Peptic Ulcer Disease Pathophysiology

[Emerenciana Mcgreal]

Apeptic ulcer is a sore on the lining of your stomach, small intestine or esophagus. A peptic ulcer in the stomach is called a gastric ulcer. A duodenal ulcer is a peptic ulcer that develops in the first part of the small intestine (duodenum). An esophageal ulcer occurs in the lower part of your esophagus.

The most common causes of peptic ulcers are infection with the bacterium Helicobacter pylori (H. pylori) and long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Advil, Motrin IB, others) and naproxen sodium (Aleve). Stress and spicy foods do not cause peptic ulcers. However, they can make your symptoms worse.

The most common peptic ulcer symptom is burning stomach pain. Stomach acid makes the pain worse, as does having an empty stomach. The pain can often be relieved by eating certain foods that buffer stomach acid or by taking an acid-reducing medication, but then it may come back. The pain may be worse between meals and at night.

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A bacterium. Helicobacter pylori bacteria commonly live in the mucous layer that covers and protects tissues that line the stomach and small intestine. Often, the H. pylori bacterium causes no problems, but it can cause inflammation of the stomach's inner layer, producing an ulcer.

Use caution with pain relievers. If you regularly use pain relievers that increase your risk of peptic ulcer, take steps to reduce your risk of stomach problems. For instance, take your medication with meals.

Work with your doctor to find the lowest dose possible that still gives you pain relief. Avoid drinking alcohol when taking your medication, since the two can combine to increase your risk of stomach upset.

If you need an NSAID, you may need to also take additional medications such as an antacid, a proton pump inhibitor, an acid blocker or cytoprotective agent. A class of NSAIDs called COX-2 inhibitors may be less likely to cause peptic ulcers, but may increase the risk of heart attack.

In uncomplicated peptic ulcer disease, the clinical findings are few and nonspecific. Alarm features" that warrant prompt gastroenterology referral [1] include bleeding, anemia, early satiety, unexplained weight loss, progressive dysphagia or odynophagia, recurrent vomiting, and a family history of gastrointestinal (GI) cancer. Patients with perforated peptic ulcer disease usually present with a sudden onset of severe, sharp abdominal pain. (See Presentation.)

In most patients with uncomplicated peptic ulcer disease, routine laboratory tests usually are not helpful; instead, documentation of peptic ulcer disease depends on radiographic and endoscopic confirmation. Testing for H pylori infection is essential in all patients with peptic ulcers. Rapid urease tests are considered the endoscopic diagnostic test of choice. Of the noninvasive tests, fecal antigen testing is more accurate than antibody testing and is less expensive than urea breath tests but either is reasonable. A fasting serum gastrin level should be obtained in certain cases to screen for Zollinger-Ellison syndrome. (See Workup.)

Upper GI endoscopy is the preferred diagnostic test in the evaluation of patients with suspected peptic ulcer disease. Endoscopy provides an opportunity to visualize the ulcer, to determine the presence and degree of active bleeding, and to attempt hemostasis by direct measures, if required. Perform endoscopy early in patients older than 45-50 years and in patients with associated so-called alarm features.

In patients with NSAID-associated peptic ulcers, discontinuation of NSAIDs is paramount, if it is clinically feasible. For patients who must continue with their NSAIDs, proton pump inhibitor (PPI) maintenance is recommended to prevent recurrences even after eradication of H pylori. [3, 4] Prophylactic regimens that have been shown to dramatically reduce the risk of NSAID-induced gastric and duodenal ulcers include the use of a prostaglandin analog or a PPI. Maintenance therapy with antisecretory medications (eg, H2 blockers, PPIs) for 1 year is indicated in high-risk patients. (See Medication.)

The indications for urgent surgery include failure to achieve hemostasis endoscopically, recurrent bleeding despite endoscopic attempts at achieving hemostasis (many advocate surgery after two failed endoscopic attempts), and perforation.

