Secondary Causes of Hyperlipidemia

Question 1

Despite the name, Secondary Causes of Hyperlipidemia should always be considered first!!

Question 2

The “baseline” lipids: determined by both
genetics (nature) & environment (nurture)
TG: mostly ___
LDL: mostly ___

Answer 2

The “baseline” lipids: determined by both
genetics (nature) & environment (nurture)
TG: mostly nurture
LDL: mostly nature

Question 3

note this flow chart

Question 4

what are the goals of therapy after you start a cholesterol lowering medication?

Answer 4

Question 5

outline drugs that can cause dyslipidemia/hyperlipidemia

Answer 5

1. anti-hypertensives– beta blockers, high dose thiazide diuretics.
2. steroids
3. protease inhibitors for HIV, anti-psychotics, retinoids, some immunosuppressants, bile acid binding resins.

Question 6

which disorders of metabolism can predispose someone to hyperlipidemia

Question 7

diseases that predispose someone to hyperlipidemia

Answer 7

n Diseases
n Chronic Renal Failure, Nephrotic Syndrome
n Liver disease
n Primary Biliary Cirrhosis, Hepatitis
n Some Autoimmune diseases

Question 8

compare and contrast a diet that causes elevated LDL-c vs a diet that elwevated triglcyerides.

Answer 8

Question 9

compare and contrast the 4D’s that cause elevated LDLc vs elevated triglycerides

Answer 9

Question 10

note the endogenous and exogenous pathway of lipid metabolism

Answer 10

Question 11

Very high triglycerides (>10 mmol/L)

Often indicates excess of the
main TG particle of the
__ cholesterol pathway

• there is an excess of __

Answer 11

Very high triglycerides (>10 mmol/L)

Often indicates excess of the
main TG particle of the
exogenous cholesterol pathway

- there is an excess of chylomicrons

Question 12

physical exam signs of high triglycerides vs high cholesterol

Answer 12

TGs; lipemia retinalis and eruptive xanthomata

Cholesterol: tendon xanthomas, xanthelasmas

Question 13

3 Common Lipid Abnormalities in Diabetes

Answer 13

High Triglycerides
Low HDL Cholesterol
LDL Cholesterol may be normal or moderately
elevated (but often small & dense)

Question 14

Answer 14

Question 16

LDL can’t be reported when ___ are too high

Answer 16

when triglycerides are too high (above 4)

Question 17

insulins role in lipoprotein metabolism

Answer 17

• insulin allows the lipid pathway to be facilitated. it allows LPL to breakdown chylomicrons and create remnants, which can be taken up by the liver.
• it also inhibits adipose tissue from producing FFAs that go to free fatty acids that tgo to the liver to produce more VLL. If wee are insulin deficient, we get more FFAs going to the liver to produce more VLDL, and then TGs go up,

therefore, in insulin resistance, there are more FFAs from adipose, more cholesterol because of more VLDL production, and less activation of LPL, which means chylomicrons stay in the blood more. You have higher TGs

Question 18

causes of increased production of VLDL (in type 2DM)

Answer 18

1. increased substrate; ie more ffas or glucose due to lipolysis or diet
2. less inhibition of VLDL synthesis by insulin
3. apoB synthesis increased ?? Does this affect LDL (insulin usually increases its DESTRUCTION)

Question 19

causes of decreased clearance of VLDL in type II DM

Answer 19

1. decreased LPL activity (LPL breaks down chylomicrons and also breaks down VLDL)

2. high ApoCIII (inhibits LPL) from low effective insulin
3. redcues cascade trhgouh IDL to LDL via HL?

Question 20

why is HDL often reduced in people with TIIDM

Answer 20

• may be a direct consequence of higher VLDL production, altering HDL composition (high TG)

- leads to higher HDL catabolism and clearance by HL

ApoA-1 usually low.

Question 21

L DL Metabolism in Type 2 DM

LDL levels increase slightly or remain stable– why?

Answer 21

in insulin resistance, there is reduced LPL activity (usually breaks down CMs and VLDLs), and therefore there is reduced LDL production

• in insulin resistance, there is retuced LDLreceptor expression and internalization
• glycosylation of Apo-B and LDL, decreased binding to LDL receptor– taken up by macrophages

- reduced LDL clearance “balances” the reduced production.

- there are also compositional changes of LDL, making them more atherogenic

Question 22

more insulin resistance = ___ LPL activity

Answer 22

reduced LPL activity. CM stay in blood, and VLDL also increases and it can’t be broken down to LDL.

Question 23

Question 24

MOA of statins

Answer 24

HMGCoAreductase inhibitors (prevent cholesterol synthesis)

Question 25

T?F statins are cardioprotective

Answer 25

true

Question 26

why does hypothyroidism cause hypercholesterolemia and hypertriglyceridemia?

Answer 26

lack of thyroid funcition
1. reduces LDL receptors (were not clearing the LDL as quickly), leading to increased LDL

2. recued LPL = high TG in blood because chylomicrons can’t be broken down.
3. reduced hepatic lipase. therefore, cholesterol remnants like IDL and VLDL backs up because they cannot be broken down to LDL (even if it did, LDL would have a reduced clearance because of 1)>

Question 27

what would you see on renal biopsy for nephrotic syndrome?

Answer 27

focal glomerular sclerosis.

• the higher maounts of cholesterol (usually LDL) causes sclerosis. There is more ApoB synthesis because it is stimulated by low albumin in proportion to urinary losses. There is reduced LDL clearance by the LDL receptors, .

No consistent HDL changes
n Risks of atherosclerosis with long standing nephrosis are unknown but probably high

Question 28

note:

Question 29

how does oral contraception cause dyslipidemia?

Answer 29

increases the production of VLDL, decreases LPL. Can lead to hypertriglyceridemic states and cause pancreatitis.

Question 30