CARDIOVASCULAR SYSTEM

OUTLINE

21.1 General Composition and Functions of 638 21.1a Components of Blood 638 21.1b Functions of Blood 638 21 21.2 639 21.2a Plasma Proteins 640 21.2b Differences Between Plasma and Interstitial Fluid 640 21.3 Formed Elements in the Blood 640 Blood 21.3a Erythrocytes 641 21.3b Leukocytes 648 21.3c 650 21.4 Hemopoiesis: Production of Formed Elements 651 21.4a 653 21.4b Thrombopoiesis 653 21.4c 653

MODULE 9: CARDIOVASCULAR SYSTEM

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ithin our bodies is a connective tissue so valuable that donat- Figure 21.2 shows the three components separated by W ing a portion of it to someone else can save that person’s centrifugation, from bottom to top in the test tube: life. This tissue regenerates itself continuously and is responsible for ■ Erythrocytes (ě-rith′rō -sı̄ t; erythros = red, kytes = cell), transporting the gases, nutrients, and hormones our bodies need for sometimes called red blood cells, form the lower layer of the proper functioning. Losing too much of this tissue can kill us, and centrifuged blood. They typically average about 44% of a yet it is something we frequently take for granted. blood sample. This valuable connective tissue is blood. Blood is considered ■ A buffy coat makes up the middle layer. This thin, a fluid connective tissue because it contains cells, a liquid ground slightly gray-white layer is composed of cells called substance (called plasma), and dissolved proteins. In this chapter, leukocytes (or white blood cells) and cell fragments we describe the components of blood, its functions, and how the called platelets. The buffy coat forms less than 1% of a body produces the various types of blood components. blood sample. ■ Plasma is a straw-colored liquid that lies above the buffy coat in the centrifuge tube; it generally makes up about 21.1 General Composition 55% of blood. and Functions of Blood Collectively, the erythrocytes and the components of the Learning Objectives: buffy coat are called the formed elements. It is best not to refer to 1. List and describe the basic components of blood. all of these structures as “cells” because platelets are merely frag- 2. Explain how blood functions in transport, regulation, and ments broken off from a larger cell. The formed elements, together protection. with the liquid plasma, compose whole blood (the substance we most commonly refer to simply as “blood”). Blood is a type of fluid connective tissue (see chapter 4). Blood is about four times more viscous than water, meaning that WHAT DO YOU THINK? it is thicker and more “goopy.” The temperature of blood is about 1°C higher than measured body temperature; thus, if your body ●1 If your body becomes dehydrated, does the plasma percentage in temperature is 37°C, your blood temperature is about 38°C. whole blood increase or decrease?

21.1a Components of Blood 21.1b Functions of Blood Whole blood can be separated into its liquid and cellular components Blood carries out a variety of important functions related to trans- by using a machine called a centrifuge, as shown in figure 21.1 and portation, regulation, and protection. described here: 1. Blood to be sampled is withdrawn from a vein and collected Transportation in a glass tube, called a centrifuge tube. Blood transports numerous elements and compounds throughout 2. The glass tube is placed into the centrifuge, which then spins the body. For example, erythrocytes and plasma carry oxygen it in a circular motion for several minutes. from the lungs to body cells and then transport the carbon diox- 3. The rotational movement separates the blood into liquid ide produced by the cells back to the lungs to diffuse from the and cellular components based on weight, thus allowing body. Blood plasma transports nutrients that have been absorbed these elements to be examined separately. from the GI tract. Plasma also transports hormones secreted

Centrifuge

Plasma (55% of whole blood)

Buffy coat: leukocytes and platelets (<1% of whole blood)

Erythrocytes Formed Whole (44% of whole blood) elements blood

1 Withdraw blood into a syringe and 2 Place the tube into a centrifuge and 3 Components of blood separate during place it into a glass centrifuge tube. 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.

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Plasma Buffy Coat

Water Proteins Other solutes Platelets Leukocytes 92% by weight 7% by weight 1% by weight 150,000-400,000 4,500-11,000 per cubic mm per cubic mm Albumins 58% Electrolytes Globulins 37% Nutrients Fibrinogen 4% Respiratory gases Lymphocytes Regulatory Waste products 20–40% proteins <1%

Neutrophils 50–70%

Erythrocytes 2–8% Erythrocytes 4.2–6.2 million per cubic mm

Eosinophils 1–4% 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 blood pressure drops to unhealthily low levels, and the tissues products from the cells to organs such as the kidneys, where swell with excess fluid. To maintain a balance of fluid between these waste products are removed. the blood and the interstitial fluid, blood contains molecules (such as salts and some proteins) to prevent excess fluid loss from the Regulation plasma. Blood regulates many body functions including body temperature. Plasma absorbs and distributes heat throughout the body. If the Protection body needs to be cooled, the blood vessels in the dermis dilate and Leukocytes help guard against infection by mounting an immune dissipate the excess heat through the integument. Conversely, when response if a pathogen or an antigen (an′ti-jen; anti = opposite, the body needs to conserve heat, the dermal blood vessels constrict, gen = producing) (a substance perceived as foreign to the body) is and the warm blood is shunted to deeper blood vessels in the body found. Antibodies (an′tē -bod-ē ; body = main part), which are mol- (see chapter 5) . ecules that can bind to antigens until a leukocyte can completely Blood also helps regulate pH levels in the body’s tissues. The kill or remove the antigen, are transported in plasma. In addition, term pH is a measure of how acidic or alkaline a fluid is. A neutral platelets and blood proteins protect the body against blood loss by pH (neither acidic nor alkaline fluid, such as water) is measured forming blood clots. 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 WHATW DID YOU LEARN? plasma contains compounds and ions that may be distributed to ●1 Erythrocytes make up what average percentage of whole blood? the fluid bathing cells within the tissues (interstitial fluid) to help maintain normal tissue pH. In addition, blood plasma pH is con- ●2 What are the protective functions of the blood? tinuously 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. 21.2 Blood Plasma If the blood pH rises above 7.4 to 7.8, alkalosis results, character- Learning Objective: ized by a hyperexcited nervous system and convulsions. 1. Outline the components of plasma. Blood maintains normal fluid levels in the cardiovascular system and prevents fluid loss. A constant exchange of fluid takes Blood plasma is a complex mixture of water, proteins, and place between the blood plasma and the interstitial fluid. If too other solutes (table 21.1). When the blood cells, platelets, and much fluid is absorbed into the blood, high blood pressure results. clotting proteins are removed from plasma, the remaining fluid is If too much fluid escapes the bloodstream and enters the tissues, termed serum (ser′um; whey).

