Blood CARDIOVASCULAR SYSTEM General Composition and Functions of Blood a Components of Blood b Functions of Blood 638

Transcription

1 CARDIOVASCULAR SYSTEM O U T L I N E 21.1 General Composition and Functions of Blood a Components of Blood b Functions of Blood Blood Plasma a Plasma Proteins b Differences Between Plasma and Interstitial Fluid Formed Elements in the Blood a Erythrocytes b Leukocytes c Platelets Hemopoiesis: Production of Formed Elements a Erythropoiesis b Thrombopoiesis c Leukopoiesis 653 Blood 21 MODULE 9: CARDIOVASCULAR SYSTEM

2 638 Chapter Twenty-One Blood W ithin our bodies is a connective tissue so valuable that donating a portion of it to someone else can save that person s life. This tissue regenerates itself continuously and is responsible for transporting the gases, nutrients, and hormones our bodies need for proper functioning. Losing too much of this tissue can kill us, and yet it is something we frequently take for granted. This valuable connective tissue is blood. Blood is considered a fluid connective tissue because it contains cells, a liquid ground substance (called plasma), and dissolved proteins. In this chapter, we describe the components of blood, its functions, and how the body produces the various types of blood components General Composition and Functions of Blood Learning Objectives: 1. List and describe the basic components of blood. 2. Explain how blood functions in transport, regulation, and protection. Blood is a type of fluid connective tissue (see chapter 4). Blood is about four times more viscous than water, meaning that it is thicker and more goopy. The temperature of blood is about 1 C higher than measured body temperature; thus, if your body temperature is 37 C, your blood temperature is about 38 C. 21.1a Components of Blood Whole blood can be separated into its liquid and cellular components by using a machine called a centrifuge, as shown in figure 21.1 and described here: 1. Blood to be sampled is withdrawn from a vein and collected in a glass tube, called a centrifuge tube. 2. The glass tube is placed into the centrifuge, which then spins it in a circular motion for several minutes. 3. The rotational movement separates the blood into liquid and cellular components based on weight, thus allowing these elements to be examined separately. Figure 21.2 shows the three components separated by centrifugation, from bottom to top in the test tube: Erythrocytes (e -rith ro -sı t; erythros = red, kytes = cell), sometimes called red blood cells, form the lower layer of the centrifuged blood. They typically average about 44% of a blood sample. A buffy coat makes up the middle layer. This thin, slightly gray-white layer is composed of cells called leukocytes (or white blood cells) and cell fragments called platelets. The buffy coat forms less than 1% of a blood sample. Plasma is a straw-colored liquid that lies above the buffy coat in the centrifuge tube; it generally makes up about 55% of blood. Collectively, the erythrocytes and the components of the buffy coat are called the formed elements. It is best not to refer to all of these structures as cells because platelets are merely fragments broken off from a larger cell. The formed elements, together with the liquid plasma, compose whole blood (the substance we most commonly refer to simply as blood ). 1 WHAT DO YOU THINK? If your body becomes dehydrated, does the plasma percentage in whole blood increase or decrease? 21.1b Functions of Blood Blood carries out a variety of important functions related to transportation, regulation, and protection. Transportation Blood transports numerous elements and compounds throughout the body. For example, erythrocytes and plasma carry oxygen from the lungs to body cells and then transport the carbon dioxide produced by the cells back to the lungs to diffuse from the body. Blood plasma transports nutrients that have been absorbed from the GI tract. Plasma also transports hormones secreted Centrifuge Plasma (55% of whole blood) Whole blood Buffy coat: leukocytes and platelets (<1% of whole blood) Erythrocytes (44% of whole blood) Formed elements 1 Withdraw blood into a syringe and place it into a glass centrifuge tube. 2 Place the tube into a centrifuge and 3 Components of blood separate during spin for about 10 minutes. centrifugation to reveal plasma, buffy coat, and erythrocytes. Figure 21.1 Whole Blood Separation. A sample of whole blood is used to determine the ratio of plasma to formed elements. The blood sample is drawn from a vein and placed into a glass tube. After centrifugation, the formed elements in the sample remain packed in the bottom of the centrifuge tube.

3 Chapter Twenty-One Blood 639 Plasma Buffy Coat Water 92% by weight Proteins 7% by weight Albumins 58% Globulins 37% Fibrinogen 4% Regulatory proteins <1% Other solutes 1% by weight Electrolytes Nutrients Respiratory gases Waste products Platelets 150, ,000 per cubic mm Leukocytes 4,500-11,000 per cubic mm Lymphocytes 20 40% Neutrophils 50 70% Erythrocytes Erythrocytes million per cubic mm Monocytes 2 8% Eosinophils 1 4% Basophils 0.5 1% Figure 21.2 Whole Blood Composition. Whole blood contains plasma (average = about 55%) and formed elements (average = about 45%). (The percentages presented in this figure are average numbers of cells, and the numbers for components of the buffy coat represent average ranges. A cubic millimeter of blood is equivalent to a microliter [μl] of blood.) by the endocrine glands. Finally, plasma carries some waste products from the cells to organs such as the kidneys, where these waste products are removed. Regulation Blood regulates many body functions including body temperature. Plasma absorbs and distributes heat throughout the body. If the body needs to be cooled, the blood vessels in the dermis dilate and dissipate the excess heat through the integument. Conversely, when the body needs to conserve heat, the dermal blood vessels constrict, and the warm blood is shunted to deeper blood vessels in the body (see chapter 5). Blood also helps regulate ph levels in the body s tissues. The term ph is a measure of how acidic or alkaline a fluid is. A neutral ph (neither acidic nor alkaline fluid, such as water) is measured at exactly 7, while acidic fluids (e.g., orange juice) are between 0 and 7, and alkaline fluids (e.g., milk) are between 7 and 14. Blood plasma contains compounds and ions that may be distributed to the fluid bathing cells within the tissues (interstitial fluid) to help maintain normal tissue ph. In addition, blood plasma ph is continuously regulated to try to maintain a value of 7.4, which is the ph level required for normal cellular functioning. If the blood ph falls below 7.4 to 7.0, the condition called acidosis results, and the central nervous system is depressed; coma and death could occur. If the blood ph rises above 7.4 to 7.8, alkalosis results, characterized by a hyperexcited nervous system and convulsions. Blood maintains normal fluid levels in the cardiovascular system and prevents fluid loss. A constant exchange of fluid takes place between the blood plasma and the interstitial fluid. If too much fluid is absorbed into the blood, high blood pressure results. If too much fluid escapes the bloodstream and enters the tissues, blood pressure drops to unhealthily low levels, and the tissues swell with excess fluid. To maintain a balance of fluid between the blood and the interstitial fluid, blood contains molecules (such as salts and some proteins) to prevent excess fluid loss from the plasma. Protection Leukocytes help guard against infection by mounting an immune response if a pathogen or an antigen (an ti-jen; anti = opposite, gen = producing) (a substance perceived as foreign to the body) is found. Antibodies (an te -bod-e ; body = main part), which are molecules that can bind to antigens until a leukocyte can completely kill or remove the antigen, are transported in plasma. In addition, platelets and blood proteins protect the body against blood loss by forming blood clots. 1 2 WHAT DID YOU LEARN? Erythrocytes make up what average percentage of whole blood? What are the protective functions of the blood? 21.2 Blood Plasma Learning Objective: 1. Outline the components of plasma. Blood plasma is a complex mixture of water, proteins, and other solutes (table 21.1). When the blood cells, platelets, and clotting proteins are removed from plasma, the remaining fluid is termed serum (ser um; whey).

