Porth's Essentials of Pathophysiology, 4e

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Disorders of Gastrointestinal Function

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are paresthesias and numbness. Cerebral manifestations range from mild personality changes and memory loss to psychosis. In contrast to the anemia, neurologic changes are not reversed by vitamin B 12 replacement therapy. 6 Chemical Gastropathy. Chemical gastropathy repre- sents the effects of chronic gastric injury resulting from reflux of alkaline duodenal contents, pancreatic secre- tions, and bile into the stomach. It is most commonly seen in persons who have had gastroduodenostomy or gastrojejunostomy surgery. A milder form may occur in persons with gastric ulcer, gallbladder disease, or vari- ous motility disorders of the distal stomach. Ulcerative Disorders The lumen of the stomach is strongly acidic, a condition that contributes to digestion, but also has the potential to damage the mucosa and produce an ulcer. Among the conditions associated with ulceration of the gastric mucosa are peptic ulcer disease, Zollinger-Ellison syn- drome, and stress ulcers. Peptic Ulcer Disease Peptic ulcer disease is a term used to describe a group of ulcerative disorders that occur in areas of the gastric and intestinal mucosa, mainly the proximal duodenum, that are exposed to acid–pepsin secretions. 6,7,20,21 Although the incidence and prevalence of peptic ulcer has declined substantially during the past 30 years, approximately 10% of people in Western industrial countries will develop a peptic ulcer during their lifetime. 7 A peptic ulcer can affect one or all layers of the stom- ach or duodenum (Fig. 29-4). The ulcer may penetrate only the mucosal surface, or it may extend into the smooth muscle layers. Occasionally, an ulcer penetrates the outer wall of the stomach or duodenum. Spontaneous remissions and exacerbations are common. Healing of the muscularis layer involves replacement with scar tissue; although the mucosal layers that cover the scarred muscle layer regenerate, the regeneration often is less than per- fect, which contributes to repeated episodes of ulceration. Etiology and Pathogenesis. A variety of risk factors have been shown to have an association with peptic ulcer disease. The two most important are infection with the bacteria H. pylori and use of aspirin and/or NSAIDs. 20,21 In contrast to peptic ulcer from other causes, NSAID- induced gastric injury often occurs without symptoms, and life-threatening complications can develop without warning. There is reportedly less gastric irritation with the newer class of NSAIDs that selectively inhibit cylco- oxygenase-2 (COX-2–selective NSAIDs), the principal enzyme involved in prostaglandin synthesis at the site of inflammation, than with the nonselective NSAIDs that also inhibit COX-1, the enzyme involved in prostaglan- din production in the gastric mucosa. Epidemiologic studies have identified independent factors that augment the effect of H. pylori infection and NSAID-produced peptic ulcer disease. These fac- tors include advancing age, a prior history of peptic

ulcer, NSAID use, and concurrent use of corticosteroid drugs. Smoking may augment the risk of peptic ulcer by impairing healing. Genetic factors may also play a role as supported by the fact that blood-group antigens correlate with peptic ulcer disease. People with type O blood and those who do not secrete antigens in their saliva or gastric juices are at greater risk of developing duodenal ulcers. 7 Clinical Manifestations. The clinical manifestations of uncomplicated peptic ulcer focus on discomfort and pain. The pain, which is described as burning, gnawing, or cramplike, usually is rhythmic and frequently occurs when the stomach is empty—between meals and at 1 or 2 o’clock in the morning. The pain usually is located over a small area near the midline in the epigastrium near the xiphoid, and may radiate below the costal margins, into the back, or, rarely, to the right shoulder. Superficial and deep epigastric tenderness and voluntary muscle guard- ing may occur with more extensive lesions. An additional characteristic of ulcer pain is periodicity. The pain tends to recur at intervals of weeks or months. During an exac- erbation, it occurs daily for a period of several weeks and then remits until the next recurrence. Characteristically, the pain is relieved by food or antacids. Complications. The most common complications of peptic ulcer are hemorrhage, perforation, and gastric outlet obstruction. Hemorrhage is caused by bleeding from granulation tissue or from erosion of an ulcer into FIGURE 29-4. Gastric ulcer.The stomach has been opened to reveal a sharply demarcated, deep peptic ulcer on the lesser curvature. (From Rubin E, Farber JL, eds. Rubin’s Pathology: Clinicopathologic Foundations of Medicine. 3rd ed. Philadelphia, PA: Lippincott Williams &Wilkins; 1999:693.)