SM_155b: Approach to Newborn with Suspected Liver Disease Flashcards
Describe the definitions of cholestasis
Cholestasis
- Physiologic: measurable decrease in bile flow
- Pathologic: histologic presence of bile pigment in hepatocytes and bile ducts
- Clinical: accumulation in bile or extrahepatic tissues of substances normally excreted in bile
Cholestasis occurs as a result of ____ or ____
Cholestasis occurs as a result of impaired bile formation or obstruction to bile flow through intrahepatic and extrahepatic biliary tree
Liver dysfunction in the neonate is associated with ____ and ____
Liver dysfunction in the neonate is associated with failure of bile secretion and conjugated hyperbilirubinemia
____ is a frequent early presenting feature in neonatal liver disease as opposed to a late feature in adults
Jaundice is a frequent early presenting feature in neonatal liver disease as opposed to a late feature in adults
Lack of bile flow in children may lead to ____
Lack of bile flow in children may lead to fat soluble vitamin malabsorption
- Vitamin D: rickets
- Vitamin K: coagulopathy
- Vitamin A: night blindness
- Vitamin E: neuropathy
Portal hypertension can present as ____ and ____
Portal hypertension can present as ascites and varices
Most infants will have ____ serum bilirubin in the first week of life
Most infants will have elevated serum bilirubin in the first week of life
Jaundice proceeds in a ____ manner
Jaundice proceeds in a cephalopedial manner
Causes of neonatal jaundice include ____, ____, and ____
Causes of neonatal jaundice include increased production of bilirubin, decreased excretion of bilirubin, and combined increased production and decreased excretion
Consider liver disease in neonates if ____ or ____
Consider liver disease in neonates if serum direct bilirubin concentration > 2 mg/dl or serum direct bilirubin > 15% of total bilirubin
Jaundice often occurs with ____ stools
Jaundice often occurs with clay-colored stools
Describe evaluation of liver disease on newborn physical exam
Evaluation of liver disease on newborn physical exam
Life-threatening causes of liver disease in children include ____ and ____
Life-threatening causes of liver disease in children include infection/sepsis and inborn errors of metabolism
- Bacterial, viral (especially HSV)
Describe diagnostic evaluation of neonatal liver disease
Diagnostic evaluation of neonatal liver disease
- Fractionated serum bilirubin
- Tests of hepatocellular and biliary disease: AST, ALT, Alk Phos, GGT
- Tests of liver function: serum albumin, prothrombin time, blood glucose, ammonia
- Ultrasonography
- Blood culture / viral serologies
- Urine reducing substances
- Thyroid panel
- Newborn screen
Neonatal cholestasis includes ____, ____, and ____
Neonatal cholestasis includes disorders of bilirubin metabolism, intrahepatic liver disease, and disorders of bile duct obstruction
Differential diagnosis of disorders of bilirubin metabolism include ____, ____, and ____
Differential diagnosis of disorders of bilirubin metabolism include Gilbert’s syndrome, Crigler Najjar Syndrome, and Dustin Johnson Syndrome
Gilbert’s syndrome results from ____
Gilbert’s syndrome results from alteration in the promoter for the bilirubin uridine diphosphate glucuronyl transferase (UDP-GT) gene
- Causes mild indirect hyperbilirubinemia
- Benign clinical course
Crigler-Najjar syndrome type I is ____
Crigler-Najjar syndrome type I is a severe form characterized by complete absence of UDP-GT
- Very high bilirubin
- Continuous phototherapy and frequent exchange transfusions are required
- Kernicterus may occur at any time
Crigler-Najjar syndrome type II is ____
Crigler-Najjar syndrome type II is partial activity of UDP-GT gene
- Hyperbilirubinemia of 10 mg/dl is usually observed and may be responsive to CYP450 compounds such as phenobarbital
Dustin Johnson Syndrome is ____
Dustin Johnson Syndrome is genetic deficiency in cMOAT/MRP2 gene which encodes the canalicular transporter of conjugated bilirubin
- Manifests as mild conjugated hyperbilirubinemia with no evidence of significant hepatocellular or canalicular injury
- Preponderance of isoform I in urinary coprophyrins
Bile flow is directly related to ____
Bile flow is directly related to bile acid excretion by the hepatocyte
Hepatic causes of neonatal cholestasis are ____, ____, ____, ____, and ____
Hepatic causes of neonatal cholestasis are inflammatory, necrosis / autoimmune, strong A1AT, bile formation, and metabolic (galactosemia, tyrosinemia)
Idiopathic neonatal hepatitis is ____
Idiopathic neonatal hepatitis is idiopathic liver disease characterized by multi-nucleated giant cells
- Premature and small for gestational age
- Jaundice and hepatosplenomegaly appearing in the first week after birth
- Diagnosis of exclusion
Gestational alloimmune liver disease is a ____ that involves ____
Gestational alloimmune liver disease is a rare neonatal condition that involves severe liver disease / failure in association with extrahepatic siderosis in a pattern of heriditary hemochromatosis
- Uron deposition
Gestational alloimmune liver disease pathogenesis involves ____
Gestational alloimmune liver disease pathogenesis involves maternal antibody crossing placenta to attack neonatal liver
Gestational alloimmune liver disease presents as ____ and ____
Gestational alloimmune liver disease presents as complement mediated hepatocyte necrosis and neonatal liver failure
- Jaundice
- Hepatic synthetic dysfunction
- Normal liver enzymes
Alpha 1 antitrypsin is ____
Alpha 1 antitrypsin is the principal serum inhibitor of proteolytic enzymes such as neutrophil elastasis
Patients with ____ alpha 1 antitrypsin deficiency have ____ phenotype and the most severe disease