4 640 Chapter Twenty-One Blood Table 21.1 Composition of Blood Plasma Plasma Component (Percentage of Plasma) WATER (~92% OF PLASMA) PLASMA PROTEINS (~7% OF PLASMA) Albumin (~58% of plasma proteins) Globulins (~37% of plasma proteins) Fibrinogen (~4% of plasma proteins) Regulatory proteins (<1% of plasma proteins) OTHER SOLUTES (~1% OF PLASMA) Electrolytes (e.g., sodium, potassium, calcium, chloride, iron, bicarbonate, and hydrogen) Nutrients (e.g., amino acids, glucose, cholesterol, vitamins, fatty acids) Respiratory gases Wastes (breakdown products of metabolism) (e.g., lactic acid, creatinine, urea, bilirubin, ammonia) Functions Acts as the solvent in which formed elements, solutes, and wastes are suspended Regulates water movement between the blood and interstitial fluid (and thus the viscosity of blood); transports some fatty acids and hormones Alpha-globulins transport lipids and some metal ions Beta-globulins transport iron ions and lipids in bloodstream Gamma-globulins are antibodies that immobilize pathogens (bacteria, viruses, etc.) Helps with blood clotting Consists of enzymes, proenzymes, and hormones Help establish and maintain membrane potentials, maintain ph balance, and regulate osmosis Energy source Oxygen and carbon dioxide Waste products are transported to the liver and kidneys where they can be removed from the blood Water is the most abundant compound in plasma, making up about 92% of plasma s total volume. Water facilitates the transport of materials in the plasma. The next most abundant compounds in plasma are the plasma proteins. 21.2a Plasma Proteins Plasma proteins make up about 7% of the plasma (see figure 21.2). Measured amounts of plasma proteins usually range between 6 and 8 grams of protein in a volume of 100 milliliters of blood (referred to as grams per deciliter [ g/dl]). The plasma proteins include albumins, globulins, fibrinogen, and regulatory proteins. Albumins (al-bu min; albumen = white of egg) are the smallest and most abundant of the plasma proteins, making up approximately 58% of total plasma proteins. They regulate water movement between the blood and interstitial fluid by providing some of the plasma solutes to drive osmosis. Secondarily, albumins act as transport proteins that carry ions, hormones, and some lipids in the blood. Globulins (glob u -lin; globules = globule) are the secondlargest group of plasma proteins, forming about 37% of all plasma proteins. The smaller alpha-globulins and the larger beta-globulins primarily bind, support, and protect certain water-insoluble or hydrophobic molecules, hormones, and ions. Gamma-globulins, also called immunoglobulins or antibodies, are soluble proteins produced by some of our defense cells to protect the body against pathogens that may cause disease. Fibrinogen (fi brin o -jen; fibra = fiber) makes up about 4% of all plasma proteins. Fibrinogen is responsible for blood clot formation. Following trauma to the walls of blood vessels, fibrinogen is converted into long, insoluble strands of fibrin, which helps form a blood clot. Regulatory proteins form a very minor class of plasma proteins (less than 1% of total plasma proteins) and include enzymes (proteins that accelerate chemical reactions), proenzymes (inactive precursors of enzymes), and hormones that are being transported to other parts of the body. 21.2b Differences Between Plasma and Interstitial Fluid Plasma is a type of extracellular fluid (ECF), meaning it is a body fluid found outside of (rather than within) cells. Plasma and interstitial fluid (the type of extracellular fluid that bathes the outside of cells) have similar concentrations of most dissolved products, nutrients, and electrolytes, with the exception of the aforementioned plasma proteins. The concentration of dissolved oxygen is higher in plasma than in interstitial fluid, because the cells take up and use the oxygen from the interstitial fluid during energy production. This difference in concentration ensures that oxygen will continue to diffuse from blood into the interstitial fluid. Similarly, the concentration of carbon dioxide is lower in blood than in interstitial fluid because cells produce carbon dioxide during energy production, and it diffuses out of the cells into the interstitial fluid. This difference in concentration ensures that carbon dioxide will readily diffuse from the interstitial fluid into the blood, where it will be carried to the lungs and leave the body. 3 4 WHAT DID YOU LEARN? What are the components of plasma? Identify the four classes of plasma proteins Formed Elements in the Blood Learning Objectives: 1. Identify the structural and functional characteristics of erythrocytes. 2. Outline the life cycle of erythrocytes. 3. Define the significance of the ABO and Rh blood groups. 4. Name the types of leukocytes and explain their functions. 5. Describe the structure of platelets and their role in blood clotting. The formed elements have three components: Erythrocytes make up more than 99% of formed elements. Their primary function is to transport respiratory gases in the blood. Leukocytes make up less than 0.01% of formed elements. All leukocytes contribute to mounting an immune response and defending the body against pathogens.

