UNIT 4 - CHAPTER 14: BLOOD LEARNING OUTCOMES: 14.1 14.2 14.3 Introduction 1. Describe the general characteristics of blood, and discuss its major functions. 2. Distinguish among the formed elements of blood and the liquid portion of blood. Blood Cells 3. Describe the origin of blood cells. 4. Explain the significance of red blood cell counts and how they are used to diagnose disease. 5. Discuss the life cycle of a red blood cell. 6. Summarize the control of red blood cell production. 7. Distinguish among the five types of white blood, cells and give the function(s) of each type. 8. Describe a blood platelet, and explain its functions. Blood Plasma 9. 14.4 14.5 Describe the functions of each of the major components of plasma. Hemostasis 10. Define hemostasis, and explain the mechanisms that help to achieve it. 11. Review the major steps in blood coagulation. 12. Explain how to prevent blood coagulation. Blood Groups and Transfusions 13. Explain blood typing and how it is used to avoid adverse reactions following blood transfusions. 14. Describe how blood reactions may occur between fetal and maternal tissues. 14-1 UNIT 4 - CHAPTER 14: BLOOD 14.1 INTRODUCTION A. B. C. D. Blood is a type of connective tissue whose cells are suspended in a liquid extracellular matrix, called plasma. Blood transports substances between body cells and the external environment and helps maintain a stable internal environment. Blood volume varies with body size, fluid and electrolyte balance, and adipose content. 1. Average blood volume (70 kg male) is 5 liters. Blood can be separated into two major components: See Fig 14.1-14.3, pages 527-528. 1. 2. 14.2 Blood cells or "formed elements" (45% by weight), which is composed mainly of red blood cells. a. Quantitative analysis of this portion of blood represents the hematocrit (HCT) reading or packed cell volume (PCV). Plasma (55% by weight), liquid portion that contains water, proteins, amino acids, carbohydrates, lipids, vitamins, hormones, electrolytes, and cellular wastes. BLOOD CELLS (or “formed elements”) Blood is composed of three types of cells, including erythrocytes (red blood cells), leukocytes (white blood cells), and thrombocytes (platelets). See Fig 14.1, page 527. A. The Origin of Blood Cells 1. Hematopoietic stem cells in red bone marrow of adults o yolk sac, liver, and spleen in fetuses 2. Specific types of hematopoietic growth factors produce differentiation resulting in specific types of cells. o myeloid stem cells o lymphoid stem cells 3. ALL BLOOD CELLS ARE FORMED FROM THE SAME LARGE PRIMITIVE CELL CALLED A HEMOCYTOBLAST . See Fig 14.4, page 529. 14-2 UNIT 4 - CHAPTER 14: BLOOD 14.2. BLOOD CELLS B. Red Blood Cells (Erythrocytes) 1. Characteristics of Red Blood Cells (RBC) = Erythrocytes See Fig 14.5, page 530. a. tiny, 7.5m diameter, biconcave disks (increased surface area) b. compose 99% of blood cells c. contain pigment hemoglobin, which is loosely bound to oxygen. See Fig 14.8, page 533. o Hemoglobin = protein (globin) + heme (iron) o oxyhemoglobin = bright red o deoxyhemoglobin = darker red, purple * See box on page 528 re: Sickle Cell Disease. d. Mature cells lack nuclei (i.e. are anucleate), leaving more room for hemoglobin and oxygen. * See box on page 528 re: Hypoxia. 2. Red Blood Cell Counts a. RBC Count (RCC) = the number of RBC's/mm3 blood. o Average RCC = 4 million-6 million RBC's/mm3 blood (in a healthy individual). 3. Red Blood Cell Production and Its Control a. Production (Erythropoiesis) o In fetuses = yolk sac, liver, spleen. o In adults = red bone marrow. b. Control of Production RBC number remains relatively stable. o Negative feedback mechanism involving the hormone erythropoietin, which is produced and secreted by the special cells in the kidney and liver. o See Fig 14.6, page 531. 1. Chemoreceptors in kidney and liver detect low blood oxygen. 2. Erythropoietin is released from kidney and liver into circulation. 3. Erythropoietin targets red bone marrow (in epiphyses of long bones and spongy bone of flat bones), stimulating erythropoiesis. 4. Dietary Factors Affecting Red Blood Cell Production a. B12, folic acid, and iron are all needed. b. Intrinsic Factor is secreted by stomach allowing B12 absorption. c. Lack of proper nutrients leads to anemia (see below). * See Table 14.1 and boxes on page 531: dietary factors and B12 and iron deficiencies. 