Blood Physiology

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Blood Physiology

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Blood Physiology

  1. 1. BLOOD PHYSIOLOGY
  2. 2. Outline <ul><li>Blood and its composition </li></ul><ul><li>Red blood cells </li></ul><ul><li>White blood cells </li></ul><ul><li>Hemostasis and Blood Coagulation </li></ul><ul><li>Blood types </li></ul>
  3. 3. BLOOD <ul><li>A suspension of cells (formed elements) in plasma (solution of salt and proteins) </li></ul><ul><li>PLASMA </li></ul><ul><ul><li>Water </li></ul></ul><ul><ul><li>Dissolved ions </li></ul></ul><ul><ul><li>Proteins (carrier proteins, immunoproteins, coagulation proteins) </li></ul></ul>
  4. 4. BLOOD <ul><li>FORMED ELEMENTS </li></ul><ul><ul><li>Red blood cells </li></ul></ul><ul><ul><ul><li>Carry oxygen to the tissues and to return to the lungs carrying carbon dioxide </li></ul></ul></ul><ul><ul><li>White blood cells </li></ul></ul><ul><ul><ul><li>Defense against infection </li></ul></ul></ul><ul><ul><li>Platelets </li></ul></ul><ul><ul><ul><li>coagulation </li></ul></ul></ul>
  5. 5. BONE MARROW <ul><li>The site of production of most blood cells </li></ul><ul><li>One of the largest and most active organ </li></ul><ul><li>75% myeloid series, 25% erythroid series </li></ul>
  6. 6. BONE MARROW
  7. 7. RED BLOOD CELLS
  8. 8. RED BLOOD CELLS <ul><li>Biconcave discs, 7.8 micrometers </li></ul><ul><li>Can be deformed into any shape </li></ul><ul><ul><li>Excess cell membrane </li></ul></ul><ul><ul><li>Less tendency for rupture </li></ul></ul><ul><ul><li>Can squeeze through capillaries </li></ul></ul><ul><li>Functions: </li></ul><ul><ul><li>To transport hemoglobin (which carries O2) </li></ul></ul><ul><ul><li>Buffer (hemoglobin) </li></ul></ul><ul><ul><li>Efficient carrier of CO2 </li></ul></ul><ul><ul><ul><li>Role of carbonic anhydrase </li></ul></ul></ul>
  9. 9. RED BLOOD CELLS <ul><li>QUANTITY OF HEMOGLOBIN IN THE CELLS </li></ul><ul><ul><li>Average: 14-15 grms/dL </li></ul></ul><ul><ul><li>Maximum: 34 grams per dL (100 ml) </li></ul></ul><ul><ul><ul><li>The metabolic limit of the cell’s hemoglobin-forming mechanism </li></ul></ul></ul><ul><ul><li>One gram of Hgb can combine with 1.34 ml of oxygen = 19-20 ml O2 per 100 ml of blood </li></ul></ul>
  10. 10. RED BLOOD CELLS <ul><li>PRODUCTION </li></ul><ul><ul><li>Yolk sac Liver (spleen, lymph nodes) bone marrow </li></ul></ul><ul><ul><li>Bone marrow </li></ul></ul><ul><ul><ul><li>All bones until 5 years old </li></ul></ul></ul><ul><ul><ul><li>Beyond 20: membranous bones (vertebrae, sternum, ribs, and ilia) </li></ul></ul></ul>
  11. 11. RED BLOOD CELLS POLYCHROMATOPHILIC NORMOBLAST PRONORMOBLAST ORTHOCHROMIC NORMOBLAST RETICULOCYTE BASOPHILIC NORMOBLAST MATURE ERYTHROCYTE
  12. 12. RED BLOOD CELLS <ul><li>Proerythrocytes </li></ul><ul><ul><li>the first cell that can be identified as belonging to the erythroid series </li></ul></ul><ul><li>Basophilic erythroblast </li></ul><ul><ul><li>Basophilic cytoplasm </li></ul></ul><ul><ul><ul><li>Little hemoglobin </li></ul></ul></ul><ul><li>Orthochromic erythroblasts </li></ul><ul><ul><li>Cytoplasm same as mature erythrocytes </li></ul></ul><ul><ul><li>Still with nucleus </li></ul></ul><ul><li>Reticulocyte </li></ul><ul><ul><li>With reticulin materials in the cytoplasm </li></ul></ul><ul><ul><li>Anucleated </li></ul></ul><ul><ul><li>Matures in 1-2 days </li></ul></ul>
