Review Question - QID 107396

The patient’s hematocrit, clinical presentation, blood smear finding, and neurologic involvement suggests anemia due to vitamin B12 deficiency. Her past medical history of Hashimoto’s thyroiditis suggest that her B12 deficiency is secondary to an autoimmune process, such as type A chronic gastritis; therefore, you would expect serum anti-intrinsic factor and anti-parietal cell antibodies.

Gastritis is a mucosal inflammatory process that is commonly due to an infectious or autoimmune etiology. Type A gastritis is an autoimmune metaplasic atrophic gastritis that can target the gastric corpus, destroying parietal cells. This subsequently leads to an increase in gastric pH due to a decrease in gastric acid production, as well as a loss of intrinsic factor production since intrinsic factor is produced by the parietal cells. This increase in pH can allow bacterial growth, leading to carcinogenic by-product production, enabling carcinogenesis. Lack of intrinsic factor impairs B12 absorption, resulting in hepatic depletion of B12 stores, and ultimately leading to pernicious anemia.

Langan et al. provides us with an update on vitamin B12 deficiency. Cobalamin deficiency is a common cause of megaloblastic anemia, central nervous system symptoms, and homocysteine level elevation. Some risk factors for this deficiency include proton pump inhibitors and metformin use.

Neumann et al. discuss the pathogenesis, pathology and management of autoimmune gastritis. Even though the cause of autoimmune gastritis is unclear, it is commonly associated with other primary autoimmune states. The diagnosis of this condition depends upon histopathologic features characteristic of this disease, and demonstration of intrinsic factor and parietal cell autoantibodies.

Illustration A shows hypersegmented neutrophils, characteristic of both vitamin B9 and vitamin B12 deficiency. Illustration B shows vitamin B12’s involvement in enzymatic reactions such as fatty acid metabolism and methionine production.

Incorrect Answers:
Answer 1: Achlorhydria (absent or low acid) would cause continuous stimulation of gastrin-secreting cells leading to the opposite of G-cell atrophy. Hypergastrinemia leads to endocrine-like cell hyperplasia in the corpus, potentially leading to the presence of neuroendocrine tumors.
Answer 3: Vitamin B12 is involved in the conversion of methylmalonyl-CoA to succinyl-CoA. Therefore, you would expect an increase in methylmalonic acid.
Answer 4: Vitamin B12 deficiency decreases the conversion of homocysteine to methionine; homocysteine has both prothrombotic and atherogenic properties. Therefore, increased homocysteine levels would not be associated with an antithrombotic state.
Answer 5: Although Diphyllobothrium latum is associated with B12 deficiency and is high-yield for the boards, it is not the best answer due to the patient’s autoimmune past medical history.