MODULE FOR STUDENTS

Dyslipidemia
Modul 16
Modul 17
Modul 18

Metabolism of lipoprotein
Differentiation of lipoprotein metabolism
Drug used in treatment of hyperlipoproteinemia

FACULTY OF MEDICINE
BRAWIJAYA UNIVERSITY
MALANG
2012
MODUL

16

: DYSLIPIDEMIA

METABOLISM OF LIPOPROTEIN
Overview

Lipoproteins are complexes of lipids and proteins that are essential for the
transport of cholesterol, triglycerides, and fat-soluble vitamins. Lipoproteins
are large macromolecular complexes that transport hydrophobic lipids
(primarily triglycerides, cholesterol, and fat-soluble vitamins) through body
fluids (plasma, interstitial fluid, and lymph) to and from tissues. Lipoproteins
play an essential role in the absorption of dietary cholesterol, long-chain fatty
acids, and fat-soluble vitamins; the transport of triglycerides, cholesterol, and
fat-soluble vitamins from the liver to peripheral tissues; and the transport of
cholesterol from peripheral tissues to the liver.

Goal

To understand the metabolism of lipoprotein and the clinical importance of

lipoprotein disorders derives chiefly from the role of lipoproteins in
atherogenesis.

Objectives

After completion of this module, you should be able to :

1. Mention the characteristic of human serum lipoprotein.
2. Understand the metabolism of lipoprotein.

Teaching strategies

Active learning with module task, group discussion, and expert lecture.

Suggested time

Lecture : 1 hours

Evaluation of
learning

Examination or assignment

References

1 . Disorders of Lipoprotein Metabolism. In : Greenspans Basic &

Clinical Endocrinology, 8th Ed. Digital Edition (2007); Chapter 20.
2. Disorders of Lipoprotein Metabolism. In : Harrisons Principles of
Internal Medicine, 17th Ed. Digital Edition (2008); Chapter 350.

Activity 1

Understanding the characteristic of human serum lipoprotein and the metabolism of

lipoprotein.
1. Characteristic of human serum lipoprotein
Lipoprotein class

Density of
flotation, g/mL

Major lipid
constituent

TG : Chol
ratio

Site of synthesis

Mechanism(s) of
catabolism

Chylomicron and
remnants
VLDL
IDL
LDL
HDL
Lp(a)

2. Whats the different between the exogenous and endogenous lipoprotein

metabolic pathways ?

3. Explain about the process of atherogenesis.

4. Why do serum LDL cholesterol become a target therapy ?

MODUL

17

: DYSLIPIDEMIA

Differentiation of Disorders of Lipoprotein Metabolism

Overview

Lipoproteins are complexes of lipids and proteins that are essential for the
transport of cholesterol, triglycerides, and fat-soluble vitamins. The clinical
importance of lipoprotein disorders derives chiefly from the role of lipoproteins
in atherogenesis. The greatly increased risk of acute pancreatitis associated
with severe hypertriglyceridemia is an additional indication for intervention.
Disordered lipid metabolism also underlies the syndrome of nonalcoholic
steatohepatitis (NASH). Characterization of dyslipidemia is important for
selection of appropriate treatment and may provide clues to underlying
primary clinical disorders.

Goal

To define the clinical differentiation of abnormal patterns of plasma

lipoproteins.

Objectives

After completion of this module, you should be able to define the clinical
differentiation of abnormal patterns of plasma lipoproteins and related
diseases.

Teaching strategies

Active learning with module task, group discussion, and expert lecture.

Suggested time

Lecture : 1 hours

Evaluation of
learning

Examination or assignment

References

1 . Disorders of Lipoprotein Metabolism. In : Greenspans Basic &

Clinical Endocrinology, 8th Ed. Digital Edition (2007); Chapter 20.
2. Disorders of Lipoprotein Metabolism. In : Harrisons Principles of
Internal Medicine, 17th Ed. Digital Edition (2008); Chapter 350.

Activity 2
1. What is the primary causes of hyperlipoproteinemia ?

2. What are some secondary causes of hyperlipidemia ?

3. What do you know about atherogenic dyslipidemia ?

4. A number of nonlipid risk factors are associated with increased CHD (coronary heart
disease) risk and must be considered in preventive efforts. What do you know about
nonlipid risk factor and their correlation with CHD ?

MODUL

18

: DYSLIPIDEMIA
Treatment of hyperlipoproteinemia

Overview

Clinical trials with effective cholesterol-lowering drugs have documented the

safety and efficacy of cholesterol-lowering therapy in preventing CHD.
Patients benefit from lowering plasma cholesterol levels regardless of gender,
age, or baseline lipid values whether or not they have a prior history of
vascular disease. Lifestyle change must be an integral part of risk reduction
therapy.

Goal

To understand essential component of therapeutic lifestyle changes (TLC) to

treat disorders of lipid metabolism and to understand the development of
safe, effective, and well-tolerated pharmacologic agents to treat disorders of
lipid metabolism.

