INTRODUCTION TO LABORATORY
MEDICINE
LIPID CHEMISTRY AND
CARDIOVASCULAR PROFILE
Main lipids in the blood are the triglycerides and
cholesterol.
 These are insoluble in the water.
 Transport in the blood is via lipoproteins.
 4 major classes of lipoproteins.

Chylomicrons
 Very low density lipoproteins (VLDL)
 Low density lipoproteins (LDL)
 High density lipoproteins (HDL)

LIPOPROTEINS COMPOSITIONS
COMPOSITION OF LIPOPROTEINS
Class
Diamete
r (nm)
%
triacylglyc
%
%
erol
% protein
phospholipi
cholesterol
&
d
cholesterol
ester
HDL
5–15
33
30
29
4
LDL
18–28
25
50
21
8
IDL
25–50
18
29
22
31
VLDL
30–80
10
22
18
50
8
7
84
Chylomicr
100-1000 <2
ons
LIPOPROTEINS





Chylomicrons carry triglycerides (fat) from
the intestines to the liver, to skeletal muscle, and
to adipose tissue.
Very-low-density lipoproteins (VLDL) carry (newly
synthesised) triglycerides from the liver to adipose tissue.
Intermediate-density lipoproteins (IDL) are intermediate
between VLDL and LDL. They are not usually detectable
in the blood.
Low-density lipoproteins (LDL) carry cholesterol from the
liver to cells of the body. LDLs are sometimes referred to
as the "bad cholesterol" lipoprotein.
High-density lipoproteins (HDL) collect cholesterol from
the body's tissues, and take it back to the liver. HDLs are
sometimes referred to as the "good cholesterol"
lipoprotein.
CHYLOMICRON STRUCTURE
LIPOPROTEIN METABOLISM
CARDIAC PROFILE TEST


ENZYMES
 Creatinine Kinase –MB(CK-MB)
 Lactate Dehydrogenase(LDH 1 and 2)
 Aspartate Aminotransferase(AST)/Serum
Glutamate Oxaloacetate Transaminase(SGOT)
 Alanine Aminotransferase(ALT)/ Serum Pyruvate
Transaminase(SGPT)
LIPID PROFILE
 CHOLESTEROL
 TRIGLYCERIDE
 HDL
 LDL
CARDIAC PROFILE
Cardiac Enzymes
Cardiac Profile assesses the function of the heart’s
muscle and the increased level of enzymes following a
myocardial infarction. The cardiac enzymes include
the following:



Aspartate aminotransferase (AST)
Lactate dehydrogenase (LD)
Creatine Kinase (CK)
ASPARTATE
AMINOTRANSFERASE (AST)
(SGOT)
found in all tissue, especially the heart, liver, and skeletal muscles
it catalyzes the transfer of the amino group of aspartic acid to alphaketoglutaric acid to form oxaloacetic acid and glutamic acid
Reaction catalyzed:
Amino group
Alpha-keto group
Oxaloacetate &
In aspartic acid
in alpha-ketoglutaric acid
Glutamate
Reference range: < 35 U/L in male and < 31 in female
Considerations in AST assays
-Serum is the best specimen
-Hemolyzed samples must be avoided
-Muscle trauma like intramuscular injections, exercise, or surgical operation
can significantly increase AST levels
CLINICAL SIGNIFICANCE

Myocardial infarction
In myocardial infarction, AST levels are usually 4-10
times the upper limit of normal
 These develop within 4-6 hours after the onset of
pain
 Peak on the 24th – 36th hour
 Usually normalize on the 4th or 5th day





Muscular dystrophy
Hepatocellular disorders
Skeletal muscle disorders
Acute pancreatitis
INCREASED LEVELS OF AST
Chronic alcohol abuse
 Drug hepatoxicity
 Pulmonary infarction
 Pericarditis
 Acute hepatitis
 Skeletal muscle disorders

DECREASED LEVELS OF AST

Pregnant women
Falsely elevated results
 Bilirubin
 Aceto-acetatae
 N-acetyl compounds
 P-aminophenol
 Sulfathiozole
 Isoniazid
 Methyldopa
 L-dopa
 Ascorbic acid
Interferences
Mercury
 Cyanide
 fluoride

LACTATE DEHYDROGENASE (LDH)
Catalyzes the reversible oxidation of lactate to
pyruvate
 Used to indicate AMI
 Is a cytoplasmic enzyme found in most cells of
the body, including the heart
 Not specific for the diagnosis of cardiac disease

DISTRIBUTION OF LD ISOENZYMES

LD1 and LD2 (HHHH, HHHM)
Fast moving fractions and are heat-stable
 Found mostly in the myocardium and erythrocytes
 Also found in the renal cortex


LD3 (HHMM)


Found in a number of tissues, predominantly in the white
blood cells and brain
LD4 and LD5 (HMMM, MMMM)
Slow moving and are heat labile
 Found mostly in the liver and skeletal muscle

CONSIDERATIONS IN LD ASSAYS
Red cells contain 150 times more LDH than
serum, therefore hemolysis must be avoided
 LDH has its poorest stability at 0°C

