Laurence Y. Cheung

The role of gastric mucosal blood flow and H^+ back-diffusion in the pathogenesis of acute gastric erosions

Abstract To evaluate the relationship between ischemia and disruption of the gastric permeability barrier in the pathogenesis of acute gastric erosions, we studied the effect of (1) hemorrhagic shock, (2) topical application of p -chloromercuribenzene sulfonate (PCMBS), and (3) shock plus PCMBS on total and mucosal blood flow, H + back-diffusion, and mucosal injury in 14 dogs. The fractional distribution of blood flow through the layers of gastric tissue remained unchanged during control, shock, and reinfusion periods. Exposure of the mucosa to PCMBS resulted in a significant increase in H + back-diffusion, which was accompanied by a rise in mucosal blood flow. Hemorrhagic shock alone caused a marked mucosal ischemia without disruption of the permeability barrier. The severest mucosal injury occurs only under experimental conditions where ischemia and increased H + back-diffusion are induced simultaneously. These results suggest that: (1) A cause-effect relationship does not exist between ischemia and barrier disruption in the pathogenesis of acute ulcerations. (2) Mucosal blood flow may play an important role in the disposal of H + permeating the mucosa. (3) The ratio of mucosal blood flow to back-diffusion of H + may determine the degree of mucosal injury.

Stress Ulcers: Their Pathogenesis, Diagnosis, and Treatment

Stress ulcers are multiple, superficial erosions which occur mainly in the fundus and body of the stomach. They develop after shock, sepsis, and trauma and are ofter found in patients with peritonitis and other chronic medical illness. Stress ulcers should be differentiated from reactivation of chronic duodenal or gastric ulcers. Cushings ulcer following head injury, or drug-induced gastritis. Digestive symptoms are usually absent, hemorrhage is the most common manifestation, and perforation and obstruction are rare. The presence of luminal acid and ischemia are necessary for the production of stress ulcer, while disruption of the gastric mucosal barrier by refluxed duodenal content may contribute to the pathogenesis. Endoscopy is the mainstay of the diagnostic procedure, and angiography should be used if endoscopy fails to identify the bleeding lesions. Medical management should include volume replacement, nasogastric aspiration, and the use of antacid. Selective intraarterial infusion of pitressin has shown encouraging preliminary results. Surgical treatment is reserved only for those patients who continue to bleed despite all medical management. The operation of choice is open to question. We prefer vagotomy, pyloroplasty, and oversewing the ulcers as an initial operation. Since the result of all forms of therapy has been poor, it seems resonable to try to prevent ulcer development. The use of vitamin A, hyperalimentation, and growth hormones is still in an experimental stage. Large clinical studies with case control are necessary before recommendations can be made. The use of potent and frequent antacid to buffer the gastric content has shown promising results; however, these observations need to be confirmed in a properly controlled and randomized study.

Direct effects of endotoxin on canine gastric mucosal permeability and morphology.

Abstract The effects of endotoxin on gastric mucosal permeability and morphology were studied by intra-arterial infusion of sublethal doses of endotoxin into a single artery perfusing an exteriorized segment of canine stomach. Endotoxin infusion produced a profound change in mucosal appearance from bright, uniform red to mottled, palewhite discoloration when exposed to acid or mannitol. Gross erosions occurred in four of 13 mucosae bathed with 0.15 N HCl within 1 hr of infusion of endotoxin in the absence of arterial hypotension. Histological changes seen in most experiments include release of mucus from surface epithelial cells and elevation of the epithelium from the basement membrane. In more advanced lesions, severe injury extended into the gastric glands and surrounding connective tissue with cellular necrosis. In spite of gross and microscopic gastric mucosal injury, no significant change was seen in hydrogen ion back diffusion or sodium efflux. These observations suggest that gastric mucosal injuries can occur in endotoxemia without systemic arterial hypotension and that anatomical mucosal injuries are not associated with the destruction of the hydrogen-sodium permeability barrier.