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DETAILED LECTURE OUTLINE Fundamentals of Anatomy and Physiology, 7th edition, ©2006 by Frederic H. Martini Prepared by Professor Albia Dugger, Miami-Dade College, Miami, Florida Please note: References to textbook headings, figures and tables appear in italics. “100 Keys” are designated by Key Important vocabulary terms are underlined. Chapter 19: Blood I. The Cardiovascular System: An Introduction, p. 640 Objective: 1. List the components of the cardiovascular system and explain the major functions. The cardiovascular system is basically a circulating transport system. It includes a pump (the heart) a conducting system (the blood vessels) and a fluid medium (the blood). The cardiovascular system transports materials such as oxygen, carbon dioxide, nutrients, waste products, hormones and immune system components to and from the cells. II. The Nature of Blood, p. 640 Objectives: 1. Describe the important components and major functions of blood 2. Identify body sites used for blood collection and list the basic physical characteristics of the blood samples drawn from these locations. Blood is a specialized fluid connective tissue that contains cells suspended in a fluid matrix. Blood has 5 basic functions; 1. The transport of dissolved gases, nutrients, hormones and metabolic wastes. 2. The regulation of the pH and ion composition of interstitial fluids. 3. The restriction of fluid losses at injury sites. 4. Defense against toxins and pathogens. 5. The stabilization of body temperature. Figure 19-1a Whole blood is composed of 2 basic subunits: 1. plasma, which is the fluid part 2. formed elements, which include all the cells and solid parts Plasma contains water, dissolved plasma proteins and other solutes. It is similar to, and exchanges fluids with, interstitial fluid. There are 3 types of formed elements suspended in the plasma: 1. red blood cells (RBCs or erythrocytes) transport oxygen 2. white blood cells (WBCs or leukocytes) are part of the immune system 3. platelets are cell fragments involved in clotting Formed elements are produced by myeloid and lymphoid stem cells in the process of hemopoiesis. Whole blood is separated or fractionated into plasma and formed elements for clinical analysis. Blood has 3 general physical characteristics: 1. A normal temperature of 38 degrees C (100.4 degrees F) 2. A high viscosity 3. A slightly alkaline pH (7.35 - 7.45) An individual’s blood volume (in liters) is about 7% of their body weight in kilograms. An adult male has about 5 - 6 liters of blood. III. Plasma, p. 642 Objective: 1. Specify the composition and functions of plasma. Figure 19.1b Plasma makes up about 50 to 60 percent of blood volume, and more than 90 percent of plasma is water. Like interstitial fluid, plasma is an extracellular fluid. Water, ions, and small solutes are continually exchanged between the plasma and interstitial fluid across the walls of capillaries. The differences between plasma and interstitial fluids are: 1. different levels of oxygen and carbon dioxide 2. different amounts and types of dissolved proteins (plasma proteins do not pass through capillary walls) Plasma Proteins, p. 642 There are 3 main classes of plasma proteins: 1. albumins (60%) 2. globulins (35%) 3. fibrinogen (4%) Albumins transport substances such as fatty acids, thyroid hormones and steroid hormones. Globulins include: 1. antibodies (immunoglobulins) 2. transport globulins (for small molecules and compounds): a. hormone-binding proteins b. metalloproteins c. apolipoproteins (lipoproteins) d. steroid-binding proteins Fibrinogen molecules form clots by producing long, insoluble strands of fibrin. Without anti-clotting treatment, the dissolved fibrinogen in a blood sample will convert to solid fibrin, leaving a liquid called serum. The remaining 1% of plasma is made up of changing quantities of specialized plasma proteins including enzymes, hormones and prohormones. Origins of plasma proteins: - 90% of plasma proteins are made in the liver - antibodies are made by plasma cells - peptide hormones are made by endocrine organs Key Your total blood volume, in liters, is roughly equal to 7% of your body weight in kilograms. Approximately half the volume of whole blood consists of cells and cell products. Plasma resembles interstitial fluid, but it contains a unique mixture of proteins not found in other extracellular fluids. IV. Red Blood Cells, p. 643 Objectives: 1. List the characteristics and functions of red blood cells. 2. Describe the structure of hemoglobin and indicate its functions. 3. Describe how the components of aged or damaged red blood cells are recycled. 4. Define erythropoiesis, identify the stages involved in red blood cell maturation, and describe the homeostatic regulation of red blood cell production. 