Peds liver disease

Question 1

What is neonatal jaundice

Answer 1

yellow discoloration of tissues (PE: skin, sclerae, mucous membranes) due to abnormal deposition of bilirubin

Question 2

Labs to test for neonatal jaundice

Answer 2

Unconjugated/indirect bilirubinemia, Conjugated/direct bilirubinemia

Question 3

Bilirubin metabolism

Answer 3

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

Question 4

Know the differential diagnosis of neonatal jaundice.

Answer 4

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

Question 5

What is physiologic jaundice

Answer 5

Most infants affected. Onset in first week of life (but not in 1st 24 hours). Increased unconjugated (indirect) bilirubin

Question 6

Physiologic jaundice mechanisms

Answer 6

Increased RBC turnover, immaturity of system for bilirubin conjugation (bilirubin conjugation system isnt mature until 2 weeks) and/or deconjugating enzymes in breast milk.

Question 7

Physiologic jaundice treatment

Answer 7

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.

Question 8

Idiopathic neonatal hepatitis

Answer 8

Elevated levels of conjugated bilirubin in neonate not caused by infection, metabolic dz, bile duct obstruction or meds

Question 9

idiopathic neonatal hepatitis path findings

Answer 9

giant cell transformation

Question 10

Time course and features of pathologic jaundice

Answer 10

Onset in 1st 24 hours or >14 days after birth. Very high total bilirubin and Increased direct bilirubin

Question 11

List types of hereditary hyperbilirubinemias

Answer 11

Unconjugated: Crigler-Najjar syndrome, Gilbert syndrome. Conjugated: Dubin-Johnson Syndrome and Rotor syndrome

Question 12

Crigler-Najjar syndrome genetics and pathophys

Answer 12

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

Question 13

Gilbert syndrome genetics and pathophys

Answer 13

Variably reduced expression of UGT1A1; recurrent, stress-induced hyperbilirubinemia; common (5-10% of population)

Question 14

Dubin-Johnson syndrome genetics and pathophys

Answer 14

Hereditary defect in excretion of conjugated bilirubin due to mutation in multi-drug resistance protein 2 (MRP2); variable hyperbilirubinemia, esp in setting of stress

Question 15

Rotor syndrome genetics and pathophys

Answer 15

Exact biochemical defect unknown; variable hyperbilirubinemia, esp in setting of stress

Question 16

Choledochal cyst

Answer 16

Congenital anomaly of intrahepatic/ extrahepatic bile ducts characterized by ductal dilation and bile stasis

Question 17

Choledochal cyst presentation and diagnosis

Answer 17

–Classic triad (40%) : pain, jaundice (conjugated/direct bilirubinemia), RUQ mass. Diagnosis: imaging and surgical exploration

Question 18

Choledochal cyst treatment and complications

Answer 18

Surgery. Complications if untreated: gallstones (stasis), cholangitis, stenosis/stricture, pancreatitis, obstructive biliary complications. If persists until adulthood, increased risk of cholangiocarcinoma

Question 19

Biliary atresia

Answer 19

obstruction of extrahepatic biliary tree with elevated conjugated/direct bilirubinemia. Congenital/embryonic or perinatal

Question 20

Embryonic/fetal biliary atresia presentation

Answer 20

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

Question 21

Perinatal biliary atresia presentation, histopathology

Answer 21

Normal at birth; new onset, progressive jaundice 1-6 weeks after birth. No associated anomalies. Histopathology: progressive destruction of biliary tree. Etiology unknown

Question 22

Post natal biliary atresia pathologic findings in liver and biliary tree

Answer 22

liver: Cholestasis in hepatocytes, canaliculi, and ducts (“bile plugs”). Reactive bile duct proliferation. Variable inflammation and fibrosis. Biliary tree: fibroinflammatory obliteration of biliary tree

Question 23

Biliary atresia treatment

Answer 23

1. 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

Question 24

Metabolic storage diseases involving liver

Answer 24

Carb metabolism (glycogen storage dz, galactosemia, fructosemia), lysosomal storage dz (Niemann-Pick, Gaucher), amino acid metabolism, iron (hemochromatosis), copper (wilson dz)

Question 25

List benign primary hepatic neoplasms

Answer 25

Mesenchymal hamartoma, Teratoma, Hepatocellular adenoma, Focal nodular hyperplasia

Question 26

List malignant primary hepatic neoplasms

Answer 26

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

Question 27

Hepatoblastoma presentation

Answer 27

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

Question 28

hepatoblastoma pathophys

Answer 28

–Wnt/beta-catenin pathway activated in 80%

Question 29

Syndromes associated with hepatoblastoma

Answer 29

Beckwith-Wiedemann Syndrome, Familial Adenomatous Polyposis (Wnt/beta-catenin mutations)

Question 30

hepatoblastoma histology

Answer 30

Epithelial: fetal and ebryonic type differentiation. Mesenchymal: primitive mesenchyme, bone, cartilage, muscle. Mixed: epithelial and mesenchyme differentiation

Question 31

Hepatoblastoma treatment

Answer 31

chemo, surgical resection, liver transplant if unresectable