Disorders of lipid metabolism

Dr. Ahmed Gaber Bakry

MD Cardiology
Lecturer of Cardiology & Medicine , Faculty of medicine , SVU
Lipid physiology:
Lipids are water insoluble and are transmitted in the blood stream as
macromoleucular complexes “Lipoproteins”.
Five principal types of lipoproteins are present in blood:

1)Chylomicrons:
They are synthesized in SI postprandially, then reach the blood
stream.
They contain triglycerides and a small amount of cholesterol, and it
provide the main mechanism for transporting the digestion product
of dietary fat to the liver and the peripheral tissues.
2) VLDL “Very low density lipoproteins”:
They are synthesized in the liver and contain most of the body
endogenous triglycerides and a small amount of cholesterol
-Very raised TG (VLDL)levels can lead to increase risk of acute
pancreatitis, and retinal vein thrombosis.
-There is a weak independent link between raised TG and CV risks.

3)LDL (Low density lipoproteins):

LDL are the main carriers to cholesterol and deliver it into the liver
and the peripheral tissues.
LDL can ppt. cholesterol into the walls of the peripheral vasculature.
Some cholesterol is oxidized into bile salts. Both cholesterol and
bile salts are excreted in bile, and both are then reabsorped into the
terminal ileum and recirculate in the enterohepatic circulation.

-There is a strong association between both total and LDL

cholesterol conc. And coronary artery risks.
4) HDL “High density lipoproteins”:
Nascent HDL are produced both in the liver and the SI, and
they are transmitted into the mature particles in the blood
stream.
-The more mature HDL particles take up cholesterol from
the cells in the peripheral tissues and deliver it into the
blood or the liver.

-Higher HDL conc. Protect against CV diseases. HDL also has

effect on the function of the platelets and on the
haemostatic cascade.
Measurement of serum lipids:
1- In fasting serum lipids: The maj. Of total cholesterol conc.
consists of LDL, with a 20-30% contribution of HDL.
The TG conc. Reflects the circulating numbers of VLDL
particles, since chylomicrons are not normally present in the
fasting state.

2-If the pt. is not fasted, the total TG conc. Will be raised
owing to the additionally presence of TG-rich chylomicrons.
 Hyperlipidaemia
Hyperlipidaemia results from genetic predisposition
interacting with an individual diet.

Classification: 1-Primary
2-Secondry
-Causes of secondary hyperlipidaemia:
1-Hypothyrodism
2-Poorly controlled DM.
3-Obesity.
4-Renal impairment.
5-Nephrotic syndrome.
6-Hepatobiliary dysfunction.
Drugs: steroids, OCC pills, thiazide diuretics, retinoids.

-Primary hyperlipidaemia:
1- Dis. Of VLDL and chylomicrons “Hyper TG”.
2-Dis of LDL “Hyper cholestrolemia”
3-Dis. Of HDL.
4-Combined hyperlipidaemia.
Clinical Picture:
1-In Hyper TG, the main presentations are:
- Recurrent attacks of acute pancreatitis.
-retinal vein thrombosis.
- Hepatosplenomegaly.
2- In hypercholesterolemia: The main presentations are:
-Xanthomatous thickening of the Achiles tendon.
-Xanthomas over the extensor tendons of the fingers.
-Xanthelasmas.
-Coronary artery dis. And increased risk of all CV
events.
3-In Dis. of HDL “Tangier dis.”; cholesterol accumulate in
the RES and arteries causing enlarged orange coloured
tonsills, hepatosplenomegally, CV dis., corneal opacities.
Treatment of hyperlipidaemia
Treatment of hyperlipidaemia:

Lipid lowering diet & Life Style changes:

1-Reduce the total fat intake:
-Reduce sources of saturated fat in diet and substitute with fish.

2-Subsititution with monounsaturates, and polyunsaturates:

Monounsaturated oils as olive oil, and polyunsaturated oils as
sunflower, corn and soya oil, should be used in cooking instead of
saturated fat –rich alternatives.
3-Reduce the dietary cholesterol intake:
-Avoid liver, and restrict eggs.

4-Increase the intake of fibre :

-Increase food rich in soluble fibre such as leafy vegetables,
root vegetables, unprocessed cereals as they help to reduce
circulating lipids.

5-Achieve an ideal body weight & Physical exercise.

PCS K9 inhibitors
Drug treatment of hyperlipidaemia;
1-Fibric acid derivatives: e.g. finofibrate. They reduces
LDL/cholesterol by 10-15% and are useful in pt. with modest
hypercholestremia.
2-Cholesterol binding resins: e.g. Cholestyramine. They
bind to bile acids in the gut and inhibit enterohepatic circulation,
and this promotes the liver to transform cholesterol into bile acids.
They cause 8-15% lowering of LDL. Fat soluble vit. Must be
supplemented.
3-HMG- CoA reductase inhibitors (Statins):
e.g. Pravastatins, Fluvastatins,….They inhibit last step in cholesterol
synthesis.
They reduce LDL/cholesterol by 30-40%.
They have been found to reduce both mortality and morbidity of
CVD in hyper cholestremic pts.
4-Nicotinc acid derivatives: Nicotinc acid They
reduce the LDL and triglycerides by 5-10%
5-Omega 3: They reduce hepatic VLDL secretion.
They reduce triglycerides in hyper-triglyceridemia..
6- Ezetimibe (cholesterol absorption inhibitor).

Management of specific hyperlipidaemias:

-Screening: Selective screening of people at high risk
of CVD should be undertaken to include those with:
1-A family hist. of CAD esp. > 50 ys.
2-a family hist. with lipid disorder.
3-The presence of xanthoma, xanthelasma, or
corneal arcus.
4-Obesity 5-DM 6-HTN.
7-Acute pancreatitis
8-Those undergoing renal replacement therapy.

-Acute severe illness as AMI can derange plasma lipid conc.

For up to 3 months. So plasma lipid conc. Should be
measured either within 48hours of an AMI or 3 months
later.