LIVER FUNCTION TESTS
Functions of liver are:
A. Metabolic functions:
1. Metabolism of carbohydrates, lipids & proteins
2. Conversion of NH3 to Urea
3. Esterification of Cholesterol
4. Conversion of absorbed Monosaccharides into Glucose
5. Catabolism & Anabolism of Nucleic acids
B. Conjugation of Bilirubin (made by Heme catabolism) & its excretion in Bile
C. Conversion of Pre-Prothrombin into Prothrombin in the presence of Vitamin K
D. Synthesis of other Clotting factors including Fibrinogen, Factor V, VII, X
E. Synthesis of Albumin takes place only in liver
F. Synthesis of Alfa & Beta Globulins
G. Storage of Glycogen, Vitamin B12 & Vitamin A
H. Blood formation in embryo
LIVER FUNCTIONS COMMONLY DONE IN LABORATORIES
1. Serum Bilirubina) Total Bilirubin
b) Conjugated / Direct Bilirubin
c) Un-conjugated / Indirect Bilirubin
2. Bilirubin in urine
3. Bile salts in urine
4. Urobilinogen in urine
LIVER FUNCTION TESTS’ HANDOUT BY DR. RENU NAGAR, DEPT. OF BIOCHEMISTRY,
DR. RPGMC, TANDA
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5. Stercobilinogen in stool
6. Serum levels of Hepatic Enzymes
a) Alanine transaminase (ALT)
b) Aspartate transaminase (AST)
c) Alkaline Phosphatase (ALP)
d) Gamma Glutamyl Transferase (GGT)
7. Serum Albumin
and Albumin: Globulin Ratio (A:G Ratio)
8. Prothrombin time (PT)
LIVER FUNCTION TESTS’ HANDOUT BY DR. RENU NAGAR, DEPT. OF BIOCHEMISTRY,
DR. RPGMC, TANDA
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SERUM BILIRUBIN
•
Normal values
•
Total bilirubin: 0.3-1.0 mg/ dl
•
Conjugated bilirubin: 0.1-0.3 mg/ dl
•
Unconjugated bilirubin: 0.2-0.8 mg/dl
•
Jaundice ( yellow discolouration of conjunctiva, mucous membranes & skin) is
seen at Bilirubin > 3mg/ dl
IN HAEMOLYTIC JAUNDICE:
•
Increased breakdown of Hb exceeds capacity of liver to conjugate the
bilirubin.
•
It is seen in Haemoglobinopathies, Spherocytosis, G-6-PD-Deficiency,
Physiological jaundice of new born, Autoimmune Haemolytic Anaemias
•
Total bilirubin is increased
•
Unconjugated bilirubin is increased
•
Conjugated bilirubin is normal
IN HEPATIC JAUNDICE:
•
Diseases of liver parenchymal cells decrease its capacity to conjugate bilirubin
along with decrease in other liver functions.
•
Damage to liver cells affects Enterohepatic circulation & increased leaking of
conjugated & unconjugated bilirubin into blood.
•
Seen in Viral hepatitis, Toxic jaundice, Gilbert’s disease, Crigler-Najjar
syndrome etc.
•
Total bilirubin is raised
•
Unconjugated bilirubin is increased
LIVER FUNCTION TESTS’ HANDOUT BY DR. RENU NAGAR, DEPT. OF BIOCHEMISTRY,
DR. RPGMC, TANDA
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•
Conjugated bilirubin is also raised
•
Late stages of Viral hepatitis show Intra Hepatic obstruction to bile flow due
to edema .Presentation at this stage is that of Obstructive jaundice.
IN OBSTRUCTIVE JAUNDICE:
•
Obstruction to flow of bile in intra/ extra hepatic ducts leads to an increase
in Total & Conjugated Bilirubin in blood.
•
As conjugated bilirubin can’t enter intestine, it is not converted to
Stercobilinogen / Stercobilin / Urobilinogen / Urobilin.
•
Intra-hepatic obstruction is seen in
1.
Later stages of Viral Hepatitis
2.
Drug induced Hepatitis due drugs like steroids
•
Extra-hepatic obstruction is seen due to Gall stones,
•
Carcinoma of Gall bladder,
•
Carcinoma of head of Pancreas,
•
•
•
Ligature on bile duct,
Lymphadenopathy at Porta Hepatitis due to metastatic liver cancer
In Intra Hepatic & Extra Hepatic obstructions, Total & Conjugated Bilirubin
are raised. Hepatic functions are normal.
