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Flashcards in lecture 2 Deck (28):
1

lipoproteins

large macromolecular complexes that transport hydrophobic lipids: TGs, cholesterol, & fat-soluble vitamins (plasma, interstitial fluid & lymph)

2

function of lipoproteins

-the absorption of dietary cholesterol, long-chain fatty acids & fat-soluble vitamins
- transport TGs, cholesterol, & fat-soluble vitamins from the liver to peripheral tissues & the transport of cholesterol from peripheral tissues to the liver

3

apolipoproteins

- activate enzymes important in lipoprotein metabolism
- ligands for cell surface receptors

4

ApoA-I, ApoA-II

HDL

5

ApoB-48

chylomicrons
intestine

6

ApoB-100

VLDL, IDL, LDL
liver

7

ApoE, ApoC

chylomicrons, VLDL, IDL
metabolism & clearance

8

ApoB does not

transfer between lipoproteins

9

primary disorders of lipoprotein metabolism

genetic
familial hypercholesterolemia

10

secondary disorders of lipoprotein metabolism

obesity
DM (esp T2)
thyroid diseases
renal diseases
liver diseases
alcohol
estrogen
lysomal storage disease
cushing's syndrome
drugs

11

familial hypercholesterolemia

an autosomal codominant disorder characterized by elevated plasma levels of LDL-C with normal TGs, tendon xanthomas & premature coronary atherosclerosis
- large # of LDL receptor mutations

12

elevated LDL-C in FH are due to

an increase in the production of LDL from IDL& delayed removal of LDL from the blood

13

TC levels in FH

>500mg/dL & can be higher than 1000mg/dL in homozygotes
200-400mg/dL in hetero

14

FH can lead to

- accelerated atherosclerosis, which can result in disability & death in childhood
- symptomatic coronary atherosclerosis before puberty (homo)
- symptoms can be atypical & sudden death is NOT uncommon

15

FH homozygous diagnosis

- family history
- skin biopsy measuring LDL receptor activity in cultured skin fibroblasts
- flow cytometry analysis of LDL receptor density on lymphocytes
- DNA sequencing to find mutations in LDL receptor gene

16

obesity

- increased adipose tissue mass
- insulin resistance
- increased FFAs are delivered to the liver from adipose tissue- VLDLs
- high insulin promotes FA synthesis in the liver
- Low HDL-C

17

secondary alterations in lipid metabolism examples

obesity
DM
hypothyroidism
renal disorders
liver disorders
alcohol

18

T1DM

- type 1 usually w/out hyperlipidemia if glycemia is under control
- ketoacidosis--hyperTGs due to increased hepatic FFA influx from adipose tissue

19

T2DM

- decreased LPL activity
- increased release of FFA from adipose
- increased synthesis of FA in the liver
- increased hepatic production of VLDLs
- elevated levels of TGs from VLDL
- increased LDL
- decreased HDL-C

20

hypothyroidism

- elevated LDL-C due to a reduction in hepatic LDL receptor function, delaued clearance of LDL
- increased circulating IDL
- some times- mild hyperTG
- all pts presenting with incr. plasma LDL-C, IDL or TGs should be screened for hypothyroidism

21

nephrotic syndrome

- characterized by significant proteinuria (3.5g/day/1.73m^3BSA)
-hypercholesterolemia or hyperTG; a combination of increased hepatic production & decreased clearance of VLDLs with increased LDL production

22

end stage renal disease (ESRD)

mild hyperTG (<300mg/dL) due to accumulation of VLDLs and remnant lipoproteins in the circulation

23

renal transplants

usually have increased lipid levels due to the effect of the drugs required for immunosuppression (cyclosporine & glucocorticoids) & present a difficult management problem since HMG-CoA reductase inhibitors must be used cautiously in these pts

24

hepatitits

increased VLDLs & mild-moderate hyperTG
- severe hepatitis & liver failure- reduced plasma cholesterol & TGs

25

choestasis

- hypercholesterolemia- free cholesterol, coupled with phospholipids, is secreted into the plasma as a constituent of a lamellar particle called LP-X. the particles can deposit in skin folds, producing lesions resembling those seen in patients with FDBL. Planar and reuptice xanthomas can also be seen in pts with cholestasis

26

alcohol

- increased plasma TG levels
increased hepatic secretion of VLDL
- regular consumption- HDL-C up

27

screening

all adults older than 20 should have plasma levels of cholesterol, TG, LDL-C, and HDL-C measured after 12-hour overnight fast

28

diagnosis

- determine the class of altered lipoproteins
- rule out secondary causes of hyperlipidemia