Cardiovascular System: Blood PDF

# The Cardiovascular System: Blood ## Chapter Introduction In this chapter we will learn: - The structure and functions of the different components of human blood - How the blood functions and flows as a whole mixture Single-celled organisms do not need blood. They obtain nutrients directly from, a...

# The Cardiovascular System: Blood ## Chapter Introduction In this chapter we will learn: - The structure and functions of the different components of human blood - How the blood functions and flows as a whole mixture Single-celled organisms do not need blood. They obtain nutrients directly from, and excrete wastes directly into, their environment. The human organism cannot do that. Our large, complex bodies need blood to deliver nutrients to and remove wastes from our trillions of cells. The heart pumps blood throughout the body in a network of blood vessels. Together, these three components: blood, heart, and blood vessels-make up the cardiovascular system. This chapter focuses on the medium of transport: blood. ## 18.1 The Composition of Blood ### Learning Objectives: By the end of this section, you will be able to: - Describe the major functions of each component of the cardiovascular system (i.e., blood, heart, blood vessels). - Describe the general composition of blood (e.g., plasma, formed elements). - Describe the functions of blood and connect those functions to the maintenance of homeostasis. - Compare and contrast bulk flow and diffusion. - Describe the composition of blood plasma. - List the major types of plasma proteins, their functions, and sites of production. - Compare and contrast the morphological features and general functions of the formed elements (i.e., erythrocytes, leukocytes, platelets). - Describe the structure and function of hemoglobin, including its breakdown products. - Define hematocrit and discuss healthy ranges for adults and common reasons for deviation from homeostasis. - List the five types of leukocytes in order of their relative prevalence in normal blood, and describe their major functions. ## 18.1a The Functions of Blood The primary function of blood is to deliver oxygen and nutrients to and remove wastes from body cells, but that is only the beginning of the story. The specific functions of blood also include defense, distribution of heat, and maintenance of homeostasis. ### Transportation Nutrients from the foods you eat are absorbed in the digestive tract. Yet, every one of the 40 trillion cells in your body needs access to those nutrients. The bloodstream enables the delivery of nutrients to body cells. We will learn more about nutrient absorption in Chapter 23. Oxygen from the air you breathe diffuses into the blood at the lungs, which we will discuss in Chapter 22. That oxygen-rich blood then travels from the lungs to the heart, which then pumps it out to the rest of the body. As we discussed in Chapter 17, 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 from each and every cell and transports them to various organs for removal. ### Defense Many types of WBCs protect the body from infection, from SARS CoV-2-the virus that causes COVID-19-to bacteria that are found on the surfaces of our environment. Other WBCs seek out and destroy internal threats, such as cancerous cells. When damage to the body results in bleeding, blood platelets and fibers dissolved in the plasma interact to seal the ruptured blood vessels, protecting the body from further blood loss. ### Maintenance of Homeostasis Recall that body temperature is regulated via a classic negative-feedback loop. If you exercise on a hot day, your rising core body temperature will trigger homeostatic mechanisms, including increased transport of blood from your core to your skin, to allow for heat loss off the surface. In contrast, on a cold day, blood is diverted away from the skin to prevent heat loss and maintain your core body temperature. 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. Blood also helps to regulate the water content of body cells. ## 18.1b Whole Blood Because of the central role in uniting and serving the different systems, organs, and cells of the body, sampling the blood of an individual can provide a lot of information about their overall health at any moment. Whole blood travels within and comes out of the body as the opaque dark red liquid you have undoubtedly seen (Figure 18.1A), but if left sitting over the course of a day, or spun quickly in a machine called a centrifuge (Figure 18.1B), the components of blood: plasma, WBC and platelets, and RBCs will separate because they have different densities (Figure 18.1C). Plasma, being the least dense, rises to the top. RBCs are the densest and settle at the bottom of the tube. A thin layer of WBCs and platelets separates the plasma from the RBCs. Throughout the study of anatomy and physiology, we