physiologic jaundice

**Pathophysiology (why newborns get jaundiced):** 1. Increased bilirubin production: neonates have a high RBC mass with shorter RBC lifespan (~70-90 days vs 120 days), so more heme is catabolized (heme → biliverdin via heme oxygenase → unconjugated bilirubin via biliverdin reductase). 2. Decreased hepatic conjugation: immature hepatic UDP-glucuronosyltransferase (UGT1A1) activity at birth, so bilirubin is not efficiently conjugated. 3. Increased enterohepatic circulation: sterile gut with few bacteria to convert conjugated bilirubin to urobilinogen/stercobilin, plus intestinal β-glucuronidase that deconjugates bilirubin so it is reabsorbed. Delayed feeding and meconium passage worsen this. 4. Reduced hepatic uptake (low ligandin/Y protein) contributes.

**Key features:** - Unconjugated (indirect) hyperbilirubinemia: direct bilirubin is <10-20% of total. - Onset after 24 hours; peak total serum bilirubin in term infants usually ≤12-13 mg/dL around days 3-5 (preterm may peak higher and later, day 5-7). - Cephalocaudal progression (face → trunk → extremities). - Infant is otherwise well, feeding normally, with normal exam. - Resolves spontaneously within ~1-2 weeks as UGT1A1 matures and feeding establishes.

**Pathologic jaundice red flags:** - Onset within the first 24 hours (think hemolysis: ABO/Rh incompatibility, G6PD deficiency, hereditary spherocytosis, TORCH/sepsis). - Rise >5 mg/dL/day (or >0.2 mg/dL/hr), or total bilirubin above the phototherapy/exchange thresholds for age and risk factors (AAP nomogram). - Direct bilirubin >1 mg/dL if total <5, or >20% of total (think biliary atresia, neonatal hepatitis, choledochal cyst, TPN cholestasis, metabolic disease). - Persists >2 weeks in term infants (3 weeks in preterm). - Signs of illness (poor feeding, lethargy, hepatosplenomegaly, pallor).

**Differential/related causes to distinguish (high-yield):** - Breastfeeding (suboptimal intake) jaundice: first week, due to dehydration/low intake and increased enterohepatic circulation. Fix with improved feeding/lactation support. - Breast milk jaundice: later onset (after day 5-7), peaks at 2 weeks, can last weeks to months; due to β-glucuronidase and other factors in milk. Benign; continue breastfeeding. - Crigler-Najjar type I (absent UGT1A1; severe, kernicterus risk, no response to phenobarbital) vs type II (reduced activity; responds to phenobarbital). Gilbert syndrome (mild reduced UGT1A1, presents later with stress/fasting). Dubin-Johnson and Rotor cause conjugated hyperbilirubinemia. - Hemolytic disease of the newborn (positive Coombs test in Rh/ABO incompatibility).

**Complications of severe unconjugated hyperbilirubinemia:** - Acute bilirubin encephalopathy → kernicterus (chronic bilirubin encephalopathy): unconjugated bilirubin is lipid soluble, crosses the immature blood-brain barrier and deposits in basal ganglia (especially globus pallidus), hippocampus, and brainstem nuclei. Features: lethargy, poor feeding, hypotonia then hypertonia/opisthotonos, high-pitched cry; sequelae include choreoathetoid cerebral palsy, sensorineural hearing loss, upward gaze palsy, and dental enamel dysplasia. - Risk factors for neurotoxicity: prematurity, hemolysis, sepsis, acidosis, hypoalbuminemia, drugs displacing bilirubin from albumin (sulfonamides, ceftriaxone).

**Management:** - Physiologic jaundice: observation, adequate feeding (frequent breastfeeding), and monitoring bilirubin (transcutaneous bilirubinometry for screening, confirm with total serum bilirubin; plot on hour-specific AAP nomogram). - Phototherapy when above age- and risk-specific thresholds: blue-green light (~460-490 nm) converts bilirubin to water-soluble isomers (lumirubin, configurational isomers) excreted without conjugation. Side effects: loose stools, skin rash, dehydration, "bronze baby" syndrome (with direct hyperbilirubinemia), and retinal damage (shield eyes). - Exchange transfusion for bilirubin near neurotoxicity thresholds or signs of acute bilirubin encephalopathy despite intensive phototherapy. - IVIG for isoimmune hemolytic disease.

**Board pearls:** - Jaundice <24 h = pathologic (hemolysis until proven otherwise). - Conjugated hyperbilirubinemia in a neonate is never physiologic. Work up for biliary atresia (acholic stools, dark urine, elevated direct bilirubin; HIDA scan/ultrasound "triangular cord sign"; Kasai procedure ideally before 8 weeks). - Cephalohematoma and bruising increase bilirubin load. - Phenobarbital induces UGT1A1 but is not first line in neonatal jaundice.