5 Chapter Twenty-One Blood 641 Table 21.2 Formed Element Characteristics of the Formed Elements Size (all measurements are for diameter) Erythrocytes 7.5 μm Transport oxygen and carbon dioxide Function Life Span Density (average number per mm 3 of blood = μl) ~120 days Females: ~4.8 million Males: ~5.4 million Leukocytes Platelets 1.5 to 3 times larger than an erythrocyte; μm Less than 1/4 the size of an erythrocyte; ~2 μm Prepare immune response, defend against antigens Varies from 12 hours (neutrophil) to years (lymphocyte) ,000 Participate in blood clotting ~8 10 days 150, ,000 Platelets make up less than 1% of formed elements and help with blood clotting. Table 21.2 summarizes the characteristics of the formed elements. The percentage of the volume of all formed elements in the blood is called the hematocrit (he mǎ-to -krit, hem ǎ-; hemato = blood, krino = to separate). This medical dictionary definition of the true hematocrit differs from the clinical definition, which equates the hematocrit to the percentage of erythrocytes. The difference between these two numbers is almost negligible, which is why the true hematocrit and the clinical hematocrit are virtually the same. Hematocrit values vary slightly and are dependent upon the age and sex of the individual. Adult males tend to have a hematocrit ranging between 42% and 56%, whereas females hematocrits range from 38% to 46%. Children s hematocrit ranges also vary among individuals and differ from adult values. In addition, altitude can affect the hematocrit. Let s say a person lives in a cabin high in the Rocky Mountains, where the air is thinner and there is less oxygen. Each time the person breathes at this altitude, she inhales relatively less oxygen than she would inhale at a lower altitude. The person s body compensates by making more erythrocytes; more erythrocytes in the blood can carry more oxygen to the tissues. This increase in erythrocytes results in an increased hematocrit. All of the components of the formed elements can be viewed by preparing a blood smear, as shown in figure 21.3 and described here: 1. A finger is pricked, and a small amount of blood is collected. 2. A blood drop is placed onto a glass slide. 3. A second slide spreads the drop of blood across the first slide, smearing a thin surface of blood along the slide (hence the name blood smear ). 4. The thin layer of blood is stained to provide contrast for viewing after the smear dries. After the stain dries, a glass coverslip is placed over the specimen to protect it. The prepared slide is then viewed using the light microscope. 21.3a Erythrocytes Although erythrocytes are commonly referred to as red blood cells, or RBCs, the term cell is a misnomer because mature erythrocytes lack nuclei and organelles. In other words, an erythrocyte is not like other cells in the body, so it is more appropriate to call it a formed element. Erythrocytes transport oxygen and carbon dioxide to and from the tissues and the lungs. Their structure enables them to carry these respiratory gases proficiently. A normal, mature Lymphocyte Erythrocytes Neutrophil Withdraw blood LM 640x Monocytes Platelet 1 Prick finger and collect Place a drop of blood a small amount of blood. on a slide. Figure 21.3 Preparing a Blood Smear. 2 3 Using a second slide, pull the 4 When viewed under the microscope, blood smear reveals the components of the formed elements. drop of blood across the slide surface, leaving a thin layer of blood on the slide. After the blood dries, apply a stain for contrast. Place a coverslip on top.

6 642 Chapter Twenty-One Blood Sectional view Superior view ~0.75 μm ~2.6 μm (a) ~7.5 μm Figure 21.4 Erythrocyte Structure. (a) An erythrocyte has the gross structure of a biconcave disc, as shown here in sectional and superior views. (b) SEM of erythrocytes shows their three-dimensional structure and a rouleaux. (b) Rouleaux Erythrocytes LM 250x CLINICAL VIEW Blood Doping To enhance their performance in endurance events, some athletes try to boost their bodies ability to deliver oxygen to the muscles by increasing the number of erythrocytes in their blood (and thus increasing their hematocrit levels). There are several ways to accomplish this result. The number of erythrocytes can be increased naturally by living and training at high altitude where the concentration of oxygen in the air is lower. The body compensates for the decreased oxygen concentration in the atmosphere by increasing the rate of erythrocyte production, thus increasing the number of erythrocytes per unit volume of blood. Athletes will often train at high altitudes to increase endurance for weeks or months before a competition. Other methods artificially increase erythrocyte counts and are banned from use in athletic competitions. Some athletes have taken agents that stimulate the hormone erythropoietin (EPO), or recombinant EPO which are used to treat people with low EPO concentrations to increase their erythrocyte counts. Blood doping is another method recently used by some athletes. In this procedure, the athlete donates erythrocytes to himself or herself. Prior to the athletic event, the individual has a unit of blood removed and stored, which stimulates erythrocyte production to replace the ones just removed. A few days before the competition, the erythrocytes from the donated unit are transfused back into the person s body. The increased number of erythrocytes increases the amount of oxygen transported in the blood, favorably affecting muscle performance, and thus athletic performance. However, by increasing the number of erythrocytes per measured volume of blood, blood doping increases the viscosity of the blood. Thus, the heart must work harder to pump this thicker more cellular blood. Eventually, temporary athletic success may be overshadowed by permanent cardiovascular damage that can even lead to death. Therefore, blood doping has now been banned from athletic competitions. erythrocyte is very small, with a diameter of approximately 7.5 micrometers (μm) (figure 21.4). Its unique, biconcave disc structure (at its narrowest point about 0.75 μm and at its widest point about 2.6 μm) allows respiratory gases to be loaded and unloaded rapidly and efficiently. Erythrocytes line up in single file, termed a rouleau (roo-lo ; pl. rouleaux; cylinder), as they pass through small blood vessels. The number of erythrocytes in the bloodstream normally ranges between 4.2 and 6.2 million per cubic millimeter of blood. Hemoglobin in Erythrocytes Every erythrocyte is filled with approximately 280 million molecules of a red-pigmented protein called hemoglobin (he -mo glo bin; haima = blood). Hemoglobin transports oxygen and carbon dioxide, and is responsible for the characteristic bright red color of arterial blood. When blood is maximally loaded with oxygen, it is termed oxygenated. Conversely, when some oxygen is lost and carbon dioxide is gained during respiratory gas exchange, blood is called deoxygenated. Deoxygenated blood has a deep red color that is perceived as blue when observed through the skin and the subcutaneous layer. Each hemoglobin molecule consists of four polypeptide chains called globins. Two of these globins are called alpha (α) chains, and the other two, which are slightly different, are called beta (β) chains (figure 21.5). These globin chains each contain a nonprotein (or heme) group that is in the shape of a ring, with an iron ion (Fe 2+ ) in its center. Oxygen binds to these iron ions for transport in the blood. Since each molecule of hemoglobin has four rings, each hemoglobin molecule has four iron ions and is capable of binding four molecules of oxygen. The oxygen binding is fairly weak to ensure rapid attachment and detachment of oxygen with hemoglobin. The result is that oxygen binds to the hemoglobin when the erythrocytes pass through the blood vessels of the lungs, and it leaves the hemoglobin when the erythrocytes pass through the blood vessels of the body tissues. This gas exchange occurs by diffusion as a result of the differences in concentration of oxygen between two areas. For example, oxygen is in higher concentration in the lungs compared to the blood, so oxygen diffuses

