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
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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
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circuit to deliver fat frm stores
fasting-->liver exports TG and cholesterol as VLDL-->LPL in blood chews it up-->becomes LDL and HDL
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apoplipoproteins function
structure
activation of enzymes
ligands for recepotrs
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apoB100
interacts wtih B receptor
useful marker for atherogenic risk
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where is LPL made?
liver, localized to endothelium
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function of LPL
when stimulated by insulin apoC2, hydrolyzes TGs to phospholipids and glycerol
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Hepatic Lipase
acts ike LPL but only in liver
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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
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CETP
cholesterol esterase transfer protein
converts cholesterol esters back to cholesterol for delivery to liver
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blocking CETP
increases HDL levels
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SCAP
SREBP cleaving protein
sensor for lower intracellular sterol
if low-->binds SREBP2-->allows cleavage and activation-->brings in more LDL
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what activates SCAP
low cholesterol diets and meds that decrease cholesterol production (niacin, statins) making cells take more cholesterol in
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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
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ABC1
transfers cholesterol to cell membrane to interact with apo1 on HDL for pickup by HDL
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LDLR
LDL receptor on hepatocytes
interacts with apoB100 to pick cholesterol from blood into hepatocyte --> then recycles it back to its surface
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PCSK9
secreted protein that binds LDLR and targets it for removal
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blocking pCSK9
increases LDLR-->decreases cholseterol
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PPARa
TF that upregulates genes involved in FA uptake and oxidation, a key determinant of VLDL synthesis
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total cholesterol=
LDL cholesterol + VLDL cholesterol (aka TG/5) + HDL cholesterol
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total cholesterol calculation only works if
relatively normal TF levels, so need to do it in fasting state
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measuring LDL does nto require
fasting- more direct measurement
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LDL cholesterol estimated=
total-HDL-TG/5 (as long as TG <250)
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as TG go up..
moer get carried by non-CLDL particles, so VLDL does not equal TG/5
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atherogenic cholesterol calculation
non-hdl cholesterol=total-HDL cholesterol
*includes VLDL LDL & apoB lipoproteins
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fasting is only required for measuring
triglycerids
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total cholesterol
<180
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HDL chol
>46
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LDL chols
<130
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chilled tube test and fasting
will remove chylomicrons unless patient has a disease that cant remove chylomicrons
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types of primary hyperlipidemias
chylomicron excess
VLDL excess
ILDL excess
LDL excess
HDL deficiency
Lipoa excess
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chylomicron excess
chylomicrons that you eat do not clear
LPL deficiency & apoCII def
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clinical consequences of chylomicron excess
TG>1000
pancreatitis
eruptive xnathomas
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VLDL excess diseases
familial hypertgemia
familial comvined hyperlipidemia
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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*
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familial combined hyperlipidemia
increased total cholesterol (TG, LDL, VLDLetc) decreased HDL
eruptive and tuberous xanthomas, ASCVD
decreased LDLR or increased apoB
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ILDL excess
familial dys-beta-lipproteinemia
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familial dysbetalipoproteinemia
must have 2 ApoE genes
remnant removal disorder- very rare
cholesterol = TG
palmar and tuberous xanthomas
ASCVD
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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
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clinical pictures of LDL excess
NO pancreatitis
LDL accumulates in extensor tendons
cholesterol between 350-550
**ASCVD
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if patient lacks both LDL R
doesnt survive past teens
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HDL deficiency diseases
tangier's
ABC1 def
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Tangier's disease
very rare decrease in HDL, ASCVD, tangier's tonsils
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ABC1 def
can't get cholesterol out of cels
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Lipoa excess
LDL molecule with a moiety on it-atherogenic marker
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increased VLDL and ILDL can cause
fatty liver
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secondary hyperlipidemias
chylomicron excess
VLDL excess
LDL excess
atherosclerosis
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chylomicron excess results from
(increased TG)
chronic renal failure
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VLDL excess results from
(increased TG and cholesterol)--alcohol, CHO inducisble, uncontrolled DM, HAART, nephrotic syndrome, estrogens
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LDL excess
(increased cholesterol)
hypothyroidism
nephritic syndrome
obstructive liver disease
high cholesterol diet
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atherosclerosis is associated wtih
increased LDL, ILDL, and small desnse VLDL
NOT associated with normal VLDL or chylomicrons
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treatment hyperlipidemia
best is statins + PCSK9 antibodies
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goal for statin therapy
reduce cholesterol to <100 mg/dl
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statins
stabilize plaque
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start therapy for high rsk patients (>20% 10 year risk for CHD)
when LDL-C exceeds ~115 mg/dl
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tx chylomicron excess
restrict fats and alcohol
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CLDL excess
restrict diet, drugs
PPAR a agonists - gemifibrizol, fenofibrate
Niacin
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ILDL excess
same as VLDL excess
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LDL excess
diet-reduce CHO and staurated fats
drugs
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drugs for LDL excess
bile acid sequestrants
HMGcoa reductase inhibitors
cholesterol transport inhibition
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cholestyramine, Welchol
bile acid sequesterants
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Statins
HMGcoa reducatse inhibitors
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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
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