Peptic ulcer disease

Abstract

In lieu of an abstract, here is a brief excerpt of the content: •62• Chapter 6 Peptic Ulcer Disease E. Q. Archampong Introduction Nothing short of a revolution has characterized our understanding of the aetiology, pathogenesis and management of peptic ulcer disease over the past century and the burning issue that arises is how far this has influenced the outcome of current management of the disease. The decline of the acid dogma,1,2 “no acid, no ulcer”, which had given rise to decades of dominance of surgical interventions (partial gastrectomies, various forms of vagotomy), was succeeded by short term antibiotic regimes aimed at elimination of helicobacter pylori infection; this ensued following the demonstration that H. pylori is a primary factor in the pathogenesis of peptic ulcer disease by Warren and Marshall3,4, for which they were awarded the Nobel Prize for Medicine and Physiology in 2005. Furthermore non-steroidal anti-inflammatory drugs (NSAIDS) and low-dose asprin are currently increasingly associated with peptic ulcer disease in H. pylori negative individuals. This article attempts to review the current practice in West Africa in the management of the various forms of peptic ulcer disease, i.e. duodenal, gastric ulcers, gastro-esophageal reflux (GOERD), and its outcome. Pathogenesis of Peptic Ulcer Disease This remains complex but basically, there is imbalance of aggressive gastric luminal agents, mainly acid and the digestive enzyme pepsin, and the defensive mucosal barrier function; so acid secretion still plays an important role. However a whole range of environmental and host factors contribute to ulcerogenesis by increasing acid or pepsin secretion or through impairment of gastric mucosal barrier function.2,5,6 •63• Peptic Ulcer Disease Among the former, tobacco use and alcoholism and drug agents have been cited but apart from NSAID use, none of these have been specifically backed by research data.2 Although emotional stress is frequently blamed for ulcerogenesis, there is more objective support for severe organic stress from sepsis, burns and head or cerebral injuries.7,8 The Influence of H. Pylori Although there is a very strong epidemiological association between H. pylori infection and duodenal and gastric ulceration, the ultimate confirmation of H. pylori as the main cause has been the demonstration of permanent cure of peptic ulcers by the eradication of H. pylori infection.9,10 The fact is that while more that 50 percent of the world’s population is chronically infected with H. pylori (and the figure reaches 75 percent in developing countries), only 5-10 per cent of those so infected develop ulcers. It seems the pattern of histological gastritis induced is one of the main determining factors. Thus in patients with duodenal ulcer, density and severity of infection are greatest in the distal and antral region, sparing the acid-secreting body mucosa, while in gastric ulcer the inflammation affects the body and antral mucosa to a similar degree, leading to much reduced gastric acid secretion, because of the more severe involvement of the acid secreting mucosa of the body of the stomach. There are also factors such as ulcerogenic strains of H. pylori and genetic factors and their influence on gastric and duodenal metaplasia. H. pylori infection impairs the negative feed-back regulation of gastrin release. Through its capacity for high urease activity, it not only protects the organism from the low gastric pH, but also prevents the D cells in the gastric mucosa from sensing the true level of gastric acidity, thus stimulating an inappropriate release of stematostatin (decrease) resulting in an increase in gastrin release, leading to excessive acid secretion.11 One of the effects of excessive gastric acid secretion is development of metaplasia in the duodenal bulb, leading to islands of colonization of the duodenal mucosa, a phenomenon more often seen in gastric •64• Chapter 6 than duodenal mucosa. The inflamed metaplasic duodenal mucosa is more susceptible to ulceration with further acid exposure. The mucosal inflammation generated in the gastric mucosa appears more severe, with induction of epithelium-derived cytokines, particularly interleukin,8 interleukin 112 producing an influx of neutrophils , macrophages with release of lysosomal enzymes, leucotrines and reactive oxygen free radicals, which impair mucosal resistance, releasing a process of immunopathogenic ulcerogenesis. In this scenario, even the reduced acid environment in the gastric mucosa, vitiated by body and antral gastritis, succumbs readily to gastric ulcer. The NSAID Factor in Ulcerogenesis This was earlier attributed to topical injury through ion trapping and reduction of mucosa gel protective activity;13 subsequently this was shown to be more likely through...