Clinical Significance
 In myocardial infarction, LD increases
3-12
hours after the onset of pain
 Peaks at 48-60 hours and remain elevated for 1014 days
 In MI, LD1 is higher than LD2, thus called
“flipped” LD pattern
FLIPPED
LDH
An inversion of the ratio of LD isoenzymes
LD1 and LD2; LD1 is a tetramer of 4 H–heart
subunits, and is the predominant cardiac LD
isoenzyme;
Normally the LD1 peak is less than that of the
LD2, a ratio that is inverted–flipped in 80% of
MIs within the first 48 hrs
DiffDx.
LD flips also occur in renal infarcts, hemolysis,
hypothyroidism, and gastric CA
INCREASED LEVELS OF LD
Trauma
 Megaloblastic anemia
 Pulmonary infarction
 Granulocyte leukemia
 Hodgekin’s disease
 Hemolytic anemia
 Infectious mononucleosis
 Progressive muscular dystrophy (PMD)

CREATINE KINASE (CK)
Is a cytosolic enzyme involved in the transfer of
energy in muscle metabolism
 Catalyzes the reversible phosphorylation of
creatine by ATP
 -Is a dimer comprised of two subunits, resulting
in three CK isoenzymes

The B, or brain form
 The M, or muscle form

Three isoenzymes isolated after
electrophoresis:



CK-BB (CK1) isoenzyme
 Is of brain origin and only found in the blood if the bloodbrain barrier has been breached
CK-MM (CK3) isoenzyme
 Accounts for most of the CK activity in skeletal muscle
CK-MB (CK2) isoenzyme
 Has the most specificity for cardiac muscle
 It accounts for only 3-20% of total CK activity in the heart
 Is a valuable tool for the diagnosis of AMI because of its
relatively high specificity for cardiac injury
 Established as the benchmark and gold standard for other
cardiac markers
Considerations in CK assays
CK is light sensitive and anticoagulants like
oxalates and fluorides inhibit its action
 CK in serum is very unstable and rapidly loss
during storage
 Exercise and intramuscular injections causes CK
elevations

Clinical Significance
-In myocardial infarction, CK will rise 4-6 hours
after the onset of pain
 -Peaks at 18-30 hours and returns to normal on
the third day
 -CK is the most specific indicator for myocardial
infarction (MI)

Raised levels of CK
 Progressive muscular dystrophy
 Polymyositis
 Acute psychosis
 Alcoholic myopathy
 Hypothyroidism
 Malignant hyperthermia
 Acute cerebrovascular disease
 Trichinosis and dermatomyositis
Normal Value:
 a. Male – 25-90 IU/mL
 b. Female – 10-70 IU/mL
CHOLESTEROL
Normal values: range varies according to age
 Total Cholesterol: 150-250mg%
 Cholesterol esters: 60-75% of the total cholesterol

CHOLESTEROL IS ADVISED IF YOU
 have been diagnosed with coronary heart disease,
stroke or mini-stroke (TIA) or peripheral arterial
disease (PAD)
 are over 40
 have a family history of early cardiovascular disease
 have a close family member with cholesterol-related
condition
 are overweight
 have high blood pressure, diabetes or a health
condition that can increase cholesterol levels, such as an
underactive thyroid
FACTORS LEADING TO RAISED
CHOLESTEROL





an unhealthy diet: some foods already contain
cholesterol (known as dietary cholesterol) but it is the
amount of saturated fat in your diet which is more
important
smoking: a chemical found in cigarettes called
acrolein stops HDL from transporting cholesterol to
the liver, leading to narrowing of the arteries
(atherosclerosis)
having diabetes or high blood pressure(hypertension)
having a family history of stroke or heart disease
There is also an inherited condition known as familial
hypercholesterolaemia (FH). This can cause high
cholesterol even in someone who eats healthy diet.
TRIGLYCERIDES




Ester derived from glycerol and three fatty acids.
Main lipids in the blood and important energy substrate.
Insoluble in water.
Hypertriglyceridemia
Not an important risk facotr for coronary artery disease.
 It can cause pancreatitis when severe.

Both hypertriglyceridemia and hypercholesterolemia are
associated with various types of cutaneous fat deposition and
xanthomatas.
Hypertension


Very common clinical problem. Usually essential type
meaning that have no identifiable cause.
Investigations for treatable causes like endocrine is
necessary.
SPECIAL CHEMISTRY
Definition
Special Chemistry is a subsection of the Chemistry
Laboratory of the Division of Clinical Pathology. This
includes the tests which are not the part of the routine
panel.
Electrophoresis
 Urine chemistry
 Radioimmunoassay.

Test
Sensitivity and specificity
Troponin test
The most sensitive and specific test for
myocardial damage. Because it has increased
specificity compared with CK-MB, troponin is a
superior marker for myocardial injury.
Myoglobin (Mb)
low specificity for myocardial infarction. Rises
very early within 1-3 hours of pain.
Pro-brain natriuretic
peptide (pro-BNP)
This is increased in patients with heart failure. It
has been approved as a marker for acute
congestive heart failure
Glycogen
phosphorylase
isoenzyme BB
• high sensitivity and specificity early after chest
pain.
• by ELISA
Normal troponin levels 12 hours after chest pain has started mean a heart
attack is unlikely

Myloperoxidase (MPO)


CRP


elevated in atherosclerosis when atheroma is about to
rupture
Oxidized LDL


Marker of atherosclerosis
Pregnancy associated plasma protein A (PAPPA)


Elevated in chronic conditions
A marker of atherosclerosis
Choline
Test of prognosis
 Rises in chest discomfort even without rise in troponin
level.
