What will we discuss in this chapter? (Outline) I. Blood composing II. Physical and chemical characteristics of blood III. Blood Cells 1. Hemopoietic process and hemopoietic stem cells 2. Hemopoietic microenvironment 3. Erythrocyte Physiology 4. Leukocyte Physiology 5. Platelet or Thrombocyte Physiology IV. Physiological Hemostasis 1. Physiological Characteristics of Platelet 2. Blood Coagulation 3. Fibrinolysis What will we discuss in this chapter? (Outline) V. Blood Group 1. RBC Agglutination 2. ABO blood group system 3. Rh blood group system 4. Relation between blood volume and clinic 5. Principle of Transfusion and Cross-match test I. Blood composing • Blood composing: plasma + blood cells • Hematocrit: blood cells occupies the percentage of total blood volume. normal value male: 40-50% female: 37-48% newborn: 55% Blood component Chemical component of plasma • Water: > 90% • Small molecule: 2%, it is electrolytes, nutriment, metabolic products, hormone, enzyme, etc. • Protein: 60-80 g/L, plasma protein include albumin (40-50 g/L), globulin (20-30 g/L,α1-, α2, β-, γ- ) and fibrinogen. • Most of albumin and globulin made from liver. • A/G and clinic. Chemical component of plasma • Function of plasma protein: (1) transportation, (2) nutrition, (3) forming colloid osmotic pressure, (4) coagulation and anticoagulation, (5) pH value buffer, (6) immunity (globulin) Chemical component of plasma H2O 90 - 91% Plasma 血浆 Interstitial fluid Intracellular fluid 组织液 细胞内液 Na+ 142 145 12 Cl- 104 117 4 Ca++ 2.5 2.4 <0.001 K+ 4.3 4.4 139 PO4- 2 2.3 29 Protein 蛋白质 14 0.4 54 (Unit:mmol/L) II. Physical and chemical characteristics of blood • Specific gravity: – total blood (1.050-1.060) more influenced by red blood cells; – plasma (1.025-1.030) more influenced by plasma protein; – RBC (1.090-1.092) more influenced by Hb. II. Physical and chemical characteristics of blood • Viscosity: – Blood relative viscosity (4~5) mainly depends on the numbers of red blood cells. – Plasma relative viscosity (1.6~2.4) is mainly involved in plasma protein II. Physical and chemical characteristics of blood • Plasma osmotic pressure is 300 mmol/L or 770kPa (1) Crystal osmotic pressure results from NaCl and modulates water distribution between inside and outside of cells. (2) Colloid osmotic pressure results from albumin and regulates water distribution between inside and outside of capillary. II. Physical and chemical characteristics of blood • Plasma pH value is about 7.35~7.45, and • usually buffer systems are: – NaHCO3/H2CO3 (20:1), protein salt/protein, – Na2HPO4/ NaH2PO4, – Hb salt/Hb, HbO salt/ HbO2, – K2HPO4/ KH2PO4, etc – [lungs and kidney mainly regulate Plasma pH value ]. Osmosis and Osmotic Pressure • Osmosis is the movement of water down its concentration gradient. • Osmosis is determined by the number of impermeable molecules. • Osmotic pressure is the force drawing water down its concentration gradient. Osmosis and Osmotic Pressure A B Water [Water] > [Water] [Salt] < [Salt] Osmotic Pressure < Osmotic Pressure Osmosis is the movement of water from a high concentration to a low concentration. In this illustration, two compartments (A and B) are separated by a semipermeable membrane (broken vertical line). The water concentration in compartment A is greater than the concentration in compartment B because of the presence of salt (X) in B. Therefore, water will move down its concentration gradient from A to B. The force needed to prevent this water movement is called osmotic pressure. Tonicity • The tonicity of a solution refers to the effect of the solution on cell volume. • A hypertonic extracellular solution is one in which the water concentration is less outside the cell than inside; water leaves the cell; cell volume decreases. • An isotonic extracellular solution is one in which the water concentration is the same inside and outside the cell; no water movement; cell volume does not change. Tonicity • A hypotonic solution is one in which the water concentration is greater outside than inside the cell; water enters the cell; cell volume increases. • An isosmotic solution may not be an isotonic solution if the particles are permeable to the cell membrane. III.Blood Cells Blood cells are erythrocyte (red blood cell, RBC), leukocyte (white blood cell, WBC) and thrombocyte (platelet, P). 