Hyperlipidemia

Question 0

lipid circuit

Answer 0

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

Question 1

lipids by size

Answer 1

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

Question 2

circuit to deliver fat frm stores

Answer 2

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

Question 3

apoplipoproteins function

Answer 3

structure
activation of enzymes
ligands for recepotrs

Question 4

apoB100

Answer 4

interacts wtih B receptor

useful marker for atherogenic risk

Question 5

where is LPL made?

Answer 5

liver, localized to endothelium

Question 6

function of LPL

Answer 6

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

Question 7

Hepatic Lipase

Answer 7

acts ike LPL but only in liver

Question 8

LCAT

Answer 8

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

Question 9

CETP

Answer 9

cholesterol esterase transfer protein

converts cholesterol esters back to cholesterol for delivery to liver

Question 10

blocking CETP

Answer 10

increases HDL levels

Question 11

SCAP

Answer 11

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

Question 12

what activates SCAP

Answer 12

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

Question 13

SREBP2

Answer 13

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

Question 14

ABC1

Answer 14

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

Question 15

LDLR

Answer 15

LDL receptor on hepatocytes

interacts with apoB100 to pick cholesterol from blood into hepatocyte –> then recycles it back to its surface

Question 16

PCSK9

Answer 16

secreted protein that binds LDLR and targets it for removal

Question 17

blocking pCSK9

Answer 17

increases LDLR–>decreases cholseterol

Question 18

PPARa

Answer 18

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

Question 19

total cholesterol=

Answer 19

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

Question 20

total cholesterol calculation only works if

Answer 20

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

Question 21

measuring LDL does nto require

Answer 21

fasting- more direct measurement

Question 22

LDL cholesterol estimated=

Answer 22

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

Question 23

as TG go up..

Answer 23

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

Question 24

atherogenic cholesterol calculation

Answer 24

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

Question 25

fasting is only required for measuring

Answer 25

triglycerids

Question 26

total cholesterol

Answer 26

<180

Question 27

HDL chol

Answer 27

>46

Question 28

LDL chols

Answer 28

<130

Question 29

chilled tube test and fasting

Answer 29

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

Question 30

types of primary hyperlipidemias

Answer 30

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

Question 31

chylomicron excess

Answer 31

chylomicrons that you eat do not clear LPL deficiency & apoCII def

Question 32

clinical consequences of chylomicron excess

Answer 32

TG>1000 pancreatitis eruptive xnathomas

Question 33

VLDL excess diseases

Answer 33

familial hypertgemia | familial comvined hyperlipidemia

Question 34

familial hyperTGemia

Answer 34

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

Question 35

familial combined hyperlipidemia

Answer 35

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

Question 36

ILDL excess

Answer 36

familial dys-beta-lipproteinemia

Question 37

familial dysbetalipoproteinemia

Answer 37

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

Question 38

4 types of LDL excess diseases

Answer 38

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

Question 39

clinical pictures of LDL excess

Answer 39

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

Question 40

if patient lacks both LDL R

Answer 40

doesnt survive past teens

Question 41

HDL deficiency diseases

Answer 41

tangier's | ABC1 def

Question 42

Tangier's disease

Answer 42

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

Question 43

ABC1 def

Answer 43

can't get cholesterol out of cels

Question 44

Lipoa excess

Answer 44

LDL molecule with a moiety on it-atherogenic marker

Question 45

increased VLDL and ILDL can cause

Answer 45

fatty liver

Question 46

secondary hyperlipidemias

Answer 46

chylomicron excess VLDL excess LDL excess atherosclerosis

Question 47

chylomicron excess results from

Answer 47

(increased TG) | chronic renal failure

Question 48

VLDL excess results from

Answer 48

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

Question 49

LDL excess

Answer 49

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

Question 50

atherosclerosis is associated wtih

Answer 50

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

Question 51

treatment hyperlipidemia

Answer 51

best is statins + PCSK9 antibodies

Question 52

goal for statin therapy

Answer 52

reduce cholesterol to <100 mg/dl

Question 53

statins

Answer 53

stabilize plaque

Question 54

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

Answer 54

when LDL-C exceeds ~115 mg/dl

Question 55

tx chylomicron excess

Answer 55

restrict fats and alcohol

Question 56

CLDL excess

Answer 56

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

Question 57

ILDL excess

Answer 57

same as VLDL excess

Question 58

LDL excess

Answer 58

diet-reduce CHO and staurated fats | drugs

Question 59

drugs for LDL excess

Answer 59

bile acid sequestrants HMGcoa reductase inhibitors cholesterol transport inhibition

Question 60

cholestyramine, Welchol

Answer 60

bile acid sequesterants

Question 61

Statins

Answer 61

HMGcoa reducatse inhibitors

Question 62

ezetemibe

Answer 62

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

Question 63

fish oil

Answer 63

good for TG but not LDL