in this action are called synergists. A synergist that makes the insertion site more stable is called a fixator. Meanwhile, a muscle with the opposite action of the prime mover is called an antagonist. Several factors contribute to the force generated by a skeletal muscle. One is the arrangement of the fascicles in the skeletal muscle. Fascicles can be parallel, circular, convergent, pennate, fusiform, or triangular. Each arrangement has its own range of motion and ability to do work. 11.2 Naming Skeletal Muscles Muscle names are based on many characteristics. The location of a muscle in the body is important. Some muscles are named based on their size and location, such as the gluteal muscles of the buttocks. Other muscle names can indicate the location in the body or bones with which the muscle is associated, such as the tibialis anterior. The shapes of some muscles are distinctive; for example, the direction of the muscle fibers is used to describe muscles of the body midline. The origin and/or insertion can also be features used to name a muscle; examples are the biceps brachii, triceps brachii, and the pectoralis major. 11.3 Axial Muscles of the Head, Neck, and Back Muscles are either axial muscles or appendicular. The axial muscles are grouped based on location, function, or both. Some axial muscles cross over to the appendicular skeleton. The muscles of the head and neck are all axial. The muscles in the face create facial expression by inserting into the skin rather than onto bone. Muscles that move the eyeballs are extrinsic, meaning they originate outside of the eye and insert onto it. Tongue muscles are both extrinsic and intrinsic. The genioglossus depresses the tongue and moves it anteriorly; the styloglossus lifts the tongue and retracts it; the palatoglossus elevates the back of the tongue; and the hyoglossus depresses and flattens it. The muscles of the anterior neck facilitate swallowing and speech, stabilize the hyoid bone and position the larynx. The muscles of the neck stabilize and move the head. The sternocleidomastoid divides the neck into anterior and posterior triangles. The muscles of the back and neck that move the vertebral column are complex, overlapping, and can be divided into five groups. The splenius group includes the splenius capitis and the splenius cervicis. The erector spinae has three subgroups. The iliocostalis group includes the iliocostalis cervicis, the iliocostalis thoracis, and the iliocostalis lumborum. The longissimus group includes the longissimus capitis, the longissimus cervicis, and the longissimus thoracis. The spinalis group includes the spinalis capitis, the spinalis cervicis, and the spinalis thoracis. The transversospinales include the semispinalis capitis, semispinalis cervicis, semispinalis thoracis, multifidus, and rotatores. The segmental muscles include the interspinales and intertransversarii. Finally, the scalenes include the anterior scalene, middle scalene, and posterior scalene. 11.4 Axial Muscles of the Abdominal Wall, and Thorax Made of skin, fascia, and four pairs of muscle, the anterior abdominal wall protects the organs located in the abdomen and moves the vertebral column. These muscles include the rectus abdominis, which extends through the entire length of the trunk, the external oblique, the internal oblique, and the transversus abdominus. The quadratus lumborum forms the posterior abdominal wall. The muscles of the thorax play a large role in breathing, especially the dome-shaped diaphragm. When it contracts and flattens, the volume inside the pleural cavities increases, which decreases the pressure within them. As a result, air will flow into the lungs. The external and internal intercostal muscles span the space between the ribs and help change the shape of the rib cage and the volume-pressure ratio inside the pleural cavities during inspiration and expiration. The perineum muscles play roles in urination in both sexes, ejaculation in men, and vaginal contraction in women. The pelvic floor muscles support the pelvic organs, resist intra-abdominal pressure, and work as sphincters for the urethra, rectum, and vagina. 11.5 Muscles of the Pectoral Girdle and Upper Limbs The clavicle and scapula make up the pectoral girdle, which provides a stable origin for the muscles that move the humerus. The muscles that position and stabilize the pectoral girdle are located on the thorax. The anterior thoracic muscles are the subclavius, pectoralis minor, and the serratus anterior. The posterior thoracic muscles are the trapezius, levator scapulae, rhomboid major, and rhomboid minor. Nine muscles cross the shoulder joint to move the humerus. The ones that originate on the axial skeleton are the pectoralis major and the latissimus dorsi. The deltoid, subscapularis, supraspinatus, infraspinatus, teres major, teres minor, and coracobrachialis originate on the scapula. The forearm flexors include the biceps brachii, brachialis, and brachioradialis. The extensors are the triceps brachii and anconeus. The pronators are the pronator teres and the pronator quadratus. The supinator is the only one that turns the forearm anteriorly. The extrinsic muscles of the hands originate along the forearm and insert into the hand in order to facilitate crude movements of the wrists, hands, and fingers. The superficial anterior compartment of the forearm produces flexion. These muscles are the flexor carpi radialis, palmaris longus, flexor carpi ulnaris, and the flexor digitorum superficialis. The deep anterior compartment produces flexion as well. These are the flexor pollicis longus and the flexor digitorum profundus. The rest of the compartments produce extension. The extensor carpi radialis longus, extensor carpi radialis brevis, extensor digitorum, extensor digiti minimi, and extensor carpi ulnaris are the muscles found in the superficial posterior compartment. The deep posterior compartment includes the abductor longus, extensor pollicis brevis, extensor pollicis longus, and the extensor indicis. Finally, the intrinsic muscles of the hands allow our fingers to make precise movements, such as typing and writing. They both originate and insert within the hand. The thenar muscles, which are located on the lateral part of the palm, are the abductor pollicis brevis, opponens pollicis, flexor pollicis brevis, and adductor pollicis. The hypothenar muscles, which are located on the medial part of the palm, are the abductor digiti minimi, flexor digiti minimi brevis, and opponens digiti minimi. The intermediate muscles, located in the middle of the palm, are the lumbricals, palmar interossei, and dorsal interossei. 11.6 Appendicular Muscles of the Pelvic Girdle and Lower Limbs The pelvic girdle attaches the legs to the axial skeleton. The hip joint is where the pelvic girdle and the leg come together. The hip is joined to the pelvic girdle by many muscles. In the gluteal region, the psoas major and iliacus form the iliopsoas. The large and strong gluteus maximus, gluteus medius, and gluteus minimus extend and abduct the femur. Along with the gluteus maximus, the tensor fascia lata muscle forms the iliotibial tract. The lateral rotators of the femur at the hip are the piriformis, obturator internus, obturator externus, superior gemellus, inferior gemellus, and quadratus femoris. On the medial part of the thigh, the adductor longus, adductor brevis, and adductor magnus adduct the thigh and medially rotate it. The pectineus muscle adducts and flexes the femur at the hip. The thigh muscles that move the femur, tibia, and fibula are divided into medial, anterior, and posterior compartments. The medial compartment includes the adductors, pectineus, and the gracilis. The anterior compartment comprises the quadriceps femoris, quadriceps tendon, patellar ligament, and the sartorius. The quadriceps femoris is made of four muscles: the rectus femoris, the vastus lateralis, the vastus medius, and the vastus intermedius, which together extend the knee. The posterior compartment of the thigh includes the hamstrings: the biceps femoris, semitendinosus, and the semimembranosus, which all flex the knee. The muscles of the leg that move the foot and toes are divided into anterior, lateral, superficial- and deep-posterior compartments. The anterior compartment includes the tibialis anterior, the extensor hallucis longus, the extensor digitorum longus, and the fibularis (peroneus) tertius. The lateral compartment houses the fibularis (peroneus) longus and the fibularis (peroneus) brevis. The superficial posterior compartment has the gastrocnemius, soleus, and plantaris; and the deep posterior compartment has the popliteus, tibialis posterior, flexor digitorum longus, and flexor hallucis longus. Review Questions Which of the following is unique to the muscles of facial expression? - They all originate from the scalp musculature. - They insert onto the cartilage found around the face. - They only insert onto the facial bones. - They insert into the skin. Which of the following helps an agonist work? - a synergist - a fixator - an insertion - an antagonist Which of the following statements is correct about what happens during flexion? - The angle between bones is increased. - The angle between bones is decreased. - The bone moves away from the body. - The bone moves toward the center of the body. Which is moved the least during muscle contraction? - the origin - the insertion - the ligaments - the joints Which muscle has a convergent pattern of fascicles? - biceps brachii - gluteus maximus - pectoralis major - rectus femoris A muscle that has a pattern of fascicles running along the long axis of the muscle has which of the following fascicle arrangements? - circular - pennate - parallel - rectus Which arrangement best describes a bipennate muscle? - The muscle fibers feed in on an angle to a long tendon from both sides. - The muscle fibers feed in on an angle to a long tendon from all directions. - The muscle fibers feed in on an angle to a long tendon from one side. - The muscle fibers on one side of a tendon feed into it at a certain angle and muscle fibers on the other side of the tendon feed into it at the opposite angle. The location of a muscle’s insertion and origin can determine ________. - action - the force of contraction - muscle name - the load a muscle can carry Where is the temporalis muscle located? - on the forehead - in the neck - on the side of the head - on the chin Which muscle name does not make sense? - extensor digitorum - gluteus minimus - biceps femoris - extensor minimus longus Which of the following terms would be used in the name of a muscle that moves the leg away from the body? - flexor - adductor - extensor - abductor Which of the following is a prime mover in head flexion? - occipitofrontalis - corrugator supercilii - sternocleidomastoid - masseter Where is the inferior oblique muscle located? - in the abdomen - in the eye socket - in the anterior neck - in the face What is the action of the masseter? - swallowing - chewing - moving the lips - closing the eye The names of the extrinsic tongue muscles commonly end in ________. - -glottis - -glossus - -gluteus - -hyoid What is the function of the erector spinae? - movement of the arms - stabilization of the pelvic girdle - postural support - rotating of the vertebral column Which of the following abdominal muscles is not a part of the anterior abdominal wall? - quadratus lumborum - rectus abdominis - interior oblique - exterior oblique Which muscle pair plays a role in respiration? - intertransversarii, interspinales - semispinalis cervicis, semispinalis thoracis - trapezius, rhomboids - diaphragm, scalene What is the linea alba? - a small muscle that helps with compression of the abdominal organs - a long tendon that runs down the middle of the rectus abdominis - a long band of collagen fibers that connects the hip to the knee - another name for the tendinous inscription The rhomboid major and minor muscles are deep to the ________. - rectus abdominis - scalene muscles - trapezius - ligamentum nuchae Which muscle extends the forearm? - biceps brachii - triceps brachii - brachialis - deltoid What is the origin of the wrist flexors? - the lateral epicondyle of the humerus - the medial epicondyle of the humerus - the carpal bones of the wrist - the deltoid tuberosity of the humerus Which muscles stabilize the pectoral girdle? - axial and scapular - axial - appendicular - axial and appendicular The large muscle group that attaches the leg to the pelvic girdle and produces extension of the hip joint is the ________ group. - gluteal - obturator - adductor - abductor Which muscle produces movement that allows you to cross your legs? - the gluteus maximus - the piriformis - the gracilis - the sartorius What is the largest muscle in the lower leg? - soleus - gastrocnemius - tibialis anterior - tibialis posterior The vastus intermedius muscle is deep to which of the following muscles? - biceps femoris - rectus femoris - vastus medialis - vastus lateralis Critical Thinking Questions What effect does fascicle arrangement have on a muscle’s action? 29.Movements of the body occur at joints. Describe how muscles are arranged around the joints of the body. 30.Explain how a synergist assists an agonist by being a fixator. 31.Describe the different criteria that contribute to how skeletal muscles are named. 32.Explain the difference between axial and appendicular muscles. 33.Describe the muscles of the anterior neck. 34.Why are the muscles of the face different from typical skeletal muscle? 35.Describe the fascicle arrangement in the muscles of the abdominal wall. How do they relate to each other? 36.What are some similarities and differences between the diaphragm and the pelvic diaphragm? 37.The tendons of which muscles form the rotator cuff? Why is the rotator cuff important? 38.List the general muscle groups of the shoulders and upper limbs as well as their subgroups. 39.Which muscles form the hamstrings? How do they function together? 40.Which muscles form the quadriceps? How do they function together?	oercommons	2025-03-18T00:36:12.102606	07/23/2019	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/56370/overview", "title": "Anatomy and Physiology, Support and Movement, The Muscular System", "author": null }
https://oercommons.org/courseware/lesson/56379/overview	The Neurological Exam Introduction Figure 16.1 Neurological Exam Health care professionals, such as this air force nurse, can rapidly assess the neurological functions of a patient using the neurological exam. One part of the exam is the inspection of the oral cavity and pharynx, which enables the doctor to not only inspect the tissues for signs of infection, but also provides a means to test the functions of the cranial nerves associated with the oral cavity. (credit: U.S. Department of Defense) CHAPTER OBJECTIVES After studying this chapter, you will be able to: - Describe the major sections of the neurological exam - Outline the benefits of rapidly assessing neurological function - Relate anatomical structures of the nervous system to specific functions - Diagram the connections of the nervous system to the musculature and integument involved in primary sensorimotor responses - Compare and contrast the somatic and visceral reflexes with respect to how they are assessed through the neurological exam A man arrives at the hospital after feeling faint and complaining of a “pins-and-needles” feeling all along one side of his body. The most likely explanation is that he has suffered a stroke, which has caused a loss of oxygen to a particular part of the central nervous system (CNS). The problem is finding where in the entire nervous system the stroke has occurred. By checking reflexes, sensory responses, and motor control, a health care provider can focus on what abilities the patient may have lost as a result of the stroke and can use this information to determine where the injury occurred. In the emergency department of the hospital, this kind of rapid assessment of neurological function is key to treating trauma to the nervous system. In the classroom, the neurological exam is a valuable tool for learning the anatomy and physiology of the nervous system because it allows you to relate the functions of the system to particular locations in the nervous system. As a student of anatomy and physiology, you may be planning to go into an allied health field, perhaps nursing or physical therapy. You could be in the emergency department treating a patient such as the one just described. An important part of this course is to understand the nervous system. This can be especially challenging because you need to learn about the nervous system using your own nervous system. The first chapter in this unit about the nervous system began with a quote: “If the human brain were simple enough for us to understand, we would be too simple to understand it.” However, you are being asked to understand aspects of it. A healthcare provider can pinpoint problems with the nervous system in minutes by running through the series of tasks to test neurological function that are described in this chapter. You can use the same approach, though not as quickly, to learn about neurological function and its relationship to the structures of the nervous system. Nervous tissue is different from other tissues in that it is not classified into separate tissue types. It does contain two types of cells, neurons and glia, but it is all just nervous tissue. White matter and gray matter are not types of nervous tissue, but indications of different specializations within the nervous tissue. However, not all nervous tissue performs the same function. Furthermore, specific functions are not wholly localized to individual brain structures in the way that other bodily functions occur strictly within specific organs. In the CNS, we must consider the connections between cells over broad areas, not just the function of cells in one particular nucleus or region. In a broad sense, the nervous system is responsible for the majority of electrochemical signaling in the body, but the use of those signals is different in various regions. The nervous system is made up of the brain and spinal cord as the central organs, and the ganglia and nerves as organs in the periphery. The brain and spinal cord can be thought of as a collection of smaller organs, most of which would be the nuclei (such as the oculomotor nuclei), but white matter structures play an important role (such as the corpus callosum). Studying the nervous system requires an understanding of the varied physiology of the nervous system. For example, the hypothalamus plays a very different role than the visual cortex. The neurological exam provides a way to elicit behavior that represents those varied functions. Overview of the Neurological Exam - List the major sections of the neurological exam - Explain the connection between location and function in the nervous system - Explain the benefit of a rapid assessment for neurological function in a clinical setting - List the causes of neurological deficits - Describe the different ischemic events in the nervous system The neurological exam is a clinical assessment tool used to determine what specific parts of the CNS are affected by damage or disease. It can be performed in a short time—sometimes as quickly as 5 minutes—to establish neurological function. In the emergency department, this rapid assessment can make the difference with respect to proper treatment and the extent of recovery that is possible. The exam is a series of subtests separated into five major sections. The first of these is the mental status exam, which assesses the higher cognitive functions such as memory, orientation, and language. Then there is the cranial nerve exam, which tests the function of the 12 cranial nerves and, therefore, the central and peripheral structures associated with them. The cranial nerve exam tests the sensory and motor functions of each of the nerves, as applicable. Two major sections, the sensory exam and the motor exam, test the sensory and motor functions associated with spinal nerves. Finally, the coordination exam tests the ability to perform complex and coordinated movements. The gait exam, which is often considered a sixth major exam, specifically assesses the motor function of walking and can be considered part of the coordination exam because walking is a coordinated movement. Neuroanatomy and the Neurological Exam Localization of function is the concept that circumscribed locations are responsible for specific functions. The neurological exam highlights this relationship. For example, the cognitive functions that are assessed in the mental status exam are based on functions in the cerebrum, mostly in the cerebral cortex. Several of the subtests examine language function. Deficits in neurological function uncovered by these examinations usually point to damage to the left cerebral cortex. In the majority of individuals, language function is localized to the left hemisphere between the superior temporal lobe and the posterior frontal lobe, including the intervening connections through the inferior parietal lobe. The five major sections of the neurological exam are related to the major regions of the CNS (Figure 16.2). The mental status exam assesses functions related to the cerebrum. The cranial nerve exam is for the nerves that connect to the diencephalon and brain stem (as well as the olfactory connections to the forebrain). The coordination exam and the related gait exam primarily assess the functions of the cerebellum. The motor and sensory exams are associated with the spinal cord and its connections through the spinal nerves. Figure 16.2 Anatomical Underpinnings of the Neurological Exam The different regions of the CNS relate to the major sections of the neurological exam: the mental status exam, cranial nerve exam, sensory exam, motor exam, and coordination exam (including the gait exam). Part of the power of the neurological exam is this link between structure and function. Testing the various functions represented in the exam allows an accurate estimation of where the nervous system may be damaged. Consider the patient described in the chapter introduction. In the emergency department, he is given a quick exam to find where the deficit may be localized. Knowledge of where the damage occurred will lead to the most effective therapy. In rapid succession, he is asked to smile, raise his eyebrows, stick out his tongue, and shrug his shoulders. The doctor tests muscular strength by providing resistance against his arms and legs while he tries to lift them. With his eyes closed, he has to indicate when he feels the tip of a pen touch his legs, arms, fingers, and face. He follows the tip of a pen as the doctor moves it through the visual field and finally toward his face. A formal mental status exam is not needed at this point; the patient will demonstrate any possible deficits in that area during normal interactions with the interviewer. If cognitive or language deficits are apparent, the interviewer can pursue mental status in more depth. All of this takes place in less than 5 minutes. The patient reports that he feels pins and needles in his left arm and leg, and has trouble feeling the tip of the pen when he is touched on those limbs. This suggests a problem with the sensory systems between the spinal cord and the brain. The emergency department has a lead to follow before a CT scan is performed. He is put on aspirin therapy to limit the possibility of blood clots forming, in case the cause is an embolus—an obstruction such as a blood clot that blocks the flow of blood in an artery or vein. INTERACTIVE LINK Watch this video to see a demonstration of the neurological exam—a series of tests that can be performed rapidly when a patient is initially brought into an emergency department. The exam can be repeated on a regular basis to keep a record of how and if neurological function changes over time. In what order were the sections of the neurological exam tested in this video, and which section seemed to be left out? Causes of Neurological Deficits Damage to the nervous system can be limited to individual structures or can be distributed across broad areas of the brain and spinal cord. Localized, limited injury to the nervous system is most often the result of circulatory problems. Neurons are very sensitive to oxygen deprivation and will start to deteriorate within 1 or 2 minutes, and permanent damage (cell death) could result within a few hours. The loss of blood flow to part of the brain is known as a stroke, or a cerebrovascular accident (CVA). There are two main types of stroke, depending on how the blood supply is compromised: ischemic and hemorrhagic. An ischemic stroke is the loss of blood flow to an area because vessels are blocked or narrowed. This is often caused by an embolus, which may be a blood clot or fat deposit. Ischemia may also be the result of thickening of the blood vessel wall, or a drop in blood volume in the brain known as hypovolemia. A related type of CVA is known as a transient ischemic attack (TIA), which is similar to a stroke although it does not last as long. The diagnostic definition of a stroke includes effects that last at least 24 hours. Any stroke symptoms that are resolved within a 24-hour period because of restoration of adequate blood flow are classified as a TIA. A hemorrhagic stroke is bleeding into the brain because of a damaged blood vessel. Accumulated blood fills a region of the cranial vault and presses against the tissue in the brain (Figure 16.3). Physical pressure on the brain can cause the loss of function, as well as the squeezing of local arteries resulting in compromised blood flow beyond the site of the hemorrhage. As blood pools in the nervous tissue and the vasculature is damaged, the blood-brain barrier can break down and allow additional fluid to accumulate in the region, which is known as edema. Figure 16.3 Hemorrhagic Stroke (a) A hemorrhage into the tissue of the cerebrum results in a large accumulation of blood with an additional edema in the adjacent tissue. The hemorrhagic area causes the entire brain to be disfigured as suggested here by the lateral ventricles being squeezed into the opposite hemisphere. (b) A CT scan shows an intraparenchymal hemorrhage within the parietal lobe. (credit b: James Heilman) Whereas hemorrhagic stroke may involve bleeding into a large region of the CNS, such as into the deep white matter of a cerebral hemisphere, other events can cause widespread damage and loss of neurological functions. Infectious diseases can lead to loss of function throughout the CNS as components of nervous tissue, specifically astrocytes and microglia, react to the disease. Blunt force trauma, such as from a motor vehicle accident, can physically damage the CNS. A class of disorders that affect the nervous system are the neurodegenerative diseases: Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis (ALS), Creutzfeld–Jacob disease, multiple sclerosis (MS), and other disorders that are the result of nervous tissue degeneration. In diseases like Alzheimer’s, Parkinson’s, or ALS, neurons die; in diseases like MS, myelin is affected. Some of these disorders affect motor function, and others present with dementia. How patients with these disorders perform in the neurological exam varies, but is often broad in its effects, such as memory deficits that compromise many aspects of the mental status exam, or movement deficits that compromise aspects of the cranial nerve exam, the motor exam, or the coordination exam. The causes of these disorders are also varied. Some are the result of genetics, such as Huntington’s disease, or the result of autoimmunity, such as MS; others are not entirely understood, such as Alzheimer’s and Parkinson’s diseases. Current research suggests that many of these diseases are related in how the degeneration takes place and may be treated by common therapies. Finally, a common cause of neurological changes is observed in developmental disorders. Whether the result of genetic factors or the environment during development, there are certain situations that result in neurological functions being different from the expected norms. Developmental disorders are difficult to define because they are caused by defects that existed in the past and disrupted the normal development of the CNS. These defects probably involve multiple environmental and genetic factors—most of the time, we don’t know what the cause is other than that it is more complex than just one factor. Furthermore, each defect on its own may not be a problem, but when several are added together, they can disrupt growth processes that are not well understand in the first place. For instance, it is possible for a stroke to damage a specific region of the brain and lead to the loss of the ability to recognize faces (prosopagnosia). The link between cell death in the fusiform gyrus and the symptom is relatively easy to understand. In contrast, similar deficits can be seen in children with the developmental disorder, autism spectrum disorder (ASD). However, these children do not lack a fusiform gyrus, nor is there any damage or defect visible to this brain region. We conclude, rather poorly, that this brain region is not connected properly to other brain regions. Infection, trauma, and congenital disorders can all lead to significant signs, as identified through the neurological exam. It is important to differentiate between an acute event, such as stroke, and a chronic or global condition such as blunt force trauma. Responses seen in the neurological exam can help. A loss of language function observed in all its aspects is more likely a global event as opposed to a discrete loss of one function, such as not being able to say certain types of words. A concern, however, is that a specific function—such as controlling the muscles of speech—may mask other language functions. The various subtests within the mental status exam can address these finer points and help clarify the underlying cause of the neurological loss. INTERACTIVE LINK Watch this video for an introduction to the neurological exam. Studying the neurological exam can give insight into how structure and function in the nervous system are interdependent. This is a tool both in the clinic and in the classroom, but for different reasons. In the clinic, this is a powerful but simple tool to assess a patient’s neurological function. In the classroom, it is a different way to think about the nervous system. Though medical technology provides noninvasive imaging and real-time functional data, the presenter says these cannot replace the history at the core of the medical examination. What does history mean in the context of medical practice? The Mental Status Exam - Describe the relationship of mental status exam results to cerebral functions - Explain the categorization of regions of the cortex based on anatomy and physiology - Differentiate between primary, association, and integration areas of the cerebral cortex - Provide examples of localization of function related to the cerebral cortex In the clinical setting, the set of subtests known as the mental status exam helps us understand the relationship of the brain to the body. Ultimately, this is accomplished by assessing behavior. Tremors related to intentional movements, incoordination, or the neglect of one side of the body can be indicative of failures of the connections of the cerebrum either within the hemispheres, or from the cerebrum to other portions of the nervous system. There is no strict test for what the cerebrum does alone, but rather in what it does through its control of the rest of the CNS, the peripheral nervous system (PNS), and the musculature. Sometimes eliciting a behavior is as simple as asking a question. Asking a patient to state his or her name is not only to verify that the file folder in a health care provider’s hands is the correct one, but also to be sure that the patient is aware, oriented, and capable of interacting with another person. If the answer to “What is your name?” is “Santa Claus,” the person may have a problem understanding reality. If the person just stares at the examiner with a confused look on their face, the person may have a problem understanding or producing speech. Functions of the Cerebral Cortex The cerebrum is the seat of many of the higher mental functions, such as memory and learning, language, and conscious perception, which are the subjects of subtests of the mental status exam. The cerebral cortex is the thin layer of gray matter on the outside of the cerebrum. It is approximately a millimeter thick in most regions and highly folded to fit within the limited space of the cranial vault. These higher functions are distributed across various regions of the cortex, and specific locations can be said to be responsible for particular functions. There is a limited set of regions, for example, that are involved in language function, and they can be subdivided on the basis of the particular part of language function that each governs. The basis for parceling out areas of the cortex and attributing them to various functions has its root in pure anatomical underpinnings. The German neurologist and histologist Korbinian Brodmann, who made a careful study of the cytoarchitecture of the cerebrum around the turn of the nineteenth century, described approximately 50 regions of the cortex that differed enough from each other to be considered separate areas (Figure 16.4). Brodmann made preparations of many different regions of the cerebral cortex to view with a microscope. He compared the size, shape, and number of neurons to find anatomical differences in the various parts of the cerebral cortex. Continued investigation into these anatomical areas over the subsequent 100 or more years has demonstrated a strong correlation between the structures and the functions attributed to those structures. For example, the first three areas in Brodmann’s list—which are in the postcentral gyrus—compose the primary somatosensory cortex. Within this area, finer separation can be made on the basis of the concept of the sensory homunculus, as well as the different submodalities of somatosensation such as touch, vibration, pain, temperature, or proprioception. Today, we more frequently refer to these regions by their function (i.e., primary sensory cortex) than by the number Brodmann assigned to them, but in some situations the use of Brodmann numbers persists. Figure 16.4 Brodmann's Areas of the Cerebral Cortex On the basis of cytoarchitecture, the anatomist Korbinian Brodmann described the extensive array of cortical regions, as illustrated in his figure. Subsequent investigations found that these areas corresponded very well to functional differences in the cerebral cortex. (credit: modification of work by “Looie496”/Wikimedia Commons, based on original work by Korvinian Brodmann) Area 17, as Brodmann described it, is also known as the primary visual cortex. Adjacent to that are areas 18 and 19, which constitute subsequent regions of visual processing. Area 22 is the primary auditory cortex, and it is followed by area 23, which further processes auditory information. Area 4 is the primary motor cortex in the precentral gyrus, whereas area 6 is the premotor cortex. These areas suggest some specialization within the cortex for functional processing, both in sensory and motor regions. The fact that Brodmann’s areas correlate so closely to functional localization in the cerebral cortex demonstrates the strong link between structure and function in these regions. Areas 1, 2, 3, 4, 17, and 22 are each described as primary cortical areas. The adjoining regions are each referred to as association areas. Primary areas are where sensory information is initially received from the thalamus for conscious perception, or—in the case of the primary motor cortex—where descending commands are sent down to the brain stem or spinal cord to execute movements (Figure 16.5). Figure 16.5 Types of Cortical Areas The cerebral cortex can be described as containing three types of processing regions: primary, association, and integration areas. The primary cortical areas are where sensory information is initially processed, or where motor commands emerge to go to the brain stem or spinal cord. Association areas are adjacent to primary areas and further process the modality-specific input. Multimodal integration areas are found where the modality-specific regions meet; they can process multiple modalities together or different modalities on the basis of similar functions, such as spatial processing in vision or somatosensation. A number of other regions, which extend beyond these primary or association areas of the cortex, are referred to as integrative areas. These areas are found in the spaces between the domains for particular sensory or motor functions, and they integrate multisensory information, or process sensory or motor information in more complex ways. Consider, for example, the posterior parietal cortex that lies between the somatosensory cortex and visual cortex regions. This has been ascribed to the coordination of visual and motor functions, such as reaching to pick up a glass. The somatosensory function that would be part of this is the proprioceptive feedback from moving the arm and hand. The weight of the glass, based on what it contains, will influence how those movements are executed. Cognitive Abilities Assessment of cerebral functions is directed at cognitive abilities. The abilities assessed through the mental status exam can be separated into four groups: orientation and memory, language and speech, sensorium, and judgment and abstract reasoning. Orientation and Memory Orientation is the patient’s awareness of his or her immediate circumstances. It is awareness of time, not in terms of the clock, but of the date and what is occurring around the patient. It is awareness of place, such that a patient should know where he or she is and why. It is also awareness of who the patient is—recognizing personal identity and being able to relate that to the examiner. The initial tests of orientation are based on the questions, “Do you know what the date is?” or “Do you know where you are?” or “What is your name?” Further understanding of a patient’s awareness of orientation can come from questions that address remote memory, such as “Who is the President of the United States?”, or asking what happened on a specific date. There are also specific tasks to address memory. One is the three-word recall test. The patient is given three words to recall, such as book, clock, and shovel. After a short interval, during which other parts of the interview continue, the patient is asked to recall the three words. Other tasks that assess memory—aside from those related to orientation—have the patient recite the months of the year in reverse order to avoid the overlearned sequence and focus on the memory of the months in an order, or to spell common words backwards, or to recite a list of numbers back. Memory is largely a function of the temporal lobe, along with structures beneath the cerebral cortex such as the hippocampus and the amygdala. The storage of memory requires these structures of the medial temporal lobe. A famous case of a man who had both medial temporal lobes removed to treat intractable epilepsy provided insight into the relationship between the structures of the brain and the function of memory. Henry Molaison, who was referred to as patient HM when he was alive, had epilepsy localized to both of his medial temporal lobes. In 1953, a bilateral lobectomy was performed that alleviated the epilepsy but resulted in the inability for HM to form new memories—a condition called anterograde amnesia. HM was able to recall most events from before his surgery, although there was a partial loss of earlier memories, which is referred to as retrograde amnesia. HM became the subject of extensive studies into how memory works. What he was unable to do was form new memories of what happened to him, what are now called episodic memory. Episodic memory is autobiographical in nature, such as remembering riding a bicycle as a child around the neighborhood, as opposed to the procedural memory of how to ride a bike. HM also retained his short-term memory, such as what is tested by the three-word task described above. After a brief period, those memories would dissipate or decay and not be stored in the long-term because the medial temporal lobe structures were removed. The difference in short-term, procedural, and episodic memory, as evidenced by patient HM, suggests that there are different parts of the brain responsible for those functions. The long-term storage of episodic memory requires the hippocampus and related medial temporal structures, and the location of those memories is in the multimodal integration areas of the cerebral cortex. However, short-term memory—also called working or active memory—is localized to the prefrontal lobe. Because patient HM had only lost his medial temporal lobe—and lost very little of his previous memories, and did not lose the ability to form new short-term memories—it was concluded that the function of the hippocampus, and adjacent structures in the medial temporal lobe, is to move (or consolidate) short-term memories (in the pre-frontal lobe) to long-term memory (in the temporal lobe). The prefrontal cortex can also be tested for the ability to organize information. In one subtest of the mental status exam called set generation, the patient is asked to generate a list of words that all start with the same letter, but not to include proper nouns or names. The expectation is that a person can generate such a list of at least 10 words within 1 minute. Many people can likely do this much more quickly, but the standard separates the accepted normal from those with compromised prefrontal cortices. INTERACTIVE LINK Read this article to learn about a young man who texts his fiancée in a panic as he finds that he is having trouble remembering things. At the hospital, a neurologist administers the mental status exam, which is mostly normal except for the three-word recall test. The young man could not recall them even 30 seconds after hearing them and repeating them back to the doctor. An undiscovered mass in the mediastinum region was found to be Hodgkin’s lymphoma, a type of cancer that affects the immune system and likely caused antibodies to attack the nervous system. The patient eventually regained his ability to remember, though the events in the hospital were always elusive. Considering that the effects on memory were temporary, but resulted in the loss of the specific events of the hospital stay, what regions of the brain were likely to have been affected by the antibodies and what type of memory does that represent? Language and Speech Language is, arguably, a very human aspect of neurological function. There are certainly strides being made in understanding communication in other species, but much of what makes the human experience seemingly unique is its basis in language. Any understanding of our species is necessarily reflective, as suggested by the question “What am I?” And the fundamental answer to this question is suggested by the famous quote by René Descartes: “Cogito Ergo Sum” (translated from Latin as “I think, therefore I am”). Formulating an understanding of yourself is largely describing who you are to yourself. It is a confusing topic to delve into, but language is certainly at the core of what it means to be self-aware. The neurological exam has two specific subtests that address language. One measures the ability of the patient to understand language by asking them to follow a set of instructions to perform an action, such as “touch your right finger to your left elbow and then to your right knee.” Another subtest assesses the fluency and coherency of language by having the patient generate descriptions of objects or scenes depicted in drawings, and by reciting sentences or explaining a written passage. Language, however, is important in so many ways in the neurological exam. The patient needs to know what to do, whether it is as simple as explaining how the knee-jerk reflex is going to be performed, or asking a question such as “What is your name?” Often, language deficits can be determined without specific subtests; if a person cannot reply to a question properly, there may be a problem with the reception of language. An important example of multimodal integrative areas is associated with language function (Figure 16.6). Adjacent to the auditory association cortex, at the end of the lateral sulcus just anterior to the visual cortex, is Wernicke’s area. In the lateral aspect of the frontal lobe, just anterior to the region of the motor cortex associated with the head and neck, is Broca’s area. Both regions were originally described on the basis of losses of speech and language, which is called aphasia. The aphasia associated with Broca’s area is known as an expressive aphasia, which means that speech production is compromised. This type of aphasia is often described as non-fluency because the ability to say some words leads to broken or halting speech. Grammar can also appear to be lost. The aphasia associated with Wernicke’s area is known as a receptive aphasia, which is not a loss of speech production, but a loss of understanding of content. Patients, after recovering from acute forms of this aphasia, report not being able to understand what is said to them or what they are saying themselves, but they often cannot keep from talking. The two regions are connected by white matter tracts that run between the posterior temporal lobe and the lateral aspect of the frontal lobe. Conduction aphasia associated with damage to this connection refers to the problem of connecting the understanding of language to the production of speech. This is a very rare condition, but is likely to present as an inability to faithfully repeat spoken language. Figure 16.6 Broca's and Wernicke's Areas Two important integration areas of the cerebral cortex associated with language function are Broca’s and Wernicke’s areas. The two areas are connected through the deep white matter running from the posterior temporal lobe to the frontal lobe. Sensorium Those parts of the brain involved in the reception and interpretation of sensory stimuli are referred to collectively as the sensorium. The cerebral cortex has several regions that are necessary for sensory perception. From the primary cortical areas of the somatosensory, visual, auditory, and gustatory senses to the association areas that process information in these modalities, the cerebral cortex is the seat of conscious sensory perception. In contrast, sensory information can also be processed by deeper brain regions, which we may vaguely describe as subconscious—for instance, we are not constantly aware of the proprioceptive information that the cerebellum uses to maintain balance. Several of the subtests can reveal activity associated with these sensory modalities, such as being able to hear a question or see a picture. Two subtests assess specific functions of these cortical areas. The first is praxis, a practical exercise in which the patient performs a task completely on the basis of verbal description without any demonstration from the examiner. For example, the patient can be told to take their left hand and place it palm down on their left thigh, then flip it over so the palm is facing up, and then repeat this four times. The examiner describes the activity without any movements on their part to suggest how the movements are to be performed. The patient needs to understand the instructions, transform them into movements, and use sensory feedback, both visual and proprioceptive, to perform the movements correctly. The second subtest for sensory perception is gnosis, which involves two tasks. The first task, known as stereognosis, involves the naming of objects strictly on the basis of the somatosensory information that comes from manipulating them. The patient keeps their eyes closed and is given a common object, such as a coin, that they have to identify. The patient should be able to indicate the particular type of coin, such as a dime versus a penny, or a nickel versus a quarter, on the basis of the sensory cues involved. For example, the size, thickness, or weight of the coin may be an indication, or to differentiate the pairs of coins suggested here, the smooth or corrugated edge of the coin will correspond to the particular denomination. The second task, graphesthesia, is to recognize numbers or letters written on the palm of the hand with a dull pointer, such as a pen cap. Praxis and gnosis are related to the conscious perception and cortical processing of sensory information. Being able to transform verbal commands into a sequence of motor responses, or to manipulate and recognize a common object and associate it with a name for that object. Both subtests have language components because language function is integral to these functions. The relationship between the words that describe actions, or the nouns that represent objects, and the cerebral location of these concepts is suggested to be localized to particular cortical areas. Certain aphasias can be characterized by a deficit of verbs or nouns, known as V impairment or N impairment, or may be classified as V–N dissociation. Patients have difficulty using one type of word over the other. To describe what is happening in a photograph as part of the expressive language subtest, a patient will use active- or image-based language. The lack of one or the other of these components of language can relate to the ability to use verbs or nouns. Damage to the region at which the frontal and temporal lobes meet, including the region known as the insula, is associated with V impairment; damage to the middle and inferior temporal lobe is associated with N impairment. Judgment and Abstract Reasoning Planning and producing responses requires an ability to make sense of the world around us. Making judgments and reasoning in the abstract are necessary to produce movements as part of larger responses. For example, when your alarm goes off, do you hit the snooze button or jump out of bed? Is 10 extra minutes in bed worth the extra rush to get ready for your day? Will hitting the snooze button multiple times lead to feeling more rested or result in a panic as you run late? How you mentally process these questions can affect your whole day. The prefrontal cortex is responsible for the functions responsible for planning and making decisions. In the mental status exam, the subtest that assesses judgment and reasoning is directed at three aspects of frontal lobe function. First, the examiner asks questions about problem solving, such as “If you see a house on fire, what would you do?” The patient is also asked to interpret common proverbs, such as “Don’t look a gift horse in the mouth.” Additionally, pairs of words are compared for similarities, such as apple and orange, or lamp and cabinet. The prefrontal cortex is composed of the regions of the frontal lobe that are not directly related to specific motor functions. The most posterior region of the frontal lobe, the precentral gyrus, is the primary motor cortex. Anterior to that are the premotor cortex, Broca’s area, and the frontal eye fields, which are all related to planning certain types of movements. Anterior to what could be described as motor association areas are the regions of the prefrontal cortex. They are the regions in which judgment, abstract reasoning, and working memory are localized. The antecedents to planning certain movements are judging whether those movements should be made, as in the example of deciding whether to hit the snooze button. To an extent, the prefrontal cortex may be related to personality. The neurological exam does not necessarily assess personality, but it can be within the realm of neurology or psychiatry. A clinical situation that suggests this link between the prefrontal cortex and personality comes from the story of Phineas Gage, the railroad worker from the mid-1800s who had a metal spike impale his prefrontal cortex. There are suggestions that the steel rod led to changes in his personality. A man who was a quiet, dependable railroad worker became a raucous, irritable drunkard. Later anecdotal evidence from his life suggests that he was able to support himself, although he had to relocate and take on a different career as a stagecoach driver. A psychiatric practice to deal with various disorders was the prefrontal lobotomy. This procedure was common in the 1940s and early 1950s, until antipsychotic drugs became available. The connections between the prefrontal cortex and other regions of the brain were severed. The disorders associated with this procedure included some aspects of what are now referred to as personality disorders, but also included mood disorders and psychoses. Depictions of lobotomies in popular media suggest a link between cutting the white matter of the prefrontal cortex and changes in a patient’s mood and personality, though this correlation is not well understood. EVERYDAY CONNECTION Left Brain, Right Brain Popular media often refer to right-brained and left-brained people, as if the brain were two independent halves that work differently for different people. This is a popular misinterpretation of an important neurological phenomenon. As an extreme measure to deal with a debilitating condition, the corpus callosum may be sectioned to overcome intractable epilepsy. When the connections between the two cerebral hemispheres are cut, interesting effects can be observed. If a person with an intact corpus callosum is asked to put their hands in their pockets and describe what is there on the basis of what their hands feel, they might say that they have keys in their right pocket and loose change in the left. They may even be able to count the coins in their pocket and say if they can afford to buy a candy bar from the vending machine. If a person with a sectioned corpus callosum is given the same instructions, they will do something quite peculiar. They will only put their right hand in their pocket and say they have keys there. They will not even move their left hand, much less report that there is loose change in the left pocket. The reason for this is that the language functions of the cerebral cortex are localized to the left hemisphere in 95 percent of the population. Additionally, the left hemisphere is connected to the right side of the body through the corticospinal tract and the ascending tracts of the spinal cord. Motor commands from the precentral gyrus control the opposite side of the body, whereas sensory information processed by the postcentral gyrus is received from the opposite side of the body. For a verbal command to initiate movement of the right arm and hand, the left side of the brain needs to be connected by the corpus callosum. Language is processed in the left side of the brain and directly influences the left brain and right arm motor functions, but is sent to influence the right brain and left arm motor functions through the corpus callosum. Likewise, the left-handed sensory perception of what is in the left pocket travels across the corpus callosum from the right brain, so no verbal report on those contents would be possible if the hand happened to be in the pocket. INTERACTIVE LINK Watch the video titled “The Man With Two Brains” to see the neuroscientist Michael Gazzaniga introduce a patient he has worked with for years who has had his corpus callosum cut, separating his two cerebral hemispheres. A few tests are run to demonstrate how this manifests in tests of cerebral function. Unlike normal people, this patient can perform two independent tasks at the same time because the lines of communication between the right and left sides of his brain have been removed. Whereas a person with an intact corpus callosum cannot overcome the dominance of one hemisphere over the other, this patient can. If the left cerebral hemisphere is dominant in the majority of people, why would right-handedness be most common? The Mental Status Exam The cerebrum, particularly the cerebral cortex, is the location of important cognitive functions that are the focus of the mental status exam. The regionalization of the cortex, initially described on the basis of anatomical evidence of cytoarchitecture, reveals the distribution of functionally distinct areas. Cortical regions can be described as primary sensory or motor areas, association areas, or multimodal integration areas. The functions attributed to these regions include attention, memory, language, speech, sensation, judgment, and abstract reasoning. The mental status exam addresses these cognitive abilities through a series of subtests designed to elicit particular behaviors ascribed to these functions. The loss of neurological function can illustrate the location of damage to the cerebrum. Memory functions are attributed to the temporal lobe, particularly the medial temporal lobe structures known as the hippocampus and amygdala, along with the adjacent cortex. Evidence of the importance of these structures comes from the side effects of a bilateral temporal lobectomy that were studied in detail in patient HM. Losses of language and speech functions, known as aphasias, are associated with damage to the important integration areas in the left hemisphere known as Broca’s or Wernicke’s areas, as well as the connections in the white matter between them. Different types of aphasia are named for the particular structures that are damaged. Assessment of the functions of the sensorium includes praxis and gnosis. The subtests related to these functions depend on multimodal integration, as well as language-dependent processing. The prefrontal cortex contains structures important for planning, judgment, reasoning, and working memory. Damage to these areas can result in changes to personality, mood, and behavior. The famous case of Phineas Gage suggests a role for this cortex in personality, as does the outdated practice of prefrontal lobectomy. The Cranial Nerve Exam - Describe the functional grouping of cranial nerves - Match the regions of the forebrain and brain stem that are connected to each cranial nerve - Suggest diagnoses that would explain certain losses of function in the cranial nerves - Relate cranial nerve deficits to damage of adjacent, unrelated structures The twelve cranial nerves are typically covered in introductory anatomy courses, and memorizing their names is facilitated by numerous mnemonics developed by students over the years of this practice. But knowing the names of the nerves in order often leaves much to be desired in understanding what the nerves do. The nerves can be categorized by functions, and subtests of the cranial nerve exam can clarify these functional groupings. Three of the nerves are strictly responsible for special senses whereas four others contain fibers for special and general senses. Three nerves are connected to the extraocular muscles resulting in the control of gaze. Four nerves connect to muscles of the face, oral cavity, and pharynx, controlling facial expressions, mastication, swallowing, and speech. Four nerves make up the cranial component of the parasympathetic nervous system responsible for pupillary constriction, salivation, and the regulation of the organs of the thoracic and upper abdominal cavities. Finally, one nerve controls the muscles of the neck, assisting with spinal control of the movement of the head and neck. The cranial nerve exam allows directed tests of forebrain and brain stem structures. The twelve cranial nerves serve the head and neck. The vagus nerve (cranial nerve X) has autonomic functions in the thoracic and superior abdominal cavities. The special senses are served through the cranial nerves, as well as the general senses of the head and neck. The movement of the eyes, face, tongue, throat, and neck are all under the control of cranial nerves. Preganglionic parasympathetic nerve fibers that control pupillary size, salivary glands, and the thoracic and upper abdominal viscera are found in four of the nerves. Tests of these functions can provide insight into damage to specific regions of the brain stem and may uncover deficits in adjacent regions. Sensory Nerves The olfactory, optic, and vestibulocochlear nerves (cranial nerves I, II, and VIII) are dedicated to four of the special senses: smell, vision, equilibrium, and hearing, respectively. Taste sensation is relayed to the brain stem through fibers of the facial and glossopharyngeal nerves. The trigeminal nerve is a mixed nerve that carries the general somatic senses from the head, similar to those coming through spinal nerves from the rest of the body. Testing smell is straightforward, as common smells are presented to one nostril at a time. The patient should be able to recognize the smell of coffee or mint, indicating the proper functioning of the olfactory system. Loss of the sense of smell is called anosmia and can be lost following blunt trauma to the head or through aging. The short axons of the first cranial nerve regenerate on a regular basis. The neurons in the olfactory epithelium have a limited life span, and new cells grow to replace the ones that die off. The axons from these neurons grow back into the CNS by following the existing axons—representing one of the few examples of such growth in the mature nervous system. If all of the fibers are sheared when the brain moves within the cranium, such as in a motor vehicle accident, then no axons can find their way back to the olfactory bulb to re-establish connections. If the nerve is not completely severed, the anosmia may be temporary as new neurons can eventually reconnect. Olfaction is not the pre-eminent sense, but its loss can be quite detrimental. The enjoyment of food is largely based on our sense of smell. Anosmia means that food will not seem to have the same taste, though the gustatory sense is intact, and food will often be described as being bland. However, the taste of food can be improved by adding ingredients (e.g., salt) that stimulate the gustatory sense. Testing vision relies on the tests that are common in an optometry office. The Snellen chart (Figure 16.7) demonstrates visual acuity by presenting standard Roman letters in a variety of sizes. The result of this test is a rough generalization of the acuity of a person based on the normal accepted acuity, such that a letter that subtends a visual angle of 5 minutes of an arc at 20 feet can be seen. To have 20/60 vision, for example, means that the smallest letters that a person can see at a 20-foot distance could be seen by a person with normal acuity from 60 feet away. Testing the extent of the visual field means that the examiner can establish the boundaries of peripheral vision as simply as holding their hands out to either side and asking the patient when the fingers are no longer visible without moving the eyes to track them. If it is necessary, further tests can establish the perceptions in the visual fields. Physical inspection of the optic disk, or where the optic nerve emerges from the eye, can be accomplished by looking through the pupil with an ophthalmoscope. Figure 16.7 The Snellen Chart The Snellen chart for visual acuity presents a limited number of Roman letters in lines of decreasing size. The line with letters that subtend 5 minutes of an arc from 20 feet represents the smallest letters that a person with normal acuity should be able to read at that distance. The different sizes of letters in the other lines represent rough approximations of what a person of normal acuity can read at different distances. For example, the line that represents 20/200 vision would have larger letters so that they are legible to the person with normal acuity at 200 feet. The optic nerves from both sides enter the cranium through the respective optic canals and meet at the optic chiasm at which fibers sort such that the two halves of the visual field are processed by the opposite sides of the brain. Deficits in visual field perception often suggest damage along the length of the optic pathway between the orbit and the diencephalon. For example, loss of peripheral vision may be the result of a pituitary tumor pressing on the optic chiasm (Figure 16.8). The pituitary, seated in the sella turcica of the sphenoid bone, is directly inferior to the optic chiasm. The axons that decussate in the chiasm are from the medial retinae of either eye, and therefore carry information from the peripheral visual field. Figure 16.8 Pituitary Tumor The pituitary gland is located in the sella turcica of the sphenoid bone within the cranial floor, placing it immediately inferior to the optic chiasm. If the pituitary gland develops a tumor, it can press against the fibers crossing in the chiasm. Those fibers are conveying peripheral visual information to