spend a lot of time discussing the movement of individual materials through the processes of diffusion, osmosis, endocytosis, and exocytosis. We often refer to a concentration gradient as being a driving force for diffusion and osmosis. It is important to note the difference here when we discuss whole blood. The movement of blood through the circulatory system is based on a pressure gradient; it will move from where there is more pressure (the contracting heart) to where there is less pressure. Since every component of blood is equally subject to that pressure, the fluid moves all together, in bulk. The term bulk flow refers to the movement of a mixture according to its pressure gradient. Whole blood is viscous and somewhat sticky to the touch. Viscosity, or thickness, is one factor in its resistance to flow. You can illustrate this for yourself by sampling two fluids through a straw. If you use the same straw to drink water and then place it in a milkshake or smoothie, you can notice how much more difficult it is to move the more viscous fluid through the straw. Blood travels through strawlike tubes—the blood vessels—and therefore its viscosity is one determining factor in its flow. The viscosity of blood is influenced by the presence of the plasma proteins and formed elements within the blood. ## 18.1c Plasma Do you know your body weight? Approximately 8 percent of adult body weight is the blood volume. As you can imagine, smaller individuals have a lower blood volume and larger individuals have a higher blood volume. Other changes to the blood occur due to anatomical and physiological differences as we will discuss throughout the chapter. Individuals who menstruate regularly may have slightly lower blood volumes than those who do not menstruate. Adult blood volume ranges from four to six liters; for consistency, we will use five liters as our reference value throughout the text. Of that five liters of whole blood volume, approximately three liters is blood plasma. Like other fluids in the body, plasma is composed primarily of water; in fact, it is about 92 percent water. Dissolved or suspended within this water is a mixture of substances, including many proteins. There are literally hundreds of substances dissolved or suspended in the plasma, although many of them are found only in very small quantities. There could not be one consistent and true list of the substances within plasma, because the plasma is a reflection of the current homeostatic state of the blood. If you have just eaten lunch, for example, your plasma may contain different substances at this moment than it will in the middle of the night while you are sleeping (and therefore not eating or digesting). ### Plasma Proteins About 7 percent of the volume of plasma-nearly all that is not water-is made of proteins. These include several plasma proteins (proteins that are unique to the plasma), plus a much smaller number of other proteins, including enzymes and hormones. The major components of plasma are summarized in Table 18.1. The three major groups of plasma proteins are as follows: * **Albumins** are the most abundant of the plasma proteins. Made by the liver, albumins serve as transport vehicles for fatty acids and steroid hormones. Recall that lipids are hydrophobic and therefore would not dissolve readily in the watery plasma, however, their binding to albumin enables them to travel in the blood. Albumin is also a regulator of osmotic pressure of blood; that is, its presence helps to retain water inside the blood vessels and prevents too much water from being drawn toward the tissues. This in turn helps to maintain both blood volume and blood pressure. Albumin is not just an abundant protein in human bodies, but it is abundant throughout the animal kingdom. Egg whites, for example, are almost entirely composed of albumin. * **The second most common plasma proteins are the globulins**. A heterogeneous group, there are three main subgroups known as alpha, beta, and gamma globulins. The alpha and beta globulins are transport proteins; they help shuttle iron, lipids, and the fat-soluble vitamins to the cells. Like albumin, they also contribute to osmotic pressure. The gamma globulins are proteins involved in immunity and are better known as antibodies or immunoglobulins. Although other plasma proteins are produced by the liver, immunoglobulins are produced by leukocytes. Antibodies and how they are made will be discussed thoroughly in Chapter 21. * **The least abundant plasma protein is fibrinogen.