Peptic Ulcer

Encompasses both gastric and duodenal ulcers. Ulcers are defined as breaks in the mucosal surface >5 mm in size, with depth to the submucosa. A peptic ulcer is a break, or an ulceration, in the protective mucosal lining of the lower esophagus, stomach, or duodenum. Approximately 14.5 million people in the United States have peptic ulcer disease 2 major risk factors are H. pylori infection of the gastric mucosa and habitual use of NSAIDs. Alcohol and smoking may influence susceptibility Psychologic stress may be a risk factor Peptic ulcers can be acute or chronic, and superficial or deep. Superficial ulcerations are called erosions because they erode the mucosa but do not penetrate the muscularis mucosae. True ulcers extend through the muscularis mucosae and damage blood vessels causing hemorrhage or perforate the gastrointestinal wall. Gastric mucosal infection with H. pylori is a major cause of peptic ulcers. Chronic use of NSAIDs suppresses mucosal prostaglandin synthesis resulting in decreased bicarbonate secretion and mucin production and increased secretion of hydrochloric acid. The interaction of NSAIDs and H. pylori in the pathogenesis of peptic ulcer is not clear Pathogenesis Peptic ulcers are produced by an imbalance between gastroduodenal mucosal defense mechanisms and the damaging forces, particularly gastric acid and pepsin. However, hyperacidity is not a prerequisite, as only a minority of patients with duodenal ulcers has hyperacidity, and it is even less common in those with gastric ulcers. Rather, gastric ulceration occurs when mucosal defenses fail, as when mucosal blood flow drops, gastric emptying is delayed, or epithelial restitution is impaired.

Diagram of causes of, and defense mechanisms against, peptic ulceration. Diagram of the base of a nonperforated peptic ulcer, demonstrating the layers of necrosis (N), inflammation (I), granulation tissue (G), and scar (S), moving from the luminal surface at the top to the muscle wall at the bottom. H. pylori infection is a major factor in the pathogenesis of peptic ulcer. It is present in virtually all patients with duodenal ulcers and in about 70% of those with gastric ulcers. Furthermore, antibiotic treatment of H. pylori

infection promotes healing of ulcers and tends to prevent their recurrence. Hence, much interest is focused on the possible mechanisms by which this tiny spiral organism tips the balance of mucosal defenses.

Duodenal Ulcers Pathophysiology Duodenal ulcers occur with greater frequency than other types of peptic ulcers and affect 10% to 15% of the population. Factors other than H. pylori and use of NSAIDs that may be associated with duodenal ulcer include: 1. Increased mass of gastric parietal cells 2. Serum gastrin levels that remain high longer than normal after eating and continue to stimulate secretion of acid and pepsin (may be caused by H. pyloriin gastric antrum) 3. Failure of the feedback mechanism whereby acid in the gastric antrum inhibits gastrin release 4. Rapid gastric emptying, which overwhelms the buffering capacity of the bicarbonate-rich pancreatic secretions 5. Acid production stimulated by cigarette smoking 6. Decreased duodenal mucosal bicarbonate secretion All these factors, singly or in combination, cause acid and pepsin concentrations in the duodenum to penetrate the mucosal barrier and lead to ulceration Gastric ulcers Pathophysiology Generally gastric ulcers develop in the antral region, adjacent to the acid-secreting mucosa of the body, and are frequently caused by H. pylori. The primary defect is an abnormality that increases the mucosal barriers permeability to hydrogen ions. Gastric secretion may be normal or less than normal and there may be a decreased mass of parietal cells. Chronic pangastritis is often associated with development of gastric ulcers and may precipitate ulcer formation by limiting the mucosas ability to secrete a protective layer of mucus.

Duodenal reflux of bile is associated with gastric ulcer (alkaline reflux gastritis), and may occur after cholescystectomy, pyloroplasty, or gastrojejunostomy. The pyloric sphincter also may fail to respond to stimuli that normally increase resting tone, such as entry of acid, protein, and fat into the duodenum. An increased concentration of bile salts disrupts the gastric mucosa. The break damages the mucosal barrier by permitting hydrogen ions to diffuse into the mucosa, where they disrupt permeability and cellular structure. A vicious cycle can be established as the damaged mucosa liberates histamine, which stimulates the increase of acid and pepsinogen production, blood flow, and capillary permeability. The disrupted mucosa becomes edematous and loses plasma proteins. Destruction of small vessels causes bleeding.

Complications Gastrointestinal Bleeding GI bleeding is the most common complication observed in PUD. It occurs in ~15% of patients and more often in individuals >60 years of age. The mortality rate is as high as 510%. The higher incidence in the elderly is likely due to the increased use of NSAIDs in this group. Up to 20% of patients with ulcer-related hemorrhage bleed without any preceding warning signs or symptoms. Perforation The second most common ulcer-related complication is perforation, being reported in as many as 67% of PUD patients. As in the case of bleeding, the incidence of perforation in the elderly appears to be increasing secondary to increased use of NSAIDs. Penetration is a form of perforation in which the ulcer bed tunnels into an adjacent organ. DUs tend to penetrate posteriorly into the pancreas, leading to pancreatitis, whereas GUs tend to penetrate into the left hepatic lobe. Gastric Outlet Obstruction Gastric outlet obstruction is the least common ulcer-related complication, occurring in 12% of patients. A patient may have relative obstruction secondary to ulcer-related inflammation and edema in the peripyloric region. This process often resolves with ulcer healing. A fixed, mechanical obstruction secondary to scar formation in the

peripyloric areas is also possible. The latter requires endoscopic (balloon dilation) or surgical intervention. Signs and symptoms relative to mechanical obstruction may develop insidiously. New onset of early satiety, nausea, vomiting, increase of postprandial abdominal pain, and weight loss should make gastric outlet obstruction a possible diagnosis.