eMedicine Specialties > Gastroenterology > Stomach

Gastritis, Atrophic

Author: Antonia R Sepulveda, MD, PhD, Associate Professor of Pathology, University of Pennsylvania School of Medicine; Director of Surgical Pathology, Director of Surgical Pathology Fellowship, Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania
Contributor Information and Disclosures

Updated: Mar 22, 2006

Introduction

Background

Atrophic gastritis is a histopathological entity characterized by chronic inflammation of the gastric mucosa with loss of gastric glandular cells and replacement by intestinal-type epithelium, pyloric-type glands, and fibrous tissue. Atrophy of the gastric mucosa is the endpoint of chronic processes, such as chronic gastritis associated with Helicobacter pylori infection, other unidentified environmental factors, and autoimmunity directed against gastric glandular cells.

The 2 main causes of atrophic gastritis result in distinct topographic types of gastritis, which can be distinguished histologically. H pylori –associated atrophic gastritis usually is a multifocal process that involves both the antrum and oxyntic mucosa of the gastric corpus and fundus, while autoimmune gastritis essentially is restricted to the gastric corpus and fundus. Individuals with autoimmune gastritis may develop pernicious anemia because of extensive loss of parietal cell mass and anti-intrinsic factor antibodies. H pylori –associated atrophic gastritis frequently is asymptomatic, but individuals with this disease are at increased risk of developing gastric carcinoma. Patients with chronic atrophic gastritis develop low gastric acid output and hypergastrinemia, which may lead to enterochromaffin-like (ECL) cell hyperplasia and carcinoid tumors.

Pathophysiology

H pylori– associated atrophic gastritis

H pylori are gram-negative bacteria that colonize and infect the stomach. The bacteria lodge within the mucous layer of the stomach along the gastric surface epithelium and the upper portions of the gastric foveolae and rarely are present in the deeper glands (see Media files 1-3). The infection usually is acquired during childhood and progresses over the lifespan of the individual if left untreated. The host response to the presence of H pylori is composed of a T-lymphocytic and B-lymphocytic response, followed by infiltration of the lamina propria and gastric epithelium by polymorphonuclear leukocytes (PMNs) that eventually phagocytize the bacteria.

Significant damage associated with the release of bacterial and inflammatory toxic products is inflicted on the gastric epithelial cells, resulting in increasing cell loss or gastric atrophy over time. During gastric mucosal atrophy, some glandular units develop an intestinal-type epithelium, and intestinal metaplasia eventually occurs in multiple foci throughout the gastric mucosa when atrophic gastritis is established. Other glands simply are replaced by fibrous tissue, resulting in an expanded lamina propria. Loss of gastric glands in the corpus, or corpus atrophy, reduces parietal cell number, which results in significant functional changes with decreased levels of acid secretion and increased gastric pH.

H pylori– associated chronic gastritis progresses with 2 main topographic patterns that have different clinicopathological consequences.

The first is antral predominant gastritis. Inflammation that is mostly limited to the antrum characterizes antral predominant gastritis. Individuals with peptic ulcers usually develop this pattern of gastritis, and it is the most frequently observed pattern in Western countries.

The second is multifocal atrophic gastritis. Involvement of the corpus, fundus, and gastric antrum with progressive development of gastric atrophy (ie, loss of gastric glands) and partial replacement of gastric glands by intestinal-type epithelium (intestinal metaplasia) characterize multifocal atrophic gastritis. Individuals who develop gastric carcinoma and gastric ulcers usually have this pattern of gastritis. This pattern is observed more often in developing countries and in Asia.

Autoimmune atrophic gastritis

The development of chronic atrophic gastritis limited to corpus-fundus mucosa and marked diffuse atrophy of parietal and chief cells characterize autoimmune atrophic gastritis (see Media file 2, Media file 4). Autoimmune gastritis is associated with serum antiparietal and antiintrinsic factor antibodies that cause intrinsic factor (IF) deficiency, which, in turn, causes decreased availability of cobalamin (vitamin B-12) and, eventually, pernicious anemia in some patients. Autoantibodies are directed against at least 3 antigens, including IF, cytoplasmic (microsomal-canalicular), and plasma membrane antigens. Two types of IF antibodies are detected (types I and II). Type I IF antibodies block the IF-cobalamin binding site, thus preventing the uptake of vitamin B-12. Cell-mediated immunity also contributes to the disease. T-cell lymphocytes infiltrate the gastric mucosa and contribute to the epithelial cell destruction and resulting gastricatrophy.

