Lipoprotein Disorders 2

LIPOPROTEIN DISORDERS
BY
EBOT WALTER OJONG

Ph.D. Chemical Pathology
LESSON OBJECTIVES
 Distinguish between primary and secondary
dyslipidaemias
 List the five classes of lipoprotein disorders.
 List the metabolic defect (etiology), biochemical
changes and features of each class
 Explain the principle of lab methods for lipoprotein
analysis, considerations and clinical significance
INTRODUCTION
 Inherited defects in lipoprotein metabolism seen in some
individuals cause primary hyper and hypolipoproteinemias
(dyslipidaemia).
 They usually occur due to genetic defect that impair lipoprotein

metabolism.
 In addition, there are secondary lipoproteinemias observed in

some diseases such as diabetes mellitus, hypothyroidism and
nephrotic syndrome.
 The type of hyperlipoproteinemias are given as per Fredrickson’s

Classification based on separation of lipoproteins seen in
electrophoresis.
CLASSIFICATION AND CHARACTERISTICS OF
HYPERLIPOPROTEINEMIAS
Hyperlipoproteinemias are elevated lipoproteins

levels that are usually associated with an
increased risk of cardiovascular disease.
There are five types

TYPE I HYPERLIPOPROTEINEMIA(FAMILIAL
LIPIPROTEIN LIPASE DEFICIENCY)
 This is due to a deficiency of lipoprotein lipase or its
activator apo C-II.
 This impairs the breakdown of triacylgycerides (TAGs)
 TAGs level are thus increased in the blood
 There is a minimal risk of cardiovascular disease which

can be treated by decreasing the fat content and
increasing the fiber content of diets.
TYPE II A and TYPE II B (FAMILIAL HYPERCHOLESTEROLAEMIA)
 Type II hyperlipoproteinemia is further classified into type II A and
type II B.
 Type II A occurs both primary and secondary to other diseases.
 Type II A is caused by a defect in LDL receptor.
 It is characterized by increased LDL and hypercholesterolemia

leading to atherosclerosis.
 Type II B occurs both primary and secondary to other diseases
 Type II B is caused by the overproduction of Apo B resulting in

increased LDL and VLDL.
 Increased cholesterol and TAG are observed in the blood.

TYPE III HYPERLIPOPROTEINEMIA(FAMILIAL HYPERBETALIPOPROTEINEMIA)
It is caused by abnormal apo E which affects

the clearance of chylomicron and VLDL
remnant receptors in the liver.
It is characterized by hypercholesterolemia,

atherosclerosis and xanthomas.
TYPE IV HYPERLIPOPROTEINEMIA(FAMILIAL HYPERTRIACYLGLYCEROLEMIA)
It is caused by overproduction of TAG in the liver

which results in increased VLDL levels in the
blood.
It is commonly associated with coronary artery

disease, obesity, Type II diabetes mellitus and
chronic alcohol abuse.
TYPE V HYPERLIPOPROTEINEMIA(FAMILIAL HYPERCHYLOMICRONEMIA)
It is mostly secondary to other diseases such as

obesity, Type II diabetes mellitus and chronic
alcohol abuse.
There is increased levels of chylomicrons and

VLDL which will increase the plasma level of TAG
and cholesterol.
The risk of coronary artery disease is increased.

TYPE LIPOPROTEIN LIPID PROFILE METABOLIC FEATURES
FRACTION DEFECT
ELEVATED
Type I Chylomicrons TAG↑↑ Lipoprotein Eruptive
lipase deficiency xanthoma,
hepatomegaly,
abdominal pain
Type II A LDL cholesterol↑↑ LDL receptor Atherosclerosis
defect CAD
Xanthomas
Type II B LDL & VLDL Cholesterol↑↑ Overproduction Corneal arcus
TAG↑ of apo B
Type III Broad beta VLDL Cholesterol↑↑ Abnormal apoE Palmar
and TAG↑ xanthomas
chylomicrons Atherosclerosis
Type IV VLDL TAG↑↑ Overproduction Associated with
cholesterol↑ of VLDL diabetes, heart
Apo CII disease, obesity
Type V VLDL & TAG↑↑ Secondary to Chronic
chylomicrons other causes pancreatitis
XANTHOMAS
 Xanthomas are lesions on the skin containing cholesterol
and fats.
 They are often associated with inherited disorders of

