Lec 18 Pathology of Atherosclerosis

Question 1

The great majority of ischemic damage to the myocardium is the result of:

Answer 1

Coronary atherosclerosis

Question 2

Components of an atherosclerotic plaque

Answer 2

Acronym: (CBTL sa SM)

o Connective tissue matrix

o Basophils

o T Lymphocytes

o Lipid- extracellular and intracellular

o Smooth muscle cells

o Macrophages

Question 3

Form of arteriosclerosis where calcium is deposited in muscular middle layer of arterial walls.

Answer 3

Monckeberg Medial Sclerosis

Question 4

RECITE THE MECHANISMS OF PLAQUE FORMATION!! TANG INA MO!

Answer 4

1. ENDOTHELIAL DYSFUNCTION rendering LDL able to move freely in and out of the intima.
2. A small proportion of LDL undergoes minor modification and then OXIDATIVE CHANGE.
3. Modified LDL acts as an inflammatory stimulus and induces endothelial cells to express ADHESION MOLECULES.
4. ADHESION OF CIRCULATING MONOCYTES to intact endothelial cells, and they undergo migration.
5. Modified LDL taken up by macrophage scavenger receptors to become FOAM CELLS.
6. Macrophages are potent source of powerful smooth muscle cell growth factors and PGDF (prostaglandin-F), a chemo-attractant, that cause the MIGRATION OF SMOOTH MUSCLE CELLS INTO THE LESION.
7. Reaction tends to AMPLIFY itself.

Question 5

Type II lesion of atherosclerosis?

Answer 5

FATTY STREAK

Lesions of atherosclerosis:

Type I: INTIMAL THICKENING - Normal accumulation of smooth muscle cells (SMCs) in the intima in the absence of lipid or macrophage foam cells.

Type II: FATTY STREAK - Earliest lesion which is visible to the naked eye and the only lesions found in children up to 10 years of age. It is a focal collection of lipid-filled macrophages

Type III: INTERMEDIATE LESION - Progression to multiple extracellular lipid cores and serves as a bridge between early and advanced lesions.

Type IV: ATHEROMA - Accumulation of extracellular lipid to form a lipid core that is separated from the lumen by a collagenous cap which is known as the “plaque cap”.

Type V: ADVANCED, RAISED LESIONS: Collagen-rich plaques with significant stenosis, calcification, few inflammatory cells, and necrotic core (may or may not be present). Subtypes: Va - fibroatheroma; Vb - calcified lesion; Vc - fibrotic lesion

Type VI: COMPLICATED LESIONS: Type IV or V lesions in which disruptions of the lesion surface, hemorrhage or thrombotic deposits have developed.

Question 6

A lesion of atherosclerosis that is an accumulation of extracellular lipid to form a lipid core that is separated from the lumen by a collagenous cap which is known as the “plaque cap”.

Answer 6

Atheroma (Type IV lesion)

Question 7

Which of the following is a non-modifiable major risk factor for atherosclerosis?

a. Age
b. Male gender
c. Family history
d. Genetic abnormalities
e. AOTA

Answer 7

e. AOTA

POTENTIALLY CONTROLLABLE

• Hyperlipidemia
• Hypertension
• Cigarette smoking
• Diabetes

OTHER RISK FACTOS

• Obesity
• Physical inactivity
• Type A personality
• Postmenopausal estrogen deficiency
• Lipoprotein A
• Homocysteine

Question 8

The most significant independent risk factor for developing atherosclerosis:

Answer 8

Hypercholesterolemia

Question 9

Areas of endothelial loss and intimal erosion over a plaque caused by inflammation below the endothelium, Which accounts for approximately 35% of thrombotic sudden coronary death and more common in young men and women.

Answer 9

Endothelial erosion

Question 10

Proteolytic enzymes from activated macrophages that destroy the plaque cap leading to plaque disruption and entry of blood into the plaque.

Answer 10

Matrix Metalloproteinases

Question 11

T-lymphocytes (part of plaque) produce interferon-γ,

which inhibits Smooth Muscle Cells to synthesize:

Answer 11

collagen

Question 12

(T/F) Vulnerable plaques have more T-cells compared to stable plaques.

Answer 12

TRUE.

T-lymphocytes (part of plaque) produce interferon-γ,
which inhibits SMC to synthesize collagen leading to a more Vulnerable plaque.

Question 13

Extrinsic factors to Atherosclerotic plaque disruption:

Answer 13

1, Adrenergic stimulation
      Increased HR, BP, vascular tone 
      Increased platelet aggregability 
2. Moderate to heavy physical activity 
3. Emotional upset/excitement

• Instrinsic factor: plaque structure & composition

Question 14

STABLE or VULNERABLE PLAQUE:

More macrophages

Answer 14

VULNERABLE PLAQUES

• More macrophages mean more matrix metalloproteinases -> plaque cap destruction -> plaque disruption -> Vulnerable Plaque

Question 15

STABLE or VULNERABLE PLAQUE:

More smooth muscle cells

Answer 15

STABLE PLAQUES

• More smooth muscle cells -> more stability

Question 16

STABLE or VULNERABLE PLAQUE:

Well-preserved lumen

Answer 16

VULNERABLE PLAQUE

Vulnerable plaques often have a well-preserved lumen because of their initial outward growth.