Frequency

United States

The frequency of atrophic gastritis is not known because chronic gastritis frequently is asymptomatic; however, prevalence parallels the 2 main causes of gastric atrophy, chronic H pylori infection (when the infection follows a course of multifocal atrophic gastritis) and autoimmune gastritis. In both conditions, atrophic gastritis develops over many years and is found later in life. The frequency of H pylori infection in the United States is similar to that found in other Western countries. In the United States, H pylori infection affects approximately 20% of persons younger than 40 years and 50% of those older than 60 years. However, subgroups of different ethnic backgrounds show different frequencies for the infection, which is more common in Asian, Hispanic, and African American persons.

International

An estimated 50% of the world's population is infected with H pylori, and, therefore, chronic gastritis is extremely common. H pylori infection is highly prevalent in Asia and in developing countries, and multifocal atrophic gastritis is more prevalent in these areas of the world. Autoimmune gastritis is a relatively rare disease, most frequently observed in individuals of northern European descent and in African Americans. The prevalence of pernicious anemia resulting from autoimmune gastritis has been estimated as 127 cases per 100,000 members of the population in the United Kingdom, Denmark, and Sweden. The incidence of pernicious anemia is increased in patients with other immunological diseases, including Graves disease, myxedema, thyroiditis, and hypoparathyroidism.

Mortality/Morbidity

Mortality and morbidity associated with atrophic gastritis are related to specific clinicopathological complications that may develop during the course of the underlying disease.

• Similar to other individuals infected with H pylori, patients who develop atrophic gastritis may complain of dyspeptic symptoms. Individuals with either H pylori– associated atrophic gastritis or autoimmune atrophic gastritis or autoimmune atrophic gastritis carry an increased risk of developing gastric carcinoid tumors and gastric carcinoma.
• The major effects of autoimmune gastritis are consequences of the loss of parietal and chief cells and include achlorhydria, hypergastrinemia, loss of pepsin and pepsinogen, anemia, and an increased risk of gastric neoplasms.
• Autoimmune atrophic gastritis represents the most frequent cause of pernicious anemia in temperate climates. The risk of gastric adenocarcinoma appears to be at least 2.9 times higher in patients with pernicious anemia than in the general population. A recent study also reported an increased frequency of esophageal squamous carcinomas in patients with pernicious anemia.
• Autoimmune atrophic gastritis and H pylori gastritis may also have a significant role in the development of unexplained or refractory iron deficient anemia.

Race

• H pylori– associated atrophic gastritis appears to be more common among Asian and Hispanic persons than people of other races.
• In the United States, H pylori infection is more common among African Americans than white persons, a difference attributed to socioeconomic factors. However, whether higher rates of H pylori– associated atrophic gastritis are observed among African Americans has not been established.
• Autoimmune atrophic gastritis is more frequent in individuals of northern European descent and African Americans and is much less frequent in southern Europeans and Asians.

Sex

• Atrophic gastritis affects both sexes similarly.
• H pylori infection affects both sexes to the same extent.
• Autoimmune gastritis has been reported to affect both sexes, with a female-to-male ratio of 3:1.

Age

• Atrophic gastritis is detected late in life because it results from the effects of long-standing damage to the gastric mucosa.
• H pylori– associated atrophic gastritis develops gradually, but extensive multifocal atrophy usually is detected in individuals older than 50 years.
• Patients with autoimmune atrophic gastritis usually present with pernicious anemia, which typically is diagnosed in individuals aged approximately 60 years; however, pernicious anemia can be detected in children (juvenile pernicious anemia).

Clinical

History

Atrophic gastritis represents the end stage of chronic gastritis, both infectious and autoimmune. In both cases, the clinical manifestations of atrophic gastritis are those of chronic gastritis, but pernicious anemia is observed specifically in patients with autoimmune gastritis and not in those with H pylori– associated atrophic gastritis.