lipid metabolism (inherited problems with the way that
fats are broken down and used).
 Xanthomas are raised, waxy-appearing, frequently

yellowish-colored skin lesions.
XANTHOMAS
XANTHOMAS
XANTHOMAS
TREATMNT OF LIPOPROTEIN DISORDERS
FOR SEVERE HYPERTRIGLYCERIDEMIA
 Fibrates
 Omega 3 fatty acids
 Niacin or nicotinic acid
FOR HYPERCHOLESTEROLEMIA
 HMG CoA reductase inhibitors
 Cholesterol absorption inhibitors
 Bile acid sequestrants

HYPOLIPOPROTEINEMIAS
Lower lipoprotein levels are usually associated
with a reduced risk of cardiovascular disease.
But resultant deficiency of fats and fat soluble

vitamins leads to retinal lesions and peripheral
neuropathy.
ABETALIPOPROTEINEMIA
 It is caused by a defect in the synthesis of apo B and

microsomal lipid transfer protein (MTP).
 Therefore apo B containing lipoproteins: chylomicrons,

VLDL, and LDL are not formed.
 TAG and cholesterol in plasma are extremely low.
 It can be treated by large doses of fat-soluble vitamins

especially vitamin E.
HYPOBETALIPOPROTEINEMIA
It is caused by a partial deficiency of apo B and

hence chylomicrons, VLDL and LDL are present
but in low concentrations.
Affected persons are healthy and long lived.

TANGIER DISEASE (HYPOALPHALIPOPROTEINEMIA)
 It is due to a defect in ATP binding cassette transporter

responsible for the transfer of cholesterol from
peripheral tissues to the HDL.
 Blood HDL is low.
 Impaired reverse cholesterol transport increases the risk

of atherosclerosis and coronary artery disease.
LIPIDS AND LIPOPROTEIN ANALYSIS
 Lipids and lipoproteins are routinely measured in clinical
practice as important indicators of Cardiovascular
Disease risk.
 Lipid profile is a group (panel) of blood tests which

measure plasma lipids. It is frequently used to determine
a person’s risk for heart attack, heart disease or stroke.
 The lipid measurements which make up a lipid profile

are: total cholesterol, triglycerides, HDL- cholesterol, and
LDL- cholesterol
LIPIDS AND LIPOPROTEIN ANALYSIS
The lipid-related risk factors for the development of
coronary artery disease are:
(i) High total cholesterol
(ii) High LDL cholesterol
(iii) Low HDL cholesterol

PATIENT PREPARATION AND CONSIDERATIONS
 The patient must fast for 9 to 12 hours (overnight fast) before the
blood sample is taken in order to assure an accurate lipid profile.
 The preferred anticoagulant for lipoprotein assays is EDTA because

it prevents oxidation of lipids and the proteolysis of apoproteins.
Lipid results may be altered by the wrong anticoagulants such as
citrate or fluoride due to high osmotic effects.
 Plasma lipids results are interpreted in line with the clinical history
of the patient.
PATIENT PREPARATION AND CONSIDERATIONS
 Lipid values are influenced by lifestyle factors such as diet

composition, body weight, physical activity, smoking, alcohol
consumption and use of contraceptives.
 Samples should be taken without excessive venostasis.
 The patient preferably should be on a normal diet, no alcohol, no

recent change in exercise/weight/diet, no recent illness/injury.
LAB METHODS FOR MEASURING TC
 Total cholesterol (TC) is measured by enzymatic method. The
enzymatic method is subject to interference from other coloured
compounds or those which compete with the oxidation reaction.
These compounds include; bilirubin, vitamin C and haemoglobin.
LAB METHODS FOR MEASURING TGs
Triglyceride is determined by enzymatic methods.

LAB METHODS FOR MEASURING HDL
 To determine HDL-cholesterol concentration, precipitation is first
carried out using polyanions to remove the non -HDL lipoproteins
from the sample. The precipitate is removed by centrifugation.
The HDL-cholesterol, is then measured in the supernatant by a
modified enzymatic method.

LAB METHODS FOR MEASURING LDL
 LDL- cholesterol can be measured by direct or indirect methods.