  13. 13. RED BLOOD CELLS <ul><li>REGULATION OF PRODUCTION </li></ul><ul><ul><li>Tissue oxygenation </li></ul></ul><ul><ul><ul><li>The most important regulator </li></ul></ul></ul><ul><ul><ul><li>Eg: anemias, persons living in high altitude </li></ul></ul></ul><ul><ul><li>Erythropoietin </li></ul></ul><ul><ul><ul><li>The principal stimulus for RBC production </li></ul></ul></ul><ul><ul><ul><li>Increased in response to hypoxia </li></ul></ul></ul><ul><ul><ul><li>90 % formed in the kidneys (renal tubular epithelial cells </li></ul></ul></ul><ul><ul><ul><li>Eg: renal failure </li></ul></ul></ul>
  14. 14. <ul><li>MATURATION </li></ul><ul><ul><li>Role of Vit B12 and Folic acid </li></ul></ul><ul><ul><ul><li>Essential for the synthesis of DNA </li></ul></ul></ul><ul><ul><ul><li>Deficiency would lead to delay in the maturation of the nucleus compared to the cytoplasm (macrocytes) </li></ul></ul></ul>RED BLOOD CELLS
  15. 15. RED BLOOD CELLS <ul><li>FORMATION OF HEMOGLOBIN </li></ul><ul><ul><li>Begins in the proerythroblasts </li></ul></ul><ul><ul><li>Starting molecule: succinyl coA </li></ul></ul><ul><ul><ul><li>Succinyl coA binds with glycine to form a pyrrole molecule </li></ul></ul></ul><ul><ul><ul><li>Four pyrroles combine to form protoporphyrin IX </li></ul></ul></ul><ul><ul><ul><li>Protoporphyrin IX combines with iron to form heme </li></ul></ul></ul><ul><ul><ul><li>Each heme combines with globin to form hemoglobin </li></ul></ul></ul>
  16. 16. THE HEMOGLOBINS 2 α 2 γ Hemoglobin F (Fetal) 2 α 2 δ Hemoglobin A2 2 α 2 β Hemoglobin A1 (Adult) Polypeptides Hemoglobin
  17. 17. RED BLOOD CELLS <ul><li>COMBINATION OF HEMOGLOBIN WITH OXYGEN </li></ul><ul><ul><li>Oxygen binds loosely with the coordination bonds of the iron atom </li></ul></ul><ul><ul><li>Reversible </li></ul></ul><ul><ul><li>Oxygen do not become ionized </li></ul></ul>
  18. 18. RED BLOOD CELLS <ul><li>IRON METABOLISM </li></ul><ul><ul><li>Total body iron: 4-5 gms </li></ul></ul><ul><ul><ul><li>65% hemoglobin </li></ul></ul></ul><ul><ul><ul><li>4 % myoglobin </li></ul></ul></ul><ul><ul><ul><li>1 % heme compounds (cytochrome, peroxidase, catalase) </li></ul></ul></ul><ul><ul><ul><li>0.1 % combined with protein transferrin </li></ul></ul></ul><ul><ul><ul><li>15-30% storage pool as ferritin (RES, liver) </li></ul></ul></ul>
  19. 19. RED BLOOD CELLS <ul><li>Daily, a normal adult, destroys 15 ml of senescent red cells and produces an equal quantity of new red cells. </li></ul><ul><li>For the daily production of erythrocytes, about 15 mg of iron is required. </li></ul><ul><li>Almost all of the iron needed is drawn from stores, which was recycled from the destruction of old red cells. </li></ul><ul><li>The vast majority of the iron is retained in the body as it is moved from one compartment to another. </li></ul><ul><li>Very little is iron is obtained from the diet. </li></ul>
  20. 20. RED BLOOD CELLS <ul><li>Transport and Storage of Iron </li></ul><ul><ul><li>Iron absorbed from the intestine combines with apotransferrin to form transferrin </li></ul></ul><ul><ul><li>Transferrin carries the iron to the cells </li></ul></ul><ul><ul><li>In the cell cytoplasm, iron combines with apoferritin to form ferritin (storage iron) </li></ul></ul><ul><ul><ul><li>When in excess, stored as insoluble hemosiderin </li></ul></ul></ul><ul><ul><li>When needed, the ferritin storage pool is transported as transferrin </li></ul></ul><ul><ul><ul><li>Transferrin binds strongly to the cell membranes of the erythroblasts </li></ul></ul></ul><ul><ul><ul><li>Ingested by the erythroblasts and iron is directly delivered to the mitochondria (heme synthesis) </li></ul></ul></ul>
