10.1 Introduction

In this chapter, you will learn about blood, a component of the cardiovascular system, which transports substances throughout the body. Specifically, you will learn about:

• The components of blood — including plasma, red blood cells, white blood cells, and platelets — and their specific functions.
• Identify the most important proteins and other solutes present in blood plasma
• Describe the formation of the formed element components of blood
• Discuss the structure and function of red blood cells and hemoglobin
• How blood is regulated to maintained homeostasis.
• Blood typing.
• Hemostasis – formation of a blood clot.
• Discuss a variety of blood disorders

The human body needs 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 vessels—makes up the cardiovascular system. This chapter focuses on the medium of transport: blood.

The average adult body contains between 4.7 and 5.7 liters of blood. More than half of that amount is fluid. Most of the rest of that amount consists of blood cells. The relative amounts of the various components in blood are illustrated in Figure 10.1 below. The components are also described in detail below.

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. 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. Moreover, 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.

Defense

Many types of white blood cells (WBCs) also known as Leucocytes, protect the body from external threats, such as disease-causing bacteria that have entered the bloodstream in a wound. Other WBCs seek out and destroy internal threats, such as 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, the fluid portion of the blood, interact to block the ruptured areas of the blood vessels involved. This protects the body from further blood loss.

Maintenance of Homeostasis

Recall that body temperature is regulated via a classic negative-feedback loop. 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 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.

Review

1. What is blood? Why is blood considered a connective tissue?
2. Identify four physiological roles of blood in the body.

The cells in blood include erythrocytes, leukocytes and platelets (thrombocytes). These different types of blood cells are shown in the photomicrograph (Figure 10.2) and described in the sections that follow.

Figure 10.2 Highly magnified blood cells in this image include doughnut-shaped red blood cells, rough-surfaced white blood cells, and small disc-shaped platelets.

Erythrocytes

The erythrocyte, commonly known as a red blood cell (or RBC), is by far the most common formed element: A single drop of blood contains millions of erythrocytes and just thousands of leukocytes. Specifically, males have about 5.4 million erythrocytes per microliter (uL) of blood, and females have approximately 4.8 million per pL. In fact, erythrocytes are estimated to make up about 25 percent of the total cells in the body. As you can imagine, they are quite small cells, with a mean diameter of only about 7-8 micrometers (um). The primary functions of erythrocytes are to pick up inhaled oxygen from the lungs and transport it to the body’s tissues, and to pick up some (about 24 percent) carbon dioxide waste at the tissues and transport it to the lungs for exhalation. Erythrocytes remain within the vascular network. Although leukocytes typically leave the blood vessels to perform their defensive functions, movement of erythrocytes from the blood vessels is abnormal.

Shape and Structure of Erythrocytes

As an erythrocyte matures in the red bone marrow, it extrudes its nucleus and most of its other organelles. Lacking mitochondria, for example, they rely on fermentation. This means that they do not utilize any of the oxygen they are transporting, so they can deliver it all to the tissues. They also lack endoplasmic reticula and do not synthesize proteins, so they are unable to repair themselves. This is why the lifespan of a red blood cell is approximately 115 days. However, during this time, the red blood cell has traveled approximately 300 miles and made approximately 170,000 circuits through the heart.

Erythrocytes are biconcave disks; that is, they are plump at their periphery and very thin in the center (Figure 10.2). Since they lack most organelles, there is more interior space for the presence of the hemoglobin molecules that, as you will see shortly, transport gases. 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. In the capillaries, the oxygen carried by the erythrocytes can diffuse into the plasma and then through the capillary walls to reach the cells, whereas some of the carbon dioxide produced by the cells as a waste product diffuses into the capillaries to be picked up by the erythrocytes. Capillary beds 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 in on themselves if they are to make their way through. Fortunately, their structural proteins are flexible, allowing them to bend over themselves to a surprising degree, then spring back again when they enter a wider vessel.

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 10.3). Each of these globin molecules is bound to a red pigment molecule called heme, which contains an ion of iron (Fe**).  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.

