Dyslipidemias

Lipid Profile
• Serum Triglycerides- 50-150 mg/dL
• Total Cholesterol- 100-200 mg/dL
• LDL cholesterol- < 100 mg/dL
• HDL - > 40 mg/dL- males
- > 50 mg/dL- females
• VLDL - 30 mg/dL
 Friedewalds Equation

• VLDL= TGL/5

• LDL = Total cholesterol- ( VLDL+ HDL)

 Novel Lipid markers
• Non- HDL cholestrol - < 130 mg/dL
• measure of the amount of
cholesterol carried by all lipoproteins
except HDL.

• LDL/HDL - < 2.5

• ApoB/Apo A1
 TERMINOLOGY
• Dyslipidemia - abnormal cholesterol (TC, LDL-
C, or HDL-C) and/or TGL levels

• Hyperlipoproteinemia - abnormally elevated

concentrations of specific lipoprotein particles
in the plasma

• Hyperlipidemia ( plasma cholesterol and/or

TAG) is present in all hyperlipoproteinemias
 PRIMARY DISORDERS OF
LIPOPROTEIN METABOLISM
 Type I: Familial chylomicronemia
• Deficiency of lipoprotein lipase/Apo CII.
• Plasma appears turbid & forms a creamy
supernatant
• TAG > 1000mg/dl, moderately elevated
cholesterol. Low LDL & HDL.
• Slow clearance of VLDL & chylomicron
• Increased risk of pancreatitis
• No increased risk of atherosclerosis.
LIPEMIC SERUM
 Type IIA: Familial hypercholesterolemia
- Defect in LDL Receptor & apo B 100
- Very highly elevated LDL , normal
TGL& HDL
- Pemature atherosclerosis,
- Xanthomas of skin and tendons
 ATHEROSCLEROSIS
PATHOGENESIS:
- Endothelial injury- triggers secretion of
adhesion molecues that bind circulating
monocytes
- transformed to macrophages- migrate to sub-
intimal space – stimulate cytokines.
- converted to foam cells & deforms endothelium
- Platelet aggregation & adhesion to exposed
sites- PLAQUE
 Familial dys--lipoproteinemia Type III
Broad beta-disease; Remnant removal disease

•Apo-E has a normal role in CM &VLDL-

remnants uptake
• Defective recognition of apo-E2 by the
lipoprotein receptors
•  VLDL-C and TG
•  HDL and LDL
• xanthomas + atherosclerosis
 Hypolipoproteinemias
• Familial hypobetalipoproteinemia:
• Apo B mutation- reduced synthesis or accelerated
catabolism of this protein- Low LDL, VLDL

• Both apo B-48 and B-100 are affected because they are
inherited from the same gene.

• Fat malabsorption occurs because chylomicrons cannot

be formed by the intestine due to lack of apo B-48.

• Absorption of fat soluble vitamins is severely

impaired resulting in degenerative changes in retina
which may lead to blindness
 Hypolipoproteinemias
•Tangiers Disease
• ABC mutation- reduces efflux of cholesterol from
peripheral tissues
• Leads to Low HDL levels (,<5 mg/dL)
SECONDARY DISORDERS OF
LIPOPROTEIN METABOLISM
 CAUSES

- Obesity
- diabetes mellitus
- Thyroid disease
- Renal & liver disease

- Alcohol
- Estrogen.
Obesity
 Diabetes Mellitus
•Increased levels of insulin due to Insulin Resistance
causes
1. Decreased LPL activity--LDL & chylomicron
•  FFA release from adipose tissue & increased FA
synthesis in liver
• Hepatic VLDL production
• High TGL, HIGH LDL & low HDL
 Hypothyroidism
•  LDL- decrease in hepatic LDL receptor activity –

• Delayed clearance of LDL

• Thyroid replacement therapy.

 Renal Diseases
• Nephrotic syndrome -  hepatic production &
reduced clearance of VLDL along with  LDL
poduction.

•ESRD-  TGL due to decreased remnant clearance

• Renal Transplant pts - effect of immunosuppressive

drugs.
 Liver Diseases
• Cholestasis- excretory pathway of cholesterol is
blocked
• Free cholesterol + PL secreted as LP- X

• Xanthoma in skin folds.

 Hypolipidemic drugs
• Statins -
•HMG-CoA reductase inhibitors-
• cholesterol synthesis & increased LDL receptor
activity -- LDL clearance

• Ezitimibe -
• Cholesterol Absorption inhibitors from intestine
 Hypolipidemic drugs
• Bile acid sequesterants-
• Promote excretion of bile acids
• liver diverts the chlesterol to bile acid syn.
•Decreased hepatic intracellular cholesterol
stimulates upregulation of LDL receptor
• Thus LDL is cleared from plasma
•Niacin-
• Reduces flux of FFA to the liver
• Reduced TGL syn & VLDL secretion from liver
 Hypolipidemic drugs
• Fibrates
• Stimulate LPL activiity- increased clearance of
Chylomicron & VLDL remnant

•Useful for lowering TGL levels in plasma

 LIPOPROTEIN (a)
• Apo B100 containing lipoprotein linked to apo(a)
through di-sulphide bonds (identical to LDL )

• Apo(a) has sequence homology with plasminogen , a

protein involved in clot resolution.

• Does not have plasminogen’s protease activity, but

impairs its action

• Elevated Lp(a) is associated with risk of CAD.