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Flashcards in Atherosclerosis Deck (48):

What dietary advice would you give to a patient at risk of atherosclerosis?

Lose weight if needed
Lipid lowering diet (decrease dairy and meat, increase fish and poultry, remove fat and skin from meat, bake and grill, avoid pastry and cake etc)
Use monounsaturated oils
Reduce dietary cholesterol
Eat refined carbohydrates which are absorbed slowly
Increase fibre intake which reduces circulating lipid
Avoid excess alcohol which can cause secondary hyperlipidaemia


What dietary factors may influence the development of atherosclerosis?

Hypertriglyceridaemia and hypercholesterolaemia caused by diets high in fats
Alcohol - moderate consumption appears protective as it increases HDL cholesterol levels
Avoidance of obesity
Good glycaemic control in diabetes
Possible protective role of vitamin E


Define arteriosclerosis and name the conditions that fall under it

Hardening of the arteries.
includes atherosclerosis, arteriolosclerosis, Monkeberg's disease


Describe atherosclerosis

Disease of the large and medium sized arteries, begins in the intima.
Produces atheromatous plaques filled with a necrotic, gruel-like material. Atheromas contain cholesterol, lipoid material and lipophages are formed within the intima and inner media of large and medium-sized arteries


Describe arteriolosclerosis

Hardening of the arterioles. Little or no connection to atherosclerosis usually secondary to severe hypertension.
Affects arterioles throughout the body but especially those in the kidney.


Describe Monkeburg's disease

Calcification of the media of large arteries


Describe the pathogenesis of atherosclerosis

Transendothelial passage of lipid droplets which become oxidised, monocytes pick up and become foam cells (endothelium intact)
Crowded foam cells cause endothelium to bulge, smooth muscle cells arise from the media. Lesion is called a fatty streak.
Growth of plaque by an increase in number of foam cells and smooth muscle cells. Some smc take up lipid. Platelets adhere where there are gaps between endothelial cells. Some smc form a roof which is reinforced by collagen, elastin and other matrix proteins (fibrous cap)
Necrosis in the plaque followed by development of cholesterol crystals, calcification, few inflammatory cells and vascularisation of the adventitia (weak and leaky - haemorrhage and thrombosis)


What size arteries does high blood cholesterol affect?

Large and medium (and only parts of these)


Where does atherosclerosis begin?

The intima (often where flow is disturbed, such as around the opening of a branch)


What is atheroma?

The necrotic core of the plaque consisting of dead cells, debris and cholestrol clefts


Where does lipid in an atheromatous plaque generally come from?

LDLs which carry cholesterol


Describe how ulceration of an atheromatous plaque can cause problems.

The core is exposed as the fibrous cap is eroded from underneath. This leads to immediate blood clotting and triggers a cascade which leads to clot enlargement, which can quickly obstruct blood flow


How can thrombus formation cause an atheroma to break up, and what problem would this cause?

It releases vasoconstrictors which causes spasms at the site of the plaque.
This can cause it to shed emboli.


What is the consequence of calcification in and around the plaque?

Arteries become stiffer


How can atherosclerosis cause an aneurysm?

Local weakening of the wall as the plaque invades the media and disrupts the elastic fibres, which causes local dilatation


Describe an aneurysm.

Local dilatations of an artery due to weakening of the arterial wall.


Describe the difference between a saccular and fusiform aneurysm.

Saccular - shaped like a sac. can be 10-15cm in the aorta. Lined and/or filled with a thrombus.

Fusiform - shaped like a spindle.


Where do dissecting aneurysms tend to occur?

In the aorta and it's major branches


Describe what causes an aneurysm to dissect.

A tear in the intima allows blood to enter and separate the media. It can sometimes re-enter the lumen through a second tear


Why is prevention important in atherosclerosis?

The course of atherosclerosis is mostly silent until secondary symptoms appear. By this time it can be too late.


Give the cellular events that can lead to atherosclerotic lesions.

Chronic endothelial damage
Endothelial dysfunction allowing monocyte and platelet adhesion, and emigration of T-lymphocyte. Growth factors and cytokines are released which are cytotoxic to endothelial and smooth muscle cells.
Platelets release factors causing migration of smooth muscle cells from the media to intima.
Smooth muscle emigrates, macrophage activation
Macrophages and smooth muscle cells engulf lipid.
Macrophages produce toxic oxygen species which oxidise LDLs which are then engulfed by macrophages to form foam cells
Smooth muscle proliferation causes collagen and other ECM deposition, extracellular lipid and neovascularisation.
PDGF causes proliferation of smooth muscle cells.


What is platelet-derived growth factor (PDGF) produced by?

Endothelial cells
Smooth muscle cells


Describe the morphological appearance of fatty streaks.

Flat and yellow, no disturbance to blood flow.
Seen in children
Contains some T-lymphocytes and extracellular lipid.


