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Department of Physiology, Medical School, Soochow University, Suzhou 215123, China
E-mail:email@example.com Tel:0512-62096158; 13506212030
I. 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. Endocrine functions of vessel endothelial cells 2. Physiological Characteristics of Platelet 3. Blood Coagulation 4. Fibrinolysis 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
What will we discuss in this chapter? (Outline) Blood composing
Blood and Internal Environmental Homeostasis
Blood is that part of extracellular fluid within the cardiovascular system Blood forming During animals’ evolution, extracellular fluid was gradually shaped from the age-old time with ocean which was mainly salty solution. At last, extracellular fluid was differentiated into plasma and interstitial fluid and blood came from plasma and cells. The role of blood in internal environmental homeostasis Blood, the most active component in extracellular fluid, display functions as follows:
(1) (2) (3) (4)
transportation; pH value buffer; temperature or thermal maintenance; immunity and defence
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 (summing-up) .
Terminology and normal value .
Most of albumin and globulin made from liver. (3) forming colloid osmotic pressure. metabolic products. Protein: 60-80 g/L. it is electrolytes.α1-. plasma protein include albumin (40-50 g/L). β-. (5) pH value buffer. A/G and clinic. globulin (20-30 g/L. γ. (4) coagulation and anticoagulation. hormone. (2) nutrition.etc. nutriment. α2. (6) immunity (globulin) .Chemical component of plasma Water: > 90% Small molecule: 2%. Function of plasma protein: (1) transportation. enzyme.) and fibrinogen.
4 4.5 4.3 2 14 145 117 2.91% Plasma 血浆 Interstitial 组织液 fluid Intracellular 细胞内液 fluid Na+ ClCa++ K+ PO4Protein 蛋白质 142 104 2.4 2.Chemical component of plasma H 2O 90 .4 12 4 <0.3 0.001 139 29 54 (Unit：mmol/L) .
Plasma pH value is about 7. KHCO3/H2CO3. Hb salt/Hb. and usually buffer systems are NaHCO3/H2CO3 (20:1).092) more influenced by Hb. Plasma relative viscosity (1.060) more influenced by red blood cells.4) is mainly involved in plasma protein 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.030) more influenced by plasma protein. .35~7. (2) Colloid osmotic pressure results from albumin and regulates water distribution between inside and outside of capillary. Viscosity: Blood relative viscosity (4~5) mainly depends on the numbers of red blood cells. Na2HPO4/ NaH2PO4. RBC (1.050-1.025-1. etc [lungs and kidney mainly regulate Plasma pH value ]. HbO salt/ HbO2. plasma (1. Physical and chemical characteristics of blood Specific gravity: total blood (1.45.II.6~2. K2HPO4/ KH2PO4. protein salt/protein.090-1.
Osmosis is determined by the number of impermeable molecules. Osmotic pressure is the force drawing water down its concentration gradient. .Osmosis and Osmotic Pressure Osmosis is the movement of water down its concentration gradient.
Therefore. 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. . water will move down its concentration gradient from A to B. In this illustration.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. The force needed to prevent this water movement is called osmotic pressure.
cell volume increases. cell volume decreases. A hypertonic extracellular solution is one in which the water concentration is less outside the cell than inside. cell volume does not change. water enters the cell. An isotonic extracellular solution is one in which the water concentration is the same inside and outside the cell. no water movement.Tonicity The tonicity of a solution refers to the effect of the solution on cell volume. water leaves the cell. An isosmotic solution may not be an isotonic solution if the particles are permeable to the cell membrane. . A hypotonic solution is one in which the water concentration is greater outside than inside the cell.
P). . leukocyte (white blood cell. RBC). WBC) and thrombocyte (platelet.Blood Cells Blood cells are erythrocyte (red blood cell.III.
g.ilium.Blood Cells The forming processes of erythrocyte (red blood cell. skull and long bone ending) rather than yellow marrow has hematopoietic functions. vertebra. RBC). e. spleen↓ (after fourth embryo month) → marrow (fetus birth time) and liver. Transfer of blood cells forming place: yolk sac hemopoiesis (early embryo period) → liver and spleen (second embryo month) → marrow↑and liver. WBC) and thrombocyte (platelet. . leukocyte (white blood cell. spleen as complementary role. red marrow (flat bones. sternum. During adulthood (after 18). rib. P) originating from hematopoietic stem cells are hemopoiesis.
Stage two: committed progenitors directional differentiation (CFU-GEMM. Hemopoietic process and hemopoietic stem cells Hemopoietic process Stage one: Hemopoietic stem cells self renewal.forming unit Stage three: precursors morphologic occurrence of various original blood cells. CFU- GM. steady numbers.1. active differentiation. . CFU-TB). CFU-MK. CFU-E. [CFU: colony.
