Mechanisms of diarrhea in collagenous colitis

Gastroenterology. 2002 Aug;123(2):433-43. doi: 10.1053/gast.2002.34784.


Background & aims: Collagenous colitis is an inflammatory disease of unknown etiology with diarrhea as the leading symptom. The aim of this study was to examine the pathogenic mechanisms of this disease.

Methods: Biopsy specimens of the sigmoid colon were obtained endoscopically. Short-circuit current and (22)Na and (36)Cl fluxes were measured in miniaturized Ussing chambers. Alternating current impedance analysis discriminated epithelial from subepithelial resistance. Tight junction proteins occludin and claudin 1-5 were characterized in membrane fractions by Western blotting. Apoptotic ratio was determined by DAPI and TUNEL staining.

Results: In collagenous colitis, net Na(+) flux decreased from 8.8 +/- 1.8 to 0.2 +/- 1.5 and net Cl(-) flux from 11.2 +/- 3.0 to -3.0 +/- 2.7 micromol x h(-1) x cm(-2), indicating a pronounced decrease in NaCl absorption. The fact that short-circuit current increased from 1.5 +/- 0.4 to 3.9 +/- 0.8 micromol x h(-1) x cm(-2), together with the negative net Cl(-) flux, points to activation of active electrogenic chloride secretion. Subepithelial resistance increased from 7 +/- 1 to 18 +/- 2 Omega x cm(2) due to subepithelial collagenous bands of 48 +/- 8-microm thickness. Epithelial resistance was diminished from 44 +/- 3 to 29 +/- 2 Omega x cm(2), and this was accompanied by a decrease in occludin and claudin-4 expression. Neither mucosal surface area nor apoptotic ratio was altered in collagenous colitis.

Conclusions: Reduced net Na(+) and Cl(-) absorption is the predominant diarrheal mechanism in collagenous colitis, accompanied by a secretory component of active electrogenic chloride secretion. The subepithelial collagenous band as a significant diffusion barrier is a cofactor. Down-regulation of tight junction molecules but not epithelial apoptoses is a structural correlate of barrier dysfunction contributing to diarrhea by a leak flux mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apoptosis
  • Chlorides / metabolism
  • Claudin-1
  • Diarrhea / etiology*
  • Electric Impedance
  • Female
  • Humans
  • Inflammatory Bowel Diseases / complications*
  • Inflammatory Bowel Diseases / metabolism
  • Inflammatory Bowel Diseases / pathology
  • Intestinal Mucosa / pathology
  • Ion Transport
  • Male
  • Membrane Proteins / analysis
  • Middle Aged
  • Occludin
  • Sodium / metabolism


  • CLDN1 protein, human
  • Chlorides
  • Claudin-1
  • Membrane Proteins
  • OCLN protein, human
  • Occludin
  • Sodium