7 Chapter Twenty-One Blood 643 α 2 globin chain β 1 globin chain from the lungs into the blood. Conversely, oxygen is in higher concentration in the blood compared to the interstitial fluid around body cells, so oxygen diffuses from the blood to the interstitial fluid. Carbon dioxide and the globin molecule (not the iron ion) have a similar weak attachment relationship for the transport of carbon dioxide molecules. β 2 globin chain α 1 globin chain Heme (a ringed molecule with iron ion [Fe 2+ ] in the center) Figure 21.5 Molecular Structure of Hemoglobin. A single molecule of hemoglobin is composed of four protein subunits, called globins, each containing a heme group that holds a single iron ion in its center. Each hemoglobin molecule transports four oxygen molecules that are weakly attracted to the iron ions. Erythrocyte Life Cycle The absence of both a nucleus and cellular organelles comes at a cost to the erythrocyte by reducing its life span. A mature erythrocyte cannot synthesize proteins to repair itself or replace damaged membrane regions. Aging and the wear-and-tear of circulation through blood vessels cause erythrocytes to become more fragile and less flexible. Therefore, the erythrocyte has a finite life span of about 120 days (figure 21.6). Every day, just under 1% of the oldest circulating erythrocytes are removed from circulation. The old erythrocytes are phagocytized in the liver and spleen by cells called macrophages (to be discussed later in this chapter). Some erythrocyte components are stored in other organs for recycling, while other components are excreted from the body, as shown in steps 4 and 5 of figure 21.6 and explained here: The heme group (minus the iron ion) in hemoglobin is converted first into a green pigment called biliverdin (bili-ver din; bilis = bile). Biliverdin is eventually converted into a yellow-green pigment called bilirubin (bil-i-roo bin). Bilirubin is a component of a digestive secretion called bile, Figure 21.6 Recycling the Components of Aged or Damaged Erythrocytes. Erythrocytes have an average life span of about 120 days. Their molecular components are then broken down and recycled or eliminated from the body. 1 Erythrocytes form in red bone marrow. 5 Erythrocyte membrane proteins and globin proteins are broken down into amino acids, some of which are used to make new erythrocytes. 2 Erythrocytes circulate in bloodstream for 120 days. 4 Heme components of blood are recycled. Heme (minus iron) Fe 2 + Fe 2+ (iron ions) Heme is converted into biliverdin and then to bilirubin, which is secreted in bile from the liver. Fe 2 + Fe 2+ Iron is transported in the blood by the protein transferrin and stored by the protein ferritin in the liver. 3 Liver Spleen Aged erythrocytes are phagocytized in the liver and spleen.

8 644 Chapter Twenty-One Blood CLINICAL VIEW: In Depth Erythrocyte Volume Disorders The number of erythrocytes in a person s blood can vary from the normal range, leading to various clinical disorders. In general, these conditions are classified as either anemia or polycythemia. Anemia (a-nē mē -ǎ; an = without) is any condition in which the count of erythrocytes per cubic millimeter of blood is less than the normal range. Anemia occurs due to either inadequate production or decreased survival of erythrocytes. The blood contains fewer erythrocytes than normal, and as a result body tissues are unable to get enough oxygen, so the heart may have to work harder. Symptoms of anemia include lethargy, shortness of breath, pallor of the skin and mucous membranes, fatigue, and heart palpitations. The types of anemia include the following: Aplastic anemia is characterized by significantly decreased formation of erythrocytes and hemoglobin due to defective red bone marrow. The causes of defective red bone marrow vary, but may include poisons, toxins, or radiation. Congenital hemolytic anemia occurs when destruction of erythrocytes is more rapid than normal, usually due to a genetic defect. It is caused by the production of abnormal membrane proteins that make the erythrocyte plasma membrane very fragile. Erythroblastic anemia is characterized by the presence of large numbers of immature, nucleated cells (called erythroblasts and normoblasts) in the circulating blood. A reduced rate of hemoglobin synthesis causes these immature cells to be present. These cells cannot function normally and thus anemia results. Familial microcytic anemia is a rare type of inherited anemia associated with a defect in iron uptake and use. Hemorrhagic anemia results from immediate blood loss due to such factors as chronic ulcers or heavy menstrual flow. Macrocytic anemia occurs when the average size of circulating erythrocytes is too large. Deficiencies in both vitamin B 12 and folic acid uptake result in the production of enlarged erythrocytes. Pernicious anemia is a chronic progressive anemia in adults caused by the body s failure to absorb vitamin B 12. A defect in the production of intrinsic factor (a glycoprotein secreted by stomach lining cells to enhance B 12 absorption in the small intestine) leads to pernicious anemia. Sickle-cell disease is an autosomal recessive anemia that occurs when a person inherits two copies of the sickle-cell gene. Erythrocytes become sickle-shaped, making them unable to flow efficiently through the blood vessels to body tissues and more prone to destruction by rupture (a process called hemolysis). Most anemias are treated by letting the patient s own bone marrow replace the erythrocytes. However, anemia is often a symptom of another disease or problem. For example, while many anemias are due to iron deficiency, this deficiency can be a result of chronic blood loss, a process that depletes the body of its iron stores over months or years. The three most common causes of such chronic blood loss are excessive menstrual bleeding, undiagnosed stomach ulcer, and colon cancer. Imagine the magnitude of the mistake a physician could make by simply placing a patient on iron supplements when the underlying cause of the iron deficiency is an undiagnosed cancer of the colon! So, while restoring the patient s erythrocyte count, a physician should also look for any underlying cause of the anemia. Polycythemia (pol ē -sī-thē mē -ǎ; poly = many, kytos = cell) is the condition of having too many erythrocytes in the blood (otherwise known as an elevated hematocrit). The affected person has the same total blood volume, but many more erythrocytes than are healthy. The blood becomes thick and viscous, putting a tremendous strain on the heart. Following are some of the different types of polycythemia: Compensatory polycythemia results from chronic hypoxia (inadequate oxygen supply to the body). Smokers develop this condition when long-term exposure to tobacco smoke and chronically high levels of carbon monoxide damage their lungs. Relative polycythemia is an increase in the number of erythrocytes in the blood per unit volume as a result of a decrease in blood plasma. For example, suppose that a child is severely dehydrated due to a serious case of diarrhea. As the child progressively loses water, his blood becomes more concentrated. This type of polycythemia is a temporary condition, and the ratio of erythrocytes to water in the blood returns to normal when the child becomes rehydrated. Erythrocytosis is an increase in erythrocytes due to an increase in the level of EPO. Polycythemia vera is a chronic form characterized by an increase in blood volume and the number of erythrocytes. This condition results when erythrocyte growth in the red bone marrow is not regulated. Red blood cell precursors continue to grow and mature, irrespective of the presence or absence of erythropoietin. SEM 400x Sickle-shaped erythrocyte SEM of blood from a person with sickle-cell disease.