** Like albumin and the alpha and beta globulins, fibrinogen is produced by the liver. It is essential for blood clotting, a process described in Section 18.3. ### Other Plasma Solutes In addition to proteins, plasma contains a wide variety of other substances. These include various ions, such as sodium, potassium, and calcium; dissolved gasses, oxygen, carbon dioxide, and nitrogen; various organic nutrients, such as vitamins, lipids, glucose, and amino acids; and metabolic wastes. Combined, all of these nonprotein solutes contribute approximately 1 percent to the total volume of plasma. ## 18.1d Erythrocytes Erythrocytes, commonly known as red blood cells (or RBCs), are by far the most common formed element. A single drop of blood contains millions of erythrocytes and just thousands of leukocytes. In fact, erythrocytes are estimated to make up about 25 percent of the total cells in the body. They are one of the smallest cell types in the human body. The function of erythrocytes is to transport gasses. Erythrocytes can carry several gasses-including carbon monoxide and carbon dioxide, as well as hydrogen ions-but their primary function is to carry oxygen. Erythrocytes are sleek and efficient carriers of blood gasses. They have few organelles and no nucleus. Without much in the way of internal contents, the shape of an erythrocytes can be described as a biconcave disc; that is, they are plump at their periphery and very thin in the center (Figure 18.2). Since they lack most organelles, there is more interior space for the presence of the hemoglobin molecules that transport gasses. The biconcave shape also provides a greater surface area across which gas exchange can occur, relative to its volume; a sphere of a similar diameter would have a lower surface area-to-volume ratio. Capillaries, the smallest blood vessels, are extremely narrow, slowing the passage of the erythrocytes and providing an extended opportunity for gas exchange to occur. However, the space within capillaries can be so minute that, despite their own small size, erythrocytes may have to fold themselves like a taco in order to make their way through. ### Hemoglobin Hemoglobin is a large molecule made up of proteins and iron. It consists of four folded chains of a protein called globin, designated alpha 1 and 2, and beta 1 and 2 (Figure 18.3). Each of these globin molecules is bound to a red pigment molecule called heme, which contains an ion of iron (Fe2+). To give you an idea of the vastness of the human blood supply, each iron ion in the heme can bind to one oxygen molecule; therefore, each hemoglobin molecule can transport four oxygen molecules. An individual erythrocyte may contain about 300 million hemoglobin molecules, and therefore can bind to and transport up to 1.2 billion oxygen molecules. When hemoglobin molecules are in oxygen-rich environments, they will bind oxygen molecules. However, in oxygen-poor environments, hemoglobin's affinity for oxygen decreases and oxygen will readily fall off the hemoglobin molecule. Therefore, when the hemoglobin-and therefore the blood environment- is carrying more oxygen, we can describe the blood as being oxygenated. Blood is the most oxygenated as it leaves the lungs, where hemoglobin picks up oxygen. The oxygenated blood then travels to the body tissues, where it releases some of the oxygen molecules, becoming deoxygenated (deoxygenated hemoglobin is sometimes referred to as reduced hemoglobin). Oxygen release depends on the need for oxygen in the surrounding tissues, so hemoglobin rarely, if ever, leaves all of its oxygen behind; in fact, "deoxygenated" blood is usually still 70-80 percent oxygenated. ## 18.1e The Life Cycle of Erythrocytes Production of erythrocytes occurs in the bone marrow. Although adults only have red bone marrow-the type of bone marrow capable of erythropoiesis- at the ends of long bones and in some of their irregular and flat bones, the average adult produces somewhere around 2 million new RBCs per second. That means you probably made about 20 million RBCs while you were reading the last sentence of this text! For this production to occur, a number of raw materials must be present in adequate amounts. These include the same nutrients that are essential to the production and maintenance of any cell, such as glucose, lipids, and amino acids. However, erythrocyte production also requires several trace elements: * **Iron.** We have said that each heme group in a hemoglobin molecule contains an ion of iron. Iron is relatively uncommon in foods and humans have limited ability to absorb the iron in our diets. In fact, less than 20 percent of the iron we consume is absorbed, and we absorb even less if our iron is in plant sources rather than meat. Therefore, humans spend energy recycling the iron that is already in the body. The bone marrow, liver, and spleen can store iron in the protein compounds ferritin and hemosiderin. When EPO stimulates the production of erythrocytes, iron is released from storage, bound to the blood protein transferrin, and carried to the red marrow, where it can be added to hemoglobin. * **B vitamins.