LIVER FUNCTION TEST ..we are describing you about liver function test

2.  Synthetic functions : synthesis of plasma proteins,
cholesterol, triacyl glycerol, lipoprotein
 Metabolic function: protein metabolism, ketogenesis, TCA
cycle, production of ATP
 Detoxification & excretion: ammonia to urea, bilirubin,
cholesterol, drug metabolites.
 Homeostasis : blood glucose regulation
 Storage function: Vitamin A,D,K,B12
 Production of bile salts

3.  Screening: They are non invasive yet sensitive modality for
liver dysfunction.
 Pattern of disease: They are helpful to recongnize pattern of
various diseases. Like being helpful in differentiating between
acute viral hapatitis and various cholestatic disorders and
chronic liver disease.(CLD)
 Assess severity : They are heplful to assess the severity and
predict the outcome of certain diseases like primary biliary
cirrhosis.
 Follow up: They are helpful in the follow up of certain liver
diseases and also helpful in evaluating response to therapy
like autoimmune hepatitis

4.  1. Tests of the liver’s capacity to transport organic
anions & to metabolise drugs-serum bilirubin, urine
bilirubin, urobilinogen etc.
 2. Tests that detect injury to hepatocytes (serum enzyme
tests)- Aminotransferases, Alkaline phosphatase, glutamyl
transpeptidase,5nucleotidase,leucine aminopeptidase etc.
 3. Tests of the liver’s biosynthetic capacity-serum
proteins, albumin, ceruloplasmin, prothrombin time etc.

5.  Jaundice
 Suspected liver metastasis
 Alcoholic liver disease
 Any undiagnosed chronic illness
 Annual checkup of diabetic patients
 Coagulation disorders
 Therapy with statins to check hepatotoxicity

6. BY
ADITYA GIRI

7. .Bilirubin is an endogenous anion derived from
catabolism of heme.
. It is conjugated by liver to form bilirubin levels ,more
than 17umol/L suggests liver disease.
 .Classification of bilirubin into direct & indirect
bilirubin is based on original van den bergh method
of measuring bilirubin.
 .Van den Bergh is a chemical reaction used to
measure bilirubin level in blood. The reaction is highly
useful in understanding the nature of jaundice.

8. .Bilirubin is the excretory product formed by the
catabolism of heme part of haemoglobin.
.Porphyrin part of heme are converted to bilirubin in
reticuloendothelial cells of liver, spleen, bone marrow.
.Unconjugated bilirubin is bound to serum albumin &
transferred to liver where it is conjugated to
glucuronate by UDP GLUCURONYL TRANSFERASE.
.Conjugated bilirubin is excreted into bile. A fraction
of bilirubin from stool is reabsorbed into blood via
portal circulation (enterohepatic circulation).

9. PRODUCTION & EXCRETION OF
URINE

10. PRINCIPLE: When diazotised sulfanilic acid reacts
with bilirubin, it forms ‘azobilirubin’ which is a
purple colour product.
.Increased conjugated bilirubin – gives colour
immediately i.e direct positive.
.Increased unconjugated bilirubin -gives colour
only after addition of methanol i.e indirect positive

11.  Hyperbilirubinemia : when the level of bilirubin
exceeds 1mg/dl in serum.
 Based on the cause it is classified into congenital
and acquired.
 Congenital hyperbilirubinemia: They result from
abnormal uptake, conjugation or excretion of
bilirubin due to inherited defects
 CRIGLER-NAJJAR SYNDROME: Here the defect is in
conjugation due to severe deficiency of enzyme
UDP-GLUCURONYL TRANSFERASE. Unconjugated
bilirubin level increases to more than 20mg/dl and
hence kernicterus occurs.

12.  GILBERT SYNDROME: it is inherited as an
autosomal dominant trait. The defect is in the
uptake of bilirubin by the liver . Bilirubin level
goes around 3mg/dl.
 DUBIN-JOHNSON SYNDROME: It is an
autosomal recessive trait leading to defective
excretion of conjugated bilirubin, so
conjugated bilirubin in bold increases. There is
defect in transport of conjugated bilirubin into
bile. Bilirubin gets deposited in the liver and
liver appears black. This condition is known as
black liver jaundice.
ROTOR SYNDROME: It is an autosomal recessive
trait. In this bilirubin exrection is defective.

