Lecture 22: Lipid Disorders Flashcards
What is the primary reason US adults do not care that much about treating their cholesterol?
They are asymptomatic for a long time.
What are lipids?
Molecules composed of both fats and fatty acids.
* Cholesterol: backbone of steroids and bile acid synthesis.
* Triglycerides: Assist of transfer of energy into cell.
also in cell membranes
What are apolipoproteins? Function?
Protein required for assembly, structure, function, and metabolism of lipoproteins.
Function: Activate enzymes for lipoprotein metabolism and acts as a ligand for cell surface receptors.
Where are apolipoproteins synthesized?
Liver and SI
What are lipoproteins?
Complex molecules made of lipids and apolipoproteins.
What do lipoproteins do?
Transport cholesterol, TGs, and fat-soluble vitamins between tissues.
What are the 5 types of lipoproteins?
- Chylomicrons
- VLDL
- IDL
- LDL
- HDL
What is denser in a lipoprotein?
Apolipoproteins are MORE dense.
TGs are less dense.
Describe the composition of a lipoprotein.
- Core: hydrophobic lipids with TGs and cholesterol esters.
- Shell: Hydrophilic lipids with phospholipids, unesterified cholesterol, and apolipoproteins.
What are the two lipid pathways?
- Exogenous: absorption of dietary lipids and formation of chylomicrons.
- Endogenous: secretion of VLDL by liver, transitioning to IDL and then LDL.
Exogenous Pathway Step 1
Where is a chylomicron formed and what is it composed of?
SI absorbs dietary TGs, cholesterol, fatty acids, and retinol (Vit A).
All of these combine with apoC, apoE, and apoB-48
Exogenous Pathway Step 2
Where are chylomicrons first absorbed into? What allows them to then enter peripheral tissue?
Into the capillaries.
To enter peripheral tissue, they use apoC.
Exogenous Pathway Step 2
What breaks down TGs? Why?
TGs are broken down by lipoprotein lipase (LPL) for release of energy to muscles and adipose tissue.
Exogenous Pathway Step 3
What happens to the chylomicron remnant?
Goes to the liver to be uptaked by LDL receptors using apoE.
Endogenous Pathway Step 1
How is VLDL derived in the liver?
Substituting the apoB-48 group on the chylomicron remnant with an apoB-100.
Endogenous Pathway Step 2
Before the VLDL leaves the liver, what is added to it and from what?
- ApoE
- ApoC
- All from HDL molecules.
Endogenous Pathway Step 3
What happens to VLDL in the peripheral tissues?
TGs broken down by LPL again.
VLDL is now IDL.
Getting denser and dense as TGs get broken down.
Endogenous Pathway Step 4
What happens to IDL once it is formed?
- 40-60% are reuptaked by the liver using apoE and LDLR.
- Remaining is broken down further by hepatic lipase to form LDL.
Endgenous Pathway Step 5
How is LDL removed from circulation?
- 70% removed via liver (ApoB & LDLR)
- 30% (lipolysis in peripheral tissues)
Endgenous Pathway Step 6
What happens to the LDL in the liver?
Broken down.
The cholesterol components are excreted into bile.
Where is HDL formed?
Immature HDL is formed in the liver and intestines.
What is the function of HDL?
Collecting all cholesterol and VLDL/chylomicrons, cleaning up the arteries.
What Apo does HDL use?
ApoA
What happens to all the cholesterol collected by the immature HDL?
Lecithin-cholesterol acetyltransferase (LCAT) converts it to cholesterol esters so it can go through the bloodstream more easily.
This is when the mature HDL is formed.
How does HDL transport cholesterol to the liver?
- Direct uptake by hepatocytes
- Transfer of cholesterol for TGs with LDL & chylomicrons
What happens to HDL once it enters the liver?
Broken down into smaller HDL molecules so it is easy to excrete.
What is bad cholesterol? Good?
- Bad: LDL, which deposits cholesterol onto the vascular wall and impedes blood flow.
- Good: HDL, which sweeps cholesterol off the vascular wall to clean it up.
What is dyslipidemia?
Increase in plasma cholesterol, TGs, or BOTH.
Often accompanied by low HDL.
What are the main etiologic factors that contribute to dyslipidemia?
- Genetic predisposition
- Environmental factors
What are the 4 main pathways that lead to dyslipidemia?
- Excessive hepatic secretion of VLDL.
- Impaired lipolysis of TG-rich lipoproteins
- Impaired hepatic uptake of ApoB containing lipoproteins (except HDL)
- Inherited low levels of HDL
How does excessive hepatic secretion of VLDL typically present lab-wise?
- Elevated fasting TGs
- Low HDL-C levels
What factors tend to increase VLDL secretion?
- Obesity
- Insulin Resistance
- High-carb diet
- Nephrotic syndrome
- ETOH use
- Cushing’s
- Exogenous estrogens
- Familial combined hyperlipidemia
- Lipodystrophy
What is the pathophysiology behind impaired lipolysis of TG-rich lipoproteins?
Lipoprotein lipase dysfunction.
Caused either by genetics or insulin resistance.
What is the pathophysiology behind impaired hepatic uptake of apoB-containing lipoproteins?
Down regulation of LDLRs in the liver lead to elevated LDL.
What are the etiologies of impaired hepatic uptake of apoB-containing lipoproteins?
- Saturated fat intake reduces LDL activity
- Hypothyroidism
- Estrogen deficiency
- CKD or liver disease
- Drugs (thiazides, cyclosporine, carbamazepine)
- Genetic disorders
What is the pathophysiology behind low HDL?
Accelerated HDL catabolism and apoA.
What are the etiologies that contribute to low HDL levels?
- Obesity
- Insulin resistance
- Genetic disorders
How is dyslipidemia typically diagnosed?
Routine lab screenings showing elevated TGs and LDL with low HDL.
What PE findings can be seen with really bad dyslipidemia?
- Eruptive xanthomas (high TGs or VLDL)
- Tendinous xanthomas (high LDL)
- Lipemia retinalis (high TGs)
- Milky serum (high TGs)
What are eruptive xanthomas? MC location?
Patches on skin, often pruiritic or painful.
MC found on the buttocks.
What are tendinous xanthomas? MC location?
Lipid deposits MC found in the tendons of the hands, feet, and heel.
How does lipemia retinalis present?
Milky arteries and veins in the retina.
What is the ACC/AHA recommendation for dyslipidemia screening?
- Screen all adults starting at age 20.
- Screen children by age 2 if FMHx of EARLY CV disease or significant primary hypercholesterolemia.