The lymphatic vessels begin as open-ended capillaries, which feed into larger and larger lymphatic vessels, and eventually empty into the bloodstream. Along the way, the lymph travels through the lymph nodes, which are commonly found near the groin, armpits, neck, chest, and abdomen. Humans have about 500 to 600 lymph nodes throughout the body (see Figure 11.1). Several organs and tissues that participate in immunity are also part of the lymphatic system.


The lymphatic capillaries empty into larger lymphatic vessels, which are similar to veins in terms of their three-tunic structure and the presence of valves. These one-way valves are located fairly close to one another, and each one causes a bulge in the lymphatic vessel, giving the vessels a beaded appearance (see Figure 11.2).


In general, superficial lymphatics follow the same routes as veins, whereas deep lymphatic vessels of the viscera generally follow the paths of arteries. The superficial and deep lymphatics eventually merge to form larger lymphatic structures known as the lymphatic trunks. On the right side of the body, the right sides of the head, thorax, and right upper limb trunks drain lymph fluid into the right subclavian vein via the right lymphatic duct (see Figure 11.3). On the left side of the body, the trunks from the remaining portions of the body drain into the larger thoracic duct, which drains into the left subclavian vein. The thoracic duct itself begins just beneath the diaphragm in the cisterna chyli.


The primary lymphoid organs are the bone marrow and thymus gland. The lymphoid organs are where lymphocytes mature, proliferate, and are selected, which enables them to attack pathogens without harming the cells of the body.


Lymphocytes develop and mature in the primary lymphoid organs, but they mount immune responses from the secondary lymphoid organs, which include the lymph nodes, spleen, and lymphoid nodules. A naïve lymphocyte is one that has left the primary organ, where it learned to function immunologically, and entered a secondary lymphoid organ where it waits to encounter an antigen against which it will mount a response (see Figure 11.5).


Lymph nodes function to remove debris and pathogens from the lymph and are thus sometimes referred to as the “filters of the lymph” (see Figure 11.6). Any bacteria that infect the interstitial fluid are taken up by the lymphatic capillaries and transported to a regional lymph node. Dendritic cells and macrophages within this organ internalize and kill many of the pathogens that pass through, thereby removing them from the body. The lymph node is also the site of adaptive immune responses mediated by T cells, B cells, and accessory cells of the adaptive immune system.


The spleen is a vascular organ that is somewhat fragile due to the absence of a capsule. It is about 12 cm long and is attached to the lateral border of the stomach. The spleen is sometimes called the “filter of the blood” because of its extensive vascularization and the presence of macrophages and dendritic cells that remove microbes and other materials from the blood, including dying red blood cells. The spleen also functions as the location of immune responses to blood-borne pathogens.


The other lymphoid tissues, the lymphoid nodules, consist of a dense cluster of lymphocytes without a surrounding fibrous capsule. These nodules are located in the respiratory and digestive tracts, areas routinely exposed to environmental pathogens.


Tonsils are lymphoid nodules located along the inner surface of the pharynx and are important in developing immunity to oral pathogens (see Figure 11.8). The tonsil located at the back of the throat, the pharyngeal tonsil, is sometimes referred to as the adenoid when swollen. Such swelling is an indication of an active immune response to infection. Tonsils have deep grooves called crypts, which accumulate all sorts of materials taken into the body through eating and breathing and actually “encourage” pathogens to penetrate deep into the tonsillar tissues where they are eliminated. A major function of tonsils is to help children’s bodies recognize, destroy, and develop immunity to common environmental pathogens so that they will be protected in their later lives. Tonsils are often removed in children who have recurring throat infections since swollen palatine tonsils can interfere with breathing and/or swallowing.


Mucosa-associated lymphoid tissue (MALT) consists of an aggregate of lymphoid follicles directly associated with mucous membrane. MALT makes up dome-shaped structures found underlying the mucosa of the gastrointestinal tract, breast tissue, lungs, and eyes. Peyer’s patches, a type of MALT in the small intestine, are especially important for immune responses against ingested substances (see Figure 11.9). Peyer’s patches contain specialized cells that sample material from the intestinal lumen and transport it to nearby follicles so that adaptive immune responses to potential pathogens can be mounted.


The immune system is a collection of barriers, cells, and soluble proteins that interact and communicate with each other in extraordinarily complex ways. The modern model of immune function is organized into a three-phase immune response (based on the timing of their effects). Ideally, this response will rid the body of a pathogen entirely (see Figure 11.10).


Think of a primary infection as a race between the pathogen and the immune system:


Barrier defenses are part of the body’s most basic innate defense mechanisms. They are not a response to infections, but rather are continuously working to protect against pathogens by preventing them from entering the body, destroying them after they enter, or flushing them out before they can establish themselves.


Innate immune responses are critical to the early control of infections. Whereas barrier defenses are the body’s first line of physical defense against pathogens, innate immune responses are the first line of physiological defense. Innate responses occur rapidly, but with less specificity and effectiveness than the adaptive immune response. Within the first few days of an infection, a series of antibacterial proteins are induced, each with activities against certain bacteria. Additionally, interferons are induced that protect cells from viruses in their vicinity. Finally, the innate immune response does not stop when the adaptive immune response is developed. In fact, both can cooperate and one can influence the other in their responses against pathogens.


Innate immune responses (and early induced responses) are in many cases ineffective at completely controlling pathogen growth but they slow pathogen growth and allow time for the adaptive immune response to strengthen and either control or eliminate the pathogen. The innate immune system also sends signals to the cells of the adaptive immune system, guiding them in how to attack the pathogen.


Media 11.2 Immune System, Part 1: Crash Course A&P #45 [Online video]. Copyright 2015 by CrashCourse.


A phagocyte is a cell that is able to surround and engulf a particle or cell, a process called phagocytosis. The phagocytes of the immune system engulf other particles or cells, either to clean an area of debris, old cells, or to kill pathogenic organisms such as bacteria. Macrophages, neutrophils, and dendritic cells are the major phagocytes of the immune system and are the body’s fast acting, front line immunological defense against organisms that have breached barrier defenses and have entered the body.


Macrophages not only participate in innate immune responses but have also evolved to cooperate with lymphocytes as part of the adaptive immune response. Macrophages exist in many tissues of the body, either freely roaming through connective tissues or fixed to reticular fibers within specific tissues such as lymph nodes. When pathogens breach the body’s barrier defenses, macrophages are the first line of defense.


A neutrophil is a phagocytic cell that is attracted via chemotaxis from the bloodstream to infected tissues. contains cytoplasmic granules, which in turn contain a variety of vasoactive mediators such as histamine. Whereas macrophages act like sentries, always on guard against infection, neutrophils can be thought of as military reinforcements that are called into a battle to hasten the destruction of the enemy.


A monocyte is a circulating precursor cell that differentiates into either a macrophage or dendritic cell, which can be rapidly attracted to areas of infection by signal molecules of inflammation.


Natural killer cells are a type of lymphocyte that have the ability to induce apoptosis in cells infected with pathogens such as intracellular bacteria and viruses. If apoptosis is induced before the virus has the ability to synthesize and assemble all its components, no infectious virus will be released from the cell, thus preventing further infection.


A cytokine is a signaling molecule that allows cells to communicate with each other over short distances. Cytokines are secreted into the intercellular space, and the action of the cytokine induces the receiving cell to change its physiology. A chemokine is a soluble chemical mediator similar to cytokines except that its function is to attract cells (chemotaxis) from longer distances.


Early induced proteins are those that are not constitutively present in the body but are made as they are needed early during the innate immune response. Interferons are an example of early induced proteins. Cells infected with viruses secrete interferons that travel to adjacent cells and induce them to make antiviral proteins. Thus, even though the initial cell is sacrificed, the surrounding cells are protected.


The hallmark of the innate immune response is inflammation. Stub a toe, cut a finger, or do any activity that causes tissue damage and inflammation will result with its four characteristics: heat, redness, pain, and swelling (“loss of function” is sometimes mentioned as a fifth characteristic). It is important to note that inflammation does not have to be initiated by an infection, but can also be caused by tissue injuries. The release of damaged cellular contents into the site of injury is enough to stimulate the response, even in the absence of breaks in physical barriers that would allow pathogens to enter (by hitting your thumb with a hammer, for example). The inflammatory reaction brings in phagocytic cells to the damaged area to clear cellular debris and encourages the entry of clotting factors to set the stage for wound repair. Inflammation also facilitates the transport of antigen to lymph nodes by dendritic cells for the development of the adaptive immune response.


The above image summarizes the following events in the inflammatory response:


Acute inflammation is a short-term innate immune response to an insult to the body. If the cause of the inflammation is not resolved, however, it can lead to chronic inflammation, which is associated with major tissue destruction and fibrosis.


Media 11.3 Immune System, Part 2: Crash Course A&P #46 [Online video]. Copyright 2015 by CrashCourse.


As stated above, lymphocytes are the primary cells of adaptive immune responses. These cells were introduced in the previous chapter and are summarized in the following table:


Immunity to pathogens, and the ability to control pathogen growth so that damage to the tissues of the body is limited, can be acquired by:


The downside to this passive immunity is the lack of the development of immunological memory. Once the antibodies are transferred, they are effective for only a limited time before they degrade.


The immune system and pathogens are in a slow, evolutionary race to see who stays on top. Early childhood is a time when the body develops much of its immunological memory that protects it from diseases in adulthood. Pathogens have shown the ability, however, to evade the body’s immune responses, as described below.


One disease of transplantation occurs with bone marrow transplants, which are used to treat various diseases, including severe combined immunodeficiency disease (SCID) and leukemia. Because the bone marrow cells being transplanted contain lymphocytes capable of mounting an immune response, and because the recipient’s immune response has been destroyed before receiving the transplant, the donor cells may attack the recipient tissues, causing graft-versus-host disease. Signs and symptoms of this disease, which usually include a rash and damage to the liver and mucosa, are variable. Attempts have been made to moderate the disease by first removing mature T cells from the donor bone marrow before transplanting it.


