Physiologic Jaundice of Infancy

• In term infants

1)     rises <5mg/24 hr

2)     peaks at 2-4 days

3)     levels at 5-6 mg/dl

• Premies

1)     variable level and rise

2)     peaks at about 4-7 days

• Work up further if:

1)     jaundice w/in the first 24 hours

2)     serum bili rises >5mg/dl/24hrs

3)     Serum bilirubin > 12 mg/dl (term) or 14 mg/dl (premies)

4)     Duration longer than one week

5)     Direct bilirubin > 1 mg/dl any time

Neonatal Hepatitis

• MOST COMMON DIAGNOSIS IN INFANTS W/ PROLONGED CHOLESTASIS
• MOST COMMON CAUSE OF HYPERBILIRUBINEMIA
• Presentation

1)     increases in serum AST, ALT, Bili

2)     preterm, male, low birth weight

• Pathology

Ø  GROSS

1)     liver may be enlarged, smooth and green

Ø  MICRO

1)     prominent giant cell transformation

2)     ballooning of hepatocytes

3)     acidophilic necrosis

4)     pseudoglandular formation

5)     lobular areas – extramedullary hematopoiesis

6)     multinucleated Giant Hepatocytes

7)     areas of cholestasis (Bilirubin built up in liver)

• Prognosis

Ø  most recover, some go on to cirrhosis

Ø  familial cases have poorer prognosis

Extrahepatic Biliary Atresia

• 2^nd most common cause of prolonged cholestasis in infancy
• total or segmental obliteration of extrahepatic duct system
• unknown etiology
• Presentation

1)     term infants with normal birth weight

2)     may be jaundiced at birth

3)     acholic stools

4)     failure to thrive with cirrhosis, spleeomegaly, portal hypertension

• No familial occurrence
• Biliary system

1)     small gallbladder, fibrotic, with epithelial degeneration

2)     obliteration of the bile duct lumen by fibrous tissue

• Porta Hepatis

Ø  are of liver where the GB receives the bile

1)     variable histologic picture

2)     total fibrous obliteration

• Pathology

Ø  GROSS

1)     early: large, firm, and bile-stained

2)     late stages: small, bile stained micronodular cirrhosis

Ø  MICRO: EARLY CHANGES

1)     bile duct proliferation around the periphery of the portal tract

2)     hepatocellular cholestasis

3)     portal fibrosis

4)     extramedullary hematopoiesis

Ø  MICRO: LATE CHANGES

1)     bile duct proliferation peaks at 8-9 months

2)     increasing portal fibrosis

3)     balooning degeneration

4)     large areas of cholestasis

• Prognosis

Ø  life expectancy if untreated – 2 years

Ø  Kasai procedure (hepatoportoenterostomy) used until a liver is found

Ø  Transplantation

a₁ – antitrypsin deficiency

• most common genetic disorder of children
• Function: inhibits specific proteases
• multiple alleles exist
• Effects

1)     neonatal hepatitis syndrome

2)     cirrhosis

3)     HCC

4)     Precocious emphysema

• Presentation

Ø  First week of life – jaundice, acholic stool,m hepatomegaly

Ø  2-4 mths – jaundice may clear

Ø  variable cource

• Pathology

Ø  GROSS

1)     micronodular cirrhosis, may be bile stained

Ø  MICRO: EARLY

1)     hepatocellular injury

2)     acidophilic necrosis

3)     pseudoacinar transfomration

4)     cholestasis

Ø  HALLMARK – PAS-positive diastase resistant globules in periportal hepatocytes

Ø  MICRO: LATE

1)     micronodular cirrhosis

2)     droplets may be visible w/ H&E

• Prognosis

Ø  50% progress to cirrhosis

Ø  increased risk of HCC  (reason for testing)

• Treatment

Ø  transplantation (no enzyme therapy yet)

Tyrosinemia

• disorder of amino acid metabolism
• autosomal recessive
• fumarlyacetoacetate hydrolase is deficient enzyme
• elevated serum levels of Tyrosine
• Presentation

Ø  Acute form

1)     onset: first few weeks or months

2)     failure to thrive, anemia, vomiting, hepatomegaly

3)     death w/in the first year of life

Ø  Chronic form

1)     onset: first year

2)     growth retardation, hepatic failure, renal tubular defects

3)     death w/in first decade

• Pathology

Ø  GROSS

1)     firm, slightly enlarged liver

2)     mixed cirrhosis (micro and macro)

Ø  MICRO

1)     regenerative nodules show steatosis

2)     pseudoacinar change

3)     cholestasis

4)     portal and lobular fibrosis

5)     Hemosiderosis and extramedullary hematopoiesis

6)     Dysplasia

• Prognosis

Ø  death from failure to thrive

Ø  survivors drastically increase their chance of developing HCC

Ø  Liver transplant

Neonatal Hemochromatosis

• iron overload and liver disease
• presents at birth
• unknown etiology
• Presentation

Ø  conjugated hyperbilirubinemia at birth

Ø  hepatomegaly, spleenomegaly

Ø  portal HTN

Ø  coagulopathy and hypoalbuminemia

• Pathology

Ø  GROSS

1)     firm normal sized to increased liver

Ø  MICRO

1)     bile and iron storage in hepatocytes

2)     pseudoacinar changes

3)     necrosis

4)     giant cell transformtaion

Ø  Iron is deposited in other organs – most common in pancrease

• Prognosis

Ø  natural history is death from liver failure shortly after birth

Ø  chelation therapy is not successful

Wilson’s Disease

• chromosome 13
• increased copper in hepatocytes
• causes chronic cholestasis
• Presentation

Ø  abnormal liver test

Ø  anemia

Ø  Kayser-Fleischer rings of sclera

• Treatment

Ø  chelation therapy and pyridoxine

Tags: acidophilic necrosis, Cholestasis, Extrahepatic Biliary Atresia, Giant Hepatocytes, hepatocytes, hepatoportoenterostomy, hyperbilirubinemia, Jaundice, Kasai procedure, Neonatal Hepatitis, pseudoglandular formation

This entry was posted on Thursday, June 18th, 2009 at 5:00 am and is filed under Pathophysiology. You can follow any responses to this entry through the RSS 2.0 feed. Responses are currently closed, but you can trackback from your own site.