Chapter 17: CVS The Blood Student Note

Objectives

Overview: Blood Composition and Functions 1. Describe the composition and physical characteristics of whole blood. Explain why it is classified as a connective tissue. 2. List eight functions of blood.

Blood Plasma 3. Discuss the composition and functions of plasma.

Formed Elements 4. Describe the structure, function, and production of erythrocytes. 5. Describe the chemical composition of hemoglobin. 6. Give examples of disorders caused by abnormalities of erythrocytes. Explain what goes wrong in each disorder. 7. List the classes, structural characteristics, and functions of leukocytes. 8. Describe how leukocytes are produced. 9. Give examples of leukocyte disorders, and explain what goes wrong in each disorder. 10. Describe the structure and function of platelets.

Hemostasis 11. Describe the process of hemostasis. List factors that limit clot formation and prevent undesirable clotting. 12. Give examples of hemostatic disorders. Indicate the cause of each condition.

Transfusion and Blood Replacement 13. Describe the ABO and Rh blood groups. Explain the basis of transfusion reactions. 14. Describe fluids used to replace blood volume and the circumstances for their use.

Diagnostic Blood Tests 15. Explain the diagnostic importance of blood testing.

Developmental Aspects of Blood 16. Describe changes in the sites of blood production and in the type of hemoglobin produced after birth. 17. Name some blood disorders that become more common with age.

Suggested Lecture Outline

I. Overview: Blood Composition and Functions (pp. 632–633; Fig. 17.1) A. Components (p. 632; Fig. 17.1) 1. Blood is a specialized connective tissue consisting of living cells, called formed elements, suspended in a nonliving fluid matrix, blood plasma. Lacks collagen & elastin but has fibrin for clotting. 2. Blood that has been centrifuged separates into three layers: erythrocytes, the buffy coat, and plasma.  Erythrocytes: (“Red”) RBCs which transport oxygen. 45% of total volume of blood sample (aka. Hematocrit or blood fraction)  Buffy Coat: Leukocytes (“white”) = body defense; Platelets: cell fragments to stop bleeding. Both = less than 1% blood volume.  Plasma: inorganic fluid; = 55% whole blood. 3. The blood hematocrit represents the percentage of erythrocytes in whole blood. Normal values: healthy males: 47% + or – 5%; females: 42% + or – 5% B. Physical Characteristics and Volume (p. 632) 1. Blood is a slightly basic (alkaline) (pH = 7.35–7.45) fluid that has a higher density and viscosity (5X more) than water, due to the presence of formed elements. Metallic taste; Temp: ~100.4oF 2. Normal blood volume in males is 5–6 liters (1.5 gal.), females: 4–5 liters (1.2 gal.) C. Functions (pp. 632–633) 1. Distribution: Blood is the medium for delivery of oxygen and nutrients, removal of metabolic wastes to elimination sites (lung & kidneys), and distribution of hormones (endocrine system). 2. Regulation: Blood aids in regulating body temperature (thermoregulation), body fluid pH (buffer – bicarbonate ions), and fluid volume (blood proteins) within fluid compartments. 3. Protection: Blood protects against excessive blood loss (platelets) through the clotting mechanism and from infection (antibodies, complement proteins, & WBCs) through the immune system. II. Blood Plasma (p. 633; Table 17.1) A. Blood plasma is straw-colored, sticky, and consists of mostly water (90%) and solutes including nutrients, gases, hormones, wastes, products of cell activity, ions (electrolytes), and proteins (p. 633; Table 17.1). Scan QR Code for Normal Blood Values 1.Water (solvent)– dissolving & suspending solutes; absorb heat 2.Solutes a. Electrolytes – helps maintain osmotic pressure & pH b. Plasma Proteins – 8% of plasma (g); osmotic pressure, water balance and transport materials b.i. Albumin – most common protein; produced by liver; blood buffer & osmotic pressure (Acidosis) b.ii. Globulin – α & β: produced by liver; transport: lipids, metal ions, & fat-soluble vitamins. ϒ (gamma): antibodies via plasma cells during immune response b.iii. Fibrinogen - produced by liver; forms fibrin for clotting 3. Nonprotein Nitrogenous Substances: b-products of cellular metabolism (urea, uric acid, creatinine, ammonium salts) a. Nutrients: carbs, proteins, lipids, & vitamins

