The Hemostatic Mechanism Transient arteriolar vasoconstriction occurs immediately after vascular injury.

Local enothelial secretion of endothelin causes the vasoconstriction. Remember that this is transient Primary Hemostasis: Formation of the primary hemostatic plug. Platelets go through 3 processes 1). Adhesion 2). the granule release reaction and 3). Aggregation and Consolidation. Platelet Adhesion Platelets adhere to subendothelial collagen that is exposed after vascular injury. The von Willebrand factor binds to collagen and then binds to the GPIb receptor on the platelet membrane bridging them together. Then another platelet glycoprotein 6 GPVI, also binds to collagen. Platelet Granule Release Reaction Platelets that adhere to collagen undergo activation where they release their granule content. The release reaction is initiated by agonist binding to cell surface receptors. ADP, epi and collagen binding activates PLA2 which eventually releases Thromboxane A2. TxA2 causes vasoconstriction by inducing a decrease in cAMP in SMC and also stimulates granule release within platelets. The granules secrete large amounts of ADP, Ca 2+, vWF. ADP specifically causes the platelets to become sticky and adhere to each other. Platelet Aggregation and Consolidation TxA2, ADP, and collagen are all potent mediators of platelet aggregation. The binding of TxA2 causes the platelets to express the membrane integrin GPIIb-IIIa. ADP triggers platelet aggregation by binding to P2Y1 and P2Y receptors. Binding of ADP changes the shape of the platelet and causes expression of functional GPIIb-IIIa. Collagen also causes the platelets to express GpIIb-IIIa. The platelets aggregate with one another by binding fibrinogen which has multiple binding sites for GPIIb-IIIa. Platelet aggregation eventually leads to the formation of a reversible clot. Secondary Hemostasis: The Coagulation Cascade: Formation of fibrin clot. The coagulation cascade is a sequence of enzymatic events where proenzymes are proteolytically cleaved by the activated factors that preceded them in the pathway. These reactions occur on phosholopid-based protein complex surfaces meaning they occur on activated platelets or activated endothelial cells and usually require a co-factor and Ca2+. There are two pathways in which this occurs. The intrinsic pathway is activated by factor 12 whereas the extrinsic pathway is initiatied by tissue factor. These two pathways converge at the activation of factor X into Xa. Xa then cleaves prothrombin into thrombin. Thromin then converts the soluble plasma protein fibrinogen into fibrin which forms long, insoluble polymer fibers and it activates factor 13 which cross links the fibrin polymers into a highly stable meshwork or clot. In addition to have procoagulatory effects by crosslinking fibrin, Thrombin exerts anti-coagulatory effects by binding to thrombin receptors on the intact vascular endothelial cells near the area of vascular injury and stimualtes these cells to release the platelet inhibitors prostacyclin PGI2 (PGI2 inhibits platelet aggregatio and platelet granule release) and NO. and tissue plasminogen activator t-PA which converts plasminogen into plasmin which degrades fibrin.

Review Final Exam Cover all 4 units. Antihypertensive drugs. Diuretics Thiazide Loop Diuretics K+ Sparing diuretics Sympatholytics Central sympatholytics a2 agonists ganglionic blockers reserpine benaguenz B-blockers metoprolol A-blockers Vasodilators decrease systemic vascular resis. Compensatory symp activation Ca 2+ channel blockers K+ channel openers stabilize SMC at its resting potential Nitrates RAAS blockers ACE Inhibitors ARBs