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Flashcards in Hyperlipidemia Deck (64)
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lipids by size

chylomicron>VLDL>IDL>LDL>HDL
increase desnity and protein
decrease in size and TG

1

lipid circuit

fat from food-->small intestine-->cylomicrons-->blood-->meet LPL (stimulated by insulin)-->release FFA from chylomicron-->chylo get smaller until picked up by liver as VLDL

2

circuit to deliver fat frm stores

fasting-->liver exports TG and cholesterol as VLDL-->LPL in blood chews it up-->becomes LDL and HDL

3

apoplipoproteins function

structure
activation of enzymes
ligands for recepotrs

4

apoB100

interacts wtih B receptor
useful marker for atherogenic risk

5

where is LPL made?

liver, localized to endothelium

6

function of LPL

when stimulated by insulin apoC2, hydrolyzes TGs to phospholipids and glycerol

7

Hepatic Lipase

acts ike LPL but only in liver

8

LCAT

interacts wtih apoA1 on HDL-creates cholesterol esters so cholesterol is easier to carry around

function is HDL maturation, does this by transferring acyl group from lecithin to chlesterol-->choelsterol ester

9

CETP

cholesterol esterase transfer protein
converts cholesterol esters back to cholesterol for delivery to liver

10

blocking CETP

increases HDL levels

11

SCAP

SREBP cleaving protein
sensor for lower intracellular sterol
if low-->binds SREBP2-->allows cleavage and activation-->brings in more LDL

12

what activates SCAP

low cholesterol diets and meds that decrease cholesterol production (niacin, statins) making cells take more cholesterol in

13

SREBP2

a TF activated by SCAP in response to low cholesterol-->increases HMGCOA expression-->increases cholseterol in LDL form-->the cell takes up more LDL

14

ABC1

transfers cholesterol to cell membrane to interact with apo1 on HDL for pickup by HDL

15

LDLR

LDL receptor on hepatocytes
interacts with apoB100 to pick cholesterol from blood into hepatocyte --> then recycles it back to its surface

16

PCSK9

secreted protein that binds LDLR and targets it for removal

17

blocking pCSK9

increases LDLR-->decreases cholseterol

18

PPARa

TF that upregulates genes involved in FA uptake and oxidation, a key determinant of VLDL synthesis

19

total cholesterol=

LDL cholesterol + VLDL cholesterol (aka TG/5) + HDL cholesterol

20

total cholesterol calculation only works if

relatively normal TF levels, so need to do it in fasting state

21

measuring LDL does nto require

fasting- more direct measurement

22

LDL cholesterol estimated=

total-HDL-TG/5 (as long as TG <250)

23

as TG go up..

moer get carried by non-CLDL particles, so VLDL does not equal TG/5

24

atherogenic cholesterol calculation

non-hdl cholesterol=total-HDL cholesterol
*includes VLDL LDL & apoB lipoproteins

25

fasting is only required for measuring

triglycerids

26

total cholesterol

<180

27

HDL chol

>46

28

LDL chols

<130

29

chilled tube test and fasting

will remove chylomicrons unless patient has a disease that cant remove chylomicrons

30

types of primary hyperlipidemias

chylomicron excess
VLDL excess
ILDL excess
LDL excess
HDL deficiency
Lipoa excess

31

chylomicron excess

chylomicrons that you eat do not clear

LPL deficiency & apoCII def

32

clinical consequences of chylomicron excess

TG>1000
pancreatitis
eruptive xnathomas

33

VLDL excess diseases

familial hypertgemia
familial comvined hyperlipidemia

34

familial hyperTGemia

TG 250-1000
pancreatitis
increased hepatic production of VLDL OR LPL def
decreases LDL, so total cholesterol not high

*NOT associated with ASCVD*

35

familial combined hyperlipidemia

increased total cholesterol (TG, LDL, VLDLetc) decreased HDL
eruptive and tuberous xanthomas, ASCVD
decreased LDLR or increased apoB

36

ILDL excess

familial dys-beta-lipproteinemia

37

familial dysbetalipoproteinemia

must have 2 ApoE genes
remnant removal disorder- very rare
cholesterol = TG
palmar and tuberous xanthomas
ASCVD

38

4 types of LDL excess diseases

familial hypercholesterolemia-LDLR def
familial defective ApoB100-defective protein
familial combined hyperlipidemia- clearing issues (LDL R)
polygenic hypercholesterolemia- high fat diet

39

clinical pictures of LDL excess

NO pancreatitis
LDL accumulates in extensor tendons
cholesterol between 350-550
**ASCVD

40

if patient lacks both LDL R

doesnt survive past teens

41

HDL deficiency diseases

tangier's
ABC1 def

42

Tangier's disease

very rare decrease in HDL, ASCVD, tangier's tonsils

43

ABC1 def

can't get cholesterol out of cels

44

Lipoa excess

LDL molecule with a moiety on it-atherogenic marker

45

increased VLDL and ILDL can cause

fatty liver

46

secondary hyperlipidemias

chylomicron excess
VLDL excess
LDL excess
atherosclerosis

47

chylomicron excess results from

(increased TG)
chronic renal failure

48

VLDL excess results from

(increased TG and cholesterol)--alcohol, CHO inducisble, uncontrolled DM, HAART, nephrotic syndrome, estrogens

49

LDL excess

(increased cholesterol)
hypothyroidism
nephritic syndrome
obstructive liver disease
high cholesterol diet

50

atherosclerosis is associated wtih

increased LDL, ILDL, and small desnse VLDL
NOT associated with normal VLDL or chylomicrons

51

treatment hyperlipidemia

best is statins + PCSK9 antibodies

52

goal for statin therapy

reduce cholesterol to <100 mg/dl

53

statins

stabilize plaque

54

start therapy for high rsk patients (>20% 10 year risk for CHD)

when LDL-C exceeds ~115 mg/dl

55

tx chylomicron excess

restrict fats and alcohol

56

CLDL excess

restrict diet, drugs
PPAR a agonists - gemifibrizol, fenofibrate
Niacin

57

ILDL excess

same as VLDL excess

58

LDL excess

diet-reduce CHO and staurated fats
drugs

59

drugs for LDL excess

bile acid sequestrants
HMGcoa reductase inhibitors
cholesterol transport inhibition

60

cholestyramine, Welchol

bile acid sequesterants

61

Statins

HMGcoa reducatse inhibitors

62

ezetemibe

cholesterol transport inhibition
--taken up by intestinal BB-->liver activates-->excreted in bile-->acts as BB to block cholesterol and bile salt uptake

decreases intrahepatic cholesterol-->increases expression of LDLR

63

fish oil

good for TG but not LDL