Pediatric Liver Disease Flashcards
Liver diseases in kids and adults
Non-alcoholic fatty liver disease
HBV and HCV hepatitis (often vertically acquired)
Autoimmune hepatitis/ Primary sclerosing cholangitis
Wilson disease (older kids)
Alpha-1-antitrypsin disease
Jaundice
yellow discoloration of tissues (PE: skin, sclerae, mucous membranes) due to abnormal deposition of bilirubin
Classification: Pre-hepatic/ hepatic/ post-hepatic (biliary drainage system) Blood chemistry: Unconjugated/indirect bilirubinemia Conjugated/direct bilirubinemia
Bilirubin
-majority comes from RBC turnover (non-protein heme group of hemoglobin; bilirubin complexed w/ albumin; transported into hepatocytes; conjugation into water soluble form, out of hepatocyte into biliary drainage system into bile ducts into duodenum)
Neonatal jaundice etiologies
Physiologic jaundice* Infection Medication Total parenteral nutrition Obstruction* -Congenital malformations -Biliary atresia Metabolic Disease* Hereditary hyperbilirubinemia* Idiopathic neonatal hepatitis*
Physiologic jaundice
-most infants
-first week (not 1st 24 h)
-increased unconjugated (indirect) bilirubin
-Mech:
increased RBC turnover
immaturity of system for bilirubin conjugation
deconjugating enz in breast milk
- usually benign, resolves 10d to 1mo
- some: phototherapy to prevent kernicterus (toxic accum of unconjugated bilirubin in neonatal brain)
Normal bilirubin metab
UGT1A1–> bilirubin glucuronides–>bile
Tx for abnormal metab/increased bili levels:
Phototherapy: bypass conjugating system of liver
Exchange transfusion
Pathologic jaundice
onset: 1st 24h or >14d after birth
- rapid increase in total bilirubin
- Very high total bilirubin
- Increased direct bilirubin
Classified into:
Unconjugated usually prehepatic:
-Hemolytic (Intrinsic (eg: sickle cell disease) Extrinsic (eg: Rh disease))
-Non-hemolytic (deficient enzyme activity in liver)
Conjugated:
Hepatic
*Post-hepatic
Crigler-Najjar syndrome
Unconjugated hyperbilirubinemia
rare
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
unconjugate hyperbilirubinemia
Variably reduced expression of UGT1A1; recurrent, stress-induced hyperbilirubinemia; common (5-10% of population)
Dubin-Johnson syndrome
conjugated hyperbilirubinemia
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
conjugated hyperbilirubinemia
defect unknown; variable hyperbilirubinemia, esp in setting of stress
Choledochal cyst
Obstructive cause of pathologic 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.
**posthepatic, defect in drainage
Biliary atresia
obstructive cause of pathologic jaundice
obstruction of extrahepatic biliary tree
1/8-12,000
Blood chemistry: conjugated/direct bilirubinemia
Two main forms:
Embryonic/fetal form (congenital): 10-35% (jaundice @ birth, abnormal devel of biliary tree, genetic w/ assoc abnormalities)
Perinatal form: 65-90% (ACQUIRED) (norm @ birth, new onset jaundice 1-6 weeks after birth, no assoc anomalies, histopathology: progressive destruction of biliary tree; etiology UNKNOWN); Likely if you can’t visualize gallbladder on U/S
Pathologic findings 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
Tx of biliary atresia
“Kasai Procedure”
Hepatoportoenterostomy
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
