Why Pernicious Anemia Causes Anemia
Pernicious anemia causes anemia because intrinsic factor deficiency prevents vitamin B12 absorption in the gastrointestinal tract, which is essential for DNA synthesis and normal red blood cell production, leading to arrested erythropoiesis and megaloblastic anemia. 1, 2
Pathophysiological Mechanism
Intrinsic Factor Deficiency
- Autoimmune destruction of gastric parietal cells leads to loss of intrinsic factor production, which is absolutely required for vitamin B12 absorption in the terminal ileum 1, 2, 3
- Parietal cell antibodies are present in 97% of patients, and intrinsic factor blocking antibodies are found in 52% of cases 4
- The autoimmune gastritis causes achlorhydria and gastric body atrophy, further impairing B12 absorption 4, 5
Vitamin B12's Critical Role in Hematopoiesis
- Vitamin B12 is essential for DNA synthesis, cell reproduction, and hematopoiesis 1, 2
- Without adequate B12, DNA synthesis becomes impaired in rapidly dividing cells, particularly erythroid precursors in the bone marrow 6
- This results in arrested erythropoiesis where immature erythroblasts undergo apoptosis due to impaired DNA synthesis 6
Megaloblastic Anemia Development
- The impaired DNA synthesis causes macrocytic anemia with mean corpuscular volume (MCV) >100 fL 7
- Red blood cells become abnormally large (megaloblastic) because nuclear maturation lags behind cytoplasmic maturation 8
- The bone marrow shows megaloblastic changes with high proliferation of immature erythroblasts that are susceptible to cell death 6
Additional Hematologic Consequences
Iron Deficiency Component
- Achlorhydria from gastric atrophy impairs iron absorption, leading to concurrent iron deficiency in many patients 4, 9
- Patients with pernicious anemia commonly develop both vitamin B12 and iron deficiencies simultaneously 4
- This dual deficiency can mask the typical macrocytosis, as iron deficiency causes microcytosis 8
Severe Complications
- In rare cases, the arrested erythropoiesis can be so severe that it triggers disseminated intravascular coagulation (DIC) due to massive release of denatured DNA from dying erythroblasts 6
- Severe B12 deficiency allowed to progress beyond 3 months produces permanent degenerative lesions of the spinal cord (subacute combined degeneration) 1, 4
Clinical Pitfalls to Avoid
Never give folic acid before treating B12 deficiency - folic acid can correct the anemia but allows neurologic damage to progress irreversibly 1
The diagnosis requires demonstrating both the anemia and the underlying cause through intrinsic factor blocking antibodies (73% sensitivity, 100% specificity) and elevated fasting gastrin levels (mean 1,518 pg/mL in PA patients) 4, 5