LESSON PLAN Sheet 1



PART 1: BLOODIntroductionThe cardiovascular system is composed of three interrelated components: the heart, vessels, and blood.Blood is a liquid connective tissue that consists of cells and cell fragments surrounded by a liquid extracellular matrix (blood plasma).Blood contributes to homeostasis by transporting oxygen, carbon dioxide, nutrients, and hormones to and from body cells. It helps regulate body pH and temperature, and provides protection against disease through phagocytosis and the production of antibodies.Health-care professionals routinely examine blood to determine cause of different diseases. Hematology is the study of blood, blood-forming tissues, and the disorders associated with them.FUNCTIONS AND PROPERTIES OF BLOODObjectivesExplain the functions of blood.Describe the physical characteristics and principal components of blood.Blood FunctionsBlood transports oxygen, carbon dioxide, nutrients, wastes, and hormones.Blood helps regulate pH, body temperature, and water content of cells.Blood provides protection through clotting and by combating toxins and microbes through certain phagocytic white blood cells or specialized plasma proteins.Blood Physical characteristicsBlood’s physical characteristics include a viscosity greater than that of water, a temperature of 38oC, and a pH of 7.35 - 7.45.Blood’s color varies with its oxygen content. Blood is bright red when oxygenated and dark red when deoxygenated.Blood volume is 5 – 6L in adult males and 4 – 5L in adult females. The sex difference in volume is due to differences in body size.Blood ComponentsBlood is about 55% blood plasma and 45% formed elements (Figure 19.1).Blood plasma is a straw-colored liquid that consists of 91.5% water and 8.5% solutes. Principal solutes include proteins (albumins, globulins, and fibrinogen), nutrients, vitamins, hormones, respiratory gases, electrolytes, and waste products. Table 19.1 describes the chemical composition of plasma.Formed elements include red blood cells (RBCs; erythrocytes), white blood cells (WBCs; leukocytes), and platelets (Figure 19.2). RBCs constitute the largest portion of formed elements. Each microliter (μL) of blood contains about 5 million RBCs. A drop of blood is about 50 μL.The hematocrit is the percentage of total blood volume occupied by RBCs - a hematocrit of 42 indicates that 42% of the blood volume is composed of RBC’s.The average hematocrit for adult females is 42. For males, it is 47. Testosterone contributes to higher hematocrits in males because the hormone stimulates RBC synthesis.Clinical Connection. An abnormally low hematocrit indicates anemia. A significant increase in hematocrit indicates polycythemia.Clinical Connection. A complete blood count (CBC) is a test that screens for anemia and various infections. It usually includes counts of RBCs, WBCs, and platelets per μL of whole blood; hematocrit and differential white blood cell count. The amount of hemoglobin in grams per ml is also determined.FORMATION OF BLOOD CELLSObjectiveExplain the origin of blood cells.Hemopoiesis is the formation of blood cells from hemopoietic stem cells in red bone marrow (Figure 19.3).Myeloid stem cells form erythrocytes, platelets, granulocytes, and monocytes.Lymphoid stem cells give rise to lymphocytes.Several hemopoietic growth factors stimulate blood cell differentiation and proliferation.Erythropoietin stimulates RBC production.Thrombopoietin stimulates platelet formation.Cytokines (e.g. colony stimulating factors and interleukins) stimulate WBC production and activity.Clinical Connection. Bone marrow examination is a way to diagnose blood diseases like leukemia and severe anemias. Hemopoietic growth factors, available through recombinant DNA technology, hold great potential for use in patients who cannot form new blood cells (e.g. cancer patients who are undergoing chemotherapy).RED BLOOD CELLSObjectiveDescribe the structure, function, production, and life cycle of red blood cells.RBC Structure and FunctionMature RBCs are anucleate biconcave discs that contain hemoglobin (Figure 19.4).Hemoglobin constitutes about 1/3 of RBC weight and is composed of a globin protein and four heme groups. Many RBC functions are carried out by hemoglobin.Red blood cells perform 4 essential functions:Oxygen transport. The iron portion of a heme group binds oxygen for transport by hemoglobin.Carbon dioxide transport. Hemoglobin transports about 20% of total carbon dioxide (the remaining CO2 is dissolved in plasma or carried as bicarbonate ion).Blood flow regulation. Hemoglobin