Epithelial barrier defects in ulcerative colitis: Characterization and quantification by electrophysiological imaging

Background & Aims: In ulcerative colitis (UC), the epithelial barrier is im paired by erosion/ulcer-type lesions and epithelial apoptosis causing local leaks, and generalized tight junction alterations increasing the basal per meability. We quantified the contribution of these mechanisms to the increa sed colonic ion permeability. Methods: Sigmoid colon was stripped, and the spatial distribution of current clamped across the viable epithelium was re corded by a microelectrode probe, using the conductance scanning method. Lo cal leaks (circumscribed conductive peaks) were marked, and structural chan ges were studied in H&E-stained series sections. Results: Overall conductiv ity increased from 8.4 +/- 0.7 mS/cm(2) (mean SEM) in controls to 11.7 +/- 0.6 in specimens with mild inflammation (i.e., with intact epithelium) and 34.4 +/- 6.2 mS/cm(2) in moderate-to-severe inflammation (i.e., with visibl e epithelial lesions). Only in part this was caused by a generalized increa se in basal conductivity (12.2 +/- 1.5 mS/cm(2) in moderate-to-severe UC vs . 8.3 +/- 0.7 in controls). More importantly, the spatial distribution of c onductivity, which was even in controls, showed dramatic leaks in UC. Leaks found in mild inflammation without epithelial lesion turned out to be foci of epithelial apoptosis. In moderate-to-severe inflammation, leaks correla ted with epithelial erosion/ulcer-type lesions or crypt abscesses. Conclusi ons: In early UC, but not in controls, seemingly intact epithelium comprise s leaks at apoptotic foci. With more intensive inflammation, erosion/ulcer- type lesions are highly conductive, even if covered with fibrin. Local leak s contribute 19% to the overall epithelial conductivity in mild and 65% in moderate-to-severe inflammation.