atherosclerosis

Question 1

epidemiology - risk factors

Answer 1

Risk to atherosclerosis to IHD
- in developed countries - stressful life style.
- western Europe > eastern and asian coutries.
- age > 40- 60
- males
- BP 160/90-95 or higher

Question 2

etiology - modifying & non modifying risk factors

Answer 2

Modifying:
1. elevated level of BP
2. high cathecholamine
3. Smoking
4. DM type II
5. Hypodynamia
6. Obesity
7. Alcohol abuse
8. Stressful life
9. Hyper- & dyslipidemia
10. 10. dyslipoproteinemia

Non modifying risk factors:
1. Age >40-60
2. sex- males
3. genetics- familial hypercholesterolemia, polygenic

Question 3

role of dyslipoproteinemia

Answer 3

Forms: free fatty acids, cholesterol, triglycerides, esthers, phospholipids Dyslipoproteidemia dev due to:
1. ↑ absorption fr GIT
2. Changes of receptor activity/ sensitivity
3. Transport systems affected
4. When cholesterol is not evacuated properly

Mechanism :
1. Initial damage to blood vessel
2. Inhibition by lipids
3. Damage of cells
4. Stimulation of smooth muscles cells
5. Formation of atherous cap containing atherosclerotic debris

1. lipoprotiens play important role in regulation cholesterol level in blood and excretion of cholesterol.
2. LDL play important role in transport of cholesterol from liver to peripheral tissues while HDL play role in transport of cholesterol from peripheral tissues to liver which later excreted in bile.
3. dyslipoproteinemia lead to disbalance of lipoprotein in circulation and cause accumulation of cholesterol in circulation which cause development of atherosceloris.
4. Receptors in dyslipoproteinemia is reset due to changes in permeability & metabolism
5. Lipid is not metabolized & deposited on membrane. This block ions & energy exchange & push organelles to aside
6. Cells that filled with lipid cannot function normally, thus cell is atrophied

Question 4

frederiks classification

primary and secondary

Answer 4

Primary dysproteinemia
1. Hyperlipoproteinemia type I (lipoprotein-lipase deficicency) -↑ chylomicrons
2. Hypercholesterolemia types IIA and IIB
 IIA – only LDL↑
 IIB – ↑ LDL and VLDL
3. Dysbetalipoproteinemia - ↑IDL
4. Hypertriglyceridemia - ↑ VLDL
5. Hyperprelipoproteinemia - ↑ chylomicrons and ↑ VLDL

Secondary dysproteinemia
1. DM, hypothyroidism
2. primary biliary cirrhosis of liver
3. nephritic syndrome
4. kidney insufficiency with uremia dev
5. alcohol, drug

Question 5

pathogenesis

major theory -

Answer 5

Major theory of atherosclerosis
1. injury theory - hypertension, high CO2, CO
2. Infective theory - Chlamydia pneumoniae, herpes, cytomegalovirus

Dysplipoproteinemia→ lipids absorbed on endothelial cells of blood vessels→ primary injury to cells→ change in permeability→ receptors activity ↓→ cholesterol becomes depot in cell, block other cell activities e.g. metabolism→ dystrophy→ intima of blood vessel disappear→ basement membrane exposed→ thrombosis covers defect, ↑ activity of smooth muscle cells (localized hypertrophy)→ intimal thickening→ formation of atherous cap containing atherosclerotic debris

Question 6

morphological stages of atheroma formation

Answer 6

1. Fatty streaks – adhesion of intima by extralipids causing formation of fatty streaks. Intimal thickening (reversible)
2. accummulation of lipid (lipoidosis) & fibrous tissue (fibrosis)
3. Migration of smooth muscle cells from tunica media to intima & smooth muscle cells elaborate extracellular matrix - leads to diffuse thickening of intima (intima is convered by fibrous cap - atheroma formation), may occlude lumen (reversible / irreversible)
4. Complication: Total scarring – unstable plaque, stress, physical activity, break fibrous cap, contents rush out cause stimulation of thrombocytes and form large thrombus→ infarction, stroke of vessels → growth of collagenic fibres→ shrinking→ calcification (irreversible)

Question 7

clinical symptoms of aorta, brain & peripheral arteries atherosclerosis

Answer 7

1. Aorta atherosclerosis
   Acute: Cause thromboembolism, leads to turbulent blood flow & thrombus formation, IHD
   Chronic: Wall of aorta is calcified, loss elasticity, thicked. Aorta atherosclerosis leads to aneurysm & aortic valve stenosis
   - symptoms of suphenic papav- rise of murmur when raise the trunk.
   - auscultation of organic murmur over aorta
   - accentuation of S2 at aorta.
2. Brain athesosclerosis - Decreased blood flow to brain & infraction of brain. Manifest as stroke, vertigo, headache, encephalitis
3. Peripheral atherosclerosis
   Acute: bilateral gangrene of both extremities
   Chronic: intermittent claudication
   - pale and cold skin
   - pain during exercise or movement of affected body part.
   - weakness
   - decrease sensation

Question 8

treatment - diet

Answer 8

Diet
1. reduce total fat intake
2. reduce dietary cholesterol intake
3. increase intake of fibre
4. reduce alcohol consumption

Medicaments
1. statins: lovastatin, prastatin, simvastatin,fluvastatin (↓ CLTRL synthesis)
2. sequesters of bile acid: cholestyramine & colestipol ( block absorption of fats fr food by GIT)
3. nicotinic acid (niacin) – (increasing lipid metabolism)
4. fibrates: clofibrate, gemfibrozil ( ↑ HDL)
5. probucol (block synthesis and CLTRL absorption)
6. Combination therapy