the opposite side of the brain, so the patient will experience “tunnel vision”—meaning that only the central visual field will be perceived. The vestibulocochlear nerve (CN VIII) carries both equilibrium and auditory sensations from the inner ear to the medulla. Though the two senses are not directly related, anatomy is mirrored in the two systems. Problems with balance, such as vertigo, and deficits in hearing may both point to problems with the inner ear. Within the petrous region of the temporal bone is the bony labyrinth of the inner ear. The vestibule is the portion for equilibrium, composed of the utricle, saccule, and the three semicircular canals. The cochlea is responsible for transducing sound waves into a neural signal. The sensory nerves from these two structures travel side-by-side as the vestibulocochlear nerve, though they are really separate divisions. They both emerge from the inner ear, pass through the internal auditory meatus, and synapse in nuclei of the superior medulla. Though they are part of distinct sensory systems, the vestibular nuclei and the cochlear nuclei are close neighbors with adjacent inputs. Deficits in one or both systems could occur from damage that encompasses structures close to both. Damage to structures near the two nuclei can result in deficits to one or both systems. Balance or hearing deficits may be the result of damage to the middle or inner ear structures. Ménière's disease is a disorder that can affect both equilibrium and audition in a variety of ways. The patient can suffer from vertigo, a low-frequency ringing in the ears, or a loss of hearing. From patient to patient, the exact presentation of the disease can be different. Additionally, within a single patient, the symptoms and signs may change as the disease progresses. Use of the neurological exam subtests for the vestibulocochlear nerve illuminates the changes a patient may go through. The disease appears to be the result of accumulation, or over-production, of fluid in the inner ear, in either the vestibule or cochlea. Tests of equilibrium are important for coordination and gait and are related to other aspects of the neurological exam. The vestibulo-ocular reflex involves the cranial nerves for gaze control. Balance and equilibrium, as tested by the Romberg test, are part of spinal and cerebellar processes and involved in those components of the neurological exam, as discussed later. Hearing is tested by using a tuning fork in a couple of different ways. The Rinne test involves using a tuning fork to distinguish between conductive hearing and sensorineural hearing. Conductive hearing relies on vibrations being conducted through the ossicles of the middle ear. Sensorineural hearing is the transmission of sound stimuli through the neural components of the inner ear and cranial nerve. A vibrating tuning fork is placed on the mastoid process and the patient indicates when the sound produced from this is no longer present. Then the fork is immediately moved to just next to the ear canal so the sound travels through the air. If the sound is not heard through the ear, meaning the sound is conducted better through the temporal bone than through the ossicles, a conductive hearing deficit is present. The Weber test also uses a tuning fork to differentiate between conductive versus sensorineural hearing loss. In this test, the tuning fork is placed at the top of the skull, and the sound of the tuning fork reaches both inner ears by travelling through bone. In a healthy patient, the sound would appear equally loud in both ears. With unilateral conductive hearing loss, however, the tuning fork sounds louder in the ear with hearing loss. This is because the sound of the tuning fork has to compete with background noise coming from the outer ear, but in conductive hearing loss, the background noise is blocked in the damaged ear, allowing the tuning fork to sound relatively louder in that ear. With unilateral sensorineural hearing loss, however, damage to the cochlea or associated nervous tissue means that the tuning fork sounds quieter in that ear. The trigeminal system of the head and neck is the equivalent of the ascending spinal cord systems of the dorsal column and the spinothalamic pathways. Somatosensation of the face is conveyed along the nerve to enter the brain stem at the level of the pons. Synapses of those axons, however, are distributed across nuclei found throughout the brain stem. The mesencephalic nucleus processes proprioceptive information of the face, which is the movement and position of facial muscles. It is the sensory component of the jaw-jerk reflex, a stretch reflex of the masseter muscle. The chief nucleus, located in the pons, receives information about light touch as well as proprioceptive information about the mandible, which are both relayed to the thalamus and, ultimately, to the postcentral gyrus of the parietal lobe. The spinal trigeminal nucleus, located in the medulla, receives information about crude touch, pain, and temperature to be relayed to the thalamus and cortex. Essentially, the projection through the chief nucleus is analogous to the dorsal column pathway for the body, and the projection through the spinal trigeminal nucleus is analogous to the spinothalamic pathway. Subtests for the sensory component of the trigeminal system are the same as those for the sensory exam targeting the spinal nerves. The primary sensory subtest for the trigeminal system is sensory discrimination. A cotton-tipped applicator, which is cotton attached to the end of a thin wooden stick, can be used easily for this. The wood of the applicator can be snapped so that a pointed end is opposite the soft cotton-tipped end. The cotton end provides a touch stimulus, while the pointed end provides a painful, or sharp, stimulus. While the patient’s eyes are closed, the examiner touches the two ends of the applicator to the patient’s face, alternating randomly between them. The patient must identify whether the stimulus is sharp or dull. These stimuli are processed by the trigeminal system separately. Contact with the cotton tip of the applicator is a light touch, relayed by the chief nucleus, but contact with the pointed end of the applicator is a painful stimulus relayed by the spinal trigeminal nucleus. Failure to discriminate these stimuli can localize problems within the brain stem. If a patient cannot recognize a painful stimulus, that might indicate damage to the spinal trigeminal nucleus in the medulla. The medulla also contains important regions that regulate the cardiovascular, respiratory, and digestive systems, as well as being the pathway for ascending and descending tracts between the brain and spinal cord. Damage, such as a stroke, that results in changes in sensory discrimination may indicate these unrelated regions are affected as well. Gaze Control The three nerves that control the extraocular muscles are the oculomotor, trochlear, and abducens nerves, which are the third, fourth, and sixth cranial nerves. As the name suggests, the abducens nerve is responsible for abducting the eye, which it controls through contraction of the lateral rectus muscle. The trochlear nerve controls the superior oblique muscle to rotate the eye along its axis in the orbit medially, which is called intorsion, and is a component of focusing the eyes on an object close to the face. The oculomotor nerve controls all the other extraocular muscles, as well as a muscle of the upper eyelid. Movements of the two eyes need to be coordinated to locate and track visual stimuli accurately. When moving the eyes to locate an object in the horizontal plane, or to track movement horizontally in the visual field, the lateral rectus muscle of one eye and medial rectus muscle of the other eye are both active. The lateral rectus is controlled by neurons of the abducens nucleus in the superior medulla, whereas the medial rectus is controlled by neurons in the oculomotor nucleus of the midbrain. Coordinated movement of both eyes through different nuclei requires integrated processing through the brain stem. In the midbrain, the superior colliculus integrates visual stimuli with motor responses to initiate eye movements. The paramedian pontine reticular formation (PPRF) will initiate a rapid eye movement, or saccade, to bring the eyes to bear on a visual stimulus quickly. These areas are connected to the oculomotor, trochlear, and abducens nuclei by the medial longitudinal fasciculus (MLF) that runs through the majority of the brain stem. The MLF allows for conjugate gaze, or the movement of the eyes in the same direction, during horizontal movements that require the lateral and medial rectus muscles. Control of conjugate gaze strictly in the vertical direction is contained within the oculomotor complex. To elevate the eyes, the oculomotor nerve on either side stimulates the contraction of both superior rectus muscles; to depress the eyes, the oculomotor nerve on either side stimulates the contraction of both inferior rectus muscles. Purely vertical movements of the eyes are not very common. Movements are often at an angle, so some horizontal components are necessary, adding the medial and lateral rectus muscles to the movement. The rapid movement of the eyes used to locate and direct the fovea onto visual stimuli is called a saccade. Notice that the paths that are traced in Figure 16.9 are not strictly vertical. The movements between the nose and the mouth are closest, but still have a slant to them. Also, the superior and inferior rectus muscles are not perfectly oriented with the line of sight. The origin for both muscles is medial to their insertions, so elevation and depression may require the lateral rectus muscles to compensate for the slight adduction inherent in the contraction of those muscles, requiring MLF activity as well. Figure 16.9 Saccadic Eye Movements Saccades are rapid, conjugate movements of the eyes to survey a complicated visual stimulus, or to follow a moving visual stimulus. This image represents the shifts in gaze typical of a person studying a face. Notice the concentration of gaze on the major features of the face and the large number of paths traced between the eyes or around the mouth. Testing eye movement is simply a matter of having the patient track the tip of a pen as it is passed through the visual field. This may appear similar to testing visual field deficits related to the optic nerve, but the difference is that the patient is asked to not move the eyes while the examiner moves a stimulus into the peripheral visual field. Here, the extent of movement is the point of the test. The examiner is watching for conjugate movements representing proper function of the related nuclei and the MLF. Failure of one eye to abduct while the other adducts in a horizontal movement is referred to as internuclear ophthalmoplegia. When this occurs, the patient will experience diplopia, or double vision, as the two eyes are temporarily pointed at different stimuli. Diplopia is not restricted to failure of the lateral rectus, because any of the extraocular muscles may fail to move one eye in perfect conjugation with the other. The final aspect of testing eye movements is to move the tip of the pen in toward the patient’s face. As visual stimuli move closer to the face, the two medial recti muscles cause the eyes to move in the one nonconjugate movement that is part of gaze control. When the two eyes move to look at something closer to the face, they both adduct, which is referred to as convergence. To keep the stimulus in focus, the eye also needs to change the shape of the lens, which is controlled through the parasympathetic fibers of the oculomotor nerve. The change in focal power of the eye is referred to as accommodation. Accommodation ability changes with age; focusing on nearer objects, such as the written text of a book or on a computer screen, may require corrective lenses later in life. Coordination of the skeletal muscles for convergence and coordination of the smooth muscles of the ciliary body for accommodation are referred to as the accommodation–convergence reflex. A crucial function of the cranial nerves is to keep visual stimuli centered on the fovea of the retina. The vestibulo-ocular reflex (VOR) coordinates all of the components (Figure 16.10), both sensory and motor, that make this possible. If the head rotates in one direction—for example, to the right—the horizontal pair of semicircular canals in the inner ear indicate the movement by increased activity on the right and decreased activity on the left. The information is sent to the abducens nuclei and oculomotor nuclei on either side to coordinate the lateral and medial rectus muscles. The left lateral rectus and right medial rectus muscles will contract, rotating the eyes in the opposite direction of the head, while nuclei controlling the right lateral rectus and left medial rectus muscles will be inhibited to reduce antagonism of the contracting muscles. These actions stabilize the visual field by compensating for the head rotation with opposite rotation of the eyes in the orbits. Deficits in the VOR may be related to vestibular damage, such as in Ménière’s disease, or from dorsal brain stem damage that would affect the eye movement nuclei or their connections through the MLF. Figure 16.10 Vestibulo-ocular Reflex If the head is turned in one direction, the coordination of that movement with the fixation of the eyes on a visual stimulus involves a circuit that ties the vestibular sense with the eye movement nuclei through the MLF. Nerves of the Face and Oral Cavity An iconic part of a doctor’s visit is the inspection of the oral cavity and pharynx, suggested by the directive to “open your mouth and say ‘ah.’” This is followed by inspection, with the aid of a tongue depressor, of the back of the mouth, or the opening of the oral cavity into the pharynx known as the fauces. Whereas this portion of a medical exam inspects for signs of infection, such as in tonsillitis, it is also the means to test the functions of the cranial nerves that are associated with the oral cavity. The facial and glossopharyngeal nerves convey gustatory stimulation to the brain. Testing this is as simple as introducing salty, sour, bitter, or sweet stimuli to either side of the tongue. The patient should respond to the taste stimulus before retracting the tongue into the mouth. Stimuli applied to specific locations on the tongue will dissolve into the saliva and may stimulate taste buds connected to either the left or right of the nerves, masking any lateral deficits. Along with taste, the glossopharyngeal nerve relays general sensations from the pharyngeal walls. These sensations, along with certain taste stimuli, can stimulate the gag reflex. If the examiner moves the tongue depressor to contact the lateral wall of the fauces, this should elicit the gag reflex. Stimulation of either side of the fauces should elicit an equivalent response. The motor response, through contraction of the muscles of the pharynx, is mediated through the vagus nerve. Normally, the vagus nerve is considered autonomic in nature. The vagus nerve directly stimulates the contraction of skeletal muscles in the pharynx and larynx to contribute to the swallowing and speech functions. Further testing of vagus motor function has the patient repeating consonant sounds that require movement of the muscles around the fauces. The patient is asked to say “lah-kah-pah” or a similar set of alternating sounds while the examiner observes the movements of the soft palate and arches between the palate and tongue. The facial and glossopharyngeal nerves are also responsible for the initiation of salivation. Neurons in the salivary nuclei of the medulla project through these two nerves as preganglionic fibers, and synapse in ganglia located in the head. The parasympathetic fibers of the facial nerve synapse in the pterygopalatine ganglion, which projects to the submandibular gland and sublingual gland. The parasympathetic fibers of the glossopharyngeal nerve synapse in the otic ganglion, which projects to the parotid gland. Salivation in response to food in the oral cavity is based on a visceral reflex arc within the facial or glossopharyngeal nerves. Other stimuli that stimulate salivation are coordinated through the hypothalamus, such as the smell and sight of food. The hypoglossal nerve is the motor nerve that controls the muscles of the tongue, except for the palatoglossus muscle, which is controlled by the vagus nerve. There are two sets of muscles of the tongue. The extrinsic muscles of the tongue are connected to other structures, whereas the intrinsic muscles of the tongue are completely contained within the lingual tissues. While examining the oral cavity, movement of the tongue will indicate whether hypoglossal function is impaired. The test for hypoglossal function is the “stick out your tongue” part of the exam. The genioglossus muscle is responsible for protrusion of the tongue. If the hypoglossal nerves on both sides are working properly, then the tongue will stick straight out. If the nerve on one side has a deficit, the tongue will stick out to that side—pointing to the side with damage. Loss of function of the tongue can interfere with speech and swallowing. Additionally, because the location of the hypoglossal nerve and nucleus is near the cardiovascular center, inspiratory and expiratory areas for respiration, and the vagus nuclei that regulate digestive functions, a tongue that protrudes incorrectly can suggest damage in adjacent structures that have nothing to do with controlling the tongue. INTERACTIVE LINK Watch this short video to see an examination of the facial nerve using some simple tests. The facial nerve controls the muscles of facial expression. Severe deficits will be obvious in watching someone use those muscles for normal control. One side of the face might not move like the other side. But directed tests, especially for contraction against resistance, require a formal testing of the muscles. The muscles of the upper and lower face need to be tested. The strength test in this video involves the patient squeezing her eyes shut and the examiner trying to pry her eyes open. Why does the examiner ask her to try a second time? Motor Nerves of the Neck The accessory nerve, also referred to as the spinal accessory nerve, innervates the sternocleidomastoid and trapezius muscles (Figure 16.11). When both the sternocleidomastoids contract, the head flexes forward; individually, they cause rotation to the opposite side. The trapezius can act as an antagonist, causing extension and hyperextension of the neck. These two superficial muscles are important for changing the position of the head. Both muscles also receive input from cervical spinal nerves. Along with the spinal accessory nerve, these nerves contribute to elevating the scapula and clavicle through the trapezius, which is tested by asking the patient to shrug both shoulders, and watching for asymmetry. For the sternocleidomastoid, those spinal nerves are primarily sensory projections, whereas the trapezius also has lateral insertions to the clavicle and scapula, and receives motor input from the spinal cord. Calling the nerve the spinal accessory nerve suggests that it is aiding the spinal nerves. Though that is not precisely how the name originated, it does help make the association between the function of this nerve in controlling these muscles and the role these muscles play in movements of the trunk or shoulders. Figure 16.11 Muscles Controlled by the Accessory Nerve The accessory nerve innervates the sternocleidomastoid and trapezius muscles, both of which attach to the head and to the trunk and shoulders. They can act as antagonists in head flexion and extension, and as synergists in lateral flexion toward the shoulder. To test these muscles, the patient is asked to flex and extend the neck or shrug the shoulders against resistance, testing the strength of the muscles. Lateral flexion of the neck toward the shoulder tests both at the same time. Any difference on one side versus the other would suggest damage on the weaker side. These strength tests are common for the skeletal muscles controlled by spinal nerves and are a significant component of the motor exam. Deficits associated with the accessory nerve may have an effect on orienting the head, as described with the VOR. HOMEOSTATIC IMBALANCES The Pupillary Light Response The autonomic control of pupillary size in response to a bright light involves the sensory input of the optic nerve and the parasympathetic motor output of the oculomotor nerve. When light hits the retina, specialized photosensitive ganglion cells send a signal along the optic nerve to the pretectal nucleus in the superior midbrain. A neuron from this nucleus projects to the Eddinger–Westphal nuclei in the oculomotor complex in both sides of the midbrain. Neurons in this nucleus give rise to the preganglionic parasympathetic fibers that project through the oculomotor nerve to the ciliary ganglion in the posterior orbit. The postganglionic parasympathetic fibers from the ganglion project to the iris, where they release acetylcholine onto circular fibers that constrict the pupil to reduce the amount of light hitting the retina. The sympathetic nervous system is responsible for dilating the pupil when light levels are low. Shining light in one eye will elicit constriction of both pupils. The efferent limb of the pupillary light reflex is bilateral. Light shined in one eye causes a constriction of that pupil, as well as constriction of the contralateral pupil. Shining a penlight in the eye of a patient is a very artificial situation, as both eyes are normally exposed to the same light sources. Testing this reflex can illustrate whether the optic nerve or the oculomotor nerve is damaged. If shining the light in one eye results in no changes in pupillary size but shining light in the opposite eye elicits a normal, bilateral response, the damage is associated with the optic nerve on the nonresponsive side. If light in either eye elicits a response in only one eye, the problem is with the oculomotor system. If light in the right eye only causes the left pupil to constrict, the direct reflex is lost and the consensual reflex is intact, which means that the right oculomotor nerve (or Eddinger–Westphal nucleus) is damaged. Damage to the right oculomotor connections will be evident when light is shined in the left eye. In that case, the direct reflex is intact but the consensual reflex is lost, meaning that the left pupil will constrict while the right does not. The Cranial Nerve Exam The cranial nerves can be separated into four major groups associated with the subtests of the cranial nerve exam. First are the sensory nerves, then the nerves that control eye movement, the nerves of the oral cavity and superior pharynx, and the nerve that controls movements of the neck. The olfactory, optic, and vestibulocochlear nerves are strictly sensory nerves for smell, sight, and balance and hearing, whereas the trigeminal, facial, and glossopharyngeal nerves carry somatosensation of the face, and taste—separated between the anterior two-thirds of the tongue and the posterior one-third. Special senses are tested by presenting the particular stimuli to each receptive organ. General senses can be tested through sensory discrimination of touch versus painful stimuli. The oculomotor, trochlear, and abducens nerves control the extraocular muscles and are connected by the medial longitudinal fasciculus to coordinate gaze. Testing conjugate gaze is as simple as having the patient follow a visual target, like a pen tip, through the visual field ending with an approach toward the face to test convergence and accommodation. Along with the vestibular functions of the eighth nerve, the vestibulo-ocular reflex stabilizes gaze during head movements by coordinating equilibrium sensations with the eye movement systems. The trigeminal nerve controls the muscles of chewing, which are tested for stretch reflexes. Motor functions of the facial nerve are usually obvious if facial expressions are compromised, but can be tested by having the patient raise their eyebrows, smile, and frown. Movements of the tongue, soft palate, or superior pharynx can be observed directly while the patient swallows, while the gag reflex is elicited, or while the patient says repetitive consonant sounds. The motor control of the gag reflex is largely controlled by fibers in the vagus nerve and constitutes a test of that nerve because the parasympathetic functions of that nerve are involved in visceral regulation, such as regulating the heartbeat and digestion. Movement of the head and neck using the sternocleidomastoid and trapezius muscles is controlled by the accessory nerve. Flexing of the neck and strength testing of those muscles reviews the function of that nerve. The Sensory and Motor Exams - Describe the arrangement of sensory and motor regions in the spinal cord - Relate damage in the spinal cord to sensory or motor deficits - Differentiate between upper motor neuron and lower motor neuron diseases - Describe the clinical indications of common reflexes Connections between the body and the CNS occur through the spinal cord. The cranial nerves connect the head and neck directly to the brain, but the spinal cord receives sensory input and sends motor commands out to the body through the spinal nerves. Whereas the brain develops into a complex series of nuclei and fiber tracts, the spinal cord remains relatively simple in its configuration (Figure 16.12). From the initial neural tube early in embryonic development, the spinal cord retains a tube-like structure with gray matter surrounding the small central canal and white matter on the surface in three columns. The dorsal, or posterior, horns of the gray matter are mainly devoted to sensory functions whereas the ventral, or anterior, and lateral horns are associated with motor functions. In the white matter, the dorsal column relays sensory information to the brain, and the anterior column is almost exclusively relaying motor commands to the ventral horn motor neurons. The lateral column, however, conveys both sensory and motor information between the spinal cord and brain. Figure 16.12 Locations of Spinal Fiber Tracts Sensory Modalities and Location The general senses are distributed throughout the body, relying on nervous tissue incorporated into various organs. Somatic senses are incorporated mostly into the skin, muscles, or tendons, whereas the visceral senses come from nervous tissue incorporated into the majority of organs such as the heart or stomach. The somatic senses are those that usually make up the conscious perception of the how the body interacts with the environment. The visceral senses are most often below the limit of conscious perception because they are involved in homeostatic regulation through the autonomic nervous system. The sensory exam tests the somatic senses, meaning those that are consciously perceived. Testing of the senses begins with examining the regions known as dermatomes that connect to the cortical region where somatosensation is perceived in the postcentral gyrus. To test the sensory fields, a simple stimulus of the light touch of the soft end of a cotton-tipped applicator is applied at various locations on the skin. The spinal nerves, which contain sensory fibers with dendritic endings in the skin, connect with the skin in a topographically organized manner, illustrated as dermatomes (Figure 16.13). For example, the fibers of eighth cervical nerve innervate the medial surface of the forearm and extend out to the fingers. In addition to testing perception at different positions on the skin, it is necessary to test sensory perception within the dermatome from distal to proximal locations in the appendages, or lateral to medial locations in the trunk. In testing the eighth cervical nerve, the patient would be asked if the touch of the cotton to the fingers or the medial forearm was perceptible, and whether there were any differences in the sensations. Figure 16.13 Dermatomes The surface of the skin can be divided into topographic regions that relate to the location of sensory endings in the skin based on the spinal nerve that contains those fibers. (credit: modification of work by Mikael Häggström) Other modalities of somatosensation can be tested using a few simple tools. The perception of pain can be tested using the broken end of the cotton-tipped applicator. The perception of vibratory stimuli can be testing using an oscillating tuning fork placed against prominent bone features such as the distal head of the ulna on the medial aspect of the elbow. When the tuning fork is still, the metal against the skin can be perceived as a cold stimulus. Using the cotton tip of the applicator, or even just a fingertip, the perception of tactile movement can be assessed as the stimulus is drawn across the skin for approximately 2–3 cm. The patient would be asked in what direction the stimulus is moving. All of these tests are repeated in distal and proximal locations and for different dermatomes to assess the spatial specificity of perception. The sense of position and motion, proprioception, is tested by moving the fingers or toes and asking the patient if they sense the movement. If the distal locations are not perceived, the test is repeated at increasingly proximal joints. The various stimuli used to test sensory input assess the function of the major ascending tracts of the spinal cord. The dorsal column pathway conveys fine touch, vibration, and proprioceptive information, whereas the spinothalamic pathway primarily conveys pain and temperature. Testing these stimuli provides information about whether these two major ascending pathways are functioning properly. Within the spinal cord, the two systems are segregated. The dorsal column information ascends ipsilateral to the source of the stimulus and decussates in the medulla, whereas the spinothalamic pathway decussates at the level of entry and ascends contralaterally. The differing sensory stimuli are segregated in the spinal cord so that the various subtests for these stimuli can distinguish which ascending pathway may be damaged in certain situations. Whereas the basic sensory stimuli are assessed in the subtests directed at each submodality of somatosensation, testing the ability to discriminate sensations is important. Pairing the light touch and pain subtests together makes it possible to compare the two submodalities at the same time, and therefore the two major ascending tracts at the same time. Mistaking painful stimuli for light touch, or vice versa, may point to errors in ascending projections, such as in a hemisection of the spinal cord that might come from a motor vehicle accident. Another issue of sensory discrimination is not distinguishing between different submodalities, but rather location. The two-point discrimination subtest highlights the density of sensory endings, and therefore receptive fields in the skin. The sensitivity to fine touch, which can give indications of the texture and detailed shape of objects, is highest in the fingertips. To assess the limit of this sensitivity, two-point discrimination is measured by simultaneously touching the skin in two locations, such as could be accomplished with a pair of forceps. Specialized calipers for precisely measuring the distance between points are also available. The patient is asked to indicate whether one or two stimuli are present while keeping their eyes closed. The examiner will switch between using the two points and a single point as the stimulus. Failure to recognize two points may be an indication of a dorsal column pathway deficit. Similar to two-point discrimination, but assessing laterality of perception, is double simultaneous stimulation. Two stimuli, such as the cotton tips of two applicators, are touched to the same position on both sides of the body. If one side is not perceived, this may indicate damage to the contralateral posterior parietal lobe. Because there is one of each pathway on either side of the spinal cord, they are not likely to interact. If none of the other subtests suggest particular deficits with the pathways, the deficit is likely to be in the cortex where conscious perception is based. The mental status exam contains subtests that assess other functions that are primarily localized to the parietal cortex, such as stereognosis and graphesthesia. A final subtest of sensory perception that concentrates on the sense of proprioception is known as the Romberg test. The patient is asked to stand straight with feet together. Once the patient has achieved their balance in that position, they are asked to close their eyes. Without visual feedback that the body is in a vertical orientation relative to the surrounding environment, the patient must rely on the proprioceptive stimuli of joint and muscle position, as well as information from the inner ear, to maintain balance. This test can indicate deficits in dorsal column pathway proprioception, as well as problems with proprioceptive projections to the cerebellum through the spinocerebellar tract. INTERACTIVE LINK Watch this video to see a quick demonstration of two-point discrimination. Touching a specialized caliper to the surface of the skin will measure the distance between two points that are perceived as distinct stimuli versus a single stimulus. The patient keeps their eyes closed while the examiner switches between using both points of the caliper or just one. The patient then must indicate whether one or two stimuli are in contact with the skin. Why is the distance between the caliper points closer on the fingertips as opposed to the palm of the hand? And what do you think the distance would be on the arm, or the shoulder? Muscle Strength and Voluntary Movement The skeletomotor system is largely based on the simple, two-cell projection from the precentral gyrus of the frontal lobe to the skeletal muscles. The corticospinal tract represents the neurons that send output from the primary motor cortex. These fibers travel through the deep white matter of the cerebrum, then through the midbrain and pons, into the medulla where most of them decussate, and finally through the spinal cord white matter in the lateral (crossed fibers) or anterior (uncrossed fibers) columns. These fibers synapse on motor neurons in the ventral horn. The ventral horn motor neurons then project to skeletal muscle and cause contraction. These two cells are termed the upper motor neuron (UMN) and the lower motor neuron (LMN). Voluntary movements require these two cells to be active. The motor exam tests the function of these neurons and the muscles they control. First, the muscles are inspected and palpated for signs of structural irregularities. Movement disorders may be the result of changes to the muscle tissue, such as scarring, and these possibilities need to be ruled out before testing function. Along with this inspection, muscle tone is assessed by moving the muscles through a passive range of motion. The arm is moved at the elbow and wrist, and the leg is moved at the knee and ankle. Skeletal muscle should have a resting tension representing a slight contraction of the fibers. The lack of muscle tone, known as hypotonicity or flaccidity, may indicate that the LMN is not conducting action potentials that will keep a basal level of acetylcholine in the neuromuscular junction. If muscle tone is present, muscle strength is tested by having the patient contract muscles against resistance. The examiner will ask the patient to lift the arm, for example, while the examiner is pushing down on it. This is done for both limbs, including shrugging the shoulders. Lateral differences in strength—being able to push against resistance with the right arm but not the left—would indicate a deficit in one corticospinal tract versus the other. An overall loss of strength, without laterality, could indicate a global problem with the motor system. Diseases that result in UMN lesions include cerebral palsy or MS, or it may be the result of a stroke. A sign of UMN lesion is a negative result in the subtest for pronator drift. The patient is asked to extend both arms in front of the body with the palms facing up. While keeping the eyes closed, if the patient unconsciously allows one or the other arm to slowly relax, toward the pronated position, this could indicate a failure of the motor system to maintain the supinated position. Reflexes Reflexes combine the spinal sensory and motor components with a sensory input that directly generates a motor response. The reflexes that are tested in the neurological exam are classified into two groups. A deep tendon reflex is commonly known as a stretch reflex, and is elicited by a strong tap to a tendon, such as in the knee-jerk reflex. A superficial reflex is elicited through gentle stimulation of the skin and causes contraction of the associated muscles. For the arm, the common reflexes to test are of the biceps, brachioradialis, triceps, and flexors for the digits. For the leg, the knee-jerk reflex of the quadriceps is common, as is the ankle reflex for the gastrocnemius and soleus. The tendon at the insertion for each of these muscles is struck with a rubber mallet. The muscle is quickly stretched, resulting in activation of the muscle spindle that sends a signal into the spinal cord through the dorsal root. The fiber synapses directly on the ventral horn motor neuron that activates the muscle, causing contraction. The reflexes are physiologically useful for stability. If a muscle is stretched, it reflexively contracts to return the muscle to compensate for the change in length. In the context of the neurological exam, reflexes indicate that the LMN is functioning properly. The most common superficial reflex in the neurological exam is the plantar reflex that tests for the Babinski sign on the basis of the extension or flexion of the toes at the plantar surface of the foot. The plantar reflex is commonly tested in newborn infants to establish the presence of neuromuscular function. To elicit this reflex, an examiner brushes a stimulus, usually the examiner’s fingertip, along the plantar surface of the infant’s foot. An infant would present a positive Babinski sign, meaning the foot dorsiflexes and the toes extend and splay out. As a person learns to walk, the plantar reflex changes to cause curling of the toes and a moderate plantar flexion. If superficial stimulation of the sole of the foot caused extension of the foot, keeping one’s balance would be harder. The descending input of the corticospinal tract modifies the response of the plantar reflex, meaning that a negative Babinski sign is the expected response in testing the reflex. Other superficial reflexes are not commonly tested, though a series of abdominal reflexes can target function in the lower thoracic spinal segments. INTERACTIVE LINK Watch this video to see how to test reflexes in the abdomen. Testing reflexes of the trunk is not commonly performed in the neurological exam, but if findings suggest a problem with the thoracic segments of the spinal cord, a series of superficial reflexes of the abdomen can localize function to those segments. If contraction is not observed when the skin lateral to the umbilicus (belly button) is stimulated, what level of the spinal cord may be damaged? Comparison of Upper and Lower Motor Neuron Damage Many of the tests of motor function can indicate differences that will address whether damage to the motor system is in the upper or lower motor neurons. Signs that suggest a UMN lesion include muscle weakness, strong deep tendon reflexes, decreased control of movement or slowness, pronator drift, a positive Babinski sign, spasticity, and the clasp-knife response. Spasticity is an excess contraction in resistance to stretch. It can result in hyperflexia, which is when joints are overly flexed. The clasp-knife response occurs when the patient initially resists movement, but then releases, and the joint will quickly flex like a pocket knife closing. A lesion on the LMN would result in paralysis, or at least partial loss of voluntary muscle control, which is known as paresis. The paralysis observed in LMN diseases is referred to as flaccid paralysis, referring to a complete or partial loss of muscle tone, in contrast to the loss of control in UMN lesions in which tone is retained and spasticity is exhibited. Other signs of an LMN lesion are fibrillation, fasciculation, and compromised or lost reflexes resulting from the denervation of the muscle fibers. DISORDERS OF THE... Spinal Cord In certain situations, such as a motorcycle accident, only half of the spinal cord may be damaged in what is known as a hemisection. Forceful trauma to the trunk may cause ribs or vertebrae to fracture, and debris can crush or section through part of the spinal cord. The full section of a spinal cord would result in paraplegia, or loss of voluntary motor control of the lower body, as well as loss of sensations from that point down. A hemisection, however, will leave spinal cord tracts intact on one side. The resulting condition would be hemiplegia on the side of the trauma—one leg would be paralyzed. The sensory results are more complicated. The ascending tracts in the spinal cord are segregated between the dorsal column and spinothalamic pathways. This means that the sensory deficits will be based on the particular sensory information each pathway conveys. Sensory discrimination between touch and painful stimuli will illustrate the difference in how these pathways divide these functions. On the paralyzed leg, a patient will acknowledge painful stimuli, but not fine touch or proprioceptive sensations. On the functional leg, the opposite is true. The reason for this is that the dorsal column pathway ascends ipsilateral to the sensation, so it would be damaged the same way as the lateral corticospinal tract. The spinothalamic pathway decussates immediately upon entering the spinal cord and ascends contralateral to the source; it would therefore bypass the hemisection. The motor system can indicate the loss of input to the ventral horn in the lumbar enlargement where motor neurons to the leg are found, but motor function in the trunk is less clear. The left and right anterior corticospinal tracts are directly adjacent to each other. The likelihood of trauma to the spinal cord resulting in a hemisection that affects one anterior column, but not the other, is very unlikely. Either the axial musculature will not be affected at all, or there will be bilateral losses in the trunk. Sensory discrimination can pinpoint the level of damage in the spinal cord. Below the hemisection, pain stimuli will be perceived in the damaged side, but not fine touch. The opposite is true on the other side. The pain fibers on the side with motor function cross the midline in the spinal cord and ascend in the contralateral lateral column as far as the hemisection. The dorsal column will be intact ipsilateral to the source on the intact side and reach the brain for conscious perception. The trauma would be at the level just before sensory discrimination returns to normal, helping to pinpoint the trauma. Whereas imaging technology, like magnetic resonance imaging (MRI) or computed tomography (CT) scanning, could localize the injury as well, nothing more complicated than a cotton-tipped applicator can localize the damage. That may be all that is available on the scene when moving the victim requires crucial decisions be made. The Coordination and Gait Exams - Explain the relationship between the location of the cerebellum and its function in movement - Chart the major divisions of the cerebellum - List the major connections of the cerebellum - Describe the relationship of the cerebellum to axial and appendicular musculature - Explain the prevalent causes of cerebellar ataxia The role of the cerebellum is a subject of debate. There is an obvious connection to motor function based on the clinical implications of cerebellar damage. There is also strong evidence of the cerebellar role in procedural memory. The two are not incompatible; in fact, procedural memory is motor memory, such as learning to ride a bicycle. Significant work has been performed to describe the connections within the cerebellum that result in learning. A model for this learning is classical conditioning, as shown by the famous dogs from the physiologist Ivan Pavlov’s work. This classical conditioning, which can be related to motor learning, fits with the neural connections of the cerebellum. The cerebellum is 10 percent of the mass of the brain and has varied functions that all point to a role in the motor system. Location and Connections of the Cerebellum The cerebellum is located in apposition to the dorsal surface of the brain stem, centered on the pons. The name of the pons is derived from its connection to the cerebellum. The word means “bridge” and refers to the thick bundle of myelinated axons that form a bulge on its ventral surface. Those fibers are axons that project from the gray matter of the pons into the contralateral cerebellar cortex. These fibers make up the middle cerebellar peduncle (MCP) and are the major physical connection of the cerebellum to the brain stem (Figure 16.14). Two other white matter bundles connect the cerebellum to the other regions of the brain stem. The superior cerebellar peduncle (SCP) is the connection of the cerebellum to the midbrain and forebrain. The inferior cerebellar peduncle (ICP) is the connection to the medulla. Figure 16.14 Cerebellar Penduncles The connections to the cerebellum are the three cerebellar peduncles, which are close to each other. The ICP arises from the medulla—specifically from the inferior olive, which is visible as a bulge on the ventral surface of the brain stem. The MCP is the ventral surface of the pons. The SCP projects into the midbrain. These connections can also be broadly described by their functions. The ICP conveys sensory input to the cerebellum, partially from the spinocerebellar tract, but also through fibers of the inferior olive. The MCP is part of the cortico-ponto-cerebellar pathway that connects the cerebral cortex with the cerebellum and preferentially targets the lateral regions of the cerebellum. It includes a copy of the motor commands sent from the precentral gyrus through the corticospinal tract, arising from collateral branches that synapse in the gray matter of the pons, along with input from other regions such as the visual cortex. The SCP is the major output of the cerebellum, divided between the red nucleus in the midbrain and the thalamus, which will return cerebellar processing to the motor cortex. These connections describe a circuit that compares motor commands and sensory feedback to generate a new output. These comparisons make it possible to coordinate movements. If the cerebral cortex sends a motor command to initiate walking, that command is copied by the pons and sent into the cerebellum through the MCP. Sensory feedback in the form of proprioception from the spinal cord, as well as vestibular sensations from the inner ear, enters through the ICP. If you take a step and begin to slip on the floor because it is wet, the output from the cerebellum—through the SCP—can correct for that and keep you balanced and moving. The red nucleus sends new motor commands to the spinal cord through the rubrospinal tract. The cerebellum is divided into regions that are based on the particular functions and connections involved. The midline regions of the cerebellum, the vermis and flocculonodular lobe, are involved in comparing visual information, equilibrium, and proprioceptive feedback to maintain balance and coordinate movements such as walking, or gait, through the descending output of the red nucleus (Figure 16.15). The lateral hemispheres are primarily concerned with planning motor functions through frontal lobe inputs that are returned through the thalamic projections back to the premotor and motor cortices. Processing in the midline regions targets movements of the axial musculature, whereas the lateral regions target movements of the appendicular musculature. The vermis is referred to as the spinocerebellum because it primarily receives input from the dorsal columns and spinocerebellar pathways. The flocculonodular lobe is referred to as the vestibulocerebellum because of the vestibular projection into that region. Finally, the lateral cerebellum is referred to as the cerebrocerebellum, reflecting the significant input from the cerebral cortex through the cortico-ponto-cerebellar pathway. Figure 16.15 Major Regions of the Cerebellum The cerebellum can be divided into two basic regions: the midline and the hemispheres. The midline is composed of the vermis and the flocculonodular lobe, and the hemispheres are the lateral regions. Coordination and Alternating Movement Testing for cerebellar function is the basis of the coordination exam. The subtests target appendicular musculature, controlling the limbs, and axial musculature for posture and gait. The assessment of cerebellar function will depend on the normal functioning of other systems addressed in previous sections of the neurological exam. Motor control from the cerebrum, as well as sensory input from somatic, visual, and vestibular senses, are important to cerebellar function. The subtests that address appendicular musculature, and therefore the lateral regions of the cerebellum, begin with a check for tremor. The patient extends their arms in front of them and holds the position. The examiner watches for the presence of tremors that would not be present if the muscles are relaxed. By pushing down on the arms in this position, the examiner can check for the rebound response, which is when the arms are automatically brought back to the extended position. The extension of the arms is an ongoing motor process, and the tap or push on the arms presents a change in the proprioceptive feedback. The cerebellum compares the cerebral motor command with the proprioceptive feedback and adjusts the descending input to correct. The red nucleus would send an additional signal to the LMN for the arm to increase contraction momentarily to overcome the change and regain the original position. The check reflex depends on cerebellar input to keep increased contraction from continuing after the removal of resistance. The patient flexes the elbow against resistance from the examiner to extend the elbow. When the examiner releases the arm, the patient should be able to stop the increased contraction and keep the arm from moving. A similar response would be seen if you try to pick up a coffee mug that you believe to be full but turns out to be empty. Without checking the contraction, the mug would be thrown from the overexertion of the muscles expecting to lift a heavier object. Several subtests of the cerebellum assess the ability to alternate movements, or switch between muscle groups that may be antagonistic to each other. In the finger-to-nose test, the patient touches their finger to the examiner’s finger and then to their nose, and then back to the examiner’s finger, and back to the nose. The examiner moves the target finger to assess a range of movements. A similar test for the lower extremities has the patient touch their toe to a moving target, such as the examiner’s finger. Both of these tests involve flexion and extension around a joint—the elbow or the knee and the shoulder or hip—as well as movements of the wrist and ankle. The patient must switch between the opposing muscles, like the biceps and triceps brachii, to move their finger from the target to their nose. Coordinating these movements involves the motor cortex communicating with the cerebellum through the pons and feedback through the thalamus to plan the movements. Visual cortex information is also part of the processing that occurs in the cerebrocerebellum while it is involved in guiding movements of the finger or toe. Rapid, alternating movements are tested for the upper and lower extremities. The patient is asked to touch each finger to their thumb, or to pat the palm of one hand on the back of the other, and then flip that hand over and alternate back-and-forth. To test similar function in the lower extremities, the patient touches their heel to their shin near the knee and slides it down toward the ankle, and then back again, repetitively. Rapid, alternating movements are part of speech as well. A patient is asked to repeat the nonsense consonants “lah-kah-pah” to alternate movements of the tongue, lips, and palate. All of these rapid alternations require planning from the cerebrocerebellum to coordinate movement commands that control the coordination. Posture and Gait Gait can either be considered a separate part of the neurological exam or a subtest of the coordination exam that addresses walking and balance. Testing posture and gait addresses functions of the spinocerebellum and the vestibulocerebellum because both are part of these activities. A subtest called station begins with the patient standing in a normal position to check for the placement of the feet and balance. The patient is asked to hop on one foot to assess the ability to maintain balance and posture during movement. Though the station subtest appears to be similar to the Romberg test, the difference is that the patient’s eyes are open during station. The Romberg test has the patient stand still with the eyes closed. Any changes in posture would be the result of proprioceptive deficits, and the patient is able to recover when they open their eyes. Subtests of walking begin with having the patient walk normally for a distance away from the examiner, and then turn and return to the starting position. The examiner watches for abnormal placement of the feet and the movement of the arms relative to the movement. The patient is then asked to walk with a few different variations. Tandem gait is when the patient places the heel of one foot against the toe of the other foot and walks in a straight line in that manner. Walking only on the heels or only on the toes will test additional aspects of balance. Ataxia A movement disorder of the cerebellum is referred to as ataxia. It presents as a loss of coordination in voluntary movements. Ataxia can also refer to sensory deficits that cause balance problems, primarily in proprioception and equilibrium. When the problem is observed in movement, it is ascribed to cerebellar damage. Sensory and vestibular ataxia would likely also present with problems in gait and station. Ataxia is often the result of exposure to exogenous substances, focal lesions, or a genetic disorder. Focal lesions include strokes affecting the cerebellar arteries, tumors that may impinge on the cerebellum, trauma to the back of the head and neck, or MS. Alcohol intoxication or drugs such as ketamine cause ataxia, but it is often reversible. Mercury in fish can cause ataxia as well. Hereditary conditions can lead to degeneration of the cerebellum or spinal cord, as well as malformation of the brain, or the abnormal accumulation of copper seen in Wilson’s disease. INTERACTIVE LINK Watch this short video to see a test for station. Station refers to the position a person adopts when they are standing still. The examiner would look for issues with balance, which coordinates proprioceptive, vestibular, and visual information in the cerebellum. To test the ability of a subject to maintain balance, asking them to stand or hop on one foot can be more demanding. The examiner may also push the subject to see if they can maintain balance. An abnormal finding in the test of station is if the feet are placed far apart. Why would a wide stance suggest problems with cerebellar function? EVERYDAY CONNECTION The Field Sobriety Test The neurological exam has been described as a clinical tool throughout this chapter. It is also useful in other ways. A variation of the coordination exam is the Field Sobriety Test (FST) used to assess whether drivers are under the influence of alcohol. The cerebellum is crucial for coordinated movements such as keeping balance while walking, or moving appendicular musculature on the basis of proprioceptive feedback. The cerebellum is also very sensitive to ethanol, the particular type of alcohol found in beer, wine, and liquor. Walking in a straight line involves comparing the motor command from the primary motor cortex to the proprioceptive and vestibular sensory feedback, as well as following the visual guide of the white line on the side of the road. When the cerebellum is compromised by alcohol, the cerebellum cannot coordinate these movements effectively, and maintaining balance becomes difficult. Another common aspect of the FST is to have the driver extend their arms out wide and touch their fingertip to their nose, usually with their eyes closed. The point of this is to remove the visual feedback for the movement and force the driver to rely just on proprioceptive information about the movement and position of their fingertip relative to their nose. With eyes open, the corrections to the movement of the arm might be so small as to be hard to see, but proprioceptive feedback is not as immediate and broader movements of the arm will probably be needed, particularly if the cerebellum is affected by alcohol. Reciting the alphabet backwards is not always a component of the FST, but its relationship to neurological function is interesting. There is a cognitive aspect to remembering how the alphabet goes and how to recite it backwards. That is actually a variation of the mental status subtest of repeating the months backwards. However, the cerebellum is important because speech production is a coordinated activity. The speech rapid alternating movement subtest is specifically using the consonant changes of “lah-kah-pah” to assess coordinated movements of the lips, tongue, pharynx, and palate. But the entire alphabet, especially in the nonrehearsed backwards order, pushes this type of coordinated movement quite far. It is related to the reason that speech becomes slurred when a person is intoxicated. Key Terms - accommodation - in vision, a change in the ability of the eye to focus on objects at different distances - accommodation–convergence reflex - coordination of somatic control of the medial rectus muscles of either eye with the parasympathetic control of the ciliary bodies to maintain focus while the eyes converge on visual stimuli near to the face - anterograde amnesia - inability to form new memories from a particular time forward - aphasia - loss of language function - ataxia - movement disorder related to damage of the cerebellum characterized by loss of coordination in voluntary movements - Babinski sign - dorsiflexion of the foot with extension and splaying of the toes in response to the plantar reflex, normally suppressed by corticospinal input - cerebrocerebellum - lateral regions of the cerebellum; named for the significant input from the cerebral cortex - check reflex - response to a release in resistance so that the contractions stop, or check, movement - clasp-knife response - sign of UMN disease when a patient initially resists passive movement of a muscle but will quickly release to a lower state of resistance - conduction aphasia - loss of language function related to connecting the understanding of speech with the production of speech, without either specific function being lost - conductive hearing - hearing dependent on the conduction of vibrations of the tympanic membrane through the ossicles of the middle ear - conjugate gaze - coordinated movement of the two eyes simultaneously in the same direction - convergence - in vision, the movement of the eyes so that they are both pointed at the same point in space, which increases for stimuli that are closer to the subject - coordination exam - major section of the neurological exam that assesses complex, coordinated motor functions of the cerebellum and associated motor pathways - cortico-ponto-cerebellar pathway - projection from the cerebral cortex to the cerebellum by way of the gray matter of the pons - cranial nerve exam - major section of the neurological exam that assesses sensory and motor functions of the cranial nerves and their associated central and peripheral structures - cytoarchitecture - study of a tissue based on the structure and organization of its cellular components; related to the broader term, histology - deep tendon reflex - another term for stretch reflex, based on the elicitation through deep stimulation of the tendon at the insertion - diplopia - double vision resulting from a failure in conjugate gaze - edema - fluid accumulation in tissue; often associated with circulatory deficits - embolus - obstruction in a blood vessel such as a blood clot, fatty mass, air bubble, or other foreign matter that interrupts the flow of blood to an organ or some part of the body - episodic memory - memory of specific events in an autobiographical sense - expressive aphasia - loss of the ability to produce language; usually associated with damage to Broca’s area in the frontal lobe - extrinsic muscles of the tongue - muscles that are connected to other structures, such as the hyoid bone or the mandible, and control the position of the tongue - fasciculation - small muscle twitch as a result of spontaneous activity from an LMN - fauces - opening from the oral cavity into the pharynx - fibrillation - in motor responses, a spontaneous muscle action potential that occurs in the absence of neuromuscular input, resulting from LMN lesions - flaccid paralysis - loss of voluntary muscle control and muscle tone, as the result of LMN disease - flaccidity - presentation of a loss of muscle tone, observed as floppy limbs or a lack of resistance to passive movement - flocculonodular lobe - lobe of the cerebellum that receives input from the vestibular system to help with balance and posture - gait - rhythmic pattern of alternating movements of the lower limbs during locomotion - gait exam - major section of the neurological exam that assesses the cerebellum and descending pathways in the spinal cord through the coordinated motor functions of walking; a portion of the coordination exam - gnosis - in a neurological exam, intuitive experiential knowledge tested by interacting with common objects or symbols - graphesthesia - perception of symbols, such as letters or numbers, traced in the palm of the hand - hemisection - cut through half of a structure, such as the spinal cord - hemorrhagic stroke - disruption of blood flow to the brain caused by bleeding within the cranial vault - hyperflexia - overly flexed joints - hypotonicity - low muscle tone, a sign of LMN disease - hypovolemia - decrease in blood volume - inferior cerebellar peduncle (ICP) - input to the cerebellum, largely from the inferior olive, that represents sensory feedback from the periphery - inferior olive - large nucleus in the medulla that receives input from sensory systems and projects into the cerebellar cortex - internuclear ophthalmoplegia - deficit of conjugate lateral gaze because the lateral rectus muscle of one eye does not contract resulting from damage to the abducens nerve or the MLF - intorsion - medial rotation of the eye around its axis - intrinsic muscles of the tongue - muscles that originate out of, and insert into, other tissues within the tongue and control the shape of the tongue - ischemic stroke - disruption of blood flow to the brain because blood cannot flow through blood vessels as a result of a blockage or narrowing of the vessel - jaw-jerk reflex - stretch reflex of the masseter muscle - localization of function - principle that circumscribed anatomical locations are responsible for specific functions in an organ system - medial longitudinal fasciculus (MLF) - fiber pathway that connects structures involved in the control of eye and head position, from the superior colliculus to the vestibular nuclei and cerebellum - mental status exam - major section of the neurological exam that assesses cognitive functions of the cerebrum - middle cerebellar peduncle (MCP) - large, white-matter bridge from the pons that constitutes the major input to the cerebellar cortex - motor exam - major section of the neurological exam that assesses motor functions of the spinal cord and spinal nerves - neurological exam - clinical assessment tool that can be used to quickly evaluate neurological function and determine if specific parts of the nervous system have been affected by damage or disease - paramedian pontine reticular formation (PPRF) - region of the brain stem adjacent to the motor nuclei for gaze control that coordinates rapid, conjugate eye movements - paresis - partial loss of, or impaired, voluntary muscle control - plantar reflex - superficial reflex initiated by gentle stimulation of the sole of the foot - praxis - in a neurological exam, the act of doing something using ready knowledge or skills in response to verbal instruction - procedural memory - memory of how to perform a specific task - pronator drift - sign of contralateral corticospinal lesion when the one arm will drift into a pronated position when held straight out with the palms facing upward - receptive aphasia - loss of the ability to understand received language, such as what is spoken to the subject or given in written form - red nucleus - nucleus in the midbrain that receives output from the cerebellum and projects onto the spinal cord in the rubrospinal tract - retrograde amnesia - loss of memories before a particular event - Rinne test - use of a tuning fork to test conductive hearing loss versus sensorineural hearing loss - Romberg test - test of equilibrium that requires the patient to maintain a straight, upright posture without visual feedback of position - rubrospinal tract - descending tract from the red nucleus of the midbrain that results in modification of ongoing motor programs - saccade - small, rapid movement of the eyes used to locate and direct the fovea onto visual stimuli - sensorineural hearing - hearing dependent on the transduction and propagation of auditory information through the neural components of the peripheral auditory structures - sensory exam - major section of the neurological exam that assesses sensory functions of the spinal cord and spinal nerves - short-term memory - capacity to retain information actively in the brain for a brief period of time - Snellen chart - standardized arrangement of letters in decreasing size presented to a subject at a distance of 20 feet to test visual acuity - spasticity - increased contraction of a muscle in response to resistance, often resulting in hyperflexia - spinocerebellar tract - ascending fibers that carry proprioceptive input to the cerebellum used in maintaining balance and coordinated movement - spinocerebellum - midline region of the cerebellum known as the vermis that receives proprioceptive input from the spinal cord - stereognosis - perception of common objects placed in the hand solely on the basis of manipulation of that object in the hand - stroke - (also, cerebrovascular accident (CVA)) loss of neurological function caused by an interruption of blood flow to a region of the central nervous system - superficial reflex - reflexive contraction initiated by gentle stimulation of the skin - superior cerebellar peduncle (SCP) - white-matter tract representing output of the cerebellum to the red nucleus of the midbrain - transient ischemic attack (TIA) - temporary disruption of blood flow to the brain in which symptoms occur rapidly but last only a short time - vermis - prominent ridge along the midline of the cerebellum that is referred to as the spinocerebellum - vestibulo-ocular reflex (VOR) - reflex based on connections between the vestibular system and the cranial nerves of eye movements that ensures that images are stabilized on the retina as the head and body move - vestibulocerebellum - flocculonodular lobe of the cerebellum named for the vestibular input from the eighth cranial nerve - Weber test - use of a tuning fork to test the laterality of hearing loss by placing it at several locations on the midline of the skull - Wernicke’s area - region at the posterior end of the lateral sulcus in which speech comprehension is localized Chapter Review 16.1 Overview of the Neurological Exam The neurological exam is a clinical assessment tool to determine the extent of function from the nervous system. It is divided into five major sections that each deal with a specific region of the CNS. The mental status exam is concerned with the cerebrum and assesses higher functions such as memory, language, and emotion. The cranial nerve exam tests the functions of all of the cranial nerves and, therefore, their connections to the CNS through the forebrain and brain stem. The sensory and motor exams assess those functions as they relate to the spinal cord, as well as the combination of the functions in spinal reflexes. The coordination exam targets cerebellar function in coordinated movements, including those functions associated with gait. Damage to and disease of the nervous system lead to loss of function. The location of the injury will correspond to the functional loss, as suggested by the principle of localization of function. The neurological exam provides the opportunity for a clinician to determine where damage has occurred on the basis of the function that is lost. Damage from acute injuries such as strokes may result in specific functions being lost, whereas broader effects in infection or developmental disorders may result in general losses across an entire section of the neurological exam. 16.4 The Sensory and Motor Exams The sensory and motor exams assess function related to the spinal cord and the nerves connected to it. Sensory functions are associated with the dorsal regions of the spinal cord, whereas motor function is associated with the ventral side. Localizing damage to the spinal cord is related to assessments of the peripheral projections mapped to dermatomes. Sensory tests address the various submodalities of the somatic senses: touch, temperature, vibration, pain, and proprioception. Results of the subtests can point to trauma in the spinal cord gray matter, white matter, or even in connections to the cerebral cortex. Motor tests focus on the function of the muscles and the connections of the descending motor pathway. Muscle tone and strength are tested for upper and lower extremities. Input to the muscles comes from the descending cortical input of upper motor neurons and the direct innervation of lower motor neurons. Reflexes can either be based on deep stimulation of tendons or superficial stimulation of the skin. The presence of reflexive contractions helps to differentiate motor disorders between the upper and lower motor neurons. The specific signs associated with motor disorders can establish the difference further, based on the type of paralysis, the state of muscle tone, and specific indicators such as pronator drift or the Babinski sign. 16.5 The Coordination and Gait Exams The cerebellum is an important part of motor function in the nervous system. It apparently plays a role in procedural learning, which would include motor skills such as riding a bike or throwing a football. The basis for these roles is likely to be tied into the role the cerebellum plays as a comparator for voluntary movement. The motor commands from the cerebral hemispheres travel along the corticospinal pathway, which passes through the pons. Collateral branches of these fibers synapse on neurons in the pons, which then project into the cerebellar cortex through the middle cerebellar peduncles. Ascending sensory feedback, entering through the inferior cerebellar peduncles, provides information about motor performance. The cerebellar cortex compares the command to the actual performance and can adjust the descending input to compensate for any mismatch. The output from deep cerebellar nuclei projects through the superior cerebellar peduncles to initiate descending signals from the red nucleus to the spinal cord. The primary role of the cerebellum in relation to the spinal cord is through the spinocerebellum; it controls posture and gait with significant input from the vestibular system. Deficits in cerebellar function result in ataxias, or a specific kind of movement disorder. The root cause of the ataxia may be the sensory input—either the proprioceptive input from the spinal cord or the equilibrium input from the vestibular system, or direct damage to the cerebellum by stroke, trauma, hereditary factors, or toxins. Interactive Link Questions Watch this video that provides a demonstration of the neurological exam—a series of tests that can be performed rapidly when a patient is initially brought into an emergency department. The exam can be repeated on a regular basis to keep a record of how and if neurological function changes over time. In what order were the sections of the neurological exam tested in this video, and which section seemed to be left out? 2.Watch this video for an introduction to the neurological exam. Studying the neurological exam can give insight into how structure and function in the nervous system are interdependent. This is a tool both in the clinic and in the classroom, but for different reasons. In the clinic, this is a powerful but simple tool to assess a patient’s neurological function. In the classroom, it is a different way to think about the nervous system. Though medical technology provides noninvasive imaging and real-time functional data, the presenter says these cannot replace the history at the core of the medical examination. What does history mean in the context of medical practice? 