Blood clotting


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Blood clotting

  1. 1. BLOOD CLOTTING When blood is shed out or collected in a container, it looses its fluidity & becomes a jelly like mass after few minutes. This process is called coagulation or clotting of blood. The clot is a mesh of thin fibrils entangling the blood cells. These fibrils consist of fibrin. The fibrin is formed from fibrinogen.
  2. 2. FACTORS INVOLVED IN BLOOD CLOTTING <ul><li>Coagulation of blood occurs through a series of reactions due to the activation of a variety of substances. Those substances necessary for clotting are called clotting factors. The clotting factors are : </li></ul>
  3. 3. <ul><li>Factor I : Fibrinogen </li></ul><ul><li>Factor II : Prothrombin </li></ul><ul><li>Factor III: Thromboplastin </li></ul><ul><li>Factor IV: Calcium </li></ul><ul><li>Factor V: Labile factor(Proaccelerin or accelerator globulin) </li></ul><ul><li>Factor VII: Stable factor </li></ul><ul><li>Factor VIII: Antihemophilic factor </li></ul><ul><li>Factor IX: Christmas factor </li></ul><ul><li>Factor X: Stuart – Prower factor </li></ul><ul><li>Factor XI: Plasma thromboplastin antecedent </li></ul><ul><li>Factor XII: Hegman factor </li></ul><ul><li>Factor XIII: Fibrin stabilizing factor </li></ul>
  4. 4. SEQUENCE OF CLOTTING MECHANISM <ul><li>Normally during circulation, the blood does not clot, because the enzymes involved in clotting are in inactive form. Slight initial activation causes clotting in which each enzyme activates another one in a sequential manner till the conversion of fibrinogen into fibrin. In general, clotting occurs in 3 stages namely: </li></ul>
  5. 5. <ul><li>Formation of prothrombin activator. </li></ul><ul><li>Conversion of prothrombin into thrombin. </li></ul><ul><li>Conversion of fibrinogen into fibrin. </li></ul><ul><li>During the process of blood clotting, the clotting factors, which are in inactive forms, are converted into active forms. And their enzymatic actions produce the successive reactions one after another in a cascading manner. </li></ul><ul><li>Thus, the various reactions involved in blood clotting are explained by Enzyme cascade theory. </li></ul>
  6. 6. Stage 1 : Formation of prothrombin activator <ul><li>Prothrombin activator is formed in two ways namely: </li></ul><ul><li>Extrinsic pathway: In this, the formation of prothrombin activator is initiated by the tissue thromboplastin. </li></ul><ul><li>Intrinsic pathway : In this, the formation of prothrombin activator is initiated by platelets, which are within the blood itself. </li></ul>
  7. 7. EXTRINSIC PATHWAY Tissue trauma ↓ Tissue thromboplastin (Protein, Glycoprotein, Phospholipid) Factor VII-> ↓ Factor X -> Activated Factor X Calcium-> ↓ ← Factor V←Thrombin Prothrombin Activator
  8. 8. INTRINSIC PATHWAY <ul><li>Tissue trauma </li></ul><ul><li>↓ </li></ul><ul><li>Factor XII -> Activated Factor XII </li></ul><ul><li>kininogen-> ↓ ←Prekallkrein </li></ul><ul><li>Factor XI ->Activated Factor XI </li></ul><ul><li>Calcium -> ↓ </li></ul><ul><li>Factor IX -> Activated Factor IX </li></ul><ul><li>Calcium -> ↓ ←Factor VIII </li></ul>
  9. 9. <ul><li>Factor X -> Activated Factor X </li></ul><ul><li>Calcium -> ↓ ← Factor V← Thrombin </li></ul><ul><li>↓ </li></ul><ul><li>Prothrombin Activator </li></ul>
  10. 10. Stage 2 : Conversion of prothrombin into thrombin <ul><li>Prothrombin activator converts Prothrombin into Thrombin in the presence of Calcium. Thrombin itself can accelerate this reaction by positive feedback mechanism. That is, the initial Thrombin activates Factor V. This in turn accelerates the formation of both Extrinsic & Intrinsic Prothrombin activator. </li></ul>
  11. 11. Stage 3 : Conversion of Fibrinogen into Fibrin <ul><li>During this, the soluble Fibrinogen is converted into insoluble Fibrin by Thrombin. Initially, the fibrinogen is converted into activated fibrinogen, which is called fibrin monomer. This polymerizes with other monomer molecules to form Fibrin. </li></ul><ul><li>The first formed fibrin contains loosely arranged strands. This is modified later into a dense tight aggregate by fibrin stabilizing factor (Factor XII) & this reaction requires the presence of calcium ions. </li></ul>
  12. 12. <ul><li>FIBRINOGEN </li></ul><ul><li>Thrombin -> ↓ </li></ul><ul><li>ACTIVATED FIBRINOGEN </li></ul><ul><li>↓ polymerization </li></ul><ul><li>FIBRIN – loose strands </li></ul><ul><li>Factor XIII-> ↓ ←Calcium </li></ul><ul><li>FIBRIN – tight clot </li></ul>
  13. 13. ANTICOAGULANTS <ul><li>The substances, which prevent or postpone coagulation of blood, are called anticoagulants. Some substances are used to prevent clotting inside the body i.e., in vivo & some substances used to prevent clotting outside the body i.e., in vitro. </li></ul>
  14. 14. The various anticoagulants are as follows: <ul><li>Heparin </li></ul><ul><li>Dicoumoral </li></ul><ul><li>Warfarin </li></ul><ul><li>EDTA(ethylenediaminetetraacetic acid) </li></ul><ul><li>Oxalate compounds </li></ul><ul><li>Citrates(sodium, ammonium or potassium citrate) </li></ul>
  15. 15. Anticoagulants are used: <ul><li>For the prophylaxis or treatment of thromboembolic disorders. </li></ul><ul><li>For preservation of stored whole blood & blood fractions (heparin & acid citrate dextrose). </li></ul><ul><li>To keep laboratory blood specimens from clotting (EDTA, citrate, oxalate & fluoride). </li></ul>
  16. 16. Tests for Clotting: <ul><li>Bleeding Time </li></ul><ul><li>Clotting Time </li></ul><ul><li>Prothrombin Time </li></ul>
  17. 18. MICROVASCULATURE <ul><li>The blood vessels are closed circuits for the transport of blood from the left heart to the metabolizing cells, & then back to the right heart. The blood containing oxygen, nutrients & metabolites is routed through ARTERIES , ARTERIOLES , CAPILLARIES , VENULES & VEINS . These blood vessels differ from each other in their structure & function. </li></ul>
  18. 19. <ul><li>Blood flows from the heart to arteries, which branch & narrow into arterioles. The arterioles give rise to metarterioles, which give rise to capillaries. After the tissue has been perfused, capillaries drain into venules , which are then widen more to become veins, & which return blood to the heart. </li></ul><ul><li>The microcirculation of each organ is specially organized to serve that organ’s own special needs – i.e., transport of nutrients to the tissues & removal of cellular excreta. </li></ul>
  19. 20. <ul><li>The “capillary bed” is the network of capillaries supplying an organ. </li></ul><ul><li>The capillaries are extremely thin structures with walls of a single layer of highly permeable endothelial cells. Here interchange of nutrients and cellular excreta occurs between the tissues & the circulating blood. </li></ul><ul><li>The walls of the arteries, arterioles & small venules contain relatively large amounts of smooth muscle. The openings of the capillaries are guarded by muscular precapillary sphincters. </li></ul>