•YELLOWISH DISCOLOURATION OF SCLERA/TISSUE DUE TO INCREASED

LEVEL OF BILIRUBIN IN BODY.

Normal level of bilirubin in body-<1MG/DL (0.3MG OF WHICH IS

CONJUGATED)

JAUNDICE

D/D OF YELLOW SKIN

• CAROTENODERMA• QUINACRINE/PHENOL POISONING• JAUNDICE

PATHOPHYSIOLOGY OF JAUNDICE

• INCREASED PRODUCTION OR DECREASED EXCRETION OF BILIRUBIN

• BILIRUBIN IS A BYPRODUCT OF METABOLISM OF HEMOPROTEIN LIKE HAEMOGLOBIN,MYOGLOBIN AND CYTOCHROMES

• 1g Hb - 34mg bilirubin• IT IS BEING PRODUCED IN RETICULOENDOTHELIAL

SYSTEM (LIVER AND SPLEEN)

• HAEM OXYGENASE

HAEM

• BILIVERDIN REDUCTASE

BILIVERDIN

BILIRUBIN

• THIS UNCONJUGATED BILIRUBIN IS BOUND TO ALBUMIN AND TRANSPORTED TO LIVER

• IN LIVER,BILIRUBIN IS BOUND TO GLUCOURONIC ACID,MEDIATED BY ENZYME UDPGT

• THIS CONJUGATED BILIRUBIN IS WATER SOLUBLE AND RELEASED INTO BILE VIA MDR-2 PROTEIN (RATE LIMITING STEP)

Bilirubin Metabolism

MEASUREMENT OF SERUM BILIRUBIN

• VAN DEN BERGH REACTION• IT IMPLIES USAGE OF SULFANILLIC ACID AND

ALCOHOL IN CONSECUTIVE STEPS• URINARY BILIRUBIN IS DETECTED BY MEAN OF

DIPSTIC TEST-ICOTEST

APPROACH TO A PATIENT OF JAUNDICE

• HISTORY (TRAVEL,RESIDENCE,DIETARY,SEXUAL,BLOOD TRANSFUSION OR ANY DRUG USAGE,ALCOHOL CONSUMPTION)

• PHYSICAL EXAMINATION (PALPATION OF LIVER,SPLEEN,STIGMAS OF CHRONIC LIVER DISEASE)

• LAB INVESTIGATIONS(SGPT,SGOT,ALP, P.T,S.PROTEIN,VIRAL MARKERS)

• IMAGING (ULTRASOUND,MRCP,ERCP)

ISOLATED HYPERBILIRUBINEMIA

• CAN BE EITHER1. CONJUGATED

HYPERBILIRUBINEMIA(>15%DIRECT BILIRUBIN) OR

2. UNCONJUGATED HYPERBILIRUBINEMIA(<15%DIRECT BILIRUBIN)

UNCONJUGATED HYPERBILIRUBINEMIA

1.CAUSED BY INCREASED PRODUCTION OF BILIRUBIN (HEMOLYTIC ANAEMIA OR INEFFECTIVE ERYTHROPOEISIS)

2.DECREASED UPTAKE OF UNCONJUGATED BILIRUBIN BY HEPATOCYTES ( DRUGS LIKE PROBENECID,RIFAMPICIN,RIBAVIRIN,BREAST MILK JAUNDICE IN NEONATE).

3.DECREASED CONJUGATION OF BILIRUBIN IN HEPATOCYTES(CRIGLER NAJJAR-I &II,GILBERT SYNDROME)

HEMOLYTIC JAUNDICE

• SPHEROCYTOSIS,ELLIPTOCYTOSIS,G6PD DEFFICIENCY,THALASSEMIA,HBS,AIHA,PNH

• SERUM BILIRUBIN LEVEL RARELY INCREASE TO MORE THAN 5MG/DL

• HIGH ASSOSCIATION WITH GALL STONES

CRIGLER NAJJAR SYNDROME

• TYPE I: RARE DISEASE,CAUSED BY COMPLETE ABSENCE OF ENZYME BILIRUBIN UDPGT.

