intrinsic-factor and Hyperplasia

Autoimmune gastritis (AG) is a corpus-restricted chronic atrophic gastritis associated with intrinsic factor deficiency, either with or without pernicious anemia. Autoimmune gastritis is a microscopic disease because patients present with no or vague symptoms, and clinicians rarely find endoscopic changes. Autoimmune gastritis only becomes a clinical disease when pathologists diagnose it in gastric biopsies performed for a variety of clinical indications. Unfamiliarity with this disease can result in misdiagnosis of patients, and thus inadequate patient management.. To review the pathogenesis, clinical features, diagnostic criteria, differential diagnoses, sequelae, and surveillance recommendations for AG.. The sources of the study include a review of the pertinent literature for AG.. Autoimmune gastritis is an important disease characterized by a loss of oxyntic mucosa and presence of metaplastic epithelium and enterochromaffin-like cell hyperplasia. Awareness and proper diagnosis are critical to prevent mismanagement of patients.

Topics: Anemia, Pernicious; Autoimmune Diseases; Biopsy; Chronic Disease; Diagnosis, Differential; Diagnostic Errors; Epithelium; Gastritis, Atrophic; Humans; Hyperplasia; Intrinsic Factor; Metaplasia; Stomach

Topics: Acetylcholine; Achlorhydria; Adenoma; Anemia, Pernicious; Atrophy; Duodenal Ulcer; Endocrine System Diseases; Gastrectomy; Gastric Juice; Gastric Mucins; Gastric Mucosa; Gastrins; Gastritis; Humans; Hyperplasia; Intrinsic Factor; Stomach Ulcer; Vagus Nerve; Zollinger-Ellison Syndrome

The orderly differentiation of cell lineages within gastric glands is regulated by a complicated interplay of local mucosal growth factors and hormones. Histamine secreted from enterochromaffin-like cells plays an important role in not only stimulated gastric acid secretion but also coordination of intramucosal growth and lineage differentiation. We have examined histidine-decarboxylase (HDC)-deficient mice, which lack endogenous histamine synthesis, to evaluate the influence of histamine on differentiation of fundic mucosal lineages and the development of metaplasia following induction of acute oxyntic atrophy. Stomachs from HDC-deficient mice and wild-type mice were evaluated at 8 wk and 12 mo of age. DMP-777 was administrated orally to 6-wk-old mice for 1 to 14 days. Sections of gastric mucosa were stained with antibodies against Mist1, intrinsic factor, H/K-ATPase, trefoil factor 2 (TFF2), chromogranin A, and Ext1 and for the cell cycle marker phospho-histone H3. HDC-deficient mice at 8 wk of age demonstrated a prominent increase in chief cells expressing Mist1 and intrinsic factor. Importantly Mist1-positive mature chief cells were present in the midgland region as well as at the bases of fundic glands, indicating a premature differentiation of chief cells. Mice dually deficient for both HDC and gastrin showed a normal distribution of chief cells in fundic glands. Treatment of HDC-deficient mice with DMP-777 led to loss of parietal cells and an accelerated and exaggerated emergence of mucous cell metaplasia with the presence of dual intrinsic factor and TFF2-expressing cells throughout the gland length, indicative of the emergence of spasmolytic polypeptide-expressing metaplasia (SPEM) from chief cells. These findings indicate that histamine, in concert with gastrin, regulates the appropriate differentiation of chief cells from mucous neck cells as they migrate toward the bases of fundic glands. Nevertheless, histamine is not required for emergence of SPEM following acute oxyntic atrophy.

Topics: Age Factors; Animals; Azetidines; Basic Helix-Loop-Helix Transcription Factors; Cell Count; Cell Differentiation; Chief Cells, Gastric; Chromogranin A; Enterochromaffin-like Cells; Enzyme Inhibitors; Gastric Fundus; Gastric Mucosa; Gastrins; Histamine; Histidine Decarboxylase; Hyperplasia; Hypertrophy; Intrinsic Factor; Metaplasia; Mice; Mice, Inbred BALB C; Mice, Knockout; Mucins; Muscle Proteins; N-Acetylglucosaminyltransferases; Parietal Cells, Gastric; Peptides; Piperazines; Trefoil Factor-2

Mucosal biopsies from multiple sites in the stomachs of 21 patients with pernicious anaemia have been examined. The histological changes almost always involved the entire gastric mucosa, including that of the pyloric antrum. Metaplastic changes were almost universal and consisted of intestinal metaplasia in the body and antrum and pyloric metaplasia in the body. The severity of the pyloric metaplasia was such as to make the distinction between body and antrum on biopsy impossible. No relationship was found between serum gastrin activity and the histological appearances of the gastric antrum or body.

Topics: Adult; Aged; Anemia, Pernicious; Antibodies; Atrophy; Female; Gastric Mucosa; Gastrins; Gastritis; Humans; Hyperplasia; Intrinsic Factor; Male; Metaplasia; Middle Aged; Pyloric Antrum