atherosclerosis

Question 1

what is arteriosclerosis?

Answer 1

hardening of the arteries

thickening and loss of elasticity of arterial walls

Question 2

what is the pattern of monkeberg medical calcific sclerosis?

Answer 2

pattern of arteriosclerosis
calcific deposits in the muscular arteries
affects persons older than 50
do not encroach the vessel lumen

Question 3

what does arteriolosclerosis affect (type of vessel)?

Answer 3

small arteries and arterioled

Question 4

when is arteriolosclerosis common (in what patient populations)?

Answer 4

in hypertension and diabetes mellitus

Question 5

what is the pathology of arteriolosclerosis?

Answer 5

thickening of the wall with narrowing of the lumen

Question 6

what types of vessels does atherosclerosis affect?

Answer 6

large arteries

Question 7

what is the pathology of atherosclerosis?

Answer 7

localized thickening of the wall with lumen thickening

Question 8

what are the three patterns of arteriosclerosis (list)?

Answer 8

1: monkeberg medical calcific sclerosis
2: arteriolosclerosis
3: atherosclerosis

Question 9

what type of disease is atherosclerosis? whom does it affect?

Answer 9

chronic inflammatory disease

affects every human being, but progresses with age and will be asymptomatic until a certain stage

Question 10

what are the six different types of atherosclerosis lesion and what are the histological identifiers for each?

Answer 10

type 1: initial lesion
- isolated macrophage foam cells

type 2: fatty streak lesion
- mainly intracellular lipid accumulation

type 3: intermediate lesion
- type II changes and small extracellular lipid pools

type 4: atheroma lesion
- type II changes and core oc extracellular lipid

type 5: fibroatheroma lesion
- lipid core and fibrotic layer, or multiple lipid cores and fibrotic layers or many calcific layers, or many fibrotic layers

type 6: complicated lesion
- surface defect, hematoma-hemorrhage, thrombus

Question 11

what is the sequence of progression of the types of atherosclerosis lesion?

Answer 11

two possible pathways:
1 –> 2 –> 3 –> 4 –> 5 –> 6
or
1 –> 2 –> 3 –> 4 –> 6

Question 12

what is the main growth mechanisms of type 1-4 lesions in atherosclerosis?

Answer 12

growth mainly by lipid accumulation

Question 13

what is the main growth mechanism of type 5 atherosclerosis lesions?

Answer 13

accelerated smooth muscle and collagen increase

Question 14

what is the main growth mechanisms of type 6 atherosclerosis lesions?

Answer 14

thrombosis, hematoma

Question 15

what are fatty streaks? (what population, where in body, precursor to?)

Answer 15

made by foam cells - occur because there's turbulent flow at these sites, and that activates the endothelial cells
in children of all populations 
most prominent in aorta, near ostea
reversible
probably precursor of atheroma

Question 16

what are the key processes of atheroma?

Answer 16

intimal thickening

lipid accumulation

Question 17

what are the features of atheroma? (ie what would you see)

Answer 17

raised focal lesions
initiate into the intima
protrude into and obstruct the vascular lumen
weaken the underlying tunica media
soft grumous core of lipids (cholesterol and CE)
covered by endothelium or a fibrous cap

Question 18

what is a fibroatheroma?

Answer 18

atheroma plus production of collagen => fibrofatty plaque

encroaches lumen

Question 19

what are the potential complications of atherosclerosis complicated plaques?

Answer 19

calcification
ulceration
thrombosis
hemorrhage into plaque
severe destruction may lead to aneurysm
atheroemboli

Question 20

what is the endothelial injury hypothesis?

Answer 20

possible explaination for the pathogenesis of atherosclerosis

says that atherosclerosis is a chronic inflammatory response of the arterial wall initiated by injury to the endothelium

Question 21

what sustains lesion progression in atherosclerosis (according to the endothelial injury hypothesis)?

Answer 21

interaction between modified (oxidized) lipoproteins, monocyte-derived macrophages, T-lymphocytes, and the normal constituents of arterial walls (endothelial cells, smooth muscle cells, matrix)

Question 22

what are the steps in the pathogenesis of atherosclerosis as posited by the endothelial injury hypothesis?

Answer 22

1: chronic endothelial injury (due to hyperlipidemia, smoking, hypertension, homocysteine, toxins, viruses, immune reactions)
2: endothelial cell dysfunction (increased permeability, leukocyte adhesion) => monocyte adhesion and emigration
3: smooth muscle emigration from media to intima, macrophage activation
4: macrophages and smooth muscle cells engulf lipid
5: smooth muscle proliferation, collagen and other ECM deposition, extracellular lipid - fibrofatty atheroma is formed

Question 23

what are the constitutional (non-modifiable) risk factors of atherosclerosis?

Answer 23

age - dominant influene
gender - males more prone
genetic - familial predisposition

Question 24

what are the modifiable risk factors for atherosclerosis?

Answer 24

hyperlidemia (low ration of HDL:LDL, hypercholesterolemia)
hypertension
cigarette smoking
diabetes mellitus
inflammation
increased blood homocysteine (due to vit B12 and folate deficiency or hypercystinuria (genetic))
metabolic syndrome
lipoprotein (a)
hemostasis imbalance
diet, obesity, lifestyle/stress, exercise

Question 25

why does hypertension lead to atherosclerosis?

Answer 25

endothelial damage
thickening of vasa vasorum => diminished blood flow to the artery wall
smooth muscle cell proliferation

Question 26

why does cigarette smoking lead to atherosclerosis?

Answer 26

nicotine is a vasoconstrictor
carbocyhemoglobin increases
nicotine inhibits prostacyclin synthesis

Question 27

why does diabetes mellitus lead to atherosclerosis?

Answer 27

several deleterious mechanisms:
increased cholsterolemia
endothelial dysfunction

Question 28

what is metabolic syndrome? how does it contribute to atherosclerosis?

Answer 28

insulin resistance, hypertension and central obesity

thought to be driven by abnormal adipose tissue signaling

mechanism: dyslipidemia –> endothelial dysfunction

Question 29

what is the hypothetical sequence of cellular interactions according to the endothelial injury hypothesis?

Answer 29

process induced by chronic injury to the endothelium
recruits platelets and monocytes
monocytes migrate in, become macrophages
these uptake lipid - become foam cells
cytokines and growth factors make SMCs move in
these take up fat too, proliferate
can eventually rupture