S.BILIRUBIN>20 MG/DLDEATH OCCUR IN INFANCY..• TYPE II:MORE COMMON,PARTIAL ABSENCE OF

ENZYME BILIRUBIN UDPGT.• S.BILIRUBIN-8 TO 25MG/DL• USUALLY SURVIVE UPTO ADULTHOOD

GILBERT SYNDROME

• COMMON CONDITION• MORE IN MALES• ALSO CAUSED BY DECREASED ACTIVITY OF

ENZYME BILIRUBIN UDPGT• S.BILIRUBIN RARELY EXCEED TO MORE THAN

6MG/DL• NO HEMOLYSIS

ISOLATED CONJUGATED HYPERBILIRUBINEMIA

• DUBIN JOHNSON SYNDROME:MUTATION IN MDR-2 PROTEIN

• ROTOR SYNDROME:CAUSED BY DEFECTIVE STORAGE OF BILIRUBIN IN HEPATOCYTES

• BOTH ARE BENIGN CONDITIONS,REQUIRE NO TREATMENT

HYPERBILIRUBINEMIA WITH ALTERED L.F.T’S

• HEPATOCELLULLAR PATTERN: ELEVATED ALT/AST OUT OF PROPORTION TO ALKALINE PHOSPATASE

• CHOLESTATIC PATTERN: ELEVATED ALKALINE PHOSPATASE OUT OF PROPORTION TO AMINO TRANSFERASE

HEPATOCELLULAR JAUNDICE

1. VIRAL HEPATITIS (HAV,HEV,HBV,HCV,..EBV,CMV)

2. ALCOHOLIC LIVER DISEASE3. DRUG INDUCED(H,R,Z,

HALOTHANE,PHENYTOIN,VALPORATE,NSAID, PI’S,NRTI’S)

4. WILSONS DISEASE5. AUTOIMMUNE HEPATITIS

CHOLESTATIC JAUNDICE

• INTRAHEPATIC CHOLESTASIS:(VIRAL HEPATITIS,ALCOHOLIC HEPATITIS,DRUG TOXICITY,PRIMARY BILLIARY CIRRHOSIS,PRIMARY SCLEROSING CHOLANGITIS,VANISHING BILE DUCT SYNDROME, T.P.N, PARANEOPLASTIC SYNDROME, GVH RXN)

• EXTRAHEPATIC CHOLESTASIS: (CHOLEDOCHOLITHIASIS,STRICTURE,PERIAMPULLARY TUMOUR,CHRONIC PANCREATITIS)

L.F.T’S AND ITS IMPLICATION IN DIAGNOSIS OF JAUNDICE

• S.BILIRUBIN AND ITS FRACTIONS (DELTA BILIRUBIN)

• LIVER ENZYMES: 1 A.L.T 2 A.S.T 3 ALP 4 GGT 5 NUCLEOTIDASE’5• S.PROTEIN• CLOTTING FACTOR• PROTHROMBIN TIME

1.SERUM BILIRUBIN

• HAS 2 COMPONENTS-DIRECT AND INDIRECT• >3MG/DL-RESPONSIBLE FOR YELLOW SCLERA• USED TO DIFFERENTIATE B/W

HEPATOCELLULAR AND CHOLESTATIC JAUNDICE

• DELTA BILIRUBIN-CONJUGATED BILIRUBIN BOUND TO ALBUMIN

LIVER ENZYMES

• A.L.T: SPECIFIC TO LIVER,VALUE INCREASED SIGNIFICANTLY IN HEPATOCELLULAR JAUNDICE.

• A.S.T:FOUND IN LIVER,CARDIAC MUSCLE,SKELTAL MUSCLE,KIDNEY, BRAIN,RBC’S &WBC’S

• AST/ALT>3:1- INDICATOR OF ALCOHOLIC LIVER DISEASE• ALP,GGT,5’NUCLEOTIDASE-MARKERS OF CHOLESTASIS

S.PROTEIN

• DECREASED ALBUMIN IS INDICATOR OF CHRONIC LIVER DISEASE

• ELEVATED GLOBULIN IS ALSO SEEN

COAGULATION FACTORS

• ALL CLOTTING FACTOR ARE SYNTHESISED IN LIVER(EXCEPT FACTOR VIII)

• FACTOR V IS MOST SPECIFIC TO LIVER INJURY

PROTHROMBIN TIME

• INCREASED IN CASE OF HEPATOCELLULAR AS WELL AS CHOLESTATIC JAUNDICE.

• IF CORRECTED BY GIVING VITAMIN K-INDICATES CHOLESTATIC COMPONENT

• ALTERED EVEN IN ACUTE LIVER INJURY

Investigations

Pre-hepatic Hepatic Post-hepatic

Urine No BilirubinUrobilinogen

? Bilirubin Urobilinogen

BilirubinUrobilinogen

Faeces Dark Pale Pale

Blood FBC - Reticulocyte countCoombs’ testBilirubin (<15% – conjugated)ALP NormalPT Normal

Bilirubin – mixed conjugated & unconjugated ALP, γGTAST, ALT PT – not correctable with Vit K

Bilirubin (>15% conjugated) ALP, γGT PT – correctable with Vit K

Management

• Symptom relief– Pain, itch

• Fluid resuscitation• Correction of coagulopathy• Treat secondary complications– Sepsis, bleeding, anaemia

• Treat underlying cause– Medical or surgical

THANK YOU