3.Read this article to learn about a young man who texts his fiancée in a panic as he finds that he is having trouble remembering things. At the hospital, a neurologist administers the mental status exam, which is mostly normal except for the three-word recall test. The young man could not recall them even 30 seconds after hearing them and repeating them back to the doctor. An undiscovered mass in the mediastinum region was found to be Hodgkin’s lymphoma, a type of cancer that affects the immune system and likely caused antibodies to attack the nervous system. The patient eventually regained his ability to remember, though the events in the hospital were always elusive. Considering that the effects on memory were temporary, but resulted in the loss of the specific events of the hospital stay, what regions of the brain were likely to have been affected by the antibodies and what type of memory does that represent? 4.Watch the video titled “The Man With Two Brains” to see the neuroscientist Michael Gazzaniga introduce a patient he has worked with for years who has had his corpus callosum cut, separating his two cerebral hemispheres. A few tests are run to demonstrate how this manifests in tests of cerebral function. Unlike normal people, this patient can perform two independent tasks at the same time because the lines of communication between the right and left sides of his brain have been removed. Whereas a person with an intact corpus callosum cannot overcome the dominance of one hemisphere over the other, this patient can. If the left cerebral hemisphere is dominant in the majority of people, why would right-handedness be most common? 5.Watch this short video to see an examination of the facial nerve using some simple tests. The facial nerve controls the muscles of facial expression. Severe deficits will be obvious in watching someone use those muscles for normal control. One side of the face might not move like the other side. But directed tests, especially for contraction against resistance, require a formal testing of the muscles. The muscles of the upper and lower face need to be tested. The strength test in this video involves the patient squeezing her eyes shut and the examiner trying to pry her eyes open. Why does the examiner ask her to try a second time? 6.Watch this video to see a quick demonstration of two-point discrimination. Touching a specialized caliper to the surface of the skin will measure the distance between two points that are perceived as distinct stimuli versus a single stimulus. The patient keeps their eyes closed while the examiner switches between using both points of the caliper or just one. The patient then must indicate whether one or two stimuli are in contact with the skin. Why is the distance between the caliper points closer on the fingertips as opposed to the palm of the hand? And what do you think the distance would be on the arm, or the shoulder? 7.Watch this video to see how to test reflexes in the abdomen. Testing reflexes of the trunk is not commonly performed in the neurological exam, but if findings suggest a problem with the thoracic segments of the spinal cord, a series of superficial reflexes of the abdomen can localize function to those segments. If contraction is not observed when the skin lateral to the umbilicus (belly button) is stimulated, what level of the spinal cord may be damaged? 8.Watch this short video to see a test for station. Station refers to the position a person adopts when they are standing still. The examiner would look for issues with balance, which coordinates proprioceptive, vestibular, and visual information in the cerebellum. To test the ability of a subject to maintain balance, asking them to stand or hop on one foot can be more demanding. The examiner may also push the subject to see if they can maintain balance. An abnormal finding in the test of station is if the feet are placed far apart. Why would a wide stance suggest problems with cerebellar function? Review Questions Which major section of the neurological exam is most likely to reveal damage to the cerebellum? - cranial nerve exam - mental status exam - sensory exam - coordination exam What function would most likely be affected by a restriction of a blood vessel in the cerebral cortex? - language - gait - facial expressions - knee-jerk reflex Which major section of the neurological exam includes subtests that are sometimes considered a separate set of tests concerned with walking? - mental status exam - cranial nerve exam - coordination exam - sensory exam Memory, emotional, language, and sensorimotor deficits together are most likely the result of what kind of damage? - stroke - developmental disorder - whiplash - gunshot wound Where is language function localized in the majority of people? - cerebellum - right cerebral hemisphere - hippocampus - left cerebral hemisphere Which of the following could be elements of cytoarchitecture, as related to Brodmann’s microscopic studies of the cerebral cortex? - connections to the cerebellum - activation by visual stimuli - number of neurons per square millimeter - number of gyri or sulci Which of the following could be a multimodal integrative area? - primary visual cortex - premotor cortex - hippocampus - Wernicke’s area Which is an example of episodic memory? - how to bake a cake - your last birthday party - how old you are - needing to wear an oven mitt to take a cake out of the oven Which type of aphasia is more like hearing a foreign language spoken? - receptive aphasia - expressive aphasia - conductive aphasia - Broca’s aphasia What region of the cerebral cortex is associated with understanding language, both from another person and the language a person generates himself or herself? - medial temporal lobe - ventromedial prefrontal cortex - superior temporal gyrus - postcentral gyrus Without olfactory sensation to complement gustatory stimuli, food will taste bland unless it is seasoned with which substance? - salt - thyme - garlic - olive oil Which of the following cranial nerves is not part of the VOR? - optic - oculomotor - abducens - vestibulocochlear Which nerve is responsible for controlling the muscles that result in the gag reflex? - trigeminal - facial - glossopharyngeal - vagus Which nerve is responsible for taste, as well as salivation, in the anterior oral cavity? - facial - glossopharyngeal - vagus - hypoglossal Which of the following nerves controls movements of the neck? - oculomotor - vestibulocochlear - spinal accessory - hypoglossal Which of the following is not part of the corticospinal pathway? - cerebellar deep white matter - midbrain - medulla - lateral column Which subtest is directed at proprioceptive sensation? - two-point discrimination - tactile movement - vibration - Romberg test What term describes the inability to lift the arm above the level of the shoulder? - paralysis - paresis - fasciculation - fibrillation Which type of reflex is the jaw-jerk reflex that is part of the cranial nerve exam for the vestibulocochlear nerve? - visceral reflex - withdrawal reflex - stretch reflex - superficial reflex Which of the following is a feature of both somatic and visceral senses? - requires cerebral input - causes skeletal muscle contraction - projects to a ganglion near the target effector - involves an axon in the ventral nerve root Which white matter structure carries information from the cerebral cortex to the cerebellum? - cerebral peduncle - superior cerebellar peduncle - middle cerebellar peduncle - inferior cerebellar peduncle Which region of the cerebellum receives proprioceptive input from the spinal cord? - vermis - left hemisphere - flocculonodular lobe - right hemisphere Which of the following tests cerebellar function related to gait? - toe-to-finger - station - lah-kah-pah - finger-to-nose Which of the following is not a cause of cerebellar ataxia? - mercury from fish - drinking alcohol - antibiotics - hereditary degeneration of the cerebellum Which of the following functions cannot be attributed to the cerebellum? - comparing motor commands and sensory feedback - associating sensory stimuli with learned behavior - coordinating complex movements - processing visual information Critical Thinking Questions Why is a rapid assessment of neurological function important in an emergency situation? 35.How is the diagnostic category of TIA different from a stroke? 36.A patient’s performance of the majority of the mental status exam subtests is in line with the expected norms, but the patient cannot repeat a string of numbers given by the examiner. What is a likely explanation? 37.A patient responds to the question “What is your name?” with a look of incomprehension. Which of the two major language areas is most likely affected and what is the name for that type of aphasia? 38.As a person ages, their ability to focus on near objects (accommodation) changes. If a person is already myopic (near-sighted), why would corrective lenses not be necessary to read a book or computer screen? 39.When a patient flexes their neck, the head tips to the right side. Also, their tongue sticks out slightly to the left when they try to stick it straight out. Where is the damage to the brain stem most likely located? 40.The location of somatosensation is based on the topographical map of sensory innervation. What does this mean? 41.Why are upper motor neuron lesions characterized by “spastic paralysis”? 42.Learning to ride a bike is a motor function dependent on the cerebellum. Why are the different regions of the cerebellum involved in this complex motor learning? 43.Alcohol intoxication can produce slurred speech. How is this related to cerebellar function?	oercommons	2025-03-18T00:36:12.209281	07/23/2019	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/56379/overview", "title": "Anatomy and Physiology, Regulation, Integration, and Control, The Neurological Exam", "author": null }
https://oercommons.org/courseware/lesson/58774/overview	Fluid, Electrolyte, and Acid-Base Balance Introduction Figure 26.1 Venus Williams Perspiring on the Tennis Court The body has critically important mechanisms for balancing the intake and output of bodily fluids. An athlete must continuously replace the water and electrolytes lost in sweat. (credit: “Edwin Martinez1”/Wikimedia Commons) CHAPTER OBJECTIVES After studying this chapter, you will be able to: - Identify the body’s main fluid compartments - Define plasma osmolality and identify two ways in which plasma osmolality is maintained - Identify the six ions most important to the function of the body - Define buffer and discuss the role of buffers in the body - Explain why bicarbonate must be conserved rather than reabsorbed in the kidney - Identify the normal range of blood pH and name the conditions where one has a blood pH that is either too high or too low Homeostasis, or the maintenance of constant conditions in the body, is a fundamental property of all living things. In the human body, the substances that participate in chemical reactions must remain within narrows ranges of concentration. Too much or too little of a single substance can disrupt your bodily functions. Because metabolism relies on reactions that are all interconnected, any disruption might affect multiple organs or even organ systems. Water is the most ubiquitous substance in the chemical reactions of life. The interactions of various aqueous solutions—solutions in which water is the solvent—are continuously monitored and adjusted by a large suite of interconnected feedback systems in your body. Understanding the ways in which the body maintains these critical balances is key to understanding good health. Body Fluids and Fluid Compartments - Explain the importance of water in the body - Contrast the composition of the intracellular fluid with that of the extracellular fluid - Explain the importance of protein channels in the movement of solutes - Identify the causes and symptoms of edema The chemical reactions of life take place in aqueous solutions. The dissolved substances in a solution are called solutes. In the human body, solutes vary in different parts of the body, but may include proteins—including those that transport lipids, carbohydrates, and, very importantly, electrolytes. Often in medicine, a mineral dissociated from a salt that carries an electrical charge (an ion) is called and electrolyte. For instance, sodium ions (Na+) and chloride ions (Cl-) are often referred to as electrolytes. In the body, water moves through semi-permeable membranes of cells and from one compartment of the body to another by a process called osmosis. Osmosis is basically the diffusion of water from regions of higher concentration to regions of lower concentration, along an osmotic gradient across a semi-permeable membrane. As a result, water will move into and out of cells and tissues, depending on the relative concentrations of the water and solutes found there. An appropriate balance of solutes inside and outside of cells must be maintained to ensure normal function. Body Water Content Human beings are mostly water, ranging from about 75 percent of body mass in infants to about 50–60 percent in adult men and women, to as low as 45 percent in old age. The percent of body water changes with development, because the proportions of the body given over to each organ and to muscles, fat, bone, and other tissues change from infancy to adulthood (Figure 26.2). Your brain and kidneys have the highest proportions of water, which composes 80–85 percent of their masses. In contrast, teeth have the lowest proportion of water, at 8–10 percent. Figure 26.2 Water Content of the Body’s Organs and Tissues Water content varies in different body organs and tissues, from as little as 8 percent in the teeth to as much as 85 percent in the brain. Fluid Compartments Body fluids can be discussed in terms of their specific fluid compartment, a location that is largely separate from another compartment by some form of a physical barrier. The intracellular fluid (ICF) compartment is the system that includes all fluid enclosed in cells by their plasma membranes. Extracellular fluid (ECF) surrounds all cells in the body. Extracellular fluid has two primary constituents: the fluid component of the blood (called plasma) and the interstitial fluid (IF) that surrounds all cells not in the blood (Figure 26.3). Figure 26.3 Fluid Compartments in the Human Body The intracellular fluid (ICF) is the fluid within cells. The interstitial fluid (IF) is part of the extracellular fluid (ECF) between the cells. Blood plasma is the second part of the ECF. Materials travel between cells and the plasma in capillaries through the IF. Intracellular Fluid The ICF lies within cells and is the principal component of the cytosol/cytoplasm. The ICF makes up about 60 percent of the total water in the human body, and in an average-size adult male, the ICF accounts for about 25 liters (seven gallons) of fluid (Figure 26.4). This fluid volume tends to be very stable, because the amount of water in living cells is closely regulated. If the amount of water inside a cell falls to a value that is too low, the cytosol becomes too concentrated with solutes to carry on normal cellular activities; if too much water enters a cell, the cell may burst and be destroyed. Figure 26.4 A Pie Graph Showing the Proportion of Total Body Fluid in Each of the Body’s Fluid Compartments Most of the water in the body is intracellular fluid. The second largest volume is the interstitial fluid, which surrounds cells that are not blood cells. Extracellular Fluid The ECF accounts for the other one-third of the body’s water content. Approximately 20 percent of the ECF is found in plasma. Plasma travels through the body in blood vessels and transports a range of materials, including blood cells, proteins (including clotting factors and antibodies), electrolytes, nutrients, gases, and wastes. Gases, nutrients, and waste materials travel between capillaries and cells through the IF. Cells are separated from the IF by a selectively permeable cell membrane that helps regulate the passage of materials between the IF and the interior of the cell. The body has other water-based ECF. These include the cerebrospinal fluid that bathes the brain and spinal cord, lymph, the synovial fluid in joints, the pleural fluid in the pleural cavities, the pericardial fluid in the cardiac sac, the peritoneal fluid in the peritoneal cavity, and the aqueous humor of the eye. Because these fluids are outside of cells, these fluids are also considered components of the ECF compartment. Composition of Body Fluids The compositions of the two components of the ECF—plasma and IF—are more similar to each other than either is to the ICF (Figure 26.5). Blood plasma has high concentrations of sodium, chloride, bicarbonate, and protein. The IF has high concentrations of sodium, chloride, and bicarbonate, but a relatively lower concentration of protein. In contrast, the ICF has elevated amounts of potassium, phosphate, magnesium, and protein. Overall, the ICF contains high concentrations of potassium and phosphate (HPO2−4HPO42− Figure 26.5 The Concentrations of Different Elements in Key Bodily Fluids The graph shows the composition of the ICF, IF, and plasma. The compositions of plasma and IF are similar to one another but are quite different from the composition of the ICF. INTERACTIVE LINK Watch this video to learn more about body fluids, fluid compartments, and electrolytes. When blood volume decreases due to sweating, from what source is water taken in by the blood? Most body fluids are neutral in charge. Thus, cations, or positively charged ions, and anions, or negatively charged ions, are balanced in fluids. As seen in the previous graph, sodium (Na+) ions and chloride (Cl-) ions are concentrated in the ECF of the body, whereas potassium (K+) ions are concentrated inside cells. Although sodium and potassium can “leak” through “pores” into and out of cells, respectively, the high levels of potassium and low levels of sodium in the ICF are maintained by sodium-potassium pumps in the cell membranes. These pumps use the energy supplied by ATP to pump sodium out of the cell and potassium into the cell (Figure 26.6). Figure 26.6 The Sodium-Potassium Pump The sodium-potassium pump is powered by ATP to transfer sodium out of the cytoplasm and into the ECF. The pump also transfers potassium out of the ECF and into the cytoplasm. (credit: modification of work by Mariana Ruiz Villarreal) Fluid Movement between Compartments Hydrostatic pressure, the force exerted by a fluid against a wall, causes movement of fluid between compartments. The hydrostatic pressure of blood is the pressure exerted by blood against the walls of the blood vessels by the pumping action of the heart. In capillaries, hydrostatic pressure (also known as capillary blood pressure) is higher than the opposing “colloid osmotic pressure” in blood—a “constant” pressure primarily produced by circulating albumin—at the arteriolar end of the capillary (Figure 26.7). This pressure forces plasma and nutrients out of the capillaries and into surrounding tissues. Fluid and the cellular wastes in the tissues enter the capillaries at the venule end, where the hydrostatic pressure is less than the osmotic pressure in the vessel. Filtration pressure squeezes fluid from the plasma in the blood to the IF surrounding the tissue cells. The surplus fluid in the interstitial space that is not returned directly back to the capillaries is drained from tissues by the lymphatic system, and then re-enters the vascular system at the subclavian veins. Figure 26.7 Capillary Exchange Net filtration occurs near the arterial end of the capillary since capillary hydrostatic pressure (CHP) is greater than blood colloidal osmotic pressure (BCOP). There is no net movement of fluid near the midpoint of the capillary since CHP = BCOP. Net reabsorption occurs near the venous end of the capillary since BCOP is greater than CHP. INTERACTIVE LINK Watch this video to see an explanation of the dynamics of fluid in the body’s compartments. What happens in the tissue when capillary blood pressure is less than osmotic pressure? Hydrostatic pressure is especially important in governing the movement of water in the nephrons of the kidneys to ensure proper filtering of the blood to form urine. As hydrostatic pressure in the kidneys increases, the amount of water leaving the capillaries also increases, and more urine filtrate is formed. If hydrostatic pressure in the kidneys drops too low, as can happen in dehydration, the functions of the kidneys will be impaired, and less nitrogenous wastes will be removed from the bloodstream. Extreme dehydration can result in kidney failure. Fluid also moves between compartments along an osmotic gradient. Recall that an osmotic gradient is produced by the difference in concentration of all solutes on either side of a semi-permeable membrane. The magnitude of the osmotic gradient is proportional to the difference in the concentration of solutes on one side of the cell membrane to that on the other side. Water will move by osmosis from the side where its concentration is high (and the concentration of solute is low) to the side of the membrane where its concentration is low (and the concentration of solute is high). In the body, water moves by osmosis from plasma to the IF (and the reverse) and from the IF to the ICF (and the reverse). In the body, water moves constantly into and out of fluid compartments as conditions change in different parts of the body. For example, if you are sweating, you will lose water through your skin. Sweating depletes your tissues of water and increases the solute concentration in those tissues. As this happens, water diffuses from your blood into sweat glands and surrounding skin tissues that have become dehydrated because of the osmotic gradient. Additionally, as water leaves the blood, it is replaced by the water in other tissues throughout your body that are not dehydrated. If this continues, dehydration spreads throughout the body. When a dehydrated person drinks water and rehydrates, the water is redistributed by the same gradient, but in the opposite direction, replenishing water in all of the tissues. Solute Movement between Compartments The movement of some solutes between compartments is active, which consumes energy and is an active transport process, whereas the movement of other solutes is passive, which does not require energy. Active transport allows cells to move a specific substance against its concentration gradient through a membrane protein, requiring energy in the form of ATP. For example, the sodium-potassium pump employs active transport to pump sodium out of cells and potassium into cells, with both substances moving against their concentration gradients. Passive transport of a molecule or ion depends on its ability to pass through the membrane, as well as the existence of a concentration gradient that allows the molecules to diffuse from an area of higher concentration to an area of lower concentration. Some molecules, like gases, lipids, and water itself (which also utilizes water channels in the membrane called aquaporins), slip fairly easily through the cell membrane; others, including polar molecules like glucose, amino acids, and ions do not. Some of these molecules enter and leave cells using facilitated transport, whereby the molecules move down a concentration gradient through specific protein channels in the membrane. This process does not require energy. For example, glucose is transferred into cells by glucose transporters that use facilitated transport (Figure 26.8). Figure 26.8 Facilitated Diffusion Glucose molecules use facilitated diffusion to move down a concentration gradient through the carrier protein channels in the membrane. (credit: modification of work by Mariana Ruiz Villarreal) DISORDERS OF THE... Fluid Balance: Edema Edema is the accumulation of excess water in the tissues. It is most common in the soft tissues of the extremities. The physiological causes of edema include water leakage from blood capillaries. Edema is almost always caused by an underlying medical condition, by the use of certain therapeutic drugs, by pregnancy, by localized injury, or by an allergic reaction. In the limbs, the symptoms of edema include swelling of the subcutaneous tissues, an increase in the normal size of the limb, and stretched, tight skin. One quick way to check for subcutaneous edema localized in a limb is to press a finger into the suspected area. Edema is likely if the depression persists for several seconds after the finger is removed (which is called “pitting”). Pulmonary edema is excess fluid in the air sacs of the lungs, a common symptom of heart and/or kidney failure. People with pulmonary edema likely will experience difficulty breathing, and they may experience chest pain. Pulmonary edema can be life threatening, because it compromises gas exchange in the lungs, and anyone having symptoms should immediately seek medical care. In pulmonary edema resulting from heart failure, excessive leakage of water occurs because fluids get “backed up” in the pulmonary capillaries of the lungs, when the left ventricle of the heart is unable to pump sufficient blood into the systemic circulation. Because the left side of the heart is unable to pump out its normal volume of blood, the blood in the pulmonary circulation gets “backed up,” starting with the left atrium, then into the pulmonary veins, and then into pulmonary capillaries. The resulting increased hydrostatic pressure within pulmonary capillaries, as blood is still coming in from the pulmonary arteries, causes fluid to be pushed out of them and into lung tissues. Other causes of edema include damage to blood vessels and/or lymphatic vessels, or a decrease in osmotic pressure in chronic and severe liver disease, where the liver is unable to manufacture plasma proteins (Figure 26.9). A decrease in the normal levels of plasma proteins results in a decrease of colloid osmotic pressure (which counterbalances the hydrostatic pressure) in the capillaries. This process causes loss of water from the blood to the surrounding tissues, resulting in edema. Figure 26.9 Edema An allergic reaction can cause capillaries in the hand to leak excess fluid that accumulates in the tissues. (credit: Jane Whitney) Mild, transient edema of the feet and legs may be caused by sitting or standing in the same position for long periods of time, as in the work of a toll collector or a supermarket cashier. This is because deep veins in the lower limbs rely on skeletal muscle contractions to push on the veins and thus “pump” blood back to the heart. Otherwise, the venous blood pools in the lower limbs and can leak into surrounding tissues. Medications that can result in edema include vasodilators, calcium channel blockers used to treat hypertension, non-steroidal anti-inflammatory drugs, estrogen therapies, and some diabetes medications. Underlying medical conditions that can contribute to edema include congestive heart failure, kidney damage and kidney disease, disorders that affect the veins of the legs, and cirrhosis and other liver disorders. Therapy for edema usually focuses on elimination of the cause. Activities that can reduce the effects of the condition include appropriate exercises to keep the blood and lymph flowing through the affected areas. Other therapies include elevation of the affected part to assist drainage, massage and compression of the areas to move the fluid out of the tissues, and decreased salt intake to decrease sodium and water retention. Water Balance - Explain how water levels in the body influence the thirst cycle - Identify the main route by which water leaves the body - Describe the role of ADH and its effect on body water levels - Define dehydration and identify common causes of dehydration On a typical day, the average adult will take in about 2500 mL (almost 3 quarts) of aqueous fluids. Although most of the intake comes through the digestive tract, about 230 mL (8 ounces) per day is generated metabolically, in the last steps of aerobic respiration. Additionally, each day about the same volume (2500 mL) of water leaves the body by different routes; most of this lost water is removed as urine. The kidneys also can adjust blood volume though mechanisms that draw water out of the filtrate and urine. The kidneys can regulate water levels in the body; they conserve water if you are dehydrated, and they can make urine more dilute to expel excess water if necessary. Water is lost through the skin through evaporation from the skin surface without overt sweating and from air expelled from the lungs. This type of water loss is called insensible water loss because a person is usually unaware of it. Regulation of Water Intake Osmolality is the ratio of solutes in a solution to a volume of solvent in a solution. Plasma osmolality is thus the ratio of solutes to water in blood plasma. A person’s plasma osmolality value reflects his or her state of hydration. A healthy body maintains plasma osmolality within a narrow range, by employing several mechanisms that regulate both water intake and output. Drinking water is considered voluntary. So how is water intake regulated by the body? Consider someone who is experiencing dehydration, a net loss of water that results in insufficient water in blood and other tissues. The water that leaves the body, as exhaled air, sweat, or urine, is ultimately extracted from blood plasma. As the blood becomes more concentrated, the thirst response—a sequence of physiological processes—is triggered (Figure 26.10). Osmoreceptors are sensory receptors in the thirst center in the hypothalamus that monitor the concentration of solutes (osmolality) of the blood. If blood osmolality increases above its ideal value, the hypothalamus transmits signals that result in a conscious awareness of thirst. The person should (and normally does) respond by drinking water. The hypothalamus of a dehydrated person also releases antidiuretic hormone (ADH) through the posterior pituitary gland. ADH signals the kidneys to recover water from urine, effectively diluting the blood plasma. To conserve water, the hypothalamus of a dehydrated person also sends signals via the sympathetic nervous system to the salivary glands in the mouth. The signals result in a decrease in watery, serous output (and an increase in stickier, thicker mucus output). These changes in secretions result in a “dry mouth” and the sensation of thirst. Figure 26.10 A Flowchart Showing the Thirst Response The thirst response begins when osmoreceptors detect a decrease in water levels in the blood. Decreased blood volume resulting from water loss has two additional effects. First, baroreceptors, blood-pressure receptors in the arch of the aorta and the carotid arteries in the neck, detect a decrease in blood pressure that results from decreased blood volume. The heart is ultimately signaled to increase its rate and/or strength of contractions to compensate for the lowered blood pressure. Second, the kidneys have a renin-angiotensin hormonal system that increases the production of the active form of the hormone angiotensin II, which helps stimulate thirst, but also stimulates the release of the hormone aldosterone from the adrenal glands. Aldosterone increases the reabsorption of sodium in the distal tubules of the nephrons in the kidneys, and water follows this reabsorbed sodium back into the blood. If adequate fluids are not consumed, dehydration results and a person’s body contains too little water to function correctly. A person who repeatedly vomits or who has diarrhea may become dehydrated, and infants, because their body mass is so low, can become dangerously dehydrated very quickly. Endurance athletes such as distance runners often become dehydrated during long races. Dehydration can be a medical emergency, and a dehydrated person may lose consciousness, become comatose, or die, if his or her body is not rehydrated quickly. Regulation of Water Output Water loss from the body occurs predominantly through the renal system. A person produces an average of 1.5 liters (1.6 quarts) of urine per day. Although the volume of urine varies in response to hydration levels, there is a minimum volume of urine production required for proper bodily functions. The kidney excretes 100 to 1200 milliosmoles of solutes per day to rid the body of a variety of excess salts and other water-soluble chemical wastes, most notably creatinine, urea, and uric acid. Failure to produce the minimum volume of urine means that metabolic wastes cannot be effectively removed from the body, a situation that can impair organ function. The minimum level of urine production necessary to maintain normal function is about 0.47 liters (0.5 quarts) per day. The kidneys also must make adjustments in the event of ingestion of too much fluid. Diuresis, which is the production of urine in excess of normal levels, begins about 30 minutes after drinking a large quantity of fluid. Diuresis reaches a peak after about 1 hour, and normal urine production is reestablished after about 3 hours. Role of ADH Antidiuretic hormone (ADH), also known as vasopressin, controls the amount of water reabsorbed from the collecting ducts and tubules in the kidney. This hormone is produced in the hypothalamus and is delivered to the posterior pituitary for storage and release (Figure 26.11). When the osmoreceptors in the hypothalamus detect an increase in the concentration of blood plasma, the hypothalamus signals the release of ADH from the posterior pituitary into the blood. Figure 26.11 Antidiuretic Hormone (ADH) ADH is produced in the hypothalamus and released by the posterior pituitary gland. It causes the kidneys to retain water, constricts arterioles in the peripheral circulation, and affects some social behaviors in mammals. ADH has two major effects. It constricts the arterioles in the peripheral circulation, which reduces the flow of blood to the extremities and thereby increases the blood supply to the core of the body. ADH also causes the epithelial cells that line the renal collecting tubules to move water channel proteins, called aquaporins, from the interior of the cells to the apical surface, where these proteins are inserted into the cell membrane (Figure 26.12). The result is an increase in the water permeability of these cells and, thus, a large increase in water passage from the urine through the walls of the collecting tubules, leading to more reabsorption of water into the bloodstream. When the blood plasma becomes less concentrated and the level of ADH decreases, aquaporins are removed from collecting tubule cell membranes, and the passage of water out of urine and into the blood decreases. Figure 26.12 Aquaporins The binding of ADH to receptors on the cells of the collecting tubule results in aquaporins being inserted into the plasma membrane, shown in the lower cell. This dramatically increases the flow of water out of the tubule and into the bloodstream. A diuretic is a compound that increases urine output and therefore decreases water conservation by the body. Diuretics are used to treat hypertension, congestive heart failure, and fluid retention associated with menstruation. Alcohol acts as a diuretic by inhibiting the release of ADH. Additionally, caffeine, when consumed in high concentrations, acts as a diuretic. Electrolyte Balance - List the role of the six most important electrolytes in the body - Name the disorders associated with abnormally high and low levels of the six electrolytes - Identify the predominant extracellular anion - Describe the role of aldosterone on the level of water in the body The body contains a large variety of ions, or electrolytes, which perform a variety of functions. Some ions assist in the transmission of electrical impulses along cell membranes in neurons and muscles. Other ions help to stabilize protein structures in enzymes. Still others aid in releasing hormones from endocrine glands. All of the ions in plasma contribute to the osmotic balance that controls the movement of water between cells and their environment. Electrolytes in living systems include sodium, potassium, chloride, bicarbonate, calcium, phosphate, magnesium, copper, zinc, iron, manganese, molybdenum, copper, and chromium. In terms of body functioning, six electrolytes are most important: sodium, potassium, chloride, bicarbonate, calcium, and phosphate. Roles of Electrolytes These six ions aid in nerve excitability, endocrine secretion, membrane permeability, buffering body fluids, and controlling the movement of fluids between compartments. These ions enter the body through the digestive tract. More than 90 percent of the calcium and phosphate that enters the body is incorporated into bones and teeth, with bone serving as a mineral reserve for these ions. In the event that calcium and phosphate are needed for other functions, bone tissue can be broken down to supply the blood and other tissues with these minerals. Phosphate is a normal constituent of nucleic acids; hence, blood levels of phosphate will increase whenever nucleic acids are broken down. Excretion of ions occurs mainly through the kidneys, with lesser amounts lost in sweat and in feces. Excessive sweating may cause a significant loss, especially of sodium and chloride. Severe vomiting or diarrhea will cause a loss of chloride and bicarbonate ions. Adjustments in respiratory and renal functions allow the body to regulate the levels of these ions in the ECF. Table 26.1 lists the reference values for blood plasma, cerebrospinal fluid (CSF), and urine for the six ions addressed in this section. In a clinical setting, sodium, potassium, and chloride are typically analyzed in a routine urine sample. In contrast, calcium and phosphate analysis requires a collection of urine across a 24-hour period, because the output of these ions can vary considerably over the course of a day. Urine values reflect the rates of excretion of these ions. Bicarbonate is the one ion that is not normally excreted in urine; instead, it is conserved by the kidneys for use in the body’s buffering systems. Electrolyte and Ion Reference Values \| Name \| Chemical symbol \| Plasma \| CSF \| Urine \| \|---\|---\|---\|---\|---\| \| Sodium \| Na+ \| 136.00–146.00 (mM) \| 138.00–150.00 (mM) \| 40.00–220.00 (mM) \| \| Potassium \| K+ \| 3.50–5.00 (mM) \| 0.35–3.5 (mM) \| 25.00–125.00 (mM) \| \| Chloride \| Cl- \| 98.00–107.00 (mM) \| 118.00–132.00 (mM) \| 110.00–250.00 (mM) \| \| Bicarbonate \| HCO3- \| 22.00–29.00 (mM) \| ------ \| ------ \| \| Calcium \| Ca++ \| 2.15–2.55 (mmol/day) \| ------ \| Up to 7.49 (mmol/day) \| \| Phosphate \| HPO2−4HPO42− \| 0.81–1.45 (mmol/day) \| ------ \| 12.90–42.00 (mmol/day) \| Table 26.1 Sodium Sodium is the major cation of the extracellular fluid. It is responsible for one-half of the osmotic pressure gradient that exists between the interior of cells and their surrounding environment. People eating a typical Western diet, which is very high in NaCl, routinely take in 130 to 160 mmol/day of sodium, but humans require only 1 to 2 mmol/day. This excess sodium appears to be a major factor in hypertension (high blood pressure) in some people. Excretion of sodium is accomplished primarily by the kidneys. Sodium is freely filtered through the glomerular capillaries of the kidneys, and although much of the filtered sodium is reabsorbed in the proximal convoluted tubule, some remains in the filtrate and urine, and is normally excreted. Hyponatremia is a lower-than-normal concentration of sodium, usually associated with excess water accumulation in the body, which dilutes the sodium. An absolute loss of sodium may be due to a decreased intake of the ion coupled with its continual excretion in the urine. An abnormal loss of sodium from the body can result from several conditions, including excessive sweating, vomiting, or diarrhea; the use of diuretics; excessive production of urine, which can occur in diabetes; and acidosis, either metabolic acidosis or diabetic ketoacidosis. A relative decrease in blood sodium can occur because of an imbalance of sodium in one of the body’s other fluid compartments, like IF, or from a dilution of sodium due to water retention related to edema or congestive heart failure. At the cellular level, hyponatremia results in increased entry of water into cells by osmosis, because the concentration of solutes within the cell exceeds the concentration of solutes in the now-diluted ECF. The excess water causes swelling of the cells; the swelling of red blood cells—decreasing their oxygen-carrying efficiency and making them potentially too large to fit through capillaries—along with the swelling of neurons in the brain can result in brain damage or even death. Hypernatremia is an abnormal increase of blood sodium. It can result from water loss from the blood, resulting in the hemoconcentration of all blood constituents. Hormonal imbalances involving ADH and aldosterone may also result in higher-than-normal sodium values. Potassium Potassium is the major intracellular cation. It helps establish the resting membrane potential in neurons and muscle fibers after membrane depolarization and action potentials. In contrast to sodium, potassium has very little effect on osmotic pressure. The low levels of potassium in blood and CSF are due to the sodium-potassium pumps in cell membranes, which maintain the normal potassium concentration gradients between the ICF and ECF. The recommendation for daily intake/consumption of potassium is 4700 mg. Potassium is excreted, both actively and passively, through the renal tubules, especially the distal convoluted tubule and collecting ducts. Potassium participates in the exchange with sodium in the renal tubules under the influence of aldosterone, which also relies on basolateral sodium-potassium pumps. Hypokalemia is an abnormally low potassium blood level. Similar to the situation with hyponatremia, hypokalemia can occur because of either an absolute reduction of potassium in the body or a relative reduction of potassium in the blood due to the redistribution of potassium. An absolute loss of potassium can arise from decreased intake, frequently related to starvation. It can also come about from vomiting, diarrhea, or alkalosis. Some insulin-dependent diabetic patients experience a relative reduction of potassium in the blood from the redistribution of potassium. When insulin is administered and glucose is taken up by cells, potassium passes through the cell membrane along with glucose, decreasing the amount of potassium in the blood and IF, which can cause hyperpolarization of the cell membranes of neurons, reducing their responses to stimuli. Hyperkalemia, an elevated potassium blood level, also can impair the function of skeletal muscles, the nervous system, and the heart. Hyperkalemia can result from increased dietary intake of potassium. In such a situation, potassium from the blood ends up in the ECF in abnormally high concentrations. This can result in a partial depolarization (excitation) of the plasma membrane of skeletal muscle fibers, neurons, and cardiac cells of the heart, and can also lead to an inability of cells to repolarize. For the heart, this means that it won’t relax after a contraction, and will effectively “seize” and stop pumping blood, which is fatal within minutes. Because of such effects on the nervous system, a person with hyperkalemia may also exhibit mental confusion, numbness, and weakened respiratory muscles. Chloride Chloride is the predominant extracellular anion. Chloride is a major contributor to the osmotic pressure gradient between the ICF and ECF, and plays an important role in maintaining proper hydration. Chloride functions to balance cations in the ECF, maintaining the electrical neutrality of this fluid. The paths of secretion and reabsorption of chloride ions in the renal system follow the paths of sodium ions. Hypochloremia, or lower-than-normal blood chloride levels, can occur because of defective renal tubular absorption. Vomiting, diarrhea, and metabolic acidosis can also lead to hypochloremia. Hyperchloremia, or higher-than-normal blood chloride levels, can occur due to dehydration, excessive intake of dietary salt (NaCl) or swallowing of sea water, aspirin intoxication, congestive heart failure, and the hereditary, chronic lung disease, cystic fibrosis. In people who have cystic fibrosis, chloride levels in sweat are two to five times those of normal levels, and analysis of sweat is often used in the diagnosis of the disease. INTERACTIVE LINK Read this article for an explanation of the effect of seawater on humans. What effect does drinking seawater have on the body? Bicarbonate Bicarbonate is the second most abundant anion in the blood. Its principal function is to maintain your body’s acid-base balance by being part of buffer systems. This role will be discussed in a different section. Bicarbonate ions result from a chemical reaction that starts with carbon dioxide (CO2) and water, two molecules that are produced at the end of aerobic metabolism. Only a small amount of CO2 can be dissolved in body fluids. Thus, over 90 percent of the CO2 is converted into bicarbonate ions, HCO3–, through the following reactions: CO2 + H2O↔H2CO3↔HCO3- + H+CO2 + H2O↔H2CO3↔HCO3- + H+ The bidirectional arrows indicate that the reactions can go in either direction, depending on the concentrations of the reactants and products. Carbon dioxide is produced in large amounts in tissues that have a high metabolic rate. Carbon dioxide is converted into bicarbonate in the cytoplasm of red blood cells through the action of an enzyme called carbonic anhydrase. Bicarbonate is transported in the blood. Once in the lungs, the reactions reverse direction, and CO2 is regenerated from bicarbonate to be exhaled as metabolic waste. Calcium About two pounds of calcium in your body are bound up in bone, which provides hardness to the bone and serves as a mineral reserve for calcium and its salts for the rest of the tissues. Teeth also have a high concentration of calcium within them. A little more than one-half of blood calcium is bound to proteins, leaving the rest in its ionized form. Calcium ions, Ca2+, are necessary for muscle contraction, enzyme activity, and blood coagulation. In addition, calcium helps to stabilize cell membranes and is essential for the release of neurotransmitters from neurons and of hormones from endocrine glands. Calcium is absorbed through the intestines under the influence of activated vitamin D. A deficiency of vitamin D leads to a decrease in absorbed calcium and, eventually, a depletion of calcium stores from the skeletal system, potentially leading to rickets in children and osteomalacia in adults, contributing to osteoporosis. Hypocalcemia, or abnormally low calcium blood levels, is seen in hypoparathyroidism, which may follow the removal of the thyroid gland, because the four nodules of the parathyroid gland are embedded in it. Hypercalcemia, or abnormally high calcium blood levels, is seen in primary hyperparathyroidism. Some malignancies may also result in hypercalcemia. Phosphate Phosphate is present in the body in three ionic forms: H2PO4−H2PO4−, HPO2−4HPO42−, and PO3−4PO43−. The most common form is HPO2−4HPO42−. Bone and teeth bind up 85 percent of the body’s phosphate as part of calcium-phosphate salts. Phosphate is found in phospholipids, such as those that make up the cell membrane, and in ATP, nucleotides, and buffers. Hypophosphatemia, or abnormally low phosphate blood levels, occurs with heavy use of antacids, during alcohol withdrawal, and during malnourishment. In the face of phosphate depletion, the kidneys usually conserve phosphate, but during starvation, this conservation is impaired greatly. Hyperphosphatemia, or abnormally increased levels of phosphates in the blood, occurs if there is decreased renal function or in cases of acute lymphocytic leukemia. Additionally, because phosphate is a major constituent of the ICF, any significant destruction of cells can result in dumping of phosphate into the ECF. Regulation of Sodium and Potassium Sodium is reabsorbed from the renal filtrate, and potassium is excreted into the filtrate in the renal collecting tubule. The control of this exchange is governed principally by two hormones—aldosterone and angiotensin II. Aldosterone Recall that aldosterone increases the excretion of potassium and the reabsorption of sodium in the distal tubule. Aldosterone is released if blood levels of potassium increase, if blood levels of sodium severely decrease, or if blood pressure decreases. Its net effect is to conserve and increase water levels in the plasma by reducing the excretion of sodium, and thus water, from the kidneys. In a negative feedback loop, increased osmolality of the ECF (which follows aldosterone-stimulated sodium absorption) inhibits the release of the hormone (Figure 26.13). Figure 26.13 The Aldosterone Feedback Loop Aldosterone, which is released by the adrenal gland, facilitates reabsorption of Na+ and thus the reabsorption of water. Angiotensin II Angiotensin II causes vasoconstriction and an increase in systemic blood pressure. This action increases the glomerular filtration rate, resulting in more material filtered out of the glomerular capillaries and into Bowman’s capsule. Angiotensin II also signals an increase in the release of aldosterone from the adrenal cortex. In the distal convoluted tubules and collecting ducts of the kidneys, aldosterone stimulates the synthesis and activation of the sodium-potassium pump (Figure 26.14). Sodium passes from the filtrate, into and through the cells of the tubules and ducts, into the ECF and then into capillaries. Water follows the sodium due to osmosis. Thus, aldosterone causes an increase in blood sodium levels and blood volume. Aldosterone’s effect on potassium is the reverse of that of sodium; under its influence, excess potassium is pumped into the renal filtrate for excretion from the body. Figure 26.14 The Renin-Angiotensin System Angiotensin II stimulates the release of aldosterone from the adrenal cortex. Regulation of Calcium and Phosphate Calcium and phosphate are both regulated through the actions of three hormones: parathyroid hormone (PTH), dihydroxyvitamin D (calcitriol), and calcitonin. All three are released or synthesized in response to the blood levels of calcium. PTH is released from the parathyroid gland in response to a decrease in the concentration of blood calcium. The hormone activates osteoclasts to break down bone matrix and release inorganic calcium-phosphate salts. PTH also increases the gastrointestinal absorption of dietary calcium by converting vitamin D into dihydroxyvitamin D (calcitriol), an active form of vitamin D that intestinal epithelial cells require to absorb calcium. PTH raises blood calcium levels by inhibiting the loss of calcium through the kidneys. PTH also increases the loss of phosphate through the kidneys. Calcitonin is released from the thyroid gland in response to elevated blood levels of calcium. The hormone increases the activity of osteoblasts, which remove calcium from the blood and incorporate calcium into the bony matrix. Acid-Base Balance - Identify the most powerful buffer system in the body - Explain the way in which the respiratory system affects blood pH Proper physiological functioning depends on a very tight balance between the concentrations of acids and bases in the blood. Acid-balance balance is measured using the pH scale, as shown in Figure 26.15. A variety of buffering systems permits blood and other bodily fluids to maintain a narrow pH range, even in the face of perturbations. A buffer is a chemical system that prevents a radical change in fluid pH by dampening the change in hydrogen ion concentrations in the case of excess acid or base. Most commonly, the substance that absorbs the ions is either a weak acid, which takes up hydroxyl ions, or a weak base, which takes up hydrogen ions. Figure 26.15 The pH Scale This chart shows where many common substances fall on the pH scale. Buffer Systems in the Body The buffer systems in the human body are extremely efficient, and different systems work at different rates. It takes only seconds for the chemical buffers in the blood to make adjustments to pH. The respiratory tract can adjust the blood pH upward in minutes by exhaling CO2 from the body. The renal system can also adjust blood pH through the excretion of hydrogen ions (H+) and the conservation of bicarbonate, but this process takes hours to days to have an effect. The buffer systems functioning in blood plasma include plasma proteins, phosphate, and bicarbonate and carbonic acid buffers. The kidneys help control acid-base balance by excreting hydrogen ions and generating bicarbonate that helps maintain blood plasma pH within a normal range. Protein buffer systems work predominantly inside cells. Protein Buffers in Blood Plasma and Cells Nearly all proteins can function as buffers. Proteins are made up of amino acids, which contain positively charged amino groups and negatively charged carboxyl groups. The charged regions of these molecules can bind hydrogen and hydroxyl ions, and thus function as buffers. Buffering by proteins accounts for two-thirds of the buffering power of the blood and most of the buffering within cells. Hemoglobin as a Buffer Hemoglobin is the principal protein inside of red blood cells and accounts for one-third of the mass of the cell. During the conversion of CO2 into bicarbonate, hydrogen ions liberated in the reaction are buffered by hemoglobin, which is reduced by the dissociation of oxygen. This buffering helps maintain normal pH. The process is reversed in the pulmonary capillaries to re-form CO2, which then can diffuse into the air sacs to be exhaled into the atmosphere. This process is discussed in detail in the chapter on the respiratory system. Phosphate Buffer Phosphates are found in the blood in two forms: sodium dihydrogen phosphate (Na2H2PO4−Na2H2PO4−Na2HPO2-4Na2HPO42- Na2HPO2-4Na2HPO42- comes into contact with a strong acid, such as HCl, the base picks up a second hydrogen ion to form the weak acid Na2H2PO4−Na2H2PO4− and sodium chloride, NaCl. When Na2HPO24−Na2HPO42− (the weak acid) comes into contact with a strong base, such as sodium hydroxide (NaOH), the weak acid reverts back to the weak base and produces water. Acids and bases are still present, but they hold onto the ions. HCl + Na2HPO4→NaH2PO4 + NaClHCl + Na2HPO4→NaH2PO4 + NaCl (strong acid) + (weak base) → (weak acid) + (salt)(strong acid) + (weak base) → (weak acid) + (salt) NaOH + NaH2PO4→Na2HPO4 + H2ONaOH + NaH2PO4→Na2HPO4 + H2O (strong base) + (weak acid) → (weak base) + (water)(strong base) + (weak acid) → (weak base) + (water) Bicarbonate-Carbonic Acid Buffer The bicarbonate-carbonic acid buffer works in a fashion similar to phosphate buffers. The bicarbonate is regulated in the blood by sodium, as are the phosphate ions. When sodium bicarbonate (NaHCO3), comes into contact with a strong acid, such as HCl, carbonic acid (H2CO3), which is a weak acid, and NaCl are formed. When carbonic acid comes into contact with a strong base, such as NaOH, bicarbonate and water are formed. NaHCO3 + HCl → H2CO3+NaClNaHCO3 + HCl → H2CO3+NaCl (sodium bicarbonate) + (strong acid) → (weak acid) + (salt)(sodium bicarbonate) + (strong acid) → (weak acid) + (salt) H2CO3 + NaOH→HCO3- + H2OH2CO3 + NaOH→HCO3- + H2O (weak acid) + (strong base)→(bicarbonate) + (water)(weak acid) + (strong base)→(bicarbonate) + (water) As with the phosphate buffer, a weak acid or weak base captures the free ions, and a significant change in pH is prevented. Bicarbonate ions and carbonic acid are present in the blood in a 20:1 ratio if the blood pH is within the normal range. With 20 times more bicarbonate than carbonic acid, this capture system is most efficient at buffering changes that would make the blood more acidic. This is useful because most of the body’s metabolic wastes, such as lactic acid and ketones, are acids. Carbonic acid levels in the blood are controlled by the expiration of CO2 through the lungs. In red blood cells, carbonic anhydrase forces the dissociation of the acid, rendering the blood less acidic. Because of this acid dissociation, CO2 is exhaled (see equations above). The level of bicarbonate