14-3 UNIT 4 - CHAPTER 14: BLOOD 14.2. BLOOD CELLS B. C. Red Blood Cells 5. Destruction of Red Blood Cells Average life-span = 120 days a. Liver and spleen macrophages destroy worn RBCs. b. Hemoglobin is broken into globin and heme. c. Iron in Hb is recycled. d. Heme is broken into biliverdin > bilirubin > bile. e. See Table 14.3, page 532 and Fig 14.9, page 533. * See Table 14.2 and Fig 14.7, page 532, Types of Anemias. White Blood Cells (Leukocytes) 1. Types and Function of WBCs There are five types of leukocytes that function to control disease. Leukocytes are divided into granulocytes and agranulocytes: a. Granulocytes (are approximately 12-14µ in diameter). 1. 2. 3. Neutrophils: See Figure 14.10, page 534. most abundant WBC = 54%-62% polymorphonucleocyte (PMN) phagocytosis of foreign particles (disease organisms and debris) increased in acute bacterial infections Eosinophils: See Figure 14.11, pages 534. 1-3% of total WBC kill parasites and are responsible for allergic reactions increased during parasitic infections (tapeworm, hookworm) release histamine during allergic reactions Basophils: See Figure 14.12, page 534. <1% of total WBC release heparin which inhibits blood clotting release histamine, a vasodilator helpful inflammatory responses (increases blood flow to damaged tissue). may leave bloodstream and develop into mast cells (antibodies attach and cause mast cell to burst, releasing allergy mediators. Discussed in greater detail in Chapter 16.) 14-4 UNIT 4 - CHAPTER 14: BLOOD 14.2 BLOOD CELLS C. White Blood Cells 1. Types and Function of WBC’s b. Agranulocytes 1. Monocytes: See Fig 14.13, page 535. 3-9% of total WBC phagocytosis largest WBC, 12-20 µ in diameter In blood = phagocyte. In tissues = macrophage. increased during typhoid fever, malaria, and mononucleosis 2. Lymphocytes: See Fig 14.14, page 535. 5-33% of total WBC live for several months to years (only leukocyte that lives more than a few days) smallest WBC, ranging in size from large (10-14) to small (6-9) function in immunity and discussed in greater detail in Chapter 16. increased during TB, whooping cough, viral infections, tissue rejection reactions, and tumors 2. Diapedesis = process by which leukocytes move through blood vessel walls to enter tissues. a. monocyte to macrophage b. basophil to mast cell See Fig 14.15, page 535. 3. White Blood Cell Counts a. Average WBC count (WCC) = 5000-10,000 WBC’s / mm3 blood 1. Number of WBC’s increases during infections o Leukocytosis = WCC > 10000. o Leukopenia = WCC < 5000. b. Differential white blood cell count (DIFF) indicates % of each particular leukocyte. c. Leukemia = abnormal (uncontrolled) production of specific types of immature leukocytes. See Clinical Application 14.1, page 538. White blood cells protect against infection in several ways. See Fig 14.16, page 536. This will be discussed in detail in Chapter 16. 4. D. Blood Platelets (Thrombocytes) 1. fragments of giant cells called megakaryocytes. See Fig 14.4, page 529. 2. Normal count = 130,000-360,000 platelets/ mm3 blood. 3. Function = blood clotting (will be discussed in detail below). * See box on page 537 re: Thrombocytopenia. 14-5 UNIT 4 - CHAPTER 14: BLOOD 14.2. BLOOD CELLS Major Blood Cell Summary Table (See Summary of Blood Cells in Table 14.5, page 537, and key at the end of this outline) Major Blood Cell Type Scientific Name Circulating Concentration/ mm3 blood General Function Key Characteristics White Blood Cell Summary Table (See key at the end of this outline) Specific WBC Function/ Event of Increase? Differential % Typical Sketch 14-6 UNIT 4 - CHAPTER 14: BLOOD 14.3 BLOOD PLASMA See Fig 14.1-Fig 14.3, pages 527-528. Blood plasma is clear, yellow liquid, composed of water, proteins, nutrients, gases, electrolytes, and many more substances. A. Water 1. 92 % 2. functions as solvent, in transport, temperature regulation, and serves as site of metabolic reactions B. Plasma Proteins: See Table 14.6, page 539. 1. 