can stimulate vessel dilation through its storage or release of nitric oxide (NO). Vasodilation improves blood flow and enhances oxygen delivery to cells near the site of NO release.Carbonic acid production. RBCs contain carbonic anhydrase, which catalyzes the conversion of CO2 and water to carbonic acid, which in turn dissociates into H+ and bicarbonate ion (HCO3-). This reaction is significant for 2 reasons:It allows about 70% of CO2 to be transported in blood plasma in the form of HCO3-.It also serves as an important pH buffer in extracellular fluid.RBC Production: ErythropoiesisErythropoiesis begins in red bone marrow with the conversion of hemopoietic stem cells into proethyroblasts. Ultimately, they eject their nuclei, become reticulocytes, and enter the circulation at the rate of at least 2 million per second. Within 1 or 2 days, the reticulocytes develop into mature red blood cells.Clinical Connection. A reticulocyte count indicates the rate of erythropoiesis and is useful in diagnosing anemia.Erythropoiesis is regulated by negative feedback. The main stimulus is hypoxia, a decrease in the oxygen-carrying capacity of blood (Figure 19.6):Some stimulus disrupts homeostasis by decreasing blood-oxygen concentration.Kidney receptors detect low oxygen levels and secrete erythropoietin into blood.Erythropoietin increases the rate of erythropoiesis in red bone marrow.More reticulocytes enter the blood and mature into RBCs.Larger numbers of RBCs in circulation increase oxygen delivery to tissues.Kidney receptors detect the return to normal oxygen levels and stop secreting erythropoietin.RBC Life CycleErythrocytes live about 120 days. They are destroyed by macrophages and the hemoglobin is recycled (Figure 19.5):Fixed macrophages in the spleen, liver, and red bone marrow phagocytize worn-out RBCs.The globin and heme portions of hemoglobin are split apart.Globin is broken down into amino acids, which can be reused to synthesize other proteins.The iron in the heme portion is reclaimed and, through a series of steps, transported back to the red bone marrow where it can take part in RBC production again.The rest of the heme molecule is converted into bilirubin, which enters the blood and travels to the liver where it becomes a component of bile.In the large intestine, bacteria convert bilirubin into urobilinogen. Some urobilinogen is absorbed back into the blood and converted into the yellow pigment urobilin, which is excreted in urine.Most urobilinogen is converted into the brown pigment stercobilin, which eliminated in feces.WHITE BLOOD CELLSObjectiveDescribe the structure, functions, and life cycle of white blood cells. WBC Structure and FunctionLeukocytes are round nucleated cells that do not contain hemoglobin.WBCs are classified as either granular or agranular, depending on the visibility of chemical-filled cytoplasmic granules (Figure 19.7).Granular LeukocytesNeutrophils. 60-70% of all WBCs.Structure. About 2x size of RBC; nucleus has 2-5 lobes connected by thin strands of chromatin; cytoplasm has very fine, pale lilac granules.Function. Phagocytosis. Destruction of bacteria with lysozyme, defensins, and strong oxidants, such as superoxide anion, hydrogen peroxide, and hypochlorite anion.Clinical Significance. High count may indicate bacterial infection, burns, stress, or inflammation. Low count may indicate radiation exposure, drug toxicity, vitamin B12 deficiency, or systemic lupus erythematosus.Eosinophils. 2-4% of all WBCs.Structure. About 3x larger than an RBC; nucleus usually has 2 lobes connected by thick strand of chromatin; large red-orange granules fill cytoplasm.Function. Combat effects of histamine in allergic reactions; phagocytize antigen-antibody complexes; destroy certain parasitic worms.Clinical Significance. High count may indicate allergic reaction, parasitic infection, or autoimmune disease. Low count may indicate drug toxicity, stress, or acute allergic reaction.Basophils. 0.5-1% of all WBCs.Structure. Slightly larger than an RBC; nucleus has 2 lobes; large cytoplasmic granules appear deep blue-purple.Function. Similar in function to mast cells in skin; liberate heparin, histamine, and serotonin in allergic reactions that intensify overall inflammatory response.Clinical Significance. High count may indicate allergic reaction, leukemia, or cancer. Low count may indicate pregnancy, ovulation, or stress.Agranular LeukocytesLymphocytes. 