9 Chapter Twenty-One Blood 645 which is produced by liver cells. When bile enters the GI tract, it helps emulsify (break down) fats. The bilirubin in the GI tract is modified into other products that appear in urine from the kidneys and feces from the GI tract. The iron ion component in hemoglobin is removed and transported by a beta-globulin protein, called transferrin (trans-fer in; trans = across, ferrum = iron), to the liver where the iron ion is passed to another protein, called ferritin (fer i-tin) for storage. Ferritin is stored in the liver and will be transported to the red bone marrow, as needed, for erythrocyte production. Erythrocyte membrane proteins and globin proteins are broken down into free amino acids, some of which the body uses for protein synthesis to make new erythrocytes. Blood Types The plasma membrane of an erythrocyte has numerous molecules called surface antigens that project from the plasma membrane surface. The most commonly identified group of antigens is the ABO blood group. This group has two surface antigens, called A and B. The presence or absence of either the A and/or B surface antigen are the criteria that determine your ABO blood type, as shown in figure 21.7a and listed here: Blood with erythrocytes having surface antigen A is called type A blood. Blood with erythrocytes having surface antigen B is called type B blood. ABO Blood Types Antigen A Antigen B Antigens A and B Neither antigen A nor B Erythrocytes Anti-B antibodies Anti-A antibodies Neither anti-a nor anti-b antibodies Both anti-a and anti-b antibodies Plasma Blood type Type A Erythrocytes with type A surface antigens and plasma with anti-b antibodies Type B Erythrocytes with type B surface antigens and plasma with anti-a antibodies Type AB Erythrocytes with both type A and type B surface antigens, and plasma with neither anti-a nor anti-b antibodies Type O Erythrocytes with neither type A nor type B surface antigens, but plasma with both anti-a and anti-b antibodies (a) Rh Blood Types Antigen D No antigen D Erythrocytes No anti-d antibodies Anti-D antibodies (after prior exposure) Figure 21.7 ABO Blood Types. The blood type of an individual is determined by the specific antigens exposed on the surface of the erythrocyte membrane. Likewise, plasma contains antibodies that react with antigens from outside the body. (a) ABO blood types. (b) Rh blood types. Plasma Blood type Rh positive Rh negative Erythrocytes with Erythrocytes with no type D surface type D surface antigens and plasma antigens and plasma with no anti-d with anti-d antibodies, antibodies only if there has been prior exposure to Rh positive blood (b)

10 646 Chapter Twenty-One Blood Blood with erythrocytes having surface antigens A and B is called type AB blood. Blood with erythrocytes having neither surface antigen A nor B is called type O blood. The ABO surface antigens on erythrocytes are accompanied by specific antibodies that travel in the blood plasma. In general, an antibody is a protein that is produced by a white blood cell (specifically, a B-lymphocyte) and designed to recognize and immobilize a specific antigen it perceives as foreign to the body. The ABO blood group has both anti-a and anti-b antibodies that react with the surface antigen A and the surface antigen B, respectively. Your blood plasma does not have antibodies that recognize the surface antigens on your erythrocytes. Within the ABO blood group, the following blood types and antibodies are normally associated: Type A blood has anti-b antibodies in its blood plasma. Type B blood has anti-a antibodies in its blood plasma. Type AB blood has neither anti-a nor anti-b antibodies in its blood plasma. Type O blood has both anti-a and anti-b antibodies in its blood plasma. Blood types become clinically important when a patient needs a blood transfusion (see Clinical View: Transfusions ). If a person is transfused with blood of an incompatible type, antibodies in the plasma bind to surface antigens of the transfused erythrocytes, and clumps of erythrocytes bind together in a process termed agglutination (ǎ-gloo-ti-na shǔn; ad = to, gluten = glue). Clumped erythrocytes can block blood vessels and prevent the normal circulation of blood. Eventually, some or all of the clumped erythrocytes may rupture, a process called hemolysis (he -mol isis; lysis = destruction). The release of erythrocyte contents and fragments into the blood often causes further reactions and ultimately may damage organs. Therefore, compatibility between donor and recipient must be determined prior to blood donations and transfusions using an agglutination test (figure 21.8). 2 WHAT DO YOU THINK? Why is an individual with type O blood called a universal donor? Likewise, why is an individual with type AB blood called a universal recipient? Study Tip! To remember which ABO blood type is associated with which specific antibody, keep in mind that each blood type has an antibody of a different letter: Type A blood does not have anti-a antibodies (since anti-a antibodies and type A blood start with the same letter); it has only anti-b antibodies. Type B blood does not have anti-b antibodies. (It can t have anti-b antibodies, because the B antibodies and type B blood start with the same letter); it has only anti-a antibodies. Type AB blood has both A and B in its name, so it has no anti-a or anti-b antibodies. Type O blood has neither an A nor a B in its name, so it has both anti-a and anti-b antibodies. Another common surface antigen on erythrocyte membranes is part of the Rh blood type. The Rh blood type is determined by the presence or absence of the Rh surface antigen, often called either Rh factor or surface antigen D. When the Rh factor is present, the individual is said to be Rh positive (Rh + ). Conversely, an individual is termed Rh negative (Rh ) when the surface antigen is lacking from the membranes of his or her erythrocytes (see figure 21.7b). In contrast to the ABO blood group, where antibodies may be found in the blood even without prior exposure to a foreign antigen, antibodies to the Rh factor appear in the blood only when an Rh negative individual is exposed to Rh positive blood. Often this occurs as a result of an inappropriate blood transfusion. Therefore, individuals who are Rh positive never exhibit Rh antibodies, because they possess the Rh antigen on their erythrocytes. Only individuals who are Rh negative can exhibit Rh antibodies, and that can occur only after exposure to Rh antigens. The potential presence of Rh antibodies is especially important in pregnant women who are Rh negative and have an Rh positive fetus. An Rh incompatibility may result during pregnancy if the mother has been previously exposed to Rh positive blood (e.g., from a previous fetus with Rh positive blood). As a result of the prior exposure to Rh positive blood, the mother has Rh antibodies that may cross the placenta and destroy the fetal erythrocytes, resulting in severe illness or death of the fetus. Giving a pregnant woman special immunoglobulins (e.g., RhoGAM) prevents her from developing the Rh antibodies during pregnancy. The ABO and Rh blood types are usually reported together. For example, types AB and Rh + together are reported as AB +. However, remember that ABO and Rh blood types are independent of each other, and neither of them interacts with or influences the presence or activities of the other group. CLINICAL VIEW Transfusions Transfusion is the transfer of blood or blood components from a donor to a recipient. Whole blood is almost never transfused today. Rather, when you donate a unit of blood, it is almost immediately divided into its different components: erythrocytes, plasma, and platelets. The plasma can be further processed to extract clotting factors. Should leukocytes be needed, they must be collected in a special apparatus that effectively filters the leukocytes from the blood and then returns the blood to the donor. (A donor with healthy red bone marrow can quickly replace the donated leukocytes.) When a person needs one of these blood products, the physician administers only what is required, thus allowing a single donation of whole blood to serve several people. Donor blood must be collected under sterile conditions. It is mixed with an anticoagulant to prevent clotting, and immediately refrigerated. Then the donated unit is tested for a variety of infectious diseases, including hepatitis and AIDS, as well as for general liver disease. Finally, the blood is separated into its components, stored, and distributed.

