Lecture 11 - Atherosclerosis Flashcards by Callum Donoher

What is Arteriosclerosis?

The thickening of the walls of arteries and arterioles often associated with loss of elasticity
(usually as a result of hypertension or diabetes Mellitus )

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What can happen as a result of Arteriosclerosis?

Poor tissue perfusion
Inelastic/weak vessels which can lead to aneurysm
Increased risk of thrombus formation

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What is Atherosclerosis?

Accumulation of intracellular and extracellular lipid in the tunica intima and media of medium - large sized arteries

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What is an Atheroma?

A necrotic core of the atherosclerotic plaque

The thickening and hardening of arterial walls as as consequence of atherosclerosis

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What is contained in the tunica adventitia of blood vessels?

Blood vessels and nerves that supply the vessels
Thick collagen and elastin layer

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What are the 2 main events that lead to the development of atherosclerotic plaques?

Endothelial damage
Inflammation

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What can lead to endothelial damage?

Hyperlipidaemia (High LDL)
Hypertension
Smoking (toxins)
Haemodynamic stressors

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What does Endothelial dysfunction lead to?

Platelet adhesion
Smooth muscle cell proliferation and migration
Lipids (LDL and cholesterol) cross into the tunica Intima
Monocytes (macrophages) cross into intima

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What cells end up forming foam cells?

Macrophages
Smooth muscle cells

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What is the function of the macrophages when the endothelial wall is damaged?

Secrete cytokines recruiting other inflammatory cells

Stimulate more smooth muscle cells

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What is the function of the proliferating/migrating smooth muscle cells when endothelial cells are damaged?

Produce matrix material forming the “roof”

Matrix made of collagen, elastin and other proteins

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How do smooth muscle cells migrate when the endothelial cells are damaged?

The endothelial cells (Tunica intima layer) is broken so the smooth muscle cells that reside in the Tunica media can slip into the lumen of the vessel

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How do macrophages become foam cells?
How do smooth muscle cells become foam cells?

Macrophages engulf oxidised lipids (like LDL)
SM takes up lipids due to receptors they have

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What do the smooth muscle cells in the intima and media begin to produce as they form the fatty streak and as the plaque develops?

Fibrous cap reinforced with collagen and elastin

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What does the formation of the fibrous cap by the migrated smooth muscle lead to?

Separates the cells in the centre of the plaque from the blood supply

Leads to a necrotic core developing

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What are the cellular components of a necrotic plaque?

Macrophages, leukocytes/white blood cells, smooth muscle cells and platelets

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What is the function of endothelial cells in atherosclerotic plaque formation?

Produce collagen
Stimulate the proliferation and migration of smooth muscle cells

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What is the function of platelets in atherosclerotic plaque formation?

Stimulates proliferation and migration of smooth muscle cells

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What is the function of smooth muscle cells in atherosclerotic plaque formation?

Take up LDL and other lipids becoming foam cells

Make collagen and proteoglycans forming the fibrous cap

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What is the function of macrophage in atherosclerotic plaque formation?

Oxidise LDL
Take up this oxidised LDL and become foam cells
Secrete proteases which modify matrix
Stimulates proliferation and migration of smooth muscle cells

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What is the function of Lymphocytes in atherosclerotic plaque formation?

Produce TNF which can affect lipoprotein metabolism
Stimulate proliferation and migration of smooth muscle cells

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What is the function of neutrophils in atherosclerotic plaque formation?

Secrete proteases leading to continued local damage and inflammation

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What is an Intima xanthoma?

Fatty streak

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What happens in the development of an atherosclerotic plaque?

Fatty streak (Intima xanthoma)
Fibrous cap atheroma (stable plaque)
Thin fibrous cap atheroma
Now prone to rupture and thrombosis

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What happens when the fatty streak forms microscopically?

Proliferation of smooth muscles Foam cells accumulate Extracellular lipid

What happens microscopically in the stable simple plaque?

Fibrosis (Fibrous cap) Necrosis Inflammatory cells

What happens when the plaque becomes unstable?

Disrupted internal elastic Lamina New vessels from the Adventitia grow into the plaque Plaque can erode and ulcerate

How does a fatty streak appear microscopically?

Slightly raised yellow area in the intima

In the blood vessel, where does the fibrous cap form and what is it in contact with?

Forms in contact with the lumen

What is the problem with the fibrous cap of an atheroma being thin?

prone to rupture since its not very strong

Why do unstable plaques usually present as yellow, red and hard?

Yellow from the fatty streaks/thrombosis Red from the haemorrhaging from the newly formed blood vessels entering the plaques from the advantitia Hard due to calcification

How does atherosclerosis appear a microscopically?

Narrowed lumen Different coloured region next to lumen = Fibrous cap Necrotic core on other side of the fibrous cap

What are the complications of Atherosclerosis?

Ulceration Thrombosis Vasospasm (vasoconstriction) Embolism Calcification Haemorrhage Aneurysm formation Rupture of atherosclerotic artery

How does ulceration occur in atheroma and what does this lead to?