13.  PHYSIOLOGICAL JAUNDICE: Also known as
neonatal jaundice. This transient
hyperbilirubinemia is due to an accelerated rate of
destruction of RBCs & also because of immature
hepatic system of conjugation of bilirubin. In all
new born infants after the 2nd day of life, mild
jaundice appears. In such cases bilirubin does not
increase above 5mg/dl.
 BREAST MILK JAUNDICE: In some breast-fed
infants, prolongation of jaundice has attributed to
high level of estrogen derivative in maternal blood,
which is excreted through the milk. This would
inhibit the glucuronyl transferase system .Sulfa
and other drugs may release bilirubin from albumin
and may cause jaundice in new born.

14.  JAUNDICE :-
Jaundice is the yellowish discolouration
of sclera, skin, mucous membrane. It
is characteristic of liver disease but
will occur when rate of hemolysis is
increased leading to the elevation of
serum albumin.

15.  Hemolytic disease of newborn:
Rh incompatibilty – Erythroblastosis fetalis
 Hemolytic diseases of Adults:
condition is seen in increased rate of hemolysis. It
usually occurs in adults. There is increase in
unconjugated bilirubin in blood, absence of
bilirubinuria & excessive excretion of UBG in urine
& SBG in feces.

16. .The most common cause is viral hepatitis, caused by
hepatitis viruses A,B,C,D or E.
.In pure hepatocellular disease, conjugation in liver is
decreased leading to increase in free bilirubin in
circulation.
.The UBG level in urine may be normal or decreased in
hepatocellular jaundice.
 .In this, a biphasic reaction is observed, because
both conj. & unconj. bilirubins are increased

17. .Conjugated bilirubin is increased in blood & it is
excreted in urine. If there is complete obstruction,
UBG will be decreased in urine or even absent.
 .In total obstruction of biliary tree, the bile
doesn’t enter the intestine. Since no pigments are
entering the gut, the feces become clay coloured.
 .Van den Bergh test is direct positive as conj.
bilirubin is elevated.

18. Types of bilirubin Class of jaundice Causes
Unconjugated Prehepatic or hemolytic Abnormal red cells;
antibodies; drugs &
toxins; thalassemia;
hemoglobinopathies.
Gilbert syndrome;
Crigler-Najjar syndrome,
GPD deficiency.
Unconjugated &
conjugated
Hepatic or hepatocellular Viral hepatitis; toxic
hepatitis; intrahepatic
cholestasis
Conjugated or
obstructive
Posthepatic .Intrahepatic cholestatis-
chronic active hepatitis,
obstructive stage of viral
hepatitis, Dubin-
johnson syndrome
.Extra hepatic
obstruction-stones in the
gallbladder or biliary
tract, carcinoma of head
of pancreas, enlarged

19. Hemolytic
jaundice
Hepatocellular
jaundice
Obstructive
jaundice
Blood, free
bilirubin
Increased Increased Normal
Blood, conj.
Bilirubin
Normal Increased Increased
Blood, ALP Normal Increased Very high
Urine, bile salts Nil Nil Present
Urine, conj.
Bilirubin
Nil Present Present
Urine bilinogens Increased Present Nil
Fecal
urobilinogen
increased Decreased Absent

20.  . The presence of urine bilirubin indicates
hepatobiliary disease. Unconjugated bilirubin is
tightly bound to albumin and not filtered by the
glomerulus and thus not present in urine.
Measurable amount of conjugated bilirubin in
serum are found only in hepatobiliary disease.
 .Because the renal threshold for conjugated
bilirubin is low and the laboratory methods can
detect low levels of bilirubin in urine so
conjugated bilirubin may be found in urine when
the serum bilirubin levels are normal. This is the
case in early acute viral hepatitis.

21.  . An increase in the urobilinogen in urine is a
sensitive indicator of hepatocellular dysfunction. It
is a good indicator of alcoholic liver damage, well
compensated cirrhosis or malignant disease of
liver. In viral hepatitis it appears early in urine. It is
markedly increased in hemolysis.
 . In cholestatic jaundice urobilinogen disappears
from urine. It is intermittently present in case of
gallstones.
 .Urobilinogen gives a purple reaction to Ehrlich’s
aldehyde reagent.