5. Explain the importance of blood typing and the basis for ABO and Rh incompatibilities. RBCs make up 99.9% of the blood’s formed elements. Abundance of RBCs, p. 644 Red blood cells can be measured in 2 ways: 1. A red blood cell count is the number of RBCs in a microliter (cubic millimeter) of whole blood. 2. The hematocrit is the percentage of packed (centrifuged) red blood cells in a whole blood sample (also called packed cell volume, PCV). In the adult male, normal red blood cell count is 4.5 to 6.3 million, and normal hematocrit is 40-52. Values for females are slightly lower. Structure of RBCs, p. 644 Figure 19.2 A red blood cell is a small, highly specialized disc -- thin in the middle and thicker around the edges. The shape and size of a red blood cell are extremely important because: 1. It gives each RBC a high surface-to-volume ratio, to quickly absorb and release oxygen. 2. It enables RBCs to form stacks, which smoothes the flow through narrow blood vessels. 3. It enables RBCs to bend and flex when entering small capillaries and branches. (A 7.8 micrometer diameter RBC can pass through a 4 micrometer capillary.) Because RBCs have no nuclei, mitochondria or ribosomes, they live only about 120 days. Hemoglobin, p. 644 Hemoglobin (Hb) is the protein molecule responsible for transporting respiratory gases. The normal hemoglobin value for adult males is 14-18 grams per deciliter of whole blood. Figure 19-3 Hemoglobin has a complex quaternary structure. Each of the 4 globular protein subunits contains a single molecule of heme. Each heme molecule contains a single iron ion which associates with oxygen to form oxyhemoglobin (a bright red pigment). Oxygen easily dissociates from the iron ion to become deoxyhemoglobin (a darker red pigment). Embryos contain a stronger form of hemoglobin called fetal hemoglobin, which can take oxygen from the mother’s hemoglobin. Each RBC can carry more than a billion molecules of oxygen bound to hemoglobin. When plasma levels of oxygen are low (in peripheral capillaries), the hemoglobin releases oxygen and binds carbon dioxide, forming carbaminohemoglobin, which is carried to the lungs. Several conditions may cause hematocrit or hemoglobin levels to fall below normal, producing anemia. RBC Formation and Turnover, p. 646 Figure 19-4 About 1% of circulating RBCs wear out and are replaced every day -- about 3 million RBCs per second. Macrophages of the liver, spleen and bone marrow monitor the condition of RBCs and try to engulf them before they rupture (hemolyze). If too much hemolysis occurs in the blood stream, the hemoglobin breaks down and is eliminated in the urine, causing hemoglobinuria. Kidney damage can cause whole red blood cells to appear in the urine (hematuria). Phagocytes break hemoglobin molecules down into their components, which are recycled: - the globular proteins are reduced to amino acids - the heme units lose their iron and become biliverdin (green) which is converted to bilirubin (yellow) (Bilirubin is excreted by the liver in bile. If bilirubin builds up, jaundice occurs.) - bacteria in the intestine convert bilirubin to compounds which (on exposure to oxygen) become urobilins and stercobilins, which color urine and feces - the iron is bound to proteins such as the plasma protein transferrin; excess iron is stored as feritin or hemosiderin Figure19-5 In adults, red blood cell production (erythropoiesis) occurs only in red bone marrow (myeloid tissue). The cell must pass through several stages of maturation to become a RBC: - hemocytoblasts (stem cells) in bone marrow divide to produce myeloid stem cells (which become RBCs) and lymphoid stem cells (which become lymphocytes) - myeloid stem cells differentiate into proerythroblasts - proerythroblasts mature in several stages, losing organelles and reducing in size to become a reticulocyte - reticulocytes are released into the blood steam and complete maturation The raw materials needed to build red blood cells include amino acids, iron and vitamins including B12, B6 and folic acid. Unavailability of vitamin B12 (due to diet or lack of absorption) results in pernicious anemia. Erythropoiesis is stimulated by hormones such as erythropoietin (EPO) or erythropoiesis stimulating hormone which appears when low oxygen levels (hypoxia) occur in peripheral tissues (due to any cause, including disease or high altitude). Table 19-1 lists blood tests used in clinical diagnosis. Key Red blood cells (RBCs) are the most numerous cells in the body. They remain in circulation approximately 4 months before being recycled; several million are produced each second. The hemoglobin inside RBCs transports oxygen from the lungs to peripheral