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Pathophysiology and laboratory diagnosis of pernicious anemia
1Department of Medicine, Southern Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, and Australian Clinicalabs, Clayton, VIC, Australia. ban-hock.toh@monash.edu.
Insights
Pernicious anemia results from autoimmune gastritis damaging stomach parietal cells, leading to intrinsic factor and acid loss. Diagnosis involves antibodies, anemia, and elevated gastrin.
Area of Science:
- Gastroenterology
- Immunology
- Hematology
Background:
- Pernicious anemia is a hematologic condition stemming from chronic atrophic gastritis affecting stomach parietal cells.
- Autoimmune gastritis, characterized by Th1 CD4 T cell activation against gastric H/K ATPase, precedes corpus atrophy by 10-20 years.
Purpose of the Study:
- To detail the pathogenesis, clinical presentation, and diagnostic criteria of pernicious anemia and its precursor, autoimmune gastritis.
- To highlight the association of autoimmune gastritis with other autoimmune conditions.
Main Methods:
- Review of the pathophysiology of autoimmune gastritis and pernicious anemia.
- Description of diagnostic laboratory findings, including antibodies and blood counts.
- Discussion of the clinical associations of autoimmune gastritis.
Main Results:
- Autoimmune gastritis involves parietal cell antibodies targeting gastric H/K ATPase, leading to loss of intrinsic factor and HCl acid.
- Intrinsic factor loss causes cobalamin deficiency, while acid loss results in iron deficiency anemia.
- Laboratory diagnosis relies on specific antibodies, megaloblastic anemia, and elevated serum gastrin.
Conclusions:
- Pernicious anemia is a complex condition with a long preclinical phase of autoimmune gastritis.
- Accurate diagnosis requires a combination of serological markers, hematologic evaluation, and assessment of acid secretion.
- Autoimmune gastritis is linked to other autoimmune disorders, suggesting a shared underlying immune dysregulation.
Abstract:
Pernicious anemia is the hematologic manifestation of chronic atrophic gastritis affecting the corpus of the stomach that denudes the gastric mucosa of gastric parietal cells. Asymptomatic autoimmune gastritis, a chronic inflammatory disease of the gastric mucosa, precedes the onset of corpus atrophy by 10-20 years. The gastritis arises from activation of pathologic Th1 CD4 T cells to gastric H/K ATPase that is normally resident on gastric mucosal secretory membranes. The onset of autoimmune gastritis is marked by circulating parietal cell antibody to gastric H/K ATPase. Gastric parietal cells produce two essential biologics: intrinsic factor and HCl acid. Pernicious anemia is a consequence of intrinsic factor loss and neutralizing intrinsic factor antibody that impairs cobalamin absorption. Acid loss leads to iron deficiency anemia that precedes cobalamin-deficient pernicious anemia by 20 years. Laboratory diagnosis rests on parietal cell antibody with or without intrinsic factor antibody, cobalamin-deficient megaloblastic anemia and elevated serum gastrin from loss of acid secretion. Autoimmune gastritis is associated with autoimmune thyroiditis and type 1 diabetes mellitus.
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