Lecture 34: Introduction to Pediatric Liver Disease Flashcards
What is cholestasis?
Reduction of bile flow from the liver
Lack of bile acids, bilirubin, cholesterol and drugs and toxins in the bowel
What is conjugated hyperbilirubinemia?
Conjugated bilirubin that is >2 mg/dl
Or >15% of total bilirubin
What are the forms of bilirubin?
- conjugated bilirubin
2. Unconjugated bilirubin
What is conjugated bilirubin?
Diconjugated to glucuronic acid in the liver
What is unconjugated bilirubin?
Lipophilic and potentially toxic species
Carried by albumin in blood
What are the types of neonatal cholestasis?
- Extra hepatic
- choledocchal cyst
- biliary atresia
- bile duct stenosis
- neoplasia/stones
- Intrahepatic
- neonatal hepatitis
- alagille syndrome
- CMV
- Neonatal GIANT CELL hepatitis
- Galactosemia
- TPN cholestasis
What are the characteristics of biliary atresia?
Defined as complete obliteration of hepatic/common bile ducts
- most common identifiable cause of infantile cholestatic jaundice
- only occurs in infants
- leading indication for liver transplantation
- can be idiopathic or part of a malformation (polysplenia, congenital cardiac disease, etc.)
- Have DARK urine, mild icterus, hepatosplenomegaly, well appearing child
- Elevated GGT, mildly elevated ALT
What is heterotaxy?
Transposition
Any abnormal position of the organs of the body
Why do babies get PHYSIOLOGIC jaundice?
Enhanced bilirubin production due to
-large RBC mass
-shortened RBC life span
-inefficient EPO
Decreased albumin binding due to lower [albumin]
Decreased hepatic uptake nd binding due to decreased ligandin, decreased conjugation
Decreased secretion
What are signs of PATHOLOGIC jaundice in neonates?
- Neonatal CHOLESTASIS is always pathologic
- is a relative emergency
- Any infant with jaundice after 2 weeks of age should have a fractionated bilirubin to asses for conjugated hyperbilirubinemia
What is the gold standard for diagnosing BA?
Operative cholangiogram
Infant stool color card developed in Taiwan
What is the surgical treatment for BA?
Kasai hepatoportoenterostomy
What are the candidate genes for biliary atresia?
GPC1 (glypican 1) seen in the zebra fish
What is the significance of kasai’s hepatoportoenterostomy?
Surgery used to treat biliary atresia for newborns
What is alagille syndrome?
Genetic disorder that affects liver, heart, kidney and other systems
Autosomal dominant
Deletion of 20p12, so embryonic development is messed up
What is GSD?
Glycogen stoarage disease
What are the characteristics of glycogen storage disease?
Metabolic liver disease
Causes HEPATOMEGALY (because too much glycogen is present)
Patients present with hypoglycemia
Glycogen accumulates in hepatocytes
What are the characteristics of Niemann Pick disease?
Metabolic liver disease
Causes HEPATOSPLENOmegaly
Abnormal LIPIDS accumulate in reticuloendothelial cells
Neurological involvement in some types
What are the characteristics of tyrosinemia?
Metabolic liver disease
A type of toxic metabolite that cause liver damage
Patients have early liver failure and cirrhosis
High risk for hepatocellular carcinoma
TOO MUCH TYROSINE
What are types of causes for inherited cirrhosis?
Alpha-1-anti trypsin deficiency in neonates
Hemochromatosis
Cystic Fibrosis
Phenlyketonuria
What is the most common type of inherited cirrhosis?
Alpha 1 anti trypsin deficiency in neonates
What are the characteristics of alpha1-antitrypsin deficiency?
- A1Antitrypsin is a serum protease inhibitor
-synthesized in liver and secreted - Primary function is to inhibit neutrophil elastase in the lung
- deficiency leads to emphysema and liver disease due to mutant protein in hepatocytes
No A1AT = neutrophils go wild and you get CIRRHOSIS
What are indications for A1AT deficiency testing?
Chronic active hepatits
Cryptogenic cirrhosis
Hepatocellular Carcinoma
Early emphysema
Why do only a subset of patients with A1AT deficiency develop liver disease?
Because proteins do not get degraded in liver in this subset