7% of plasma volume 2. all produced in the liver 3. Three types: a. albumin o maintains osmotic pressure of cells (0.9%) o transports fatty acids b. globulins ( α, β , γ ) o antibodies c. fibrinogen o blood clotting * See box on page 539 re: decreased plasma proteins and edema. C. Plasma Gases 1. oxygen (needed for cellular respiration) 2. carbon dioxide (produced by cell respiration) 3. nitrogen (use unknown) * See box on page 539 re: laboratory evaluation of blood gases. D. Plasma Nutrients 1. amino acids 2. monosaccharides (i.e. glucose) E. Nonprotein Nitrogenous Substances (Plasma Wastes) 1. urea (amino acid metabolism) 2. uric acid (nucleotide metabolism) 3. creatinine (creatine metabolism) 4. creatine (CP to recycle ADP to ATP in muscle & brain) 5. bilirubin (hemoglobin metabolism) F. Plasma Electrolytes 1. includes sodium, potassium, calcium, magnesium, chloride, bicarbonate, phosphate, and sulfate 2. maintain osmotic pressure, resting membrane potential, and pH. G. Regulatory Substances 1. enzymes 2. hormones 14-7 UNIT 4 - CHAPTER 14: BLOOD 14.4 HEMOSTASIS A. B. Definition: Hemostasis = stoppage of bleeding from a blood vessel. 3 steps involved: See Table 14.7, page 541. 1. Blood Vessel Spasm (vessel walls constrict) a. vasospasm b. reduces blood flow 2. Platelet Plug Formation See Fig 14.17, page 540. a. Platelets become sticky and adhere to one another. b. Platelets also release the hormone serotonin, which causes further vasoconstriction of the vessel. 3. Blood Coagulation = formation of a blood clot. a. complex cascade of events (positive feedback mechanism) b. requires calcium ions c. 2 possible starting pathways o Extrinsic Clotting Mechanism 1. Starts when platelet contacts damaged tissue or tissue outside of blood vessel (hence, extrinsic). 2. Cascade leads to prothrombin activator (PA) release by platelets. 3. PA and Ca2+ cause prothrombin to convert to thrombin. 4. Thrombin catalyzes the final step, (polymerization of) fibrinogen to fibrin. 5. Fibrin threads make up meshwork of clot. o Intrinsic Clotting Mechanism (all factors normally found in blood) 1. Starts when blood contacts a foreign substance. 2. Cascade again leads to same final step as above. a. Final step = fibrinogen → fibrin. d. Fate of Blood Clots ○ A formed clot retracts and pulls the edges of a broken blood vessel together. 1. A thrombus is an abnormal blood clot in a vessel. 2. An embolus is a clot or fragment of a clot that moves in a vessel. ○ Fibroblasts invade a clot, forming connective tissue throughout. ○ Protein-splitting enzymes may eventually destroy a clot. e. See scanning electron micrograph of fibrin threads, Fig 14.18, page 541. f. See Fig 14.19, page 542 and Tables 14.8 and 14.9, page 543, illustrating the complex, positive feedback mechanisms of blood coagulation. g. See boxes and 543 re: PT/PTT lab tests and inherited bleeding disorders. 14-8 UNIT 4 - CHAPTER 14: BLOOD 14.4 HEMOSTASIS C. Prevention of Coagulation (Fibrinolytic System) 1. Fibrinolytic system provides checks and balances so that blood clotting does not go awry. 2. See Table 14.10, page 545 re: Factors That Inhibit Blood Clot Formation. 3. Definitions: a. Thrombus = abnormal clot. b. Embolus = floating clot (abnormal). c. Embolism = when embolus gets lodged in a small vessel obstructing blood flow. 4. Fibrinolytic substances include: a. tissue plasminogen activator (TPA): o naturally produced o injected quickly (within 1 hour) post-MI to dissolve coronary thrombus(i). o injected quickly (within 3 hours) post-stroke to dissolve a cerebral blockage. o See box on page 544. b. Heparin is an anticoagulant: o o c. naturally produced by basophils and mast cells also used a pharmacologic agent extracted from lung tissues of animals used during open-heart surgery and hemodialysis used immediately following thrombus detection (i.e deep vein thrombosis, DVT, see below) Warfarin (Coumadin) is another anticoagulant: o o given to patients prone to thrombosis slower acting than heparin * See box on page 541 re: Disseminated Intravascular Clotting (DIC). * See Fig 14.20, page 544 re: Atherosclerosis. * See Clinical Application 14.2, page 545 re: Deep Vein Thrombosis (DVT). 14-9 UNIT 4 - CHAPTER 14: BLOOD 14.5 BLOOD GROUPS AND TRANSFUSIONS A. Antigens and Antibodies 1. There are antigens present on the cell membrane surface of our erythrocytes (red blood cells). 2. Our plasma contains substances called antibodies that are produced against non-self antigens. 3. If the RBC antigen (donor) and plasma antibody (recipient) are the same, the serious condition of hemolysis (bursting) of RBC will occur. * * See box on page 546 re: telltale signs of agglutination following blood mismatch. In the laboratory, this situation can be simulated, however the result is termed agglutination = clumping of red blood cells. See Fig 14.22, page 548. B. ABO Blood Group: See Fig 14.21 and Table 14.12, page 547. 1. inherited trait 2. determined by the antigens on a person's RBC 3. 