Clinical Pathology – Lipids and Dyslipoproteinemia

Question-and-Answer flashcards covering lipoprotein structure, apolipoproteins, metabolism, laboratory measurement, clinical guidelines, and lipid disorders

What composes the hydrophobic core of a lipoprotein particle?

Triglycerides, free fatty acids, and cholesteryl esters

Which lipoprotein has the largest diameter and lowest density?

Chylomicron

Which major lipoprotein contains the highest percentage of protein?

HDL

By electrophoresis, where do chylomicrons migrate?

They remain at the point of origin

What apolipoprotein mediates secretion of chylomicrons from the intestine to lymphatics?

ApoB-48

Which apolipoprotein activates lipoprotein lipase (LPL)?

ApoC-II

What is the mnemonic for ApoC-II’s function?

ApoC-II cuts and cleaves (hydrolyzes TG into FA)

Which apolipoprotein mediates hepatic uptake of remnants?

ApoE

What is the mnemonic for ApoE’s function?

Apo-Eats the remnants

Which apolipoprotein binds LDL receptors on peripheral cells?

ApoB-100

What is the mnemonic for ApoB-100’s effect?

ApoB-100 makes you gain 100 lbs (delivers cholesterol to tissues)

Which apolipoprotein activates LCAT to convert nascent HDL to mature HDL?

ApoA-I

What organ secretes VLDL?

Liver

Into what does VLDL first transform during metabolism?

IDL (Intermediate-density lipoprotein)

What particle delivers cholesterol from liver to peripheral tissues and is considered "bad"?

LDL

What particle removes cholesterol from peripheral tissues to liver and is considered "good"?

HDL

Name the receptor responsible for LDL endocytosis into cells.

LDL receptor (LDLR)

Which enzyme esterifies cholesterol in HDL?

LCAT (Lecithin-cholesterol acyltransferase)

Which receptor selectively uptakes cholesteryl ester from HDL in the liver?

SR-B1 receptor

What is the main apolipoprotein of HDL?

ApoA-I

What abnormal lipoprotein accumulates in obstructive biliary disease?

LpX

What abnormal lipoprotein is enriched in apoE and accumulates in type III hyperlipoproteinemia?

β-VLDL (floating β)

Which lipoprotein abnormality is primarily genetically determined and linked to premature ASCVD when >200–300 mg/L?

Lipoprotein(a) / Lp(a)

Which enzyme hydrolyzes triglycerides in CM and VLDL at the capillary endothelium?

Lipoprotein lipase (LPL)

What are the preferred blood sampling conditions before a lipid panel that includes TG and LDL-C?

12-hour fasting, patient seated 5 minutes, tourniquet <2 minutes

Which anticoagulant is preferred for lipoprotein analysis in plasma?

EDTA

State one limitation of Friedewald’s LDL-C formula.

Cannot be used if TG >400 mg/dL, non-fasting sample, or type I/III dyslipoproteinemia

What adjustable LDL-C estimation method improves accuracy over Friedewald at high TG levels?

Martin-Hopkins calculation

Give the fasting plasma triglyceride categories for hypertriglyceridemia.

Normal <150, Borderline 150-199, High 200-499, Very High ≥500 mg/dL

List two genetic causes of very high triglycerides linked to pancreatitis.

LPL deficiency and ApoC-II deficiency

Which lipid disorder shows creamy, "milky" plasma after standing due to excess chylomicrons?

Type I hyperchylomicronemia (LPL or ApoC-II deficiency)

Which familial lipid disorder is characterized by tendon xanthomas and elevated LDL with normal TG?

Familial hypercholesterolemia (Type IIa)

What class of LDLR defect involves complete absence of receptor synthesis?

Class I LDLR defect

Which rare disorder allows intestinal absorption of plant sterols causing premature atherosclerosis and hemolytic anemia?

Sitosterolemia (ABCG5/ABCG8 mutation)

Define metabolic syndrome triglyceride and HDL criteria.

TG ≥150 mg/dL and HDL-C <40 mg/dL in men or <50 mg/dL in women

What is the primary goal of statin therapy per current guidelines?

Lower LDL-C

Which four patient groups automatically qualify for moderate- or high-intensity statin per ACC/AHA 2013?

(1) Clinical ASCVD, (2) LDL-C ≥190 mg/dL, (3) Diabetes age 40-75 with LDL-C 70-189, (4) 10-year ASCVD risk ≥7.5% age 40-75 without ASCVD/diabetes

High-intensity statin aims to reduce LDL-C by what percentage?

≥50% from baseline

What lipid measurement is most affected by posture change?

Triglycerides (about 15% decrease when supine)

Name two substances that falsely lower enzymatic total cholesterol readings.

Ascorbic acid and hemoglobin (via pseudo-peroxidase activity)

Name one substance that spectrally interferes with triglyceride assays.

Bilirubin

What is the preferred method for measuring HDL-C in automated analyzers?

Homogeneous (direct) two-reagent assay

Why are frozen samples unsuitable for ultracentrifugal lipoprotein analysis?

Triglyceride-rich lipoproteins are damaged by freezing

Which dyslipidemia is commonly associated with visceral adiposity and insulin resistance?

Atherogenic dyslipidemia (high TG, low HDL, small dense LDL)

What waist circumference thresholds define abdominal obesity in metabolic syndrome (NCEP/ATP III 2004)?

≥102 cm (men), ≥88 cm (women)

What childhood lipid screening is recommended for those without risk factors?

Fasting or non-fasting non-HDL-C once between 9-11 y and again 18-21 y

Which abnormal lipoprotein is found in familial LCAT deficiency?

LpX

How does insulin influence lipoprotein lipase activity?

Insulin activates LPL, promoting FA uptake and weight gain

What type of lipoprotein particles are considered most atherogenic within LDL subclasses?

Small, dense LDL particles

Above what plasma concentration should Lp(a) prompt concern for CHD risk?

200–300 mg/L

Which gene mutation causes gain-of-function PCSK9 hypercholesterolemia?

PCSK9 gene mutation (autosomal dominant)

Name the enzyme deficiency causing Familial Lecithin-Cholesterol Acyltransferase (LCAT) deficiency.

LCAT deficiency

What is the recommended storage temperature for serum if long-term lipid analysis is required?

−70 °C or lower

What laboratory artifact can falsely elevate total cholesterol in jaundiced patients?

Bilirubin absorption at 500 nm

How often should cholesterol screening be repeated in adults per NCEP due to age-related changes?

Every 5 years

Which Apo mutation interferes with LDL binding leading to familial defective ApoB?

ApoB-100 R3500Q mutation

What is the effect of apoC-III excess on lipoprotein metabolism?

Inhibits LPL and LDLR binding, raising TG and CHD risk

Why can glycerol blanks be necessary in triglyceride assays?

To correct for endogenous or contaminant free glycerol that falsely elevates TG

State one drug class that commonly raises triglyceride levels.

Estrogens (oral) or thiazide diuretics (accept either)

What lipid abnormality produces turbid plasma due to small dense LDL excess?

High levels of small dense LDL (atherogenic dyslipidemia)

Which dyslipidemia phenotype is characterized by elevated both LDL and VLDL (hypercholesterolemia + hypertriglyceridemia)?

Fredrickson Type IIb

What is the hallmark clinical feature of Type III hyperlipoproteinemia?

Palmar xanthomas with β-VLDL accumulation

Which lipoprotein disease presents in childhood with pancreatitis and eruptive xanthomas?

Familial LPL deficiency (Type I)

What effect does standing to supine posture have on total cholesterol levels?

Up to 10% decrease due to hemodilution