Chapter 198 Peptic Ulcer—Duodenal and Gastric
Peptic ulcer formation occurs in the stomach (gastric ulcer) and the first portion of the small intestine (duodenal ulcer). Duodenal ulcers are more common, with an estimated prevalence of 6% to 12% in the United States. Approximately 10% of the U.S. population have clinical evidence of duodenal ulcer at some time in their life. It is four times more common in men than in women and four to five times more common than clinically evident benign gastric ulcer.
Although symptoms of a peptic ulcer may be absent or quite vague, most peptic ulcers are associated with abdominal discomfort noted 45 to 60 minutes after meals or during the night. In the typical case the pain is described as gnawing, burning, cramplike, aching, or “heartburn.” Eating or using antacids usually results in great relief. In the elderly, the presentation of peptic ulcer disease may also be subtle and atypical when compared with that in younger patients, leading to a delay in diagnosis.
Even though duodenal and gastric ulcers occur at different locations, they appear to be the result of similar mechanisms. Specifically, the development of a duodenal or gastric ulcer is due to damage to the protective factors that line the stomach and duodenum.
In the past, the focus has primarily been on the acidic secretions of the stomach as the primary cause of both gastric and duodenal ulcers. However, more recently the focus has been on the bacterium Helicobacter pylori and nonsteroidal anti-inflammatory drugs (NSAIDs).
Gastric acid is extremely corrosive, with a pH of 1 to 3. To protect against ulcers, the lining of the stomach and small intestine is protected by a layer of mucin. In addition, the constant renewal of intestinal cells and the secretion of factors that neutralize the acid when it comes in contact with the stomach and intestinal linings also protect against ulcer formation.
Excessive gastric acid output is rarely a factor in gastric ulcers, because in these patients gastric acid output is usually normal or reduced. In contrast, almost one half of patients with duodenal ulcers have increased gastric acid output. This increase may be due to an increase in the number of parietal cells. As a group, patients with duodenal ulcers have twice as many parietal cells as normal controls.
Even with an increase in gastric acid output, under normal circumstances there are enough protective factors to prevent ulcer formation. However, when the integrity of these protective factors is impaired, an ulcer can form. A loss of integrity can be due to H. pylori, NSAIDs, alcohol, nutrient deficiency, stress, and many other factors. Of these factors, H. pylori and NSAIDs are by far the most significant.
Several chronic diseases have also been associated with an increased risk of developing peptic ulcers. These include Crohn’s disease, chronic renal failure, liver cirrhosis, cystic fibrosis, chronic obstructive pulmonary disease, systemic mastocytosis (a condition in which there are too many immune mast cells in the body), and myeloproliferative disorders (polycythemia vera, chronic myelogenous leukemia, agnogenic myeloid metaplasia, and essential thrombocythemia).1
The role of H. pylori in peptic ulcer disease has been extensively investigated. It has been shown that 90% to 100% of patients with duodenal ulcers, 70% with gastric ulcers, and about 50% of those above age 50 test positive for H. pylori.2 However, more than 80% of H. pylori–infected people never actually develop an ulcer.3 Although it is has been discovered that certain genotypic strains of H. pylori may confer additional cytotoxic risk for gastric pathologies,4 conflicting information warrants further research.5,6 The presence of H. pylori is determined by testing the level of antibodies to H. pylori in the blood or saliva or by culturing material collected during an endoscopy as well as measuring the breath for urea.
Low gastric output as well as low antioxidant content in the gastrointestinal mucosa is thought to predispose to H. pylori colonization. This increases gastric pH, thereby setting up a positive feedback scenario and increasing the likelihood for the colonization of the stomach and duodenum with other organisms.7
Aspirin and other NSAIDs are associated with a significant risk of peptic ulcer. In addition, the combination of NSAID use and smoking is particularly harmful to the ulcer patient.8 Although most studies documenting the relative frequency of peptic ulcers as a consequence of NSAID use have focused on NSAIDs in the treatment of arthritis and headaches, the risk of gastrointestinal bleeding due to peptic ulcers was recently evaluated for aspirin at daily doses of 300, 150, and 75 mg—doses commonly recommended to prevent heart attacks and strokes.9
A study conducted at five test hospitals in England found an increased risk of gastrointestinal bleeding due to peptic ulcer at all dosage levels. However, the dosage of 75 mg/day was associated with 40% less bleeding than 300 mg/day and 30% less bleeding than 150 mg/day. The researchers concluded: “No conventionally used prophylactic aspirin regimen seems free of the risk of peptic ulcer complications.”
