Pernicious anemia

Autoimmune process with antibodies to parietal cells an or intrinsic factor.

Peak age about 60 years.

The median age ranges from 70-80 years, in large studies.

More common among African or European individuals, then those of Asian ancestry.

Prevalence in Africa or European populations is 4.3 and 4.0, respectively.

Pernicious anemia, a condition that affects 1%–2% of older adults is characterized by a lack of intrinsic factor. 

More common in men than women.

Prevalence ranges from 50-4000 cases per 100,000 persons, depending on diagnostic criteria.

Associated with gastric mucosa is atrophic and the secretion of intrinsic factor is defective.

In older adults 20% will have a mild form of atrophic gastritis with hypochlorhydria and an inability to release dietary protein-bound vitamin B12.

Typically patients have gastritis involving the fundus and spares the antrum.

Achlorhydria can lead to vitamin B12 deficiency because the vitamin B 12 and protein carrier complex do not dissociate to allow intrinsic factor to bind to vitamin B 12.

Autoantibodies are present to parietal cells, intrinsic factor in the serum and in gastric secretions.

Autoimmune destruction of the gastric parietal and zymogenic cells inhibits intrinsic factor production.

Intrinsic factor antibodies may be present and bind to existing intrinsic factor.

Results in a selective malabsorption of vitamin B12.

Individuals with pernicious anemia cannot properly absorb vitamin B12 in the gastrointestinal tract.

Antiparietal antibodies target the H+/K+-ATPase in parietal cells that causes gastric atrophy and achlorhydria.

Parietal cell antibodies found in the serum of approximately 90% of patients.

Approximately 30% of first degree relatives have parietal antibodies.

2-8% of the normal population have low titers of parietal antibodies.

The most common cause of clinically significant vitamin B12 deficiency affecting between 50/100000 to 400/100000 persons in the US

Antibodies to intrinsic factor found in approximately 50-60% of patients with pernicious anemia.

Associated with other autoimmune diseases, especially thyroid diseases, type I diabetes mellitus and vitiligo.

The B12 assay for vitamin B 12 can lead to spuriously elevated results in patients with high levels of circulating autoantibodies, including those to intrinsic factor.

In a series of patients with pernivciuos anemia the B12 dependent interference from intrinsic factor antibodies occurs in 22-35% of patients.p

Type I autoantibodies block B12 binding to intrinsic factor and type II autoantibodies bind to a different epitomes of intrinsic factor and is present in 35-40% of patients.

Leads to B12 deficiency which causes ineffective erythropoiesis with megaloblastic features.

Leads to disturbances in myelopoiesis, megakaryocytic maturation, neurologic and mucocutaneous symptoms.

Autoimmune gastritis may cause malabsorption of iron, with clinical iron deficiency developing early in life and eventually progressing to malabsorption of vitamin B 12.

The reticulocyte count is low in relation to the degree of anemia present.

Bone marrow examination reveals hypercellularity, with decreased myeloid/erythroid ration with a marked increase in the red blood cell series.

Laboratory findings are related to ineffective erythropoiesis with increased LDH and increased uncongugated bilirubin.

Serum levels of B12 low or very low and increased urinary excretion of methylmalonic acid.

Serum levels of homocysteine increased in vitamin B12 deficiency.

More common in the elderly and the people of Northern European and African descent.

The urinary methylmalonic acid excretion level and homocysteine levels may be more sensitive indicators of B12 deficiency than the B12 level.

Schilling test, an absorption test, that can be performed with radioactive labeled vitamin B12 given orally, following intramuscularly unlabeled B12 to saturate the vitamin B12 binding sites: urine collection over 24 hours determines if the oral vitamin B12 was absorbed.

A normal Schilling test reflects a 10-20% absorption of ingested vitamin B12, while an absorption of less than 3% indicates pathological uptake.

Administration of intrinsic factor should improve pathological Schilling test to normal absorption levels.

In most cases the onset is insidious.

Symptoms include fatigue, dyspnea, pallor, and appear mildly icteric.

Tongue frequently beefy red and can be painful (Hunter’s glossitis).

Many patients suffer with angular stomatitis, and esophagitis with dysphasia.

Many persons with early disease have normal blood counts and the B12 level is incidentally found for unrelated processes.

Some patients with pernicious anemia can have enterochromaffin cell hyperplasia with hypergastrinemia and development of gastric carcinoid tumors.

1-7% of patients with pernicious anemia develop gastric carcinoid tumors.

Traditionally treated with parenteral vitamin B12 because of the potential poor absorption of oral vitamin B 12.

Parenteral B12 produces rapid clinical improvement, however trials comparing oral versus intramuscular repletion show no difference in long term hematologic on neurologic responses.

Pernicious anemia is usually treated with intramuscular vitamin B12. 


However, approximately 1% of oral vitamin B12 can be absorbed passively in the absence of intrinsic factor  suggesting that high oral doses of vitamin B12 might also be an effective treatment.


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