Blood Coagulation

Circulatory System

Blood Coagulation/Clotting

Fundamentals:

• Initiated by a cascade process
  • Two routes: Intrinsic and Extrinsic
  • Intrinsic - damaged surface (Factor 9) - LINK TO APOTOSIS in which the caspase 9 initiates intrinsic route
  • Extrinsic - trauma (Factor 7)
• Enzymes and Zymogens working to make a system of band-aid patches from a hole created
  • Platelets come into contact with exposed Collagen --> evidence of injury and release their contents and begin to aggregate

Purpose/Function:

• Protect the circulatory system/homeostasis
  • Aggregation of a clot to prevents pathological loss of blood

Components/Anatomy:

• Factor 1 = Fibrinogen
• Factor 2 = Prothrombin
  • Thrombin (serine protease)
• Factor 3 = Tissue Factor/Thromboplastin
• Factor 4 = Calcium
• Factor 5 = Proaccelerin
• Factor 6 = ?
• Factor 7 = Proconvertin
• Factor 8 = Antihemophilic Factor
• Factor 9 = Christmas Factor
• Factor 10 = Stuart-Prower Factor
• Factor 11 = Plasma Thromboplastin Antecednet
• Factor 12 = Hageman Factor
• Factor 13 = Fibrin-stabilizing Factor
• Factor 14 = ?
• Factor 15 = ?
• Prekalikerin = Fletcher Factor

Mechanism:

• Thromboplastin + Prothrombin --> Thrombin (w/ cofactors such Ca and ViK)
• Thrombin + Fibrinogen --> Fibrin
• Fibrin creates a net capturing RBCs and platelets
• Clott forms
• Attachment activates the quiescent alpha11beta3integrin molecules causing them to adhere to circulating proteins
• Other causes of blood clots:
  • Injury
  • Extreme inactivity
  • Hypercoagulateable state

Disorders/Diseases:=

• Pulmonary thromboemboli
  • Block segments of the pulmonary arteireis
  • S&S - produce rapid labored breathing and chest pain

General Information Necessary vitamins and minerals Calcium Vitamin K Function: Hemostasis: no bleeding PHASES (remain in balance) 1)Concerted Phases 1a)Procoaculation: clot formation Proteins are used up and not recycled 1b)Anticoagulation: stop clot formation 2)Fibrinolysis: clot dissolution Proteins are used up and not recycled Details 0) Injury Activates Tissue Factor (TF) 1a) Phase 1 and Zymogens Prothrombin/Fibrinogen Key = Activate FX (from FX to FXa) - FX -(TF)-FXa Prothrombin -(FXa&Vitamin K)- Thrombin Thrombin: making the clot, Fibrin formation and a host of other factors ALSO activates a platelet receptor
Tissue Factor acts as a receptor for FVII Fibrinogen -(Thrombin)- Fibrin Fibrinogen: cut by thrombin allowing it to aggregate (activated Fibrin) Platelets -(Ag Fibrin)- Act Platelets Aided by a thrombin receptor (activated by thrombin) So why not anywhere else? No exposed receptors Activators are not at high enough concentrations Endothelium secretes postacyclin which inhibits platelet aggregation. 1b) Phase 2 and Inhibitors - immediately w/ Phase 1a Inhibitors bind with active proteins and enzymes INH activity INC Zymogens are activated meaning they are activated to return to a stable zymogen form? Intensity INC as Phase 1a Lenghtens Coagulation stops and complexes are removed by the liver. 2) Phase 3 and Zymogens Plasminogen Plasminogen -(tissue plasminogen activator)- Plasmin Plasmin: hydrolyzes the clot to soluble proteins. Plasminogen has a high affinity for Fibrin. TP-A also binds to fibrin Summary The eye uses several known biochemical events. Glycolysis and Pentose Phosphate Shunt for energy Protein mechanical “kinetic” changes upon excitation by photon. G-proteins for signal transduction. Membrane voltage potentials to convey electrical impulses. Cataracts are states which result in light scattering through the lens. Blood clotting is a unique biochemical event. Key factors include: TF Thrombin Fibrin Plasminogen Follows the steps of procoagulation, anticoagulation, and fibrinolysis. Anticoagluation begins with procoagulation. Each step is controlled by a combination of “revealed” proteins due to damage, activated factors, and generally available materials.