It is clear that with some cancers, like Kaposi’s sarcoma (see Figure 11.14), for example, that a healthy immune system does a good job at controlling them. This disease, which is caused by the human herpes virus, is almost never observed in individuals with strong immune systems. Other examples of cancers caused by viruses include liver cancer, caused by the hepatitis B virus, and cervical cancer, caused by the human papillomavirus. As these last two viruses have vaccines available for them, getting vaccinated can help prevent these two types of cancer by stimulating the immune response.


On the other hand, as cancer cells are often able to divide and mutate rapidly, they may escape the immune response, just as certain pathogens such as the human immunodeficiency virus (HIV) do.


There are three stages in the immune response to many cancers:


This fact has led to extensive research in trying to develop ways to enhance the early immune response to completely eliminate the early cancer and thus prevent a later escape. One method that has shown some success is the use of cancer vaccines. These differ from other vaccines in that they are directed against the cells of one’s own body. Treated cancer cells are injected into cancer patients to enhance their anti-cancer immune response and thereby prolong survival. The immune system has the capability to detect these cancer cells and proliferate faster than the cancer cells do, thus overwhelming the cancer in a similar way as they do for viruses. Cancer vaccines are being developed for malignant melanoma and renal (kidney) cell carcinoma.


One well-established interaction of the immune, nervous, and endocrine systems is the effect of stress on immune health. In the human vertebrate evolutionary past, stress was associated with the fight-or-flight response, largely mediated by the central nervous system and the adrenal medulla. This stress was necessary for survival since fighting or fleeing usually resolved the problem in one way or another. It has been found that short-term stress diverts the body’s resources towards enhancing innate immune responses. This has the ability to act fast and would seem to help the body prepare better for possible infections associated with the trauma that may result from a fight-or-flight exchange.


On the other hand, there are no physical actions to resolve most modern day stresses, including short-term stressors like taking examinations and long-term stressors such as being unemployed or losing a spouse. The effect of stress can be felt by nearly every organ system, and the immune system is no exception (see Table 11.3). Chronic stress, unlike short-term stress, may inhibit immune responses even in otherwise healthy adults. The suppression of both innate and adaptive immune responses is clearly associated with increases in some diseases.


Many terms and phrases related to the lymphatic and immune systems are abbreviated. Learn these common abbreviations by expanding the list below.


The immune response can be under-reactive or over-reactive, leading to a state of disease. The factors that maintain immunological homeostasis are complex and incompletely understood.


Lymphedema is a condition in which lymphatic fluid builds up in the body’s soft tissues. Lymphedema often occurs in the arms and legs, although other body parts may be affected. There are two types of lymphedema: primary and secondary. Primary lymphedema may be congenital and is caused by abnormalities in the lymph system. Secondary lymphedema occurs when the lymph system is damaged or blocked due to injury, cancer, or cancer treatment. Signs and symptoms include swelling of the limbs and digits, difficulty moving the joints in the arms and legs, and the sensation that the skin is too tight. Lymphedema is rarely cured. Instead, treatment such as the use of pressure garments, light exercise, massage therapy, and surgery can reduce symptoms and lower the risk of complications. Patients with severe cases of lymphedema are at an increased risk of developing lymphangiosarcoma, an aggressive cancer of the lymph vessels (National Cancer Institute, 2021; Sleigh & Manna, 2021). For more information, visit the Mayo Clinic’s web page on lymphedema.


Suppressed immunity can result from inherited genetic defects or by acquiring viruses.


New treatments for SCID using gene therapy, inserting non-defective genes into cells taken from the patient and giving them back, have the advantage of not needing the tissue match required for standard transplants. Although not a standard treatment, this approach holds promise, especially for those in whom standard bone marrow transplantation has failed.


After seroconversion, the amount of virus circulating in the blood drops and stays at a low level for several years. During this time, the levels of CD4 T cells decline steadily, until at some point, the immune response is so weak that opportunistic disease and eventually death result.


Treatment for the disease consists of drugs that target virally encoded proteins that are necessary for viral replication but are absent from normal human cells. By targeting the virus itself and sparing the cells, this approach has been successful in significantly prolonging the lives of HIV-positive individuals.


The worst cases of the immune system overreacting are autoimmune diseases in which the immune systems begin to attack cells of the patient’s own body, causing chronic inflammation and significant damage. The trigger for these diseases is often unknown, although environmental and genetic factors are likely involved. Treatments are usually based on resolving the symptoms using immunosuppressive and anti-inflammatory drugs. Figure 11.15 below provides two examples of autoimmune diseases: rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).


Overall, there are more than 80 different autoimmune diseases, which are a significant health problem in the elderly. Table 11.5 below lists several of the most common autoimmune diseases, the antigens that are targeted (autoantigen or “self” antigen), and the resulting tissue damage.


Lymphoma is a form of cancer in which masses of malignant T and/or B lymphocytes collect in lymph nodes, the spleen, the liver, and other tissues. As in leukemia, the malignant leukocytes do not function properly, and the patient is vulnerable to infection. Some forms of lymphoma tend to progress slowly and respond well to treatment. Others tend to progress quickly and require aggressive treatment, without which they are rapidly fatal.


Medical Specialties and Procedures Related to the Lymphatic and Immune Systems


Clinical immunologists and allergists diagnose and treat diseases of the immune system (National Center for O*Net Development, 2021). For more information, please visit the American Academy of Allergy, Asthma, and Immunology’s web page on careers in immunology.


Skin testing (for allergies) is done by a clinical immunologist/allergist to identify allergens in Type I hypersensitivity. In skin testing, allergen extracts are injected into the epidermis, and a positive result of the wheal and flare response usually occurs within 30 minutes. The soft center is due to fluid leaking from the blood vessels and the redness is caused by the increased blood flow to the area that results from the dilation of local blood vessels at the site.


Virtually every cell, tissue, organ, and system in the body is impacted by the circulatory system. This includes the generalized and more specialized functions of transport of materials, capillary exchange, maintaining health by transporting white blood cells and various immunoglobulins (antibodies), hemostasis, regulation of body temperature, and helping to maintain acid-base balance. Table 10.1 summarizes the important relationships between the circulatory system and the other body systems.


Media 10.1 Blood Vessels, Part 1 – Form and Function: Crash Course A&P #27 [Online video]. Copyright 2015 by CrashCourse.


Blood pumped by the heart flows through a series of vessels known as arteries, arterioles, capillaries, venules, and veins before returning to the heart.


Both arteries and veins have the same three distinct tissue layers, called tunics, for the garments first worn by ancient Romans. From the most interior layer to the outer, these tunics are the tunica intima, the tunica media, and the tunica externa (see Figure 10.3). The smooth muscle in the middle layer, the tunica media, provides the vessel with the ability to vasoconstrict and vasodilate as needed to ensure sufficient blood flow.


Arteries and veins transport blood in two distinct circuits: the systemic circuit and the pulmonary circuit. Systemic arteries provide blood rich in oxygen to the body’s tissues. The blood returned to the heart through systemic veins has less oxygen, since much of the oxygen carried by the arteries has been delivered to the cells. In contrast, in the pulmonary circuit, arteries carry blood low in oxygen exclusively to the lungs for gas exchange. Pulmonary veins then return freshly oxygenated blood from the lungs to the heart to be pumped back out into systemic circulation.


Each time the heart ejects blood forcefully into the circulation, the arteries must expand and then recoil to accommodate the surge of blood moving through them. This expansion and recoiling of the arterial wall is called the pulse and allows us to measure heart rate. Pulse can be palpated manually by placing the tips of the fingers across an artery that runs close to the body surface, such as the radial artery or the common carotid artery. These sites and other pulse sites are shown in the figure below.


Both the rate and the strength of the pulse are important clinically. A high or irregular pulse rate can be caused by physical activity or other temporary factors, but it may also indicate a heart condition. The pulse strength indicates the strength of ventricular contraction and cardiac output. If the pulse is strong, then systolic pressure is high. If it is weak, systolic pressure has fallen, and medical intervention may be warranted.


The Composition (Anatomy) of Blood and the Functions of the Components


In normal blood, about 45% of a sample is erythrocytes, which is referred to as the hematocrit. The hematocrit of any one sample can vary significantly, however, about 36 to 50%, according to gender and other factors. Not counting the buffy coat, which makes up less than 1% of the blood, we can estimate the mean plasma percentage to be the percent of blood that is not erythrocytes: approximately 55%.


Like other fluids in the body, plasma is composed primarily of water. In fact, it is about 92% water. Dissolved or suspended within this water is a mixture of substances, most of which are proteins. The major components of plasma and their functions are summarized in the table above.


The table below summarizes the main facts about the formed elements in blood.


In children, hemopoiesis can occur in the medullary cavity of long bones; in adults, the process is largely restricted to the cranial and pelvic bones, the vertebrae, the sternum, and the proximal epiphyses of the femur and humerus. Throughout adulthood, the liver and spleen maintain their ability to generate the formed elements. This process is referred to as extramedullary hematopoiesis. When a disease such as bone cancer destroys the bone marrow, causing hemopoiesis to fail, extramedullary hematopoiesis may be initiated .


All formed elements arise from stem cells of the red bone marrow, called hematopoietic stem cells, or hemocytoblast. Hemopoiesis begins when the hematopoietic stem cell is exposed to appropriate chemical stimuli collectively called hemopoietic growth factors, which prompt it to divide and differentiate. One daughter cell remains a hematopoietic stem cell, allowing hemopoiesis to continue. The other daughter cell becomes either of two types of more specialized stem cells. Follow the chart below from top to bottom to learn how stem cells become mature formed elements of blood.