b. Respiratory gases: O2 & CO2 c. Hormones: Steroids & thyroid hormones III. Formed Elements (pp. 634–646; Figs. 17.2–17.12; Table 17.2) – blood “cells” (WBCs are true cells); 3 major types Most live for few days; don’t divide & are continuously replaced by stem cells locates in RBM. A. Erythrocytes (Red Blood Cells) (pp. 634–640; Figs. 17.2–17.8; Table 17.2) 1. Erythrocytes, or RBCs, are strong, flexible (spectrin), small cells that are biconcave in shape, lack nuclei (anucleated) & most organelles, and contain mostly * hemoglobin (Hb); antioxidants enzymes – rid free radicals. a. The size and shape of erythrocytes provide a *larger surface-to-volume ratio for gas exchange. b. The lack of organelles and anaerobic ATP synthesis means that erythrocytes *do not consume any oxygen they carry. *contribute to gas transport

2. Erythrocytes function to transport respiratory gases (O2 & CO2) in the blood on hemoglobin. Makes RBCs red

carries most O2 in the body. a. The normal range for hemoglobin in the blood is 13–18 g/100 ml (males) 12-16g/100ml (females). 3. Hemoglobin is a protein consisting of four polypeptide chains, globin proteins ( α&β), each with a ring-like heme. Hb can transport 4 molecules of O2 revesibly. Hb contained in RBCs prevents from:  breaking into frgments in bloodstream  making blood more viscous & raising osmotic pressure a. Each heme contains an atom of iron that serves as the binding site for a molecule of oxygen. b. Oxygen diffuses into the blood in the lungs and binds to hemoglobin, forming bright red oxyhemoglobin. c. At body tissues, oxygen detaches from iron, forming dark red deoxyhemoglobin. d. About 20% of the carbon dioxide carried in the blood is bound to amino acids on the globins, forming carbaminohemoglobin. 4. Production of Erythrocytes a. Hematopoiesis, or blood cell formation, occurs in the red bone marrow (Blood Sinusoids – network of reticular tissue with immature blood cells, macrophages, fat cells, & reticular cells on capillaries). Where is RBM located in adults vs. children? b. All blood cells form from a common hematopoietic stem cell (HSC), the hemocytoblast (aka: pluripotent stem cell). c. Erythropoiesis, the formation of erythrocytes, begins when a myeloid stem cell is transformed to a proerythroblast, which progresses through several successive stages. d. During the first two phases of development, hemoglobin is synthesized, and iron accumulates. After accumulating all its hemoglobin, the reticulocyte (immature erythrocyte) ejects most organelles, the nucleus degenerates, and the cell assumes its biconcave shape. Fig. 17.5: (HSC) hemocytoblast myeloid stem cell  proerythroblast  Basophilic erythroblast  Polychromic erythroblast  Orthochromtic  reticulocyte (ejects nucleus) Erythrocyte e. The hematopoietic process takes about 15 days, at which time the reticulocyte enters the bloodstream, where it becomes a fully mature, oxygen-carrying cell within two days. Reticulocytes = 1-2% of all erythrocytes in healthy people (Reticular count – rough indication of RBC formation) 5. Erythrocyte production ( Erythropiesis ) is controlled by the hormone erythropoietin (EPO), produced mostly by the kidneys (& liver) when certain kidney cells become hypoxic (oxygen deprivation). (HIF: hypoxia- Inducible Factor) (Refer to Figure 17.5) HST to Reticulocyte takes 15 days; Erythrocytes mature in 2 days. a. Erythropoietin production is triggered by excessive loss of RBCs or reduced availability of oxygen. ( Fig: 17.7 p. 638) Ex. hemorrhage, RBC destruction, Fe deficiency, decreased oxygen (high altitudes), testosterone b. Decreased EPO d/t too many RBCs, excessive oxygen, renal dialysis. EPO injections: athlete hematocrit 45% to 65% = clots, stroke or heart failure when dehydrated. 6. Dietary requirements for erythrocyte formation include iron (stored in liver, spleen, & bone marrow as

ferritin & hemosiderin; transported by transferrin) , vitamin B12 & folic acid (DNA synthesis) , as well as proteins, lipids, and carbohydrates . 7. Blood cells have a life span of 100–120 days due to the lack of nuclei and organelles. Unable to synthesize proteins, grow or divide). Go to spleen “RBC Graveyard” 8. Destruction of dead or dying blood cells is accomplished by macrophages in the spleen, which split the heme from the globin, break globins down to amino acids (recycled), bind iron as hemosiderin or ferritin, and convert the remainder of the heme to bilirubin, to be eliminated by the liver  urobilinogen  stercobilin (feces) & female thru menstration. 9. Erythrocyte Disorders: D/t blood loss, decreased RBC production & RBC destruction. a. Anemias are characterized by a deficiency in RBCs that may originate from several causes: Individuals are fatigued, pale, short of breath, & chilled. 1. Blood loss: i. Hemorrhagic anemia - resulting from excessive blood loss. Can be chronic or acute. 2. Decreased RBC production i. Iron-deficiency - usually results from hemorrhagic anemia or inadequate intake of iron-sources; mi