Multi. Hemopoietic stem cells produce about 1×1011 blood cells releasing to blood for use. Lin: systemic specific antigen on the hemopoietic cells. Surface sign According to CFU (colony forming unit). using fluorescence-activated cell sorting (FACS). constant from young to old age. .Hemopoietic stem cells Basic characteristics Self renewal in high degree. its main surface sign is CD34+CD38-Lin-and CD34-CD38-Lin-. Note CD: cluster of differentiation of antigen on the white blood cells.directional differentiation Large potential proliferation.
endothelial cell.2. such as collagen (typeI. another is membrane-combined adhesive molecule. hyaluronic acid and sulfate dermatin. reticulocyte. engulfing cell. III. II. Stromal cells supply two material: one is soluble hemopoietic growth factor. ectoblast cell. Stromal cells in the marrow come from fibrocyte. laminin. sulfate heparin. IV). hemopoieticnectin ) and protein amylose (sulfate cartilagetin. . monocyte. etc). glycoprotein (fibronectin.Hemopoietic microenvironment Hemopoietic microenvironment: It includes stromal cell secreting extracellular matrix (ECM). hemopoietic nerves and blood vessels. Extracellular stroma synthesized and secreted by marrow stromal cell filling cellular interstice contains big molecules. Hemopoietic cells must adhere to stromal cell and is in the hemopoietic microenvironment for survival. osteoblast and osteoclast. multihemopoietic regulating factor.
Hemopoietic process .
Hemopoietic process .
Hemopoietic process .
Erythrocyte Physiology Shape and number of red blood cells (RBC) Shape of RBC: like biconcave disc Its diameter is about 7~8 µm.3.5 µm. . peripheral thickness about 2. central thickness about 1 µm and cubage about 90 µm3.
Reason for shape of RBC biconcave disc like .
numbers of RBC and Hb are relatively more (because of compensation for anoxia). Hb in female adult. Hb in male adult.0×1012/L Protein within RBC is hemoglobin (Hb).8~4. 3. numbers of RBC and Hb are relatively less (because of more plasma). average. .6× 1012/L. 110~150 g/L. 4. Dweller lived in plateau.0×1012/L Female adult.5~5. average. Hb in newborn (within 5 days). 4.5×1012/L. 120~160 g/L. ≥ 200 g/L Pregnant female.Erythrocyte Physiology Number of RBC: It is most numbers in the blood. Normal value about RBC Male adult. 5.2×1012/L Newborn. ≥ 6.
Physiological Characteristics and Functions of RBC
① Characteristics of RBC Permeability: semipermeable membrane, gas and urea freely passing through, negative ions easily in or out of RBC, and positive ions not. There are NaK ATPase as pump on the membrane of RBC and low-temperature-stored plasma easily has high kalium. Why? 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
④ Characteristics of RBC 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.
[clinic relation] Process of erythropoiesis: Hemopoietic stem cells→multi systemic hemopoietic progenitor cells→RBC-committed progenitor cells (BFU-E→CFUE)→original RBC→ earlier infantile RBC→medium-term infantile RBC→terminal infantile RBC→reticular RBC→mature RBC→blood for circulation.Erythropoiesis Hemopoietic material for erythropoiesis: iron (Fe++) and protein. This process requires 6~7 days. [mitosis several times] [apoptosis] . [reason for anemia] Influencing factors of RBC maturity: Vitamin B12 and folic acid (DNA metabolism).
. Aother place is liver.Place for Erythropoiesis Main place for Erythropoiesis is bone marrow.
EPO which is also a glycoprotein. CFU-E. BUF-E.Regulation of Erythropoiesis 0. half life 5 hours. . important to terminal erythropoiesis. BPA outside body. 160×106 RBC production every minute. depends on stimulation of burst promoting activity. 34000. BPA made by leucocyte is a glycoprotein whose molecular weight is about 25000~40000 Colony forming unit-erythroid. plasma concentration 10 pmol/L. important to earlier erythropoiesis. molecular weight. that is to say. Burst forming unit-erythroid.8% of total RBCs has self renewal. depends on erythropoietin. increasing release when anoxia.