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Table 21.1 Composition of Blood Plasma Plasma Component (Percentage of Plasma) Functions WATER (~92% OF PLASMA) Acts as the solvent in which formed elements, solutes, and wastes are suspended PLASMA PROTEINS (~7% OF PLASMA) Albumin (~58% of plasma proteins) Regulates water movement between the blood and interstitial fl uid (and thus the viscosity of blood); transports some fatty acids and hormones Globulins (~37% of plasma proteins) 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.) Fibrinogen (~4% of plasma proteins) Helps with blood clotting Regulatory proteins (<1% of plasma proteins) Consists of enzymes, proenzymes, and hormones OTHER SOLUTES (~1% OF PLASMA) Electrolytes (e.g., sodium, potassium, calcium, chloride, iron, Help establish and maintain membrane potentials, maintain pH balance, and bicarbonate, and hydrogen) regulate osmosis Nutrients (e.g., amino acids, glucose, cholesterol, vitamins, fatty acids) Energy source Respiratory gases Oxygen and carbon dioxide Wastes (breakdown products of metabolism) (e.g., lactic acid, Waste products are transported to the liver and kidneys where they can be removed creatinine, urea, bilirubin, ammonia) from the blood

Water is the most abundant compound in plasma, making up interstitial fluid (the type of extracellular fluid that bathes the about 92% of plasma’s total volume. Water facilitates the transport outside of cells) have similar concentrations of most dissolved of materials in the plasma. The next most abundant compounds in products, nutrients, and electrolytes, with the exception of the plasma are the plasma proteins. aforementioned plasma proteins. The concentration of dissolved oxygen is higher in plasma than in interstitial fluid, because the 21.2a Plasma Proteins cells take up and use the oxygen from the interstitial fluid during Plasma proteins make up about 7% of the plasma (see figure 21.2). energy production. This difference in concentration ensures that Measured amounts of plasma proteins usually range between oxygen will continue to diffuse from blood into the interstitial 6 and 8 grams of protein in a volume of 100 milliliters of blood fluid. Similarly, the concentration of carbon dioxide is lower in (referred to as grams per deciliter [g/dL]). The plasma proteins blood than in interstitial fluid because cells produce carbon diox- include albumins, globulins, fibrinogen, and regulatory proteins. ide during energy production, and it diffuses out of the cells into Albumins (al-bū′ min; albumen = white of egg) are the smallest the interstitial fluid. This difference in concentration ensures that and most abundant of the plasma proteins, making up approximately carbon dioxide will readily diffuse from the interstitial fluid into 58% of total plasma proteins. They regulate water movement between the blood, where it will be carried to the lungs and leave the body. the blood and interstitial fluid by providing some of the plasma solutes to drive osmosis. Secondarily, albumins act as transport proteins that WHATW DID YOU LEARN? carry ions, hormones, and some lipids in the blood. ●3 What are the components of plasma? Globulins (glob′ū -lin; globules = globule) are the second- largest group of plasma proteins, forming about 37% of all plasma ●4 Identify the four classes of plasma proteins. 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, 21.3 Formed Elements in the Blood also called immunoglobulins or antibodies, are soluble proteins produced by some of our defense cells to protect the body against Learning Objectives: pathogens that may cause disease. 1. Identify the structural and functional characteristics of Fibrinogen (fi′brin′ō -jen; fibra = fiber) makes up about 4% of erythrocytes. all plasma proteins. Fibrinogen is responsible for blood clot formation. 2. Outline the life cycle of erythrocytes. Following trauma to the walls of blood vessels, fibrinogen is converted 3. Define the significance of the ABO and Rh blood groups. into long, insoluble strands of fibrin, which helps form a blood clot. 4. Name the types of leukocytes and explain their functions. Regulatory proteins form a very minor class of plasma pro- 5. Describe the structure of platelets and their role in blood teins (less than 1% of total plasma proteins) and include enzymes clotting. (proteins that accelerate chemical reactions), proenzymes (inactive precursors of enzymes), and hormones that are being transported The formed elements have three components: to other parts of the body. ■ Erythrocytes make up more than 99% of formed elements. Their primary function is to transport respiratory gases in 21.2b Differences Between Plasma the blood. and Interstitial Fluid ■ Leukocytes make up less than 0.01% of formed elements. Plasma is a type of extracellular fluid (ECF), meaning it is a body All leukocytes contribute to mounting an immune response fluid found outside of (rather than within) cells. Plasma and and defending the body against pathogens.

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Table 21.2 Characteristics of the Formed Elements Formed Element Size (all measurements Function Life Span Density (average number are for diameter) per mm3 of blood = μL) Erythrocytes 7.5 μm Transport oxygen and carbon ~120 days Females: ~4.8 million dioxide Males: ~5.4 million

Leukocytes 1.5 to 3 times larger than an Prepare immune response, Varies from 12 hours 4500–11,000 erythrocyte; 11.25–22.5 μm defend against antigens () to years (lymphocyte) Platelets Less than 1/4 the size of an Participate in blood clotting ~8–10 days 150,000–400,000 erythrocyte; ~2 μm

■ Platelets make up less than 1% of formed elements and help viewed by preparing a blood smear, as shown in figure 21.3 and with blood clotting. described here:

Table 21.2 summarizes the characteristics of the formed 1. A finger is pricked, and a small amount of blood is elements. collected. The percentage of the volume of all formed elements in the 2. A blood drop is placed onto a glass slide. blood is called the hematocrit (hē′ maˇ-tō -krit, hem′aˇ-; hemato = 3. A second slide spreads the drop of blood across the first blood, krino = to separate). This medical dictionary definition slide, smearing a thin surface of blood along the slide (hence of the true hematocrit differs from the clinical definition, which the name “blood smear”). equates the hematocrit to the percentage of erythrocytes. The dif- 4. The thin layer of blood is stained to provide contrast ference between these two numbers is almost negligible, which for viewing after the smear dries. After the stain dries, is why the true hematocrit and the clinical hematocrit are virtu- a glass coverslip is placed over the specimen to protect ally the same. Hematocrit values vary slightly and are dependent it. The prepared slide is then viewed using the light upon the age and sex of the individual. Adult males tend to have microscope. 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 addi- 21.3a Erythrocytes tion, altitude can affect the hematocrit. Let’s say a person lives in Although erythrocytes are commonly referred to as red blood cells, a cabin high in the Rocky Mountains, where the air is thinner and or RBCs, the term “cell” is a misnomer because mature erythrocytes there is less oxygen. Each time the person breathes at this altitude, lack nuclei and organelles. In other words, an erythrocyte is not she inhales relatively less oxygen than she would inhale at a lower like other cells in the body, so it is more appropriate to call it a altitude. The person’s body compensates by making more eryth- formed element. rocytes; more erythrocytes in the blood can carry more oxygen to Erythrocytes transport oxygen and carbon dioxide to and the tissues. This increase in erythrocytes results in an increased from the tissues and the lungs. Their structure enables them hematocrit. All of the components of the formed elements can be to carry these respiratory gases proficiently. A normal, mature