in the blood is controlled through the renal system, where bicarbonate ions in the renal filtrate are conserved and passed back into the blood. However, the bicarbonate buffer is the primary buffering system of the IF surrounding the cells in tissues throughout the body. Respiratory Regulation of Acid-Base Balance The respiratory system contributes to the balance of acids and bases in the body by regulating the blood levels of carbonic acid (Figure 26.16). CO2 in the blood readily reacts with water to form carbonic acid, and the levels of CO2 and carbonic acid in the blood are in equilibrium. When the CO2 level in the blood rises (as it does when you hold your breath), the excess CO2 reacts with water to form additional carbonic acid, lowering blood pH. Increasing the rate and/or depth of respiration (which you might feel the “urge” to do after holding your breath) allows you to exhale more CO2. The loss of CO2 from the body reduces blood levels of carbonic acid and thereby adjusts the pH upward, toward normal levels. As you might have surmised, this process also works in the opposite direction. Excessive deep and rapid breathing (as in hyperventilation) rids the blood of CO2 and reduces the level of carbonic acid, making the blood too alkaline. This brief alkalosis can be remedied by rebreathing air that has been exhaled into a paper bag. Rebreathing exhaled air will rapidly bring blood pH down toward normal. Figure 26.16 Respiratory Regulation of Blood pH The respiratory system can reduce blood pH by removing CO2 from the blood. The chemical reactions that regulate the levels of CO2 and carbonic acid occur in the lungs when blood travels through the lung’s pulmonary capillaries. Minor adjustments in breathing are usually sufficient to adjust the pH of the blood by changing how much CO2 is exhaled. In fact, doubling the respiratory rate for less than 1 minute, removing “extra” CO2, would increase the blood pH by 0.2. This situation is common if you are exercising strenuously over a period of time. To keep up the necessary energy production, you would produce excess CO2 (and lactic acid if exercising beyond your aerobic threshold). In order to balance the increased acid production, the respiration rate goes up to remove the CO2. This helps to keep you from developing acidosis. The body regulates the respiratory rate by the use of chemoreceptors, which primarily use CO2 as a signal. Peripheral blood sensors are found in the walls of the aorta and carotid arteries. These sensors signal the brain to provide immediate adjustments to the respiratory rate if CO2 levels rise or fall. Yet other sensors are found in the brain itself. Changes in the pH of CSF affect the respiratory center in the medulla oblongata, which can directly modulate breathing rate to bring the pH back into the normal range. Hypercapnia, or abnormally elevated blood levels of CO2, occurs in any situation that impairs respiratory functions, including pneumonia and congestive heart failure. Reduced breathing (hypoventilation) due to drugs such as morphine, barbiturates, or ethanol (or even just holding one’s breath) can also result in hypercapnia. Hypocapnia, or abnormally low blood levels of CO2, occurs with any cause of hyperventilation that drives off the CO2, such as salicylate toxicity, elevated room temperatures, fever, or hysteria. Renal Regulation of Acid-Base Balance The renal regulation of the body’s acid-base balance addresses the metabolic component of the buffering system. Whereas the respiratory system (together with breathing centers in the brain) controls the blood levels of carbonic acid by controlling the exhalation of CO2, the renal system controls the blood levels of bicarbonate. A decrease of blood bicarbonate can result from the inhibition of carbonic anhydrase by certain diuretics or from excessive bicarbonate loss due to diarrhea. Blood bicarbonate levels are also typically lower in people who have Addison’s disease (chronic adrenal insufficiency), in which aldosterone levels are reduced, and in people who have renal damage, such as chronic nephritis. Finally, low bicarbonate blood levels can result from elevated levels of ketones (common in unmanaged diabetes mellitus), which bind bicarbonate in the filtrate and prevent its conservation. Bicarbonate ions, HCO3-, found in the filtrate, are essential to the bicarbonate buffer system, yet the cells of the tubule are not permeable to bicarbonate ions. The steps involved in supplying bicarbonate ions to the system are seen in Figure 26.17 and are summarized below: - Step 1: Sodium ions are reabsorbed from the filtrate in exchange for H+ by an antiport mechanism in the apical membranes of cells lining the renal tubule. - Step 2: The cells produce bicarbonate ions that can be shunted to peritubular capillaries. - Step 3: When CO2 is available, the reaction is driven to the formation of carbonic acid, which dissociates to form a bicarbonate ion and a hydrogen ion. - Step 4: The bicarbonate ion passes into the peritubular capillaries and returns to the blood. The hydrogen ion is secreted into the filtrate, where it can become part of new water molecules and be reabsorbed as such, or removed in the urine. Figure 26.17 Conservation of Bicarbonate in the Kidney Tubular cells are not permeable to bicarbonate; thus, bicarbonate is conserved rather than reabsorbed. Steps 1 and 2 of bicarbonate conservation are indicated. It is also possible that salts in the filtrate, such as sulfates, phosphates, or ammonia, will capture hydrogen ions. If this occurs, the hydrogen ions will not be available to combine with bicarbonate ions and produce CO2. In such cases, bicarbonate ions are not conserved from the filtrate to the blood, which will also contribute to a pH imbalance and acidosis. The hydrogen ions also compete with potassium to exchange with sodium in the renal tubules. If more potassium is present than normal, potassium, rather than the hydrogen ions, will be exchanged, and increased potassium enters the filtrate. When this occurs, fewer hydrogen ions in the filtrate participate in the conversion of bicarbonate into CO2 and less bicarbonate is conserved. If there is less potassium, more hydrogen ions enter the filtrate to be exchanged with sodium and more bicarbonate is conserved. Chloride ions are important in neutralizing positive ion charges in the body. If chloride is lost, the body uses bicarbonate ions in place of the lost chloride ions. Thus, lost chloride results in an increased reabsorption of bicarbonate by the renal system. DISORDERS OF THE... Acid-Base Balance: Ketoacidosis Diabetic acidosis, or ketoacidosis, occurs most frequently in people with poorly controlled diabetes mellitus. When certain tissues in the body cannot get adequate amounts of glucose, they depend on the breakdown of fatty acids for energy. When acetyl groups break off the fatty acid chains, the acetyl groups then non-enzymatically combine to form ketone bodies, acetoacetic acid, beta-hydroxybutyric acid, and acetone, all of which increase the acidity of the blood. In this condition, the brain isn’t supplied with enough of its fuel—glucose—to produce all of the ATP it requires to function. Ketoacidosis can be severe and, if not detected and treated properly, can lead to diabetic coma, which can be fatal. A common early symptom of ketoacidosis is deep, rapid breathing as the body attempts to drive off CO2 and compensate for the acidosis. Another common symptom is fruity-smelling breath, due to the exhalation of acetone. Other symptoms include dry skin and mouth, a flushed face, nausea, vomiting, and stomach pain. Treatment for diabetic coma is ingestion or injection of sugar; its prevention is the proper daily administration of insulin. A person who is diabetic and uses insulin can initiate ketoacidosis if a dose of insulin is missed. Among people with type 2 diabetes, those of Hispanic and African-American descent are more likely to go into ketoacidosis than those of other ethnic backgrounds, although the reason for this is unknown. Disorders of Acid-Base Balance - Identify the three blood variables considered when making a diagnosis of acidosis or alkalosis - Identify the source of compensation for blood pH problems of a respiratory origin - Identify the source of compensation for blood pH problems of a metabolic/renal origin Normal arterial blood pH is restricted to a very narrow range of 7.35 to 7.45. A person who has a blood pH below 7.35 is considered to be in acidosis (actually, “physiological acidosis,” because blood is not truly acidic until its pH drops below 7), and a continuous blood pH below 7.0 can be fatal. Acidosis has several symptoms, including headache and confusion, and the individual can become lethargic and easily fatigued (Figure 26.18). A person who has a blood pH above 7.45 is considered to be in alkalosis, and a pH above 7.8 is fatal. Some symptoms of alkalosis include cognitive impairment (which can progress to unconsciousness), tingling or numbness in the extremities, muscle twitching and spasm, and nausea and vomiting. Both acidosis and alkalosis can be caused by either metabolic or respiratory disorders. As discussed earlier in this chapter, the concentration of carbonic acid in the blood is dependent on the level of CO2 in the body and the amount of CO2 gas exhaled through the lungs. Thus, the respiratory contribution to acid-base balance is usually discussed in terms of CO2 (rather than of carbonic acid). Remember that a molecule of carbonic acid is lost for every molecule of CO2 exhaled, and a molecule of carbonic acid is formed for every molecule of CO2 retained. Figure 26.18 Symptoms of Acidosis and Alkalosis Symptoms of acidosis affect several organ systems. Both acidosis and alkalosis can be diagnosed using a blood test. Metabolic Acidosis: Primary Bicarbonate Deficiency Metabolic acidosis occurs when the blood is too acidic (pH below 7.35) due to too little bicarbonate, a condition called primary bicarbonate deficiency. At the normal pH of 7.40, the ratio of bicarbonate to carbonic acid buffer is 20:1. If a person’s blood pH drops below 7.35, then he or she is in metabolic acidosis. The most common cause of metabolic acidosis is the presence of organic acids or excessive ketones in the blood. Table 26.2 lists some other causes of metabolic acidosis. Common Causes of Metabolic Acidosis and Blood Metabolites \| Cause \| Metabolite \| \|---\|---\| \| Diarrhea \| Bicarbonate \| \| Uremia \| Phosphoric, sulfuric, and lactic acids \| \| Diabetic ketoacidosis \| Increased ketones \| \| Strenuous exercise \| Lactic acid \| \| Methanol \| Formic acid* \| \| Paraldehyde \| β-Hydroxybutyric acid* \| \| Isopropanol \| Propionic acid* \| \| Ethylene glycol \| Glycolic acid, and some oxalic and formic acids* \| \| Salicylate/aspirin \| Sulfasalicylic acid (SSA)* \| Table 26.2 *Acid metabolites from ingested chemical. The first three of the eight causes of metabolic acidosis listed are medical (or unusual physiological) conditions. Strenuous exercise can cause temporary metabolic acidosis due to the production of lactic acid. The last five causes result from the ingestion of specific substances. The active form of aspirin is its metabolite, sulfasalicylic acid. An overdose of aspirin causes acidosis due to the acidity of this metabolite. Metabolic acidosis can also result from uremia, which is the retention of urea and uric acid. Metabolic acidosis can also arise from diabetic ketoacidosis, wherein an excess of ketones is present in the blood. Other causes of metabolic acidosis are a decrease in the excretion of hydrogen ions, which inhibits the conservation of bicarbonate ions, and excessive loss of bicarbonate ions through the gastrointestinal tract due to diarrhea. Metabolic Alkalosis: Primary Bicarbonate Excess Metabolic alkalosis is the opposite of metabolic acidosis. It occurs when the blood is too alkaline (pH above 7.45) due to too much bicarbonate (called primary bicarbonate excess). A transient excess of bicarbonate in the blood can follow ingestion of excessive amounts of bicarbonate, citrate, or antacids for conditions such as stomach acid reflux—known as heartburn. Cushing’s disease, which is the chronic hypersecretion of adrenocorticotrophic hormone (ACTH) by the anterior pituitary gland, can cause chronic metabolic alkalosis. The oversecretion of ACTH results in elevated aldosterone levels and an increased loss of potassium by urinary excretion. Other causes of metabolic alkalosis include the loss of hydrochloric acid from the stomach through vomiting, potassium depletion due to the use of diuretics for hypertension, and the excessive use of laxatives. Respiratory Acidosis: Primary Carbonic Acid/CO2 Excess Respiratory acidosis occurs when the blood is overly acidic due to an excess of carbonic acid, resulting from too much CO2 in the blood. Respiratory acidosis can result from anything that interferes with respiration, such as pneumonia, emphysema, or congestive heart failure. Respiratory Alkalosis: Primary Carbonic Acid/CO2 Deficiency Respiratory alkalosis occurs when the blood is overly alkaline due to a deficiency in carbonic acid and CO2 levels in the blood. This condition usually occurs when too much CO2 is exhaled from the lungs, as occurs in hyperventilation, which is breathing that is deeper or more frequent than normal. An elevated respiratory rate leading to hyperventilation can be due to extreme emotional upset or fear, fever, infections, hypoxia, or abnormally high levels of catecholamines, such as epinephrine and norepinephrine. Surprisingly, aspirin overdose—salicylate toxicity—can result in respiratory alkalosis as the body tries to compensate for initial acidosis. INTERACTIVE LINK Watch this video to see a demonstration of the effect altitude has on blood pH. What effect does high altitude have on blood pH, and why? Compensation Mechanisms Various compensatory mechanisms exist to maintain blood pH within a narrow range, including buffers, respiration, and renal mechanisms. Although compensatory mechanisms usually work very well, when one of these mechanisms is not working properly (like kidney failure or respiratory disease), they have their limits. If the pH and bicarbonate to carbonic acid ratio are changed too drastically, the body may not be able to compensate. Moreover, extreme changes in pH can denature proteins. Extensive damage to proteins in this way can result in disruption of normal metabolic processes, serious tissue damage, and ultimately death. Respiratory Compensation Respiratory compensation for metabolic acidosis increases the respiratory rate to drive off CO2 and readjust the bicarbonate to carbonic acid ratio to the 20:1 level. This adjustment can occur within minutes. Respiratory compensation for metabolic alkalosis is not as adept as its compensation for acidosis. The normal response of the respiratory system to elevated pH is to increase the amount of CO2 in the blood by decreasing the respiratory rate to conserve CO2. There is a limit to the decrease in respiration, however, that the body can tolerate. Hence, the respiratory route is less efficient at compensating for metabolic alkalosis than for acidosis. Metabolic Compensation Metabolic and renal compensation for respiratory diseases that can create acidosis revolves around the conservation of bicarbonate ions. In cases of respiratory acidosis, the kidney increases the conservation of bicarbonate and secretion of H+through the exchange mechanism discussed earlier. These processes increase the concentration of bicarbonate in the blood, reestablishing the proper relative concentrations of bicarbonate and carbonic acid. In cases of respiratory alkalosis, the kidneys decrease the production of bicarbonate and reabsorb H+ from the tubular fluid. These processes can be limited by the exchange of potassium by the renal cells, which use a K+-H+ exchange mechanism (antiporter). Diagnosing Acidosis and Alkalosis Lab tests for pH, CO2 partial pressure (pCO2), and HCO3– can identify acidosis and alkalosis, indicating whether the imbalance is respiratory or metabolic, and the extent to which compensatory mechanisms are working. The blood pH value, as shown in Table 26.3, indicates whether the blood is in acidosis, the normal range, or alkalosis. The pCO2 and total HCO3– values aid in determining whether the condition is metabolic or respiratory, and whether the patient has been able to compensate for the problem. Table 26.3 lists the conditions and laboratory results that can be used to classify these conditions. Metabolic acid-base imbalances typically result from kidney disease, and the respiratory system usually responds to compensate. Types of Acidosis and Alkalosis \| pH \| pCO2 \| Total HCO3– \| \| \|---\|---\|---\|---\| \| Metabolic acidosis \| ↓ \| N, then ↓ \| ↓ \| \| Respiratory acidosis \| ↓ \| ↑ \| N, then ↑ \| \| Metabolic alkalosis \| ↑ \| N, then↑ \| ↑ \| \| Respiratory alkalosis \| ↑ \| ↓ \| N, then ↓ \| Table 26.3 Reference values (arterial): pH: 7.35–7.45; pCO2: male: 35–48 mm Hg, female: 32–45 mm Hg; total venous bicarbonate: 22–29 mM. N denotes normal; ↑ denotes a rising or increased value; and ↓ denotes a falling or decreased value. Metabolic acidosis is problematic, as lower-than-normal amounts of bicarbonate are present in the blood. The pCO2 would be normal at first, but if compensation has occurred, it would decrease as the body reestablishes the proper ratio of bicarbonate and carbonic acid/CO2. Respiratory acidosis is problematic, as excess CO2 is present in the blood. Bicarbonate levels would be normal at first, but if compensation has occurred, they would increase in an attempt to reestablish the proper ratio of bicarbonate and carbonic acid/CO2. Alkalosis is characterized by a higher-than-normal pH. Metabolic alkalosis is problematic, as elevated pH and excess bicarbonate are present. The pCO2 would again be normal at first, but if compensation has occurred, it would increase as the body attempts to reestablish the proper ratios of bicarbonate and carbonic acid/CO2. Respiratory alkalosis is problematic, as CO2 deficiency is present in the bloodstream. The bicarbonate concentration would be normal at first. When renal compensation occurs, however, the bicarbonate concentration in blood decreases as the kidneys attempt to reestablish the proper ratios of bicarbonate and carbonic acid/CO2 by eliminating more bicarbonate to bring the pH into the physiological range. Key Terms - antidiuretic hormone (ADH) - also known as vasopressin, a hormone that increases the volume of water reabsorbed from the collecting tubules of the kidney - dehydration - state of containing insufficient water in blood and other tissues - dihydroxyvitamin D - active form of vitamin D required by the intestinal epithelial cells for the absorption of calcium - diuresis - excess production of urine - extracellular fluid (ECF) - fluid exterior to cells; includes the interstitial fluid, blood plasma, and fluids found in other reservoirs in the body - fluid compartment - fluid inside all cells of the body constitutes a compartment system that is largely segregated from other systems - hydrostatic pressure - pressure exerted by a fluid against a wall, caused by its own weight or pumping force - hypercalcemia - abnormally increased blood levels of calcium - hypercapnia - abnormally elevated blood levels of CO2 - hyperchloremia - higher-than-normal blood chloride levels - hyperkalemia - higher-than-normal blood potassium levels - hypernatremia - abnormal increase in blood sodium levels - hyperphosphatemia - abnormally increased blood phosphate levels - hypocalcemia - abnormally low blood levels of calcium - hypocapnia - abnormally low blood levels of CO2 - hypochloremia - lower-than-normal blood chloride levels - hypokalemia - abnormally decreased blood levels of potassium - hyponatremia - lower-than-normal levels of sodium in the blood - hypophosphatemia - abnormally low blood phosphate levels - interstitial fluid (IF) - fluid in the small spaces between cells not contained within blood vessels - intracellular fluid (ICF) - fluid in the cytosol of cells - metabolic acidosis - condition wherein a deficiency of bicarbonate causes the blood to be overly acidic - metabolic alkalosis - condition wherein an excess of bicarbonate causes the blood to be overly alkaline - plasma osmolality - ratio of solutes to a volume of solvent in the plasma; plasma osmolality reflects a person’s state of hydration - respiratory acidosis - condition wherein an excess of carbonic acid or CO2 causes the blood to be overly acidic - respiratory alkalosis - condition wherein a deficiency of carbonic acid/CO2 levels causes the blood to be overly alkaline Chapter Review 26.1 Body Fluids and Fluid Compartments Your body is mostly water. Body fluids are aqueous solutions with differing concentrations of materials, called solutes. An appropriate balance of water and solute concentrations must be maintained to ensure cellular functions. If the cytosol becomes too concentrated due to water loss, cell functions deteriorate. If the cytosol becomes too dilute due to water intake by cells, cell membranes can be damaged, and the cell can burst. Hydrostatic pressure is the force exerted by a fluid against a wall and causes movement of fluid between compartments. Fluid can also move between compartments along an osmotic gradient. Active transport processes require ATP to move some solutes against their concentration gradients between compartments. Passive transport of a molecule or ion depends on its ability to pass easily through the membrane, as well as the existence of a high to low concentration gradient. 26.2 Water Balance Homeostasis requires that water intake and output be balanced. Most water intake comes through the digestive tract via liquids and food, but roughly 10 percent of water available to the body is generated at the end of aerobic respiration during cellular metabolism. Urine produced by the kidneys accounts for the largest amount of water leaving the body. The kidneys can adjust the concentration of the urine to reflect the body’s water needs, conserving water if the body is dehydrated or making urine more dilute to expel excess water when necessary. ADH is a hormone that helps the body to retain water by increasing water reabsorption by the kidneys. 26.3 Electrolyte Balance Electrolytes serve various purposes, such as helping to conduct electrical impulses along cell membranes in neurons and muscles, stabilizing enzyme structures, and releasing hormones from endocrine glands. The ions in plasma also contribute to the osmotic balance that controls the movement of water between cells and their environment. Imbalances of these ions can result in various problems in the body, and their concentrations are tightly regulated. Aldosterone and angiotensin II control the exchange of sodium and potassium between the renal filtrate and the renal collecting tubule. Calcium and phosphate are regulated by PTH, calcitriol, and calcitonin. 26.4 Acid-Base Balance A variety of buffering systems exist in the body that helps maintain the pH of the blood and other fluids within a narrow range—between pH 7.35 and 7.45. A buffer is a substance that prevents a radical change in fluid pH by absorbing excess hydrogen or hydroxyl ions. Most commonly, the substance that absorbs the ion is either a weak acid, which takes up a hydroxyl ion (OH-), or a weak base, which takes up a hydrogen ion (H+). Several substances serve as buffers in the body, including cell and plasma proteins, hemoglobin, phosphates, bicarbonate ions, and carbonic acid. The bicarbonate buffer is the primary buffering system of the IF surrounding the cells in tissues throughout the body. The respiratory and renal systems also play major roles in acid-base homeostasis by removing CO2 and hydrogen ions, respectively, from the body. 26.5 Disorders of Acid-Base Balance Acidosis and alkalosis describe conditions in which a person's blood is, respectively, too acidic (pH below 7.35) and too alkaline (pH above 7.45). Each of these conditions can be caused either by metabolic problems related to bicarbonate levels or by respiratory problems related to carbonic acid and CO2 levels. Several compensatory mechanisms allow the body to maintain a normal pH. Interactive Link Questions Watch this video to learn more about body fluids, fluid compartments, and electrolytes. When blood volume decreases due to sweating, from what source is water taken in by the blood? 2.Watch this video to see an explanation of the dynamics of fluid in the body’s compartments. What happens in tissues when capillary blood pressure is less than osmotic pressure? 3.Read this article for an explanation of the effect of seawater on humans. What effect does drinking seawater have on the body? 4.Watch this video to see a demonstration of the effect altitude has on blood pH. What effect does high altitude have on blood pH, and why? Review Questions Solute contributes to the movement of water between cells and the surrounding medium by ________. - osmotic pressure - hydrostatic pressure - Brownian movement - random motion A cation has a(n) ________ charge. - neutral - positive - alternating - negative Interstitial fluid (IF) is ________. - the fluid in the cytosol of the cells - the fluid component of blood - the fluid that bathes all of the body’s cells except for blood cells - the intracellular fluids found between membranes The largest amount of water comes into the body via ________. - metabolism - foods - liquids - humidified air The largest amount of water leaves the body via ________. - the GI tract - the skin as sweat - expiration - urine Insensible water loss is water lost via ________. - skin evaporation and in air from the lungs - urine - excessive sweating - vomiting or diarrhea How soon after drinking a large glass of water will a person start increasing their urine output? - 5 minutes - 30 minutes - 1 hour - 3 hours Bone serves as a mineral reserve for which two ions? - sodium and potassium - calcium and phosphate - chloride and bicarbonate - calcium and bicarbonate Electrolytes are lost mostly through ________. - renal function - sweating - feces - respiration The major cation in extracellular fluid is ________. - sodium - potassium - chloride - bicarbonate The major cation in intracellular fluid is ________. - sodium - potassium - chloride - bicarbonate The major anion in extracellular fluid is ________. - sodium - potassium - chloride - bicarbonate Most of the body’s calcium is found in ________. - teeth - bone - plasma - extracellular fluids Abnormally increased blood levels of sodium are termed ________. - hyperkalemia - hyperchloremia - hypernatremia - hypercalcemia The ion with the lowest blood level is ________. - sodium - potassium - chloride - bicarbonate Which two ions are most affected by aldosterone? - sodium and potassium - chloride and bicarbonate - calcium and phosphate - sodium and phosphate Which of the following is the most important buffer inside red blood cells? - plasma proteins - hemoglobin - phosphate buffers - bicarbonate: carbonic acid buffer Which explanation best describes why plasma proteins can function as buffers? - Plasma proteins combine with bicarbonate to make a stronger buffer. - Plasma proteins are immune to damage from acids. - Proteins have both positive and negative charges on their surface. - Proteins are alkaline. The buffer that is adjusted to control acid-base balance is ________. - plasma protein - hemoglobin - phosphate buffer - bicarbonate: carbonic acid buffer Carbonic acid levels are controlled through the ________. - respiratory system - renal system - digestive system - metabolic rate of cells Bicarbonate ion concentrations in the blood are controlled through the ________. - respiratory system - renal system - digestive system - metabolic rate of cells Which reaction is catalyzed by carbonic anhydrase? - HPO2-4+H+↔H2PO4-HPO42-+H+↔H2PO4- - CO2 + H2O↔H2CO3CO2 + H2O↔H2CO3 - H2PO4−+OH−↔HPO2−4+H2OH2PO4−+OH−↔HPO42−+H2O - H2CO3↔HCO3−+ H+H2CO3↔HCO3−+ H+ Which of the following is a cause of metabolic acidosis? - excessive HCl loss - increased aldosterone - diarrhea - prolonged use of diuretics Which of the following is a cause of respiratory acidosis? - emphysema - low blood K+ - increased aldosterone - increased blood ketones At a pH of 7.40, the carbonic acid ratio is ________. - 35:1 - 4:1 - 20:1 - 3:1 Which of the following is characterized as metabolic alkalosis? - increased pH, decreased pCO2, decreased HCO3– - increased pH, increased pCO2, increased HCO3– - decreased pH, decreased pCO2, decreased HCO3– - decreased pH, increased pCO2, increased HCO3– Critical Thinking Questions Plasma contains more sodium than chloride. How can this be if individual ions of sodium and chloride exactly balance each other out, and plasma is electrically neutral? 32.How is fluid moved from compartment to compartment? 33.Describe the effect of ADH on renal collecting tubules. 34.Why is it important for the amount of water intake to equal the amount of water output? 35.Explain how the CO2 generated by cells and exhaled in the lungs is carried as bicarbonate in the blood. 36.How can one have an imbalance in a substance, but not actually have elevated or deficient levels of that substance in the body? 37.Describe the conservation of bicarbonate ions in the renal system. 38.Describe the control of blood carbonic acid levels through the respiratory system. 39.Case Study: Bob is a 64-year-old male admitted to the emergency room for asthma. His laboratory results are as follows: pH 7.31, pCO2 higher than normal, and total HCO3– also higher than normal. Classify his acid-base balance as acidosis or alkalosis, and as metabolic or respiratory. Is there evidence of compensation? Propose the mechanism by which asthma contributed to the lab results seen. 40.Case Study: Kim is a 38-year-old women admitted to the hospital for bulimia. Her laboratory results are as follows: pH 7.48, pCO2 in the normal range, and total HCO3– higher than normal. Classify her acid-base balance as acidosis or alkalosis, and as metabolic or respiratory. Is there evidence of compensation? Propose the mechanism by which bulimia contributed to the lab results seen.	oercommons	2025-03-18T00:36:12.300129	10/14/2019	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/58774/overview", "title": "Anatomy and Physiology, Energy, Maintenance, and Environmental Exchange, Fluid, Electrolyte, and Acid-Base Balance", "author": null }
https://oercommons.org/courseware/lesson/72076/overview	Chapter 5 Reading Guide Overview This reading guide is intended to be used with the Open Stax Anatomy and Physiology textbook. Open Stax Anatomy and Physiology Chapter 5 Reading Guide 5.1 layers of the skin - The skin and its accessory structures make up the ___________________________. - The integumentary system provides the body with overall protection. - The Epidermis - The ________________ is composed of keratinized, stratified squamous epithelium. - Avascular - _____________________________ - Composed of four layers (thin skin) most skin is thin skin. - Stratum __________ – most deep layer - Stratum __________ – superficial to basale - Stratum __________ – superficial to spinosum - Stratum __________ – most superficial layer - “Thick skin,” has a fifth layer, stratum __________, which is only found on the palms of the hands the soles of the feet. - Located between the corneum and granulosum layers. - ______________, the cells found in all the layers except for the basale layer. - These cells manufacture and store __________. - A protein that gives hair, nails, and skin their hardness and waterproofing properties. - Keratinocytes are dead in the stratum corneum, and regularly shed away and replaced by cells from the deeper layers. ___________________________ - The deepest epidermal layer - Attaches the epidermis to the basal lamina, below which are the layers of the dermis. - The basement membrane binds the stratum basale to the underlying dermis. - _______________________ - Fingerlike projections or folds found in the superficial portion of the dermis. - Increase the strength of connection between the epidermis and dermis. - Result in your fingers as fingerprints - Consists of a single cell layer composed of __________ cells. - Stem cells that are precursors to keratinocytes - Other cell types associated with the basale layer - __________ cells, function as sensory receptors, perceive touch - __________ which produce the pigment __________. Stratum __________ - Characteristics - Spiny appearance in microscope due to __________. - Consists of eight to ten layers of keratinocytes and dendritic cells called __________cells. - Langerhans cells function as macrophages, eat bacteria, engulf foreign particles and damaged cells. Stratum __________ - Characteristics - Consists of three to five layers of keratinocytes - Cells flatten, thicker cell membranes, generate large quantities of the protein's keratin and __________ - Cellular organelles disintegrate leaving behind cell membranes and proteins. Stratum __________ - Characteristics - Found only in thick skin (soles of feet, and palms of hands) - Smooth, translucent layer found above the granulosum layer and below the corneum layer. - Dead, flattened cells that contain the protein __________, which is derived from keratohyalin. Stratum __________ - Most superficial epidermal layer, consisting of 15 to 30 layers of cells. - Functions - Protection from microbe penetration, and dehydration. - Provides mechanical protection from abrasions. - Cells are repeatedly shed and replaced by cells from deeper layers __________ - Characteristics - Deep to the epidermis - Contains blood vessels, nerves, sweat glands, and hair follicles. - Made of two layers of connective tissues which form an interconnected mesh of elastin and collagen produced by fibroblasts Layers of the Dermis __________ layer: - Loose, areolar connective tissue, forms finger-like dermal papillae that project into the stratum basale - Contain fibroblasts, adipocytes, phagocytes, and blood vessels. - Also contains lymphatic capillaries, nerve fibers, and Meissner corpuscles (touch receptors). __________ layer - Deep to the papillary layer - Dense, irregular connective tissue - Well vascularized, rich nerve supply - Elastin fibers for a tight meshwork which provides elasticity. - Collagen fibers provide structure and tensile strength _______dermis - Also known as the subcutaneous layer or superficial fascia. - Connects the skin to the underlying fascia of the muscles and bones. - It is composed of areolar and adipose tissues - Functions in fat storage, insulation, and cushioning of the integument Pigmentation - Skin color is influence by the presence of melanin, carotene, and hemoglobin - Melanin Production: - Melanin is produced by melanocytes in the stratum basale. - Melanin is transferred to other keratinocytes by cellular vesicles called _____________. - Melanin occurs in two forms - __________ is black and brown - _____________ is a red color - Darker-skinned individuals produce more melanin than lighter-skinned individuals. - Exposure to UV rays causes melanin to be produced. - Increased melanin production protects the DNA in epidermal cells from UV damage and breakdown of folic acid. - Can interfere with the production of Vitamin D. 5.2 Accessory Structures of the Skin Hair - A keratinized filament that originate from __________follicles. - Hair ________ – the part of the hair that grows out of the hair follicle. - Hair ______ – the part of the hair attached to the hair follicle. - Hair ________ – is where the root ends in the dermis which contains a layer of mitotically active cells called the hair matrix. - Hair ________ – surrounded by the hair bulb which is made of connective tissue and contains nerve endings and blood capillaries. Hair Hair follicles originate in the epidermis and have many different parts. Process of Hair Formation - The basal cells of the hair bulb divide push cells outward in the hair root and shaft. - _________ forms the central core of the hair shaft, surrounded by the __________, and an outer layer called the __________. - Hair texture (straight, curly) is determined by the shape and structure of the cortex - The external hair (visible to you) is dead cells composed entirely of keratin. - Hair follicle structure: - Three concentric cell layers - __________ root sheath a layer of cells that surround the root of the growing hair - External root ________ is a cell layer that encloses the hair root. - Glassy _________ – connective tissue sheath Functions of Hair - Protection, sensory input, thermoregulation, and communication. - Each hair root is connected to a smooth muscle called the _________ pili. - Goose bumps or hair standing on end. Hair Growth - Occurs in three phases - ________ – cells divide rapidly at the root, push the hair shaft up and out. - __________ – transition from active growth to no growth. - __________ – hair follicle at rest with no active growth Hair Color - Is due to the pigment melanin produced by melanocytes in the hair papilla. Nails - Found at the tips of fingers and toes. - Structure of nails - Nail _______ forms on the ________ bed. - Protects the tips of fingers and toes. - Nail _______ forms the nail body. - Nail ________– overlaps the nail on the sides to anchor the nail body - Nail cuticle (_______________) the proximal end of the nail body - _________ – a thickened layer of epithelium over the nail matrix. - _____________ – the area below the free edge of the nail. Sweat Glands - _____________ glands produce sweat to cool the body - __________ glands produce secretions by exocytosis through a duct - _________ sweat gland – produce a hypotonic sweat for thermoregulation. - This sweat is mostly water with dissolved salts, antibodies, metabolic wastes and dermicidin (antimicrobial peptide). - __________ sweat gland is associated with hair follicles in the armpits and genital regions - Produce a thicker, sweat that is subject to bacterial decomposition and smell. - Sebaceous Glands - Oil glands to help lubricate and waterproof the skin and hair. - Excrete __________ a mixture of lipids. - Activated by puberty hormones 5.3 functions of the integumentary system __________ - Protection from wind, water and UV sunlight. - Protection from dehydration - Protection from abrasion, microbes, and chemicals __________ Function - Sense organ because the epidermis, dermis and hypodermis contain sensory receptors. - __________ (tactile) corpuscle responds to light touch - __________ (lamellated) corpuscle respond to vibrations - __________ cells mentioned earlier - Sensory nerves connected to each hair follicle - Pain and temperature receptors scattered throughout the skin. - Motor nerves innervate the arrector pili and glands in the skin. Thermoregulation - Through association with the __________ nervous system (SNS) (flight or f______ responses). - The SNS monitors body temperature and executes an appropriate motor response (i.e. sweating). - Arterioles in the dermis dilate so that excess heat dissipates through the skin into the surrounding environment. - The same arterioles will constrict to minimize heat loss when it is cold. Vitamin D Synthesis - Occurs in the epidermal layer - In the presence of sunlight: - Vitamin D3 (cholecalciferol – a derivative of cholesterol) is synthesized. - In the liver cholecalciferol is converted to calcidiol, which in the kidneys is converted to calcitriol (the active form of _____________). - Vitamin D is essential for the normal absorption of calcium and phosphorus for health bones. - Absence of sunlight and vitamin D leads to __________ in children. - In elderly individual's vitamin D deficiency causes __________ which is a softening of the bone. - Vitamin D is needed for general immunity and lack of it may predispose one to cancer. 5.4: Diseases, disorders, and injuries of the integumentary system - Skin cancer is one of the most talked about diseases in human beings. - Cancer is a disease characterized by abnormal cells dividing uncontrollably. - One out of five Americans will experience some type of skin cancer - Chief cause is overexposure to UV radiation. - Many tumors are benign (harmless) - But some produce cells that can mobilize and move into other body parts and start growing there (__________) - Cancers are characterized by their ability to metastasize. Basal Cell Carcinoma - ______________carcinoma affects the stem cells in the stratum basale. - Most common form of all cancers that occur in the United States. - Caused by overexposure to UV rays, and other forms of radiation along with arsenic. - Open sores, tattoos, burns, may be predisposing factors - Start in the stratum basale and spread out from there. - Respond very well to early treatment Squamous cell carcinoma - _____________ cell carcinoma affects the cells of the stratum spinosum. - Most commonly presents as lesions on the scalp, ears, and hands. - Second most common form of skin cancer. - More aggressive than basal cell carcinoma, can metastasize if not removed early. Melanoma - _____________ is a cancer caused by uncontrollable growth of melanocytes, typically develop from a mole - The most fatal of all skin cancers, highly metastatic and can spread easily before detection. - Usually appear as asymmetrical brown and black patches - The ABC’s of early diagnosis of melanoma - When observing moles displaying the following signs it is wise to consult a doctor immediately - A__________ – the two sides are not symmetrical - B__________ – the edges are irregular in shape. - C__________ – the color is varied shades of brown and black. - D__________ – it is larger than 6 mm (0.24 in). - E__________ – its shape has changed. - Additional signs to look for as suggested by specialists for nodular melanoma (most serious form). - E__________ – it is raised on the skin surface - F__________ – it feels hard to the touch. - G__________ – it is getting larger. Skin Disorders - Two common disorders are eczema and acne - __________ an inflammatory condition that results from an allergic reaction - Manifests itself as swelling of the skin, flaking, rashes, and bleeding - Most suffers have antibodies against dust mites in their blood. - __________ involves clogging of pores which can lead to infection, and inflammation. - Most common in adolescents - Occurs in areas rich in sebaceous glands (face and back). - Most common during puberty - Androgens stimulate the release of sebum, an overproduction and accumulation can block hair follicles - The infection is caused by acne – causing bacteria. Injuries - Burns - Burns result from intense heat, radiation, electricity, or chemicals. - Damage results in the death of skin cells which leads to loss of fluids - Burn Classifications - (rule of nines) determines the total surface area of the body affected, - Degree of severity - _________-degree burn – is superficial and only affects the epidermis. Reddening of the skin and some swelling - __________-degree burn – is deeper, affects the epidermis and upper dermis. Result in swelling and blisters. - __________-degree burns - results in destruction of the epidermis and dermis, much more serious, require medical attention. - __________-degree burns – Most severe affects underlying muscle and bone. Scars and Keloids - Scar is collagen-rich skin formed due to repair of skin damage but no regeneration of the original skin structure. - Keloid is the result of collagen formation that continues after the wound is healed. This results in the formation of a raised scar. Bedsores and Stretch Marks - A bedsore (__________ ulcer) results from long-term, unrelieved pressure on body parts that are bony, reducing blood flow, and leading to necrosis. - A stretch mark is caused by pressure associated with rapid growth. They result when the dermis is stretched beyond its limits of elasticity Calluses - Calluses form on parts of the body that are subjected to constant sources of abrasion. - This results in thickening of the skin at the abrasion point to protect the rest of the body from further damage. - Corns – specialized callus, form on your feet and toes.	oercommons	2025-03-18T00:36:12.349611	09/04/2020	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/72076/overview", "title": "Chapter 5 Reading Guide", "author": "Bryon Spicci" }
https://oercommons.org/courseware/lesson/124438/overview	4Ms of Age Friendly Care Micro-credential - Common Cartridge (Blackboard) V 1.2 Micro-credential Resources and Guidance Documents 4Ms of Age Friendly Care Micro-credential Overview This resource contains the full course content for the 4Ms of Age Friendly Care Micro-credential for healthcare and nursing students. This course was developed by the CT SHIP grant in collaboration with the COACH 4Ms grant - covering the 4Ms of Age friendly care; Mentation, What Matters, Medicine, and Mobility. This professional enhancement level micro-credential takes 2-3 hours to complete and includes content formats such as powerpoint lectures, videos, articles, links, and images, assessments, as well as some interactive content. All content was created in collaboration with healthcare employers and SMEs in the healthcare field. Within this resource you will find: all course files, IMSCC file for embedding into Blackboard LMS, and resources and guidance documents for implementation. Course Files and Resources Course Description Certified Nurse Assistants are valuable members of the healthcare team providing day-to-day care. They address complex needs of patients in a changing healthcare landscape requiring more training strategies. The Age-Friendly 4Ms are a framework to help guide effective care for the older adult patient. Certified Nurse Assistants engaged in this micro-credential will gain the fundamental knowledge and skills in the 4Ms: what matters most, medication management, mentation, and mobility, as well as improved attitudes toward the geriatric population and ultimately, improve care to their patients. Skills: 4Ms Framework \| Age-Friendly Care \| Cognitive Health \| Dementia Care \| Medication Management \| Mobility Assessment \| Non-Pharmacological Interventions \| Patient-Centered Care \| Safe Medication Use \| Supporting Mental Health About: The micro-credential is intended to be taken online independently. It should take between 2-3 hours to complete. It is a Professional Enhancement level micro-credential, and has been developed with healthcare industry professionals from large healthcare employers in the state of CT. Course Files (ZIP Folder): This folder contains all course files, including PowerPoint presentations, images, and external documents. It also includes a course roadmap, which outlines the intended sequence for building the course from scratch. The embedded links document provides all resource links used within the micro-credential. SCORM File: This Common Cartridge file is designed to directly embed the entire course and its content into a compatible Learning Management System (LMS). It was used in Blackboard Ultra and is formatted to SCORM 1.2. Resources and Guidance Documents (ZIP Folder): This folder contains instructional resources and guidance for instructors on how to effectively use the provided materials. Grant Disclaimer This content was created as part of the CT SHIP grant, lead by CT State Community College - Norwalk. https://ctstate.edu/workforce-development/microcredentials The total cost of CT Statewide Healthcare Industry Pathway project (CT SHIP) was $6.9M. $3.4M (49%) was funded through a U.S. Department of Labor – Employment and Training Administration grant and another $3.5M (51%) was committed through non-federal state and local resources. The Workforce product was funded by the grant awarded by the U.S Department of Labor's Employment and Training Administration. The product was created by the grantee and does not necessarily reflect the official position of the U.S Department of Labor. The U.S Department of Labor makes no guarantees, warranties, or assurances of any kind, express or implied, with respect to such information, including any information on any linked sites and include, but not limited to, the accuracy of the information or its completeness, timeliness, usefulness, adequacy, continued availability, or ownership.	oercommons	2025-03-18T00:36:12.374707	02/06/2025	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/124438/overview", "title": "4Ms of Age Friendly Care Micro-credential", "author": "Renee Dunbar" }
https://oercommons.org/courseware/lesson/108654/overview	Open Educational Resources (OER) in Texas Statewide Playbook Overview The Open Educational Resources (OER) in Texas Statewide Playbook is a resource developed by practitioners and advocates actively involved in the labor of open education to guide new and expanding OER work at institutions of higher education. The Playbook is the result of partnerships between the Division of Digital Learning, the Institution for the Study of Knowledge Management in Education (ISKME) – creators of OER Commons and experts in open education practice and research – and faculty, librarians, staff, and administrators from institutions and systems across Texas. It aims to support institutions as they work to build capacity and drive systems change around OER. It also serves as a guiding document for institutions that have not yet engaged in OER work or taken advantage of existing programs and opportunities. The hope is that the Texas OER Playbook will serve as a companion on the journey towards OER awareness and advocacy at your institution. The Open Educational Resources (OER) in Texas Statewide Playbook is a resource developed by practitioners and advocates actively involved in the labor of open education to guide new and expanding OER work at institutions of higher education. The Playbook is the result of partnerships between the Division of Digital Learning, the Institution for the Study of Knowledge Management in Education (ISKME) – creators of OER Commons and experts in open education practice and research – and faculty, librarians, staff, and administrators from institutions and systems across Texas. The creation of the Texas OER Playbook was one of the core initiatives identified in the 2021 OER landscape report, “Advancing an Ecosystem for Open Educational Resources: OER in Texas Higher Education, Biennial Report 2021.” It aims to support institutions as they work to build capacity and drive systems change around OER. It also serves as a guiding document for institutions that have not yet engaged in OER work or taken advantage of existing programs and opportunities. The hope is that the Texas OER Playbook will serve as a companion on the journey towards OER awareness and advocacy at your institution. In the spirit of open, the Playbook is Creative Commons licensed and freely available for all to use and adapt. In it, users will find foundational information on OER, helpful tools for navigating institutional OER policies and programs, and examples of the extraordinary work being done at Texas institutions and systems. The playbook was built for continual evolution and improvement, and user voices can strengthen it as a community resource. Please share your experience with the Texas OER Playbook at digitallearning@highered.texas.gov.	oercommons	2025-03-18T00:36:12.393473	Kylah Torre	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/108654/overview", "title": "Open Educational Resources (OER) in Texas Statewide Playbook", "author": "Textbook" }
https://oercommons.org/courseware/lesson/76961/overview	NGSS Toolkit Overview This Wakelet is a collection of links to free online resources that address all areas of teaching the Next Generation Science Standards (NGSS). The resources are grouped together in smaller, topic-based collections. A range of resources are provided for K-12, and additional links will be continually added to the collection. NGSS Toolkit Wakelet Collection Click to access the entire Toolkit collection: NGSS Toolkit Wakelet Click below to access the individual topic collections: NGSS 101:Standards and Dimensions: Phenomena for NGSS Science and Engineering Practices (SEPs) Crosscutting Concepts (CCCs) DisciplinaryCore Ideas (DCIs) Learning Design for NGSS - K-5 Activity, Lesson and Unit Resources - Climate Science and Human Sustainability Resources Classroom Discourse for Science Engineering Resources C-E-R: Claim-Evidence-Reasoning (Rebuttal) Informational Reading Resources for Science Interactive Maps/Data/Simulations/Videos Virtual Field Trips Why Teach K-5 Science? Educational Technology for Science Three-Dimensional Assessment Supports for Principals and Coaches Are My Materials aligned to NGSS? Key NGSS People and Groups to Follow Careers in STEM Free Image Collections and Slide Decks Attributions and Disclaimer Disclaimer: This listing of links to third party resources freely available online is provided as information only for the convenience of educators. This does not imply any affiliation, endorsement, sponsorship, monitoring or responsibility for the contents or for their use. Educators are responsible for previewing and evaluating any and all materials before using them with students. All trademarks and logos are the property of their respective owners. Images are either auto-filled by Wakelet from the sites themselves or are selected from Unsplash or Deeper Learning.	oercommons	2025-03-18T00:36:12.456748	Elementary Education	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/76961/overview", "title": "NGSS Toolkit", "author": "Chemistry" }
https://oercommons.org/courseware/lesson/67850/overview	Education Standards NGSS_Grade9_Course_1_Bundle_2_DisappearingBodies-2020 NGSS_Grade9_Course_1_Bundle_3_BoatOnABuilding-2020 NGSS_Grade9_Course_1_Bundle_4_GiantSequoias-2020 NGSS_Grade9_Course_1_Bundle_5_BioLite-2020 NGSS_Grade9_Course_1_Bundle_6_Snapchat-2020 High School Integrated Physics and Chemistry Course Overview The High School Integrated Conceptual Science Program (ICSP) is a NGSS-aligned curriculum that utilizes the conceptual progressions model for bundling of the NGSS, High School Conceptual Model Course 1 and strategies from Ambitious Science Teaching (AST) to focus on teaching practices needed to engage students in science discourse and learning. Course 1 is the High School Integrated Physics and Chemsitry Course. The goal of these units is to encourage students to continue in STEM by providing engaging and aligned curriculum. The focus of this year long course is on the first year of high school (freshman). While the course is designed to be taught as a collection of the units, each unit could be taught as a separate unit in a science course. A video about the new course shared its unique approach to learning and teaching. Wenatchee School District, one of the participating districts, wanted a way to share the program with the community. https://youtu.be/9AGk19YUi2o Course 1 of the ICSP development was funded by Northwest Earth and Space Sciences Pipeline (NESSP) which is funded through the NASA Science Mission Directorate and housed with Washington NASA Space Grant Consortium at the University of Washington. Course 1 Bundle 1: Colliding Galaxies In this unit students observe the phenomenon of collision between objects in space. As they seek to make sense of the phenomenon, they will engage in activities to learn about Newton's Laws of Motion, Keplar's Laws, Doppler Effect, light waves, and galaxy motion. Course 1 Bundle 2: Dissolving Bodies In this unit students explore the phenonmenon of a person disappearing after falling into a hot spring at Yellowstone National Park. As students make sense of this phenomenon, they engage in activities to learn about atoms, bonding, solubility, and the conservation of matter. Course 1 Bundle 3: Boat on a Building In this unit students explore how a large boat ended up on top of a house. In 2011, a 9.0 magnitude earthquake struck off the coast of Tōhoku, Japan. After the earthquake, a massive and devastating tsunami occurred that caused extensive damage to coastal areas in Japan and elsewhere. As studnets make sense of this phenomenon, they will engae in activities to learn about plate tectonics, energy transfer, convection currents, and radioactive isotope decay. Course 1 Bundle 4: Giant Sequoia In this unit students explore the phenomenon of how a massive tree can grow from a tiny seed. As students make sense of this phenomenon, they engage in activities to learn about photosynthesis, glucose, conservation of matter and energy, and bonding. Course 1 Bundle 5: Biolite In this unit students explore the Biolite campstove that cooks food while also charging a cellphone. As students make sense of this phenomenon, they engage in activities to learn about the conservation of energy, the flow of energy into, out of, and within a system, and how to evaluate and design a solution to a complex, real-world problem. Course1 Bundle 6: Snapchat In this unit students explore how an image can be sent to and from a cell phone. As they make sense of this phenomenon they will engage in activities to learn about waves, the electromagnetic spectrum, photons, and the photoelectric effect.	oercommons	2025-03-18T00:36:12.484531	Assessment	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/67850/overview", "title": "High School Integrated Physics and Chemistry Course", "author": "Activity/Lab" }
https://oercommons.org/courseware/lesson/69225/overview	Learning Domain: Reading for Literacy in History/Social Studies Standard: Determine the central ideas or information of a primary or secondary source; provide an accurate summary of the source distinct from prior knowledge or opinions. Learning Domain: Reading for Literacy in History/Social Studies Standard: Integrate visual information (e.g., in charts, graphs, photographs, videos, or maps) with other information in print and digital texts. Learning Domain: Reading for Literacy in History/Social Studies Standard: Cite specific textual evidence to support analysis of primary and secondary sources. Learning Domain: Reading for Literacy in History/Social Studies Standard: Determine the central ideas or information of a primary or secondary source; provide an accurate summary of the source distinct from prior knowledge or opinions. Learning Domain: Reading for Literacy in History/Social Studies Standard: Integrate visual information (e.g., in charts, graphs, photographs, videos, or maps) with other information in print and digital texts. Learning Domain: Reading for Literacy in History/Social Studies Standard: Cite specific textual evidence to support analysis of primary and secondary sources. Cluster: Key Ideas and Details. Standard: Determine the central ideas or information of a primary or secondary source; provide an accurate summary of the source distinct from prior knowledge or opinions. Cluster: Integration of Knowledge and Ideas. Standard: Integrate visual information (e.g., in charts, graphs, photographs, videos, or maps) with other information in print and digital texts. Cluster: Key Ideas and Details. Standard: Cite specific textual evidence to support analysis of primary and secondary sources.	oercommons	2025-03-18T00:36:12.504262	06/30/2020	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/69225/overview", "title": "Ancient Egypt Inquiry Unit", "author": "Beky Erickson" }
https://oercommons.org/courseware/lesson/93229/overview	OER Standards Criteria for Evaluation_pdf Open Textbooks OER Standards Open Textbooks OER Standards PDF Version Open Textbooks for Rural Arizona - OER Standards Overview The purpose of these standards is to guide faculty who are designing OER for the Open Textbooks for Rural Arizona Project, and they can be used for both a formal and/or informal review. The document includes 7 sections: Open Textbooks for Rural Arizona Grant Requirements Quality Appropriateness & Alignment Technical OER Review Supplemental or Ancillary Materials Criteria for Evaluation (for any standard using a 1-5 rating scale) Overview The purpose of these standards is to guide faculty who are designing OER for the Open Textbooks for Rural Arizona Project, and they can be used for both a formal and/or informal review. The document includes 7 sections: Open Textbooks for Rural Arizona Grant Requirements Quality Appropriateness & Alignment Technical OER Review Supplemental or Ancillary Materials Criteria for Evaluation (for any standard using a 1-5 rating scale) This checklist of OER textbook standards is a remix of: - B.C. Open Textbooks Review Rubric [Word file] (CC BY 4.0 International License.) Accessed https://open.bccampus.ca/use-open-textbooks/review-an-open-textbook/ - Checklist for Evaluating Open Educational Resources (OER) by Texas State University Libraries is licensed under CC BY 4.0. accessed https://digital.library.txstate.edu/handle/10877/12236 - The Affordable Learning Georgia (ALG) Quality Standards for Open Educational Resources (OER) by University System of Georgian (USG) under an attribution of 4.0 International License CC BY. Accessed https://www.affordablelearninggeorgia.org/find_textbooks/selecting_textbooks Open Textbooks for Rural Arizona Grant Requirements Licensing OER content is CC-BY or CC-BY NC or Public Domain Licensing. \| Y N \| \|---\| Accessibility Content meets general accessibility standards Web Content Accessibility Guidelines 2.0, Level AA. The consoritum has prepared guidelines and a checklist to support this process. \| Y N \| Shareability The content can meaningfully and efficiently be combined or assembled with other materials. \| Y N \| \|---\|---\| The learning object does not require specialized skills or software to read/remix. \| Y N \| Quality Currency & Logevity The OER content is up to date but does not present information that will become obsolete quickly. \| 1 2 3 4 5 \| The OER content reflects significant, topical, and recent scholarship in terms of the subject matter. \| 1 2 3 4 5 \| Clarity & Accuracy The OER content is well-written and contains no grammatical, spelling, or typographical errors. \| 1 2 3 4 5 \| The OER content information is factual and verifiable via other external sources. \| 1 2 3 4 5 \| The OER content is understandable and does not need to be augmented with additional explanation or material. \| 1 2 3 4 5 \| Comprehensiveness The OER content scope covers all areas necessary for a particular college course or set of courses or specific course learning outcomes or module/unit learning objectives. \| Y N \| Readability The OER content is understandable for the target higher education students. \| Y N \| The OER provides adequate context for any jargon/technical terminology. \| Y N \| The OER content contains clear instructions explaining how students and instructors are expected to use the content. \| Y N \| Source Transparency & Attributions & Copyrighted Materials OER content cites references and sources appropriately. \| Y N \| OER content contains appropriate attributions for openly licensed content that you share or adapt. \| Y N \| OER content links out to all copyrighted content. \| Y N \| Refer to the Code of Best Practices in Fair Use for OpenCourseWare for all other copyright content that falls under Educational Fair Use. \| Y N \| Pedagogical Methods The OER content includes multiple modalities (e.g., graphics, tables, and information other than text) to support student learning. \| Y N \| The OER content promotes active learning, class participation, and/or collaboration. \| Y N \| Organization & Format The OER content provides an effective index or glossary, table of contents, or content outline when appropriate. \| Y N \| OER content reflects a sound organizational structure and approach. \| Y N \| Appropriatness & Alignment Alignment The OER content is appropriate for the course level. \| Y N \| The OER content clearly states student learning outcomes or unit/module learning objectives and demonstrates alignment. \| Y N \| Any relationships between the use of the OER course, textbook, and/or ancillary OER is clearly explained. \| Y N \| The OER content can be applied in some way that aids a learner’s understanding. \| Y N \| The OER content facilitates the use of a mix of instructional approaches, if it is a larger object, like a unit. \| Y N \| OER assessments clearly describe how the assessment is scored using either a grading rubric or other scoring system. \| Y N \| Cultural Relevance & Sensitivity The OER content is free of insensitivity or cultural stereotypes within the context of the subject matter. \| Y N \| The OER reflects diversity and inclusion regarding culture, gender, ethnicity, national origin, age, disability sexual orientation, education, and religion whenever possible, considering the context of the subject. \| Y N N/A \| Technical Modularity & Adaptability The text is easily and readily divisible into meaningful, smaller sections that can be reorganized. \| Y N \| The text is free of significant self-reference or interface issues, including navigation, that may disrupt if content sequence is modified. \| Y N \| Technical Quality The image resolution and sound quality are up to current standards for target viewing devices (e.g., mobile devices). \| Y N \| The interface and design are easy to navigate. \| Y N \| OER Review OER content has been reviewed by Instructional Designers, Librarians, and/or Subject Matter experts through an OER review process. \| Y N \| Supplemental or Ancillary Materials OER content that includes supporting resources such as study guides, labs, simulations, self-practice or assessment activities also meet these OER standards. \| 1 2 3 4 5 \| Criteria for Evaluation Note: The consortium recognizes that these are all guidelines, and there will be exceptions to each item depending on the content. The OER content is up to date but does not present information that will become obsolete quickly. The OER content is up to date but does not present information that will become obsolete quickly. 1 \| 2 \| 3 \| 4 \| 5 \| OER content >10 years old OER information is out-of-date for the topic \| OER content is about 7-10 years old OER information is somewhat up-to-date for the topic \| OER content is between 5-7 years old OER information is up-to-date for the topic \| OER content between 2-5 years old OER information is up-to-date for the topic If appropriate, the OER content has been revised \| OER content <2 years old OER information is up-to-date for the topic If appropriate, the OER content has also been recently revised \| The OER content reflects significant, topical, and recent scholarship in terms of the subject matter. 1 \| 2 \| 3 \| 4 \| 5 \| OER content is not significant, topical, or representative of recent scholarship in terms of the subject matter. \| Most OER content does not reflect significant, topical, or recent scholarship in terms of the subject matter. \| OER content more or less reflects significant, topical, and representative of recent scholarship in terms of the subject matter. \| OER content is likely to reflect significant, topical, and representative of recent scholarship in terms of the subject matter. \| OER content reflects highly significant, topical, and recent scholarship in terms of the subject matter. \| The OER content is well-written and contains no grammatical, spelling, or typographical errors. 1 \| 2 \| 3 \| 4 \| 5 \| OER content is riddled with >10 grammar, spelling, and typographical errors that distract the audience. \| OER content has 5-10 grammar, spelling, or typographical errors that are distracting to the audience. \| OER content has 3-5 grammar, spelling, or typographical errors that are somewhat distracting to the audience. \| OER content has between 1-3 grammar, spelling, or typographical errors that are not distracting to the audience. \| OER content has no grammar, spelling, or typographical errors. \| The OER content information is factual and verifiable via other external sources. 1 \| 2 \| 3 \| 4 \| 5 \| OER content is neither factual nor verifiable via other external reputable sources. \| OER content is not likely to be factual and verifiable via other external reputable sources. \| OER content is more or less factual and verifiable via other external reputable sources. \| OER content is mostly factual and verifiable via other external reputable sources. \| OER content is highly factual and verifiable via other external reputable sources. It has also been peer reviewed or refereed. \| The OER content is presented with clarity and requires little to no additional explanation. 1 \| 2 \| 3 \| 4 \| 5 \| OER content is unclear and requires significant additional explanation. \| OER content is not presented with clarity and requires additional explanation or material. \| OER content is somewhat presented with clarity and requires little to no additional explanation. \| OER content is mostly presented with clarity and requires little to no additional explanation. \| OER content is presented with clarity and requires little to no additional explanation. \| OER content that includes supporting resources such as study guides, labs, simulations, self-practice or assessment activities also meet these OER standards. 1 \| 2 \| 3 \| 4 \| 5 \| OER content does not include supporting resources such as study guides, labs, simulations, self-practice or assessment activities. \| OER content includes <2 supporting resources such as guides, labs, simulations, self-practice, or assessment activities, but not all of them meet these OER standards. \| OER content includes 2-3 supporting resources such as guides, labs, simulations, self-practice, or assessment activities, and a majority of them meet these OER standards. \| OER content includes several 4-5 supporting resources such as study guides, labs, simulations, self-practice or assessment activities that also meet these OER standards. \| OER content includes numerous >5 supporting resources such as study guides, labs, simulations, self-practice or assessment activities that also meet these OER standards. \|	oercommons	2025-03-18T00:36:12.586095	Linda Neff	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/93229/overview", "title": "Open Textbooks for Rural Arizona - OER Standards", "author": "Megan Crossfield" }
