Intrinsic Factor Secretion
Intrinsic factor is primarily secreted by gastric parietal cells in the stomach, though some secretion also occurs in chief cells and enteroendocrine cells at the margins of gastric regions.
Primary Source of Intrinsic Factor
Gastric parietal cells are the main cellular source of intrinsic factor in humans. These cells are distributed along the length of the oxyntic glands in the stomach, with the highest density found in the neck and base of these glands 1. Parietal cells have a dual secretory function:
- Hydrochloric acid (HCl) secretion
- Intrinsic factor secretion
Cellular Mechanism of Intrinsic Factor Secretion
The secretion of intrinsic factor from parietal cells involves a specific cellular pathway:
- Intrinsic factor is initially associated with tubulovesicles scattered throughout the cytoplasm and some in rough endoplasmic reticulum (RER) 2
- Upon stimulation (e.g., by pentagastrin), these tubulovesicles migrate to the periphery of secretory canaliculi
- The intrinsic factor is then secreted via membrane-associated vesicular transport 2
- This process supports a membrane translocation-fusion mechanism for parietal cell secretion
Secondary Sources of Intrinsic Factor
While parietal cells are the predominant source, immunohistochemical studies have identified additional cellular sources of intrinsic factor in the human stomach:
- A subpopulation of chief cells, particularly at the margins of anatomical gastric regions (cardia/fundus, body/antrum) 3
- Some enteroendocrine cells 3
- Endothelial cells of the lamina propria capillaries underlying enteroendocrine cells 3
Clinical Significance
The secretion of intrinsic factor is essential for vitamin B12 absorption. Intrinsic factor binds to vitamin B12 in the stomach and facilitates its absorption in the terminal ileum 1. This process is critical because:
- Vitamin B12 absorption depends on binding to intrinsic factor to form intrinsic factor-cobalamin complexes
- These complexes are absorbed through receptor-mediated endocytosis in the terminal ileum 1
- Deficiency of intrinsic factor leads to pernicious anemia, characterized by antibody-induced destruction of gastric parietal cells 1
Pathological Considerations
In pernicious anemia, autoimmune destruction of parietal cells results in intrinsic factor deficiency:
- Antibodies target the gastric parietal cells that produce intrinsic factor 1
- This leads to impaired vitamin B12 absorption and subsequent megaloblastic anemia
- Patients with pernicious anemia secrete between 0 and 240 units of intrinsic factor during the first hour after gastric stimulation, compared to 1,600-39,000 units in patients with other conditions 4
Monitoring and Management
For patients at risk of vitamin B12 deficiency due to intrinsic factor insufficiency:
- Serum vitamin B12 levels and methylmalonic acid (MMA) testing are recommended 5
- For indeterminate results (total B12 between 180-350 ng/L), additional testing may be needed 5
- Treatment typically involves vitamin B12 supplementation at 1000 μg monthly via intramuscular injection or 250-350 μg daily oral supplementation 5
Understanding the cellular sources of intrinsic factor is crucial for diagnosing and managing conditions related to vitamin B12 malabsorption, particularly pernicious anemia and other causes of vitamin B12 deficiency.