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Flashcards in Pediatric Liver Disease Deck (17):
1

Jaundice definition/classification

  • yellow discoloration of tissues (PE: skin, sclerae, mucous membranes) due to abnormal deposition of bilirubin
  • Classification: Pre-hepatic/ hepatic/ post-hepatic
  • Blood chemistry:
    • Unconjugated/indirect bilirubinemia
    • Conjugated/direct bilirubinemia
       

2

Etiologies of neonatal jaundice

  • Physiologic jaundice*
  • Infection
  • Medication
  • Total parenteral nutrition
  • Obstruction*
    • Congenital malformations
    • Biliary atresia
  • Metabolic Disease*
  • Hereditary hyperbilirubinemia*
  • Idiopathic neonatal hepatitis*
     

3

Physiologic vs. Pathologic jaundice @ neonates

  • Physiologic
    • occurs w/in first week, but NOT first 24 hours
    • increased unconjugated (indirect) bilirubin
    • benign, resolves 10 days - 1 month
  • Pathologic
    • Onset in 1st 24 hours or >14 days after birth
    • Rapid increase in total bilirubin
    • Very high total bilirubin
    • Increased direct bilirubin
       

4

Types of hereditary hyperbilirubinemias

  • unconjugated hyperbilirubinemia
    • Crigler-Najjar (Type I & II)
    • gilbert syndrome
  • conjugated hyperbilirubinemia
    • Dubin-Johnson syndrome
    • Rotor syndrome

5

Mutations that lead to unconjugated hyperbilirubinemia + consequences

  • Crigler-Najjar
    • mutation = bilirubin-UDP-glucuronosyltransferase (UGT1A1) which conjugates bilirubin
    • Type I = no enzyme
      • requires phototherapy/ transplantation b/c markedly elevated bilirubin levels in neonates result in neurotoxicity
  • Type II = reduced enzyme activity
  • Gilbert syndrome
    • variably reduced UGT1A1 ==> recurrent stress-induced hyperbilirubinemia
    • relatively common

6

Mutations that lead to conjugated hyperbilirubinemia + consequences

  • 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
       

7

Obstructive causes of pathologic neonatal jaundice

  • choledochal cyst
  • biliary atresia

8

Pathology, blood chemistry, forms of biliary atresia

  • Pathology: Obstruction of extrahepatic biliary tree
  • Blood chemistry: conjugated/direct bilirubinemia
  • Two main forms:
    • Embryonic/fetal form (congenital): 10-35%
    • Perinatal form: 65-90%
       

9

Presentation of embryonic/fetal form of biliary atresia

–Jaundice at birth
–Abnormal development of biliary tree
–Genetic abnormality; associated with other anomalies
 

10

Presentation of 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

11

Pathologic findings in perinatal form of biliary atresia

  • Liver
    • Cholestasis in hepatocytes, canaliculi, and ducts (“bile plugs”)
    • Reactive bile duct proliferation
    • Variable inflammation and fibrosis
  • Biliary remnant
    • Fibroinflammatory obliteration of biliary tree

12

Tx of biliary atresia

  • “Kasai Procedure”
    • Hepatoportoenterostomy
    • Better prognosis if performed < day of life 60
  • Transplantation
    • BA is most common indication for transplantation in pediatric age group
  • At this time, no non-surgical therapeutic options
     

13

Most common benign primary hepatic neoplasms in pediatric patients

–Mesenchymal hamartoma
–Teratoma
–Hepatocellular adenoma
–Focal nodular hyperplasia
 

14

Most common malignant primary hepatic neoplasms in pediatric patients

–Hepatoblastoma (usually < 5 yrs old)
–Hepatocellular Carcinoma (usually > 5 yrs old)
–Undifferentiated/Embryonal Sarcoma
 

15

Presentation of hepatoblastoma

  • anorexia
  • weight loss
  • nausea, vomiting
  • pain; abdominal enlargement/mass
  • 90% have markedly elevated serum alpha-fetoprotein level (useful tumor marker)
     

16

Dx of hepatoblastoma

  • Tumor histology recapitulates features of hepatic development
  • Histology
    • –Epithelial
      • Fetal and embryonal-type differentiation most common
    • –Mesenchymal
      • Primitive mesenchyme, bone, cartilage, muscle
    • –Mixed
      • Epithelial and mesenchymal differentiation
         

17

Tx of hepatoblastoma

–Chemotherapy and surgical resection
–Liver transplantation is option in unresectable cases without metastasis
–Overall survival: 65-70%