Congenital chloridorrhoea. A question of reversed brush border transport processes and varying junctional tightness.

The surprising results of intestinal perfusion studies in an 8-month-old child with congenital chloridorrhoea offered a unique opportunity not only to elucidate the underlying defect, but also to test the adequacy of proposed models for normal intestinal transport. In ileum Na, K and Cl as well as water were secreted and HCO3 absorbed. Lumen was 91 mV negative to blood. Only Cl was transported against both electrical and chemical gradients, but discrepancies between observed and predicted Na flux ratios suggested the presence of a Na-absorbing mechanism as well. Mucosa was impermeable to Cl from the lumen side. 2.5 mM glycochenodeoxycholic acid (GCDC) mediated Na and water absorption and abolished any transport of Cl. PD was -95 mV. In colon a similar pattern was observed and mucosa to serosa fluxes of Cl were abnormally low. Rectal PD was -116 mV. GCDC made the epithelium more absorptive in function, but contrary to ileum the effect was due to an increase of Na and Cl fluxes from mucosa to serosa. The patient was at that time in severe electrolyte imbalance. He was reinvestigated three months later when he was in a good clinical condition with normal serum electrolytes. Net transfer of electrolytes and water and bidirectional fluxes of Cl and K were unchanged while bidirectional Na fluxes had increased considerably and PD decreased to -18 mV. Rectal PD was -45 mV. In jejunum water and electrolyte transport were normal and PD -3 mV. It is tentatively concluded that the abnormal transport in ileum is due to an inversion of the brush border transport processes, which also satisfies the paradoxical effects of GCDC. Furthermore, Na and Cl seem to migrate through separate pathways. A varying degree of junctional tightness, which is almost completely cationic, may be responsible for the functional differences observed in resonse to improvement of the general electrolyte status.