Pepsinogen release and acid secretion from human and Guinea pig gastric mucosa compromised by hypoxia, endotoxin, or critical illness

J. M. Modlin, M. D. Basson, T. E. Adrian, J. Sussman

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Despite blockade and neutralization of gastric acid, acute gastric lesions cause substantial morbidity and mortality in critically ill patients. Pepsinogen release in response to noxious stimuli such as hypoxia and endotoxin might contribute to mucosal damage. Guinea pig fundic mucosa was mounted in Ussing chambers. Acid secretion, pepsinogen release, potential difference (PD), and resistance were monitored. Gassing with room air or nitrogen diminished acid secretion and PD but increased pepsinogen release 9.7- and 15.5-fold, respectively (both p < 0.001). Similarly, endotoxin (0.01 and 0.1 units/ml) dose-dependently inhibited acid secretion and PD but increased pepsinogen release 3.3- and 6.1-fold (both p < 0.05). Endotoxic and air-gassed tissues were edematous with scattered cellular damage by light and transmission electron microscopy; nitrogen-exposed membranes appeared necrotic. Pepsin release may therefore have resulted from cell damage rather than exocytosis. Intragastric peptic activity in critically ill H2-receptor-blocked patients (n = 20) was 5490 ± 1701 U/ml.The gastric juice of H2-blocked convalescing surgical patients(n = 20) contained 315 ± 101 U/ml (p < 0.0001). Occult blood correlated with intragastric peptic activity (r = 0.59, p < 0.0001) but not with gastric pH (r = 0.04, p = 0.6). These data suggest that the complex of pathophysiologic abnormalities common in critical illness causes substantial pepsin release. Efflux of this potent mucolytic barrier breaker may damage gastric mucosa in severely stressed patients.

Original languageEnglish
Pages (from-to)865-875
Number of pages11
JournalScandinavian Journal of Gastroenterology
Volume25
Issue number9
DOIs
Publication statusPublished - 1990
Externally publishedYes

Keywords

  • Acid
  • Endotoxin
  • Hypoxia
  • Pepsin
  • Ussing chamber

ASJC Scopus subject areas

  • Gastroenterology

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