Oesophageal mucosal injury by acid and bile salt

The work of this thesis is broadly divisible into three parts. The establishment of an animal model to investigate the effect of acid and sodium taurocholate on the oesophageal epithelium. This model was then used to investigate in detail the alterations which occur in epithelial permeability and morphology when the rabbit oesophagus is exposed to acid and bile salt. Finally, the effect of a prostaglandin and an inhibitor of prostaglandin synthesis, indomethacin, were assessed with regard to their ability to alter the observed degree of injury. A rabbit model was developed to study the action of hydrochloric acid and sodium taurocholate on oesophageal epithelum. This model was employed to determine the action of these agents on permeability of the epithelium and cellular injury. The rabbit oesophagus was unaffected by low centrations of H⁺ even over prolonged periods of exposure. Similarly low concentrations of sodium taurocholate in a neutral environment were without effect on either mucosal permeability or integrity. However when the oesophagus was exposed simultaneously to these agents a characteristic sequence of injury was observed and this was associated with an increased epithelial permeability to H⁺. With the aid of the transmission electron microscope the characteristics and sequence of this injury were elucidated. The damage begins within the stratum granulosum and appears to take the form of an osmotic cellular injury. No damage occurs in the absence of bile salt absorption. Despite subsequent progression of the cellular injury to involve the deeper layers of the epithelium the integrity of the stratum corneum is relatively preserved. Because this sequence of events occurs only following taurocholate absorption and the effect is observed at bile acid concentrations below those associated with the detergent action of the bile acid, it is concluded that this injury is not dependent on membrane solubilization. This model was then employed to assess the role of prostaglandin and indomethacin in protecting the oesophagus from injury mediated by acid and bile. Neither of these agents decreased the observed injury or preserved the normal epithelium's impermeability to hydrogen ion.Thesis (MS.) -- University of Adelaide, Dept. of Surgery, 198