Pathophysiology of Atheroma Flashcards
What is atheroma ?
Formation of focal elevated lesions (plaques)in intima of large and mediam sized arteries
Give an example of atheroma
In coronary arteries, atheromatous plaques narrow lumen which leads to ischaemia. This has serious cosequences of angina (chest pain) which results in myocardial ischaemia. It is complicated by thromboembolism.
What is seen in early stages of Atheroma ?
- Earliest signifcant lesion in atheroma is called a fatty streak.
- It can be seen in young children.
- It is a yellow linear elevation of intimal lining
- It comprises masses of lipid-laden macrophages
- Not thought of a clinical significance and many may dissapear.
- In patients at risk they can develop to form atheromatous plaques
What is seen in fully developed atheromatous plaques?
- In fully developed atheromas plaques there is a lipid core with a fibrous tissue cap, this is covered by arterial endothelium. It forms at arterial branching points/bifurcations
- Central lipid core rich in cellular lipids/debris are derived from macrophages ehich have died in the plaque.
- Collagens produced by the smooth muscle cells in the cap procide structural strength.
- Inflammatory cells (macrophages, T-lymphocytes and mast cells) reside in the fibrous cap and are recruited by arterial endothelium.
- Artheromatous plaque is soft, highly thrombogenic and often have a rim of “foamy” macrophages . (”foamy” due to uptake of oxidised lipoproteins via specialised membrane bound scavenger receptor)
What is a complicated atheroma?
Has features of established atheromatous plaque (fibrous cap, lipid core) plus other features. Additional features can heamorhage into the plaque (healed heamorhage results in calfication). There may be plaque rupture/fissuring or you may have thrombosis. These lead to serious clinical consequences.
What is Arterioscelerosis?
Age related change in muscular arteries. There is smooth muscle hypertrophy, apparent reduplication of internal elactic laminae and intimal fibrosis. This reduces the vessel diameter. This contributes to high frequency of cardiac cerebral, colonic and renal ischaemia in elderly.
What is the clinical effects of arterioscelerosis?
Clinical effects of arteriosceloros are morst apparent when the cardiovascular system is stressed by something else like haemorrhage, major surgery, infection and shock
What causes atheroma?
Hypercholesterolaemia (type of hyperlipidaemia) is the most important risk factor. It causes plaque formation and growth in absence of other known risk factors
What is the signs of hyperlipideamia?
- It can be primary (familial) or secondary (idiopathic)
- Biochemical signs: Blood tests can check for LDL, HDL total cholesterol and triglycerides
- Signs on a patient can be seen as corneal arcus, tendon xanthomata (seen on knuckels or achilles) and xanthelasmasta (small yellow spots under the eye)
What are the other risk factors of Atheroma?
- Smoking
- Hypertension
- Diabetes mellitus
- Elderly patients
How do athermatous plaque develop?
It is a two step process:
- There is an injury to the endothelial lining of the artery
- Then the secondary response is chronic inflammation and healing response of vascular wall to agent causing injury
Explain athermatous plaque development in detail
- Injury to endothelium and dysfunction
- Since the wall isn’t working properly there can be accumulation of lipo protein in vessel wall.
- Then there is monocyte adhesion to endothelium which migrate into the intima and transform the foamy macrophages
- There can also be platlet adhesion, activated platelets release tissue factors and there is recruitment of smooth muscle cells.
- Smooth muscle cells proliferate and there is deposition of extracellular matrixand there is also T-lmyphocyte recruitment
- End result is lipid accumulation in cells with foamy macrophages and outwith the cells
What is involved in advanced plaque formation?
- Large number of macrophages, T-lymphocytes.
- The lipid-macrophages die through apoptosis, the lipid then gets into the lipid core.