** The B vitamins folate and vitamin B12 facilitate DNA synthesis. Thus, both are critical for the synthesis of new cells, including erythrocytes. Erythrocytes live up to 120 days in the circulation, after which the worn-out cells are removed by the liver and spleen. Typically, the rate of breakdown of old erythrocytes balances the production of erythrocytes in order to maintain a constant hematocrit. The following text and Figure 18.5 summarize the further breakdown of the components of the degraded erythrocytes' hemoglobin. * **Globin**, the protein portion of hemoglobin-is broken down into amino acids, which can be sent back to the bone marrow to be used in the production of new erythrocytes. Hemoglobin that is not phagocytized is broken down in the circulation, releasing alpha and beta chains that are removed from circulation by the kidneys. * **The iron contained in the heme portion of hemoglobin may be stored in the liver or spleen, primarily in the form of ferritin or hemosiderin, or carried through the bloodstream by transferrin to the red bone marrow for recycling into new erythrocytes.** * **The non-iron portion of heme is degraded into the waste product biliverdin, a green pigment, and then into another waste product, bilirubin, a yellow pigment.** Bilirubin is removed from the blood by the liver, which uses it in the manufacture of bile, a compound released into the intestines to help emulsify dietary fats. It is then eliminated from the body in the feces. The brown color of feces is due to the breakdown products of bilirubin within. The breakdown pigments formed from the destruction of hemoglobin can be seen under the skin during bruising in many individuals. At the beginning of the bruise, blood collects under the skin due to broken blood vessels. Over time, local cells break down and recycle the hemoglobin. As the hemoglobin is converted to biliverdin, the bruise may turn various shades of green. As it is further converted to bilirubin, the bruise may appear yellow. ## 18.1f Leukocytes and Platelets Leukocytes, commonly known as white blood cells (WBCs), are the soldiers of the immune response. Leukocytes protect the body against invading microorganisms, eliminate body cells with mutated DNA, and clean up debris. See the "Anatomy of Leukocytes" feature for a summary of leukocyte types. It is helpful to note that only a tiny fraction of the body's leukocyte population can be found in the blood. These cells spend most of their time in other structures and tissues of the body. We will explore leukocytes in much more detail in Chapter 21. Platelets are essential for the repair of blood vessels when damage to them has occurred; they also provide growth factors for healing and repair. ### Characteristics of Leukocytes Leukoyctes and erythrocytes both originate from stem cells in the bone marrow; the term for the production of these blood cells is hematopoiesis. Leukocytes and erythrocytes are very different from each other in many significant ways. For instance, leukocytes are far less numerous than erythrocytes: Recall that all of the leukocytes together represent just a thin line of the hematocrit. Leukocytes are much larger than erythrocytes and are the only formed elements of the blood that are complete cells, possessing a nucleus and organelles. And although there is just one type of erythrocyte, there are many types of leukocytes. While erythrocytes are regularly replaced after 120 days on average, leukocytes have variable lifespans depending on their type and the current immune responses ongoing in the body. Some leukocyte types live only few hours (or even a few minutes in the case of acute infection), while others can circulate for years. One of the most distinctive characteristics of leukocytes is their movement. Whereas erythrocytes spend their days circulating within the blood vessels, leukocytes routinely leave the bloodstream to perform their defensive functions in the body's tissues. For leukocytes, the vascular network is simply a highway they travel and soon exit to reach their true destination. As shown in Figure 18.6, they leave the capillaries-the smallest blood vessels-through a process known as diapedesis, in which they squeeze between the cells that make up the blood vessel wall. Once they have exited the capillaries, some leukocytes will take up residence in lymphatic tissue, bone marrow, the spleen, the thymus, or other organs. Others will move about through the tissue spaces wandering freely or moving in the direction of chemical signals. Leukocytes may call to each other to recruit help when fighting an infection by secreting chemical signals. This attracting of leukocytes occurs because of positive chemotaxis. Because each type of leukocyte specializes in a particular type of immune response, taking a count of the types and percentages of leukocytes present in a blood sample can provide evidence as to the type of infection and help lead to a diagnosis and treatment. ### 