Analysis of epithelial electrophysiological function in paediatric intestinal biopsies

Abstract: Intestinal biopsies are routinely taken from children under investigation of failure to thrive, diarrhoea, abdominal pain and/or malnutrition. These biopsies are usually only evaluated morphologically, i.e. no information is collected with regard to mucosal function. The aim of this work was to study electrogenic membrane transport, in particular electrogenic chloride secretion, in biopsies from the duodenum in children, and to evaluate the relation between morphological and functional disturbances. Intestinal biopsies from children with morphologically normal epithelia were obtained from different parts of the duodenum. A more pronounced reactivity of the prostaglandin E2 induced, cAMP mediated chloride secretion, was seen in the distal part of duodenum while the acetylcholine induced, Ca2+ mediated secretion, was expressed along the whole duodenum. Cysteinyl leukotrienes (LTC4 and LTD4) were shown to be secretagogues since they induced chloride secretion with similar pattern as the prostaglandins along the duodenum. The secretory response was also studied in children with coeliac disease in different stages. Biopsies with partial mucosal atrophy showed an enhanced response to most secretagogues, compared to controls. The magnitude of this electrogenic response was significantly related to serum levels of IgA gliadin antibodies. The response to leukotrienes was reduced, and this effect was reversed by pre-treatment with indomethacin, suggesting a complex interaction within the arachidonic acid cascade. The effects of prostaglandin E2 and acetylcholine on electrogenic chloride secretion was studied in biopsies from patients with cystic fibrosis. No response was seen in the ´F508 homozygotes. In other genotypes, secretion corresponded to the severity of the known mutations, the acetylcholine response being better preserved in mild phenotypes. A novel method to measure epithelial resistance, reflecting epithelial permeability, was used. The permeability was not affected by the secretagogues. Biopsies from children with coeliac disease or cystic fibrosis showed lower resistances, compared to controls, verifying earlier studies showing increased permeability in these diseases. The Ussing-technique can successfully be used in studies of secretion and permeability in duodenal biopsies in children. The technique offers possibilities to combine functional and morphological analysis of the same biopsy. Its role in practical gastroenterology remains to be determined, but our results encourage an introduction of this technique in at least tertiary care paediatric gastroenterological centres.

  This dissertation MIGHT be available in PDF-format. Check this page to see if it is available for download.