crocytes. TX: increase Fe intake. TX: B12 injections or gel iI. Pernicious - autoimmune disease often affect elderly. Stomach damage intrinsic factor cells,

necessary for B12 absorption, results in macrocytes. iii. Renal anemia resulting from a lack of EPO, which leads to underproduction of erythrocytes. TX: synthetic EPO 3. RBC destruction i. Hemolytic anemias in which erythrocytes are prematurely destroyed. Ex: Hb abnormlities, transfusion mismatch, infections. ii. Thalassemias, inherited mc Mediterranean ancestery, characterized by an abnormality in one or more globin chains that compromises the oxygen-carrying ability of RBCs. iii. Sickle-cell anemia, in which hemoglobin changes shape when oxygen levels are low, causing “sickle-shaped” cells to rupture easily and block small blood vessels. S/SX: gasping for air, extreme pain, infection, and stroke. TX: blood transfusion, nitric oxide. Affiliated with malaria belt b. Polycythemia (hematocrit over 65% to ~80%) is characterized by an excess of RBCs due to oxygen deficiency or disease, which may increase blood viscosity, causing poor blood flow and oxygen delivery. i. Secondary polycythemia: d/t high altitude. Blood doping – athletes induce polycythemia to increase oxygen-carrying capacity. Watch this video to see doctors discuss the dangers of blood doping in sports. What are the some potential side effects of blood doping? B. Leukocytes (White Blood Cells) (pp. 640–645; Figs. 17.9–17.12; Table 17.2) 1. Leukocytes, or white blood cells, are the only formed elements that are complete cells and make up less than 1% of total blood volume. 2. Leukocytes are critical to our defense against disease, (against bacteria, virus, parasites, toxins, & tumor cells) and can leave the blood to enter the tissues, a process called diapedesis, and move through the tissue by amoeboid movement. Assists in inflammatory response & triggered by cell adhesion molecules displayed by endothelial cells. a. Leukocytes exhibit positive chemotaxis, pinpoint areas of tissue damage by following chemical trails of molecules from damaged cells, to migrate toward areas of tissue damage and infection. b. Leukocytosis, a white blood cell count of over 11,000, is characteristic as a consequence of an infection. 3. Granulocytes (BEN) are a main group of leukocytes characterized as large cells with lobed nuclei and visibly staining granules; all are phagocytic. Most to least abundant ( N ever L et M onkeys E at B ananas) a. Neutrophils, 50–70% (most common) of all leukocytes, are chemically attracted to sites of inflammation and are active phagocytes. Nucleus = 3-6 lobes aka. PMNs (polymorphonuclear Leukocytes). Active against acute bacterial infection (ex: meningitis & appendicitis); “defensins – form “spears” that pierce holes in foe. b. Eosinophils - 2–4% of all leukocytes, attack parasitic worms ex: flatworms (tapeworm & flukes) & roundworms (pinworms & hookworms) usully ingested by raw fish. Located in loose connective tissues. Have a role in asthma & allergies. “old fashioned telephone” nucleus. c. Basophils are the rarest leukocyte, 0.5–1% of all WBCs, and release histamine to promote inflammation = vasodilator; Ig E; similar to mast cells (located in CT)  Granulocytes are stored in BM (10X more than blood) production ratio vs RBCs = 3:1. Life span 0.25-9 days) 4. Agranulocytes are lymphocytes & monocytes that lack visibly staining granules. a. Lymphocytes comprise 5%+ of all WBCs and are found throughout the body (associated w/ lyph tissue: lymph nodes, spleen, etc.)—but relatively few are found in the blood. i. T lymphocytes directly attack virus-infected & tumor cells ii. B lymphocytes  plasma cells produce antibodies. b. Monocytes make up 3–8% of all WBCs, become actively phagocytic macrophages as they enter tissues, & activate T lymphocytes. Defend against viruses, certin intracellular bacterial parasites, & chronic infections like TB. Distinctive U or kidney shaped nucleus. 5. Production and Life Span of Leukocytes a. Leukopoiesis, the formation of white blood cells, is regulated by the production of interleukins and colony-stimulating factors (CSF). b. Leukopoiesis involves differentiation of hemocytoblasts along two pathways: lymphoid stem cells that give rise to lymphocytes (B & T) and myeloid stem cells that give rise to all other WBCs. c. Monocytes have a life span of a few months, while lymphocytes live for months to years. 