20-25% of all WBCs.Structure. Small lymphocytes are about the size of an RBC, large lymphocytes are about the size of a neutrophil; nucleus is round or slightly indented; cytoplasm forms rim around nucleus that looks sky blue; the larger the cell, the more cytoplasm is visible. The functional significance of the size difference is unclear, but the distinction is clinically useful because an increase in the number of large lymphocytes indicates acute viral infection.Function. Mediate immune responses, including antigen-antibody reactions. B cells develop into plasma cells, which secrete antibodies (particularly effective against bacteria). T cells attack invading viruses, cancer cells, and transplanted tissue cells. Natural killer cells attack wide variety of infectious microbes and certain spontaneously arising tumor cells.Clinical Significance. High count may indicate viral infections, some leukemias, or infectious mononucleosis. Low count may indicate prolonged illness, HIV infection, immunosuppression, or cortisol treatment.Monocytes. 3-8% of all WBCs.Structure. About 4x larger than an RBC; nucleus is kidney- or horseshoe-shaped; cytoplasm is blue-gray and appears foamy.Function. Phagocytosis (after transforming into fixed or wandering macrophages); Take longer to reach site than neutrophils, but arrive in larger numbers and destroy more bacteria.Clinical Significance. High count may indicate viral or fungal infections, tuberculosis, some leukemias, or chronic disease. Low count may indicate bone marrow suppression or cortisol treatment.WBC Life CycleNormal blood contains 5,000-10,000 leukocytes/ μL.Leukocytosis refers to an increase in the number of WBCs. It is a normal response to stresses such as invading organisms and strenuous exercise. Leukopenia refers to an abnormally low number of WBCs. It is never beneficial, and may be caused by shock, radiation, and chemotherapy.Most WBCs live for only a few hours or a few days. Some lymphocytes can live for years.WBCs leave the blood stream to combat inflammation and infection.WBCs leave the blood stream by emigration and collect at sites of pathogen invasion or inflammation (Figure 19.8). The chemical attraction of WBCs to a disease or injury site is termed chemotaxis.Once granular leukocytes and monocytes emigrate, they never return to the bloodstream. Lymphocytes continually recirculate – only 2% of the total lymphocyte population is circulating in the blood; the rest are in lymphatic fluid and organs such as the skin, lungs, lymph nodes, and spleen.PLATELETS ObjectiveDescribe the structure, function, production, and life cycle of platelets. Platelet Structure and FunctionPlatelets are disc-shaped cell fragments containing granules, but no organelles. The granules contain chemicals that, once released, promote blood clotting.Normal blood contains 150,000-400,00 platelets/ μL. About 1/3 of all platelets are sequestered in the spleen.Platelets help stop blood loss from damaged vessels by forming a platelet plug.Platelet ProductionUnder the influence of thrombopoietin, myeloid stem cells develop into megakaryoblasts, which transform into megakaryocyte. Megakaryocytes fragment into platelets (Figure 19.3).Platelet Life cyclePlatelets have a life span of about 10 days; aged and dead platelets are removed by fixed macrophages in the spleen and liver.HEMOSTASISObjectivesDescribe the three mechanisms that contribute to hemostasis.Explain the various factors that promote and inhibit blood clotting.Hemostasis is a series of carefully controlled responses that stops bleeding. It involves vascular spasm, platelet plug formation, and blood coagulation (clotting).When successful, hemostasis prevents hemorrhage – large volume blood loss.Vascular SpasmIn vascular spasm, the smooth muscle of a vessel wall contracts slow blood loss. Spasm is probably caused by damage to the smooth muscle, by substances released from activated platelets, and by reflexes initiated by pain receptors.Platelet Plug FormationPlatelet plug formation involves the aggregation of platelets to stop bleeding (Figure 19.9). Platelet plug formation occurs as follows:Platelet adhesion – platelets stick to damaged endothelium and exposed collagen of a vessel.Platelet release reaction – Platelets stuck to the damaged vessel release several chemicals essential to hemostasis and repair: Liberated ADP and thromboxane A2 activate nearby platelets. Serotonin and thromboxane A2 cause and sustain vascular spasm. Platelet-derived growth factor stimulates proliferation of vascular endothelial cells, vascular smooth muscle fibers, and fibroblasts to help repair the damaged vessel.Platelet aggregation – Other platelets are attracted by ADP released