Lymphocyte Erythrocytes Neutrophil

Withdraw blood

LM 640x

Monocytes

1 Prick finger and collect 2 Place a drop of blood 3 Using a second slide, pull the 4 When viewed under the microscope, a small amount of blood. on a slide. drop of blood across the slide blood smear reveals the components surface, leaving a thin layer of of the formed elements. blood on the slide. After the blood dries, apply a stain for contrast. Place a coverslip on top. Figure 21.3 Preparing a Blood Smear.

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Sectional view Superior view

~0.75 μm ~2.6 μm ~7.5 μm (a)

Figure 21.4 Erythrocyte Structure. (a) An erythrocyte has the gross structure LM 250x of a biconcave disc, as shown here in sectional and superior views. ( b) SEM of erythrocytes shows their three-dimensional structure and Rouleaux Erythrocytes a rouleaux. (b)

CLINICAL VIEW erythrocyte is very small, with a diameter of approximately 7.5 micrometers (μm) (figure 21.4). Its unique, biconcave disc Blood Doping 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 To enhance their performance in endurance events, some ath- unloaded rapidly and efficiently. Erythrocytes line up in single letes try to boost their bodies’ ability to deliver oxygen to the file, termed a rouleau (roo-lō′ ; pl. rouleaux; cylinder), as they muscles by increasing the number of erythrocytes in their blood pass through small blood vessels. The number of erythrocytes in (and thus increasing their hematocrit levels). There are several the bloodstream normally ranges between 4.2 and 6.2 million per ways to accomplish this result. The number of erythrocytes can cubic millimeter of blood. be increased naturally by living and training at high altitude where the concentration of oxygen in the air is lower. The body Hemoglobin in Erythrocytes compensates for the decreased oxygen concentration in the Every erythrocyte is filled with approximately 280 million mol- atmosphere by increasing the rate of erythrocyte production, thus ecules of a red-pigmented protein called hemoglobin (hē -mō - increasing the number of erythrocytes per unit volume of blood. glō′ bin; haima = blood). Hemoglobin transports oxygen and carbon Athletes will often train at high altitudes to increase endurance dioxide, and is responsible for the characteristic bright red color of for weeks or months before a competition. arterial blood. When blood is maximally loaded with oxygen, it is termed oxygenated. Conversely, when some oxygen is lost and Other methods artificially increase erythrocyte counts and are carbon dioxide is gained during respiratory gas exchange, blood banned from use in athletic competitions. Some athletes have is called deoxygenated. Deoxygenated blood has a deep red color taken agents that stimulate the hormone erythropoietin (EPO), that is perceived as blue when observed through the skin and the or recombinant EPO—which are used to treat people with low subcutaneous layer. EPO concentrations to increase their erythrocyte counts. Blood Each hemoglobin molecule consists of four polypeptide doping is another method recently used by some athletes. In this chains called globins. Two of these globins are called alpha (α) procedure, the athlete donates erythrocytes to himself or herself. Prior chains, and the other two, which are slightly different, are called to the athletic event, the individual has a unit of blood removed and beta (β) chains (figure 21.5). These globin chains each contain stored, which stimulates erythrocyte production to replace the ones a nonprotein (or heme) group that is in the shape of a ring, with just removed. A few days before the competition, the erythrocytes an iron ion (Fe2+) in its center. Oxygen binds to these iron ions for from the donated unit are transfused back into the person’s body. The transport in the blood. Since each molecule of hemoglobin has four increased number of erythrocytes increases the amount of oxygen rings, each hemoglobin molecule has four iron ions and is capable transported in the blood, favorably affecting muscle performance, of binding four molecules of oxygen. The oxygen binding is fairly and thus athletic performance. However, by increasing the number of weak to ensure rapid attachment and detachment of oxygen with erythrocytes per measured volume of blood, blood doping increases hemoglobin. The result is that oxygen binds to the hemoglobin the viscosity of the blood. Thus, the heart must work harder to pump when the erythrocytes pass through the blood vessels of the this “thicker” more cellular blood. Eventually, temporary athletic lungs, and it leaves the hemoglobin when the erythrocytes pass success may be overshadowed by permanent cardiovascular damage through the blood vessels of the body tissues. This gas exchange that can even lead to death. Therefore, blood doping has now been occurs by diffusion as a result of the differences in concentration banned from athletic competitions. of oxygen between two areas. For example, oxygen is in higher concentration in the lungs compared to the blood, so oxygen diffuses

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α β 2 globin chain 1 globin chain from the lungs into the blood. Conversely, oxygen is in higher con- centration 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. 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 erythro- cyte cannot synthesize proteins to repair itself or replace damaged Heme (a ringed molecule membrane regions. Aging and the wear-and-tear of circulation with iron ion [Fe2+] through blood vessels cause erythrocytes to become more fragile in the center) 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 (to be discussed later in this chapter). Some erythrocyte components are stored in other organs for recycling, β globin chain α globin chain 2 1 while other components are excreted from the body, as shown in Figure 21.5 steps 4 and 5 of figure 21.6 and explained here: Molecular Structure of Hemoglobin. A single molecule of ■ The heme group (minus the iron ion) in hemoglobin is hemoglobin is composed of four protein subunits, called globins, each converted first into a green pigment called biliverdin (bil- containing a heme group that holds a single iron ion in its center. i-ver′din; bilis = bile). Biliverdin is eventually converted Each hemoglobin molecule transports four oxygen molecules that are into a yellow-green pigment called bilirubin (bil-i-roo′bin). weakly attracted to the iron ions. Bilirubin is a component of a digestive secretion called bile,

Figure 21.6 1 Erythrocytes form in red bone marrow. 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.

