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4. hemostasis; hemodynamic disorders

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4. hemostasis; hemodynamic disorders

  1. 1. Hemodynamic Disorders Hemodynamic Disorders  Edema  Edema  Hyperemia and Congestion  Hyperemia and Congestion  Hemorrhage  Hemorrhage  Hemostasis and Thrombosis  Hemostasis and Thrombosis  Embolism  Embolism  Infarction  Infarction  Shock  Shock 1 Dr. Krishna Tadepalli, MD, www.mletips.com
  2. 2. Feature Hemostasis Thrombosis What is it? Blood clot Blood clot Where is it? Site of vascular injury In an uninjured vessel Why is it? Trauma (common) Atherosclerosis What happens later? Stops blood loss Produce (deserved effect) complications (Emboli) 2 Dr. Krishna Tadepalli, MD, www.mletips.com
  3. 3. Hemostasis Hemostasis  Events following vascular injury  Events following vascular injury  1. transient vasoconstriction ( by neurogenic  1. transient vasoconstriction ( by neurogenic mechanisms, Endothelin – vasoconstrictor of mechanisms, Endothelin – vasoconstrictor of Endothelial cells), reduce blood loss Endothelial cells), reduce blood loss  2. Primary Hemostasis  formation of Primary  2. Primary Hemostasis  formation of Primary haemostatic plug (( by platelet adhesion, activation haemostatic plug by platelet adhesion, activation & Aggregation), & Aggregation),  3. Secondary Hemostasis  Platelets + Fibrin  3. Secondary Hemostasis  Platelets + Fibrin (( from coagulation pathways- either intrinsic or from coagulation pathways- either intrinsic or extrinsic), forms secondary haemostatic plug extrinsic), forms secondary haemostatic plug 3 Dr. Krishna Tadepalli, MD, www.mletips.com
  4. 4. Hemostasis Hemostasis  Role of Endothelium  Role of Endothelium  1. Produce Pro-thrombotic (( Plasminogen  1. Produce Pro-thrombotic Plasminogen activator inhibitors – PAI, Tissue factor, vWF) activator inhibitors – PAI, Tissue factor, vWF) and Anti-thrombotic factors (( Vasodilators – and Anti-thrombotic factors Vasodilators – PGI2, NO; tPA, Heparin like molecules & PGI2, NO; tPA, Heparin like molecules & Thombomodulin) Thombomodulin)  2. Balance of these factors determine the end result  2. Balance of these factors determine the end result (( clot or dissolution of clot) clot or dissolution of clot) 4 Dr. Krishna Tadepalli, MD, www.mletips.com
  5. 5. PAI 5 Dr. Krishna Tadepalli, MD, www.mletips.com
  6. 6. Coagulation pathway Coagulation pathway  Role of Platelets  Role of Platelets  Granules  α granules( contain clotting factors &  Granules  α granules( contain clotting factors & Growth factors), Dense or δ granules (( ADP, Ca++++, Growth factors), Dense or δ granules ADP, Ca , Neuropeptides, Epinephrine) Neuropeptides, Epinephrine)  Response to injury  bind to sub-endothelial  Response to injury  bind to sub-endothelial ECM (( vWF + Gp -Ib) Adhesion ECM vWF + Gp -Ib) Adhesion  Expose Phospholipid complexes (helps in intrinsic  Expose Phospholipid complexes (helps in intrinsic clotting pathway) & release ADP& Ca++++ clotting pathway) & release ADP& Ca  Aggregate with other platelets (( with fibrin by Gp  Aggregate with other platelets with fibrin by Gp IIb-IIIa on platelet surfaces IIb-IIIa on platelet surfaces 6 Dr. Krishna Tadepalli, MD, www.mletips.com
  7. 7. Hemostasis 7 Dr. Krishna Tadepalli, MD, www.mletips.com
  8. 8. Aspirin in patients at risk for coronary thrombosis8 It irreversibly acetylates and inactivates cyclooxygenase-1  due to its ability to block TxA2 synthesis EQ Dr. Krishna Tadepalli, MD, www.mletips.com
  9. 9. 9 Dr. Krishna Tadepalli, MD, www.mletips.com
