Pediatric Liver Disease

Question 1

what is Physiologic jaundice

Answer 1

Increased unconjugated (indirect) bilirubin

Onset in first week of life (but not in 1st 24 hours)

Most infants affected

Question 2

what are 3 mechanisms that cause Physiologic Jaundice

Answer 2

Increased red blood cell turnover
Immaturity of system for bilirubin conjugation
Deconjugating enzymes in breast milk

Question 3

what is kernicterus

Answer 3

toxic accumulation of unconjugated bilirubin in neonatal brain

Question 4

how long can you expect physiologic jaundice to resolve

Answer 4

10 days to 1 month

Question 5

how does phototherapy work?

Answer 5

converts bilirubin into photoisomers and oxidation products that can be excreted in the urine.

Question 6

describe pathologic jaundice

Answer 6

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

Question 7

name the 2 Unconjugated hyperbilirubinemias

Answer 7

Crigler-Najjar Syndrome

Gilbert syndrome

Question 8

name the 2 conjugated hyperbilirubinemias

Answer 8

Dubin-Johnson syndrome

Rotor Syndrome

Question 9

describe the difference between conjugated vs unconjugated bilirubin

Answer 9

bilirubin is conjugated to glucuronate by glucuronyl transferase in the liver. Conjugated (direct) bilirubin is excreted into bile.

Question 10

what is Crigler-Najjar Syndrome

Answer 10

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 11

what is gilbert syndrome

Answer 11

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

Question 12

what is the pathophys of Dubin-Johnson Syndrome

Answer 12

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 13

what is the pathophysiology of rotor syndrome

Answer 13

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

Question 14

what is a choledochal cyst

Answer 14

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

Question 15

what are the 2 forms of Biliary Atresia and which one is more common

Answer 15

Embryonic/fetal form: 10-35% (jaundice at birth)

Perinatal form: 65-90% (Normal at birth; new onset, progressive jaundice 1-6 weeks after birth)

Question 16

In Biliary Atresia:, what are 3 Pathologic findings (post-natal form) in the liver

Answer 16

1) Cholestasis in hepatocytes, canaliculi, and ducts (“bile plugs”)
2) Reactive bile duct proliferation
3) Variable inflammation and fibrosis

Fibroinflammatory obliteration of biliary tree

Question 17

what is the treatment for Biliary Atresia

Answer 17

1)“Kasai Procedure”, Hepatoportoenterostomy
Better prognosis if performed before day of life 60
2)Transplantation
BA is most common indication for transplantation in pediatric age group

Question 18

describe what happens in a kasai procedure (Hepatoportoenterostomy)

Answer 18

defective biliary tree removed -> take a loop of intestine and hook it up to the porta hepatis to make a pseudo drainage system

Question 19

25-40% of cases of neonatal cholestasis is classified as

Answer 19

Idiopathic Neonatal Hepatitis

Question 20

“giant cell transformation” on histology is a pathologic finding that is a hallmark of what disease?

Answer 20

Neonatal Hepatitis

Question 21

what is the clinical presentation of Hepatoblastoma

Answer 21

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

Question 22

Beckwith-Wiedemann Syndrome and

Familial Adenomatous Polyposis (Wnt/beta-catenin mutations) increase the incidence of ______

Answer 22

Hepatoblastoma

Question 23

what is the tx of hepatoblastoma

Answer 23

Chemotherapy and surgical resection

Question 24

what is the most important prognostic factor of hepatoblastoma

Answer 24

STAGE of cancer at time of resection

Question 25

what are the malignant hepatic cancers in childeren

Answer 25

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