in step 2. Accumulation and attachment of large numbers of platelets to the damaged vessel form a platelet plug.Blood ClottingA blood clot is a network of insoluble protein fibers (fibrin) that traps formed elements (Figure 19.10).Clinical Significance. Clotting in an unbroken blood vessel is called thrombosis. A thrombus (clot), bubble of air, fat from broken bones, or piece of debris transported by the bloodstream that moves from its site of origin is called an embolus.The chemicals involved in clotting are known as clotting factors. Their synthesis often requires vitamin K (K stands for “koagulationsvitamin” in German). Vitamin K deficiency can cause uncontrolled bleeding.Blood clotting involves a cascade of reactions (Figure 19.11):Formation of prothrombinase via extrinsic or intrinsic pathways.Conversion of prothrombin into thrombin via the common pathway.Conversion of fibrinogen into fibrin, and clot retraction.Many blood-clotting reactions require Ca2+ (clotting factor IV). Calcium deficiency can cause uncontrolled bleeding.The Extrinsic PathwayThe extrinsic pathway gets its name from the fact that it is initiated by tissue factor (thromboplastin), which leaks into the blood from damaged cells outside blood vessels. The pathway involves a cascade of reactions that ultimately form prothrombinase:Tissue factor begins a sequence of calcium-dependent reactions that ultimately activate clotting factor X (thrombokinase).Factor X combines with factor V (proaccelerin) in the presence of Ca2+, forming prothrombinase.The extrinsic pathway occurs rapidly – within seconds if the trauma is severe.The Intrinsic PathwayThe intrinsic pathway gets its name from the fact that its activators are either in direct contact or contained within blood; tissue damage is not needed. The pathway involves a cascade of reactions that ultimately form prothrombinase:Damaged endothelial cells, exposed vascular collagen fibers, and damaged platelets begin a sequence of calcium dependent reactions, ultimately activating clotting factor XII (Hageman factor).Factor XII initiates a sequence of reactions requiring calcium and phospholipids from activated platelets, eventually activating clotting factor X.Factor X combines with factor V in the presence of Ca2+, forming prothrombinase.The intrinsic pathway occurs more slowly than the extrinsic pathway, usually requiring several minutes.The Common PathwayThe common pathway gets its name from the fact that it is initiated by prothrombinase, the end product of both extrinsic and intrinsic pathways. It involves a cascade of reactions that ultimately form thrombin:Prothrombinase and Ca2+ catalyze the conversion of prothrombin (clotting factor II) into thrombin.Thrombin and Ca2+ catalyze the conversion of the soluble protein fibrinogen (clotting factor I) into insoluble fibrin threads.Thrombin also activates clotting factor XIII (fibrin-stabilizing factor), which strengthens and stabilizes the fibrin threads into a sturdy clot.Thrombin has 2 positive feedback effects on hemostasis:It acts on clotting factor V to accelerate the formation of prothrombinase in both extrinsic and intrinsic pathways.It activates platelets, which strengthens platelet plug formation and releases platelet phospholipids. Recall that platelet phospholipid is involved in the activation of clotting factor X in the intrinsic pathway.Clot RetractionNormal coagulation is followed by clot retraction. Fibrin threads in the clot contract as platelets pull on them. As the clot tightens, the edges of the damaged vessel are pulled closer together. Permanent repair of the blood vessel can then take place. In time, fibroblasts form connective tissue in the ruptured area, new endothelial cells repair the vessel lining, and fibrinolytic mechanisms break down the clot.Prevention of Inappropriate Blood Clot FormationBecause hemostasis involves positive feedback loops that amplify coagulation, the prevention of inappropriate blood clot formation is essential. Several mechanisms are involved:In addition to dissolving clots at a site of damage once the damage is repaired, the fibrinolytic system breaks down inappropriate clots. An important component of this system is plasmin, which dissolves clots by digesting fibrin and inactivating coagulation factors.Prostacyclin, produced by endothelial cells and WBCs, inhibits thromboxane A2 and platelet plug formation.Anticoagulants in the blood (e.g. antithrombin and heparin) block thrombin formation.Clinical Significance. At low doses aspirin inhibits vasoconstriction and platelet