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Regulation of Hemostasis


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Regulation of Hemostasis

  2. 2. HEMOSTASIS?1. Hemostasis = prevention of blood loss2. When there is vessel ruptures, hemostasis is achieved by: • Vascular constriction • Platelet plug formation • Blood clot formation • Fibrous tissue growth or dissolution
  3. 3. Vascular ConstrictionWhen the blood vessels rupture, the vesselscontract by:1. Myogenic spasm2. Local autacoid factors (local mediators) from traumatized tissue3. Nervous reflexes by pain nerve impulses initiation4. Vasoconstrictor substances from platelets eg. Thromboxane A2
  4. 4. Platelet Plug Formation Platelets come in contact with subendothelial collagenPlatelet aggregation The activation of and formation of platelet (formation platelet plug of pseudopods to become sticky) Secretion of multiple ADP & Thromboxane active factors eg. A2 activate nearby ADP & Thromboxane platelets A2
  5. 5. Blood Clot FormationTwo pathways:1. Extrinsic pathway: begins when traumatized vascular wall or traumatized extravascular tissues that come in contact with the blood2. Intrinsic pathway: begins with trauma to the blood itself or exposure of the blood to collagen from a traumatized blood vessel wall
  6. 6. Extrinsic pathway Tissue factor aka ThromboplastinThromboplastin + VIIa + Ca2+activate factor XXa + Va + Thromboplastin + Ca2+becomes prothrombin activatorcomplexProthrombin activator complex +platelet phospholipid + Ca2+ activate prothrombin
  7. 7. Intrinsic pathwayBlood trauma causes activation ofXII and platelet activation torelease platelet phospholipids VIII VIIIaIXa + VIIIa + Platelet phospholipid +Ca2+ Thrombi Activate factor X n
  8. 8. Fibrin Formation Factor XIII aka fibrin stabilizing factor Thrombin FibrinFibrinogen monomer Factor XIIIa aka activated fibrin stabilizing factor Fibrin fibre
  9. 9. Dissolution tissue plasminogen activator (t-PA) released by endotheliumPlasminogen aka Plasmin aka profibrinolysin fibrinolysin Digest fibrin fibres, fibrinogen, Factor V, Factor VIII, prothrombin, and Factor XII
  10. 10. Prevention of Clotting1. Endothelial surface factors• Smoothness of vascular wall  prevent intrinsic pathway activation• Glycocalyx layer that repels clotting factors and platelets• Thrombomodulin (on endothelial surface) which: bind to thrombin  prevent coagulation activates protein C inactivate Va and VIIIa
  11. 11. Prevention of Clotting2. Antithrombin action of fibrin andantithrombin• Thrombin are adsorbed into fibrin mesh and prevent further coagulation• Unadsorbed thrombin binds to antithrombin and inactivates it
  12. 12. Prevention of Clotting3. Heparin action• Heparin released by mast cells and basophils.• It enhances the antithrombin action and more• The heparin-antithrombin complex removes other activated factors eg. XIIa, XIa, Xa, IXa