Revision lecture B31 Flashcards
What are the 3 major steps of Haemostasis
1) vascular spasm
2) formation of platelet plug
3) blood coagulation (clotting)
Why must Haemostasis be appropriately controlled
To avoid inappropriate clot formation
Clots must be eventually degraded
Clots are temporarily solution
What si the vascular spasm
Vasoconstriction
Muscle cell contracts reducing blood flow nd limit blood loss
Opposing endothelial cell surfaces are pressed together and adhere
What si the vascular spasm mediated by
Platelet derived products - serotonin and thromboxane A2
What does normal endothelium produce
Vasodilators - nitric oxide
And inhibitors of aggregation - prostaglandin
What are platelets also known as
Thrombocytes
Where are platelets derived form
Megakaryocytes in the bone marrow
What doe platelets contain
No nuclei but other organelles for energy production
Contain high concentrations of actin and myosin therefore can contract
What are some factors involved in platelet activation
ADP - released by platelets, erythrocytes and endothelial cells
Thrombin - made by enzyme cleavage of prothrombin
Collagen - in the connective tissue, exposed by vessel damage
PAF - platelet activating factor (phospholipid) form the vessel wall and other cells
What are the effects of platelet activation
Change shape form disc to sphere with extended pseudopodia which facilitate aggregation and coagulant activity
Release compounds involved in Haemostasis
Aggregate
Adhere to vessel wall
Synthesis thromboxane A2 a potent labile mediator of platelet activation and vasoconstriction
What si the general formation of the platelet plug
Platelets aggregate to form primary plug
To prevent being washed away by blood flow platelets release Chems which enhance blood coagulation, incomrp fibrin
What is vWF
Von Willebrand Factor
What sit he role of vWF
Binding platelets together
What are Gplb and Gpllb/llla
Glycoproteins and receptors
What si the most common defect with platelets
Von Willebrand disease which is a group of autosomal dieases affecting vWF
What are less common disorders affecting platelets
Affect the receptors found in the platelet membrane involved in platelet adhesion and aggregation
Wat are anti platelet drugs used to treat
Arterial thrombosis blood clot in a vessel
How do anti ppateelt durgs work
They decrease platelet aggregation and inhibit thrombus formation
What are some examples of anti platelet drugs
Aspirin (reduces thromboxane A2)
Platelet receptor antagonists (target Gpllb which binds vWF)
Platelet ADP receptor antagonist
What do blood coagulation factors interact to form
The secondary fibrin rich, Haemostatic plug in small vessels and the secondary fibrin thrombus In arteries and veins
What si the intrinsic pathway for blood coagulation
Activated by exposure of flowing blood to subendothelial collagen exposed by damaged vessel
What is the extrinsic pathway of blood coagulation
Activated by tissue damage which exposes flowing blood to a protein called tissue factor
What does the intrinsic and extrinsic pathways of blood coagulation lead to
A final common pathway resulting in conversion of fibrinogen to fibrin
What is the clot formation
Fibrin clot from red by interaction of intrinsic, extrinsic and final common pathways
A clot on top of platelet plug strengthens the lug reinforces the seal
What is fibrin
Insoluble, threadlike molecule
Forms a loose, mesh that trans blood cells
Generated form fibrinogen which is a large soluble plasm protein syn by the liver
What si the key role of thrombin
Catalyses conversion of fibrinogen to fibrin
Activated factor 13
Where do cross links form
Between adjacent fibrin strands
Strengthens and stabilises clot
Catalysed by factor 13
What si the blood clotting cascade in intrinsic pathway
Initiates clotting in a damaged vessel
Activated by factor 12 comes into contact with collagen or foreign stance
Aggregated platelets secrete platelet factor (PF3) which is essential for the cascade and platelet aggregation
Activation of factor 10 a protease can digest prothrombin to thrombin
What si the blood clotting cascade for the extrinsic pathway
Requires contact with tissue factors to blood
Traumatised tissue = release tissue factor which with factor 7 activates factor 10
What si fibrinogen
Soluble plasma protein
6 polypeptide chains
What does thrombin do
Converts fibrinogen to fibrin
Cleaves four peptide bonds in fibrinogen relapsing fibrinopeptides and fibrin monomers
What do the fibrin monomers do
Spontaneously assemble into ordered fibrous arrays called fibrin whci is insoluble
What factor causes the cross linking of fibrin
Factor 13
What si thrombins dual action
Catalyses formation of fibrin but also initaties the deactivation of the clotting cascade
As well as thrombin in terminating clotting what else is essential
Specific inhibitors
Clotting factors are labile and short lived due to …
Dilution by blood flow
Removal by liver
Degradation by proteases
What si the complete list of the roles of thrombin
1) converts fibrinogen to fibrin
2) activates factor 13 to stabilise the fibrin meshwork by cross linking
3) stimulates its own activation by positive feedback
4) enhances platelet aggregation
What si vitamin k essential for
Synthesis of prothrombin and other clotting factors (8, 9 and 10)
What does prothrombin have in its N terminus
Glutamate residues
What is vitamin k enzymatic ally converted to, where and how
Conv to - gamma- carboxyglutamate in the liver
What does the gamma carboxyglutamate do
Binds calcium which facial takes conversion to thrombin
What si the role of calcium
Binding of calcium anchors prothrombin to the platelet mem surfaces after injury
Brings prothrombin knot proximity of clotting factors required for its activation to thrombin
Activation frees thrombin
What are some examples of vitamin k antagonists
Discoumarol
Warfarin - anti coagulant sun prothrombin without gamma carboxyglutamate
What sit he substance which prevents inappropriate clotting
Anti- thrombin
Heparin
Protein C
Tissue factor pathway inhibitor
Where is anti thrombin produced
In the liver
What does anti thrombin do
Inactivates thrombin
Where is heparin syn and what does it do
Syn in mast cell
Activates anti thrombin and used as an anti coag
Where is protein c and its cofactors syn and what do they do
Syn in the liver
Degrade clotting factors
What does the tissue factor pathway inhibitor do
Inhibit the tissue factor VIIa complex blocking activation of factor 10
What is fibrinolysis
Dissolving the clot
What happens in fibrinolysis
Circulating plasminogen binds to fibrin
Factor 12 activates conversion to plasmin
Plasmin slowly degrades fibrin (phagocytes remove debris)
Tissue plasminogen activator also activates plasmin to do this
What is plasminogen
A serum protein which is produced int he liver
Excessive bleeding may result from
congenital or acquired disease of any of the stages of Haemostasis
What does congenital mean
Present form birth
What are some congenital reasons for excessive bleeding
Disorder collagen syn - vessel wall VWF deficiency (or receps) - platelets Coag factors deficiency (factors) - coagulation Anti plasmin deficiency - fibrinolysis
What are some acquired disorders for excessive bleeding
Vit c deficiency - vessel wall
Anti platelet drugs - platelets
Vit k def - coagulation
Fibrinolytic drugs - fibrinolysis
What is Haemostasis
The arrest of bleeding
