Artherosclerosis

Question 1

What happens to the vascular wall normally as we age? How does it occur?

Answer 1

Diffuse intimal thickening due to the recruitment of smooth muscles cells from the tunica intima. These then secrete ECM

Question 2

What is atherosclerosis?

Answer 2

is a form of arteriosclerosis that is characterized by fibrofatty lesions (aka atheromas) in the tunica intima

Question 3

What is an atheroma?

Answer 3

A fatty lesion comprised of oxidized LDL produced by atherosclerosis.

Question 4

What forms over atheromas?

Answer 4

A fibrous cap d/t elaboration of ECM

Question 5

What are the precursors of Atheromas? What type of stain would you use to highlight them?

Answer 5

Fatty streaks that can be highlighted by Sudan Red

Question 6

Where do atheromes occur?

Answer 6

In areas of turbulent blood flow such as at point of bifurcation

Question 7

What are the cells that have a foamy cytoplasm that are present in ateromes?

Answer 7

Macrophages

Question 8

What are the four major, non-modifiable risk factors for atherosclerosis?

Answer 8

Increasing age
Family history
Male
Genetic abnormalities

Question 9

What are the five major modifiable risk factors for atherosclerosis?

Answer 9

Hyperlipidemia
Cigarette smoking
C-reactive protein
HTN
DM

Question 10

The incidence of MI increases how many times between the ages of 40 and 60?

Answer 10

5x

Question 11

When does the risk of MI for men and women become equal?

Answer 11

70-80 years of age

Question 12

What are the guidelines for:

1. Total cholesterol
2. LDL
3. HDL
4. Triglycerides

Answer 12

1. < 200 mg/dL total
2. < 130 mg/dL LDL
3. > 45 mg/dL HDL
4. Triglycerides < 150 mg/dl

Question 13

What is the clinical significance of CRP in terms of heart disease?

Answer 13

Endothelial cells become prothrombotic, and increase their adhesiveness for WBCs

Question 14

What is the significance of smoking in terms or artherosclerosis?

Answer 14

> 1 ppd = 200% risk increase

Question 15

What is the significance of DM in terms of MIs?

Answer 15

2x more likely to get a MI with DM

Question 16

What is the first step in the pathogenesis of atherosclerosis?

Answer 16

Injury to the endothelium, leading to
1. increased permeability and

2. endothelial cell synthesis of cell adhesion molecules on lumen side

Question 17

How do endothelial cells become injured?

Answer 17

Hyperlipidemia
HTN
Smoking
Homocysteine etc

Question 18

What is the second key event of the development of athreosclerosis?

Answer 18

Accumulation of LDL and monocytes in the endothelium

Question 19

What is the third step of the pathogenesis of atherosclerosis, after monocytes and LDL accumulate?

Answer 19

Smooth muscle cells migrate into the intima and macrophages are activated

Question 20

Where do the smooth muscle cells that migrate into the endothelial compartment come from? What change do they undergo when they get there?

Answer 20

Come from the tunica media and blood.

transition from their contractile phenotype into a proliferative-synthetic phenotype

Question 21

What role do the macrophages play in the development of atherosclerosis?

Answer 21

Ingest LDL and oxidize it

Question 22

What is the dominant foam cell type in artherosclerosis?

Answer 22

Macrophages

Smooth muscle cells contribute other, smaller part

Question 23

What is the fifth step the pathogenesis of atheroscleorsis, after macrophages have engulfed LDL?

Answer 23

Smooth muscle proliferation, and resulting collagen and other ECM deposition

Question 24

What forms that cap of a fibrofatty atheroma? The center?

Answer 24

Cap of collagen

Center = lipid debris

Question 25

What is perhaps the most important step (the step that may be a target for drug therapy) in the formation of atheromas?

Answer 25

LDL oxidation by macrophages

Question 26

What role does NO play in atherosclerosis? How is it brought about?

Answer 26

injured endothelial cells results in decreased nitric oxide, which normally prevents platelets from sticking

Question 27

What is the most frequently involved coronary artery in MIs?

Answer 27

LAD (40-50%)

Question 28

What is the 2nd most frequently involved coronary artery in MIs?

Answer 28

Right coronary (30-40%)

Question 29

What is the 3rd most frequently involved coronary artery in MIs?

Answer 29

Circumflex artery (15-20%)

Question 30

What is the wavefront phenomenon of cardiac necrosis?

Answer 30

Cell death occurs in the inner wall of the myocardium (subendomyocardium) and proceeds outward toward the subepicardium

Question 31

What is the cause of te wavefront phenomenon?

Answer 31

Increased work of the inner layer of the myocardium

Question 32

What is the chemical basis for using the stain triphenytetrazolium in looking at a sample of necrotic heart tissue?

Answer 32

Binds to LDH heart isozyme that will not be expressed in dead tissue (obviously)

Question 33

What are the histological characteristics of necrotic heart tissue?

Answer 33

Lots of blue staining collagen and red staining muscle that remains

Question 34

Myocardial ischemia and infarction may result in what four things?

Answer 34

a. Arrythmias
b. Acute rupture of the cardiac wall or IV septum
c. Rupture of papillary muscles
d. Ventricular aneurysm

Question 35

What are the four steps that occur in a cerebral infarction on a microscopic level?

Answer 35

Eosiniphilia of neurons

Neutrophils infiltrate to clean

Macrophages infiltrate (10 days out)

Reactive gliosis