10. Atherosclerosis Flashcards
Which type of blood vessels does atherosclerosis affect?
Arteries, does not affect veins or capillaries
At what percentage lumen reduction is blood flow significantly affected?
70-80%
What is the key event in atherscleosis?
Focal accumulation of lipid and cells beneath the endothelium which forms a raised flat plaque. The plaque is usually about 1-2mm thick
Which part of arteries does atherscleosis occur?
in patches of the intima often where flow is disturbed, e.g., around the opening of a branch
In which arteries do plaques usually form?
In elastic arteries (such as aorta, carotid and iliac arteries) and large and medium sized muscular arteries (such as coronary and popliteal arteries). It is commoner in the abdominal rather than the thoracic aorta9405
Define arteriosclerosis.
hardening of the arteries
- walls are thickened and lose their elasticity
What 3 diseases does arteriosclerosis encompass?
- atherosclerosis
- arteriolosclerosis
- Monkeberg’s disease
Define 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). The plaques often calcify.
Define 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.
What is Monkeberg’s disease?
An uncommon disease where there is calcification of the media of large arteries
What is atheroma and what does it consist of?
Necrotic core of the atherosclerotic plaque. It consists of dead cells, debris and cholesterol crystals
What is the atherosclerotic plaque?
The basic lesion of atherosclerosis
What are the 3 basic components of the atheroscleotic plaque?
- Cells: macrophages, leucocytes, smooth muscle cells
- Intra and extracellular lipid,
- Extracellular matrix: collagen, elastin, proteoglycans.
Describe plaque formation.
- Chronic endothelial insult result in endothelial dysfunction
- Lipid droplets, mainly from LDLs, and monocytes cross the endothelium and accumulate in the intima. The lipids become oxidised and the macrophages ingest the lipid.
- lots 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
- 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.
- Fibrous cap forms. 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. Small blood vessels grow into the plaque from the adventitia and the plaque may undergo calcification
What may cause chronic endothelial insult?
Conditions such as hyperlipidaemia, hypertension, smoking or from haemodynamic factors
What is and forms the fibrous cap?
Layer of fibrous connective tissue that covers a plaque
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
What are macrophages that ingest lipids called?
Foam cells
What are cholesterol clefts?
when cells in the centre of the plaque dies and release cholesterol, cholesterol crystals appear. These are removed during tissue processing for microscopy leaving behind linear holes in the tissue section = cholesterol clefts
What contribute to fatty streaks and what effects do they have on blood flow?
Consist of intimal foam cells, some smooth muscle cells and some extracellular lipid
- are flat and cause no disturbance to blood flow
What forms as fatty streaks grow?
Plaques
What contributes to plaques?
Fibrosis, necrosis, cholesterol clefts, disruption of the internal elastic lamina, extension into the media and ingrowth of small vessels from the adventitia
Describe the appearance of simple and complicated plaques.
The Simple Plaque: ● Raised yellow/white ● Irregular outline ● Widely distributed ● Enlarge and coalesce
The Complicated Plaque ● Thrombosis ● Haemorrhage into plaque ● Calcification ● Aneurysm formation
What are some plaque complication?
- Ulceration
- Thrombosis on the plaque
- Spasm at the site of the plaque
- Embolisation
- Calcification
- Haemorrhage
- Aneurysm formation
- Rupture of the atherosclerotic artery
What is plaque ucleration?
Fibrous cap is eroded from underneath and the
core of the plaque is exposed to the blood. This core is highly thrombogenic
When might plaque thrombus form and what is the implication of this?
often on an ulcerated plaque, however it can sometimes occur on a plaque with intact endothelium
Occludes vessel lumen
How do spasms at sites of plaque occur?
Caused by vasoconstrictors released from thrombi.
What can embolise from plaque?
Pieces of exposed atheroma or overlying thrombus
Where does calcification of plaque occur and what does this result in?
in and around the plaque making the artery even stiffer
Where does plaque haemorrhage occur and what does this result in?
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
Why might plaque lead to aneurysm?
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
Why might plaque lead to rupture of the atherosclerotic artery?
This occurs as a result of a weakened media.
– with resulting bleeding
Where is rupture of an atherosclerotic artery usually seen?
Cerebral arteries when the patient has hypertension in addition to atherosclerosis
What are aneurysms?
Aneurysms are local dilutions of an artery due to weakening of the arterial wall.
The vessel wall is stretched during systole, however it’s lost its ability to recoil back to its original shape and size so it remains dilated.
In large arteries they are almost always secondary to atherosclerosis. Like atherosclerosis, they are a disease of arteries.
What are dilated veins called?
Varices
What are saccular and fusiform aneurysms shaped like?
Saccular: shaped like a sac
Fusiform: shaped like a spindle
Where do saccular aneuryms usually occur?
Abdominal aorta
What are saccular aneurysms line/filled with and why is this important?
lined and/or filled by thrombus, which may be adventitious as it can protect the aneurysm from bursting
What are the 2 major complications of aortic aneurysms?
If large they may rupture and thrombus or plaque material within them may embolise
Where do dissecting aneurysms occur?
Occur virtually only in the aorta and its major branches
What are dissecting aneurysms?
Aneurysm in which the inner wall of the artery tears open
What happens in a dissecting aneurysm?
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?