18.1g Classification of Leukocytes When scientists first began to observe stained blood slides, it quickly became evident some leukocytes were marked with dots all over their cytoplasm. These dots are granules, specialized vesicles that contain chemicals used in the cell's response to a pathogen, a disease-causing agent. Leukocytes can be divided into two groups, according to whether they contain granules: * **Granular leukocytes** contain abundant granules within the cytoplasm. They include neutrophils, eosinophils, and basophils. See the "Anatomy of Leukocytes" feature and Figures 18.7A-C. * **Agranular leukocytes** have far fewer and less obvious granules. Agranular leukocytes include monocytes and lymphocytes (see Figures 18.7D and 18.7E). #### Granular Leukocytes We will consider the granular leukocytes in order from most common to least common. All of these are produced in the red bone marrow and have a short lifespan of hours to days. They typically have a lobed nucleus and are classified according to which type of stain best highlights their granules. The most common of all the leukocytes, neutrophils will normally comprise 40-60 percent of the total leukocytes in the blood. Their granules are numerous but appear a faint, light purple color. The nucleus has a distinct lobed appearance and may have two to five lobes; the number increases as the cell ages. Neutrophils are rapid responders to the site of infection and will quickly phagocytize, or engulf, bacteria. Their granules include enzymes that can break down bacterial cell walls. High counts of neutrophils indicate infection, most likely bacterial infection. **Eosinophils** typically represent 2-4 percent of total leukocyte count. The granules of eosinophils stain best with an acidic stain known as eosin. The nucleus of the eosinophil will typically have two to three lobes and the granules will have a bright pink or red color. Some eosinophil granules contain molecules toxic to parasitic worms, which can enter the body through the integument, or when an individual consumes raw or undercooked fish or meat. High counts of eosinophils are typical of patients experiencing allergies, parasitic worm infestations, and some autoimmune diseases. Low counts may be due to drug toxicity and stress. **Basophils** are the least common leukocytes, typically comprising less than 1 percent of the total leukocyte count. The granules of basophils stain best with basic (alkaline) stains. Basophils contain large granules that pick up a dark blue stain and are so common they may make it difficult to see the two-lobed nucleus. The granules of basophils release histamine, an inflammatory chemical. High counts of basophils are associated with allergies, parasitic infections, and hypothyroidism. Low counts are associated with pregnancy, stress, and hyperthyroidism. #### Agranular Leukocytes Agranular leukocytes contain smaller, less visible granules in their cytoplasm than do granular leukocytes. The nucleus is simple in shape, sometimes with an indentation but without distinct lobes. There are two major types of agranulocytes: lymphocytes and monocytes. **Lymphocytes** form initially in the bone marrow; much of their subsequent development and reproduction occurs in the lymphatic tissues. Lymphocytes are the second most common type of leukocyte, accounting for about 20-30 percent of all leukocytes, and are essential for the immune response. Lymphocytes are typically smaller than the other leukocytes with a large nucleus that takes up almost the entire cell. The three major groups of lymphocytes include natural killer (NK) cells, B lymphocytes, and T lymphocytes, all of which play prominent roles in defending the body against specific pathogens. While the three different types of leukocytes have very different roles, we cannot distinguish among them under the light microscopes. We will discuss the functions of these subclasses in more detail in Chapter 21. Abnormally high lymphocyte counts are characteristic of viral infections as well as some types of cancer. Abnormally low lymphocyte counts are characteristic of prolonged (chronic) illness or immunosuppression, including that caused by HIV infection and drug therapies that often involve steroids. **Monocytes** are easily recognized by their large size and horseshoe-shaped nuclei. Monocytes are cells in transit, but once they leave the blood and reside in the tissues they differentiate into macrophages, cells capable of phagocytizing debris, foreign pathogens, worn-out erythrocytes, and many other damaged cells. Macrophages also release antimicrobial chemicals that harm pathogens and attract other leukocytes to the site of an infection. Whereas some macrophages occupy fixed locations, others wander through the tissue fluid. Abnormally high counts of monocytes are associated with viral or fungal infections, tuberculosis, and