Conditions · Vitamins and minerals
Pernicious anaemia !
An autoimmune disease that destroys the stomach cells making intrinsic factor; without it vitamin B12 cannot be absorbed.
Updated 2026-11-01
Structures involved
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In biochemistry
In immunology
In histology
In the clinical exam
In physiology
- Anemia physiology and compensation
- Gastric acid secretion
- Absorption of iron, calcium and vitamin B12
- Patterns of malabsorption
- Vitamins and minerals: a physiological overview
Why it happens
- Vitamin deficiencies: what each one does to tissue
- Precancerous conditions: when chronic inflammation, metaplasia or hyperplasia raise the risk
What it is
Autoimmune atrophic gastritis of the gastric body and fundus with loss of parietal cells and intrinsic factor, leading to vitamin B12 deficiency, megaloblastic anaemia and nerve damage.
Who gets it
The most common cause of severe B12 deficiency in adults, especially after age 60 and in women. It is linked to other autoimmune diseases.
Causes
- Antibodies to the parietal-cell H⁺/K⁺-ATPase
- Antibodies to intrinsic factor (block its binding to B12)
- Genetic and autoimmune predisposition
Risk factors
- Age over 60
- Hashimoto thyroiditis, Graves disease, type 1 diabetes, vitiligo, Addison disease
- Family history
- Northern European ancestry
Pathophysiology
T cells and antibodies destroy parietal cells: acid (achlorhydria) and intrinsic factor are lost. Without intrinsic factor B12 is not absorbed in the terminal ileum and, after years of draining liver stores, methionine synthase fails (megaloblastic anaemia through the folate trap) and so does methylmalonyl-CoA mutase (myelin damage). Achlorhydria raises gastrin, which stimulates enterochromaffin-like cells: risk of gastric carcinoid tumours. Iron absorption also falls.
Symptoms and signs
- Tiredness, pallor with a yellow tint, breathlessness
- Smooth, red, sore tongue
- Tingling and numbness of feet and hands, unsteady walking
- Memory loss, depression, irritability
- Loss of appetite and weight
Diagnosis
- Clinical
- Macrocytic anaemia or neurological symptoms in an adult, often with another autoimmune disease.
- Tests
- Low serum B12, high methylmalonic acid and homocysteine; antibodies to intrinsic factor (very specific) and to parietal cells (sensitive); high gastrin and low pepsinogen I; blood count with high MCV.
- Imaging
- Upper GI endoscopy with biopsy: atrophy of the gastric body, intestinal metaplasia; spinal MRI if there is myelopathy.
Treatment
- Medical
- Lifelong vitamin B12, intramuscular or high-dose oral
- Follow-up
- Blood count, potassium and reticulocytes at the start; periodic B12 and thyroid checks
- Follow-up
- Surveillance endoscopy according to the risk of gastric cancer and carcinoid tumours
- Rehabilitation
- Physiotherapy if neurological deficits remain
Drugs for this condition
Complications
- Subacute combined degeneration of the spinal cord
- Gastric cancer and gastric carcinoid tumours
- Associated iron deficiency
- Reversible dementia if treated early
Prognosis
With lifelong B12 the anaemia corrects fully; nerve damage improves if treated early but may persist.
Prevention
- Not preventable; early detection avoids nerve damage
Test yourself
Think of the answer, then tap the question to see it.
What does the autoimmunity destroy in pernicious anaemia?
The parietal cells of the gastric body and fundus, which make acid and intrinsic factor.
Which antibody is most specific for pernicious anaemia?
Anti-intrinsic factor antibody; anti-parietal cell antibody is more sensitive but less specific.
Why can high-dose oral B12 treat it?
A small fraction of B12 is absorbed by passive diffusion along the gut, without intrinsic factor.
Why is the risk of gastric carcinoid tumours higher?
Achlorhydria raises gastrin, which drives proliferation of enterochromaffin-like cells.
Related conditions
- Megaloblastic anaemia (B12 or folate deficiency)
- Helicobacter pylori gastritis
- Gastric cancer
- Hypothyroidism
- Type 1 diabetes mellitus
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Pernicious anemia: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Vitamin B12: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Vitamin B12 level: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Methylmalonic Acid (MMA) Test: MedlinePlus Medical Test (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).
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