  21. 21. <ul><li>Recycling of the iron by the body is not a tight system. </li></ul><ul><li>A normal healthy person loses around 1 to 2 mg of iron everyday. </li></ul><ul><ul><li>Menstruation </li></ul></ul><ul><ul><li>GIT (sloughed epithelium) </li></ul></ul><ul><ul><li>Exfoliated skin </li></ul></ul>
  22. 23. RED BLOOD CELLS <ul><li>ABSORPTION OF IRON FROM THE GIT </li></ul><ul><ul><li>Liver secretes apotransferrin to the bile </li></ul></ul><ul><ul><li>In the duodenum, the apotransferrin binds with free iron and other iron compounds (hemoglobin and myoglobin) to form transferrin </li></ul></ul><ul><ul><li>Transferrin binds to the receptors in the membranes of the intestinal epithelial cells </li></ul></ul><ul><ul><li>By pinocytosis, the transferrin is absorbed into the epithelial cells and released into the blood capillaries </li></ul></ul>
  23. 24. IRON CYCLE
  24. 25. RED BLOOD CELLS <ul><li>IRON REGULATION </li></ul><ul><ul><li>Through altering the rate of absorption </li></ul></ul><ul><ul><li>When all the apoferritin in the storage areas are filled up with iron, the rate of GIT absorption slows down </li></ul></ul><ul><ul><li>Increase in the absorption occurs with iron depletion </li></ul></ul>
  25. 26. RED BLOOD CELLS <ul><li>LIFE SPAN and DESTRUCTION </li></ul><ul><ul><li>120 days </li></ul></ul><ul><ul><ul><li>Less pliable </li></ul></ul></ul><ul><ul><li>The senescent red cell ruptures when it pass through the spleen (red pulp) </li></ul></ul><ul><ul><li>Hemoglobin </li></ul></ul><ul><ul><ul><li>Upon release, phagocytosed by macrophages (spleen, liver, bone marrow) </li></ul></ul></ul><ul><ul><ul><li>The iron is released back into the blood and recycled </li></ul></ul></ul><ul><ul><ul><li>Porphyrin converted to bilirubin </li></ul></ul></ul>
  26. 27. RED BLOOD CELLS <ul><li>ANEMIAS </li></ul><ul><ul><li>Deficiency of hemoglobin </li></ul></ul><ul><ul><li>Causes: </li></ul></ul><ul><ul><ul><li>Blood loss anemia </li></ul></ul></ul><ul><ul><ul><li>Aplastic anemia </li></ul></ul></ul><ul><ul><ul><li>Megaloblastic anemia </li></ul></ul></ul><ul><ul><ul><li>Hemolytic anemias </li></ul></ul></ul><ul><ul><li>Effects on the body </li></ul></ul><ul><ul><ul><li>Decreases blood viscosity, increases venous return and increases cardiac output </li></ul></ul></ul><ul><ul><ul><li>Hypoxia causes peripheral vessel dilatation </li></ul></ul></ul>
  27. 28. RED BLOOD CELLS <ul><li>POLYCYTHEMIA </li></ul><ul><ul><li>Secondary </li></ul></ul><ul><ul><ul><li>Hypoxia stimulates production of erythropoietin </li></ul></ul></ul><ul><ul><ul><li>Eg: those living in high altitudes, cyanotic CHD </li></ul></ul></ul><ul><ul><li>Polycythemia vera </li></ul></ul><ul><ul><ul><li>Myeloproliferative disorder </li></ul></ul></ul><ul><ul><ul><li>Normal erythropoietin </li></ul></ul></ul><ul><ul><ul><li>Normal oxygen saturation </li></ul></ul></ul>
  28. 29. RED BLOOD CELLS <ul><li>Effect of polycythemia </li></ul><ul><ul><li>Increased blood viscosity diminishes blood flow </li></ul></ul><ul><ul><li>Decreases venous return to the hear </li></ul></ul><ul><ul><li>Arterial pressure often normal </li></ul></ul>
  29. 30. LEUKOCYTES <ul><li>Mobile units of the body’s resistance to infection </li></ul><ul><li>Formed in the bone marrow and some in the lymph nodes </li></ul><ul><li>Six types: </li></ul><ul><ul><li>Neutrophils </li></ul></ul><ul><ul><li>Eosinophils </li></ul></ul><ul><ul><li>Basophils </li></ul></ul><ul><ul><li>Monocytes </li></ul></ul><ul><ul><li>Lymphocytes </li></ul></ul><ul><ul><li>Plasma cells </li></ul></ul>
