Jaundice

Jaundice: Excerpt from The 5-Minute Pediatric Consult

Kathleen M. Loomes, MDPeter C. Wilmot, DO (4th Edition)J. Fernando del Rosario, MD (4th Edition)

Jaundice - BASICS

Jaundice - description

• Jaundice is derived from the French word jaune, which means “yellow.”
• Jaundice: A yellow or green/yellow hue to the skin, sclera, and mucous membranes that can be appreciated at serum bilirubin levels >2 mg/dL. Intensity of color is related directly to the serum bilirubin level.
• Unconjugated bilirubin: 80% is due to hemoglobin turnover and 20% is from degradation of hepatic and renal heme proteins. It is a hydrophobic compound that must be carried to the liver by albumin for processing.
• Conjugated bilirubin: Conjugated to glucuronic acid in the liver, a water-soluble derivative that helps lipid emulsification and absorption
• Conjugated hyperbilirubinemia (direct hyperbilirubinemia): A conjugated bilirubin of >2 mg/dL or >20% of the total bilirubin.

Jaundice - etiology

The most common causes of pathologic jaundice:

• Newborn period: Biliary atresia, idiopathic neonatal hepatitis, α1-antitrypsin deficiency, infection
• Older child: Autoimmune hepatitis, viral hepatitis, Wilson disease, biliary obstruction

Jaundice - DIAGNOSIS

Approach to the patient:

• Step 1: Determine if the hyperbilirubinemia is unconjugated or conjugated.
• Step 2: If unconjugated hyperbilirubinemia:
  • Obtain CBC and indices.
  • Reticulocyte count
  • Coombs test: If Coombs test is positive, the diagnosis is isoimmune; if Coombs test is negative, then consider polycythemia, extravascular bleed, or RBC structural or enzyme defects.
• Step 3: If conjugated hyperbilirubinemia:
  • Alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltranspeptidase (GGT)
  • PT/PTT/International normalized ratio
  • Ultrasound of the liver/pancreas/gallbladder and biliary tree
  • Rule out those etiologies of conjugated hyperbilirubinemia that may adversely affect the outcome if diagnosis is delayed (biliary atresia, tyrosinemia, galactosemia, inborn error of bile acid synthesis, hereditary fructose intolerance, panhypopituitarism).

Jaundice - signs & symptoms

Jaundice - history

• Unexplained itching: Cholestatic liver disease (conjugated hyperbilirubinemia)
• History of poor school performance, change in mental status, handwriting: Wilson disease
• History of other family members having prolonged jaundice, hepatic failure, or sudden death in infancy: Suggests an underlying inborn error of metabolism such as tyrosinemia, galactosemia, or a fatty acid oxidation defect.
• History of IV drug abuse or exposure to blood or blood products, especially prior to 1992: The patient may have transfusion-associated hepatitis (e.g., hepatitis C).

Jaundice - physical exam

• Scratch marks: Pruritus secondary to cholestasis
• Spider angiomata, palmar erythema: Chronic liver disease
• Petechiae, purpura, microcephaly, thrombocytopenia: Congenital TORCH infection
• Heart murmur: Alagille syndrome (peripheral pulmonic stenosis)
• Splenomegaly: Suggests acute hemolysis (in unconjugated hyperbilirubinemia) or chronic liver disease and portal hypertension (conjugated hyperbilirubinemia)
• Ascites: Suggests portal hypertension
• Acholic stool: Severe cholestasis or biliary obstruction

Jaundice - tests

Jaundice - lab

• Total with fractionation into unconjugated, conjugated bilirubin, and delta fractions: Direct versus indirect hyperbilirubinemia.

If unconjugated hyperbilirubinemia, investigation is initiated with:

