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?

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?

24
Q

What are examples of resins that prevent cholesterol absorption?

A

Cholestyramine
Colestipol

25
What are the side effects of resins?
Unpleasant gritty taste GI tract discomfort Interference of vitamin or drug absorption
26
What is the mechanism of action for resins?
Non-absorbable macromolecules that bind cholesterol preventing reabsorption into cut
27
Which drugs reduce VLDL secretion?
Niacin
28
What are examples of Niacin that reduce VLDL secretion?
Nicotinic acid Vitamin B3
29
What is the mechanism of action for reducing VLDL secretion?
Decrease in secretion of VLDL particles from liver
30
What are the side effects of Niacin?
Flush with rash BUT reduced with aspirin
31
Which drugs increase synthesis of lipoprotein lipase?
Fibrates
32
What are examples of fibrates?
Gemfibrozil Fenofibrate
33
What is the mechanism of action for fibrates?
Activate peroxisome proliferation-activated receptor alpha Increase lipoprotein lipase synthesis + beta-oxidation of lipids
34
What are the side effects of fibrates?
Nausea Skin rash Occasional risk of gallstones