title: Pathophysiology and laboratory diagnosis of pernicious anemia.
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.
authors.affiliation: Department 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.
authors.forename: Ban-Hock
authors.initials: BH
authors.lastname: Toh
mesh_terms: D000752:Anemia, Pernicious / Q000175:diagnosis* / Q000209:etiology*; D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology; D005757:Gastritis, Atrophic / Q000150:complications* / Q000175:diagnosis*; D006801:Humans
keywords: Cobalamin; Gastrin; Intrinsic factor antibody; Iron deficiency anemia; Parietal cell antibody