The direct methods are based on selective precipitation followed
by enzymatic method. LDL- cholesterol can also be measured by
complex techniques using a mixture of polyclonal antibodies to
apoA-I and apo E.
 LDL- cholesterol determination or estimation is carried out

indirectly by using the Friedewald equation (formula):
LDL-c (mg/dL) = TC (mg/dL) − HDL-c (mg/dL) − TG (mg/dL)/5

LABORATORY METHODS FOR MEASURING LIPOPROTEIN
 The separation and quantitation of serum
lipoproteins, is based on their differences in physical
properties, such as density, size, charge, and
apoprotein content.
 Chemical precipitation methods used in laboratories

depend on particle size, charge, and differences in
the apoprotein content.
 Antibodies specific to apoproteins can be used to

bind and separate lipoprotein classes.
LABORATORY METHODS FOR MEASURING LIPOPROTEIN
Chromatographic methods take advantage of
size differences in molecular sieving methods or
composition in affinity methods.
Electrophoretic methods allow separation and

quantitation of major lipoprotein classes based
on their size and charge.
APPEARANCE OF PLASMA AFTER OVERNIGHT REFRIGERATION
 Creamy layer present - increased chylomicrons
 Creamy layer and turbid infranatant – increased chylomicrons and

VLDL
 Turbid - increased VLDL or IDL
 Clear - normal VLDL and IDL
 Appearance of serum after refrigeration does not assess levels of

cholesterol-rich LDL or HDL

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LIPOPROTEIN DISORDERS

EBOT WALTER OJONG

 They usually occur due to genetic defect that impair lipoprotein

 In addition, there are secondary lipoproteinemias observed in

 The type of hyperlipoproteinemias are given as per Fredrickson’s

Hyperlipoproteinemias are elevated lipoproteins

There are five types

 This impairs the breakdown of triacylgycerides (TAGs)

 TAGs level are thus increased in the blood

 There is a minimal risk of cardiovascular disease which

 Type II A occurs both primary and secondary to other diseases.

 Type II A is caused by a defect in LDL receptor.

 It is characterized by increased LDL and hypercholesterolemia

 Type II B occurs both primary and secondary to other diseases

 Type II B is caused by the overproduction of Apo B resulting in

 Increased cholesterol and TAG are observed in the blood.

It is caused by abnormal apo E which affects

It is characterized by hypercholesterolemia,

It is caused by overproduction of TAG in the liver

It is commonly associated with coronary artery

It is mostly secondary to other diseases such as

There is increased levels of chylomicrons and

The risk of coronary artery disease is increased.

 They are often associated with inherited disorders of

 Xanthomas are raised, waxy-appearing, frequently

 Omega 3 fatty acids

 Niacin or nicotinic acid

 HMG CoA reductase inhibitors

 Cholesterol absorption inhibitors

 Bile acid sequestrants

But resultant deficiency of fats and fat soluble

 It is caused by a defect in the synthesis of apo B and

 Therefore apo B containing lipoproteins: chylomicrons,

 TAG and cholesterol in plasma are extremely low.

 It can be treated by large doses of fat-soluble vitamins

It is caused by a partial deficiency of apo B and

Affected persons are healthy and long lived.

TANGIER DISEASE (HYPOALPHALIPOPROTEINEMIA)

 It is due to a defect in ATP binding cassette transporter

 Blood HDL is low.

 Impaired reverse cholesterol transport increases the risk

 Lipid profile is a group (panel) of blood tests which

 The lipid measurements which make up a lipid profile

(i) High total cholesterol

(ii) High LDL cholesterol

(iii) Low HDL cholesterol

 The preferred anticoagulant for lipoprotein assays is EDTA because

 Lipid values are influenced by lifestyle factors such as diet

 Samples should be taken without excessive venostasis.

 The patient preferably should be on a normal diet, no alcohol, no

Triglyceride is determined by enzymatic methods.

 To determine HDL-cholesterol concentration, precipitation is first

carried out using polyanions to remove the non -HDL lipoproteins

from the sample. The precipitate is removed by centrifugation.

The HDL-cholesterol, is then measured in the supernatant by a

modified enzymatic method.

 LDL- cholesterol can be measured by direct or indirect methods.

 LDL- cholesterol determination or estimation is carried out

LDL-c (mg/dL) = TC (mg/dL) − HDL-c (mg/dL) − TG (mg/dL)/5

 Chemical precipitation methods used in laboratories