Atherosclerosis Flashcards
Define atherosclerosis
Accumulation of intracellular and extracellular lipid in the intima and media of large and medium sized arteries
Define arteriosclerosis
Thickening of the walls of arteries and arterioles usually as a result of hypertension or diabetes mellitus
Define atheroma
Thickening and hardening of arterial walls as a consequence of atherosclerosis
What are the components of atherosclerotic plaque
Cells - macrophages, smooth muscle cells, leucocytes
Intra and extracellular lipid
Extracellular matrix - collagen, elastin, proteoglycans
Describe the cellular events leading to the formation of atherosclerotic lesions
- Chronic endothelial injury from hyperlipidaemia, hypertension, smoking etc
- Lipid droplets (mainly from LDL) and monocytes cross epithelium and accumulate in the intima
Macrophages ingest the lipid and become foam cells - Crowded foam cells cause endothelium to bulge
Smooth muscle cells migrate into legion from media and start to proliferate, creating a fatty streak - Plaque grows as foam cells and smooth muscle cells increase
Some smooth muscle cells lie over the plaque and reinforced by collagen, elastin and other matrix proteins to form a fibrous cap
As the endothelium stretches over the plaque, gaps form which are filled by platelets - Cells in the center of the plaque die and necrosis develops
Dead cells release cholesterol and small blood vessels grow in plaques
Describe the morphological appearance of atherosclerosis
Fatty streaks occur early and cause no disturbance to blood flow - consist of foam cells, extracellular lipid, smooth muscle cells
Plaques - white to yellow colour and impinge on lumen of artery
Fibrosis, necrosis, cholesterol clefts, disruption of the internal elastic lamina, extension into the media and ingrowth of small vessels from the adventitia
How can plaque complications occur
Ulceration - plaque eroded from underneath and core of plaque exposed - highly thrombogenic Thrombosis on the plaque Spasm at site of plaque Embolisation Calcification Haemorrhage - of one of the new vessels in the plaque Aneurysm formation Rupture of atherosclerotic artery
What are aneurysms
Local dilations of artery due to weakening of arterial wall
What are dissecting aneurysms
Occur only in aorta and major branches
Inner layer of vessel tears, blood enters and splits media into 2 layers
As the tear fills with blood, the lumen can become occluded
Occasionally blood can push back into the lumen through a second tear
What are some clinical effects of atherosclerosis
Heart - myocardial infarction, chronic ischaemic heart disease, arrhythmias, cardiac failure and sudden cardiac death
Brain – transient ischaemic attacks (TIAs), cerebral infarction, multi-infarct dementia
Kidneys – hypertension, renal failure
Legs – peripheral vascular disease, gangrene
Bowel - ischaemic colitis, malabsorption, bowel infarction
Explain the response to injury hypothesis
Atherosclerosis is a chronic inflammatory response of the arterial wall initiated by injury to the endothelium
Macrophage, T lymphocyte and lipoprotein interactions sustain the lesion progression
Explain the insudation theory
LDL carrying lipids are taken up by endothelial cells and engulfed by macrophages
Explain the encrustation theory
Plaques are formed by repeated thrombi overlying thrombi
Explain the monoclonal theory
Genetic change in smooth muscle cells cause proliferation - together with damage of endothelial by chronic inflammation
What is the role of smooth muscle cells in atherosclerosis
Take up LDL and other lipids to become foam cells
Synthesise collagen and proteoglycans
