This document provides an overview of approaches to evaluating and diagnosing jaundice. It discusses the production and metabolism of bilirubin, measurement of bilirubin levels, clinical history and examination of patients, and laboratory and imaging tests used to classify jaundice as pre-hepatic, hepatocellular, or cholestatic. Common etiologies of each type are outlined, including inherited and acquired conditions.
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.
5.
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
7.
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.
12.
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.
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.
19.
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.
29.
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