In the lungs, hemoglobin picks up oxygen, which binds to the iron ions, forming oxyhemoglobin. The bright red, oxygenated hemoglobin travels to the body tissues, where it releases some of the oxygen molecules, becoming darker red deoxyhemoglobin. Oxygen release depends on the need for oxygen in the surrounding tissues, so hemoglobin rarely if ever leaves all of its oxygen behind. In the capillaries, carbon dioxide enters the bloodstream. About 76 percent dissolves in the plasma, some of it remaining as dissolved COs, and the remainder forming bicarbonate ion. About 23—24 percent of it binds to the amino acids in hemoglobin, forming a molecule known as carbaminohemoglobin. From the capillaries, the hemoglobin carries carbon dioxide back to the lungs, where it releases it for exchange of oxygen.

Figure 10.3 (a) A molecule of hemoglobin contains four globin proteins, each of which is bound to one molecule of the iron-containing pigment heme. (b) A single erythrocyte can contain 300 million hemoglobin molecules, and thus more than 1 billion oxygen molecules.

Lifecycle of Erythrocytes

Production of erythrocytes in the marrow occurs at the staggering rate of more than 2 million cells per second. 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, copper, zinc, and several types of B vitamins.

All types of blood cells are made in red marrow within the medullary cavity of bones in a process called hematopoiesis. Formation of blood cells occurs by the proliferation of stem cells in the marrow. These stem cells are self-renewing — when they divide, some of the daughter cells remain stem cells, so the pool of stem cells is not used up. Other daughter cells follow various pathways to differentiate into the variety of blood cell types. Once the cells have differentiated, they cannot divide to form copies of themselves.

The production of erythrocytes is regulated by a negative feedback mechanism to maintain homeostasis.  Levels of oxygen in the blood are monitored and when there are decreased levels a signal is sent to cells within the kidney.  The kidney responds by increasing the release of a hormone called erythropoietin.  Erythropoietin stimulates stem cells in the bone marrow to differentiate into erythrocytes.  the increased number of erythrocytes brings the oxygen levels back to normal.

Eventually, blood cells die and must be replaced through the formation of new blood cells from proliferating stem cells. Erythrocytes live up to 120 days in the circulation, after which the worn-out cells are removed by a type of phagocytic cell called a macrophage, located primarily within the bone marrow, liver, and spleen. The components of the degraded erythrocytes’ hemoglobin are further processed, with some being retained by the body and others being released in the urine and feces.

The components of the degraded erythrocytes’ hemoglobin are further processed as follows:

• 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 or carried through the bloodstream to the red bone marrow for recycling into new erythrocytes.
• The non-iron portion of heme is degraded into the waste product, bilirubin, a yellow pigment. Bilirubin binds to albumin and travels in the blood to the liver, which uses it in the manufacture of bile, a compound released into the intestines to help emulsify dietary fats. In the large intestine, bacteria break the bilirubin apart from the bile and converts it to urobilinogen and then into stercobilin. It is then eliminated from the body in the feces. The breakdown pigments formed from the destruction of hemoglobin can be seen in a variety of situations. At the site of an injury, bilirubin from damaged RBCs produces some of the dramatic colors associated with bruising. With a failing liver, bilirubin cannot be removed effectively from circulation and causes the body to assume a yellowish tinge associated with jaundice.

Disorders of Erythrocytes

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, and more than 3.5 million Americans suffer from this condition. 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. The effects of the various anemias are widespread, because reduced numbers of RBCs or hemoglobin will result in lower levels of oxygen being delivered to body tissues. Since oxygen is required for tissue functioning, anemia produces fatigue, lethargy, and an increased risk for infection. An oxygen deficit in the brain impairs the ability to think clearly, and may prompt headaches and irritability. Lack of oxygen leaves the patient short of breath, even as the heart and lungs work harder in response to the deficit.

Anemias caused by faulty or decreased RBC production include sickle cell anemia, iron deficiency anemia, vitamin deficiency anemia, and diseases of the bone marrow and stem cells.

Figure 10.4 Anemia has wide-ranging effects on the human body because oxygen is essential for normal functioning of cells in every organ system.

