- The primary cause of pernicious anemia is a deficiency of Vitamin B12 (cobalamin).
- This condition results from an autoimmune destruction of gastric parietal cells, which leads to a lack of intrinsic factor, a protein essential for the absorption of Vitamin B12 in the terminal ileum.
- Without intrinsic factor, Vitamin B12 cannot be adequately absorbed, leading to its deficiency.

- Vitamin B12 is crucial for DNA synthesis, particularly in red blood cell production.
- Its deficiency causes megaloblastic anemia, characterized by the presence of large, immature red blood cells.
- Pernicious anemia is a specific form of megaloblastic anemia caused primarily by impaired absorption of Vitamin B12 rather than inadequate dietary intake.

Other vitamins like Vitamin B6 (pyridoxine) and folic acid also play roles in hematopoiesis, but their deficiencies lead to different clinical presentations and are not the underlying cause of pernicious anemia. Vitamin C deficiency results in scurvy, which does not involve anemia of the pernicious type.

Reference: Harrison's Principles of Internal Medicine, 20th Edition, Chapter 117