Lecture 6 - Atheroma Flashcards
Define Atheroscelrosis
-The thickening and hardening of large and medium sized arteries, as a consequence of atheroma, beginning in the intima, progressing to the media
Define atheroma
The accumulation of intracellular and extracellular lipid in the intima and media of medium and large sized vessels
Define Arteriosclerosis
-The thickening and hardening of the walls of small arteries and arterioles (especially in the kidney), usually as a result of hypertension or diabetes mellitus
Define Monkeberg’s disease
-Uncommon calcification of the media of large arteries
What are the two major risk factors for atherosclerosis?
- Age
- Nutrition (high blood cholesterol)
What are the three types of lesion in atherosclerosis?
- Fatty streak
- Simple plaque
- Complex plaque
Describe the pathogenesis of atherosclerosis
1) Chronic endothelial injury leads to oxidised lipid droplets accumulating in the intima of arteries (transendothelial passage)
2) Endothelial dysfunction attracts monocytes which engulf the lipid and become foam cells. Gaps appear in the endothelium and platelets adhere. Monocytes and platelets secrete cytokines and growth factors which cause smooth muscles cell migration from the media (fatty streak formed)
3) Fatty streak grows into a simple plaque as the number of foam cells and smooth muscle cells increases, bulging of the endothelium occurs. Some smooth muscle cells lie beneath the endothelium and produce collagen, elastin and other matrix proteins producing a fibrous cap
5) The simple plaque progresses to a complex plaque: necrosis occurs, followed by the development of cholesterol crystals, calcification and vascularisation from the adventitia
What are the macroscopic features of a fatty streak?
-Yellow and slightly raised streak
What are the macroscopic features of a simple plaque?
- Raised yellow/white
- Irregular outline
Where does atherosclerosis often occur?
-In patches where flow is disturbed, such as around the opening of a branch
When do problems begin to arise in atherosclerosis pathogenesis?
-It is location dependant, can be as soon as 1-2mm in narrow arteries eg coronary
What is in the core of an atherosclerotic plaque?
-Necrotic and dead cells, debris and cholesterol clefts
Where does the majority of lipid come from which forms the plaques in atherosclerosis?
-Low density Lipoproteins
What happens when ulceration of the fibrous cap of a atherosclerotic plaque occurs?
-Fibrous cap is eroded from underneath and the core is exposed which can lead to thrombosis
When can thrombosis of an atherosclerotic plaque occur?
- When there is ulceration and rupture of the fibrous cap
- When gaps appear between endothelia
How can atheromatous emboli occur?
-Part of the atheroma can break up and move to distal site where it can cause an occlusion
What is the result of calcification of the plaque?
-Increases the stiffness of the arteries
How does haemorrhage of an atherosclerotic plaque occur?
-One of the vessels from vascularisation may break and haemorrhage into the plaque, causing it to break open
Why can aneurysms occur from atherosclerotic plaques?
-Loss of elastic tissue leading to permanent abnormal dilation
Define aneurysm
-Local dilatation of an artery due to weakening of the arterial wall
What is the most frequent cause of aneurysms in large arteries?
-Secondary to atherosclerosis
What is a dissecting aneurysm?
- Occur in the aorta and its branches; the initma tears open and blood flows into the media and separates the two layers
- Usually fatal and occur in a couple of minutes
Is atherosclerosis reversible?
-Upto a point - fatty streaks can disappear and plaques can shrink if a low cholesterol diet is instituted
Is atherosclerosis symptomatic?
-No, usually silent until a complication with the plaque arises
What type of endothelial ‘injury’ results in onset of atherosclerosis?
- Hyperlipidaemia
- Hypertension
- Smoking
What causes the migration of smooth muscle cells into the fatty streak?
-Platelets and macrophages release cytokines (PDGF) which stimulate migration
What influences monocyte adhesion in the pathogenesis of atherosclerosis?
-Endothelial dysfunction
What two cells engulf lipid in atherosclerotic plaques?
-Macrphages and smooth muscle cells
Where do atheromatous plaques often occur?
- Aorta, carotid and iliac elastic arteries
- Coronary and ppliteal muscular arteries
What are the possible presentations of ischaemic heart disease?
- MI
- Angina pectoris
- Arrythmias
- Cardiac failure
What is angina pectoris?