https://oercommons.org/courseware/lesson/66255/overview	Introduction: The Texas State Constitution and the American Federal System Overview Introduction: The Texas State Constitution and the American Federal System Learning Objective By the end of this chapter, you will be able to: - Explain the origin and development of the Texas State Constitution Introduction A constitution is a body of fundamental principles or established precedents according to which a state or other organization is acknowledged to be governed. Another way of thinking about it is that a constitution outlines the structure of the government, defines the powers of the government, and enumerates limits on the government. When it comes to structure, this can include the creation of branches as well as how each branch is organized. For example, the Texas government has three branches in which the legislative branch is bicameral, the executive branch is plural, and the judicial branch is bifurcated. As for powers, the legislature makes law, the executive enforces law, and the judicial branch adjudicates and interprets the law. Finally, limits on powers come in the form of the Bill of Rights. A bill of rights, sometimes called a declaration of rights or a charter of rights, is a list of the most important rights to the citizens. The purpose is to protect those rights against infringement from public officials and private citizens. The Texas Bill of Rights outlines the limits on the powers of the government that would violate our rights. What distinguishes Texas from other states is its unique history as an entity—a state, a republic, a nation—and the documents that actually created what became the Texas we know today. This chapter discusses the development of Texas' constitutions, from the Constitution of 1876 through the current constitution References and Further Reading The Texas Bill of Rights. The Texas Constitution. Licenses and Attributions CC LICENSED CONTENT, ORIGINAL Revision and Adaptation. Authored by: Kris S. Seago. License: CC BY: Attribution	oercommons	2025-03-18T00:36:12.605858	05/05/2020	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/66255/overview", "title": "Texas Government 2.0, The Texas State Constitution and the American Federal System, Introduction: The Texas State Constitution and the American Federal System", "author": "Kris Seago" }
https://oercommons.org/courseware/lesson/66255/overview	Introduction: The Texas State Constitution and the American Federal System Overview Introduction: The Texas State Constitution and the American Federal System Learning Objective By the end of this chapter, you will be able to: - Explain the origin and development of the Texas State Constitution Introduction A constitution is a body of fundamental principles or established precedents according to which a state or other organization is acknowledged to be governed. Another way of thinking about it is that a constitution outlines the structure of the government, defines the powers of the government, and enumerates limits on the government. When it comes to structure, this can include the creation of branches as well as how each branch is organized. For example, the Texas government has three branches in which the legislative branch is bicameral, the executive branch is plural, and the judicial branch is bifurcated. As for powers, the legislature makes law, the executive enforces law, and the judicial branch adjudicates and interprets the law. Finally, limits on powers come in the form of the Bill of Rights. A bill of rights, sometimes called a declaration of rights or a charter of rights, is a list of the most important rights to the citizens. The purpose is to protect those rights against infringement from public officials and private citizens. The Texas Bill of Rights outlines the limits on the powers of the government that would violate our rights. What distinguishes Texas from other states is its unique history as an entity—a state, a republic, a nation—and the documents that actually created what became the Texas we know today. This chapter discusses the development of Texas' constitutions, from the Constitution of 1876 through the current constitution References and Further Reading The Texas Bill of Rights. The Texas Constitution. Licenses and Attributions CC LICENSED CONTENT, ORIGINAL Revision and Adaptation. Authored by: Kris S. Seago. License: CC BY: Attribution	oercommons	2025-03-18T00:36:12.624483	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/66255/overview", "title": "Texas Government 2.0, The Texas State Constitution and the American Federal System", "author": null }
https://oercommons.org/courseware/lesson/66269/overview	The Evolution of the Texas State Constitution Overview The Evolution of the Texas State Constitution Learning Objective By the end of this section, you will be able to: Discuss the evolution of the Texas State Constitution and how it came to be in its modern-day form Introduction: The Role of a State Constitution A state constitution is the governing document of the state in much the same way the U.S. Constitution sets up the framework of the nation as a whole. Many of the ideas found in the U.S. Constitution are also found in the Texas state constitutions, including individual rights, separation of powers, checks and balances, and republican government. The First Texas Constitutions Between the years of 1824 and 1876, Texas was at times a part of the United States of Mexico, an independent republic, a state within the Confederate States of America, and a state within the United States of America. Beginning in 1824, what we now know as Texas passed through many iterations—each with founding documents that can be accessed in this course. These founding documents legally established the entity of Texas, set forth the rights and responsibilities of its people, and defined the scope and powers of its government. Texas State Constitutions - Federal Constitution of the United Mexican States of 1824 - Constitution of Coahuila y Tejas 1827 - The Republic of Texas Constitution, 1836 - The State Constitution of 1845 - The Confederate Constitution of 1861 - The Post-Civil War Constitution of 1866 - The Reconstruction Constitution of 1869 - The Texas Constitution of 1876 References and Further Reading Texas Constitutions 1824-1876, Tarlton Law Library. University of Texas School of Law Licenses and Attributions CC LICENSED CONTENT, ORIGINAL Revision and Adaptation: The Evolution of the Texas State Constitution. Authored by: John Osterman. License: CC BY: Attribution Introduction: Constitutions of Texas. Authored by: Kris S. Seago. License: CC BY: Attribution	oercommons	2025-03-18T00:36:12.655606	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/66269/overview", "title": "Texas Government 2.0, The Texas State Constitution and the American Federal System", "author": null }
https://oercommons.org/courseware/lesson/66256/overview	Federal Constitution of the United Mexican States (1824) Overview Federal Constitution of the United Mexican States (1824) Learning Objective By the end of this section, you will be able to: - Understand the Federal Constitution of the United Mexican States (1824)’s role in Texas history Introduction This section discusses the Federal Constitution of the United Mexican States (1824)’s role in Texas history. Federal Constitution of the United Mexican States of 1824 Constitutional government in Texas began with the Mexican Federal Constitution of 1824, which, to some degree, was patterned after the United States Constitution but resembled more the Spanish Constitution of 1812. Congress was made the final interpreter of the document; the Catholic religion was made the state faith; and the church was supported by the public treasury. The president and vice president were elected for four-year terms by the legislative bodies of the states, the lower house of Congress to elect in case of a tie or lack of a majority. There were numerous limitations on the powers of the president. The Congress was composed of two houses meeting annually from January 1 to April 15. The president could prolong the regular session for an additional thirty days and could call extra sessions. Deputies in the lower house served two years, while senators were selected by their state legislatures for four- year terms. The judicial power was vested in a Supreme Court and superior courts of departments and districts. The Supreme Court was composed of eleven judges and the attorney general. There was no particular effort to define the rights of the states in the confederacy. They were required to separate executive, legislative, and judicial functions in their individual constitutions, which were to be in harmony with the national constitution, but local affairs were independent of the general government. Link to Learning More information on the Federal Constitution of the United Mexican States (1824) may be found at the Texas Constitutions 1824-1876 project of the Tarlton Law Library, Jamail Center for Legal Research at the University of Texas School of Law, the University of Texas at Austin. The project includes digitized images and searchable text versions of the constitutions. References and Further Reading Federal Constitution of the United Mexican States (1824) may be found at the Texas Constitutions 1824-1876 project of the Tarlton Law Library, Jamail Center for Legal Research at the University of Texas School of Law, the University of Texas at Austin. Licenses and Attribution CC LICENSED CONTENT, ORIGINAL Revision and Adaptation. Authored by: Kris S. Seago. License: CC BY: Attribution	oercommons	2025-03-18T00:36:12.676304	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/66256/overview", "title": "Texas Government 2.0, The Texas State Constitution and the American Federal System", "author": null }
https://oercommons.org/courseware/lesson/66257/overview	Constitution Of Coahuila And Texas (1827) Overview Constitution Of Coahuila And Texas (1827) Learning Objectives By the end of this section, you will be able to: - Understand the Constitution Of Coahuila And Texas (1827)’s role in Texas history Introduction This section discusses the Constitution Of Coahuila And Texas (1827)’s role in Texas history. Constitution Of Coahuila And Texas (1827) The Constitution of 1824 of the Republic of Mexico provided that each state in the republic should frame its own constitution. The state of Coahuila and the former Spanish province of Texas were combined as the state of Coahuila and Texas. The legislature for the new state was organized at Saltillo in August 1824, with the Baron de Bastrop representing Texas. The Constitution of Coahuila and Texas divided the state into three departments, of which Texas, as the District of Bexar, was one. The Catholic religion was made the state religion; citizens were guaranteed liberty, security, property, and equality; slavery was forbidden after promulgation of the constitution, and there could be no import of slaves after six months. Citizenship was defined and its forfeiture outlined. Legislative power was delegated to a unicameral legislature composed of twelve deputies elected by popular vote; Texas was allowed two of the twelve. The body, which met annually from January through April and could be called in special session, was given wide and diverse powers. In addition to legislative functions, it could elect state officials if no majority was shown in the regular voting, could serve as a grand jury in political and electoral matters, and could regulate the army and militia. It was instructed to promote education and protect the liberty of the press. Executive power was vested in a governor and vice governor, elected for four-year terms by popular vote. The governor could recommend legislation, grant pardons, lead the state militia, and see that the laws were obeyed. The vice governor presided over the council and served as police chief at the capital. The governor appointed for each department a chief of police, and an elaborate plan of local government was set up. Judicial authority was vested in state courts having charge of minor crimes and civil cases. The courts could try cases but could not interpret the law; misdemeanors were tried by the judge without a jury. Military men and ecclesiastics were subject to rules made by their own orders. Trial by jury, promised by the constitution, was never established, nor was the school system ever set up. The laws were published only in Spanish, which few Anglo-Texans could read. Because of widespread objections to government under this document, the Convention of 1833 proposed a new constitution to give Texas statehood separate from Coahuila Link to Learning More information on the Constitution Of Coahuila And Texas (1827) may be found at the Texas Constitutions 1824-1876 project of the Tarlton Law Library, Jamail Center for Legal Research at the University of Texas School of Law at the University of Texas at Austin. The project includes digitized images and searchable text versions of the constitutions. References and Further Reading Vito Alessio Robles, Coahuila y Texas en la época colonial (Mexico City: Editorial Cultura, 1938; 2d ed., Mexico City: Editorial Porrúa, 1978). Nettie Lee Benson, "Texas as Viewed from Mexico, 1820–1834," Southwestern Historical Quarterly 90 (January 1987). The Constitution of Mexico, and of the State of Coahuila and Texas (New York: Ludwig and Tolefree, 1832). Hans Peter Nielsen Gammel, comp., Laws of Texas, 1822–1897 (10 vols., Austin: Gammel, 1898). Henderson K. Yoakum, History of Texas from Its First Settlement in 1685 to Its Annexation to the United States in 1846 (2 vols., New York: Redfield, 1855). Handbook of Texas Online, S. S. McKay, "CONSTITUTION OF COAHUILA AND TEXAS," accessed August 23, 2019. Licenses and Attributions CC LICENSED CONTENT, ORIGINAL Revision and Adaptation. Authored by: Kris S. Seago. License: CC BY: Attribution Revision and Adaptation: Constitution of Coahuila and Texas. Authored by: John Osterman. License: CC BY: Attribution	oercommons	2025-03-18T00:36:12.700735	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/66257/overview", "title": "Texas Government 2.0, The Texas State Constitution and the American Federal System", "author": null }
https://oercommons.org/courseware/lesson/66258/overview	Constitution of the Republic of Texas (1836) Overview Constitution of the Republic of Texas (1836) Learning Objectives By the end of this section, you will be able to: - Understand the Constitution of the Republic of Texas (1836)’s role in Texas history Introduction This section discusses Constitution of the Republic of Texas (1836)’s role in Texas history. Constitution of the Republic of Texas (1836) The Constitution of the Republic of Texas (1836), the first Anglo-American constitution to govern Texas, was drafted by a convention of fifty-nine delegates who assembled at Washington-on-the-Brazos on March 1, 1836. A constitution was adopted by the convention fifteen days later and ratified by a vote of the people of the republic on the first Monday in September 1836. The ever-present threat of attack by Mexican cavalry tended to stifle originality in the document. Almost of necessity the haste to complete their task led delegates to lift portions from the Constitution of the United States and from several contemporary state constitutions. The use of such models produced a document embodying some familiar features. Like the United States Constitution it was admirably brief (less than 6,500 words) and contained generous grants of power to state officials, especially the chief executive. Furthermore, great numbers of specific limitations and restrictions upon government often found in state constitutions of the time were avoided. Finally, the well-known words and phrases of older American constitutions were preserved, making understanding easier. Typical American features included a short preamble; separation of the powers of government into three branches- legislative, executive, and judicial; checks and balances; slavery; citizenship, with “Africans, the descendents of Africans, and Indians excepted”; a Bill of Rights; male suffrage; and method of amendment. The legislature was bicameral, the two houses being the Senate and the House of Representatives. The executive resembled the American presidency, and the four-tiered judiciary system comprised justice, county, district, and supreme courts, of which the district courts were the most important. Some of the constitution’s atypical provisions undoubtedly reflected Jacksonian ideas current in the states from which many delegates had come; fourteen, for example, came from Tennessee. Ministers and priests were declared ineligible to hold public office. Imprisonment for debt was abolished, and monopolies, primogeniture, and entailment were prohibited. Terms of office were short, ranging from one year for representatives to four years for some judges. Annual elections were required. Among the most important provisions adapted from Spanish- Mexican law were community property, homestead exemptions and protections, and debtor relief. Contrary to common-law practice in the American states, Texas courts were not separated into distinct courts of law and equity. The amending process was so complex that, although in the ten-year life span of the constitution several amendments were suggested, none was ever adopted. Amendments could be proposed in one session of Congress, referred to the next session for a second approval, and then submitted to a popular vote. Of nearly paramount importance at the time of adoption were provisions relating to land. The document sought in many ways to protect the rights of people in the unoccupied lands of the republic, lands that were the main attraction to the immigrants who had come to Texas. In its “Schedule,” for example, the constitution affirmed “that all laws now in force in Texas…shall remain in full force.” Later, in the “General Provisions,” a citizen who had not received his land grant was guaranteed “one league and one labor of land” if the head of a family; single men over seventeen years were assured of “the third part of one league of land”; and orphan children “whose parents were entitled to land” were declared eligible for all property rights of their deceased parents. The constitution also sought to void all “unjust and fraudulent claims.” Preference of the predominantly Anglo-American settlers for the legal system they had known “back in the states” is apparent in a provision that called for the introduction of the common law of England as early as practicable and declared it the rule to be used in deciding all criminal cases. Although the constitution of 1836 was a revolutionary document written and adopted in haste, it was a product of the social and economic conditions of the time as well as of the constitutional and legal heritage of Texas, the southern and western states, and the United States. Therefore, Anglo-Americans immigrating to the Republic of Texas found institutions of law and government in accord with their experience. Link to Learning More information on the Constitution of the Republic of Texas (1836) may be found at the Texas Constitutions 1824-1876 project of the Tarlton Law Library, Jamail Center for Legal Research at the University of Texas School of Law, the University of Texas at Austin. The project includes digitized images and searchable text versions of the constitutions. License and Attribution CC LICENSED CONTENT, ORIGINAL Revision and Adaptation. Authored by: Kris S. Seago. License: CC BY: Attribution	oercommons	2025-03-18T00:36:12.720957	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/66258/overview", "title": "Texas Government 2.0, The Texas State Constitution and the American Federal System", "author": null }
https://oercommons.org/courseware/lesson/66259/overview	Constitution of 1845 Overview Constitution of 1845 Learning Objectives By the end of this section, you will be able to: - Understand the Constitution of 1845’s role in Texas history Introduction This section discusses the Constitution of 1845’s role in Texas history. Constitution of 1845 The Constitution of 1845, which provided for the government of Texas as a state in the United States, was almost twice as long as the Constitution of the Republic of Texas. The framers, members of the Convention of 1845, drew heavily on the newly adopted Constitution of Louisiana and on the constitution drawn by the Convention of 1833 , but apparently used as a working model the Constitution of the republic for a general plan of government and bill of rights. The legislative department was composed of a Senate of from nineteen to thirty-three members and a House of Representatives from forty- five to ninety. Representatives, elected for two years, were required to have attained the age of twenty-one. Senators were elected for four years, one-half chosen biennially, all at least thirty years old. Legislators’ compensation was set at three dollars a day for each day of attendance and three dollars for each twenty-five miles of travel to and from the capital. All bills for raising revenue had to originate in the House of Representatives. Austin was made the capital until 1850, after which the people were to choose a permanent seat of government. A census was ordered for each eighth year, following which adjustment of the legislative membership was to be made. Regular sessions were biennial. Ministers of the Gospel were ineligible to be legislators. The governor’s term was two years, and he was made ineligible for more than four years in any period of six years. He was required to be a citizen and a resident of Texas for at least three years before his election and to be at least thirty years of age. He could appoint the attorney general, secretary of state, and supreme and district court judges, subject to confirmation by the Senate; but the comptroller and treasurer were elected biennially by a joint session of the legislature. The governor could convene the legislature and adjourn it in case of disagreement between the two houses and was commander-in-chief of the militia. He could grant pardons and reprieves. His veto could be overruled by two- thirds of both houses. The judiciary consisted of a Supreme Court, district courts, and such inferior courts as the legislature might establish, the judges of the higher courts being appointed by the governor for six-year terms. The Supreme Court was made up of three judges, any two of whom constituted a quorum. Supreme and district judges could be removed by the governor on address of two-thirds of both houses of the legislature for any cause that was not sufficient ground for impeachment. A district attorney for each district was elected by joint vote of both houses, to serve for two years. County officers were elected for two years by popular vote. The sheriff was not eligible to serve more than four years of any six. Trial by jury was extended to cases in equity as well as in civil and criminal law. The longest article of the constitution was Article VII, on General Provisions. Most of its thirty-seven sections were limitations on the legislature. One section forbade the holding of office by any citizen who had ever participated in a duel. Bank corporations were prohibited, and the legislature was forbidden to authorize individuals to issue bills, checks, promissory notes, or other paper to circulate as money. The state debt was limited to $100,000, except in case of war, insurrection, or invasion. Equal and uniform taxation was required; income and occupation taxes might be levied; each family was to be allowed an exemption of $250 on household goods. A noteworthy section made exempt from forced sale any family homestead, not to exceed 200 acres of land or city property not exceeding $2,000 in value; the owner, if a married man, could not sell or trade the homestead except with the consent of his wife. Section XIX recognized the separate ownership by married women of all real and personal property owned before marriage or acquired afterwards by gift or inheritance. Texas was a pioneer state in providing for homestead protection and for recognition of community property. In the article on education the legislature was directed to make suitable provision for support and maintenance of public schools, and 10 percent of the revenue from taxation was set aside as a Permanent School Fund. School lands were not to be sold for twenty years but could be leased, the income from the leases becoming a part of the Available School Fund. Land provisions of the Constitution of 1836 were reaffirmed, and the General Land Office was continued in operation. By a two-thirds vote of each house an amendment to the constitution could be proposed. If a majority of the voters approved the amendment and two-thirds of both houses of the next legislature ratified it, the measure became a part of the constitution. Only one amendment was ever made to the Constitution of 1845. It was approved on January 16, 1850, and provided for the election of state officials formerly appointed by the governor or by the legislature. The Constitution of 1845 has been the most popular of all Texas constitutions. Its straightforward, simple form prompted many national politicians, including Daniel Webster, to remark that the Texas constitution was the best of all of the state constitutions. Though some men, including Webster, argued against the annexation of Texas, the constitution was accepted by the United States on December 29, 1845. Link to Learning More information on the Constitution of Texas (1845) may be found at the Texas Constitutions 1824-1876 project of the Tarlton Law Library, Jamail Center for Legal Research at the University of Texas School of Law, the University of Texas at Austin. The project includes digitized images and searchable text versions of the constitutions. References and Further Reading Hans Peter Nielsen Gammel, comp., Laws of Texas, 1822–1897 (10 vols., Austin: Gammel, 1898). Annie Middleton, "The Texas Convention of 1845," Southwestern Historical Quarterly 25 (July 1921). John Sayles, The Constitutions of the State of Texas (1872; 4th ed., St. Paul, Minnesota: West, 1893). Vernon's Annotated Constitution of the State of Texas (Kansas City: Vernon Law Book Company, 1955). Handbook of Texas Online, S. S. McKay, "CONSTITUTION OF 1845," accessed August 23, 2019. License and Attribution CC LICENSED CONTENT, ORIGINAL Revision and Adaptation. Authored by: Kris S. Seago. License: CC BY: Attribution	oercommons	2025-03-18T00:36:12.743917	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/66259/overview", "title": "Texas Government 2.0, The Texas State Constitution and the American Federal System", "author": null }
https://oercommons.org/courseware/lesson/66260/overview	Constitution of 1861 Overview Constitution of 1861 Learning Objective By the end of this section, you will be able to: Understand the Constitution of 1861’s role in Texas history Introduction This sections dicusses the Constitution of 1861’s role in Texas history Constitution of 1861 After the Texas voters ratified secession from the Union on February 23, 1861, the Secession Convention reconvened. Convention delegates believed it their duty to direct the transition of Texas from a state in the United States to one of the Confederate States of America. As part of that duty, they amended the Constitution of 1845. In most instances, the wording of the older constitution was kept intact, but some changes were required to meet new circumstances. The words United States of America were replaced with Confederate States of America. Slavery and states’ rights were more directly defended. A clause providing for emancipation of slaves was eliminated, and the freeing of slaves was declared illegal. All current state officials were required to take an oath of loyalty to the Confederacy, and all existing laws not in conflict with the constitutions of Texas or the Confederate States were declared valid. Amending the constitution was also made easier. This constitution was as remarkable for what it did not do as for what it did. It did not legalize the resumption of the African slave trade, a move advocated by some leaders of the secession movement. It did not take an extreme position on the issue of states’ rights. It did not substantially change any important law. It was a conservative document partly designed to allay fears of the radical nature of the secessionists and to ease the transition of Texas into the Confederacy. . Link to Learning More information on the More information on the Constitution of the State of Texas (1861) may be found at the Texas Constitutions 1824-1876 project of the Tarlton Law Library, Jamail Center for Legal Research (http://tarlton.law.utexas.edu/) at the University of Texas School of Law (http://www.utexas.edu/law/), The University of Texas at Austin (http://www.utexas.edu/). The project includes digitized images and searchable text versions of the constitutions. References and Further Reading Walter L. Buenger, Secession and the Union in Texas (Austin: University of Texas Press, 1984). Handbook of Texas Online, Walter L. Buenger, "CONSTITUTION OF 1861" accessed August 23, 2019. License and Attribution CC LICENSED CONTENT, ORIGINAL Revision and Adaptation. Authored by: Kris S. Seago. License: CC BY: Attribution	oercommons	2025-03-18T00:36:12.764735	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/66260/overview", "title": "Texas Government 2.0, The Texas State Constitution and the American Federal System", "author": null }
https://oercommons.org/courseware/lesson/66261/overview	Constitution of 1866 Overview Constitution of 1866 Learning Objectives By the end of this section, you will be able to: - Understand the Constitution of 1866’s role in Texas history Introduction This section discusses the Constitution of 1866’s role in Texas history, Constitution of 1866 The Constitutional Convention of 1866, in addition to other actions in compliance with presidential Reconstruction, proposed a series of amendments to the fundamental law, which came to be known as the Constitution of 1866. The governor’s term was increased to four years and his salary from $3,000 to $4,000 a year. He was prohibited from serving more than eight years in any twelve-year period. For the first time the governor was given the line-item veto on appropriations. He was empowered to convene the legislature at some place other than the state capital should the capital become dangerous “by reason of disease or the public enemy.” The comptroller and treasurer were elected by the voters to hold office for four years. The Senate was set to number from nineteen to thirty-three members and the House from forty-five to ninety; legislators were required to be white men with a prior residence of five years in Texas. Terms of office were to remain the same as before, but salaries of legislators were raised from three dollars a day to eight dollars, and mileage was increased to eight dollars for each twenty-five miles. A census and reapportionment, based on the number of white citizens, was to be held every ten years. The Supreme Court was increased from three judges to five, with a term of office of ten years and a salary of $4,500 a year. The chief justice was to be selected by the five justices on the court from their own number. District judges were elected for eight years at salaries of $3,500 a year. The attorney general was elected for four years with a salary of $3,000. Jurisdiction of all courts was specified in detail. A change was made in the method of constitutional revision in that a three-fourths majority of each house of the legislature was required to call a convention to propose changes in the constitution, and the approval of the governor was required. Elaborate plans were made for a system of internal improvements and for a system of public education to be directed by a superintendent of public instruction. Separate schools were ordered organized for black children. Lands were set aside for the support of public schools, for the establishment and endowment of a university, and for the support of eleemosynary institutions. The legislature was empowered to levy a school tax. An election in June ratified the proposed amendments by a vote of 28,119 to 23,400; the small majority was attributed to dissatisfaction of many citizens with the increase in officials’ salaries. Link to Learning More information on the Constitution of the State of Texas (1866) may be found at the Texas Constitutions 1824-1876 project of the Tarlton Law Library, Jamail Center for Legal Research at the University of Texas School of Law, the University of Texas at Austin. The project includes digitized images and searchable text versions of the constitutions. References and Further Reading Hans Peter Nielsen Gammel, comp., Laws of Texas, 1822–1897 (10 vols., Austin: Gammel, 1898). Charles W. Ramsdell, Reconstruction in Texas (New York: Columbia University Press, 1910; rpt., Austin: Texas State Historical Association, 1970). John Sayles, The Constitutions of the State of Texas (1872; 4th ed., St. Paul, Minnesota: West, 1893). Vernon's Annotated Constitution of the State of Texas (Kansas City: Vernon Law Book Company, 1955). Handbook of Texas Online, S. S. McKay, "CONSTITUTION OF 1866," accessed August 23, 2019. License and Attribution CC LICENSED CONTENT, ORIGINAL Revision and Adaptation. Authored by: Kris S. Seago. License: CC BY: Attribution	oercommons	2025-03-18T00:36:12.788427	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/66261/overview", "title": "Texas Government 2.0, The Texas State Constitution and the American Federal System", "author": null }
https://oercommons.org/courseware/lesson/66262/overview	Constitution of 1869 Overview Constitution of 1869 Learning Objectives By the end of this section, you will be able to: - Understand the Constitution of 1869’s role in Texas history Introduction This section discusses the Constitution of 1869’s role in Texas history. Constitution of 1869 The Constitutional Convention of 1868–69, called in compliance with the Congressional Reconstruction Acts of 1867, broke up without completing a constitution. Its work was gathered up under orders of the military officers, published as the Constitution of 1869, and accepted by the electorate. The preface of the bill of rights of the new document reflected the sentiments of its makers in its condemnation of nullification and secession. The Constitution of the United States was declared to be the supreme law. Slavery was forbidden, and the equality of all persons before the law was recognized. The House of Representatives was set at ninety members and the Senate at thirty. One-third of the senators were chosen biennially, and their term of office was increased from four to six years. Sessions were held annually. The salary of the governor was increased to five thousand dollars a year. The attorney general and secretary of state were appointed by the governor; other officials were elected by the voters. The Supreme Court was reduced from five to three judges and the term reduced to nine years, one new judge to take office every third year. All judicial offices were appointive. All elections were held at the county seat and had to continue through four consecutive days. A poll tax was authorized; its receipts, along with the income from the school lands and one- fourth of the annual taxes, went to the school fund. The office of state superintendent of public instruction was continued, and school attendance was made compulsory. An immigration bureau was authorized; county and local government was outlined in detail; blacks were included as voters; homesteads were to be given gratis to actual settlers; mineral rights were released to landowners; the legislature was forbidden to grant divorces or authorize lotteries; all qualified voters were to be qualified jurors; and the legislature was permitted to prohibit the sale of liquor near colleges, except at county seats. Permission for the legislature to call a new constitutional convention was withheld, but the amendment procedure was unchanged. This constitution, formulated under pressure from Washington, was disputed by a large constituency of Texans. Many felt that it was one of the longest and most unsatisfactory of Texas constitutions. Over the years, however, alternate interpretations have pointed out some positive goals that delegates tried to achieve such as the establishment of a common school system, centralized law enforcement, and broader civil rights. The programs, implemented by greater taxation, drew heavy criticism from many citizens, and though it may have laid some of the foundations for a strong educational system, as well as strengthening the branches of state government, the Constitution of 1869 sparked much controversy among political and social factions in Texas. Links to Learning More information on the Constitution of the State of Texas (1869) may be found at the Texas Constitutions 1824-1876 project of the Tarlton Law Library, Jamail Center for Legal Research at the University of Texas School of Law, the University of Texas at Austin. The project includes digitized images and searchable text versions of the constitutions. References and Further Reading Hans Peter Nielsen Gammel, comp., Laws of Texas, 1822–1897 (10vols., Austin: Gammel, 1898). Charles W. Ramsdell, Reconstruction in Texas (New York: Columbia University Press, 1910; rpt., Austin: Texas State Historical Association, 1970). Betty Jeffus Sandlin, The Texas Constitutional Convention of 1868–1869 (Ph.D. dissertation, Texas Tech University, 1970). John Sayles, The Constitutions of the State of Texas (2d ed., St. Louis: Gilbert, 1884; 4th ed., St. Paul, Minnesota: West, 1893). Handbook of Texas Online, S. S. McKay, "CONSTITUTION OF 1869," accessed August 23, 2019. Licenses and Attributions CC LICENSED CONTENT, ORIGINAL Revision and Adaptation. Authored by: Kris S. Seago. License: CC BY: Attribution	oercommons	2025-03-18T00:36:12.811682	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/66262/overview", "title": "Texas Government 2.0, The Texas State Constitution and the American Federal System", "author": null }
https://oercommons.org/courseware/lesson/66263/overview	The Texas Constitution of 1876 Overview The Texas Constitution of 1876 Learning Objectives By the end of this section, you will be able to: - Understand the Constitution of 1876’s role in Texas Introduction This section discusses the Constitution of 1876’s role in Texas. The Texas Constitution of 1876 Texas Democrats gained control of Congress in 1873 and decided it was time to draft a new constitution for Texas. The Texas Constitutional Convention of 1875 met in Austin with the purpose of replacing the Constitution of 1869; it was believed that the new constitution should restrict the state government and hand the power back to the people. Some examples of how the government was restricted were: - Legislative sessions moved from annual to biennial sessions - Creation of a plural executive - Mandated a balanced budget - State Judges would be elected by the people - The people would vote on the ratification of amendments The structure of the current constitution of Texas (Constitution of 1876) is a Preamble, 17 Articles, and 491 Amendments (Since 2015)3. The Texas Constitution does not contain a “necessary and proper clause” like the U.S. Constitution, therefore making it the second-longest state constitution in America (2nd only to Alabama’s). You Might Be Wondering... Why is the Texas Constitution So Dang Long? Find out from TexPlainer at the Texas Tribune. \| Table 2.2 Articles of the Texas Constitution of 1876 Articles \| Description \| Article 1: Bill of Rights \| The Texas Constitution's Bill of Rights Similar civil liberties and civil rights as in the U.S. Constitution’s Bill of Rights \| Article 2: The Powers of the Government \| Establishes three branches of government with separation of powers \| Article 3: Legislative Department \| Specifics about the Texas Legislature \| Article 4: Executive Department \| Specifics about the plural executive \| Article 5: Judicial Department \| Specifics about the Texas Judicial system \| Article 6: Suffrage \| Forbids the following from voting: -any non-US citizen, -any non-registered Texas voter, -any convicted felon who has not completed their sentence, or -any person deemed mentally incompetent by the courts. \| Article 7: Education \| Mandates an "efficient" free public school system. Established the Permanent School Fund \| Article 8: Taxation and Revenue \| Places limits on the raising and spending of public funds \| Article 9: Counties \| Authorizes the Texas Legislature to create county governments \| Article 10: Railroads \| Regulates the railroad system \| Article 11: Municipal Corporations \| Specifics regarding local governments, including empowering them to tax, and how to charter cities \| Article 12: Private Corporations \| Specifics regarding public businesses, including how they would be regulated \| Article 13: Spanish and Mexican Land Titles \| Specifics on which land with previous claims would become state property \| Article 14: Public Lands and Land Office \| Established the Land Office which regulated land titles \| Article 15: Impeachment \| Specifics on how to remove a public official from office \| Article 16: General Provisions \| Miscellaneous regulations, ie., forbidding the legislature from printing money, forbidding U.S. public officials from holding a state office \| Article 17: Mode of Amending the Constitution of this State \| 2/3rds proposal from the legislature Registered voters vote on approval. With a majority vote, the amendment is ratified. \| Link to Learning More information on the Constitution of the State of Texas (1876) may be found at the Texas Constitutions 1824-1876 project of the Tarlton Law Library, Jamail Center for Legal Research at the University of Texas School of Law, the University of Texas at Austin. The project includes digitized images and searchable text versions of the constitutions. References and Further Reading Texans to decide whether to update their aging constitution. Fort Worth Star-Telegram. Anna M. Tinsley. October 8, 2018. Texas State Library and Archives Commission.The 1870s: The Constitutional Convention of 1875 Licensing and Attribution CC LICENSED CONTENT, ORIGINAL Revision and Adaptation. Authored by: Kris S. Seago. License: CC BY: Attribution	oercommons	2025-03-18T00:36:12.847742	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/66263/overview", "title": "Texas Government 2.0, The Texas State Constitution and the American Federal System", "author": null }
https://oercommons.org/courseware/lesson/66264/overview	Texas State and Local Politics Overview Texas State and Local Politics Learning Objectives By the end of this section, you will be able to: - Describe how state and local political systems in Texas relate to the federal government Introduction This section discusses how state and local political systems in Texas interact with the federal government. How Do State and Local Political Systems Relate to the Federal Government? As you probably have learned by now, the United States operates under a federal system of government. That means there is a national government that works along with the 50 states governments in successfully managing the nation as a whole and in parts. This relationship between the national government and the states was set up in the U.S. Constitution without specifically mentioning the word federalism. Furthermore, Article VI of the U.S. Constitution tells us that the national government is supreme over the states. This simply means that the national government will ultimately have the final say in matters of conflict between the states and between the states and the national government. Article IV tells us that there will be comity among the states. This means that the states have to get along with each other by respecting their laws and people. In Constitutional law, the Comity Clause refers to Article IV, § 2, Clause 2 of the U.S. Constitution (also known as the Privileges and Immunities Clause), which ensures that “The Citizens of each State shall be entitled to all Privileges and Immunities of Citizens in the several States.” The result of all of this is that the state governments and the national government are all going to get along. That national government will take care of the affairs of the nation as a whole according to the powers set out in Article 1, Section 8, and the states are going to take care of their affairs as understood by the Tenth Amendment. The question now concerns local governments. Since the U.S. Constitution is silent on local government, it is understood that states will have power over local governments. This arrangement is referred to as a unitary government. In other words, the state government has the central authority and power over all local governments within the state even though local governments may have some degree of autonomy. For example, a city can make its own laws and enforce them as long as they do not violate the state constitution. In Texas, there are cities, counties, and special districts. You will learn more about these in another chapter. The key thing to remember here is that we don't exist in a vacuum. In other words, the policies of the national government regarding trade can impact states, and the policies of states can impact cities. Since this nation of ours is designed as a system, all of the parts have to work together. Often times that does not happen. The positive and negative actions of the national government tend to roll downhill and take the states and local governments with them. For example, proponents for enforcement of federal immigration laws argue that lack of enforcement creates 1) problems for states, which then have to provide social welfare services to illegal immigrants, and 2) problems for local governments, who have to deal with crime and education. Each level or layer of government has its own constituencies. This means that the Houston has residents that are most concerned with what goes on in Houston; however, they are not at all concerned about what goes on in Dallas. City officials of each community must respond to the needs of their constituents. Residents of Texas probably don't care much what people do or think in Maine. Therefore, the elected officials in Texas must consider the needs of residents of Texas. A member of Congress should be concerned with the affairs of their state and district; however, districts might cut through multiple local governments and not all people in the state see the needs of the state the same way. As a result, members of Congress may have to think about what is good for the nation as a whole rather than its parts. The product of all of these elected officials responding to the needs of their respective constituencies produces the policies we see today. That is one of the reasons there is so much political conflict. The good news is that compromise often comes from the conflict. That means we don't have to go to war over our differences and we can debate them in a public forum. The best ideas can sometimes win out over bad ideas. Regular elections determine which ideas will get implemented. References and Further Reading Cornell Law School: Legal Information Institute. Comity. Accessed August 25, 2019. Licenses and Attributions CC LICENSED CONTENT, ORIGINAL Revision and Adaptation: Authored by: John Osterman. License: CC BY: Attribution	oercommons	2025-03-18T00:36:12.868309	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/66264/overview", "title": "Texas Government 2.0, The Texas State Constitution and the American Federal System", "author": null }
https://oercommons.org/courseware/lesson/66265/overview	The Evolution of Federalism Overview The Evolution of Federalism Learning Objectives By the end of this section, you will be able to: - Analyze the state and federal powers in a constitutional context Introduction This section discusses how our federal system has evolved over time. The Evolution of Federalism Federalism is a system of government that creates two relatively autonomous levels of government, each possessing authority granted to them by the national constitution. Federal systems like the one in the United States are different from unitary systems, which concentrate authority in the national government, and from confederations, which concentrate authority in subnational governments. The Constitution sketches a federal framework that aims to balance the forces of decentralized and centralized governance in general terms; it does not flesh out standard operating procedures that say precisely how the states and federal governments are to handle all policy contingencies imaginable. Therefore, officials at the state and national levels have had some room to maneuver as they operate within the Constitution’s federal design. This has led to changes in the configuration of federalism over time, changes corresponding to different historical phases that capture distinct balances between state and federal authority. The U.S. Constitution allocates powers to the states and federal government, structures the relationship between these two levels of government, and guides state-to-state relationships. Federal, state, and local governments rely on different sources of revenue to enable them to fulfill their public responsibilities. Cooperative Federalism The Great Depression of the 1930s brought economic hardships the nation had never witnessed before. Between 1929 and 1933, the national unemployment rate reached 25 percent, industrial output dropped by half, stock market assets lost more than half their value, thousands of banks went out of business, and the gross domestic product shrunk by one- quarter. Given the magnitude of the economic depression, there was pressure on the national government to coordinate a robust national response along with the states. Cooperative federalism was born of necessity and lasted well into the twentieth century as the national and state governments each found it beneficial. Under this model, both levels of government coordinated their actions to solve national problems, such as the Great Depression and the civil rights struggle of the following decades. In contrast to dual federalism, it erodes the jurisdictional boundaries between the states and national government, leading to a blending of layers as in a marble cake. The era of cooperative federalism contributed to the gradual incursion of national authority into the jurisdictional domain of the states, as well as the expansion of the national government’s power in concurrent policy areas. The New Deal programs President Franklin D. Roosevelt proposed as a means to tackle the Great Depression ran afoul of the dual-federalism mindset of the justices on the Supreme Court in the 1930s. The court struck down key pillars of the New Deal—the National Industrial Recovery Act and the Agricultural Adjustment Act, for example—on the grounds that the federal government was operating in matters that were within the purview of the states. The court’s obstructionist position infuriated Roosevelt, leading him in 1937 to propose a court-packing plan that would add one new justice for each one over the age of seventy, thus allowing the president to make a maximum of six new appointments. Before Congress took action on the proposal, the Supreme Court began leaning in support of the New Deal as Chief Justice Charles, Evans Hughes, and Justice Owen Roberts changed their view on federalism. In National Labor Relations Board (NLRB) v. Jones and Laughlin Steel, for instance, the Supreme Court ruled the National Labor Relations Act of 1935 constitutional, asserting that Congress can use its authority under the commerce clause to regulate both manufacturing activities and labor-management relations. The New Deal changed the relationship Americans had with the national government. Before the Great Depression, the government offered little in terms of financial aid, social benefits, and economic rights. After the New Deal, it provided old-age pensions (Social Security), unemployment insurance, agricultural subsidies, protections for organizing in the workplace, and a variety of other public services created during Roosevelt’s administration. In the 1960s, President Lyndon Johnson’s administration expanded the national government’s role in society even more. Medicaid (which provides medical assistance to the indigent), Medicare (which provides health insurance to the elderly and disabled), and school nutrition programs were created. The Elementary and Secondary Education Act (1965), the Higher Education Act (1965), and the Head Start preschool program (1965) were established to expand educational opportunities and equality. The Clean Air Act (1965), the Highway Safety Act (1966), and the Fair Packaging and Labeling Act (1966) promoted environmental and consumer protection. Finally, laws were passed to promote urban renewal, public housing development, and affordable housing. In addition to these Great Society programs, the Civil Rights Act (1964) and the Voting Rights Act (1965) gave the federal government effective tools to promote civil rights equality across the country. While the era of cooperative federalism witnessed a broadening of federal powers in concurrent and state policy domains, it is also the era of a deepening coordination between the states and the federal government in Washington. Nowhere is this clearer than with respect to the social welfare and social insurance programs created during the New Deal and Great Society eras, most of which are administered by both state and federal authorities and are jointly funded. The Social Security Act of 1935, which created federal subsidies for state-administered programs for the elderly; people with handicaps; dependent mothers; and children, gave state and local officials wide discretion over eligibility and benefit levels. The unemployment insurance program, also created by the Social Security Act, requires states to provide jobless benefits, but it allows them significant latitude to decide the level of tax to impose on businesses in order to fund the program as well as the duration and replacement rate of unemployment benefits. A similar multilevel division of labor governs Medicaid and Children’s Health Insurance. Thus, the era of cooperative federalism left two lasting attributes on federalism in the United States. First, a nationalization of politics emerged as a result of federal legislative activism aimed at addressing national problems such as marketplace inefficiencies, social and political inequality, and poverty. The nationalization process expanded the size of the federal administrative apparatus and increased the flow of federal grants to state and local authorities, which have helped offset the financial costs of maintaining a host of New Deal- and Great Society–era programs. The second lasting attribute is the flexibility that states and local authorities were given in the implementation of federal social welfare programs. One consequence of administrative flexibility, however, is that it has led to cross-state differences in the levels of benefits and coverage. The Struggle Between National Power and State Power As George Washington’s secretary of the treasury from 1789 to 1795, Alexander Hamilton championed legislative efforts to create a publicly chartered bank. For Hamilton, the establishment of the Bank of the United States was fully within Congress’s authority, and he hoped the bank would foster economic development, print and circulate paper money, and provide loans to the government. Although Thomas Jefferson, Washington’s secretary of state, staunchly opposed Hamilton’s plan on the constitutional grounds that the national government had no authority to create such an instrument, Hamilton managed to convince the reluctant president to sign the legislation. When the bank’s charter expired in 1811, Jeffersonian Democratic-Republicans prevailed in blocking its renewal. However, the fiscal hardships that plagued the government during the War of 1812, coupled with the fragility of the country’s financial system, convinced Congress and then-president James Madison to create the Second Bank of the United States in 1816. Many states rejected the Second Bank, arguing that the national government was infringing upon the states’ constitutional jurisdiction. A political showdown between Maryland and the national government emerged when James McCulloch, an agent for the Baltimore branch of the Second Bank, refused to pay a tax that Maryland had imposed on all out-of-state chartered banks. The standoff raised two constitutional questions: Did Congress have the authority to charter a national bank? Were states allowed to tax federal property? In McCulloch v. Maryland, Chief Justice John Marshall argued that Congress could create a national bank even though the Constitution did not expressly authorize it. Under the necessary and proper clause of Article I, Section 8, the Supreme Court asserted that Congress could establish “all means which are appropriate” to fulfill “the legitimate ends” of the Constitution. In other words, the bank was an appropriate instrument that enabled the national government to carry out several of its enumerated powers, such as regulating interstate commerce, collecting taxes, and borrowing money This ruling established the doctrine of implied powers, granting Congress a vast source of discretionary power to achieve its constitutional responsibilities. The Supreme Court also sided with the federal government on the issue of whether states could tax federal property. Under the supremacy clause of Article VI, legitimate national laws trump conflicting state laws. As the court observed, “the government of the Union, though limited in its powers, is supreme within its sphere of action and its laws, when made in pursuance of the constitution, form the supreme law of the land.” Maryland’s action violated national supremacy because “the power to tax is the power to destroy.” This second ruling established the principle of national supremacy, which prohibits states from meddling in the lawful activities of the national government. Defining the scope of national power was the subject of another landmark Supreme Court decision in 1824. In Gibbons v. Ogden, the court had to interpret the commerce clause of Article I, Section 8; specifically, it had to determine whether the federal government had the sole authority to regulate the licensing of steamboats operating between New York and New Jersey. Aaron Ogden, who had obtained an exclusive license from New York State to operate steamboat ferries between New York City and New Jersey, sued Thomas Gibbons, who was operating ferries along the same route under a coasting license issued by the federal government. Gibbons lost in New York state courts and appealed. Chief Justice Marshall delivered a two-part ruling in favor of Gibbons that strengthened the power of the national government. First, interstate commerce was interpreted broadly to mean “commercial intercourse” among states, thus allowing Congress to regulate navigation. Second, because the federal Licensing Act of 1793, which regulated coastal commerce, was a constitutional exercise of Congress’s authority under the commerce clause, federal law trumped the New York State license-monopoly law that had granted Ogden an exclusive steamboat operating license. As Marshall pointed out, “the acts of New York must yield to the law of Congress.” Various states railed against the nationalization of power that had been going on since the late 1700s. When President John Adams signed the Sedition Act in 1798, which made it a crime to speak openly against the government, the Kentucky