Epithelial Ion Transport in the Heal J-Pouch after Proctocolectomy in the Rat

Abstract

In ulcerative colitis and polyposis coli, creation of an ileal pouch with ileoanal anastomosis after proctocolectomy has become a common surgical method. The aim of our study was to characterize the adaptation of the epithelial ion transport function in the pouch by using electrophysiologic techniques. Proctocolectomy and ileoanal anastomosis was performed in rats either with (pouch) or without (control) creation of an ileal J-pouch. To characterize the epithelial barrier function, impedance analysis was performed 6 months after surgery. Epithelial resistance was 29 ± 2 Ω · cm² in controls and was unchanged in the pouch (28 ± 4 Ω · cm²; NS). In contrast, subepithelial resistance increased from 33 ± 3 Ω · cm² to 54 ± 5 Ω · cm² (p < 0.01) owing to work hypertrophy of the muscle layers in the pouch. To detect changes in net ion transport, ion tracer fluxes were measured in the Ussing chamber. In control ileum, absorptive net Na and Cl fluxes of similar magnitude were present, indicating that electroneutral NaCl absorption was the predominant ion transport system. Neither I_sc nor net Na and Cl fluxes were significantly altered in the pouch. Glucose-coupled Na absorption was measured as the 3-o-methyl-glucose-induced increase in I_sc. K_m remained unaltered, while V_max decreased from 7.5 ± 2.1 μeq · h^-1 cm^-2 in controls to 1.7 ± 0.8 μeq · h^-1 cm^-2 (p < 0.05) in the pouch. Then, maximal transport capacity for electrogenic Cl secretion was measured as the Cl-induced increase in I_sc blockable by serosal bumetanide (in the presence of theophylline and prostaglandin E₁). K_m remained unaltered, while V_max decreased from 4.2 ± 0.7 μeq · h^-1 cm^-2 in controls to 1.9 ± 0.7 μeq · h^-1 cm^-2 (p < 0.05) in the pouch. Microdissection showed increased crypt depth and villus height in the pouch as seen in the early state of hyperregenerative transformation. We conclude that the mucosa of the pouch exhibits a hyperregenerative transformation. It is characterized by an impaired transport capacity for glucose-coupled Na absorption and, less pronounced, electrogenic Cl secretion, while the epithelial barrier function was unaffected. The adaptational pattern resembles that observed in the blind loop syndrome and may share common mechanisms—in particular, bacterial overgrowth. Thus, pouch creation can improve functional results of resective surgery due to an enlarged reservoir but is threatened by impaired mucosal function. A decrease in Na-glucose cotransport of the ileal mucosa after pouch creation could contribute to diarrhea in these patients.

Key Words:

• Cl secretion
• Na glucose cotransport
• pouch
• tight junction