11 Chapter Twenty-One Blood 647 Donor blood type + Recipient blood type = Agglutination reaction Antigen A + = Type A blood of donor (has surface antigen A) Type A blood of recipient (contains anti-b antibodies) Antigen and antibody do not match No agglutination No clumping seen. Successful blood type match. Antigen A + = Type A blood of donor (has surface antigen A) Type B blood of recipient (contains anti-a antibodies) Antigen and antibody match and connect Agglutination Clumping seen. Hemolysis occurs. Unsuccessful blood type match. (a) Agglutination test Type B recipient erythrocyte Blood from type A donor Anti-A antibody in recipient plasma Type A donor erythrocyte Agglutinated erythrocytes from type A donor block small vessels (b) Erythrocyte agglutination Figure 21.8 Agglutination Reaction. Antibodies in the blood plasma bind to their corresponding surface antigens on the erythrocyte plasma membranes, causing agglutination. (a) In a test between plasma and erythrocyte samples, a successful match (no clumping) is compared to an unsuccessful match (clumping). (b) If a person receives mismatched blood, erythrocytes agglutinate and block small blood vessels.

12 648 Chapter Twenty-One Blood WHAT DID YOU LEARN? Why does an erythrocyte lack cellular organelles, and how is this related to its life span? How do transferrin and ferritin participate in recycling erythrocyte components after the cells break down? Should a person with blood type AB donate blood to a person with blood type A? Why or why not? 21.3b Leukocytes Leukocytes help initiate an immune response and defend the body against pathogens. Leukocytes are true cells in that they contain a nucleus and cellular organelles. Leukocytes also differ from erythrocytes in that leukocytes are about 1.5 to 3 times larger in diameter and they do not contain hemoglobin. The number of leukocytes in the bloodstream normally ranges between 4500 and 11,000 per cubic millimeter of blood in adults. Infants normally have a higher number than children or adults. Abnormal numbers of leukocytes result from various pathologic conditions. For example, a reduced number of leukocytes causes a serious disorder called leukopenia (loo-ko -pe ne -ǎ; penia = poverty). This condition may result from viral or bacterial infection, certain types of leukemia, or toxins that damage the bone marrow. Conversely, leukocytosis (loo ko -sı -to sis) results from an elevated leukocyte count (greater than 11,000 per cubic millimeter of blood) and is often indicative of infection, inflammatory reaction, or extreme physiologic stress. Leukocytes are motile and remarkably flexible. In fact, most leukocytes are found in body tissues (as opposed to the bloodstream). Leukocytes enter the tissue by a process called diapedesis (dı ǎ-pě-de sis; dia = through, pedesis = a leaping), whereby they leave the vessel by squeezing between the endothelial cells of the blood vessel wall. Chemotaxis (ke -mo -tak sis; taxis = orderly arrangement) is a process whereby leukocytes are attracted to the site of infection by molecules released by damaged cells, dead cells, or invading pathogens. The five types of leukocytes are divided into two distinguishable classes granulocytes and agranulocytes based upon the presence or absence of visible organelles termed granules (table 21.3). When a normal blood smear is observed under the microscope, erythrocytes outnumber leukocytes by 500- to 1000-fold. Granulocytes Granulocytes (gran u -lo -sı t; granulum = small grain) have granules in their cytoplasm that are clearly visible when viewed with a microscope. When a blood smear is stained to provide contrast, three types of granulocytes can be distinguished: neutrophils, eosinophils, and basophils. Neutrophils The most numerous leukocyte in the blood is the neutrophil (noo tro -fil; neuter = neither), constituting about 50 70% of the total number of leukocytes. The neutrophil is named for its neutral or pale-colored granules within a light lilac cytoplasm. They are about 1.5 times larger in diameter than an erythrocyte and exhibit a multilobed nucleus with as many as five lobes interconnected by thin strands. Because of the various shapes of their nuclei, neutrophils also may be called polymorphonuclear (PMN) leukocytes. Neutrophils usually remain in circulation for about 10 to 12 hours before they exit the blood vessels and enter the tissue spaces, where they phagocytize infectious pathogens, especially bacteria. Specifically, neutrophils target and kill bacteria by secreting lysozyme, an enzyme that helps destroy components of bacterial cell walls. The number of neutrophils in a person s blood rises dramatically during a bacterial infection as more neutrophils are produced to target the bacteria. Eosinophils Eosinophils (e -o -sin o -fil; eos = dawn) have reddish or pink-orange granules in their cytoplasm. Typically, eosinophils constitute about 1 4% of the total number of leukocytes. Their nucleus is bilobed, with the two lobes connected by a thin strand. An eosinophil is about 1.5 times larger in diameter than an erythrocyte. Eosinophils increase in number when they encounter and react to or phagocytize antigen-antibody complexes or allergens (antigens that initiate a hypersensitive or allergic reaction). If the body is infected by parasitic worms, the eosinophils release chemical mediators that attack the worms. Basophils Basophils (ba so -fil; basis = base) are usually about 1.5 times larger in diameter than erythrocytes. They are the least numerous of the granulocytes, constituting about 0.5 1% of the total number of leukocytes. For this reason, it is sometimes difficult to find a basophil on a blood smear. Basophils exhibit a bilobed nucleus and abundant blue-violet granules in the cytoplasm that often obscure the nucleus. Basophils are similar to neutrophils and eosinophils in that they may exit the circulation and migrate through interstitial spaces. The primary components of basophil granules are histamine and heparin, which are released during anti-inflammatory or allergic reactions. When histamine is released from these granules, it causes an increase in the diameter of blood vessels (vasodilation), resulting in a decrease in blood pressure along with classic allergic symptoms such as swollen nasal membranes, itchy and runny nose, and watery eyes. The release of heparin from basophils inhibits blood clotting ( anticoagulation). 3 WHAT DO YOU THINK? Which type of granulocyte may increase in number if you develop strep throat (infection of the throat by Streptococcus bacteria)? Agranulocytes Agranulocytes (ǎ-gran u -lo -sı t) are leukocytes that have such small granules in their cytoplasm that they are frequently overlooked hence the name agranulocyte (a = without). Agranulocytes include both lymphocytes and monocytes. Lymphocytes As their name implies, most lymphocytes (lim fo sı t) reside in lymphatic organs and structures. Typically, lymphocytes constitute about 20 40% of the total number of leukocytes. Their dark-staining nucleus is usually rounded or slightly indented, and smaller lymphocytes exhibit only a thin rim of blue-gray cytoplasm around the nucleus. When activated, lymphocytes grow larger and have proportionally more cytoplasm. Thus, some of the smaller, nonactivated lymphocytes may have a diameter less than that of an erythrocyte, while activated lymphocytes may be two times the diameter of an erythrocyte. There are three categories of lymphocytes. T-lymphocytes (T-cells) manage and direct an immune response; some directly

