LIVER FUNCTION

TEST AND
INTERPRETATIONS
BY: DR ANUBHAB
MODERATOR : DR SOMESH (AP)
INTRODUCTION
LIVER FUNCTION TESTS ARE USEFUL FOR :
1. THE DIAGNOSIS
2. ASSESSMENT OF PROGNOSIS
3. MONITORING OF LIVER DISEASES.
ADVANTAGES AND LIMITATIONS OF LFT
LIVER FUNCTIONS

1. EXCRETORY FUNCTION
• LIVER IS INVOLVED IN THE UPTAKE, CONJUGATION AND EXCRETION OF BILIRUBIN
DERIVED FROM DEGRADATION OF HEME IN RETICULOENDOTHELIAL SYSTEM.
• THE CONJUGATED BILIRUBIN IS EXCRETED VIA BILE.
• LIVER ALSO DETOXIFIES AMMONIA, DRUG METABOLITES AND XENOBIOTICS.
2. METABOLIC FUNCTIONS
• CARBOHYDRATE METABOLISM - GLYCOGEN METABOLISM, GLUCONEOGENESIS, BLOOD
GLUCOSE MAINTENANCE.
• LIPID METABOLISM - CHOLESTEROL METABOLISM, BILE ACID SYNTHESIS, METABOLISM OF
LIPOPROTEINS, VLDL SYNTHESIS, SYNTHESIS OF TRIACYGLYCEROL.
• PROTEIN METABOLISM - CATABOLISM OF PROTEINS, SYNTHESIS OF NON- ESSENTIAL AMINO
ACIDS, FORMATION OF UREA FROM AMMONIA
3. SYNTHESIS OF PLASMA PROTEINS
• LIVER SYNTHESIZES ALBUMIN, COAGULATION FACTORS SUCH AS PROTHROMBIN.
4. STORAGE FUNCTION
• VITAMIN A, D, K, B12, IRON AS FERRITIN ARE STORED IN LIVER.
SERUM ENZYMES
IN LIVER CELL DAMAGE, LIVER TISSUE ENZYMES LEAK INTO CIRCULATION AND THEIR
LEVELS ARE INCREASED IN PLASMA.
• ASPARTATE TRANSAMINASE (AST)
• ALANINE TRANSAMINASE (ALT)
• ALKALINNE PHSOPHATASE (ALP)
• GAMMA GLUTAMYL TRANSPEPTIDASE (GGT)
BILIRUBIN METABOLISM
• HEME IS DEGRADED IN RETICULOENDOTHELIAL SYSTEM.
• IRON IS REUTILIZED.
• GLOBIN PROTEIN - CATABOLIZED INTO AMINO ACIDS
• THE BILIRUBIN IS FORMED FROM PORPHYRIN RING OF HEME WHICH IS WATER INSOLUBLE
• IT IS CALLED UNCONJUGATED BILIRUBIN.
• UNCONJUGATED BILIRUBIN IS TRANSPORTED BY ALBUMIN TO LIVER.
ROLE OF LIVER
• IT IS INVOLVED IN THE UPTAKE OF UNCONJUGATED BILIRUBIN AND CONJUGATES THEM TO
BILIRUBIN DIGLUCURONIDE BY THE ENZYME UDP-GLUCURONYL TRANSFERASE USING
UDP-GLUCURONIC ACID, THE ACTIVE DONOR OF GLUCURONYL UNITS. THE CONJUGATED
BILIRUBIN IS WATER SOLUBLE AND EXCRETED IN BILE.
• IN THE INTESTINE- CONJUGATED BILIRUBIN GETS DECONJUGATED BY BACTERIAL BETA-
GLUCURONIDASE ENZYME IN THE TERMINAL ILEUM AND LARGE INTESTINE.
• THE PIGMENT IS FURTHER REDUCED BY FECAL FLORA TO A GROUP OF COLORLESS, TETRA
PYRROLIC COMPOUNDS KNOWN AS UROBILINOGENS.
• A SMALL FRACTION OF UROBILINOGENS IS ABSORBED IN THE TERMINAL ILEUM AND RE-
EXCRETED BY LIVER.
• THIS IS CALLED ENTEROHEPATIC CIRCULATION.
• THEN SOME OF THE UROBILINOGENS BEING WATER SOLUBLE, ESCAPE INTO URINE NORMALLY.
• IN THE INTESTINE, FURTHER REDUCTION OF UROBILINOGENS FORM STERCOBILINOGEN
WHICH IS EXCRETED IN FECES.
• SOME UROBILINOGEN GETS BACK TO LIVER AND RE-EXCRETED INTO INTESTINE VIA BILE.
THIS IS ENTEROHEPATIC CIRCULATION.
