A 65-year-old woman comes to the emergency department with progressive fatigue and lower-extremity paresthesias. Medical history is otherwise insignificant and the patient takes no medications. Laboratory studies show a mean corpuscular volume of 112 fL. Upper gastrointestinal endoscopy shows atrophic mucosa in the gastric body and fundus and a normal-appearing antrum. Destruction of which of the following gastric layers is most likely responsible for this patient's symptoms?

Question

A 65-year-old woman comes to the emergency department with progressive fatigue and lower-extremity paresthesias.  Medical history is otherwise insignificant and the patient takes no medications.  Laboratory studies show a mean corpuscular volume of 112 fL.  Upper gastrointestinal endoscopy shows atrophic mucosa in the gastric body and fundus and a normal-appearing antrum.  Destruction of which of the following gastric layers is most likely responsible for this patient's symptoms?

Quizplus · Accepted Answer

11ec160b_378f_e07d_9249_63b66faefee7_MD0001_00 The combination of lower-extremity paresthesias, macrocytic red blood cells (RBCs), and gastric body and fundal atrophy is highly suggestive of pernicious anemia (PA). PA is an autoimmune disorder caused by the cell-mediated destruction of parietal cells, oxyntic (pale pink) cells found predominantly in the upper glandular layer of the gastric body and fundus. Over time, progressive parietal cell destruction leads to chronic atrophic gastritis (ie, autoimmune gastritis), characterized histologically by a CD4-predominate inflammatory infiltrate, oxyntic gland atrophy, and intestinal metaplasia (ie, replacement of normal epithelia with goblet cells). Parietal cells are responsible for the secretion of hydrochloric acid and intrinsic factor, a glycoprotein that is involved in the absorption of B₁₂ (cobalamin, an essential nutrient). After a critical number of parietal cells are destroyed and hepatic stores of cobalamin are depleted, patients develop B₁₂ deficiency. This results in a megaloblastic anemia, characterized by macro-ovalocytes (elevated mean corpuscular volume, oval-shaped RBCs) and hypersegmented neutrophils. Patients also develop neurologic dysfunction due to demyelination of the dorsal and lateral spinal tracts, resulting in paresthesias and ataxia. (Choice A) This region contains simple columnar epithelial cells that secrete mucus to protect the gastric lining from acid. (Choice C) In contrast to the parietal cell-rich superficial gastric glands, the deeper region of the gastric glands has a preponderance of small, basophilic, granular chief cells that synthesize and secrete pepsinogen. Pyloric glands contain enteroendocrine cells with apical nuclei and light cytoplasm that produce gastrin and somatostatin. (Choice D) This region contains the muscularis mucosae, which separates the lamina propria from the submucosa. (Choice E) This region contains the submucosa, which consists of well-vascularized connective tissue. Educational objective: Pernicious anemia is an autoimmune disorder caused by the cell-mediated destruction of parietal cells in the superficial upper glandular layer of the gastric body and fundus. Parietal cells are responsible for the secretion of hydrochloric acid and intrinsic factor, a glycoprotein involved in the absorption of B₁₂. Deficiency leads to megaloblastic anemia and neurologic dysfunction.

A 65-Year-Old Woman Comes to the Emergency Department with Progressive