aggregation thereby reducing the chance of thrombus formation. Thrombolytic agents (e.g. streptokinase or tissue plasminogen activator) can be injected into the body to dissolve clots that have already formed. BLOOD GROUPS AND BLOOD TRANSFUSIONS ObjectivesDistinguish between the ABO and Rh blood groups.Explain why it is important to match donor and recipient blood types before administering a transfusion.RBC plasma membranes are studded with a genetically determined assortment of antigens. Blood is categorized into different groups based on the presence or absence of antigens. The major blood groups are ABO and Rh.ABO Blood GroupThe ABO blood group is based on 2 antigens with unknown functions called A and B (Figure 19.12).Type A blood contains RBCs with only antigen A (42% of Canadians).Type B blood contains RBCs with only antigen B (9% of Canadians).Type AB blood contains RBCs with antigen A and antigen B (3% of Canadians).Type O blood contains RBCs with neither antigen A nor antigen B (46% of Canadians).Blood plasma usually contains antibodies that react with A or B antigens. Type A blood plasma contains anti-B antibodies.Type B blood plasma contains anti-A antibodies.Type AB blood plasma does not contain anti-A or anti-B antibodies.Type O blood plasma contains both anti-A and anti-B antibodies.Although agglutinins appear in the blood within a few months after birth, the reason for their presence is not clear. Perhaps they are formed in response to bacteria that normally inhabit the GI tract.Because the antibodies are large IgM-type antibodies that do not cross the placenta, ABO incompatibility between a mother and her fetus rarely causes problems.Rh Blood GroupThe Rh blood group is based on the presence or absence of an antigen with unknown function. Individuals whose RBCs have Rh antigens (labeled D) are classified as Rh+. Those who lack the antigen are Rh-.Normally, blood plasma does not contain anti-Rh antibodies. If an Rh- person is exposed to Rh+ blood, their immune system will begin to produce anti-Rh antibodies. Subsequent exposure to Rh+ blood will cause severe problems.Clinical Significance. Hemolytic disease of the newborn can occur if the fetus has Rh+ blood and the mother produces anti-Rh antibodies. The disorder is treatable, but also preventable.Blood TransfusionBlood is the most easily and commonly shared of human tissues. In Canada, over 400 000L of blood are transfused every year.Knowledge of blood type is essential to safe blood transfusion – an incompatible blood transfusion can cause kidney failure and death.Donor blood cannot be transfused into recipients who have blood antibodies against donor blood antigens. Donor-recipient ABO blood group compatibility is summarized in Table 19.6.A can only receive blood from A and O.B can only receive blood from B and O.AB can receive blood from A, B, AB, and O; AB is the universal receiver.O can only receive blood from O; O is the universal donor.PART 1: BLOODreview questionsWhat are the functions of the cardiovascular system? _______________________________________________________________________________What are the main components of the cardiovascular system? _______________ __________________________________________________________What are the main components of blood? _______________________________________________________________________________________Where are blood cells manufactured? ________________________________Name three kinds of hemopoietic growth factors. __________________________________________________________________________________What are the main functions of a red blood cell? ___________________________________________________________________________________What is erythropoiesis? ___________________________________________________________________________________________________Which parts of hemoglobin are recycled and reused? ______________________Which white blood cells are agranular? _______________________________Which white blood cell is normally the most prevalent? ____________________What are three platelet functions? ____________________________________________________________________________________________What are the three steps of hemostasis? ________________________________________________________________________________________What are the three main steps of blood clotting? __________________________________________________________________________________Which antigen(s) and antibody(s) are found in type A blood? ________________ ................
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