  10. 10. Coagulation pathway Coagulation pathway 10 Dr. Krishna Tadepalli, MD, www.mletips.com
  11. 11. Coagulation pathway Coagulation pathway  Most important step in this pathway  Most important step in this pathway (either intrinsic or extrinsic)  formation of (either intrinsic or extrinsic)  formation of Thrombin Thrombin  Thrombin produces it effects  through  Thrombin produces it effects  through PARS( Protease activated receptors – 7 GPCR PARS( Protease activated receptors – 7 GPCR family) family)  Major effects of Thrombin  Major effects of Thrombin  Fibrin formation from Fibrinogen  Fibrin formation from Fibrinogen  On Platelets TxA2  On Platelets TxA2  On Endothelial cells NO, tPA, PGI2  On Endothelial cells NO, tPA, PGI2  act also on Lymphocytes, Neutrophils, Monocytes  act also on Lymphocytes, Neutrophils, Monocytes 11 Dr. Krishna Tadepalli, MD, www.mletips.com
  12. 12. Coagulation pathway Coagulation pathway  Thrombin  Thrombin 12 Dr. Krishna Tadepalli, MD, www.mletips.com
  13. 13. Anti -- Coagulants Anti Coagulants Natural ones Natural ones  1. Antithrombins( AT-III)  inactivate Thrombin;  1. Antithrombins( AT-III)  inactivate Thrombin; Factors IX to XII; bind to heparin like molecule on Factors IX to XII; bind to heparin like molecule on endothelium endothelium  2. Proteins – C & S  produced by liver; need Vit. K for  2. Proteins – C & S  produced by liver; need Vit. K for activation; inactivate Factors V, VIII activation; inactivate Factors V, VIII  Tissue Factor Pathway Inhibitors (TFPI)  inhibit  Tissue Factor Pathway Inhibitors (TFPI)  inhibit factors VII, X factors VII, X Clinical significance Clinical significance Heparin act through AT-III; Monitor PTT (Intrinsic pathway), Antidote is Heparin act through AT-III; Monitor PTT (Intrinsic pathway), Antidote is Protamine, can produce HIT (heparin induced thrombocytopenia); can be Protamine, can produce HIT (heparin induced thrombocytopenia); can be given in pregnancy (as it can’t cross placenta); need frequent injections given in pregnancy (as it can’t cross placenta); need frequent injections Warfarin  act through inhibition of Vit K mediated carboxylation of Warfarin  act through inhibition of Vit K mediated carboxylation of clotting factors (II,VII, IX, X); Extrinsic pathway Monitor PT; Antidote is 13 clotting factors (II,VII, IX, X); Extrinsic pathway Monitor PT; Antidote is Vit.K contraindicated in pregnancy (teratogenic) Vit.K1 1;;contraindicated in pregnancy (teratogenic) Dr. Krishna Tadepalli, MD, www.mletips.com
  14. 14. Fibrinolytic pathway Fibrinolytic pathway  Most important step in this pathway  Most important step in this pathway  formation of Plasmin from Plasminogen  formation of Plasmin from Plasminogen  Tissue Plasminogen activator (tPA) is important in this  Tissue Plasminogen activator (tPA) is important in this conversion conversion  Plasmin  breaks down excess Fibrin  Fibrin split  Plasmin  breaks down excess Fibrin  Fibrin split products or Fibrin degradation products (FSP or FDP) products or Fibrin degradation products (FSP or FDP)  Most important component of FDP  D-dimer  Most important component of FDP  D-dimer Clinical significance Clinical significance D-dimer positivity (≥200 ng) patient had clot and it is lysed by D-dimer positivity (≥200 ng) patient had clot and it is lysed by Plasmin Plasmin Conditions where D-dimer is positive  DIC, DVT, PE Conditions where D-dimer is positive  DIC, DVT, PE 14 Dr. Krishna Tadepalli, MD, www.mletips.com
  15. 15. Fibrinolytic pathway Fibrinolytic pathway 15 Dr. Krishna Tadepalli, MD, www.mletips.com

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