In contrast to anemia, an elevated RBC count is called polycythemia 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 water losses are excessive, the plasma volume falls. As a result, the hematocrit rises. For reasons mentioned earlier, 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 (from the Greek vera = “true”) 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 elderly patients those over 60 years of age.

Review

1. Fill in the blanks: The blood cells responsible for carrying oxygen around the body are  _____________. These cells carry the oxygen on a protein called ______________.
2. Which of the following statements about mature, circulating erythrocytes is true?
   a. They have no nucleus.
   b. They are packed with mitochondria.
   c. They survive for an average of 4 days.
   d. All of the above
3. A molecule of hemoglobin
   a. is shaped like a biconcave disk packed almost entirely with iron
   b. contains four glycoprotein units studded with oxygen
   c. consists of four globin proteins, each bound to a molecule of heme
   d. can carry up to 120 molecules of oxygen
4. Aging and damaged erythrocytes are removed from the circulation by
   a. myeloblasts
   b. monocytes
   c. macrophages
   d. mast cells
5. Which of the following statements about erythropoietin is true?
   a. It facilitates the proliferation and differentiation of the erythrocyte lineage.
   b. It is a hormone produced by the thyroid gland.
   c. It is a hemopoietic growth factor that prompts lymphoid stem cells to leave the bone marrow.
   d. Both a and b are true.

Leukocytes

Leukocytes (also called white blood cells) are cells in blood that defend the body against invading microorganisms and other threats. White blood cells are part of the body’s immune system. Although leukocytes and erythrocytes both originate from hematopoietic stem cells in the bone marrow, they are very different from each other in many significant ways. For instance, leukocytes are far less numerous than erythrocytes: Typically, there are only 5000 to 10,000 per µL. They are also larger than erythrocytes and are the only formed elements that are complete cells, possessing a nucleus and organelles. And although there is just one type of erythrocyte, there are many types of leukocytes. Most of these types have a much shorter lifespan than that of erythrocytes, some as short as a few hours or even a few minutes in the case of acute infection. They destroy and remove old or abnormal cells and cellular debris, as well as attack pathogens and foreign substances. There are five main types of white blood cells, which are described in Table 10.1: neutrophils, eosinophils, basophils, lymphocytes, and monocytes. 

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.

Classification of Leukocytes

When scientists first began to observe stained blood slides, it quickly became evident that leukocytes could be divided into two groups, according to whether their cytoplasm contained highly visible granules:

• Granular leukocytes contain abundant granules within the cytoplasm. They include neutrophils, eosinophils, and basophils.
• While granules are not totally lacking in agranular leukocytes, they are far fewer and less obvious. Agranular leukocytes include monocytes, which mature into macrophages that are phagocytic, and lymphocytes, which arise from the lymphoid stem cell line.

Figure 10.5:  Five types of leukocytes: from left to right, lymphocyte, basophil, eosinophil, neutrophil, and monocytes.

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.

NEUTROPHILS

Neutrophils are leukocytes that travel throughout the body in the blood. They are called neutrophils because their granules show up most clearly with stains that are chemically neutral (neither acidic nor basic). They are usually the first immune cells to arrive at the site of an infection. They are the most numerous types of phagocytes, and they normally make up at least half of the total circulating leukocytes. The bone marrow of a normal healthy adult produces more than 100 billion neutrophils per day. During acute inflammation, more than ten times that many neutrophils may be produced each day. Many neutrophils are needed to fight infections, because after a neutrophil phagocytizes just a few pathogens, it generally dies.

Abnormally high counts of neutrophils indicate infection and/or inflammation, particularly triggered by bacteria, but are also found in burn patients and others experiencing unusual stress. A burn injury increases the proliferation of neutrophils in order to fight off infection that can result from the destruction of the barrier of the skin. Low counts may be caused by drug toxicity and other disorders and may increase an individual’s susceptibility to infection.

EOSINOPHILS

Eosinophils are non-phagocytic leukocytes that are related to neutrophils. 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, if stained properly, the granules will have a distinct red to orange color. The granules of eosinophils include antihistamine molecules, which counteract the activities of histamines, inflammatory chemicals produced allergic reactions and asthma. They specialize in defending against parasites. They are very effective in killing large parasites (such as worms) by secreting a range of highly toxic substances when activated.

