Atherosclerosis (Session 6) Flashcards
What vasculature does atherosclerosis affect and what does it not affect?
- Affects arteries
- Does not affect veins or capillaries
What is the most common stage of life for atherosclerosis to be seen?
generally seen in middle to later life
What does atherosclerosis result in? (3)
- Stenosis of the arterial lumen.
- It can result in myocardial infarction and stroke
and is therefore the biggest killer in the Western world.
Flow through a stenosed tube or artery is not significantly affected until…
Until the lumen is reduced by 70-80%
What occurs to the tissue if less than 70-80% of the lumen is reduced?
Give an example
- The functional reserve of the affected tissue is reduced,
e.g., in moderate coronary artery atherosclerosis the heart may not get enough blood during exercise.
Where does atherosclerosis develop?
n patches of the intima often where flow is disturbed, e.g., around the opening of a branch.
Describe the key event that occurs in atherosclerosis (3)
- A focal accumulation of lipid and cells beneath the endothelium which forms a raised flat plaque.
- The plaque is usually about 1-2mm thick.
- This doesn’t sound very impressive but it can be a major obstacle to flow in arteries with a lumen of approximately 3 mm, such as coronary arteries.
How long does the process of plaque formation take?
Many years
Describe the arteries in which atherosclerosis occurs in
In elastic arteries (such as aorta, carotid and iliac arteries) and large and medium sized muscular arteries (such as coronary and popliteal arteries)
Which aorta is atherosclerosis commoner in? As opposed to what?
It is commoner in the abdominal rather than the thoracic aorta.
1) Define ARTERIOsclerosis
2) What happens in this condition
3) Which 3 diseases does it include?
1) Hardening of the arteries.
2) Walls of arteries are thickened and lose their elasticity.
3) * Atherosclerosis
* Arteriolosclerosis
* Monkeberg’s disease
Describe atherosclerosis
- a disease of large and medium sized arteries that begins in the intima.
- Plaques are formed in the arterial wall and these are filled with atheroma (a necrotic gruel- like material (athere is Greek for porridge)).
- The plaques often calcify.
Describe Arteriolosclerosis
- Hardening of the arterioles.
- This disease affects arterioles throughout the body but especially those of the kidney.
- It has little or no connection with atherosclerosis and usually occurs secondary to severe hypertension or in diabetes mellitus.
Describe Monkeberg’s disease
an uncommon disease where there is calcification of the media of large arteries.
What is an atheroma?
What does it consist of? (3)
The necrotic core of the atherosclerotic plaque.
It consists of dead cells, debris and cholesterol crystals.
1) What is the basic leison of atherosclerosis?
2) Name and describe the 3basic components that it has
1) The plaque
2) The plaque has three basic components:
- Cells – macrophages, leucocytes, smooth muscle cells,
- Intra- and extracellular lipid,
- Extracellular matrix – collagen, elastin, proteoglycans.
Describe step 1 of plaque formation
- Chronic endothelial insult from conditions such as hyperlipidaemia, hypertension, smoking or from haemodynamic factors result in endothelial dysfunction.
Describe step 2 of plaque formation
- Lipid droplets, mainly from low density lipoproteins (LDLs), and monocytes cross the endothelium and accumulate in the intima. The lipids become oxidised and the macrophages ingest the lipid. When they do so their cytoplasm appears bubbly microscopically and they are called foam cells.
Describe step 3 of plaque formation
- The crowded foam cells cause the endothelium to bulge. Smooth muscle cells migrate into the lesion from the media and start to proliferate. The lesion at this stage is called a fatty streak.
Describe step 4 of plaque formation
- The plaque grows as the number of foam cells and smooth muscle cells increases. Some smooth muscle cells will also take up lipid and appear foamy. Some smooth muscle cells will lie over the plaque but beneath the endothelium forming a ‘roof’. This roof is reinforced by collagen, elastin and other matrix proteins and the result is a fibrous cap. As the endothelium stretches over the plaque gaps appear between the endothelial cells. Platelets adhere to the gaps.
Describe step 5 of plaque formation
- Cells in the centre of the plaque die and necrosis develops. The dead cells release cholesterol and cholesterol crystals appear in the plaque (these are removed during tissue processing for microscopy leaving behind linear holes in the tissue section = cholesterol clefts). Small blood vessels grow into the plaque from the adventitia and the plaque may undergo calcification.
Summarise all the steps of plaque formation
- Chronic endothelial insult from conditions such as hyperlipidaemia, hypertension, smoking or from haemodynamic factors result in endothelial dysfunction.
- Lipid droplets, mainly from low density lipoproteins (LDLs), and monocytes cross the endothelium and accumulate in the intima. The lipids become oxidised and the macrophages ingest the lipid. When they do so their cytoplasm appears bubbly microscopically and they are called foam cells.
