Atheresclerosis

Slide 1 : Atherosclerosis

Normal Heart: : Normal Heart: Size of fist. 300 gm. 6000 litres/d No rest …!

Coronary Arteries – for the heart : Coronary Arteries – for the heart

Coronary Atheorsclerosis : Coronary Atheorsclerosis Left Coronary Artery. Anterior Descending (LAD) Left Circumflex (LCx) Right Coronary Artery. LCx LAD

Definition : Definition " Ischaemia " refers to an insufficient amount of  blood. The coronary arteries are the only source of  blood for the heart muscle. If this coronary arteries are blocked, the blood supply will reduce.

Pathophysiology : Pathophysiology CELL INJURY CELL SWELLING TRANSUDATION OF FLUID ? INTRACOMPARTMENT PRESSURE ? CAPILLARY TRANSUDATE TISSUE PRES. = CAP. HYDR. PRES. ISCHEMIA ? VENULAR PRESSURE NO NUTRIENT FLOW

Risk Factors for Ischemic Heart Disease : Risk Factors for Ischemic Heart Disease Obesity Genetics Diabetes Mellitus Tobacco Use Latent Life Style (lack of exercise) Hypertension Hypercholesterolemia Age

Risk Factors: Atherosclerosis : Risk Factors: Atherosclerosis Non modifiable Age – middle to late. Sex – Males, complications Genetic - Hypercholesterolemia Family history. Potentially Modifiable Hyperlipidemia – HDL/LDL ratio Hypertension Smoking Diabetes Life style, diet, exercise

Slide 9 : Blood Lipid Fraction Desirable Borderline High LDL Cholesterol (mg/dl) <130 130-159 >160 Total Cholesterol (mg/dl) <200 200-239 >240 Triglycerides (Fasting; mg/dl) <200 200-400 >400 VLDL (estimated Trig/5) <40 40-80 >80 LDL:HDL ratio: > 5.0 indicates risk for men > 4.5 indicates risk for women Risk Factors: Cholesterol

Good vs. BAD cholesterol : Good vs. BAD cholesterol LDL is known as bad cholesterol. It has a tendency to increase risk of CHD. LDL’s are a major component of the atherosclerotic plaque that clogs arteries. Levels should be <130, but Begin treatment LDL Cholesterol (mg/dl) With CHD: >100 Without CHD + one risk factor: >160 Without CHD + > 2 risk factors: >130

Good vs. BAD cholesterol : Good vs. BAD cholesterol HDL is known as the good cholesterol. It helps carry some of the bad cholesterol out of the body. It does not have the tendency to clog arteries. Levels should be >35. High levels of HDL >60 can actually negate one other risk factor. VLDL – used to transport triglycerides – bad >80

Good Fats & Bad FatsWhat is Cholesterol?LDL? HDL? Unsaturated? Saturated? : Good Fats & Bad FatsWhat is Cholesterol?LDL? HDL? Unsaturated? Saturated?

Coronary Arteries : Coronary Arteries Mono unsaturated fats Poly unsaturated fats Omega-3 fatty acids (Fish) Lower LDL, Increase HDL No cholesterol in any vegetable oil, but they form cholesterol in liver.

Hyperlipidemia : Hyperlipidemia High saturated fat in the blood Cholesterol is a fat produced in the liver or small intestine and should remain below 200 (milligrams/deciliter) in the blood count It is necessary in the manufacture of hormones and nerve cell lining Triglycerides are components of lipoproteins Low density lipoproteins (LDL) Very low density lipoproteins (VLDL)

Atherosclerosis : Atherosclerosis Chronic inflammatory disorder of intima of large blood vessels characterized by formation of fibro fatty plaques called atheroma. Artery break down due to clogging Clogging is due to excess plaque Saturated fats penetrate arterial wall Muscle elasticity of the lumen degenerates Cholesterol and triglycerides are also responsible for the destruction of the artery Arteriosclerosis is the hardening of the artery due to atherosclerosis and the damage is irreversible

Slide 16 : Why would there be an insufficient blood supply to the heart? Remember that the coronary arteries are the only source of fuel to the heart The coronary arteries may become partially/completely occluded: Atherosclerotic Plaques

Atherosclerotic Plaque: Definition and Formation : Atherosclerotic Plaque: Definition and Formation Focal accumulation of smooth muscle cells, foam cells, cholesterol crystals and lipid under the endothelium of the artery (within the Tunica Intima) Given time, this plaque can protrude into the lumen of the vessel reducing blood flow Often develops at branch points or curves within the vasculature ? blood is slowed and/or turbulent

Atheroma/ Atherosclerotic Plaque : Atheroma/ Atherosclerotic Plaque Where does the plaque begin? ? within the Tunica Intima, the innermost wall of the artery What is a plaque made of? Superficial fibrous cap made of smooth muscle cells, collagen, elastin and proteins Also contains Macrophages, Foam Cells, T Cells Necrotic Center of cholesterol crystals, lipids, Apolipoprotein B ? LDL

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atheroma : atheroma Atheroma (fatty layer) Cross Section Longitudinal Section