some forms of leukemia and other chronic diseases. Abnormally low counts are typically caused by suppression of the bone marrow. When examining leukocytes under the microscope, a few questions can be used to differentiate among the leukocyte types and determine what kind of cell is being examined (Figure 18.8). ## 18.1h Platelets Platelets are not cells but rather fragments of cytoplasm surrounded by a plasma membrane. Platelets are produced by megakaryocytes, a type of cell found in the bone marrow. Megakaryocytes release thousands of cytoplasmic fragments, each enclosed by a bit of plasma membrane. These enclosed fragments are platelets. Each megakaryocyte releases 2000-3000 platelets during its lifespan (Figure 18.9). Platelets are small, but numerous. After entering the circulation, approximately one-third migrate to the spleen for storage for later release in response to any rupture in a blood vessel. They are critical to hemostasis, the stoppage of blood flow following damage to a vessel. They also secrete a variety of growth factors essential for growth and repair of tissue, particularly connective tissue. ## 18.2 Production of the Formed Elements ### Learning Objectives: By the end of this section, you will be able to: - Describe the locations of hematopoiesis (hemopoiesis) and the significance of the hematopoietic stem cell (HSC or hemocytoblast). - Explain the basic process of erythropoiesis, the significance of the reticulocyte, and regulation through erythropoietin (EPO). - Explain the basic process of thrombopoiesis. - Explain the basic process of leukopoiesis. The lifespan of the formed elements is very brief. Although one type of leukocyte called memory cells can survive for years, most erythrocytes, leukocytes, and platelets normally live only a few hours to a few weeks. Thus, the body must form new blood cells and platelets quickly and continuously. When you donate a unit of blood, your body typically replaces the donated plasma within 24 hours, but it takes about 4-6 weeks to replace the blood cells. This restricts the frequency with which donors can safely contribute their blood. The process by which this replacement occurs is called hematopoiesis. ### 18.2a Sites of Hematopoiesis Most hematopoiesis occurs in the red bone marrow, a connective tissue within the spaces of spongy (cancellous) bone tissue. In children, red bone marrow occupies all of the hollow spaces within bones but 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. ### 18.2b Differentiation of Formed Elements from Stem Cells Hematopoietic stem cells reside in the bone marrow and give rise to all of the formed elements of blood. Hematopoiesis begins when the hematopoietic stem cell divides. One of the daughter cells remains a stem cell and the other differentiates into one of two types of stem cells (Figure 18.10): * **Lymphoid stem cells** give rise to lymphocytes, which include the T cells, B cells, and natural killer (NK) cells, all of which function in immunity. * **Myeloid stem cells** give rise to all the other formed elements, including the erythrocytes; and the other leukocytes: neutrophils, eosinophils, and basophils and monocytes. Lymphoid and myeloid stem cells do not immediately divide and differentiate into mature formed elements. As you can see in Figure 18.10, there are intermediate stages of precursor cells. ### 18.2c Hemopoietic Growth Factors Development from stem cells to precursor cells to mature cells is guided by secreted chemicals called growth factors. These include the following: * **Erythropoietin (EPO)** is a hormone secreted by the kidneys in response to low oxygen levels. It prompts the production of erythrocytes, which is called erythropoiesis. * **Thrombopoietin**, another hormone, is produced by the liver and kidneys. It triggers the development of megakaryocytes into platelets. * **Cytokines** are chemical signals secreted by a wide variety of cells, including red bone marrow, leukocytes, macrophages, fibroblasts, and endothelial cells. They act locally as autocrine or paracrine factors, stimulating the proliferation of progenitor cells and helping to stimulate both nonspecific and specific resistance to disease. Some of these cytokines stimulate leukopoiesis, the production of leukocytes from hematopoietic stem and progenitor cells. ## 18.3 Hemostasis ### Learning Objectives: By the end of this section, you will be able to: - Describe the vascular phase of hemostasis, including the role of endothelial cells. - Describe the role of platelets in hemostasis and the steps involved in the formation of the platelet plug. - Explain how the positive feedback loops in the platelet and coagulation phases promote hemostasis. - Describe the basic steps of coagulation resulting in the formation of the insoluble fibrin clot. - Differentiate among the intrinsic (contact activation), extrinsic (cell