Peds liver disease Flashcards
What is neonatal jaundice
yellow discoloration of tissues (PE: skin, sclerae, mucous membranes) due to abnormal deposition of bilirubin
Labs to test for neonatal jaundice
Unconjugated/indirect bilirubinemia, Conjugated/direct bilirubinemia
Bilirubin metabolism
Heme from erythrocytes are broken down by heme oxygenase and biliverdin reductase in mononuclear phagocytes into bilirubin > bilirubin-albumin complex enters blood > enter liver > hepatocytes breakdown bilirubin > enters bile duct and duodenum > removed in feces
Know the differential diagnosis of neonatal jaundice.
Physiologic jaundice, Infection, Medication, Total parenteral nutrition, Obstruction (Congenital malformations, Biliary atresia), Metabolic Disease, Hereditary hyperbilirubinemia, Idiopathic neonatal hepatitis*
What is physiologic jaundice
Most infants affected. Onset in first week of life (but not in 1st 24 hours). Increased unconjugated (indirect) bilirubin
Physiologic jaundice mechanisms
Increased RBC turnover, immaturity of system for bilirubin conjugation (bilirubin conjugation system isnt mature until 2 weeks) and/or deconjugating enzymes in breast milk.
Physiologic jaundice treatment
usually self limiting but phototherapy can be used to prevent kernicterus (toxic accumulation of unconjugated bilirubin in neonatal brain). Phototherapy transforms bilirubin into isomers, which can be excreted in bile and urine.
Idiopathic neonatal hepatitis
Elevated levels of conjugated bilirubin in neonate not caused by infection, metabolic dz, bile duct obstruction or meds
idiopathic neonatal hepatitis path findings
giant cell transformation
Time course and features of pathologic jaundice
Onset in 1st 24 hours or >14 days after birth. Very high total bilirubin and Increased direct bilirubin
List types of hereditary hyperbilirubinemias
Unconjugated: Crigler-Najjar syndrome, Gilbert syndrome. Conjugated: Dubin-Johnson Syndrome and Rotor syndrome
Crigler-Najjar syndrome genetics and pathophys
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 genetics and pathophys
Variably reduced expression of UGT1A1; recurrent, stress-induced hyperbilirubinemia; common (5-10% of population)
Dubin-Johnson syndrome genetics and pathophys
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 genetics and pathophys
Exact biochemical defect unknown; variable hyperbilirubinemia, esp in setting of stress
Choledochal cyst
Congenital anomaly of intrahepatic/ extrahepatic bile ducts characterized by ductal dilation and bile stasis
Choledochal cyst presentation and diagnosis
–Classic triad (40%) : pain, jaundice (conjugated/direct bilirubinemia), RUQ mass. Diagnosis: imaging and surgical exploration
Choledochal cyst treatment and complications
Surgery. Complications if untreated: gallstones (stasis), cholangitis, stenosis/stricture, pancreatitis, obstructive biliary complications. If persists until adulthood, increased risk of cholangiocarcinoma
Biliary atresia
obstruction of extrahepatic biliary tree with elevated conjugated/direct bilirubinemia. Congenital/embryonic or perinatal
Embryonic/fetal biliary atresia presentation
Jaundice at birth, Abnormal development of biliary tree. Genetic abnormality; associated with other anomalies
Perinatal biliary atresia presentation, histopathology
Normal at birth; new onset, progressive jaundice 1-6 weeks after birth. No associated anomalies. Histopathology: progressive destruction of biliary tree. Etiology unknown
Post natal biliary atresia pathologic findings in liver and biliary tree
liver: Cholestasis in hepatocytes, canaliculi, and ducts (“bile plugs”). Reactive bile duct proliferation. Variable inflammation and fibrosis. Biliary tree: fibroinflammatory obliteration of biliary tree
Biliary atresia treatment
- Kasai procedure: hepatoportoenterostomy- extrahepatic biliary system is excised and a loop of small bowel in connected to the hepatic hilum to allow for bile drainage. best before day 60. 2. Transplant
Metabolic storage diseases involving liver
Carb metabolism (glycogen storage dz, galactosemia, fructosemia), lysosomal storage dz (Niemann-Pick, Gaucher), amino acid metabolism, iron (hemochromatosis), copper (wilson dz)
List benign primary hepatic neoplasms
Mesenchymal hamartoma, Teratoma, Hepatocellular adenoma, Focal nodular hyperplasia
List malignant primary hepatic neoplasms
Hepatoblastoma (usually < 5 yrs old), Hepatocellular Carcinoma (usually > 5 yrs old), Undifferentiated/Embryonal Sarcoma
Hepatoblastoma presentation
–anorexia, weight loss, nausea, vomiting, pain; abdominal enlargement/mass; 90% have markedly elevated serum alpha-fetoprotein level (useful tumor marker)
hepatoblastoma pathophys
–Wnt/beta-catenin pathway activated in 80%
Syndromes associated with hepatoblastoma
Beckwith-Wiedemann Syndrome, Familial Adenomatous Polyposis (Wnt/beta-catenin mutations)
hepatoblastoma histology
Epithelial: fetal and ebryonic type differentiation. Mesenchymal: primitive mesenchyme, bone, cartilage, muscle. Mixed: epithelial and mesenchyme differentiation
Hepatoblastoma treatment
chemo, surgical resection, liver transplant if unresectable
