Revision: Atheroma Flashcards
Definitions of atheroma, atherosclerosis, arteriosclerosis
atheroma: accumulation of IC and EC lipid in the intima/media of medium/large arteries
atherosclerosis: thickening and hardening of arterial walls as a consquence of atheroma
arteriosclerosis: thickening of walls of arteries and arterioles usually due to hypertension/diabetes mellitus
Macroscopic appearance of an atheroma
1 Fatty streak: lipid deposits in intima, yellow and slightly raised appearance
2 Then->Simple plaque: irregular outline, raised and yellow/white, widely distributed, enlarges and coalesces
3 Then->Complicated plaque: Thrombosis, haemorrhage into plaque, calcification, aneurysm formation
microscopic appearance of an atheroma
Earliest changes: proliferation of SMCs, accumulation of foam cells, EC lipid
Later changes: fibrosis, necrosis, cholesterol clefts, +/- inflammatory cells
Last changes: disruption of internal elastic lamella, damage extends into media, ingrowth of blood vessels, plaque fissuring
Cellular events leading to formation of an atherosclerotic lesion
1 endothelial damage -> platelets -> PDGF -> SMC proliferation
2 proliferation and migration of SMCs takes lipid w/ it
3 macrophages arrive and phagocytose fat, beoming foam cells
effects of severe atherosclerosis in 4 different sites
1 Coronary arteries -> ischaemic heart disease: sudden death, MI, angina pectoris, arrhythmias, cardiac failure
2 Cerebral ischaemia: transient ischaemic necrosis, cerebral infarction/stroke, multi-infarct dementia
3 Mesenteric ischaemia: intestinal infarction, malabsorption, ischaemic colitis
4 Peripheral vascular disease: intermittent claudication, Leriche syndrome (atherosclerosis in abdominal aorta a/o both iliac arteries), ischaemic rest pain, gangrene
Risk factors for atheromas
Non-environmental: Age (slowly progresses over adult years), Gender (women seem relatively more protected pre-menopause- possible hormonal basis), Familial hypercholesterolaemia (gen. abnormality of lipoproteins -> early development of atheromas -> arcus, tendon xanthomas, xanthelasmas- xanthelasmas tend to be a subclass of xanthomas as they are smaller, not nodular, not reaching tumorous proportions) leading to hyperlipidaemia (high plasma cholesterol, LDLs are significant whereas HDLs are protective), Diab Mell (2x risk of IHD, also associated w/ high risk of cerebro- and peripheral vascular disease)
Environmental: Obesity, Smoking, Diab Mell, hyperlipidaemia, hypertension (link to IHD, may be due to endothelial damage from raised pressure, NSExactly why though), infections (chlamydia pneumoniae, helicobacter pylori, cytomegalovirus), lack of exercise, soft water, oral contraceptives, stress and personality type?, Alcohol (>5 units/day inc. risk of IHD)
Non-environmental risk factors for atheromas
age (inc. over adult yrs)
gender - women relatively more protected pre-menopausal
familial hypercholesterolaemia (gen. abnormality of LPs -> ealry development of atheromas -> arcus (white ring around eye), tendon xanthomas and xanthelasmas (latter is generally smaller, less nodular, not tumorous proportions)
Diab. Mell (Inc. risk of IHD, assoc. w/ inc. risk of cerebro- and peripheral vascular disease)
personality type, NSThough
Environmental risk factors for atheromas
hyperlipidaemia (high plasma cholesterol, LDLs cause problems, HDLs protect)
Alcohol (>5 units/day inc. risk of IHD)
smoking (risk factor for IHD)
diab. mell. (2x IHD risk, associated w/ inc. risk of cerebro- and peripheral vasc. disease)
infection (chlamydia pneumoniae, helicobacter pylori and cytomegalovirus)
hypertension (high press. may damage endoth. (NSThough), link to IHD)
obesity, soft water, oral contraceptives, lack of exercise, stress
Hypotheses for atheroma formation
Response to injury: Damaged endoth. lead to formation of plaques -> injury inc. permeability and allows platelet adhesion -> monocytes penetrate endothelium -> SMCs prolif and migrate
Monoclonal: each plaque formed is monoclonal - could represent abnormal growth control -> benign tumour possible
Unifying - discussed later
Unifying hypothesis for atheroma formation
1 endothelial damage from hypertension, haemodynamic stress, raised LDLs, toxins eg cig. smoke
2 This causes: platelet adhesion, PDGF release -> SMC prolif. and migration
- insudation of lipid, LDL oxidation, uptake of lipid by SMCs and macrophages
- migration of monocytes into intima
3 Resulting in: stim. SMCs produces matrix material, foam cells secrete cytokines that further stimulate SMCs and recruit other inflammatory cells
Cells involved in an atheroma and their roles
endothelia: secretion of collagen, altered permeability to LPs, stim. of prolif. and mig. of SMCs, Key role in haemostasis
platelets: key role in haemostasis, stim. prolif. and migration of SMCs from PDGF
SMCs: take up LDLs and other lipids to become foam cells, synth. collagen and proteoglycans
macrophages: oxidise LDLs, take up lipids to become foam cells, synth. proteases that modify the matrix, stim. prolif. and mig. of SMCs
lymphocytes: TNF can affect LP metabolism, stim. prolif. and mig. of SMCs
neutrophils: synth. proteases that cause continued local damage and inflamm
All but SMCs and neutrophils stim. prolif and mig. of SMCs
SMCs and macrophages both take up lipids to become foam cells
endothelia, macrophages, SMCs and neutrophils all produce ECM material, through w/ different consequences
Both endothelia and platelets have key roles in haemostasis
prevention and treatment of an atheroma
Prevention: no smoking, exercise, low fat intake, treatment of hypertension, little alcohol
Intervention: modify diet, stop smoking, treat Diab. Mell. and hypertension, lipid lowering drugs
