Chemical Pathology - Lipoprotein Metabolism

Question 1

What are some causes of primary hypercholesterolaemia?

Answer 1

• Familial hypercholesterolaemia (type II)
• Polygenic hypercholesterolaemia
• Familial hyperα-lipoproteinaemia
• Phytosterolaemia

Question 2

What is the inheritance pattern and mutations of familial hypercholesterolaemia (type II)?

Answer 2

• AD: LDLR, apoB, PCSK9
• AR: LDLRAP1

Question 3

What are the mutations that cause polygenic hypercholesterolaemia?

Answer 3

Several polymorphisms

Question 4

What is the deficiency that causes familial hyperα-lipoproteinaemia?

Answer 4

CETP

Question 5

What are the markers that cause phytosterolaemia?

Answer 5

ABC G5 + G8

Question 6

What are some causes of primary hypertriglyceridaemia?

Answer 6

• Familial Type I
• Familial Type V
• Familial Type IV

Question 7

What are the markers causing in Familial Type I Hypertrigliceridaemia?

Answer 7

Lipoprotein Lipase or ApoC II deficiency

Question 8

What deficiency causes in Familial Type V Hypertrigliceridaemia?

Answer 8

ApoA V (sometimes)

Question 9

What causes Familial Type IV Hypertrigliceridaemia?

Answer 9

An increase in the synthesis of TG

Question 10

What are some causes of Primary Mixed Hyperlipidaemia?

Answer 10

• Familial Combined Hyperlipidaemia
• Familial Dysβlipoproteinaemia
• Familial Hepatic Lipase Deficiency

Question 11

What are some causes of Hypolipidaemia?

Answer 11

• Aβ-lipoproteinaemia
• Hypoβ-lipoproteinaemia
• Tangier Disease
• Hypoα-lipoproteinaemia

Question 12

A deficiency in what causes Aβ-lipoproteinaemia?

Answer 12

MTP

Question 13

What causes Hypoβ-lipoproteinaemia?

Answer 13

Truncated ApoB Protein

Question 14

A deficiency in what causes Tangier Disease?

Answer 14

HDL

Question 15

Mutations in what, cause Hypoα-lipoproteinaemia?

Answer 15

ApoA-I (sometimes)

Question 16

What is the order of density of lipoproteins?

Answer 16

(Most-Least)
1. HDL
2. IDL
3. LDL
4. VLDL
5. FFA
6. Chylomicron

Question 17

How does PCSK9 work?

Answer 17

• PCSK9 binds to LDLR and promotes its degradation
• LDLR removes LDL from blood
• IF: loss of function mutation in PCSK9 it lowers LDL levels

Novel form of LDL-lowering therapy is Anti-PCSK9 MAb

Question 18

What is lipoprotein A a RF for and what is its treatment?

Answer 18

RF = CVD
Tx = Nicotinic acid

Question 19

What is the management of hyperlipidaemia?

Answer 19

1. Conservative: Dietary modifcations + exercise
2. Statin therapy:
   - MHG-CoA Reductase inhibitor
   - Reduces intrinsic synthesis of cholesterol in liver
3. Other agents rarely used e.g. Ezetimibe

Question 20

What are some side effects to statin therapy?

Answer 20

• Myopathy/rhabdomyolysis
• Fatigue

Question 21

What is the management of obesity?

Answer 21

Conservative measures

Medical:
- No medication safely proven to provide sustained weight loss
- Orlistat (Pancreatic lipase inhibitor)
- Rimonabant (cannabinoid antagonist) - trialled but discontinued due to increased suicide risk

Surgical:
- Bariatric surgery: Pts with BMI >40, or >35 with comorbidity a/w obesity
- Requires extensive screening + must commit to long term follow up

Question 22

What are the side effects of orlistat?

Answer 22

• Profound flatus
• Diarrhoea
• Sometimes too cumbersome for patients to tolerate