Define atheroma.
- accumulation of intracellular and extracellular lipid in intima and media of large and medium sized arteries.
Define atheroscelrosis.
- thickening and hardening of arterial walls as consequence of atheroma.
Define ARTERIOsclerosis.
- thickening of walls of arteries and arterioles usually due to hypertension or diabetes mellitus.
what are the macroscopic features of atherosclerosis?
- fatty streak : yellow, slightly raised lipid in intima.
- simple plaque : raised, yellow/ white widely distributed, enlarge and coalesce.
- complicated plaque : thrombosis, haemorrhage into plaque, calcified, aneurysm forms.
name some common sites for atherosclerosis.
- aorta : esp. abdominal.
- coronary arteries.
- carotid arteries.
- cerebral arteries.
- leg arteries.
what are some microscopic features of atheroscelrosis?
- proliferation of smooth muscle.
- accumulation of foam cells.
- extracellular lipid.
- later.
- fibrosis, necrosis, cholesterol clefts, inflammatory cells + or -
- disruption to elastic intima and media, ingrowth of blood vessels, plaque fissuring and rupture.
what are some clinical effects seen in atherosclerosis?
- ischaemic heart disease : sudden death, MI, angina, arrhythmias, cardiac failure.
- cerebral ischaemia : transient ischaemic attack, infarction/ stroke, multi infarct dementia.
- Mesenteric ischaemia (small intestine injury) : ischaemic colitis, malabsorption, intestinal infarction.
- peripheral vascular disease : ischaemic rest pain, intermittent claudication, leriche syndrome, gangrene.
what factors may predispose you into atherosclerosis?
- age.
- gender : women more protected before menopause.
- hyperlipidaemia : high plasma cholesterol, LDL.
- cigarette smoking : for ischaemic HD, affects coagulation, increases platelet aggregation.
- hypertension : ischaemic HD, endothelial damage?
- diabetes mellitus : doubles IHD risk, protective in women lost after menopause.
- alcohol consumption : for IHD, associated with other risks.
- infection : helicobacter pylori, chlamydia pneumoniae
- lack of exercise, obesity, stress.
- family predisposition die to Apo receptor/ metabolism variations.
differentiate among chylomicrons, VLDL, LDL, HDL.
- chylomicrons : lipid transport from intestine to liver.
- VLDL : carries chol and TG from liver, when TG removed it leaves LDL.
- LDL : rich in cholesterol, carries it to non liver cells. higher half life. more likely to be made to foam cells.
- HDL : chol from periphery to liver.
what is the link between atherosclerosis and apolipoprotein E?
comment in familial hyperlipidaemia.
- genetic variation in Apo E associated with changes in LDL, so markers for risk assessment.
- abnormalities of lipoproteins, early atherosclerosis, associated signs of corneal arcus, tendon xanthomas, xanthelasma.
what does thrombogenic theory by Rokitansky suggest as the pathogenesis of atherosclerosis?
- repeated thrombi forms plaques.
- lipid derived from thrombi.
- overlying fibrous cap.
what does Virchow’s insudation theory suggest as the pathogenesis of atherosclerosis?
- endothelial injury.
- inflammation.
- increased permeability to lipid from plasma.
what does Ross and Glomset and their reaction to injury theory suggest as the pathogenesis of atherosclerosis?
- plaques in endothelial injury caused by hypercholesterolaemia.
- injury increases permeability and allows platelet adhesion.
- monocytes penetrate endothelium and smooth muscles proliferate and migrate.
Ross : endothelial injury subtle LDL when oxidised may damage endothelium.
what does Benditt and Benditt and their monoclonal hypothesis suggest as the pathogenesis of atherosclerosis?
- crucial role of smooth proliferation.
- plaque monoclonal.
- each plaque benign tumour.
- viral aetiology?
what are the cells involved in atherosclerosis and their role?
- endothelial : haemostasis, altered lipid permeability, collagen, proliferation and migration of smooth.
- platelets : haemostasis, proliferation and migration of smooth.
- smooth muscle : take up LDL, foam cells, synthesis collagen and proteoglycans.
- macrophages : oxidise LDL, foam cells, proteases to modify matrix, stimulate smooth proliferation, migrate.
- lymphocytes : stimulate smooth, TNF protect lipoprotein metabolism.
- neutrophil : proteases, local damage and inflammation.
what are some plausible unifying hypotheses for atherosclerosis?
- endothelial injury due to raised LDL, toxins in cigar, hypertension, haemodynamic stress.
- injury causes platelet adhesion, insudation of lipid, migration of monocytes to intima.
- foam cells secrete cytokines which recruit others.
how could you prevent atherosclerosis?
- no smoking.
- reduce fat intake (genetics still affects).
- treat hypertension.
- not too much alcohol.
- regular exercise/ weight control.
- some still may develop.
what interventions could you give for those with atheroscelrosis?
- stop smoking.
- modify diet.
- treat hypertension.
- treat diabetes.
- lipids lowering drugs : statins, aspirin prophylaxis.
- stents, coronary artery bypass, thrombolysis etc.