The most abundant formed elements in blood, erythrocytes are basically sacs packed with an oxygen-carrying compound called hemoglobin. Production of erythrocytes in the red bone marrow occurs at the staggering rate of more than 2 million cells per second. For this production to occur, raw materials including iron, copper, zinc B-vitamins, glucose, lipids, and amino acids must be present in adequate amounts. Erythrocytes live only 120 days on average, and thus must be continually replaced. Worn-out erythrocytes are phagocytized by macrophages and their hemoglobin is broken down. The breakdown products are recycled or removed as wastes.


Leukocytes routinely leave the bloodstream to perform their defensive functions in the body’s tissues, where they are often given distinct names, such as macrophage or microglia, depending on their function. As shown in Figure 10.11 below, they leave the capillaries—the smallest blood vessels—or other small vessels through a process known as emigration or diapedesis in which they squeeze through adjacent cells in a blood vessel wall.


Once they have exited the capillaries, some leukocytes will take up fixed positions in lymphatic tissue, bone marrow, the spleen, the thymus, or other organs. Others will move about through the tissue spaces, sometimes wandering freely, and sometimes moving toward the direction in which they are drawn by chemical signals, a mechanism known as positive chemotaxis.


Lymphocytes are a type of leukocyte. The three major groups of lymphocytes include natural killer cells, B cells, and T cells.


After entering the circulation, approximately one-third of the newly-formed platelets migrate to the spleen for storage for later release in response to any rupture in a blood vessel. They then become activated to perform their primary function, which is to limit blood loss. Platelets remain only about 10 days, then are phagocytized by macrophages.


Platelets are key players in hemostasis, the process by which the body seals a ruptured blood vessel and prevents further loss of blood. Although rupture of larger vessels usually requires medical intervention, hemostasis is quite effective in dealing with small, simple wounds. There are three steps to the process: vascular spasm, the formation of a platelet plug, and coagulation (blood clotting). Failure of any of these steps will result in hemorrhage. The figure below summarizes the steps of hemostasis.


Fibrinolysis is the process in which a clot is degraded in a healing vessel. An anticoagulant is any substance that opposes coagulation. Several circulating plasma anticoagulants play a role in limiting the coagulation process to the region of injury and restoring a normal, clot-free condition of blood.


Although carrying oxygen and nutrients to cells and removing wastes from cells is the main function of blood, it is important to realize that blood also serves in defense, distribution of heat, and maintenance of homeostasis.


Nutrients from the foods you eat are absorbed in the digestive tract. Most of these travel in the bloodstream directly to the liver, where they are processed and released back into the bloodstream for delivery to body cells.


Oxygen from the air you breathe diffuses into the blood, which moves from the lungs to the heart, which then pumps it out to the rest of the body.


Endocrine glands scattered throughout the body release their products, called hormones, into the bloodstream, which carries them to distant target cells.


Blood also picks up cellular wastes and byproducts, and transports them to various organs for removal. For instance, blood moves carbon dioxide to the lungs for exhalation from the body, and various waste products are transported to the kidneys and liver for excretion from the body in the form of urine or bile.


Leukocytes protect the organism from disease-causing bacteria, cells with mutated DNA that could multiply to become cancerous, or body cells infected with viruses.


When damage to the vessels results in bleeding, blood platelets and certain proteins dissolved in the plasma, interact to block the ruptured areas of the blood vessels involved. This protects the body from further blood loss.


If you were exercising on a warm day, your rising core body temperature would trigger several homeostatic mechanisms, including increased transport of blood from your core to your body periphery, which is typically cooler. As blood passes through the vessels of the skin, heat would be dissipated to the environment, and the blood returning to your body core would be cooler. In contrast, on a cold day, blood is diverted away from the skin to maintain a warmer body core. In extreme cases, this may result in frostbite.


Blood helps to regulate the water content of body cells. Blood also helps to maintain the chemical balance of the body. Proteins and other compounds in blood act as buffers, which thereby help to regulate the pH of body tissues. The pH of blood ranges from 7.35 to 7.45.


In order to understand blood types, it is important to understand several terms that relate to the body’s immune functions (discussed in detail in the next chapter).


ABO blood types are genetically determined. Each type is determined by the presence or absence of certain antigens on the individual’s red blood cell membrane, as well as the presence or absence of certain antibodies. Normally the body must be exposed to a foreign antigen before an antibody can be produced. This is not the case for the ABO blood group, in which some blood types come preloaded with their own set of antibodies against another type. The table below shows the ABO blood group as well as the universal donor and recipient in relation to blood transfusions.


The Rh blood group is classified according to the presence or absence of a second erythrocyte antigen identified as Rh. Those who have the Rh D antigen present on their erythrocytes are described as Rh positive (Rh+) and those who lack it are Rh negative (Rh−). Note that the Rh group is distinct from the ABO group, so any individual, no matter their ABO blood type, may have or lack this Rh antigen. When identifying a patient’s blood type, the Rh group is designated by adding the word positive or negative to the ABO type. For example, A positive (A+) means ABO group A blood with the Rh antigen present, and AB negative (AB−) means ABO group AB blood without the Rh antigen.


Antibodies to the Rh antigen are produced only in Rh− individuals after exposure to the antigen. This process, called sensitization, occurs following a transfusion with Rh-incompatible blood or, more commonly, with the birth of an Rh+ baby to an Rh− mother.


To avoid transfusion reactions, it is best to transfuse only matching blood types; that is, a type B+ recipient should ideally receive blood only from a type B+ donor and so on. That said, in emergency situations, when acute hemorrhage threatens the patient’s life, there may not be time for cross-matching to identify blood type. In these cases, blood from a universal donor may be transfused.


Arteriosclerosis is normally defined as the more generalized loss of compliance, or “hardening of the arteries.” Atherosclerosis is a more specific term for the build-up of plaque in the walls of the vessel and is a specific type of arteriosclerosis.


When arteriosclerosis causes vessel compliance to be reduced, pressure and resistance within the vessel increase. This is a leading cause of hypertension and coronary heart disease, as it causes the heart to work harder to overcome this resistance. Any artery in the body can be affected by these pathological conditions, and individuals who have pathologies like coronary artery disease, may also be at risk for other vascular injuries, like strokes or peripheral arterial disease.


Atherosclerosis is a type of arteriosclerosis in which plaques form when circulating triglycerides, cholesterol and other substances seep between the damaged endothelial lining cells and become trapped within the artery wall, resulting in narrowed arteries and impaired blood flow (see Figure 10.16).


Sometimes a plaque can rupture, causing microscopic tears in the artery wall that allow blood to leak into the tissue on the other side. When this happens, platelets rush to the site to clot the blood. This clot can further obstruct the artery and—if it occurs in a coronary or cerebral artery—cause a sudden heart attack or stroke. Alternatively, plaque can break off and travel through the bloodstream as an embolus until it blocks a more distant, smaller artery.


Peripheral arterial disease (PAD; also called peripheral vascular disease [PVD]), occurs when atherosclerosis affects arteries in the legs. A major risk factor for both arteriosclerosis and atherosclerosis is advanced age, as the conditions tend to progress over time. There is also a distinct genetic component, and pre-existing hypertension and/or diabetes also greatly increase the risk. However, obesity, poor nutrition, lack of physical activity, and tobacco use all are major risk factors.


Treatment of atherosclerosis includes lifestyle changes, such as weight loss, smoking cessation, regular exercise, and adoption of a diet low in sodium and saturated fats. Medications to reduce cholesterol and blood pressure may be prescribed. For blocked coronary arteries, angioplasty or coronary artery bypass graft (CABG) surgery may be warranted. In a carotid endarterectomy, plaque is surgically removed from the walls of the carotid artery, which is the main source of oxygenated blood for the brain.


Despite the presence of valves and the contributions of other anatomical and physiological adaptations that assist in moving blood through veins, over the course of a day, some blood will inevitably pool, especially in the lower limbs, due to the pull of gravity. Any blood that accumulates in a vein will increase the pressure within it, which can then be reflected back into the smaller veins, venules, and eventually even the capillaries. This increased pressure in the capillaries will push fluids out of the capillaries and into the interstitial fluid, causing a condition called edema.


Most people experience a daily accumulation of tissue fluid, especially if they spend much of their work-life on their feet (like most health professionals). However, clinical edema goes beyond normal swelling and requires medical treatment. Edema has many potential causes, including hypertension and heart failure, severe protein deficiency, renal failure, and many others. In order to treat edema, which is a sign rather than a discrete disorder, the underlying cause must be diagnosed and alleviated.


Edema may be accompanied by varicose veins, especially in the superficial veins of the legs (see Figure 10.17). This disorder arises when defective valves allow blood to accumulate within the veins, causing them to distend, twist, and become visible on the surface of the skin. Varicose veins may occur in both sexes, but are more common in women and are often related to pregnancy. More than simple cosmetic blemishes, varicose veins are often painful and sometimes itchy or throbbing. Without treatment, they tend to grow worse over time. The use of a support hose, as well as elevating the feet and legs whenever possible, may be helpful in alleviating this condition.


Hypertension is defined as chronic and persistent blood pressure measurements of 140/90 mm Hg or above. Pressures between 120/80 and 140/90 mm Hg are defined as prehypertension. Hypertension is typically a silent disorder and patients may fail to recognize the seriousness of their condition and fail to follow their treatment plan, putting them at risk for a heart attack or stroke. Hypertension may also lead to an aneurysm, peripheral arterial disease, chronic kidney disease, or heart failure.


Minor blood loss is managed by hemostasis and repair. Hemorrhage is a loss of blood that cannot be controlled by hemostatic mechanisms. Initially, the body responds to hemorrhage by initiating mechanisms aimed at increasing blood pressure and maintaining blood flow. Ultimately, however, blood volume will need to be restored, either through physiological processes or through medical intervention. If blood loss is less than 20% of total blood volume, fast-acting homeostatic mechanisms causing increased cardiac output and vasoconstriction, would usually return blood pressure to normal and redirect the remaining blood to the tissues. Blood volume will then need to be restored via slower-acting homeostatic mechanisms, to increase body fluids and erythrocyte production.