  30. 31. LEUKOCYTES <ul><li>Neutrophils and monocytes protect the body by phagocytosis </li></ul><ul><li>Lymphocytes and plasma cells – through humoral and cell mediated immunity </li></ul>
  31. 32. LEUKOCYTES
  32. 33. LEUKOCYTES <ul><li>LIFE SPAN </li></ul><ul><ul><li>Granulocytes: 4 to 8 hours in the blood, 4 to 5 days in the tissues </li></ul></ul><ul><ul><li>Monocytes: 10-20 hours in the blood, months in the tissues as macrophages </li></ul></ul><ul><ul><li>Lymphoctyes: circulates continually, weeks to months </li></ul></ul>
  33. 34. LEUKOCYTES <ul><li>NEUTROPHILS and MACROPHAGES </li></ul>
  34. 35. LEUKOCYTES <ul><li>Neutrophils – can attack and destroy even in the blood </li></ul><ul><li>Monocytes – macrophages in the blood </li></ul><ul><li>Macrophages – monocytes that enter the tissues </li></ul><ul><li>Diapedesis – the process by which neutrophils and monocytes squeeze through the pores of the blood capillaries </li></ul><ul><li>White blood cells move through tissue spaces by ameboid motion </li></ul>
  35. 36. LEUKOCYTES <ul><li>CHEMOTAXIS </li></ul><ul><ul><li>Chemical substances in the tissues cause neutrophils and macrophages to move toward the source </li></ul></ul><ul><ul><li>Some chemotactins: </li></ul></ul><ul><ul><ul><li>Bacterial or viral toxins </li></ul></ul></ul><ul><ul><ul><li>Degenerative products of the inflammed tissue </li></ul></ul></ul><ul><ul><ul><li>Products of the complements activated by the inflammation </li></ul></ul></ul><ul><ul><ul><li>Reaction products caused by plasma clotting in the area of inflammation </li></ul></ul></ul>
  36. 37. LEUKOCYTES <ul><li>CHEMOTAXIS </li></ul><ul><ul><li>Unidirectional movement. </li></ul></ul><ul><ul><li>Concentration of the substance greatest near the source. </li></ul></ul><ul><ul><li>Effective up to 100 micrometers away </li></ul></ul><ul><ul><li>No tissue area is more than 50 micrometers away from a capillary </li></ul></ul>
  37. 38. LEUKOCYTES <ul><li>PHAGOCYTOSIS </li></ul><ul><ul><li>Cellular ingestion of foreign bodies </li></ul></ul><ul><ul><li>The most important function of the neutrophils and macrophages </li></ul></ul><ul><ul><li>Selective and does not attack normal tissues: </li></ul></ul><ul><ul><ul><li>Smooth surfaces </li></ul></ul></ul><ul><ul><ul><li>Protective protein coats </li></ul></ul></ul><ul><ul><ul><li>Antibodies (with C3) adhere to the bacteria (opsonization) </li></ul></ul></ul>
  38. 39. LEUKOCYTES <ul><li>PHAGOCYTOSIS BY NEUTROPHILS </li></ul><ul><ul><li>Neutrophils are already mature </li></ul></ul><ul><ul><li>Pseudopods meet to form a chamber </li></ul></ul><ul><ul><li>Phagosome breaks off from the wall </li></ul></ul><ul><ul><li>Can phagocytize 3 to 20 bacteria before it becomes inactivated and dies </li></ul></ul>
  39. 40. LEUKOCYTES <ul><li>PHAGOCYTOSIS BY MACROPHAGES </li></ul><ul><ul><li>End stage product of monocytes </li></ul></ul><ul><ul><li>Activated by the immune system </li></ul></ul><ul><ul><li>As many as 100 bacteria, and larger particles </li></ul></ul>
  40. 41. LEUKOCYTES <ul><li>PHAGOCYTOSIS </li></ul><ul><ul><li>Once ingested, particles are digested by intracellular enzymes </li></ul></ul><ul><ul><li>Bactericidal agents in the peroxisome: superoxide, hydrogen peroxide, hydroxyl ions </li></ul></ul>
