Basics
Description
Yellow pigmentation of tissues and body fluids due to hyperbilirubinemia, usually present at levels of >2.5 mg/dL ‚
Etiology
- Unconjugated (indirect) hyperbilirubinemia: Unconjugated bilirubin is the direct breakdown product of heme, is water insoluble, and is measured as indirect bilirubin:
- Hemolytic:
- Excessive production of unconjugated bilirubin
- Hepatic:
- Decreased hepatobiliary excretion of bilirubin by:
- Defective uptake (drugs, Crigler " “Najjar syndrome)
- Defective conjugation (Gilbert syndrome drugs)
- Defective excretion of bilirubin by the liver cell (drugs, Dubin " “Johnson syndrome)
- Conjugated (direct) hyperbilirubinemia:
- Conjugated bilirubin is water soluble and measured as direct bilirubin.
- In conjugated hyperbilirubinemia, bilirubin is returned to the bloodstream after conjugation in the liver instead of draining into the bile ducts.
- Hepatocellular dysfunction:
- Hepatitis
- Cirrhosis
- Tumor invasion
- Toxic injury
- Intrahepatic (nonobstructive) cholestasis
- Extrahepatic (obstructive) cholestasis
Diagnosis
Signs and Symptoms
History
- Cholestasis:
- Pruritus
- Pale stools
- Dark urine
- Malignancy:
- Anorexia
- Weight loss
- Malaise
- Abdominal pain
Physical Exam
- Icterus of sclera and tongue base (levels >2.5 mg/dL)
- Right upper quadrant tenderness:
- Courvoisier rule:
- Painless jaundice and a palpable, nontender gallbladder represent malignant common duct obstruction.
- Stigmata of cirrhosis:
- Abdominal collateral circulation including caput medusae, hepatosplenomegaly, or hepatic atrophy
- Ascites
- Spider telangiectasia
- Palmar erythema
- Dupuytren contractures
- Asterixis
- Encephalopathy
- Gynecomastia
- Palpable gallbladder
- Hepatomegaly
- Splenomegaly
- Abdominal mass
- Evidence of cachexia
- Excoriations (primary biliary cirrhosis, obstruction)
- Kayser " “Fleischer rings:
Essential Workup
- History and physical exam, together with routine lab tests, will suggest the diagnosis in ¢ ˆ ¼80% of patients with jaundice.
- Bilirubin level " ”severity may suggest cause:
- Malignancy causes highest levels (10 " “30 mg/dL).
- Choledocholithiasis rarely exceeds 15 mg/dL.
Diagnosis Tests & Interpretation
Lab
- Urine dipstick is 74% sensitive for bilirubin.
- Alkaline phosphatase:
- If no bone disease and not pregnant, then elevation suggests impaired biliary tract function.
- 2X normal: Hepatitis and cirrhosis
- 3X normal: Extrahepatic biliary obstruction (i.e., choledocholithiasis) and intrahepatic cholestasis (i.e., drug-induced and biliary cirrhosis)
- Aminotransferases " ”provide evidence of hepatocellular damage:
- Alanine aminotransferase (ALT, SGPT): Primarily in the liver
- Aspartate aminotransferase (AST, SGOT): Liver, heart, kidney, muscle, and brain
- Ž ³-Glutamyl transpeptidase " ”throughout hepatobiliary system, pancreas, heart, kidneys, and lungs:
- May be the most sensitive indicator of biliary tract disease.
- Confirms hepatic origin of an elevated alkaline phosphatase.
- 5 " ²-Nucleotidase " ”widespread tissue distribution:
- Confirms hepatic origin of an elevated alkaline phosphatase level.
- Albumin: Decreased with severe liver disease
- PT: Elevation is an important prognostic indicator in patients with acute hepatitis.
Imaging
- US: Most effective initial imaging technique:
- >90% effective in identifying cholelithiasis
- Ductal dilation is a reliable indicator of extrahepatic obstruction:
- A dilated common bile duct (CBD) and gallbladder suggest distal obstruction, whereas dilation of the intrahepatic ducts (without CBD dilation) suggests proximal obstruction.
- Tumors of the liver and head of pancreas are usually well visualized.
- Distinguishes solid liver tumors from cystic structures.
- Plain radiographs:
- May show evidence of hepatic and splenic enlargement or biliary calcifications
- Hepatic nuclear scan (hepatobiliary iminodiacetic acid scan):
- Accurate method of diagnosing acute cholecystitis or cystic duct obstruction
- Time consuming (usually several hours)
- CT:
- Superior to US in detecting pancreatic and intra-abdominal tumors.
- Can help differentiate fluid-containing structures.
Diagnostic Procedures/Surgery
Endoscopic retrograde cholangiopancreatography (ERCP): ‚
- Diagnostic:
- Stones are seen as filling defects within bile duct lumen.
- Malignancies are seen as strictures.