13 Chapter Twenty-One Blood 649 Table 21.3 Leukocytes LM 1600x Eosinophil LM 1600x LM 1600x Neutrophil Basophil Granulocytes Agranulocytes LM 1600x LM 1600x Lymphocyte Monocyte Type Characteristics Functions Approximate % GRANULOCYTES Neutrophils Eosinophils Basophils AGRANULOCYTES Lymphocytes Nucleus is multilobed (as many as five lobes) Cytoplasm contains neutral or pale, distinct granules (when stained) Nucleus is bilobed Cytoplasm contains reddish or pink-orange granules (when stained) Nucleus is bilobed Cytoplasm contains deep blue-violet granules (when stained) Round or slightly indented nucleus (fills the cell in smaller lymphocytes) Nucleus is usually darkly stained Thin rim of cytoplasm surrounds nucleus Phagocytize pathogens, especially bacteria Release enzymes that target pathogens Phagocytize antigen-antibody complexes and allergens Release chemical mediators to destroy parasitic worms Release histamine (vasodilator) and heparin (anticoagulant) during inflammatory or allergic reactions Attack pathogens and abnormal/infected cells Coordinate immune cell activity Produce antibodies 50 70% of total leukocytes 1 4% of total leukocytes 0.5 1% of total leukocytes 20 40% of total leukocytes Monocytes Kidney-shaped or C-shaped nucleus Nucleus is generally pale staining Abundant cytoplasm around nucleus Can exit blood vessels and become macrophages Phagocytize pathogens, cellular debris, dead cells 2 8% of total leukocytes attack foreign cells and virus-infected cells. B-lymphocytes (B-cells) are stimulated to become plasma cells and produce antibodies. Natural killer cells (NK cells) attack abnormal and infected tissue cells. Lymphocytes are examined in detail in chapter 24. Monocytes A monocyte (mon o -sı t; monos = single) can be up to three times the diameter of an erythrocyte. Monocytes usually constitute about 2 8% of all leukocytes. The pale-staining nucleus of a monocyte is kidney-shaped or C-shaped. After approximately

14 650 Chapter Twenty-One Blood Red bone marrow Megakaryocyte Megakaryocytes Blood flow through vessel (a) LM 1600x (b) Endothelial cells Proplatelets Platelets Figure 21.9 Origin of Platelets. Platelets are derived from megakaryocytes in the red bone marrow. (a) Photomicrograph of megakaryocytes in red bone marrow. (b) Megakaryocytes extend long processes (called proplatelets) through the blood vessel wall. These proplatelets are spliced by the force of the blood flow into platelets. 3 days in circulation, monocytes exit blood vessels and take up residence in the tissues, where they change into large phagocytic cells called macrophages (mak ro -fa j; macros = large, phago = to eat). Macrophages phagocytize bacteria, cell fragments, dead cells, and debris. 21.3c Platelets Platelets (pla t let; platys = flat) are irregular, membrane-enclosed cellular fragments that are about 2 micrometers in diameter (less than one-fourth the size of an erythrocyte). In stained preparations, they exhibit a dark central region. Platelets are sometimes called thrombocytes (throm bo -sı t; thrombos = clot), although that name is inappropriate because they are cell fragments that never had a nucleus, whereas the suffix -cyte implies a complete, nucleated cell. Platelets are continually produced in the red bone marrow by cells called megakaryocytes (meg-ǎ-kar e -o -sı t; megas = big) (figure 21.9). Megakaryocytes are easily distinguished both by their large size (about 100 micrometers in diameter) and their dense, multilobed nucleus. Megakaryocytes extend long processes (called proplatelets) through the blood vessel wall. These proplatelets are spliced by the force of the blood flow into platelets. Normally, the concentration of platelets in an adult ranges from 150,000 to about 400,000 per cubic millimeter of blood. Severe trauma to a blood vessel causes the blood to coagulate, or clot. A complex process involving components in the plasma produces a web of fibrin that traps erythrocytes and platelets to halt blood flow (figure 21.10). If not used to form clots or small platelet plugs to stop small vessel leaks, platelets circulate in the blood for 8 to 10 days. Thereafter, they are broken down, and their contents are recycled. An abnormally small number of platelets in circulating blood is termed thrombocytopenia WHAT DID YOU LEARN? What is meant when a patient is said to have leukopenia? What function do basophils carry out? What are megakaryocytes, and what is their function? Study Tip! The mnemonic Never let monkeys eat bananas is a simple way to recall the leukocytes in order of their relative abundance: Never = Neutrophil (most abundant) Let = Lymphocyte Monkeys = Monocyte Eat = Eosinophil Bananas = Basophil (least abundant) SEM 4100x Fibrin Platelets Erythrocytes Figure Blood Clot. Severe trauma to a blood vessel causes the blood to coagulate, or clot. In a complex process, components in the plasma produce a web of fibrin that traps erythrocytes and platelets and halts blood flow. This SEM shows erythrocytes, fibrin, and platelets within a forming clot.