Regulation of Erythropoiesis .
each RBC circulates 27 km averagely in vessels. Clinic relation. very toxic if it get into blood. spleen and lymphatic node. and after breakage. about 4 months.Life and breakage of RBC Life-span: 120 days. . Hb released from RBC immediately combine with plasma α2-globulin (Hb touched protein) which is taken in by liver for iron reuse. Hb. it can be metabolized into bile pigment in liver. normally. short life-span for aged RBC Breakage: places are liver.
eosinophil. monocyte and lymphocyte.0~10)×109/L Classification: It is granulocyte (neutrophil. WBC): (4. .Leukocyte Physiology Classification and numbers of Leukocyte Number of Leukocyte (white blood cells.4. basophil).
04~0.5 Neutrophil (foliiform nucleus) Eosinophil Basophil Monocyte Lymphocyte 2.1 0.Classification and numbers of Leukocyte TABLE.5~5 0~1 3~8 20~40 For Clinic Use Percentage (%) Neutrophil (bacilliform nucleus) 0.12~0.0~7.0 .8~4.0~10.8 0.0 1~5 50~70 0.02~0. Classification and normal value of Leukocyte Absolute Value (×109/L) Total numbers of leukocytes 4.5 0.0 0.0~0.
return to original level after action stop. and during parturition. mainly. number return to original level. after birth 3 or 4 days to 3 months. and after parturition 2~5 days. 15×109/L. ache and mood excitation: Number of WBC is remarkably higher. 70%. secondarily. . Terminal pregnancy of female: Numbers changes in 12~17×109/L.Physiological Changes in Numbers of Leukocyte Newborn: Number is higher. about 35×109/L. 34×109/L. neutrophil. Circadian changes: Number of WBC is more in the afternoon than in the morning. being about 10×109/L. Food taking. Heavy exercise and laboring: Increasing numbers. lymphocyte.
toxin.Physiological Characteristics and Functions of WBC Terminology Diapedisis: Metamorphosed WBCs pass through vessel wall getting into interstitial fluid. Chemotaxis: It is a process that WBCs shift to some chemical material (metabolic production. etc). bacteria. WBC Diapedisis Blood Vessel Metamorphose . Phagocytosis: It is a process that WBCs enclose and engulf exotic or extraneous material. and use intracellular enzyme digesting them. antigen-antibody complex.
Physiological Characteristics and Functions of WBC ① Neutrophil Another name. PMN. Clinic relation: Number of neutrophil greatly increase occurring in acute inflammation and earlier time of chronic inflammation. such as bacteria. virus. . etc. diapedisis. 6~8 h in the vessels. number decrease of neutrophil will result in poor resistibility and easily suffering from infection. polymorphonuclear. chemotaxis and phagocytosis (using its hydrolyzed enzyme) Function: It plays a very important role in nonspecific cellular immunity system which is against pathogenic microorganism. parasite.
Physiological Characteristics and Functions of WBC ② Eosinophil Circadian changes: Its number is lower in the morning and higher at night. It is involved in immune reaction against worm with opsonization. It limits and modulates the effects of basophil on fast allergic reaction. Clinic relation: Its number increase when person suffers from parasite infection or allergic reaction. . 2. Function: 1.
. Histamine and chronic reactive material increase permeability of capillary and contract bronchia smooth muscle. chemotactic factors and chronic reactive material for allergic reaction. Heparin serves as lipase cobase and speeds up fatty decomposition. Eosinophil chemotactic factor A released by basophil can attract eosinophil collection and modify eosinophil function. histamine. 2. 3.Physiological Characteristics and Functions of WBC ③ Basophil Circulatory time: 12 hours Basogranules contain heparin. 1. Function: It is also involved in allergic reaction. asthma. and result in allergic reaction such as measles.
etc. such as colony stimulating factor (CSF). TNFα.β . Monocyte. it change name called macrophage activating monocyte. As soon as monocytes get into tissue from blood . Cytokins induced by monocyte may modulate other cells growth. IL-6. . INF-α. IL-1. It contains many nonspecific lipase and displays the powerful phagocytosis.macrophage system to release many cytokins. 3.Physiological Characteristics and Functions of WBC ④ Monocyte Its body is large. diameter about 15~30 µm without granule Function: 1.macrophage system plays a very important role in specific immune responsive induction and regulation. IL-3. 4. 2.
B. 2. T.Lymphocytes involved in humoral immunity.Physiological Characteristics and Functions of WBC ⑤ Lymphocyte Classification: It can be separated into T. Function: 1.Lymphocyte and B. Lymphocytes serve as a nuclear role in immune responsive reaction.Lymphocyte. Clinic relation: Numbers increase of lymphocytes occur in . 3.Lymphocytes involved in cellular immunity.
