Porth's Essentials of Pathophysiology, 4e

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Gastrointestinal and Hepatobiliary Function

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the glandular epithelium of the stomach. There are three major types of chronic gastritis: Helicobacter pylori gas- tritis, autoimmune gastritis, and chemical gastropathy. 7 Helicobacter pylori Gastritis. H. pylori gastritis is a chronic inflammatory disease of the antrum and body of the stomach caused by the bacterium H. pylori . 6,7,18,19 It is the most common cause of chronic gastritis in the United States and is estimated to infect more than half of the world’s population, particularly in developing countries. H. pylori are small, S-shaped, gram-negative rods that can colonize the mucus-secreting epithelial cells of the stomach (Fig. 29-3). The mode of transmission is not well-defined, although oral–oral, fecal–oral, and environ- mental spread are among the possible routes. H. pylori have multiple flagella, which allow them to move through the mucous layer of the stomach, and they secrete urease, which enables them to produce sufficient ammonia to buffer the acidity of their immediate environment. These properties help to explain why the organism is able to survive in the acidic environment of the stomach. H. pylori produce enzymes and toxins that have the capacity to interfere with the local protection of the gastric mucosa against acid and produce a continuous inflammatory response. This inflammatory response ini- tially consists of recruitment of neutrophils, followed by T and B lymphocytes. The inflammation may be confined to the superficial gastric epithelium or extend deeper into the gastric glands, resulting in varying degrees of atrophy (atrophic gastritis) and metaplasia that converts the gastric epithelium into intestinal-type epithelium.

Several H. pylori proteins are immunogenic and may induce intense systemic and mucosal immune responses. This antibody production does not lead to eradication of infection but may contribute to tissue damage. The clinical course of H. pylori infection is highly variable and is influenced by both microbial and host factors. Acute infection with H. pylori may cause a tran- sient illness characterized by nausea and abdominal pain that lasts for several days. After these symptoms resolve, most individuals progress to an asymptomatic infection with chronic mucosal inflammation. Chronic infection with H. pylori can lead to gastric atrophy and peptic ulcer, and is associated with increased risk of gastric ade- nocarcinoma and low-grade B-cell gastric lymphoma. Noninvasive testing for the presence of H. pylori infec- tion can be performedwith the urea breath test or fecal anti- gen test. Blood tests to obtain serologic titers of H. pylori antibodies also can be done. The serologic test can estab- lish that a person has been infected with H. pylori, but it cannot distinguish how recently the infection occurred. The goal for H. pylori gastritis treatment is complete elimination of the organism. Current treatment requires combination therapy that includes the use of two antibi- otics (clarithromycin, amoxicillin, metronidazole) with a proton pump inhibitor. H. pylori mutate rapidly to develop antibiotic-resistant strains. The combination of two or more antimicrobial agents increases the rates of cure and reduces the risk of resistant strains developing. In geographic areas with clarithromycin resistant strains of H. pylori , quadruple therapy that includes bismuth is recommended. The proton pump inhibitors raise the intragastric pH to suppress bacterial growth and opti- mize antibiotic efficacy. Chronic Autoimmune Gastritis. Autoimmune gastri- tis accounts for less than 10% of cases of chronic gas- tritis and is often associated with other autoimmune disorders such as type 1 diabetes mellitus, Hashimoto thyroiditis, and Addison disease. 6 The disorder is char- acterized by autoantibodies to the gastric parietal cells and the intrinsic factor, defective gastric acid secretion, and vitamin B 12 deficiency. 6,7 In contrast to H. pylori gastritis, autoimmune gastritis typically affects the body and fundus of the stomach, sparing the antrum. Lack of intrinsic factor disables vitamin B 12 absorption, leading to a B 12 deficiency and slow-onset megaloblastic anemia (pernicious anemia, see Chapter 13). Atrophy of the fundic pyloric and chief cells can lead to development of metaplastic changes that predispose to the development of gastric adenocarcinoma. Chronic autoimmune gastritis is noted for its slow onset and progression. Antibodies to parietal cells and intrinsic factor are present early in disease; progression to gastric atrophy probably occurs over several decades. Because of the slow onset and variable progression, persons with the disorder are diagnosed only after being affected for a number of years. Clinical presentation may be related to anemia. In addition, vitamin B 12 deficiency may cause atro- phic glossitis, in which the tongue becomes smooth and beefy red; malabsorptive diarrhea; and neuropathies. The most frequent manifestations of peripheral neuropathy

FIGURE 29-3. Infective gastritis. Helicobacter pylori appear on silver staining as small, curved rods on the surface of the gastric mucosa. (From Mitros FA. Atlas of Gastrointestinal Pathology. NewYork, NY: Grower Medical Publishing; 1988.)