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S2 Case 5 - Heart Failure & Cardiac Arrhythmias > Atherosclerosis + Hypercholesterolaemia > Flashcards

Atherosclerosis + Hypercholesterolaemia Flashcards

1
Q

Describe cholesterol transport

A

Chylomicrons transport lipids from the gut to periphery
In liver bind to LDL receptors via ApoE
Endocytosed + deliver triglycerides, cholesterol + cholesterol esters
Activate LPL with their ApoCII = fatty acids released

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2
Q

Describe how hypercholesterolemia works

A

Elevated cholesterol-rich LDL in serum
Increases binding of LDL to scavenger receptor
= mediates incorporation of cholesterol in macrophages, skin + vessel walls

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3
Q

What is atherosclerosis?

A

Slowly progressing arterial disease in which intima thickened by fibrous deposits that narrow the lumen + become site of thrombus formation

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4
Q

What happens later on with atherosclerosis as it progresses?

A

Fibrous plaque forms

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5
Q

Describe the formation of plaque

A

In response to endothelial injury
Monocytes adhere to endothelial cells
Move to intima + transformed to macrophages
Macrophages consume excess modified lipoprotein = become foam cells
Release growth factors + cytokines that stimulate migration of smooth muscles
Proliferate to produce collagen

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6
Q

What type of plaque is most vulnerable to rupture?

A

Soft

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7
Q

When does a fibrous cap develop?

A

Smooth muscle migrate to intima = tough fibrous matrix that glues cells together

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8
Q

Describe structure of unstable plaque

A

Lipid-core rich + substantial inflammatory cell infiltration
Thin fibrous cap

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9
Q

What is unstable plaque prone to?

A

Plaque disruption by ulceration
= thrombus formation

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10
Q

Describe the structure of stable plaque

A

Thick fibrous cap

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11
Q

Describe the evolution of plaque

A

Initial lesion
Fatty streak
Intermediate lesion
Atheroma
Fibroatheroma
Complicated lesion

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12
Q

What are the causes of the atherosclerosis?

A

Hyperlipidaemia
Smoking
Primary inherited disorders
Secondary lipid disorders

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13
Q

What is hyperlipidaemia?

A

Serum cholesterol >6.85 mmol/L

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14
Q

What is an example of a primary inherited disorder?

A

Familial hypercholesterolaemia

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15
Q

What are examples of secondary lipid disorders?

A

Liver disease
Nephrotic syndromes
Hypothyroidism

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16
Q

Describe the consequences of atherosclerosis

A

Narrowing of lumen leads to ischaemic heart disease
Stiffening of vessel wall
Bleeding
Thrombus formation = peripheral emboli

17
Q

What are the clinical options for atherosclerosis?

A

Dietary changes to reduce cholesterol + lipids
Cessation of smoking
Control of BP
Control of diabetes
Exercise
Drugs to reduce plasma cholesterol

18
Q

What are the different strategies for lipid lowering drugs?

A

Inhibition of cholesterol synthesis
Prevention of cholesterol reabsorption
Reduction of VLDL secretion
Increased synthesis of lipoprotein lipase

19
Q

Which drugs inhibit cholesterol synthesis?

A

Statins

20
Q

What are examples of statins that inhibit cholesterol synthesis?

A

Lovastatin
Atorvastatin

21
Q

What is the mechanism of action for the inhibition of cholesterol synthesis?

A

Inhibit HMG-CoA reductase

22
Q

What are the side effects of statins?

A

May damage skeletal muscle or liver
Interfere with myelination in infants (contraindicated in pregnancy)

23
Q

Which drugs prevent cholesterol absorption?

A

Resins

24
Q

What are examples of resins that prevent cholesterol absorption?

A

Cholestyramine
Colestipol

25
Q

What are the side effects of resins?

A

Unpleasant gritty taste
GI tract discomfort
Interference of vitamin or drug absorption

26
Q

What is the mechanism of action for resins?

A

Non-absorbable macromolecules that bind cholesterol preventing reabsorption into cut

27
Q

Which drugs reduce VLDL secretion?

A

Niacin

28
Q

What are examples of Niacin that reduce VLDL secretion?

A

Nicotinic acid
Vitamin B3

29
Q

What is the mechanism of action for reducing VLDL secretion?

A

Decrease in secretion of VLDL particles from liver

30
Q

What are the side effects of Niacin?

A

Flush with rash BUT reduced with aspirin

31
Q

Which drugs increase synthesis of lipoprotein lipase?

A

Fibrates

32
Q

What are examples of fibrates?

A

Gemfibrozil
Fenofibrate

33
Q

What is the mechanism of action for fibrates?

A

Activate peroxisome proliferation-activated receptor alpha
Increase lipoprotein lipase synthesis + beta-oxidation of lipids

34
Q

What are the side effects of fibrates?

A

Nausea
Skin rash
Occasional risk of gallstones

S2 Case 5 - Heart Failure & Cardiac Arrhythmias (12 decks)

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