S6 Atherosclerosis Flashcards
What is an atheroma?
Accumulation of intracellular and extracellular lipid in the intima and media of large and medium sized arteries
What is atherosclerosis?
The thickening and hardening of arterial walls as a consequence of an atheroma
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
What are the 3 macroscopic features of atherosclerosis?
- fatty streak
- simple plaque
- complicated plaque
What is the fatty streak? How does it appear?
Lipid deposits in the intima
Yellow and slightly raised
What is the simple plaque - how does it appear?
It’s raised, yellow/white and irregular
Widely distributed and they enlarge and coalesce (join)
What is the complicated plaque?
Occurs when something else has happened - thrombosis, haemorrhage into the plaque, calcification or aneurysm formation
What are 5 common sites of atherosclerosis?
- aorta (abdominal)
- coronary arteries
- carotid arteries
- cerebral arteries
- leg arteries
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
What are the early stage microscopic features of atherosclerosis?
- proliferation of smooth muscle cells
- accumulation of foam cells
- extracellular lipid
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
What are the clinical effects of atherosclerosis on the heart?
Ischaemic heart disease
- sudden death
- MI
- angina pectoris
- arrythmias
- cardiac failure
What are the clinical effects of atherosclerosis on the brain?
Cerebral ischaemia
- transient ischaemic attack
- cerebral infarction (stroke)
- multi-infarct dementia
What are the clinical effects of atherosclerosis on the lower GI tract?
Mesenteric ischaemia
- ischaemic colitis
- malabsorption
- intestinal infarction
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
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
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
