Hyperlipidemia

Question 1

LPL

Answer 1

catalyzes hydrolysis of TGs into FFA for entry into cells

• enzyme made by liver
• on endothelial cells
• stimulated by insulin and apoliprotein CII

Question 2

hepatic lipase

Answer 2

acts on LDL and HDL borne TGs

• enzyme on endothelium w/in liver
• functions like LPL but only for liver cells
• converts HDL2 to HDL3

Question 3

LCAT

Answer 3

transfers acyl groups from lecithin to cholesterol to create cholesterol esters

• enzyme made in liver
• interacts w/ apoA1 on HDL
• converts HDL1–>HDL2 and HDL2–>HDL3

Question 4

CETP

Answer 4

cholesterol ester transferase protein
converts cholesterol esters back to cholesterol for delivery to the liver
acts w/in HDL particle

Question 5

describe SCAP/SREBP-2 system

Answer 5

if intracellular chol is low: SCAP binds SREBP2 –> goes into nucleus and increases LDLR –> cell takes in more LDL and makes more cholesterol
if intracellular cholesterol is high: SCAP floats around in cytoplasm, doesn’t do anything

Question 6

ABC1

Answer 6

ATP binding casette protein 1

way for cells to get rid of excess cholesterol

Question 7

how does LDLR recognize LDL?

Answer 7

through B100 apolipoprotein

Question 8

PCSK9

Answer 8

secreted protein that binds to LDLR and targets it for degradation

Question 9

PPAR alpha

Answer 9

transcription activating factor, works w/ RXR factors

key determinant of VLDL synthesis

Question 10

what is quantitatively the most important determinant of circulating cholesterol levels?

Answer 10

LDLR

Question 11

how to calculate VLDL cholesterol

Answer 11

TG/5 - as long as the pt has a relatively normal TG level –> must be fasting for this measurement

Question 12

total chol =

Answer 12

LDL + VLDL + HDL

Question 13

desirable lipid measurements

Answer 13

TC < 180
TG < 150
LDL < 130
HDL >45
"non HDL cholesterol" < 150

Question 14

chilled tube test

Answer 14

in FASTING blood
excess chylos = white layer on top of clear serum
excess VLDL = cloudy

Question 15

primary hyperlipidemias - chylomicron excess

Answer 15

1. LPL deficiency
2. apoCII deficiency

sx: eruptive xanthomas, TG 1000-20000, pancreatitis
inheritance: very rare, R

Question 16

primary hyperlipidemia - VLDL excess

Answer 16

1. familial hypertriglyceridemia

2. familial combined hyperlipidemia

Question 17

familial hypertriglyceridemia

Answer 17

sx: TG 250-1000 / pancreatitis
inheritance: D
freq: 1%

Question 18

familial combined hyperlipidemia

Answer 18

elevated cholesterol, TD, LDL, varying presentation b/c family members

sx: eruptive and tuberous xanthomas, ASCVD
inheritance: D

Question 19

primary hyperlipidemia - ILDL excess

Answer 19

Remnant removal disease - 2 copies of ApoE2 –> accumulate ILDL
sx: cholesterol = TG, palmar and tuberous xanthomas, ASCVD

Question 20

primary hyperlipidemia - LDL excess

Answer 20

1. familial hypercholesterolemia
2. familial defective apo B100
3. familial combined hyperlipidemia
4. polygenic hypercholesterolemia

Question 21

familial hypercholesterolemia

Answer 21

freq 0.2% / Inher: D
Heterozygous: chol 350-550, ASCVD, tendon xanthomas
Homozygous: chol >650, ASCVD death b/f 20, tendon xanthomas

Question 22

familial defective apoB100

Answer 22

freq 0.02% / Inher: R

chol 350-500, ASCVD, tendon xanthomas

Question 23

polygenic hypercholesterolemia

Answer 23

eating badly, etc… –> ASCVD

Question 24

xanthalasma

Answer 24

fatty deposits around eyes

seen in high LDL but non-specific

Question 25

primary hyperlipidemia - HDL deficiency

Answer 25

Tangier's disease (ABC1 def). chol accumulation. very rare low HDL, ASCVD

Question 26

primary hyperlipidemia - lipo (a) excess

Answer 26

picked up in pts w/ high non-HDL cholesterol (included in this #) LDL molecule attached to a peptide - not included in LDL measurement

Question 27

secondary hyperlipidemia - chylomicron excess

Answer 27

renal failure

Question 28

secondary hyperlipidemia - VLDL excess

Answer 28

Alcohol, carbs, renal failure, uncontrolled diabetes, HAART, nephrotic syndrome, estrogens

Question 29

secondary hyperlipidemias - LDL excess

Answer 29

hypothyroidism, nephrotic syndrome, obstructive liver disease

Question 30

fibrates

Answer 30

bind PPARalpha, activate it --> reduced VLDL --> reduces TG and chol, increases HDL

Question 31

statins

Answer 31

inhibit HMGcoA reductase --> can't make intracellular chol --> increased LDLR expression decreased chol by 30-60% SE: Myositis

Question 32

Ezetimibe

Answer 32

blocks cholesterol absorption in intestines by preventing bile from helping w/ cholesterol absorption --> decreases LDL medication absorbed

Question 33

cholestyramine

Answer 33

binds bile salts and prevents chol reabsorption | medication not absorbed

Question 34

niacin

Answer 34

reduces VLDL production by liver --> reduces TG and chol, increases HDL

Question 35

Ab to PCSK-9

Answer 35

blocks PCSK-9 --> less LDLR degradation

Question 36

tx chylomicron excess

Answer 36

dietary restriction of saturated fat | avoid alcohol

Question 37

tx VLDL excess

Answer 37

``` dietary restriction of fats, carbs, alcohol PPARalpha agonists (fibrates) Niacin ```

Question 38

tx ILDL

Answer 38

same as VLDL = dietary restriction of fats, carbs, alcohol PPARalpha agonists (fibrates) Niacin

Question 39

tx LDL excess

Answer 39

dietary restrictions of cholesterol and saturated fats Bile acid sequestrants - cholestyramine HMGcoA reductase inhibitor - statin Cholesterol transport inhibition - ezetimibe

Question 40

which hyperlipidemia drug is bad in diabetes?

Answer 40

Niacin - increases blood sugar