Because many surgical procedures for peptic ulcer disease entail some type of vagotomy, a discussion concerning the vagal innervation of the abdominal viscera is appropriate (see image below). The left (anterior) and the right (posterior) branches of the vagus nerve descend along either side of the distal esophagus. As they enter the lower thoracic cavity, they can communicate with each other through several cross-branches that comprise the esophageal plexus. However, below this plexus, the two vagal trunks again become separate and distinct before the anterior trunk branches to form the hepatic, pyloric, and anterior gastric (also termed the anterior nerve of Latarjet) branches. The posterior trunk branches to form the posterior gastric branch (also termed the posterior nerve of Latarjet) and the celiac branch.

The parietal cell mass of the stomach is segmentally innervated by the terminal branches from each of the anterior and posterior gastric branches. These terminal branches are divided during highly selective vagotomy. The gallbladder is innervated from efferent branches of the hepatic division of the anterior trunk. Consequently, transection of the anterior vagus trunk (performed during truncal vagotomy) can result in a dilated gallbladder with inhibited contractility and subsequent cholelithiasis. The celiac branch of the posterior vagus innervates the entire midgut (with the exception of the gallbladder). Thus, division of the posterior trunk during truncal vagotomy may contribute to postoperative ileus.

Peptic ulcers are defects in the gastric or duodenal mucosa that extend through the muscularis mucosa. The epithelial cells of the stomach and duodenum secrete mucus in response to irritation of the epithelial lining and as a result of cholinergic stimulation. The superficial portion of the gastric and duodenal mucosa exists in the form of a gel layer, which is impermeable to acid and pepsin. Other gastric and duodenal cells secrete bicarbonate, which aids in buffering acid that lies near the mucosa. Prostaglandins of the E type (PGE) have an important protective role, because PGE increases the production of both bicarbonate and the mucous layer.

In the event of acid and pepsin entering the epithelial cells, additional mechanisms are in place to reduce injury. Within the epithelial cells, ion pumps in the basolateral cell membrane help to regulate intracellular pH by removing excess hydrogen ions. Through the process of restitution, healthy cells migrate to the site of injury. Mucosal blood flow removes acid that diffuses through the injured mucosa and provides bicarbonate to the surface epithelial cells.

Under normal conditions, a physiologic balance exists between gastric acid secretion and gastroduodenal mucosal defense. Mucosal injury and, thus, peptic ulcer occur when the balance between the aggressive factors and the defensive mechanisms is disrupted. Aggressive factors, such as nonsteroidal anti-inflammatory drugs (NSAIDs), H pylori infection, alcohol, bile salts, acid, and pepsin, can alter the mucosal defense by allowing the back diffusion of hydrogen ions and subsequent epithelial cell injury. The defensive mechanisms include tight intercellular junctions, mucus, bicarbonate, mucosal blood flow, cellular restitution, and epithelial renewal.

The gram-negative spirochete H pylori was first linked to gastritis in 1983. Since then, further study of H pylori has revealed that it is a major part of the triad, which includes acid and pepsin, that contributes to primary peptic ulcer disease. The unique microbiologic characteristics of this organism, such as urease production, allows it to alkalinize its microenvironment and survive for years in the hostile acidic environment of the stomach, where it causes mucosal inflammation and, in some individuals, worsens the severity of peptic ulcer disease.

When H pylori colonizes the gastric mucosa, inflammation usually results. The causal association between H pylori gastritis and duodenal ulceration is now well established in the adult and pediatric literature. In patients infected with H pylori, high levels of gastrin and pepsinogen and reduced levels of somatostatin have been measured. In infected patients, exposure of the duodenum to acid is increased. Virulence factors produced by H pylori, including urease, catalase, vacuolating cytotoxin, and lipopolysaccharide, are well described.

Most patients with duodenal ulcers have impaired duodenal bicarbonate secretion, which has also proven to be caused by H pylori because its eradication reverses the defect. [5] The combination of increased gastric acid secretion and reduced duodenal bicarbonate secretion lowers the pH in the duodenum, which promotes the development of gastric metaplasia (ie, the presence of gastric epithelium in the first portion of the duodenum). H pylori infection in areas of gastric metaplasia induces duodenitis and enhances the susceptibility to acid injury, thereby predisposing to duodenal ulcers. Duodenal colonization by H pylori was found to be a highly significant predictor of subsequent development of duodenal ulcers in one study that followed 181 patients with endoscopy-negative, nonulcer dyspepsia. [6]

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