Platelets physiology


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Platelets physiology

  1. 1. Hemostasis Defination: Prevention of blood loss.
  2. 2. Events Involved In Hemostasis
  3. 3. <ul><li>Whenever a vessel is ruptured, hemostasis is achieved by: </li></ul><ul><li>Vascular constriction </li></ul><ul><li>Formation of a platelet plug </li></ul><ul><li>Formation of a blood clot as a result of blood coagulation. </li></ul><ul><li>Eventual growth of fibrous tissue into the blood clot to close the hole in the vessel permanently. </li></ul>
  4. 4. Vascular Constriction
  5. 5. <ul><li>In ruptured blood vessel </li></ul><ul><li>1. Pain impulses from the site of trauma reach the spinal cord. </li></ul><ul><li>From the spinal cord order signal arise. </li></ul>
  6. 6. <ul><li>through the sympathatic nerves </li></ul><ul><li>Lead to spasm of the vessel . </li></ul><ul><li>2. Local muscle also contribute to the vascular vasospasm. </li></ul><ul><li>3. local autacoid factors from the traumatized tissues and blood platelets. </li></ul>
  7. 7. <ul><li>The vasospasm lasts for almost half an hour and it is directly proportional to the intensity of trauma . </li></ul>
  8. 8. <ul><li>In the smaller vessels , the platelets are responsible for much of the vasoconstriction by releasing a vasoconstrictor substance , thromboxane A 2 . </li></ul>
  9. 9. Formation of the Platelet Plug
  10. 10. Platelets
  11. 11. <ul><li>Platelets or thrombocytes are small colorless , non nucleated cells. </li></ul><ul><li>Shape is spherical or rod shaped and become oval or disc shaped when inactivated. </li></ul><ul><li>Size: 1 to 4 micrometers in diameter. </li></ul><ul><li>Life span: 10 - days </li></ul>
  12. 14. <ul><li>Development: From the pluripotentstem </li></ul><ul><li>cells in the bone marrow. </li></ul><ul><li>CFU-M Colony forming megakaryocytes </li></ul><ul><li>Megakaryoblast </li></ul><ul><li>Promegakaryoctye </li></ul><ul><li>Megakaryocytes </li></ul><ul><li>Platelets </li></ul>
  13. 15. <ul><li>Normal concentration : </li></ul><ul><li>150,000 to 300,000 per microliter. </li></ul><ul><li>Structure: </li></ul><ul><li>Cell membrane </li></ul><ul><li>Cytoplasm </li></ul>
  14. 16. Cell Membrane of Platelet
  15. 17. <ul><li>It is 6 nm thick and contain lipids (phospholipids, cholesterol and glycolipids), Carbohydrates (glycocalyx), Proteins and glycoproteins. </li></ul><ul><li>Out of all glycoprotein and phospholipids are functionally important. </li></ul>
  16. 18. Glycopropteins <ul><li>Prevents the adherence of platelets to normal endothelium. </li></ul><ul><li>Accelerates the adherence of platelets to collagen and damaged endothelium in ruptured blood vessels. </li></ul><ul><li>Forms a receptor for ADP and thrombin. </li></ul>
  17. 20. Cytoplasm <ul><li>The cytoplasm of the platelets include: </li></ul><ul><li>Golgi apparatus </li></ul><ul><li>Endoplasmic reticulum </li></ul><ul><li>Mitochondria </li></ul><ul><li>Microtubule </li></ul><ul><li>Microvessels </li></ul><ul><li>Microfilaments </li></ul><ul><li>Granules </li></ul>
  18. 21. <ul><li>Cytoplasm also contains: </li></ul><ul><li>Proteins </li></ul><ul><li>Enzymes </li></ul><ul><li>Hormones. </li></ul><ul><li>Chemical substances </li></ul>
  19. 22. Proteins <ul><li>The major proteins present are contractile proteins which are responsible for the contraction of platelets : </li></ul><ul><li>Actin </li></ul><ul><li>Myosin </li></ul><ul><li>Thrombosthenin </li></ul>
  20. 23. Chemical substances : <ul><li>Calcium ions </li></ul><ul><li>Mg- ions. </li></ul><ul><li>Adenosine triphosphate (ATP) </li></ul><ul><li>Adenosine diphosphate (ADP) </li></ul>
  21. 24. Function Of Platelets <ul><li>Its surface has glycoprotein coat that adhere it to injured endothelial cells… …. preventing bleeding . </li></ul><ul><li>Actin, myosin & thrombosthenin that are contractile proteins…. cause clot retraction. </li></ul>
  22. 25. <ul><li>Secretes growth factor that promotes growth & multiplication of vascular endothelial cells, vascular smooth cells & fibroblasts…. repair damaged vascular wall. </li></ul><ul><li>Its membrane has phospholipids that activate intrinsic system of blood clotting </li></ul>
  23. 26. Life span Of Platelets <ul><li>Platelets are eliminated from the circulation mainly by the tissue macrophage system in the spleen. </li></ul>
  24. 27. Mechanism of the Platelet Plug <ul><li>When platelets come in contact with a damaged vascular surface, platelets attach to the exposed collagen fibers in the vascular wall. </li></ul><ul><li>Platelets immediately change their own characteristics. </li></ul>
  25. 28. <ul><li>Platelets begin to swell and assume irregular forms with numerous irradiating pseudopods protruding from their surfaces </li></ul><ul><li>Contractile proteins in the platelets contract forcefully and cause the release of granules that contain multiple active factors </li></ul>
  26. 30. <ul><li>Adenosine diphosphate (ADP) is released which causes surface of nearby circulating platelets to become sticky and it adheres to the first layer of aggregated platelets </li></ul>
  27. 33. <ul><li>The aggregated platelets adhere to the von Willebrand factor that leaks into the traumatized tissue from the plasma </li></ul><ul><li>It leads to the release of more ADP , which cause more platelets to pile up at the defected site. </li></ul>
