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VASCULAR DISEASE
Atherosclerosis
Jagdish Butany ,MBBS,MS,FRCPC,
Prof. Dept Lab Med & Pathobiol.,
Pathologist , UHN-Toronto Gen/Hosp
416 340 3003
[email protected]
Fac. Pharmacy Nov ‘07.
Vascular disease
1.Atherosclerosis
2.Degenerative disease
3.Collagen vascular diseases
4.Tobacco related diseaseT.A.O./Buergers
J.
Butany
ATHEROSCLEROSIS
Atheros:
Soft gruel-like
Scleros:
Hardening
Atherosclerosis
A chronic disease of elastic and
large and medium sized arteries.
Arterial Wall
• Intima - lined by endothelial cell layer
• Media - muscle and elastic tissue
• Adventitia - collagen, elastic fibers
small vessels (Vasa
Vasorum)
Atherosclerosis
•
“Disease” of the intima
• Secondary damage to media
• Adventitia - generally uninvolved
Atherosclerosis
The root of ALL (almost ??)
Cardiovascular Evil!!
Ischemic Heart Disease
•
The SCOURGE of Affluent Societies- ?
• 50% of Deaths
• Even more Significant : MORBIDITY
Atherosclerosis
Risk Factors: ??
N.B. * Increase risk x4.
Atherosclerosis
Risk Factors:
• Age
• Gender
• Genetics
• Lipids-hyperlipidemia*
• Hypertension*
?Acclerating
factors?
N.B. * Increase risk x4.
• Cigarette Smoking*
• Elevated homocysteine
(plasma)
• Other Factors
• Lack of Exercise
• Stress
• Weight gain
• [Alcohol- Beneficial
effect
• High intake of
cholesterol/
Saturated fats
Endothelial Cells – Complex Functions
• 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
Endothelial Cells
Molecular/Gene Changes
• Adhesion molecules
• Cytokines/Chemokines
• Growth factors
• Vasoactive peptides
• MHC molecules
• Coagulation factors
• Others
[Nuclear factor |< B (NF - |<B)
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
Atherosclerosis Lesions
Incidence:
Aorta
Coronaries
Popliteal
Internal carotid
Circle of Willis
Atherosclerosis Lesions
Site: Abdominal
>
Thoracic
Bifurcation
>
Rest of Aorta
Branch points
>
Straight segments
ATHEROSCLEROSIS
Lesion:
1. Raised intimal “plaque”
• Lipid core
• Fibrous cap
• On the IEL/Media
2. Fatty, fibrous, Fibrofatty
Lipid, Fibrolipid
Complex
Atherosclerotic Plaque
Composition:
• Varies with age
• Mature plaque
• Cells
• Connective tissue
• Lipid-intra/extra cellular
[cholesterol/esters]
Atherosclerotic Plaque
Complications: • Rupture and/or
ulceration
• Plaque Hemorrhage
• Thrombosis
• Calcification
Atherosclerosis
Endothelial injury:
1. Repetitive denuding injury - thrombus repair
- atheroma
2. “Non-denuding” injury - E. dysfunction
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
Hypertension
•
Malignant hypertension
• Secondary hypertension