  41. 42. LEUKOCYTES <ul><li>RETICULOENDOTHELIAL SYSTEM </li></ul><ul><ul><li>Monocyte-Macrophage cell system </li></ul></ul><ul><ul><li>The total combination of monocytes, mobile macrophages, fixed tissue macrophages and a few specialized endothelial cells in the bone marrow, spleen, and lymph nodes </li></ul></ul><ul><ul><li>Generalized phagocytic system located in all tissues esp in areas where large quantities of unwanted substances must be destroyed </li></ul></ul>
  42. 43. LEUKOCYTES <ul><li>RETICULOENDOTHELIAL SYSTEM </li></ul><ul><ul><li>Histiocytes: in the skin and subcutaneous tissue </li></ul></ul><ul><ul><li>Macrophages in the lymph nodes – in the sinuses </li></ul></ul><ul><ul><li>Alveolar macrophages in the lungs </li></ul></ul><ul><ul><ul><li>as integral components of the alveolar walls </li></ul></ul></ul><ul><ul><ul><li>If the particle is digestible, the digestive prodcuts are released into the lymph </li></ul></ul></ul><ul><ul><ul><li>If not digestible, they form a “giant cell” capsule (e.g. tuberculosis </li></ul></ul></ul>
  43. 44. LEUKOCYTES <ul><li>RETICULOENDOTHELIAL SYSTEM </li></ul><ul><ul><li>Liver sinusoids: Kupffer cells </li></ul></ul><ul><ul><li>Macrophages in the spleen and marrow </li></ul></ul><ul><ul><ul><li>The macrophages become entrapped by the reticular meshwork </li></ul></ul></ul>
  44. 45. LEUKOCYTES <ul><li>INFLAMMATION </li></ul><ul><ul><li>Vasodilatation </li></ul></ul><ul><ul><ul><li>Increase local blood flow </li></ul></ul></ul><ul><ul><li>Increased capillary permeability </li></ul></ul><ul><ul><ul><li>Leakage of large quantities of fluid into the interstitial spaces </li></ul></ul></ul><ul><ul><li>Coagulation </li></ul></ul><ul><ul><ul><li>Because of fibrinogen </li></ul></ul></ul><ul><ul><li>Migration of the phagocytes </li></ul></ul><ul><ul><ul><li>chemotaxis </li></ul></ul></ul><ul><ul><li>Swelling of the tissue cells </li></ul></ul>
  45. 46. LEUKOCYTES <ul><li>INFLAMMATION </li></ul><ul><ul><li>Walling effect </li></ul></ul><ul><ul><ul><li>Fibrinogen clots block off the inflammed area </li></ul></ul></ul><ul><ul><ul><li>Delays the spread of bacteria or toxic products </li></ul></ul></ul><ul><ul><ul><li>Intensity depend on the degree of tissue injury </li></ul></ul></ul>
  46. 47. LEUKOCYTES <ul><li>Macrophage and Neutrophil Responses during Inflammation </li></ul><ul><ul><li>First line of defense: macrophages in the tissues </li></ul></ul><ul><ul><li>Second line: Neutrophil invasion </li></ul></ul><ul><ul><li>Third line: Second macrophage invasion </li></ul></ul><ul><ul><li>Fourth line : Increased production of granulocytes and monocytes by the marro </li></ul></ul>
  47. 48. LEUKOCYTES <ul><li>Macrophage and Neutrophil Responses during Inflammation </li></ul><ul><ul><li>First line of defense: macrophages in the tissues </li></ul></ul><ul><ul><ul><li>Rapid enlargement of the cells </li></ul></ul></ul><ul><ul><ul><li>Macrophages becomes mobile </li></ul></ul></ul><ul><ul><ul><li>Immediate phagocytosis </li></ul></ul></ul>
  48. 49. LEUKOCYTES <ul><li>Macrophage and Neutrophil Responses during Inflammation </li></ul><ul><ul><li>Second line: Neutrophil invasion </li></ul></ul><ul><ul><ul><li>Products from inflamed tissues initiate the following reactions: </li></ul></ul></ul><ul><ul><ul><li>Margination – alteration of the endothelium causing neutrophils to stick to the walls </li></ul></ul></ul><ul><ul><ul><li>Increased capillary permeability facilitating diapedesis </li></ul></ul></ul><ul><ul><ul><li>Release of chemotaxins </li></ul></ul></ul><ul><ul><li>Neutrophilia within hours after onset </li></ul></ul><ul><ul><ul><li>Caused by products of inflammation which are transported to the marrow and act on the stored neutrophils to mobilize these into the circulating blood </li></ul></ul></ul>
