Intrinsic Factor: Definition, Secretion Process and Diseases Associated with This Glycoprotein Deficiency

It is a glycoprotein mainly secreted by the parietal cells of the stomach.

Secretion process

Its secretion is governed by the same biochemical processes that regulate acid secretion, and its action is to help the absorption of vitamin B to be released from dietary proteins by the action of pepsin and then combine with the binders R (haptocorrins), glycoproteins secreted by the stomach, which assists in its protection against acid degradation.

It is subsequently cleaved from the R-binder complexes by pancreatic proteolysis in the duodenum and binds to intrinsic factors. Vitamin B 12 forms a resistant complex taken up by ileal cell receptors (tubulin).

Causes of intrinsic factor deficiency

The most common cause of intrinsic factor deficiency is autoimmunity; requesting intrinsic factor antibody measurement usually reveals a low plasma vitamin B concentration, a cause of macrocytic anemia and various neurological disorders.

The diagnosis of pernicious anemia is based on finding a low plasma B concentration in conjunction with the presence of anti-parietal cell antibodies and intrinsic factor antibodies.

Current automated trials of vitamin B 12 evidence in different amounts:

  • Intrinsic factor antibody interference.
  • Alternative strategies for the evaluation of B 12.
  • Holotranscobalamin concentrations.

Other causes of intrinsic factor deficiency that lead to low plasma B include gastrectomy, achlorhydria, and congenital absence of intrinsic factor, which is rare.


Vitamin B deficiency can also occur due to poor intake (e.g., in vegans, starvation, or reduced food intake from any cause) or small bowel disease affecting the terminal ileum.

Gastric biopsies showing histopathological features of atrophic gastritis may be helpful. There are some indications that patients should undergo surveillance endoscopies once the diagnosis is made due to an increased incidence of gastric cancer.

Wireless capsule enteroscopy or CT / MRI enteroclysis (specialized techniques in which a contrast medium is infused into the small intestine) is the choice for treatment in suspected small bowel disease patients. Diagnosis.

Previously, when finding a low concentration of vitamin B, it was common to request a Schilling test, which had the potential to aid in the differential diagnosis. Still, this test has become obsolete as imaging techniques have improved.

Intrinsic factor deficiency diseases


Pernicious anemia

After gastrectomy, pernicious anemia eventually develops as a consequence of vitamin B 12 deficiency due to a lack of intrinsic factors unless replacement therapy is instigated.

However, vitamin B 12 is stored in the liver, and pernicious anemia does not develop until the reserves are depleted, probably after several years.

The bone marrow produces immature (large) abnormal macrocytic red cells in pernicious anemia. The patient’s blood tests would show a low red blood cell count and a high mean cell volume in the cells. The preferred treatment is intramuscular injections of vitamin B 12 every three months.

Iron deficiency anemia

After removing the stomach, iron deficiency anemia can develop because the acid in the stomach tends to convert dietary ferric iron (Fe 3+) to the ferrous form, the only non-heme form of iron that any appreciable measure can absorb.

Even if only the antrum of the stomach is removed, an iron deficiency can develop due to the removal of gastrin-secreting G cells, as gastrin is an essential stimulus for acid secretion in the stomach.

The body’s iron stores are more limited than vitamin B 12. Iron deficiency anemia can manifest within a few months of a partial gastrectomy, while pernicious anemia may not occur for about two years.

Iron deficiency is characterized by small red blood cells (microcytosis), although after gastrectomy, this may be obscured by pernicious anemia in which the red blood cells are macrocytic.