Fibrous cap becomes thin and breaks Thrombus can form

How may embolism occur as a result of atherosclerosis?

Bits of the atherosclerotic plaque may break off

How can vessels rupture as a result of atherosclerosis?

Calcification happens making vessels stiffer with less elastic recoil This can lead to vessels rupturing

What can arterial narrowing and occlusion cause?

Ischaemia Infarction It depends on the site and whether there is a lot of collateral circulation

How is haemorrhage caused by atherosclerosis bad?

New vessels grow into the plaque from the adventitia Bleeding into the plaque narrows the blood vessel since the plaque swells

What affects can atherosclerosis of arteries that lead to the brain have?

Cerebral ischaemia causing: Transient ischaemic attack Cerebral infarction = STROKE Vascular dementia Cerebral haemorrhage (stroke) due to artheromatous arteries being weaker and hypertensive leading to artery rupture

How can atherosclerosis affect the carotid arteries?

Transient Ischaemic attack (TIA) Possible embolism of atheromatous deposits to cerebral circulation

How can atherosclerosis affect the heart?

Sudden death Myocardial infarction Angina pectoris Arrhythmias Cardia failure The Umbrella term is ischaemic heart disease

What is the difference between stable angina and unstable angina?

stable = pain on exercise Unstable = pain anytime

If somebody survives a myocardial infarction, why are they likely to develop an arrhythmia?

Fibrous scar tissue replaces the specialised conduction cardiac myocytes Fibrous scar tissues cant conduct electrical currents as well

What can atherosclerosis of the Mesenteric artery cause?

Mesenteric ischaemia: Acute Mesenteric ischaemia - intestinal infarction Chronic Mesenteric ischaemia - Ischaemic colitis can lead to malabsorption

How does a normal bowel visibly differ to an ischaemic bowel?

Ischaemic bowel much darker and very easily broke/perforated when touched

What can be the consequence of atherosclerosis affecting peripheral arteries?

Acute limb ischaemia Intermittent claudication Ischaemic rest pain Gangrene

What are the 6 P’s for Acute and Chronic limb ischaemia?

Pain Pale/pallor Perishingly cold Parasthesia (Tingly) Paralysis Pulseless

How can atherosclerosis of the abdominal aorta have further negative affects?

Rupture of Abdominal aortic atheromatous material can lead to an embolus (Can cause acute limb ischaemia) Can lead to Aneurysmal formation, due to calcification once the artery expands it cant recoil so it stays enlarged Thrombosis

What risk factors increase the risk of atherosclerosis?

Age Gender Hyperlipidaemia Cigarette smoking Hypertension Diabetes mellitus Alcohol Infection Obesity Lack of exercise

How does gender increase the risk of atherosclerosis?

Women protected quite well before menopause Men more affected than women

What are the 2 main contributors of Hyperlipidaemia that is key to atherosclerosis?

Cholesterol LDL (Longest half life of lipoproteins)

What is the general structure of a lipoprotein?

Hydrophobic lipid core Hydrophilic outer layer of phospholipids and apolipoproteins

What is the very helpful lipoprotein particle and why?

HDL Removes cholesterol from cholesterol laden tissues to the liver to be metabolised

What affect do the Apolipoprotein defects ApoA1 deficiency /variants have?

Absent/reduced HDL

What happens if there is a defect in the Lipoprotein lipase enzyme? What is the function of Lipoprotein Lipase?

Type 1 Hyperlipidaemia Breaks down the TAG contained in a lipoprotein releasing it as fatty acids

What effect does a defect in the LDL receptors cause?

Elevated LDL levels

What is Famililal Hyperlipidaemia?

Genetic abnormalities of lipoproteins which can lead to early development of atherosclerosis

What are the associated signs of familial Hyperlipidaemia?

Corneal arcus Tendon Xanthomas Xanthelasma

What is a Xanthelasma?

Fatty deposits around the eye

How can you help treat familial Hyperlipidaemia?

Decrease total cholesterol and LDL in the diet Lipid lowering drugs (Statins Low fat and high fibre diet Aspirin

Why is smoking likely to increase chances of ischaemic heart disease?

Likely makes blood more coagulable Increased platelet activation

What is the likely mechanism that hypertension increases risk of atherosclerosis?

Endothelial cell damage as a result of the raised pressure allows migration of smooth muscle cells

How can atherosclerosis lead to an aortic /arterial aneurysm?

Calcification leads to the vessels losing their elasticity Once expanded via systole its difficult for them to return to their original size

What can help reduce the burden of atherosclerosis??

Statins Anti-hypertensives Exercise Normal BMI Non mover Alcohol (in moderation) Diabetic medication

Why does LDL have the longest half life making it more likely to get oxidised leading to the formation of foam cells, fatty streaks then atherosclerotic plaques?

Does not have the peripheral Apolipoproteins ApoC and ApoE So doesn’t bind to ApoC and ApoE receptors and the liver So it takes longer for receptor mediated endocytosis