The loss of too much blood may lead to circulatory shock, a life-threatening condition in which the circulatory system is unable to maintain blood flow to adequately supply sufficient oxygen and other nutrients to the tissues to maintain cellular metabolism. It should not be confused with emotional or psychological shock. Typically, the patient in circulatory shock will demonstrate an increased heart rate but decreased blood pressure. Urine output will fall dramatically, and the patient may appear confused or lose consciousness. Unfortunately, shock is an example of a positive-feedback loop that, if uncorrected, may lead to the death of the patient.


Changes in the levels of RBCs can have significant effects on the body’s ability to effectively deliver oxygen to the tissues.


The size, shape, and number of erythrocytes, and the number of hemoglobin molecules can have a major impact on a person’s health. When the number of RBCs or hemoglobin is deficient, the general condition is called anemia. There are more than 400 types of anemia.


Anemia can be broken down into three major groups: those caused by blood loss, those caused by faulty or decreased RBC production, and those caused by excessive destruction of RBCs. In addition to these causes, various disease processes also can lead to anemias. These include chronic kidney diseases often associated with a decreased production of EPO, hypothyroidism, some forms of cancer, lupus, and rheumatoid arthritis.


Polycythemia is an elevated RBC count and is detected in a patient’s elevated hematocrit. It can occur transiently in a person who is dehydrated; when water intake is inadequate or when water losses are excessive, the plasma volume falls. As a result, the hematocrit rises. A mild form of polycythemia is chronic, but normal, in people living at high altitudes. Some elite athletes train at high elevations specifically to induce this phenomenon. Finally, a type of bone marrow disease called polycythemia vera causes an excessive production of immature erythrocytes. Polycythemia vera can dangerously elevate the viscosity of blood, raising blood pressure and making it more difficult for the heart to pump blood throughout the body. It is a relatively rare disease that occurs more often in men than women, and is more likely to be present in patients over 60 years of age.


Thrombocytosis is a condition in which there are too many platelets. This may trigger thrombosis, a potentially fatal disorder. A thrombus (plural = thrombi) is an aggregation of platelets, erythrocytes, and even WBCs typically trapped within a mass of fibrin strands. While the formation of a clot is a normal step in hemostasis, thrombi can form within an intact or only slightly damaged blood vessel, adhering to the vessel wall and decreasing or obstructing the flow of blood.


Thrombophilia, also called hypercoagulation, is a condition in which there is a tendency to form thrombosis. This may be an inherited disorder or may be caused by other conditions including lupus, immune reactions to heparin, polycythemia vera, thrombocytosis, sickle cell disease, pregnancy, and even obesity.


When a portion of a thrombus breaks free from the vessel wall and enters the circulation, it is referred to as an embolus. An embolus that is carried through the bloodstream can be large enough to block a vessel critical to a major organ. When it becomes trapped, an embolus is called an embolism. In the heart, brain, or lungs, an embolism may accordingly cause a heart attack, a stroke, or a pulmonary embolism.


Thrombocytopenia is a condition in which there is an insufficient number of platelets, possibly leading to ineffective blood clotting and excessive bleeding.


Hemophilia is a group of related genetic disorders in which certain plasma clotting factors are lacking or inadequate or nonfunctional. Patients with hemophilia bleed from even minor internal and external wounds, and leak blood into joint spaces after exercise and into urine and stool. Regular infusions of clotting factors isolated from healthy donors can help prevent bleeding in hemophilia patients. At some point, genetic therapy will become a viable option.


Leukopenia is a condition in which too few leukocytes are produced. If this condition is pronounced, the individual may be unable to ward off disease.


Leukocytosis is excessive leukocyte proliferation. Although leukocyte counts are high, the cells themselves are often nonfunctional, leaving the individual at increased risk for disease.


Leukemia is cancer involving an abundance of leukocytes. It may involve only one specific type of leukocyte from either the myeloid line (myelocytic leukemia) or the lymphoid line (lymphocytic leukemia). In chronic leukemia, mature leukocytes accumulate and fail to die. In acute leukemia, there is an overproduction of young, immature leukocytes. In both conditions the cells do not function properly.


Many terms and phrases related to the blood vessels and blood are abbreviated. Learn these common abbreviations by expanding the list below.


Medical Specialties and Procedures Related to the Blood Vessels and Blood


Vascular surgery is a specialty in which the physician treats diseases of the blood and lymphatic vessels. This includes repair and replacement of diseased or damaged vessels, removal of plaque from vessels, minimally invasive procedures including the insertion of venous catheters, and traditional surgery. For more information, please visit the Society for Vascular Surgery web page.


Hematologists are specialist physicians that diagnose and treat blood disorders (National Cancer Institute, n.d.). To learn more about hematologists, visit the American Society of Hematology.


Diagnostic vascular technologists are specialists that image the vascular system. Most diagnostic vascular technologists have professional certification (Bureau of Labor Statistics, 2021a.). To learn more, visit the Society for Vascular Ultrasound’s web page.


Phlebotomists are professionals trained to draw blood. When more than a few drops of blood are required, phlebotomists perform a venipuncture, typically of a surface vein in the arm. They perform a capillary stick on a finger, an earlobe, or the heel of an infant when only a small quantity of blood is required. An arterial stick is collected from an artery and used to analyze blood gases. After collection, the blood may be analyzed by medical laboratories or perhaps used for transfusions, donations, or research.


Medical or clinical laboratories employ a variety of individuals in technical positions. Two specialized positions are medical laboratory technologists and technicians. Technologists and technicians operate laboratory equipment, analyze body fluids, and discuss their findings with physicians. Technologists generally perform more complex procedures than technicians. Some states require certification (Bureau of Labor Statistics, 2021b).


Sometimes, a healthcare provider will order a bone marrow biopsy, a diagnostic test of a sample of red bone marrow, or a bone marrow transplant, a treatment in which a donor’s healthy bone marrow—and its stem cells—replaces the faulty bone marrow of a patient. These tests and procedures are often used to assist in the diagnosis and treatment of various severe forms of anemia, such as thalassemia major and sickle cell anemia, as well as some types of cancer, specifically leukemia.


In the past, bone marrow sampling or transplant was very painful, as the procedure involved inserting a large-bore needle into the region near the iliac crest of the pelvic bones. Now, direct sampling of bone marrow can often be avoided as stem cells can be isolated in just a few hours from a sample of a patient’s blood. The isolated stem cells are then grown in culture using the appropriate hemopoietic growth factors and analyzed or sometimes frozen for later use.


For an individual requiring a transplant, a matching donor is essential to prevent the immune system from destroying the donor cells—a phenomenon known as tissue rejection. To treat patients with bone marrow transplants, it is first necessary to destroy the patient’s own diseased marrow through radiation and/or chemotherapy. Donor bone marrow stem cells are then infused into the recipient’s bloodstream so that they can establish themselves in the recipient’s bone marrow.


A disease caused by the human immunodeficiency virus (HIV). People with acquired immunodeficiency syndrome are at an increased risk for developing certain cancers and for infections that usually occur only in individuals with a weak immune system (National Cancer Institute, n.d.)


An acute hypersensitivity reaction due to exposure to a previously encountered antigen.


A condition in which the number of red blood cells or hemoglobin is deficient.


Weakening of the wall of a blood vessel, causing it to thin and balloon out, and possibly eventually burst, resulting in internal bleeding.


A procedure in which an occlusion is mechanically widened with a balloon.


Proteins made by plasma cells (a type of white blood cell) in response to an antigen (a substance that causes the body to make a specific immune response). Each antibody can bind to only one specific antigen. The purpose of this binding is to help destroy the antigen.


Substances that provokes an immune response. This happens because the immune system sees the antigen as foreign, or ‘non-self” (does not belong in that body).


A condition in which the aortic valve becomes rigid and may calcify over time.


A hardening of the arteries that involves the accumulation of fatty plaque.


The large artery in the upper arm near the biceps muscle.


The smallest type of blood vessel. A capillary connects an arteriole (small artery) to a venule (small vein) to form a network of blood vessels in almost all parts of the body.


The measurement of blood flow from the heart through the ventricles and is usually measured in liters per minute. Any factor that causes cardiac output to increase, by elevating heart rate or stroke volume or both, will elevate blood pressure and promote blood flow.


A potentially fatal condition in which excess fluid builds within the pericardial space, preventing the heart from beating effectively.


Located in the neck, it is one of the three major branches of the aortic arch.


Process of using a rotating machine to generate centrifugal force to separate substances of different densities, remove moisture, or simulate gravitational effects.


Movement in response to chemicals; a phenomenon in which injured or infected cells and nearby leukocytes emit the equivalent of a chemical “911” call, attracting more leukocytes to the site.


The ability of the blood vessels to dilate and constrict as needed.


Surgery in which a healthy blood vessel taken from another part of the body is used to make a new path for blood around a blocked artery leading to the heart. This restores the flow of oxygen and nutrients to the heart.


A disease in which there is a narrowing or blockage of the coronary arteries.


A condition in which the gastrointestinal tract is inflamed over a long period of time.


The migration of blood cells through the intact walls of blood vessels into the surrounding tissue.


An obstruction such as a blood clot or plaque that blocks the flow of blood in an artery or vein.


A hormone produced by the kidneys that triggers the production of red blood cells.


The number of times the heart beats within a certain time period, usually a minute.


A lab test which measures the percentage red blood cells in a sample of whole blood.


A pool of mostly clotted blood that forms in an organ, tissue, or body space.


Chemical messengers which promote the proliferation and differentiation of formed elements and include erythropoietin, thrombopoietin, colony-stimulating factors, and interleukins.


The process by which the body seals a ruptured blood vessel to prevent further blood loss.


The decreased ability of the body to fight infections and other diseases.


