The reason why one patient will develop a peptic ulcer and another will not is still unclear. Acid must be present for PUD to occur. The usual pH of the stomach is approximately 1. If an ulcer develops in a patient who is known to be achlorhydric, a gastric malignancy is the likely cause for the ulceration.

There are several protective mechanisms that play a role in preventing PUD. Disruption in any of these factors may result in ulcer formation. The gastric mucosal barrier is the main defense mechanism of the stomach. Another protective mechanism is cytoprotection. Tight junctions between mucosal cells help prevent leakage of acid into the gastric lining. There is always a small degree of leakage of hydrogen ions into these mucosal cells, but the rich vascular supply of the stomach helps sweep away these hydrogen ions. A third factor is the secretion of protective mucus and bicarbonate by the gastric mucosa.

Reversible culprits that can reduce the effectiveness of these protective factors include smoking, the presence of Helicobacter pylori, and the use of nonsteroidal anti-inflammatory agents (NSAIDs).

There are several proposed mechanisms by which cigarette smoking can cause PUD. Smoking may alter blood flow, with resultant hypoxic damage to the mucosa and ulcer formation. Smoking also increases basal and maximal acid secretion and has been reported to decrease gastric mucosal prostaglandin production (Endoh & Leung, 1994).

Recently, the eradication of H. pylori in PUD became a standard of care. H. pylori is a gram-negative rod found in the antrum of the stomach. It is also found in the duodenal bulb, where islands of gastric mucosa are commonly found. Originally called Campylobacter pylori, this organism’s ability to survive in the acidic environment of the stomach comes from its ability to secrete urease and other enzymes into the mucous layer of the mucosa. This damages the protective barrier and allows ulcer formation. H. pylori is associated with 65% to 70% of gastric ulcers and 90% to 95% of duodenal ulcers (Tytgat & Rauws, 1990; Hojgaard et al, 1996). The incidence of H. pylori increases in frequency with age: at age 50 years, it is found in about 50% of the general population, increasing by approximately 10% each decade thereafter.

The use of NSAIDs is strongly associated with PUD. NSAIDs are mainly associated with gastric ulcers; approximately 70% of ulcers caused by these agents occur in the stomach. NSAIDs work by inhibiting mucosal prostaglandin production. This results in an interference in mucous secretion, reduced gastric mucosal blood flow, and decreased bicarbonate secretion (Selling, 1987). Aspirin (acetylsalicylic acid) is the prototype NSAID and therefore damages the gastric mucosa as described above. It is also a weak acid, and in the potent acid environment of the stomach, it becomes un-ionized and penetrates the gastric mucosal cells, causing further damage.

There are marked differences in the incidence of gastric and duodenal ulcers. Duodenal ulcers have a lifetime prevalence, in both men and women, of approximately 10% (Bernersen et al, 1990), whereas gastric ulcers occur much less frequently. However, the incidence of gastric ulcers rises sharply when NSAIDs are involved. PUD used to occur mainly in men; now it occurs almost equally in both sexes (Kurata et al, 1985). The increase in smoking, one of the contributors to PUD, among young women may help explain this increase.

Often the diagnosis of “ulcer disease” is made on clinical grounds. The patient presents with a classical history of PUD, a therapeutic trial of appropriate agents is started, and if the patient improves, the diagnosis is considered validated. This is often the clinical scenario. However, a definitive diagnosis of PUD can be made only by radiologic studies or endoscopy.

Although the history of a patient with PUD may vary from no symptoms at all to severe crushing chest pains mimicking a myocardial infarction, PUD is classically described as a burning or gnawing epigastric pain. Ulcer disease can cause early morning awakening (typically 2 to 4 AM), believed to be secondary to the circadian changes in acid secretion (Sleisenger & Fordtran,). Although acid secretion is low in the early morning, there is typically no food in the stomach to buffer the acid; thus, even low levels of acid secretion may aggravate ulcer disease. Epigastric pain occurs in both duodenal and gastric ulcer disease,
but radiation of the pain to the back is more common in duodenal ulcer disease, especially that found on the posterior wall of the duodenal bulb. The association of food with pain should be established. Eating often helps alleviate symptoms of duodenal ulcers but may exacerbate the pain of gastric ulcers.