  49. 50. LEUKOCYTES <ul><li>Macrophage and Neutrophil Responses during Inflammation </li></ul><ul><ul><li>Third Line: Second macrophage invasion </li></ul></ul><ul><ul><ul><li>Requires several days </li></ul></ul></ul><ul><ul><ul><li>Storage pool of monocytes in the marrow is low </li></ul></ul></ul><ul><ul><ul><li>Takes 8 hours for the monocytes to mature </li></ul></ul></ul>
  50. 51. LEUKOCYTES <ul><li>Macrophage and Neutrophil Responses during Inflammation </li></ul><ul><ul><li>Fourth line: production of granulocytes and monocytes by the marrow </li></ul></ul><ul><ul><ul><li>Results from stimulation of the granulocytic and monocytic progenitor cells </li></ul></ul></ul><ul><ul><ul><li>Takes 3 to 4 days </li></ul></ul></ul>
  51. 52. LEUKOCYTES <ul><li>CONTROL OF THE MACROPHAGE AND NEUTROPHIL RESPONSES </li></ul><ul><ul><li>Tumor necrosis factor </li></ul></ul><ul><ul><li>Interleukin 1 </li></ul></ul><ul><ul><li>GM-CSF </li></ul></ul><ul><ul><li>G-CSF </li></ul></ul><ul><ul><li>M-CSF </li></ul></ul>
  52. 53. LEUKOCYTES <ul><li>Formation of pus </li></ul><ul><ul><li>Cavity in the inflamed tissue composed of necrotic tissue, dead neutrophils and macrophages and tissue fluid </li></ul></ul><ul><ul><li>Autolyze over a period of days </li></ul></ul>
  53. 54. LEUKOCYTES <ul><li>EOSINOPHILS </li></ul><ul><ul><li>Weak phagocytes </li></ul></ul><ul><ul><li>Important in parasitic infection - attach to the parasite and release substances that can kill </li></ul></ul><ul><ul><ul><li>By releasing hydrolytic enzymes </li></ul></ul></ul><ul><ul><ul><li>Release of highly reactive forms of oxygen </li></ul></ul></ul><ul><ul><ul><li>Release of major basic protein, a larvacidal polypeptide </li></ul></ul></ul>
  54. 55. LEUKOCYTES <ul><li>EOSINOPHILS </li></ul><ul><ul><li>Accumulate in the tissues in which allergic reaction occur because the mast cells and basophils release an eosinophilic chemotactic factor </li></ul></ul><ul><ul><li>Detoxify some of the substances released by mast cells and basophils </li></ul></ul>
  55. 56. LEUKOCYTES <ul><li>BASOPHILS </li></ul><ul><ul><li>Basophils in the circulating blood, mast cess in the tissues </li></ul></ul><ul><ul><li>Can release heparin, histamin, bradykinin and serotonin </li></ul></ul><ul><ul><li>Role in allergic reactions </li></ul></ul>
  56. 57. HEMOSTASIS AND BLOOD COAGULATION
  57. 58. HEMOSTASIS AND BLOOD COAGULATION <ul><li>HEMOSTASIS </li></ul><ul><ul><li>Means prevention of blood loss </li></ul></ul><ul><ul><li>Events </li></ul></ul><ul><ul><ul><li>Vascular constriction </li></ul></ul></ul><ul><ul><ul><li>Formation of a platelet plug </li></ul></ul></ul><ul><ul><ul><li>Formation of a blood clot </li></ul></ul></ul><ul><ul><ul><li>Growth of fibrous tissue </li></ul></ul></ul>
  58. 59. Normal hemostasis Vessel injury Collagen exposure TXA2, ADP Platelet aggregation 1  hemostatic plug Stable hemostatic plug Vasoconstriction  blood flow Tissue thromboplastin Blood coag. Fibrin
  59. 60. HEMOSTASIS AND BLOOD COAGULATION <ul><li>VASCULAR CONSTRICTION </li></ul><ul><ul><li>Trauma causes the smooth muscles in the vessel walls to contract </li></ul></ul><ul><ul><li>Local myogenic spasm </li></ul></ul><ul><ul><ul><li>Direct damage to the vessel wall </li></ul></ul></ul><ul><ul><li>Local autacoid factors from the traumatized tissues and blood platelets </li></ul></ul><ul><ul><ul><li>Thromboxane A2 from platelets </li></ul></ul></ul><ul><ul><li>Nervous reflexes </li></ul></ul><ul><ul><ul><li>Initiated by pain nerve impulses or other sensory impulses that originate from the traumatized vessel or nearby tissues </li></ul></ul></ul>
