Pediatric Liver Disease Flashcards
What is physiologic jaundice?
Enhanced BR production due to large RBC mass, shortened RBC life span or inefficient erythropoiesis
Decreased albumin binding
Decreased hepatic uptake/binding due to decreased lignin
Decreased conjugation
Decreased secretion
Neonatal cholestasis: Describe intrhepatic (2) and extrahepatic (2) causes
Neonatal cholestasis is an emergency
Intrahepati causes: Neonatal hepatitis and alagille syndrome
Extrahepatic: choledochal cyst and biliary atresia
Describe the epidemiology of biliary atresia
Most common cause of infantile cholestatic jaundice
Only occurs in infants
Leading indication for liver tx
Biliary Atresia: What are the classifications?
Idiopathic isolated biliary atresia (80%) Malformation related (20-30%)
Biliary Atresia: presentation
Well appearing child with echoic stools and dark urine, mild icterus, hepatosplenomegaly
Lab: Elevated conjugated BR, ALT, GGT
What are tests that are run in case of neonatal cholestasis?
Ultrasound: detect abnormalities (choledochal cyst, bile duct stones, perforation of common bile duct, polysplenia) Disida scintiscan to look out excretion and rule out biliary atresia Percutaneous liver biopsy Operative cholangiogram (gold standard)
What is histological finding on biopsy of biliary atresia? (3)
Bile duct proliferation
Ductal bile plugs
Portal fibrosis
What is treatment strategy for biliary atresia?
What factors influence outcome? (2)
What measurement signals success/failure?
Kasai hepatoportoenterostomy– outcome is influenced by age at surgery (
What are the complications associated with biliary atresia? (list)
Persistent jaundice Intratable pruritis Ascending cholangitis portal hypertension, splenomegaly Variceal hemorrhage Fat-soluble vitamin deficiencies Failure to grow Liver tx (chronic liver failure)
Describe models for pathogenesis of biliary atresia
Perinatal: environmental factors, inflammatory response, genetic predisposition (Notch, HLA, immune)==>Immune response
Embryonic: Genetic predisposition, abnormal biliary development, common bile duct obstruction==>Bile flow injury
What is candidate gene for biliary atresia?
Deletion of GPC1 on chromosome 2 results in abnormal biliary development
Glyogen storage disease: Presentation (2), biopsy findings
Hepatomegaly and hypoglycemia
On biopsy, observe glycogen granules in hepatocytes on PAS stain. In some types of GSD may also see glycogen in muscle
Which storage disease is associated with hepatosplenomegaly?
Riemann Pick Disease– abnormal lipids accumulate in reticuloendothelial cells
Some types have neurologic involvement
How do patients with tyrosinemia present?
How can you improve liver function?
Coagulapathy, early liver failure or cirrhosis
High risk of HCC
Improve liver function via drug to block metabolic pathway
What are leading inherited causes of cirrhosis in kids? (5)
A1AT deficiency PFIC CF Wilson's disease Hemochromatosis
What is major leading cause of inherited cirrhosis in adults?
Hemochromatosis….A1AT ranked second
What is A1-Antitrypsin deficiency?
Autosomal recessive deficiency in serum protease inhibitor that inhibits neutrophil elastase in lung
What is presentation of A1AT deficiency?
Early emphysema in 3rd/4th decade
A subset develop liver disease due to accumulation of mutant protein in hepatocytes– observe neonatal hepatitis, chronic hepatitis, cryptogenic cirrhosis, HCC
A1AT Deficiency: Diagnosis
Which phenotype of A1AT is associated with liver/pulmonary disease?
PCR stuff to identify protein phenotypes–
PIMM=full functional activity
PIZZ=liver/pulmonary disease
How is A1AT deficiency managed? (4)
No smoking
Treat complications
Monitor for HCC
Liver/lung tx
What is a new approach for A1AT?
Enhance autophagy==>carbamazepine to destroy cells with protein accumulation
What is Wilson Disease?
Copper accumulation in liver and brain due to defective hepatic excretion of copper (gene is ATP7B on chromosome 13)
Describe copper trafficking in Wilson Disease
Defective ATP7B cannot transport copper into golgi for exocytosis and transport via ceruloplasmin.
Accumulation of copper in cytoplasm causes mitochondrial damage and cellular damage
What is clinical presentation of Wilson Disease?
Hepatic disease at school age: elevated ALT/AST, hepatomegaly, chronic hepatitis, cirrhosis, fulminant hepatitis, autoimmune hepatitis appearing
Neuro: dystonia with rigidity, tremors, dysarthria, dysphonia, gait disturbance, choreiform movements
Other: renal disease, psych disease, cardiomyopathy, arthritis
Wilson Disease: Diagnosis
Ceruloplasmin level (
Wilson Disease: Treatment (4)
Oral chelating agents (penicillamine, trientene, tetrathiomolybdate)
Zinc: blocks Cu absoprtion
Liver tx: fulminant/chronic liver disease
Low copper diet and antioxidants
What is genetic hemochromatosis?
How common is it?
Autosomal recessive disorder resulting in deposition of iron in parenchymal cells and cell damage and functional abnormalities
Prevalence: 1/200 white people (less than 1/300 are symptomatic)
Describe normal iron homeostasis
What is the role of hepcidin?
Iron absorption tightly controlled by enterocytes
Recycling by macrophages
Storage by hepatocytes
Hepcidin=hormone synthesized in liver based on iron levels, infection, inflammation, anemia
What factors are important in having clinical manifestations of disease? (4)
Diet, blood loss, alcohol
HFE mutation
What is the classic triad of hereditary hemochromatosis?
What are other symptoms may be visible
Hepatomegaly, DM, skin pigmentation
Abdominal pain, weakness, lethargy, arthralgias, cardiac disease, infections may also be signs
What is epidemiology of hereditary hemochromatosis? Age, sex
Mean age=50yo
M>W (blood loss due to menses may be protective)
Diagnostic criteria for hereditary hemochromatosis
Slightly elevated serum Fe
High transferrin saturation
Very high ferritin
Very high hepatic Fe content
What is therapy for hemochromatosis?
Removal of Fe by phlebotomy weekly/biweekly
This does not improve fixed tissue complications so it is important to identify disease early and start treatment
