Presentation on theme: "Atherosclerosis D S O’Briain April 2007. Atherosclerosis Arteriosclerosis (hardening of the arteries) 3 types: 1.Atherosclerosis (athero=porridge) plaques."— Presentation transcript:
Atherosclerosis D S O’Briain April 2007
Atherosclerosis Arteriosclerosis (hardening of the arteries) 3 types: 1.Atherosclerosis (athero=porridge) plaques of lipid and fibrous tissue in vessel wall Less important forms of arteriosclerosis 2. Medial calcification (Monckeberg) 3. Small vessel (arteriolosclerosis) hyaline or hyperplastic
Atheromatous Plaque, Macroscopic Distribution: Abdominal aorta> coronary > popliteal > descending thoracic >internal carotid > circle of Willis. Spared: upper extremities, renal, mesenteric (except ostia). Fibrous cap (white), deeper portion (grumous, yellow) mm diameter, raised, coalesce. Scanty to numerous
Effects of Atheromatous Plaque Different effects in narrow (coronary) and wide (aorta) vessels Clinically silent Most plaques have no effect. Calcification: Identify on imaging. Complicated plaques Fissure Ulcerate: atheroemboli. Thrombose: occlude, embolise Haemorrhage: occlude. Consequences Stenose: Ischaemia, atrophy. Occlude (by thrombus or haemorrhage): Infarct. Aneurysm: pressure effects, leak (rupture)
Fatty streak Possible precursor of atheroma. Spot (1mm), Streak (1x10mm). Composition: Macrophages filled with lipid (foam cells) later smooth muscle cells with lipid droplets, extracellular lipid, T-lymphocytes, proteoglycans, collagen, elastin. Incidence: More frequent with high milk/fat diet: 10% first decade, 30% third decade, May recede, persist or convert to fibrous plaque Distribution: Aorta - unlike atheroma, Coronary arteries - like atheroma.
Intimal Cushion White areas of diffuse intimal thickening composed of intimal smooth muscle and matrix (little collagen, no lipid), gelatinous lesion. Degenerate effect of blood pressure and time. But occur at ostia (atheroma sites).
Monckeberg’s Calcific Medial Sclerosis Calcification of medium or small arteries Both sexes, over 50 Arteries: Femoral, radial, ulnar, genital. Cause: vasotonic factors, adrenaline, nicotine. Effect: none, visible in imaging
Atherosclerosis Risk Factors Hyperlipidemia.LDL (low density lipoprotein) Hypertension: 160/95 V s 140/90,- Risk X 5. Increases: Atheroma, IHD, CVD. Risk decreases with therapy. Cigarettes: More AS, more sudden death, Risk increased by %. Decreases after cessation. Diabetes: More AS, MI x 2, Increased CVD, PVD risk increased x Other: Physical activity, stress, obesity, oral contraceptives, hyperuricemia, high carbohydrate intake, male, age, family history, homocystinemia. Multiple Factors:More than additive. NOTE: IHD ischaemic heart disease, CVD cerebrovascular disease, PVD peripheral vascular disease AS atherosclerosis, MI myocardial infarction,
Role of lipid in Atherosclerosis 1. Found in plaque 2. Experimentally raised lipid -> AS 3. Hyperlipidemias -> AS 4. Populations with high lipids -> high AS rate 5. Treat hyperlipidemia - decrease AS.
Risk of Atherosclerosis High: Raised LDL (70% cholesterol), triglyceride and VLDL. Low: Raised HDL. Risk increases with increased cholesterol level (risk x 5 with cholesterol increase 220 to 265) Increased intake cholesterol and triglycerides - increases serum cholesterol. Omega 3 fatty acids (fish) protective
How Hyperlipidemia may damage intima More serum LDL, more cellular penetration. LDL with proteoglycan - avid uptake. LDL modified - lysosomal uptake. LDL - directly damages endothelial cell. Oxidised lipoproteins: Endothelial injury, smooth muscle injury, foam cells - scavenger receptor, chemotactic.
Smooth muscle proliferation Origin: From media (or myointima) Stimulus: PDGF (from platelets, macrophages, endothelial and smooth muscle cells), FGF, EGF, TGF. Inhibit: Heparin, TGF-B. Result: Smooth muscle cells produce extracellular matrix and foam cells (atheroma)
Arterial Injury Permeability increases. Adhesion of platelets, monocytes Factors released Smooth muscle migrates to intima, proliferates and produces extracellular matrix, collagen, elastin, proteoglycans Monocytes - phagocytose Lipid deposited
Other Theories of Atherogenesis Primary smooth muscle proliferation: monoclonal growth (as a form of leiomyoma) Cause: Exogenous (hydrocarbon, virus), endogenous (cholesterol) Experimentally: Plaques in Marek chicken virus, anthracycline, herpes mRNA in plaque
Ischaemic Heart Disease Epidemic Causes 80% of cardiac mortality Peaked in US in 1960s, 40% decline since Different patterns in some Western countries Cause of decline: Changing lifestyle (diet, smoking, exercise) Better therapy (CCU, thrombolysis, arrhythmia therapy, CABG, angioplasty)