Physiology Topics
Platelets are cell fragments from megakaryocytes that have chattered into pieces. They do not retain nuclear materialsd, but retain granules containing seratonin, Ca+2, ADP, ATP, enzymes and platelet-derived growth factor (PDGF). Platelets help stop blood loss from damaged vessels by forming a platelet plug. Thrombocytopenia is a very low platelet count resulting in a tendency to bleed from capillaries.
Hemostasis prevents blood loss in four stages: (1) local vasoconstriction, (2) platelet plug, (3) blood clotting, and (4) clot dissolution. After initial muscle contraction, platelets stick to parts of the damage vessel. This activates the platelets to increase their interactions with each other and and liberate seratonin, ADP, thromboxane A2 and prostaglandin H in order to activate nearby platelets. Seratonin and thromboxane A2 act as vasoconstrictors. All these agents are short lived, so platelet activation is limited.
Clotting occurs by a series of chemical reactions culminating in formation of fibrin threads that trap blood cells into a gel. I starts with the formation of prothrombinase, which can the convert prothrombin (a plasma protein synthesized in the liver) into the enzyme thrombin. This later reaction needs Ca+2 as a cofactor. Thrombin converts fibrinogen (another plasma protein from the liver) into fibrin. This process involves many intermediate reactions catalyzed by clotting factors I through XII. Vitamin K is required for the synthesis of prothrombin and factors VII, IX and X.
Formation of prothrombinase is initiated by either of two pathways: extrinsic or intrinsic. The extrinsic pathway has fewer steps, occurs in seconds, and starts when the protein tissue factor (TF) leaks into the blood through a broken vessel. The intrinsic pathway is more complex, occurs in minutes, and is activated by factors either in direct contact or within the blood.
Deficiencies in clotting factors will prevent the clotting cascade and cause hemorrhage. Hemophilia is a genetic deficit of factor VIII. Afibrinogenemia and hypothrombinemia are deficiencies of fibrinogen and prothrombin, respectively, usually due to liver disease.
A cloth formed in an unbroken blood vessel is a thrombus. These are usually dissolved by the clot dissolution mechanisms described below. If the thrombus detaches and flows with the blood is called an embolus, which may get stuck in capillaries and block blood flow to vital organs.
Clot retraction and dissolution starts with the plasma protein plasminogen, which may be activated to plasmin by any of several factors: thrombin, factor XII, or tissue plasminogen activator (t-PA). Plasmin dissolves the clot by digesting fibrin threats and inactivating fibrinogen, prothrombin and factors V, VIII and XII. Blood also contain anticoagulants like antithrombin III (blocks thrombin and other clotting factors), protein C (blocks factors V and VIII and enhances the activity of t-PA) and heparin (produced by basophils, blocks thrombin). Warfarin is a drug that antagonizes vitamin K, blocking the synthesis of prothrombin and factors VII, IX and X. Ca+2 chelators are added to blood in vitro to prevent coagulation by inhibiting thrombin synthesis.
Disseminated intravascular clotting is a disorder characterized by simultaneous and unregulated blood clotting and hemorrhage throughout the body. Common causes are infection (dengue, ebola?), hypoxia, low blood flow rates, trauma, tumors, hypotension and hemolysis.
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