- Heart
- Brain
- Kidneys
- Legs
- Bowel
conditions are either due to narrowing/blockage of vessels or embolism of plaque material or thrombus that has formed on a plaque
What effects does atheorsclerosis have on the heart?
Myocardial infarction, chronic ischaemic heart disease, arrhythmias, cardiac failure and sudden cardiac death.
These conditions are caused by reduced blood flow to cardiac tissue due to atherosclerotic plaques in the coronary arteries.
What effects does atherosclerosis have on the brain?
In the brain you can develop cerebral Ischaemia.
This is caused by a sudden decrease in blood supply to the brain.
This can be due to a carotid or cerebral artery atherosclerosis, thromboembolism, haemorrhage or cardiac arrest.
This causes:
Transient ischaemic attacks (TIAs), cerebral infarction,
multi-infarct dementia
What effects does atherosclerosis have on the kidneys?
- Hypertension:
Renal artery stenosis causes a reduction renal perfusion resulting in an increase in systemic blood pressure through activation of RAAS. - Renal failure:
Renal artery stenosis can cause chronic kidney disease and end stage kidney failure
What effects does atherosclerosis have on the legs?
In the legs you can develop a group of conditions know as peripheral vascular disease.
These present as:
1. Intermittent claudication -
Cramping pain in the legs induced by exercise and relieved by rest caused by stenosis of the arteries to the legs.
2. Leriche syndrome -
Stenosis of the iliac arteries, causes cramping pain in the buttocks and legs, and impotence.
3. Ischaemic rest pain - continuous pain in the lower limb caused by ischaemia.
4. Gangrene - loss of blood supply resulting in tissue death.
What effects does atherosclerosis have on the bowel?
Mesenteric ischaemia is ischaemia caused by a reduction in blood supply to the bowel.
It can cause:
- Ischaemic colitis -
Inflammation and injury to the large bowel due to inadequate blood supply, it can result in acute ulceration and haemorrhage. - Malabsorption
Resulting from chronic mesenteric ischaemia. - Bowel infarction
Occlusion of an artery supplying the intestines resulting in infarction.
What are the 3 different hypotheses of atherogenesis?
- The response to injury hypothesis
- The encrustation hypothesis / thrombogenic theory
- The monoclonal hypothesis
What is the response to injury hypothesis for atherogenesis?
Postulates that 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
What is the encrustation hypothesis for atherogenesis?
In this model plaques are formed by repeated thrombi overlying thrombi. The lipid core is derived from the thrombi
What is the monoclonal hypothesis for atherogenesis and why hasn’t this theory gained popularity?
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.
List the common sites for atherosclerosis
- Aorta (particularly abdominal)
- Coronary arteries
- Carotid arteries
- Cerebral arteries
- Leg arteries
What are the early and later changes due to atherosclerosis?
Early changes
● proliferation of smooth muscle cells
● accumulation of foam cells
● extracellular lipid
Later changes ● fibrosis ● necrosis ● cholesterol clefts ● +/- inflammatory cells ● disruption of internal elastic lamina ● damage extends into media ● ingrowth of blood vessels ● plaque fissuring
What are the non-modifiable risk factors for atherosclerosis?
- age
- gender
- genetic predisposition
Which gender does atherosclerosis affect more?
Men
Which women are affected more by atherosclerosis and why?
After menopause, becuase oestrogen is protective.
What are some genetic predispositions to atherosclerosis?
Some people are genetically predisposed to conditions such as hypertension, hyperlipidaema, diabetes mellitus.
It can also be due to derangements in lipoprotein metabolism resulting in high lipid levels, e.g.
homozygous familial hypercholesterolaemia.
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.
Why is diabetes mellitus associated with atherosclerosis?
It causes hypercholesterolaemia
What are the modifiable risk factors for atherosclerosis?
- Hyperlipidaemia
- Hypertension (damages blood vessels)
- Cigarette smoking
- Geography
- Obesity
- Infection
Explain what homozygous familial hypercholesterolaemia is
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.
How is hyperlipidaemia a risk for 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.
What can increase or decrease HDL levels?
Increase: exercise, moderate alcohol
Decrease: obesity, smoking
How does smoking increase risk of atherosclerosis?
Number of mechanisms including:
- inflammation in and damage to the blood vessel wall
- increased predisposition to thrombosis
- and oxidation of lipids
- decrease HDL
How does obesity increase risk of atherosclerosis?
Produces hypertension, diabetes mellitus, hypertriglyceridaemia and reduced HDL,
How does hypertension increase risk of atherosclerosis?
as the increased pressure damages blood vessel walls which predisposes to plaque formation
Infections with what bacteria have shown to be associated with increase risk of atherosclerosis?
Chlamydia pneumoniae or cytomegalovirus (CMV)
How is excess alcohol associated with atherosclerosis?
Excess alcohol produces secondary hyperlipidaemia
What are the prevention strategies for atherosclerosis?
- Decreasing total and LDL cholesterol and increasing HDL. 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
- Treating diabetes mellitus,
- Anti-oxidants, such as vitamin E, may be protective.
What are intervention strategies for atherosclerosis?
- Lipid-lowering drugs, e.g., statins, and aspirin prophylaxis,
- Thrombolysis, angioplasty, stents, and coronary artery bypass grafts (CABG).
