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Path Y > Chemical Pathology - Lipoprotein metabolism, CVD and obesity > Flashcards

Chemical Pathology - Lipoprotein metabolism, CVD and obesity Flashcards

1
Q

What is the role of HDL?

A

Picks up excess cholesterol from the periphery and transports it to liver

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2
Q

What is the role of the enzyme CETP in cholesterol metabolism?

A

movement of cholesterol from HDL to VLDL conversion
movement of triglyceride from VLDL to HDL

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3
Q

What is the key enzyme involved in cholesterol synthesis?

A

HMG CoA reductase

rate determining step that converts HMG Coa to mevalonate in the synthesis of cholesterol

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4
Q

Which enzyme converts cholesterol to cholesteryl ester?

A

ACAT

Acyl-coenzyme A:cholesterol acyltransferases

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5
Q

What is VLDL constituted of?

A

ApolipoproteinB, cholesteryl ester and triglyceride

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6
Q

What is the function of 7-alpha hydroxase in cholesterol metabolism?

A

Converts cholesterol to bile acids

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7
Q

What is the main component of mixed micelles?

A

Bile acids

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8
Q

Where are bile acids resorbed?

A

Terminal ileum

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9
Q

What controls the amount of cholesterol resorbed into the intestine?

A

Balance of 2 transporters : NPC1L1 and ABC G5/G8

NPC1L1 mediates intestinal cholesterol absorption and it may also limit hepatobiliary cholesterol excretion,

responsible for biliary and transintestinal secretion of cholesterol and dietary sterols.

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10
Q

What is the inheritance pattern of familial hypercholesterolaemia type II?

A

dominant

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11
Q

What name is given to an inherited predeliction to high HDL, and what mutation causes this?

A

Familial hyperalphalipoproteinaemia
= CETP deficiency

Cholesteryl ester transfer protein

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12
Q

What condition is caused by ABC G5/G8 mutation?

A

Phytosterolaemia

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13
Q

What is phytosterolaemia?

A

AR Inherited condition that allows plant sterols to enter the plasma freely, which are more athrogenic than cholesterol itself causing premature atherosclerosis

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14
Q

Recall 3 clinical signs of hypercholesterolaemia

A

Xanthalasma
Arcus
Tendon xanthoma

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15
Q

How can you examine for tendon xanthoma?

A

Feel back of ACL

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16
Q

What are the different types of primary hypertriglyceridaemia? what’s the inheritance

A

I, IV and V
all dominant
characterized by the liver overproducing very-low-density lipoproteins (VLDL

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17
Q

What is A-beta-lipoproteinaemia?

A

MTP deficiency causing hypolipidaemia

Inability to absorb fat results in deficiencies of lipids and various essential vitamins

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18
Q

Recall 4 inherited conditions that can cause hypolipidaemia

A

A-beta-lipoproteinaemia - AR
Hypo-beta-lipoproteinaemia - AD
Tangier disease (HDL deficiency)
hypo-alpha-Lipoproteinaemia

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19
Q

What is the effect of statins on cholesterol levels?

A

Very effective at reducing LDL, also reduce triglyceride and HDL

20
Q

What is the effect of fibrate drugs on cholesterol levels?

A

Very effective at reducing triglycerides,

e.g fenofibrate

also reduces LDL

21
Q

What is the role of PCSK9?

A

Binds LDLR and promotes its degradation

22
Q

What is the mechanism of action of statins?

A

HMG coA reductase inhibition

23
Q

What is the most potent pharmacological agent at reducing low density lipoprotein concentration in blood?

A

evolocumab - pcsk9 inhibitor

another pcsk9 inhibitor is alirocumab

24
Q

what enzyme converts cholesterol in liver to bile acids

A

7a hydroxylase

25
Q

what packages cholesterol esters

A

Microsomal triglyceride transfer protein (MTP)

26
Q

what packages free cholesterol from periphery into HDLs

A

ABC A1

27
Q

give 4 types of primary hypercholesterolaemia

A

Familial hypercholesterolaemia (FH)
Polygenic hypercholesterolaemia
Familial hyper-a-lipoproteinaemia
phytosterolaemia

28
Q

give 3 mutations seen in FH

A

LDL-R
apoB
PCSK9

29
Q

result of a loss vs gain mutation in pcsk9

A

Gain-of-function mutations in PCSK9 have been associated to hypercholesterolemia and to an increase in cardiovascular risk. = FH!
In contrast, loss-of-function mutations in PCSK9 result in low LDL-c levels and seem to decrease the risk of coronary heart disease, without having any known negative impact on human health

30
Q

what 2 proteins in implicated in familial type 1 hypertriglyceridaemia

A

apoC 2 deficiency or lipoprotein lipase def (elevated chylomicrons)

31
Q

what gene in implicated in type 5 hypertriglyceridaemia

A

apoA-V deficiency

32
Q

what is mixed hyperlipadaemia, give an example of a disease

A

characterised by raised triglyceride AND cholesterol levels
familial dysbetalipoproteinemia

type 3 hyperlipoproteinameia aka

33
Q

what polymorphism in type 3 Hyperlipoproteinemia/familial dysbetalipo

A

Apoe2

(Apoe4 increases Alzheimers, ApoE2 decreases it)

34
Q

wat 2 signs are diagnostic of dysbetalipoproteinemia/type 3 Hyperlipoproteinemia

A

Yellow infiltration of the palmar creases
xanthoma on the elbows.

35
Q

what mutation in hypoalphalipoproteinaemia and hypobetalipoproteinaemia

A

hypo alpha = apoA-I mutations

hypo beta = truncated apoB

36
Q

mutation in ABC A1 causes

A

tangier disease
mutation causes HDL def

37
Q

Tangier disease is most often characterized by

A

enlarged orange- or yellow-colored tonsils. This discoloration is due to fatty deposits accumulating in the tonsils

38
Q

state a MTP inhibitor

A

lomitapide

39
Q

give an antiPCSK9 monoclonal antibody

A

REGN727 aka Alirocumab

40
Q

give a drug that inhibits inhibits apolipoprotein B 100 (apoB) protein synthesis

A

mipomersen
risk of liver damage

41
Q

give 3 drugs to treat FH

A

hetero - statins
homo - mipomersen, lomitapide

42
Q

give a CVD risk marker

A

lipoprotein a an ldl

43
Q

what drug to manage high lipoprotein a

A

nicotinic acid aka niacin
It is unique among the various lipid therapies in that it can not only reduce all of atherogenic lipid fractions (total cholesterol, low-density lipoprotein, very low-density lipoprotein, non-HDL lipoproteins, and triglycerides), but is also the most effective agent for raising high-density lipoprotein (specifically Apolipoprotein A-1). It is also the only lipid therapy that can lower lipoprotein (a).

44
Q

give 2 surgeries for obesity, which is better

A

billiopancreatic diversion > gastric bypass

(both better than medical therapy)

45
Q

ezetimibe targets what

A

NPC 1L1

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