Pathology: Atheroma and Thrombosis Flashcards
What are the risk factors for atheroma?
Smoking Diabetes Hypertension Hyperlipidemia Hypercholesterolaemia Age Gender Genetics
Why does diabetes as an independent risk factor increase your risk of endothilial injury?
1) Increases cholesterol levels
2) Increased sugar levels => Advanced Glycation End Products
3) Abnormal cross linking in the vessel wall making it stiff (loss of elasticity increases the impact of injury
4) Traps LDL cholesterol
Why does being male as an independent risk factor increase your risk of atherosclerosis?
Oestrogen has a protective effect- therefore there is no difference after the menopause
What is the pathogenisis of atheroma?
1) Endothelial injury
2) Accumulation of lipids and macrophages
3) Migration of smooth muscle cells
4) Progression and increase in size. Fatty streak, fatty plaque, complicated plaque
Pathogenesis of atheroma: Explains what follows endothilial injury?
1) Endothilial dysfunction. Increased permeability
2) Increase WBC adhesion due to increased expression of VCAM/ICAM. Monocytes adhere and trans-endothilially migrate to become macrophages.
Pathogenesis of atheroma: Explains what causes accumulation of lipid and macrophages?
1) Macrophages engulf cholesterol that cannot be easily digested
2) While the volume of cholesterol is low it remains in the cell but when it increases LDL is deposited => fatty streak
3) HDL cholesterol shuttles back to the liver
Pathogenesis of atheroma: Explains what causes migration of smooth muscle cells?
1) Smooth muscle migrates from the tunica media to the tunica intima => expansion of intima
2) In response to cytokines, it creates an extracellular matrix of collagen
3) Fatty streak becomes a fibrofatty plaque
Pathogenesis of atheroma: What does progression and more cholesterol, macrophages, smooth muscle and collogen cause?
A pool of extracellular collagen at the centre of the plaque
What is a complicated plaque?
Atheroma with overlying thrombosis
How does the flow rate through a vessel vary with the radius of the vessel?
Radius to the power 4. A small change in radius will dramatically reduce flow.
When is critical arterial disease more common?
When its the only artery supplying an organ (no collateral circulation)
The artery diamer is small
Overall blood flow is reduced
What is arterial stenosis?
Narrowing of the arterial lumen
What are the consequences of arerial ischemia?
Reduced elasticity, reduced flow in systole and tissue ischemia
What are the clinical effects of cardiac ischemia?
Reduced exercise tolerance
Angina (stable -> unstable)
MI and cardiac failure
What are the clincial effects of cardiac fibrosis?
Loss of cardiac myocytes and replacement by fibrous tissue
Loss of contractility and elasticity and reduced filling
What is an aneurysm?
Abnormal and persistent dilation of an artery due to a weakness in its wall.
What are the causes of aneurysm?
Atheroma, congenital, dissection, mycotic, traumatic
Where is the most common site for aneurysm formation?
Abdominal aorta
What is arterial dissection?
Splitting within the media by flowing blood creating a false lumen within the media but the media doesn’t rupture through to the outside
What are the symptoms of aortic dissection?
Sudden death/collapse
Very acute excrutating pain
What conditions predispose you to arterial dissection?
Hypertension, trauma, pregnancy, marfans syndrome, coarctation
What is coarctation?
Congenital narrowing of the aorta?
What is a clot?
Extravascular coagulation- bruising
What is a thrombus?
Intravascular coagulation
What is exanguination?
blood loss
How do you measure the intrinsic pathway of the coagulation cascade?
PT- prothrombin time
How do you measure the extrinsic pathway of the coagulation cascade?
aPTT- activated partial prothrombin time
What is the precursor to thrombin?
Prothrombin
What is the function of thrombin?
To convert fibrinogen to fibrin
What is Virchows triad?
1) Endothilial injury
2) Turbulent blood flow
3) Hypercoaguable blood
What is primary vasculitis?
Inflammation of vessel walls (increases thrombophilic tendencies)
What are some of the primary causes of increased viscosity?
Factor V (Leiden) Protein C deficiency Protein S deficiency Antithrombin deficiency
What is an embolism?
Obstruction of an artery?
What is the typical CXR sign of PE a few hours after the event?
Wedged shaped infarct
What is ischemia?
Insufficient blood supply
What is infarction?
Death of a tissue as a result of ischemia
What are the different types of emboli?
Air, Amneotic fluid, fat, tumour, septic and thrombo
Explain the bends?
Breathing at high pressure results in more disolved gas in the blood. As the pressure reduces (coming up from the dive) nitrogen comes out of solution forming multiple bubbles => decompression sickness
How does an amneotic fluid emboli occur?
Tear in the placenta or uterine vessels with secondary infusion of amneotic fluid or foetal material. Identify fetal skin and hair in pulmonary vessels
How does a fat embolism occur?
Large skeletal injuries where marrow contents are embolised. Delayed onset of 1-3 days post major trauma
When does septic emboli occur?
Specific intravascular infections. Thrombus froms in association with an infectious agent. Infective endocarditis or mycotic aneurysm
