Clinical Manifestations

Three categories of patients may exhibit the endoscopic and histological changes of chemical gastropathy: patients with alkaline reflux after partial gastrectomy, patients with duodenogastric bile reflux as part of a poorly understood dysmotility syndrome, and patients who take NSAIDs.

Postgastrectomy alkaline reflux may present with a syndrome characterized by burning midepigastric pain unresponsive to antacids and aggravated by eating and recumbency. Bilious vomiting, anemia, and weight loss may occur. Endoscopic confirmation of bile reflux and documentation of the characteristic histopathological findings support the diagnosis, and corrective surgery (e.g., creation of a 40- to 50-cm Roux-en-Y gastrojejunostomy) is successful in about half of all cases.

Duodenogastric bile reflux secondary to gastroduodenaldysmotility or to cholecystectomy is a controversial condition, rarely considered in the differential diagnosis of dyspepsia in patients with an intact stomach. Thus, the frequency of endoscopic or histological changes of chemical gastropathy in these patients is unknown.

Millions of persons take daily doses of NSAIDs for indefinite periods, in many cases for life, to control pain caused by osteoarthritis, rheumatoid arthritis, or other chronic conditions. Unknown numbers of these NSAID users experience epigastric pain; approximately 10% per year develop erosions or ulcers, and 1% to 2% per year have a major gastric bleeding episode. Reactive gastropathy has been documented histopathologically in 10% to 45% of long-term users of NSAIDs, but no relationship could be established between the appearance of the mucosa and dyspeptic symptoms.

Pathogenesis

Duodenogastric reflux (with alkaline pancreaticoduodenal secretions as well as acids, bile salts, and lysolecithin) disrupts the mucous barrier and directly damages the gastric surface epithelium. This combined injury leads to accelerated exfoliation of surface epithelial cells and a histamine-mediated vascular response that manifests as edema and hyperemia. Persistent epithelial damage may lead to the release of other proinflam­matory agents, such as platelet-derived growth factor, which among its many actions stimulates smooth muscle and, later on, fibroblastic proliferation. Epithelial injury after exposure to NSAIDs appears to be mediated by reduced prostaglandin synthesis. Prostaglandins are important cytoprotective agents in the gastric mucosa and exert their effects by maintaining mucosal blood flow, by increasing secretion of mucus and bicarbonate ions, and by augmenting epithelial defense against cytotoxic injury. Thus, NSAID-inflicted injury can be partially prevented by simultaneous administration of prostaglandin analogs such as misoprostol and by suppression of gastric acid production with proton pump inhibitors. Newer selective cyclooxygenase 2 inhibitors (inhibitors, second-generation NSAIDs, or selective NSAIDs) are reportedly better tolerated by the gastric mucosa. Whether the initial encouraging results will hold true when these drugs become widely used, remains to be evaluated.

Дата добавления: 2015-11-14