Chapter 3 — Lipids, Lipoproteins and Lipid Status

What is dyslipidemia?

A disorder of plasma lipoprotein metabolism.

What factors contribute to dyslipidemia?

Diet, physical inactivity, obesity and genetic factors.

What is secondary dyslipidemia?

Dyslipidemia caused by another disease or condition.

Name causes of secondary dyslipidemia.

Diabetes mellitus, hypothyroidism, renal impairment, cholestasis and pregnancy.

What does the Fredrickson classification use?

Total cholesterol, triglycerides and serum appearance after refrigeration.

What does Fredrickson Type I show?

Elevated chylomicrons with very high triglycerides and creamy surface layer.

What does Fredrickson Type IIa show?

Elevated LDL with high total cholesterol and normal triglycerides.

What does Fredrickson Type IIb show?

Elevated LDL and VLDL with high cholesterol and triglycerides.

What does Fredrickson Type III show?

Elevated IDL/remnants with high cholesterol and triglycerides.

What does Fredrickson Type IV show?

Elevated VLDL with high triglycerides.

What does Fredrickson Type V show?

Elevated VLDL and chylomicrons with very high triglycerides.

What is lipoprotein lipase deficiency?

A rare disorder causing severe hyperchylomicronemia and pancreatitis risk.

Why does apo C-II deficiency cause hyperchylomicronemia?

Apo C-II activates lipoprotein lipase.

What causes familial hypercholesterolemia?

Defective LDL receptor expression or function.

Why is familial hypercholesterolemia dangerous?

It causes very high LDL cholesterol and high atherogenic risk.

What causes familial defect of apo B-100?

Reduced affinity of apo B-100 for LDL receptors.

What is hypoalphalipoproteinemia?

Low HDL cholesterol.

Which defects can cause low HDL cholesterol?

Apo A-I defects, LCAT deficiency and ABCA1 transporter mutations.

What is atherosclerosis?

Lipid accumulation in arterial walls forming plaques.

Where does atherosclerosis often occur?

Coronary, carotid and femoral arteries.

What are fatty streaks?

Early atherosclerotic lesions containing lipid-filled foam cells.

What are foam cells?

Macrophages filled with lipids.

Which lipoproteins are atherogenic?

LDL and remnants.

Which lipoprotein is anti-atherogenic?

HDL.

Why are chylomicrons not directly atherogenic?

They are too large to enter the subendothelial space.

Why are small dense LDL particles especially atherogenic?

They are more easily oxidized in the arterial wall.

What is the atherogenic lipid triad?

High triglycerides, low HDL and small dense LDL.

What is oxidized LDL?

LDL modified by oxidation in the subendothelial space.

Why is oxidized LDL important?

It attracts monocytes, promotes macrophage uptake and foam cell formation.

What are the four basic lipid status parameters?

Total cholesterol, triglycerides, HDL-cholesterol and LDL-cholesterol.

Why is total cholesterol alone insufficient?

It does not show whether cholesterol is in atherogenic LDL or protective HDL.

What is the target value for total cholesterol in Chapter 3?

4.1–5.2 mmol/L.

What is the target value for LDL-cholesterol?

What is the target value for triglycerides?

0.3–1.7 mmol/L.

What is the target value for HDL-cholesterol?

1.00–2.00 mmol/L.

How should blood for complete lipid status be collected?

In the morning after 12–14 hours fasting.

Why is fasting important for lipid status?

Food increases chylomicrons and triglycerides.

What is the Friedewald formula in mmol/L?

LDL-C = total cholesterol − HDL-C − triglycerides/2.2.

What is the Friedewald formula in mg/dL?

LDL-C = total cholesterol − HDL-C − triglycerides/5.

When can the Friedewald formula be used?

Only if triglycerides are below 4.0 mmol/L and chylomicrons are absent.

What is apolipoprotein A-I?

The main protein of HDL and activator of LCAT.

What does low apo A-I indicate?

Increased risk of atherosclerosis.

What is apolipoprotein B-100?

The main protein of LDL, IDL and VLDL.

What does high apo B-100 indicate?

Increased risk of atherosclerosis.

What lipids are present in plasma?

Cholesterol, triglycerides, phospholipids and free fatty acids.

Why are lipoproteins needed?

Lipids are water-insoluble and need transport particles in plasma.