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) Fe2+ Fe2+ (iron ions)

Heme is converted Fe2+ Fe2+ into biliverdin and Iron is transported in then to bilirubin, the blood by the protein which is secreted transferrin and stored Spleen in bile from the liver. Liver by the protein ferritin in the liver. 3 Aged erythrocytes are phagocytized in the liver and spleen.

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CLINICAL VIEW: In Depth Erythrocyte Volume Disorders another disease or problem. For example, while many anemias are due to iron deficiency, this deficiency can be a result of chronic blood The number of erythrocytes in a person’s blood can vary from the loss, a process that depletes the body of its iron stores over months normal range, leading to various clinical disorders. In general, these or years. The three most common causes of such chronic blood loss are conditions are classified as either anemia or polycythemia. excessive menstrual bleeding, undiagnosed stomach ulcer, and colon cancer. Imagine the magnitude of the mistake a physician could make Anemia (a-ne¯ ′me¯ -aˇ; an = without) is any condition in which the count by simply placing a patient on iron supplements when the underlying of erythrocytes per cubic millimeter of blood is less than the normal cause of the iron deficiency is an undiagnosed cancer of the colon! range. Anemia occurs due to either inadequate production or decreased So, while restoring the patient’s erythrocyte count, a physician should survival of erythrocytes. The blood contains fewer erythrocytes than also look for any underlying cause of the anemia. 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 Polycythemia (pol′e¯ -sı¯-the¯′me¯ -aˇ; poly = many, kytos = cell) is the lethargy, shortness of breath, pallor of the skin and mucous mem- condition of having too many erythrocytes in the blood (otherwise branes, fatigue, and heart palpitations. The types of anemia include known as an elevated hematocrit). The affected person has the same the following: total blood volume, but many more erythrocytes than are healthy. The blood becomes thick and viscous, putting a tremendous strain on ■ Aplastic anemia is characterized by significantly decreased the heart. Following are some of the different types of polycythemia: formation of erythrocytes and hemoglobin due to defective red bone marrow. The causes of defective red bone marrow vary, but ■ Compensatory polycythemia results from chronic hypoxia may include poisons, toxins, or radiation. (inadequate oxygen supply to the body). Smokers develop this ■ Congenital hemolytic anemia occurs when destruction of condition when long-term exposure to tobacco smoke and erythrocytes is more rapid than normal, usually due to a chronically high levels of carbon monoxide damage their lungs. genetic defect. It is caused by the production of abnormal ■ Relative polycythemia is an increase in the number of membrane proteins that make the erythrocyte plasma erythrocytes in the blood per unit volume as a result of a membrane very fragile. decrease in blood plasma. For example, suppose that a child ■ Erythroblastic anemia is characterized by the presence is severely dehydrated due to a serious case of diarrhea. of large numbers of immature, nucleated cells (called As the child progressively loses water, his blood becomes erythroblasts and normoblasts) in the circulating blood. A more concentrated. This type of polycythemia is a temporary reduced rate of hemoglobin synthesis causes these immature condition, and the ratio of erythrocytes to water in the blood cells to be present. These cells cannot function normally and returns to normal when the child becomes rehydrated. thus anemia results. ■ Erythrocytosis is an increase in erythrocytes due to an ■ Familial microcytic anemia is a rare type of inherited anemia increase in the level of EPO. associated with a defect in iron uptake and use. ■ Polycythemia vera is a chronic form characterized by an increase ■ Hemorrhagic anemia results from immediate blood loss due to in blood volume and the number of erythrocytes. This condition such factors as chronic ulcers or heavy menstrual flow. results when erythrocyte growth in the red bone marrow is ■ Macrocytic anemia occurs when the average size of not regulated. precursors continue to grow and circulating erythrocytes is too large. Deficiencies in both mature, irrespective of the presence or absence of erythropoietin.

vitamin B12 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 B12. A defect in the production of intrinsic factor (a glycoprotein secreted

by stomach lining cells to enhance B12 absorption in the small intestine) leads to pernicious anemia. ■ Sickle-cell disease is an autosomal recessive anemia that Sickle-shaped occurs when a person inherits two copies of the sickle-cell gene. erythrocyte 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). SEM 400x

Most anemias are treated by letting the patient’s own bone marrow SEM of blood from a person with sickle-cell replace the erythrocytes. However, anemia is often a symptom of disease.

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which is produced by liver cells. When bile enters the GI Blood Types tract, it helps emulsify (break down) fats. The bilirubin in The plasma membrane of an erythrocyte has numerous molecules the GI tract is modified into other products that appear in called surface antigens that project from the plasma membrane urine from the kidneys and feces from the GI tract. surface. The most commonly identified group of antigens is the ■ The iron ion component in hemoglobin is removed and ABO blood group. This group has two surface antigens, called A transported by a beta-globulin protein, called transferrin and B. The presence or absence of either the A and/or B surface ′ = = (trans-fer in; trans across, ferrum iron), to the liver antigen are the criteria that determine your ABO blood type, as where the iron ion is passed to another protein, called shown in figure 21.7a and listed here: 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. ■ Blood with erythrocytes having surface antigen A is called ■ Erythrocyte membrane proteins and globin proteins are broken type A blood. down into free amino acids, some of which the body uses ■ Blood with erythrocytes having surface antigen B is called for protein synthesis to make new erythrocytes. 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 Both anti-A and anti-B antibodies anti-B antibodies

Plasma

Type A Type B Type AB Type O Erythrocytes with Erythrocytes with Erythrocytes with Erythrocytes with type A surface type B surface both type A and neither type A nor Blood type antigens and plasma antigens and plasma type B surface type B surface with anti-B antibodies with anti-A antibodies antigens, and plasma antigens, but plasma with neither anti-A with both anti-A and nor anti-B antibodies anti-B antibodies

(a)

Rh Blood Types Antigen D No antigen D

Figure 21.7 Erythrocytes 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 No anti-D antibodies Anti-D antibodies (after prior exposure) types.

Plasma

Rh positive Rh negative Erythrocytes with Erythrocytes with no type D surface type D surface Blood type 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)

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

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Donor blood type + Recipient blood type = Agglutination reaction

Antigen A

+ =

Type A blood of donor Type A blood of recipient Antigen and (has surface antigen A) (contains anti-B antibodies) antibody do not match No agglutination No clumping seen. Successful blood type match.

