L21

Question 1

Define atherosclerosis

Answer 1

Hardening of ARTERIES

Question 2

What layer of arteries does atherosclerosis start in? Name all the layers for completeness.

Answer 2

Intima

Endothelium - intima - media - adventitia

Question 3

What is CAD become once symptomatic?

Answer 3

CHD that might present as:

• Chronic, stable angina
• Acute coronary syndromes
• CHF
• Sudden death

Question 4

What is the earliest visible sign of atherosclerosis?

Answer 4

Fatty streak

Earliest b/c visible but no change to blood flow

Question 5

Which 3 molecules are released by endothelium for anti-thrombotic and anti-vasoconstriction?

Answer 5

NO
Prostacyclin
Bradykinin
Clot representative!

Question 6

If you +ACh to functioning endothelium, what should the response be?

Answer 6

NO –> smooth muscle relaxation = vasodilation

Dysfxnal endothelium: no change or constriction to same stimulus

Question 7

Test to eval health of endothelium non-invasively?

Answer 7

Brachial artery reactivity test

- 5 mins BP cuff –> let go –> shear stress should induce vasodilation

Question 8

How does high cholesterol effect endothelial fxn?

Answer 8

High cholesterol –> worse endo fxn

Question 9

Factors that cause abnormal endothelial response

Answer 9

High cholesterol
HTN
Diabetes
Age
Smoking

Question 10

Pathogenesis of plaque formation

Answer 10

1. • Risk factor for endo fxn
2. LDL into the intima
3. LDL oxidized - increases cytokine production
4. Increased VCAM 1 = adhesion molecules
5. Monocytes bind and enter endothelium –> macrophages –> phagocytose oxidized LDL –> = FOAM CELLS

Question 11

Define foam cell

Answer 11

Macrophage in intimia that has phagocytosed oxidized LDL

Question 12

How do you go from foam cell –> fatty streak

Answer 12

Foam cell - attract smooth muscle cells from media
SM proliferates & secretes ECM proteins
Foam cells die - increasing ECM and lipid deposits
Net: calcification and capillary in-growth

Question 13

3 things in the necrotic core of plaques

Answer 13

1. Degenerating foam cells
2. ECM
3. Cholesterol crystals

Question 14

Components of fibrous cap

Answer 14

Connective tissue w/ SM

Question 15

Which areas of arteries are higher risk for clot formation?

Answer 15

Branch pts b/c low shear stress here

Question 16

How does arterial disease progress - through which arteries in which order

Answer 16

Aorta 
Coronary arteries
Peripheral arteries
Cerebral arteries
- Pts who have cerebrovas disease or peripheral vas disease often have cardiac atherosclerosis

Question 17

What is the remodeling hypothesis?

Answer 17

Add plaque into intima
Get some vessel narrowing - increased shear stress
1st vessels dilate to compensate
But hit a max - stop dilating, start narrowing only moving towards moderate & severe occlusion

Question 18

Which pt population displays reverse remodeling?

Answer 18

Diabetics

Question 19

Stable plaque –> what disease does this cause

Answer 19

1. Small lipid core
2. Large CT matrix
3. Thick fibrous cap
   NO inflam cells
   Stable angina as narrow lumens w/o plaque breaking off b/c stable

Question 20

Unstable plaque –> what disease does this cause

Answer 20

1. Large lipid core
2. Thin fibrous cap
   YES inflam cells
   Little SM
   Likely to rupture -> thrombus -> ACUTE MI

Question 21

What is a mechanism that contributes to plaque rupture?

Answer 21

UNSTABLE plaques:
Endothelial disruption at shoulder region
Activated SM releases proteolytic enzymes - degrade collagen of cap

Question 22

What is a pathology mechanism to cause thrombus in women over 50 yo w/ h/o smoking

Answer 22

Plaque erosion > rupture

Question 23

4 non-modifiable risk factors for atherosclerosis

Answer 23

Fam history of premature CHD
Older
Men
Genetic history

Question 24

What factors are included in the Framingham risk score? What does this # estimate?

Answer 24

10 yr CHD risk
Age
LDL, HDL
BP
Diabetes
Smother