2. BILIRUBIN IN URINE
•
Conjugated bilirubin is water soluble & can pass through glomerular filter.
•
Unconjugated bilirubin is hydrophobic & is transported in blood with Albumin &
can’t pass through glomerular filter.
.
•
Conjugated Bilirubin is found in urine in Obstructive jaundice
•
Usually no Bilirubin is found in urine in Haemolytic jaundice
LIVER FUNCTION TESTS’ HANDOUT BY DR. RENU NAGAR, DEPT. OF BIOCHEMISTRY,
DR. RPGMC, TANDA
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3. BILE SALTS IN URINE
Sodium Glyco-Cholate & Sodium Tauro- Cholate are normally excreted in Bile, BUT
NOT SEEN IN URINE.
•
Obstruction to Bile flow leads to regurgitation of Bile salts into Systemic
circulation & then their excretion in urine.
•
Bile salts are, therefore, seen in urine in Obstructive jaundice & in
Obstructive phase of Hepatic jaundice.
•
Bile salts reduce the surface tension of urine and so, their presence is
detected by sinking of Sulfur particles in Urine (Hay’s Sulfur test)
4. URINE UROBILINOGEN
•
Normally only traces are present in urine
•
In Haemolytic jaundice more Urobilinogen is found in urine
•
In Obstructive jaundice as bilirubin cannot enter intestine and get converted
to Urobilinogen so, no Urobilinogen is found in urine
•
In Hepatic jaundice more Urobilinogen is seen in urine due to damage to
hepatic cells affecting Entero - Hepatic circulation (Circulation of blood from
Intestine to Liver via Portal vein)
5. FECAL STERCOBILINOGEN
•
•
It is increased in Haemolytic jaundice so dark faeces are passed
Decreased or absent in Obstructive jaundice so clay coloured faeces are
passed.
6. SERUM LEVELS OF HEPATIC ENZYMES.
A.
ALANINE TRANSAMINASE(ALT)
•
Normal value (3-15 IU / L).
•
It is found mainly in liver (but also in other tissues).
LIVER FUNCTION TESTS’ HANDOUT BY DR. RENU NAGAR, DEPT. OF BIOCHEMISTRY,
DR. RPGMC, TANDA
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•
It is entirely cytoplasmic.
•
ALT is markedly raised in Liver diseases
•
In Jaundice
1. ALT is markedly increased in Hepatic Jaundice
2. Slightly raised in Obstructive Jaundice
( <300 IU / L)
3. Normal in Hemolytic Jaundice
B. ASPARTATE TRANSAMINASE (AST)
•
Normal value 4-17 IU / L
•
High concentrations is liver cells and myocardium.
•
Also found in muscles, pancreas, kidney etc.
•
It is Cytoplasmic and mitochondrial.
•
So, AST is raised in
•
(a) Liver diseases( but, lesser than ALT).
•
(b) In muscular dystrophies
•
(c) Acute pancreatitis
•
(d) Leukemias
•
(e) After severe exercise.
•
•
In Jaundice:
•
AST is markedly raised in Liver diseases ie, in Hepatic Jaundice
•
AST is slightly raised in Obstructive Jaundice
•
•
( <300 IU / L)
AST is normal in Hemolytic Jaundice
LIVER FUNCTION TESTS’ HANDOUT BY DR. RENU NAGAR, DEPT. OF BIOCHEMISTRY,
DR. RPGMC, TANDA
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C. ALKALINE PHOSPHATASE.(ALP)
•
Normal value 25-90 IU / L
•
It is found in liver and bones and in smaller amounts in small intestines, kidney
and placenta.
•
ALP is raised in serum as a result of more synthesis.
(a)
It is raised in Hepatic jaundice (upto 250 IU / L)
(b)
Much higher levels are found in obstructive jaundice (even upto 1500
IU/L)
•
(c)
In Bone diseases like-Paget’s disease, Carcinomas of bone, Osteoporosis
(d)
Due to bone growth in children.
(e)
In Acute renal failure (ARF) and Chronic renal
(f)
In pregnancy.
failure (CRF).