Colony stimulating factor. HGF which are glycoprotein secreted by lymphocyte. fibrous cell and endothelial cell. Leukocyte breakage: site are liver. G-CSF. originating from hemopoietic stem cells. and leukopoiesis process is similar to RBC. Multi-CSF (IL-3) also influence Leukopoiesis. such as GM-CSF. CSF. Pus or purulence forming . Regulation and Breakage Birth place: bone marrow. differentiation and growth are influenced by hemopoietic growth factor. M-CSF. monocytemacrophage. Life span: several hours to 3 or 4 days.Leukopoiesis. Leukopoiesis. spleen and lymphatic node.
Dense body: It contains ADP. lysin peroxide enzyme. Ca2+.etc. Complicated structure: under the electronic microscope.etc. Source: Platelet comes from megakaryocyte fractionlet release in the marrow. dense body. 5-HT. there are α-granule. opening tubular system. ATP. average cubage 8 µm3.Platelet or Thrombocyte Physiology Shape: Biconvex disk like. epinephrine. canaliculus. dense tubular system.5. . diameter about 2~4 µm.
pregnacy↑. abnormal immune reaction.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. purpuric symptom. Platelet and clinic relation: decrease of platelet. It is involved in physiological hemostasis. *Functions: 1. after sport↑. more in the venous blood than capillary. 2. more in winter than in spring. will results in hemorrhage or bleeding. . It maintains capillary endothelial cells smooth and integrated (repairing endothelium and providing nutrition).
originating from hemopoietic stem cells. and into megakaryocyte. then continuously into CFU-MK.Platelet Forming and Regulation Platelet forming: Birth place is bone marrow. Mpl. megakaryocyte and platelet. and its ligand named thrombopoietin. BFU-MK. (one megakaryocyte can produce 200~7700 platelet). expressed by c-mpl (oncogene) exists in CD34+ located at hemopoietic stem cells/ committed progenitors. TPO was discovered in 1994 which promoted hemopoietic stem cells differentiating into megakaryocyte as hemopoietic stem cells positive regulating factor. found by Methin in 1993. and differentiating into burst forming unitmegakaryocyte. DMS. demarcation membrane system. Regulation: Protein. . into fractionlet release to the blood requiring 8~10 days.
Life. .Span and Breakage of Platelet Life-span: Averagely. Breakage: Aged platelet can be processed by phagocytosis in liver. spleen and lymphatic node. 7~14 days in the blood. It can be consumed when it displays physiological functions.
Process of hemostasis: 1. aggregation. TXA2. thromboxane A2.IV. fibrin. Platelet thrombosis forming (made by platelet adhesion. Normal time is 1~3 min and it is longer when platelet decrease. clot forming and maintenance (made by blood coagulation activation) . Physiological Hemostasis *Definition: The process from vessel bleeding to automatic hemostasia. release and contraction) 3. Blood vessel contraction or convulsion (induced by neuroreflex. 5-hydroxytryptamine. ET ) 2. endothelin.5-HT. *Bleeding time: The time from vessel bleeding to automatic hemostasia.
Physiological Hemostasis .
plasminogen activator (PA). IV). thrombomomodulin (TM). protein enzyme inhibitor. TNFα. elastin. adhesive amylose. protein C. protein enzyme. vWF. PGI2. collagen (III. blood clotting factor V. etc. fibronectin. laminin. ectonectin. tissue-type plasminogen activator (tPA). plasminogen activator inhibitor (PAI-1. NO). Promoting coagulative material: Tissue factor. von Willebrand factor (vWF). uPA. etc.1.Endocrine functions of vessel endothelial cells ① Material related to hemostasis are basal membrane. ATIII. ② ③ ④ . PAI-2. Vessel constricting and relaxing modulators: endothelin1 (ET-1). interleukin-1 (IL-1). endothelium-derived relaxing factor (EDRF or nitric oxide. Anticoagulative material: They are prostacyclin (PGI2). EDRF (NO). microfibril. ATIII). ADPase. heparin sulfate.
As soon as collagen expose to blood. At the same time. ② ③ . lasting about 60 sec. ET-1. etc) making vessel convulsion. Stimulated vessel endothelial cells release coagulative factors and Promoting coagulative material to realize. hemostasis of platelet is immediately activated to form thrombus blocking wounded vessels. speed up blood coagulation. 5-HT. Platelet activation can releases constrictive factors (TXA2. cells also release anticoagulative factors and fibrinolysis material to modify blood coagulation. collagen) and blood.Roles of Vessel Endothelial Cells in Physiological Hemostasis Roles are close related to its endocrine functions ① Vessel endothelium serves as barrier between underendothelial structure (namely.
Inactive Platelet Under the electronic microscope .
