Pediatric Liver Disease Flashcards
Neonatal Jaundice: definition
Jaundice (icterus): yellow discoloration of tissues (PE: skin, sclerae, mucous membranes) due to abnormal deposition of bilirubin
Pre-hepatic/ hepatic/ post-hepatic
Neonatal Jaundice: etiologies
Physiologic jaundice* Infection Medication Total parenteral nutrition Obstruction* Congenital malformations Biliary atresia Metabolic Disease* Hereditary hyperbilirubinemia* Idiopathic neonatal hepatitis*
Physiologic jaundice (how common is it, why, and prognosis)
Most infants affected
Onset in first week of life (but not in 1st 24 hours)
Increased unconjugated (indirect) bilirubin
Mechanisms include:
Increased red blood cell turnover
Immaturity of system for bilirubin conjugation
Deconjugating enzymes in breast milk
Generally benign, resolving in 10 days to 1 month, although some cases may require phototherapy to prevent kernicterus (toxic accumulation of unconjugated bilirubin in neonatal brain)
What’s the functional difference btwn the conjugated and non-conjugated forms of bilirubin?
conjugated is water-soluble
Treatment for physiologic jaundice
phototherapy
Pathologic jaundice (when to be concerned)
Onset in 1st 24 hours or >14 days after birth
Rapid increase in total bilirubin
Very high total bilirubin
Increased direct bilirubin
Classification of pathologic jaundice
Classified into: Unconjugated Hemolytic Intrinsic (eg: sickle cell disease) Extrinsic (eg: Rh disease) Non-hemolytic Conjugated Hepatic Post-hepatic
Pathologic jaundice:Hereditary Hyperbilirubinemias
Unconjugated hyperbilirubinemia:
Crigler-Najjar Syndrome- Mutation in bilirubin-UDP-glucuronosyltransferase (UGT1A1), which conjugates bilirubin
Type I (AR): no functional enzyme; require phototherapy/ transplantation (markedly elevated bilirubin levels in neonates result in neurotoxicity)
Type II (AD): decreased enzyme activity; less severe
Gilbert Syndrome- Variably reduced expression of UGT1A1; recurrent, STRESS-INDUCED hyperbilirubinemia; common (5-10% of population)
Conjugated hyperbilirubinemia:
Dubin-Johnson Syndrome- Hereditary defect in excretion of conjugated bilirubin due to mutation in multi-drug resistance protein 2 (MRP2); variable hyperbilirubinemia, esp in setting of stress
Rotor Syndrome- Exact biochemical defect unknown; variable hyperbilirubinemia, esp in setting of stress
choledochal cyst (definition, presentation, diagnosis, treatment, and complications)
Obstructive cause of jaundice
Congenital anomaly of intrahepatic/ extrahepatic bile ducts characterized by ductal dilation and bile stasis
Presentation:
Usually by age 10
Classic triad (40%) : pain, jaundice (conjugated/direct bilirubinemia), RUQ mass
Diagnosis: imaging; surgical exploration
Treatment: surgery
Complications (if untreated): gallstones (stasis), cholangitis, stenosis/stricture, pancreatitis, obstructive biliary complications if persists until adulthood, increased risk of cholangiocarcinoma.
biliary atresia (incidence, path, blood chemistry, forms)
Obstructive cause of jaundice
Posthepatic problem
Incidence: 1 in 8,000-12,000
Pathology: Obstruction of extrahepatic biliary tree
Blood chemistry: conjugated/direct bilirubinemia
Two main forms:
Embryonic/fetal form (congenital): 10-35%
Perinatal form: 65-90%
Embryonic form of biliary atresia
Jaundice at birth
Abnormal development of biliary tree
Genetic abnormality; associated with other anomalies
Perinatal form of biliary atresia
Normal at birth; new onset, progressive jaundice 1-6 weeks after birth
No associated anomalies
Histopathology: progressive destruction of biliary tree
Etiology remains unknown; proposed, but unproven, disease mechanisms include: viral, toxic, autoimmune, vascular, genetic
Pathlogy:
Liver- Cholestasis in hepatocytes, canaliculi, and ducts (“bile plugs”)
Reactive bile duct proliferation
Variable inflammation and fibrosis
Biliary remnant
Fibroinflammatory obliteration of biliary tree
Biliary Atresia: Treatment
“Kasai Procedure”- Hepatoportoenterostomy (making a neo-bile duct from small intestine)
Better prognosis if performed before day of life 60
Transplantation- BA is most common indication for transplantation in pediatric age group
At this time, no non-surgical therapeutic options
Idiopathic Neonatal Hepatitis
25-40% of cases of neonatal cholestasis
Diagnosis of exclusion (exclude known infectious, metabolic, anatomic, genetic disorders)
85-90% sporadic
10-15% familial
Prognosis
Sporadic form: 75% recovery, 7% chronic liver disease, 19% fatal
Familial form: 22% recovery, 16% chronic liver disease, 63% fatal
Neonatal Hepatitis: pathologic findings – hallmark
giant cell transformation