In addition to the patient’s abdominal complaints, the provider must also focus on exacerbating factors. Asking the patient about alcohol consumption (which may aggravate ulcer disease but is not a direct cause of ulcer disease) and smoking is essential. Inquiring about use of NSAIDs and steroids is also necessary. Often direct questioning needs to be done to elicit NSAID use because many patients do not consider over-the-counter medications to be “medicines.” Identifying these culprits will help in both treatment and prevention of recurrent PUD.

The physical examination of patients with PUD may be unrevealing. It should focus on identifying complications of PUD. Vital signs and orthostatic pressures should be obtained to help identify blood loss secondary to gastrointestinal (GI) bleeding. Pain-free GI bleeding occurs most frequently in the elderly, especially when NSAIDs are involved. A thorough abdominal examination must be done, noting any masses and any signs of an acute abdomen (eg, rigidity and lack of bowel sounds), which occur with perforation of an ulcer and resultant peritonitis. A rectal examination should be done to reveal any occult blood or frank bleeding.

Although PUD is a common, usually benign, disease, complications of PUD may be fatal. Complications include perforation of the ulcer with resultant peritonitis; penetration of the ulcer into the pancreas, which can result in pancreatitis; excessive edema around the ulcer, causing an outlet obstruction; and bleeding significant enough to cause death.

Esophagogastroduodenoscopy (EGD) is considered the gold standard for evaluating the upper GI tract. It has several advantages over barium studies, including the ability to diagnose subtle mucosal lesions, to take samples of lesions for biopsy, and to perform therapeutic measures (eg, cauterization or injection therapy of bleeding ulcers). Endoscopy tends to take less time to perform than barium studies and is more appropriate in an acute setting. Disadvantages of EGD include the need for sedation, discomfort, and the invasiveness of the procedure, with the accompanying risk of tears and perforation. Patients with respiratory difficulties tend to have more difficulty with the procedure because they fear the endoscope will obstruct their airway. EGD may also be contraindicated in patients with recent myocardial infarctions. Endoscopy tends to cause excessive catecholamine release, possibly leading to arrhythmias. In addition, the rubbing of the endoscope as it passes next to the right atrium (while in the esophagus) may also cause arrhythmias.

Barium studies (an upper GI series) remain a useful tool in diagnosing various types of pathology in the upper GI tract, especially when EGD is contraindicated. They are also useful when community resources and access to an endoscopist are limited.

EGD or barium studies may be done when the patient presents initially, but they must be done if the disease does not respond to the treatment plan. Ulcers are often described as active, chronic, or healed or old. Active and chronic ulcers must be addressed with appropriate medications and lifestyle changes. Healed or old ulcers with scarring do not necessarily require medications, but lifestyle modifications (described below) should begin.

Testing for H. pylori is often done when the diagnosis of PUD is made. However, a diagnosis of PUD cannot be made by the presence or absence of H. pylori. There are several methods of testing. Serologic testing for antibodies to H. pylori may reveal exposure to H. pylori but may not indicate active infection. Titers often remain positive after eradication of the organism (Cutler, 1996). Endoscopy with biopsy of the prepyloric area and placement of the tissue in a rapid urease test kit is another method to detect the organism. The advantages of this method are its high sensitivity and specificity (93% and 92%, respectively). The disadvantage is the need to perform an invasive procedure to obtain the tissue. A newer method is the urease breath test, which tests for the presence of urease in expelled air and avoids the need for endoscopy.

Testing for Zollinger-Ellison syndrome should be done when a patient presents with multiple ulcers in the upper GI tract or ulcers refractory to the usual treatment modalities. This is done by measuring the fasting serum gastrin level. An elevated level (800 to 1200 pg/mL) strongly suggests Zollinger-Ellison syndrome. The next step to help confirm the diagnosis is the secretin stimulation test. If a gastrinoma is present (usually located in the head of the pancreas or the second portion of the duodenum), the serum gastrin levels will rise rapidly in the presence of secretin. After a bolus of secretin is given intravenously, multiple venous blood samples are obtained at predetermined intervals, and the gastrin levels are then measured in each sample. If there is a rise of more than 200 pg/mL in any of the samples after the secretin is given, compared to the gastrin level before the secretin, a diagnosis of Zollinger-Ellison syndrome can be made.

Biopsy samples for PUD should be obtained based on the location of the ulcer. Samples should be taken for biopsy from all gastric ulcers and re-evaluated by endoscopy after 4 to 6 weeks of treatment. Duodenal ulcers do not need to be evaluated by biopsy. A biopsy sample must be taken in any ulcer in which healing cannot be documented.