Lesions of the mucosal wall that occur in the stomach or duodenum are referred to as peptic ulcer disease. Although certain drugs can cause ulcers (in particular non-steroidal anti-inflammatory drugs, or NSAIDs), the great majority of cases of peptic ulcer disease stem from infection with the bacterium Helicobacter pylori (H. pylori). Acid in the stomach kills many bacteria, but H. pylori can evade destruction by burrowing into the protective mucus layer. H. pylori also expresses urease, an enzyme that hydrolyzes urea to produce ammonia, which is used to buffer acid in the immediate environment of the bacterium.
Infection with H. pylori causes chronic gastritis, which is inflammation of the stomach lining. Many individuals who are infected with H. pylori may never experience symptoms. The severity of the gastritis depends in part upon the virulence of the strain of infecting bacteria, but is mostly due to the immune response of the infected individual. Inflammation causes the recruitment of white blood cells and the production of cytokines, which have effects on the physiology of cells in the stomach epithelium.
Peptic ulcer disease takes two very different courses, depending on the predominant location of the gastritis in the stomach.
Some individuals produce excessive quantities of acid, and this leads to development of a duodenal ulcer. This type of response occurs when gastritis is localized in the pyloric region. The cytokines released in response to inflammation disrupt the regulation of the endocrine cells located in the pylorus. G cells are stimulated to secrete more gastrin, while somatostatin secretion is inhibited. Gastrin stimulates parietal cell proliferation and increased parietal cells along with decreased somatostatin leads to acid hypersecretion. The acid-neutralizing mechanisms (pancreatic and duodenal bicarbonate secretion) become overwhelmed, and the duodenal tissue becomes damaged.
If gastritis is located predominantly in the body of the stomach, the disease progresses in an entirely different manner, called atrophic gastritis. The inflammation induces apoptosis of parietal cells, and there is eventual atrophy of the gastric glands. The result is hyposecretion of acid, or hypochlorhydria. Continued tissue damage may lead to development of a gastric ulcer.
H. pylori is classified as a carcinogen because infection increases the risk of developing certain types of gastric cancer. This increased risk is almost exclusively associated with atrophic gastritis and gastric ulcer. What happens is that the atrophic gastric glands undergo a further change known as intestinal metaplasia. The growth pattern of the epithelium changes, and it begins to resemble an intestinal epithelium, with villi and goblet cells. This change in the epithelium is thought to be the first step in further growth changes involved in the development of cancer.
Treatment of peptic ulcer disease involves eradication of H. pylori through the use of antibiotics. Along with antibiotics, drugs that reduce acid secretion are also administered. Reducing the acidity in the stomach lumen promotes healing, and it also increases the effectiveness of the antibiotics.
There are two main types of drugs that reduce acid secretion.