11 - Pediatric Diseases of the Liver Flashcards
(45 cards)
Cholestasis
Impairment in bile flow From: Defects in intrahepatic production Transmembrane transport Mechanical obstruction
Cholestasis - Manifestations
Retention of bile components Elevated serum bile acids - Pruritis Hyperbilirubinemia - Jaundice Hypercholesterolemia - Xanthomas Impaired copper excretion - fibrosis Neonatal cholestasis > 2 weeks affects 1 in 2500 births
Cholestasis Consequences - Impaired Bile Salt Excretion
Fat Malabsorption - Nutritional Impairment
Fat Soluble Vitamin Deficiency
Cholestasis Consequences - Hepatocellular Injury
Progressive fibrosis, evolving to cirrhosis
Portal hypertension
Loss of hepatic synthetic function
Most common cause of neonatal cholestasis, but least understood
Idiopathic Neonatal Hepatitis
Idiopathic Neonatal Hepatitis
30 - 40% of neonatal cholestasis Jaundice in the first week of life 33% FTT or fulminant course Hepatomegaly +/- Splenomegaly Acholic stool possible
Two forms of Idiopathic Neonatal Hepatitis
Sporadic (60 - 70% full recovery)
Familial (20 - 30% recovery, 10 - 15% cirrhosis)
Idiopathic Neonatal Hepatitis - Pathology
Severe diffuse hepatocellular disease
Marked infiltration by inflammatory cells
Focal hepatocellular necrosis
GIANT CELL HEPATITIS
Not present:
Bile ductular proliferation
Bile duct paucity
Biliary Atresia
Uncommon
No familiar pattern
Icteric by first week
Acholic stools
Biliary Atresia - Associated abnormalities
Polysplenia
Heterotaxia
Intra-abdominal vascular abnormalities
Biliary Atresia - Cause
Unknown
Can be induced via infectious agents (Reovirus III, CMV)
Biliary Atresia - Investigations
Abdominal ultrasound (to rule out biliary obstruction like a choledochal cyst)
HIDA scan with phenobarb x 5D (good for ruling out)
Liver biopsy
Intra-op cholangiogram
If you give phenobarb to a pediatric patient, what are the two ways they can go about bile absorption?
Bile acid dependent (main/only pathway in adults)
Bile acid independent (about 10% of the pathway in kids, can induce this pathway with phenobarb)
Biliary Atresia - Pathology
Infantile obstructive cholangiopathy Bile ductular proliferation Portal expansion with edema +/- fibrosis Bile plugs Intact lobular architecture Giant cells may be present
Biliary Atresia - Treatment
Kasai hepatic porto-enterostomy
Performed in the first few months of life (
Alagille Syndrome
Autosomal Dominant Arteriohepatic dysplasia Variable penetrance JAG 1 (notch ligand) mutation (>90%) Chromosome 20p12 Intrahepatic interlobular bile duct paucity
Alagille syndrome - Abnormalities
Face - Broad forehead, underdeveloped mandible, straight nose (95%)
Ocular - Posterior embryotoxon - finding in the eye, doesn’t change vision(88%)
Cardiovascular - Peripheral Pulmonic Stenosis or Tetralogy of Fallot (85%)
Vertebral - Butterfly vertebrae (87%)
Minor abnormalities - Renal disease, short stature, pancreatic insufficiency
Alagille’s Syndrome - Prognosis
Prolonged survival good (80% without OLT)
Pruritus
Xanthoma - Lipoprotein X
Neurologic complications (Vitamin E deficiency)
Defective spermatogenesis
Growth retardation
CNS anyeurisms
Progressive Familial Intrahepatic Cholestasis (PFIC)
Byler’s-like syndrome
Autosomal Recessive
PFIC-1 defect in P-type ATPase gene (ATP8B1)
FIC-1 gene localized to chromosome 18q21
Defect in biliary canalicular membrane phospholipid transport
PFIC-2 - defective bile salt export pump (BSEP) - You can stain for this on biopsy now!!
Normal GGTP (it’s a transport defect!)
Post transplant sometimes you end up with bile salty diarrhea
Choledocal Cyst
Congenital biliary dilatation
Common bile duct affected
Cyst wall - fibrous tissue lacking epithelium
Malignant potential - Merits resection
Early
Choledocal Cyst - Type 1
50 - 80%
Diffuse fusiform dilatation of the common bile duct
Choledocal Cyst - Type 2
Diverticulum of common bile duct
Choledocal Cyst - Type 3
Within the duodenal wall
Choledocal Cyst - Type 4
Type 1 (diffuse fusiform dilatation) with intrahepatic duct cyst