injury), and common pathways of the coagulation cascade. - Explain the role of vitamin K in blood clotting. - Describe the process of fibrinolysis, including the roles of plasminogen, tissue plasminogen activator, and plasmin. Hemostasis is the stoppage of bleeding. It consists of three processes: vascular spasm, platelet plug formation, and coagulation. Hemostasis begins with vascular spasm, in which blood vessels vasoconstrict to restrict blood loss. Then, the exposed collagen from the wall of the broken blood vessel signals for platelet activation and a platelet plug is formed. This limits further blood loss. The final and most effective phase of hemostasis is coagulation, in which liquid plasma is converted into a solid gel, and fib in threads provide a network to stabilize the clot. Coagulation occurs as a stepwise cascade of chemical reactions. Fibrinolysis occurs after healing has occurred, to restore normal blood flow to the previously affected area. ## 18.4 Blood Typing ### Learning Objectives: By the end of this section, you will be able to: - Explain the role of surface antigens on erythrocytes in determining blood groups. - Describe how the presence or absence of Rh antigen results in blood being classified as positive or negative. - List the type of antigen and the type of antibodies present in each ABO blood type. - Describe the development and clinical significance of anti-Rh antibodies. - Predict which blood types are compatible and what happens when the incorrect ABO or Rh blood type is transfused. The term antigen refers to a molecule or group of molecules that the body does not recognize as belonging to the "self" and that therefore trigger a defensive response from the leukocytes of the immune system. In Chapter 21 we will discuss the antigens of pathogens in detail, and you may have heard of "antigen testing" as a way to check for the presence of certain viruses or other pathogens. Here, scientists named the molecules on the surface of erythrocytes as antigens because these molecules triggered the immune reactions, called transfusion reactions, that made some forms of blood incompatible with others. One of our immune tools is a small protein called an antibody that is made in response to an antigen (Figure 18.13). More than 50 antigens have been identified on the surface of erythrocytes, but only three are strongly antigenic, meaning that they are the most likely to provoke an immune response in certain blood transfusion recipients. These antigens are known as antigen A, antigen B, and antigen D, which is also called the Rh factor (Figure 18.14). Although the ABO blood group name consists of three letters, ABO blood typing designates the presence or absence of just two antigens, A and B. Both are glycoproteins. People whose erythrocytes have A antigens on their erythrocyte membrane surfaces are designated blood type A, and those whose erythrocytes have B antigens are blood type B. People can also have both A and B antigens on their erythrocytes, in which case they are blood type AB. People with neither A nor B antigens are designated blood type O. ABO blood types are genetically determined. 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. Individuals with type A blood- without any prior exposure to incompatible blood- have preformed antibodies to the B antigen circulating in their blood plasma. These antibodies, referred to as anti-B antibodies, will cause agglutination and hemolysis if they ever encounter erythrocytes with B antigens. Similarly, an individual with type B blood has pre-formed anti-A antibodies. Individuals with type AB blood, which has both antigens, do not have preformed antibodies to either of these. People with type O blood lack antigens A and B on their erythrocytes, but both anti-A and anti-B antibodies circulate in their blood plasma. Table 18.3 summarizes the characteristics of the blood types in the ABO blood group. The Rh blood group is classified according to the presence or absence of a second erythrocyte antigen identified as Rh. (The Rh is short for "rhesus"; it was first discovered in a rhesus macaque, a type of primate often used in research because its blood is similar to that of humans.) Although dozens of Rh antigens have been identified, only one (designated D) is clinically important. Those who have the Rh D antigen present on their erythrocytes-about 85 percent of Americans- 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 (Figure 18.15). 