How are free fatty acids transported?

Bound to albumin.

How are lipoproteins classified by density?

Chylomicrons, VLDL, IDL, LDL and HDL.

Which lipoprotein has the lowest density?

Chylomicrons.

Which lipoprotein has the highest density?

HDL.

How are lipoproteins classified by electrophoresis?

Alpha, pre-beta, beta, broad beta/pre-beta and chylomicrons.

Which electrophoretic fraction corresponds to HDL?

Alpha-lipoproteins.

Which electrophoretic fraction corresponds to VLDL?

Pre-beta-lipoproteins.

Which electrophoretic fraction corresponds to LDL?

Beta-lipoproteins.

Which lipoproteins remain at the starting point in electrophoresis?

Chylomicrons.

Which lipoprotein is richest in triglycerides?

Chylomicrons.

Which lipoprotein is richest in cholesterol?

LDL.

Which lipoprotein is richest in protein?

HDL.

What is the exogenous lipid pathway?

Transport of dietary lipids by chylomicrons from intestine to tissues and liver.

What is the endogenous lipid pathway?

Transport of liver-made lipids by VLDL to tissues.

What is reverse cholesterol transport?

HDL removes excess cholesterol from peripheral tissues and transports it to the liver.

Where are chylomicrons formed?

In enterocytes of the small intestine.

What apolipoprotein is characteristic of chylomicrons?

Apo B-48.

What do nascent chylomicrons receive from HDL?

Apo C and apo E.

Which enzyme breaks down triglycerides in chylomicrons?

Lipoprotein lipase.

What activates lipoprotein lipase?

Apo C-II.

What are chylomicron remnants?

Particles remaining after most chylomicron triglycerides are hydrolyzed.

Which apolipoprotein helps chylomicron remnant uptake by liver?

Apo E.

What does VLDL transport?

Endogenous triglycerides from the liver.

Where is VLDL produced?

In hepatocytes.

Which apolipoprotein is characteristic of VLDL?

Apo B-100.

What does VLDL become after triglyceride removal?

IDL.

What can IDL become?

LDL.

What does LDL deliver to cells?

Cholesterol.

How does LDL enter cells?

Apo B-100 binds to LDL receptors.

What does intracellular cholesterol inhibit?

LDL receptor synthesis and HMG-CoA reductase activity.

What is HMG-CoA reductase?

A key enzyme in endogenous cholesterol synthesis.

What is the function of HDL?

Removal of excess cholesterol from tissues and transport to the liver.

Where is HDL synthesized?

Liver and small intestine.

What transporter helps cholesterol enter nascent HDL?

ABCA1.

What enzyme esterifies cholesterol in HDL?

LCAT.

What activates LCAT?

Apo A-I.

What are additional HDL protective effects?

Antioxidant, anti-inflammatory and anticoagulant effects.

What is the total cholesterol protocol reaction idea?

Cholesterol ester → cholesterol → H₂O₂ → colored dye.

Which method measures total cholesterol?

CHOD-PAP method.

What does cholesterol esterase do?

Hydrolyzes cholesterol esters to cholesterol and fatty acids.

What does cholesterol oxidase do?

Oxidizes cholesterol and produces H₂O₂.

What does peroxidase do in cholesterol testing?

Uses H₂O₂ to form quinoneimine dye.

What is the triglyceride protocol reaction idea?

Triglycerides → glycerol → H₂O₂ → colored dye.

Which method measures triglycerides?

GPO-PAP method.

What does lipase do in the triglyceride protocol?

Hydrolyzes triglycerides into glycerol and fatty acids.

What does glycerol kinase do?

Converts glycerol to glycerol-3-phosphate using ATP.

What does glycerol-3-phosphate oxidase do?

Produces H₂O₂ from glycerol-3-phosphate.

Why can free glycerol interfere with triglyceride measurement?

It can be measured as if it came from triglycerides.

What is the HDL-cholesterol protocol principle?

Precipitate non-HDL lipoproteins, then measure cholesterol in the HDL supernatant.

Which particles are precipitated in the HDL method?

Chylomicrons, VLDL and LDL.

What remains in the supernatant in the HDL method?

HDL.

What reagents precipitate non-HDL particles in the HDL method?

Phosphotungstic acid and magnesium chloride.