- The crowded foam cells cause the endothelium to bulge. Smooth muscle cells migrate into the lesion from the media and start to proliferate. The lesion at this stage is called a fatty streak.
- The plaque grows as the number of foam cells and smooth muscle cells increases. Some smooth muscle cells will also take up lipid and appear foamy. Some smooth muscle cells will lie over the plaque but beneath the endothelium forming a ‘roof’. This roof is reinforced by collagen, elastin and other matrix proteins and the result is a fibrous cap. As the endothelium stretches over the plaque gaps appear between the endothelial cells. Platelets adhere to the gaps.
- Cells in the centre of the plaque die and necrosis develops. The dead cells release cholesterol and cholesterol crystals appear in the plaque (these are removed during tissue processing for microscopy leaving behind linear holes in the tissue section = cholesterol clefts). Small blood vessels grow into the plaque from the adventitia and the plaque may undergo calcification.
1) What is the earliest leison in atherosclerosis?
2) Describe the appearance of the fatty streak
3) What do fatty streaks not do?
4) When do fatty streaks occur?
5) Describe the microscopic appearance of fatty streaks
The fatty streak
1) As fatty streaks grow, what do they become?
2) Describe the appearance of fatty streaks
3) Describe the microscopic appearance of fatty streaks
State and describe the various ways that plaques can become complicated (8)
- Ulceration – the fibrous cap is eroded from underneath and the core of the plaque is exposed to the blood. This core is highly thrombogenic.
- Thrombosis on the plaque – often on an ulcerated plaque, however it can sometimes occur on a plaque with intact endothelium. The thrombus may occlude the vessel lumen.
- Spasm at the site of the plaque – caused by vasoconstrictors released from thrombi.
- Embolisation – of pieces of exposed atheroma or overlying thrombus.
- Calcification – in and around the plaque making the artery even stiffer.
- Haemorrhage – of one of the new vessels within the plaque. This suddenly expands the
plaque which can result in vessel occlusion or the pressure from the haemorrhage may break
the plaque open. - Aneurysm formation – a local dilatation may result when elastic tissue within the arterial wall
is destroyed by the plaque. This weakens the wall and may result in rupture of the vessel. - Rupture of the atherosclerotic artery – with resulting bleeding. This occurs as a result of a weakened media. It is especially seen in cerebral arteries when the patient has hypertension
in addition to atherosclerosis.
1) What is an aneurysm?
2) In large arteries, what are aneurysms almost always secondary to?
3) What are aneurysms a disease of?
1) local dilatations of an artery due to weakening of the arterial wall
2) Atherosclerosis
3) The arteries
What do you call dilatations in veins?
Varices
1) What is a saccular aneurysm?
2) Where do they commonly occur?
3) What is the diameter range?
4) What do they usually have in them?
5) Why might this be a benefit?
1) One that is shaped like a sac
2) In the abdominal aorta
3) 10-15cm in diameter
4) Generally lined and/or filled by thrombus
5) as it can protect the aneurysm from bursting.
What is a fusiform aneurysm?
An aneurysm that is shaped like a spindle
What are the 2 major complications that aortic aneurysms may have?
1) if large they may rupture
2) thrombus or plaque material within them may embolise.
1) Where do dissecting aneurysms only occur?
2) How long do they take to form?
3) What is the chance of survival like?
1) Only in the aorta and its major branches
2) Within a couple of minutes
3) Rare
Describe what happens in a dissecting aneurysm
- The inner layer of the arterial wall tears open, blood enters the tear and separates the media into two layers.
- As the tear fills with blood the lumen of the artery can be occluded.
- Occasionally blood can push its way back into the lumen by means of a second tear.
Where do symptoms of atherosclerosis usually occur? (5)
- Heart
- Brain
- Kineys
- Legs
- Bowel
State the heart conditions that atherosclerosis can lead to (5)
- Myocardial infarction
- Chronic ischaemic heart disease
- Arrhythmias
- Cardiac failure
- Sudden cardiac death,
State the brain conditions that atherosclerosis can lead to (3)
- Transient ischaemic attacks (TIAs)
- Cerebral infarction
- Multi-infarct dementia
State the kidney conditions that atherosclerosis can lead to (2)
- Hypertension
- Renal failure
State the leg conditions that atherosclerosis can lead to (2)
- Peripheral vascular disease
- Gangrene
State the bowel conditions that atherosclerosis can lead to (3)
- Ischaemic colitis
- Malabsorption
- Bowel infarction
Atherosclerosis can cause symptoms and conditions in the heart, brain, kidneys, legs or bowel. What are these conditions due to?
- Either due to narrowing/blockage of vessels
- OR embolism of plaque material or thrombus that has formed on a plaque.
State the possible mechanisms of atherogenesis hypothesis (3)
- The response to injury hypothesis
- The encrustation hypothesis
- The monoclonal hypothesis
Describe the response to injury hypothesis
- Atherosclerosis is a chronic inflammatory response of the arterial wall initiated by injury to the endothelium.