Although there has been a reduction in ulcers induced by NSAIDs with the development of the selective cyclooxygenase-2 inhibitors (Rofecoxib, Celecoxib) for arthritic conditions, aspirin-induced ulcers continue to remain an ongoing issue owing to the increased use of aspirin for protection against cardiovascular events.8
Individuals experiencing any symptoms of a peptic ulcer need competent medical care. Peptic ulcer complications such as hemorrhage, perforation, and obstruction represent medical emergencies that require immediate hospitalization.
Stress is universally believed to be an important factor in the pathogenesis of peptic ulcers. However, this belief is based on uncontrolled observations. The medical literature is controversial, and every substantial attempt to examine this assumption has been fraught with methodologic errors.10
This problem is further complicated by the observation that men and women with peptic ulcers appear to have distinctly different psychological profiles. In addition, several studies have shown that the number of stressful life events is not significantly different in peptic ulcer patients as compared with carefully selected, ulcer-free controls. These data suggest that it is not simply the amount of stress but rather the patient’s response to it that is the significant factor. A large prospective study of 4000 persons who had no history of peptic ulcer disease revealed that those who perceived more significant stress in their lives were at increased risk for developing peptic ulcers11 (see Chapter 60 for a more complete discussion).
Psychological factors are probably important in some patients with peptic ulcer disease but not in others. As a group, ulcer patients have been characterized as tending to repress emotions, patients should be encouraged to discover enjoyable outlets of self-expression and emotion.
Increased frequency, decreased response to peptic ulcer therapy, and an increased mortality due to peptic ulcers are all related to smoking. Three postulated mechanisms for this association are the following11:
Bile salts are extremely irritating to the stomach and initial portions of the duodenum. Bile salt reflux induced by smoking appears to be the most likely factor responsible for the greater incidence of peptic ulcer among smokers. However, the psychological aspects of smoking are also important, because the chronic anxiety and psychological stress associated with smoking appear to worsen ulcer activity.
Clinical and experimental evidence points to food allergy as a prime etiologic factor.12–15 The lesions of peptic ulcers and the Arthus reaction (a local inflammatory response due to deposition of immune complexes in tissues) show the same microanatomic changes.2 In one study, 98% of patients with radiographic evidence of a peptic ulcer had coexisting lower and upper respiratory tract allergic disease.14 In another study, 25 of 43 allergic children had x-ray–diagnosed peptic ulcers.15 Clinically, an elimination diet has been used with great success in treating and preventing recurrent ulcers.13,14 Food allergy is also consistent with the high recurrence rate of peptic ulcers.
Ironically, many people with peptic ulcers soothe themselves by consuming milk, a highly allergic food. Milk should be avoided on this basis alone. However, there is additional evidence suggesting that milk should be avoided by patients with peptic ulcers; for example, population studies show that the higher the milk consumption, the greater the likelihood of ulcer, and milk significantly increases the production of stomach acid.16
A diet rich in fiber and low in refined sugar is associated with a reduced rate of duodenal ulcers as compared with a low-fiber diet.3 The therapeutic use of a high-fiber diet in patients with recently healed duodenal ulcers reduces the recurrence rate by one half.17 This is probably a result of fiber’s ability to delay gastric emptying of the liquid phase, counteracting the rapid movement of this phase into the duodenum, which is normally seen in ulcer patients. Although several fibers often used to supplement the diet (e.g., pectin, guar gum, psyllium) have been shown to produce beneficial effects, a diet rich in plant foods is best.18,19