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. In contrast to the ABO group antibodies, which are preformed, antibodies to the Rh antigen are produced only in Rh negative individuals after exposure to the antigen. This process, called sensitization, occurs following a transfusion with Rh negative incompatible blood or, more commonly, with the birth of an Rh positive baby to an Rh negative mother. Problems are rare in a first pregnancy, since the fetus's Rh+ cells rarely cross the placenta (the organ of gas and nutrient exchange between the baby and the mother). However, during the process of birth, the Rh negative mother can be exposed to the baby's Rh positive cells. After exposure, the mother's immune system begins to generate anti-Rh antibodies. If the mother should then conceive another Rh positive fetus, the Rh antibodies she has produced can cross the placenta into the fetal bloodstream and destroy the fetal RBCs. This condition, known as hemolytic disease of the newborn (HDN) or erythroblastosis fetalis, may cause anemia in mild cases, but the agglutination and hemolysis can be so severe that without treatment the fetus may die in the womb or shortly after birth. ### Transfusion Reactions Antibodies are Y-shaped and have two antigen-binding sites. During an antibody response, clumps of antigen-bearing erythrocytes can form. This process is called agglutination (see Figure 18.15). The clumps of erythrocytes block small blood vessels throughout the body, depriving tissues of oxygen and nutrients. As the erythrocyte clumps are degraded, in a process called hemolysis, their hemoglobin is released into the bloodstream. This hemoglobin travels to the kidneys, which are responsible for filtration of the blood. However, the load of hemoglobin released can easily overwhelm the kidney's capacity to clear it, and the patient can quickly develop kidney failure. Therefore an individual can only receive blood from blood types that they do not have antibodies against. If, for example, a person is A+ (A positive) they can receive blood in which the RBCs contain A and/or Rh antigens, but they would react against B antigens and therefore should not receive any blood type that includes B antigens (type B or AB). ## 18.3 Hemostasis ### Learning Objectives: By the end of this section, you will be able to: - Describe the vascular phase of hemostasis, including the role of endothelial cells. - Describe the role of platelets in hemostasis and the steps involved in the formation of the platelet plug. - Explain how the positive feedback loops in the platelet and coagulation phases promote hemostasis. - Describe the basic steps of coagulation resulting in the formation of the insoluble fibrin clot. - Differentiate among the intrinsic (contact activation), extrinsic (cell injury), and common pathways of the coagulation cascade. - Explain the role of vitamin K in blood clotting. - Describe the process of fibrinolysis, including the roles of plasminogen, tissue plasminogen activator, and plasmin. Hemostasis is the stoppage of bleeding. It consists of three processes: vascular spasm, platelet plug formation, and coagulation. Hemostasis begins with vascular spasm, in which blood vessels vasoconstrict to restrict blood loss. Then, the exposed collagen from the wall of the broken blood vessel signals for platelet activation and a platelet plug is formed. This limits further blood loss. The final and most effective phase of hemostasis is coagulation, in which liquid plasma is converted into a solid gel, and fibrin threads provide a network to stabilize the clot. Coagulation occurs as a stepwise cascade of chemical reactions. Fibrinolysis occurs after healing has occurred, to restore normal blood flow to the previously affected area. ## 18.4. Blood Typing ### Learning Objectives: By the end of this section, you will be able to: - Explain the role of surface antigens on erythrocytes in determining blood groups. - Describe how the presence or absence of Rh antigen results in blood being classified as positive or negative. - List the type of antigen and the type of antibodies present in each ABO blood type. - Describe the development and clinical significance of anti-Rh antibodies. - Predict which blood types are compatible and what happens when the incorrect ABO or Rh blood type is transfused. The term antigen refers to a molecule or group of molecules that the body does not recognize as belonging to the "self" and that therefore trigger a defensive response from the leukocytes of the immune system. In Chapter 21 we will discuss the antigens of pathogens in detail, and you may have heard of "antigen testing" as a way to check for the presence of certain viruses or other pathogens. Here, scientists named the molecules on the surface of erythrocytes as antigens because these molecules triggered the immune reactions, called transfusion reactions, that made some forms of blood incompatible with others. One of our immune tools is a small protein called an antibody that is made in response to an antigen (Figure 18.13). More than 50 antigens have been identified on the surface of erythrocytes, but only three are strongly antigenic, meaning that they are the most likely to provoke an immune response in certain blood transfusion recipients