Atherosclerosis

Question 1

Is tunica intima thickening a normal occurrence?

Answer 1

yes, it is a normal consequence of aging

Question 2

What is atherosclerosis characterized by?

Answer 2

fibrofatty lesions (atheromas)

Question 3

Which layer are fibrofatty lesions located?

Answer 3

tunica intima

Question 4

The fibrofatty lesions protrude into the vascular lumen thereby producing obstruction and they weaken…

Answer 4

the tunica media

Question 5

Obstruction of the vascular lumen leads to…

Answer 5

ischemia and/or infction

Question 6

A weakened tunica media may lead to the development of..

Answer 6

an aneurysm

Question 7

What are fatty streaks?

Answer 7

early changes in tunica intima (subendothelial compartment), precursor for development of atheroma

Question 8

What are the 5 key events in the pathogenesis of atherosclerosis?

Answer 8

1) chronic endothelial “injury”
2) endothelial dysfunction. monocyte adhesion and emigration
3) smooth muscle recruitment
4) macrophages and smooth muscle cells engulf lipid
5) smooth muscle proliferation, collagen and other ECM deposition, extracellular lipid

Question 9

Hyperlipidemia, hypertension, smoking, homocysteine, hemodynamic factors, toxins, viruses, and immune reactions are all examples of what?

Answer 9

factors that can lead to chronic endothelial “injury”

Question 10

What is the consequence of chronic endothelial “injury”?

Answer 10

endothelial dysfunction (increased permeability where LDL can get into the subendothelial compartment) and monocyte adhesion and emigration

Question 11

Where do monocytes emigrate to?

Answer 11

the site of injury, in tunica intima, where they become macrophages

Question 12

Where do smooth muscles get recruited to?

Answer 12

tunica intima. this is where they shift phenotype from being contractile to proliferative/synthetic

Question 13

Once macrophages move into tunica intima, what do they do?

Answer 13

they start engulfing oxidized LDL in the subendothelial compartment

Question 14

What is a foam cell?

Answer 14

macrophages that have engulfed oxidized LDL giving them a foam cell type of appearance. smooth muscle cells can also engulf LDL but macrophages are the PREDOMINANT

Question 15

When do fatty streaks start to appear?

Answer 15

when macrophages have engorged themselves with oxidized LDL

Question 16

What is a fibrous cap?

Answer 16

deposition and elaboration of ECM components (collagen fibers) leading to cap over the lesion

Question 17

When does the lesion become fibrofatty atheroma?

Answer 17

once smooth muscle becomes proliferative, collagen and ECM buildup leading to presence of fibrous cap, and lipid debris in the center

Question 18

How do leukocytes know to attach to site of injury?

Answer 18

expression of adhesion molecules

Question 19

What is the normal role of NO (nitric oxide)?

Answer 19

prevents the adhesion of leukocytes and platelets onto the endothelium

Question 20

How do injured endothelial cells affect NO? What does it lead to?

Answer 20

injured ECs means decreased NO which leads to increased adhesion of leukocytes and platelets

Question 21

What is the order of the most frequent critical stenosis of coronary arteries?

Answer 21

1) anterior interventricular a. (branch of left coronary a) - most frequent
2) right coronary a.
3) circumflex a. (branch of left coronary a.)

Question 22

What is the wavefront phenomenon of necrosis (cell death)?

Answer 22

cells die from inner wall of myocardium first then proceed outward

Question 23

What four things may result from myocardial ischemia or infarction?

Answer 23

1) arrythmias
2) acute rupture of cardiac wall of IV septum
3) rupture of papillary muscles
4) ventricular aneurysm

Question 24

What is a cerebral infarction?

Answer 24

occlude blood flow to brain

Question 25

What is the order/timing of microscopic changes in a cerebral infarction?

Answer 25

1) 12-24 hours: eosinophilia of neurons (red neurons)
2) neutrophil infiltration occurs at sites where blood vessels are intact
3) macrophages and reactive gliosis (scar tissue forming within CNS - 10 days post)

Question 26

What are some non-modifiable risk factors for IHD (ischemic heart disease)?

Answer 26

1) increasing age (increases 5-fold between 40-60)
2) family history
3) male gender (post menopause, both genders are equal)
4) genetic abnormalities

Question 27

What are some modifiable risk factors for IHD?

Answer 27

1) hyperlipidemia
2) cigarette smoking
3) c-reactive protein (inflammatory)
4) hypertension
5) diabetes mellitus

Question 28

Are atherosclerotic lesions reversible?

Answer 28

no, it is non-reversible

Question 29

What is the key event in prevention of formation of fibrofatty atheroma?

Answer 29

inhibit the oxidation of LDL, macrophages would not become foam cells thus decelerate the entire process