  28. 35. <ul><li>The aggregating process is reinforced by the formation of Thromboxane A 2. </li></ul><ul><li>It directly promotes platelet aggregation and further enhances it indirectly by triggering the release of even more ADP from the platelet granules. </li></ul><ul><li>Formation of platelet plug takes place </li></ul>
  29. 36. <ul><li>Thirdly, the platelet plug release other chemical substances that play a role in blood clotting. </li></ul><ul><li>Platelet plugging mechanism alone is sufficient to seal tears in the capillaries and small vessels but, large holes require formation of blood clot to stop bleeding. </li></ul>
  30. 37. Limitation of Platelet Plug <ul><li>Normal endothelium of the vessel release Prostacyclin which prevents platelet aggregation. </li></ul><ul><li>So, platelet plug is limited to the defected part of the vessel and does not spread to the normal vascular tissue. </li></ul>
  31. 38. Formation Of Blood Clot <ul><li>If there is a large defect in the vessel then blood clot + platelet plug are required to stop bleeding. </li></ul><ul><li>A clot on the top of platelet plug supports it and reinforces the seal over the break in the vessel. </li></ul>
  32. 39. <ul><li>Onset Of Formation Of Blood Clot: </li></ul><ul><li>15 – 20 sec …… in severe trauma. </li></ul><ul><li>1 – 2 min …… in minor trauma. </li></ul>
  33. 40. <ul><li>Ultimate step in clot formation is the conversion of fibrinogen which is a soluble protein that is produced by the liver and is normally always present in the plasma to fibrin which is insoluble thread like molecule. </li></ul><ul><li>thrombin </li></ul><ul><li>Fibrinogen Fibrin </li></ul>
  34. 41. <ul><li>Fibrin molecules adhere to the damaged vessel surface forming a loose netlike meshwork that traps the cellular elements of blood . </li></ul><ul><li>The clot appears red because of abundance of RBC that are trapped in it. </li></ul>
  35. 43. <ul><li>The original fibrin web is weak because the fibrin threads are loosely interlaced. </li></ul><ul><li>Rapidly, various chemical linkages are formed between adjacent strands to strengthen and stabilize the clot mesh work. </li></ul>
  36. 44. <ul><li>The cross linkage process which is catalyzed by a clotting factor known as factor XIII (Fibrin stabilizing factor). </li></ul>
  37. 46. Fibrous Organization or Dissolution of the Blood Clot
  38. 47. <ul><li>Once a blood clot has formed , it can follow one of two courses: </li></ul><ul><li>It can become invaded by fibroblast s , which subsequently form connective tissue all through the clot. </li></ul><ul><li>It can dissolve. </li></ul>
  39. 48. <ul><li>The usual course for a clot that forms in a small hole of a vessel wall…… is invasion by fibroblasts , beginning within a few hours after the clot is formed. </li></ul><ul><li>This event is promoted at least partially by growth factor secreted by platelets. </li></ul>
  40. 49. <ul><li>Complete organization of the clot into fibrous tissue takes place within 1 to 2 weeks. </li></ul><ul><li>When excess blood has leaked into the tissues and tissue clots have occurred where they are not needed. </li></ul>
  41. 50. <ul><li>Special substances within the clot itself usually become activated. These function as enzymes to dissolve the clot. </li></ul>
  42. 51. Mechanism of Blood Coagulation
  43. 52. <ul><li>Procoagulants: </li></ul><ul><li>Substances that cause or affect blood coagulation that have been found in the blood and in the tissues…. promote coagulation </li></ul><ul><li>Anticoagulants: </li></ul><ul><li>Substances that inhibit coagulation are called Anticoagulants. </li></ul>
  44. 53. <ul><li>Whether blood will coagulate depends on the balance between these two groups of substances. </li></ul><ul><li>In the blood stream, the anticoagulants normally predominate, so that the blood does not coagulate while it is circulating in the blood vessels. </li></ul>
  45. 54. <ul><li>But when a vessel is ruptured, procoagulants from the area of tissue damage become “activated” and override the anticoagulants, and then a clot does develop. </li></ul>
  46. 55. Three Essential Steps Involved In Clotting:
  47. 56. <ul><li>(1) In response to rupture of the vessel or damage to the blood itself, a complex cascade of chemical reactions occurs in the blood involving more than a dozen blood coagulation factors. </li></ul><ul><li>Formation of a complex of activated substances collectively called prothrombin activator. </li></ul>
  48. 57. <ul><li>(2) The prothrombin activator catalyzes conversion of prothrombin into thrombin in the presence of sufficient amounts of ionic Ca++ . </li></ul><ul><li>(3) The thrombin acts as an enzyme to convert fibrinogen into fibrin fibers that mesh with platelets, blood cells, and plasma to form the clot . </li></ul>
  49. 59. <ul><li>The clotting cascade may be triggered by the intrinsic pathway or the extrinsic pathway: </li></ul><ul><li>The intrinsic pathway precipitates clotting within damaged vessels as well as clotting of blood samples in test tubes. </li></ul>
  50. 60. <ul><li>All elements necessary to bring about clotting by means of the intrinsic pathway are present in the blood. </li></ul>
  51. 62. Extrinsic pathway for initiating clotting