UNCONJUGATED (INDIRECT) HYPERBILIRUBINEMIA
Rate of bilirubin production exceeds the rate of bilirubin elimination
Increase total serum bilirubin (TSB) concentration — hyperbilirubinemia (jaundice)
Almost every newborn infant
First week of life (2nd-3rd day)
If develops in 1st 24 h of life — considered pathologic until proven otherwise
Unconj bilirubin level >12.9 mg/dL in term
Unconj bilirubin level > 15 in preterm
Bilirubin level increase at rate >5 mg/dL/day
Jaundice in the 1st 24 h of life
Conj bilirubin level >2 mg/dL
Clinical jaundice persisting >1 week in full
term or >2 weeks in preterm
Increase bil load because the larger RBC volume, the
shorter life span of RBC, increase enterohepatic
recirc of bil in newborn.
Defective uptake by the liver because
Decrease concentration of bil binding protein (ligandin).
Defective conjugation because decrease glucoronyl
Impaired excretion into bile.
Overall impairment/immaturity of liver function.
RBC defects: def G6PD, def piruvat kinase,
Acquired hemolytic anemia: ABO
Polycitemia. The liver not have capacity to metabolize the increase bil load à increase blood vol
Defects of conjugation
Congenital def of glucoronyl transferase
Cligler-Najjar syndrome type I: severe def uridine diphosphate (UDP) glucoronyl transf.
àUnresposive to phenobarbital therapy.
Cligler-Najjar syndrome type II: moderate def UPD glucoronyl transf à responsive to phenobarbital therapy.
Gilbert syndrome: mild def UDP) glucoronyl
transf àresponsive to pheno therapy
Glucoronil transferase inhibition:
Lucey-Driscoll syndrome: unspecified
maternal gesation hormone in infant
interferes with the conj of bil.
Breast milk jaundice (late onset)
Prolongation of increaseenterohepatic circ of bil because of a factor in human milk that promote intestinal absorbtion.
Higher peak (10-30 mg/dL) by days 10-15.
Metabolic disorders: galactosemia, hypothyroidism, maternal diabetes, ect.
increase enteohepatic recirc: pyloric stenosis, duodenal atresia, ileus, ect.
Unconj bil à cross blood brain barrier à brain cell à neuronal dysfunction à depress O2 consumption à death.
Post mortem diagnosis
Risk if bi level >25 mg/dL
Joundice at face, especially at nose, descending to the torso and lower extremities.
Areas of bleeding (cephalhematoma, ptechiae) indicates blood extravasation.
Hepatosplenomegaly (hemolytic disease, liver disease, or infection)
Sign of prematurity, IUGR, postmaturity.
Pallor (hemolytic disease)
Neurologic signs: lethargy, poor feeding, vomiting, hypotonia.
Total and direct bilirubin
Complete blood cell count and reticulocyte count.
Blood type and Rh status in mother and infant
Direct Coomb’s test
Measurement of serum albumin
Radiologis studies: intestinal obstruction
Transcutaneous bilirubimentry (TcB)
measures the degree of yellow color by selective wavelength reflection.
Expired carbon monoxide breath analyzer.
TSB level 20 mg/dL ar 48 h of life maybe treated initially with phototherapy.
If TSB decrease by 1-2 mg/dL within 4-6 h, exchange transfusion maybe not necessary.
Light source: blue fluorescent tubes.
Distance from the light to the infant: 12-16 inches
Eye should be covered with opaque patches
Termination of phototherapy: bil level is low enough to eliminate the risk of kernicterus and the infants is old enough to handle the bil load.
Complication: retinal degradation, increased insensible water loss (à increasefluid requirements by 25%), bronze baby syndrome (destruction of protoporphirin àurine and skin become bronze)
TSB 25-30 mg/dL (increasebil >0.5 mg/dL/h)
Presence of hypoxia, acidosis, sepsis or hypoproteinemia.
Albumin transfusions maybe useful if bil level >20 mg/dL and serum albumin level ❤ g/dL.
Infusion of 1 g of albumin 1 h before exchange transfusion may improve the yield of bil removal.
increaseligandin in liver, increase production of glucoronyl transferase, and enhancing bil excretion.
Takes 3-7 day to become effective à less effective in the newborn
More useful to give pheno 1-2 week before delivery to pregnant woman whose fetus documented hemolytic disease.
Inhibit heme oxygenase (HO) by acting as a competitive inhibitor.
Supportive management breast feed
CONJUGATED (DIRECT) HYPERBILIRUBINEMIA
A sign of hepatobiliary dysfunction
After the first week of life
Direct bil level > 2.0 mg/dL or is >20% of the TSB
Caused by a defect or insufficiency in bile secretion, biliary flow, or both resulting in an inability to remove conj bil from the body.
Extrahepatic biliary disease
Choledochal cysts — dilatations of extrahepatic tree.
Biliary diseases: duct stenosis, cholelithiasis, and neoplasm.
Intrahepatic biliary disease
Intrahepatic bile duct paucity
Progressive intrahepatic cholestasis
Metabolic and genetic defects: cystic fibrosis, Dubin-Johnson and Rotor’s Syndrome, Galactosemia, etc.
Total parenteral nutrition (TPN) cholestasis
Idiopathic neonatal hepatitis
Miscellaneous: shock or hyperperfusion
Failure to thrive
Alagille’s syndrone: peripheral pulmonal stenosis, vertebral anomalies, peculiar faces
Zellweger’s syndrome or cerebrohepatorenal syndrome: hypotonia, seizures, dysmorphic features.
Congenital infection: microcephaly, intracranial calcifications, IUGR.
Bilirubin levels (total and direct)
Liver function test
Prothrombin time an partial trhomboplastin time
Gamma-glutamil transpeptidase, 5-nucleaotidase, serum bile aced: increase in cholestasis
A complete blood cell count and reticulocyte count
Serum cholesterol, triglycerides, and albumin levels: assessment of liver failure
Ammonia levels: assessment of liver failure
Serum glucose levels
Other tests: hepatitis, sepsis, metabolic disorders.
Radiologic studies: USG, hepatobiliary imaging.
Other studies: persutaneus liver biopsy, exploratory laparatomy.
Cholestiramine: increasefecal excretion of bile salts and increasehepatic synthesis of bile salt from cholesterol.
Actigall (ursodeoxycholic acid), sucsessfully used in conjunction with phenobarbital and cholestyramine.
Medium-chain triglycerida (MCT): can be absorbed without the action of bile salt.
Vitamin supplementation: A,D,E, and K
Dietary restriction: removal galactose, lactose,fructose, and sucrose may prevent cirrhosis.
Laparatomy with biopsy
Kasai procedure: to establish biliary drainage
Infectious diseases (hepatitis, bacterial infections)
TPN-induced conjugated hyperbilirubinemia: will usually resolve once TPN is stopped.