Physiology 5 ‘ Hemostasis PDF

Physiology 5 ‘ Hemostasis PLATELETS Formed in bone marrow, 150-400,000 /µl, Sequestered in spleen (30%), 2-4 µm in diameter life span 8-12 days no nucleus. Active Cytoplasm : Membrane: Enzyme synthesis...

Physiology 5 ‘ Hemostasis PLATELETS Formed in bone marrow, 150-400,000 /µl, Sequestered in spleen (30%), 2-4 µm in diameter life span 8-12 days no nucleus. Active Cytoplasm : Membrane: Enzyme synthesis Receptors : Thrombin, ADP, serotonin. storage of calcium Adhesion proteins: VWF, bronectin, collagen, brinogen. Synthesis of prostaglandins Coat of glycoproteins: Adhesion to injured areas. Granules containing ADP, serotonin and ATP Phospholipids: Activation of intrinsic pathway α–-granules ( brinogen, PDGF (Platelet- derived Growth Factor), Adenylate cyclase, cAMP: Activate other platelets VWF (Von Willebrand Factor), bronectin) Fibrin stabilizing factor HEMOSTASIS Hemostasis refers to the stoppage of bleeding ( hemo = blood ; stasis = standing ) — Stages of hemostasis: Blood vessel spasm Platelet plug formation Blood coagulation i Stage 1: Blood Vessel Spasm : Triggered by -Pain receptors, -Local myogenic spasm -Local release of Thromboxane A2 [ TXA2 ] , 5HT, serotonin” Results : Smooth muscle in blood vessel contracts. Purpose : to minimize the ow of blood from the wound site. Stage 2 Platelet plug formation Triggered by exposure of platelets to collagen Result : Platelets adhere to rough surface to form a plug Steps of Platelet Plug Formation : 1. Platelet adhesion Von Willebrand factor (VWF) 2. Platelet activation(secretion) Ca++ release Pseudopodia Granule discharge Thromboxane formation (TXA2) 3. Platelet aggregation Stage 3 Blood Coagulation: Triggered by cellular damage and blood contact with foreign surfaces Result: A blood clot forms : This is a hemostatic mechanism causes the formation of a blot clot via a series of reactions which activates the next in a cascade. Clotting Cascade Occurs extrinsically ( tissue factor pathway ) or intrinsically ( contact activation pathway ) I — Intrinsic pathway — Extrinsic pathway Involves seven separate steps Requires contact with tissue factors external to the blood Set o when factor XII (Hageman factor) — Tissue thromboplastic Activated by coming into contact with exposed collagen released from traumatized tissue directly activates factor X in injured vessel or foreign surface such as glass test tube  After a blood clot forms it retracts and pulls the edges of a broken blood vessel together while squeezing the uid serum from the clot Platelet-derived growth factor stimulates smooth muscle cells and broblasts to repair damaged blood vessel walls —> De ne the serum ? —> Di erentiate between the serum and plasma ? Serum is the liquid that remains after the blood has clotted. Plasma is the liquid that remains when clotting is prevented with the addition of an anticoagulant. FATE OF BLOOD CLOTS Plasmin digests the blood clots PREVENTION OF BLOOD CLOTTING WITHIN NORMAL VASCULAR SYSTEM The smooth lining of blood vessels discourages the accumulation of platelets and clotting factors Fibrin absorbs thrombin and prevents the clotting reaction from spreading Some cells such as basophils and mast cells secrete heparin ( an anticoagulant ) The dynamic blood ow ABNORMAL BLOOD CLOTTING — Thrombus : Abnormal intravascular clot attached to a vessel wall — Emboli : Freely oating clots Factors that can cause thromboembolism Roughened vessel surfaces associated with atherosclerosis Imbalances in the clotting-anticlotting systems Slow-moving blood Occasionally triggered by release of tissue thromboplastin into blood from large amounts of traumatized tissue COAGULATION DEFECTS I. Vitamin C de ciency : lack of stable collagen (elderly, alcoholics) II. Hepatic failure : almost all clotting factors are made in the liver III. Vitamin K de ciency : required for II (prothrombin), VII, IX, and X Also fat malabsorption due to lack of bile secretion IV. Hemophilia : Excessive bleeding caused by de ciency of one of the factors in the clotting cascade — Factor VIII (hemophilia A 1/10,000), — Factor IX (hemophilia B 1/100,000) V. Thrombocytopenia : bleeding small capillaries and blood vessels mucosal, skin ANTIHEMOSTATIC DRUGS Heparin : Potentiates antithrombin III. Aspirin: is an important inhibitor of platelet activation. By virtue of inhibiting the activity of cyclooxygenase (COX), aspirin reduces the production of Thromboxane A2 (TXA2) by platelets Clopidogrel :is an irreversible inhibitor of the ADP receptor on platelet membranes. When ADP binds to platelets they are activated and aggregate leading to ampli cation of the coagulation response Warfarin : Decreases blood clotting by blocking an enzyme called vitamin K epoxide reductase that reactivates vitamin K1Without su cient active vitamin K1 , clotting factors II, VII, IX, and X have decreased clotting ability Streptokinase (an enzyme from the Streptococcibacterium) is another plasminogen activator TESTS FOR HEMOSTASIS — PLATELET DISORDER Bleeding time – 2-6 min. Increased in thrombocytopenia — COAGULATION DISORDERS Clotting time – 5-11 min. Increased in hemophilia Partial thromboplastin time (PTT) For intrinsic & common pathway Normally less than 45 sec. Prothrombin time (PT) For extrinsic & common pathway Leena omair Feb’23 Good luck