• CBC with indices, reticulocyte count, and peripheral blood smear for RBC morphology: Polycythemia in neonate, hemolysis or other red cell evidence of increased destruction
• Coombs test: Isoimmune and autoimmune hemolytic anemia
• PT/PTT/International normalized ratio, platelet count: Coagulopathy associated with hemorrhage that causes an increased bilirubin load
• Sepsis evaluation (blood, urine, and spinal fluid): Sepsis can impair conjugation and excretion of bilirubin, result in poor feeding with bile sludging and subsequent formation of gallstones.
• Free T3, T4, and thyroid-stimulating hormone: Congenital hypothyroidism
• Serum aminotransferases (alanine aminotransferase, aspartate aminotransferase): Ongoing liver inflammation/destruction
• Alkaline phosphatase/γglutamyltranspeptidase: Biliary tree obstruction/cholestasis
• Serum albumin, PT, PTT fibrinogen, cholesterol: Liver synthetic function
• Stool color: Acholic (white) stools suggest biliary atresia due to the lack of bile salts in the stool.
• α1-Antitrypsin serum levels and Pi phenotype: Serum α1-antitrypsin levels will be low in inherited protease inhibitor deficiency:
  • Levels can be falsely elevated due to the fact that α1-antitrypsin is an acute-phase reactant.
• Urine dipstick for glucose and reducing substances: Positive reducing substances seen in galactosemia and hereditary fructose intolerance
• Urine for bile acid analysis: Inborn error of bile acid metabolism

Jaundice - imaging

• Ultrasound:
  • A noninvasive method to examine the overall liver appearance, size, and density
  • Allows for examination of the biliary tree and gallbladder to rule out choledochal cysts, sludge/stones, and ductal dilatation indicating possible obstruction
• Hepatobiliary scintigraphy (HIDA scan): Tracer secretion into the duodenum excludes biliary atresia or extrahepatic biliary obstruction

Jaundice - diag proced-surgery

Percutaneous liver biopsies: Liver pathology—hepatocyte and other cell histology, fibrosis, and pathologic features

Jaundice - differencial diagnosis

• Unconjugated hyperbilirubinemia:
  • Congenital/Anatomic:
    • Placental dysfunction/insufficiency resulting in polycythemia (e.g., infants of diabetic mothers)
    • Upper GI tract obstruction (e.g., pyloric stenosis, duodenal web, atresia)
    • Congenital hypothyroidism
  • Infectious:
    • Sepsis
  • Trauma/Delivery complications:
    • Cephalohematoma/bruising
    • Delayed cord clamping, twin–twin transfusion, maternal–fetal transfusion leading to polycythemia
    • Intrauterine hypoxia (secondary to cocaine abuse, high altitude) resulting in polycythemia
    • Induction of labor with oxytocin
    • Prematurity
  • Genetic/Metabolic:
    • Inherited red cell enzyme, membrane defects (e.g., spherocytosis, glucose 6-phosphate dehydrogenase deficiency, phosphokinase deficiency, elliptocytosis)
    • Red cell abnormalities (sickle cell anemia, thalassemia)
    • Defect in hepatic bilirubin conjugation (e.g., Crigler-Najjar types I and II, Gilbert)
    • Inborn errors of metabolism
    • Cystic dilation of the intrahepatic bile ducts
    • Congenital hepatic fibrosis/polycystic kidney and liver disease
  • Allergic/Inflammatory/Immunologic:
    • Isoimmunization (ABO, Rh, Kell, other incompatibility)
  • Functional:
    • Physiologic jaundice—peaks during the day
    • Breast-feeding–associated jaundice
    • Swallowed maternal blood
    • Increased bilirubin load due to infant bleeding from a clotting disorder
    • Familial benign unconjugated hyperbilirubinemia in mother and neonate (Lucey-Driscoll syndrome)
• Conjugated hyperbilirubinemia:
  • Extrahepatic:
    • Extrahepatic biliary atresia
    • Choledochal cysts and other abnormalities of the choledochopancreatic ductal junction
    • Spontaneous perforation of the bile duct
    • Bile or mucous plug or biliary sludge
    • Gallstones
  • Infectious etiologies:
    • Bacterial: Gram-negative sepsis, UTI
    • Viral: Cytomegalovirus; echovirus; herpes simplex virus; rubella; Epstein-Barr virus; HIV, hepatitis A, B, C, D, and E
    • Toxoplasmosis
    • Pneumocystis carinii
    • Entamoeba histolytica
    • Mycobacterium tuberculosis
    • M. avium-intracellulare
    • Syphilis
  • Toxic/Environmental/Drugs
  • Postnecrotizing enterocolitis
  • Postshock or post-asphyxia (ischemic injury to liver)
    • Drugs: Acetaminophen, valproate, chlorpromazine, Amanita toxin
    • Hyperalimentation (total parenteral nutrition)
  • Tumor:
    • Neuroblastoma, hepatic, biliary, pancreatic, duodenal, peritoneal
    • Portal hepatis nodes
  • Genetic/Metabolic:
    • Arteriohepatic dysplasia (Alagille syndrome)
    • Progressive familial intrahepatic cholestasis (including Byler disease and MDR3 deficiency)
    • Benign recurrent intrahepatic cholestasis
    • Defects in bile acid metabolism
    • Defects in amino acid metabolism
    • Defects in lipid metabolism: Wolman disease, Niemann-Pick disease, Gaucher disease
    • Defects in carbohydrate metabolism: Galactosemia, hereditary fructose intolerance, glycogenosis type IV
    • Defects in mitochondrial DNA and respiratory chain defects
    • α1-Antitrypsin deficiency
    • Cystic fibrosis
    • Multiple acyl coenzyme A dehydrogenase deficienc
    • Wilson disease (older children
    • Inherited noncholestatic conjugated jaundice syndromes (e.g., Dubin-Johnson and Rotor syndrome
    • Hereditary cholestasis with lymphedema (Aegenaes syndrome)
  • Inflammatory/Immunologic/Endocrine:
    • Idiopathic neonatal hepatitis
    • Neonatal iron storage disease
    • Idiopathic hypopituitarism
    • Autoimmune hepatitis (children and adolescents)
    • Sclerosing cholangitis (children and adolescents, unless neonatal form)

