Hemostasis

1. Hemostasis RK Goit, Lecturer Department of Physiology

2. Hemostasis means prevention of blood loss from a broken blood vessel achieved by several mechanisms: vascular constriction platelet plug formation blood coagulation

3. Vascular Constriction trauma to vessel wall causes the smooth muscle to contract contraction results from local myogenic spasm factors from the traumatized tissues & platelets nervous reflexes

4. Platelets (thrombocytes) smallest (1-4 µm in diameter) formed elements of blood anuclear fragments of megakaryocytes a single megakaryocytes typically produces about 1000 platelets develop in response to hormone thrombopoietin they are removed from circulation by the tissue macrophages 150,000-300,000/µl half life 5 to 12 days

5. cytoplasm contains: actin, myosin, thrombosthenin endoplasmic reticulum & Golgi apparatus, mitochondria Dense granules phospholipids Serotonin Calcium ADP ATP α granules von Willebrand factor clotting factors- V & XIII platelet derived growth factor (PDGF )

6. Functions of platelets serotonin released by platelets contributes to the vasoconstriction p latelets aggregate to plug the vascular injury p latelets provide the clotting factors c ontractile protein of the platelets bring about clot retraction p latelets have a growth factor which stimulates mitosis in the vascular wall

7. Blood Coagulation coagulation of blood occurs due to activation of clotting factors occurs in three major stages: Formation of prothrombin activator Extrinsic pathway Intrinsic pathway Conversion of prothrombin to thrombin Conversion of fibrinogen to fibrin

8. Dissolution of clots clot is composed of a meshwork of fibrin fibers running in all directions & entrapping blood cells, platelets, & plasma a large amount of plasminogen is also trapped in the clot tissue plasminogen activator (t-PA) converts plasminogen to plasmin plasmin digests fibrin fibers & some other protein coagulants such as Factors I, II, V , VIII , & XII

9. Prevention of blood clotting endothelial surface factors smoothness of endothelial cell surface, which prevents contact activation of the intrinsic clotting system a layer of glycocalyx on the endothelium which repels clotting factors & platelets t hrombomodulin binds thrombin thrombomodulin - thrombin complex also activates protein C that inactivates Factors V & VIII

10. Fibrin 85 to 90% of the thrombin becomes adsorbed to the fibrin fibers ↓ prevent the spread of thrombin ↓ prevents the excessive spread of clot Antithrombin III thrombin that does not adsorb to the fibrin fibers soon combines with antithrombin III

11. Bleeding disorders liver diseases can depress the clotting system vitamin K deficiency can lead to serious bleeding tendencies Hemophilia abnormality or deficiency of Factor VIII & IX abnormality is located on the sex chromosome X almost never will a woman have hemophilia because at least one of her 2 X chromosomes will have appropriate gene P urpura a group of disease that occurs due to thrombocytopenia

12. Blood coagulation tests Bleeding Time time from the onset of bleeding till the stoppage of bleeding (1-5 min) Clotting Time time from the onset of bleeding till the clot formation (2-8 min) Prothrombin Time time required for coagulation to take place (12-16 s )

13. Anticoagulants anticoagulants act by binding calcium ions- in vitro (sodium citrate, potassium oxalate & EDTA) Heparin is another popular anticoagulant- in vivo & in vitro Vitamin K antogonists such as Dicumarol & Warfarin are suitable as anticoagulants- in vivo

14. References Review of Medical Physiology, 22/E Ganong Textbook of Medical Physiology, 14/E Guyton & Hall Understanding Medical Physiology, 4/E Bijlani & Manjunatha

15. Thank You