Lipid Flashcards
Sort the 5 Plasma Lipoproteins by Density and Size, Trigliceride and cholesterole Content
Recall Cholesterole synthesis and absorption as well as the drugs that can reduce Cholesterole like that?
- Synthesis from Acetyl CoA HMG-CoA –> by HMG-COA reductase (inhibited by statins, rate-limiting step) –> Mevalonate –> Cholesterol –> Bile Acids
- Absorption in Small intestine (blocked bxy Ezetimibe)
* Cholesterol enters via NPC 1L1 and ABC G5/ G8
* Dietary absorption of Cholesterol inhibits HMG-CoA reductase activity (by binding to hepatic remnant receptors)
What is a Lipoprotein?
Molecule with hydrophobic core
(cholesterol/triglycerides) and hydrophilic shell consisting of apolipoproteins transport lipid in the blood)
What are Chylomicrons?
What is their main role?
Chylomicrons are the lipoproteins that transport dietary absorbed cholesterole to the tisse
- Produced by enterocytes and transport fatty acids and cholesterol to the tissue
- Lipoprotein Lipase releases Free-Fatty acids from Chylomicrons
What is VLDL?
What is the main role?
- Synthesised in and released by the liver; **transports fatty acids and cholesterol to the tissues **
- Can be absorbed directly by the liver or converted into IDL –> LDL (Via Lipoprotein Lipase, which relases Free Fatty Acids from VLDL to convert it into IDL)
- Mostly triglycerides
* Fibrates, Niacin and Fish oil all inhibit VLDL secretion from the liver
What is LDL?
What is the main role of LDL?
- IDL are converted by Hepatic Lipase into LDL (with release of Free Fatty Acids into Blood)
- Delivers Cholesterol to the tissues (or can be re-absorbed by the liver)
What lab tests would be ordered in a lipid profile?
What do they indicate?
- LDL
- HDL
- VLDG (used for measuring Triglycerides due to high TG contents - only valid in fasting lipids)
What are the 4 most important disorders of lipoprotein metabolism?
- Primary Hypercholesteraemia
- Primary Hypertrigliceridaemia
- Secondary Hyper
- Hypolipidaemia
What is primary hypercholesteraemia?
What is the most common cause?
Inherited disorder of lipoportein metabolsm (1:500 heterozygous)
Most commonly: Familial Hypercholesterolaemia = autosomal dominant conditions with different mutations affecting the
- LDL receptor (most common) –> decreased reabsorption of LDL –> higher LDL
- apoB (common)
- PCSK9 (rare) genes –> gain of function mutation that then causes increased rate of LDL receptor degradation
What is primary hypertriglicerdaemia?
How can it be diagnosed?
Fridge test: let plasma rest over night, to determine which form it is (Chylomicrons float (type I) , VLDL does not float (type IV ), mix of both (V)
Primary disorder of lipid metabolism causing
1. increased production of triglicerides
2. decreased breakdown (usually due to enzyme deficiency)
What is the approach to treatment for Hyperlipidaemia?
- Conservative: lifestyle modification
- Medical: many drugs generally
First line
* Statins
Then Add
* Ezetimibe
* ? PCSK9 inhibitors
Other agents more rarely used
What is the MOA and clinical effectiveness of statins?
What are the main side-effects?
HMG-CoA reductase inhibitor
* Reduces intrinsic synthesis of cholesterol in the liver
* Causes a mean reduction in LDL by 50%
* Side effects – myopathy/rhabdomyolysis, fatigue
What are the indications of use of PCSK9 inhibitors?
What is the MOA and clinical use?
MOA: inhibition of PCSK9 –> reduced breakdown of LDL receptors –> increased LDL uptake
Can be used as add-on when
* high LDL despite high dose-statin and ezetimibe
What is Ezetimibe?
What is the MOA and clinical indications?
Use as first-line lipidl-lowering agent if Stating are contraindicated or for add on to statin therapy
MOA: Decreased cholesterole absorbtion
What are the benefits and risk associated with bariatric surgery?
- Success = >50% reduction in excess weight (actual weight - ideal)
- Diabetis decreasees (-72%)
- Serum tryglyceride reduction (-50-60%) and HDL cholesterol increase (13-47%)
- Fatty liver reduction
- reduces hypertension
- Post-op mortality 0.1-2%