Activated Platelet for Hemostasis Under the electronic microscope .
fibrinogen and energy consumption. tissue hydrolyzed enzyme from lysosome. thrombin sensitive protein from α-granule.etc and by pathological factors like bacteria. Ca2+↑. histamine. The process can be separated into two phases: phase one is reversible aggregation and phase two irreversible aggregation. Thrombocyte aggregation: induced by physiological factors such as ADP.2. collagen. Ip3↑. PDGF. Mechanism: Exposed collagen+vWF →vWF changes →platelet membrane glycoprotein+changed vWF → Thrombocyte adhesion. vWF (plasma component). Two phases require Ca2+. thrombin. 5-HT.Physiological Characteristics of Platelet Thrombocyte adhesion: its membrane glycoprotein (GP. and acid protein hydrolyzed enzyme. 5-HT. prostacyclin. and β-platelet globin. collagen (underendothelial structure). cGMP↑→ platelet aggregation. Thrombocyte release: ADP. GPIb/IX and GPIIa/IIIb). drugs. epinephrine. PFV. Mechanism : Various factors+corresponding receptors on the platelet →changes in the second messenger within platelet →cAMP↓. PF4. thromboxane A2 (TXA2). virus. vWF. Thrombocyte contraction: Loose platelet thrombus could turn into compact platelet thrombus by Ca2+ release and cytoskeleton movement (filament/canaliculus) within platelet. ATP. etc. Ca2+ released from dense body. . fibrinogen. fibrinogen are involved in adhesion. immune complex.
FXIII to speed up coagulation. 3. aggregation. release and contraction. Loose platelet thrombus forming: First phase of hemostasis. Blood coagulation activation by platelet: Fibrin net forming. second phase of hemostasis. Activated platelets supply lecithoid (phospholipid) surface for blood clotting factor and involve in activating factor X and prothrombin.Roles of Platelet in Hemostasis Activation of platelet: Stimulus brings about thrombocyte adhesion. *Roles of platelet in hemostasis: 1. 2. 4. FV. . Activated platelets release α-granule which contains fibrinogen to intensify fibrin forming and blood coagulation. Activated platelets contract clot with its contractive protein to solidify blood coagulation. Surface of platelet membrane combine with many blood clotting factor. such as fibrinogen. FXI.
Two Phases of Physiological Hemostasis First Phase Second Phase .
Mechanism1 of Platelet in Hemostasis .
Mechanism2 of Platelet in Hemostasis .
others are in fresh plasma synthesized by liver with VitK . FXI. Blood coagulation is a series of complicated biochemical reactions with various enzymes. FIX.3. phospholipid，other factors being protein. Fx. Serum: Light yellow fluid after blood coagulation. . There are 12 factors named Roman numerals. Difference between serum and plasma mainly consists in no fibrinogen in serum. FXIII]. FVII. FXII. except Ca2+. and except FIII (TF). Blood clotting enzymes have two type: inactive and activated type [FII.Blood Coagulation Blood Clotting Factor Definition: The process of blood flow from flowing liquid to gel or gelatin. Blood clotting factor: Material which are directly involved in blood coagulation.
Prekallikrein. platelet Liver (with Vit K) Liver Liver (with Vit K) 4~5 d 3d 12~15 h 4~7 h 8~10 h 24 h Half life Chromsome site 4 11 1 13 Ⅹ Ⅹ Liver (with Vit K) Liver Liver Liver.PTC(Christmas factor) Ⅹ Stuart-Prower Factor 10 Ⅺ Plasma thromoboplastin 5 antecedent.PTA Ⅻ Contact factor or Hageman factor 40 XIII Fibrin-stabilizing factor 10 .1 3 4 .AHF 0.High-molecular weight 80 kininogen. platelet Liver Liver 2d 2~3 d 24 h 8d - 13 4 5 6.HMW-K .1 Ⅸ Plasma thromboplastic 5 component.Blood Clotting Factor Factor Name Plasma Concentration I Fibrinogen 3000 II Prothrombin 100 III Tissue factor IV Ca2+ 100 V Proaccelerin 10 Ⅶ Proconvertin 0.Pre-K or Fletcher factor 35 Synthesizing site Liver Liver (with Vit K) Endothelial cell Endothelial cell.5 Ⅷ Antihemophilic factor.
