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Chapter 3 Blood Section 1 Blood components and its properties 生理教研室:潘敬运 教授 Functions of blood 1. Place of exchange of substances between interstitial fluid and external environment 2. Transport 3. Buffer function 4. To keep body temperature relatively constant 5. Hemostasis 6. Defense function 1. Components of blood plasma blood cells: red blood cells (erythrocytes) white blood cells platelets Blood volume: 70-80ml/Kg, 7-8% of body weight Hematocrit men is about 40~50%, women is about 37~48%. 2. Physical and chemical properties of blood (1) Specific gravity blood: 1.050~1.060. RBC number plasma: 1.025~1.030. Content of plasma proteins RBC:1.090 ~1.092. hemoglobin (2) Viscosity Viscosity of plasma is 1.2-1.3 times that of water, viscosity of whole blood is 2.4 times of plasma. Factors of affecting viscosity a. hemotocrit b. Shear rate Shear is a ratio of velocity difference of adjacent layers to distance between two fluid layers in laminar flow. (3) plasma osmolality — 313 mOsm/Kg H20. 1 gram mole of non-ionizable substance is equal to 1 osmole. If a substance ionizes into 2 ions, 0.5 gram mole of the substance equals 1 osmole. Osmotic pressure is determined by the number of particle, instead of the mass of the solute. The osmolal concentration of a solution is called its osmolality, expressed by osmole perKg. H20. At 37℃, 1 osmolality will cause 19300 mmHg osmotic pressure. Plasma osmolality is 0.313Osm /Kg. H20 0.313×19300 = 5330 mmHg Colloid osmotic pressure: maintain intra-and extracapillary water equilibrium Crystal osmotic pressure: maintain intra-and extracellular water equilibrium Isoosmotic solution hyperosmotic solution hypoosmotic solution Isotonic solution 4. RBC fragility. 0.42% NaCl solution--begin hemolysis 0.35%NaCl solution--complete hemolysis 5. Plasma pH 7.35-7.45 Section 2 Genesis of blood cells A. Genesis of blood cells (hemopoiesis) Section 3 Physiology of red blood cell 1. Number and shape of RBC. men, 5.0×1012 /L women 4.2×1012 /L Hemoglobin: men 150g/L women 140g/L Function of RBC: transport oxygen and carbon dioxide . 2. Physiologic characteristics of RBC (1) Permeability of RBC membrane (2) Flexibility of RBC (3) Suspension stability of RBC Rouleaux formation Erythrocyte sedimentation rate (ESR) men: 0-15mm/h woman: 0-20mm/h. ESR: fibrinogen, globulins, cholesterone ESR: albumin, lecithin. 3. Genesis and regulation of red blood cells CFU-GEMM BFU-E CFU-E Proerythroblast→ Basophil erythroblast →Polythromatophil erythroblast → Orthochromatic erythroblast → Reticulocyte → erythrocytes Maturation of red blood cell Vitamin B12 and folic acid are essential for the synthesis of DNA. Lack of either vitamin B12 or folic acid causes diminished DNA synthesis and consequently failure of nuclear maturation and division. Materials needed to production of RBC (1) Absorption of vitamin B12 Intrinsic factor combines with vitamin B12 in the following way: 1)The intrinsic factor binds to vitamin B12 2) intrinsic factor binds to specific receptor of ileal entocyte 3) Vitamin B12 is transported into blood. B12 binds to transcobalamine II marrow bone (2). Absorption of folic acid 蝶酰多谷氨酸 Pteroypolyglutamate (PteGlun) 蝶酰单谷氨酸 pteroyglutamate (PteGlu) 二氢叶酸还原酶 dihydrofolate reductase 刷毛缘水解酶 Brush border hydrolase (3) Iron Required amount 20-30mg/d Absorb 1mg iron from iron-containing food. 95% of required iron is from iron recycling. Fe