8. Arteriosclerosis Flashcards Preview

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Flashcards in 8. Arteriosclerosis Deck (22):
1

Briefly describe arteriosclerosis

This is a thickening of the arterial wall which then loses elasticity (sclerosis = hardening)
The most common type is atherosclerosis
Due to the formation of fatty plaques in blood vessels

2

What are the three stages of development of arteriosclerosis?

1. Endothelial damage
2. Uptake of modified LDL particles, adhesion and infiltration of macrophages
3. Smooth muscle proliferation and formation of a fibrous cap

3

Describe the general function of the endothelium

Extremely vasoactive - controls vasomotor tone e.g. Nitric oxide acts on the smooth muscles to cause vasodilation of the endothelium
It also expresses inflammatory factors and cellular adhesion molecules (vCAM and iCAM) - these cellular adhesion molecules are expressed by the endothelium wall and protrude outwards, allowing monocytes to stick to them as they flow past

4

How might endothelial damage occur? (first stage of arteriosclerosis)

Sheer stress i.e. blood flow, especially turbulent blood flow
Toxic damage e.g. from free radicals, high levels of lipids, high levels of glucose (all impact oxidative stress i.e. more pro-oxidants and less anti-oxidants)
Viral or bacterial infection

5

What is a damaged endothelium known as and describe how it funcitons

Damaged endothelium = activated endothelium
This endothelium type is dysfunctional - has more pro-coagulants and less anti-coagulants, expresses more cellular adhesion molecules and produces more vasoconstrictors

6

What are the different types of lipoproteins?

What is the function of lipoproteins?

Chylomicrons
VLDL
IDL
LDL
HDL

These function to transport fat in the blood

7

Which is the 'good' and which is the 'bad' lipoprotein?

Good - HDL made up mainly of protein

Bad - LDL made up mainly of cholesterol

8

How does LDL modification occur? (second stage of arteriosclerosis)

Oxidation - LDLs become oxidised in environments of increased oxidative stress e.g. via the presence of reactive oxygen species - this can be prevented by the presence of antioxidants e.g. vitamins E and C

Glycation - (bonding of sugar molecule to protein/lipid) - prevalence in diabetes mellitus

9

What is the impact of oxidised LDL on the endothelium?

The oxidised LDL stimulates the expression of inflammatory mediators e.g. adhesion molecules for monocytes (remember these are precursors to macrophages)

10

How does infiltration of macrophages occur at the arterial wall? (second part of stage 2)

The oxidative stress (presence of CAMs) cause monocytes to stick to and bind to the endothelium - these can then cross the endothelium (nb. this is natural occurrence in an inflammatory process
Once they have crossed the endothelium, they can transform into macrophages
These macrophages pick up LDL and grow larger
As they grow in size, they become foam cells

11

What is a foam cell?

Fat laden macrophage present in atherosclerosis - is indicative of plaque build up

12

Why does the macrophage transform into a foam cell in atherosclerosis?

SO normal LDL gets endocytosed by the macrophages due to the presence of apoprotein B100 receptor
This receptor is controlled by a negative feedback mechanism and usually only a certain amount is taken up before the receptor is switched off
BUT due to the modified LDL (oxidised), it is not recognised by apoprotein B100 and is instead picked up by a scavenger receptor
This scavenger receptor has no negative feedback and so the cell just continues to take up all the modified LDL and this results in the development of the foam cell

13

How does smooth muscle cell proliferation and the formation of a fibrous cap occur at the endothelium? (stage three of ateriosclerosis)

The activated endothelial cels and the infiltrating macrophages release growth factors, especially platelet derived growth factors (PDGF)
These attract the smooth muscle cells from the tunica media and causes them to migrate towards the PDGFs
These smooth muscle cells then start to proliferate and become like fibroblasts and lay down collagen - results in the formation of a fibrous cap of the atheromatous plaque

14

Describe the fibrous cap at the plaque and how it can lead to a clot

This cap is fragile and can rupture - if it ruptures, this means that there is an exposure of ECM i.e. of the collagen in the lumen of the vessel
Platelets will then stick to this collagen and form a thrombus

15

What are the common sites of atheroma formation and why?

Plaques mainly occur at the junctions of vessels i.e. where turbulent/sheer stress levels are increased

Carotid bifurcation (this can impact BP due to the presence of barorecptors at the aortic sinus)
Aortic bifurcation - the distal point
Lateral walls of common iliac arteries
Coronary arteries

16

What are the risk factors for the formation of atherosclerosis? (unmodifiable vs. modifiable)

Unmodifiable:
Age
Sex (men more at risk than women)
Family history

Modifiable:
Smoking
Hypertension
Diabetes Mellitus
Physical activity

17

Why might infection be a potential risk factor for atherosclerosis?

It is thought that infection may result in increased presence of toxins that can activate the endothelium

18

What treatment is possible for atherosclerosis?

Lifestyle changes
Statins - to reduce plasma lipid levels
Nitrates - vasodilator
Aspirin - anti-platelet
Beta blocker
ACE inhibitor
Diuretic

19

What complications can arise from atheroma formation?

Coronary artery disease - angina, MI
Peripheral vascular disease - ulcers, peripheral neuropathy, gangrene
Stroke
Aneurysm
Renal artery stenosis

20

What surgical treatment may be possible for atherosclerosis?

Insertion of a stent
CABG

21

What is contained within the polypill?

Aspirin
Statin and diuretic
Beta blocker and ACE inhibitor - reduce BP

22

Through what artery is a stent usually inserted for atherosclerosis?

Radial artery