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VASCULAR DISEASE Atherosclerosis

VASCULAR DISEASE Atherosclerosis. Jagdish Butany ,MBBS,MS,FRCPC, Prof. Dept Lab Med & Pathobiol., Pathologist , UHN-Toronto Gen/Hosp 416 340 3003 jagdish.butany@uhn.on.ca Fac. Pharmacy Nov ‘07. Vascular disease. 1. Atherosclerosis 2.Degenerative disease 3.Collagen vascular diseases

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VASCULAR DISEASE Atherosclerosis

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  1. VASCULAR DISEASEAtherosclerosis Jagdish Butany ,MBBS,MS,FRCPC, Prof. Dept Lab Med & Pathobiol., Pathologist , UHN-Toronto Gen/Hosp 416 340 3003 jagdish.butany@uhn.on.ca Fac. Pharmacy Nov ‘07.

  2. Vascular disease 1.Atherosclerosis 2.Degenerative disease 3.Collagen vascular diseases 4.Tobacco related disease-T.A.O./Buergers

  3. J. ButanyATHEROSCLEROSIS Atheros: Soft gruel-like Scleros: Hardening

  4. Atherosclerosis A chronic disease of elastic and large and medium sized arteries.

  5. Arterial Wall • Intima - lined by endothelial cell layer • Media - muscle and elastic tissue • Adventitia - collagen, elastic fibers • small vessels (Vasa • Vasorum)

  6. Atherosclerosis • “Disease” of the intima • Secondary damage to media • Adventitia - generally uninvolved

  7. Atherosclerosis The root of ALL (almost ??) Cardiovascular Evil!!

  8. Ischemic Heart Disease • The SCOURGE of Affluent Societies- ? • 50% of Deaths • Even more Significant : MORBIDITY

  9. Atherosclerosis Risk Factors: ?? N.B. * Increase risk x4.

  10. Atherosclerosis • Risk Factors: • Age • Cigarette Smoking* • Gender • Elevated homocysteine • Genetics (plasma) • Lipids-hyperlipidemia* • Other Factors • Hypertension* • Lack of Exercise • • Stress • • Weight gain • • [Alcohol- Beneficial effect • High intake of • cholesterol/ • Saturated fats • ?Acclerating factors? N.B. * Increase risk x4.

  11. Endothelial Cells – ComplexFunctions • Lining of Cardiovascular System • Homeostasis • Nonthrombogenic Surface • Multifunctional Tissue • “Mechanical” function • Regulate vascular tone • Regulate Immune/Inflammatory Reactions. • “Synthetic” Function • “Metabolic” Function • Semipermeable membrane • Thrombosis/Thrombolysis • Initiate atherosclerosis

  12. Endothelial Cells • Molecular/Gene Changes • Adhesion molecules • Cytokines/Chemokines • Growth factors • Vasoactive peptides • MHC molecules • Coagulation factors • Others • [Nuclear factor |< B (NF - |<B)

  13. Atherosclerosis-Theories • Pathogenesis: Response to Injury • Basis: • Focal, chronic endothelial injury • Endothelial Dysfunction • Insudation of Lipoprotein • Adhesion of Blood Cells • Platelets • Macrophages • Migration of Smooth Muscle • Accumulation of Lipid • Role of Hemodynamics

  14. Atherosclerosis Lesions Incidence: Aorta Coronaries Popliteal Internal carotid Circle of Willis

  15. Atherosclerosis Lesions Site: Abdominal > Thoracic Bifurcation > Rest of Aorta Branch points > Straight segments

  16. ATHEROSCLEROSIS Lesion: 1. Raised intimal “plaque” • Lipid core • Fibrous cap • On the IEL/Media 2. Fatty, fibrous, Fibrofatty Lipid, Fibrolipid Complex

  17. Atherosclerotic Plaque Composition: • Varies with age • Mature plaque • Cells • Connective tissue • Lipid-intra/extra cellular [cholesterol/esters]

  18. Atherosclerotic Plaque Complications: • Rupture and/or ulceration • Plaque Hemorrhage • Thrombosis • Calcification

  19. Atherosclerosis Endothelial injury: 1. Repetitive denuding injury - thrombus - repair - atheroma 2. “Non-denuding” injury - E. dysfunction

  20. Hypertension • Common problem • Easily diagnosed • Easily treated (not cured) - 90% • Asymptomatic - Long periods • BP High: Diastolic > 90 mmHg • Systolic > 140 mmHg • Incidence: 25% • Black people 2x > Caucasians

  21. Hypertension • Malignant hypertension • Secondary hypertension

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