B. FXI in the blood. Eyewinker surface with negative charges (collagenin) on the endothelium of blood vessel activates blood FXII as beginning of coagulation named surface activation. FIX. . Extrinsic pathway of blood coagulation is faster than intrinsic pathway of blood coagulation because its steps are more simple. respectively.Blood Coagulation Intrinsic pathway of blood coagulation: All blood clotting factors involved in blood coagulation come from blood. *Basic steps of blood coagulation [typical positive feedback]: Prothrombin activator forming [FXa-Va-Ca2+-phospholipid] Step 1 Prothrombin thrombin Step 2 Fibrinogen fibrin (clot) Step 3 Hemophilia A. C in the clinic results from deficiency of FVIII. Extrinsic pathway of blood coagulation: Stimulus activates tissue factor (FIII) as beginning of coagulation.
Process of Blood Coagulation Extrinsic pathway （Tissue Factor，TF） TF+Ⅶ Ca2+ Ⅶ-TF Ⅹa Ⅶa-TF Ca2+ PL Ⅹ PL: phospholipid Intrinsic pathway （ Eyewinker surface ） Ⅻ Ⅺ Ⅸ Ca2+ HK Ⅻa Ⅺa S K PK Ca2+ ，PL Ⅸa Ca2+ Ⅷa PL Ⅹa Ca2+ Ⅴa PL ⅩⅢ CL: cross linking fibrin HK: high molecular weight kininogen S: Subendothelium PK: prekallikrein K: kallikrein Ⅱ Ⅱa ⅩⅢa Ca2+ Ⅰ Ⅰa CLⅠa .
Mechanism of Blood Coagulation .
[lower molecular weight heparin is less hemorrhage] Anticoagulative system in blood . ②It stimulates vessel endothelial cell greatlu releasing TFPI and other anticoagulative material. Amino acid protease inhibitors in blood include antithrombin III. 4. ②It blocks FXa combining with platelet phospholipid membrane to reduce prothrombin activation. 2. tissue factor. 3. ③It stimulates plasminogen activators release to trigger fibrinolysis. ④ Protein S is a coenzyme of PC and greatly intensify functions of PC. FXa. Clinhibitor. α1 antitrypsin. protein S and Protein C inhibitors. Main functions of PC consist in ①It inactivates FVa. ③It intensifies PC activation and stimulates vessel endothelial cell releasing plasminogen activators to increase fibrinolysis. Heparin used in the clinic widely is due to ①It combines with antithrombin III to increase functions of antithrombin III. prothrombin complex and soluble fibrin monomer. thrombomodulin (TM). FVIIIa with phospholipid and Ca2+. Heparin can intensify functions of antithrombin III. Protein C system are protein C (PC). FXIa. Tissue factor pathway inhibitor (TFPI) mainly coming from vessel endothelial cells inhibits FXa and inactivates FVIIa-TF complex to block extrinsic pathway of coagulation with negative feed back. α2 antiplasmin. heparin coenzyme II. α2 huge globin. FXIIa and thrombin and then inactivate them for anticoagulation. Humoral anticoagulative system: 1. protease nexin-1 (PN-1) to combine with FIXa. Cellular anticoagulative system: Liver cell and reticular endothelial cell could engulf blood clotting factor.
Basic steps: Endothelial cells (Extrinsic pathway ) (Urokinase. mesothelial cell and platelet to engulf and digest fibrin. uPA) Kallikrein (Intrinsic pathway) Cl-inhibitors uPAG tPA Plasminogen uPA PAI-1 α2-antiplasmin α2-huge globin Plasmin Fibrin dissolution Fibrin or fibrinogen . endothelial cell. macrophage.Fibrinolysis Fibrinolytic system is involved in fibrinolysis.4. plasmin. tissue repair and vessel rebirth. The latter is plasminogen activators (PA) and its inhibitors (PAI). The former is leucocyte. Two fibrinolytic systems: cellular one and plasma one. plasminogen.
Blood Coagulation and Fibrinolysis .
IL-1. alexin C1 inhibitor.Antifibrinolysis: Fibrinolytic Inhibitors and Its Functions Main fibrinolytic inhibitors: They are plasminogen activator inhibitor type-1 (PAI-1. megakaryocyte is stored in platelet with inactive form. α1-antitrypsin. α2-huge globin. PAI-1 function: It inhibits tPA (tissue-type plasminogen activator) limiting local fibrinolysis of thrombus. PAI-1 synthesis and release: PAI-1 made by endothelial cell. . etc stimulate its release from platelet. TNFα. (3) Combine with fibrin αchain and block fibrinolysis Clinic relation: Innate deficiency of α2-antiplasmin often brings about serious hemorrhage. smooth muscular cell. in platelet). α2-antiplasmin characteristics: (1) Quick effect. antithrombin III. Some factors such as thrombin. α2antiplasmin (in liver). mesothelial cell. (2) Inhibit plasminogen adhering to fibrin.