tissues; it also carries carbon dioxide from those tissues to the lungs. Blood Types, p. 650 The body’s immune system identifies cells in the body as normal or foreign by substances on the surface of the cell called surface antigens. Normal cells are ignored, foreign cells are attacked. Your blood type is determined (genetically) by the presence or absence of specific surface antigens on the membrane of the RBC. The most important RBC surface antigens are A, B and Rh. Figure 19-6a The 4 basic blood types are: - A, which has only surface antigen A - B, which has only surface antigen B - AB, which has both antigens A and B - O, which has neither antigen Whichever antigens (also called agglutinogens) are on the surface of your RBCs, your immune system will identify as normal. However, your plasma carries antibodies that will attack (agglutinate) any blood cells with a different blood antigen. (i.e. Type A blood has Type B antibodies in the plasma; Type B blood has Type A antibodies; Type O blood has both A and B antibodies.) In addition, the blood can be either Rh positive (Rh+) or Rh negative (Rh-) depending on the presence or absence of the Rh antigen (also called the D antigen). Unlike the ABO system, type Rh- blood does not normally carry anti-Rh antibodies, unless the individual has been sensitized by previous exposure. The most common blood type is O+. Figure 19-6b Before a blood transfusion can be administered, it is important to determine if the blood types of the donor and recipient are compatible. If plasma antibodies meet their specific antigens, the blood will agglutinate and hemolyze in a cross-reaction or transfusion reaction. Figure 19-7 A blood-type test is performed to determine blood type and compatibility. Clumping occurs when the sample contains the specified surface antigens. In an emergency in which there is no time to cross-match for blood type, type O- blood may be administered, since it has neither Type A, Type B or Rh surface antigens. If time allows, a cross-match test is performed on the donor and recipient blood to confirm compatibility. V. White Blood Cells, p. 654 Objective: 1. Categorize the various white blood cells on the basis of their structures and functions and discuss the factors that regulate the production of each type. Unlike red blood cells, white blood cells (WBCs) or leukocytes have no hemoglobin, but they do have nuclei and other organelles. WBCs defend the body against pathogens, and they remove toxins, wastes and abnormal cells. Most WBCs are found in connective tissue proper or organs of the lymphatic system. Only a small number (6000 to 9000 per microliter) circulate in the blood. As WBCs circulate, they monitor the body and can leave the bloodstream to enter damaged areas. WBC Circulation and Movement, p. 654 Circulating WBCs have 4 characteristics: 1. All can migrate out of the bloodstream. 2. All are capable of amoeboid movement. 3. All are attracted to specific chemical stimuli (positive chemotaxis). 4. Some are capable of phagocytosis (neutrophils, eosinophils, and monocytes) Types of WBCs, p. 655 Figure 19-9 There are 5 major types of WBCs: 1. neutrophils 2. eosinophils 3. basophils 4. monocytes 5. lymphocytes Neutrophils (polymorphonuclear leukocytes) make up 50 to 70 % of all circulating WBCs. Their cytoplasm is packed with pale granules containing lysosomal enzymes and bacteria-killing compounds (hydrogen peroxide and superoxide anions). Neutrophils are very active and are generally the first to attack bacteria at the site of an injury. Neutrophils engulf pathogens and attack them with several types of chemicals including peptides called defensins which are obtained from lysosomes in the cytoplasm in a process called degranulation (removing granules from the cytoplasm). While digesting pathogens, neutrophils release prostaglandins that affect local capillaries, and leukotrienes that attract other phagocytes. The breakdown of used neutrophils in an infected wound forms pus. Eosinophils (acidophils) make up about 2-4 percent of circulating WBCs. Their main mode of attack is to excrete toxic compounds such as nitric oxide and cytotoxic enzymes, which are effective against parasites that are too large to engulf. Eosinophils are also sensitive to allergens and increase during allergic reactions. They control the spread of inflammation by releasing enzymes that counteract the inflammatory effects of neutrophils and mast cells. Basophils are small and make up less than 1% of circulating WBCs. They accumulate in damaged tissue and release histamine, which dilates blood vessels, and heparin, which prevents blood clotting. Monocytes are large, spherical cells that make up 2 to 8% of circulating WBCs. Monocytes enter peripheral tissues to become tissue