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Flashcards in Disorders of lipid metabolism Deck (23):

Normal lipid serum values

Total cholesterol: 3.6-5.2 mmol/L
LDL cholesterol: <3.4 mmol/L
HDL cholesterol: male > 1.0 mmol/L, female: > 1.3 mmol/L, total triglycerol: 0.8-1.7 mmol/L


Key enzymes and cofactors in lipid metabolism

HMG-CoA reductase; rate-limiting step in cholesterol synthesis
LPL (lipoprotein lipase): digests the Triacylglycerol core of chylomicrons and VLDL
HL (hepatic lipase): conversion of IDL to LDL
CETP: transfers cholesteryl esters from HDL to other lipoproteins in exchange for triacylglyerides
LCAT: conversion of cholesterol to cholesterol esters
Apolipoprotein A: major protein of HDL
Apolipoprotein B: major structural protein of VLDL, IDL and LDL
Apolipoprotein CII and apolipoprotein E: obtained from HDL to CMC and VLDL for activation of LPL and receptor recognition



fatty oxidation disorders or lipid storage disorder. Inborn errors of metabolism, enzyme defects which affect the ability to oxidize FFA in order to produce energy within muscles, liver etc.


Significance of cholesterol and oxidized LDL

Cholesterol is a major risk factor for coronary heart disease.
Oxidized LDL is unable to bind to hepatic receptors and rather bind to scavenger receptor on macrophages, thus forming Foam cells.


Types of dyslipidemia

Type I: Famlilial hyperchylomicronemia (low LDL, altered CII)
Type IIa: Familial hypercholesterolemia (decreased LDL-R)
Type IIb: Familial combined hypercholesterolemia (decreased LDL-R and increased Apo-B)
Type III: Familial dysbetalipoproteinemia (ApoE2 synthesis defect)
Type IV: Familial hyperlipidemia (Increased VLDL prod, decreased VLDL elimination)
Type V: Familial hypertriglyceridemia (Increased VLDL prod, decreased LPL)


Type I

Serum abnormality: Increased Chylomicron.
Clinical features: pancreatitis, lipemia, retinalis, skin eruptions, Xanthoma, hepatosplenomegaly.
Treatment: Diet.


Type IIa

Serum abnormality: Increased LDL
Clinical features: Xanthelasma, arcus senilis, tendon xanthomas.
Treatment: Cholestyramine or Cholesterol, Statins, Niacin


Type IIb

Serum abnormality: increased LDL and VLDL.
Treatment: Statins, niacin, fibrate


Type III

Serum abnormality: increased IDL.
Clinical features: Turbo-eruptive xanthomas, palmar xanthoma.
Treatment: Fibrate, statins


Type IV

Serum abnormality: Increased VLDL
Treatment: Statins, Niacin, Fibrate


Type V

Serum abnormality: Increased VLDL and decreased LPL
Treatment: Niacin and Fibrate



Lipemic serum
High serum TG (TG above 10 mmol/L) with normal or moderately increased serum cholesterol
Fredewald equation: LDL-C= Chol-HDL-C - (TG/2.2) (mmol/L) can be used if TG is less than 4.5 mmol/L
Direct determination of LDL-C (immunological determination)


Adult treatment panel III (NCEP)

Repeat once every 5 years.
If non-fasting sample is obtained and HDL is lower or Cholesterol is higher: fasting profile is recommended. If no significant change in HDL and cholesterol, rescreen in 5 years.



Diet with lipid restriction
Moderate length-chain triacylglycerides (MCT)
Substitution of ApoCII with FFP
Statins - HMG-CoA reductase inhibitors
Fibrates - increases LPL activity
Resins: binds colic acids - decreases serum LDL-C
Nicotinic acid - decreased lipolysis and VLDL synthesis
Ezetimibe - selective inhibitor of cholesterol uptake in the small intestine
Fish oil - promotes intracellular breakdown of ApoB-100


Secondary dyslipidemia

Very common. Hyperlipidemia which develops in normolipidemic patients due to other diseases.


Diseases causing secondary dyslipidemia

Type 1 DM: VLDL incr, LDL incr, HDL decr
Type 2 DM: VLDL incr, LDL incr, HDL decr
Hypothyroidism: VLDL incr, LDL incr, HDL incr
Obesity: VLDL incr, LDL incr, HDL decr
Alcoholism: VLDL incr, LDL incr, HDL incr
Nephrosis: VLDL incr, LDL incr, HDL decr
Chronic kidney disease: VLDL incr, LDL incr, HDL decr
Cholestasis: VLDL - , LDL incr, HDL decr
Hepatocellular diseases: IDL incr, LDL -, HDL decr
Hyperuricemia: VLDL incr, LDL - , HDL decr
Pregnancy: VLDL incr, LDL incr, HDL incr


Metabolic syndrome

Coexistence of at least 3 of the following factors:
- Central obesity, waist circumference > 102cm (men), >88cm (women)
- Fasting glucose >6.1 mmol/L
- Hypertension
- Serum triglycerides increased >1.7 mmol/L
- HDL cholesterol: Men <1.0mmol/L, women <1.3mmol/L



Blood test: cholesterol, triglycerides, HDL, glucose, electrolytes


Treatment for metabolic syndrome

Lifestyle changes, diet, regular physical activity, medical treatment for each risk factor


Congenital enzyme defects

Lipid storage disorders:
Autosomal recessive or X-linked recessive - leads to accumulation of lipids within cells and leads to permanent damage to cells and tissue damage over time (especially brain, PNS, Liver, spleen, bone marrow). They are collectively a part of the lysosomal storage diseases.


Lysosomal storage diseases

GM1 & GM2 gangliosidoses (GM2 is also called Tay-Sachs)
Gaucher disease - deficiency of glucocerebrosidase
Metachromatic leukopathy
Krabbe disease
Wolman disease


Treatments of lysosomal storage diseases

Enzyme replacement
Bone marrow replacement - Last resort



Whipple disease
- Systemic tissue damage due to macrophages loaded with Tropheryma Whippelii organisms
- Also known as Bassen-Kornzweig syndrome. Rare
- Autosomal recessive deficiency of apolipoprotein B-48 and B-100, leads to malabsorption as there is defective Chylomicron formation