A chronic, inflammatory, connective tissue disease that can affect the joints and many organs.


A form of cancer in which masses of malignant T and/or B lymphocytes collect in lymph nodes, the spleen, the liver, and other tissues. These leukocytes do not function properly, and the patient is vulnerable to infection.


A large cell derived from a monocyte; they participate in innate immune responses.


A part of the brain stem responsible for control of heart rate and breathing.


A condition in which there is a lower-than-normal number of red and white blood cells and platelets in the blood.


The process by which certain cells are able to “eat” other cells or substances by engulfing them.


A medical professional trained to draw blood, typically by performing a venipuncture of a surface vein of the arm.


A procedure in which a needle is used to take blood from a vein, usually for laboratory testing.


The organ that supplies oxygen and nutrients to the fetus, excretes waste products, and produces and secretes estrogens and progesterone.


A fatty material including cholesterol, connective tissue, white blood cells, and some smooth muscle cells.


A type of B lymphocyte that produces antibodies which bind to specific foreign or abnormal antigens, in order to destroy them.


A procedure in which a machine is used to separate the plasma from the blood cells.


A type of bone marrow disease that causes an excessive production of immature erythrocytes.


An autoimmune disorder in which the body mounts an immune response against its own joint tissues, causing inflammation and damage to the joints.


An inherited disease in which the red blood cells have an abnormal crescent shape, block small blood vessels, and do not last as long as normal red blood cells; also called sickle cell anemia.


A blood pressure cuff attached to a measuring device, or gauge.


The arterial pressure resulting from the ejection of blood during ventricular contraction, or systole.


A genetic disorder characterized by abnormal synthesis of globin proteins and excessive destruction of erythrocytes.


A condition in which there is an insufficient number of platelets.


Inflammation of a vein that occurs when a blood clot forms.


Aggregation of fibrin, platelets, and erythrocytes in an intact artery or vein.


The process of breaking up a thrombus that is blocking blood flow.


The recipient’s immune system recognizes the transplanted tissue as non-self and mounts an immune response against it, ultimately destroying it.


The physiological narrowing of blood vessels by contraction of the vascular smooth muscle.


The physiological widening of blood vessels by relaxing the vascular smooth muscle.


Bureau of Labor Statistics. (2021a). Medical sonographers and cardiovascular technologists. In Occupational outlook handbook. U.S. Department of Labor. https://www.bls.gov/ooh/healthcare/diagnostic-medical-sonographers.htm


Bureau of Labor Statistics. (2021b). Clinical laboratory technologists and technicians. In Occupational outlook handbook. U.S. Department of Labor. https://www.bls.gov/ooh/healthcare/clinical-laboratory-technologists-and-technicians.htm


CrashCourse. (2015, July 20). Blood vessels, part 1 – form and function: Crash course A&P #27 [Video]. YouTube. https://youtu.be/v43ej5lCeBo


National Cancer Institute. (n.d.). Definition of hematologist. National Institute of Health, U.S. Department of Health and Human Services. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/hematologist


The cardiovascular system is made of three components: the heart, vessels, and blood. The heart is a fist-sized vital organ that has one job: to pump blood. If one assumes an average heart rate of 75 beats per minute, a human heart would beat approximately 108,000 times in one day, more than 39 million times in one year, and nearly 3 billion times during a 75-year lifespan. At rest, each of the major pumping chambers of the heart ejects approximately 70 mL of blood per contraction in an adult. This would be equal to 5.25 liters of blood per minute and approximately 14,000 liters per day. Over one year, that would equal 10,000,000 liters of blood sent through roughly 100,000 km of blood vessels. In order to understand how that happens, it is necessary to understand the anatomy and physiology of the heart.


Media 9.1. The Heart, Part 1 – Under Pressure: Crash Course A&P #25 [Online video]. Copyright 2015 by CrashCourse.


The human heart is located within the thoracic cavity, between the lungs in the space known as the mediastinum. Figure 9.1 shows the position of the heart within the thoracic cavity. Within the mediastinum, the heart is separated from the other mediastinal structures by a tough membrane known as the pericardium, or pericardial sac, and sits in its own space called the pericardial cavity. The great vessels, which carry blood to and from the heart, are attached to the superior surface of the heart, which is called the base. The base of the heart is located at the level of the third costal cartilage. The inferior tip of the heart, the apex, lies just to the left of the sternum between the junction of the fourth and fifth ribs.


The heart and the roots of the great vessels are surrounded by a membrane known as the pericardium or pericardial sac. The pericardium consists of two distinct sub layers:


The interventricular septum is a muscular wall that separates the right and left ventricles. The interatrial septum separates the right and left atria.


The atrium and ventricle on each side of the heart are separated by an atrioventricular (AV) valve:


1. Circulation Through the Heart: The Heart as a Pump


The heart pumps blood to two distinct but linked circulatory systems called the pulmonary and systemic circuits. The pulmonary circuit transports blood to and from the lungs, where it picks up oxygen and drops off carbon dioxide. The systemic circuit transports freshly oxygenated blood to virtually all of the tissues of the body and returns relatively deoxygenated blood and carbon dioxide to the heart to be sent back to the pulmonary circulation.


2. The Heart as an Organ: The Coronary Blood Supply


Follow the path of each of these three arteries to try to determine which parts of the myocardium each artery (along with its many smaller branches) supplies with blood.


3. The Heart’s Electrical Conduction System


Media 9.2. The Heart, Part 2 – Heart Throbs: Crash Course A&P #26 [Online video]. Copyright 2015 by CrashCourse.


We can detect and record the electrical activity of the heart’s conduction system using an electrocardiogram (ECG or EKG). Figure 9.7 shows the electrical impulse originating in the SA node (step 2) and traveling through the heart’s conduction system, allowing the heart to complete one cardiac cycle. Each waveform on the ECG tracing represents electricity moving through and affecting a different part of the heart. Did you notice that the AV valves close when the electrical impulse reaches the ventricles, just before systole occurs?


Many terms and phrases related to the cardiovascular system are abbreviated. Learn these common abbreviations by expanding the list below.


The heart of a well-trained athlete can be considerably larger than the average person’s heart. This is because exercise results in an increase in muscle cells called hypertrophy. Hearts of athletes can pump blood more effectively at lower rates than those of non-athletes. However, when an enlarged heart is not the result of exercise, it may be due to hypertrophic cardiomyopathy. The cause of an abnormally enlarged heart muscle is unknown, but the condition is often undiagnosed and can cause sudden death in apparently otherwise healthy young people.


Cardiomyopathy may also be caused by myocardial infarctions, myocardial infections, pregnancy, alcohol or cocaine abuse, autoimmune and endocrine diseases. Because the myocardium is responsible for contracting and pumping blood, patients with cardiomyopathy experience impaired heart function which may lead to heart failure (Centers for Disease Control and Prevention, n.d.-a). To learn more, visit the Centers for Disease Control and Prevention’s web page on cardiomyopathy.


Heart failure is defined as the inability of the heart to pump enough blood to meet the needs of the body. It is also called congestive heart failure (CHF). This condition causes swelling in the lower extremities and shortness of breath, due to a buildup of fluid in the lungs. It may be caused by cardiomyopathy, and it may lead to hypertension and heart valve disorders (Heart & Stroke, n.d.). To learn more, visit the American Heart Association’s web page on heart failure.


The four heart valves open and close at specific times during the cardiac cycle, in order to ensure that blood flows in only one direction through the heart. This requires that these valves open and close completely. Infections such as rheumatic disease or bacterial endocarditis can affect the heart valves and result in scar tissue formation which interferes with valve function. Other causes of heart valve disease include congenitally malformed valves, autoimmune diseases, and other cardiovascular diseases such as aortic aneurysms and atherosclerosis (Centers for Disease Control and Prevention, n.d.-b).


Heart valve disease may be asymptomatic or cause dyspnea, arrhythmias, fatigue and other symptoms. It is often detected when a heart murmur is heard through a stethoscope (Centers for Disease Control and Prevention, n.d.-b).


Visit the Center for Disease Control and Prevention’s web page on valvular heart disease to learn more.


An aneurysm is a defect in the wall of an artery in which the wall becomes thin and weak and starts to balloon out as blood pulses against the vessel wall. This can happen to any artery and even to the myocardial walls. Aneurysms sometimes occur in the portion of the aorta that is in the thorax (see Figure 9.8). If these aneurysms start to leak between layers of the vessel wall, the condition is known as aortic dissection. If an aortic or cardiac aneurysm bursts, there is sudden, massive internal bleeding (Centers for Disease Control and Prevention, n.d.-c).


People who smoke or have hypertension, hypercholesterolemia, and/or atherosclerosis have an increased risk of developing aneurysms. Having a family history of aneurysms or certain genetic diseases may also increase a person’s risk of developing an aneurysm.


Aneurysms can be asymptomatic and may be detected during diagnostic tests that are done for other reasons. They are sometimes repaired surgically and sometimes treated with medications such as antihypertensives (Centers for Disease Control and Prevention, n.d.-c; National Heart, Lung, and Blood Institute, n.d.). Visit the National Heart, Lung, and Blood Institute’s web page on aortic aneurysms to learn more.


Fetal circulation is different from postnatal circulation. There are two extra openings in the fetal heart, the foramen ovale and the ductus arteriosus, which allow blood circulation that bypasses the immature fetal lungs. The fetal blood is reoxygenated by the mother’s lungs and transported between mother and fetus via the placenta. These two openings usually close around the time of birth.


Septal defects are commonly first detected through auscultation. Unusual heart sounds may be detected because blood is not flowing and valves are not closing correctly. Medical imaging is ordered to confirm or rule out a diagnosis. In many cases, treatment may not be needed.