• Acute H pylori infection usually is not detected clinically, but experimental infection results in a clinical syndrome characterized by epigastric pain, fullness, nausea, vomiting, flatulence, malaise, and, sometimes, fever. The symptoms resolve in approximately a week, regardless of whether H pylori organisms are eliminated.
• Persistence of the organism causes H pylori chronic gastritis, which usually is asymptomatic or may manifest as gastric pain and, rarely, nausea, vomiting, anorexia, or significant weight loss. Symptoms associated with complications of chronic H pylori– associated atrophic gastritis may develop, including gastric ulcers and gastric adenocarcinoma.
• Autoimmune atrophic gastritis clinical manifestations primarily are related to deficiency in cobalamin, which is not absorbed adequately because of IF deficiency resulting from severe gastric parietal cell atrophy. The disease has an insidious onset and progresses slowly. Cobalamin deficiency affects the hematological, GI, and neurologic systems.
  • Hematologic manifestations: The most significant manifestation is megaloblastic anemia, but, rarely, purpura due to thrombocytopenia may develop. Symptoms of anemia include weakness, light-headedness, vertigo and tinnitus, palpitations, angina, and symptoms of congestive failure.
  • GI manifestations: The lack of cobalamin is associated with megaloblastosis of the GI tract epithelium. Patients sometimes complain of a sore tongue. Anorexia with moderate weight loss occasionally associated with diarrhea may result from malabsorption associated with megaloblastic changes in the epithelium of the small intestine.
  • Neurologic manifestations: These result from demyelination, followed by axonal degeneration and neuronal death. The affected sites include peripheral nerves, posterior and lateral columns of the spinal cord, and the cerebrum. Signs and symptoms include numbness and paresthesias in the extremities, weakness, and ataxia. Sphincter disturbances may be present. Mental function disturbances vary from mild irritability to severe dementia or psychosis. Neurologic disease may occur in patients with normal hematocrit and normal red cell parameters.
  • Pernicious anemia: Patients with pernicious anemia have an increased frequency of gastric polyps and have a 2.9-fold increase in gastric cancer.
  • Additionally, patients with autoimmune atrophic gastritis and H pylori infection may manifest iron deficient anemia that may be refractory to oral iron treatment. H pylori eradication in combination with continued oral iron therapy was shown to result in a significant increase in hemoglobin levels.

Physical

Physical examination is of little contributory value in atrophic gastritis; however, some findings are associated specifically with the complications of H pylori– associated atrophic gastritis and autoimmune atrophic gastritis.

• In uncomplicated H pylori– associated atrophic gastritis, clinical findings are few and nonspecific.
  • Epigastric tenderness may be present.
  • If gastric ulcers coexist, guaiac-positive stool may result from occult blood loss.
• Findings in a patient with autoimmune atrophic gastritis result from the development of pernicious anemia and neurologic complications.
• With severe cobalamin deficiency, the patient is pale and has slightly icteric skin and eyes. The pulse is rapid, and the heart may be enlarged. Auscultation usually reveals a systolic flow murmur.

Causes

Atrophic gastritis usually is associated with either chronic H pylori infection or with autoimmune gastritis. The environmental subtype of atrophic gastritis corresponds mostly with H pylori– associated atrophic gastritis, although other unidentified environmental factors may play a role in the development of gastric atrophy.

• Chronic gastritis caused by H pylori infection of the stomach
  • H pylori infection of the stomach is by far the most common cause of chronic atrophic gastritis.
  • Whether H pylori infection follows the multifocal atrophic gastritis pathway or the nonatrophic antral gastritis pathway may be related to genetic susceptibility factors, environmental factors that modulate the host-bacterial interaction, or bacterial strains.
  • Although H pylori possessing the cag (cytotoxin-associated gene) pathogenicity island have been shown to have increased virulence, to cause higher levels of mucosal inflammation, and to be present more frequently in individuals infected with H pylori who develop gastric cancer, no specific virulence factors have been identified that might be useful to predict specific H pylori disease outcome.
  • Host factors or the effects of other environmental agents are likely to be the determinant elements modulating patterns of disease progression. For example, family relatives of individuals with gastric cancer develop pangastritis more frequently in response to H pylori infection and they also develop multifocal intestinal metaplasia more often, a preneoplastic lesion of the stomach and a component of H pylori– associated atrophic gastritis.
• Autoimmune atrophic gastritis
  • Autoimmune atrophic gastritis is a type of chronic atrophic gastritis limited to corpus-fundus mucosa and characterized by marked diffuse atrophy of parietal and chief cells.
  • Autoimmune gastritis is associated with serum antiparietal and anti-IF antibodies that cause IF deficiency, which, in turn, causes decreased availability of cobalamin and, eventually, pernicious anemia in some patients.
  • In some families, the disease appears to be transmitted with an autosomal dominant pattern of inheritance.

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