• OXIDIZED PRODUCTS FORM UROBILIN AND STERCOBILIN WHICH ARE YELLOW COLORED.

JAUNDICE IS THE YELLOWISH DISCOLORATION OF SKIN, MUCOUS MEMBRANE AND SCLERA. IT IS

DUE TO HYPERBILIRUBINEMIA. NORMAL SERUM BILIRUBIN LEVEL IS 0.2 - 1 MG/DL.
• HYPERBILIRUBINEMIA MAY BE OF CONJUGATED OR UNCONJUGATED OR BOTH.
• NORMAL SERUM UNCONJUGATED BILIRUBIN LEVEL IS 0.2-0.8 MG/DL AND CONJUGATED
BILIRUBIN LEVEL IS 0.2-0.4 MG/DL.
• JAUNDICE CLINICALLY APPEARS WHEN THE SERUM BILIRUBIN LEVEL GOES BEYOND 3 MG/DL.
BILIRUBIN METABOLISM
VANDEN BERGH TEST :
• BILIRUBIN REACTS WITH DIAZOTIZED SULFANILIC ACID TO FORM PURPLE COLORED
COMPLEX AZOBILIRUBIN.
• CONJUGATED BILIRUBIN GIVES COLOR IN AQUEOUS MEDIUM IMMEDIATELY AND IS DIRECT
POSITIVE.
• UNCONJUGATED BILIRUBIN, IN METHANOL ONLY COLOR DEVELOPS AND IS INDIRECT
POSITIVE.
• IF BOTH FRACTIONS ARE THERE, THE COLOR DEVELOPED IN AQUEOUS MEDIUM DEEPENS
ON ADDING METHANOL AND IS CALLED BIPHASIC.
• VAN DEN BERGH TEST IS INDIRECT POSITIVE IN HEMOLYTIC JAUNDICE, DIRECT POSITIVE
IN OBSTRUCTIVE JAUNDICE AND BIPHASIC IN HEPATIC JAUNDICE.
HEMOLYTIC JAUNDICE
HEMOLYTIC JAUNDICE OR PRE-HEPATIC JAUNDICE OR UNCONJUGATED HYPERBILIRUBINEMIA.
INVESTIGATIONS
• SERUM UNCONJUGATED BILIRUBIN IS INCREASED.
• URINE BILE SALTS AND BILE PIGMENTS WILL BE NEGATIVE.
• SO IT IS CALLED AS ACHOLURIC JAUNDICE.
• URINE UROBILINOGEN WILL BE EXCESS.
• MOTION IS HIGH COLORED (DARK BROWN).
CAUSES
HEMOLYTIC ANEMIA, HEMOGLOBINOPATHIES, MISMATCHED BLOOD TRANSFUSION.
INBORN ERRORS
GILBET'S SYNDROME (GS):
• IS THE MOST COMMON HEREDITARY CAUSE OF INCREASED BILIRUBIN
• CHARACTERIZED BY ELEVATED LEVELS OF UNCONJUGATED BILIRUBIN IN THE
BLOODSTREAM.
• ENZYME GLUCURONYLTRANSFERASE DEFICIENCY.
CRIGLER NAJJAR SYNDROME:
• IT IS A RARE, AR DISORDER WITH HIGH LEVELS OF UNCONJUGATED
• HYPERBILIRUBINEMIA AFFECTING BRAIN.
• UDP-GLUCURONYL TRANSFERASE ENZYME IS DEFECTIVE.
OBSTRUCTIVE JAUNDICE OR POST HEPATIC JAUNDICE OR CONJUGATED
HYPERBILIRUBINEMIA
• SERUM CONJUGATED BILIRUBIN IS INCREASED. URINE BILE SALTS, BILE PIGMENTS WILL
BE POSITIVE.
• URINE UROBILINOGEN WILL BE LESS OR ABSENT.
• MOTION IS CLAY COLORED.
CAUSES
BILIARY DUCT OBSTRUCTION - DUE TO GALL STONES, TUMOR IN THE BILE DUCT, CARCINOMA
HEAD OF PANCREAS, LYMPH NODE ENLARGEMENT IN PORTA HEPATIS,
INBORN ERRORS
DUBIN JOHNSON SYNDROME:
• AR DISORDER
• INCREASE OF CONJUGATED BILIRUBIN IN THE SERUM WITHOUT ELEVATION OF LIVER
ENZYMES (ALT, AST).
• DEFECTIVE SECRETION OF CONJUGATED BILIRUBIN INTO THE BILE. LIVER CELL ARE
PIGMENTED.
ROTOR SYNDROME:
• RARE, AR DISORDER WITH INCREASE IN CONJUGATED BILIRUBIN
• SIMILAR TO DUBIN JOHNSON SYNDROME EXCEPT THAT THE LIVER CELLS ARE NOT
PIGMENTED.
