Peptic ulcers (Stomach Ulcers) are common, affecting 15% of individuals in the Western world. In many cases, they cause only mild symptoms and little damage, but in others they can be life-threatening. The treatment of peptic ulcer has dramatically changed following our improved understanding of its pathogenesis, representing a triumph of the power of scientific medicine.The surface epithelium of the stomach or duodenum is damaged and ulcerates, and the resulting inflammation extends into the underlying mucosa and submucosa. Gastric acid and digestive enzymes penetrate into the tissues, causing further damage, for example to blood vessels and adjacent tissues.
Peptic Ulcer Causes
Gastric acid (HCl) production is stimulated by gastrin secreted by G cells in the antrum, acetylcholine released by the vagus nerve, and histamine released by enterochromaffin-like (ECL) cells, all of which stimulate receptors on the acid-producing parietal cells.Duodenal ulcers are exceedingly rare in people who do not produce gastric acid, and multiple, recurrent ulcers occur when acid production is greatly increased, for example by gastrin-secreting tumours . However, gastric acid production is usually low in people with gastric ulcers, and this may be the result of chronic gastritis.
The risk of peptic ulcer is increased in patients who use non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, which inhibit prostaglandin production by epithelial cells. Furthermore, the risk of peptic ulcer is reduced by an artificial prostaglandin E2 agonist, misoprostol.
Smoking, alcohol, genetics and stress.
Other risk factors include smoking tobacco and drinking alcohol, although the mechanisms by which these act are unknown. In addition, there is a small genetic predisposition. There is little evidence that stress or lifestyle factors play any role.
Spiral bacteria in the stomach had been noted for over a hundred years, yet their significance only became apparent in 1982 when Warren and Marshall cultured H. pylori from 11 patients with gastritis, and Dr Marshall then demonstrated that it caused gastritis by ingesting a test dose himself. He was subsequently cured by antibiotic treatment.
Helicobacter pylori infection is present in the majority of patients with peptic ulcer, although only about 15% of infected people develop ulcers. Eradicating H. pylori infection permanently cures peptic ulcer in the majority of cases.
Helicobacter pylori infection of the gastric antrum, which stimulates gastrin production, causes the greatest hyperacidity and duodenal ulceration, while infection of the gastric corpus, where most parietal cells are present, tends to reduce stomach acid production and is associated with gastritis, gastric ulcer, gastric cancer and gastric lymphoma. Strains of H. pylori vary in pathogenicity and virulence, determined by various bacterial gene clusters. Thus, both host factors and the bacterial strain determine the outcome of infection. Peptic ulceration results from an imbalance between gastroprotective factors, such as the mucus layer and prostaglandins, and aggressive factors, such as stomach acid and the effects of smoking, alcohol and NSAIDs. Helicobacter pylori infection dramatically tips the balance against protection.
Epigastric pain, often aggravated by hunger or by meals and relieved by antacids, suggests peptic ulceration or gastritis. There may be nausea, vomiting and anorexia. Anaemia may develop from chronic haemorrhage. Peptic ulcer may cause major acute bleeding, leading to haematemesis and/or melaena, which is a medical emergency. Similarly, peptic ulcers may perforate the stomach or duodenum, causing peritonitis. Peptic ulcer may penetrate into the pancreas and cause pancreatitis. Scarring of the duodenum by chronic ulceration may cause intestinal obstruction.
Peptic Ulcer Diagnosis
Upper gastrointestinal endoscopy is the best diagnostic test. Ulcers can also be detected by barium contrast X-rays. Helicobacter pylori infection can be diagnosed serologically, or by the urease breath test, in which 13C-labelled urea is taken orally and the resulting 13CO2 released by the urease enzyme is measured on the breath. Helicobacter pylori organisms can be demonstrated histologically, and the urease enzyme can be detected using a simple colorimetric test (CLO test, for Campylobacter-like organism) in mucosal biopsies taken during endoscopy. Gastric ulcers may be caused by carcinoma or lymphoma, so they must always be biopsied to check that they are not malignant. Duodenal ulcers are very rarely malignant.
Peptic Ulcer Treatment
Except for emergencies and persisting diagnostic uncertainty, surgical treatment is now obsolete. Partial gastrectomy to remove part of the gastrin-producing, G-cell-rich antrum was once routinely performed. Another approach was to selectively section branches of the vagus nerve (selective vagotomy) that stimulated acid secretion, sparing fibres that controlled the pyloric sphincter.
Simple antacids and anticholinergics are relatively ineffective, have to be taken frequently and produce side-effects. The first effective medical treatment for peptic ulcer emerged when selective histamine H2 receptor antagonists were developed. For some time, drugs such as cimetidine and ranitidine were the most widely prescribed medications worldwide.
Proton pump inhibitors
Proton pump inhibitors, which irreversibly block acid production by parietal cells, have overtaken the H2 receptor antagonists, and omeprazole, the first proton pump inhibitor, accounts for the greatest worldwide expenditure on a single drug.
Helicobacter pylori eradication
Helicobacter pylori eradication provides a permanent cure for most cases of peptic ulcer. Successful eradication requires combined therapy with an acid suppressor and two or three antibiotics. Most standard regimes are successful in up to 90% of cases, although antibiotic resistance is emerging.
Peptic Ulcer Emergency treatment.
Bleeding or perforation may require emergency surgical or endoscopic therapy, such as injection of adrenaline around an exposed vessel with coaptive coagulation therapy or metal clips, to arrest haemorrhage.