Antigen A

+=

Type A blood of donor Type B blood of recipient Antigen and (has surface antigen A) (contains anti-A antibodies) antibody match Clumping seen. Agglutination and connect 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.

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WHATW DID YOU LEARN? pathogens, especially bacteria. Specifically, target and kill bacteria by secreting lysozyme, an enzyme that helps destroy ●5 Why does an erythrocyte lack cellular organelles, and how is this related to its life span? components of bacterial cell walls. The number of neutrophils in a person’s blood rises dramatically during a bacterial infection as ●6 How do transferrin and ferritin participate in recycling erythrocyte more neutrophils are produced to target the bacteria. components after the cells break down? ●7 Should a person with blood type AB donate blood to a person Eosinophils (ē -ō -sin′ō -fil; eos = dawn) have reddish with blood type A? Why or why not? or pink-orange granules in their cytoplasm. Typically, eosinophils constitute about 1–4% of the total number of leukocytes. Their 21.3b Leukocytes nucleus is bilobed, with the two lobes connected by a thin strand. Leukocytes help initiate an immune response and defend the An is about 1.5 times larger in diameter than an eryth- body against pathogens. Leukocytes are true “cells” in that they rocyte. Eosinophils increase in number when they encounter and contain a nucleus and cellular organelles. Leukocytes also differ react to or phagocytize antigen-antibody complexes or allergens from erythrocytes in that leukocytes are about 1.5 to 3 times larger (antigens that initiate a hypersensitive or allergic reaction). If the in diameter and they do not contain hemoglobin. The number of body is infected by parasitic worms, the eosinophils release chemi- leukocytes in the bloodstream normally ranges between 4500 and cal mediators that attack the worms. 11,000 per cubic millimeter of blood in adults. Infants normally have a higher number than children or adults. Basophils Basophils (bā ′sō -fil; basis = base) are usually about Abnormal numbers of leukocytes result from various patho- 1.5 times larger in diameter than erythrocytes. They are the least logic conditions. For example, a reduced number of leukocytes numerous of the , constituting about 0.5–1% of the causes a serious disorder called leukopenia (loo-kō -pē ′nē -aˇ; total number of leukocytes. For this reason, it is sometimes dif- penia = poverty). This condition may result from viral or bacterial ficult to find a on a blood smear. Basophils exhibit a infection, certain types of leukemia, or toxins that damage the bilobed nucleus and abundant blue-violet granules in the cyto- bone marrow. Conversely, leukocytosis (loo′kō -sı̄ -tō′ sis) results plasm that often obscure the nucleus. Basophils are similar to neu- from an elevated leukocyte count (greater than 11,000 per cubic trophils and eosinophils in that they may exit the circulation and millimeter of blood) and is often indicative of infection, inflamma- migrate through interstitial spaces. The primary components of tory reaction, or extreme physiologic stress. basophil granules are histamine and heparin, which are released Leukocytes are motile and remarkably flexible. In fact, most during anti-inflammatory or allergic reactions. When histamine leukocytes are found in body tissues (as opposed to the blood- is released from these granules, it causes an increase in the stream). Leukocytes enter the tissue by a process called diapedesis diameter of blood vessels (vasodilation), resulting in a decrease (dı̄′ aˇ-peˇ-dē ′sis; dia = through, pedesis = a leaping), whereby they in blood pressure along with classic allergic symptoms such as leave the vessel by squeezing between the endothelial cells of swollen nasal membranes, itchy and runny nose, and watery the blood vessel wall. Chemotaxis (kē -mō -tak′sis; taxis = orderly eyes. The release of heparin from basophils inhibits blood clotting arrangement) is a process whereby leukocytes are attracted to the ( anticoagulation). site of infection by molecules released by damaged cells, dead cells, or invading pathogens. The five types of leukocytes are divided into two distinguish- WHAT DO YOU THINK? able classes—granulocytes and —based upon the pres- ●3 Which type of may increase in number if you ence or absence of visible organelles termed granules (table 21.3). develop “strep throat” (infection of the throat by Streptococcus When a normal blood smear is observed under the microscope, bacteria)? erythrocytes outnumber leukocytes by 500- to 1000-fold. Granulocytes Agranulocytes Granulocytes (gran′ū -lō -sı̄ t; granulum = small grain) have gran- Agranulocytes (aˇ-gran′ū -lō -sı̄ t) are leukocytes that have such small ules in their cytoplasm that are clearly visible when viewed with granules in their cytoplasm that they are frequently overlooked— a microscope. When a blood smear is stained to provide contrast, hence the name (a = without). Agranulocytes include three types of granulocytes can be distinguished: neutrophils, both lymphocytes and monocytes. eosinophils, and basophils. Lymphocytes As their name implies, most lymphocytes (lim′fō - Neutrophils The most numerous leukocyte in the blood is sı̄t) reside in lymphatic organs and structures. Typically, lympho- the neutrophil (noo′trō-fil; neuter = neither), constituting about cytes constitute about 20–40% of the total number of leukocytes. 50–70% of the total number of leukocytes. The neutrophil is Their dark-staining nucleus is usually rounded or slightly indented, named for its neutral or pale-colored granules within a light lilac and smaller lymphocytes exhibit only a thin rim of blue-gray cyto- cytoplasm. They are about 1.5 times larger in diameter than an plasm around the nucleus. When activated, lymphocytes grow erythrocyte and exhibit a multilobed nucleus with as many as larger and have proportionally more cytoplasm. Thus, some of the five lobes interconnected by thin strands. Because of the various smaller, nonactivated lymphocytes may have a diameter less than shapes of their nuclei, neutrophils also may be called polymorpho- that of an erythrocyte, while activated lymphocytes may be two nuclear (PMN) leukocytes. Neutrophils usually remain in circula- times the diameter of an erythrocyte. tion for about 10 to 12 hours before they exit the blood vessels There are three categories of lymphocytes. T-lymphocytes and enter the tissue spaces, where they phagocytize infectious (T-cells) manage and direct an immune response; some directly

