Inherited Metabolic Liver Disease Flashcards
A blockage of bile flow presents on labs as:
increase in conjugated bilirubin
How high must bilirubin be to qualify as conjugated hyperbilirubinemia?
> 2 or >15% of total
How is unconjugated bilirubin transported?
by albumin in blood –>potentially toxic
At what bilirubin level do we find jaundice?
> 5-7 in newborns, >2 in older children
What are some common causes of physiologic jaundice?
decreased albumin, decreased hepatic uptake due to decreased ligandin, decreased conjugation/secretion, infants have enhanced bilirubin production due to large RBC mass, short RBC lifespan, and inefficient erythropoeisis
T/F neonatal cholestasis is always pathologic
T –>relative emergency
How do we distinguish pathologic from physiologic jaundice in neonates/infants?
conduct fractionated bilirubin: conjugated bilirubin is 0 in physiologic jaundice
2 causes of extrahepatic neonatal cholestasis
choledochal cyst, biliary atresia
Most common cause of conjugated hyperbilirubinemia
biliary atresia
Complete obliteration of the hepatic/common bile ducts
biliary atresia
Clinical findings in biliary atreia
acholic stools, dark urine, mild icterus, hepatosplenomegaly, conjugated bilirubin, mildly elevated AST, elevated GGT
Imaging of abnormalities in liver/bile ducts
ultrasound + disida scintiscan
Histologic findings of biliary atresia
bile duct proliferation, ductal bile plugs, portal fibrosis
Bile duct paucity
metabolic disorders, alagille syndrome
Gold standard for dx of biliary atresia
operative cholangiogram
Tx of biliary atresia
kasai hepatoportoenterostomy
Prognostic factors in kasai surgery
age at surgery, experience of surgeon
Complications of biliary atresia
persistent jaundice, intractable pruritis, ascending cholangitis, portal hypertension, variceal hemorrhage, vitamin deficiencies, liver failure
What gene may be implicated in biliary atresia?
GPC1 –> cell surface heparan sulfate proteoglycan
Clinical finding of glycogen storage disease
hypoglycemia + hepatomegaly
Clinical finding of Niemann Pick disease
abnormal lipids in reticuloendothelial cells + neurologic involvement in some types
Clinical finding of tyrosinemia
early liver failure, cirrhosis, risk of carcinoma, direct toxic metabolic damage
alpha1 Antitrypsin deficiency
primary function is to inhibit neutrophil elastase in lung –> deficiency = early emphysema in 3rd/4th decade of life + liver disease due to accumulation of mutant protein
Dx of A1AT deficiency
isoelectric focusing of specific protein phenotypes
Tx of A1AT deficiency
modify risk factors (smoking), tx of complications, surveillance for cancer, transplants, augmenting autophagy (valproic acid, carbamazepine)
Findings in wilson’s disease
aminotransferase elevation, hepatomegaly, hepatitis, cirrhosis, copper ring in eye, dystonia, tremors, choreiform movements, hemolytic anemia, renal disease, cardiomyopathy
Wilson’s disease gene
ATP7B –> hepatic biliary excretion of copper
Normal copper trafficking pathway
copper enters via Ctr1 channel –> bound to metallothionein or Atox1 –> enters golgi via ATP7B –> transported to bile canaliculus via Murr1
Dx of Wilson’s
slit lamp exam, ceruloplasmin (ends up as apocerulosplasmin due to failure of copper binding), 24 hour urine copper –> low ceruloplasmin, +/-rings, high copper –> liver biospy, histology, etc.
- screen family members
Tx of Wilson’s
chelating agents like trientene and zinc, liver transplant
_____ is the pathologic deposition of excessive iron in parenchymal cells of organs leading to cell damage and functional abnormalities.
hemochromatosis
Most common variant of hereditary hemochromatosis.
HFE associated: c282Y or H63D gene
Unifying hypothesis for hereditary hemochromatosis
lack/low of hepcidin results in a massive release of iron in body
How long does tissue damage take in hemochromatosis?
decades
Triad of hemochromatosis
diabetes, hepatomegaly, skin pigmentation –>more in men
Tx of hemochromatosis
phlebotomy