and Virginia legislatures passed resolutions declaring the act null on the grounds that they retained the discretion to follow national laws. In effect, these resolutions articulated the legal reasoning underpinning the doctrine of nullification—that states had the right to reject national laws they deemed unconstitutional. A nullification crisis emerged in the 1830s over President Andrew Jackson’s tariff acts of 1828 and 1832. Led by John Calhoun, President Jackson’s vice president, nullifiers argued that high tariffs on imported goods benefited northern manufacturing interests while disadvantaging economies in the South. South Carolina passed an Ordinance of Nullification declaring both tariff acts null and void and threatened to leave the Union. The federal government responded by enacting the Force Bill in 1833, authorizing President Jackson to use military force against states that challenged federal tariff laws. The prospect of military action coupled with the passage of the Compromise Tariff Act of 1833 (which lowered tariffs over time) led South Carolina to back off, ending the nullification crisis. The ultimate showdown between national and state authority came during the Civil War. Prior to the conflict, in Dred Scott v. Sandford, the Supreme Court ruled that the national government lacked the authority to ban slavery in the territories. But the election of President Abraham Lincoln in 1860 led eleven southern states to secede from the United States because they believed the new president would challenge the institution of slavery. What was initially a conflict to preserve the Union became a conflict to end slavery when Lincoln issued the Emancipation Proclamation in 1863, freeing all slaves in the rebellious states. The defeat of the South had a huge impact on the balance of power between the states and the national government in two important ways. First, the Union victory put an end to the right of states to secede and to challenge legitimate national laws. Second, Congress imposed several conditions for readmitting former Confederate states into the Union; among them was ratification of the Fourteenth and Fifteenth Amendments. In sum, after the Civil War the power balance shifted toward the national government, a movement that had begun several decades before with McCulloch v. Maryland (1819) and Gibbons v. Odgen (1824). The period between 1819 and the 1860s demonstrated that the national government sought to establish its role within the newly created federal design, which in turn often provoked the states to resist as they sought to protect their interests. With the exception of the Civil War, the Supreme Court settled the power struggles between the states and national government. From a historical perspective, the national supremacy principle introduced during this period did not so much narrow the states’ scope of constitutional authority as restrict their encroachment on national powers. Dual Federalism The late 1870s ushered in a new phase in the evolution of U.S. federalism. Under dual federalism, the states and national government exercise exclusive authority in distinctly delineated spheres of jurisdiction. Like the layers of a cake, the levels of government do not blend with one another but rather are clearly defined. Two factors contributed to the emergence of this conception of federalism. First, several Supreme Court rulings blocked attempts by both state and federal governments to step outside their jurisdictional boundaries. Second, the prevailing economic philosophy at the time loathed government interference in the process of industrial development. Industrialization changed the socio-economic landscape of the United States. One of its adverse effects was the concentration of market power. Because there was no national regulatory supervision to ensure fairness in market practices, collusive behavior among powerful firms emerged in several industries. To curtail widespread anti-competitive practices in the railroad industry, Congress passed the Interstate Commerce Act in 1887, which created the Interstate Commerce Commission. Three years later, national regulatory capacity was broadened by the Sherman Antitrust Act of 1890, which made it illegal to monopolize or attempt to monopolize and conspire in restraining commerce. In the early stages of industrial capitalism, federal regulations were focused for the most part on promoting market competition rather than on addressing the social dislocations resulting from market operations, something the government began to tackle in the 1930s. The late 1870s ushered in a new phase in the evolution of U.S. federalism. Under dual federalism, the states and national government exercise exclusive authority in distinctly delineated spheres of jurisdiction. Like the layers of a cake, the levels of government do not blend with one another but rather are clearly defined. Two factors contributed to the emergence of this conception of federalism. First, several Supreme Court rulings blocked attempts by both state and federal governments to step outside their jurisdictional boundaries. Second, the prevailing economic philosophy at the time loathed government interference in the process of industrial development. Industrialization changed the socio-economic landscape of the United States. One of its adverse effects was the concentration of market power. Because there was no national regulatory supervision to ensure fairness in market practices, collusive behavior among powerful firms emerged in several industries. The case came about when the government, using its regulatory power under the Sherman Act, attempted to override American Sugar’s purchase of four sugar refineries, which would give the company a commanding share of the industry. Distinguishing between commerce among states and the production of goods, the court argued that the national government’s regulatory authority applied only to commercial activities. If manufacturing activities fell within the purview of the commerce clause of the Constitution, then “comparatively little of business operations would be left for state control,” the court argued. In the late 1800s, some states attempted to regulate working conditions. For example, New York State passed the Bakeshop Act in 1897, which prohibited bakery employees from working more than sixty hours in a week. In Lochner v. New York, the Supreme Court ruled this state regulation that capped work hours unconstitutional, on the grounds that it violated the due process clause of the Fourteenth Amendment. In other words, the right to sell and buy labor is a “liberty of the individual” safeguarded by the Constitution, the court asserted. The federal government also took up the issue of working conditions, but that case resulted in the same outcome as in the Lochner case. New Federalism During the administrations of Presidents Richard Nixon (1969–1974) and Ronald Reagan (1981–1989), attempts were made to reverse the process of nationalization—that is, to restore states’ prominence in policy areas into which the federal government had moved in the past. New federalism is premised on the idea that the decentralization of policies enhances administrative efficiency, reduces overall public spending, and improves policy outcomes. During Nixon’s administration, general revenue sharing programs were created that distributed funds to the state and local governments with minimal restrictions on how the money was spent. The election of Ronald Reagan heralded the advent of a “devolution revolution” in U.S. federalism, in which the president pledged to return authority to the states according to the Constitution. In the Omnibus Budget Reconciliation Act of 1981, congressional leaders together with President Reagan consolidated numerous federal grant programs related to social welfare and reformulated them in order to give state and local administrators greater discretion in using federal funds. However, Reagan’s track record in promoting new federalism was inconsistent. This was partly due to the fact that the president’s devolution agenda met some opposition from Democrats in Congress, moderate Republicans, and interest groups, preventing him from making further advances on that front. For example, his efforts to completely devolve Aid to Families With Dependent Children (a New Deal-era program) and food stamps (a Great Society-era program) to the states were rejected by members of Congress, who feared states would underfund both programs, and by members of the National Governors’ Association, who believed the proposal would be too costly for states. Reagan terminated general revenue sharing in 1986. Several Supreme Court rulings also promoted new federalism by hemming in the scope of the national government’s power, especially under the commerce clause. For example, in United States v. Lopez, the court struck down the Gun-Free School Zones Act of 1990, which banned gun possession in school zones. It argued that the regulation in question did not “substantively affect interstate commerce.” The ruling ended a nearly sixty-year period in which the court had used a broad interpretation of the commerce clause that by the 1960s allowed it to regulate numerous local commercial activities. However, many would say that the years since the 9/11 attacks have swung the pendulum back in the direction of central federal power. The creation of the Department of Homeland Security federalized disaster response power in Washington, and the Transportation Security Administration was created to federalize airport security. Broad new federal policies and mandates have also been carried out in the form of the Faith-Based Initiative and No Child Left Behind (during the George W. Bush administration) and the Affordable Care Act (during Barack Obama’s administration) Cooperative Federalism Versus New Federalism Morton Grodzins coined the cake analogy of federalism in the 1950s while conducting research on the evolution of American federalism. Until then most scholars had thought of federalism as a layer cake, but according to Grodzins the 1930s ushered in “marble-cake federalism”: “The American form of government is often, but erroneously, symbolized by a three-layer cake. A far more accurate image is the rainbow or marble cake, characterized by an inseparable mingling of differently colored ingredients, the colors appearing in vertical and diagonal strands, and unexpected whirls. As colors are mixed in the marble cake, so functions are mixed in the American federal system.” Cooperative federalism has several merits: Because state and local governments have varying fiscal capacities, the national government’s involvement in state activities such as education, health, and social welfare is necessary to ensure some degree of uniformity in the provision of public services to citizens in richer and poorer states. The problem of collective action, which dissuades state and local authorities from raising regulatory standards for fear they will be disadvantaged as others lower theirs, is resolved by requiring state and local authorities to meet minimum federal standards (e.g., minimum wage and air quality). Federal assistance is necessary to ensure state and local programs (e.g., water and air pollution controls) that generate positive externalities are maintained. For example, one state’s environmental regulations impose higher fuel prices on its residents, but the externality of the cleaner air they produce benefits neighboring states. Without the federal government’s support, this state and others like it would underfund such programs. New federalism has advantages as well: Because there are economic, demographic, social, and geographical differences among states, one-size-fits-all features of federal laws are suboptimal. Decentralization accommodates the diversity that exists across states. By virtue of being closer to citizens, state and local authorities are better than federal agencies at discerning the public’s needs. Decentralized federalism fosters a marketplace of innovative policy ideas as states compete against each other to minimize administrative costs and maximize policy output. Federalism in the United States has gone through several phases of evolution during which the relationship between the federal and state governments has varied. In the era of dual federalism, both levels of government stayed within their own jurisdictional spheres. During the era of cooperative federalism, the federal government became active in policy areas previously handled by the states. The 1970s ushered in an era of new federalism and attempts to decentralize policy management. References and Further Reading The Lehrman Institute. “The Founding Trio: Washington, Hamilton and Jefferson” McCulloch v. Maryland, 17 U.S. 316 (1819). Gibbons v. Ogden, 22 U.S. 1 (1824). Gibbons v. Ogden, 22 U.S. 1 (1824). W. Kirk Wood. 2008. Nullification, A Constitutional History, 1776–1833. Lanham, MD: University Press of America. Dred Scott v. Sandford, 60 U.S. 393 (1857). Joseph R. Marbach, Troy E. Smith, and Ellis Katz. 2005. Federalism in America: An Encyclopedia. Westport, CT: Greenwood Publishing. Marc Allen Eisner. 2014. The American Political Economy: Institutional Evolution of Market and State. New York: Routledge. Eisner, The American Political Economy; Stephen Skowronek. 1982. Building a New American State: The Expansion of National Administrative Capacities, 1877– 1920. Cambridge, MA: Cambridge University Press. United States v. E. C. Knight, 156 U.S. 1 (1895). Lochner v. New York, 198 U.S. 45 (1905). Hammer v. Dagenhart, 247 U.S. 251 (1918). Nicholas Crafts and Peter Fearon. 2010. “Lessons from the 1930s Great Depression,” Oxford Review of Economic Policy 26: 286–287; Gene Smiley. “The Concise Encyclopedia of Economics: Great Depression” Marbach et al, Federalism in America: An Encyclopedia. ↵ Jeff Shesol. 2010. Supreme Power: Franklin Roosevelt vs. The Supreme Court. New York: W. W. Norton. National Labor Relations Board (NLRB) v. Jones & Laughlin Steel, 301 U.S. 1 (1937). Lawrence R. Jacobs and Theda Skocpol. 2014. “Progressive Federalism and the Contested Implemented of Obama’s Health Reform,” In The Politics of Major Policy Reform in Postwar America, eds. Jeffrey A. Jenkins and Sidney M. Milkis. New York: Cambridge University Press. R. Kent Weaver. 2000. Ending Welfare as We Know It. Washington, DC: The Brookings Institution. Dilger, “Federal Grants to State and Local Governments,” 30–31. United States v. Lopez, 514 U.S. 549 (1995). See Printz v. The United States, 521 U.S. 898 (1997). Morton Grodzins. 2004. “The Federal System.” In American Government Readings and Cases, ed. P. Woll. New York: Pearson Longman, 74–78. Licensing and Attribution CC LICENSED CONTENT, ORIGINAL Revision and Adaptation. Authored by: Daniel M. Regalado. License: CC BY: Attribution CC LICENSED CONTENT, SHARED PREVIOUSLY American Government. Authored by: OpenStax. Provided by: OpenStax; Rice University. Located at: http://cnx.org/contents/5bcc0e59-7345- 421d-8507-a1e4608685e8@18.11 License: CC BY: Attribution License Terms: Download for free at http://cnx.org/contents/5bcc0e59-7345-421d-8507-a1e4608685e8@18.11.	oercommons	2025-03-18T00:36:12.913272	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/66265/overview", "title": "Texas Government 2.0, The Texas State Constitution and the American Federal System", "author": null }
https://oercommons.org/courseware/lesson/66266/overview	Federalism: A Division of Powers Overview Federalism: A Division of Powers Learning Objective By the end of this section, you will be able to: - Explain how the separation of powers and checks and balances function in practice in Texas Introduction: Separation of Powers Modern democracies divide governmental power in two general ways; some, like the United States, use a combination of both structures. The first and more common mechanism shares power among three branches of government—the legislature, the executive, and the judiciary. The second, federalism, apportions power between two levels of government: national and subnational. In the United States, the term federal government refers to the government at the national level, while the term states refers to governments at the subnational level. Federalism Defined and Contrasted Federalism is an institutional arrangement that creates two relatively autonomous levels of government, each possessing the capacity to act directly on behalf of the people with the authority granted to it by the national constitution. Although today’s federal systems vary in design, five structural characteristics are common to the United States and other federal systems around the world, including Germany and Mexico. First, all federal systems establish two levels of government, with both levels being elected by the people and each level assigned different functions. The national government is responsible for handling matters that affect the country as a whole, for example, defending the nation against foreign threats and promoting national economic prosperity. Subnational, or state governments, are responsible for matters that lie within their regions, which include ensuring the well-being of their people by administering education, health care, public safety, and other public services. By definition, a system like this requires that different levels of government cooperate, because the institutions at each level form an interacting network. In the U.S. federal system, all national matters are handled by the federal government, which is led by the president and members of Congress, all of whom are elected by voters across the country. All matters at the subnational level are the responsibility of the fifty states, each headed by an elected governor and legislature. Thus, there is a separation of functions between the federal and state governments, and voters choose the leader at each level. While each level of government is somewhat independent of the others, a great deal of interaction occurs among them. In fact, the ability of the federal and state governments to achieve their objectives often depends on the cooperation of the other level of government. For example, the federal government’s efforts to ensure homeland security are bolstered by the involvement of law enforcement agents working at local and state levels. On the other hand, the ability of states to provide their residents with public education and health care is enhanced by the federal government’s financial assistance. The second characteristic common to all federal systems is a written national constitution that cannot be changed without the substantial consent of subnational governments. In the American federal system, the twenty-seven amendments added to the Constitution since its adoption were the result of an arduous process that required approval by two-thirds of both houses of Congress and three-fourths of the states. The main advantage of this supermajority requirement is that no changes to the Constitution can occur unless there is broad support within Congress and among states. The potential drawback is that numerous national amendment initiatives—such as the Equal Rights Amendment (ERA), which aims to guarantee equal rights regardless of sex—have failed because they cannot garner sufficient consent among members of Congress or, in the case of the ERA, the states. Some consider an ERA to be unnecessary due to the equal protection afforded by the 14th Amendment. Third, the constitutions of countries with federal systems formally allocate legislative, judicial, and executive authority to the two levels of government in such a way as to ensure each level some degree of autonomy from the other. Under the U.S. Constitution, the president assumes executive power, Congress exercises legislative powers, and the federal courts (e.g., U.S. district courts, appellate courts, and the Supreme Court) assume judicial powers. In each of the fifty states, a governor assumes executive authority, a state legislature makes laws, and state-level courts (e.g., trial courts, intermediate appellate courts, and supreme courts) possess judicial authority. Another common characteristic of federalism around the world is that national courts commonly resolve disputes between levels and departments of government. In the United States, conflicts between states and the federal government are adjudicated by federal courts, with the U.S. Supreme Court being the final arbiter. The resolution of such disputes can preserve the autonomy of one level of government, as illustrated recently when the Supreme Court ruled that states cannot interfere with the federal government’s actions relating to immigration. In other instances, a Supreme Court ruling can erode that autonomy, as demonstrated in the 1940s when, in United States v. Wrightwood Dairy Co., the Court enabled the federal government to regulate commercial activities that occurred within states, a function previously handled exclusively by the states. Finally, subnational governments are always represented in the upper house of the national legislature, enabling regional interests to influence national lawmaking. In the American federal system, the U.S. Senate functions as a territorial body by representing the fifty states: Each state elects two senators to ensure equal representation regardless of state population differences. Thus, federal laws are shaped in part by state interests, which senators convey to the federal policymaking process. Division of power can also occur via a unitary structure or confederation. In contrast to federalism, a unitary system makes subnational governments dependent on the national government, where significant authority is concentrated. Before the late 1990s, the United Kingdom’s unitary system was centralized to the extent that the national government held the most important levers of power. Since then, power has been gradually decentralized through a process of devolution, leading to the creation of regional governments in Scotland, Wales, and Northern Ireland as well as the delegation of specific responsibilities to them. Other democratic countries with unitary systems, such as France, Japan, and Sweden, have followed a similar path of decentralization. In a confederation, authority is decentralized, and the central government’s ability to act depends on the consent of the subnational governments. Under the Articles of Confederation (the first constitution of the United States), states were sovereign and powerful while the national government was subordinate and weak. Because states were reluctant to give up any of their power, the national government lacked authority in the face of challenges such as servicing the war debt, ending commercial disputes among states, negotiating trade agreements with other countries, and addressing popular uprisings that were sweeping the country. As the brief American experience with confederation clearly shows, the main drawback with this system of government is that it maximizes regional self-rule at the expense of effective national governance. Federalism and the Constitution The Constitution contains several provisions that direct the functioning of U.S. federalism. Some delineate the scope of national and state power, while others restrict it. The remaining provisions shape relationships among the states and between the states and the federal government. The enumerated powers of the national legislature are found in Article I, Section 8. These powers define the jurisdictional boundaries within which the federal government has authority. In seeking not to replay the problems that plagued the young country under the Articles of Confederation, the Constitution’s framers granted Congress specific powers that ensured its authority over national and foreign affairs. To provide for the general welfare of the populace, it can tax, borrow money, regulate interstate and foreign commerce, and protect property rights, for example. To provide for the common defense of the people, the federal government can raise and support armies and declare war. Furthermore, national integration and unity are fostered with the government’s powers over the coining of money, naturalization, postal services, and other responsibilities. The last clause of Article I, Section 8, commonly referred to as the elastic clause or the necessary and proper cause, enables Congress “to make all Laws which shall be necessary and proper for carrying” out its constitutional responsibilities. While the enumerated powers define the policy areas in which the national government has authority, the elastic clause allows it to create the legal means to fulfill those responsibilities. However, the open-ended construction of this clause has enabled the national government to expand its authority beyond what is specified in the Constitution, a development also motivated by the expansive interpretation of the commerce clause, which empowers the federal government to regulate interstate economic transactions. The powers of the state governments were never listed in the original Constitution. The consensus among the framers was that states would retain any powers not prohibited by the Constitution or delegated to the national government. However, when it came time to ratify the Constitution, a number of states requested that an amendment be added explicitly identifying the reserved powers of the states. What these Anti-Federalists sought was further assurance that the national government’s capacity to act directly on behalf of the people would be restricted, which the first ten amendments (Bill of Rights) provided. The Tenth Amendment affirms the states’ reserved powers: “The powers not delegated to the United States by the Constitution, nor prohibited by it to the States, are reserved to the States respectively, or to the people.” Indeed, state constitutions had bills of rights, which the first Congress used as the source for the first ten amendments to the Constitution. Some of the states’ reserved powers are no longer exclusively within state domain, however. For example, since the 1940s, the federal government has also engaged in administering health, safety, income security, education, and welfare to state residents. The boundary between intrastate and interstate commerce has become indefinable as a result of broad interpretation of the commerce clause. Shared and overlapping powers have become an integral part of contemporary U.S. federalism. These concurrent powers range from taxing, borrowing, and making and enforcing laws to establishing court systems. Article I, Sections 9 and 10, along with several constitutional amendments, lay out the restrictions on federal and state authority. The most important restriction Section 9 places on the national government prevents measures that cause the deprivation of personal liberty. Specifically, the government cannot suspend the writ of habeas corpus, which enables someone in custody to petition a judge to determine whether that person’s detention is legal; pass a bill of attainder, a legislative action declaring someone guilty without a trial; or enact an ex post facto law, which criminalizes an act retroactively. The Bill of Rights affirms and expands these constitutional restrictions, ensuring that the government cannot encroach on personal freedoms. The states are also constrained by the Constitution. Article I, Section 10, prohibits the states from entering into treaties with other countries, coining money, and levying taxes on imports and exports. Like the federal government, the states cannot violate personal freedoms by suspending the writ of habeas corpus, passing bills of attainder, or enacting ex post facto laws. Furthermore, the Fourteenth Amendment, ratified in 1868, prohibits the states from denying citizens the rights to which they are entitled by the Constitution, due process of law, or the equal protection of the laws. Lastly, three civil rights amendments—the Fifteenth, Nineteenth, and Twenty-Sixth—prevent both the states and the federal government from abridging citizens’ right to vote based on race, sex, and age. This topic remains controversial because states have not always ensured equal protection. The supremacy clause in Article VI of the Constitution regulates relationships between the federal and state governments by declaring that the Constitution and federal law are the supreme law of the land. This means that if a state law clashes with a federal law found to be within the national government’s constitutional authority, the federal law prevails. The intent of the supremacy clause is not to subordinate the states to the federal government; rather, it affirms that one body of laws binds the country. In fact, all national and state government officials are bound by oath to uphold the Constitution regardless of the offices they hold. Yet enforcement is not always that simple. In the case of marijuana use, which the federal government defines to be illegal, twenty-three states and the District of Columbia have nevertheless established medical marijuana laws, others have decriminalized its recreational use, and four states have completely legalized it. The federal government could act in this area if it wanted to. For example, in addition to the legalization issue, there is the question of how to treat the money from marijuana sales, which the national government designates as drug money and regulates under laws regarding its deposit in banks. Various constitutional provisions govern state-to-state relations. Article IV, Section 1, referred to as the full faith and credit clause or the comity clause, requires the states to accept court decisions, public acts, and contracts of other states. Thus, an adoption certificate or driver's license issued in one state is valid in any other state. The movement for marriage equality has put the full faith and credit clause to the test in recent decades. In light of Baehr v. Lewin, a 1993 ruling in which the Hawaii Supreme Court asserted that the state's ban on same-sex marriage was unconstitutional, a number of states became worried that they would be required to recognize those marriage certificates. To address this concern, Congress passed and President Clinton signed the Defense of Marriage Act (DOMA) in 1996. The law declared that "No state (or other political subdivision within the United States) need recognize a marriage between persons of the same sex, even if the marriage was concluded or recognized in another state." The law also barred federal benefits for same-sex partners. DOMA clearly made the topic a state matter. It denoted a choice for states, which led many states to take up the policy issue of marriage equality. Scores of states considered legislation and ballot initiatives on the question. The federal courts took up the issue with zeal after the U.S. Supreme Court in United States v. Windsor struck down the part of DOMA that outlawed federal benefits. That move was followed by upwards of forty federal court decisions that upheld marriage equality in particular states. In 2014, the Supreme Court decided not to hear several key case appeals from a variety of states, all of which were brought by opponents of marriage equality who had lost in the federal courts. The outcome of not hearing these cases was that federal court decisions in four states were affirmed, which, when added to other states in the same federal circuit districts, brought the total number of states permitting same-sex marriage to thirty. Then, in 2015, the Obergefell v. Hodges case had a sweeping effect when the Supreme Court clearly identified a constitutional right to marriage based on the Fourteenth Amendment. The privileges and immunities clause of Article IV asserts that states are prohibited from discriminating against out-of-staters by denying them such guarantees as access to courts, legal protection, property rights, and travel rights. The clause has not been interpreted to mean there cannot be any difference in the way a state treats residents and non-residents. For example, individuals cannot vote in a state in which they do not reside, tuition at state universities is higher for out-of-state residents, and in some cases individuals who have recently become residents of a state must wait a certain amount of time to be eligible for social welfare benefits. Another constitutional provision prohibits states from establishing trade restrictions on goods produced in other states. However, a state can tax out-of-state goods sold within its borders as long as state-made goods are taxed at the same level. The Distribution of Finances Federal, state, and local governments depend on different sources of revenue to finance their annual expenditures. In 2014, total revenue (or receipts) reached $3.2 trillion for the federal government, $1.7 trillion for the states, and $1.2 trillion for local governments. Two important developments have fundamentally changed the allocation of revenue since the early 1900s. First, the ratification of the Sixteenth Amendment in 1913 authorized Congress to impose income taxes without apportioning it among the states on the basis of population, a burdensome provision that Article I, Section 9, had imposed on the national government. With this change, the federal government’s ability to raise revenue significantly increased and so did its ability to spend. The second development regulates federal grants, that is, transfers of federal money to state and local governments. These transfers, which do not have to be repaid, are designed to support the activities of the recipient governments, but also to encourage them to pursue federal policy objectives they might not otherwise adopt. The expansion of the federal government’s spending power has enabled it to transfer more grant money to lower government levels, which has accounted for an increasing share of their total revenue. The sources of revenue for federal, state, and local governments are detailed in Figure 3. Although the data reflect 2013 results, the patterns we see in the figure give us a good idea of how governments have funded their activities in recent years. For the federal government, 47 percent of 2013 revenue came from individual income taxes and 34 percent from payroll taxes, which combine Social Security tax and Medicare tax. For state governments, 50 percent of revenue came from taxes, while 30 percent consisted of federal grants. Sales tax—which includes taxes on purchased food, clothing, alcohol, amusements, insurance, motor fuels, tobacco products, and public utilities, for example—accounted for about 47 percent of total tax revenue, and individual income taxes represented roughly 35 percent. Revenue from service charges (e.g., tuition revenue from public universities and fees for hospital-related services) accounted for 11 percent. The tax structure of states varies. Alaska, Florida, Nevada, South Dakota, Texas, Washington, and Wyoming do not have individual income taxes. Figure 2.20 illustrates yet another difference: Fuel tax as a percentage of total tax revenue is much higher in South Dakota and West Virginia than in Alaska and Hawaii. However, most states have done little to prevent the erosion of the fuel tax’s share of their total tax revenue between 2007 and 2014 (notice that for many states the dark blue dots for 2014 are to the left of the light blue numbers for 2007). Fuel tax revenue is typically used to finance state highway transportation projects, although some states do use it to fund non-transportation projects. The most important sources of revenue for local governments in 2013 were taxes, federal and state grants, and service charges. For local governments the property tax, a levy on residential and commercial real estate, was the most important source of tax revenue, accounting for about 74 percent of the total. Federal and state grants accounted for 37 percent of local government revenue. State grants made up 87 percent of total local grants. Charges for hospital-related services, sewage and solid- waste management, public city university tuition, and airport services are important sources of general revenue for local governments. Intergovernmental grants are important sources of revenue for both state and local governments. When economic times are good, such grants help states, cities, municipalities, and townships carry out their regular functions. However, during hard economic times, such as the Great Recession of 2007–2009, intergovernmental transfers provide much- needed fiscal relief as the revenue streams of state and local governments dry up. During the Great Recession, tax receipts dropped as business activities slowed, consumer spending dropped, and family incomes decreased due to layoffs or work-hour reductions. To offset the adverse effects of the recession on the states and local governments, federal grants increased by roughly 33 percent during this period. In 2009, President Obama signed the American Recovery and Reinvestment Act (ARRA), which provided immediate economic-crisis management assistance such as helping local and state economies ride out the Great Recession and shoring up the country’s banking sector. A total of $274.7 billion in grants, contracts, and loans was allocated to state and local governments under the ARRA. The bulk of the stimulus funds apportioned to state and local governments was used to create and protect existing jobs through public works projects and to fund various public welfare programs such as unemployment insurance. How are the revenues generated by our tax dollars, fees we pay to use public services and obtain licenses, and monies from other sources put to use by the different levels of government? A good starting point to gain insight on this question as it relates to the federal government is Article I, Section 8, of the Constitution. Recall, for instance, that the Constitution assigns the federal government various powers that allow it to affect the nation as a whole. A look at the federal budget in 2014 shows that the three largest spending categories were Social Security (24 percent of the total budget); Medicare, Medicaid, the Children’s Health Insurance Program, and marketplace subsidies under the Affordable Care Act (24 percent); and defense and international security assistance (18 percent). The rest was divided among categories such as safety net programs (11 percent), including the Earned Income Tax Credit and Child Tax Credit, unemployment insurance, food stamps, and other low-income assistance programs; interest on federal debt (7 percent); benefits for federal retirees and veterans (8 percent); and transportation infrastructure (3 percent). It is clear from the 2014 federal budget that providing for the general welfare and national defense consumes much of the government’s resources—not just its revenue, but also its administrative capacity and labor power. Figure 2.22 compares recent spending activities of local and state governments. Educational expenditures constitute a major category for both. However, whereas the states spend comparatively more than local governments on university education, local governments spend even more on elementary and secondary education. That said, nationwide, state funding for public higher education has declined as a percentage of university revenues; this is primarily because states have taken in lower amounts of sales taxes as internet commerce has increased. Local governments allocate more funds to police protection, fire protection, housing and community development, and public utilities such as water, sewage, and electricity. And while state governments allocate comparatively more funds to public welfare programs, such as health care, income support, and highways, both local and state governments spend roughly similar amounts on judicial and legal services and correctional services. References and Further Reading See John Kincaid. 1975. “Federalism.” In Civitas: A Framework for Civil Education, eds. Charles Quigley and Charles Bahmueller. Calabasas, CA: Center for Civic Education, 391–392; William S. Riker. 1975. “Federalism.” In Handbook of Political Science, eds. Fred Greenstein and Nelson Polsby. Reading, MA: Addison-Wesley, 93–172. Garry Willis, ed. 1982. The Federalist Papers by Alexander Hamilton, James Madison and John Jay. New York: Bantam Books, 237. Arizona v. United States, 567 U.S. (2012). United States v. Wrightwood Dairy Co., 315 U.S. 110 (1942). Ronald L. Watts. 1999. Comparing Federal Systems, 2nd ed. Kingston, Ontario: McGill-Queen’s University, 6–7; Daniel J. Elazar. 1992. Federal Systems of the World: A Handbook of Federal, Confederal and Autonomy Arrangements. Harlow, Essex: Longman Current Affairs. Jack Rakove. 2007. James Madison and the Creation of the American Republic. New York: Pearson; Samuel H. Beer. 1998. To Make a Nation: The Rediscovery of American Federalism. Cambridge, MA: Harvard University Press. Elton E. Richter. 1929. “Exclusive and Concurrent Powers in the Federal Constitution (http://scholarship.law.nd.edu/cgi/viewcontent.cgi? article=4416&context=ndlr),” Notre Dame Law Review 4, No. 8: 513–542. Baehr v. Lewin. 1993. 74 Haw. 530. United States v. Windsor, 570 U.S. (2013). Adam Liptak, “Supreme Court Delivers Tacit Win to Gay Marriage,” New York Times, 6 October, 2014. Obergefell v. Hodges, 576 U.S. (2015). Data reported by http://www.usgovernmentrevenue.com/federal_revenue (https://www.google.com/url? q=http://www.usgovernmentrevenue.com/federal_revenue&sa=D&ust=1552679317723000). State and local government figures are estimated. Pollock v. Farmers’ Loan & Trust Co., 158 U.S. 601 (1895). See Robert Jay Dilger, “Federal Grants to State and Local Governments: A Historical Perspective on Contemporary Issues,” Congressional Research Service, Report 7-5700, 5 March 2015. Jeffrey L. Barnett et al. 2014. 2012 Census of Governments: Finance-State and Local Government Summary Report, Appendix Table A-1. December 17. Washington, DC: United States Census Bureau, 2. Dilger, “Federal Grants to State and Local Governments,” 4. James Feyrer and Bruce Sacerdote. 2011. “Did the Stimulus Stimulate? Real Time Estimates of the Effects of the American Recovery and Reinvestment Act” (Working Paper No. 16759 (http://www.nber.org/papers/w16759.pdf)), Cambridge, MA: National Bureau of Economic Research. Data reported by the Center on Budget and Policy Priorities. 2015. “Policy Basics: Where Do Our Federal Tax Dollars Go? (http://www.cbpp.org/research/policy- basics-where-do-our-federal-tax-dollars-go)” March 11. Licensing and Attribution CC LICENSED CONTENT, ORIGINAL Revision and Adaptation. Authored by: Daniel M. Regalado. License: CC BY: Attribution CC LICENSED CONTENT, SHARED PREVIOUSLY American Government. Authored by: OpenStax. Provided by: OpenStax; Rice University. Located at: http://cnx.org/contents/5bcc0e59-7345- 421d-8507-a1e4608685e8@18.11. License: CC BY: Attribution License Terms: Download for free at http://cnx.org/contents/5bcc0e59-7345-421d-8507-a1e4608685e8@18.11.	oercommons	2025-03-18T00:36:12.960922	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/66266/overview", "title": "Texas Government 2.0, The Texas State Constitution and the American Federal System", "author": null }
https://oercommons.org/courseware/lesson/66267/overview	Glossary Overview Glossary Glossary: The Texas State Constitution and Federalism bill of attainder: a legislative action declaring someone guilty without a trial; prohibited under the Constitution bill of rights: (sometimes called a declaration of rights or a charter of rights) a list of the most important rights to the citizens. The purpose is to protect those rights against infringement from public officials and private citizens. coercive federalism: federal policies that force states to change their policies to achieve national goals comity: the legal principle that political entities (such as states, nations, or courts from different jurisdictions) will mutually recognize each other’s legislative, executive, and judicial acts. The underlying notion is that different jurisdictions will reciprocate each other’s judgments out of deference, mutuality, and respect. concurrent powers: shared state and federal powers that range from taxing, borrowing, and making and enforcing laws to establishing court systems Confederacy: The Confederate States of America, those southern states that seceded from the United States in late 1860 and 1861 and argued that the power of the states was more important the power of the central government constituent: a person living in the district from which an official is elected constitution: the legal structure of a government which establishes its power and authority, as well as the limits on that power cooperative federalism: a type of federalism existing since the New Deal era in which grants-in-aid have been used to encourage states and localities (without commanding them) to pursue nationally defined goals; also known as "intergovernmental cooperation" devolution: a process in which powers from the central government in a unitary system are delegated to subnational units dual federalism: the system of government that prevailed in the U.S. from 1789 to 1937, during which most fundamental governmental powers were strictly separated between the federal and state governments elastic clause: the last clause of Article I, Section 8, which enables the national government “to make all Laws which shall be necessary and proper for carrying” out all its constitutional responsibilities ex post facto law: a law that criminalizes an act retroactively; prohibited under the Constitution federalism: an institutional arrangement that creates two relatively autonomous levels of government, each possessing the capacity to act directly on the people with authority granted by the national constitution. full faith and credit: clause found in Article IV, Section 1, of the Constitution, this clause requires states to accept court decisions, public acts, and contracts of other states; also referred to as the comity provision line-item veto: In United States government, the line-item veto, or partial veto, is the power of executive authority to nullify or cancel specific provisions of a bill, usually a budget appropriations bill, without vetoing the entire legislative package. poll tax: a state tax imposed on voters as a prerequisite for voting; poll taxes were determined unconstitutional in national elections by the Twenty-Fourth Amendment, and in state elections by the Supreme Court in 1966 privileges and immunities clause: found in Article IV, Section 2, of the Constitution, this clause prohibits states from discriminating against out-of- staters by denying such guarantees as access to courts, legal protection, and property and travel rights separation of powers: the division of governmental power among several institutions that must cooperate in decision making. states: governments at the subnational level suffrage: term referring to the right to vote unitary system: a centralized system of government in which the subnational government is dependent on the central government, where substantial authority is concentrated writ of habeas corpus: a petition that enables someone in custody to petition a judge to determine whether that person’s detention is legal References and Further Reading Cornell Law School: Legal Information Institute. Comity. Accessed August 25, 2019 Licensing and Attribution CC LICENSED CONTENT, ORIGINAL The Texas State Constitution and the American Federal System: Glossary. Authored by: John Osterman. License: CC BY: Attribution	oercommons	2025-03-18T00:36:12.984751	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/66267/overview", "title": "Texas Government 2.0, The Texas State Constitution and the American Federal System", "author": null }
https://oercommons.org/courseware/lesson/66268/overview	Assessment Overview This is a quiz for Chapter Two Texas Government Chapter Two Quiz Check your knowledge of Chapter Two by taking the quiz linked below. The quiz will open in a new browser window or tab. This is a quiz for Chapter Two Check your knowledge of Chapter Two by taking the quiz linked below. The quiz will open in a new browser window or tab.	oercommons	2025-03-18T00:36:13.002148	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/66268/overview", "title": "Texas Government 2.0, The Texas State Constitution and the American Federal System", "author": null }
https://oercommons.org/courseware/lesson/15207/overview	Competitive Federalism Today Learning Objectives By the end of this section, you will be able to: - Explain the dynamic of competitive federalism - Analyze some issues over which the states and federal government have contended Certain functions clearly belong to the federal government, the state governments, and local governments. National security is a federal matter, the issuance of licenses is a state matter, and garbage collection is a local matter. One aspect of competitive federalism today is that some policy issues, such as immigration and the marital rights of gays and lesbians, have been redefined as the roles that states and the federal government play in them have changed. Another aspect of competitive federalism is that interest groups seeking to change the status quo can take a policy issue up to the federal government or down to the states if they feel it is to their advantage. Interest groups have used this strategy to promote their views on such issues as abortion, gun control, and the legal drinking age. CONTENDING ISSUES Immigration and marriage equality have not been the subject of much contention between states and the federal government until recent decades. Before that, it was understood that the federal government handled immigration and states determined the legality of same-sex marriage. This understanding of exclusive responsibilities has changed; today both levels of government play roles in these two policy areas. Immigration federalism describes the gradual movement of states into the immigration policy domain.Carol M. Swain and Virgina M. Yetter. (2014). “Federalism and the Politics of Immigration Reform.” In The Politics of Major Policy Reform in Postwar America, eds. Jeffery A. Jenkins and Sidney M. Milkis. New York: Cambridge University Press. Since the late 1990s, states have asserted a right to make immigration policy on the grounds that they are enforcing, not supplanting, the nation’s immigration laws, and they are exercising their jurisdictional authority by restricting illegal immigrants’ access to education, health care, and welfare benefits, areas that fall under the states’ responsibilities. In 2005, twenty-five states had enacted a total of thirty-nine laws related to immigration; by 2014, forty-three states and Washington, DC, had passed a total of 288 immigration-related laws and resolutions.National Conference of State Legislatures. “State Laws Related to Immigration and Immigrants.” http://www.ncsl.org/research/immigration/state-laws-related-to-immigration-and-immigrants.aspx (June 23, 2015). Arizona has been one of the states at the forefront of immigration federalism. In 2010, it passed Senate Bill 1070, which sought to make it so difficult for illegal immigrants to live in the state that they would return to their native country, a strategy referred to as “attrition by enforcement.”Michele Waslin. 2012. “Discrediting ‘Self Deportation’ as Immigration Policy,” February 6. http://www.immigrationpolicy.org/special-reports/discrediting-%E2%80%9Cself-deportation%E2%80%9D-immigration-policy The federal government filed suit to block the Arizona law, contending that it conflicted with federal immigration laws. Arizona’s law has also divided society, because some groups, like the Tea Party movement, have supported its tough stance against illegal immigrants, while other groups have opposed it for humanitarian and human-rights reasons (Figure). According to a poll of Latino voters in the state by Arizona State University researchers, 81 percent opposed this bill.Daniel González. 2010. “SB 1070 Backlash Spurs Hispanics to Join Democrats,” June 8. http://archive.azcentral.com/arizonarepublic/news/articles/2010/06/08/20100608arizona-immigration-law-backlash.html In 2012, in Arizona v. United States, the Supreme Court affirmed federal supremacy on immigration.Arizona v. United States, 567 U.S. __ (2012). The court struck down three of the four central provisions of the Arizona law—namely, those allowing police officers to arrest an undocumented immigrant without a warrant if they had probable cause to think he or she had committed a crime that could lead to deportation, making it a crime to seek a job without proper immigration papers, and making it a crime to be in Arizona without valid immigration papers. The court upheld the “show me your papers” provision, which authorizes police officers to check the immigration status of anyone they stop or arrest who they suspect is an illegal immigrant.Arizona v. United States, 567 U.S. __ (2012). However, in letting this provision stand, the court warned Arizona and other states with similar laws that they could face civil rights lawsuits if police officers applied it based on racial profiling.Julia Preston, “Arizona Ruling Only a Narrow Opening for Other States,” New York Times, 25 June 2012. All in all, Justice Anthony Kennedy’s opinion embraced an expansive view of the U.S. government’s authority to regulate immigration and aliens, describing it as broad and undoubted. That authority derived from the legislative power of Congress to “establish a uniform Rule of Naturalization,” enumerated in the Constitution. Arizona’s Senate Bill 1070 has been the subject of heated debate. Read the views of proponents and opponents of the law. Marital rights for gays and lesbians have also significantly changed in recent years. By passing the Defense of Marriage Act (DOMA) in 1996, the federal government stepped into this policy issue. Not only did DOMA allow states to choose whether to recognize same-sex marriages, it also defined marriage as a union between a man and a woman, which meant that same-sex couples were denied various federal provisions and benefits—such as the right to file joint tax returns and receive Social Security survivor benefits. In 1997, more than half the states in the union had passed some form of legislation banning same-sex marriage. By 2006, two years after Massachusetts became the first state to recognize marriage equality, twenty-seven states had passed constitutional bans on same-sex marriage. In United States v. Windsor, the Supreme Court changed the dynamic established by DOMA by ruling that the federal government had no authority to define marriage. The Court held that states possess the “historic and essential authority to define the marital relation,” and that the federal government’s involvement in this area “departs from this history and tradition of reliance on state law to define marriage.”United States v. Windsor, 570 U.S. __ (2013). Edith Windsor: Icon of the Marriage Equality Movement Edith Windsor, the plaintiff in the landmark Supreme Court case United States v. Windsor, has become an icon of the marriage equality movement for her successful effort to force repeal the DOMA provision that denied married same-sex couples a host of federal provisions and protections. In 2007, after having lived together since the late 1960s, Windsor and her partner Thea Spyer were married in Canada, where same-sex marriage was legal. After Spyer died in 2009, Windsor received a $363,053 federal tax bill on the estate Spyer had left her. Because her marriage was not valid under federal law, her request for the estate-tax exemption that applies to surviving spouses was denied. With the counsel of her lawyer, Roberta Kaplan, Windsor sued the federal government and won (Figure). Because of the Windsor decision, federal laws could no longer discriminate against same-sex married couples. What is more, marriage equality became a reality in a growing number of states as federal court after federal court overturned state constitutional bans on same-sex marriage. The Windsor case gave federal judges the moment of clarity from the U.S. Supreme Court that they needed. James Esseks, director of the American Civil Liberties Union’s (ACLU) Lesbian Gay Bisexual Transgender & AIDS Project, summarizes the significance of the case as follows: “Part of what’s gotten us to this exciting moment in American culture is not just Edie’s lawsuit but the story of her life. The love at the core of that story, as well as the injustice at its end, is part of what has moved America on this issue so profoundly.”James Esseks. 2014. “Op-ed: In the Wake of Windsor,” June 26. http://www.advocate.com/commentary/2014/06/26/op-ed-wake-windsor (June 24, 2015). In the final analysis, same-sex marriage is a protected constitutional right as decided by the U.S. Supreme Court, which took up the issue again when it heard Obergefell v. Hodges in 2015. What role do you feel the story of Edith Windsor played in reframing the debate over same-sex marriage? How do you think it changed the federal government’s view of its role in legislation regarding same-sex marriage relative to the role of the states? Following the Windsor decision, the number of states that recognized same-sex marriages increased rapidly, as illustrated in Figure. In 2015, marriage equality was recognized in thirty-six states plus Washington, DC, up from seventeen in 2013. The diffusion of marriage equality across states was driven in large part by federal district and appeals courts, which have used the rationale underpinning the Windsor case (i.e., laws cannot discriminate between same-sex and opposite-sex couples based on the equal protection clause of the Fourteenth Amendment) to invalidate state bans on same-sex marriage. The 2014 court decision not to hear a collection of cases from four different states essentially affirmed same-sex marriage in thirty states. And in 2015 the Supreme Court gave same-sex marriage a constitutional basis of right nationwide in Obergefell v. Hodges. In sum, as the immigration and marriage equality examples illustrate, constitutional disputes have arisen as states and the federal government have sought to reposition themselves on certain policy issues, disputes that the federal courts have had to sort out. STRATEGIZING ABOUT NEW ISSUES Mothers Against Drunk Driving (MADD) was established in 1980 by a woman whose thirteen-year-old daughter had been killed by a drunk driver. The organization lobbied state legislators to raise the drinking age and impose tougher penalties, but without success. States with lower drinking ages had an economic interest in maintaining them because they lured youths from neighboring states with restricted consumption laws. So MADD decided to redirect its lobbying efforts at Congress, hoping to find sympathetic representatives willing to take action. In 1984, the federal government passed the National Minimum Drinking Age Act (NMDAA), a crosscutting mandate that gradually reduced federal highway grant money to any state that failed to increase the legal age for alcohol purchase and possession to twenty-one. After losing a legal battle against the NMDAA, all states were in compliance by 1988.South Dakota v. Dole, 483 U.S. 203 (1987). By creating two institutional access points—the federal and state governments—the U.S. federal system enables interest groups such as MADD to strategize about how best to achieve their policy objectives. The term venue shopping refers to a strategy in which interest groups select the level and branch of government (legislature, judiciary, or executive) they calculate will be most advantageous for them.Frank Baumgartner and Bryan Jones. 1993. Agendas and Instability in American Politics. Chicago: University of Chicago Press. If one institutional venue proves unreceptive to an advocacy group’s policy goal, as state legislators were to MADD, the group will attempt to steer its issue to a more responsive venue. The strategy anti-abortion advocates have used in recent years is another example of venue shopping. In their attempts to limit abortion rights in the wake of the 1973 Roe v. Wade Supreme Court decision making abortion legal nationwide, anti-abortion advocates initially targeted Congress in hopes of obtaining restrictive legislation.Roe v. Wade, 410 U.S. 113 (1973). Lack of progress at the national level prompted them to shift their focus to state legislators, where their advocacy efforts have been more successful. By 2015, for example, thirty-eight states required some form of parental involvement in a minor’s decision to have an abortion, forty-six states allowed individual health-care providers to refuse to participate in abortions, and thirty-two states prohibited the use of public funds to carry out an abortion except when the woman’s life is in danger or the pregnancy is the result of rape or incest. While 31 percent of U.S. women of childbearing age resided in one of the thirteen states that had passed restrictive abortion laws in 2000, by 2013, about 56 percent of such women resided in one of the twenty-seven states where abortion is restricted.Elizabeth Nash et al. 2013. “Laws Affecting Reproductive Health and Rights: 2013 State Policy Review.” http://www.guttmacher.org/statecenter/updates/2013/statetrends42013.html (June 24, 2015). Some policy areas have been redefined as a result of changes in the roles that states and the federal government play in them. The constitutional disputes these changes often trigger have had to be sorted out by the Supreme Court. Contemporary federalism has also witnessed interest groups engaging in venue shopping. Aware of the multiple access points to our political system, such groups seek to access the level of government they deem will be most receptive to their policy views. Which statement about immigration federalism is false? - The Arizona v. United States decision struck down all Arizona’s most restrictive provisions on illegal immigration. - Since the 1990s, states have increasingly moved into the policy domain of immigration. - Federal immigration laws trump state laws. - States’ involvement in immigration is partly due to their interest in preventing illegal immigrants from accessing public services such as education and welfare benefits. Hint: A Which statement about the evolution of same-sex marriage is false? - The federal government became involved in this issue when it passed DOMA. - In the 1990s and 2000s, the number of state restrictions on same-sex marriage increased. - United States v. Windsor legalized same-sex marriage in the United States. - More than half the states had legalized same-sex marriage by the time the Supreme Court made same-sex marriage legal nationwide in 2015. Which statement about venue shopping is true? - MADD steered the drinking age issue from the federal government down to the states. - Anti-abortion advocates have steered the abortion issue from the states up to the federal government. - Both MADD and anti-abortion proponents redirected their advocacy from the states to the federal government. - None of the statements are correct. Hint: D What does venue shopping mean?	oercommons	2025-03-18T00:36:13.027357	07/10/2017	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15207/overview", "title": "American Government, Students and the System, American Federalism, Competitive Federalism Today", "author": null }
https://oercommons.org/courseware/lesson/90357/overview	Teaching The Future With Will: A Free ESL Lesson Plan Overview ESL students love talking about their future plans, and this lesson does just that! This lesson helps students differentiate between will and going to, understand how to use shall, and learn how to make predictions. If you want additional lesson plans and support, including teachers’ notes, be sure to register for a free Off2Class account. Off2Class English language teachers usually teach the simple future tense after teaching the future with going to. It’s important to differentiate when we use will and when we use going to, and this lesson does just that! This ready-to-teach lesson plan focuses on the positive form of will and even introduces the term shall. Students will also learn about when to use will versus going to. Finally, you will teach students how to make predictions. This lesson is easy to follow and perfect as an introduction to the simple future tense. It is complete with picture-prompt activities and gap-fill exercises so your students will have ample opportunity to practice. You can access more helpful teacher notes like this for free by signing up for a free Off2Class account.	oercommons	2025-03-18T00:36:13.046063	Christine Chan	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/90357/overview", "title": "Teaching The Future With Will: A Free ESL Lesson Plan", "author": "Teaching/Learning Strategy" }