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Table 21.3 Leukocytes

LM 1600x

Eosinophil

LM 1600x LM 1600x

Neutrophil Basophil

Granulocytes

Agranulocytes

LM 1600x LM 1600x

Lymphocyte

Type Characteristics Functions Approximate % GRANULOCYTES Neutrophils Nucleus is multilobed (as many as fi ve lobes) Phagocytize pathogens, especially bacteria 50–70% of total leukocytes Cytoplasm contains neutral or pale, distinct Release enzymes that target pathogens granules (when stained) Eosinophils Nucleus is bilobed Phagocytize antigen-antibody complexes and 1–4% of total leukocytes Cytoplasm contains reddish or pink-orange allergens granules (when stained) Release chemical mediators to destroy parasitic worms Basophils Nucleus is bilobed Release histamine (vasodilator) and heparin 0.5–1% of total leukocytes Cytoplasm contains deep blue-violet granules (anticoagulant) during infl ammatory or allergic (when stained) reactions AGRANULOCYTES Lymphocytes Round or slightly indented nucleus (fi lls the cell Attack pathogens and abnormal/infected cells 20–40% of total leukocytes in smaller lymphocytes) Coordinate immune cell activity Nucleus is usually darkly stained Produce antibodies Thin rim of cytoplasm surrounds nucleus

Monocytes Kidney-shaped or C-shaped nucleus Can exit blood vessels and become macrophages 2–8% of total leukocytes Nucleus is generally pale staining Phagocytize pathogens, cellular debris, dead cells Abundant cytoplasm around nucleus

attack foreign cells and virus-infected cells. B-lymphocytes (B-cells) Monocytes A monocyte (mon′ō -sı̄t; monos = single) can be up are stimulated to become plasma cells and produce antibodies. to three times the diameter of an erythrocyte. Monocytes usually Natural killer cells (NK cells) attack abnormal and infected tissue constitute about 2–8% of all leukocytes. The pale-staining nucleus cells. Lymphocytes are examined in detail in chapter 24. of a monocyte is kidney-shaped or C-shaped. After approximately

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Red bone marrow

Megakaryocyte

Megakaryocytes

vessel through Blood flow

LM 1600x

Endothelial cells Proplatelets Platelets (a) (b) Figure 21.9 Origin of Platelets. Platelets are derived from 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 Study Tip! cells called macrophages (mak′rō -fā j; macros = large, phago = to The mnemonic “Never let monkeys eat bananas” is a simple way to eat). Macrophages phagocytize bacteria, cell fragments, dead cells, recall the leukocytes in order of their relative abundance: and debris. Never = Neutrophil (most abundant) 21.3c Platelets Let = Lymphocyte Platelets (plāt ′let; platys = flat) are irregular, membrane-enclosed Monkeys = Monocyte cellular fragments that are about 2 micrometers in diameter (less than one-fourth the size of an erythrocyte). In stained preparations, Eat = Eosinophil they exhibit a dark central region. Platelets are sometimes called Bananas = Basophil (least abundant) thrombocytes (throm′bō -sı̄ 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-aˇ-kar′ē -ō -sı̄ 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 pro- platelets 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 Fibrin complex process involving components in the plasma produces a Platelets 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 Erythrocytes 8 to 10 days. Thereafter, they are broken down, and their contents are recycled. An abnormally small number of platelets in circulat- SEM 4100x ing blood is termed thrombocytopenia. Figure 21.10 WHATW DID YOU LEARN? Blood Clot. Severe trauma to a blood vessel causes the blood to ●8 What is meant when a patient is said to have leukopenia? coagulate, or clot. In a complex process, components in the plasma produce a web of fibrin that traps erythrocytes and platelets and halts ●9 What function do basophils carry out? blood flow. This SEM shows erythrocytes, fibrin, and platelets within ●10 What are megakaryocytes, and what is their function? a forming clot.

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A number of hormones and growth factors influence the 21.4 Hemopoiesis: Production maturation and division of the blood stem cells. Review figure 21.11 as you read this section to see where each growth factor of Formed Elements acts. These so-called colony-stimulating factors (CSFs), or colony- Learning Objectives: forming units (CFUs), include the following: 1. Define and outline the process of hemopoiesis. ■ Multi-CSF is a growth factor that increases the formation 2. Explain the origin and maturation of each type of formed of erythrocytes, as well as all classes of granulocytes, element. monocytes, and platelets from myeloid stem cells. ■ GM-CSF is a growth factor that accelerates the formation of Because formed elements have a relatively short life span, all granulocytes and monocytes from their progenitor cells. new ones are continually produced by the process of hemopoiesis ■ G-CSF is a growth factor that stimulates the formation of ′ ′ = (hē mō -poy-ē sis; poiesis a making), also called hematopoiesis. granulocytes from cells. Hemopoiesis occurs in red bone marrow ( see chapter 6). The process ■ M-CSF is a growth factor that stimulates the production of ′ starts with hemopoietic stem cells called hemocytoblasts (hē -mō - monocytes from . ′ sı̄ tō -blast) (figure 21.11). Hemocytoblasts are considered pluri- ■ Thrombopoietin is a growth factor that stimulates both the potent cells, meaning that they can differentiate and develop into production of megakaryocytes in the bone marrow and the many different kinds of cells. Hemocytoblasts produce two lines for subsequent formation of platelets. ′ = blood cell development: the myeloid (mı̄ eˇ-loyd; myelos marrow) ■ Erythropoietin (EPO) is a hormone produced by the line forms erythrocytes, megakaryocytes, and all leukocytes except kidneys to increase the rate of production and maturation of ′ lymphocytes; the lymphoid (lim foyd) line forms lymphocytes. erythrocyte progenitor and erythroblast cells.

