Pathophysiology of Atheroma

Question 1

what is atheroma/atherosclerosis?

Answer 1

the formation of focal elevated lesions (plaques) in intima of large/medium sized arteries

Question 2

what is arteriosclerosis?

Answer 2

this is age-related change in muscular arteries where the smooth muscle hypertrophy’s, there is reduplication of internal elastic lamina and internal fibrosis. all of these changes results in a decreased vessels diameter

Question 3

what may increase the clinical effects of arteriosclerosis?

Answer 3

> haemorrhage
major surgery
infection
shock

Question 4

what is the fatty streak in atheroma?

Answer 4

this is the earliest significant lesion of atheroma and is a yellow linear elevation of the intimal lining. it can be found in you children

Question 5

what is the significance of fatty streak?

Answer 5

there is no clinical significance and may disappear. in some patients with risk factors however it goes on to become the atheromatous plaque

Question 6

describe the early atheromatous plaque

Answer 6

it is seen in young adults onwards and consists of smooth yellow patches in intima with lipid laden macrophages.

Question 7

describe the structure of a fully developed atheromatous plaque?

Answer 7

there is a central lipid core with a fibrous tissue cap that is covered by arterial endothelium

Question 8

what provides structural strength in the atheromatous plaque?

Answer 8

collagens that are produced by the smooth muscle cells

Question 9

where do inflammatory cells reside in a fully developed atheromatous plaque?

Answer 9

in the fibrous cap, they are recruited from the arterial endothelium

Question 10

where do the cellular lipids/debris in the central lipid core in a fully developed atheromatous plaque come from?

Answer 10

from macrophages that have died in the plaque

Question 11

why are macrophages found in a fully developed atheromatous plaque foamy?

Answer 11

due to the uptake of oxidised lipoproteins via a specialised membrane bound scavenger receptor

Question 12

what can occur in late plaque development?

Answer 12

dystrophic calcification

Question 13

why do plaques form at arterial branching points and bifurcations?

Answer 13

due to the turbulent flow

Question 14

what is a confluent plaque?

Answer 14

a late stage plaque that covers large area

Question 15

what three things can complicate an atheromatous plaque?

Answer 15

> haemorrhage into the plaque
plaque rupture/fissuring
thrombosis

Question 16

what occurs in the plaque if they survive the haemorrhage?

Answer 16

calcification

Question 17

what is the affect hypercholesterolaemia?

Answer 17

there is a lack of LDL cell membrane receptors so there is elevated plasma levels of LDL’s. this can cause plaque formation and growth in the absence of other risk factors

Question 18

what is xanthelasmata?

Answer 18

this is fatty lump on the eyes

Question 19

what is tendon xanthomata?

Answer 19

this is fatty lumps on the tendons

Question 20

what are corneal arcus, tendon xanthomata and xanthelasmata signs of?

Answer 20

major hyperlipidaemia

Question 21

what risk factors are there for atheroma?

Answer 21

smoking
hypertension
diabetes mellitus
elderly
male

Question 22

what is the 2 step process of atheromatous plaque development?

Answer 22

1. injury to the endothelial lining of artery

2. chronic inflammatory and healing response of vascular wall to agent causing injury

Question 23

during the development of an atheromatous plaque what accumulates in the vessel wall?

Answer 23

lipoproteins

Question 24

what happens to monocytes during atheromatous plaque formation?

Answer 24

they adhere to the endothelium and migrate to the intima where they transform into foamy macrophages

Question 25

what is the affect of the factor released by activated platelets?

Answer 25

this causes smooth muscle cell recruitment which then proliferate

Question 26

name two of the most prominent causes of the development of an atheromatous plaque

Answer 26

> haemodynamic disturbances (turbulent flow) | > hypercholesterolemia

Question 27

what is the affect of hypercholesterolemia on endothelial cells?

Answer 27

it impairs the endothelial cell function by increasing the production of reactive oxygen species

Question 28

what are the effects of free radicals produced by endothelial cells?

Answer 28

they modify lipoproteins aggregated in intima

Question 29

what happens to the LDL's that are modified by free radicals?

Answer 29

they are accumulated by macrophages but not completely degraded producing foamy macrophages

Question 30

what are the affects of foamy macrophages?

Answer 30

they are toxic to endothelial cells and release growth factors such as cytokines

Question 31

in what way are the injured endothelial cells functionally altered?

Answer 31

> enhanced expression of cell adhesion molecules > high permeability for low density lipoproteins > increased thrombogenicity

Question 32

what are the effects of growth factors during the development of an atheromatous plaque?

Answer 32

> proliferation of intimal smooth muscle cells > subsequent synthesis collagen > synthesis of elastin > synthesis of mucopolysaccharide

Question 33

what secretes growth factors in the development of an atheromatous plaque?

Answer 33

> platelets > injured endothelium > macrophages > smooth muscle cells

Question 34

what are formed at denuded areas of plaque surface?

Answer 34

microthrombi

Question 35

in established plaques what may also initiate plaque growth?

Answer 35

small areas of endothelial loss

Question 36

by how much does a vessel lumen need to be occluded by to create reversible ischemia of the tissue?

Answer 36

>50-75% for there to be a critical reduction in blood flow in a distal arterial bed

Question 37

what would a stenosed atheromatous coronary artery cause?

Answer 37

a stable angina

Question 38

what would cause intermittent claudication with reference to atheroma?

Answer 38

Ilial, femoral or popliteal artery stenosis

Question 39

what happens to the blood vessel if a plaque ruptures?

Answer 39

this exposes highly thrombogenic contents to the blood stream so there is an activation of coagulation cascade and a thrombotic occlusion in a short space of time

Question 40

what happens if there is total occlusion of a vessel?

Answer 40

there is irreversible ischemia leading to necrosis (infarction) of tissues

Question 41

what happens in embolism of an atheroma?

Answer 41

small thrombus fragment detach rom the atheromatous plaque and embolises to a vessel distal to the plaque this can cause infarcts to organs

Question 42

what can carotid artery atheromatous debris cause?

Answer 42

stroke, cerebral infarct

Question 43

what is a ruptured atheromatous abdominal aortic aneurysm?

Answer 43

this is when the media beneath the atheromatous plaque is gradually weakened causing gradual dilatation of the vessel

Question 44

what is a sudden rupture of an atheromatous abdominal aortic plaque aneurysm called?

Answer 44

a massive retroperitoneal haemorrhage

Question 45

how dilated is an aneurysm when there is a high risk of rupture?

Answer 45

more than 5cm

Question 46

what is a mural thrombosis?

Answer 46

when an atheromatous abdominal aortic aneurysm embolises to the legs

Question 47

how can you identify atheromatous plaques that are going to rupture with subsequent thrombosis?

Answer 47

they have distinct morphological features, typically with a large fibrous cap, lipid core and prominent inflammation

Question 48

what is the effect of prominent inflammatory activity of the plaque?

Answer 48

it degrades and weakens the plaque increasing risk of rupture

Question 49

what preventative therapy is there for atheroma's?

Answer 49

``` > smoking cessation >blood pressure control > weight-loss > regular exercise > dietary modifications ```

Question 50

what drugs can you give to treat atheroma's?

Answer 50

> cholesterol lowering drugs | > aspirin to inhibit platelet aggregation decreasing risk of thrombus on established atheromatous plaques