Restraint‐induced stress ulcer. II. biochemical and ultrastructural studies of gastric mucosa

Abstract

The aim of these studies was to evaluate the light and electron microscopic changes of the gastric mucosa of restrained rats, and to determine if there were correlations between structural changes, histidine decarboxylase activity, histamine content, and gastric secretion.In areas with high-grade mucosal lesions, signs of functional hyperactivity of the oxyntic and chief cells and cytoplasmic degranulation of the enterochromaffin-like cells were observed. These changes were not influenced by vagotomy. The hyperactivity of the chief cells was related to a higher proteolytic activity of the gastric juice and to an increased excretion of uropepsinogen (p < 0.01). The hyperactivity of the oxyntic cells was not accompanied by an increase in total acidity, which could be explained by hydrogen ion back-diffusion through a damaged gastric mucosal barrier. The increase in histidine decarboxylase activity (p < 0.01) and the decrease of histamine content (p < 0.01) in the glandular mucosa of restrained rats, together with the microscopic and ultrastructural observations, suggest that the early microcirculatory changes are due to local alterations in the metabolism of vasoactive amines.Among the mechanisms involved in the pathogenesis of restraint ulcers, special significance has been attributed to acid hypersecretion, damage to the gastric mucosal barrier with H + back-diffusion, andPresented at the XXVIIth Congress of the Socidt6 Internationale de Chirugie, Kyoto, Japan, September 3-8, 1977.Reprint requests: Professor J.L. Balibrea, Department of Surgery, Autonomous University of Barcelona, Bellaterra (Barcelona), Spain. At present, special attention is directed toward the properties of the enterochromaffin cell system, described in the gastric mucosa of the rat by H~kan-son et al. [7], because of its high histidine and dopa decarboxylase activities. The existence of increased histidine decarboxylase activity in the mucosa of restrained rats [8] suggests a role for histamine in the genesis of restraint-induced ulcers, both through its influence on acid and peptic secretions and through microcirculatory effects that might disrupt the gastric mucosal barrier [9].The purpose of the experiments described in this report was to study the effects of restraint stress, in the absence of biliary reflux, on acid and mucus secretion and on proteolytic activity of gastric juice. Histidine decarboxylase and histamine content of the gastric mucosa and the effects of vagotomy on

Somatostatin in the Management of Gastrointestinal Hemorrhage: Bleeding Ulcers

“…In stress ulcer, at electron microscopy, oxyntic and chief cells did not show impor tant changes [7]; therefore, it is difficult to incriminate hydrochloric acid in the pathogenesis of these ulcers, since its secretion needs a large energetic expenditure by parietal cells: then, instead of showing the ultrastructural picture of a hypersecretory state, these oxyntic cells showed enlarged intracellular ducts and sparse microvil li. The most relevant finding in our study was a marked increment in the histidine-decarboxylase activity which explains the important participation of histamine in the pathogenesis of stress ulcer: histamine acts on submuco sal microcirculation and, through the activation of phos pholipase A, is responsible for the phospholipid compo nent of cell membrane degradation, and for the inhibi tion of prostaglandin synthesis.…”

Gastric Mucosal Energy Metabolism in Stress Ulcer

“…Among the mechanisms involved in the pathogenesis o f experimental stress ulcer, special significance has been attributed to damage to the gastric mucosal barrier with H+ back-diffusion [5], and to microcirculatory changes caused by the effect o f vasoactive amines [3], Biochemical changes resulting from these vascular alterations have been demonstrated, both in the restraint-rat model and in the animal model o f hemorrhagic shock. There is both a marked drop in DNA synthesis and a loss o f RNA content in the epithelial cells [25], as well as an early decrease in the total levels o f ATP and adenosine phosphates, leading up to a mucosal energy deficit [17], Fur thermore, a role for histamine in the genesis of stress-induced ulceration has been suggested through its influence on the activation o f phospholipases [7].…”