CLINICAL VIEW Leukemia the presence of large numbers of immature granulocytes in the circulat- ing blood. Lymphocytic leukemia is characterized by increased numbers Leukemia (loo-ke¯′me¯ -aˇ) is a malignancy (cancer) in the leukocyte- of malignant lymphocytes and/or lymphocytic precursors (lymphoblasts) forming cells. There are several varieties of leukemia, but all are marked in the bone marrow and circulating blood. This type of leukemia often by abnormal development and proliferation of leukocytes, in both the involves lymph nodes and the spleen. Monocytic leukemia is a rare bone marrow and in the circulating blood. Leukemias are classified form characterized by an increased number of malignant and immature based on their duration as either acute or chronic. monocytic cells in the bone marrow and circulating blood. Acute leukemia progresses rapidly, and death occurs within a few Leukemias represent a malignant transformation of a leukocyte cell months after the onset of symptoms (severe anemia, hemorrhages, line. As abnormal leukocytes increase in number, the erythrocyte and and recurrent infections). Acute leukemia tends to occur in children megakaryocytic lines virtually always decrease in number because the and young adults. Chronic leukemia progresses more slowly; survival proliferating malignant cells literally squeeze them out. This decrease in typically exceeds 1 year from the onset of symptoms, which include erythrocyte and platelet production results in the anemia and bleeding anemia and a tendency to bleed. Chronic leukemia usually occurs in that are often the first signs of leukemia. Fortunately, great strides have middle-aged and older individuals. been made in treating some leukemias over the past two decades, especially acute childhood leukemia. Childhood leukemia, once an unquestioned Leukemia can also be classif ied based on the type of cell that has become death sentence, stands a good chance of being completely cured today malignant. Granulocytic leukemia is characterized by uncontrolled pro- due to improved bone marrow transplant technology in recent years. liferation of immature cells in the myeloid stem cell lines, as well as by

Lymphoblasts (immature lymphocytes)

LM 1000x LM 500x

(a) Normal bone marrow sample (b) Bone marrow sample in ALL (acute lymphoblastic leukemia)

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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 Myeloblast M-CSF

EPO Early erythroblast Thrombopoietin G-CSF

Late erythroblast M-CSF

Thrombopoietin Normoblast Eosinophilic Basophilic Neutrophilic myelocyte myelocyte

Nucleus ejected

Erythrocyte Thrombopoietin Eosinophil Basophil Neutrophil Monocyte B-lymphocyte T-lymphocyte Platelets

Figure 21.11 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).

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21.4a Erythropoiesis processes: granulocyte maturation, monocyte maturation, and Erythrocyte production is called erythropoiesis (eˇ-rith′rō -poy-ē′ sis). lymphocyte maturation. Normally, erythrocytes are produced at the rate of about 3 mil- Granulocyte Maturation lion per second, controlled by the hormone erythropoietin (EPO). Erythropoiesis begins with a myeloid stem cell that forms a pro- All three types of granulocytes (neutrophils, basophils, and eosin- genitor cell. The progenitor cell forms a , which is ophils) are derived from a myeloid stem cell along the myeloid line. a large, nucleated cell. This cell then becomes an erythroblast, a This stem cell forms a progenitor cell, which then forms a myelo- ′ slightly smaller cell that is forming hemoglobin in its cytoplasm. blast (mı̄ eˇ-lō -blast), which ultimately differentiates into one of the The next stage, called a normoblast, is a still smaller cell with three types of granulocytes. more hemoglobin in the cytoplasm; its nucleus has been ejected. Monocyte Maturation Eventually, a cell called a reticulocyte (re-tik′ū -lō -sı̄ t) is produced. The reticulocyte has lost all organelles except some ribosomes, but it Like granulocytes, monocytes are also derived from a myeloid stem continues to produce hemoglobin. The transformation from myeloid cell. In this case, the myeloid stem cell differentiates into a progeni- stem cell to reticulocyte takes about 5 days. enter the tor cell, which then forms a monoblast (instead of a myeloblast, as circulation, and within 1 to 2 days the remaining organelles degen- with granulocytes). The monoblast matures into a promonocyte, erate, and the reticulocyte becomes a mature erythrocyte. which then forms a monocyte. 21.4b Thrombopoiesis Lymphocyte Maturation The production of platelets is called thrombopoiesis (throm′bō - Lymphocytes are derived from a lymphoid stem cell along the lym- poy-ē ′sis). From the myeloid stem cell, a committed cell called a phoid line. The lymphoid stem cell differentiates into B-lymphoblasts megakaryoblast is produced. It matures under the influence of and T-lymphoblasts. B-lymphoblasts mature into B-lymphocytes, thrombopoietin to form a megakaryocyte. Each megakaryocyte while T-lymphoblasts mature into T-lymphocytes. Some lymphoid produces thousands of platelets. stem cells differentiate directly into NK cells. 21.4c Leukopoiesis WHATW DID YOU LEARN? The production of leukocytes is called leukopoiesis (loo′kō - poy-ē ′sis). Leukopoiesis involves three different maturation ●11 What are hemocytoblasts?

Clinical Terms

cyanosis (sı̄ -aˇ-nō ′sis; kyanos = blue color) Dark bluish or purplish Halt in blood loss. discoloration of the skin and mucous membranes septicemia (sep-ti-sē ′mē -aˇ; sepsis = putrefaction) Systemic disease as a result of deficient oxygenation of the blood. caused by the spread of microorganisms and their toxins hemoglobinuria (hē ′mō -glō -bi-noo′rē -aˇ; ouron = urine) Presence of through the circulating blood. hemoglobin in the urine. hemophilia (hē -mō -fil′ē -aˇ) Inherited disorder characterized by a tendency to hemorrhage uncontrollably because of a defect in the blood-coagulating mechanism.

Chapter Summary

21.1 General ■ Blood is a fluid connective tissue composed of formed elements, plasma, and dissolved proteins. Composition and Functions 21.1a Components of Blood 638 of Blood 638 ■ Centrifugation separates whole blood into three components: erythrocytes, a buffy coat composed of leukocytes and platelets, and plasma, a straw-colored fluid. 21.1b Functions of Blood 638 ■ Blood transports nutrients, wastes, and respiratory gases; regulates body temperature, pH, and water levels; and protects the body against the loss of blood volume and the activities of pathogens. 21.2 Blood ■ Blood plasma is a mixture of water, proteins, and other solutes. Plasma 639 21.2a Plasma Proteins 640 ■ Plasma proteins are divided into four classes based on their structure and function: Albumins are small proteins that regulate water movement and assist with transport; globulins transport proteins of the immune system; fibrinogen aids in clot formation; and regulatory proteins include enzymes and hormones. 21.2b Differences Between Plasma and Interstitial Fluid 640 ■ Plasma is a component of blood; interstitial fluid bathes body cells.