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

Basophils are non-phagocytic leukocytes that are also related to neutrophils. They are the least numerous of all white blood cells. typically comprising less than one 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. Basophils secrete two types of chemicals that aid in body defenses: histamines and heparin. Histamines are responsible for dilating blood vessels and increasing their permeability in inflammation. Heparin inhibits blood clotting, and also promotes the movement of leukocytes into an area of infection.

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

Lymphocytes are the only formed element of blood that arises from lymphoid stem cells. Although they 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. T

The three major groups of lymphocytes include natural killer cells, B cells, and T cells. Natural killer (NK) cells are capable of recognizing cells that do not express “self” proteins on their plasma membrane or that contain foreign or abnormal markers. These “non self” cells include cancer cells, cells infected with a virus, and other cells with atypical surface proteins. Thus, they provide generalized, nonspecific immunity. The larger lymphocytes are typically NK cells.

B cells and T cells, also called B lymphocytes and T lymphocytes, play prominent roles in defending the body against specific pathogens (disease-causing microorganisms) and are involved in specific immunity. One form of B cells (plasma cells) produces the antibodies or immunoglobulins that bind to specific foreign or abnormal components of plasma membranes. This is also referred to as humoral (body fluid) immunity. T cells provide cellular-level immunity by physically attacking foreign or diseased cells. A memory cell is a variety of both B and T cells that forms after exposure to a pathogen and mounts rapid responses upon subsequent exposures. Unlike other leukocytes, memory cells live for many years. B cells undergo a maturation process in the bone marrow, whereas T cells undergo maturation in the thymus. This site of the maturation process gives rise to the name B and T cells. The functions of lymphocytes are complex and will be covered in detail in the chapter covering the lymphatic system and immunity. Smaller lymphocytes are either B or T cells, although they cannot be differentiated in a normal blood smear.

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

Monocytes originate from myeloid stem cells. They normally represent 2–8 percent of the total leukocyte count. They are typically easily recognized by their large size and indented or horseshoe-shaped nuclei. Macrophages are monocytes that have left the circulation and phagocytize debris, foreign pathogens, worn-out erythrocytes, and many other dead, worn out, or damaged cells. Macrophages also release chemicals that attract other leukocytes to the site of an infection. Some macrophages occupy fixed locations, whereas 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.

Lifecycle of Leukocytes

Most leukocytes have a relatively short lifespan, typically measured in hours or days. Production of all leukocytes begins in the bone marrow under the influence of CSFs and interleukins. Secondary production and maturation of lymphocytes occurs in specific regions of lymphatic tissue known as germinal centers. Lymphocytes are fully capable of mitosis and may produce clones of cells with identical properties. This capacity enables an individual to maintain immunity throughout life to many threats that have been encountered in the past.

PHAGOCYTOSIS

Phagocytosis is an important feature of innate immunity that is performed by cells classified as phagocytes. In the process of phagocytosis, phagocytes engulf and digest pathogens or other harmful particles. Phagocytes generally patrol the body searching for pathogens, but they can also be called to specific locations by the release of certain chemicals called cytokines when inflammation occurs. Some phagocytes reside permanently in certain tissues.

As shown in Figure 10.5, when a pathogen such as a bacterium is encountered by a phagocyte, the phagocyte extends a portion of its plasma membrane, wrapping the membrane around the pathogen until it is enveloped. Once inside the phagocyte, the pathogen becomes enclosed within an intracellular vesicle called a phagosome. The phagosome then fuses with another vesicle called a lysosome, forming a phagolysosome. Digestive enzymes and acids from the lysosome kill and digest the pathogen in the phagolysosome. The final step of phagocytosis is excretion of soluble debris from the destroyed pathogen through exocytosis. Types of leukocytes that kill pathogens by phagocytosis include neutrophils and macrophages.

Figure 10.6 Phagocytosis is a multi-step process in which a pathogen is engulfed and digested by immune cells called phagocytes.

