Gastric ulcer disease in dogs and cats (Proceedings)
Aug 01, 2008
CVC IN KANSAS CITY PROCEEDINGS
The stomach plays a key initial role in digestion through its mixing actions, and through the secretion of gastric acid and pepsin, which are important for the activation of key digestive enzymes. The gastric epithelium is remarkably resistant to the deleterious effects of low pH because of the presence of a number of protective forces that prevent acid-induced injury. However, if gastric acid secretion increases to the point that the protective forces are overwhelmed, and/or there is a breakdown or loss in these protective forces, a gastric ulcer can develop.
Gastric acid secretion
The principle protective forces of the gastric mucosa are an adequate blood flow, a mucus/bicarbonate layer, and epithelial cells that are capable of rapidly spreading to cover defects in the mucosa. Locally synthesized prostaglandins, primarily PGE2, support many of these protective forces. Mucosal blood flow is maintained by adequate concentrations of PGE2. The anatomy of the mucosal capillary bed promotes delivery of an HCO3 - ion, generated during the production of acid, to the capillaries underlying the surface epithelium where they can be available to neutralize any protons that have diffused back to the epithelial surface. Secretion of mucus is also promoted by PGE2. The mucus layer itself has a pH gradient, with the highest (most basic) pH situated at the epithelial surface. The gastric epithelial cells are capable of altering their shape to become flatter and more spread out to quickly cover any superficial epithelial layer defects, a process known as restitution. Gastric epithelial cells can also, under the right stimuli (growth factors, cytokines, inflammatory mediators), undergo rapid proliferation to fill larger breaches like ulcers in the epithelial barrier.
Gastric ulcer pathogenesis
Gastric ulcers develop when there is an excess of harmful substances, primarily acid and pepsin, or there is a breakdown in a local protective force. Most causes of ulcers in dogs and cats reflect one or both of these pathophysiological processes. Diseases that are known to increase secretion of gastric acid production often do so as a consequence of increases in gastrin or histamine. Examples of the former include renal failure (acute or chronic), and gastrinomas. Mast cell tumors predispose to gastric ulcers as a consequence of increased circulating concentrations of histamine. Studies of dogs with mast cell tumors have documented increased blood histamine concentrations as compared to normal dogs. A recent study of gastric ulcers in cats found systemic mast cell tumors the most common cause of ulcers in that study population.