This document provides an overview of the clinical approach to jaundice. It discusses the production and metabolism of bilirubin, measurement of bilirubin levels, causes of hyperbilirubinemia including hepatic and extrahepatic sources, and the approach to evaluating a patient with jaundice through history, physical exam, and laboratory tests. Common etiologies like viral hepatitis, drug toxicity, and biliary obstruction are reviewed. A thorough workup is needed to determine if the source of jaundice is from overproduction, impaired clearance, or obstruction of bilirubin.

1. CLINICAL
APPROACH TO
JAUNDICE
DR.R.KARTHIKA-POST GRADUATE
INTERNAL MEDICINE-M1
8/1/14

2. JAUNDICE
 Yellowish discoloration of skin resulting from depostition of bilirubin.
 Sign of liver disease or hemolytic disorder.
 Imbalance between production and clearance of bilirubin.
 Degree of elevation by physical examination.
 Sclera- high affinity because of elastin content-3mg/dl
 Normal day light, limitation.
 Yellow-green.

3.  Yellowing of skin
 Carotenoderma-yellow color imparted to the skin because of carotenes.
 Carrots, green leafy vegetables, squash, peaches and oranges.
 Palms, soles, forehead and nasolabial folds.
 Spares the sclera.
 Quinacrine-4-37% yellowish discoloration of skin, also sclera.

4. PRODUCTION AND METABOLISM OF
BILIRUBIN.
 Tetrapyrrole pigment
 Break down product of heme-ferroprotoporphyrin IX
 70-80% breakdown of hemoglobin from senescent red blood cells.
 Prematurely destroyed erythroid cells in the bone marrow, myoglobin,
cytochromes.
 Reticuluendothelial cells of the spleen and liver.

6.  Bilirubin is insoluble
 Reversible covalent binding to albumin.
 Hepatocytes – glutathione superfamily.
 Prevents efflux back into serum
 Uridine diphosphate glucuronyl transferase.
 Conjugated bilirubin from the ER to the canalicular membrane of bile duct by
energy dependent mechanism involving MDR protein -2

8. MEASUREMENT OF SERUM BILIRUBIN
 Van der Bergh reaction.
 Bilirubin is exposed to diazotized sulfanilic acid
 Dipyrrylmethene azopigments which absorbs light maximally at 540nm
 Direct bilirubin.
 Total BR after the addition of alcohol.
 Normal-1mg/dl
 0.3mg-DBR
 DELTA FRACTION-albumin linked bilirubin fraction in pts with cholestasis and
hepatobiliary disease.

9.  Because of the longer half life of albumin-12-14 days
 Conjugated hyperbilirubinemia donot exhibit bilirubinuria because
 Albumin bound BR not excreted in renal glomeruli
 Serum BR also falls slowly.

10. MEASUREMENT OF URINE BILIRUBIN
 Unconjuated bilirubin – not found in urine.
 Conjugated bilirubin filtered by the glomerulus and reabsorbed by the prox
tubules.
 Urine dipstick test- ICTOTEST
 False negative in prolonged cholestasis due to conjugated BR bound to
albumin.

11. APPROACH TO THE PATIENT
 HYPERBILIRUBINEMIA
 Overproduction of BR
 Impaired uptake , conjuagation or excretion of bilirubin.
 Regurgitation of unconjugated or conjugated from damaged hepatocytes or
bileducts.

13. HISTORY
 Single most important part of the evaluation of the patient with unexplained
jaundice
 Duration of jaundice
 Use or exposure to medication-OTC, physician prescribed
 Complementary or alternative medicine-herbal or vitamin preparations or anabolic
steroids
 Parenteral exposures-transfusions, iv abuse
 Tattoos, sexual activity and alcohol history.
 Loss of weight or appetitite.
 Bleeding diathesis.

