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Biochemistry And Endocrinology > Cholesterol, Lipoproteins And Cardiovascular Disease > Flashcards

Cholesterol, Lipoproteins And Cardiovascular Disease Flashcards

1
Q

Clinical patterns of Hyperlipidaemia - what do doctors measure?

A

Total cholesterol
Triglycerides
HDL
LDL

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2
Q

What are the biochemical markers of pure hyper cholesterolaemia?

A

Raised LDL cholesterol

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3
Q

What are the biochemical features of mixed Hyperlipidaemia?

A

Raised LDL cholesterol
Raised triglycerides
Low HDL cholesterol

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4
Q

What is mixed Hyperlipidaemia common in?

A

NAFLD, T2 diabetes, obesity, PCOS

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5
Q

Biochemical features of hypertriglyceridaemia? - what disease is this associated with?

A

Raised triglycerides associated with acute pancreatitis

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6
Q

What does pure hypercholesterolaemia and mixed Hyperlipidaemia put you more at risk of?

A

CVD

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7
Q

What are genetic causes of Hyperlipidaemia?

A

FH

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8
Q

Genetic causes of Hyperlipidaemia - What causes Hyperlipidaemia in FH?

A

A single gene change in:
- LDLR (LDL receptor) - makes the body less able to get rid of LDL so increased LDL in the body
- ApoB - LDL particle can’t attach to LDL receptor = increased LDL in system
- PCSK9 - destroys LDL receptors - gain of function leads to less LDL receptor and more LDL in system

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9
Q

What do all the genetic changes seen in FH cause?

A

Hypercholesterolaemia

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10
Q

Genetic Causes of Hyperlipidaemia - what is the genetic condition LPL deficiency? What specific illness does this lead to?

A

Less functional LPL leading to triglycerides not being able to be broken down and LPL hanging around in the blood.

Leads to hypertriglyceridaemia

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11
Q

Genetic Causes of Hyperlipidaemia - what causes the mixed Hyperlipidaemia - type 3 hyper lipoproteinaemia and what does this do?

A

Genetic change in ApoE causing limited uptake of chylomicrons, chylomicron remnants and IDL. This results in high cholesterol an triglycerides as these cannot be taken into hepatic cells.

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12
Q

Non-gentic causes of Hyperlipidaemia?

A

Other diseases - obesity, PCOS, obesity which all confer insulin resistance.

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13
Q

What does insulin resistance do to cause mixed Hyperlipidaemia?

A

Lowers LPL which increases VLDL which causes the overloading of HDL with triglycerides and then the HDL is targeted by LPL which lowers HDL.

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14
Q

How does NAFLD, ALD cause Hyperlipidaemia?

A

Increases hepatic triglycerides which increases VLDL

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15
Q

How does cholestasis lead to hyperlipidaemia?

A

leads to hepatic cholesterol accumulation and LDLR decrease and LDL increase.

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16
Q

Hormones can cause hyperlipidaemia - what disease causes this and how?

A

Hyperthyroidism, Cushing and exogenous glucocorticoids through decreasing LPL which increases VLDL and decreasing LDLR which increases LDL.

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17
Q

How does post menopausal status with reduced oestradiol cause hyperlipidaemia?

A

Decreases LDLR and increases LDL

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18
Q

Age and lifestyle including a diet high in saturated fats can cause hyperlipidaemia how does this affect biochemistry?

A

Food increases cholesterol which lowers LDLR and therefore increases LDL

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19
Q

Can all these cause CVD’s?

A

Yes

20
Q

What type of CBVD’s can hyperlipidaemia cause?

A

Stroke, MI

21
Q

Prevention and treatment - how do you treat an acute MI?

A

Re-perfusion via primary PCI, drug eluding stents (this involves putting a wire through the artery and inflating the balloon to unblock artery and leave a stent to keep artery open.

22
Q

What are the two classes of CVD?

A

Primary (stopping healthy individuals having a CVD) and secondary (stopping someone who has already had one having further CVD’s).

23
Q

Lifestyle changes to prevent a CVD?

A

Stopping smoking
Lose weight
excessive

24
Q

What drugs do you get after having an MI?

A

ACE-inhibitor, beta blocker - reduces post MI mortality
Aspirin and clopidogrel
Statins

25
Q

Is Statins used in primary prevention and secondary prevention?

A

Yes

26
Q

What are the most common primary prevention?

A

Lifestyle change

27
Q

Who would you treat with drugs in primary prevention?

A

Treat those at highest risk of a CVD in the next ten years and those with lowest risk of side affects.

28
Q

How do you work out risk?

A

Use ASSIGN score which assess and gives you a percentage risk of CVD in next ten years.

29
Q

Postcode - who is more likely to get CVD?

A

Least affluent

30
Q

How do they decide who would get given the drugs - intervention in primary prevention?

A

Mainly due to cost of prescribing drugs

31
Q

They want to give everyone over what age statins because they are cheap?

A

40

32
Q

Why are people not wanting to take drugs in primary prevention?

A

They don’t think they need it as they don’t actually have any disease, lack of education

33
Q

What do statins do?

A

Reduce LDL cholesterol and lowers CVD risk

34
Q

What does Ezetimibe do?

A

Lowers LDL cholesterol and lowers risk or coronary heart disease
Usually adjunct to statins

35
Q

What do fibrates do?

A

Reduce LDL cholesterol and triglycerides and increases HDL cholesterol
Only beneficial though if you ave have low HDL and high triglycerides
Usually an adjunct to statin

36
Q

How do statins work?

A

They are HMG-CoA reductase inhibitors which inhibit the rate limiting step of cholesterol synthesis meaning there is less intracellular cholesterol and therefore higher LDL uptake.

37
Q

How does ezetimibe work?

A

Inhibits cholesterol absorption at small intenstine and binds to NPC1L1 protein which is a critical mediator for cholesterol absorption in the GI epithelial cells

38
Q

How do fibrates work?

A

Stimulate PPAR which is a nuclear transcription factor.
Causes increased LPL activity, hepatic fatty acid oxidation
enhanced IDL, LDL uptake and reduced VLDL synthesis

39
Q

what are the two forms of PCSK9-inhibitors?

A

Monoclonal antibodies (allrocuamab, evolocumab) nd siRNA therapy (inclusiran)

40
Q

How does the monoclonal antibodies affect PCSK9-inhibitors?

A

Binds PCSK9 to inhibit function
It’s a 2 week injection
Is adjunct to statin

41
Q

How does the siRNA therapy affect PCSK9?

A

Suppresses translation of mRNA into PCSK9 protein
6 monthly injection
Is adjunct to statin

42
Q

Do all these drugs reduce CVD risk?

A

Yes

43
Q

What are some future lipid lowering drugs? (Still in trial)

A

Vaccine (AFFITOPE) and Crispr-cas9 (adenovirus deliver)

44
Q

How would a vaccine help lower lipids with PCSK9?

A

Stimulate endogenous antibodies to inhibit PCSK9 and would be needed in an annual booster

45
Q

How would crisper-cas9 lower lipids?

A

Gene editing to definitively reduce PCSK9 levels and this would be a one off life long treatment.

Biochemistry And Endocrinology (16 decks)

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