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Heart

1. ATHEROSCLEROSIS Name: Sanika Patil Roll no: 76 Topic: Atherosclerosis Date: 05/04/24 Subject Incharge : Supriya Bhamre

2. ATHEROSCLEROSIS Disease of cardiovascular system affecting vessel wall (medium sized muscular arteries and large elastic arteries). It leads to the narrowing of arteries or complete bloc k age. Its main components are en d othelial dysfunction, lipid deposition, inflammatory reaction in the vascular wall. Remodeling of vessel wall.

3. Intense cross-talk between Endothelial Cells, Vascular Smooth Muscle Cells, plasma-derived inflammatory cells, lymphocytes (involves array of chemokines, cytokines, growth factors). Attraction of cells to the sites of atherosclerotic lesion . Migration, proliferation, apoptosis, excess production of extracellular matrix.

4. Non modifiable Age Male Sex, Genetic - Hypercholesterolemia Family history Potentially Modifiable Hyperlipidemia – HDL/LDL ratio. Hypertension. Smoking. Diabetes. Life style – sedentary Obesity Oral contraceptives RISK FACTORS FOR ATHEROSCLEROSIS

5. Lesser, or Non quantitated risk factors Obesity Physical inactivity Stress Postmenopausal estrogen deficiency High carbohydrate intake Alcohol Lipoprotein A Hardened unsaturated fat intake Chlamydia pneumoniae

6. ARTERIAL WALL Normally arterial endothelium repels cells and inhibits blood clotting. The lumen of healthy arterial wall is lined by confluent layer of endothelial cells. There are Three layers: Intima (sub endothelial layer) Media (middle layer) with smooth muscle cells Adventitia (outer layer) with connective tissue and nerves

7. Endothelium controls important function: 1. the ability of blood vessels to dilatate (vaso dilatation ) 2. the ability of blood vessels to constrict (vasoconstriction) Endothelium regulates tissue and organ blood flow. Endothelium releases variety of substances to control vasomotor tone: prostacyclines hyperpolarizing factor endothelin Nitric Oxide

8. Exercise is an important mechanical stimulus mediated by shear stress to increased blood flow. Shear stress –represents the frictional force that the flow of blood exerts at the endothelial surface of the vessel wall. The flow-dependent dilatation of pre-capillary resistance as well as conductance allows blood flow to increase according metabolic demands. In the case of intact endothelium, the stimulus for vasodilatation : mechanical stimulation by  blood flow Other factors: catecholamines, bradykinin, platelets-released serotonin stimulate specific receptors

9. In the case of e ndothelium dysfunction: No vasodilator effect this action leads to paradoxical vasoconstriction (Hypercholesterolemia and other cardiovascular risk factors are associated with endothelial dysfunction).

10. THE DEVELOPMENT OF ATHEROSCLEROSIS The key event – damage to the endothelium caused by excess of lipoproteins, hypertension, diabetes, components of cigarette smoke. Endothelium becomes more permeable to lipoproteins. Lipoproteins move below the endothelial layer (to intima ). Endotheliu m loses its c ell-repellent quality . Inflammatory cells move it n o the vascular wall.

11. MAIN FEATURES OF THE INJURY HYPOTHESIS : Chronic endothelial injury. Insudation of lipoproteins into the vessel wall mainly LDL with high cholestrol content then o xidation of lesional lipoprotein. Adhesion of blood monocytes & other leukocytes to the endothelium , & their migration into the intima & their transformation into macrophages & foam cells. Adhesion of platelets. Release of factors from activated platelets , macrophages or vascular endothelial cells that cause migration of Smooth Muscle Cells (SMCs) from media into the intima. Proliferation of SMCs in the intima , elaboration of extracellular matrix , leading to accumulation of collagen & proteoglycans . Enhanced accumulation of lipids within macrophages & SMCs & extracellularly

12. THE PROCESS OF ATHEROGENESIS

13. PATHOGENESIS IN SHORT: Intimal injury Inflammation, Necrosis Lipid – Cholesterol accumulation (soft atheroma) Fibrosis, smooth muscle proliferation (hard atheroma) Extension of lesion and destruction of vessel Complications - Thrombosis, embolism, aneurism, dissection & rupture.

14. MORPHOLOGY OF ATHEROMA Atheromatous plaque consists of: A raised focal lesion , soft , yellow core of lipids (mainly cholesterol & cholesterol esters), covered by a firm, white fibrous cap . 0.3-1.5 cms i n diameter, sometimes combine to form larger lesions. Involve partial circumference of arterial wall ( eccentric ), patchy & variable along the length of vessel. First the patches are focal & sparse then gradually increase in size & become diffuse

15. Fatty dots Not raised , so do not cause obstruction to the flow Multiple, yellow , flat spots < than 1mm in diameter Composed of lipid laden foam cells Fatty streaks = C ombination of multiple fatty dots Elongated, 1 cms longer or more Contain T- lymphocytes & extracellular lipid < than plaques Appear in aorta in some children younger than 1 year & all children older than 10 years 3. Fatty streaks may be precursor of plaque but not all fatty streaks are converted into fibrous plaque or more advanced lesions

16. COMPONENTS OF ATHEROMATOUS PLAQUE (MP) Superficial fibrous cap is composed of SMCs & relatively dense collagen Cellular zone containing, SMCs , macrophages, Lymphocytes (T cells) Foam cells : Foam cells are monocytes derived from blood & SMCs can also become foam cells Deep to the fibrous cap is central necrotic core: containing a disorganized mass of lipids (cholesterol & cholesterol esters) cholesterol clefts, debris from dead cells, foam cells, fibrin

17. The white arrow denotes the most prominent fatty streak in the photo, but there are other fatty streaks scattered over the aortic surface. Fatty streaks are the earliest lesions seen with atherosclerosis in arteries.

18. COMPLICATIONS & CLINICAL SIGNIFICANCE ATH mostly involves arteries supplying the heart , brain, Kidneys & lower extremities Myocardial infarction (heart attack) Cerebral infarction (stroke) Chronic Ischemic Heart Disease (reduced blood flow) Ischemic encephalopathy (reduced blood flow) Aortic aneurysms Peripheral vascular disease (gangrene of the legs) Mesenteric occlusion (reduced blood flow) Sudden cardiac death

19. cardiovascular risk and its asses s ment Plasma concentration of lipoproteins (LDL-cholesterol, HDL-cholesterol, and triacylglycerols) –  5.2 mmol/L (200 mg/dL) increases the risk. Optimal level of LDL-cholesterol -  2.6 mmol/L (100 mg/dL)

20. Thank you!