Pivoting from blood to stomach
The most common cause of vitamin B12 deficiency is pernicious anemia. What is the primary pathology in pernicious anemia, i.e., the most proximate cause?
The scheme below, which you saw in the previous section, highlights the pathway of vitamin B12 from stomach to blood.
Before going any further, let’s consider a broader differential diagnosis for vitamin B12 deficiency:
- Impaired gastrointestinal absorption of vitamin B12:
- Atrophic gastritis (pernicious anemia)
- Gastrectomy (deficiency in intrinsic factor, hypo- or achlorhydria)
- Bariatric surgery (hypo- or achlorhydria)
- Corpus-predominant Helicobacter pylori gastritis (hypo- or achlorhydria)
- Long-term proton pump inhibitor therapy (hypo- or achlorhydria)
- Intestinal causes of impaired absorption:
- Blind loop syndrome
- Ileal disease or resection
- Fish tapeworm from eating uncooked fish
- Pancreatic insufficiency (lack of vitamin B12 release from haptocorrin complex due to inadequate pancreatic enzyme activity)
- Decreased intake of vitamin B12:
- Vegan diet (about 50% of vegans have B12 deficiency)
- Vegetarian diet (about 7% have B12 deficiency)
- Inherited causes of defective vitamin B12 absorption or metabolism
Which of the following would support the diagnosis of pernicious anemia?
There are two antibodies associated with pernicious anemia, anti-intrinsic factor (IF) antibodies and anti-parietal cell antibodies:
|Parameter||Anti-IF antibodies||Anti-parietal cell antibodies|
|Antibody target||Intrinsic factor||Gastric enzyme H+/K+-ATPase on gastric parietal cells|
|Sensitivity||40-60%||80%-90%, especially during early stages of disease|
Only anti-intrinsic factor antibodies were ordered in this patient. They were positive:
The database, then, is consistent with a diagnosis of pernicious anemia, caused by atrophic gastritis, and leading to malabsorption of vitamin B12 and macrocytic anemia. Again, note that the primary lesion is in the stomach, not the bone marrow. The bone marrow (and neurological system) suffer collateral damage.