48 - Vascular Pathology II Flashcards
Example of a factor on platelets, and its ligand on vascular endothelium
GP1b on platelets sticks to exposed Von Willebrand factor
What do platelets do when activated?
Change shape, release granules (factors, fibrinogen)
Thrombomodulin
Changes thrombin from activator of clotting to an inhibitor
Effector of fibrinolysis
Tissue plasminogen activator (tPA)
Mechanism of tissue plasminogen activator action
Tissue plasminogen activator binds to fibrin, activates plasmin. Plasmin degrades fibrin.
Thrombus
A blood clot within an intact, living cardiovascular system.
Contents of a thrombus
RBC, WBC, platelets
Appearance of a thrombus
Red and white stripes (layers of RBC and platelets+fibrin) - called ‘lines of Zahn’.
Difference in appearance between arterial and venous thrombi
Arterial are white.
Venous are red.
Why do arterial thrombi appear white?
Greater proportion of platelets and fibrin.
Why do venous thrombi appear red?
Higher proportion of RBC
What are arterial thrombi mostly associated with?
Endothelial dysfunction or damage
What are venous thrombi mostly associated with?
Blood stasis, hypercoagulability
Useful drug for preventing arterial thrombi
Aspirin (interferes with platelet thromboxane production)
Useful drug for preventing venous thrombi
Warfarin (interferes with coagulation cascade)
Outcome of laminar flow in blood vessels
Blood cells don’t touch vascular wall
Why do thrombi form?
Virchow’s triad of factors influencing clotting:
1) Endothelium (EG: injury)
2) Blood flow (EG: non-laminar flow)
3) Blood composition (EG: hypercoagulability)
How might endothelial abnormality occur (Virchow 1)
Endothelial activation or dysfunction from:
Inflammation (EG: from smoking, infection, toxins, hypertension, etc)
How can abnormal blood flow (Virchow 2) lead to thrombus formation?
1)
2)
3)
Turbulence, stasis, or loss of laminar flow:
1) Endothelium is activated
2) Platelets come into contact with vascular wall
3) Allows any activated clotting factors to accumulate, initiate cascade
How can abnormal blood coagulability (Virchow 3) come about?
1) Genetic (primary) - EG: Factor V Leiden
2) Non-genetic (secondary) - Oestrogen (contraceptive pill, pregnancy), cancer, smoking, obesity, age
Factor V Leiden
Mutant of factor V protein in coagulation cascade. Confers hypercoagulability.
If heterozygous, 5x risk of thrombosis.
If homozygous, 50x risk of thrombosis.
Examples of secondary risk factors for thrombosis 1) 2) 3) 4) 5) 6)
1) Prolonged immobilisation
2) Myocardial infarct
3) Atrial fibrillation
4) Tissue injury (EG: surgery, burn, fracture)
5) Cancer
6) Smoking
Things that can happen to a thrombus 1) 2) 3) 4)
1) Dissolution - Fibrinolysis (with tissue plasminogen activator, protein C and S). Becomes less likely with age.
2) Organisation and recanalisation (granulation tissue formation
3) Propagation (grows)
4) Embolisation
Embolus
Intravascular mass carried in the bloodstream (solid, liquid or gaseous- EG the bends)
Examples of emboli causing disease
1)
2)
1) Pulmonary embolus
2) Arterial thromboembolism
Where do emboli that result in pulmonary emboli often forM?
Usually in legs as a DVT
Where do emboli that result in arterial thromboembolism often form?
Usually from atheroma (EG: atherosclerosis) or heart
Outcomes of pulmonary embolism
Can be asymptomatic, cause transient hypoxia, sudden death
Where do emboli causing pulmonary embolism often lodge?
Travels through right heart, lodges in pulmonary arteries.
What does the formation of an arterial thromboembolism often involve?
Turbulence and/or platelets adhering to a dysfunctional blood vessel surface (EG: atherosclerosis, myocardial infarct, atrial fib)
Where is it rare for emboli from the heart to lodge?
In the coronary arteries
Difference between ischaemia and infarction
Ischaemia means ‘not enough blood supply.’
Infarction is tissue death as a result of too little blood supply
Difference between ischaemia and hypoxia
Ischaemia is too little blood supply.
hypoxia is too little oxygen.
EG: If severely anaemic, can have hypoxia without ischaemia.
Examples of acute ischaemia
1)
2)
1) Coronary thrombosis leading to myocardial infarct.
2) Shock, reducing blood supply to everything
Examples of chronic ischaemia
1)
2)
1) Atherosclerotic disease leading to atrophy of lower limbs
2) Renal artery stenosis leading to renal atrophy
Most common cause of infarction
Arterial occlusion
Time taken for neurons to die from hypoxia
3-4 minutes
Two appearances of infarctions
1) Red infarction
2) White infarction
Red infarction
When there is haemorrhage in infarcted tissue
Situations that could lead to red infarction 1) 2) 3) 4)
1) Dual blood supply to an organ (EG: Lungs)
2) Collateral blood supply (EG: intestine)
3) Venous infarction (EG: testicular torsion)
4) Reperfusion (common in emboli to the brain)
How can reperfusion lead to a red infarct?
Infarction of tissue causes necrosis, breakdown of structure.
Blockage of artery is removed, blood enters now-damaged organ and leaks out into surrounding tissues.
Pale infarction
When there is no bleeding in infarcted tissues
When are pale infarcitons more common?
Due to a blocked end artery
Why can an infarct lead to a thrombosis?
Abnormal, inflamed endothelium overlies infarct.