Coronary artery disease occurs when the buildup of plaque in the coronary arteries obstructs the flow of blood and decreases compliance of the vessels. This condition is called atherosclerosis. As the disease progresses and coronary blood vessels become more and more narrow, cells of the myocardium become ischemic which causes symptoms of angina pectoris, in some patients. If untreated, coronary artery disease can lead to myocardial infarction (MI).


occurs when the buildup of plaque in the coronary arteries obstructs the flow of blood and decreases compliance of the vessels. This condition is called atherosclerosis. As the disease progresses and coronary blood vessels become more and more narrow, cells of the myocardium become ischemic which causes symptoms of


angina pectoris, in some patients. If untreated, coronary artery disease can lead to myocardial infarction (MI).


The image below shows the blockage of coronary arteries on an angiogram.


CAD is progressive and chronic. Risk factors include smoking, family history, hypertension, obesity, diabetes, high alcohol consumption, lack of exercise, stress, and hyperlipidemia. Treatments may include medication, changes to diet and exercise, angioplasty with a balloon catheter, insertion of a stent, or coronary artery bypass graft (CABG).


Myocardial infarction (MI) is the medical term for a heart attack.


A MI normally results from a lack of blood flow to a region of the heart, resulting in death of the cardiac muscle cells. A MI often occurs when a coronary artery is blocked by the buildup of atherosclerotic plaque. It can also occur when a piece of an atherosclerotic plaque breaks off and travels through the coronary arterial system until it lodges in one of the smaller vessels. MIs may be triggered by excessive exercise, in which the partially occluded artery is no longer able to pump sufficient quantities of blood, or severe stress, which may induce spasm of the smooth muscle in the walls of the vessel.


In the case of acute MI (AMI), there is often sudden pain beneath the sternum (retrosternal pain) called angina pectoris, often radiating down the left arm in males but not in female patients. Other common signs and symptoms include dyspnea, palpitations, nausea and vomiting, diaphoresis, anxiety, and syncope. Many of the symptoms are shared with other medical conditions, including anxiety attacks and simple indigestion, so differential diagnosis is critical.


MIs may induce dangerous heart rhythms and even cardiac arrest. Important risk factors for MI include coronary artery disease, age, smoking, high blood levels of LDL, low levels of HDL, hypertension, diabetes mellitus, obesity, lack of physical exercise, chronic kidney disease, excessive alcohol consumption, and use of illegal drugs.


The heart’s natural pacemaker, the sinoatrial (SA) node initiates an electrical impulse 60 to 90 times per minute in a resting adult. This impulse travels through the heart’s conduction system in order to ensure a smooth, coordinated pumping action. This electrical activity can be detected and recorded through the skin using an electrocardiograph. Arrhythmias may occur when the SA node fails to initiate an impulse, or when the conduction system fails to transmit that impulse through the heart.


In the event that the electrical activity of the heart is severely disrupted, cessation of electrical activity or fibrillation may occur. In fibrillation, the heart beats in a wild, uncontrolled manner, which prevents it from being able to pump effectively.


The most common treatment is defibrillation which uses special paddles to apply a charge to the heart from an external electrical source in an attempt to establish a normal sinus rhythm. A defibrillator effectively stops the heart so that the SA node can trigger a normal conduction cycle. External automated defibrillators (EADs) are being placed in areas frequented by large numbers of people, such as schools, restaurants, and airports. These devices contain simple and direct verbal instructions that can be followed by non-medical personnel in an attempt to save a life.


Bradycardia is the condition in which resting adult heart rate drops below 60 beats per minute (bpm). A client exhibiting signs and symptoms such as weakness, fatigue, dizziness, syncope, chest discomfort, palpitations, or respiratory distress may indicate that the heart is not providing sufficient oxygenated blood to the tissues. If the patient is not exhibiting symptoms then bradycardia is not considered clinically significant. The term relative bradycardia may be used with a patient who has a heart rate in the normal range but is still suffering from these symptoms. Most patients remain asymptomatic as long as the heart rate remains above 50 bpm.


Tachycardia is the condition in which the resting rate is above 100 bpm. Tachycardia is not normal in a resting patient and may be detected in pregnant women or individuals experiencing extreme stress. Some individuals may remain asymptomatic, but when present, signs and symptoms may include dizziness, shortness of breath, rapid pulse, heart palpitations, chest pain, or syncope. Treatment depends upon the underlying cause but may include medications, ablation,  implantable cardioverter defibrillators, or surgery.


A heart block refers to an interruption in the normal conduction pathway. Heart blocks are generally named after the part of the conduction system that is causing the problem. For example, bundle branch blocks occur within either the left or right atrioventricular bundle branches.


AV blocks are often described by degrees. A first-degree or partial block indicates a delay in conduction between the SA and AV nodes. A second-degree or incomplete block occurs when some impulses from the SA node reach the AV node and continue, while others do not. In the third-degree or complete block, there is no correlation between atrial activity and ventricular activity. This means that none of the impulses generated by the SA node get transmitted to the rest of the heart and the AV node must take over as the primary pacemaker, initiating contractions at 40 to 60 bpm, which is adequate to maintain consciousness.


In order to speed up the heart rate and restore full sinus rhythm, a cardiologist can implant an artificial pacemaker, which delivers electrical impulses to the heart muscle to ensure that the heart continues to contract and pump blood effectively. These artificial pacemakers are programmable by the cardiologists and can either provide stimulation temporarily upon demand or on a continuous basis. Some devices also contain built-in defibrillators.


Cardiologists are medical doctors that specialize in diagnosing and treating heart diseases. After completing medical school, cardiologists must complete at least six more years of training (Betts et al., 2013). Thoracic surgeons provide surgical treatments on the heart and other thoracic organs (National Cancer Institute, n.d.). For more information, visit the American College of Cardiology Foundation’s web page on cardiologists.


Cardiology technologists complete a college training program and perform diagnostic tests such as electrocardiography and stress testing, as well as pacemaker monitoring (Bureau of Labor Statistics, 2021). Please visit the Bureau of Labor Statistics’ web page on cardiology technologists for more information.


Cardiovascular perfusionists complete a college training program and are responsible for operation of the heart-lung bypass machine during open heart surgery. They also monitor the patient’s vitals and administer medications (New York State Education Department, 2020). For more information, please read this job description from the American Board of Cardiovascular Perfusion (PDF).


Chest pain. It may be a symptom of coronary artery disease and myocardial infarction.


An x-ray or computer image (CT scan or MRI) of the blood vessels and blood flow in the body. A dye may be injected through a catheter (small tube) into an artery or vein to make the blood vessels easier to see.


A deviation from the normal pattern of impulse conduction and contraction of the heart.


A hardening of the arteries that involves the accumulation of plaque.


The area of the heart where the atria and ventricles meet.


Mitral (bicuspid) valve that allows blood to flow from left atrium to left ventricle and tricuspid valve that allows blood to flow from right atrium to right ventricle.


A condition in which the heart beats slower than 50 beats per minute.


An enzyme that catalyzes the conversion of creatine to phosphocreatine, consuming ATP.


A condition in which the oxygen supply is restricted, causing the skin to look blue.


A disease in which the body does not control the amount of glucose (a type of sugar) in the blood and the kidneys make a large amount of urine. This disease occurs when the body does not make enough insulin or does not use it the way it should.


Period of time when the heart muscle is relaxed and the chambers fill with blood.


A temporary connection between pulmonary trunk and aorta in the fetal heart.


A computer picture of the heart created by bouncing high-energy sound waves (ultrasound) off internal tissues or organs of the chest.


A procedure that uses high-energy sound waves (ultrasound) to look at tissues and organs inside the chest.


The instrument that generates an electrocardiogram (ECG); 10 electrodes are placed in standard locations on the patient’s skin to record heart function.


A condition in which the tissues lining the inside of the heart and the heart valves become inflamed.


An opening between right and left atria, which is normal in the fetal heart.


Include the superior vena cava, inferior vena cava, aorta and pulmonary trunk.


A small device placed by surgery in the chest or abdomen that is used to correct a heartbeat that is abnormal. Wires are passed through a vein to connect the device to the heart. When it detects abnormal heartbeats, it sends an electrical shock to the heart to restore the heartbeat to normal.


One of the two largest veins in the body. It carries deoxygenated blood from the torso and legs back to the heart.


The wall of myocardium that separates the right and left ventricles.


A procedure in which radio waves and a powerful magnet linked to a computer are used to create detailed pictures of areas inside the body.


Located at the opening between the left atrium and left ventricle; also known as the bicuspid valve.


Heart attack, caused by lack of blood flow and oxygen to the heart.


A rare condition in which the heart muscle becomes thick and inflamed and may also become weak.


An electronic device that is implanted in the body to monitor heart rate and rhythm. It gives the heart electrical stimulation when it does not beat normally.


Watery fluid produced in the serous and visceral pericardium surrounding the surface of the heart.


Surgical puncture to aspirate fluid from the (sac) surrounding the heart.


A rare disorder in which the bone marrow produces an abnormally large amount of blood cells.


The very large artery referred to as a trunk, a term indicating that the vessel gives rise to several smaller arteries.


The part of each great vessel (aorta, pulmonary trunk, inferior vena cava, superior vena cava) that connects to the base of the heart.


One of the thin membranes that cover the walls and organs in the thoracic and abdominopelvic cavities.


An instrument used to hear sounds produced by the heart, lungs, or other parts of the body.


One of two large veins in the body, which carries deoxygenated blood from the head and upper extremities back to the heart.


A condition in which the resting rate is above 100 bpm.


The widening of a stenosed heart valve using a balloon catheter.


