The Effect of Bilirubin on the Function of Hamster Small Intestine

Abstract

Summawintestinal secretion. rather than malabsomtion of dietarv carboJaundice phototherapy is associated with a significant incidence of watery diarrhea. We have postulated that acute intestinal secretion, rather than malabsorption of dietary carbohydrate, is an effect of a photoproduct of bilirubin upon the intestinal mucosa. Because a major effect of phototherapy is the hepatic excretion of nonconjugated bilirubin, we investigated the effect of bilirubin on small intestinal function in the hamster in vivo.The entire small intestine was luminally perfused in vivo with solutions containing bilirubin (0.125 to 0.75 mmole/liter) and net water and sodium fluxes were measured. Control animals absorbed both water (J, ": ? = 58.9 pl/min/g) and sodium (JEZt SpeculationThese data seem consistent with the hypothesis that jaundice phototherapy causes watery diarrhea by enhancing the hepatic excretion of nonconjugated bilirubin, which, in turn, causes intestinal secretion.A recent survey has estimated that 10% of infants born in the United States receive phototherapy for neonatal jaundice (16). Such therapy is associated with a significant (9.5%) incidence of watery diarrhea (19), characterized by increased fecal water loss (26) and decreased gut transit time (29). The pathogenesis of this diarrhea has not been established, but a photoproduct of bilirubin is presumed to be involved in the mechanism because both light and hyperbilirubinemia are required for its development (29). Although intestinal lactase deficiency has been found in affected infants (I), recent data indicate that lactose intolerance cannot be demonstrated in these infants (13,14). We have observed diarrhea to develop within a few hours of light exposure and in the absence of oral intake. These observations lead us to postulate that acute hydrate, is an effect of a photoproduct of bilirubin.Phototherapy induces hepatic excretion of nonconjugated bilirubin through a postulated mechanism involving configurational isomerization of bilirubin, Z-Z bilirubin IXa, to "photobilirubin," composed of the two Z-E and the E-E bilirubin IXa configurational isomers, a pigment which is readily excreted by the liver. The kinetics of reversion of photobilirubin to bilirubin have not been elucidated, but the Z-E isomers are presumably unstable and revert to Z-Z bilirubin within the biliary tract or the gut (6,20,24,27). Overall, a major effect of phototherapy is the hepatic excretion of nonconjugated bilirubin into the gut.We have tested the possibility that bilirubin causes intestinal secretion by measuring the effects of bilirubin on the small intestinal function of hamsters. The results indicate that bilirubin itself can induce intestinal secretion and suggest that the watery diarrhea often witnessed in jaundiced infants treated by phototherapy may be a consequence of the high concentrations of bilirubin within the intestinal lumen. MATERIALS AND METHODS PERFUSION TECHNIQUEFed, male Syrian golden hamsters (Sprague-Dawley, Madison, WI) weighing between 80 and 110 g were a...

Molecular Physiology and Pathophysiology of Bilirubin Handling by the Blood, Liver, Intestine, and Brain in the Newborn

“…A suggestion that diarrhea in infants under phototherapy for NNJ might be of the secretory type seemed supported by findings from in vivo studies of perfused hamster small intestines, in which perfusion with bilirubin solution caused secretion of sodium and water, while control animals exhibited absorption of both (174,706). Bile from Gunn rats receiving phototherapy had antiabsorptive effects when perfused through the jejunum of Wistar rats, and UCB had a dosedependent secretory effect on transport of water and electrolytes in the same system (255).…”

“…Bile from Gunn rats receiving phototherapy had antiabsorptive effects when perfused through the jejunum of Wistar rats, and UCB had a dosedependent secretory effect on transport of water and electrolytes in the same system (255). Other studies had also shown UCB to be an intestinal secretagogue (255,706). A rectal dialysis bag was used to study water, sodium chloride, and potassium absorption and showed that absorption was impaired in infants who received phototherapy, but impairment was transient and abated when jaundice receded and phototherapy was discontinued (173).…”

Effect of Phototherapy on the Physiologic Cholestasis of the Neonate

“…Previous data suggested that diarrhea could be linked to a lactase deficiency (18), even though more recent evidence does not confirm this hypothesis (16,19). In 1981 Whitington (20) presented data showing that bilirubin induced water secretion in hamster small intestine and suggested that this could be the main cause of loose stools and increased bowel water loss. As an additional mechanism, it is possible to speculate that the diarrhea is "bile acid diarrhea," the increased bile flow and biliary bile salt output, recently shown also in Gunn rats (21), being followed by intestinal malabsorption of bile acid which then favors water and stool loss.…”

Impaired Renal Function in Obstructive Jaundice: Roles of the Thromboxane and Endothelin Systems

“…It was also shown in infants that hyperbilirubinemia results in a rela tive decrease in G F R and an increase in fractional sodium excretion in response to salt and water loading [33]. Since high concentration of unconjugated bilirubin promotes the secretion of sodium and water in the isolated perfused intestine of the hamster [34], bilirubin seems to interfere with epithelial cell transport function. Thus, in the toad bladder it was shown that short-term exposure to biliru bin results in an impaired vasopressin-stimulated active sodium transport without effects on the hvdroosmotic response to AVP [35].…”