3.Erythrocyte Physiology Shape and number of red blood cells (RBC) • Shape of RBC: like biconcave disc Its diameter is about 7~8 µm, peripheral thickness about 2.5 µm, central thickness about 1 µm and cubage about 90 µm3. Reason for shape of RBC biconcave disc like Erythrocyte Physiology Number of RBC: It is most numbers in the blood. Normal value about RBC Male adult, 4.5~5.5×1012/L; average, 5.0×1012/L Female adult, 3.8~4.6× 1012/L; average, 4.2×1012/L Newborn, ≥ 6.0×1012/L Protein within RBC is hemoglobin (Hb). Hb in male adult, 120~160 g/L; Hb in female adult, 110~150 g/L; Hb in newborn (within 5 days), ≥ 200 g/L Pregnant female, numbers of RBC and Hb are relatively less (because of more plasma). Dweller lived in plateau, numbers of RBC and Hb are relatively more (because of compensation for anoxia). Physiological Characteristics and Functions of RBC ① Characteristics of RBC Permeability: semi permeable membrane, gas and urea freely passing through, negative ions easily in or out of RBC, and positive ions not. There are Na-K ATPase as pump on the membrane of RBC and lowtemperature-stored plasma easily has high kalium. Why? ② Plasticity and metamorphose: Plasticity and metamorphose depend on: 1) surface area-cubage ratio, 2) viscosity of Hb, 3) membrane elasticity and viscosity. Physiological Characteristics and Functions of RBC Characteristics of RBC ③ Suspension stability: it cab be described by erythrocyte sedimentation rate (ESR) which is RBC descending distance per hour and suspension stability is inverse proportion to ESR. Normal value of ESR: male, 0~15 mm/h; female, 0~20 mm/h. ESR and clinic: some diseases bring about rouleaux formation (mainly involved in plasma component, e.g. globulin, fibrinogen, cholesterol) and speed up ESR. Physiological Characteristics and Functions of RBC Characteristics of RBC ④ Osmotic fragility: Changes in RBC put into lower osmotic salty solution. Osmotic fragility of aged RBC is large and easily results in rupture (hemolysis and ghost cell). Isosmotic solution, e.g. 0.85% NaCl, 1.4%NaHCO3, 5% glucose, etc. Isotonic solution, e.g. 0.85% NaCl Isosmotic solution does not equal to isotonic solution. Isosmotic solution, isotonic solution and clinic Physiological Characteristics and Functions of RBC Functions of RBC • • RBC can be used for transportation of O2 and CO2 in the blood. RBC can be served as pH buffer. Erythropoiesis • Hemopoietic material for erythropoiesis: iron (Fe++) and protein, [reason for anemia] • Influencing factors of RBC maturity: Vitamin B12 and folic acid (DNA metabolism), [clinic relation] • Process of erythropoiesis: Hemopoietic stem cells→multi systemic hemopoietic progenitor cells→RBC-committed progenitor cells (BFU-E→CFU-E)→original RBC→ earlier infantile RBC→medium-term infantile RBC→terminal infantile RBC→reticular RBC→mature RBC→blood for circulation. This process requires 6~7 days. [mitosis several times] [apoptosis] Place for Erythropoiesis Main place for Erythropoiesis is bone marrow. Aother place is liver. Regulation of Erythropoiesis • 0.8% of total RBCs has self renewal, that is to say, 160×106 RBC production every minute. • Burst forming unit-erythroid, BUF-E, important to earlier erythropoiesis, depends on stimulation of burst promoting activity, BPA outside body. BPA made by leucocyte is a glycoprotein whose molecular weight is about 25000~40000 • Colony forming unit-erythroid, CFU-E, important to terminal erythropoiesis, depends on erythropoietin, EPO which is also a glycoprotein, molecular weight, 34000, plasma concentration 10 pmol/L, half life 5 hours, increasing release when anoxia. Regulation of Erythropoiesis Life and breakage of RBC • Life-span: 120 days, about 4 months, each RBC circulates 27 km averagely in vessels, short life-span for aged RBC • Breakage: places are liver, spleen and lymphatic node, and after breakage, Hb released from RBC immediately combine with plasma α2-globulin (Hb touched protein) which is taken in by liver for iron reuse. • Hb, very toxic if it get