What occurs immediately after blood vessel damage?
Myogenic contraction (vasoconstriction)
What occurs after a severe injury to a blood vessel?
Neurogenic vasospasm - increased sympathetic nerve firing + vasoconstriction via a spinal (pain) reflex
How long do myogenic and neurogenic contractions last?
What types of humoral responses cause vasoconstriction?
Serotonin Thromboxane A2 Prostaglandins (PGFs)
How long does humorally-triggered vasoconstriction last?
What happens when subendothelial connective tissue is exposed to blood during injury?
Platelet adhesion to subendothelial collagen
What is Von Willebrand Factor (VWF)?
A plasma protein factor synthesized by endothelial cells that promotes platelet adhesion and clotting factor VIII. Missing/non-functioning VWF = Hereditary Von Willebrand disease.
What is platelet release reaction?
Alterations in shape and release of granules mediated by binding of VWF or thrombin to platelet membrane receptors. Causes release of calcium, serotonin, and ADP.
What is the relationship between ADP levels and clotting?
ADP levels must be above a critical concentration for platelets to maintain clumping. Release of additional ADP from storage sites accelerates clumping.
In addition to ADP, what is another potent aggregating agent?
What prevents platelets from spreading?
Nearby cells secrete a powerful inhibitor, prostacyclin (PGI3).
What effect does aspirin have on clotting?
Reduces clotting by inhibiting cyclo-oxygenase which is needed to form thromboxane A2.
What is primary hemostasis?
Vasoconstriction + platelet plug formation
What is secondary hemostasis?
What is fibrinogen?
Circulating precursor to fibrin
What is prothrombin?
Circulating precursor to thrombin
What is thrombin?
Proteolytic enzyme that converts fibrinogen to fibrin.
What is thromboplastic activity?
Factors released from injured tissue that causes conversion of prothrombin to thrombin (in the presence of calcium)
What is the genetic cause of hemophilia?
Sex-linked congenital deficiency of factor VIII.
What are the proteins of the intrinsic pathway?
1. Prekallikrein 2. HMW kininogen 3. Factor XI
What is the first step to activate the intrinsic clotting pathway?
Binding of clotting factor XII to the subendothelial connective tissues exposed by blood vessel injury.
What other factors convert factor X to factor Xa?
VIII, IXa, Ca2+, platelet phospholipid
How is prothrombin II activated to IIa?
Factor V is cleaved by factor Xa in the presence of calcium.
How are fibrin networks formed?
Factor XIIIa helps form covalent bonds among fibrin strands
What is the first factor in the extrinsic clotting pathway?
Exposure of "tissue factor" (factor III/CD142) on the surface of subendothelial cells.
Does thrombin act as a positive feedback mechanism on the intrinsic pathway? What does it do to extrinsic?
Yes Shuts down extrinsic
How quickly does the extrinsic pathway take to activate? Intrinsic?
Extrinsic: 10-15 seconds Intrinsic: 1-3 minutes
How do many anticoagulants work?
Chelate calcium ions to prevent clotting.
What clotting factors use calcium?
II, VII, IX, X
What residues bind calcium and what substance aids their carboxylation/formation?
gamma-carboxygltuamic acid residues carboxylated by Vitamin K.
What is coumarin?
Anticoagulation drug that acts by blocking carboxylation.
What causes clot retraction?
What circulating plasma protein is the major inhibitor of thrombin? What drug enhances it?
Antithrombin III activity increased by heparin
Although thrombin has a positive feedback system, it also has a negative feedback system carried out via proteins ____ and ___.
C and S Blocks factors VIII and V
What proteolytic enzyme digests fibrin and fibrinogen and what activates it?
Plasmin made from plasminogen in response to tPA
How is tPA used therapeutically?
Can be used to restore blood flow to inappropriately ischemic tissues.
What effect does serotonin have on blood vessels?
What effect does histamine have on blood vessels?
Increases vessel leakiness after injury to prevent infection.
What lesions form in people lacking primary hemostasis?