W2.2HEMA2LEC

• Monohydroxyperoxide to 13 HODE enzyme:

  peroxidase
• Linoleic acid becomes monohydroxy peroxide enzymes

  Lipooxygenase
• 13-hydroxyoctadecadienoic acid


  Metabolite of linoleic acid in endothelial cells
• Monohydroperoxide to 12 HETE enzyme

  Peroxidase
• Arachidonic acid oxides to become monohydroperoxide enzyme

  Lipooxygenase
• 12 hydroxyeicosatetraenoic acid


  metabolite of arachidonic acid from platelet cytosol
• Endoperoxide become PG12

  PG12 synthetase
• Prostascyclin (PG12)


  metabolite of arachidonic acid from endothelial cells

  
  

  - induces plt adhesion
• Endoperozide becomes TxA2

  TX synthase
• Arachidonic acid will be oxidized to endoperoxides enzyme

  Cyclooxygenase
• Metabolite of arachidonic acid from

  platelet membrane
• Thromboxane A2 (TxA2)


  vasoconstriction

  - promotes platelet activation and aggregation acts with ADP
• Thrombin


  - stimulates platelets to release ADP to induced aggregation

  
  

  -Activates membrane phospholipaseswhich initiates the formation of TxA2
• release dense granules in reponse to ____

  collagen, epinephrine, thrombin and TXA2
• Glanzmann's Thrombasthenia

  - congenital disease

  -leads to excessive bleeding

  - abnormal platelet functioning
• mediates ADP induced aggregation

  Gp IIb IIIa with calcium and fibrinogen
• major contractile protein

  Calcium and Thrombostenin
• contraction of microfilaments due to __

  ADP released
• platelet release reaction stimulated by

  - Collagen

  - Thrombin

  - Epinephrine

  - Thromboxane A2
• release of platelet granules

  alpha & dense granules
• 12 HETE


  - from cytosol of platelet

  - promotes platelet adhesion
• 13 HODE

  - form endothelial cells

  - inhibitsplatelet adhesion
• Platelet adhere to collagen via

  - Plasma: VIII: vWF

  - Platelets: Glycoprotein 1b
• Collagen type I and II


  - promotes platelet adhesion, aggregation and release reaction

  
  

  - synthesized by smooth muscle

  - Location: deep regions of BV wall
• Exposure of platelets

  - Collagen

  - Fibronectin

  - Basement membrane
• Fibrionolysis


  Release of tPA to avoid excessive coagulation
• Tissue thromboplastin release


  activates extrinsic pathway
• Collagen exposure


  - causes adherence of platelets to site injury

  -activates the contact phase of coagulation
• Vasoconstriction

  Neurogenic reponses
• Physiologic responses

  1. Vasoconstriction

  2. Collagen exposure

  3. Tissue thromboplastin release

  4. Fibrionolysis
• Von Willebrand Factor

  required for platelet adhesion
• tPA


  converts plaminogen to plasmin
• Heparin sulphate


  enhances activity of antithrombin III
• Protein C


  inactivates I and VIII
• Thrombomodulin

  - inactivates thrombin

  - Enhances anticoagulant activity of Protein C
• Adenosine

  induces vasodilation
• Prostacyclin


  - inhibits platelet aggregation

  - induces vasodilation
• vascular response -- substances released

  prostacyclin

  adenosine

  thrombomodulin

  heparan sulfate

  TPA

  VWF

  13-HODE
• Primary hemostasis two responses

  1. Vascular responses

  2. Platelet responses
• Stages in hemostasis (blood vessel damage)

  1. Vasoconstriction

  2. Platelet activation

  3. Coagulation

  4. Fibrinolysis

  5. Tissue repair