In Jaundice:
•
•
ALP is raised in Hepatic jaundice. (upto 250 IU / L)
Much higher levels of ALP are found in Obstructive jaundice. (even
upto 1500 IU / L)
•
ALP is normal in Hemolytic Jaundice
D. GAMMA GLUTAMYL TRANSFERASE(GGT)
•
Normal value 10- 47 IU / L
•
It is a Microsomal enzyme
•
Found in liver as well as other tissues.
•
GGT is induced by:
(a) Drugs like Phenobarbitone, Phenytoin & Warfarin
(b) Alcohol : GGT is used to diagnose Alcoholic Hepatitis.
(c) GGT is raised in Obstructive jaundice.
In Jaundice:
•
Very high GGT is seen in Alcoholic Hepatitis
LIVER FUNCTION TESTS’ HANDOUT BY DR. RENU NAGAR, DEPT. OF BIOCHEMISTRY,
DR. RPGMC, TANDA
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•
Very high levels of GGT are found in Obstructive jaundice
•
•
•
GGT is raised in Hepatic jaundice
GGT is normal in Hemolytic Jaundice
6. SERUM ALBUMIN
•
Normal value Albumin 3.5- 5gm/dl.
•
Albumin: globulin ratio(A:G)::(1.5-2):1
•
Albumin is synthesized only in liver.
•
Synthesis of Albumin decreases when liver functions are affected, as in
Hepatic jaundice & Cirrhosis.
•
Beta and Gamma Globulin synthesis is increased in Infectious Hepatitis, Chronic
liver diseases and Cirrhosis.
•
Therefore, decreased Albumin and increased Globulins change the A:G ratio.
•
Therefore in Hepatic Jaundice, Albumin is decreased and A:G ratio reversed.
•
Albumin levels are normal in Obstructive and Hemolytic Jaundice.
•
Low Albumin is also seen in Kidney diseases (Albuminuria) and in Malnutrition
(Due to low intake)
7. PROTHROMBIN TIME (PT)
•
Normal Value 10-16 seconds.
•
In Hepatic Jaundice / Parenchymatous liver disease,
PT is increased due to low Prothrombin synthesis:
PT =
22-150 seconds :10-16 seconds
(patient) : (control)
•
In Obstructive Jaundice, PT is increased due to decreased Vitamin K
absorption in absence of bile salts.
LIVER FUNCTION TESTS’ HANDOUT BY DR. RENU NAGAR, DEPT. OF BIOCHEMISTRY,
DR. RPGMC, TANDA
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•
In Hemolytic Jaundice, PT is normal.
PHYSIOLOGICAL JAUNDICE OF NEW BORN
•
Due to Haemolysis: as Fetal Hb (Hb F) must be replaced by Adult Hb (Hb A1).
•
Jaundice appears on 2nd day after birth; Doesn’t exceed 15mg%; Disappears
after 7 days.
•
It is Haemolytic Jaundice so, Total and Unconjugated Bilirubin are raised.
•
Liver of newborn is immature and can’t conjugate all the Bilirubin.
•
In case the Bilirubin exceeds 20mg%, it can cross Blood Brain Barrier and
cause permanent brain damage, known as Kernicterus.
•
Risk of Kernicterus is more in Premature babies as Liver is more immature and
Blood Brain Barrier (BBB) is not well developed.
•
Treatment is by:
1. Phototherapy that converts Unconjugated Bilirubin to Water soluble form which
can be excreted in Urine
2.
or, by Exchange transfusion of blood.
