LIVER FUNCTION TESTS

A LIVER DISEASE CAN BE CLINICALLY EVALUATED BY 1.TAKING CLEAR HISTORY INCLUDING THE MAJOR RISK

FACTORS LIKE ALCOHOLISM,ILLICIT DRUG USE,BLOOD TANSFUSIONS,OCCUPATIONAL EXPOSURE TO TOXINS,GENETIC DISEASES SUCH AS WILSONS,HEAMOCHROMATOSIS,ALPHA 1 ANTI TRYPSIN DEFICIENCY.

2.CLINICAL FINDINGS WHICH MAY BE MILD, NON SPECIFIC LIKE LOSS OF APPETITE, EASYFATIGABILITY, MALAISE, ALTERED SLEEP PATTERNS, CHANGES IN PERSONALITY, PRURITUS, ABDOMINAL PAIN, INDIGESTION, CHANGES IN URINE AND STOOL COLOUR AND PHYSICAL EXAMINATION WHICH MAINLY FOCUSES ON ICTERUS, JAUNDICE, ASCITES, SPIDER ANGIOMASA, XANTHELASMA, ENCEPHALOPATHY, PALMAR ERYTHEMA AND FETOR HEPATICUS

3.LIVER FUNCTION TESTS

LIVER FUNCTION TESTS CAN BE BROADLY BE CLASSIFIED INTO

1.STANDARD LABORATORY TESTS 2.QUANTITATIVE LIVER TESTS3.MEASUREMENT OF LIVER BLOOD FLOW 4.RADIOLOGIC AND ENDOSCOPIC METHODS

STANDARD LABORATORY TESTS: DETECTION OF HEPATOCELLULAR INJURY. ASSESMENT OF PROTIEN SYNTHESIS. EVALUATING CHOLESTATIC DISORDERS

DETECTION OF HEPATOCELLULAR INJURY: 1.AMINOTRANSFERASES-ALT AND AST.

ALT-ALANINE AMINOTRANSFERASE/SERUM GLUTAMIC PYRUVIC TRANSAMINASE.

AST-ASPARTATE AMINOTRANSFERASE/SERUM GLUTAMIC OXALOACETIC TRANSAMINASE.

THESE CATALYSE OF AMINE GROUP TO ALPHA KETO GLUTARATE TO YIELD GLUTAMATE AND PYRUVATE(ALT),OXALOACETATE(AST).

ALT-CYTOPLASMIC LIVER ENZYME.

AST-FOUND ION MANY EXTRAHEPATIC TISSUES(HEART, MUSCLE, BRAIN, KIDNEY, PANCREAS, ADIPOSE TISSUE, BLOOD).

RANGES-MILD-100 TO 249 IU/L,MODERATE-250-999IU/L,LARGE-1000 TO 1999 IU/L,EXTREME-MORE THAN 2000.

DE RITI’S RATIO –BETWEEN AST/ALT. >4-WILSONS DISEASE. 2 TO 4-ALCOHOLIC LIVER DISEASE. <1-NON ALCOHOLIC LIVER DISEASE

2.LDH: FOUND IN LIVER AND ALSO IN EXTRAHEPATIC

TISSUES ALSO.

BOTH DISORDERS LIKE IN LIVER DISEASE AND EXTRA HEPATRIC LIVER DISORDERS LIKE IN HEMOLYSIS, RHABDOMYOLYSIS, ACUTE CVA, MI, TUMOUR NECROSIS, RENAL INFARCTION IT IS ELEVATED.

PROLONGED CONCURRENT INCREASE IN LDH +ALP IS DIAGNOSTIC OF MALIGNANT INFILTRATION OF LIVER.

EXTREME INCREASE IS INDICATIVE OF FULMINAT VIRAL HEPATITIS,DRUG INDUCED, HYPOXIC HEPATITIS, ALLWAYS ACCOMPANIOED WITH INCREASE IN ALT AND AST IN HEPATOCELLULAR INJURY

3.GLUTHATHIONE-S-TRANSFERASE: BOTH SENSITIVE AND SPECIFIC FOR DRUG

INDUCED LIVER INJURY. PLASMA HALF LIFE OF 90MINS AND IS

RELEASED RAPIDLY INTO CIRCULATION AFTER HEPATOCYTE INJURY.

