Atheroma & Myocardial Infarction PDF

Atherosclerosis and Myocardial Infarction Dr. Sine Phelan Overview – Learning Outcomes Pathogenesis of atherosclerosis & risk factors Reaction to injury theory Complications of atherosclerosis Coronary artery disease & Myocardial Infarction Complications of Myocardial Infarction Major Risk Factors f...

Atherosclerosis and Myocardial Infarction Dr. Sine Phelan Overview – Learning Outcomes Pathogenesis of atherosclerosis & risk factors Reaction to injury theory Complications of atherosclerosis Coronary artery disease & Myocardial Infarction Complications of Myocardial Infarction Major Risk Factors for Atherosclerosis Non-modifiable: Increasing Age Family History Male Gender Genetic (e.g. hyperlipproteinaemias) Major risk factors for Atherosclerosis Modifiable Cigarette Smoking Hypertension Hyperlipidaemia (HDL160mg/dl ) Diabetes Mellitus Minor risk factors Obesity Physical Inactivity Homocysteine Postmenopausal Oestrogen drop Alcohol “Trans-” type unsaturated fat (artificially hardened vegetable fats) High carbohydrate intake Other Proposed Risk factors Increased plasma Angiotensin II – alters vascular smooth muscles – increases risk Triglyceride – rich lipoprotein ( in particular those that contain apolipoprotein C3) Mitochondrial DNA damage may also plays role. Arteriosclerosis Thickening & loss of elasticity of arterial walls : Atherosclerosis (Atheroma) – large & medium sized arteries Monckeberg’s Medial Calcification – calcium deposits in arteries in people >50 years Arteriolosclerosis (hyaline and hyperplastic) – associated with hypertension and diabetes mellitus Atherosclerosis Acute Myocardial Infarction and Stroke 50% of all deaths Males > Females Age Related Elastic and Muscular Arteries Begins in, primarily involves, intima Atherosclerosis: Mechanisms Response to Injury theory – Atherosclerosis is a chronic inflammatory response of the arterial wall initiated by some form of injury to the vessel wall Early lesion = Fatty Streak Advanced lesion = Fibrous Plaque Response to Injury Theory: Sequence First Step: Endothelial cell injury: CO/toxins in cigarette smoke, raised LDL, viral, immunological, turbulence, hyperglycemia, hyperhomocysteinemia lead to endothelial dysfunction Next: Monocytes (CD8, CD4) adhere to abnormal endothelium (adhesion molecules) & migrate into vessel wall. Secrete Cytokines (Growth factors) Attract Smooth muscle cells & Activate macrophages Next: Macrophages and smooth muscle cells Ingest LDL-CH to form Foam Cells—Fatty Streaks Fatty Streaks Confined to intima Composed of lipid filled foam cells. Flat, no blood flow disturbance. Multiple 1mm yellow spots, coalesce into streaks >1cm Response to Injury: 2 Fatty Streaks enlarge and Disrupt Endothelial Surface Platelets adhere Platelets release PDGF More Smooth Muscle Proliferation Response to Injury: 3 Injured Endothelial Cells and Macrophages Produce Free Radicals Oxidise LDL (Oxidised LDL: More Atherogenic) - Chemotactic for Monocytes - Stimulates release of growth factors - Neutralised by Antioxidants Progression of lesion Over time Smooth muscle proliferates Collagen and other Extracellular matrix is deposited. Extracellular lipid is deposited - - intimal plaque is formed Intimal plaque – Central aggregation of foam cells, some of which have died and released lipid , surrounded by smooth muscle cells, with connective tissue on intimal aspect Complicated plaque Plaques can undergo disruption, with superimposed thrombus, rupture --- known as complicated (vulnerable) plaque Myocardial infarction, stroke etc. Atherosclerosis Develops in Areas of Damage / Turbulence Abdominal Aorta Coronary Arteries Popliteal artery Descending Thoracic Aorta Internal Carotid Artery Circle of Willis General Complications of Atherosclerosis Obstruction:- enlargement of atheroma - hemorrhage into atheroma - formation of thrombus Embolism :– -infarcts Aneurysm: -Rupture Organ Specific Complications Coronary Arteries: Angina, Myocardial Infarct Peripheral Vascular Disease – Peripheral ischaemia Circle of Willis/ Vertebrobasilar/ Internal Carotids: Stroke, TIAs Renal Arteries: Hypertension (Secondary) Coeliac, Sup./Inf. Mesenterics: Ischaemia and Infarction of Intestine Coronary Artery Disease Left Coronary Artery: LAD, LCA Right Coronary Artery Ischaemic Heart Disease (IHD) Most common cause of death!! Manifestations: Angina pectoris, Acute myocardial infarction, Sudden cardiac death syndrome, Chronic IHD, Cardiac arrhythmias Myocardial Infarction (MI) Necrosis (death) of part of myocardium due to loss of blood supply (occlusion/ vasospasm) Transmural – involves full thickness Subendocardial – limited to inner 1/3 of wall Loss of blood supply to myocardium Cessation of aerobic glycolysis Accumulation of lactic acid Cell death ( myocyte necrosis) Cell death leads to release of cytoplasmic proteins into serum (Troponin) which can be measured to confirm diagnosis) Outcome depends on -: - Location/severity of occlusion - Duration of occlusion (thrombolysis, angioplasty) - collateral circulation - BP, heart rate Presents with retrosternal chest pain ( can be referred pain to left arm/jaw/abdomen), sudden weakness/ collapse, sudden death “Silent MI” occurs in elderly /diabetic patients Consequences & Complications Death ( arrhythmia) Contractile dysfunction ( acute cardiac failure, chronic congestive failure) Arrhythmias Myocardial rupture (haemopericardium/tamponade) – classically 3-7 days post infarct. Pericarditis ( early or late – Dressler’s syndrome – immune mediated ) Infarct extension or expansion Ventricular aneurysm mural thrombus Papillary muscle dysfunction/rupture Histological Changes in MI 0-12 hours – None 12-24hrs – Pyknosis of nuclei, early neutrophilic infiltrate 1- 3 days – Necrosis:- Loss of nuclei, neutrophilic infiltrate 3-7 days – Macrophages, phagocytosis 7-14 days –granulation tissue formation 2- 8 weeks – collagen deposition > 2 months - scar Neutrophilic infiltrate, myocyte necrosis Macrophages join the infiltrate, phagocytosis of necrotic debris Collagenous scar formation Summary – – – Major risk factors Atherosclerosis, fatty streaks Reaction to injury theory Complications of atherosclerosis Coronary artery disease Myocardial infarction Causes Histopathology Complications Questions?