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
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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

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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
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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


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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.
LIVER
Anatomy of liver
LIVER HISTOLOGY
FUNCTIONS OF LIVER
Metabolic
 Synthesis
 Breakdown
 Other functions – storage of vitamin A,D,B12,F…
 Excretion of waste products from bloodstream
into bile
 Vascular – storage of blood
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SYNTHESIS
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Protein metabolism
Synthesis of amino acids
Carbohydrate metabolism
Gluconeogenesis
Glycogenolysis
Glycogenesis
Lipid metabolism
Cholesterol synthesis
Lipogenesis
Production of coagulation factors I, II, V, VII, IX, X and XI,
and protein C, protein S and antithrombin
Main site of red blood cell production
Produces insulin-like growth factor 1 (IGF-1), a polypeptide
protein – anabolic effects
Production of trombopoetin
BREAKDOWN
Breaks down insulin and other hormones
 Breaks down hemoglobin
 Breaks down or modifies toxic substances
(methylation) → sometimes results in toxication
 Converts ammonia to urea

OTHER FUNCTIONS
Produces albumin, the major osmolar component
of blood serum
 Synthesizes angiotensinogen, the hormone
responsible for raising blood pressure when
activated by renin (enzyme released when the
kidney senses low blood pressure)

LIVER PROFILE
The typical Liver Profile test includes
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ALT
AST
Alkaline Phosphatase
GGTP
Bilirubin
Prothrombin time
Protein
LDL
Albumin
Globulin.
pathogenesis
Different cells have different enzymes inside them,
depending on the function of the cell. Liver cells
happen to have lots of AST, ALT, and GGTP inside
them. When cells die or are damaged, the enzymes
leak out causing the blood level of these enzymes to
rise; that is why the levels of these enzymes in the
blood are considered
good indicators of liver cell damage. ALT is more
specific for liver disease than AST because AST is
found in more types of cell (e.g. heart, intestine,
muscle). The AST, for instance, will rise after a heart
attack or bruised kidney. GGTP and AP are said to be
more specific for evaluating biliary disease since they
are made in bile duct cells. In liver disease caused by
excess alcohol ingestion, the AST tends to exceed the
ALT, while the reverse is true to for viral hepatitis.
AMINOTRANSFERASES
The normal range is 5-40 IU/L
ALKALINE PHOSPHATASE
Sites
 Liver

Gallstone
 tumor blocking the common bile duct
 alcoholic liver disease
 drug-induced hepatitis

o
o
Bone, placenta, and intestine.
GGT is utilized as a supplementary test
GGT (OR GGTP) (0-30 IU/L)
Gamma Glutamyl Transpeptidase. This enzyme
level is elevated in case of liver disorders. In
contrast to the alkaline phosphatase, the GGT
tends not to be elevated in diseases of bone,
placenta, or intestine
BILIRUBIN
Jaundice
 breakdown of a substance in red blood cells called
"heme.
 less than 1.1 mg/dL
 Increased production
 Decreased excretion
ALBUMIN
3.5- 5.2 g/dL
chronic liver disease
Kidney diseases (20 mg/ g of creatinine)
GIT diseases
Edema and ascites.

PROTHROMBIN TIME
good correlation between abnormalities in
prothrombin time and the degree of liver dysfunction.
 Expressed in seconds and compared to a normal
control patient's blood

SPECIALIZED TESTS
 serum iron,
 the percent of iron saturated in blood,
 the storage protein ferritin for hemochromatosis.
 accumulation of copper in the liver in wilson disease.
RENAL PANEL
Glucose
 BUN
 Creatinine
 Potassium
 Phosphorous
 Sodium
 Albumin
 BUN/Creatinine Ratio
 Calcium
 Chloride
 Carbon Dioxide (CO2), Total

GLUCOSE (
To find out the cause of renal disease.
 Diabetic nephropathy.