  60. 61. HEMOSTASIS AND BLOOD COAGULATION <ul><li>PLATELETS: formation of the platelet plug </li></ul><ul><ul><li>Formed from megakaryocytes </li></ul></ul><ul><ul><li>Membranes: </li></ul></ul><ul><ul><ul><li>Glycoproteins: prevent adherence to normal endothelium and yet causes adherence to injured areas </li></ul></ul></ul><ul><ul><ul><li>Phospholipids: important in blood clotting </li></ul></ul></ul><ul><ul><li>Cytoplasm: </li></ul></ul><ul><ul><ul><li>Contractile proteins: Actin, myosin, thrombasthenin </li></ul></ul></ul><ul><ul><ul><li>Residuals of ER and golgi apparatus (enzymes and Calcium ions) </li></ul></ul></ul><ul><ul><ul><li>Mitochondria (ATP and ADP) </li></ul></ul></ul><ul><ul><ul><li>Enzyme systems (prostaglandins) </li></ul></ul></ul><ul><ul><ul><li>Fibrin stabilizing factor </li></ul></ul></ul><ul><ul><ul><li>Growth factor </li></ul></ul></ul>
  61. 62. MECHANISM OF THE PLATELET PLUG <ul><li>Platelets come in contact with a damaged vascular surface </li></ul><ul><li>Platelet change: swelling, assume irregular forms with numerous pseudopods </li></ul><ul><li>Contractile proteins contract forcefully and cause release of granules that contain multiple active factors </li></ul><ul><li>They become sticky and adhere to collagen in the tissues and to vWF </li></ul><ul><li>They secret ADP and thromboxane A2- activates other platelets </li></ul><ul><li>Formation of a platelet plug </li></ul>
  62. 63. HEMOSTASIS AND BLOOD COAGULATION <ul><li>Importance of the Platelet plug </li></ul><ul><ul><li>For closing minute irregular rupture in very small blood vessels which occur many times daily </li></ul></ul>
  63. 64. HEMOSTASIS AND BLOOD COAGULATION <ul><li>FORMATION OF BLOOD CLOT </li></ul><ul><ul><li>15 to 20 seconds if trauma is severe </li></ul></ul><ul><ul><li>1 to 2 minutes in minor trauma </li></ul></ul><ul><ul><li>Within 3 to 6 minutes the entire opening is filled with clot </li></ul></ul><ul><ul><li>After 20 minutes to an hour, the clot retracts </li></ul></ul>
  64. 65. HEMOSTASIS AND BLOOD COAGULATION <ul><li>Mechanism of blood coagulation </li></ul><ul><ul><li>Balance between the procoagulants and anticoagulants </li></ul></ul><ul><ul><li>In the blood, the anti-coagulants predominate </li></ul></ul><ul><ul><li>When a vessel is ruptured, procoagulants become “activated” </li></ul></ul>
  65. 66. MECHANISM OF BLOOD COAGULATION <ul><li>Three essential steps: </li></ul><ul><ul><li>Formation of prothrombin activator </li></ul></ul><ul><ul><li>Conversion of prothrombin into thrombin </li></ul></ul><ul><ul><li>Conversion of fibrinogen to fibrin </li></ul></ul>
  66. 67. MECHANISM OF BLOOD COAGULATION <ul><li>Rate limiting factor: the formation of the prothrombin activator </li></ul><ul><ul><li>Extrinsic pathway </li></ul></ul><ul><ul><ul><li>Begins with trauma to the vascular wall </li></ul></ul></ul><ul><ul><li>Intrinsic pathway </li></ul></ul><ul><ul><ul><li>Begins in the blood itself </li></ul></ul></ul>
  67. 68. MECHANISM OF BLOOD COAGULATION <ul><li>EXTRINSIC PATHWAY </li></ul><ul><ul><li>Begins with a traumatized vascular wall or traumatized extravascular tissues </li></ul></ul><ul><ul><li>Release of tissue factor (TPL) from the traumatized tissues: activates factor VII </li></ul></ul><ul><ul><li>Activation of factor X: by the TF, F V, Ca and FVIIa complex </li></ul></ul><ul><ul><li>F Xa + F V + Ca forms prothrombin activator </li></ul></ul><ul><ul><li>Prothrombin splits to form thrombin </li></ul></ul>