Agglutination: Combination of the same antigen (or named agglutinogen. Platelet antigens such as PI. Human leukocyte antigen. glycoprotein/glycolipid on the membrane of blood cell) and antibody (or named agglutinin. etc may bring about fever heat when transfusion occur. . HLA have widespread distribution in the body and involves in immune repulsive reaction of organ transplant. Zw. Ko. r-globin in serum) results in harmful immune reactions showing hemolysis. Blood Group History: ABO blood group system was firstly found by Landsteiner in 1901. Definition for blood group*: Types of specific antigens on the blood cell.V.
1. RBC Agglutination Antigen-Antibody Harmful immune Reaction Blood Coagulation RBC Agglutination .
Genotpye is genetic gene in blood group system and phenotype is antigen produced by corresponding genetic gene and amorph is noneffective allele. namely. expressed gene. .Antigen of Blood Group Antigen: Its genes are located at allele on euchromosome. Genes in the blood system decide differential specific antigen on the membrane with control of enzymatic activity.
Immune antibody: Various extraordinary RBC antigens (transfusion or parturition) sensitize lymphatic cells producing antibody such as Rh. Kell. IgM in ABO blood group system which can not pass through placenta for the sake of big molecule. which belong to IgG (small molecule) and IgM (big molecule).Antibody of Blood Group Crude antibody: It is the unexposed antibody to correlative RBC. . e.g. kidd.. Duffy.
ABO blood group system: Antigen on the RBC A B Antibody in the serum Anti-B Anti-A Anti-A+Anti-B Blood group A B AB O A+B . 193 antigens. more important blood groups are ABO. MNSs. duff. etc and all of them could result in hemolysis during transfusion. kidd. Lewis. Rh. Lutheran. kell.Blood Group of RBC Number: 23 types.
2. ABO blood group system Antigen (agglutinogen) and antibody (agglutinin) in ABO blood subgroup system Blood group A B AB A1B A2B O A1 A2 Antigen on the RBC A+ A1 A B A+ A1 +B A+B Antibody in the serum Anti-B Anti-B+ Anti-A1 Anti-A Anti-A1 Anti-A+Anti-B .
Antigen of blood group Ushering material ABH Antigen chemical structure in ABO blood group system O(H)-antigen A-antigen B-Antigen Galactose Sugar N-acetamide Glucose Glucose N-acetamide galactose .
Inheritance of ABO blood group Inheritance: The A. H agglutinogen in ABO blood group system controlled by gene which is located at allele on No. AO BB.2). B. Genotype and Phenotype: Genotype and Phenotype in ABO blood group system Genotype OO AA. BO AB phenotype O A B AB .9 chromosome (9q34.1-q34.
A O. AB ____ O. B.Inheritance of ABO blood group Genetic relationship of ABO blood group Parents’ blood group Offspring possible blood group Offspring impossible blood group O×O A×A O O. AB O O AB×AB A . AB A. AB O . AB A. B. B. A A. B. AB A. AB B.B A . B O. B. AB B. AB A×O B×B B×O B×A AB×O AB×A AB×B O. B O. AB A . A.
Type B 28. Type AB 9.06%. Type B 10%. America aborigines: Type O 90%. Type O 40%.31%.86%. China Han nationality: Type A 31. Type AB 6%. Type O 30. Bloog group can be used in research on anthropology .77%. Other chinese minority is different.Distribution of ABO blood group Mid Europe: Type A 40%.
B Serum .Mensuration of ABO blood group Anti-B Serum Anti-A Serum Anti-A.
otherwise. E. C. Rh negative. IgG. e and most important is D antigen. Rh blood group characteristics: Immune antobody and incomplete antibody. Rh blood group system Rh antigen (Rh factor) is about 40 kinds and Rh factors related to clinic are D. c. Most of people (99％) are Rh Positive and less than 1% persons are Rh negative. while ABO blood group. Membrane of RBC has D antigen meaning Rh Positive.3. Rh blood group system and clinic work Transfusion and pregnacy [Clinic meaning] .IgM. crude antibody and complete antibody.
Circulatory system is essentially a closed container including a volume of blood equal to approximately 5 liters or 70-80mL/Kg of the body weight (in kilograms). .Quantification of Blood Volume Blood volume is an important determinant of systemic arterial pressure.