6. Leukocyte Disorders a. Leukopenia is an abnormally low white blood cell count, possibly due to drugs, such as glucocorticoids or anticancer drugs. b. Leukemias are cancerous conditions in which clones of a single white blood cell remain unspecialized and divide out of control. Results in overproduction of leukocytes. Different types: named by cell type (myeloid or lymphocytic) & whether acute (children) or chronic (elderly). S/Sx: severe anemia, bleeding, fever, weight loss, & bone pain. TX: stem cell transplants. c. Infectious mononucleosis (aka: kissing disease) is a disease caused by the Epstein-Barr virus, characterized by excessive numbers of agranulocytes (leukocytes). Highly contagious. And most common in young adults. S/Sx: tired, achy, chronic sore throat & low-grade fever. C. Platelets (pp. 645–646; Fig. 17.12) 1. Platelets are not complete cells, but fragments of large cells called megakaryocytes, and have a short life span of around 10 days because anucleated. 2. Platelets are critical to the clotting process, forming the temporary seal when a blood vessel breaks. 3. Thrombopoietin is a hormone that regulates the formation of platelets. 4. Platelets are formed by repeated mitoses of megakaryocytes without cytokinesis. 5. Platelets enter the blood when a megakaryoblast sends cytoplasmic extensions through a sinusoid wall, ruptures, and releases platelets. IV. Hemostasis (pp. 646–651; Figs. 17.13–17.15; Table 17.3) A. A break in a blood vessel stimulates hemostasis, a fast, localized response to reduce blood loss through clotting B. Step 1: Vascular spasms are the immediate vasoconstriction response to blood vessel injury and become more efficient with increased tissue damage (p. 646). C. Step 2: Platelet Plug Formation (pp. 646–647; Fig. 17.13) 1. When endothelium is damaged, platelets become sticky and spiky, adhering to each other and the damaged vessel wall. 2. Once attached, other platelets are attracted to the site of injury, activating a positive feedback loop for clot formation. D. Step 3: Coagulation, or blood clotting, is a multistep process in which blood is transformed from a liquid to a gel (pp. 647–649; Figs. 17.13–17.15; Table 17.3). 1. Factors that promote clotting are called clotting factors, or procoagulants; those that inhibit clot formation are called anticoagulants. Most clotting factors are produced by the liver 2. The clotting process involves three phases: formation of prothrombin activator, conversion of prothrombin to thrombin, and the formation of fibrin mesh from fibrinogen in the plasma. 3. There are two pathways to the formation of prothrombin activator: a. The intrinsic pathway so named because all factors necessary are present within the blood, is a slower clotting pathway and may be triggered by negatively charged surfaces, such as activated platelets, collagen, or glass. b. The extrinsic pathway is triggered through an endothelium-derived protein factor, called tissue factor (TF) or factor III ( produced by tissue cells), and can occur very rapidly. 4. Thrombin catalyzes the reactions that convert fibrinogen to fibrin, which forms strands that form the structure of a clot. E. Step 4: Clot Retraction & Fibrinolysis (p. 649) 1. Clot retraction is a process in which the contractile proteins within platelets contract and pull on neighboring fibrin strands, squeezing plasma from the clot and pulling damaged tissue edges together. 2. Repair is stimulated by platelet-derived growth factor (PDGF). 3. Fibrinolysis removes unneeded clots through the action of the fibrin-digesting enzyme, plasmin. F. Factors Limiting Clot Growth or Formation (p. 649) 1. Two mechanisms limit the size of clots as they form: a. Rapidly moving blood disseminates clotting factors before they can initiate a clotting cascade. b. Activated clotting factors are inhibited. 2. Thrombin that is not bound to fibrin is inactivated by antithrombin III and protein C, as well as heparin. (natural anticoagulant contained in basophil & mast cell granules as well as surface of endothelium; inhibits intrinsic pathway) 3. As long as the vascular endothelium is smooth and intact, platelets are prevented from clotting. Nitric oxide & prostacyclin. G. Disorders of Hemostasis (pp. 650–651) 1. Thromboembolic disorders result from conditions that cause undesirable clotting, such as roughening of vessel endothelium, slow-flowing blood, or blood stasis. a. A clot that forms and persists in an unbroken vessel is called a thrombus and, if large enough, may block blood flow to tissues. b. A thrombus that breaks away from a vessel wall is called an embolus, which may become lodged in a small diameter vessel, also restricting blood flow. 2. Anticoagulant drugs, such as aspirin, heparin, and warfarin, are used clinically to prevent undesirable clotting. 