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Chapter Blood
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Blood Blood is a liquid tissue
Blood flows everywhere through the human body Main founction of blood is to transport Blood is composed of cellular part and non-cellular part
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Self-study: 1. What’s blood? 2. Blood composition and its functions
3. Blood volume in human body 4. The physical and chemical characteristics of blood 5. Crystal and colloid osmotic pressure and their functions 6. Some important terms in clinic: hematocrit、 plasma osmotic pressure, plasma pH, blood viscosity, specific density of blood, suspension stability of RBC and erythrocyte sedimentation, osmotic fragility of RBC, isosmotic solution, isotonic solution Hematocrit血细胞比容;p specific density of blood血液比重 blood viscosity血液粘度; erythrocyte sedimentation 血沉; osmotic fragility of RBC 渗透脆性
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Physiological Hemostasis
Part 1 Physiological Hemostasis
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I. Physiological Hemostasis
Definition: The physiological process arresting blood leakage when a vessel is damaged Index — Bleeding Time The time from the start to the arrest of bleeding(1-3 min normally) Process:
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Vascular constriction
Formation of the platelet plug 3. Formation of the blood clot (blood coagulation)
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Hemostasis: BV Injury Coagulation Blood Vessel Platelet Neural
Stable Hemostatic Plug Coagulation Activation Blood Vessel Constriction Platelet Aggregation Primary Hemostatic Plug Reduced Blood Flow Stoppage of Bleeding
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Formation of Platelet Plug
Platelets in normal state Actived platelets
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Platelet Activation Pathways (1)
ADP Adrenaline Collagen Thrombin ADP GpIIb/IIIa Aggregation GpIIb/IIIa Aggregation GpIIb/IIIa Aggregation GpIIb/IIIa Adhesion Platelet GpIb Adrenaline Adhesion vWF Exposed collagen Endothelium
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Chen J, Lopez JA. Hartwig JH.
Interactions of platelets with subendothelium and endothelium. Microcirculation Apr-May;12(3): Hartwig JH. The platelet: form and function. Semin Hematol Jan;43(1 Suppl 1):S
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Platelet Activation Pathways (2)
Thrombin ADP TXA2 Platelet Fibrinogen binding site Fibrinogen Platelet aggregation
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Blood Coagulation Process of conversion of blood from fluid to gel Process of conversion of fibrinogen to fibrin Blood in fluid Blood in gel
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Clotting Factors(1) Factors Synonyms Factors Synonyms I IX fibrinogen
antihemophilic f. B II prothrombin X Stuart-Prower f. III tissue factor XI antihemophilic f. C IV Ca++ XII contact factor V proaccelerin XIII fibrin-stabilizing f. proconvertin HMW-K (kininogen) Prekallikrein (PK) VII VIII antihemophilic f. A
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Clotting Factors(2) All exist in blood except III
All are proteins except Ca2+ Many are synthesized by liver Synthesization is dependent on Vit K: II,VII,IX,X
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Clotting Factors(3) Many are proteolytic proenzymes that need
be actived
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Structure of Clotting Factors(4)
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Three Basic Stages Intrinsic pathway XII Extrinsic pathway III 1.
Formation of prothrombin activator II→IIa (prothrombin→thrombin) 2. I→ Ia (fibrinogen→ fibrin) 3.
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Structure of Fibrinogen
Fibrinogen molecules are comprised of two sets of disulfide-bridged , , and chains Therefore, composed of six polypeptide chains
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Fibrin Polymerization
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Scanning Electron Micrograph of Blood Clot, Showing Red and White Blood Cells Caught in Fibrin Mesh
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Initiation of Coagulation
in Vivo
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Clot Retraction 30-60 minutes Platelets contain actomyosin
As the clot is contracted,serum is squeezed from the mass Serum
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II.Control of Coagulation
Antithrombin III and Heparin Proteins C and S TFPI – balance Procoagulants Anticoagulants
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Heparin and Antithrombin
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Protein C and S (1) EPCR Blood Flow Protein C APC Thrombin Thrombus
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Protein C and S (2) Blood Flow VIIIa Va Thrombus Vai VIIIai PS APC APC
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TFPI
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III.Fibrinolysis
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IV.Abnormalities of Hemostasis
1.Hemophilia Cause: deficiency of VIII,IX,XI Therapy: injection of purified clotting factors 2.Throbocytopenia Cause: the number of platelet< 50,000/ul (normally: 150,000 ~ 300,000/ul)
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Part 2 Blood Groups
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Blood Fact If someone is in an accident, has surgery or gets cancer, they may need another person’s blood to help them survive. There is no substitute for blood transfusion. This blood comes from blood donors.
