L38 – Abnormal lipid metabolism; atherosclerosis Flashcards Preview

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Flashcards in L38 – Abnormal lipid metabolism; atherosclerosis Deck (66):
1

What are the 2 pathways for transportation of lipids by lipoproteins?

Exogenous and Endogenous pathways

2

What is first released in the exogenous pathway?

Mucosal cells in small intestine produce NASCENT CHYLOMICRONS from dietary lipids

3

Describe the nascent chylomicron secreted by small intestine mucosal cells at the start of exogenous pathway?

Contains apo B-48
TAG rich (TAG > CE, C)

4

What happens to nascent chylomicron in exogenous pathway?

HDL transfer apo C-II and apo E to n. chylomicron

n. chylomicron now has apo C-II, apo E and apo B48

5

What happens to chylomicron in capillaries of tissue in exogenous pathway?

After gaining apo E and apo C-II from HDL >
apo C-II activates lipoprotein lipase (LPL) >
TAG in chylomicron degraded into Fatty acid + glycerol

6

Fate of molecules released from chylomicron in exogenous pathway to tissue?

TAG in chylomicron broken down into FA and glycerol by LPL

FA enter into tissue
Glycerol to liver

7

After TAG break down in chylomicron at tissue in exogenous pathway, what happens to chylomicron?

Apo C-II is returned to HDL (previous given by HDL to activate LPL)

Becomes Chylomicron Remnant (CE-rich)

8

What apolipoproteins does chylomicron remnant contain?

Only apo E and apo B48

9

What happens to chylomicron remnant in exogenous pathway?

Chylomicron remnants bind through apo E to specific
receptors on liver > endocytosed

10

In the endogenous pathway , what is secreted to start the transport?

Liver secretes NASCENT VLDL (unlike exogenous where n. chylomicron is secreted)

11

Describe nascent VLDL in endogenous pathway.

TAG-rich

contain primarily endogenously synthesized lipids, apo B-100

12

What happens to nascent VLDL to turn it into mature VLDL in endogenous pathway?

HDL transfers apo C-II, apo E to nascent VLDL via cholesteryl ester transfer protein (CETP)

13

Describe mature VLDL.

TAG rich
apo B-100, apo E, apo C-II

14

What happens to mature VLDL in exogenous pathway?

Extracellular LPL activated by apo C-II on mature VLDL at capillaries > degradation of TAG into FA and glycerol

15

Fate of TAG breakdown by LPL in endogenous pathway?

TAG > FA + glycerol

FA enter into tissue
glycerol to liver

16

What processes turns mature VLDL to LDL in endogenous pathway?

mature VLDL return apo C-II and apo- E to HDL

No longer TAG-rich
CE- rich, only apo B-100

17

What happens to LDL in endogenous pathway?

LDL binds through apo B-100 to receptors on liver OR extrahepatic tissue to be endocytosed

18

What is the difference in the ultimate fate of lipid transport between endogenous and exogenous pathways?

Endogenous > LDL to either liver or extrahepatic tissue

Exogenous > Chylomicron remnant to liver

Both use different apo. to enter cells (LDL= apo B100, CR= apo E)

19

What forms nascent HDL? *

Free apo A1 + excess cholesterol from peripheral cell via ABCA1 channel

20

How does nascent HDL pick up even more cholesterol? *

from peripheral cells via ABCG1 channel

21

What converts all the cholesterol HDL picks up into internalized Cholesterylester (CE) ? *

LCAT on HDL surface

22

What is the role of HDL?

Bring cholesterol from peripheral tissue to liver

23

What receptor is important in the uptake of HDL to liver and steroid hormone-producing tissue? *

SR-B1 receptor

24

What receptor is for transfer of cholesterol to VLDL, LDL, IDL to move into liver? *

CETP channel

25

What is the role of Apo B-100?

Found on VLDL, LDL (and IDL)

For LDL receptor binding upon returning to liver/ enter extrahepatic tissue in endogenous pathway

26

What is the role of apo B-48?

Found in n. chylomicron, chylomicron, chylomicron remnant

For secretion of chylomicron (and VLDL)

27

What is the role of apo E?

Found on chylomicrons, HDL, LDL, VLDL

For chylomicron remnant receptor binding to uptake to liver in exogenous pathway

28

What is the role of apo A1 (and A2)? *

for formation of HDL (and chylomicron)

Act as LCAT activator on HDL > turn TAG into internalized CE

29

Role of apo C-II?

Found in HDL, CHylomicron, VLDL (and IDL)

For activation of Lipoprotein lipase to break down TAG into FA and glycerol

30

What is used in the centrifuge of blood to separate blood into its components?

