Exam 3: Atherosclerosis

Question 1

Diffuse intimal thickening

Answer 1

occurs in injury and as normal part of aging
Happens by recruitment of smooth muscle cells to the tunica intima, they divide and elaborate ECM causing intima to thicken

Question 2

Atherosclerosis

Answer 2

form of arteriosclerosis characterized by fibrofatty lesions in the tunica intima
Lesions protrude into vascular lumen - obstruct lumen and weaken tunica media
Leads to ischemia, infarction, and possible development of aneurysm

Question 3

Atherosclerosis is characterized by

Answer 3

fibrofatty lesions (atheromas), fatty streaks, plaques, and lesions (occurring at an earlier age)

Question 4

Fatty streak

Answer 4

early changes in tunica intima
precursor to development of atheroma
Points of bifurcation and differentiation
Thickening of intima, slight separation of subendothelium from internal membrane
Foam cells present (macrophages most abundant)

Question 5

Non-modifiable risk factors

Answer 5

Age - MI increases 5x between 40-60 years
Sex: Men > premenopausal women. Post menopause, incidence in women increase (equal by 70-80 for sexes)
Family history
Genetics

Question 6

Modifiable risk facors

Answer 6

Hyperlipidemia and cholesterol intake (<200 mg/dL total cholesterol)
Hypertension
Smoking (one or more packs per day increase risk 200%)
Diabetes mellitus: 2x high in diabetics
Elevated C-reactive protein

Question 7

First key event in pathogenesis of atherosclerosis

Answer 7

Injury to endothelial cells - leads to their dysfunction

Cells become more permeable and synthesize cell adhesion molecules attached to their adluminal plasma membranes

Question 8

Chronic endothelial injury

Answer 8

Hyperlipidemia, hypertension, smoking, homocysteine, hemodynamic factors, toxins, viruses, immune reactions

Question 9

Following injury, what accumulates in vascular wall?

Answer 9

LDL (lipoproteins) & macrohages
LDL enters subendothelial compartment Monocytes adhere to new adhesion molecules and emigrate into subendothelial space where they become macrophages

Question 10

What important step in pathogenesis of atherosclerosis happens to LDL?

Answer 10

LDL is oxidized by endothelial cells, smooth muscle cells, and macrophages
Inhibition of oxidation protects against atherosclerosis

Question 11

What happens to oxidized LDL

Answer 11

phagocytosed by macrophages that reside in connective tissue compartment of subendothelium

Question 12

Foam cells

Answer 12

macrophages engorged with lipids
Have foamy appearance
Can also be formed from smooth muscle cells

Question 13

Decreased NO from injured endothelial cells causes

Answer 13

increased adhesion of platelets and leukocytes

Question 14

Growth factors released by platelets, endothelial cells, and macrophages cause

Answer 14

recruitment of smooth muscle cells into subendothelial compartment of tunica intima
Either from smooth myocytes from tunica media (enter through fenestrae in internal elastic membrane) or from smooth muscle precursors in blood

Question 15

Smooth muscle cells in subendothelium transition from

Answer 15

contractile into proliferative-synthetic - smooth muscle increases in number and deposits ECM into subendothelial compartment

Question 16

Proliferation and deposition of smooth muscle in subendothelial

Answer 16

leads to thickening of tunica intima & decrease in patency of vascular lumen

Question 17

Most frequent stenotic artery on heart is

Answer 17

Anterior interventricular artery (Left anterior descending)

Question 18

Descending order of frequency of coronary arteries involved in critical stenoses

Answer 18

Anterior interventricular artery (highest, 40-50%)
Right coronary artery (30-40%)
Circumflex artery (15-20%)

Question 19

Wavefront phenomenon of cell death

Answer 19

Cell death occurs in inner wall of myocardium (subendomyocardium) and then proceeds outward toward subepicardium
Necrosis spreads toward obstructed coronary artery - inner part uses most nutrients, so it is first to die off

Question 20

Myocardial ischemia and infarction may result in

Answer 20

Arrythmias
Acute rupture of cardiac wall or IV septum
Rupture of papillary muscles
Ventricular aneurysm

Question 21

Microscopic changes of cerebral infarcts

Answer 21

Early acute microscopic change (12-24 h) is eosinophilia (acidophilia) of neurons - red neurons
Neutrophil infiltration at sites where blood vessels are intact - clean up debris (couple days)
Macrophages enter and reactive gliosis (scar tissue) form (10 days)