Patients with homozygous alpha 1 antitrypsin deficiency have PiZZ phenotype and the most severe disease
Alpha 1 antitrypsin deficiency presents with ____, ____, ____, and ____
Alpha 1 antitrypsin deficiency presents with neonatal cholestasis, juvenile cirrhosis, chronic hepatitis, and hepatocellular carcinoma
- Cholestatic juandice
- Advanced liver disease with ascites or GI bleeding rarely
- Associated with emphysema in young adulthood
Disorders of bile formation are ____
Disorders of bile formation are progressive familial intraheptic cholestasis
PFIC-1 (Byler’s disease) is ____ characterized by ____
PFIC-1 (Byler’s disease) is FIC1 deficiency characterized by severe cholestasis with normal GGT
- Children with characteristic granular bile seen on electron microscopy
PFIC-2 (BSEP disease) is ____ characterized by ____
PFIC-2 (BSEP disease) is Bile Salt Export Protein deficiency characterized by severe cholestasis with normal GGT
- Associated with increase in hepatocellular carcinoma
PFIC-3 is ____ characterized by ____
PFIC-3 is deficiency of hepatocyte membrane transporter MDR3 characterized by severe cholestasis with an elevated GGT
Describe formation and excretion of bile
Formation and excretion of bile
Describe partial external biliary diversion
Partial external biliary diversion (surgery)
- Isoperistaltic jejundal conduit between the done of the gallbladder and abdominal wall
- Interrupts enterohepatic circulation of bile acids -> decreased influx of bile into gut -> less reuptake and overall decrease of bile acid pool
- Used in Alagille syndrome / PFIC
Metabolic causes of liver injury involve ____
Metabolic causes of liver injury involve buildup of toxic metabolites in liver
- Often genetic defects causing deficient enzyme
- Examples: galactosemia, tyrosinemia
Galactosemia is caused by deficiency of ____ leading to buildup of toxic metabolites ____ and ____
Galactosemia is caused by deficiency of galactose-1-phosphate uridyl transferase leading to buildup of toxic metabolites galactose-1-phosphate and galactitiol
- Presents as lethargy, vomiting, acidosis, cataracts, FTT, jaundice, UTI, gram negative sepsis (E. coli), and hemolytic anemia
- Treatment is dietary therapy
Tyrosinemia is caused by ____
Tyrosinemia is caused by deficiency of fumarylacetoacetate hydrolase
- Last enzyme in tyrosine degradation pathway
- Autosomal recessive
- Presents in infancy: acute liver dysfunction, jaundice, hepatomegaly, FTT, anorexia, ascites coagulopathy, rickets, hemolytic anemia, renal tubular dysfunction with fanconi syndrome
- Urine succinyl acetone is diagnostic
Disorders of bile duct obstruction are ____, ____, ____, and ____
Disorders of bile duct obstruction are anatomic intrahepatic (Alagille’s syndroem), cystic fibrosis, anatomic extrahepatic (choledochal cyst), and inflammatory
Alagille’s Syndrome is caused by ____ which ____
Alagille’s Syndrome is caused by a genetic defect on chromosome 20 in the Jagged 1 gene which disrupts the NOTCH signaling pathway involved in biliary development
- Characterized by reduced interlobular bile ducts and associated cardiac, skeletal, ocular, facial, renal, and neurodevelopmental abnormalities
Alagille’s syndrome presents as ____
Alagille’s syndrome presents as jaundice in newborn period with conjugated hyperbilirubinemia
Alagille’s Syndrome face is ____
Alagille’s Syndrome face is broad prominent forehead, deep-set eyes, and a small, pointed chin
- Xanthomas develop in patients with chronic hypercholesterolemia
- Vascular anomalies cause most mortality
- 15% progressive to cirrhosis and liver failure
Alagille’s syndrome involves a paucity of ____
Alagille’s syndrome involves a paucity of bile ducts (unable to see bile ducts in portal triad)
Cystic fibrosis results from a mutation in ____
Cystic fibrosis results from a mutation in CFTR channel
(Cl- transporter)
Cystic fibrosis liver disease pathology is ____
Cystic fibrosis liver disease pathology is mucin plugs in the bile ducts
Anatomic extrahepatic disorder of bile duct obstruction is ____
Anatomic extrahepatic disorder of bile duct obstruction is choledochal cyst
Choledochal cyst presentation age ____ and classic triad includes ____, ____, and ____
Choledochal cyst presentation age varies and classic triad includes abdominal pain, jaundice, and palpable RUQ pain
- Plurality in first year of life
- Other symptoms include fever, nausea, vomiting w/ or w/o pancreatitis
- Ultrasound is most valuable test
- High incidence of biliary malignancy detected in middle age (cholangiocarcinoma)
Biliaery atresia is ____
Biliaery atresia is extrahepatic obstruction of bile ducts leading to cholestasis, cirrhosis, and liver failure if left untreated
Biliary atresia presents in ____ period with ____ and ____
Biliary atresia presents in neonatal period with jaundice and pale colored stools
Biliary atresia types are ____ and ____
Biliary atresia types are splenic malformation
- Biliary atresia splenic malformation: associated with polysplenia, laterality defects, of embryonic origin
- Perinatal: due to virla infection which directs inflammation against bile ducts
Biliary atresia pathology involves ____ and portal triad involves ____
Biliary atresia pathology involves progressive fibrosis of bile ducts and portal triad involves many bile ducts
This is ___
This is biliary atresia
Biliary atresia is treated with ____
Biliary atresia is treated with hepatic portoenterostomy (Kasai procedure)
- Can restore bile flow in some patients if diagnosed in first 2-3 months of life
- Total bilirubin > 2 at 3 months of age (indicating poor bile drainage) is strong predictor of transplant
- Many have portal hypertension even if had procedure
