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Unit Six: Blood Cells, Immunity, and Blood Coagulation. Chapter 36: Hemostasis and Blood Coagulation. Guyton and Hall, Textbook of Medical Physiology, 12 th edition. Events in Hemostasis. Vascular Constriction Local myogenic spasm-most effective Local autacoid factors
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Unit Six: Blood Cells, Immunity, and Blood Coagulation Chapter 36: Hemostasis and Blood Coagulation Guyton and Hall, Textbook of Medical Physiology, 12th edition
Events in Hemostasis • Vascular Constriction • Local myogenic spasm-most effective • Local autacoid factors • Nervous reflexes-from pain receptors • Formation of a Platelet Plug • Small cut in a vessel; have a plug • instead of the complete clotting • mechanism
Events in Hemostasis • Platelets • Fragmented megakaryocytes • 150,000-300,000 • Do not have nuclei and cannot reproduce • Contain actin and myosin (thrombosthenin) • Produce ATP • Release prostaglandins • Release endothelial cell growth factor • Surface glycoproteins for adherence to damaged • vessels • i. Half-live of 8-12 days
Events in Hemostasis • Mechanism of the Platelet Plug • Platelets swell; irregular shape with pseudopods • Become sticky and adhere to collagen • Thromboxane A2 and ADP enhance adherence • Damaged wall activates increasing numbers of • platelets • Important in closing small tears or ruptures in very • small vessels
Blood Coagulation • Basic Theory • Depends on the activation of 50 or more possible • blood procoagulants • Formation of prothrombin activator • Conversion of prothrombin to thrombin • Conversion of fibrinogen to fibrin
Blood Coagulation • Conversion of Prothrombin to Thrombin • Prothrombin activator is formed as a result of • damage to a blood vessel • In the presence of Ca++ causes the conversion • of prothrombin to thrombin • Thrombin causes the polymerization of • fibrinogen molecules into fibrin fibers • Prothrombin attaches to receptors on platelets • Prothrombin is a plasma protein formed • continually by the liver • Vitamin K is required for the production of • prothrombin
Blood Coagulation • Conversion of Fibrinogen into Fibrin • Fibrinogen is produced by the liver • In the early stages of polymerization, the molecules • are held together by hydrogen bonds • Fibrin-stabilizing factor is released by platelets; • acts as an enzyme to form covalent bonding and • multiple cross-linkages
Blood Coagulation • Blood Clot • Meshwork of fibrin fibers running in all directions • and entrapping blood cells, platelets, and plasma • Within a few minutes the clot contracts and • expresses fluid (serum) • Platelets contribute directly by activation • thrombosthenin and myosin (contractile proteins) • Positive Feedback of Clot Formation
Blood Coagulation • Initiation of Coagulation • Trauma to the vascular wall and adjacent tissues • Trauma to the blood • Contact of the blood with damaged endothelial • cells or collagen and other tissue elements • d. All lead to the formation of prothrombin activator
Blood Coagulation • Extrinsic Pathway • Release of tissue factor • Activation of Factor X-role of Factor VII and tissue • factor • Effect of Xa to form prothrombin activator-role of • Factor V in the presence of calcium to split • prothrombin to thrombin
Blood Coagulation • Intrinsic Pathway • Blood trauma causes activation Factor XII and • release of platelet phospholipids • Activation of Factor XI • Activation of Factor IX by activated XI • Activation of Factor X-role of Factor VIII • Action of activated Factor X to form prothrombin • activator-role of Factor V
Blood Coagulation • Role of Calcium in Extrinsic and Intrinsic Pathways • Except for the first two steps in the intrinsic • pathway, calcium ions are required for promotion • or acceleration of all blood clotting reactions • Normally, calcium levels do not fall low enough to • affect blood clotting mechanisms
Blood Coagulation • Interaction Between Extrinsic and Intrinsic Pathways • Clotting occurs by both pathways simultaneously • Extrinsic pathway is more explosive and faster (as little • as 15 seconds) • Intrinsic is slower requiring 1-6 minutes
Blood Coagulation • Intravascular Anticoagulants- prevention of blood • clotting in the normal vascular system • Endothelial surface factors-smoothness, glycocalyx, • thrombomodulin (binds thrombin), protein C (inhibits • Factors V and VIII • Antithrombin action of fibrin and antithrombin III • Heparin-released by basophils and mast cells • Plasmin-digests fibrin fibers and other clotting factors • (from plasminogen-serum protein trapped in clot)
Excessive Bleeding • Decreased Prothrombin, Factors VII, IX, and X Caused • By Vitamin K Deficiency • Hemophilia • Thrombocytopenia