22. BY
AALOK KUMAR

23.  A large number of enzyme estimations are available
which are used to ascertain liver function.
 They are be divided into two groups:
A). Enzymes indicating hepatocellular damage.
B). Enzymes indicating cholestasis (obstruction).
 In liver cells injury , damage to the membrane of cells &
organelles allows intracellular enzymes to leak into the
blood

24. ENZYMES THAT DETECT
HEPATOCELLUAR
NECROSIS
• ALT
• AST
ENZYMES THAT DETECT
CHOLESTASIS
• ALKALINE PHOSPHATASE
• 5 NUCLEOTIDASE
• LEUCINE AMINOPEPTIDASE

25. ALKALINE PHOSPHATASE
SERUM TRANSFRASE
ALT AST
GGT
5’NT

27.  AST (Aspartate transaminase)/SGOT (serum glutamate oxaloacetate
transaminase)
 ALT (Alanine transaminase)/SGPT (serum glutamate pyruvate
transaminase)
SGOT
SGPT

28.  Normal range: 10-45 U/L.
 AST is found in both cytoplasm & mitochondria
 AST/GOT also reflects damage to the hepatic cells
& is less specific for liver disease.
 It is a cardiac marker.
 AST help diagnose various heart, muscle or brain
disorders, such as a myocardial infarct (heart
attack).

29.  Acute hemolytic anemia
 Cirrhosis of the liver
 Hepatitis
 Acute pancreatitis or inflammation of pancreas
 Acute renal failure or loss of kidney function.
 Heart attack
 Primary muscle disease
 Recent surgery

30.  Normal Range: 5-40 U/L.
 ALT is a cytoplasmic enzyme.
 The activity of these enzymes is low in normal
serum.
 ALT is specific for liver disease.
 Its elevations favor liver cell necrosis as a
cholestasis.

31.  Alcoholic liver disease
 Cancer of liver
 Hepatitis or inflammation of the liver
 Noncancerous tumor of the liver
 Use of medicines or drugs toxic to the liver
 Cirrhosis or scarring of the liver
 Death of liver tissue.

32. • Normal ratio is 0.7 to 1.4
• Useful in Wilson disease, chronic liver disease and alcoholic
liver disease
• AST/ALT ratio of > 2:1 is suggestive of and >3:1 is highly
suggestive of Alcoholic liver disease
• AST in Alcoholic live disease is rarely >300 IU/L.
• ALT is usually normal in alcoholic liver disease ; can be sometimes
low due to an alcohol induced deficiency of pyridoxal phosphate
• AST/ALT <1 is seen in NASH and viral hepatitis.

33. • mAST/total AST ratio – marker of chronic alcohol
consumption
• This distinguishes those who consume excess alcohol
from normal subjects irrespective of the presence or
absence of liver disease

35. •ALKALINE PHOSPHATASE
•Y-GLUTAMYL TRANSPEPTIDASE
•5-NUCLEOTIDASE

36.  ALP occurs in in all tissues, especially liver, bone, bile duct, kidney &
the placenta.
 The ALP used to help diagnose certain liver diseases and bone
disorders.
 Normal range: 30 - 95 IU/L (3-13 kings unit)
 ALP is a hydrolase enzyme responsible for removing phosphate
groups from many types of molecules, including nucleotides &
proteins.
 Levels are significantly higher in growing children.
 A rise in serum ALP (normal 3-13 KA units/dl), usually associated
with elevated serum bilirubin is an indicator of biliary obstruction
(obstructive/post hepatic jaundice).
 ALP is also elevated in cirrhosis of liver & hepatic tumors.

38.  Normal range: 10-15 U/L
 This is a microsomal enzyme widely distributed in body tissues,
including liver.
 Measurement of γ - glutamyl transpeptidase (GGT) activity provides
a sensitive index to asses liver abnormality.
 Serum GGT is highly elevated in biliary obstruction & alcoholism.
 GGT elevation parallels than of ALP.
 Increased level of GGT are observed in chronic alcoholism ,pancreatic
disease ,MI ,renal failure ,diabetes mellitus.
 Several drugs (e.g. phenytoin) induce (liver synthesis) & increase this
enzyme in circulation.

39.  Normal range: 2-15 U/L
 The serum activity of 5'-nucleotidase is elevated
in hepatobiliary disease & this parallels ALP.
 It is highest in post-hepatic obstructive jaundice.
 The 5'-nucleotidase is normal in patients with
bone disease where as serum ALP increased .

