Atherosclerosis 2024 PDF

ATHEROSCLEROSIS PROF. MANAL M. SAMI  LEARNING OUTCOMES By the end of this learning activity you should be able to: 1. Appraise the etiopathogenesis and complications of atherosclerosis STRUCTURE& REGIONAL SPECIALIZATIONS OF THE VASCULATURE r...

ATHEROSCLEROSIS PROF. MANAL M. SAMI  LEARNING OUTCOMES By the end of this learning activity you should be able to: 1. Appraise the etiopathogenesis and complications of atherosclerosis STRUCTURE& REGIONAL SPECIALIZATIONS OF THE VASCULATURE recoilwith diastol medium sizevessel IE Altee arterial wall normallythicker  ARTERIOSCLEROSIS Hardning of vesselwal Atherosclerosis Arteriolosclerosis Most frequent & clinically small arteries& arterioles important Hyaline& Hyperplastic Large BV Intima seen on translation Fibromuscular intimal hyperplasia Calcification on muscular artery muscular arteries larger than Mönckeberg medial sclerosis arterioles. calcific deposits in muscular due to inflammation (transplant- arteries associated arteriopathy; age over 50 or mechanical injury ( associated no compromise of lumen with stents or balloon angioplasty  EPIDEMIOLOGY Harding of vessel wall due to deposition of lipied Atherosclerosis is the cause of more than half of all deaths in the Western World. Increasing prevalence of IHD in developing nations over the last few decades due to adoption of western lifestyles. The death rate for coronary artery disease in Africa, India& Southeast Asia now exceeds that in the USA; eastern European countries have rates 3- 5 times higher than the USA &7- 12 times higher than Japan Secondary to 6 Deaths from myocardial infarction (20-25 % of all deaths) are mostly related to underlying atherosclerosis.  Risk Factors for Atherosclerosis Major Minor NON-modifiable You cannot changeit_ Genetic abnormalities (Familial Hypercholesterolemia) mama 0 Lipoprotein Lp(a) Metabolic Syndrome apnea Family history (polygenic) Stress ("type A" personality) manmade Increasing age (5folds risk of MI between Obesity age 40-60yrs) Male gender Physical inactivity Homocystinuria change it Is Modifiable you can Postmenopausal estrogen deficiency Hyperlipidemia Alcohol Hypertension (increase risk of IHD by Factors affecting hemostasis appr.60%) Chlamydophila pneumoniae, Cigarette smoking (doubles death from IHD) the risk herpesvirus, CMV Way Diabetes Double no time (2-&100-fold risk of MI& gangrene respectively) Eppingonitsefanincrease Inflammation (C-reactive protein (CRP) the rate atherosclerosis  Etheory magnesterAs You PATHOGENESIS Response to Injury Theory The model views atherosclerosis as a chronic inflammatory and healing response of the arterial wall to endothelial injury. Lesion progression occurs through the interaction of modified lipoproteins, monocyte-derived macrophages, and T lymphocytes with the ECs and SMCs of the arterial wall Specilized Squamous Single highly2 cell The three most important causes of endothelial dysfunction are - Hemodynamic disturbances (turbulent, non-laminar flow at ostia of exiting BV, branch points& post. aorta) - hypercholesterolemia (dyslipoproteinemia: increased LDL& Lp(a) and decreased HDL) - Inflammation.  Chronic endothelial injury→ EC dysfunction →increased permeability, leukocyte adhesion& thrombotic potential. Accumulation of lipoproteins, mainly LDL, with its high cholesterol content in the vessel wall. Modification of the lesional LDL by oxidation. Adhesion of blood monocytes to the endothelium →migration into the intima → transformation into foamy macrophages. Platelet adhesion. Release of factors from activated platelets, macrophages& EC (e.g. PDGF) →migration of SMCs from media into intima. Proliferation of SMCs in the intima, elaboration of ECM → accumulation of collagen& proteoglycans. Enhanced accumulation of lipids both within macrophages and SMCs and extracellularly my day the atherosclerosis CELLULAR INTERACTIONS IN ATHEROSCLEROSIS intima Toni a  Narrowing construction complete weakness of the Source: 2nd Year MBBS (2019-20)students presentation well  DISTRIBUTION OF ATHEROSCLEROSIS Aorta Classic Localization of Atherosclerosis Lower abdominal >> thoracic Ila ostia of major branches. 111ᵗʰ Other sites (in descending order) Iliac arteries Wanamy cause Athercosis 2 coronary arteries or popliteal arteries 9 internal carotid arteries 5 vessels of the circle of Willis fified.a Small BV & Veins: Never affected. Atherosclerosis is accentuated at sites of vessel branching, due in part to increased turbulence. In this example stenosis involve the ostia of the aortic branches. Atherosclerosis in the cerebral vessels of the circle of Willis also is worst at branch points. aurticdi tion  Important MORPHOLOGY flat region presentinaortain fate Fatty streaks: -Composed of lipid-filled foamy macrophages -Beginning as small flat yellow macules -Eventually coalesce into elongated streaks 1 cm long or longer Fatty streak, a collection of foamy macrophages in the intima. A, Aorta with fatty streaks (arrows), associated largely with the ostia of branch vessels. B, Photomicrograph of fatty streak in an experimental hypercholesterolemic rabbit, demonstrating intimal, macrophage-derived foam  ATHEROSCLEROTIC PLAQUE Superficial FIBROUS CAP: composed of SMCs and dense collagen& ECM. Beneath and to the sides of the cap, the SHOULDER is a cellular area consisting of macrophages, SMCs& T lymphocytes. Deep to the cap is a NECROTIC CORE containing a disorganized mass of lipid, cholesterol