. Relation between blood volume and clinic When you donate 10 % of total blood volume. and the volume is replaced through the normal ingestion of fluids. dazzled. etc) Blood loss more than 40 % of total blood volume will threaten the life. force-lacked. Volume loss up to 30-40 % of total blood volume can be tolerated if the loss is corrected within 30 min (e.g. artery contraction increases peripheral resistance but artery blood pressure can not maintain the normal levels which occur in symptoms such as light-headed. your body compensates so that blood pressure does not change. results in shock and the measures in the hospital should be immediately taken for life survival [Transfusion].4.
Identification of blood group must be taken before transfusion. Cross-match test must be done before transfusion.5. Principle of Transfusion Transfusion is widely used in clinic treatment. small amount and slow import and if condition is better. 4. . changes in the same tpyes of blood group for transfusion. 2. The different tpyes of blood group for transfusion should be very careful. 3. The same tpyes of blood group for transfusion should be firstly considered. Principle of transfusion*: 1.
transfusion 不合，不能输血 Transfusion under emergency 应急情况下输血 × +: Agglutination.Cross-match test for transfusion RBC 红细胞 Donator RBC 红细胞 供 血 者 Receiver 受 血 者 Serum Main side of 主侧凝集反应 agglutination 血清 Serum 血清 Subordinary side 次侧凝集反应 of agglutination Decision + - +. -: No agglutination . transfusion 相合，可以输血 No match. + Perfect match.
transfusion of blood components Autologous transfusion has some advantages: It decreases infection. whole blood transfusion.Types of Transfusion According to source of transfusion. According to component of transfusion. autologous transfusion. It blocks syndrome (fever. ③ It stimulates bone marrow hemopoiesis towards RBC. . ① ② Transfusion of blood components is good. hemolysis) induced by allogenetic transfusion. allogenetic transfusion (more use).
Summarization PLEASE TAKE DOWN .
Please describe classification and main effects of leucocyte. What is the elementary process of blood coagulation and main factors which have participated in blood coagulation? 3. Please describe the principle of classification and blood transfusion of ABO blood group system.Consideration after class 【本章节问题思考】 1. . 2.
Human physiology. Bardin F. 8. 全国高等学校医学规划教材. 人类红细胞血型学实用理论与实验技术. 人体生理学（二版）. Fox SI. 王庭槐主编. 上海: 上海医科大学出版社. 2001. 贺福初. Ann N Y Acad Sci. Guyton AC. Stanton BA.B. 2002. Hall JE. 贺石林. 吴祖泽. Functional isolation and characterization of human hematopoietic stem cells. 范少光. 秦晓群主编. 2001. 1999. 临床生理学. molecular. 第五版. 10. Physiology. Blood. 2004. 1999. 3. 5. Kidd C.Guide of Reference 【本章节学习参考书单】 姚泰主编. Levine JD. 2000. et al. Lu S. Koeppen BMI. Wang A. 12. 2005. 北京: 人民卫生出版社. 潘伟丰主编. . 6(9): 1611-1616. Kaushansky K. 996: 39-43. St Louis: Mosby Electronic Production. 北京: 中国科学技术出版社. Batchu R. 北京: 高等教育出版社. Ding L. et al. 汤浩. 267(5194): 104-108. 1996. 北京: 北京医科大学出版社. et al. 2003. 杨贵贞主编. 李俊成. 生理学. 11. 4. New York: McGraw-Hill Co Inc. Science. Bone marrow stromal cells as a vehicle for gene transfer. Blakeley AGH.Davies A. Levy MN. 87(3): 949-955. 5th ed. 1. 生理学. Philadelphia: W. 6. 李勇. 7th ed. 2000. Human physiology. 2000. 13. Phenotypic. Berne RM. Humeau L. 造血调控. 1995. Saunders Co. 9. 2000. TEXTBOOK OF MEDICAL PHYSIOLOGY. Gene Ther. CD34+/Thy1+ cells. 10th ed. and functional characterization of human peripheral blood. Thrombopoietin: accumulating evidence for an important biological effect on the hematopoietic stem cell. 7. Edinburgh: Churchill Livingston. Maroc C. 裴雪涛主编. 北京: 科学出版社. 2. Berardi AC. 14.
h tml 4.http://www.kr/PHYSIOLOGY%2 0BLUE.inform.http://www.ac.com/HEM38.edu/cliniweb/G9/G9.Navigation for Web Address 【本章节课后学习导航网站】 1.umd.http://bioresearch.ohsu.htm 5.mednote.188.co.htm .html 2.uk/browse/mesh/detai l/c0005811L0005811.fpnotebook.http://www.edu/EdRes/Colleges /HONR/HONR269U/Jenn/ 3.http://www.
BLOOD PHYSIOLOGY QUESTIONS ANSWERS .
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