BUN (7 to 20 mg/dl)
Formed in the liver by the metabolism of the
proteins.
 Kidney function
 May be low if there is liver pathology even if
kidneys are normal

BUN/CREATININE RATIO
BUN-to-creatinine ratio can help your doctor
check for problems, such as dehydration, that
may cause abnormal BUN and creatinine levels.
 High BUN-to-creatinine ratios occur with sudden
(acute) kidney failure, which may be caused by
shock or severe dehydration. A low BUN-tocreatinine ratio may be associated with a diet low
in protein, a severe muscle injury called
rhabdomyolysis, pregnancy, cirrhosis or
syndrome of inappropriate antidiuretic hormone
secretion (SIADH).

Normal Results: 10:1 to 20:1
CREATININE (0.8 TO 1.4 MG/DL)



It is a breakdown product of creatine (muscle proteine).
Formed in liver and kidney.
Excretion is via klidneys so level raises when kidney is
diseased.
POTASSIUM(3.7 to 5.2 mEq/L)


the amount of potassium in the blood
High blood potassium levels may be caused by damage or
injury to the kidneys
PHOSPHORUS
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Phosphorus is a mineral that makes up 1% of a person's total
body weight.
High levels of phosphorus in blood only occur in people with
severe kidney disease or severe dysfunction of their calcium
regulation.
Along with excess calcium they may calcify in the soft tissues.
SODIUM(135 TO 145 MEQ/L)
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High levels of sodium can increase the chance of high
blood pressure.
If your total body water is low, high sodium levels
may be due to fluid loss from excessive sweating,
diarrhea, use of diuretics or burns.
If your total body water is normal, high sodium levels
may be due diabetes insipidus or too little of the
hormone vasopressin.
If your total body water is high, high sodium levels
may indicate hyperaldosteronism, Cushing syndrome,
or a diet that's too high in salt or sodium bicarbonate
Low total body water and sodium levels may be due to
dehydration, vomiting, diarrhea, over diuresis, or
ketonuria
An increase in total body water and low sodium levels
may indicate congestive heart failure, nephrotic
syndrome or other kidney disease, or cirrhosis of the
liver
ALBUMIN (3.4 TO 5.4 G/DL)

The albumin test measures the amount of albumin in
serum, the clear liquid portion of blood and
determines if the liver is making enough albumin.
This test helps in determining if a patient has liver
disease or kidney disease, or if not enough protein is
being absorbed by the body. Albumin is one of the two
major proteins in the blood, the other is
Globulin. Albumin also helps carry some medicines
and other substances through the blood and is
important for tissue growth and healing. Because
albumin is made by the liver, decreased serum
albumin may result from liver disease. It can also
result from kidney disease which allows albumin to
escape into the urine. Decreased albumin may also
be explained by malnutrition or a low protein diet
CO2 (TOTAL)


This test measures the amount of carbon dioxide in
the liquid part of your blood. Carbon dioxide (CO2) is
a gaseous waste product made from metabolism. The
blood carries carbon dioxide to your lungs, where it is
exhaled. Changes in your CO2 level suggest you may
be losing or retaining fluid, cause an imbalance in
your body's electrolytes. Electrolytes are minerals in
your blood and other body fluids.
Abnormal levels of carbon dioxide suggest your body
is having trouble maintaining its acid-base balance
and your electrolyte balance is upset.
Normal Results: 20 to 29 mEq/L
CALCIUM (8.5 TO 10.2 MG/DL)
To build and fix bones and teeth
 help nerves work
 make muscles contraction
 help blood clot
 and help the heart to work.
 The Calcium test screens for problems with the
parathyroid glands or kidneys, certain types of cancers and
bone problems, inflammation of the pancreas (pancreatitis),
and kidney stones.
CHLORIDE (96 to 106 mEq/L)
Chloride levels can be used to help monitor high blood
pressure, heart failure and kidney disease. High levels of
chloride, known as hyperchloremia, typically indicate
dehydration, metabolic acidosis and other
conditions. Decreased levels of chloride, known as
hypochloremia, can indicate kidney disorder, Addison's
disease, congestive heart failure and other conditions.

BONE METABOLISM
Bone is constantly remodelling
 Bone resorption= bone formation
 Why remodelling is necessary?

To withstand changing environment
 To cope with workload
 To repair damage caused by recurrent microtraumas
BONE METABOLISM
Osteoclasts and Osteoblasts
Osteocytes
Encased osteoblasts which are connected to each other
by long cellular processes forming a network
connected by gap junctions.