into blood, normally, it can be metabolized into bile pigment in liver. • Clinic relation. Physiological Changes in Numbers of Leukocyte • Newborn: Number is higher, 15×109/L, after birth 3 or 4 days to 3 months, being about 10×109/L, mainly, neutrophil, 70%; secondarily, lymphocyte. • Circadian changes: Number of WBC is more in the afternoon than in the morning. • Food taking, ache and mood excitation: Number of WBC is remarkably higher. • Heavy exercise and laboring: Increasing numbers, about 35×109/L, return to original level after action stop. • Terminal pregnancy of female: Numbers changes in 12~17×109/L, and during parturition, 34×109/L, and after parturition 2~5 days, number return to original level. Normal Value and Function of Platelet • Normal value: 100×109 ~ 300×109, range from 6%~10% • Normal changes: more number in the afternoon than in the morning, more in winter than in spring, more in the venous blood than capillary, after sport↑, pregnacy↑. • *Functions: 1. It maintains capillary endothelial cells smooth and integrated (repairing endothelium and providing nutrition). 2. It is involved in physiological hemostasis. • Platelet and clinic relation: decrease of platelet, abnormal immune reaction, will results in hemorrhage or bleeding, purpuric symptom. Life- Span and Breakage of Platelet • Life-span: Averagely, 7~14 days in the blood. It can be consumed when it displays physiological functions. • Breakage: Aged platelet can be processed by phagocytosis in liver, spleen and lymphatic node. Physiological Hemostasis Blood Clotting Factor Factor Name Plasma Concentration Synthesizing site Half life Chromsome site I Fibrinogen 3000 Liver 4~5 d 4 II Prothrombin 100 Liver (with Vit K) 3 d 11 III Tissue factor Endothelial cell IV Ca2+ 100 V Proaccelerin 10 Endothelial cell, platelet 12~15 h 1 Ⅶ Proconvertin 0.5 Liver (with Vit K) 4~7 h 13 Ⅷ Antihemophilic factor,AHF 0.1 Liver 8~10 h Ⅹ Ⅸ Plasma thromboplastic 5 Liver (with Vit K) 24 h Ⅹ component,PTC(Christmas factor) Ⅹ Stuart-Prower Factor 10 Liver (with Vit K) 2d 13 Ⅺ Plasma thromoboplastin 5 Liver 2~3 d 4 antecedent,PTA Ⅻ Contact factor or Hageman factor 40 Liver 24 h 5 XIII Fibrin-stabilizing factor 10 Liver, platelet 8d 6,1 - High-molecular weight 80 Liver 3 kininogen,HMW-K - Prekallikrein,Pre-K or Fletcher factor 35 Liver 4 - Body sites to palpate pulse Fig. 19.11 Principles of Animal Physiology Circulatory Systems Circulatory Fluids • Blood Cell Production (Hemopoiesis) 1) Erythrocytes (continued): Disorders • Anemia – blood has abnormally low oxygen-carrying capacity – It is a symptom rather than a disease itself – Blood oxygen levels cannot support normal metabolism – Signs/symptoms include: • fatigue, paleness, shortness of breath, and chills • Types – Hemorrhagic anemia – result of loss of blood – Hemolytic anemia – prematurely ruptured RBCs – Aplastic anemia – destruction/inhibition of red bone marrow – Iron-deficiency anemia results from lack of iron – Pernicious anemia results from either deficiency of vitamin B12 or lack of intrinsic factor needed for absorption of B12 Treatment is intramuscular injection of B12 – Thalassemias – absent or faulty globin chain in Hb – Sickle-cell anemia – results from a defective gene & causes RBCs to become sickle-shaped in low oxygen situations 2) Leukocytes (continued): Granulocytes • Granulocytes – neutrophils, eosinophils, and basophils – Are larger and usually shorter-lived than RBCs – Have lobed nuclei – ALL are phagocytic cells • Three types A. Neutrophils B. Eosinophils C. Basophils Neutrophils Eosinophils Basophil 2. Leukocytes (continued): Agranulocytes • Agranulocytes – Lack visible cytoplasmic granules – Are similar structurally, but are functionally distinct and unrelated cell types • Two types: – A. Lymphocytes – B. Monocytes: Lymphocyte Monocyte Summary of Formed Elements Table 17.2.1 Summary of Formed Elements Table 17.2.2 Physiological Factors Affecting Red Cell Count * Age: it is high in newly born infants and low in old individuals * Sex: it s higher in males than in females for two reasons: a. androgens stimulate the production of RBC b. women lose blood via menstration * High altitude 41