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Peptic ulcer disease (PUD) is a heterogeneous group of disorders involving the upper gastrointestinal (GI) tract. A peptic ulcer is a defined, excoriated area of the GI mucosa, typically located in the stomach or the first few centimeters of the duodenum.(1) Peptic ulcers can be acute or chronic. Duodenal and gastric ulcers are the most common types of chronic peptic ulcers.
Investigators have divided PUD into three etiologic groups based on pathophysiology: 1) those with massive acid secretion (i.e., Zollinger-Ellison syndrome); 2) ulcers of infectious etiology; and 3) those caused by nonsteroidal anti-inflammatory drugs (NSAIDs).(2)
The body and fundus of the stomach are made up of oxyntic glands, which contain parietal and chief cells. When stimulated by a physiologic event (for instance, a meal), the parietal cells secrete hydrochloric acid and intrinsic factor into the gastric lumen, while the chief cells secrete pepsinogen. In an acidic environment, pepsinogen forms pepsin. The secretion of gastric acid, enzymes, and mucus is regulated by nervous and hormonal mechanisms mediated by histamine, the hormone gastrin, and acetylcholine.
Several mechanisms preserve the gastric mucosa and protect it from the digestive effects of pepsin and acid. Surface epithelial cells and mucus cells act as first line defenses by secreting mucus and bicarbonate throughout the gastric area. Bicarbonate, along with mucus, is thought to provide a layer over epithelial cells where the pH is neutral. Beneath the surface epithelium, a dense network of capillaries provides another level of defense.
Another way in which the epithelium resists injury from acids is through rapid and continual cell renewal. Prostaglandins play an additional role in enhancing gastroduodenal mucosal resistance to injury by inhibiting gastric acid secretion. Prostaglandins may also maintain mucosal blood flow and stimulate mucus and bicarbonate production.
A number of factors can predispose an individual to PUD, including:
- Hypersecretion of gastric acid in people with increased parietal cell mass (Zollinger-Ellison syndrome)
- Inflammatory response associated with Helicobacter pylori
- Prostaglandin inhibition and direct irritation of the GI mucosa; NSAIDs and ASA can induce ulcer formation
- Cigarette smoking – stimulation of gastric acid, alteration of mucosal blood flow, and reduction in prostaglandin synthesis
- Genetic predisposition
- Diet, use of alcohol
- Psychological stress
One contributor to recurrent peptic ulcer disease is an organism called Helicobacter pylori (H. pylori), a spiral shaped bacterium discovered in 1982 that is found in the gastric mucus layer or adherent to the epithelial lining of the stomach.(3) This organism is found in 95 percent of patients with duodenal ulcers and 70 percent of patients with gastric ulcers.(4) Eradication of the organism significantly decreases the recurrence rate and accelerates the healing rate of ulcers.(5) The mechanism by which H. pylori causes tissue injury may include production of cytotoxin, breakdown of mucosal defenses, and adherence to epithelial cells.
It is not known how H. pylori is transmitted, but it is most likely spread from person to person through fecal-oral or oral-oral routes. The prevalence of H. pylori increases with age. It is not known exactly how the bacteria causes damage because many people infected with H. pylori never develop ulcers.(6) H. pylori causes chronic active, chronic persistent, and atrophic gastritis in adults and children as well as duodenal and gastric ulcers. Persons with active gastric or duodenal ulcers or a documented history of ulcers should be tested for H. pylori, and if found to be infected, should be treated. Identification of H. pylo
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