  68. 69. MECHANISM OF BLOOD COAGULATION <ul><li>Intrinsic pathway </li></ul><ul><ul><li>Begins with trauma to the blood itself or exposure of the blood to collagen </li></ul></ul><ul><ul><li>Blood trauma causes activation of FXII and release of phospholipids </li></ul></ul><ul><ul><li>FXIIa activates FXI (with the help of HMWK), accelerated by prekallikrein </li></ul></ul><ul><ul><li>FXIa activates FIX </li></ul></ul><ul><ul><li>FIXa with F VIIIa (activated by thrombin) plus Calcium becomes the prothrombin activator </li></ul></ul>
  69. 73. HEMOSTASIS AND BLOOD COAGULATION <ul><li>Role of calcium </li></ul><ul><ul><li>Needed n all the steps except in the first 2 steps of the intrinsic pathway </li></ul></ul><ul><ul><li>Calcium ion concentration in the body seldom falls low enough to affect blood clotting </li></ul></ul>
  70. 74. PREVENTION OF BLOOD CLOTTING <ul><li>Endothelial surface factors </li></ul><ul><ul><li>Smoothness of the surface </li></ul></ul><ul><ul><li>Layer of glycocalyx: repels clotting factors and platelets </li></ul></ul><ul><ul><li>Thrombomodulin </li></ul></ul><ul><ul><ul><li>binds thrombin and slow down the clotting process </li></ul></ul></ul><ul><ul><ul><li>Activates protein C which inactivates F V and VIII </li></ul></ul></ul>
  71. 75. PREVENTION OF BLOOD CLOTTING <ul><li>Fibrin and anti-thrombin III </li></ul><ul><ul><li>The fibrin fibers adsorb the thrombin formed limiting the spread of the clot </li></ul></ul><ul><ul><li>Antithrombin III blocks the effect of thrombin </li></ul></ul><ul><li>Heparin </li></ul><ul><ul><li>Normally low in concentration </li></ul></ul><ul><ul><li>Accelerates the action of antithrombin III </li></ul></ul>
  72. 76. HEMOSTASIS AND BLOOD COAGULATION <ul><li>LYSIS OF BLOOD CLOTS </li></ul><ul><ul><li>Tissue plasminogen activator: </li></ul></ul><ul><ul><ul><li>from the injured tissues and vascular endothelium </li></ul></ul></ul><ul><ul><ul><li>Converts plasminogen to plasmin </li></ul></ul></ul><ul><ul><ul><li>Plasmin digests fibrin fibers, fibrinogen, FV, VIII, prothrombin and FXII </li></ul></ul></ul>
  73. 77. BLOOD TYPES none A and B AB AB Anti- A B B O/B or B/B Anti-B A A O/A or A/A Anti-A and anti-B - O O/O Agglutinins Agglutinogens Blood Types Genotypes
  74. 78. BLOOD TYPES <ul><li>Relative frequencies </li></ul><ul><ul><li>Type O 47% </li></ul></ul><ul><ul><li>Type A 41% </li></ul></ul><ul><ul><li>Type B 9% </li></ul></ul><ul><ul><li>Type AB 3% </li></ul></ul>
  75. 79. BLOOD TYPES <ul><li>Agglutinins </li></ul><ul><ul><li>At birth, no agglutinins present </li></ul></ul><ul><ul><li>Two to 8 months: production of agglutinins </li></ul></ul><ul><ul><li>Maximum titer achieved at 8 to 10 years </li></ul></ul><ul><ul><li>Most are IgG and IgM </li></ul></ul><ul><ul><li>Produced by the bone marrow and lymph nodes </li></ul></ul><ul><ul><li>Naturally occuring </li></ul></ul>
  76. 80. RH BLOOD TYPES <ul><li>Six Rh antigens: C, D, E, c, d, e </li></ul><ul><li>The presence of D antigen confers Rh positivity </li></ul><ul><li>Spontaneous Rh agglutinins never occur, the person must first be exposed to an Rh antigen to form agglutinins </li></ul><ul><li>An Rh negative mother having her first Rh positive child will have no problems </li></ul><ul><li>Rh incompatibility can be prevented by injecting anti-D to the mother </li></ul>

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