4 types: A, B, AB, O a. b. c. d. 4. Type A blood = antigen A on RBC Type B blood = antigen B on RBC Type AB blood = both antigen A & B on RBC Type O = neither A or B antigen on RBC Antibodies in plasma: (See above figure) a. Shortly after birth, we spontaneously develop antibodies against RBC antigens that are not our own (i.e. non-self). b. Antibodies formed include: o Persons with Type A blood, develop Anti-B antibodies o Persons with Type B blood, develop Anti-A antibodies o Persons with Type AB blood, do not develop either Anti-A or Anti-B antibodies o Persons with Type O blood, develop both Anti-A and AntiB antibodies. 14-10 UNIT 4 - CHAPTER 14: BLOOD 14.5 BLOOD GROUPS AND TRANSFUSIONS B. ABO Blood Group 5. Summary of ABO Interactions: (keyed at the end of this outline) When considering blood transfusion reactions, the most important factor to consider is the antibodies present in the recipient's plasma! BLOOD TYPE ANTIGEN ON RBC ANTIBODIES IN PLASMA COMPATIBLE DONORS INCOMPATIBLE DONORS GENOTYPE PHENOTYPE * A person with type O blood is considered the universal donor. * A person with type AB blood is considered the universal recipient. * See From Science to Technology 14.1, page 546 re: Blood Typing and Matching: From Serology to DNA Chips. * See Table 14.11, page 547 re: ABO Blood Type Frequencies (%) within the United States. * See box on page 548 re: Bombay Phenotype. 14-11 UNIT 4 - CHAPTER 14: BLOOD 14.5 BLOOD GROUPS AND TRANSFUSIONS C. Rh Blood Group: 1. inherited trait 2. studied in rhesus monkeys (thus, Rh) 3. Group of antigens present on RBC = Rh positive; Lack of antigens on RBC = Rh negative. 4. Rh antibodies do not form spontaneously, but will form in Rh-negative persons in response to stimulation: 5. a. Initial exposure (transfusion, etc.) does not produce harmful effects, however the Rh-negative person has now been sensitized (i.e. they can produce anti-Rh antibodies) b. Additional exposure (transfusion, etc.) causes serious hemolysis to occur. Erythroblastosis fetalis = hemolytic disease of the newborn (HDN). See Figure 14.23 and box on page 549. a. Scheme: o o o o o b. Rh-negative mother becomes pregnant with Rh-positive fetus. Pregnancy uneventful, but during birth, baby's blood enters the mother's circulation and causes her to produce anti-Rh antibodies. Mother conceives a second Rh-positive fetus. Mother's anti-Rh antibodies can now pass through the placenta and enter the fetus’ circulation. The fetus’ RBC hemolyze resulting in this fatal condition. Usually, no longer a significant problem because of the administration of a drug called RhoGAM, which destroys the mother's anti-Rh antibodies before they can cross the placenta and destroy the fetus’ red blood cells. 14-12 UNIT 4 - CHAPTER 14: BLOOD OTHER INTERESTING TOPIC: A. Universal Precautions. See Introduction on page 526. CHAPTER SUMMARY – see pages 550-552. CHAPTER ASSESSMENTS – see page 552. INTEGRATIVE ASSESSMENTS/ CRITICAL THINKING– see page 553. Major Blood Cell Summary Table Major Blood Cell Type red blood cell white blood cell platelet Scientific Name Erythrocyte leukocyte thrombocyte Circulating Concentration/ mm3 blood 4-6 million/ mm3 blood 5-10,000/ mm3 blood 130,000-360,000/ mm3 blood General Function transportation of oxygen fight infection/ control disease blood clotting Key Characteristic see page 3 see page 4-5 are fragments of giant megakaryocyte 14-13 UNIT 4 - CHAPTER 14: BLOOD White Blood Cell Summary Table) Specific WBC Function/ Event of Increase? Differential % Typical Sketch (refer to text) neutrophil general phagocytosis; acute bacterial infections 54%-62% see page 534 eosinophil kills parasites; involved in inflammation and allergic reactions 1%-3% see page 534 basophil Inflammatory reactions: releases heparin (natural anticoagulant) and histamine (inflammation) less than 1% see page 534 monocyte phagocytosis of large particles; typhoid, malaria, mononucleosis 3%-9% see page 535 lymphocyte produce antibodies/immunity; viral infections, tissue rejection, tumors, TB, whooping cough 25%-33% see page 535 Summary of ABO Interactions BLOOD TYPE A B AB O Antigen on RBC A B A and B neither A or B Antibodies in plasma B A neither A or B Both A and B Compatible donors A, O B, O AB, A, B, O O Incompatible donors B, AB A, AB NONE A, B, AB Genotype IAIA OR IAi IBIB, IBi IAIB ii Phenotype type A type B type AB type O 14-14
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