WHILE ALT AND AST –ACINAR ZONE 1, GLUTHATHIONE-S-TRANSFERASE-ACINAR ZONE 3(CENTRILOBULAR REGION)

ASSESMENT OF HEPATIC PROTEIN SYNTHESIS

1.SERUM ALBUMIN- 12 -15gm/day Total body pool-500 gm YIELDS INFORMATION ABOUT

HEPATOCELLULAR FUNCTION(PROTIEN SYNTHESIS).

CAN BE USED TO EVALUATE CHRONIC LIVER DISEASE.

HAS A PLASMA HALF LIFE OF 3 WEEKS.

BEFORE RULING OUT HEPATIC CAUSE FOR HYPOALBUMINEMIA WE SHOULD RULE OUT OTHER CAUSES LIKE RENAL LOSSES, INCREASED ALBUMIN CATABOLISM, EXPANSION OF BLOOD VOLUME, MALDISTRIBUTION OF TOTAL BODY ALBUMIN.

NO CLEAR RELATIONSHIP BETWEEN SERUM. ALBUMIN AND INSTANTANEOUS RATE OF ALBUMIN SYNTHESIS.

2.PROTHROMBIN TIME: ALL ARE LIVER DERIVED

PROCOAGULANTS EXCEPT 3,4,8. LIVER DERIVED PROCOAGULANTS HAVE

SHORTER HALF LIVES RANGING FROM 4HRS FOR FACTOR 7 TO 4 DAYS FOR FIBRINOGEN.

PT/INR IS USED TO ASEESS AND MONITOR ACUTE LIVER DYSFUNCTION.

PROLONGED PT DUE TO LIVER FAILURE-DUE TO DECREASED LEVELS OF FACTOR 7a.

SERUM TOTAL PROTEINS-BIURET METHOD.

SERUM ALBUMIN-BCG DYE BINDING METHOD.

TOTAL PROTEINS-ALBUMIN=GLOBULIN

DETECTION OF CHOLESTATIC DISORDERS:

1. ALKALINE PHOSPHATASE: TO SCREE FOR DISORDERS OF LIVER AND

BILIARY TREE. ALP ISOENZYMES EXIST IN PLASMA

MEMBRANES OF BONE , INTESTINE, KIDNEY, PLACENTA(THIRD TRIMESTER OF GESTATION), LEUCOCYTES, NEOPLASMS.

INCREASED ALP-DUE TO INCREASED PRODUCTION/RELEASE OF ALP FROM CELLS.NOT DUE TO DECREASED CLEARANCE.

ALP INCREASE IN CHOLESTATIC DISORDERS IS DUE TO ACTION OF BILE SALTS ON PLASMA MEMBRANES OF HEPATOCYTES.

HALF LIFE –1WEEK. INTIIALLY ALP LEVELS REMAIN LOW IN

BILiARY OBSTRUCTION UNLESS INCREASES IN PRODUCTION.

EXTREME INCREASE: 1.BLOCK IN BILIARY TREE AS IN PRIMARY

BILIARY CIRRHOSIS AND CHOLEDOCHOLITHIASIS

2.HEPATIC MALIGNANCY COMPRESSING

3.5’NUCLEOTIDASE AND GGTP: USED TO DISTINGUISH BETWEEN

HEPATIC AND EXTRAHEPATIC ALP SOURCES.

5’NT EXISTS IN MANY TISSUES BUT MORE RELEASED FROM HEPATOCYTES DUE TO ACTION OF BILE SALTS.

IN BILIARY OBSTRUCTION ALP AND GGTP BOTH INCREASE SIMULTANEOUSLY.

SHORTHLY AFTER 5’NT BEGINS TO INCREASE

BILURUBIN

Bilirubin is a breakdown product of heme About 4 mg/kg body weight of bilirubin is

produced each day Heme is converted to biliverdin by the

microsomal enzyme heme oxygenase. Biliverdin is then converted to bilirubin by the cytosolic enzyme biliverdin reductase.