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I. Definition of Blood Groups
Blood Groups (Types) Types of the specific antigens of the red blood cells antigens Antigen——Agglutinogen Antibody——Agglutinin
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II. Major RBC Blood Group System
1. ABO System (Karl Landsteiner, 1901) Antigens: A and B agglutinogens
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Blood Types A O B AB B Antigen A & B Antigens Neither A nor B Antigens
Antibodies bind with antigens to cause clumping of blood cells (agglutination) so people with type A blood have circulating antibodies for type B, while people with blood type AB have neither A nor B antibodies and people with blood type O circulate both A and B antibodies. A Antigen
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RBC Agglutination Blood Group Ag. Antibody (Agglutination) 26
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Incompatible Transfusion
Transfusion Reaction Incompatible Transfusion Transfusion Reaction Agglutination Hemolysis
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Antibodies: Anti-A and Anti-B agglutinin (Natural Antibodies; Ig M)
Significance: Serious transfusion reaction occurs in the first imcompatible blood transfusion
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There are 4 main blood types, distinguished by their carbohydrate antigens
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A transferase H A antigen A gene B transferase H B antigen B gene
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ABO genes:A and B—dominant,O—recessive
ABO phenotypes and genotypes: 1. Group A phenotype = A/A or A/O genotype 2. Group B phenotype = B/B or B/O genotype 3. Group O phenotype = O/O genotype 4. Group AB phenotype = A/B genotype
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A Antigen B Antigen H Substance A and B Antigens Precursor Substance
AA,AO genes BB,BO genes B Antigen H Substance A and B Antigens HH,Hh genes AB genes OO genes Precursor Substance H Substance hh genes ANY GENES Precursor Substance No Antigen Bombay
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ABO System Three alleles A, B, O.
A & B genes code for glycosyltransferases, add terminal sugar to H substance (l.fucose) galactosamine by A (A1 is stronger than A2) galactose by B Bombay group – absent H substance
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Subgroups of A type:Decreased amounts of A antigen on the red blood cells;inherited conditions
Significance: Distinguish A2 and O,A2B and B
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Article1 Article2
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Blood Typing Test Type A Type B Type AB Type O anti-A anti-B anti-A
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Incidence (%) of ABO Blood Groups in the US Population
ABO Group Whites Blacks O 45 49 A 40 27 B 11 20 AB 4
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2. Rh System (Landsteiner & Weiner, 1940)
Antigen ——Rhesus factor( D, E, C, c, e) Grouping: Antigen D Rh positive Rh negative – Antibodies: No natural antibodies; Ig G Incidence: - 0.2% in Chengdu’s population
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Hemolytic Disease of the Newborn
If father D+, mother D-, & fetus is D+ First pregnancy not affected – Fetal D+ RBCs enter mother’s circulation in the last trimester and during delevery Mother makes anti-D weeks later In the next pregnancy (if baby is Rh+) these IgG cross the placenta and cause hemolytic disease in baby Anti-D immunization after birth prevents
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Hemolytic Disease of the Newborn
First Preg Later Next Preg 28
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III. Principles of Blood Transfusion
1. Blood transfusion is allowed among people with same type of bloods 2. Cross-matching test must be carried out in any case
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Cross-matching Test RBC RBC Donor Recipient Serum Serum Primary side:
secondary side Primary side: the donor’s blood cells with the recipient’s serum
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Secondary Blood Primary Transfusion Side (a little amount,
— — — (a little amount, slowly, observed)
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References 1.Human Physiology From Cells to Systems,
4th edition,Lauralee Sberwood 北京:中国协和医科大学出版社,2002 2.Textbook of Medical Physiology,10th edition, Guyton & Hall 北京:北京医科大学出版社,2002 3.生理学(七、八年制教材),姚泰 北京:人民卫生出版社,2005
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Review questions 1. What is hemostasis and its basic process?
2. What is blood coagulation its basic process ? 3. What is serum and its difference from plasma 4. What is clotting factors and their characteristics ? 5. What are the characteristics of intrinsic and extrinsic pathways and the relationship between two pathways? 6. What are the roles of platelet in hemostasis? 7. What are there physiological anticoagulants in the body? 8. What are the composition of fibrinolysis and its siginificance 9.What is blood type and principles of blood transfusion ?How is ABO blood type determined?
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