Chem Path: Brief lipid update

Question 1

What is the cholesterol distribution in fasting plasma

Answer 1

13% VLDL
70% LDL
17% HDL

Question 2

What are mixed micelles?

Answer 2

They are the major component of bile acids

Question 3

Which enzyme facilitates transport of mixed micelles from the small intestine to the lymphatics/liver?

Answer 3

NPC1L1

Question 4

Which enzymes facilitate movement of cholesterol from lymphatics back to the small intestine

Answer 4

ABC G5 and G8

Question 5

What does cholesterol downregulate in the liver

Answer 5

HMG CoA reductase

Question 6

Where do bile acids get absorbed

Answer 6

Terminal ileum

Question 7

What are the 2 fates of cholesterol in the liver?

Answer 7

They can get hydroxylased into bile acids

They get turned into esters by ACAT

Question 8

What happens to cholesterol esters in the liver

Answer 8

Get attached to VLDL by MTP and apoB TG

Question 9

What is the difference between HDL and LDL

Answer 9

HDL brings cholesterol from peripheral cells to the liver, while LDL does the opposite

Question 10

How does HDL collect cholesterol from the cells

Answer 10

Via ABC A1

Question 11

What happens to VLDL

Answer 11

It is the precursor to LDL

It also get converted to HDL vis CETP and cholesterol esters and HDL gets turned into VLDL via CETP and triglycerides

Question 12

What is the triglyceride distribution in fasting plasma

Answer 12

55% VLDL
29% LDL
11% HDL
Transient increase in chylomicrons after eating

Question 13

How are triglycerides processed and transported in the capillaries

Answer 13

Fatty foods are broken down into FAs, which are further broken down into triglycerides, which are transported as chylomicrons

Chylomicrons are then broken down into FFAs by lipoprotein lipase

FFAs are taken up by liver and adipose tissue

Liver resynthesises FFA into triglycerides and exports them as VLDL

VLDL will also be broken down into FFAs by lipoprotein lipase

Question 14

What are the 4 types of primary hypercholesterolaemia and what gene mutations are they usually associated with

Answer 14

Familial - LDLR, ApoB or PCSK9 - autosomal recessive

Polygenic - NPC1L1, HMG Co reductase

Familial hyper A lipoproteinaemia - Increase in HDL, CETP defic

Phytosterolaemia - ABC G5 and G8, - absorb plant sterols freely so increased risk of atherosclerosis

Question 15

For FH, is hetero or homo more common?

Answer 15

Heterozygous

Question 16

What are some signs of heterozygous FH

Answer 16

Corneal arcus
Xantholasma
Tendon xanthoma

Question 17

What happens in PCSK 9 mutation?

Answer 17

PCSK 9. degrades LDLR. Mutations can either increase rate of degradation of LDLR to reduce rate of degradation

Question 18

What are the 3 types of hypertriglyceridaemia

Answer 18

1 - Lipoprotein lipase or ApoC 2 def
4 - increased triglyceride production
5 - ApoA 5 def

Question 19

What would you be able to see in type 1 hyperlipidaemia

Answer 19

Eruptive xanthoma

Question 20

How can you differentiate between types 1 4 and 5 hyperlipidaemias?

Answer 20

Fridge test - chylomicrons at the top for types 1 and 5, VLDL a the top for type 4

Question 21

There is a clearance problem in which type of hyperlipidaemia?

Answer 21

Type 1

Question 22

What are the 3 types of primary mixed hyperlipidaemia

Answer 22

Familial combined hyperlipidaemia - some have high cholesterol some have high triglycerides

Familial hepatic lipase deficiency

Familial dys beta lipoproteinaemia

Question 23

what is Familial dys beta lipoproteinaemia ApeE 4/4 associated with

Answer 23

Alzheimer’s

Question 24

What is the classical sign of Familial dys beta lipoproteinaemia

Answer 24

Yellow palmar crease and eruptive xanthomas

Question 25

When would you get secondary hyperlipidaemia

Answer 25

Nephrotic syndrome, pregnancy,

Question 26

What other reasons can cause high triglycerides

Answer 26

``` Exogenous sex hormones diabetes gout obesity progressive partial lipodystrophy chronic renal failure alcohol ```

Question 27

What other reasons can cause high cholesterol

Answer 27

Nephrotic syndrome | Obstructive liver disease

Question 28

What are the 4 types of hypolipidaemia

Answer 28

AB lipoproteinaemia - Autosomal recessive - MTP deficiency - Very low LDL and VLDL HypoB lipoprotienaemia - Autosomal dominant - ApoB Tangier disease. - HDL deficiency - ABC A1 mutation Hypo alpha lipoproteinaemia - ApoA1 mutation

Question 29

What do statins do

Answer 29

Lower LDL greatly Mild increase in HDL Mild decrease in TG

Question 30

How does nicotinic acid work

Answer 30

Decrease in LDL | Great increase in HDL

Question 31

How do fibrates work

Answer 31

Decrease TG

Question 32

What does exetimibe do?

Answer 32

Reduces LDL

Question 33

What are 3 medications in the pipeline now

Answer 33

MTP inhibitor Anti PCSK9 - reduces LDL Anti sense apoB oligonucleotide - reduces LDL

Question 34

What is orlistat

Answer 34

Prevents fat abosrption

Question 35

What are the 3 surgical interventions for obesity

Answer 35

Gastric banding Roux en Y gastric bypass Biliopancreatic diversion