3. Bleeding disorders arise from abnormalities that prevent normal clot formation. a. Thrombocytopenia is a deficiency in circulating platelets and may result from any condition that suppresses or destroys red bone marrow. Results from BM malignancy, ionizing radition, certain drugs. Petechiae – small purplish spots on skin b. Impaired liver function results in a lack of synthesis of procoagulants, which may be due to a shortage of vitamin K, or diseases such as hepatitis or cirrhosis. c. Hemophilia is a genetic condition that results in a deficiency of factors VIII (antihemophilic factor), IX, or XI. X-linked; occurs mostly in males TX: blood transfusions or injections of clooting factors. 4. Disseminated intravascular coagulation (DIC) is a situation leading to widespread clotting throughout intact vessels and may occur as a complication of pregnancy, septicemia, or incompatible blood transfusions. V. Transfusion and Blood Replacement (pp. 651–653; Fig. 17.16; Table 17.4) A. Transfusion of whole blood is routine when blood loss is substantial or when treating thrombocytopenia 1. Humans have different blood types based on specific antigens, called agglutinogens, on RBC membranes. 2. At least 30 groups of RBC antigens occur in humans, but the ABO and Rh antigens cause strong transfusion reactions. a. ABO blood groups are based on the presence or absence of two types of heritable agglutinogens: type A, and type B. b. Preformed antibodies (agglutinins) are present in blood plasma and are of the opposite type as the individual’s blood. 3. The Rh factor is a group of RBC antigens that are either present in Rh+ blood or absent in Rh– blood. a. Rh antibodies form in Rh – individuals only after exposure to the Rh antigen. 4. A transfusion reaction occurs if the agglutinogens in donor blood type are attacked by the recipient’s blood plasma agglutinins, resulting in agglutination (RBC clumping) & hemolysis (RBC lysis) of the donor cells. Problems: 1) transferred blood cannot transport oxygen 2) clumped RBCs hinder flow in small vessels = acute renal failure. a. Since group O blood contains no A or B antigens, it is the universal donor type; the AB blood group has neither A nor B antibodies in the plasma and can potentially receive any ABO blood type—the universal recipient. 5. Blood typing involves determination of possible transfusion reactions prior to transfusion between the donor and recipient blood types. Cross matching. B. Blood volume expanders are given in cases of extremely low blood volume (p. 653). 1. Isotonic salt solutions, such as Ringer’s solution, mimic the normal electrolyte concentrations of plasma. 2. Plasma expanders mimic the osmotic properties of albumin in the blood, but actually provide no benefit over electrolyte solutions. VI. Diagnostic Blood Tests (pp. 653–654) A. Changes in some of the visual properties of blood can signal diseases such as anemia, heart disease, and diabetes (p. 653). B. Differential white blood cell counts are used to detect differences in relative amounts of specific blood cell types (pp. 653–654). C. Prothrombin time, which measures the amount of prothrombin in the blood, and platelet counts evaluate the status of the hemostasis system (p. 654). D. SMAC, and a complete blood count (CBC) give comprehensive values of the condition of the blood (p. 654). VII. Developmental Aspects of Blood (p. 654) A. Prior to birth, blood cell formation occurs within the fetal yolk sac, liver, and spleen, but by the seventh month, red bone marrow is the primary site of hematopoiesis (p. 654). B. Fetal blood cells form hemoglobin F, which has a higher affinity for oxygen than adult hemoglobin, hemoglobin A (p. 654). After birth, liver rapidly destroys fetal RBCs.

Homeostatic Imbalances: Recombinant EPO Blood Doping Hematopoietic Hormones Leukopenia Leukemias Infectious Mononucleosis DIC Thrombi vs. Emboli Anticoagulant Drugs Thrombocytopenia Impaired Liver Function Hemophilias Erythroblastosis fetalis *Blood Chemistry Test *Blood Fraction *Bone Marrow Biopsy *Exchange transfusion *Hematology *Hematoma *Hemochromatosis *Myeloproliferative D/O *Plasmapheresis *Septicemia *At the Clinic p. 657