-Episodic chest pain caused by occlusion of the coronary vessels to a lesser extent than that of MI. Often experienced with exercise/stress when thee is a higher O2 demand
What are the possible presentations of cerebral ischaemia?
- TIA (less than 24hrs)
- Stroke
- multi-infarct dementia
What are the possible consequences of severe atherosclerosis in the mesenteric artery?
- Malabsorption
- Mesenteric ischaemia causing ischaemic colitis or infarction
What are the most common presentations of atherosclerosis?
- MI
- Cerebral infarction
- Aortic aneurysm
- Peripheral vascular disease
What is the most common cause of cerebral ischaemia due to atherosclerosis?
-Atherosclerosis in carotid arteries produces an embolus which travels to the brain
What is multi-infarct dementia?
-Multiple infarct which leads to dementia due to vascular problems
Why can mesenteric ischaemia occur in atherosclerosis?
-Atherosclerotic plaque forms in opening of superior mesenteric artery, reducing bloodflow to an inadequate level
What is peripheral vascular disease?
-Stenosis of the peripheral arteries of the legs caused by atherosclerosis
What are the possible presentations of peripheral vascular disease?
- Intermittent claudication
- Leriche syndrome
- Ishcaemic rest pain
- Gangrene
What is intermittent claudication?
-Intermittent pain in the calf due to relative ischaemia (often femoral), with the claudication distance getting progressively shorter and it is relieved by rest
What is leriche syndrome?
- Identical to intermittent claudication but the patient suffers intermittent pain in the buttock instead of the calf (often iliac)
- Patient may also have impotence
What is ischaemic rest pain?
-Develops from intermittent claudication, where the pain is felt even at rest
What is an angiography?
- X-ray imaging of blood vessels after injection of contrast medium
- Used to visualise blood flow
Where do aortic aneurysms, associated with atherosclerosis, usually occur?
-In the abdomen (abdominal aortic aneurysm)
Why are aneurysms prone to thrombus formation?
-Abnormal flow
-Abnormal vessel wall
(2 of virchows triad)
What is the most common type of dyslipidaemia which leads to atherosclerosis?
-Familial hypercholesterolaemia causing an increased LDL due to decreased hepatic uptake because of an defective LDL receptor
List the risk factors for atherosclerosis
- Age (rarely seen in young people unless congenital)
- Gender
- Hyperlipidaemia
- Smoking
- Hypertension
- Diabetes
Why is age a major risk factor in athersclerosis?
-Slow progressive accumulation of fatty streak/plaque
Why is gender a risk factor for atherosclerosis?
-Women are relatively protected before menopause
How is atheroma formation assiciated with apolipoprotein E?
-Genetic variations in Apoe are associated with changes in LDL levels
What are the associated physical signs of hyperlipidaemia?
- Xanthoma
- Xanthalasma
- Corneal arcus
Why is smoking a risk factor of atherosclerosis?
-Makes blood hypercoagulable and increases platelet aggregation
What role do endothelial cells play in atherosclerosis?
- May have altered permeability to lipoproteins
- Play a key role in haemostasis -> damage cause platelet adhesion
- Stimulate proliferation and migration of smooth muscle
What role do platelets have in atherosclerosis?
- Adhere to endothelia , contributing to plaque
- Stimulate proliferation and migration of smooth muscle (PDGF)
What role do smooth muscle cells play in atherosclerosis?
- Secrete ECM to form a fibrous cap on the plaque
- Take up LDL to become foam cells
What role to macrophages play in athersclerosis?
- Oxidise LDL
- Form fatty streak
- Take up lipid and become foam cells
- Secrete proteases to modify matrix
- Stimulate proliferation and migration of smooth muscle cells
What luekocytes can be present in athersclerotic plaques?
-Lymphocytes, neutrophils
What role do lymphocytes play in atherosclerosis?
- TNF may affect lipoprotein metabolism
- Stimulate proliferation and migration of smooth muscle cells
What role do neutrophils play in atherosclerosis?
-Secrete proteases leading to continued local damage and inflammation
How is atherosclerosis prevented?
Nb. some people will always develop atheromas (genetically predisposed)
- No smoking
- Reduced fat intake
- Treat hyperension
- Reduce alcohol
- Regular exercise
