Menon, Rachel Anne; (1998) Colonic structural and functional relationships in health and inflammation. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

In health colonic function includes fluid and electrolyte salvage to produce dehydrated, formed stools. Effective salvage requires the removal of luminal sodium against considerable electrochemical and concentration gradients. This is made possible by the relatively tight structure of colonic epithelium impeding the leakage of absorbed sodium back into the lumen. This generates a transepithelial osmotic gradient necessary for water absorption and faecal dehydration. Colonic structure and function are therefore inextricably linked. The significance of these interrelationships was studied in health and inflammatory conditions of the human colon. The use of concentration polarisation of impermeant fluorescent dyes and confocal microscopy, to measure colonic crypt concentration capacity in vitro, has been well established in a number of animal species. Data ore presented to show the successful adaptation of this technology for use with endoscopic biopsies of human paediatric colon and in the study of colonic function in health and inflammation in children. Structural information, regarding crypt density, architecture and F-actin component of the pericryptal cytoskeleton was also assessed using specific fluorescent probes visualised by confocal microscopy. Inflammation altered normal colonic structural and functional relationships with the nature of the inflammatory response emerging as an important factor. Eosinophilic colitis was associated with impaired crypt absorptive capacity despite normal structure. Predominant neutrophil infiltration, which featured in ulcerative colitic patients studied, was accompanied by a physical reduction in the number of functioning crypts. Neutrophils cause tissue damage by both oxidative free radical and non-oxidative enyzmic mechanisms. Free radical assays revealed elevated levels in inflamed colonic tissue with a positive correlation between superoxide production and neutrophil infiltration. Maintenance of colonic structure and functional relationships found in health form an important focus for future research in the quest for knowledge regarding the distressing inflammatory bowel diseases of childhood.

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