Download - Visual Diagnosis
Visual Diagnosis
Sources:1. Slack Health Care Books, http://www.slackbooks.com2. Fischer & Vandemark. (1945). J Bone Joint Surg Am.;27:695-698.
Pediatrics Morning Report:A 6 week old with direct
hyperbilirubinemiaRobyn Rogers, MD
Sahar Rooholamini, MDDecember 9, 2009
Case Presentation
• You’re the Green Team (GI) resident and you’re called to admit a patient.
• You’re told: “This is a 6 week old male from an outside hospital who has direct hyperbilirubinemia and needs a work-up.”
• What is your initial differential diagnosis?• What do you want to know?
Learning Objectives
• Generate and understand the differential diagnosis for conjugated hyperbilirubinemia in an infant
• Understand the essential elements of the history and physical in conjugated hyperbilirubinemia
• Learn the general diagnostic and therapeutic approaches to conjugated hyperbilirubinemia
Physiologic vs. Non-physiologic Jaundice
Physiologic • Caused by structural and
functional immaturity of neonatal hepatobiliary system
• Almost always unconjugated hyperbilirubinemia
• Expected to resolve by 2 weeks of life
• Ex: breastfeeding and breast milk jaundice
Non-physiologic• Variety of causes• Present at birth or
persistent beyond 2 weeks of life
• Conjugated hyperbilirubinemia is a potential RED FLAG at any age and requires follow-up
• Associated with other signs or symptoms
Definitions and Epidemiology• Conjugated hyperbilirubinemia = Serum direct
bili > 1 mg/dL (if total bili <5 mg/dL), or > 20% of total bilirubin
• AKA “neonatal cholestasis” • Affects 1 in 2500 births• Most common causes:
– Neonatal Hepatitis 70-80% of cases, – Biliary Atresia usually term infants
– Alpha-1 Antitrypsin Deficiency• 10-15% of cases
Bilirubin conjugation and excretion
Bloomer J (2006). Gastroenterology and Hepatology: Liver. Edited by Mark Feldman (series editor). Published by Current Medicine Group. Obtained through Lane Medical Library.
Differential Diagnosis of Conjugated Hyperbilirubinemia
• Anatomic approach–Intrahepatic vs. extrahepatic causes
• Physiologic approach–Impaired bile formation (hepatocyte
problem) vs. obstruction to bile flow (either within or outside liver)
Impaired bile formation– Acute liver damage (hypoxia, ischemia, acidosis)– Infection/sepsis
• Bacterial: E. coli, GBS, Listeria, TB, syphilis• Viral: HIV, hepatitides, Rubella, CMV, HSV• Parasitic: Toxoplasma
– Genetic/Metabolic diseases (abbreviated list)• Alpha-1 antitrypsin deficiency• IEM: Galactosemia, tyrosinemia; lipid and bile salt metabolic defects• Cystic Fibrosis
– Endocrine disorders (hypothyroidism, hypopituitarism)
– Toxin or Drug-induced damage– TPN-related liver disease– Idiopathic Neonatal Hepatitis (dx of exclusion)
Obstruction to Bile Flow
• Congenital anomalies– Biliary atresia– Choledochal cyst– Alagille syndrome (paucity of intrahepatic bile ducts)– Bile duct stenosis
• Other anatomic anomalies– Bile duct perforation or compression– Cholelithiasis/sludging
Alagille Syndrome(Arteriohepatic dysplasia)
History & Physical
• Family history • Prenatal, neonatal hx• Dietary hx, weight gain• Stooling pattern, color• Urine color• History of bruising or
bleeding• Irritability, seizures
• VS and growth parameters• Neurologic exam (e.g.,
tone, symmetry, reflexes)• Eye exam• Dysmorphic features• Jaundice• Heart murmur• Hepatosplenomegaly• Bruising/petechiae• Urine and stool
Initial Work-Up• A thorough H&P should guide subsequent testing.• Total/direct bilirubin• Transaminases, Alkaline phosphatase, GGT• Synthetic liver function tests (coags, albumin)• UA, Ucx; blood and CSF cultures if indicated• CBC with reticulocyte count• Hepatitis panel, TORCH titers• TSH, Free T4• Serum Alpha 1-AT level +/- phenotype• Sweat chloride• Serum and urine organic/amino acids
Further Work-Up & Imaging• Ultrasound
– Keep patient NPO– Try to feed during exam to show gallbladder
contraction• Hepatobiliary scintigraphy (HIDA scan)
– Perform after 3-5 days of phenobarbital to promote bile flow, at 5 mg/kg/day
• Duodenal aspirate• MRCP/ERCP (not routinely recommended)
• Liver biopsy
Additional Case History
• Patient’s test results and hospital course• Post-discharge follow-up• This patient was initially admitted for a liver
biopsy for concern for biliary atresia…would you have biopsied him?
Management of Conjugated Hyperbilirubinemia
• Medical Management– Phenobarbital– Ursodiol– Rifampin– Cholestyramine
• Diet – Medium-chain triglycerides– Fat-soluble vitamin supplementation
• Surgical interventions– Kasai portoenterostomy– Liver transplantation
Summary and Take-Home Points
• Maintain a healthy skepticism about the working diagnosis on all of your patients.
• Approach conjugated hyperbilirubinemia with a broad differential diagnosis but focused work-up.
• A patient with jaundice persisting beyond 2-3 weeks of age needs further work-up, beginning with total and direct bilirubin measurements.
Thank you, Drs. Kerner and Fuentebella!
ReferencesFischer & Vandemark (1945). Sagittal Cleft (Butterfly) Vertebra.
Journal of Bone and Joint Surgery; 27:695-698.NASPGHAN (2004). Guideline for the Evaluation of Cholestatic
Jaundice in Infants. Journal of Pediatric Gastroenterology and Nutrition; 39:115–128.
Slack Health Care Books. Posterior Embryotoxon (image). http://www.slackbooks.com.
Venigalla & Gourley (2004). Neonatal cholestasis. Seminars in Perinatology; 28:348-355.
More clinical guidelines can be found here:http://www.naspghan.org/