https://oercommons.org/courseware/lesson/117167/overview	1b. Tribes, Exploration, and Expansion (pdf) 2. Part 1 - Teacher Slides 3. Part 1 - Student Notebook 4. Lesson 5-Spokane Tribal Practices 5. Part 2 - Teacher Slides 6. Lesson 7-Early Explorer Texts 7. Lesson 9-Corps of Discovery united_states_1803_org WA Topographic Map Blank for Long Ago Story Pacific Northwest: Tribes, Exploration, and Expansion Overview In this unit from Central Valley School District in Washington, students dive into inquiry, engaging with compelling questions to help learn about the culture of some of their tribal neighbors and the forces that brought change to the northwest: fur trade era and exploration. The module includes detailed teaching notes for planning and executing instruction, emphasizing close reading of complex texts and specific strategies for supporting students' evidence-based reading and writing. It provides clear requirements for student work, along with summative assessments, central texts, key resources, and protocols to facilitate learning. Introduction Note that the emphasis here is on the Spokane Tribe as one of our closest tribal neighbors. In no way is this an exhaustive study nor should the tribal cultures be generalized to other tribes of the region. We understand that each tribe in our region and North America was and continues to be unique in its culture, practices, lifeways, and traditions. For tips to remember when teaching about American Indians with respect, accuracy, and complexity, see these websites: - National Museum of the Native American Indian \| Smithsonian Institution - Tips for teaching about Native peoples \| Burke Museum - Support for Indian Education and Culture \| Washington Office of Superintendent of Public Instruction – Office of Native Education We honor teachers as professionals, and expect teachers would modify and refine the lessons to meet the needs of their students and context. This is offered as one concrete example, an invitation, and an inspiration to others to extend this and to do their own work. Who are some of our closest tribal neighbors, and what have been their lifeways since time immemorial? Why do people explore, and how does this lead to expansion? ________________________________________________ The module will help teachers achieve two goals: To build students’ content understanding and to help students develop the content literacy skills needed for College and Career Readiness. The unit has two parts. In each, students dive into inquiry to answer the compelling questions. - Part 1 is focused on the examination of the northwest and some of the original inhabitants. Through these questions students will learn about the culture of some of their closest tribal neighbors, the Spokane Indians. The final project for Part 1 is a cultural investigation display, in which students will show what they know about the culture of the Spokane Tribe. - In Part 2, Students will also learn about forces that brought change to the northwest: fur trade era and exploration. Students will ultimately learn about the Corps of Discovery and the Oregon Trail and know the impact each had on the west. Students will finish Part 2 with a timeline activity that will reflect choice and build upon student strengths according to their skill set. Finally, a lesson on a Tribe of the Columbia Plateau is offered as an extension, but it is strongly recommended that students get to experience this lesson. Unit Desired Results Understandings/Big Ideas - Native Americans have lived on this land since time immemorial and tribal stories tell the history of our region. - The Spokane Tribe’s homeland has changed drastically over time. - Tribes are still here and continue to thrive within their communities; we speak about tribes in the present-tense as much as possible. - Interactions between different groups of people cause great change to the environment and cultures. - Exploration caused irreversible change. - Today’s tribal people not only govern themselves, but they also continue to practice their tribal traditions in many ways. Unit Compelling Questions - Who are some of our closest tribal neighbors and what have they valued for generations? - How did the Spokane Tribe use their environment to meet their needs and wants? - How do Tribal stories help us understand the history of our region? - Why do people explore, and how does this lead to expansion? - How did exploration and interaction affect tribes in the northwest? - How do maps help explain the movement of people? - What were the costs and benefits to exploration and westward expansion? Students will: - Identify and explain how the Spokane Tribe used the environment to meet their needs and wants. - Connect the origin story of the Spokane Tribe to local geography and history. - Identify the different people who explored the northwest and analyze their impact on the region. - Engage in discussions about people, movement, exchanges, and culture. Students will be skilled at: - Citing text evidence - Analyzing primary and secondary sources - Writing expository text based on knowledge gained from reading a variety of primary and secondary sources - Comparing and contrasting ideas and opinions - Drawing conclusions and synthesizing multiple texts - Supporting thinking/writing with evidence from text - Collaboratively discussing text, thinking, analysis and evidence in a group Lessons The lessons are presented in two parts: 1-5 are on the Spokane Tribe; 6-10 are on westward expansion. All lesson time suggestions are included in each lesson and are approximations, but the entire unit should take no longer than 5-6 weeks. Part 1: Spokane Tribe Teacher Digital Instructional Slides Student Digital Slides - Lesson 1: Homeland ~ What is homeland? - Lesson 2: Gallery walk ~ Images of Columbia Plateau Tribes - Lesson 3: The Long Ago Story ~ Origin of the Spokane People, as told by Pauline Flett, Spokane Tribal Elder - Lesson 4: Spokane Tribal Homelands - Lesson 5: Spokane People’s Culture and Traditions - Final product: Cultural Investigation Display (see lesson 5 for directions) Part 2: Exploration & Westward Expansion Digital Instructional Slides - Lesson 6: Artifacts and the Fur Trade Era (Part 2 final product: Timeline Project is introduced. Students will gather events along the way to create a timeline that tells the “story” of exploration and westward expansion.) - Lesson 7: Early Explorers ~ Who impacted the northwest? - Lesson 8: Mapping the West~ Changing territory maps - Lesson 9: Lewis and Clark ~ Who were these explorers and what did they accomplish? - Lesson 10: Westward Expansion - Final product: Timeline (see lesson 6 for directions) - Lesson 11 (Extension): A River Lost Vocabulary Vocabulary words have been identified for each of the lessons and are listed within each lesson. Use the strategy of your choice to introduce these words to students. Attribution and License Written by: Leslie Heffernan, Central Valley School District Edited, field tested, and revised by: - Morgen Larsen, Teacher Librarian - Stephen Hart, Teacher - Holli Parker, Teacher - Aleah Thompson, Teacher - Andrea Framstad, Teacher - Sarah Schmaltz, Teacher - Kathryn Teske, Professional Development - Emily Fletcher, Professional Development - Elisa Cayce, Professional Development In addition to material created by the authors, this unit includes instructional materials adapted from other sources. Links are provided to content produced by other organizations which may use a different license. Please confirm the license status of these third-party resources and understand their terms of use before reusing them. Links to third-party websites are provided for your convenience only and do not constitute Central Valley School District’s endorsement, sponsorship, warranty or approval of such linked websites or any product, service or content offered on such linked websites. Alternate material licenses with different levels of user permission are clearly indicated here and above/next to the specific content in the unit. Prior to making this course publicly available, we have reviewed its contents extensively to determine the correct ownership of the material and make sure the appropriate open licenses or copyright permission is in place. We will promptly remove any material that is determined to be violating the rights of others. If you believe that a portion of this unit infringes another's copyright, contact Central Valley School District at lheffernan@cvsd.org. Except where otherwise noted, this unit, copyright Central Valley School District, is available under a Creative Commons Attribution License. All logos and trademarks are property of their respective owners. Sections used under fair use doctrine (17 U.S.C. § 107) are marked	oercommons	2025-03-18T00:36:13.091497	Reading Informational Text	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/117167/overview", "title": "Pacific Northwest: Tribes, Exploration, and Expansion", "author": "Elementary Education" }
https://oercommons.org/courseware/lesson/102941/overview	Substratum A Foundational Guide to English Composition PDF Substratum: A Foundational Guide to English Composition Overview This OER textbook has been developed to support Developmental English courses at rural Arizona community colleges. It includes content to help students form coherent sentences, paragraphs, and essays. The content on essays relates to the 5-paragraph essay form. For content on dynamic essay forms, please see the OER textbook Relaying and Responding: A Guide to College Writing. Title Page ABOUT THIS BOOK This book, which can be accessed by downloading the attached MS Word document or PDF, has been developed to support Developmental English courses at rural Arizona community colleges. It includes content to help students form coherent sentences, paragraphs, and essays. The content on essays relates to the 5-paragraph essay form. For content on dynamic essay forms, please see the OER textbook Relaying and Responding: A Guide to College Writing. AUTHORS This book has been assembled by Erik Wilbur, John Hansen, and Beau Rogers at Mohave Community College. Most of the content in this book has been sourced from creative commons licensed materials. Attributions for this borrowed and/or adapted and remixed content can be found at the end of each chapter. Any text, graphic, or video without an attribution should be attributed to Mohave Community College by using the license below. LICENSE Substratum: A Foundational Guide to English Composition by Mohave Community College is licensed under a Creative Commons Attribution 4.0 License except where otherwise noted.	oercommons	2025-03-18T00:36:13.113350	04/15/2023	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/102941/overview", "title": "Substratum: A Foundational Guide to English Composition", "author": "Erik Wilbur" }
https://oercommons.org/courseware/lesson/114963/overview	Using Creative Commons Tools & Licenses to Create Open Educational Resources: A Professional Development Module for Adopting & Adapting OER Overview "Using Creative Commons Tools & Licenses to Create Open Educational Resources" is a professional development module designed to train faculty in the adoption and adaptation of open educational resources. This module explotres what OER are and how CC licenses make them possible, how to use and adopt OER for courses, and how to adapt OER and license new adaptations and creations. This module will prepare faculty to adopt, adapt, or create OER through their understanding and use of Creative Commons tools and licenses. Start here to begin professional development module! Welcome to "Using Creative Commons Tools & Licenses to Create Open Educational Resources"! In this module, we will explore what OER are and how CC licenses make them possible, how to use and adopt OER for courses, and how to adapt OER and license new adaptations and creations. This module will prepare faculty to adopt, adapt, or create OER through their understanding and use of Creative Commons tools and licenses. Objectives - Module participants will define Open Educational Resources. - Participants will paraphrase the relationship between copyright and Creative Commons licenses. - Participants will express the differences between types of Creative Commons licenses. - Participants will write attribution statements. - Participants will write licensing statements. - Participants will evaluate an OER for adoption. - Participants will adapt and share an OER. Except where otherwise indicated, "Using Creative Commons Tools & Licenses to Create Open Educational Resources" ©2024 by Veronica Goosey is licensed under a Creative Commons Attribution 4.0 international licenseLinks to an external site.. What are OER? Reading: What are OER? sway PDF of What are OER? Assignment: Unit 1 Assignment: What are OER? Create an open educational resource that teaches others how to recognize OER. Objectives - Module participants will define Open Educational Resources. - Participants will paraphrase the relationship between copyright and Creative Commons licenses. - Participants will express the differences between types of Creative Commons licenses. - Participants will write an attribution statement. - Participants will write a licensing statement. Assignments Create a video, slide presentation, or infographic (or choose another medium) in which you describe Open Educational Resources, as well as how and when they might be useful to your institutions’ work. At a minimum, include the following: - a definition of OER, - a description of the relationship between traditional copyright and Creative Commons licenses, Links to an external site. - descriptions of the six Creative Commons licenses, - an evaluation of how OER use could benefit your institution, - an attribution statement for the works used in your creation, and - a licensing statement for your own work. The DownloadsLinks to an external site. page of Creative Commons' website may be a helpful media resource if you're creating a visual assignment. That page includes downloadable CC license and element icons, and more. Remember to cite and attribute your sources and license your work with a Creative Commons license. Help and directions on citations, adding attribution statements, and licensing your work can be found at the links below: - How to add a Creative Common license to your workLinks to an external site. - Citing and attributing sourcesLinks to an external site. Links to an external site. Post your video, slide presentation, infographic, or other work online, then provide the link to your work. Alternately, you can upload your work. Rubric: Unit 1 Assignment Rubric \| Criteria \| Ratings \| Pts \| \|\| \|---\|---\|---\|---\|---\| \| CC License & Attributions Work is licensed under a Creative Commons license. If other sources are used, work includes applicable references or attribution for those sources. \| \| 2 pts \| \|\| \| OER Definition Work defines OER. \| \| 2 pts \| \|\| \| CC & Copyright Work describes the relationship between CC and copyright. \| \| 2 pts \| \|\| \| CC Licenses Work describes all 6 CC licenses and the differences between them. \| \| 2 pts \| \|\| \| OER at your Institution Work evaluates how OER use could benefit an educational institution. \| \| 2 pts \| \|\| Total Points: 10 \| OER Adoption Reading: OER Adoption sway PDF of OER Adoption Assignment: Unit 2 Assignment: OER Adoption Create an open resource that assesses an OER for adoption in a specific course. Objectives - Participants will evaluate an OER for adoption. - Participants will write an attribution statement. - Participants will write a licensing statement. Assignments Create a video, slide presentation, or essay (or choose another medium) in which you assess an OER for a course and explain how and when it might be useful to your institutions’ work. At a minimum, include the following: - an identification of the work to be replaced and course in which it is used and an identification of the OER under consideration, - a detailed assessment of the OER according to the criteria on the OER assessment checklist, - a description of desired adaptations to make before using the text, - aaLinks to an external site.aan attribution statement for the work being assessed, and - a licensing statement for your own work. The DownloadsLinks to an external site. page of Creative Commons' website may be a helpful media resource if you're creating a visual assignment. That page includes downloadable CC license and element icons, and more. Remember to cite and attribute your sources and license your work with a Creative Commons license. Help and directions on citations, adding attribution statements, and licensing your work can be found at the links below: - How to add a Creative Common license to your workLinks to an external site. - Citing and attributing sourcesLinks to an external site. Links to an external site. Post your video, slide presentation, essay, or other work online, then provide the link to your work. Alternately, you can upload your work. Rubric: Unit 2 Assignment Rubric \| CC Licenses & Attributions Work is licensed under a Creative Commons license. If other sources are used, work includes applicable references or attribution for those sources. \| \| 2 pts \| \|\| \| Identification Work identifies the text/resource to be replaced and the course in which it is used. Work identifies the OER under consideration for adoption. \| \| 2 pts \| \|\| \| Assessment Work assesses the OER under consideration in the following categories, noting benefits and concerns: \| \| 4 pts \| \|\| \| Adaptation Needs Work describes the adaptions that would be necessary and/or desirable to be made to the work before it could be adopted for use in the course. \| \| 2 pts \| \|\| Total Points: 10 \| OER Adapatation Reading: OER Adaptation sway PDF of OER Adaptation Assignment: Unit 3 Assignment: OER Adaptation Adapt and share an open educational resource for a specific course. Objectives - Participants will adapt and share an OER. - Participants will write an attribution statement. - Participants will write a licensing statement. Assignments Create a video, slide presentation, document, (or choose another medium) which can be used as an educational resource in a specific course. While working on this project, consider the following: - License permissions for the work you want to adapt, - Assessment checklist elements (review unit 2), - Accessibility requirements, - Keep a record of your adaptations, - How you will license the work, and - Where/how you will publish the work. At a minimum, include the following: - a detailed record of adaptations that identifies the work being adapted, - a link to your published adaptation/derivative work OR upload the work, - an attribution statement for the works used in your creation, and - a licensing statement for your own work which indicates how your derivative work has altered the original work. The DownloadsLinks to an external site. page of Creative Commons' website may be a helpful media resource if you're creating a visual assignment. That page includes downloadable CC license and element icons, and more. Remember to cite and attribute your sources and license your work with a Creative Commons license. Help and directions on citations, adding attribution statements, and licensing your work can be found at the links below: - How to add a Creative Common license to your workLinks to an external site. - Citing and attributing sourcesLinks to an external site. Links to an external site. Post your video, slide presentation, document, or other work online, then provide the link to your work. Alternately, you can upload your work. Rubric: Unit 3 Assignment Rubric \| Criteria \| Ratings \| Pts \| \|\| \|---\|---\|---\|---\|---\| \| CC License & Attribution Statements Work is licensed under a Creative Commons license; the licensing statement includes a description of significant changes and a link to the original work and its license. Work includes applicable references or attribution for sources that are used. \| 2 pts Full Marks \| 0 pts No Marks \| 2 pts \| \| \| Adaptation Record Work identifies the work being adapted and provides a detailed record of changes made to the original work. \| 4 pts Full Marks \| 0 pts No Marks \| 4 pts \| \| \| Published Adaptation Derivative work/adaptation is uploaded here and/or made publicly available on a blog or OER repository. \| 4 pts Full Marks \| 0 pts No Marks \| 4 pts \| \| Total Points: 10 \| Appendix: OER Repositories and Open Resources Appendix: OER Repositories & Open Resources There are many sites hosting OER repositories, and even more referatories and guides. There are also a wide range of open resources that can be used for educational purposes, and more that can be used to create educational resources. While this list is by no means complete, it should give you a good start on identifying resources that you can adopt or adapt. Textbooks - BCcampus OpenEd Resources access British Columbia’s open textbook library and information about the BC campus open textbook project. - COERLL The Center for Open Educational Resources and Language Learning produces and disseminates language OER for the internet public. - DOAB: Directory of Open Access Books directory open to all publishers who publish academic, peer reviewed books in Open Access and should contain as many books as possible, provided that these publications are in Open Access and meet academic standards. - Galileo Open Learning Materials textbooks, ancillary materials, and other learning resources from Affordable Learning Georgia, an initiative of the University System of Georgia - InTech - Technology Open Access Journals and Books one of the largest multidisciplinary open access collections of books covering the fields of science, technology and medicine. - Internet Sacred Text Archive freely available archive of electronic texts about religion, mythology, legends and folklore, and occult and esoteric topics. Texts are presented in English translation and, where possible, in the original language. - JSTOR Open Access eBooks ebooks freely available for anyone in the world to use. Each ebook carries one of six Creative Commons licenses determined by the publisher. Users will not need to register or log in to JSTOR. - Libretext multi-institutional collaborative project to develop open textbooks and other OER. Use the Explore the Collections menu to search academic discipline areas. - Lumen Candela Catalog browseable by subject but not searchable. Textbooks are only available online in HTML format (not PDF, ePub, etc.) - MIT OCW Textbooks many people are aware that MIT posts its course materials (e.g. syllabi, lecture slides) online, but they also have a page specifically for open textbooks used in courses at MIT. - Oapen - online library and publication platform OAPEN Library contains freely accessible academic books, mainly in the area of Humanities and Social Sciences. OAPEN works with publishers to build a quality-controlled collection of Open Access books, and provides services for publishers, libraries and research funders in the areas of dissemination, quality assurance and digital preservation. - Open Michigan collection of open educational resources (OER) from University of Michigan. Access a range of course materials, videos, lectures, student work and more. Nearly all of the content here is openly licensed for reuse under Creative Commons. - Open Textbook Library The Open Textbook Library (OTL) is a project of the Open Education Network. To be included in the OTL, an open textbook must be affiliated with a university, scholarly society, or professional organization OR currently be in use at multiple institutions. Books in the OTL are peer reviewed and allow editing, and most of them are available in multiple formats. - OpenStax OpenStax is the gold standard for open textbooks. Their books are created at Rice University using grant funding from the Gates and Hewlett Foundations. All of their books are peer-reviewed and available in multiple formats, including in print. Most of them are accompanied by free instructor resources (available only after you have been verified as a faculty member) and student resources. - Pressbooks Pressbooks Directory is a free, searchable catalog of open access books published using Pressbooks. It's easy to copy, revise, remix, and redistribute any openly licensed content. - Saylor Academy Open Textbooks. open textbooks developed or adapted by Saylor Academy for use in their open online courses. Ancillary Materials - Applied Math and Science Education Repository AMSER is a portal of educational resources and services built specifically for use by those in community and technical colleges but free for anyone to use. - Creative Commons Search: OERs search for openly licensed content on several large, public platforms, including Google and YouTube. It will help you to find OERs that might otherwise slip through the cracks because they are not listed in OER repositories. - DNA from the Beginning content and animations related to the study of modern genetics. - Internet Archive’s OER Repository this library contains hundreds of free courses, video lectures, and supplemental materials from universities in the United States and China. - MERLOT peer-reviewed digital repository of over OER created and supported by a user community. Resources are crowd-sourced, so check licensing before using them. A project of the California State University System and other institutions. - OER Commons project of the Institute for the Study of Knowledge Management in Education (ISKME), OER Commons is a hub for open resources for all grade levels up to the graduate level. A variety of course materials including modules, lesson plans, assignments, and 265 textbooks for community college-level courses. - PhET: Biology interactive simulations in Biology from the University of Colorado at Boulder. - PhET: Chemistry interactive simulations in Chemistry from the University of Colorado at Boulder. - PhET: Earth Science interactive simulations in Earth Sc ience from the University of Colorado at Boulder. - PhET: Math interactive simulations in Math from the University of Colorado at Boulder. - PhET: Physics interactive simulations from the University of Colorado at Boulder - Skills Commons repository of open workforce development resources developed in partnership with local industries, reviewed by subject matter experts, and focused on business skills. All resources free to use. - Virtual Lab and Science Resource Directory (2020) from BCcampus Open Education, this Pressbooks text lists free science resources designed to support remote science education. Please note that while all resources in this directory are free, not all are open. Search by Discipline - Mason OER Metafinder searches several OER repositories at once. If you check the "deeper search" box, it will also search older materials that are in the public domain. - Oasis a search tool developed at Milne Library at SUNY Geneseo that aims to make the discovery of open content easier. It searches many smaller OER repositories at once, particularly institutional repositories. It is also browsable by subject and type of material. Disciplinary Referatories/Resource Guides - American Institute of Mathematics Open Textbook Initiative approved list of open mathematical textbooks for traditional undergraduate college courses. - BC Campus OER by Discipline Guide frequently updated guide that lists popular OER by subject. - Find Open Educational Resources by Open Michigan includes lists for nursing, sciences, education, and languages. - Iowa Colleges and Universities OER in these collections have been adopted, created, or recommended by faculty in the state of Iowa; they are primarily focused on the sciences, including agriculture, engineering, and education. - OER by Discipline Directory A reference of OER listed by subject area and discipline edited by Lauri M. Aesoph and Josie Gray. The BCcampus Open Education OER by Discipline Directory lists a wide range of open educational resources organized by discipline. This directory is updated as new resources are identified. Note that textbooks in the B.C. Open Collection are not included in this directory. - Open Educational Resources by Discipline semi-regularly updated OER resource lists from the Academic Senate for California Community Colleges including math, science, social sciences, and humanities. Open Media - AllTheFreeStock an aggregator for stock photos, videos, music, and icons, most of them in the public domain. - Artstor Images, videos, documents, and audio files from public institutional collections. When doing a search, freely available items are labeled as "OPEN ARTSTOR" and should have a Creative Commons Zero (CC0) license. - Audio Library a YouTube channel dedicated to search, catalog, sort and publish free music. - ccMixter community of sharing and open music. Explore remixes, samples and pells with CC-BY licensed music. - Disabled and Here Collection a disability-led effort to provide free & inclusive stock images with photos and illustrations celebrating disabled Black, Indigenous, people of color (BIPOC). - EDUimages a free library of photos celebrating students and the educators who teach them in seven schools across the US. Licensed: CC BY-NC 4.0 - Flickr Commons numerous participating institutions share images from the world's public photography archives. Use the "Any license" drop down menu and select "All creative commons" licenses. - Free Music Archive access to independent artists and original music; PRO option provides a wider range of royalty-free music. - The Gender Spectrum Collection contains a stock photo library featuring CC BY-NC-ND 4.0 licensed images of trans and non-binary models. - Google Images Use Google's Advanced Image Search to limit the usage rights with the menu option "Creative Commons licenses." - LibriVox free public domain audiobooks read by volunteers from around the world. - The Metropolitan Museum of Art the Met's Open Access Initiative makes all images of public domain artworks and basic data on all accessioned works in its collection available for unrestricted use. Use "Show Only: Open Access" when doing a search to identify works in the public domain. These will have the "OA" symbol. - The Noun Project collection of images, symbols, and icons. - NappyLinks to an external site. a free library of high resolution photos of Black and Brown people. - NegativeSpace stock images are in the public domain or have a CC0 license. Free to use, edit, and modify for personal and commercial uses. - Openclipart All clipart in Openclipart is in the public domain. Images can be downloaded in various sizes and formats. - Open Content Program of the Getty Museum includes digital images to which the J. Paul Getty Museum holds the rights or that are in the public domain. When using the Getty Search Gateway to look for images, make sure the "Open Content Images" filter is selected. - Openverse Formerly CC (Creative Commons) Search, this search engine includes visual and audio resources with CC licenses or are in the public domain. Use the filter tool to search by CC license preference. - PBS Frontline full-length programs on current social, political, business, and public health issues. - Pexels more than 3 million free, open (Pexels license), high-resolution photos and videos. - Picnoi Free stock photos of people of color with no attribution required. They ask that users link photos back to this site. - Pixabay database of more than 2.6 million photos, illustrations, vector graphics and videos released with the Pixabay open license and no required attribution. - Pixneofree, high quality public domain images that are tagged and categorized. - Smithsonian Open Access includes over 2 million CC0 digital images from the 19 Smithsonian museums, as well as research centers, libraries, archives, and the National Zoo. When performing your search, be sure the "Open Access Media" box (before the search box) is checked off for CC0 images. - SnagFilms full length documentaries and lesser-known movies for free. - TED-Ed a library of curated educational videos, many of which represent collaborations between talented educators and animators nominated through the TED-Ed platform. - Unsplash Free high-resolution images gifted by the global community of photographers for commercial and noncommercial use. Utilizes the Unsplash open license. Attribution is a courtesy. - VADS online resource for visual arts that includes a collection of over 140,000 images available for non-commercial educational and research use (copyright notice). - Wikimedia Commons a database housing millions of media files that are either in the public domain or have a CC license. Please refer to each individual item to view the licensing. - WorldImages database provides access to the California State University IMAGE Project. It contains approximately 100,000 images from around the world that are available under the CC license: CC BY-NC 2.5. For more information about use of images check the “Conditions of Use of Website Images” section available from the main page. Open Resources - American Memory-Library of Congress provides free and open access through the Internet to written and spoken words, sound recordings, still and moving images, prints, maps, and sheet music that document the American experience. Materials from the collections of the Library of Congress and other institutions chronicle historical events, people, places, and ideas that continue to shape America, serving the public as a resource for education and lifelong learning. - Bloomsbury Publishing Open Content selected research publications are published on open content licenses, meaning that the full text is available online for free in html format. - Digital Commons Network free, full-text scholarly articles from hundreds of universities and colleges worldwide, including a growing collection of peer-reviewed journal articles, book chapters, dissertations, working papers, conference proceedings, and other original scholarly work. - Digital Public Library of America access thousands of primary sources (images, documents, films, etc.). Refine search by type, date, source, and subject. - The Directory of Open Access Journals (DOAJ)repository of open-access journals - HathiTrust Digital Librarya partnership of academic & research institutions, offering a collection of millions of titles digitized from libraries around the world. - National Criminal Justice Reference Service a federally funded resource offering justice and drug-related information to support research, policy, and program development worldwide. - National Library of Medicine Digital Collections free online repository of biomedical resources including books, still images, videos, and maps. All of the content is freely available worldwide and, unless otherwise indicated, in the public domain. - The New York Public Libraries' Digital Collections public domain objects from the NYPL Digital Collections - Open Book Publishers free academic non-fiction - Open Humanities Press free scholarly books and journals focusing on the humanities from an international open publishing collective. - PLOS (Public Library of Science) nonprofit organization of scientists and physicians striving to make scientific literature freely available to the public. All PLOS content is available without restriction, as long as the author and the original source are properly attributed according to the Creative Commons Attribution License (CC BY). - Project Gutenbergover 70,000 free ebooks with an emphasis on public domain texts - Social Science Research Network eLibrary provides 726,225 research papers from 335,176 researchers across 30 disciplines. - Ubiquity PressLinks to an external site. open access publisher of peer-reviewed academic journals, books and data. - WorldBank Open Knowledge Repository nonfiction books and reports on international topics. - World Digital Library cultural heritage materials gathered during the World Digital Library (WDL) project, including thousands of items contributed by partner organizations worldwide as well as content from Library of Congress collections. - Most U.S. government-produced creative works are public domain; see here for exceptions.	oercommons	2025-03-18T00:36:13.160276	Reading	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/114963/overview", "title": "Using Creative Commons Tools & Licenses to Create Open Educational Resources: A Professional Development Module for Adopting & Adapting OER", "author": "Module" }
https://oercommons.org/courseware/lesson/15039/overview	Introduction No one knows exactly when viruses emerged or from where they came, since viruses do not leave historical footprints such as fossils. Modern viruses are thought to be a mosaic of bits and pieces of nucleic acids picked up from various sources along their respective evolutionary paths. Viruses are acellular, parasitic entities that are not classified within any kingdom. Unlike most living organisms, viruses are not cells and cannot divide. Instead, they infect a host cell and use the host’s replication processes to produce identical progeny virus particles. Viruses infect organisms as diverse as bacteria, plants, and animals. They exist in a netherworld between a living organism and a nonliving entity. Living things grow, metabolize, and reproduce. Viruses replicate, but to do so, they are entirely dependent on their host cells. They do not metabolize or grow, but are assembled in their mature form.	oercommons	2025-03-18T00:36:13.177494	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15039/overview", "title": "Biology, Biological Diversity", "author": null }
https://oercommons.org/courseware/lesson/15040/overview	Viral Evolution, Morphology, and Classification Overview By the end of this section, you will be able to: - Describe how viruses were first discovered and how they are detected - Discuss three hypotheses about how viruses evolved - Recognize the basic shapes of viruses - Understand past and emerging classification systems for viruses Viruses are diverse entities. They vary in their structure, their replication methods, and in their target hosts. Nearly all forms of life—from bacteria and archaea to eukaryotes such as plants, animals, and fungi—have viruses that infect them. While most biological diversity can be understood through evolutionary history, such as how species have adapted to conditions and environments, much about virus origins and evolution remains unknown. Discovery and Detection Viruses were first discovered after the development of a porcelain filter, called the Chamberland-Pasteur filter, which could remove all bacteria visible in the microscope from any liquid sample. In 1886, Adolph Meyer demonstrated that a disease of tobacco plants, tobacco mosaic disease, could be transferred from a diseased plant to a healthy one via liquid plant extracts. In 1892, Dmitri Ivanowski showed that this disease could be transmitted in this way even after the Chamberland-Pasteur filter had removed all viable bacteria from the extract. Still, it was many years before it was proven that these “filterable” infectious agents were not simply very small bacteria but were a new type of very small, disease-causing particle. Virions, single virus particles, are very small, about 20–250 nanometers in diameter. These individual virus particles are the infectious form of a virus outside the host cell. Unlike bacteria (which are about 100-times larger), we cannot see viruses with a light microscope, with the exception of some large virions of the poxvirus family. It was not until the development of the electron microscope in the late 1930s that scientists got their first good view of the structure of the tobacco mosaic virus (TMV) () and other viruses (Figure). The surface structure of virions can be observed by both scanning and transmission electron microscopy, whereas the internal structures of the virus can only be observed in images from a transmission electron microscope. The use of these technologies has allowed for the discovery of many viruses of all types of living organisms. They were initially grouped by shared morphology. Later, groups of viruses were classified by the type of nucleic acid they contained, DNA or RNA, and whether their nucleic acid was single- or double-stranded. More recently, molecular analysis of viral replicative cycles has further refined their classification. Evolution of Viruses Although biologists have accumulated a significant amount of knowledge about how present-day viruses evolve, much less is known about how viruses originated in the first place. When exploring the evolutionary history of most organisms, scientists can look at fossil records and similar historic evidence. However, viruses do not fossilize, so researchers must conjecture by investigating how today’s viruses evolve and by using biochemical and genetic information to create speculative virus histories. While most findings agree that viruses don’t have a single common ancestor, scholars have yet to find a single hypothesis about virus origins that is fully accepted in the field. One such hypothesis, called devolution or the regressive hypothesis, proposes to explain the origin of viruses by suggesting that viruses evolved from free-living cells. However, many components of how this process might have occurred are a mystery. A second hypothesis (called escapist or the progressive hypothesis) accounts for viruses having either an RNA or a DNA genome and suggests that viruses originated from RNA and DNA molecules that escaped from a host cell. A third hypothesis posits a system of self-replication similar to that of other self-replicating molecules, likely evolving alongside the cells they rely on as hosts; studies of some plant pathogens support this hypothesis. As technology advances, scientists may develop and refine further hypotheses to explain the origin of viruses. The emerging field called virus molecular systematics attempts to do just that through comparisons of sequenced genetic material. These researchers hope to one day better understand the origin of viruses, a discovery that could lead to advances in the treatments for the ailments they produce. Viral Morphology Viruses are acellular, meaning they are biological entities that do not have a cellular structure. They therefore lack most of the components of cells, such as organelles, ribosomes, and the plasma membrane. A virion consists of a nucleic acid core, an outer protein coating or capsid, and sometimes an outer envelope made of protein and phospholipid membranes derived from the host cell. Viruses may also contain additional proteins, such as enzymes. The most obvious difference between members of viral families is their morphology, which is quite diverse. An interesting feature of viral complexity is that the complexity of the host does not correlate with the complexity of the virion. Some of the most complex virion structures are observed in bacteriophages, viruses that infect the simplest living organisms, bacteria. Morphology Viruses come in many shapes and sizes, but these are consistent and distinct for each viral family. All virions have a nucleic acid genome covered by a protective layer of proteins, called a capsid. The capsid is made up of protein subunits called capsomeres. Some viral capsids are simple polyhedral “spheres,” whereas others are quite complex in structure. In general, the shapes of viruses are classified into four groups: filamentous, isometric (or icosahedral), enveloped, and head and tail. Filamentous viruses are long and cylindrical. Many plant viruses are filamentous, including TMV. Isometric viruses have shapes that are roughly spherical, such as poliovirus or herpesviruses. Enveloped viruses have membranes surrounding capsids. Animal viruses, such as HIV, are frequently enveloped. Head and tail viruses infect bacteria and have a head that is similar to icosahedral viruses and a tail shape like filamentous viruses. Many viruses use some sort of glycoprotein to attach to their host cells via molecules on the cell called viral receptors (Figure). For these viruses, attachment is a requirement for later penetration of the cell membrane, so they can complete their replication inside the cell. The receptors that viruses use are molecules that are normally found on cell surfaces and have their own physiological functions. Viruses have simply evolved to make use of these molecules for their own replication. For example, HIV uses the CD4 molecule on T lymphocytes as one of its receptors. CD4 is a type of molecule called a cell adhesion molecule, which functions to keep different types of immune cells in close proximity to each other during the generation of a T lymphocyte immune response. Among the most complex virions known, the T4 bacteriophage, which infects the Escherichia coli bacterium, has a tail structure that the virus uses to attach to host cells and a head structure that houses its DNA. Adenovirus, a non-enveloped animal virus that causes respiratory illnesses in humans, uses glycoprotein spikes protruding from its capsomeres to attach to host cells. Non-enveloped viruses also include those that cause polio (poliovirus), plantar warts (papillomavirus), and hepatitis A (hepatitis A virus). Enveloped virions like HIV, the causative agent in AIDS, consist of nucleic acid (RNA in the case of HIV) and capsid proteins surrounded by a phospholipid bilayer envelope and its associated proteins. Glycoproteins embedded in the viral envelope are used to attach to host cells. Other envelope proteins are the matrix proteins that stabilize the envelope and often play a role in the assembly of progeny virions. Chicken pox, influenza, and mumps are examples of diseases caused by viruses with envelopes. Because of the fragility of the envelope, non-enveloped viruses are more resistant to changes in temperature, pH, and some disinfectants than enveloped viruses. Overall, the shape of the virion and the presence or absence of an envelope tell us little about what disease the virus may cause or what species it might infect, but they are still useful means to begin viral classification (Figure). Art Connection Which of the following statements about virus structure is true? - All viruses are encased in a viral membrane. - The capsomere is made up of small protein subunits called capsids. - DNA is the genetic material in all viruses. - Glycoproteins help the virus attach to the host cell. Types of Nucleic Acid Unlike nearly all living organisms that use DNA as their genetic material, viruses may use either DNA or RNA as theirs. The virus core contains the genome or total genetic content of the virus. Viral genomes tend to be small, containing only those genes that encode proteins that the virus cannot get from the host cell. This genetic material may be single- or double-stranded. It may also be linear or circular. While most viruses contain a single nucleic acid, others have genomes that have several, which are called segments. In DNA viruses, the viral DNA directs the host cell’s replication proteins to synthesize new copies of the viral genome and to transcribe and translate that genome into viral proteins. DNA viruses cause human diseases, such as chickenpox, hepatitis B, and some venereal diseases, like herpes and genital warts. RNA viruses contain only RNA as their genetic material. To replicate their genomes in the host cell, the RNA viruses encode enzymes that can replicate RNA into DNA, which cannot be done by the host cell. These RNA polymerase enzymes are more likely to make copying errors than DNA polymerases, and therefore often make mistakes during transcription. For this reason, mutations in RNA viruses occur more frequently than in DNA viruses. This causes them to change and adapt more rapidly to their host. Human diseases caused by RNA viruses include hepatitis C, measles, and rabies. Virus Classification To understand the features shared among different groups of viruses, a classification scheme is necessary. As most viruses are not thought to have evolved from a common ancestor, however, the methods that scientists use to classify living things are not very useful. Biologists have used several classification systems in the past, based on the morphology and genetics of the different viruses. However, these earlier classification methods grouped viruses differently, based on which features of the virus they were using to classify them. The most commonly used classification method today is called the Baltimore classification scheme and is based on how messenger RNA (mRNA) is generated in each particular type of virus. Past Systems of Classification Viruses are classified in several ways: by factors such as their core content (Table and Figure), the structure of their capsids, and whether they have an outer envelope. The type of genetic material (DNA or RNA) and its structure (single- or double-stranded, linear or circular, and segmented or non-segmented) are used to classify the virus core structures. \| Virus Classification by Genome Structure and Core \| \| \|---\|---\| \| Core Classifications \| Examples \| \| \| \| \| \| \| \| \| Viruses can also be classified by the design of their capsids (Figure and Figure). Capsids are classified as naked icosahedral, enveloped icosahedral, enveloped helical, naked helical, and complex (Figure and Figure). The type of genetic material (DNA or RNA) and its structure (single- or double-stranded, linear or circular, and segmented or non-segmented) are used to classify the virus core structures (Table). \| Virus Classification by Capsid Structure \| \| \|---\|---\| \| Capsid Classification \| Examples \| \| Naked icosahedral \| Hepatitis A virus, polioviruses \| \| Enveloped icosahedral \| Epstein-Barr virus, herpes simplex virus, rubella virus, yellow fever virus, HIV-1 \| \| Enveloped helical \| Influenza viruses, mumps virus, measles virus, rabies virus \| \| Naked helical \| Tobacco mosaic virus \| \| Complex with many proteins; some have combinations of icosahedral and helical capsid structures \| Herpesviruses, smallpox virus, hepatitis B virus, T4 bacteriophage \| Baltimore Classification The most commonly used system of virus classification was developed by Nobel Prize-winning biologist David Baltimore in the early 1970s. In addition to the differences in morphology and genetics mentioned above, the Baltimore classification scheme groups viruses according to how the mRNA is produced during the replicative cycle of the virus. Group I viruses contain double-stranded DNA (dsDNA) as their genome. Their mRNA is produced by transcription in much the same way as with cellular DNA. Group II viruses have single-stranded DNA (ssDNA) as their genome. They convert their single-stranded genomes into a dsDNA intermediate before transcription to mRNA can occur. Group III viruses use dsRNA as their genome. The strands separate, and one of them is used as a template for the generation of mRNA using the RNA-dependent RNA polymerase encoded by the virus. Group IV viruses have ssRNA as their genome with a positive polarity. Positive polarity means that the genomic RNA can serve directly as mRNA. Intermediates of dsRNA, called replicative intermediates, are made in the process of copying the genomic RNA. Multiple, full-length RNA strands of negative polarity (complimentary to the positive-stranded genomic RNA) are formed from these intermediates, which may then serve as templates for the production of RNA with positive polarity, including both full-length genomic RNA and shorter viral mRNAs. Group V viruses contain ssRNA genomes with a negative polarity, meaning that their sequence is complementary to the mRNA. As with Group IV viruses, dsRNA intermediates are used to make copies of the genome and produce mRNA. In this case, the negative-stranded genome can be converted directly to mRNA. Additionally, full-length positive RNA strands are made to serve as templates for the production of the negative-stranded genome. Group VI viruses have diploid (two copies) ssRNA genomes that must be converted, using the enzyme reverse transcriptase, to dsDNA; the dsDNA is then transported to the nucleus of the host cell and inserted into the host genome. Then, mRNA can be produced by transcription of the viral DNA that was integrated into the host genome. Group VII viruses have partial dsDNA genomes and make ssRNA intermediates that act as mRNA, but are also converted back into dsDNA genomes by reverse transcriptase, necessary for genome replication. The characteristics of each group in the Baltimore classification are summarized in Table with examples of each group. \| Baltimore Classification \| \|\|\| \|---\|---\|---\|---\| \| Group \| Characteristics \| Mode of mRNA Production \| Example \| \| I \| Double-stranded DNA \| mRNA is transcribed directly from the DNA template \| Herpes simplex (herpesvirus) \| \| II \| Single-stranded DNA \| DNA is converted to double-stranded form before RNA is transcribed \| Canine parvovirus (parvovirus) \| \| III \| Double-stranded RNA \| mRNA is transcribed from the RNA genome \| Childhood gastroenteritis (rotavirus) \| \| IV \| Single stranded RNA (+) \| Genome functions as mRNA \| Common cold (pircornavirus) \| \| V \| Single stranded RNA (-) \| mRNA is transcribed from the RNA genome \| Rabies (rhabdovirus) \| \| VI \| Single stranded RNA viruses with reverse transcriptase \| Reverse transcriptase makes DNA from the RNA genome; DNA is then incorporated in the host genome; mRNA is transcribed from the incorporated DNA \| Human immunodeficiency virus (HIV) \| \| VII \| Double stranded DNA viruses with reverse transcriptase \| The viral genome is double-stranded DNA, but viral DNA is replicated through an RNA intermediate; the RNA may serve directly as mRNA or as a template to make mRNA \| Hepatitis B virus (hepadnavirus) \| Section Summary Viruses are tiny, acellular entities that can usually only be seen with an electron microscope. Their genomes contain either DNA or RNA—never both—and they replicate using the replication proteins of a host cell. Viruses are diverse, infecting archaea, bacteria, fungi, plants, and animals. Viruses consist of a nucleic acid core surrounded by a protein capsid with or without an outer lipid envelope. The capsid shape, presence of an envelope, and core composition dictate some elements of the classification of viruses. The most commonly used classification method, the Baltimore classification, categorizes viruses based on how they produce their mRNA. Art Connections Review Questions Which statement is true? - A virion contains DNA and RNA. - Viruses are acellular. - Viruses replicate outside of the cell. - Most viruses are easily visualized with a light microscope. Hint: B The viral ________ plays a role in attaching a virion to the host cell. - core - capsid - envelope - both b and c Hint: D Viruses_______. - all have a round shape - cannot have a long shape - do not maintain any shape - vary in shape Hint: D Free Response The first electron micrograph of a virus (tobacco mosaic virus) was produced in 1939. Before that time, how did scientists know that viruses existed if they could not see them? (Hint: Early scientists called viruses “filterable agents.”) Hint: Viruses pass through filters that eliminated all bacteria that were visible in the light microscopes at the time. As the bacteria-free filtrate could still cause infections when given to a healthy organism, this observation demonstrated the existence of very small infectious agents. These agents were later shown to be unrelated to bacteria and were classified as viruses.	oercommons	2025-03-18T00:36:13.215891	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15040/overview", "title": "Biology, Biological Diversity", "author": null }
