Cholesterol and Lipoprotein Metabolism Flashcards Preview

Cardiology > Cholesterol and Lipoprotein Metabolism > Flashcards

Flashcards in Cholesterol and Lipoprotein Metabolism Deck (30)
Loading flashcards...
1
Q

Which particle(s) contains ApoB-48?

A

Only chylomicrons. (and chylomicron remnants)

2
Q

Which particle(s) contains ApoB-100?

A

VLDL, IDL, and LDL

3
Q

Which particle(s) contains ApoE?

A

VLDL and HDL (and chylomicron remnants)

4
Q

Which particle(s) contains ApoC-II?

A

Chylomicrons and VLDL

5
Q

What makes the absorption of fats in chylomicrons via lymphatics special compared to the absorption of other nutrients?

A

These lymphatics bypass the liver, and fat can go straight to adipose for storage.

6
Q

When a chylomicron transitions to a chylomicron remnant, what lipoprotein(s) does it lose/gain?

A

It loses ApoC-II and picks up ApoE.

7
Q

How is are chylomicron remnants taken up by the liver?

A

The LDL receptor (LDLR) in hepatocytes binds ApoE on chylomicron remnants.

8
Q

What form of ApoB does this liver make? (and thus, what’s on all the transport particles made by the liver?)

A

ApoB-100

9
Q

What does LDLR recognize to take up particles?

A

ApoB-100 and ApoE

10
Q

7 non-genetic (“secondary”) causes of hyperlipoproteinemia?

not a list to memorize, but it shouldn’t surprise you

A
Diet
Alcohol (-> high TGs)
Insulin resistance / T2DM
Hypothyroidism
Nephrotic syndrome
Chronic renal failure
Meds (lots of them)
11
Q

What’s the mechanism for insulin resistance / T2DM leading to hyperlipoproteinemia?

A

Because glucose can’t be used, free fatty acids (FFAs) are liberated.
Increased FFA flux to liver leads to increased VLDL production.

12
Q

Which mutations cause Familial Chylomicronemia Syndromes? How? What “Frederickson/Levy” type are these?

A

Mutatations in ApoC-II or lipoprotein lipase (LPL).
With either missing, TGs can’t be removed from chylomicrons… and they build up.
These are Type I.

13
Q

What skin lesion is associated with Familial Chylomicronemia Syndromes (esp. LPL deficiency)? When will they erupt?

A

Eruptive xanthomas are associated with lipoprotein lipase deficiency. Eruptions tend to occur after high TG intake.

14
Q

What’s the major clinical issue associated with chylomicrons being too high?

A

Pancreatitis.

15
Q

What’s the genetic mutation in Familial dysbetalipoproteinemia? (it’s a poor name)
What “type” is this?

A

ApoE - such that it can’t bind LDLR.

This is Type III.

16
Q

What two processes is ApoE very important in? What do patients with ApoE mutations thus have in their blood?

A

Chylomicron remnant clearance.
IDL uptake into liver.
Pts without functional ApoE have high levels of “remnants” i.e. chylomicron remnants, and LDL.

17
Q

What skin lesions are associated with ApoE defects / aka dysbetalipoproteinemia / aka Type III hyperlipoproteinemia?

A

Tuberous xanthomas.

Palmar xanthomas.

18
Q

What clinical problem is associated with ApoE defects?

A

Increased coronary artery disease (from high LDL).
(Apparently the chylomicron remnants don’t do much harm? - not to be confused with chylomicrons, high levels of which can cause pancreatitis)

19
Q

What’s defective in Familial hypercholesteremia (FH)?

What “type” of hyperlipoproteinemia is this?

A
LDLR defect (heterozygous is bad, homozygous is worse).
This is Type IIa hyperlipoproteinemia.
20
Q

Which xanthomas are most specifically associated with FH?

A

Tendon xanthomas - on Achilles’ and tendons of hands.
(corneal arcus and xanthelasma can be present, but are less specific… for example xanthelasma happen in primary billiary sclerosis.)

21
Q

When do you see cutaneous xanthomas?

A

homozygous FH

22
Q

What do ApoB-100 mutations act just like? Why?

A

ApoB-100 is the ligand on LDL for LDLR.

Thus, ApoB-100 mutations “phenocopy” FH.

23
Q

What is mutated in autosomal dominant hypercholesterolemia 3 (ADH3)? What hyperlipoproteinemia type is this?

A

Pcsk9, with a gain of function mutation.

This is also type IIa hyperlipoproteinemia.

24
Q

What effect does a gain of function mutation in Pcsk9 have? Why is this effect dominant?

A

Pcsk9 targets LDLR for degredation. Too much Pcsk9 activity causes elevated levels of LDL (similar to FH). This is dominant because… it’s a gain of function mutation… one overactive copy of the gene will affect all the LDLRs.

25
Q

What causes familial hypertriglyceridemia? Which hyperlipoproteinemia type is this?

A

Defects in processing VLDL (removing TGs from the particles.)
This is type IV or V, where V is more severe.

26
Q

But wait. Doesn’t a defect in removing TGs from particles also cause familial hyperchylomicronemia?

A

Yes, though these are not mutations in LPL. If the defect if bad enough, chylomicron processing is affected, and you get Type V.
Type V = Type I + IV, which is cute.
(he didn’t go into what accounts for the difference in severity. The etiology is unknown.)

27
Q

What is elevated in Familial combined hyperlipidemia? What hyperlipoproteinemia type is this?

A

VLDL production is increased, but this also leads to elevations in LDL. This is Type IIb.
(the etiology is unknown)

28
Q

What’s the deal with lipoprotein(a) “little a”?

A

Lp(a) is an independent risk factor for CHD and has levels that are highly genetically determined.
Its function is unknown, though it’s homologous to plasminogen…

29
Q

Why has HDL long been though to be protective against atherosclerotic disease?

A

It is involved in reverse transport that removes cholesterol from places like macrophages (helping them not become nasty foam cells?) and brings it back to the liver.

30
Q

Does HDL really lower CHD risk?

A

We don’t know… People with SOME defects in HDL production (ApoA-1, LCAT) don’t have increased CHD risk. Other defects in HDL production/function (ABCA1) possibly do increase risk.