macrophages which can engulf large particles and pathogens. They secrete substances that attract other immune system cells and fibroblasts to the injured area. Lymphocytes, slightly larger than RBCs, make up 20 to 30% of circulating WBCs. They migrate in and out of the blood, and spend most of their time in the body’s connective tissues and lymphatic organs. Lymphocytes are part of the body’s specific defense system. There are 3 functional classes of lymphocytes: 1. T cells (cell-mediated immunity) attack foreign cells directly 2. B cells (humoral immunity) differentiate into plasma cells which synthesize antibodies 3. Natural killer (NK) cells detect and destroy abnormal tissue cells such as cancers The Differential Count and Changes in WBC Profiles, p. 657 A differential count of circulating WBCs can detect characteristic changes in the WBC population that indicate pathogenic infections, inflammation and allergic reactions. - leukopenia is an abnormally low number of circulating WBCs - leukocytosis is an abnormally high number of circulating WBCs - extreme leukocytosis may indicate leukemia Table 19-3 shows the normal range for each type of WBC. Key White blood cells (WBCs) are usually outnumbered by RBCs by a ratio of 1000:1. WBCs are responsible for defending the body against infection, foreign cells, or toxins, and for assisting in the cleanup and repair of damaged tissues. The most numerous are neutrophils, which engulf bacteria, and lymphocytes, which are responsible for the specific defenses of the immune response. WBC Production, p. 657 Figure 19-10 All blood cells originate from hemocytoblasts, which produce myeloid stem cells and lymphoid stem cells. Myeloid stem cells differentiate into progenitor cells, which produce all of the WBCs except lymphocytes (which are produced by the lymphoid stem cells). All WBCs except monocytes develop fully in the bone marrow. (Monocytes develop into macrophages in peripheral tissues.) Some lymphoid stem cells migrate to peripheral lymphoid tissues (thymus, spleen and lymph nodes) which also produce lymphocytes (the process of lymphopoiesis). Four hormones called colony-stimulating factors (CSFs) help regulate certain blood cell populations: 1. M-CSF stimulates the production of monocytes. 2. G-CSF stimulates the production of granulocytes (neutrophils, eosinophils, and basophils). 3. GM-CSF stimulates the production of both granulocytes and monocytes. 4. Multi-CSF accelerates the production of granulocytes, monocytes, platelets and RBCs. Chemical communication between lymphocytes and other WBCs coordinate the immune response. Table 19-3 summarizes the formed elements of the blood. VI. Platelets, p. 660 Objective: 1. Describe the structure, function and production of platelets. In humans, platelets are cell fragments involved in the clotting system -- along with plasma proteins and cells of the vascular system. (Non-mammalian vertebrates have nucleated cells called thrombocytes.) Platelets circulate for 9-12 days before being removed by the spleen. About 1/3 of the body’s platelets are circulating, the rest are held in reserve for bleeding emergencies. Normal platelet concentration is 150,000 to 500,000 platelets per microliter. - thrombocytopenia is an abnormally low platelet count - thrombocytosis is an abnormally high platelet count The 3 main functions of platelets are: 1. The release of chemicals important to the clotting process. 2. The formation of a temporary patch in the walls of damaged blood vessels. 3. Active tissue contraction after clot formation has occurred. Platelet production (thrombocytopoiesis) occurs in bone marrow. Giant cells called megakaryocytes manufacture platelets by shedding cytoplasm packets until they are used up. The process is controlled by thrombopoietin (TPO), inteleukin-6 (IL-6), and multi-CSF. VII. Hemostasis, p. 661 Objective: 1. Discuss mechanisms that control blood loss after an injury, and describe the reaction sequences responsible for blood clotting. Hemostasis (the cessation of bleeding) consists of 3 phases: 1. the vascular phase 2. the platelet phase 3. the coagulation phase The Vascular Phase, p. 661 Figure 19-11a Cutting the wall of a blood vessel triggers a vascular spasm which contracts the diameter of the blood vessel at the site of the injury for about 30 minutes (the vascular phase). During the vascular phase: 1. The endothelial cells contract and expose the underlying basal lamina to the bloodstream. 2. The endothelial cells begin releasing chemical factors (ADP, tissue factor and prostacyclin) and local hormones (endothelins) that stimulate smooth muscle contraction and cell division. 