10. INTESTINE
CHYLOMICRONS
THORACIC DUCT
SYSTEMIC CIRCULATION
LIPOPROTEIN LIPASE(HEART, ADIPOSE TISSUE, MUSCLE)
CHYLOMICRON REMNANTS
UPTAKE BY LIVER
LIVER
VLDL
SYSTEMIC CIRCULATION
LIPOPROTEIN LIPASE(HEART, ADIPOSE TISSUE, MUSCLE)
IDL
HEPATIC LIPASE
LDL
UPTAKE BY LIVER LDL R
PERIPHERAL TISSUES CHOLESTEROL
HDL
SR B1
UPTAKE BY LIVER
CHYLOMOCRON VLDL
CETP CETP
1 EXCESSIVE SECRETION VLDL
2 IMPAIRED LIPOLYIS
3DECREASED UPTAKE OF Apo B
Exogenous Endogenous
11. 1) Assembly and secretion of TG-rich VLDLs by the liver
2) Lipolysis of TG-rich lipoproteins by LPL
Familial chylomicronemia (lipoprotein lipase deficiency)
Familial hypertriglyceridemia
3) Receptor-mediated uptake of apoB-containing lipoproteins
by the liver
familial hypercholesterolemia(LDL Receptor mutation)
4) Very low HDL
Apo A-I Deficiency
Tangier Disease ( ABCA1 Deficiency)
Familial LCAT Deficiency
Familial hypoalphalipoprotenemia
12. EXCESSIVE SECRETION OF VLDL
• SECONDARY(high
TG/low HDL)
– High carbohydrate diet
– Obesity & Insulin
resistance
– Nephrotic syndrome
– Cushing syndrome
– Alcohol (high TG/high
HDL)
• PRIMARY (1 in 100)
• Familial combined
hyperlipidemia
– TG-200 – 600 mg/dL
– Total cholesterol – 200 –
400 mg/dL
– HDL-C < 40 in men, <50
in women
– Family h/o dyslipidemia
or premature CAD
16. Abetalipoprotenemia
• Microsomal TG transfer protein (MTP; gene name MTTP)
• Fat malabsorption
• Ataxia, peripheral neuropathy
• Retinitis pigmentosa
• Star-shaped red blood cells (acanthocytosis)
• Plasma levels of cholesterol
and TGare extremely low.
chylomicrons, VLDLs, LDLs,
and apoB are undetectable
in plasma
17. Tangiers disease
• ABCA1 (ATP-binding cassette transporter A1)
• ABCA1 mediates the efflux of cholesterol and
phospholipids to lipid poor apolipoproteins (apo
A1 & apo E)
• Low HDL-C, low Apo-A1
• Hypertriglyceridemia
• Orange/yellow tonsils
• Hepatosplenomegaly
• Corneal clouding
18. Familial LCAT deficiency
• enzyme is activated by apoA-I and mediates
the esterification of cholesterol to form
cholesteryl esters
• Partial LCAT (alph LCAT) deficiency
– Fish eye disease (corneal clouding)
• Complete LCAT deficiency
– Corneal clouding + Hemolytic anemia +
hepatosplenomegaly + renal failure
19. • Fasting lipid profile after 12 hours fast
• Friedewald formula:
LDL-C = Total cholesterol – (TG/5) – HDL-C
– Invalid if TG > 400 mg/dL
20. Management of Severe Triglyceridemia
prevent pancreatitis
• Treat if TG > 500 mg/dL
– Avoid alcohol
– Exercise
– Reduce dietary fat
– Fibrates – fenofibrate 145 mg(T. Stanlip)
• Gallstones
• Myopathy (along with statins)
– Omega 3 fatty acids
• 3 to 4 gm/day
22. Cholesterol Absorption Inhibitors
• Ezetimibe (10 mg)
• Binds inhibits NPC1L1 (Niemann-Pick C1-Like 1)
and blocks the intestinal absorption
of cholesterol
• Drug of choice
in sitosterolemia
23. Bile Acid Sequestrants (Resins)
• Reduce plasma LDL-C levels but can cause
an increase in plasma TGs
• Drug of choice in pregnancy
– Cholestyramine (Choltran 4 gm satchet)
– Colestipol
– colesevelam
Lipoproteins contain a core of hydrophobic lipids (TGs and cholesteryl esters) surrounded by a shell of hydrophilic lipids (phospholipids, unesterified cholesterol) and proteins (called apolipoproteins) that interact with body fluids
Niemann-Pick C1-Like 1 (NPC1L1)
Lipemia retinalis - creamy appearance of the retinal blood vessels
Eruptive xanthomas-small, yellowish-white papules in clusters on the back,buttocks, and extensor surfaces of the arms and legs