15 Chapter Twenty-One Blood Hemopoiesis: Production of Formed Elements Learning Objectives: 1. Define and outline the process of hemopoiesis. 2. Explain the origin and maturation of each type of formed element. Because formed elements have a relatively short life span, new ones are continually produced by the process of hemopoiesis (he mo -poy-e sis; poiesis = a making), also called hematopoiesis. Hemopoiesis occurs in red bone marrow ( see chapter 6). The process starts with hemopoietic stem cells called hemocytoblasts (he -mo sı to -blast) (figure 21.11). Hemocytoblasts are considered pluripotent cells, meaning that they can differentiate and develop into many different kinds of cells. Hemocytoblasts produce two lines for blood cell development: the myeloid (mı ě-loyd; myelos = marrow) line forms erythrocytes, megakaryocytes, and all leukocytes except lymphocytes; the lymphoid (lim foyd) line forms lymphocytes. A number of hormones and growth factors influence the maturation and division of the blood stem cells. Review figure as you read this section to see where each growth factor acts. These so-called colony-stimulating factors (CSFs), or colonyforming units (CFUs), include the following: Multi-CSF is a growth factor that increases the formation of erythrocytes, as well as all classes of granulocytes, monocytes, and platelets from myeloid stem cells. GM-CSF is a growth factor that accelerates the formation of all granulocytes and monocytes from their progenitor cells. G-CSF is a growth factor that stimulates the formation of granulocytes from myeloblast cells. M-CSF is a growth factor that stimulates the production of monocytes from monoblasts. Thrombopoietin is a growth factor that stimulates both the production of megakaryocytes in the bone marrow and the subsequent formation of platelets. Erythropoietin (EPO) is a hormone produced by the kidneys to increase the rate of production and maturation of erythrocyte progenitor and erythroblast cells. CLINICAL VIEW Leukemia Leukemia (loo-kē mē -ǎ) is a malignancy (cancer) in the leukocyteforming cells. There are several varieties of leukemia, but all are marked by abnormal development and proliferation of leukocytes, in both the bone marrow and in the circulating blood. Leukemias are classified based on their duration as either acute or chronic. Acute leukemia progresses rapidly, and death occurs within a few months after the onset of symptoms (severe anemia, hemorrhages, and recurrent infections). Acute leukemia tends to occur in children and young adults. Chronic leukemia progresses more slowly; survival typically exceeds 1 year from the onset of symptoms, which include anemia and a tendency to bleed. Chronic leukemia usually occurs in middle-aged and older individuals. Leukemia can also be classified based on the type of cell that has become malignant. Granulocytic leukemia is characterized by uncontrolled proliferation of immature cells in the myeloid stem cell lines, as well as by the presence of large numbers of immature granulocytes in the circulating blood. Lymphocytic leukemia is characterized by increased numbers of malignant lymphocytes and/or lymphocytic precursors (lymphoblasts) in the bone marrow and circulating blood. This type of leukemia often involves lymph nodes and the spleen. Monocytic leukemia is a rare form characterized by an increased number of malignant and immature monocytic cells in the bone marrow and circulating blood. Leukemias represent a malignant transformation of a leukocyte cell line. As abnormal leukocytes increase in number, the erythrocyte and megakaryocytic lines virtually always decrease in number because the proliferating malignant cells literally squeeze them out. This decrease in erythrocyte and platelet production results in the anemia and bleeding that are often the first signs of leukemia. Fortunately, great strides have been made in treating some leukemias over the past two decades, especially acute childhood leukemia. Childhood leukemia, once an unquestioned death sentence, stands a good chance of being completely cured today due to improved bone marrow transplant technology in recent years. Lymphoblasts (immature lymphocytes) LM 1000x LM 500x (a) Normal bone marrow sample (b) Bone marrow sample in ALL (acute lymphoblastic leukemia)

16 652 Chapter Twenty-One Blood Hemocytoblast (blood stem cell) Myeloid line Lymphoid line Myeloid stem cell Lymphoid stem cell Multi-CSF Multi-CSF Multi-CSF Erythropoiesis Thrombopoiesis Leukopoiesis Progenitor cell Progenitor cell GM-CSF B-lymphoblast T-lymphoblast Progenitor cell Proerythroblast Megakaryoblast Myeloblast M-CSF Monoblast EPO Early erythroblast Thrombopoietin Promegakaryocyte G-CSF Promyelocytes Late erythroblast M-CSF Promonocyte Thrombopoietin Normoblast Megakaryocyte Eosinophilic myelocyte Basophilic myelocyte Neutrophilic myelocyte Nucleus ejected Reticulocyte Erythrocyte Thrombopoietin Eosinophil Basophil Neutrophil Monocyte B-lymphocyte T-lymphocyte Platelets Figure Origin, Differentiation, and Maturation of Formed Elements. All formed elements are derived from common hemopoietic stem cells called hemocytoblasts. Both myeloid stem cells and lymphoid stem cells are derived from hemocytoblasts. Myeloid stem cells give rise to erythrocytes, platelets, and to all leukocytes except lymphocytes. Lymphoid stem cells give rise to B- and T-lymphocytes and NK cells (not shown).