The role of pepsin in acid injury to esophageal epithelium.

OBJECTIVES: The development of reflux esophagitis in humans is a process resulting from esophageal exposure to refluxed gastric contents. There is no doubt that damage to the esophageal epithelium requires exposure to gastric acid; however, the role of refluxed pepsin as contributor to this damage seems to be underappreciated. METHODS: The role of physiological concentrations of pepsin was examined in Ussing chambered rabbit esophageal epithelium and in cultured esophageal epithelial cells. RESULTS: The results of this investigation reaffirmed the ability of pepsin to increase the rate and degree of esophageal cell and tissue damage at acidic pH, although the range of activity was limited to pH < 3.0. Moreover, the increased rate of tissue damage by acidified pepsin rapidly (within 15 min) produced a lesion that was irreversible, whereas, in a similar time frame, acid alone produced a lesion that was completely reversible. This early lesion by acidified pepsin was localized by performance of mannitol fluxes in apparently undamaged esophageal epithelium on light microscopy to the intercellular junctional complex. Further acid produced similar degrees of cell killing as acidified pepsin at pH < 3.0 in rabbit esophageal epithelial cells in suspension but not when growing on coverslips or present within intact epithelium. CONCLUSIONS: These studies suggest that acidified pepsin plays a key role in the development of reflux esophagitis by producing an early irreversible lesion that results in an increase in paracellular permeability, which indirect evidence suggests is due to damage to the junctional complex. The irreversibility of the increase in paracellular permeability is likely to aid conversion of nonerosive to erosive damage to the epithelium by permitting luminal acid greater access to the basolateral membrane of esophageal epithelial cells, which is known to be acid permeable.

Effect of heat stress on rabbit esophageal epithelium.

Hot beverages expose the esophageal epithelium to temperatures as high as 58 degrees C. To study the impact of such temperatures, rabbit esophageal epithelium was exposed to luminal heat or both luminal and serosal heat while mounted in Ussing chambers. Luminal heat, mimicking exposure to hot beverages, reduced potential difference (PD) and resistance (R) when applied at >/=49 degrees C and reduced short-circuit current (Isc) at >/=60 degrees C. At >/=60 degrees C, subepithelial blisters developed. Higher temperatures reduced R only moderately and reversibly. In contrast, the Isc declined sharply and irreversibly once threshold was reached. Luminal and serosal heat also reduced PD, Isc, and R, although the threshold for reduction in Isc was now similar to that for R. Additionally, luminal and serosal heat reduced Isc more than R for any given temperature and resulted in blisters at lower temperatures (50 degrees C) than luminal heat alone. The heat-induced decline in Isc was attributed in part to inactivation of Na-K-ATPase activity, although other transport systems could have been equally affected, and the decline in R to an increase in paracellular permeability. The latter effect on R also contributed to an increase in tissue sensitivity to luminal acid damage. Consumption of hot beverages exposes the esophagus to temperatures that can negatively impact epithelial structure and function. Impaired barrier function by heat increases the risk of esophageal damage by subsequent contact with (refluxed) gastric acid. These findings help explain in part the association between esophageal disease and consumption of hot beverages.

Effect of ethanol on the structure and function of rabbit esophageal epithelium.

Epidemiological studies indicate a relationship between alcohol consumption and esophageal epithelial disease. We therefore sought the contribution of the direct effects of ethanol on esophageal epithelial structure and (transport and barrier) function. Epithelium from the rabbit was mounted in Ussing chambers and exposed luminally for 1 h to 1-40% ethanol. At concentrations of 1-5% potential difference (PD) increased, and at 10-40% PD decreased. The increase in PD with 1-5% ethanol was accompanied by an increase in short-circuit current (Isc), and this increase in Isc could be blocked by ouabain pretreatment. The decrease in PD with 10-40% ethanol was associated with a decrease in electrical resistance (R), and this decrease in R was paralleled by an increase in transepithelial [14C]mannitol flux. Reversibility of these changes was limited at ethanol concentrations > or = 10%, and these were associated morphologically by patchy or diffuse tissue edema. Moreover, as with ethanol exposure in vitro, exposure in vivo produced dose-dependent changes in PD, Isc, R, and morphology. These observations indicate that exposure to ethanol in concentrations and under conditions reflecting alcohol consumption in humans can alter and impair esophageal epithelial transport and barrier functions. Such impairments are likely to contribute to the observed increase in risk of esophageal disease with regular consumption of alcoholic beverages.

[Pseudosarcoma of the bladder. Apropos of a case of inflammatory tumor of the bladder]. / Pseudo-sarcome de la vessie. A propos d'une observation de tumeur inflammatoire de la vessie.

The authors report a case of benign pseudosarcoma of the bladder and emphasize the endoscopic features of the tumour, which were highly suggestive of malignancy, leading to the decision to perform cystectomy. The diagnosis was corrected by endoscopic resection and histology. Treatment usually consists of partial cystectomy, but can sometimes be limited to one or several endoscopic resections.