Lipoprotein metabolism Flashcards
What types of lipoprotein conditions are there?
- Primary hypercholesteraemia
- Primary triglyceridaemia
- Primary mixed hyperlipidaemia
- Hypolipidaemia
What 4 primary hypercholesteraemias are there?
Familial hypercholesteraemia type II
Polygenic
Familial Hyperalphalipoproteinemia
Phytosterolaemia
What is familial hypercholesterolaemia?
High cholesterol / VERY HIGH LDL levels
Autosomal dominant : LDLR gene
Autosomal recessive : LDLRAP1 gene
Can see tendom xanthomas, corneal arcus, xanthalasma
What is polygenic hypercholesterolaemia?
Multiple genes : NPC1L1, HMGCR etc
dont need to recall
What is familial hyperalphalipoproteinaemia
High HDL = good
reduces risk of Coronary heart disease
What is phytosterolaemia?
Mutation in ABC G5 and ABC G8
Causes high plant sterols in plasma
= premature atherosclerosis / xanthomas
What 3 types of primary hypertriglyceridaemias are there?
Familial type 1
Familial Type 4
Familial type 5
What deficiency is seen in familial type I hypertriglyceridaemia?
Lipoprotein lipase or
apoC II def
What deficiency is seen in familial type 5 hypertriglyceridaemia?
apo A V def
What causes familial type 4 hypertriglyceridaemia?
Increase synthesis of TG
What primary mixed hyperlipidaemias are there?
Familial combined hyperlipidaemia
Familial hepatic lipase deficiency
Familial Dysbetalipoproteinaemia
What is seen in familial combined hyperlipidaemia?
Some will have high cholesterol and other high TGq
What is seen in familial dysbetalipoproteinaemia?
Yellowing of palmer crease
Which types of familial hypertriglycerideaemia has
- High VLFL
- High Chylomicrons
- High VLDL + High chylomicrons
- High VLFL : type 4
- High Chylomicrons : type 1
- High VLDL + High chylomicrons : type 5
What hypolipidaemias are there?
A-beta lipoproteinaemia
hypoalpha-lipoproteinaemia
Hypobeta-lipoproteinaemia
Tangier disease
What causes A-beta lipoproteinaemia
MTP deficiency
What causes hypoalpha-lipoproteinaemia
ApoA1 gene def
What causes hypobeta-lipoproteinaemia
ApoB gene def
+ low LDLs
What is Tangier disease?
ABCA1 gene mutation
- lipid and cholesterol cannot leave organs so accumulate
- organomegaly, enlarged orange tonsils in children
Low HDL! = increased risk of CVD
What are PCSK9 inhibitors
💊 Evolocumab = PCSK9 inhibitor (prevents LDL receptor degradation, increasing LDL clearance)
How can high LDL levels be treated?
Nicotinic acid
How to manage hyperlipidaemia
🟢 1st line = Lifestyle changes (diet + exercise)
💊 Statins (HMG-CoA reductase inhibitors)
➡️ ↓ Hepatic cholesterol synthesis
⚠ Side effects: Myopathy, rhabdomyolysis, fatigue
🩺 Other agents (less common):
🔹 Ezetimibe – ↓ Intestinal cholesterol absorption
How to manage obesity medically?
Medical (limited efficacy)
Orlistat (lipase inhibitor) – ⚠ GI side effects (flatus, diarrhea)
Rimonabant (cannabinoid antagonist) – ❌ withdrawn (suicide risk)
How to manage obesity surgically?
Surgical (bariatric)
BMI ≥40 or ≥35 + comorbidity
Requires extensive screening + lifelong follow-up