41. Function test Pre-hepatic Jaundice Hepatic Jaundice Post-hepatic Jaundice
Total bilirubin Normal / Increased Increased
Conjugated bilirubin Normal Increased Increased
Unconjugated
bilirubin
Normal / Increased Increased Normal
Urobilinogen Normal / Increased Increased Decreased / Negative
Urine Color Normal
Dark (urobilinogen +
conjugated bilirubin)
Dark (conjugated
bilirubin)
Stool Color Normal Normal/Pale Pale
Alkaline phosphatase
levels
Normal
Increased
Alanine transferase
and Aspartate
transferase levels
Increased
Conjugated Bilirubin
in Urine
Not Present Present
Splenomegaly Present Present Absent
Table of diagnostic tests

42. BY
CHANCHAL KUMAR SAHU

43. Plasma
proteins
Prothrombin
time
TESTS BASED ON SYNTHETIC
FUNCTION

44. PROTEIN
•Liver is the sole site for synthesis of most plasma
proteins except immunoglobulins (gamma
globulins)
•Serum albumin comprises 60% of all plasma
proteins
TESTS FOR PROTEINS INCLUDE-
1. Total serum proteins
2. Serum albumin
3. Albumin/globulin ratio
4. Serum protein electrophoresis
5. Prealbumin
6. Procollagen III peptide
7. Ceruloplasmin
8. Alpha fetoprotein
9. Alpha antitrypsin

45. ALBUMIN
•Synthesized exclusively by liver
•Its half life is 18-20 days
•Due to its slow turn over – not a good indicator of acute
or mild hepatic dysfunction
• In hepatitis - <3g/dl of albumin – possibility of chronic
liver disease
•Non hepatic causes of Hypoalbuminemia -
• Protein losing enteropathy
• Nephrotic syndrome

46. PREALBUMIN /TRANSTHYRETIN
• Levels fall in liver disease
• Half life – 2 days
• Sensitive indicator of any changes affecting its synthesis
and catabolism
• PAB is a negative acute phase reactant
• Particularly useful in drug-induced hepatotoxicity

47. • Normal plasma levels - 0.2-0.4g/L
• Acute phase protein
• Decreased in multiple conditions –
1. Wilson’s disease
2. Menkes disease
3. Aceruloplasminemia
4. Copper deficiency
CERULOPLASMIN
• Increased in –
1. Copper toxicity
2. Pregnancy
3. OCPs

48. PROCOLLAGEN III PEPTIDE
• Cleavage product of the type III procollagen
molecule
• Radioimmunoassay
• Elevated Conc. Of PIIIP- the transformation of
viable hepatic tissue into connective
tissue/fibrosis

49. • AFP is a gp and MW – 70,000 daltons
• Normally present in fetus
• Liver, yolk sac and small intestine
• AFP- ELISA
HCC
Non seminomatous testicular
cancer
Ataxia telangiectasia
Hereditary tyrosinemia
Neonatal hyperbilirubinemia
Chronic active hepatitis
α- FETO PROTEIN

50. COAGULATION FACTORS
•With the exception of F-VIII , all other factors are synthesized
in liver
•Half life ranges from 6hrs for F-VII to 5 days for fibrinogen
• So their measurement is the single best measure of hepatic
synthetic function
• Tests – Serum prothrombin time
•Marked increase in PT >5secs above the control and not
corrected by Vit K administration – is a poor prognostic sign in
acute viral hepatitis and other acute and
chronic liver disease

51.  Prothrombin is synthesized by liver
 Half life – 6 hrs so it indicate – present function of liver
 PT :blood test, time taken by blood to clot
 Normal value : 10 to 15 sec.
 PT is Prolonged - liver losses 80% of reserve capacity
 Commonly PT is used for detecting liver coagulopathies
 Note : Vit K deficiency Prolongs PT time
 But In case of LIVER diseases : PT remains prolonged even
after parenteral administration of Vit. K

52.  Lack sensitivity: The LFT may be normal in certain disesliver
disease like cirrhosis, non cirrhotic portal fibrosis ,cogenital hepatic
fibrosis
 Lack specificity: They lack specificity and are not specific for any
particular disease. Serum albumin may be decreased in chronic
disease and also in nephrotic syndrome.
Amino-transferase may be raised in cardiac diseases and hepatic
diseases.
Except for serum bile acids the LFT are not specific for liver
diseases
Thus, we see that LFT have certain advantages as well as limitation
at the same time