Chronic Atrophic Gastritis and Pernicious Anaemia
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Direct answer
Pernicious anaemia is a megaloblastic anaemia caused by vitamin B12 malabsorption from autoimmune chronic atrophic gastritis, in which antibodies destroy parietal cells. Antibodies against the proton pump and against intrinsic factor block acid secretion and B12 absorption in the body and fundus of the stomach. Diagnosis rests on a low serum B12 with anti-intrinsic factor antibodies, and treatment is lifelong intramuscular hydroxocobalamin.
What you must remember
- Pathogenesis: autoimmune destruction of parietal cells, with antibodies to the H+/K+ ATPase proton pump, causing achlorhydria and loss of intrinsic factor.
- Intrinsic factor antibodies: highly specific for pernicious anaemia but less sensitive, so a negative result does not exclude a strong clinical picture.
- Haematology: macrocytic megaloblastic anaemia with hypersegmented neutrophils and a raised MCV, often with mild pancytopenia.
- Neurology: B12 deficiency causes subacute combined degeneration of the dorsal columns and lateral corticospinal tracts, and neurological signs can precede the anaemia.
- Gastric neoplasia: hypergastrinaemia drives ECL-cell hyperplasia, which can progress to type 1 gastric carcinoid, and adenocarcinoma risk is also raised.
- Treatment: lifelong intramuscular hydroxocobalamin, because absorption by mouth depends on intrinsic factor.
- Associations: Hashimoto thyroiditis, Addison disease, vitiligo and type 1 diabetes often coexist.
- Helicobacter pylori: usually absent in classic autoimmune gastritis, which affects the body and fundus rather than the antrum.
A woman with numbness and a macrocytic anaemia
A 48-year-old woman has tingling in both feet, mild pallor and a raised MCV. Her serum B12 is low, and she has a history of thyroid disease.
| Feature | Autoimmune (type A) gastritis | Helicobacter-associated gastritis |
|---|---|---|
| Main site | Body and fundus | Antrum, often spreading to the body |
| Acid output | Achlorhydria | Usually normal or raised |
| Antibodies | Anti-parietal cell and anti-intrinsic factor | No specific antibodies |
| Vitamin B12 | Malabsorption | Usually normal |
| Neoplastic risk | Type 1 gastric carcinoid, adenocarcinoma | Adenocarcinoma, MALT lymphoma |
| Treatment | B12 replacement, lifelong | Eradication of the infection |
Achlorhydria with antibodies and B12 malabsorption points to autoimmune disease, while antral-predominant disease with a treatable infection points to Helicobacter pylori. The examiner usually expects the first pattern when a patient has neurological symptoms with a macrocytic anaemia.
Folate deficiency must be excluded before treatment starts, because folic acid alone can correct the blood count while the neurological damage from B12 deficiency progresses. Serum folate and B12 are therefore measured together, and the blood film and reticulocyte count confirm that the marrow is megaloblastic.
Where the examiner tests the work-up
Errors cluster around the tests and the route of treatment.
- Trap: starting with a stool antigen test for Helicobacter pylori as the main work-up Correct: the key tests are serum B12 and anti-intrinsic factor antibodies, since autoimmune gastritis is usually infection-negative.
- Trap: treating a negative anti-intrinsic factor test as proof against pernicious anaemia Correct: these antibodies are specific but insensitive, so a low B12 with the clinical picture still stands.
- Trap: giving oral B12 as the standard treatment Correct: lifelong intramuscular hydroxocobalamin is the usual route, because absorption depends on intrinsic factor.
Frequently asked questions
Which antibodies are most specific for pernicious anaemia?
Anti-intrinsic factor antibodies are the most specific test for pernicious anaemia, although parietal cell antibodies are more sensitive. A positive anti-intrinsic factor result confirms the diagnosis, but a negative result does not exclude it when the clinical picture is strong.
Why does autoimmune gastritis raise the risk of gastric carcinoid tumours?
Loss of acid secretion removes the normal negative feedback on gastrin, so gastrin levels rise and enterochromaffin-like cells proliferate. This hypergastrinaemia can lead to type 1 gastric carcinoid tumours, which are often multiple and small.
What is the standard treatment for pernicious anaemia?
Pernicious anaemia is treated with lifelong intramuscular hydroxocobalamin, given as an initial loading course followed by maintenance doses at intervals. The parenteral route is used because absorption of oral B12 depends on intrinsic factor, which these patients lack.
Which neurological features does vitamin B12 deficiency cause?
Vitamin B12 deficiency causes subacute combined degeneration of the spinal cord, affecting the dorsal columns and lateral corticospinal tracts. Patients develop symmetrical paraesthesia, impaired proprioception and gait ataxia, and these features can appear before the anaemia is obvious.
Why is Helicobacter pylori usually absent in autoimmune atrophic gastritis?
Autoimmune gastritis affects the body and fundus, where acid secretion is already lost, and this environment is unfavourable for H. pylori colonisation. That is why H. pylori testing is not the key investigation in classic pernicious anaemia.