Objectives

After completion of this module, you should be able to :

1. understand essential component of therapeutic lifestyle changes
(TLC) to treat disorders of lipid metabolism
2. understand the development of safe, effective, and well-tolerated
pharmacologic agents to treat disorders of lipid metabolism.

Teaching strategies

Active learning with module task, group discussion, and expert lecture.

Suggested time

Lecture : 1 hours

Evaluation of
learning

Examination or assignment

References

Disorders of Lipoprotein Metabolism. In : Greenspans Basic & Clinical

Endocrinology, 8th Ed. Digital Edition (2007); Chapter 20.
Disorders of Lipoprotein Metabolism. In : Harrisons Principles of Internal
Medicine, 17th Ed. Digital Edition (2008); Chapter 350.
Drug Therapy for Hypercholesterolemia and Dyslipidemia. In Goodman
& Gilmans The Pharmacological Basis of Therapeutics. Digital Edition
(2008); Section XXXV.

Third Report of the National Cholesterol Education Program (NCEP)

Expert Panel on Detection, Evaluation, and Treatment of High Blood
Cholesterol in Adults (Adult Treatment Panel III), 2002

Activity 3.1
Aim : to understand the essential component of therapeutic lifestyle changes (TLC) to treat
disorders of lipid metabolism.
According to the NCEP-ATP III, what is the essential component of therapeutic lifestyles
changes (TLC) to lower LDL cholesterol and reduce CHD risk ?

Mention about the ATP III LDL-C Goals and cutpoints for TLC and drug therapy in different
risk categories.

Activity 3.2
Aim : to understand the development of safe, effective, and well-tolerated pharmacologic
agents to treat disorders of lipid metabolism.
What kind of drugs can be used to treat disorders of lipid metabolism ?

Activity 3.3
This activity will help you to identification the differentiation and management of disorders of
lipoprotein metabolism by a case study.
CASE 1
A 33-year old white male has a long standing history of type 2 DM treated with
glibenclamide 10 mg. He complaints of frequent attacks of abdominal pain and also
hyperpigmentation and hyperkeratosis in the skin folds (neck and axilla). HbA1C was 10%, total
cholesterol 898 mg/dl; fasting plasma glucose 147 mg/dl. Appearance of the plasma after
overnight refrigeration shows a cream layer at the top of the tube with a turbid, opaque
infranatant.
Physical examination demonstrates an obese male, 172 cm, 110 kg, blood pressure
188/92 mmHg, pulse rate 80 x/min.
1. What physical findings is illustrated in this mans axilla ?

2. Effective treatment of this mans hyperlipidemia would include (true or false) :

a. gemfibrozil
b. cholestyramine
c. insulin
d. nicotinic acid
e. probucol
f. lovastatin
g. fish oil capsules from the health-food store
Two months later, he comes to the emergency room with acute abdominal pain
localized to the midepigastic area. Serum lipase is 1030 IU/L (normal 4-24), amylase
is 575 IU/L (normal 2-20), and triglycerides are 5432 mg/dl (normal 150-200). Plain
film of the abdomen is unremarkable; gallbladder ultrasound show no gallstones.
3. What is wrong with this man now ?

CASE 2,
A 20-year-old white male has a history of hypercholesterolemia dating back to age 12,
when total cholesterol was 315 mg/dL, triglycerides 64. This was discovered after screening,
since his mother has a history of hypercholesterolemia. His LDL cholesterol has been
consistently well over 250 mg/dl in the past. He was started on cholestyramine, but he has ad
relatively poor compliance and therefore has not had much improvement. He has seen a
dietician and appears to follow a fairly reasonable diet.
His mother was found to have cholesterol over 400 mg/dL at age 23 and was placed on
medication. She is currently on cholestyramine and pravastatin, but with LDL cholesterol
consistently over 200. Despite being 55 years of age, she has no history of cardiac disease. His
father is known to have normal cholesterol. His younger brother has elevated cholesterol to a
milder degree.
Physical examination demonstrates a thin male, height 185 cm, weight 72 kg, blood
pressure 118/74 mmHg, pulse 68x/min. There are no xanthomas, corneal arcus, or
xanthelasmas. The examination is completely normal.
1. What type of hyperlipidemia does this man probably have ?
2. Is it likely to respond to diet ?
3. Why does his mother not have significant cardiovascular disease ?
4. A recent lipid profile shows LDL cholesterol 213 mg/dL. Triglycerides are normal,and
HDL is low at 32 mg/dL. What therapy would you recommend ?
CASE 3
A 43 year old man has heterozygous familial hyperlipidemia. His serum concentration of
total cholesterol and LDL are markedly elevated. His serum concentration of HDL cholesterol,
VLDL cholesterol and triglyceride are normal or slightly elevated. This patients mother and older
brother died of myocardial infarctions before the age of 50. This patient has recently
experienced mild chest pain when walking up stairs and has been diagnosed as having angina
of effort. The patient is somewhat overweight. He drinks alcohol most evenings and smokes
about one pack of cigarettes per week.
1. If the patient has a history of gout, what drugs is most likely to exacerbate this condition?
Describe your reason.

2. Explain the mechanism why alcohol drinking is associated with cholesterol changes in
serum lipid concentration.