Gastric Intrinsic Factor Secretion
Gastric intrinsic factor is primarily secreted from parietal cells in the gastric mucosa. 1
Primary Source of Intrinsic Factor
- Parietal cells in the gastric mucosa are the predominant source of intrinsic factor production in humans 1, 2
- Parietal cells secrete both gastric acid and intrinsic factor, though through different secretory mechanisms 2
- Intrinsic factor secretion is stimulated via the same pathways that stimulate gastric acid secretion: histamine, gastrin, and acetylcholine 2
Cellular Mechanism of Intrinsic Factor Secretion
- In parietal cells, intrinsic factor is associated with tubulovesicles scattered throughout the cytoplasm and some in rough endoplasmic reticulum 3
- Upon stimulation (e.g., by pentagastrin), these tubulovesicles migrate to the periphery of secretory canaliculi 3
- Intrinsic factor secretion depends on membrane-associated vesicular transport, supporting a membrane translocation-fusion hypothesis for parietal cell secretion 3
- The highest density of intrinsic factor is found on endocytic and apical membranes of parietal cells 4
Secondary Sources of Intrinsic Factor
- While parietal cells are the primary source, immunohistochemical studies have identified intrinsic factor in other cell types 4
- At the margins of anatomical gastric regions (e.g., cardia/fundus, body/antrum), clusters of gastric chief cells may contain intrinsic factor 4
- Some individual enteroendocrine cells have also been found to contain intrinsic factor 4
- Exocrine secretory granules of a subpopulation of chief cells may contain intrinsic factor 4
Clinical Significance
- Intrinsic factor is essential for the absorption of vitamin B12 (cobalamin) in the terminal ileum 5
- Deficiency of intrinsic factor, most commonly due to autoimmune destruction of parietal cells (autoimmune atrophic gastritis), leads to pernicious anemia 6
- In autoimmune atrophic gastritis, autoantibodies against parietal cells and intrinsic factor, along with T-cell-mediated destruction of gastric oxyntic mucosa, leads to corpus-predominant atrophy 6
- Patients with chronic atrophic gastritis, particularly autoimmune gastritis, are at increased risk of developing gastric neuroendocrine tumors and gastric adenocarcinoma 6
Diagnostic Considerations
- Diagnosis of autoimmune atrophic gastritis can be suggested by the presence of hypochlorhydria or achlorhydria, elevated gastrin levels, and anti-parietal cell or anti-intrinsic factor antibodies 6
- Following bariatric surgery, vitamin B12 deficiency may develop due to reduced intrinsic factor production, requiring regular monitoring 6
In conclusion, while option (a) parietal cells is the correct answer as the primary source of gastric intrinsic factor, some evidence suggests limited production may also occur in chief cells and enteroendocrine cells at specific anatomical locations in the stomach.