Mechanisms of diarrhea in collagenous colitis.
Gastroenterology
; 123(2): 433-43, 2002 Aug.
Article
em En
| MEDLINE
| ID: mdl-12145796
ABSTRACT
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.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Inflamatórias Intestinais
/
Diarreia
Limite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Gastroenterology
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
Alemanha