 

Disorders of Leukocytes

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. Excessive leukocyte proliferation is known as leukocytosis. Although leukocyte counts are high, the cells themselves are often nonfunctional, leaving the individual at increased risk for disease.

Leukemia is a 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.

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.

Review

1.Which of the following describes a neutrophil?
a. abundant, agranular, especially effective against cancer cells
b. they are the first immune cells to arrive at the site of an infection
c. rare, agranular, releases antimicrobial defensins
d. rare, granular, contains multiple granules packed with histamine

2. T and B lymphocytes ________.
a. are polymorphonuclear
b. are involved with specific immune function
c .proliferate excessively in leukopenia
d. are most active against parasitic worms3. The blood cells which are part of the immune system are __________________. These cells come in a variety of types and have the job of cleaning up cellular debris and engulfing and destroying __________________.4. What is phagocytosis? 5. Which type of leukocyte defends against parasites?6. What is the difference between granular and agranular leukocytes?

Platelets

Platelets (Thrombocytes) are actually cell fragments of a cell called a megakaryocyte. Like erythrocytes, they lack a nucleus and are more numerous than white blood cells. There are about 150 thousand to 400 thousand thrombocytes per microliter of blood.

The main function of thrombocytes is blood clotting, or coagulation. This is the process by which blood changes from a liquid to a gel, forming a plug in a damaged blood vessel. If blood clotting is successful, it results in hemostasis, which is the cessation of blood loss from the damaged vessel. A blood clot consists of both platelets and proteins, especially the protein fibrin. You can see a scanning electron microscope photomicrograph of a blood clot in Figure 10.6.

Figure 10.7 Erythrocytes become trapped in a coagulating clot so they cannot escape through a break in a blood vessel.

Platelets 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. Infusions of concentrated platelets are now being used in some therapies to stimulate healing.

HEMOSTASIS

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—excessive bleeding.

Vascular Spasm

When a vessel is severed or punctured, or when the wall of a vessel is damaged, vascular spasm occurs. In vascular spasm, the smooth muscle in the walls of the vessel contracts dramatically. This smooth muscle has both circular layers; larger vessels also have longitudinal layers. The circular layers tend to constrict the flow of blood, whereas the longitudinal layers, when present, draw the vessel back into the surrounding tissue, often making it more difficult for a surgeon to locate, clamp, and tie off a severed vessel. The vascular spasm response is believed to be triggered by several chemicals called endothelins that are released by vessel-lining cells and by pain receptors in response to vessel injury. This phenomenon typically lasts for up to 30 minutes, although it can last for hours.

Formation of the Platelet Plug

In the second step, platelets, which normally float free in the plasma, encounter the area of vessel rupture with the exposed underlying connective tissue and collagenous fibers. The platelets begin to clump together, become spiked and sticky, and bind to the exposed collagen and endothelial lining.

A platelet plug can temporarily seal a small opening in a blood vessel. Plug formation, in essence, buys the body time while more sophisticated and durable repairs are being made. In a similar manner, even modern naval warships still carry an assortment of wooden plugs to temporarily repair small breaches in their hulls until permanent repairs can be made.

Figure 10.8 The shape of platelets (thrombocytes) after they are activated helps them to stick together and form a plug for a damaged blood vessel.

Coagulation

Those more sophisticated and more durable repairs are collectively called coagulation, the formation of a blood clot. The process is sometimes characterized as a cascade, because one event prompts the next as in a multi-level waterfall. The result is the production of a gelatinous but robust clot made up of a mesh of fibrin—an insoluble filamentous protein derived from fibrinogen, the plasma protein in which platelets and blood cells are trapped.

Hemophilia refers to any of several genetic disorders that cause dysfunction in the blood clotting process. People with hemophilia are prone to potentially uncontrollable bleeding, even with otherwise inconsequential injuries. They also commonly suffer bleeding into the spaces between joints, which can cause crippling.