LIVER FUNCTION TESTS’ HANDOUT BY DR. RENU NAGAR, DEPT. OF BIOCHEMISTRY,
DR. RPGMC, TANDA
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PARAMETER
HAEMOLYTIC
JAUNDICE
HEPATIC JAUNDICE
OBSTRUCTIVE JAUNDICE
BILIRUBIN TOTAL
INCREASED
(3-5 MG/DL)
INCREASED
(UPTO 20MG/DL)
INCREASED
(UPTO 50MG/DL)
BILIRUBIN CONJUGATED
NORMAL
INCREASED
INCREASED
BILIRUBIN
UNCONJUGATED
INCREASED
INCREASED
NORMAL
URINE BILIRUBIN
& BILE SALTS
ABSENT
INCREASED
MARKEDLY INCREASED
FAECAL
STERCOBILINOGEN
MARKEDLY
INCREASED
DECREASED
DECREASED/ABSENT
URINE
UROBILINOGEN
MARKEDLY
INCREASED
NORMAL/INCREASED
DECREASED/ABSENT
AST
NORMAL
MARKEDLY INCREASED
INCREASED
ALT
NORMAL
MARKEDLY INCREASED
(ALT>AST)
INCREASED
ALP
NORMAL
INCREASED
MARKEDLY INCREASED
GGT
NORMAL
NORMAL/INCREASED
MARKEDLY INCREASED
ALBUMIN
NORMAL
DECREASED
NORMAL
PROTHROMBIN TIME
NORMAL
INCREASED
INCREASED
SERUM ELECTROPHORESIS
1. Pre-Albumin is reduced in Hepatic jaundice
2. Albumin synthesis is reduced in Hepatic jaundice and Cirrhosis
3. Alfa-1 Globulins (Hormone binding Globulins & Glycoproteins) are reduced
•
in Hepato-cellular damage
•
increased in Febrile illness & malignancy
4. Alfa-2 Globulins & Beta Globulins are increased in Biliary obstruction
5. Gamma Globulins are increased in Cirrhosis.
Therefore in Biliary Cirrhosis there is:
•
Reduced Albumin,
•
Increased Alfa-2 Globulins,
•
Increased Beta Globulins,
LIVER FUNCTION TESTS’ HANDOUT BY DR. RENU NAGAR, DEPT. OF BIOCHEMISTRY,
DR. RPGMC, TANDA
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•
Increased Gamma Globulin
•
and Beta-Gamma Bridging (Loss of dip between beta & gamma peaks)
TESTS FOR SYNTHETIC FUNCTIONS OF LIVER
1. Serum Albumin: Solely synthesized by Liver, long half life: Reduced in Chronic
liver diseases.
Alb-3.5-5 gm/dl; Glob 3.5-5 gm/dl
A: G RATIO IS REVERSED [NORMAL A:G:: (1.5-2): 1]
2. Serum Globulin: Alfa & Beta Glob synthesized mainly by Liver, Gamma by Blymphocytes (increased in chronic illnesses).
Gamma globulins are increased in Chronic hepatitis, Cirrhosis, Auto immune
hepatitis (IgG), Primary biliary cirrhosis (Ig M), Alcoholic liver disease (Ig A).
3. Prothrombin time
4. Alfa-feto protein (AFP): Onco-fetal marker. Disappears within weeks after birth.
Mild increase in: Chronic hepatitis, cirrhosis
Marked increase in: Hepatocellular carcinoma, Germ cell tumour, Teratomas
Maternal AFP is increased in: Neural tube defect, Fetal death, Multiple fetuses.
Maternal AFP is decreased in: Down’s syndrome in fetus
N. range 30 ng/ml (upto 1 yr), 15 ng/ml (adults- males & non preg. females), 2578 ng/ml (pregnant upto 20 wks).
5. Ceruloplasmin: Synthesized by Liver (mainly) & lymphocytes.
Increased in Active Hepatitis, Biliary cirrhosis,Hemochromatosis, Obstructive
jaundice. Decreased in Wilson’s Hepato-lenticullar degeneration.
6. Pre Albumin (Transthyretin): Produced by Liver.Transports T3 & T4. Short ½
life=2 days: Early detector of Liver damage.
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DR. RPGMC, TANDA
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7. Alfa-1-antitrypsin (AAT): Acute phase protein. Synthesized & secreted by Liver.
Inactivates Elastases & Collagenases. Has many alleles: Pi ZZ Allele has low activity &
makes person prone to Cirrhosis.
AAT is low in Neonatal Cholestasis, Progressive juvenile Cirrhosis, Micronodular
Cirrhosis in adults, Emphysema.
AAT is high in Acute Trauma, infection, after Estrogen therapy, Cancer.
8. Haptoglobin (Hp): Synthesized by Liver. Short ½ life: early detection of liver
damage. Acute phase protein.Transports free Hb to RE cells. Hb can not pass thru’
glomerular filter when bound to Hp & Hb-Hp is transported to RE cells for
degradation: So, in case of severe Hemolysis, Hp is rapidly depleted.
Free Hb can cause ARF due to precipitation in renal tubules.
Hp is low in Hepatocellular disease (Low synthesis) & in Hemolytic disease (Increased
degradation). Increased in Acute Trauma, infection, inflammation & MI
9. Serum Electrophoresis
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