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INTRODUCTION

Hyperbilirubinemia presents as either unconjugated hyperbilirubinemia or conjugated hyperbilirubinemia. The two forms involve different pathophysiologic causes with distinct potential complications. In contrast to unconjugated hyperbilirubinemia, which can be transient and physiologic in the newborn period, conjugated hyperbilirubinemia is always pathologic and requires thorough investigation. See Chapter 99 for a discussion of unconjugated hyperbilirubinemia and Chapters 62 and 63 for rapid “on-call” assessment and management.

Bilirubin is the end product of the catabolism of heme derived primarily from the breakdown of red blood cell hemoglobin in the reticuloendothelial system. Bilirubin circulates in the blood predominantly bound to serum albumin (unconjugated) before uptake in the liver where it becomes conjugated. Inside liver cells, unconjugated bilirubin is bound immediately to intracellular proteins, the most important one being ligandin. It is then converted into an excretable and soluble form through the process of conjugation that consists of transfer of 1 or 2 glucuronic acid residues from uridine diphosphate glucuronic acid to form a monoglucuronide or diglucuronide conjugate. Uridine diphosphate glucuronyl transferase (UDPGT) is the major enzyme involved in this process. Conjugation is impaired in newborns due to reduced UDPGT activity and a relatively low level of uridine diphosphate glucuronic acid. Conjugated bilirubin is water soluble and can be excreted in the urine, but most of it is rapidly excreted as bile into the intestine. Conjugated bilirubin is further metabolized by bacteria in the intestine into urobilin/stercobilin and excreted in feces (and urine).

I. DEFINITION

Conjugated hyperbilirubinemia is defined as direct reacting bilirubin of >1.0 mg/dL (>17 µmol/L) if the total serum bilirubin is ≤5 mg/dL, or >20% of total serum bilirubin when the total bilirubin is >5 mg/dL. It is a biochemical marker of reduced bile flow/formation leading to biliary substance retention within the liver, a condition called cholestasis.

II. INCIDENCE

Conjugated hyperbilirubinemia affects approximately 1 in every 2500 infants and is much less common than unconjugated hyperbilirubinemia.

III. PATHOPHYSIOLOGY

Normal bile production involves 2 main processes: bile acid uptake by the hepatocytes from the blood and bile excretion into the biliary canaliculus. Bile uptake from the blood is an active process facilitated by 2 main receptors at the basolateral membranes, whereas bile secretion at the canalicular membrane is mediated largely by the bile salt export pump. In healthy newborns, the cellular processes that regulate bile flow are immature and do not function at the normal adult level, making them more susceptible to cholestasis.

IV. RISK FACTORS

Well-known risk factors include congenital infections, sepsis, neonatal hepatitis, hemolysis (biliary sludging), trisomy 21, and the use of parenteral nutrition (PN).

V. CLINICAL PRESENTATION

Prolonged clinical jaundice is the main presenting feature of conjugated hyperbilirubinemia, along with pale (acholic) stools and dark urine. The North American Society for Pediatric Gastroenterology, ...

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