Session 6 - Atherosclerosis

Question 1

• Define Atheroscelorosis
• what blood vessels does it affect?
• what can it lead to?
• what % occlusion leads to flow impairment?
• why can atherosclerosis develop?
• Main overview of what happens?

Answer 1

• Atheroscelorosis:** 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, the placques often calcify.
• *Blood vessels:** Common disease that affects arteries, does not affect veins or capillaries.
• *Can lead to:** stenosis of the arterial lumen, can result in a myocardial infarction and stroke
• *Flow impairment:** Flow is not significantly affected until the lumen is reduced by 70-80%
• *Why can atherosclerosis develop?** Artherosclerosis develops in patches of the intima often where flow is disturbed e.g. around the opening of a branch
• *Main overview of what happens?** Key event is a focal accumulation of lipid and cells beneath the endothelium which forms a raised flat placque.

Question 2

The atherosclerotic plaque
- three major components

Answer 2

• Cells – macrophages, leucocytes, smooth muscle cells
• Intra- and extracellular lipid
• Extracellular matrix – collagen, elastin, proteoglycans

Question 3

Formation of the placque

Answer 3

1. Chronic endothelial insult - from conditions like hyperlidaemia, hypertension, smoking or from haemodynamic factors result in endothelial dysfunction
2. Lipid droplets accumulate in the INTIMA - 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.
3. Fatty streak forms - Smooth muscle cells migrate into the lesion from the media and start to proliferate, the lesion is called a fatty streak.
4. Placque grows and fibrous cap forms- 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 placque but beneath the endothelium forming a ‘roof’. The roof is reinforced by collagen, elastin and other matrix proteins.
5. Cells in the centre of the placque die and necrosis develops - The dead cells release cholesterol and cholesterol crystals appear in the placque (these are removed during tissue processing for microscopy leaving behind linear holes in the tissue = cholesterol clefts). Small blood vessles grow into the plaque from the adventitia and the plaque may undergo calcification.

Question 4

Changes in the placque - microscopic changes

Answer 4

Early changes:

• proliferation of smooth muscle cells
• accumulation of foam cells
• extracellular lipid

Later changes:

• fibrosis
• necrosis
• cholesterol clefts
• may have inflammatory cells
• disruption of internal elastic intima
• damage to blood vessels
• ingrowth of blood vessels
• placque fissuring

Question 5

Changes in the placque - 3 Morphological appearance - goes with ‘formation’ stages

Answer 5

1. Fatty streak - These are flat and cause no disturbance to blood flow. They occur early in life and can be seen in children. Microscopically they consist of intimal foam cells, some smooth muscle cells and some extracellular lipid.
2. Simple placque - As fatty streaks grow they become plaques. These are white to yellow in colour and impinge on the lumen of the artery. They usually measure between 0.3-1.5 cm in diameter and are usually only partly circumferential. Microscopically there is fibrosis, necrosis, cholesterol clefts, disruption of the internal elastic lamina, extension into the media and ingrowth of small vessels from the adventitia.
3. Complicated placque - Next flashcards

Question 6

Plaque complications

Answer 6

1. Ulceration – the fibrous cap is eroded from underneath and the core of the plaque is exposed to the blood. This core is highly thrombogenic.
2. 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.
3. Spasm at the site of the plaque – caused by vasoconstrictors released from thrombi.
4. Embolisation – of pieces of exposed atheroma or overlying thrombus
5. Calcification – in and around the plaque making the artery even stiffer.
6. 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.
7. 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.
8. 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

Question 7

• What are aneurysm?
• What usually causes an aneurysm?
• What is a dialation of a vein called?
• Types of aneurysms
• Complications of aortic aneurysms

Answer 7

artheroscelrosis - Damages the tunica media

What are aneurysms: These are local dilatations of an artery due to weakening of the arterial wall.
When do aneurysms often occur? In large arteries they are almost always secondary to atherosclerosis. Like atherosclerosis, they are a disease of arteries.
Dilatations in veins are called varices.
Types of aneurysm:
- A saccular aneurysm is one that is shaped like a sac. They commonly occur in the abdominal aorta and can be 10-15cm in diameter. They are generally lined and/or filled by thrombus, which may be adventitious as it can protect the aneurysm from bursting.
- A fusiform aneurysm is one that is shaped like a spindle.
Complications of aortic aneurysms:
Aortic aneurysms have two major complications; if large they may rupture and thrombus or plaque material within them may embolise. Dissecting aneurysms occur virtually only in the aorta and its major branches. They form within a couple of minutes and survival is rare. 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.

Question 8

Effects of artherosclerosis

Answer 8

Symptoms usually occur in the heart, brain, kidneys, legs or bowel. Atherosclerosis can cause conditions such as:
 Heart - myocardial infarction, chronic ischaemic heart disease, arrhythmias, cardiac failure and sudden cardiac death,
 Brain – transient ischaemic attacks (TIAs), cerebral infarction, multi-infarct dementia,
 Kidneys – hypertension, renal failure,
 Legs – peripheral vascular disease, gangrene,
 Bowel - ischaemic colitis, malabsorption, bowel infarction. These conditions are either due to narrowing/blockage of vessels or embolism of plaque material or thrombus that has formed on a plaque.

Question 9

Risk factors for atherosclerosis

• non-modifable risk factors
• modificable risk factors

Answer 9

Non-modifiable Risk factors:

• Age
• Gender - 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.
• Genetic predisposition – this 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

Modifiable Risk Factors:

• Hyperlipidaemia – (especially hypercholesterolaemia) 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,
• Hypertension – as the increased pressure damages blood vessel walls which predisposes to plaque formation,
• Cigarette smoking – via a number of mechanisms including inflammation in and damage to the blood vessel wall, increased predisposition to thrombosis and oxidation of lipids,
• Obesity – produces hypertension, diabetes mellitus, hypertriglyceridaemia and reduced HDL,
• Infection - with Chlamydia pneumoniae or CMV has been reported by some to increase the risk of atherosclerosis

Question 10

Prevention of and intervention in Atherosclerosis

Answer 10

• 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.

Intervention strategies include:

• Lipid-lowering drugs, e.g., statins, and aspirin prophylaxis,
• Thrombolysis, angioplasty, stents, and coronary artery bypass grafts (CABG).