3. The endothelial cell membranes become “sticky,” sealing off blood flow. The Platelet Phase, p. 661 Figure 19-11b In the platelet phase (within 15 seconds after injury) platelets attach to sticky endothelial surfaces, basal laminae and exposed collagen fibers (platelet adhesion). Many platelets stick together (platelet aggregation) to form a platelet plug that closes small breaks. Platelets arriving at an injury site become activated, releasing several compounds including: - adenosine diphosphate (ADP) which stimulates platelet aggregation - thromboxane A2 and serotonin which stimulate vascular spasms - clotting factors - platelet-derived growth factor (PDGF) which promotes vessel repair - calcium ions required for clotting The size of a platelet plug is limited to the immediate site of the injury by: 1. prostacyclin, which inhibits platelet aggregation 2. inhibitory compounds released by other white blood cells in the area 3. circulating enzymes that break down ADP 4. negative (inhibitory) feedback from high concentrations of serotonin 5. development of a blood clot which isolates the area The Coagulation Phase, p. 662 Figure 19-12a The coagulation phase does not begin until 30 seconds or more after the injury. Blood clotting (coagulation) involves a series of steps leading to the conversion of circulating fibrinogen into the insoluble protein fibrin. The fibrin network covers the platelet plug and traps blood cells, forming a blood clot that seals off the area. Normal blood clotting depends on the presence of clotting factors (procoagulants) in the plasma. Table 19-4 lists the 13 plasma clotting factors, including the calcium ion and 11 proteins. During the coagulation phase, enzymes and proenzymes react in chains or cascades that form 3 pathways: 1. the extrinsic pathway, which begins in the vessel wall, outside the blood stream 2. the intrinsic pathway, which begins with a circulating proenzyme within the bloodstream 3. the common pathway, where intrinsic and extrinsic pathways converge The extrinsic pathway begins with the release of Factor III or Tissue Factor (TF) by damaged cells. TF combines with a series of other compounds which activate Factor X, the first step in the common pathway. The intrinsic pathway begins with the activation of enzymes exposed to collagen at the injury site. Platelets release several factors (including PF-3) involved in a series of reactions that lead to the activation of Factor X. The common pathway begins with the activation of Factor X, forming the enzyme prothrombinase which converts the protein prothrombin to the enzyme thrombin. Thrombin converts soluble fibrinogen to insoluble fibrin. Thrombin stimulates blood clotting by: (1) stimulating the formation of tissue factor, and (2) stimulating the release of PF-3, which forms a positive feedback loop with the intrinsic and extrinsic pathways, accelerating clotting. A small puncture wound usually stops bleeding in 1-4 minutes (bleeding time). The body produces several substances that restrict clotting to the wound area, including: 1. anticoagulant plasma proteins (e.g. antithrombin-III, alpha-2macroglobulin) 2. heparin 3. protein C (activated by thrombomodulin) 4. prostacyclin Other factors essential to the clotting process are calcium ions and vitamin K. Once the clot has formed, platelets contract to pull the torn area together and stabilize it. This process (called clot retraction) takes about 30 to 60 minutes. Fibrinolysis, p. 664 Fibrinolysis is the process in which the clot slowly dissolves: 1. The proenzyme plasminogen is activated by the enzymes thrombin and tissue plasminogen activator (t-PA). 2. Plasminogen produces the enzyme plasmin, which digests the fibrin strands. Key Platelets are involved in the coordination of hemostasis (blood clotting). When platelets are activated by abnormal changes in their local environment, they release clotting factors and other chemicals. Hemostasis is a complex cascade that establishes a fibrous patch that can subsequently be remodeled and removed as the damaged area is repaired. SUMMARY In chapter 19 we learned: - the basic functions of the cardiovascular system - the 5 basic functions of blood - the division of whole blood into plasma and formed elements - the process of blood cell formation (hemopoiesis) - the 3 classes of plasma proteins (albumins, globulins and fibrinogen) - the structure and function of red blood cells - the structure and function of hemoglobin - the production and recycling of red blood cells - blood types - the structure and function of white blood cells - the 5 basic types of WBCs (neutrophils, eosinophils, basophils, monocytes, lymphocytes) - the differential blood count and disease - the production of white blood cells - the structure and function of platelets - the 3 phases of hemostasis (vascular, platelet, coagulation) and fibrinolysis