ATHEROSCLEROSIS By Joshua BowerEaster Revision 2014J.Bower@warwick.ac.uk

Distinguish arteriosclerosis, atherosclerosis and arteriolosclerosis

• ARTERIOSCLEROSIS – generic term meaning ‘hardening of the arteries’ which encompasses the other 2

• ATHEROSCLEROSIS – intimal lesions of arteries caused by atheromas

• ARTERIOLOSCLEROSIS – arteriolar hardening seen in HTN and DM

Intima:• Endothelium• BM• Subendothelial connective tissue• Internal elastic lamina

Media:• SMCs• Connective Tissue

Externa/Adventitia• Connective tissue• External elastic lamina• Vasa vasorum

What are vasa vasorum?

• Network of small blood vessels supplying walls of large blood vessels• Provide blood supply and nourishment to tunica adventitia and outer

part of tunica media

What is an atheroma?

• Chronic intimal lesion occurring in arteries• Causes lumen narrowing and weakening of vessel wall

Atheromas are characterised by accumulation of what FOUR things? [4]

• Vascular SMCs (vascular smooth muscle cells)• ECM• Inflammatory cells• Lipids

List FOUR modifiable and non-modifiable risk factors for atherosclerosis

• Hyperlipidaemia• HTN• Smoking• DM

• Older• Male• FHx• Genetics (e.g. ?)

Modifiable Non-modifiable

Give an example of a genetic abnormality which may contribute to atheroma development

• Apolipoproteins• APLs package fats e.g. LDL• Some APLs act as ligand for receptors for uptake into cells

• Abnormal APL or receptors means:• Reduced uptake• Reduced excretion

• Thus increased serum LDL

What are the THREE key features of chronic inflammation? [3]

• Ongoing inflammation• Ongoing tissue destruction• Ongoing tissue repair

List the steps leading to atheroma development [6]

1. Chronic endothelial injury (e.g. HTN, smoking)2. Endothelial dysfunction (becomes more permeable, cholesterol-rich

LDLs enter and becomes oxidised3. Monocytes enter, becomes macrophages and attempt to digest the

cholesterol – become foam cells (visible as a fatty streak) 4. Foam cells release growth factors, stimulating SMC infiltration from

the media, which then proliferate5. Collagen and ECM becomes deposited, forming fibrofatty plaque6. SMCs calcify as they degenerate in aged plaques, making them

more vulnerable to rupture

Suggest THREE outcomes of atheroma [3]

Atheroma

Chronic Narrowing of lumen

Chronic reduction in blood flow

Chronic ischaemia

Weakening of vessel wall

AneurysmPlaque rupture

Bleeding into atheroma

Thrombus

Occlusion

Embolus

List THREE features of vessels which may make them more vulnerable to atheroma development [3]

• High pressure• Bifurcation (e.g. abdominal aorta)• Narrow lumen with high flow (e.g. cerebral vasculature)

An obese 67yo diabetic male presents to his GP with pain in his lower leg which becomes worse after he has been walking for a while. Diagnosis?

• Peripheral vascular disease• Intermittent claudication• Pain at rest• Ischaemic limb

• These are atherosclerotic blockages outside of the coronary tree – usually lower limb

The effects of the atheroma on distal tissue is dependent on what THREE things? [3-5]• Size of lumen• Stability of plaque• Degree of degeneration of underlying wall• Natural Hx of plaque• Type of blood supply

How can atheroma be treated? [3]

• Reduce risk• Stenting by PCTA• Bypass grafting via CABG

QUESTIONS? By Joshua BowerEaster Revision 2014J.Bower@warwick.ac.uk