Blood (II) Huawei Liang, PhD

Transcription

1 Blood (II) Huawei Liang, PhD

2 Physiological hemostasis 生理止血 The arrest of bleeding from a broken blood vessel -- that is, the stoppage of hemorrhage ( 出血 ) Three major events: Vascular constriction 受损血管收缩 Formation of a platelet plug 血小板血栓的形成 Blood coagulation (clotting) 血液凝固

3 Vascular constriction 血管挛缩 Slowing blood flow through the defect and thus minimizes blood loss Immediate constriction response is due to neural reflexes initiated by pain Also related to the release of 5-HT (5- 羟色胺 ), TXA 2 ( 血栓烷 A 2 ) and endothelin ( 内皮素 ) form the endothelium & platelets at the injury site

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5 Formation of a platelet plug 血小板血栓形成

6 Blood coagulation (clotting) 血液凝固 Transformation of blood from a liquid into a solid gel ( 凝胶 ) by changing a soluble molecule (fibrinogen 纤维蛋白原 ) to an insoluble polymer (fibrin 纤维蛋白 )

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8 Role of vascular endothelium ( 血管内皮细胞 ) Vasoconstriction: reduced blood flow facilitates contact activation of platelets and coagulation factoors ( 凝血因子 ) Exposure of sub-endothelial basement membrane and collagen Release of tissue thromboplastins ( 促凝血酶原激酶 ) Synthesis of basement membrane components, tissue factors, vwf, plasminogen activators, antithrombin III, thrombomodulin

9 Role of platelets Release of vasoconstricting substances Formation of the platelet plug Promotion of blood clotting Providing a phospholipid surface (PF3) and receptors for the binding of coagulation factors Clot retraction To reduce residual bleeding and stabilizing the injury site To make it easier to complete repairs

10 Clotting factors 凝血因子 Substances involved in blood coagulation 编号 Synonyms ( 同 义 名 ) 因子 I 纤维蛋白原 (fibrinogen) 因子 II 凝血酶原 (prothrombin) 因子 III 组织凝血激酶 (tissue thromboplastin, tissue factor) 因子 IV Ca 2+ 因子 V 前加速素 (proaccelerin) 因子 VII 前转变素 (proconvertin) 因子 VIII 抗血友病因子 (antihemophilic factor) 因子 IX 血浆凝血激酶 (plasma thromboplastin component) 因子 X Stuart-Prower 因子 因子 XI 血浆凝血激酶前质 (plasma thromboplastin antecedent) 因子 XII 接触因子 (contact factor) 因子 XIII 纤维蛋白稳定因子 (fibrin-stabilizing factor)

11 Coagulation cascade 内源性途径 2 pathways Intrinsic pathway Extrinsic pathway 3 processes Prothrombinase complex 凝血酶原复合物 Thrombin 凝血酶 Fibrin 纤维蛋白 Ca 2+ Ca 2+ Ca 2+ PL Ca 2+ PL 外源性途径

12 The Intrinsic Pathway Initiated by the activation of factor XII Requires factor XII, XI, IX, and VIII Long and Slow Partial thromboplastin time (PTT) is seconds

13 The Extrinsic Pathway Initiated by the generation of the tissue factor-factor VIIa complex Requires factor III and VII Short and fast Prothrombin time (PT) is seconds

14 Prothrombinase complex ( 凝血酶原酶复合物 ) Composed of the platelet phospholipids, phosphatidylinositol and phosphatidylserine, Ca 2+, factors Va and Xa, and prothrombin ( 凝血酶原 ) Converting the zymogen prothrombin (II) to the active serine protease thrombin (IIa) by proteolytic removal of the fragment 1.2 (F1.2) portion of prothrombin

15 Thrombin ( 凝血酶 ) To convert Fibrinogen to Fibrin To stabilize the fibrin network by activating factor XIII To exert a profound positive feedback effect on its own formation

16 Factors affect blood clotting Calcium ions is required as cofactors at various steps of the clotting process Vitamin K is a cofactor needed for the synthesis of factors II, VII, IX & X in the liver. So a deficiency of Vitamin K predisposes to bleeding A deficiency of a clotting factor can lead to uncontrolled bleeding: hemophilia ( 血友病 )

17 Difference between serum ( 血清 ) and plasma Serum = plasma fibrinogen & some of the other clotting factors + substances released by platelets

18 Anticlotting system 抗凝系统 Serine protease inhibitor 丝氨酸蛋白酶抑制物 Antithrombin III (ATIII) 抗凝血酶 III Inhibiting thrombin Inhibiting factors IXa, Xa, XIIa, XIa and the complex of factor VIIa and tissue factor The presence of heparin ( 肝素 ) increases the activity of ATIII by

19 Protein C 蛋白质 C Vitamin K-dependent protein Synthesized in the liver as an inactive form Activated by thrombin Degrading Factor Va and Factor VIIIa Its activity is markedly enhanced by its cofactor Protein S

20 Tissue factor pathway inhibitor (TFPI) 组织因子途径抑制物 TFPI has three Kunitz domains which can bind to and inhibit serine proteases

21 Heparin 肝素 Produced by the tissue mast cells ( 肥大细胞 ) and the basophils ( 嗜碱性粒细胞 ) of circulating blood Interfering primarily with the action of thrombin after combing with antithrombin III

22 The Fibrinolytic System 纤维蛋白溶解系统 Fibrinolysis 纤维蛋白溶解 The process by which the fibrin clot is removed from the site of vascular injury during the healing process Components of plasma fibrinolysis system Plasminogen 纤维蛋白溶解酶原 Plasmin 纤溶酶 Plasminogen activator Plasminogen inhibitor Processes of fibrinolysis Activation of plasminogen Degradation of fibrin

23 2 pathways of plasminogen Activation

24 Plasminogen activators 纤溶酶激活物 Tissue plasminogen activator (t-pa) Urokinase 尿激酶 Factor XII Kallikrein 激肽释放酶 Plasminogen inhibitors 纤溶酶抑制物 Plasminogen activator inhibitor type-1 (PAI-1) α 2 -antiplasmin α 2 抗纤溶酶 Antithrombin III

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27 Blood group 血型 Created by antigens present on the surface of red blood cells ABO type Rhesus (Rh) type

28 ABO blood group system

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30 Rh Blood Group System

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32 Blood volume & blood transfusion Blood volume 血量 The total blood volume is 7~8% of body weight. For a 70 kg male, it is 5.0~5.5 L

33 Blood transfusion 输血 To be the process of transferring blood or blood-based products from one person into the circulatory system of another

34 Risk from Transfusion Allergic reactions ( 变态反应 ) to the blood or one of its components Hemolytic reaction 溶血反应 Diseases transmission, such as HIV, Hepatitis B, C virus

35 Guideline Tests screening for Hepatitis virus, HIV in blood donated Ensuring that transfusion recipients ( 受血者 ) and donors ( 供血者 ) have compatible blood group -- cross-matching test ( 交叉配血试验 )

36 Cross-matching

37 Type of blood transfusion Allogenetic transfusion 异体输血 Autologous transfusion 自体输血 Transfusion of whole blood 全血输血 Transfusion of blood components 成分输血

38 Summary Terms Hemostasis Blood coagulation Antithrombin III Blood typing Name the common blood types, and describe how blood is typed and cross-matched Describe the blood clotting and anti-clotting systems and the clinical importance of each system

39 GENERAL QUESTIONS Why is blood clotting abnormal in patients with Vitamin K deficiency? How dose human body prevent blood clotting in the normal vascular system?