14. HISTORY TAKING

15.  Recent travel history
 Exposure of patients with jaundice
 Occupational history-contact with rats
 Place of origin-carriage of hepatitis
 Exposure to contaminated foods or water.
 Family history- hemolytic anemias, congenital hyperbilurbinemias and hepatitis
 Travel history
 Dyspepsia , fat intolerance or biliary colic
 Accompanying symptoms- arthralgia, myalgias, rash, anorexia, weight loss,
abdominal pain-choledocholithiasis and ascending cholangitis
 Fever
 Pruritis
 Changes in color of urine and stools

16. PHYSICAL EXAMINATION
 Assessment of patients nutritional status
 Temporal and proximal muscle wasting- long standing disease like ca or cirrhosis
 Scratch marks, purpura, fetor hepaticus
 Stigmata of chronic liver disease –spider nevi,
 palmar erythema,
 gynecomastia,
 caput medusa,
 dupuytrens contractures,
 parotid enlargement or testicular atrophy.- advanced alcoholic cirrhosis

17.  Enlarged left supraclavicular lymphnode
 Periumblical nodule-sister mary josephs
 Jvp-right heart failure
 Right sides pleural effusion
 Pedal edema, nails- clubbing and white nails.
 Tremors or flaps, KF ring.
 Abdominal examination-
 Size and consistency of liver and spleen.
 Enlarged left lobe of liver.

18.  Enlarged nodular liver-malignancy
 Tender hepatomegaly-alcoholic, viral or parasites, amyloid, hepatic
congestion.
 MURPHYS sign-cholecystitis.
 Palpable gall bladder and courvoiser law
 Ascites with jaundice- cirrhosis or malignancy with peritoneal spread
 Abdominal veins.

20. LABORATORY TESTS
 Total and direct serum bilirubin
 Aminotransferases
 Alkaline phosphatases
 Albumin
 Low-chronic
 Normal acute viral or choledocholithiasis.
 Prothromin time-prolonged jaundice, malabsorption of vit k or significant
hepatocellular dysfunction.
 Failure to correct with parenteral administration of vit k-severe hepatocellular injury.

21. UNCONJUGATED HYPERBILURUBINEMIA
 HEMOLYTIC DISORDERS
 ACQUIRED OR INHERITED
 Sickle cell anemia, heriditary spherocytosis or thalasemmia etc
 SBR rarely exceed 5mg/dl
 Higher levels when there is coexistent renal or hepatic dysfunction or crisis.
 Pigmented calcium bilirubinate gallstones and choledocholithiasis
 Acquired-HUS, PNH, malaria or babesiosis,
 Ineffective erythropoiesis-cobalamin, folate deficiency or iron def.

22.  Problem with hepatic uptake and conjugation of BR
 Rifampicin, probenicis, ribavirin
 Genetic- impaired conjugated
 Crigler najjar type I-rare
 Neonated
 SBR>20mg/dl
 Neurological impairment-kernicterus
 Death in infancy or childhood
 Complete absence of UDPGT actitivy

23.  Type ii
 Common, adulthood, SBR-6-25mg/dl
 Reduced UDPGT activity
 Induced by phenobarbital
 Susceptible to kernicterus under stress or illness
 GILBERT SYNDROME-1/3 UDPGT activity
 Very common-3-12% of general population.
 Mild unconjugated hyper bilirubinemia- less than 6mg/dl
 Serum levels fluctuate and identified during periods of fasting.
 Male predominance of 2-7:1

24. CONJUGATED HYPERBILIRUBINEMIA
 DUBIN JOHHSON
 ROTOR-hepatic storage of BR
 Asymptomatic jaundice
 Second generation of life
 Multiple drug resistance protein 2
 Altered excretion into bileducts
 Benign.

25. HEPATOCELLULAR JAUNDICE
 Viral hepatitis-IgM for hep A, Hep B surface antigen, core IgM antibody and
Hepatitis C viral RNA.
 Wilsons disease-ceruloplasmin, urinary copper, serum copper, hepatic copper
 Auto immune hepatitis young and middle aged women of any age
 ANA, SMA, LKM,
 Alcoholic hepatitis- AST:ALT> 2, AST rarely exceed 300IU/L
 Acute viral hepatitis and toxin related hepatitis aminotransferase >500U/L
 Cirrhosis –normal or only slight elevation in aminotranferasses.

26. DRUG INDUCED HEPATOTOXICITY
 Predictable drug reactions-dose dependent
 and affect all pts who ingest a toxic dose of the drug.
 Eg. Acetaminophen
 Unpredictable or idiosyncratic approach-not dose dependent
 Occurs in minority – eg isoniazid
 Environmental toxins- vinyl chloride, herbal preparations, pyrrolizidine
alkaloids, Jamaica bush tea, mushrooms.