excreted—0.6mg, 0.7mg in menses Iron-deficiency anemia or Microcytic hypochromic anemia Hemochromatosis 5. Regulation of RBC production CFU-GEMM BFU-E CFU-E Proerythroblast→ Basophil erythroblast →Polythromatophil erythroblast → Orthochromatic erythroblast → Reticulocyte → erythrocytes (1) Burst promoting activator (BPA) BFU-E BPA Go S (2) Deficiency oxygen increases the rate of RBC production. Erythropoietin(EPO): Glycoprotein. Site of formation of EPO: 80 to 90% EPO is formed in kidneys, remainder mainly in the liver. Effect of EPO on erythrogenesis. EPO stimulates production of proerythroblasts from hemopoietic stem cells in bone marrow. EPO causes these cells to pass more rapidly through different erythroblastic stages, speeding up production of new cells. 4. Destruction of red blood cells Life time 120 days Intravascular and extravascular Destruction. Hemolysis hemoglobin release Release iron bile pigment-bilirubin. C. Platelet Function: (1) Maintain integrity of vessel wall (2) Platelet activation and homeostasis Regulation of thrombocytopoiesis Platelets are formed from megakaryocytes in the bone marrow. normal value: 100 — 300X109/L. Half-life: 8 to 12 days. Receptor: Mpl, Proto-oncogen mpl Ligand: thrombopoietin TPO Effect: proloferation, differentiation, muturation and release Platelet contents: Dense granule: ADP, ATP, 5-HT, Ca2+ -granule: clotting factor, PDGF, fibrin- stabilizing factor, vW factor, fibrinogen contractile protein: Actin, myosin and thrombomsthenin Store of Ca2+ in endoplasmic reticulum Enzymes: synthesize PGs, phospholipase Membrane of platelets: glycoproteins, phospholipids, platelet factor 3 (PF3). Physical and chemical characteristics of platelets: Adhesion Aggregation Aggregation agents: ADP, thrombin, collagen, thromboxane A2 Primary aggregation: revesible Secondary aggregation: irreversible cAMP, IP3, Ca2+ , cGMP 1) ADP Dose dependent Primary agregation Secondary agregation ATP, Ca2+, fibrinogen 2)Thromboxane A2 (TXA2) Strong aggregation agent and vasoconstricyion Prostacyclin (PGI) Anti-aggregation and vasodilation 细胞膜磷脂 membrane phospholipids 磷脂酶A2 phosphlipase A2 花生四烯酸 arachidomic acid 环氧化酶 cyclooxygenase 前列环素合成酶 prostacyclin synthetase 血栓素合成酶 thromboxane synthetase 3) Collagen Secondary aggregation Release of ADP, TXA2 4) Thrombin Similar to ADP action, but no need of fibrinogen Release Platelets discharge granule contents into surrounding area. Release is energydependent and requires ATP. Release of contents of dense granule, granule and lysosome D. Events in homeostasis 1. Vascular constriction 2. Formation of platelet plug 3. Blood coagulation in ruptured vessel. Formation of blood clot. 4. Fibrous organization or dissolution of blood clot. Section 3 Blood groups and transfusion ABO blood groups Agglutinogens: Glycoprotein, A and B 4 major blood types: types A, B, AB and O. Agglutinins: natural body, IgM Anti-A Anti-B Summary of ABO blood system. Blood type O A1 (A,A1) A2 (A) B A1B A2 B Agglutinins in Plasma Anti-A, Anti-B Anti-B Anti-B, anti A1 Anti-A None Anti A1 Plasma agglutinates Red Cells of Type A1,A1B, B, A2B, A2 B, A1 B, A2B, B, A1 B, A2 B, A1, A1B, A2, A2B, None A1, A1B Rh group Rh factor named for rhesus monkey Antigen D, Rh-positive Anti-Rh agglutinin, immune antibody, IgG Blood typing across-matching RBC donor recipient plasma Incompatible blood type Transfusion reactions Type AB: “universal recipients” Type O: “universal donors”