A 45-year-old man complains of recurrent nausea and abdominal distress. A gastric biopsy shows atrophy of the mucosa in the fundus and body, with marked lymphocytic infiltration. Blood studies show severe macrocytic anemia with a mean corpuscular volume of 110 mm3. In addition, numerous hypersegmented neutrophils are appreciated on a blood smear. Which of the following is the MOST likely pathogenetic mechanism of this patient’s anemia?

**Core Concept**
The patient's severe macrocytic anemia with hypersegmented neutrophils suggests a deficiency in either vitamin B12 or folate, leading to impaired DNA synthesis and cell division. The gastric biopsy showing atrophy of the mucosa in the fundus and body, with marked lymphocytic infiltration, is indicative of autoimmune gastritis, which is a common cause of vitamin B12 deficiency.

**Why the Correct Answer is Right**
Autoimmune gastritis leads to the destruction of parietal cells in the stomach, which are responsible for the production of intrinsic factor, a protein necessary for vitamin B12 absorption. Without intrinsic factor, vitamin B12 cannot be absorbed from the diet, resulting in a deficiency. This deficiency impairs DNA synthesis, leading to the production of abnormally large red blood cells (macrocytosis) and hypersegmented neutrophils. The marked lymphocytic infiltration in the gastric biopsy further supports the diagnosis of autoimmune gastritis.

**Why Each Wrong Option is Incorrect**
**Option A:** Folate deficiency would also cause macrocytic anemia, but the patient's gastric biopsy showing atrophy of the mucosa in the fundus and body, with marked lymphocytic infiltration, does not support a diagnosis of folate deficiency.
**Option B:** Iron deficiency would cause microcytic anemia, not macrocytic anemia, and would not explain the patient's hypersegmented neutrophils.
**Option C:** Chronic disease would cause normocytic anemia, not macrocytic anemia, and would not explain the patient's hypersegmented neutrophils.

**Clinical Pearl / High-Yield Fact**
Autoimmune gastritis can be associated with other autoimmune disorders, such as pernicious anemia, type 1 diabetes, and Addison's disease. This association is due to the shared genetic predisposition to autoimmune diseases.

**Correct Answer: C. Impaired vitamin B12 absorption due to autoimmune gastritis leading to a deficiency.**

✓ Correct Answer: A. Autoantibodies to intrinsic factor