(continued on next page)

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Chapter Summary (continued) 21.3 Formed ■ Erythrocytes are the major formed element. Less than 1% of the formed elements consist of leukocytes and cell fragments Elements in the called platelets. A hematocrit is the percentage of the volume of all formed elements in the blood. Blood 640 21.3a Erythrocytes 641 ■ Erythrocytes have a biconcave disc structure that facilitates the exchange of respiratory gases into and out of the cells. ■ Hemoglobin is a pigmented protein that fills mature erythrocytes; it transports oxygen and carbon dioxide. ■ Aged erythrocytes are broken down and their components recycled after about 120 days in the blood. ■ Erythrocyte plasma membranes have molecules called surface antigens; blood plasma has antibodies. ■ When antibodies bind to surface antigens, agglutination may result in hemolysis of the erythrocytes. ■ The Rh blood group is determined by the presence or absence of the Rh surface antigen. 21.3b Leukocytes 648 ■ Leukocytes are white blood cells that defend against invading pathogens; reduce the activities of abnormal cells; and remove damaged cells, debris, and antigen-antibody complexes. ■ A disorder in which leukocytes are reduced in number is called leukopenia; a slightly elevated leukocyte count is termed leukocytosis. ■ Leukocytes are either granulocytes (neutrophils, eosinophils, and basophils) or agranulocytes (lymphocytes and monocytes) based on the presence (or lack) of granules in their cytoplasm. 21.3c Platelets 650 ■ Platelets, or thrombocytes, are the smallest components of the formed elements. These membrane-enclosed packets of cytoplasm are derived from megakaryocytes. ■ An abnormal number of platelets causes a condition called thrombocytopenia. 21.4 Hemopoiesis: ■ Formed elements have a relatively short life span. They are constantly renewed by the process of hemopoiesis. Production ■ Hemopoietic stem cells are pluripotent cells called hemocytoblasts located in red bone marrow. of Formed Elements 651 21.4a Erythropoiesis 653 ■ Erythropoiesis is the production of erythrocytes. The hormone erythropoietin (EPO) controls the rate of proerythroblast maturation to become an erythrocyte. 21.4b Thrombopoiesis 653 ■ Thrombopoiesis is the production of platelets. A megakaryoblast is produced, and it matures under the influence of thrombopoietin to form a megakaryocyte. 21.4c Leukopoiesis 653 ■ The production of leukocytes is called leukopoiesis. This process begins in the bone marrow with the division of hemocytoblasts.

Challenge Yourself Matching Multiple Choice Match each numbered item with the most closely related lettered Select the best answer from the four choices provided. item. ______1. In the adult, the stem cells for leukocytes reside in ______1. monocyte a. immature form of erythrocyte the with a nucleus a. bloodstream. ______2. fibrinogen b. red bone marrow. b. the most abundant plasma protein ______3. neutrophil c. liver. c. formation of erythrocytes d. muscle. ______4. erythroblast ______2. Which type of leukocyte increases during allergic d. agranulocyte that can ______5. hemopoiesis reactions and parasitic worm infections? develop into a. basophil ______6. albumin e. the most abundant b. eosinophil ______7. antibody compound in plasma c. lymphocyte d. neutrophil ______8. water f. the most numerous leukocyte ______3. Which cell forms platelets in the red bone marrow? ______9. erythropoiesis g. transport protein in plasma a. lymphocyte ______10. globulin h. blood cell formation and b. megakaryocyte development c. eosinophil d. reticulocyte i. binds to antigens j. protein that can be converted into blood clot fibers

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______4. Which of the following is not a function of blood? Content Review a. prevention of fluid loss 1. How does blood help regulate body temperature? b. nutrient and waste transport c. maintenance of constant pH levels 2. What are globulins? What do they do? d. production of hormones 3. When blood is centrifuged, a thin, gray-white layer called ______5. A person with blood type A has the buffy coat covers the layer of packed erythrocytes. What a. anti-B antibodies in her blood plasma. are the components of the buffy coat? b. anti-A antibodies in her blood plasma. 4. What is the shape of an erythrocyte, and why is this shape c. both anti-A and anti-B antibodies in her blood advantageous to its function? plasma. 5. How is oxygen carried by erythrocytes? d. no antibodies in her blood plasma. 6. What are the anatomic characteristics of each type of ______6. The hematocrit is a measure of leukocyte? How can you tell these leukocytes apart when a. water concentration in the plasma. viewing a blood smear under the microscope? b. the percentage of formed elements in the blood. 7. How do the functions of basophils differ from those of c. the number of platelets in the blood. lymphocytes? d. antibody concentration in the plasma. 8. Briefly describe the origin, structure, and functions of ______7. Oxygen attaches to a(n) ______ion in hemoglobin. platelets. a. calcium b. sodium 9. What is hemopoiesis? What is a hemocytoblast? Briefly c. iron describe the two lines of blood cells that develop during d. potassium hemopoiesis. ______8. During the recycling of components following the 10. What are colony-stimulating factors? Where would normal destruction of erythrocytes, globin is broken they be found in the body, and what is their general down, and its components are function? a. used to synthesize new proteins. b. stored as iron in the liver. Developing Critical Reasoning c. eliminated from the body in the bile. 1. While taking a clinical laboratory class, Marilyn prepared d. removed in the urine. and examined blood smears from several donors. One ______9. The type of leukocyte that produces antibodies is a (an) of the smears had an increased percentage (about 10% a. eosinophil. of observed leukocytes) of cells containing reddish- b. basophil. orange granules. Discuss the type of cell described c. T-lymphocyte. and the condition that may have caused this increase d. B-lymphocyte. in the donor. ______10. Which of the following is not a characteristic of a 2. Abby is a nurse on duty in a hospital emergency room mature erythrocyte? when a critically injured patient is brought in. The a. biconcave disc shape physician calls for an immediate blood transfusion, but the b. absence of organelles patient’s blood type is unknown. What blood type should c. life span of about 12 months the patient be given and why? d. filled with hemoglobin

Answers to “What Do You Think?”

1. When you become dehydrated, the plasma percentage with type AB blood is considered a “universal recipient” decreases because the primary component of plasma is water. because his blood plasma has no antibodies to the ABO 2. A person with type O blood is considered a “universal blood types. Thus, the AB recipient may receive any type of donor” because her erythrocytes have no surface antigens. blood and not worry about the donor’s erythrocytes being Without surface antigens, the type O erythrocytes will destroyed. not be destroyed through agglutination and hemolysis by 3. Neutrophils increase in number when you get “strep throat” antibodies in the recipient’s plasma. Likewise, a person because they target bacteria.

www.mhhe.com/mckinley3 Enhance your study with practice tests and activities to assess your understanding. Your instructor may also recommend the interactive eBook, individualized learning tools, and more.

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