coagulation and inflammation Flashcards
what does tissue factor do
it triggers the clotting cascade
what do anticoagulants and anti-platelets do
block calcium signals to spot them from activating
what does antithrombin III do
it helps to stop the coagulation pathway from carrying on further down the blood vessesl
what happens to the blood vessels when there is damage
- subendothelial lining is removed
- barrier stopping clotting cascade has gone
- platelets begin to bind
how do platelets start to bind after damage to the vessel
bind to the subendothelial matric through collagen receptors
what does reflex vasoconstriction do
reduces the blood flow to the damaged vessels
why does reflex vasoconstriction occur
-endothelin release from endothelium vasoconstricts
- loss of NO causes smooth muscle cells to be disinhibited
- serotonin release maintains vasoconstriction
what is primary haemostasis
the platelets plug the hole in the damaged vessel
why does primary haemostasis occur
- platelets stick to subendothelial collagen by von Willebrand Factor
what happens in a loss of von willebrand factor
causes bleeding disorders and platelets can’t bind to subendothelial layer
how are platelets activated
adhesion via glycoproteins trigger their activation by a rise in cytosolic Ca concentration
what happens once platelets bind
- positive feedback
- pathway triggers more platelets to bind
what do activated platelets produces
- secretory vesicles/ granules released - ATP, ADP and serotonin
- produce thromboxane A2
what do activated platelets trigger
conversion of glycoprotein IIb/IIIa into active form
- platelets can adhere to fibrogen to create a plug to restrict blood flow
why are ADP antagonists used to treat for antiplatelets
- block the positive feedback loop
- stop the clotting you don’t want but don’t stop it fully
what is immune thrombocytopenia
- bleeding disorder from a low platelet count
- cytotoxic T cells target own platelets
- more blood leaves in microvascular damage making small spots
what is secondary haemostasis
fibrin production stabilises and strengthens the growing clot
why is thrombin needed in secondary haemostasis
it cleaves fibrinogen to fibrin
how does fibrin stabilise the clot
cross linking due to factor 13 increase strength, making an insoluble fibrin mesh to stop clot movement
what does the extrinsic pathway do in clotting
it initiates coagulation
how is excessive blood clotting prevented by fibrin
- circulating tissue factor bind to the platelet plasma membrane (calcium-dependent)
- helps localise all components of coagulation cascade to platelet surface
when does fibrinogen do
helps the wall to contract to get endothelial wall build up to replace the platelets
how does warfarin work
- inhibits vitamin K of clotting factors in the liver
- means platelets cant bind to platelets plasma membrane
how does haemophilia A work
- factor VIII deficiency
- prevents normal production of tenase complex
how is the clotting cascade ‘turned off’
- thrombin mediated
- protein C bind to surface of endothelial cell
- it binds and becomes activated and cleave factor 5 and 8a
what is the triad of death
- coagulopathy
- acidosis
- hypothermia
how does the triad of death
- fluid resuscitation dilutes coagulopathy
- loss bicarbonate you go into acidosis
- acidosis slows down the clotting cascade
what causes systemic activation of coagulation
- pregnancy complications
- hyperthermia
- sepsis
- burns
- trauma
- cancer
- transfusion
what happens in fibrinolysis
resolution of clot by breaking down fibrin
how is fibrin broken down
- endothelial cells release tissue plasminogen activation
- thrombin activates protein C to disinhibit t-PA
- t-PA activates plasminogen
- plasmin then cleaves fibrin to break down clot
what does recombinant tPA do
used to remove unwanted clots formed during a stroke
what does TXA do
prevents heavy nose or menstrual bleeding following trauma or surgery
what causes venous thrombosis
endothelial inflammation due to loss of blood flow triggering vWF
how are white blood cells involved in acute inflammation
- inflammatory mediators triggered causing redness, heat and swelling
- more blood flow to area makes if read and warm
why is the swelling in acute inflammation
- more filtration as intracellular junction broken down
- fluid and proteins can move faster causing swelling
what does factor 12 trigger
- 12 -> prekallikrein -> kallikrein -> joins HMW kininogen -> bradykinin (inflmation)
- 12 -> prekallikrein -> kallikrein -> joins plasminogen -> plasmin
what does serotonin cause
- vasodilation
- increased vascular permeability
what does histamine cause
- vasodilation
- increased vascular permeability
what do leukocytes and platelets cause
- PGD2 - vasodilation
- PGE2 - vasodilation and pain
