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Flashcards in Disorders of lipid metabolism Deck (23):
1

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

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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

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Dyslipidemia

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.

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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.

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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)

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Type I

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

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Type IIa

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

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Type IIb

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

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Type III

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

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Type IV

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

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Type V

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

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Diagnosis

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)

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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.

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Treatment

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

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Secondary dyslipidemia

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

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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

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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

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Diagnosis

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

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Treatment for metabolic syndrome

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

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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.

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Lysosomal storage diseases

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

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Treatments of lysosomal storage diseases

Enzyme replacement
Bone marrow replacement - Last resort

23

Malabsorption

Whipple disease
- Systemic tissue damage due to macrophages loaded with Tropheryma Whippelii organisms
Abetalipoproteinemia
- 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