Review

1. ___________________ are actually fragments of cells and are responsible for blood clotting. When activated, these blood cells become “sticky” and will clump together to form blood clots.
2. The first step in hemostasis is ________.
   a. vascular spasm
   b. formation of a platelet plug
   c. coagulation
   d. conversion of fibrinogen to fibrin

 

10.6 Blood Typing and Transfusions

Blood transfusions in humans were risky procedures until the discovery of the major human blood groups by Karl Landsteiner, an Austrian biologist and physician, in 1900. Until that point, physicians did not understand that death sometimes followed blood transfusions, when the type of donor blood infused into the patient was incompatible with the patient’s own blood. Blood groups are determined by the presence or absence of specific marker molecules, called antigens, on the plasma membranes of erythrocytes. With their discovery, it became possible for the first time to match patient-donor blood types and prevent transfusion reactions and deaths.

Antigens are substances that the body does not recognize as belonging to the “self” and that therefore trigger a defensive response from the leukocytes (WBC) of the immune system. Here, we will focus on the role of immunity, antigens, and antibodies in blood transfusion reactions.

Antigens are generally large proteins, but may include other classes of organic molecules, including carbohydrates, lipids, and nucleic acids. Following an infusion of incompatible blood, erythrocytes with foreign antigens appear in the bloodstream and trigger an immune response. Proteins called antibodies (immunoglobulins), which are produced by certain B lymphocytes called plasma cells, attach to the antigens on the plasma membranes of the infused erythrocytes and cause them to stick to one another (i.e. agglutinate). 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.

More than 50 antigens have been identified on erythrocyte membranes, but the most significant in terms of their potential harm to patients are classified in two groups: the ABO blood group and the Rh blood group.

The ABO Blood Group

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.

Blood type is important for medical reasons. A person who needs a blood transfusion must receive blood of a compatible type. Blood that is compatible lacks antigens that the patient’s own blood also lacks. For example, for a person with type A blood (no B antigen), compatible types include any type of blood that lacks the B antigen. This would include type A blood or type O blood, but not type AB or type B blood. If incompatible blood is transfused, it may cause a potentially life-threatening reaction in the patient’s blood.

Figure 10.9 Each of the ABO blood types is characterized by different glycoproteins on red blood cells.

Rh Blood Groups

The Rh blood group is classified according to the presence or absence of a second erythrocyte antigen identified as Rh. (It was first discovered in a type of primate known as a rhesus macaque, which is 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. 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+ 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. Problems are rare in a first pregnancy, since the baby’s Rh+ cells rarely cross the placenta (the organ of gas and nutrient exchange between the baby and the mother). However, during or immediately after birth, the Rh- mother can be exposed to the baby’s Rh+ cells. Research has shown that this occurs in about 13-14 percent of such pregnancies. After exposure, the mother’s immune system begins to generate anti-Rh antibodies. If the mother should then conceive another Rh+ baby, 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.

A drug known as RhoGAM, short for Rh immune globulin, can temporarily prevent the development of Rh antibodies in the Rh” mother, thereby averting this potentially serious disease for the fetus. RhoGAM antibodies destroy any fetal Rh* erythrocytes that may cross the placental barrier. RhoGAM is normally administered to Rh mothers during weeks 26-28 of pregnancy and within 72 hours following birth. It has proven remarkably effective in decreasing the incidence of HDN. Earlier we noted that the incidence of HDN in an Rh* subsequent pregnancy to an Rh mother is about 13-14 percent without preventive treatment. Since the introduction of RhoGAM in 1968, the incidence has dropped to about 0.1 percent in the United States.

Determining ABO Blood Types

Clinicians are able to determine a patient’s blood type quickly and easily using commercially prepared antibodies. An unknown blood sample is allocated into separate wells. Into one well a small amount of anti-A antibody is added, and to another a small amount of anti-B antibody. If the antigen is present, the antibodies will cause visible agglutination of the cells (Figure 10.10 ). The blood should also be tested for Rh antibodies.

Schatz, P. (1999-2004). Erythrocytes. In Anatomy and Physiology. PhilSchatz.com. [Creative Commons Attribution 4.0 International License]. Available at: http://cnx.org/contents/14fb4ad7-39a1-4eee-ab6e-3ef2482e3e22@11.1