Bureau of Labor Statistics. (2021). Medical sonographers and cardiovascular technologists and technicians. In Occupational outlook handbook. U.S. Department of Labor. https://www.bls.gov/ooh/healthcare/diagnostic-medical-sonographers.htm


Centers for Disease Control and Prevention. (n.d.-a). Cardiomyopathy. CDC. https://www.cdc.gov/heartdisease/cardiomyopathy.htm


Centers for Disease Control and Prevention. (n.d.-b). Valvular heart disease. CDC. https://www.cdc.gov/heartdisease/valvular_disease.htm


Centers for Disease Control and Prevention. (n.d.-c). Aortic aneurysm. CDC. https://www.cdc.gov/heartdisease/aortic_aneurysm.htm


CrashCourse. (2015, July 6). The heart, part 1 – under pressure: Crash course A&P #25 [Video]. YouTube. https://youtu.be/X9ZZ6tcxArI


CrashCourse. (2015, July 13). The heart, part 2 – heart throbs: Crash course A&P #26 [Video]. YouTube. https://youtu.be/FLBMwcvOaEo


National Heart, Lung, and Blood Institute. (n.d.). Aortic aneurysm. National Institutes of Health, U.S. Department of Health and Human Services. https://www.nhlbi.nih.gov/health-topics/aneurysm


National Cancer Institute. (n.d.). Definition of thoracic surgeon. National Institutes of Health, U.S. Department of Health and Human Services.. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/thoracic-surgeon


New York State Education Department. (2020). Perfusionist. Retrieved November 1, 2021, from http://www.op.nysed.gov/careers/perfprofile.htm


The picture you have in your mind of the nervous system probably includes the brain, the nervous tissue contained within the cranium, and the spinal cord, the extension of nervous tissue within the vertebral column. That suggests it is made of two organs—and you may not even think of the spinal cord as an organ—but the nervous system is a very complex structure. Within the brain, many different and separate regions are responsible for many different and separate functions. It is as if the nervous system is composed of many organs that all look similar and can only be differentiated using tools such as the microscope or electrophysiology.


Media 8.1 The Nervous System, Part 1: Crash Course A&P #8 [Online video]. Copyright 2015 by CrashCourse.


Nervous tissue, present in both the CNS and PNS, contains two basic types of cells: neurons and glial cells. Neurons are the primary type of cell that most anyone associates with the nervous system. They are responsible for the computation and communication that the nervous system provides. They are electrically active and release chemical signals to target cells. Glial cells, or glia, are known to play a supporting role for nervous tissue. Ongoing research pursues an expanded role that glial cells might play in signaling, but neurons are still considered the basis of this function. Neurons are important, but without glial support, they would not be able to perform their function. A glial cell is one of a variety of cells that provide a framework of tissue that supports the neurons and their activities. The neuron is the more functionally important of the two, in terms of the communicative function of the nervous system. To describe the functional divisions of the nervous system, it is important to understand the structure of a neuron.


Neurons are cells and therefore have a soma, or cell body, but they also have extensions of the cell; each extension is generally referred to as a process. There is one important process that every neuron has called an axon, which is the fiber that connects a neuron with its target. Another type of process that branches off from the soma is the dendrite. Dendrites are responsible for receiving most of the input from other neurons.


Looking at nervous tissue, some regions predominantly contain cell bodies and regions that are largely composed of just axons. These two regions within nervous system structures are often referred to as gray matter (the regions with many cell bodies and dendrites) or white matter (the regions with many axons). Figure 8.2 demonstrates the appearance of these regions in the brain and spinal cord. The colors ascribed to these regions are what would be seen in “fresh,” or unstained, nervous tissue. Gray matter is not necessarily gray. It can be pinkish because of blood content, or even slightly tan, depending on how long the tissue has been preserved. White matter is white because axons are insulated by a lipid-rich substance called myelin. Lipids can appear as white (“fatty”) material, much like the fat on a raw piece of chicken or beef. Gray matter may have that color ascribed to it because next to the white matter, it is just darker—hence, gray.


The distinction between gray matter and white matter is most often applied to central nervous tissue, which has large regions that can be seen with the unaided eye. When looking at peripheral structures, often a microscope is used and the tissue is stained with artificial colors. That is not to say that central nervous tissue cannot be stained and viewed under a microscope, but unstained tissue is most likely from the CNS—for example, a frontal section of the brain or cross-section of the spinal cord.


The iconic gray mantle of the human brain, which appears to make up most of the mass of the brain, is the cerebrum (see Figure 8.3). The wrinkled portion is the cerebral cortex, and the rest of the structure is beneath that outer covering. There is a large separation between the two sides of the cerebrum called the longitudinal fissure. It separates the cerebrum into two distinct halves, a right and left cerebral hemisphere. Deep within the cerebrum, the white matter of the corpus callosum provides the major pathway for communication between the two hemispheres of the cerebral cortex.


Many of the higher neurological functions, such as memory, emotion, and consciousness, are the result of cerebral function. The complexity of the cerebrum is different across vertebrate species. The cerebrum of the most primitive vertebrates is not much more than the connection for the sense of smell. In mammals, the cerebrum comprises the outer gray matter that is the cortex (from the Latin word meaning “bark of a tree”) and several deep nuclei that belong to three important functional groups. The basal nuclei are responsible for cognitive processing, the most important function being that associated with planning movements. The basal forebrain contains nuclei that are important in learning and memory. The limbic cortex is the region of the cerebral cortex that is part of the limbic system, a collection of structures involved in emotion, memory, and behavior.


The cerebrum is covered by a continuous layer of gray matter that wraps around either side of the forebrain—the cerebral cortex. This thin, extensive region of wrinkled gray matter is responsible for the higher functions of the nervous system. A gyrus (plural = gyri) is the ridge of one of those wrinkles, and a sulcus (plural = sulci) is the groove between two gyri. The pattern of these folds of tissue indicates specific regions of the cerebral cortex.


The head is limited by the size of the birth canal, and the brain must fit inside the cranial cavity of the skull. Extensive folding in the cerebral cortex enables more gray matter to fit into this limited space. If the gray matter of the cortex were peeled off of the cerebrum and laid out flat, its surface area would be roughly equal to one square meter.


The folding of the cortex maximizes the amount of gray matter in the cranial cavity. During embryonic development, as the telencephalon expands within the skull, the brain goes through a regular course of growth that results in everyone’s brain having a similar pattern of folds. The surface of the brain can be mapped based on the locations of large gyri and sulci. Using these landmarks, the cortex can be separated into four major regions, or lobes (see Figure 8.4). The lateral sulcus that separates the temporal lobe from the other regions is one such landmark. Superior to the lateral sulcus is the parietal lobe and frontal lobe, which are separated from each other by the central sulcus. The posterior region of the cortex is the occipital lobe, which has no obvious anatomical border between it and the parietal or temporal lobes on the lateral surface of the brain. From the medial surface, an obvious landmark separating the parietal and occipital lobes is called the parieto-occipital sulcus. The fact that there is no obvious anatomical border between these lobes is consistent with the functions of these regions being interrelated.


The thalamus is a collection of nuclei that relay information between the cerebral cortex and the periphery, spinal cord, or brainstem. All sensory information, except for the sense of smell, passes through the thalamus before processing by the cortex. For example, the portion of the thalamus that receives visual information will influence what visual stimuli are important, or what receives attention.


The cerebrum also sends information down to the thalamus, which usually communicates motor commands. This involves interactions with the cerebellum and other nuclei in the brainstem. The cerebrum interacts with the basal nuclei, which involves connections with the thalamus. The primary output of the basal nuclei is to the thalamus, which relays that output to the cerebral cortex. The cortex also sends information to the thalamus that will then influence the effects of the basal nuclei.


Inferior and slightly anterior to the thalamus is the hypothalamus, the other major region of the diencephalon. The hypothalamus is a collection of nuclei that are largely involved in regulating homeostasis. The hypothalamus is the executive region in charge of the autonomic nervous system and the endocrine system through its regulation of the anterior pituitary gland. Other parts of the hypothalamus are involved in memory and emotion as part of the limbic system.


The midbrain and hindbrain (composed of the pons and the medulla) are collectively referred to as the brain stem (see Figure 8.6). The structure emerges from the ventral surface of the forebrain as a tapering cone that connects the brain to the spinal cord. Attached to the brain stem but considered a separate region of the adult brain is the cerebellum. The midbrain coordinates sensory representations of the visual, auditory, and somatosensory perceptual spaces. The pons is the main connection with the cerebellum. The pons and the medulla regulate several crucial functions, including the cardiovascular and respiratory systems and rates.


The cranial nerves connect through the brain stem and provide the brain with the sensory input and motor output associated with the head and neck, including most of the special senses. The major ascending and descending pathways between the spinal cord and brain, specifically the cerebrum, pass through the brain stem.


One of the original regions of the embryonic brain, the midbrain is a small region between the thalamus and pons. It is separated into the tectum and tegmentum, from the Latin words for roof and floor, respectively. The cerebral aqueduct passes through the center of the midbrain, such that these regions are the roof and floor of that canal.


The word pons comes from the Latin word for bridge. It is visible on the anterior surface of the brain stem as the thick bundle of white matter attached to the cerebellum. The pons is the main connection between the cerebellum and the brain stem. The bridge-like white matter is only the anterior surface of the pons; the gray matter beneath that is a continuation of the tegmentum from the midbrain. Gray matter in the tegmentum region of the pons contains neurons receiving descending input from the forebrain that is sent to the cerebellum.


The medulla is the region known as the myelencephalon in the embryonic brain. The initial portion of the name, “myel,” refers to the significant white matter found in this region—especially on its exterior, which is continuous with the white matter of the spinal cord. The tegmentum of the midbrain and pons continues into the medulla because this gray matter is responsible for processing cranial nerve information. A diffuse region of gray matter throughout the brain stem, known as the reticular formation, is related to sleep and wakefulness, such as general brain activity and attention.


The cerebellum, as the name suggests, is the “little brain.” It is covered in gyri and sulci like the cerebrum and looks like a miniature version of that part of the brain (see Figure 8.7). The cerebellum is largely responsible for comparing information from the cerebrum with sensory feedback from the periphery through the spinal cord. It accounts for approximately 10% of the mass of the brain.


