What is the pathophysiology of pernicious anemia?

• A. Vitamin B12 absorption enhanced due to gastric mucosal changes
• B. Iron deficiency due to chronic blood loss
• C. Autoimmune destruction of RBC precursors
• D. Autoimmune destruction of gastric parietal cells leading to intrinsic factor deficiency and impaired B12 absorption

Answer: (D)

Pernicious anemia results from autoimmune destruction of gastric parietal cells, which produce intrinsic factor. Without intrinsic factor, vitamin B12 cannot be absorbed in the terminal ileum, so B12 deficiency develops. B12 is essential for DNA synthesis in rapidly dividing cells, including red blood cell precursors; its deficiency leads to defective DNA replication, producing large, immature red cells (megaloblastic anemia) and often neurologic symptoms due to impaired myelin synthesis. Anti-parietal cell antibodies or anti-intrinsic factor antibodies commonly accompany this condition, reinforcing the loss of IF and B12 absorption. In short, autoimmune loss of intrinsic factor causes impaired B12 absorption and the resulting megaloblastic anemia.