Lecture 13 Flashcards
What is the sympathetic response to injury
for blood vessels to constrict in order to slow down blood loss
Stopping the bleeding steps (4)
- injury damages vascular endothelium and exposes sub-endothelial collagen
- vWF cements platelets to collagen to form a cellular ring
- fibrin deposits on platelet plug and later contracts by covalent crosslinking
- plasmin digests fibrin clot and endothelium regenerates
Hemostatic events to tissue injury(5)
- Vasoconstriction (neural)
- platelet activation-adhesion and aggregation
- coagulation-blood clot-thrombin generation-fibrin polymerization
- fibrinolysis-blood clot dissolution
- vascular patency restored
What are platelets(4)
shed from megakaryocytes
store secretory products in granules
increased [ ] of actin and myosin to facilitate the formation of a solid platelet plug via contraction
Binding of platelets to collagen mediated by vWF with high avidity (strength)
Platelets can be activated in response to…(3)
collagen, vWF, and tissue factor (bigger injury)
Platelet aggregation end point
rise in cystolic Ca which induces platelet activation/aggregation
Sequence of events leading to formation of a platelet plug and vasoconstriction of a blood vessel wall (6)
- vessel damage->
- altered endothelial surface (collagen exposed)->
- platelet activation/aggregation->
- discharge of mediators and synthesis of TXA2->platelet plug
- chemical mediators and TXA2-> blood vessels contraction of VSM cells
- > vasoconstriction
Coagulation what does it do?
provides strength and support to the platelet plug
ultimately=fibrinogen+thrombin= fibrin
What strengthens the clot
crosslinking-transglutaminase
Activation of platelets causes(2)
expression of negatively charges phospholipids (on cell surface(->attachment of Ca+2)) Clotting factors (2,7,9,10) attach to Ca+2 ions
Intrinsic pathway(within damaged blood vessel)
- 7 steps set off by factor 12 (hageman factor)
- occurs simultaneously with platelet plug formation
- Platelets secrete PF3: essential for clotting cascade and enhanced platelet aggregation
Phospholipid PF3
- expressed by…
- Acceleration of coagulation cascade by:(3)
activated platelets
- promotes platelet recruitment
- aggregation
- fibrin formation
Extrinsic pathway(3)
4 steps- happens quicker than intrinsic
requires contact with tissue factor
thromboplastin directly activates factor 10
Actions of thrombin-pro coagulant
cleaves fibrinogen to fibrin
activates clotting factors 5, 8, 11, 13
Stimulate platelet activation
Actions of thrombin- anticoagulant
activates protein C which inactivates clotting factors 5, 8
Thrombin is critical to
coagulation
Cross linking of fibrin
initial soft plug characterized by H bonding
covalent cross linking provides strength
mediated by transglutaminase (factor 8)
what limits clot formation to the site of injury?(3)
anticoagulant mechanisms(3)
labile clotting factors-slow blood down to interact more often
- diluted by blood flow
- removed by liver
tissue factor pathway inhibitor (TFPI)
thrombomodulin
Anti thrombin 3(enhanced by heparin
Thrombomodulin- how is it anticoagulant
forms complex with thrombin->activation of protein C->inactivation of factors 5 and 8 through proteolytic cleavage
Anticlotting roles of Endothelial cells
-normally provide an intact barrier between blood and subendothelial collagen
platelet aggregation and formation of tissue factor 8 not triggered
Anti clotting roles of EC
-synthesize and release PGI2 and NO
inhibit platelet activation and aggregation
Anti clotting roles of EC
-Secrete tissue plasminogen activator
catalyzes the formation of plasmin which dissolves clots
Fibrinolysis
Plasmin degrades fibrin into peptides dissolving the blood clot
Plasminogen is activated by tissue plasminogen activator (tPA) ONLY when bound to fibrin
Thus fibrin promotes its own breakdown
