Thrombosis and Embolism Flashcards
What is haemostasis?
A normal physiological response to blood vessel injury, that prevents blood vessels leaking. It is actively switched off in healthy vessels.
How do endothelial cells inhibit haemostasis?
Physically insulates tissue from blood; production of NO and prostacylins (inhibit platelets); produces surface antithrombin which inhibits circulating thrombin.
How is haemostasis accomplished?
endothelial cells, platelets and the clotting cascade
How do endothelial cells promote haemostasis? (4)
- endothelin causes vasoconstriction
- loss of endothelial barrier exposes tissue which activates platelets and clotting factors
- von Willebrand factor, promotes platelet adhesion to ECM
- tissue factor thromboplastin produced which activate tissue cascade
How do platelets promote heaemostasis?
- They bind to ECM and are activated
- they secrete chemical signals such as thromoxane A2, vasoactive amines and ADP
- These causes further vasoconstriction and aggregation of platelets.
Proof of reduced platelts will be spontaneous haemorrhage and purpura
How will the coagulation system promote haemostasis?
It is a cascade of proteolytic reactions where zymogen precursors are cleaved, and is initiated by things such as tissue factor.
The penultimate step is the activation of thrombin (will also activate earlier parts on the sequence), which cleaves fibrinogen to fibrin monomers, and thu forms a mesh over the wound.
What is thrombosis?
When haemostasis occurs inappropriately.
( A thrombus is a mass formed of blood constituents within circulation)
Can form in arteries and veins, they obstruct BV’s. If a part breaks off, this is an embolus.
What is a thrombus composed of?
Fibrin, platelets and entrapped RBC’s an WBC’s
What is a blood clot?
A blood clot occurs in STATIC blood and involves primarily the coagulation system.
What factors cause thrombosis?
Virchows triad: enothelial injury; abnornal blood flow; hypercoagubility/ change n blood constituents.
Endothelial injury and thrombus
Injury can cause these changes in the endothelial vessel wall eg atherosclerosis, hypoxia, infection, trauma
Can thrombi form on artificial vessels?
Yes! Normally endothelium will turn off haemostasis, so artificials will activate the intrinsic coagulation pathway and bind pro inflammatory substances.
Thus they mist take anti coagulants.
Changes in blood flow and thrombus
Turbulence (arteries): caused by narrowing (atherosclerosis); aneurysms; abnormal rhythm or valvular heart disease
Stasis in veins: blood pooling in right sided heart failure; varicose veins, immobilisation; blood viscosity
Overall these changes may cause more platelet contact with endothelium, impaired removal of pro coagulants/impaired delivery of anticoagulants; injury!
Change of blood constituents and thrombus
An increased tendency to coagulate due to
Genetic factors: defieciency of antithrombin 3 or protein C
Acquired causes: tissue damage (liver acute phase response); contraceptive pill; smoking; malignancy, post operation
What are some mechansims of limiting coagulation?
- 3 natural anticoagulants in antithormbins, protein C and S, tissue factor pathway inhibitor.
- fibrinolytic cascade limits size of final clot through action of plasmin.