Centrifuge blood with jelly (lighter than red cells, heavier than serum) > separate blood into serum and RBCs

31

Which bit of centrifuged blood is used to assess lipid abnormalities?

The serum

32

What is the colour of serum in fasted vs lipemia ?

Fasted = clear

Lipemia = cloudy

33

What 2 tests can be done to test for cholesterol in blood? *

Standing plasma test
Lipoprotein electrophoresis

34

What is Type I phenotype in Frederickson classification? Rare or not? What is in the blood? *

Chylomicronaemia

Rare

Accumulation of chylomicron in blood, very high TAG, cholesterol normal or slightly high

35

What causes Type I phenotype? *

Defective apo C2 (main reason)

LPL not activated by defect apo C-II, chylomicron not converted to c. remnant, accumulate in blood




36

What is the appearance of serum in Type I phenotype? *

Cream layer

chylomicron form distinct opaque band

Infranatant

37

What is one Type IIa phenotype? *

familial hypercholesterolaemia

38

What is defective to cause Type IIa ? Common or not? *

Deficient/ defective LDL receptor

in endogenous pathway LDL clearance into liver is hampered > accumulate of LDL


Most common

39

Appearance of serum of Type IIa?

Clear (LDL cant be seen)

40

What causes type IIb phenotype? *

Deficient/ defective LDL receptor AND Apo B-100

B-100 is found in LDL, VLDL, IDL

Defect leads to accumulation of all three

41

Appearance of serum in type IIb? *

Turbid to opaque

42

What is one type III phenotype?

familial dysbetalipoproteinemia

43

What is defective in type III? Common or Rare?

Apo E

present in chylomicron, chylomicron remnant, VLDL and IDL

IDL and Chylomicron remnant accumulate

Very rare

44

Appearance of serum in type III?

THIN cream layer (unlike type I thick cream)

Infranatant

45

Name one type IV phenotype? Common?

Sporadic hypertriglyceridemia

Very common

46

Cause of type IV?

unknown

Very high VLDL levels

Could be eating habits, diabetes, metabolic defects

47

Appearance of serum?

No cream

Turbid to opaque

48

Name one type of Type V phenotype?

familial hypertriglyceridemia

49

What causes type V?

low LPL

very high Chylomicrons and VLDL

rare

50

Appearance of type V serum?

Cream layer

Infranatant

51

What 2 genes are defective in Type IIa phenotype?

ARH and PCSK9

52

Which type of lipemia phenotype has no clinical findings/ subsequent diseases?

Familial hypertriglyceridemia

Type IV or V

53

Except for familial hypertriglyceridemia, what are the two common clinical findings for lipemia?

Xanthomas
Premature atherosclerosis

54

What is mixed hyperlipidemia?

Both hypercholesterolemia and hypertriglyceridemia

55

What is Hypertriglyceridemia associated with?

(e.g. type IV, V): elevated TAG is associated with increased insulin resistance

56

What is the remedy for Hypertriglyceridemia ?

Diet control

57

What is Hypercholesterolemia associated with?

type II

elevated serum LDL-cholesterol contribute to atherosclerosis / formation of atheroma

58

What is the remedy for Hypercholesterolemia ?

drug management

59

Which phenotype is associated with PCSK9 defect?

Type IIa

60

Which lipid is high in plasma in hypocholesterolemia?

LDL

Cholesterol rich, apo B

61

Explain action of PCSK9 on LDL regulation

LDL receptor expression is regulated by PCSK9

Normally, PCSK9 complexes with LDL receptor and degrades it

Type IIa defect: PCSK9 inhibited > prolong expression of LDL uptake > increase LDL uptake to cells

62

How come increased LDL uptake into cell in hypercholesterolemia (e.g. type IIa phenotype) is bad?

Increased plasma LDL >
LDL is small, infiltrate endothelium by passive diffusion > form atheroma/ lesion of fibrous plaque

63

What is the difference between activated and normal endothelial cells?

Activated endothelium = more permeable, more inflammatory cytokines and leukocyte adhesion molecules

Less antithrombotic molecules

64

What is the difference between activated and normal arterial smooth muscle cells?

Activated: more inflammatory cytokines, increase ECM synthesis and migration + proliferation into intima

65

What is the Ultimate complication of atherosclerosis?

Fibrous cap erupt > thrombosis > Stroke, Coronary artery disease, Myocardia infarction

66

Compare how common or rare the phenotypes are?

Type I, III - very rare
Type V - rare
Type IV - very common
Type IIa, IIb - MOST common

From rare to common:

1,3,5,4,2

Decks in MBBS I CPRS Class (78):