Bilirubin formed in the reticuloendothelium is lipid soluble and virtually insoluble in water . This process of making insoluble to soluble by liver is called conjugation.

Vandenbergh Reaction The terms direct and indirect bilirubin, which correspond

roughly to conjugated and unconjugated bilirubin, respectively.

Test is called as vandenbergh test or diazo reaction. In this assay, bilirubin is exposed to diazotized sulfanilic

acid. The conjugated fraction of bilirubin reacts promptly, or

“directly,” with the reagent without the need for an accelerant ,and thereby allows measurement of the conjugated bilirubin fraction by photometric analysis within 30 to 60 seconds.

The total bilirubin is measured 30 to 60 minutes after the addition of an accelerant such as alcohol or caffeine.

The unconjugated, or indirect, fraction is then determined by subtracting the direct component from the total bilirubin.

Total serum bilirubin 1.0 -1.5 mg/dL, with 95% of a normal population falling between 0.2 and 0.9 mg/dL.

If the direct acting fraction is less than 15% of the total, the bilirubin can be considered to be entirely indirect.

The most frequently reported upper limit of normal for conjugated bilirubin is 0.3 mg/dL.

Indirect component 0.8-1.2 mg/dL.

Presence of conjunctival icterus suggests a total serum bilirubin level of at least 3.0 mg/dL but does not allow differentiation between conjugated and unconjugated hyperbilirubinemia.

Tea- or cola-colored urine may indicate the presence of bilirubinuria and thus conjugated hyperbilirubinemia

PATTERNS OF HYPERBILURUBINEMIA

Isolated elevation of the serum bilirubin level

Patient with an elevated bilirubin associated with elevated liver enzyme levels

Indirect Hyperbilirubinemia

Hemolytic Disorders Ineffective Erythropoiesis Drugs like Rifampin, Probenecid

impairs hepatocellular uptake. Inherited Conditions : Crigler-Najjar

syndrome types I and II and Gilbert’s syndrome causes Impaired conjugation of bilirubin.

Hematoma most common in neonates.

Direct Hyperbilirubinemia Inherited Conditions causing impaired

excretion of conjugated bilurubin. Dubin-Johnson syndrome  Rotor’s syndrome

 Quantitive Liver Tests: Total hepato cellular mass can be

assessed by clearance of a substance that is extracted by liver like bromsulphalein, ICG, Rose Bengal.

Factors affecting : Variations in Blood flow

Extra hepatic retention or clearance of substance Hepato Biliary function

Drug Metabolising Capacity: Caffeine Clearance Galactose Elemination Capacity Amino pyrine breath test Antipyrine clearance Monoethylglycinexylidide(MEGX)

Measurement of Liver Blood Flow: Clearance Technique- ICG Dye, propranolol, lidocaine, colloidal particles Indicator Dilution Techniques – Radio Label Indicator(Iodinated

albumin) Direct Measurement

Radiologic and Endoscopic Methods: ERCP- Provides intraductal access

to the biliary tree and pancreatic duct. To Diagnose and treat extrahepatic

biliary disorders such as gallstones, tumors, inflammatory strictures or post surgical anastomotic leaks

Complication – Pancreatities etc PTHC- Percutaneus Trans Hepatic

Cholangiography Evaluation of Intra hepatic bileduct

Esophagogastroscopy Splenoportography Portal Venography Fibroscan Test Fibrosure/ Fibro Test- Alpha2 Macroglobulin, HaptoGlobulin,

Apolipo protein A1, Bilurubin, GGT, ALT

Testing for Specific Diseases: Serologic Testing to identify viral,

autoimmune, microbial causes Genetic Testing to identify hereditary

disorders Tumour Markers for malignancy

PATTERN RECOGNITION

NORMAL RANGES1. TOTAL BILURUBIN - 0.3-1.3 mg/dl2. DIRECT - 0.1-0.4 mg/dl3. INDIRECT - 0.2-0.9 mg/dl4. AST - 12- 38 IU/L5. ALT - 7- 41 IU/L6. TOTAL PROTEINS- 5.5 -9.0 gm/dl7. ALBUMIN – 3.5- 5.5 gm/dl8. Globulin – 2.0- 3.3 gm/dl

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