clefts, debris, foam cells, fibrin, variably organized thrombus & other plasma proteins. At the periphery: NEOVASCULARIZATION. anemone most I in thepreply LDT  Ñhhhh ATHEROSCLEROTIC PLAQUE 8083 Cells Smooth Muscle Cells macrophages T lymphocytes ECM collagen elastic fibers proteoglycans Intracellular and extracellular lipid Calcium (later stages) MORPHOLOGIC TYPES: proliferation muscel of smooth production of Jstor collages will gradully happen Narrowing of or fatty streak Fatty dots F.Atheroma Plaques Complicated  qgapathmn.aeggaiItta ATHEROMATOUS PLAQUE (CORONARY A) a plaque 11 Lumen (L), Fibrous Cap Arrow: Media thinning, Inflammatory cells, (F), Lipid Core (C) internal& external calcification (arrowhead) elastic membranes and neovascularization attenuation (arrows)  will give Cholesterol you Needle shaped Crytal because its dissolved while Collectingthesamples Needle shaped washed out spaces in arteries, are cholesterol clefts, and can be nothing else, and like all other fat, yellow grossly, white microscopically.  COMPLICATIONS Advanced Lesion is at risk of: 1. Focal rupture, ulceration or erosion of the luminal surface. 2. Superimposed thrombosis→ partial or complete occlusion of the lumen/enlargement of the plaque. once we have focal 3. Hemorrhage into a plaque. area of rupture of plaque elastic will have 4. Atheroembolism due 10 of lesion you 54 thrombus formation 5. Aneurysmal dilation resulting from ischemic atrophy of the underlying media, with loss of elastic tissue. Atherosclerotic plaque rupture. A, Plaque rupture without plaque thrombformation superimposed thrombus, in a patient who died suddenly. B, Acute coronary thrombosis pL to superimposed on an atherosclerotic plaque with focal disruption of the fibrous cap, those nothereto T fusion triggering fatal myocardial infarction. In both A and B, an arrow points to the site of plaque rupture ATHEROMA CORONARY ourassissment concern is to for make ARTERY: the atherghen slide giventhe Calcium blue dark Calcification Them addpic in the cam Thrombosis  8m beginning 1_ a Atherosclerotic plaque formation, activities, and outcomes. In a lesion-prone area along with other risk factors, a reversible fatty streak is formed, which can progress to atherosclerosis. Compensatory enlargement initially prevents a reduction of blood flow through the vessel. A plaque can become a thin cap plaque (unstable, vulnerable), a thick cap plaque (stable), or a fibrotic plaque (stable). Thin cap plaques are the most prone to plaque rupture, generally leading to sudden cardiac death. Stable plaques can undergo surface erosion and thrombosis, rapidly expanding the plaque size and leading to more prominent calcifications. This event can lead to sudden cardiac death. Extensive narrowing of the luminal diameter from large plaques generally results in critical stenosis, reducing blood supply to the heart and resulting in angina.  ATHEROSCLEROTIC SYNDROMES Cardiovascular, Cerebrovascular & Peripheral vascular Atherosclerotic Stenosis In small arteries, atherosclerotic plaques gradually occlude vessel lumens, compromising blood flow & causing ischemic injury. Critical stenosis: the stage at which the occlusion is sufficiently severe to cause tissue ischemia. (occurs at appro 70-75% fixed occlusion) Consequences: angina on exertion (so-called stable angina, mesenteric occlusion and bowel ischemia, chronic IHD, ischemic encephalopathy, and intermittent claudication (diminished extremity perfusion) Acute Plaque Change Plaque rupture/fissuring is typically promptly followed by partial or complete vascular thrombosis , resulting in acute tissue infarction (e.g., myocardial or cerebral infarction). Plaque changes: Erosion/ulceration & Hemorrhage into the atheroma Triggering events include both intrinsic factors (e.g., plaque structure & composition) and extrinsic factors (e.g., blood pressure, platelet reactivity)  http://hin.nhlbi.nih.gov/atpiii/calculator.asp?usertype=pub ATPIII Executive Summary Case 1: The development of atheromatous plaque formation with subsequent complications is observed in an experiment. Atherosclerotic plaques are shown to change slowly but constantly in ways that can promote clinical events, including acute coronary syndromes. In some cases, however, changes occurred that were not significantly associated with acute coronary syndromes. Which of the following plaque alterations is most likely to have such an association? A. Thinning of the media. B. Ulceration of the plaque surface. C. Thrombosis. D. Hemorrhage into the plaque substance. E. Intermittent platelet aggregation. Case 2: A pharmaceutical company is developing an antiatheroscelrosis agent. An experiment investigates mechanisms of action of several potential drugs to determine their efficacy in reducing atheroma formation. Which of the following mechanisms of action is likely to have the most effective antiatherosclerotic effect? O A-Inhibits the release of platelet-derived growth factor and macrophage-mediated lipoprotein oxidation. B- Promotes the release of PDGF and inhibits macrophage-mediated lipoprotein oxidation. C- Inhibits the release of PDGF and promotes macrophage-mediated lipoprotein oxidation. D- Decreases the level of HDL and inhibits macrophage-mediated lipoprotein oxidation. E- Increases the level of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells and increases endothelial permeability. https://webpath.med.utah.edu/CVHTML/CV020.html