The description of the CNS is concentrated on the structures of the brain, but the spinal cord is another major organ of the system. Whereas the brain develops out of expansions of the neural tube into primary and then secondary vesicles, the spinal cord maintains the tube structure and is only specialized into certain regions. As the spinal cord continues to develop in the newborn, anatomical features mark its surface. The anterior midline is marked by the anterior median fissure, and the posterior midline is marked by the posterior median sulcus. Axons enter the posterior side through the dorsal (posterior) nerve root, which marks the posterolateral sulcus on either side. The axons emerging from the anterior side do so through the ventral (anterior) nerve root. Note that it is common to see the terms dorsal (dorsal = “back”) and ventral (ventral = “belly”) used interchangeably with posterior and anterior, particularly in reference to nerves and the structures of the spinal cord. You should learn to be comfortable with both.


On the whole, the posterior regions are responsible for sensory functions and the anterior regions are associated with motor functions. This comes from the initial development of the spinal cord, which is divided into the basal plate and the alar plate. The basal plate is closest to the ventral midline of the neural tube, which will become the anterior face of the spinal cord and gives rise to motor neurons. The alar plate is on the dorsal side of the neural tube and gives rise to neurons that will receive sensory input from the periphery.


The length of the spinal cord is divided into regions that correspond to the regions of the vertebral column. The name of a spinal cord region corresponds to the level at which spinal nerves pass through the intervertebral foramina. Immediately adjacent to the brain stem are the following divisions of the spinal cord:


The spinal cord is not the full length of the vertebral column because the spinal cord does not grow significantly longer after the first or second year, but the skeleton continues to grow. The nerves that emerge from the spinal cord pass through the intervertebral foramina at the respective levels. As the vertebral column grows, these nerves grow with it and result in a long bundle of nerves that resembles a horse’s tail and is named the cauda equina. The sacral spinal cord is at the level of the upper lumbar vertebral bones. The spinal nerves extend from their various levels to the proper level of the vertebral column.


Neurons are the cells considered to be the basis of nervous tissue. They are responsible for the electrical signals that communicate information about sensations, and that produce movements in response to those stimuli, along with inducing thought processes within the brain. An important part of the function of neurons is in their structure or shape. The three-dimensional shape of these cells makes the immense number of connections within the nervous system possible.


As you learned in the first section, the main part of a neuron is the cell body, which is also known as the soma (soma = “body”). The cell body contains the nucleus and most of the major organelles. What makes neurons special is that they have many extensions of their cell membranes, which are generally referred to as processes. Neurons are usually described as having one, and only one, axon—a fiber that emerges from the cell body and projects to target cells. That single axon can branch repeatedly to communicate with many target cells. It is the axon that propagates the nerve impulse, which is communicated to one or more cells. The other processes of the neuron are dendrites, which receive information from other neurons at specialized areas of contact called synapses. The dendrites are usually highly branched processes, providing locations for other neurons to communicate with the cell body. Information flows through a neuron from the dendrites, across the cell body, and down the axon. This gives the neuron a polarity—meaning that information flows in this one direction. Figure 8.8 shows the relationship of these parts to one another.


Where the axon emerges from the cell body, there is a special region referred to as the axon hillock. This is a tapering of the cell body toward the axon fiber. Within the axon hillock, the cytoplasm changes to a solution of limited components called axoplasm. Because the axon hillock represents the beginning of the axon, it is also referred to as the initial segment.


Many axons are wrapped by an insulating substance called myelin, which is made from glial cells. Myelin acts as insulation much like the plastic or rubber that is used to insulate electrical wires. A key difference between myelin and the insulation on a wire is that there are gaps in the myelin covering of an axon. Each gap is called a node of Ranvier and is important to the way that electrical signals travel down the axon. The length of the axon between each gap, which is wrapped in myelin, is referred to as an axon segment. At the end of the axon is the axon terminal, where there are usually several branches extending toward the target cell, each of which ends in an enlargement called a synaptic end bulb. These bulbs are what make the connection with the target cell at the synapse.


There are many neurons in the nervous system—a number in the trillions. And there are many different types of neurons. They can be classified by many different criteria. The first way to classify them is by the number of processes attached to the cell body. Using the standard model of neurons, one of these processes is the axon, and the rest are dendrites. Because information flows through the neuron from dendrites or cell bodies toward the axon, these names are based on the neuron’s polarity (see Figure 8.9).


Unipolar cells have only one process emerging from the cell. True unipolar cells are only found in invertebrate animals, so the unipolar cells in humans are more appropriately called “pseudo-unipolar” cells. Invertebrate unipolar cells do not have dendrites.


Bipolar cells have two processes, which extend from each end of the cell body, opposite to each other. One is the axon and one the dendrite. Bipolar cells are not very common. They are found mainly in the olfactory epithelium (where smell stimuli are sensed), and as part of the retina.


Multipolar neurons are all of the neurons that are not unipolar or bipolar. They have one axon and two or more dendrites (usually many more). With the exception of the unipolar sensory ganglion cells, and the two specific bipolar cells mentioned above, all other neurons are multipolar.


Neurons can also be classified on the basis of where they are found, who found them, what they do, or even what chemicals they use to communicate with each other. Some neurons referred to in this section on the nervous system are named on the basis of those sorts of classifications (see Figure 8.10). For example, a multipolar neuron that has a very important role to play in a part of the brain called the cerebellum is known as a Purkinje (commonly pronounced per-KIN-gee) cell. It is named after the anatomist who discovered it (Jan Evangilista Purkinje, 1787–1869).


Glial cells, or neuroglia or simply glia, are the other type of cell found in nervous tissue. They are considered to be supporting cells, and many functions are directed at helping neurons complete their function for communication. The name glia comes from the Greek word that means “glue,” and was coined by the German pathologist Rudolph Virchow, who wrote in 1856, “This connective substance, which is in the brain, the spinal cord, and the special sense nerves, is a kind of glue (neuroglia) in which the nervous elements are planted.” Today, research into nervous tissue has shown that there are many deeper roles that these cells play, and research may find much more about them in the future.


There are six types of glial cells. Four of them are found in the CNS and two are found in the PNS. Table 8.1 outlines some common characteristics and functions.


One cell providing support to neurons of the CNS is the astrocyte, so named because it appears to be star-shaped under the microscope (astro- = “star”). Astrocytes have many processes extending from their main cell body (not axons or dendrites like neurons, just cell extensions). Those processes extend to interact with neurons, blood vessels, or the connective tissue covering the CNS that is called the pia mater (see Figure 8.11). Generally, they are supporting cells for the neurons in the central nervous system. Some ways in which they support neurons in the central nervous system are by maintaining the concentration of chemicals in the extracellular space, removing excess signaling molecules, reacting to tissue damage, and contributing to the blood-brain barrier (BBB). The blood-brain barrier is a physiological barrier that keeps many substances that circulate in the rest of the body from getting into the central nervous system, restricting what can cross from circulating blood into the CNS. Nutrient molecules, such as glucose or amino acids, can pass through the BBB, but other molecules cannot. This actually causes problems with drug delivery to the CNS. Pharmaceutical companies are challenged to design drugs that can cross the BBB as well as have an effect on the nervous system.


Like a few other parts of the body, the brain has a privileged blood supply. Very little can pass through by diffusion. Most substances that cross the wall of a blood vessel into the CNS must do so through an active transport process. Because of this, only specific types of molecules can enter the CNS. Glucose—the primary energy source—is allowed, as are amino acids. Water and some other small particles, like gases and ions, can enter, but most everything else cannot, including white blood cells, which are one of the body’s main lines of defense. While this barrier protects the CNS from exposure to toxic or pathogenic substances, it also keeps out the cells that could protect the brain and spinal cord from disease and damage. The BBB also makes it harder for pharmaceuticals to be developed that can affect the nervous system. Aside from finding efficacious substances, the means of delivery is also crucial.


Oligodendrocyte, sometimes called just “oligo,” is the glial cell type that insulates axons in the CNS. The name means “cell of a few branches” (oligo- = “few”; dendro- = “branches”; -cyte = “cell”). There are a few processes that extend from the cell body. Each one reaches out and surrounds an axon to insulate it in myelin.


Microglia are, as the name implies, smaller than most of the other glial cells. Ongoing research into these cells, although not entirely conclusive, suggests that they may originate as white blood cells, called macrophages, that become part of the CNS during early development. While their origin is not conclusively determined, their function is related to what macrophages do in the rest of the body. When macrophages encounter diseased or damaged cells in the rest of the body, they ingest and digest those cells or the pathogens that cause disease. Microglia are the cells in the CNS that can do this in normal, healthy tissue, and they are therefore also referred to as CNS-resident macrophages.


The ependymal cell is a glial cell that filters blood to make cerebrospinal fluid (CSF), the fluid that circulates through the CNS. Because of the privileged blood supply inherent in the BBB, the extracellular space in nervous tissue does not easily exchange components with the blood. Ependymal cells line each ventricle, one of four central cavities that are remnants of the hollow center of the neural tube formed during the embryonic development of the brain. They also have cilia on their apical surface to help move the CSF through the ventricular space. The relationship of these glial cells to the structure of the CNS is seen in Figure 8.11.


One of the two types of glial cells found in the PNS is the satellite cell. Satellite cells are found in sensory and autonomic ganglia, where they surround the cell bodies of neurons. This accounts for the name, based on their appearance under the microscope. They provide support, performing similar functions in the periphery as astrocytes do in the CNS—except, of course, for establishing the BBB.


The second type of glial cell is the Schwann cell, which insulates axons with myelin in the periphery. Schwann cells are different from oligodendrocytes in that a Schwann cell wraps around a portion of only one axon segment and no others. Oligodendrocytes have processes that reach out to multiple axon segments, whereas the entire Schwann cell surrounds just one axon segment. The nucleus and cytoplasm of the Schwann cell are on the edge of the myelin sheath. The relationship of these two types of glial cells to ganglia and nerves in the PNS is seen in Figure 8.12.