Atherosclerosis, vascular damage, thrombosis - Gustafson

Question 1

what are the most important vascular bed affected by atherosclerosis?

Answer 1

-heart and brain*

Question 2

what do you see on angiogram?

Answer 2

• tissue in angiogram is subtracted –> do not see intima, media, adventitia
• only see the dye in the lumen*

Question 3

where do atherosclerotic plaques reside most?

Answer 3

• bifurcations where turbulent flow is present

- turbulent flow can rupture plaque leading to thrombosis*

Question 4

endothelial cell injury

Answer 4

• inducers of endothelial activation if there is injury –> cytokines/bacteria (elicit inflammation), hemodynamic stress, lipid products, glycation end products (diabetes), viruses, complement, hypoxia**
• these risk factors start the atherosclerotic/plaque process*
• activated endothelial cells produce cell adhesion molecules/cytokines/GFs/chemokines/vasoactive molecules/MHC complex/pro-anti-coagulants
• smooth muscle releases NO (vasodilate) and endothelin (vasoconstrict)

Question 5

further endothelial damage

Answer 5

• activated/inducible injured endothelial cells –> recruit medial smooth muscle cells into intimal layer –> begin forming extracellular matrix and thickening the intima** (neointima layer)
• smooth muscle cells proliferate and change phenotype (regulated by cytokines/GFs)

-damaged enothelial cells –> further activate other endothelial cells exacerbating the process

Question 6

HTN in atherosclerotic heart disease

Answer 6

• major risk factor
• chronic HTN –> common cause of LVH –> cardiovascular risk and ischemic heart disease
• decrease in stroke by treating HTN bc it affects smaller arteries, but not much effect in heart disease**

Question 7

rupture of atherosclerotic plaque aka acute plaque change

Answer 7

• plaque erosion or rupture from vascular shear forces –> expose thrombogenic constituents –> infarction (MI, cerebral)
• hemorrhage into atheroma expands the volume of atheroma
• asymptomatic plaques (mild stenosis) before acute plaque change
• symptoms depend on which vascular bed is affected*
• large elastic arteries (aorta, carotid, iliac) and medium muscular arteries (coronary, popliteal) are major targets**
• lead to MI, stroke, aortic aneurysm, peripheral vascular disease

Question 8

composition of plaques

Answer 8

• foam cells
• extracellular lipids
• lipid streaks, fatty deposits
• fibrous caps containing smooth muscle cells/inflammatory cells

Question 9

vulnerable vs stable plaque

Answer 9

1. vulnerable
   - thin fibrous cap
   - larger lipid core
   - more likely to rupture
2. stable
   - thick fibrous cap
   - smaller lipid core
   - less likely to rupture

Question 10

atherosclerotic and vessel wall changes

Answer 10

• may result in aneurysm –> expansion of media and adventitia (hematoma)
• weakened wall due to loss of smooth muscle cells
• atherosclerotic thickening of intima –> decrease O2 perfusion –> weak wall –> aneurysm
• systemic HTN –> narrowing of vasa vasorum –> outer medial hypertrophy and ischemia
• medial ischemia –> cystic medial degeneration (marfan and scurvy)

Question 11

2 most common causes of aortic aneurysms***

Answer 11

1. atherosclerosis (men,smokers) –> greater factor in AAAs and common iliac arteries**
2. HTN –> greater factor in ascending thoracic aorta aneurysms**
   - 10cm from aortic valve
   - marfan syndrome also risk of thoracic aorta

• dissection can rupture through adventitia and hemorrhage –> cardiac tamponade and death
• HTN is major risk factor for dissection** (men 40-60)
• connective tissue abnormalities (ex. marfan/ehlers danlos) also risk factor

-aneurysms >5cm –> aggressive management

Question 12

other factors that lead to aneurysms

Answer 12

• congenital defects –> berry aneurysms in circle of willis
• infections –> mycotic/infectious aneurysms (distal cerebral vessels) –> seen in infectious endocarditis

Question 13

thrombosis

Answer 13

• caused by disrupted plaque
• risk of acute coronary syndrome
• mural thrombi in coronary artery can embolize –> microinfarcts –> death

Question 14

effects of thoracic aortic aneurysm

Answer 14

• compress lung/airway –> respiratory difficulity
• compress esophagus –> trouble swallowing
• compress recurrent laryngeal nerve –> cough
• erosion of bone
• myocardial ischemia
• rupture

Question 15

clinical consequence of AAAs*

Answer 15

• rupture into peritoneal cavity –> fatal hemorrhage
• obstructing aortic branches –> ischemia to distal vascular beds (iliac, renal, mesenteric, vertebral)
• embolism from atheroma
• compress adjacent structures (ex. ureter)