S6 Atherosclerosis Flashcards by Emily Sidaway

What is an atheroma?

Accumulation of intracellular and extracellular lipid in the intima and media of large and medium sized arteries

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What is atherosclerosis?

The thickening and hardening of arterial walls as a consequence of an atheroma

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What is arteriosclerosis?

The thickening of the walls of arteries and arterioles usually as a exult of hypertension or diabetes mellitus

Usually occurs in smaller vessels

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What are the 3 macroscopic features of atherosclerosis?

fatty streak
simple plaque
complicated plaque

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What is the fatty streak? How does it appear?

Lipid deposits in the intima

Yellow and slightly raised

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What is the simple plaque - how does it appear?

It’s raised, yellow/white and irregular

Widely distributed and they enlarge and coalesce (join)

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What is the complicated plaque?

Occurs when something else has happened - thrombosis, haemorrhage into the plaque, calcification or aneurysm formation

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What are 5 common sites of atherosclerosis?

aorta (abdominal)
coronary arteries
carotid arteries
cerebral arteries
leg arteries

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What is the normal structure of an artery (from lumen outwards)

endothelium
sub-endothelial connective tissue
internal elastic lamina
muscular media
external elastic lamina
adventitia

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What are the early stage microscopic features of atherosclerosis?

proliferation of smooth muscle cells
accumulation of foam cells
extracellular lipid

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What are the later stage microscopic features of atherosclerosis?

fibrosis
necrosis
cholesterol clefts
inflammatory cells
disruption of internal elastic lamina
ingrowth of blood vessels
plaque fissuring/splits

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What are the clinical effects of atherosclerosis on the heart?

Ischaemic heart disease

sudden death
MI
angina pectoris
arrythmias
cardiac failure

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What are the clinical effects of atherosclerosis on the brain?

Cerebral ischaemia

transient ischaemic attack
cerebral infarction (stroke)
multi-infarct dementia

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What are the clinical effects of atherosclerosis on the lower GI tract?

Mesenteric ischaemia

ischaemic colitis
malabsorption
intestinal infarction

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What are the clinical effects of atherosclerosis on the peripheral vasculature?

Peripheral vascular disease

intermittent claudication
Leriche syndrome (pain in bum on exercise)
ischaemic rest pain
gangrene

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What are the risk factors for atherosclerosis?

age (more common the older you are)
gender (more common in males)
hyperlipidaemia
smoking
hypertension
diabetes mellitus
alcohol
infection

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Why are women less likely to develop atherosclerosis?

There’s a presumed hormonal basis that means women pre-menopause are protected more against atherosclerosis

Why is hyperlipidaemia a risk factor for atherosclerosis?

Hyperlipidaemia results in high plasma cholesterol e.g. LDL associated with atherosclerosis

How are lipids (cholesterol and TAGs) in the blood carried?

Carried on lipoproteins which have a hydrophobic lipid core and a hydrophilic outer layer of phospholipid and apolipoproteins (A-E)

What is associated with changes in LDL levels? How is this linked to atherosclerosis?

Genetic variations in Apo E (6 phenotypes - polymorphisms of the gene can be used as risk markers for atherosclerosis)

What is familial hyperlipidaemia? What are the physical signs of it?

Genetically determined abnormalities of lipoproteins that lead to early development of atherosclerosis

corneal arcus
tendon xanthomas
xanthelasma

What is diabetes mellitus a risk factor for?

atherosclerosis
ischaemic heart disease - doubles the risk
cerebrovascular disease
peripheral disease

What are 3 examples of infections that are risk factors for atherosclerosis?

Chlamydia pneumoniae
Helicobacter pylori
Cytomegalovirus

What are 5 other risk factors for atherosclerosis?

lack of exercise
obesity
soft water
oral contraceptives

Atherosclerosis has a genetic predisposition, what is this possibly due to?

* variations in apolipoprotein metabolism | * variations in apolipoprotein receptors

What are the 4 theories for the pathogenesis of atherosclerosis?

* thrombogenic theory * insudation theory * monoclonal hypothesis * reaction to injury hypothesis

What is the thrombogenic theory for atherosclerosis?/

That plaques are formed by repeated thrombi, the lipid is derived from the thrombi and there’s an overlying fibrous cap

What is the insudation theory for atherosclerosis?

Occurs due to endothelial injury which leads to inflammation and increased permeability to lipid from the plasma

What is the reaction to injury hypothesis for atherosclerosis?

* plaques form in response to endothelial injury e.g. hypercholesterolaemia leads to endothelial damage (+ oxidised LDL may damage endothelium) * the injury increases permeability and allows platelet adhesion * monocytes penetrate the endothelium * smooth muscle cells proliferate and migrate * the injury can be subtle and undetectable visually

What is the monoclonal hypothesis for atherosclerosis?

* smooth muscle proliferation * each plaque is monoclonal * maybe represents abnormal growth control? E.g. could each plaque be a benign tumour? * could atherosclerosis have a viral aetiology?

What is the process involved in atherosclerosis?

* thrombosis * lipid accumulation * production of intercellular matrix * interactions between cell types

What are the cells involved in atherosclerosis?

* endothelial cells * platelets * smooth muscle cells * macrophages * lymphocytes * neutrophils

How are endothelial cells involved in atherosclerosis?

* role in haemostasis * result in altered permeability to lipoproteins * produce collagen * stimulate proliferation and migration of smooth muscle cells

How are platelets involved in atherosclerosis?

* role in haemostasis | * stimulate proliferation and migration of smooth muscle cells via platelet derived growth factor

How are smooth muscle cells involved in atherosclerosis?

* take up LDL and other lipids to become foam cells | * synthesise collagen and proteoglycans

How are macrophages involved in atherosclerosis?

* oxidise LDLs * take up lipids to become foam cells * secrete proteases which modify the matrix * stimulate proliferation and migration of smooth muscle cells

How are neutrophils involved in atherosclerosis?

* secrete proteases leading to continues local damage and inflammation

What is the current hypothesis for atherosclerosis?

* endothelial injury is due to raised LDL, toxins, hypertension and haemodynamic stress * the injury causes platelet adhesion, PDGF release, smooth muscle cell proliferation and macrophages and migration of monocytes into intima * stimulated smooth muscle cells produce matrix material * foam cells secrete cytokines causing further smooth muscle cell stimulation and recruitment of other inflammatory cells

How can you prevent atherosclerosis?

* no smoking * reduce fat intake * treat hypertension * not too much alcohol * regular exercise/weight control

What are interventions for atherosclerosis?

* stop smoking * modify diet * treat hypertension * treat diabetes * lipid lowering drugs