Atheroma Formation: The Hypothesized Process : Atheroma Formation: The Hypothesized Process (1) Via damage to the arterial endothelium via turbulent blood flow, toxins such as those from tobacco, hypertension, high concentration of fats or genetic factors there is now a “hole” within the endothelium Remember that the endothelium is only 1 cell layer thick (2) Blood and whatever the blood contains (LDL, toxins…) can leak into this hole irritating the vessel (3) Because of this irritation, there is a stimulated increase in smooth muscle cells and collagen matrix (4) Platelets and monocytes adhere to the injured area of the endothelium and release cytokines creating a wave of chemotaxis. These cells also cause an upregulation of adhesion factors for inflammatory cells on the endothelial cell surface (5) More monocytes and T cell are able to enter the endothelial hole via these receptors (6) Once monocytes have entered the vascular wall they can differentiate into macrophages (7) Via lipid receptors on the Macrophages, lipids are phagocytized creating foam cells (8) This process continues and the atheroma enlarges (9) Foam cells can eventually act to disrupt the fibrous cap of the atheroma via proteolytic degradation resulting in ulceration of the plaque and adherence of platelets (thrombus) and emboli formation (10) A plaque, thrombus or emboli can cause partial or full occlusion of a blood vessel

Atheroma: Continued : Atheroma: Continued As the atheroma within the coronary arteries enlarges, the blood flow to the heart decreases and therefore so does the O2 supply The heart is not in danger of hypoxia until 50% of the vessel is occluded As the heart senses a decrease in O2, there is attempted compensation: Increase Heart Rate Increase Blood Pressure Aggravation/Worsening of the atheroma When 70% of the artery is occluded, Angina Pectoris will occur

Atheroma Coronary Artery: : Atheroma Coronary Artery:

Atheroma Coronary Artery: : Atheroma Coronary Artery: Calcification

Atheroma with Thrombosis: : Atheroma with Thrombosis:

Development of Coronary Atherosclerosis: : Development of Coronary Atherosclerosis:

atherosclerosis : atherosclerosis Atheroma Artery wall Blood within the artery Atheroma (fatty deposits) building up Fat deposits develop, restricting blood flow through the artery

coronary artery with atheroma : coronary artery with atheroma Atheroma Coronary Artery with atherosclerosis Coronary Artery

Coronary Narrowing in Atherosclerosis: : Coronary Narrowing in Atherosclerosis:

Pathogenesis: Atherosclerosis : Pathogenesis: Atherosclerosis Unknown etiology – Hyperlipidemia, life style, hypertension, smoking, genetic, etc. Starts with Initial intimal injury, inflammation, necrosis, Lipid accumulation, Fibrosis - Atheroma. Leads to Obstruction or destruction of vessel Organ damage due to ischemia Complications - Thrombosis, embolism, aneurism, dissection and rupture

Pathophysiology of Atherosclerosis : Pathophysiology of Atherosclerosis Atheroma – porridge; Sclerosis – hardening Response to endothelial injury hypothesis Loss of barrier function, antiadhesive properties and antiproliferative influence on underlying SMCs Migration and proliferation of SMCs ? production of ECM Oxidized lipid accumulation in vessel walls Recruitment of macrophages and lymphocytes Adherence of platelets to dysfunctional endothelium, exposed matrix, and macrophages

Critical Diameter : Critical Diameter Adaptive arterial enlargement preserves luminal caliber until a critical plaque mass is reached

Common Sites: Atherosclerosis : Common Sites: Atherosclerosis Aorta, Carotid and Iliac (large vessels) Major Vessels - Heart, Brain & Kidney Coronary Renal Abdominal Limbs

Morphology: Atherosclerosis : Morphology: Atherosclerosis Fatty Dots Fatty Streaks Atheromatous – Soft Plaque Fibrofatty – Hard Plaque Complications Ulceration, Rupture, Hemorrhage, Thrombosis Atheroemboli or cholesterol emboli.

Atherosclerosis : Atherosclerosis

Coronary Atheresclerosis : Coronary Atheresclerosis

Coronary Atherosclerosis with Thrombus : Coronary Atherosclerosis with Thrombus

Stages of Atheroma - Aorta : Stages of Atheroma - Aorta Stage VI III II

Atheroma Coronary Artery: : Atheroma Coronary Artery:

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Signs & symptoms : Signs & symptoms Signs and symptoms usually develop gradually. At first, symptoms may occur only after vigorous exertion, when changed arteries can't supply muscles with enough oxygen and nutrients. But, as the narrowing worsens, it takes less and less exertion to surpass the ability of the artery to supply adequate blood. Arteriosclerosis and atherosclerosis most often affects arteries in the heart, brain, kidneys, abdominal aorta and legs.

Atherosclerosis - complications : Atherosclerosis - complications

Coronary Angioplasty: : Coronary Angioplasty:

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Diagnostic Modalities : Diagnostic Modalities Non-invasive ABIs Segmental limb pressures Limb plethysmography Exercise testing Doppler & duplex ultrasound MR angiography Invasive Contrast arteriography CT angiography