Describe the morphological appearance of atherosclerotic plaques.

White/yellow and impinge on the lumen
Raised lesion initiating within the intima with a soft, yellow core of lipid covered by a firm, fibrous cap.
Tend to be partly circumferential and occur more in the abdominal than thoracic aorta.


Describe the difference between a simple and complex atherosclerotic plaque

Simple - Irregular outline, wide distribution, enlarge and coalesce.

Complex - Haemorrhage/thrombosis/calcification


What are the components of atherosclerotic plaques?

Cells - smooth muscle, macrophages, lymphocytes

ECM - collagen, elastic fibres, proteoglycans

Intra- and extracellular lipid


Describe the effects of decreased perfusion in different areas caused by atherosclerosis.

Mesenteric occlusions
Sudden cardiac death
Chronic ischaemic heart disease causing angina pectoris (episodic chest pain)
Ischaemic encephalopathy
Cardiac failure


Describe the difference in symptoms between angina pectoris and myocardial infarction.

Angina can be relieved by stopping the activity that is causing it.


Describe peripheral vascular disease

Intermittent claudication causing calf pain on exercise if lower down in the leg like the popliteal artery.
Leriche syndrome which causes pain in the buttocks.
These can progress to resting pain and gangrene.


Describe the effects of cerebral ischaemia

Transient ischaemic attack - neurological symptoms lasting less than 24 hours

Stroke - neurological symptoms lasting less than 24 hours, or interrupted by death.

Multi-infarct dementia - vascular dementia which is caused by a series of strokes.


Describe effects of mesenteric ischaemia

Ischaemic colitis
Infarction - usually fatal if it involves the whole of the small bowel.


Describe the 'response to injury' hypothesis for the mechanism of atherogenesis

Atherosclerosis is a chronic inflammatory response of the arterial wall, initiated by injury to the endothelium.
Lesion progress is sustained by interaction between modified lipoproteins, macrophages, T-lymphocytes and cells of the arterial wall.


Describe dyslipidaemias that promote atherosclerosis (generally)

Increased LDL cholesterol
Decreased HDL cholesterol
Increased abnormal lipoprotein (aLp)


Describe homozygous familial hypercholesterolaemia

Caused by defects to the LDL receptors or apoB100
High risk of MI before 20
Corneal arcus - cholesterol deposit around the cornea
Xanthoma - in skin/on tendon
Xanthelasma - by the eye


How can hypothyroidism increase the risk of premature and severe atherosclerosis?

Can cause hypercholesterolaemia


Describe how age increases your risk of atherosclerosis

The disease is progressive throughout adulthood.
Risk factors operate over years.


Describe how your sex increases your risk of atherosclerosis

Occurs more in men than women as female hormones are thought to be protective.
After menopause this protective element is lost, and risk is the same around 70-80 years of age.


Why can statins decrease your risk of atherosclerosis?

They inhibit HMG-CoA reductase which is required for cholesterol biosynthesis. Will reduce hyperlipidaemia


How can cigarette smoking increase the risk of atheromatous plaques?

Causes hypercoaguability
Decrease prostaglandin I2 which is a vasodilator and inhibits platelet action
Slow decrease in risk after stopping


How can homocysteinuria (or high circulating homocysteine from vitamin B deficiency) increase your risk of atherosclerosis?

Homocysteine impairs endothelial function, increases oxidant stress and induces thrombosis.


How can geography affect your risk of developing atherosclerosis?

Ubiquitous among developed nations.
Migrants to these places who adopt the new lifestyles and diet have the same risk as the new location.


Give some risk markers for atherosclerosis.

Apolipoprotein E genotype causing changes in LDL levels
Angiotensin converting enzyme (high causes hypertension)
Genetic polymorphisms of apoE


Describe some interventions for atherosclerosis

Lipid lowering drugs
Aspirin prophylaxis
Coronary artery bypass grafting
Control of arrhythmias


What consequence can haemorrhage into a plaque cause?

Expand the plaque or cause rupture


Give some possible complications of myocardial infarction (other than death).

Cardiogenic shock - systemic vascular failure from the heart
Heart block - very slow. Damage to the SAN so the AVN takes over.
Cardiac failure
Mitral regurgitation due to weakness of the papillary muscles
Ventricular aneurysm (can also cause mitral regurgitation) due to scarring. Can throw a thrombus up to the brain/peripheral gangrene/bowel ischaemia
Pericarditis if transmural as inflammatory cells leak.


Describe grey Turner's sign

Discolouration or bruising in the flanks, indicates a retrospective ruptured aneurysm.


What can cause haemopericardium?

MI, trauma, dissecting aorta


What complication could an aortic aneurysm cause?

Aortic duodenal fistula
Thromboembolism to the legs
Arotic dissection
Rupture, leads to death (90-95%)