Jaundice - TREATMENT

Clinical pearls:

• Treat Crigler-Najjar syndrome promptly with phototherapy and phenobarbital to prevent kernicterus.
• Older children with Wilson disease may present with profound hemolysis and may have predominantly unconjugated hyperbilirubinemia with severe parenchymal liver disease and fulminant liver failure.

Jaundice - FOLLOW UP

Jaundice - disposition

Jaundice - issues for referral

When to refer:

• Any infant with jaundice beyond 10–14 days of age should have a fractionated bilirubin sent.
  • Any infant with conjugated hyperbilirubinemia should be referred immediately to a pediatric gastroenterologist for further workup.

Jaundice - bibliography

1. Balistreri WF, Bezerra JA. Whatever happened to “neonatal hepatitis”? Clin Liv Dis. 2006;10(1):27–53.
2. Davenport M, Betalli P, D’Antiga L, et al. The spectrum of surgical jaundice in infancy. J Pediatr Surg. 2003;38:1471–1479.
3. Emerick KM, Whitington PF. Neonatal liver disease. Pediatric Ann. 2006;35(4):280–286.
4. Kanegawa K, Akasaka Y, Kitamura E, et al. Sonographic diagnosis of biliary atresia in pediatric patients using the “triangular cord” sign versus length and contraction. Amer J Roentgenol. 2003;181:1387–1390.
5. Subcommittee on hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2004;114(1):297–316.
6. Takaya J, Muneyuki M, Tokuhara D, et al. Congenital dilation of the bile duct: Changes in diagnostic tools over the past 20 years. Pediatr Int. 2003;45:383–387.

Jaundice - CODES

Jaundice - icd9

• 782.4 Icterus (see also Jaundice)
• 782.4 Jaundice (yellow)

Jaundice - FAQ

• Q: Are there any characteristic findings in neonatal jaundice that are specifically concerning?
• A: These findings are concerning until proven otherwise:

  Development of jaundice before 36 hours of life

  Persistent jaundice beyond 10 days of life

  Serum bilirubin concentration >12 mg/dL

  Elevation of direct bilirubin >2 mg/dL or 20% of total bilirubin at any time
• Q: Are there any ethnic/social factors associated with higher bilirubin levels?
• A: Factors that have been associated with high serum bilirubin levels are low birth weight, certain ethnic groups (Asian, Native American, Greek), delayed meconium passage after birth, breast-feeding. Factors that have been associated with lower serum levels in neonates include maternal smoking, black race, and certain drugs, such as phenobarbital.

Book Source Details

• Book Title: The 5-Minute Pediatric Consult
• Author(s): M. William Schwartz MD; et al.
• Year of Publication: 2008
• Copyright Details: The 5-Minute Pediatric Consult, Copyright © 2008 Lippincott Williams & Wilkins.

More About Neonatal Jaundice

• Back to disease: Neonatal Jaundice: Introduction
• Next Book Extract About Neonatal Jaundice: Surveys relating to Neonatal Jaundice
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Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.

More About This Book: Title: The 5-Minute Pediatric Consult Authors: M. William Schwartz MD; et al. Publisher: Lippincott Williams & Wilkins Copyright: 2008 ISBN: 0-7817-7577-9

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