HEPATIC JAUNDICE
• BOTH UNCONJUGATED AND CONJUGATED BILIRUBIN LEVELS ARE INCREASED IN SERUM.
• URINE BILE SALTS, BILE PIGMENTS ARE POSITIVE.
• URINE UROBILINOGEN IS LESSER THAN NORMAL AMOUNTS.
• MOTION IS PALE YELLOW COLORED.
CAUSES
• ALCOHOLIC HEPATITIS, VIRAL HEPATITIS, DRUG INDUCED INTRA HEPATIC CHOLESTASIS.
TESTS BASED ON SYNTHESIS OF PLASMA PROTEINS
• SERUM ALBUMIN LEVEL - HALF-LIFE IS 20 DAYS.
• IN LIVER CIRRHOSIS, ALBUMIN LEVEL IS DECREASED. NORMAL SERUM ALBUMIN LEVEL IS 3.5-
4.5 GM/DL AND GLOBULIN LEVEL IS 2.5-3.5 GM/DL.
• NORMAL ALBUMIN GLOBULIN RATIO (AG RATIO) IS 1.2 TO 1.8 1. IN CIRRHOSIS, AG RATIO IS
REVERSED SERUM GLOBULINS ARE INCREASED IN CHRONIC ACTIVE HEPATITIS AND
CIRRHOSIS OF LIVER.
PROTHROMBIN TIME:
• NORMAL - 10-14 SECS.
• IN LIVER DYSFUNCTION, IT IS PROLONGED.
• IT IS NOT RECOVERED BY VITAMIN K ADMINISTRATION.
• IN VITAMIN K DEFICIENCY DUE TO OBSTRUCTIVE JAUNDICE ALSO, THERE WILL BE PROLONGED
PROTHROMBIN TIME
• BUT THAT WILL RECOVER AFTER PARENTERAL ADMINISTRATION OF VITAMIN K.
TUMOR MARKER-A-FETOPROTEIN (AFP) :
• IS ELEVATED IN HEPATOCELLULAR CARCINOMA.
CERULOPLASMIN:
• IS LEVEL IS DECREASED IN WILSON'S DISEASE.
SERUM PROTEIN ELECTROPHORESIS:
• IN CIRRHOSIS OF LIVER, ALBUMIN IS DECREASED AND GAMMA GLOBULINS ARE INCREASED.
• IN BILIARY OBSTRUCTION, A2 AND ẞ2 GLOBULINS ARE INCREASED.
SERUM ENZYMES
HEPATOCELLULAR DAMAGE
• SERUM AMINO TRANSFERASES- ASPARTATE AMINO TRANSFERASE (AST) AND ALANINE
AMINO TRANSFERASE (ALT) ARE ELEVATED.
• NORMALLY BOTH ARE LESSER THAN 40 U/L.
• IN ACUTE HEPATITIS, MAY INCREASE TO MORE THAN 1000 U/L.
• ALT IS FOUND IN CYTOSOL AND IS MORE LIVER SPECIFIC.
• AST/ALT RATIO IS LESSER THAN 1.BUT IN ALCOHOLIC HEPATITIS, AST IS INCREASED MORE
THAN ALT AND THE RATIO IS MORE THAN 2. THIS IS DUE TO RELEASE OF AST FROM
MITOCHONDRIA.
CAUSES OF DERANGED ALT & AST:
OBSTRUCTIVE LIVER DISEASE
• SERUM ALKALINE PHOSPHATASE (ALP) LEVEL IS INCREASED IN CASE OF CHOLESTASIS,
HEPATIC CARCINOMA AND BILIARY TRACT OBSTRUCTION.
• ALP IS PRESENT IN BONE, LIVER, INTESTINE AND PLACENTA.
• IN THE ABSENCE OF BONE DISEASE OR PREGNANCY, ALP ELEVATION INDICATES
CHOLESTASIS.
• GAMMA GLUTAMYL TRANSFERASE (Y-GT) LEVEL IS INCREASED IN OBSTRUCTIVE
JAUNDICE.
• ITS LEVEL IS A SENSITIVE BIOMARKER OF ALCOHOL ABUSE OR ALCOHOLIC LIVER DISEASE.
• 5-NUCLEOTIDASE ENZYME IS INCREASED IN HEPATOBILIARY DISEASE.
CAUSES OF DERANGED ALP:
CUASES OF HIGH GGT:
BLOOD AMMONIA
• IT IS INCREASED IN SEVERE HEPATOCELLULAR DAMAGE EITHER ACUTE OR CHRONIC. NORMAL
BLOOD AMMONIA LEVEL - 15- 60 ΜG/DL.
SERUM BILE ACIDS
• THEY ARE INCREASED IN LIVER DISEASE WITH CHOLESTASIS.
THANKYOU