27. CHOLESTATIC JAUNDICE
 Intra hepatic or extrahepatic cholestasis
 History, physical examination and lab test
 USG-high degree of sensitivity and specificity
 Inexpensive and non invasive
 But not the site or cause of obstruction especially distal CBD due to overlying
bowel gas.
 False negative test- partial obstruction to the common bile ducts
 Cirrhosis
 Primary sclerosing cholangitis-scarring prevent intrahepatic radicals to dilate

28.  MRCP, ERCP
 CT with MRCP- assessing head of pancreas and choledocholithiasis
 ERCP- gold standard- side viewing endoscopy per orally into the duodenum
 Catheter advanced.
 Injection of dye allows visualization of CBD.
 Removal of CBD stones, placement of stents.

30.  Fibrosing cholestatic hepatitis- in hepatis B and C
 Alcohol hepatitis
 Drugs- pure cholestasis- anabolic and contraceptive steroids
 Cholestatic hepatitis-chlorpromazine, erythromycin, imipramine, tolbutamide,
sulindac, cimetidine , TMP-SMX, ampicillin, dicloxacillin and clavulinic acid.
 Chronic cholestasis- chlorpromazine and prochlorperazine

31.  Primary biliary cirrhosis
 Autoimmune- middle aged women
 Progressive destruction of interlobular bile ducts
 Presence of antimitochondrial antibodies- 95%
 Primary sclerosing cholangitis
 Destruction and fibrosis of larger bile ducts
 Intrahepatic and extrahepatic –95%
 Multiple strictures of bile ducts with dilatations proximal to strictures.
 75% inflammatory bowel disease.

32.  Vanishing bile duct syndrome and adult bile ductopenia-
 Rare
 Decreased number of bile ducts in liver biopsy
 Chronic rejection after liver transplantation and
 Graft versus host reaction after BMT
 Sarcoidosis
 drugs

33. FAMILIAL
 Progressive intrahepatic cholestasis PFIC1-3 bile salt export pump, multidrug
resistant protein
 Benign recurrent cholestasis
 Autosommal recessive
 Manifests in childhood
 Recurrent episodes of jaundice and pruritis
 Self limited but can be debilitating.

34.  CHOLESTASIS OF PREGNANCY
 Second or third trimester
 Resolves after delivery
 Cause is unknown
 Inherited and cholestasis can be triggered by estrogen administration.

35.  TPN
 Non hepatobiliary sepsis
 Bening post operative cholestasis
 Paraneoplastic conditions
 Hodgkins lymphoma, medullary thyroid ca, renal cell ca, sarcoma, prostate
and gi ca
 STAUFFER’S syndrome- intrahepatic cholestasis with renal cell ca
 ICU- sepsis, shock liver , TPN,
 Jaundice with BMT- venoocclusive disease or GVHD

36.  Plasmodium falcifarum– combination of indirect BR from hemolysis and
cholestatic and hepatocellular jaundice.
 Poor outcomes in jaundice with encephalopathy and renal failure
 Weils disease-severe presentation of leptospirosis-jaundice, with renal failure
ass with headache and myalgias.

37. EXTRAHEPATIC CHOLESTATSIS
 MALIGNANT- pancreatic, gall bladder , ampullary and cholangiocarcinoma
 Similar to primary sclerosing cholangitis.
 Ampullary ca highest surgical cure rates and present as painless jaundice
 Hilar lymphadenopathy due to metastasis from other ca

38.  Extra hepatic cholestatis- benign
 Choledocholithiasis
 Mild upper right quadrant pain with only minimal elevation of enzymes to ascending
cholangitis , jaundice, sepsis and shock.
 Strictures.
 Chronic pancreatitis- rarely strictures of distal CBD.
 AIDS cholangiopathy- infection of bile duct epithelium with CMV or crytosporidia-
cholangiographic appreance similar to PSC.
 Elevated Serum alkaline phosphatase – mean 800IU/L
 Mirizzi syndrome
 Parasitic disease like ascariasis

39. TAKE HOME MESSAGE
 Jaundice is a hallmark of liver disease
 Through clinical examination and history becomes vital in all cases
 Classified as pre hepatic, hepatocellular and cholestatis although overlaps do
occur
 Biochemical and radiological evaluation helps in making a diagnosis.
 This is just a overview

40. THANK YOU.

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