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Description : Check out this medical presentation on Aortic Aneurysm, which is titled "Atheroma", to know about atheroma and mechanisms of atherogenesis, etc.

Tags : Aortic Aneurysm, Atheroma, mechanisms

Published on : Jun 02, 2021 | Views : 2764 | Downloads : 1

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Slide 1-

Leicester Warwick Medical School Atheroma Dr Mark Bamford Department of Pathology
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Atheroma - Objectives 1 Definition of atheroma Macroscopic appearances Microscopic appearances Effects
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Atheroma - Objectives 2 Mechanisms of atherogenesis encrustation insudation monoclonal response to injury Epidemiology Prevention/Intervention
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Atheroma Definition Atheroma is the accumulation of intracellular and extracellular lipid in the intima of large and medium sized arteries
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Atherosclerosis Definition The thickening and hardening of arterial walls as a consequence of atheroma
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Arteriosclerosis Definition The thickening of the walls of arteries and arterioles usually as a result of hypertension or diabetes mellitus
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Atheroma - Macroscopic Features Fatty streak Simple plaque Complicated plaque
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Atheroma - The Fatty Streak Lipid deposits in intima Yellow, slightly raised Relationship to atheroma somewhat debatable
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Atheroma - The Simple Plaque Raised yellow/white Irregular outline Widely distributed Enlarge and coalesce
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Atheroma - The Complicated Plaque Thrombosis Haemorrhage into plaque Calcification Aneurysm formation
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Atheroma - Common Sites Aorta - especially abdominal Coronary arteries Carotid arteries Cerebral arteries Leg arteries
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Normal Arterial Structure Endothelium Sub-endothelial c.t. Internal elastic lamina Muscular media External elastic lamina Adventitia
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Atheroma - Microscopic Features Early changes proliferation of smooth muscle cells accumulation of foam cells extracellular lipid
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Endothelium Smooth muscle cell Lipid Matrix
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Atheroma - Microscopic Features Later changes fibrosis necrosis cholesterol clefts +/- inflammatory cells
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Atheroma - Microscopic Features Later changes disruption of internal elastic lamina damage extends into media ingrowth of blood vessels plaque fissuring
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Atheroma - Coronary Artery
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Atheroma - Clinical Effects Ischaemic heart disease sudden death myocardial infarction angina pectoris arrhythmias cardiac failure
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Atheroma – myocardial infarction
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Atheroma – myocardial infarction
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Atheroma - Clinical Effects Cerebral ischaemia transient ischaemic attack cerebral infarction (stroke) multi-infarct dementia
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Atheroma – cerebral infarction
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Atheroma - Clinical Effects Mesenteric ischaemia ischaemic colitis malabsorption intestinal infarction
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Atheroma – intestinal infarction
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Atheroma - Clinical Effects Peripheral vascular disease intermittent claudication Leriche syndrome ischaemic rest pain gangrene
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Atheroma – peripheral vascular disease
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Atheroma – Abdominal Aortic Aneurysm
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Atheroma - Pathogenesis Age Gender Hyperlipidaemia Cigarette smoking Hypertension Diabetes mellitus Alcohol Infection
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Atheroma Age slowly progressive throughout adult life risk factors operate over years Gender women protected relatively before menopause presumed hormonal basis
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Atheroma Hyperlipidaemia high plasma cholesterol associated with atheroma LDL most significant HDL protective
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Atheroma - Lipid Metabolism Lipid in the blood is carried on lipoproteins Lipoproteins carry cholesterol and triglycerides (TG) Hydrophobic lipid core Hydrophilic outer layer of phospholipid and apolipoprotein (A-E)
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Atheroma - Lipid Metabolism Chylomicrons transport lipid from intestine to liver VLDL carry cholesterol and TG from liver TG removed leaving LDL LDL rich in cholesterol carry cholesterol to non-liver cells HDL carry cholesterol from periphery back to liver
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Atheroma and Apolipoprotein E Genetic variations in Apo E are associated with changes in LDL levels Polymorphisms of the genes involved lead to at least 6 Apo E phenotypes Polymorphisms can be used as risk markers for atheroma
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Familial Hyperlipidaemia Genetically determined abnormalities of lipoproteins Lead to early development of atheroma Associated physical signs arcus tendon xanthomas xanthelasma
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Xanthelasma
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Atheroma - Cigarette Smoking Powerful risk factor for IHD Risk falls after giving up Mode of action uncertain coagulation system reduced PGI2 increased platelet aggregation
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Atheroma - Hypertension Strong link between IHD and high systolic/diastolic blood pressure Mechanism uncertain ? endothelial damage caused by raised pressure
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Atheroma - Diabetes Mellitus DM doubles IHD risk Protective effect in premenopausal women lost DM also associated with high risk of cerebrovascular and peripheral vascular disease ?related to hyperlipidaemia and hypertension
Slide 40-