- Therapeutic:
- Extraction of CBD stones and insertion of stents to bypass malignant obstructions
- Biopsy under direct vision
Differential Diagnosis
- Prehepatic:
- Hemolysis (sickle cell, other hemoglobinopathies)
- Ineffective erythropoiesis
- Drugs
- Gilbert syndrome: Usually benign inherited form of unconjugated hyperbilirubinemia
- Crigler " “Najjar syndrome
- Prolonged fasting
- Hepatocellular:
- Hepatitis (infectious, alcoholic, autoimmune, toxin, drug induced)
- Cirrhosis
- Postischemic
- Hemochromatosis
- Intrahepatic cholestasis:
- Idiopathic cholestasis of pregnancy
- Drugs
- Dubin " “Johnson syndrome
- Rotor syndrome
- Benign recurrent cholestasia
- Familial syndromes
- Sepsis
- Postoperative jaundice
- Lymphoma
- Extrahepatic obstruction:
- Common duct stone
- Biliary stricture
- Bacterial cholangitis
- Sclerosing cholangitis
- Carcinoma (ampulla, gallbladder, pancreas), cholangiosarcoma
- Pancreatitis, pancreatic pseudocyst
- Hemobilia
- Duodenal diverticula
- Ascariasis
- Postlaparoscopic cholecystectomy complications
- Congenital biliary atresia
- Congenital choledochal cyst
Intrahepatic cholestasis: ‚
- Cardiovascular (congenital heart disease, congestive heart failure, shock, asphyxia)
- Metabolic or genetic (α1-antitrypsin deficiency, trisomy 18 and 21, cystic fibrosis, Gaucher disease, Niemann " “Pick disease, glycogen storage disease type IV)
- Infectious (bacterial sepsis, cytomegalovirus, enterovirus, herpes simplex virus, rubella, syphilis, TB, varicella, viral hepatitis)
- Hematologic (severe isoimmune hemolytic disease)
Treatment
Initial Stabilization/Therapy
- Isotonic IV fluid therapy if dehydrated
- Toxic-appearing patients:
- Supplemental oxygen, cardiac monitoring
- Nasogastric suction and bladder catheterization
Ed Treatment/Procedures
- For bacterial cholangitis/sepsis, obtain blood cultures and administer parenteral antibiotics:
- Ampicillin, gentamicin, and metronidazole or
- Ticarcillin, or piperacillin, and metronidazole or
- Cefoxitin and tobramycin
- Obstructive extrahepatic jaundice:
- Choledocholithiasis:
- ERCP papillotomy, balloon or basket retrieval, or open surgery
- Obstructive intrahepatic or nonobstructive jaundice:
- Medical management:
- Withdraw causative drug, ethanol
- Interferon for chronic hepatitis B and C
- Penicillamine and phlebotomy for Wilson disease and hemochromatosis
- Corticosteroids for chronic hepatitis of autoimmune origin
- Exchange transfusion:
- Emergent treatment of markedly elevated bilirubin (>20 mg/dL in full-term infants) and for correction of anemia caused by isoimmune hemolytic disease
- Phototherapy " ”for neonatal jaundice when bilirubin = 17 mg/dL:
- Measure bilirubin once to twice daily and stop when bilirubin has been reduced by about 4 " “5 mg/dL.
- Phenobarbital: In sepsis and drug-induced causes; decreases conjugated bilirubin.
- Metalloporphyrins: Investigational inhibitors of heme oxygenase
Medication
- Ampicillin: 2 g IV q6h (peds: 25 mg/kg IV q6 " “8h)
- Cefoxitin: 2 g IV q6h (peds: 40 " “160 mg/kg/d div. q6 " “12h)
- Gentamicin: 5 " “2 mg/kg IV q8h
- Metronidazole: 7.5 mg/kg IV q6h (peds: Same)
- Piperacillin/tazobactam: 3.375 g IV q6h (peds: 300 mg/kg/d div. q6h [>2 mo of age])
- Ticarcillin/clavulanate: 3.1 g IV q6h (peds: 75 " “100 mg/kg/d div. q6h)
- Tobramycin: 1 mg/kg IV q6h (peds: Same)
Follow-Up
Disposition
Admission Criteria
- Bacterial cholangitis
- Intractable pain
- Intractable emesis
- Associated pancreatitis
- Elevated PT
Discharge Criteria
- No evidence of infection (evaluate as outpatient)
- Tolerating liquids
Additional Reading
- Addley ‚ J, Mitchell ‚ RM. Advances in the investigation of obstructive jaundice. Curr Gastroenterol Rep. 2012;14:511 " “519
- Maisels ‚ MJ, McDonagh ‚ AF. Phototherapy for neonatal jaundice. N Engl J Med. 2008;358:920 " “928.
- Roche ‚ SP, Kobos ‚ R. Jaundice in the adult patient. Am Fam Physician. 2004;69:299 " “304.
- Udell ‚ JA, Wang ‚ CS, Tinmouth ‚ J, et al. Does this patient with liver disease have cirrhosis? JAMA. 2012;307(8):832 " “842.
- Wang ‚ Q, Gurusamy ‚ KS, Lin ‚ H, et al. Preoperative biliary drainage for obstructive jaundice. Cochrane Database Syst Rev. 2008;16(3):CD005444.
Codes
ICD9
- 277.4 Disorders of bilirubin excretion
- 774.6 Unspecified fetal and neonatal jaundice
- 782.4 Jaundice, unspecified, not of newborn
ICD10
- E80.6 Other disorders of bilirubin metabolism
- P59.9 Neonatal jaundice, unspecified
- R17 Unspecified jaundice
- E80.5 Crigler-Najjar syndrome
- E80.4 Gilbert syndrome
SNOMED
- 18165001 Jaundice (finding)
- 14783006 Hyperbilirubinemia (disorder)
- 281610001 neonatal hyperbilirubinemia (disorder)
- 28259009 Crigler-Najjar syndrome (disorder)
- 27503000 Gilberts syndrome (disorder)
- 44553005 Dubin-Johnson syndrome (disorder)
- 7752002 Unconjugated hyperbilirubinemia (disorder)
- 9326001 Conjugated hyperbilirubinemia (disorder)