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Flashcards in Pediatric Liver Disease Deck (21)
1

Neonatal Jaundice: definition

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

Pre-hepatic/ hepatic/ post-hepatic

2

Neonatal Jaundice: etiologies

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

3

Physiologic jaundice (how common is it, why, and prognosis)

Most infants affected

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

Increased unconjugated (indirect) bilirubin

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

Generally benign, resolving in 10 days to 1 month, although some cases may require phototherapy to prevent kernicterus (toxic accumulation of unconjugated bilirubin in neonatal brain)

4

What's the functional difference btwn the conjugated and non-conjugated forms of bilirubin?

conjugated is water-soluble

5

Treatment for physiologic jaundice

phototherapy

6

Pathologic jaundice (when to be concerned)

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

7

Classification of pathologic jaundice

Classified into:
Unconjugated
Hemolytic
Intrinsic (eg: sickle cell disease)
Extrinsic (eg: Rh disease)
Non-hemolytic
Conjugated
Hepatic
Post-hepatic

8

Pathologic jaundice:Hereditary Hyperbilirubinemias

Unconjugated hyperbilirubinemia:

Crigler-Najjar Syndrome- 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- Variably reduced expression of UGT1A1; recurrent, STRESS-INDUCED hyperbilirubinemia; common (5-10% of population)

Conjugated hyperbilirubinemia:

Dubin-Johnson Syndrome- 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- Exact biochemical defect unknown; variable hyperbilirubinemia, esp in setting of stress

9

choledochal cyst (definition, presentation, diagnosis, treatment, and complications)

Obstructive cause of 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.

10

biliary atresia (incidence, path, blood chemistry, forms)

Obstructive cause of jaundice

Posthepatic problem

Incidence: 1 in 8,000-12,000

Pathology: Obstruction of extrahepatic biliary tree

Blood chemistry: conjugated/direct bilirubinemia

Two main forms:
Embryonic/fetal form (congenital): 10-35%
Perinatal form: 65-90%

11

Embryonic form of biliary atresia

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

12

Perinatal form of biliary atresia

Normal at birth; new onset, progressive jaundice 1-6 weeks after birth

No associated anomalies

Histopathology: progressive destruction of biliary tree

Etiology remains unknown; proposed, but unproven, disease mechanisms include: viral, toxic, autoimmune, vascular, genetic

Pathlogy:
Liver- Cholestasis in hepatocytes, canaliculi, and ducts (“bile plugs”)
Reactive bile duct proliferation
Variable inflammation and fibrosis
Biliary remnant
Fibroinflammatory obliteration of biliary tree

13

Biliary Atresia: Treatment

“Kasai Procedure”- Hepatoportoenterostomy (making a neo-bile duct from small intestine)
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

14

Idiopathic Neonatal Hepatitis

25-40% of cases of neonatal cholestasis

Diagnosis of exclusion (exclude known infectious, metabolic, anatomic, genetic disorders)

85-90% sporadic
10-15% familial

Prognosis
Sporadic form: 75% recovery, 7% chronic liver disease, 19% fatal
Familial form: 22% recovery, 16% chronic liver disease, 63% fatal

15

Neonatal Hepatitis: pathologic findings -- hallmark

giant cell transformation

16

Metabolic storage diseases

Many involve liver
Liver biopsies can show you a specific pattern of injury

17

Primary hepatic neoplasms (benign vs malignant)

Benign:
Mesenchymal hamartoma
Teratoma
Hepatocellular adenoma
Focal nodular hyperplasia

Malignant:
Hepatoblastoma (usually 5 yrs old)
Undifferentiated/Embryonal Sarcoma

18

Hepatoblastoma (demographics, presentation, pathobiology)

Demographics:
90% present before age 5 yr, 68%

19

Hepatoblastoma -- pathologic findings

Tumor histology recapitulates features of hepatic development

Histology:
Epithelial- Fetal and embryonal-type differentiation most common

Mesenchymal-Primitive mesenchyme, bone, cartilage, muscle

Mixed- Epithelial and mesenchymal differentiation

20

Hepatoblastoma treatment

Chemotherapy and surgical resection
Liver transplantation is option in unresectable cases without metastasis
Overall survival: 65-70%

21

What's the most important prognostic factor for hepatoblastoma

STAGE at time of resection

Stage 1: ~100% survival
Complete resection
Stage 2: 75-80% survival
Microscopic residual tumor
Stage 3: 65% survival
Gross residual tumor, lymph nodes positive, tumor spill into abdomen
Stage 4: 0-27% survival
Metastatic disease