https://oercommons.org/courseware/lesson/15041/overview	Virus Infections and Hosts Overview By the end of this section, you will be able to: - List the steps of replication and explain what occurs at each step - Describe the lytic and lysogenic cycles of virus replication - Explain the transmission and diseases of animal and plant viruses - Discuss the economic impact of animal and plant viruses Viruses can be seen as obligate, intracellular parasites. A virus must attach to a living cell, be taken inside, manufacture its proteins and copy its genome, and find a way to escape the cell so that the virus can infect other cells. Viruses can infect only certain species of hosts and only certain cells within that host. Cells that a virus may use to replicate are called permissive. For most viruses, the molecular basis for this specificity is that a particular surface molecule known as the viral receptor must be found on the host cell surface for the virus to attach. Also, metabolic and host cell immune response differences seen in different cell types based on differential gene expression are a likely factor in which cells a virus may target for replication. The permissive cell must make the substances that the virus needs or the virus will not be able to replicate there. Steps of Virus Infections A virus must use cell processes to replicate. The viral replication cycle can produce dramatic biochemical and structural changes in the host cell, which may cause cell damage. These changes, called cytopathic (causing cell damage) effects, can change cell functions or even destroy the cell. Some infected cells, such as those infected by the common cold virus known as rhinovirus, die through lysis (bursting) or apoptosis (programmed cell death or “cell suicide”), releasing all progeny virions at once. The symptoms of viral diseases result from the immune response to the virus, which attempts to control and eliminate the virus from the body, and from cell damage caused by the virus. Many animal viruses, such as HIV (human immunodeficiency virus), leave the infected cells of the immune system by a process known as budding, where virions leave the cell individually. During the budding process, the cell does not undergo lysis and is not immediately killed. However, the damage to the cells that the virus infects may make it impossible for the cells to function normally, even though the cells remain alive for a period of time. Most productive viral infections follow similar steps in the virus replication cycle: attachment, penetration, uncoating, replication, assembly, and release (Figure). Attachment A virus attaches to a specific receptor site on the host cell membrane through attachment proteins in the capsid or via glycoproteins embedded in the viral envelope. The specificity of this interaction determines the host—and the cells within the host—that can be infected by a particular virus. This can be illustrated by thinking of several keys and several locks, where each key will fit only one specific lock. Link to Learning This video explains how influenza attacks the body. Entry The nucleic acid of bacteriophages enters the host cell naked, leaving the capsid outside the cell. Plant and animal viruses can enter through endocytosis, in which the cell membrane surrounds and engulfs the entire virus. Some enveloped viruses enter the cell when the viral envelope fuses directly with the cell membrane. Once inside the cell, the viral capsid is degraded, and the viral nucleic acid is released, which then becomes available for replication and transcription. Replication and Assembly The replication mechanism depends on the viral genome. DNA viruses usually use host cell proteins and enzymes to make additional DNA that is transcribed to messenger RNA (mRNA), which is then used to direct protein synthesis. RNA viruses usually use the RNA core as a template for synthesis of viral genomic RNA and mRNA. The viral mRNA directs the host cell to synthesize viral enzymes and capsid proteins, and assemble new virions. Of course, there are exceptions to this pattern. If a host cell does not provide the enzymes necessary for viral replication, viral genes supply the information to direct synthesis of the missing proteins. Retroviruses, such as HIV, have an RNA genome that must be reverse transcribed into DNA, which then is incorporated into the host cell genome. They are within group VI of the Baltimore classification scheme. To convert RNA into DNA, retroviruses must contain genes that encode the virus-specific enzyme reverse transcriptase that transcribes an RNA template to DNA. Reverse transcription never occurs in uninfected host cells—the needed enzyme reverse transcriptase is only derived from the expression of viral genes within the infected host cells. The fact that HIV produces some of its own enzymes not found in the host has allowed researchers to develop drugs that inhibit these enzymes. These drugs, including the reverse transcriptase inhibitor AZT, inhibit HIV replication by reducing the activity of the enzyme without affecting the host’s metabolism. This approach has led to the development of a variety of drugs used to treat HIV and has been effective at reducing the number of infectious virions (copies of viral RNA) in the blood to non-detectable levels in many HIV-infected individuals. Egress The last stage of viral replication is the release of the new virions produced in the host organism, where they are able to infect adjacent cells and repeat the replication cycle. As you’ve learned, some viruses are released when the host cell dies, and other viruses can leave infected cells by budding through the membrane without directly killing the cell. Art Connection Influenza virus is packaged in a viral envelope that fuses with the plasma membrane. This way, the virus can exit the host cell without killing it. What advantage does the virus gain by keeping the host cell alive? Link to Learning Watch a video on viruses, identifying structures, modes of transmission, replication, and more. Different Hosts and Their Viruses As you’ve learned, viruses are often very specific as to which hosts and which cells within the host they will infect. This feature of a virus makes it specific to one or a few species of life on Earth. On the other hand, so many different types of viruses exist on Earth that nearly every living organism has its own set of viruses that tries to infect its cells. Even the smallest and simplest of cells, prokaryotic bacteria, may be attacked by specific types of viruses. Bacteriophages Bacteriophages are viruses that infect bacteria (Figure). When infection of a cell by a bacteriophage results in the production of new virions, the infection is said to be productive. If the virions are released by bursting the cell, the virus replicates by means of a lytic cycle (Figure). An example of a lytic bacteriophage is T4, which infects Escherichia coli found in the human intestinal tract. Sometimes, however, a virus can remain within the cell without being released. For example, when a temperate bacteriophage infects a bacterial cell, it replicates by means of a lysogenic cycle (Figure), and the viral genome is incorporated into the genome of the host cell. When the phage DNA is incorporated into the host cell genome, it is called a prophage. An example of a lysogenic bacteriophage is the λ (lambda) virus, which also infects the E. coli bacterium. Viruses that infect plant or animal cells may also undergo infections where they are not producing virions for long periods. An example is the animal herpesviruses, including herpes simplex viruses, the cause of oral and genital herpes in humans. In a process called latency, these viruses can exist in nervous tissue for long periods of time without producing new virions, only to leave latency periodically and cause lesions in the skin where the virus replicates. Even though there are similarities between lysogeny and latency, the term lysogenic cycle is usually reserved to describe bacteriophages. Latency will be described in more detail below. Art Connection Which of the following statements is false? - In the lytic cycle, new phage are produced and released into the environment. - In the lysogenic cycle, phage DNA is incorporated into the host genome. - An environmental stressor can cause the phage to initiate the lysogenic cycle. - Cell lysis only occurs in the lytic cycle. Animal Viruses Animal viruses, unlike the viruses of plants and bacteria, do not have to penetrate a cell wall to gain access to the host cell. Non-enveloped or “naked” animal viruses may enter cells in two different ways. As a protein in the viral capsid binds to its receptor on the host cell, the virus may be taken inside the cell via a vesicle during the normal cell process of receptor-mediated endocytosis. An alternative method of cell penetration used by non-enveloped viruses is for capsid proteins to undergo shape changes after binding to the receptor, creating channels in the host cell membrane. The viral genome is then “injected” into the host cell through these channels in a manner analogous to that used by many bacteriophages. Enveloped viruses also have two ways of entering cells after binding to their receptors: receptor-mediated endocytosis, or fusion. Many enveloped viruses enter the cell by receptor-mediated endocytosis in a fashion similar to some non-enveloped viruses. On the other hand, fusion only occurs with enveloped virions. These viruses, which include HIV among others, use special fusion proteins in their envelopes to cause the envelope to fuse with the plasma membrane of the cell, thus releasing the genome and capsid of the virus into the cell cytoplasm. After making their proteins and copying their genomes, animal viruses complete the assembly of new virions and exit the cell. As we have already discussed using the example of HIV, enveloped animal viruses may bud from the cell membrane as they assemble themselves, taking a piece of the cell’s plasma membrane in the process. On the other hand, non-enveloped viral progeny, such as rhinoviruses, accumulate in infected cells until there is a signal for lysis or apoptosis, and all virions are released together. As you will learn in the next module, animal viruses are associated with a variety of human diseases. Some of them follow the classic pattern of acute disease, where symptoms get increasingly worse for a short period followed by the elimination of the virus from the body by the immune system and eventual recovery from the infection. Examples of acute viral diseases are the common cold and influenza. Other viruses cause long-term chronic infections, such as the virus causing hepatitis C, whereas others, like herpes simplex virus, only cause intermittent symptoms. Still other viruses, such as human herpesviruses 6 and 7, which in some cases can cause the minor childhood disease roseola, often successfully cause productive infections without causing any symptoms at all in the host, and thus we say these patients have an asymptomatic infection. In hepatitis C infections, the virus grows and reproduces in liver cells, causing low levels of liver damage. The damage is so low that infected individuals are often unaware that they are infected, and many infections are detected only by routine blood work on patients with risk factors such as intravenous drug use. On the other hand, since many of the symptoms of viral diseases are caused by immune responses, a lack of symptoms is an indication of a weak immune response to the virus. This allows for the virus to escape elimination by the immune system and persist in individuals for years, all the while producing low levels of progeny virions in what is known as a chronic viral disease. Chronic infection of the liver by this virus leads to a much greater chance of developing liver cancer, sometimes as much as 30 years after the initial infection. As already discussed, herpes simplex virus can remain in a state of latency in nervous tissue for months, even years. As the virus “hides” in the tissue and makes few if any viral proteins, there is nothing for the immune response to act against, and immunity to the virus slowly declines. Under certain conditions, including various types of physical and psychological stress, the latent herpes simplex virus may be reactivated and undergo a lytic replication cycle in the skin, causing the lesions associated with the disease. Once virions are produced in the skin and viral proteins are synthesized, the immune response is again stimulated and resolves the skin lesions in a few days by destroying viruses in the skin. As a result of this type of replicative cycle, appearances of cold sores and genital herpes outbreaks only occur intermittently, even though the viruses remain in the nervous tissue for life. Latent infections are common with other herpesviruses as well, including the varicella-zoster virus that causes chickenpox. After having a chickenpox infection in childhood, the varicella-zoster virus can remain latent for many years and reactivate in adults to cause the painful condition known as “shingles” (Figureab). Some animal-infecting viruses, including the hepatitis C virus discussed above, are known as oncogenic viruses: They have the ability to cause cancer. These viruses interfere with the normal regulation of the host cell cycle either by either introducing genes that stimulate unregulated cell growth (oncogenes) or by interfering with the expression of genes that inhibit cell growth. Oncogenic viruses can be either DNA or RNA viruses. Cancers known to be associated with viral infections include cervical cancer caused by human papillomavirus (HPV) (Figure), liver cancer caused by hepatitis B virus, T-cell leukemia, and several types of lymphoma. Link to Learning Visit the interactive animations showing the various stages of the replicative cycles of animal viruses and click on the flash animation links. Plant Viruses Plant viruses, like other viruses, contain a core of either DNA or RNA. You have already learned about one of these, the tobacco mosaic virus. As plant cells have a cell wall to protect their cells, these viruses do not use receptor-mediated endocytosis to enter host cells as is seen with animal viruses. For many plant viruses to be transferred from plant to plant, damage to some of the plants’ cells must occur to allow the virus to enter a new host. This damage is often caused by weather, insects, animals, fire, or human activities like farming or landscaping. Additionally, plant offspring may inherit viral diseases from parent plants. Plant viruses can be transmitted by a variety of vectors, through contact with an infected plant’s sap, by living organisms such as insects and nematodes, and through pollen. When plants viruses are transferred between different plants, this is known as horizontal transmission, and when they are inherited from a parent, this is called vertical transmission. Symptoms of viral diseases vary according to the virus and its host (Table). One common symptom is hyperplasia, the abnormal proliferation of cells that causes the appearance of plant tumors known as galls. Other viruses induce hypoplasia, or decreased cell growth, in the leaves of plants, causing thin, yellow areas to appear. Still other viruses affect the plant by directly killing plant cells, a process known as cell necrosis. Other symptoms of plant viruses include malformed leaves, black streaks on the stems of the plants, altered growth of stems, leaves, or fruits, and ring spots, which are circular or linear areas of discoloration found in a leaf. \| Some Common Symptoms of Plant Viral Diseases \| \| \|---\|---\| \| Symptom \| Appears as \| \| Hyperplasia \| Galls (tumors) \| \| Hypoplasia \| Thinned, yellow splotches on leaves \| \| Cell necrosis \| Dead, blackened stems, leaves, or fruit \| \| Abnormal growth patterns \| Malformed stems, leaves, or fruit \| \| Discoloration \| Yellow, red, or black lines, or rings in stems, leaves, or fruit \| Plant viruses can seriously disrupt crop growth and development, significantly affecting our food supply. They are responsible for poor crop quality and quantity globally, and can bring about huge economic losses annually. Others viruses may damage plants used in landscaping. Some viruses that infect agricultural food plants include the name of the plant they infect, such as tomato spotted wilt virus, bean common mosaic virus, and cucumber mosaic virus. In plants used for landscaping, two of the most common viruses are peony ring spot and rose mosaic virus. There are far too many plant viruses to discuss each in detail, but symptoms of bean common mosaic virus result in lowered bean production and stunted, unproductive plants. In the ornamental rose, the rose mosaic disease causes wavy yellow lines and colored splotches on the leaves of the plant. Section Summary Viral replication within a living cell always produces changes in the cell, sometimes resulting in cell death and sometimes slowly killing the infected cells. There are six basic stages in the virus replication cycle: attachment, penetration, uncoating, replication, assembly, and release. A viral infection may be productive, resulting in new virions, or nonproductive, which means that the virus remains inside the cell without producing new virions. Bacteriophages are viruses that infect bacteria. They have two different modes of replication: the lytic cycle, where the virus replicates and bursts out of the bacteria, and the lysogenic cycle, which involves the incorporation of the viral genome into the bacterial host genome. Animal viruses cause a variety of infections, with some causing chronic symptoms (hepatitis C), some intermittent symptoms (latent viruses such a herpes simplex virus 1), and others that cause very few symptoms, if any (human herpesviruses 6 and 7). Oncogenic viruses in animals have the ability to cause cancer by interfering with the regulation of the host cell cycle. Viruses of plants are responsible for significant economic damage in both agriculture and plants used for ornamentation. Art Connections Figure Which of the following statements is false? - In the lytic cycle, new phage are produced and released into the environment. - In the lysogenic cycle, phage DNA is incorporated into the host genome. - An environmental stressor can cause the phage to initiate the lysogenic cycle. - Cell lysis only occurs in the lytic cycle. Hint: Figure C Review Questions Which statement is not true of viral replication? - A lysogenic cycle kills the host cell. - There are six basic steps in the viral replication cycle. - Viral replication does not affect host cell function. - Newly released virions can infect adjacent cells. Hint: D Which statement is true of viral replication? - In the process of apoptosis, the cell survives. - During attachment, the virus attaches at specific sites on the cell surface. - The viral capsid helps the host cell produce more copies of the viral genome. - mRNA works outside of the host cell to produce enzymes and proteins. Hint: B Which statement is true of reverse transcriptase? - It is a nucleic acid. - It infects cells. - It transcribes RNA to make DNA. - It is a lipid. Hint: C Oncogenic virus cores can be_______. - RNA - DNA - neither RNA nor DNA - either RNA or DNA Hint: D Which is true of DNA viruses? - They use the host cell’s machinery to produce new copies of their genome. - They all have envelopes. - They are the only kind of viruses that can cause cancer. - They are not important plant pathogens. Hint: A A bacteriophage can infect ________. - the lungs - viruses - prions - bacteria Hint: D Free Response Why can’t dogs catch the measles? Hint: The virus can’t attach to dog cells, because dog cells do not express the receptors for the virus and/or there is no cell within the dog that is permissive for viral replication. One of the first and most important targets for drugs to fight infection with HIV (a retrovirus) is the reverse transcriptase enzyme. Why? Hint: Reverse transcriptase is needed to make more HIV-1 viruses, so targeting the reverse transcriptase enzyme may be a way to inhibit the replication of the virus. Importantly, by targeting reverse transcriptase, we do little harm to the host cell, since host cells do not make reverse transcriptase. Thus, we can specifically attack the virus and not the host cell when we use reverse transcriptase inhibitors. In this section, you were introduced to different types of viruses and viral diseases. Briefly discuss the most interesting or surprising thing you learned about viruses. Hint: Answer is open and will vary. Although plant viruses cannot infect humans, what are some of the ways in which they affect humans? Hint: Plant viruses infect crops, causing crop damage and failure, and considerable economic losses.	oercommons	2025-03-18T00:36:13.259283	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15041/overview", "title": "Biology, Biological Diversity", "author": null }
https://oercommons.org/courseware/lesson/15042/overview	Prevention and Treatment of Viral Infections Overview By the end of this section, you will be able to: - Identify major viral illnesses that affect humans - Compare vaccinations and anti-viral drugs as medical approaches to viruses Viruses cause a variety of diseases in animals, including humans, ranging from the common cold to potentially fatal illnesses like meningitis (Figure). These diseases can be treated by antiviral drugs or by vaccines, but some viruses, such as HIV, are capable of both avoiding the immune response and mutating to become resistant to antiviral drugs. Vaccines for Prevention While we do have limited numbers of effective antiviral drugs, such as those used to treat HIV and influenza, the primary method of controlling viral disease is by vaccination, which is intended to prevent outbreaks by building immunity to a virus or virus family (Figure). Vaccines may be prepared using live viruses, killed viruses, or molecular subunits of the virus. The killed viral vaccines and subunit viruses are both incapable of causing disease. Live viral vaccines are designed in the laboratory to cause few symptoms in recipients while giving them protective immunity against future infections. Polio was one disease that represented a milestone in the use of vaccines. Mass immunization campaigns in the 1950s (killed vaccine) and 1960s (live vaccine) significantly reduced the incidence of the disease, which caused muscle paralysis in children and generated a great amount of fear in the general population when regional epidemics occurred. The success of the polio vaccine paved the way for the routine dispensation of childhood vaccines against measles, mumps, rubella, chickenpox, and other diseases. The danger of using live vaccines, which are usually more effective than killed vaccines, is the low but significant danger that these viruses will revert to their disease-causing form by back mutations. Live vaccines are usually made by attenuating (weakening) the “wild-type” (disease-causing) virus by growing it in the laboratory in tissues or at temperatures different from what the virus is accustomed to in the host. Adaptations to these new cells or temperatures induce mutations in the genomes of the virus, allowing it to grow better in the laboratory while inhibiting its ability to cause disease when reintroduced into conditions found in the host. These attenuated viruses thus still cause infection, but they do not grow very well, allowing the immune response to develop in time to prevent major disease. Back mutations occur when the vaccine undergoes mutations in the host such that it readapts to the host and can again cause disease, which can then be spread to other humans in an epidemic. This type of scenario happened as recently as 2007 in Nigeria where mutations in a polio vaccine led to an epidemic of polio in that country. Some vaccines are in continuous development because certain viruses, such as influenza and HIV, have a high mutation rate compared to other viruses and normal host cells. With influenza, mutations in the surface molecules of the virus help the organism evade the protective immunity that may have been obtained in a previous influenza season, making it necessary for individuals to get vaccinated every year. Other viruses, such as those that cause the childhood diseases measles, mumps, and rubella, mutate so infrequently that the same vaccine is used year after year. Link to Learning Watch this NOVA video to learn how microbiologists are attempting to replicate the deadly 1918 Spanish influenza virus so they can understand more about virology. Vaccines and Anti-viral Drugs for Treatment In some cases, vaccines can be used to treat an active viral infection. The concept behind this is that by giving the vaccine, immunity is boosted without adding more disease-causing virus. In the case of rabies, a fatal neurological disease transmitted via the saliva of rabies virus-infected animals, the progression of the disease from the time of the animal bite to the time it enters the central nervous system may be 2 weeks or longer. This is enough time to vaccinate an individual who suspects that they have been bitten by a rabid animal, and their boosted immune response is sufficient to prevent the virus from entering nervous tissue. Thus, the potentially fatal neurological consequences of the disease are averted, and the individual only has to recover from the infected bite. This approach is also being used for the treatment of Ebola, one of the fastest and most deadly viruses on earth. Transmitted by bats and great apes, this disease can cause death in 70–90 percent of infected humans within 2 weeks. Using newly developed vaccines that boost the immune response in this way, there is hope that affected individuals will be better able to control the virus, potentially saving a greater percentage of infected persons from a rapid and very painful death. Another way of treating viral infections is the use of antiviral drugs. These drugs often have limited success in curing viral disease, but in many cases, they have been used to control and reduce symptoms for a wide variety of viral diseases. For most viruses, these drugs can inhibit the virus by blocking the actions of one or more of its proteins. It is important that the targeted proteins be encoded by viral genes and that these molecules are not present in a healthy host cell. In this way, viral growth is inhibited without damaging the host. There are large numbers of antiviral drugs available to treat infections, some specific for a particular virus and others that can affect multiple viruses. Antivirals have been developed to treat genital herpes (herpes simplex II) and influenza. For genital herpes, drugs such as acyclovir can reduce the number and duration of episodes of active viral disease, during which patients develop viral lesions in their skin cells. As the virus remains latent in nervous tissue of the body for life, this drug is not curative but can make the symptoms of the disease more manageable. For influenza, drugs like Tamiflu (oseltamivir) (Figure) can reduce the duration of “flu” symptoms by 1 or 2 days, but the drug does not prevent symptoms entirely. Tamiflu works by inhibiting an enzyme (viral neuraminidase) that allows new virions to leave their infected cells. Thus, Tamiflu inhibits the spread of virus from infected to uninfected cells. Other antiviral drugs, such as Ribavirin, have been used to treat a variety of viral infections, although its mechanism of action against certain viruses remains unclear. By far, the most successful use of antivirals has been in the treatment of the retrovirus HIV, which causes a disease that, if untreated, is usually fatal within 10–12 years after infection. Anti-HIV drugs have been able to control viral replication to the point that individuals receiving these drugs survive for a significantly longer time than the untreated. Anti-HIV drugs inhibit viral replication at many different phases of the HIV replicative cycle (Figure). Drugs have been developed that inhibit the fusion of the HIV viral envelope with the plasma membrane of the host cell (fusion inhibitors), the conversion of its RNA genome into double-stranded DNA (reverse transcriptase inhibitors), the integration of the viral DNA into the host genome (integrase inhibitors), and the processing of viral proteins (protease inhibitors). When any of these drugs are used individually, the high mutation rate of the virus allows it to easily and rapidly develop resistance to the drug, limiting the drug’s effectiveness. The breakthrough in the treatment of HIV was the development of HAART, highly active anti-retroviral therapy, which involves a mixture of different drugs, sometimes called a drug “cocktail.” By attacking the virus at different stages of its replicative cycle, it is much more difficult for the virus to develop resistance to multiple drugs at the same time. Still, even with the use of combination HAART therapy, there is concern that, over time, the virus will develop resistance to this therapy. Thus, new anti-HIV drugs are constantly being developed with the hope of continuing the battle against this highly fatal virus. Everyday Connection Applied Virology The study of viruses has led to the development of a variety of new ways to treat non-viral diseases. Viruses have been used in gene therapy. Gene therapy is used to treat genetic diseases such as severe combined immunodeficiency (SCID), a heritable, recessive disease in which children are born with severely compromised immune systems. One common type of SCID is due to the lack of an enzyme, adenosine deaminase (ADA), which breaks down purine bases. To treat this disease by gene therapy, bone marrow cells are taken from a SCID patient and the ADA gene is inserted. This is where viruses come in, and their use relies on their ability to penetrate living cells and bring genes in with them. Viruses such as adenovirus, an upper respiratory human virus, are modified by the addition of the ADA gene, and the virus then transports this gene into the cell. The modified cells, now capable of making ADA, are then given back to the patients in the hope of curing them. Gene therapy using viruses as carrier of genes (viral vectors), although still experimental, holds promise for the treatment of many genetic diseases. Still, many technological problems need to be solved for this approach to be a viable method for treating genetic disease. Another medical use for viruses relies on their specificity and ability to kill the cells they infect. Oncolytic viruses are engineered in the laboratory specifically to attack and kill cancer cells. A genetically modified adenovirus known as H101 has been used since 2005 in clinical trials in China to treat head and neck cancers. The results have been promising, with a greater short-term response rate to the combination of chemotherapy and viral therapy than to chemotherapy treatment alone. This ongoing research may herald the beginning of a new age of cancer therapy, where viruses are engineered to find and specifically kill cancer cells, regardless of where in the body they may have spread. A third use of viruses in medicine relies on their specificity and involves using bacteriophages in the treatment of bacterial infections. Bacterial diseases have been treated with antibiotics since the 1940s. However, over time, many bacteria have developed resistance to antibiotics. A good example is methicillin-resistant Staphylococcus aureus (MRSA, pronounced “mersa”), an infection commonly acquired in hospitals. This bacterium is resistant to a variety of antibiotics, making it difficult to treat. The use of bacteriophages specific for such bacteria would bypass their resistance to antibiotics and specifically kill them. Although phage therapy is in use in the Republic of Georgia to treat antibiotic-resistant bacteria, its use to treat human diseases has not been approved in most countries. However, the safety of the treatment was confirmed in the United States when the U.S. Food and Drug Administration approved spraying meats with bacteriophages to destroy the food pathogen Listeria. As more and more antibiotic-resistant strains of bacteria evolve, the use of bacteriophages might be a potential solution to the problem, and the development of phage therapy is of much interest to researchers worldwide. Section Summary Viruses cause a variety of diseases in humans. Many of these diseases can be prevented by the use of viral vaccines, which stimulate protective immunity against the virus without causing major disease. Viral vaccines may also be used in active viral infections, boosting the ability of the immune system to control or destroy the virus. A series of antiviral drugs that target enzymes and other protein products of viral genes have been developed and used with mixed success. Combinations of anti-HIV drugs have been used to effectively control the virus, extending the lifespans of infected individuals. Viruses have many uses in medicines, such as in the treatment of genetic disorders, cancer, and bacterial infections. Review Questions Which of the following is NOT used to treat active viral disease? - vaccines - antiviral drugs - antibiotics - phage therapy Hint: C Vaccines_______. - are similar to viroids - are only needed once - kill viruses - stimulate an immune response Hint: D Free Response Why is immunization after being bitten by a rabid animal so effective and why aren’t people vaccinated for rabies like dogs and cats are? Hint: Rabies vaccine works after a bite because it takes week for the virus to travel from the site of the bite to the central nervous system, where the most severe symptoms of the disease occur. Adults are not routinely vaccinated for rabies for two reasons: first, because the routine vaccination of domestic animals makes it unlikely that humans will contract rabies from an animal bite; second, if one is bitten by a wild animal or a domestic animal that one cannot confirm has been immunized, there is still time to give the vaccine and avoid the often fatal consequences of the disease.	oercommons	2025-03-18T00:36:13.285432	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15042/overview", "title": "Biology, Biological Diversity", "author": null }
https://oercommons.org/courseware/lesson/15043/overview	Other Acellular Entities: Prions and Viroids Overview By the end of this section, you will be able to: - Describe prions and their basic properties - Define viroids and their targets of infection Prions and viroids are pathogens (agents with the ability to cause disease) that have simpler structures than viruses but, in the case of prions, still can produce deadly diseases. Prions Prions, so-called because they are proteinaceous, are infectious particles—smaller than viruses—that contain no nucleic acids (neither DNA nor RNA). Historically, the idea of an infectious agent that did not use nucleic acids was considered impossible, but pioneering work by Nobel Prize-winning biologist Stanley Prusiner has convinced the majority of biologists that such agents do indeed exist. Fatal neurodegenerative diseases, such as kuru in humans and bovine spongiform encephalopathy (BSE) in cattle (commonly known as “mad cow disease”) were shown to be transmitted by prions. The disease was spread by the consumption of meat, nervous tissue, or internal organs between members of the same species. Kuru, native to humans in Papua New Guinea, was spread from human to human via ritualistic cannibalism. BSE, originally detected in the United Kingdom, was spread between cattle by the practice of including cattle nervous tissue in feed for other cattle. Individuals with kuru and BSE show symptoms of loss of motor control and unusual behaviors, such as uncontrolled bursts of laughter with kuru, followed by death. Kuru was controlled by inducing the population to abandon its ritualistic cannibalism. On the other hand, BSE was initially thought to only affect cattle. Cattle dying of the disease were shown to have developed lesions or “holes” in the brain, causing the brain tissue to resemble a sponge. Later on in the outbreak, however, it was shown that a similar encephalopathy in humans known as variant Creutzfeldt-Jakob disease (CJD) could be acquired from eating beef from animals with BSE, sparking bans by various countries on the importation of British beef and causing considerable economic damage to the British beef industry (Figure). BSE still exists in various areas, and although a rare disease, individuals that acquire CJD are difficult to treat. The disease can be spread from human to human by blood, so many countries have banned blood donation from regions associated with BSE. The cause of spongiform encephalopathies, such as kuru and BSE, is an infectious structural variant of a normal cellular protein called PrP (prion protein). It is this variant that constitutes the prion particle. PrP exists in two forms, PrPc, the normal form of the protein, and PrPsc, the infectious form. Once introduced into the body, the PrPsc contained within the prion binds to PrPc and converts it to PrPsc. This leads to an exponential increase of the PrPsc protein, which aggregates. PrPsc is folded abnormally, and the resulting conformation (shape) is directly responsible for the lesions seen in the brains of infected cattle. Thus, although not without some detractors among scientists, the prion seems likely to be an entirely new form of infectious agent, the first one found whose transmission is not reliant upon genes made of DNA or RNA. Viroids Viroids are plant pathogens: small, single-stranded, circular RNA particles that are much simpler than a virus. They do not have a capsid or outer envelope, but like viruses can reproduce only within a host cell. Viroids do not, however, manufacture any proteins, and they only produce a single, specific RNA molecule. Human diseases caused by viroids have yet to be identified. Viroids are known to infect plants (Figure) and are responsible for crop failures and the loss of millions of dollars in agricultural revenue each year. Some of the plants they infect include potatoes, cucumbers, tomatoes, chrysanthemums, avocados, and coconut palms. Career Connection Virologist Virology is the study of viruses, and a virologist is an individual trained in this discipline. Training in virology can lead to many different career paths. Virologists are actively involved in academic research and teaching in colleges and medical schools. Some virologists treat patients or are involved in the generation and production of vaccines. They might participate in epidemiologic studies (Figure) or become science writers, to name just a few possible careers. If you think you may be interested in a career in virology, find a mentor in the field. Many large medical centers have departments of virology, and smaller hospitals usually have virology labs within their microbiology departments. Volunteer in a virology lab for a semester or work in one over the summer. Discussing the profession and getting a first-hand look at the work will help you decide whether a career in virology is right for you. The American Society of Virology’s website is a good resource for information regarding training and careers in virology. Section Summary Prions are infectious agents that consist of protein, but no DNA or RNA, and seem to produce their deadly effects by duplicating their shapes and accumulating in tissues. They are thought to contribute to several progressive brain disorders, including mad cow disease and Creutzfeldt-Jakob disease. Viroids are single-stranded RNA pathogens that infect plants. Their presence can have a severe impact on the agriculture industry. Review Questions Which of the following is not associated with prions? - replicating shapes - mad cow disease - DNA - toxic proteins Hint: C Which statement is true of viroids? - They are single-stranded RNA particles. - They reproduce only outside of the cell. - They produce proteins. - They affect both plants and animals. Hint: A Free Response Prions are responsible for variant Creutzfeldt-Jakob Disease, which has resulted in over 100 human deaths in Great Britain during the last 10 years. How do humans obtain this disease? Hint: This prion-based disease is transmitted through human consumption of infected meat. How are viroids like viruses? Hint: They both replicate in a cell, and they both contain nucleic acid.	oercommons	2025-03-18T00:36:13.308846	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15043/overview", "title": "Biology, Biological Diversity", "author": null }
https://oercommons.org/courseware/lesson/15044/overview	Introduction In the recent past, scientists grouped living things into five kingdoms—animals, plants, fungi, protists, and prokaryotes—based on several criteria, such as the absence or presence of a nucleus and other membrane-bound organelles, the absence or presence of cell walls, multicellularity, and so on. In the late 20th century, the pioneering work of Carl Woese and others compared sequences of small-subunit ribosomal RNA (SSU rRNA), which resulted in a more fundamental way to group organisms on Earth. Based on differences in the structure of cell membranes and in rRNA, Woese and his colleagues proposed that all life on Earth evolved along three lineages, called domains. The domain Bacteria comprises all organisms in the kingdom Bacteria, the domain Archaea comprises the rest of the prokaryotes, and the domain Eukarya comprises all eukaryotes—including organisms in the kingdoms Animalia, Plantae, Fungi, and Protista. Two of the three domains—Bacteria and Archaea—are prokaryotic. Prokaryotes were the first inhabitants on Earth, appearing 3.5 to 3.8 billion years ago. These organisms are abundant and ubiquitous; that is, they are present everywhere. In addition to inhabiting moderate environments, they are found in extreme conditions: from boiling springs to permanently frozen environments in Antarctica; from salty environments like the Dead Sea to environments under tremendous pressure, such as the depths of the ocean; and from areas without oxygen, such as a waste management plant, to radioactively contaminated regions, such as Chernobyl. Prokaryotes reside in the human digestive system and on the skin, are responsible for certain illnesses, and serve an important role in the preparation of many foods.	oercommons	2025-03-18T00:36:13.325089	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15044/overview", "title": "Biology, Biological Diversity", "author": null }
https://oercommons.org/courseware/lesson/15045/overview	Prokaryotic Diversity Overview By the end of this section, you will be able to: - Describe the evolutionary history of prokaryotes - Discuss the distinguishing features of extremophiles - Explain why it is difficult to culture prokaryotes Prokaryotes are ubiquitous. They cover every imaginable surface where there is sufficient moisture, and they live on and inside of other living things. In the typical human body, prokaryotic cells outnumber human body cells by about ten to one. They comprise the majority of living things in all ecosystems. Some prokaryotes thrive in environments that are inhospitable for most living things. Prokaryotes recycle nutrients—essential substances (such as carbon and nitrogen)—and they drive the evolution of new ecosystems, some of which are natural and others man-made. Prokaryotes have been on Earth since long before multicellular life appeared. Prokaryotes, the First Inhabitants of Earth When and where did life begin? What were the conditions on Earth when life began? Prokaryotes were the first forms of life on Earth, and they existed for billions of years before plants and animals appeared. The Earth and its moon are thought to be about 4.54 billion years old. This estimate is based on evidence from radiometric dating of meteorite material together with other substrate material from Earth and the moon. Early Earth had a very different atmosphere (contained less molecular oxygen) than it does today and was subjected to strong radiation; thus, the first organisms would have flourished where they were more protected, such as in ocean depths or beneath the surface of the Earth. At this time too, strong volcanic activity was common on Earth, so it is likely that these first organisms—the first prokaryotes—were adapted to very high temperatures. Early Earth was prone to geological upheaval and volcanic eruption, and was subject to bombardment by mutagenic radiation from the sun. The first organisms were prokaryotes that could withstand these harsh conditions. Microbial Mats Microbial mats or large biofilms may represent the earliest forms of life on Earth; there is fossil evidence of their presence starting about 3.5 billion years ago. A microbial mat is a multi-layered sheet of prokaryotes (Figure) that includes mostly bacteria, but also archaea. Microbial mats are a few centimeters thick, and they typically grow where different types of materials interface, mostly on moist surfaces. The various types of prokaryotes that comprise them carry out different metabolic pathways, and that is the reason for their various colors. Prokaryotes in a microbial mat are held together by a glue-like sticky substance that they secrete called extracellular matrix. The first microbial mats likely obtained their energy from chemicals found near hydrothermal vents. A hydrothermal vent is a breakage or fissure in the Earth’s surface that releases geothermally heated water. With the evolution of photosynthesis about 3 billion years ago, some prokaryotes in microbial mats came to use a more widely available energy source—sunlight—whereas others were still dependent on chemicals from hydrothermal vents for energy and food. Stromatolites Fossilized microbial mats represent the earliest record of life on Earth. A stromatolite is a sedimentary structure formed when minerals are precipitated out of water by prokaryotes in a microbial mat (Figure). Stromatolites form layered rocks made of carbonate or silicate. Although most stromatolites are artifacts from the past, there are places on Earth where stromatolites are still forming. For example, growing stromatolites have been found in the Anza-Borrego Desert State Park in San Diego County, California. The Ancient Atmosphere Evidence indicates that during the first two billion years of Earth’s existence, the atmosphere was anoxic, meaning that there was no molecular oxygen. Therefore, only those organisms that can grow without oxygen—anaerobic organisms—were able to live. Autotrophic organisms that convert solar energy into chemical energy are called phototrophs, and they appeared within one billion years of the formation of Earth. Then, cyanobacteria, also known as blue-green algae, evolved from these simple phototrophs one billion years later. Cyanobacteria (Figure) began the oxygenation of the atmosphere. Increased atmospheric oxygen allowed the development of more efficient O2-utilizing catabolic pathways. It also opened up the land to increased colonization, because some O2 is converted into O3 (ozone) and ozone effectively absorbs the ultraviolet light that would otherwise cause lethal mutations in DNA. Ultimately, the increase in O2 concentrations allowed the evolution of other life forms. Microbes Are Adaptable: Life in Moderate and Extreme Environments Some organisms have developed strategies that allow them to survive harsh conditions. Prokaryotes thrive in a vast array of environments: Some grow in conditions that would seem very normal to us, whereas others are able to thrive and grow under conditions that would kill a plant or animal. Almost all prokaryotes have a cell wall, a protective structure that allows them to survive in both hyper- and hypo-osmotic conditions. Some soil bacteria are able to form endospores that resist heat and drought, thereby allowing the organism to survive until favorable conditions recur. These adaptations, along with others, allow bacteria to be the most abundant life form in all terrestrial and aquatic ecosystems. Other bacteria and archaea are adapted to grow under extreme conditions and are called extremophiles, meaning “lovers of extremes.” Extremophiles have been found in all kinds of environments: the depth of the oceans, hot springs, the Artic and the Antarctic, in very dry places, deep inside Earth, in harsh chemical environments, and in high radiation environments (Figure), just to mention a few. These organisms give us a better understanding of prokaryotic diversity and open up the possibility of finding new prokaryotic species that may lead to the discovery of new therapeutic drugs or have industrial applications. Because they have specialized adaptations that allow them to live in extreme conditions, many extremophiles cannot survive in moderate environments. There are many different groups of extremophiles: They are identified based on the conditions in which they grow best, and several habitats are extreme in multiple ways. For example, a soda lake is both salty and alkaline, so organisms that live in a soda lake must be both alkaliphiles and halophiles (Table). Other extremophiles, like radioresistant organisms, do not prefer an extreme environment (in this case, one with high levels of radiation), but have adapted to survive in it (Figure). \| Extremophiles and Their Preferred Conditions \| \| \|---\|---\| \| Extremophile Type \| Conditions for Optimal Growth \| \| Acidophiles \| pH 3 or below \| \| Alkaliphiles \| pH 9 or above \| \| Thermophiles \| Temperature 60–80 °C (140–176 °F) \| \| Hyperthermophiles \| Temperature 80–122 °C (176–250 °F) \| \| Psychrophiles \| Temperature of -15-10 °C (5-50 °F) or lower \| \| Halophiles \| Salt concentration of at least 0.2 M \| \| Osmophiles \| High sugar concentration \| Prokaryotes in the Dead Sea One example of a very harsh environment is the Dead Sea, a hypersaline basin that is located between Jordan and Israel. Hypersaline environments are essentially concentrated seawater. In the Dead Sea, the sodium concentration is 10 times higher than that of seawater, and the water contains high levels of magnesium (about 40 times higher than in seawater) that would be toxic to most living things. Iron, calcium, and magnesium, elements that form divalent ions (Fe2+, Ca2+, and Mg2+), produce what is commonly referred to as “hard” water. Taken together, the high concentration of divalent cations, the acidic pH (6.0), and the intense solar radiation flux make the Dead Sea a unique, and uniquely hostile, ecosystemBodaker, I, Itai, S, Suzuki, MT, Feingersch, R, Rosenberg, M, Maguire, ME, Shimshon, B, and others. Comparative community genomics in the Dead Sea: An increasingly extreme environment. The ISME Journal 4 (2010): 399–407, doi:10.1038/ismej.2009.141. published online 24 December 2009. (Figure). What sort of prokaryotes do we find in the Dead Sea? The extremely salt-tolerant bacterial mats include Halobacterium, Haloferax volcanii (which is found in other locations, not only the Dead Sea), Halorubrum sodomense, and Halobaculum gomorrense, and the archaea Haloarcula marismortui, among others. Unculturable Prokaryotes and the Viable-but-Non-Culturable State Microbiologists typically grow prokaryotes in the laboratory using an appropriate culture medium containing all the nutrients needed by the target organism. The medium can be liquid, broth, or solid. After an incubation time at the right temperature, there should be evidence of microbial growth (Figure). The process of culturing bacteria is complex and is one of the greatest discoveries of modern science. German physician Robert Koch is credited with discovering the techniques for pure culture, including staining and using growth media. His assistant Julius Petri invented the Petri dish whose use persists in today’s laboratories. Koch worked primarily with the Mycobacterium tuberculosis bacterium that causes tuberculosis and developed postulates to identify disease-causing organisms that continue to be widely used in the medical community. Koch’s postulates include that an organism can be identified as the cause of disease when it is present in all infected samples and absent in all healthy samples, and it is able to reproduce the infection after being cultured multiple times. Today, cultures remain a primary diagnostic tool in medicine and other areas of molecular biology. Some prokaryotes, however, cannot grow in a laboratory setting. In fact, over 99 percent of bacteria and archaea are unculturable. For the most part, this is due to a lack of knowledge as to what to feed these organisms and how to grow them; they have special requirements for growth that remain unknown to scientists, such as needing specific micronutrients, pH, temperature, pressure, co-factors, or co-metabolites. Some bacteria cannot be cultured because they are obligate intracellular parasites and cannot be grown outside a host cell. In other cases, culturable organisms become unculturable under stressful conditions, even though the same organism could be cultured previously. Those organisms that cannot be cultured but are not dead are in a viable-but-non-culturable (VBNC) state. The VBNC state occurs when prokaryotes respond to environmental stressors by entering a dormant state that allows their survival. The criteria for entering into the VBNC state are not completely understood. In a process called resuscitation, the prokaryote can go back to “normal” life when environmental conditions improve. Is the VBNC state an unusual way of living for prokaryotes? In fact, most of the prokaryotes living in the soil or in oceanic waters are non-culturable. It has been said that only a small fraction, perhaps one percent, of prokaryotes can be cultured under laboratory conditions. If these organisms are non-culturable, then how is it known whether they are present and alive? Microbiologists use molecular techniques, such as the polymerase chain reaction (PCR), to amplify selected portions of DNA of prokaryotes, demonstrating their existence. Recall that PCR can make billions of copies of a DNA segment in a process called amplification. The Ecology of Biofilms Until a couple of decades ago, microbiologists used to think of prokaryotes as isolated entities living apart. This model, however, does not reflect the true ecology of prokaryotes, most of which prefer to live in communities where they can interact. A biofilm is a microbial community (Figure) held together in a gummy-textured matrix that consists primarily of polysaccharides secreted by the organisms, together with some proteins and nucleic acids. Biofilms grow attached to surfaces. Some of the best-studied biofilms are composed of prokaryotes, although fungal biofilms have also been described as well as some composed of a mixture of fungi and bacteria. Biofilms are present almost everywhere: they can cause the clogging of pipes and readily colonize surfaces in industrial settings. In recent, large-scale outbreaks of bacterial contamination of food, biofilms have played a major role. They also colonize household surfaces, such as kitchen counters, cutting boards, sinks, and toilets, as well as places on the human body, such as the surfaces of our teeth. Interactions among the organisms that populate a biofilm, together with their protective exopolysaccharidic (EPS) environment, make these communities more robust than free-living, or planktonic, prokaryotes. The sticky substance that holds bacteria together also excludes most antibiotics and disinfectants, making biofilm bacteria hardier than their planktonic counterparts. Overall, biofilms are very difficult to destroy because they are resistant to many common forms of sterilization. Art Connection Compared to free-floating bacteria, bacteria in biofilms often show increased resistance to antibiotics and detergents. Why do you think this might be the case? Section Summary Prokaryotes existed for billions of years before plants and animals appeared. Hot springs and hydrothermal vents may have been the environments in which life began. Microbial mats are thought to represent the earliest forms of life on Earth, and there is fossil evidence of their presence about 3.5 billion years ago. A microbial mat is a multi-layered sheet of prokaryotes that grows at interfaces between different types of material, mostly on moist surfaces. During the first 2 billion years, the atmosphere was anoxic and only anaerobic organisms were able to live. Cyanobacteria evolved from early phototrophs and began the oxygenation of the atmosphere. The increase in oxygen concentration allowed the evolution of other life forms. Fossilized microbial mats are called stromatolites and consist of laminated organo-sedimentary structures formed by precipitation of minerals by prokaryotes. They represent the earliest fossil record of life on Earth. Bacteria and archaea grow in virtually every environment. Those that survive under extreme conditions are called extremophiles (extreme lovers). Some prokaryotes cannot grow in a laboratory setting, but they are not dead. They are in the viable-but-non-culturable (VBNC) state. The VBNC state occurs when prokaryotes enter a dormant state in response to environmental stressors. Most prokaryotes are social and prefer to live in communities where interactions take place. A biofilm is a microbial community held together in a gummy-textured matrix. Art Connections Figure Compared to free-floating bacteria, bacteria in biofilms often show increased resistance to antibiotics and detergents. Why do you think this might be the case? Hint: Figure The extracellular matrix and outer layer of cells protects the inner bacteria. The close proximity of cells also facilitates lateral gene transfer, a process by which genes such as antibiotic resistance genes are transferred from one bacterium to another. And even if lateral gene transfer does not occur, one bacterium that produces an exo-enzyme that destroys antibiotic may save neighboring bacteria. Review Questions The first forms of life on Earth were thought to be_________. - single-celled plants - prokaryotes - insects - large animals such as dinosaurs Hint: A Microbial mats __________. - are the earliest forms of life on Earth - obtained their energy and food from hydrothermal vents - are multi-layered sheet of prokaryotes including mostly bacteria but also archaea - all of the above Hint: D The first organisms that oxygenated the atmosphere were - cyanobacteria - phototrophic organisms - anaerobic organisms - all of the above Hint: A Halophiles are organisms that require________. - a salt concentration of at least 0.2 M - high sugar concentration - the addition of halogens - all of the above Hint: A Free Response Describe briefly how you would detect the presence of a non-culturable prokaryote in an environmental sample. Hint: As the organisms are non-culturable, the presence could be detected through molecular techniques, such as PCR. Why do scientists believe that the first organisms on Earth were extremophiles? Hint: Because the environmental conditions on Earth were extreme: high temperatures, lack of oxygen, high radiation, and the like.	oercommons	2025-03-18T00:36:13.358930	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15045/overview", "title": "Biology, Biological Diversity", "author": null }
https://oercommons.org/courseware/lesson/15046/overview	Structure of Prokaryotes Overview By the end of this section, you will be able to: - Describe the basic structure of a typical prokaryote - Describe important differences in structure between Archaea and Bacteria There are many differences between prokaryotic and eukaryotic cells. However, all cells have four common structures: the plasma membrane, which functions as a barrier for the cell and separates the cell from its environment; the cytoplasm, a jelly-like substance inside the cell; nucleic acids, the genetic material of the cell; and ribosomes, where protein synthesis takes place. Prokaryotes come in various shapes, but many fall into three categories: cocci (spherical), bacilli (rod-shaped), and spirilli (spiral-shaped) (Figure). The Prokaryotic Cell Recall that prokaryotes (Figure) are unicellular organisms that lack organelles or other internal membrane-bound structures. Therefore, they do not have a nucleus but instead generally have a single chromosome—a piece of circular, double-stranded DNA located in an area of the cell called the nucleoid. Most prokaryotes have a cell wall outside the plasma membrane. Recall that prokaryotes are divided into two different domains, Bacteria and Archaea, which together with Eukarya, comprise the three domains of life (Figure). The composition of the cell wall differs significantly between the domains Bacteria and Archaea. The composition of their cell walls also differs from the eukaryotic cell walls found in plants (cellulose) or fungi and insects (chitin). The cell wall functions as a protective layer, and it is responsible for the organism’s shape. Some bacteria have an outer capsule outside the cell wall. Other structures are present in some prokaryotic species, but not in others (Table). For example, the capsule found in some species enables the organism to attach to surfaces, protects it from dehydration and attack by phagocytic cells, and makes pathogens more resistant to our immune responses. Some species also have flagella (singular, flagellum) used for locomotion, and pili (singular, pilus) used for attachment to surfaces. Plasmids, which consist of extra-chromosomal DNA, are also present in many species of bacteria and archaea. Characteristics of phyla of Bacteria are described in Figure and Figure; Archaea are described in Figure. The Plasma Membrane The plasma membrane is a thin lipid bilayer (6 to 8 nanometers) that completely surrounds the cell and separates the inside from the outside. Its selectively permeable nature keeps ions, proteins, and other molecules within the cell and prevents them from diffusing into the extracellular environment, while other molecules may move through the membrane. Recall that the general structure of a cell membrane is a phospholipid bilayer composed of two layers of lipid molecules. In archaeal cell membranes, isoprene (phytanyl) chains linked to glycerol replace the fatty acids linked to glycerol in bacterial membranes. Some archaeal membranes are lipid monolayers instead of bilayers (Figure). The Cell Wall The cytoplasm of prokaryotic cells has a high concentration of dissolved solutes. Therefore, the osmotic pressure within the cell is relatively high. The cell wall is a protective layer that surrounds some cells and gives them shape and rigidity. It is located outside the cell membrane and prevents osmotic lysis (bursting due to increasing volume). The chemical composition of the cell walls varies between archaea and bacteria, and also varies between bacterial species. Bacterial cell walls contain peptidoglycan, composed of polysaccharide chains that are cross-linked by unusual peptides containing both L- and D-amino acids including D-glutamic acid and D-alanine. Proteins normally have only L-amino acids; as a consequence, many of our antibiotics work by mimicking D-amino acids and therefore have specific effects on bacterial cell wall development. There are more than 100 different forms of peptidoglycan. S-layer (surface layer) proteins are also present on the outside of cell walls of both archaea and bacteria. Bacteria are divided into two major groups: Gram positive and Gram negative, based on their reaction to Gram staining. Note that all Gram-positive bacteria belong to one phylum; bacteria in the other phyla (Proteobacteria, Chlamydias, Spirochetes, Cyanobacteria, and others) are Gram-negative. The Gram staining method is named after its inventor, Danish scientist Hans Christian Gram (1853–1938). The different bacterial responses to the staining procedure are ultimately due to cell wall structure. Gram-positive organisms typically lack the outer membrane found in Gram-negative organisms (Figure). Up to 90 percent of the cell wall in Gram-positive bacteria is composed of peptidoglycan, and most of the rest is composed of acidic substances called teichoic acids. Teichoic acids may be covalently linked to lipids in the plasma membrane to form lipoteichoic acids. Lipoteichoic acids anchor the cell wall to the cell membrane. Gram-negative bacteria have a relatively thin cell wall composed of a few layers of peptidoglycan (only 10 percent of the total cell wall), surrounded by an outer envelope containing lipopolysaccharides (LPS) and lipoproteins. This outer envelope is sometimes referred to as a second lipid bilayer. The chemistry of this outer envelope is very different, however, from that of the typical lipid bilayer that forms plasma membranes. Art Connection Which of the following statements is true? - Gram-positive bacteria have a single cell wall anchored to the cell membrane by lipoteichoic acid. - Porins allow entry of substances into both Gram-positive and Gram-negative bacteria. - The cell wall of Gram-negative bacteria is thick, and the cell wall of Gram-positive bacteria is thin. - Gram-negative bacteria have a cell wall made of peptidoglycan, whereas Gram-positive bacteria have a cell wall made of lipoteichoic acid. Archaean cell walls do not have peptidoglycan. There are four different types of Archaean cell walls. One type is composed of pseudopeptidoglycan, which is similar to peptidoglycan in morphology but contains different sugars in the polysaccharide chain. The other three types of cell walls are composed of polysaccharides, glycoproteins, or pure protein. \| Structural Differences and Similarities between Bacteria and Archaea \| \|\| \|---\|---\|---\| \| Structural Characteristic \| Bacteria \| Archaea \| \| Cell type \| Prokaryotic \| Prokaryotic \| \| Cell morphology \| Variable \| Variable \| \| Cell wall \| Contains peptidoglycan \| Does not contain peptidoglycan \| \| Cell membrane type \| Lipid bilayer \| Lipid bilayer or lipid monolayer \| \| Plasma membrane lipids \| Fatty acids \| Phytanyl groups \| Reproduction Reproduction in prokaryotes is asexual and usually takes place by binary fission. Recall that the DNA of a prokaryote exists as a single, circular chromosome. Prokaryotes do not undergo mitosis. Rather the chromosome is replicated and the two resulting copies separate from one another, due to the growth of the cell. The prokaryote, now enlarged, is pinched inward at its equator and the two resulting cells, which are clones, separate. Binary fission does not provide an opportunity for genetic recombination or genetic diversity, but prokaryotes can share genes by three other mechanisms. In transformation, the prokaryote takes in DNA found in its environment that is shed by other prokaryotes. If a nonpathogenic bacterium takes up DNA for a toxin gene from a pathogen and incorporates the new DNA into its own chromosome, it too may become pathogenic. In transduction, bacteriophages, the viruses that infect bacteria, sometimes also move short pieces of chromosomal DNA from one bacterium to another. Transduction results in a recombinant organism. Archaea are not affected by bacteriophages but instead have their own viruses that translocate genetic material from one individual to another. In conjugation, DNA is transferred from one prokaryote to another by means of a pilus, which brings the organisms into contact with one another. The DNA transferred can be in the form of a plasmid or as a hybrid, containing both plasmid and chromosomal DNA. These three processes of DNA exchange are shown in Figure. Reproduction can be very rapid: a few minutes for some species. This short generation time coupled with mechanisms of genetic recombination and high rates of mutation result in the rapid evolution of prokaryotes, allowing them to respond to environmental changes (such as the introduction of an antibiotic) very quickly. Evolution Connection The Evolution of ProkaryotesHow do scientists answer questions about the evolution of prokaryotes? Unlike with animals, artifacts in the fossil record of prokaryotes offer very little information. Fossils of ancient prokaryotes look like tiny bubbles in rock. Some scientists turn to genetics and to the principle of the molecular clock, which holds that the more recently two species have diverged, the more similar their genes (and thus proteins) will be. Conversely, species that diverged long ago will have more genes that are dissimilar. Scientists at the NASA Astrobiology Institute and at the European Molecular Biology Laboratory collaborated to analyze the molecular evolution of 32 specific proteins common to 72 species of prokaryotes.Battistuzzi, FU, Feijao, A, and Hedges, SB. A genomic timescale of prokaryote evolution: Insights into the origin of methanogenesis, phototrophy, and the colonization of land. BioMed Central: Evolutionary Biology 4 (2004): 44, doi:10.1186/1471-2148-4-44. The model they derived from their data indicates that three important groups of bacteria—Actinobacteria, Deinococcus, and Cyanobacteria (which the authors call Terrabacteria)—were the first to colonize land. (Recall that Deinococcus is a genus of prokaryote—a bacterium—that is highly resistant to ionizing radiation.) Cyanobacteria are photosynthesizers, while Actinobacteria are a group of very common bacteria that include species important in decomposition of organic wastes. The timelines of divergence suggest that bacteria (members of the domain Bacteria) diverged from common ancestral species between 2.5 and 3.2 billion years ago, whereas archaea diverged earlier: between 3.1 and 4.1 billion years ago. Eukarya later diverged off the Archaean line. The work further suggests that stromatolites that formed prior to the advent of cyanobacteria (about 2.6 billion years ago) photosynthesized in an anoxic environment and that because of the modifications of the Terrabacteria for land (resistance to drying and the possession of compounds that protect the organism from excess light), photosynthesis using oxygen may be closely linked to adaptations to survive on land. Section Summary Prokaryotes (domains Archaea and Bacteria) are single-celled organisms lacking a nucleus. They have a single piece of circular DNA in the nucleoid area of the cell. Most prokaryotes have a cell wall that lies outside the boundary of the plasma membrane. Some prokaryotes may have additional structures such as a capsule, flagella, and pili. Bacteria and Archaea differ in the lipid composition of their cell membranes and the characteristics of the cell wall. In archaeal membranes, phytanyl units, rather than fatty acids, are linked to glycerol. Some archaeal membranes are lipid monolayers instead of bilayers. The cell wall is located outside the cell membrane and prevents osmotic lysis. The chemical composition of cell walls varies between species. Bacterial cell walls contain peptidoglycan. Archaean cell walls do not have peptidoglycan, but they may have pseudopeptidoglycan, polysaccharides, glycoproteins, or protein-based cell walls. Bacteria can be divided into two major groups: Gram positive and Gram negative, based on the Gram stain reaction. Gram-positive organisms have a thick cell wall, together with teichoic acids. Gram-negative organisms have a thin cell wall and an outer envelope containing lipopolysaccharides and lipoproteins. Art Connections Figure Which of the following statements is true? - Gram-positive bacteria have a single cell wall anchored to the cell membrane by lipoteichoic acid. - Porins allow entry of substances into both Gram-positive and Gram-negative bacteria. - The cell wall of Gram-negative bacteria is thick, and the cell wall of Gram-positive bacteria is thin. - Gram-negative bacteria have a cell wall made of peptidoglycan, whereas Gram-positive bacteria have a cell wall made of lipoteichoic acid. Hint: Figure A Review Questions The presence of a membrane-enclosed nucleus is a characteristic of ________. - prokaryotic cells - eukaryotic cells - all cells - viruses Hint: B Which of the following consist of prokaryotic cells? - bacteria and fungi - archaea and fungi - protists and animals - bacteria and archaea Hint: D The cell wall is ________. - interior to the cell membrane - exterior to the cell membrane - a part of the cell membrane - interior or exterior, depending on the particular cell Hint: B Organisms most likely to be found in extreme environments are ________. - fungi - bacteria - viruses - archaea Hint: B Prokaryotes stain as Gram-positive or Gram-negative because of differences in the cell _______. - wall - cytoplasm - nucleus - chromosome Hint: A Pseudopeptidoglycan is a characteristic of the walls of ________. - eukaryotic cells - bacterial prokaryotic cells - archaean prokaryotic cells - bacterial and archaean prokaryotic cells Hint: C The lipopolysaccharide layer (LPS) is a characteristic of the wall of ________. - archaean cells - Gram-negative bacteria - bacterial prokaryotic cells - eukaryotic cells Hint: B Free Response Mention three differences between bacteria and archaea. Hint: Responses will vary. A possible answer is: Bacteria contain peptidoglycan in the cell wall; archaea do not. The cell membrane in bacteria is a lipid bilayer; in archaea, it can be a lipid bilayer or a monolayer. Bacteria contain fatty acids on the cell membrane, whereas archaea contain phytanyl. Explain the statement that both types, bacteria and archaea, have the same basic structures, but built from different chemical components. Hint: Both bacteria and archaea have cell membranes and they both contain a hydrophobic portion. In the case of bacteria, it is a fatty acid; in the case of archaea, it is a hydrocarbon (phytanyl). Both bacteria and archaea have a cell wall that protects them. In the case of bacteria, it is composed of peptidoglycan, whereas in the case of archaea, it is pseudopeptidoglycan, polysaccharides, glycoproteins, or pure protein. Bacterial and archaeal flagella also differ in their chemical structure.	oercommons	2025-03-18T00:36:13.396783	null	{ "license": "Creative Commons - Attribution - https://creativecommons.org/licenses/by/4.0/", "url": "https://oercommons.org/courseware/lesson/15046/overview", "title": "Biology, Biological Diversity", "author": null }

Subsets and Splits

No community queries yet

The top public SQL queries from the community will appear here once available.