Atheroma - Alcohol Consumption >5 units /day associated with increased risk of IHD Alcohol consumption often associated with other risk factors eg smoking and high BP but still an independent risk factor Smaller amounts of alcohol may be protective
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Atheroma-Infection Chlamydia pneumoniae Helicobacter pylori Cytomegalovirus
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Atheroma - Other Risk Factors Lack of exercise Obesity Soft water Oral contraceptives Stress
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Atheroma - Genetic Predisposition Familial predisposition well known Possibly due to variations in apolipoprotein metabolism variations in apolipoprotein receptors
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Atheroma - Pathogenesis Thrombogenic theory Insudation theory Monoclonal hypothesis Reaction to injury hypothesis
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Atheroma - Thrombogenic Theory 1852 Karl Rokitansky plaques formed by repeated thrombi lipid derived from thrombi overlying fibrous cap
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Atheroma - Insudation Theory 1856 Rudolf Virchow endothelial injury inflammation increased permeability to lipid from plasma
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Atheroma - Reaction to Injury Hypothesis 1972 Ross and Glomset plaques form in response to endothelial injury hypercholesterolaemia leads to endothelial damage in experimental animals injury increases permeability and allows platelet adhesion monocytes penetrate endothelium smooth muscle cells proliferate and migrate
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Atheroma - Reaction to Injury Hypothesis 1986 Ross endothelial injury may be very subtle and be undetectable visually LDL, especially oxidised, may damage endothelium
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Atheroma - The Monoclonal Hypothesis Benditt and Benditt crucial role for smooth muscle proliferation each plaque is monoclonal might represent abnormal growth control is each plaque a benign tumour? could atheroma have a viral aetiology?
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Atheroma - The Processes Involved Thrombosis Lipid accumulation Production of intercellular matrix Interactions between cell types
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Atheroma - The Cells Involved Endothelial cells Platelets Smooth muscle cells Macrophages Lymphocytes Neutrophils
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Atheroma - Endothelial Cells Key role in haemostasis Altered permeability to lipoproteins Secretion of collagen Stimulation of proliferation and migration of smooth muscle cells
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Atheroma - Platelets Key role in haemostasis Stimulate proliferation and migration of smooth muscle cells (PDGF)
Slide 55-

Atheroma - Smooth Muscle Cells Take up LDL and other lipid to become foam cells Synthesise collagen and proteoglycans
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Atheroma - Macrophages Oxidise LDL Take up lipids to become foam cells Secrete proteases which modify matrix Stimulate proliferation and migration of smooth muscle cells
Slide 57-

Atheroma - Lymphocytes TNF may affect lipoprotein metabolism Stimulate proliferation and migration of smooth muscle cells
Slide 58-

Atheroma - Neutrophils Secrete proteases leading to continued local damage and inflammation
Slide 59-

Atheroma - A Unifying Hypothesis 1 Endothelial injury due to raised LDL ‘toxins’ eg cigarette smoke hypertension haemodynamic stress
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Atheroma - A Unifying Hypothesis 2 Endothelial injury causes platelet adhesion, PDGF release, SMC proliferation and migration insudation of lipid, LDL oxidation, uptake of lipid by SMC and macrophages migration of monocytes into intima
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Atheroma - A Unifying Hypothesis 3 Stimulated SMC produce matrix material Foam cells secrete cytokines causing further SMC stimulation recruitment of other inflammatory cells
Slide 62-

Atheroma and Apolipoprotein E Genetic variations in Apo E are associated with changes in LDL levels Polymorphisms of the genes involved lead to at least 6 Apo E phenotypes Polymorphisms can be used as risk markers for atheroma
Slide 63-

Atheroma - Prevention No smoking Reduce fat intake Treat hypertension Not too much alcohol Regular exercise/weight control BUT some people will still develop atheroma!
Slide 64-

Atheroma - Intervention Stop smoking Modify diet Treat hypertension Treat diabetes Lipid lowering drugs
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