- Lesion progression is sustained by interaction between modified lipoproteins, macrophages, T lymphocytes and cells of the arterial wall.
Describe the encrustation hypothesis
- plaques are formed by repeated thrombi overlying thrombi.
- The lipid core is derived from the thrombi.
Describe the monoclonal hypothesis:
- This hypothesis arose following the finding that some plaques are monoclonal or oligoclonal.
- This raised the question of whether plaques are benign neoplastic growths, perhaps induced by cholesterol or a virus.
- However as some areas of normal arteries are clonal this theory hasn’t gained widespread popularity
What are the subcategories of risk factors for atherosclerosis?
Modifiable and non-modifiable
What kind of effect does the presence of multiple risk factors for atherosclerosis have?
A multiplicative effect
Atherosclerosis can also occur without…
Without presence of any risk factors
Name 3 non-modifiable risk factors
- Age
- Gender
- Genetic predisposition
Describe gender as a risk factor for atherosclerosis
- atherosclerosis is more common in men than in women but the incidence in women increases after the menopause as oestrogen is protective.
- The incidence of atherosclerosis in women equals that of men by age 70-80 years.
Describe genetic predisposition as a risk factor for atherosclerosis (6)
- Most commonly results from a clustering of other risk factors, e.g., hypertension, diabetes mellitus,
- but occasionally it is due to derangements in lipoprotein metabolism resulting in high lipid levels, e.g., homozygous familial hypercholesterolaemia.
- People with this condition have defects in the LDL receptor which result in decreased hepatic uptake of LDL and therefore increased circulating LDL.
- Such people tend to have myocardial infarctions before the age of 20 years.
- A further genetic risk factor is a person’s apolipoprotein E genotype.
- Some of the genotypes are associated with high LDL levels and therefore a predisposition to atherosclerosis.
Name 6 modifiable risk factors for atherosclerosis
- Hyperlipidaemia (especially hypercholesterolaemia)
- Hypertension
- Cigarette smoking
- Geography
- Obesity
- Infection
Describe hyperlipidaemia (especially hypercholesterolaemia) as a modifiable risk factor for atherosclerosis
- Results in premature and severe atherosclerosis.
- Any increase in LDL cholesterol (which delivers cholesterol to the peripheral tissues) is associated with an increased incidence of atherosclerosis.
- HDL removes cholesterol from atheromatous plaques and delivers it to the liver for excretion in bile. HDL is therefore protective.
- Levels of HDL are increased with exercise and moderate alcohol and decreased with obesity and smoking.
- The reason that diabetes mellitus is associated with atherosclerosis is that it causes hypercholesterolaemia,
Describe hypertension as a modifiable risk factor for atherosclerosis
- As the increased pressure damages blood vessel walls which predisposes to plaque formation,
Describe cigarette smoking as a modifiable risk factor for atherosclerosis
Via a number of mechanisms including:
- Inflammation in and damage to the blood vessel wall
- Increased predisposition to thrombosis
- Oxidation of lipids
Describe geography as a modifiable risk factor for atherosclerosis
- Atherosclerosis is common among developed nations but has a lower incidence in South America, Africa and Asia.
- Migrants who immigrate to high risk locations and adopt the new lifestyles and diet will eventually have the same risk as the location to which they have moved
Describe obesity as a modifiable risk factor for atherosclerosis
- Produces hypertension, diabetes mellitus, hypertriglyceridaemia and reduced HDL,
Describe infection as a modifiable risk factor for atherosclerosis
Infection with Chlamydia pneumoniae or CMV has been reported by some to increase the risk of atherosclerosis.
1) What kind of disease is atherosclerosis for most of it’s course?
2) When do symptom eventually arise?
3) By then, what may happen?
4) Thus, what is key?
1) Totally silent
2) When plaques become complicated
3) Atherosclerosis may be well advanced and difficult to treat.
4) Prevention
When should prevention strategies of atherosclerosis begin?
1) In childhood
Describe 7 prevention strategies of atherosclerosis
- Decreasing total and LDL cholesterol and increasing HDL. This is probably the most important strategy and can generally be achieved with diet and lipid-lowering drugs. Dietary measures include a low fat and high fibre diet. Food high in soluble fibre reduces circulating lipid,
- Stopping smoking,
- Controlling hypertension,
- Controlling weight and regular exercise,
- Sensible alcohol intake. A moderate intake (1-2 units/day) appears protective. Excess alcohol
produces secondary hyperlipidaemia, - Treating diabetes mellitus,
- Anti-oxidants, such as vitamin E, may be protective.
Describe some atherosclerosis intervention strategies
- Lipid-lowering drugs, e.g., statins, and aspirin prophylaxis,
- Thrombolysis, angioplasty, stents, and coronary artery bypass grafts (CABG).
