Vitamin B₁₂ deficiency and pernicious anaemia

Vitamin B₁₂ absorption and storage:

• Only found in animal sources:
• Meat
• Fish
• Eggs
• Milk
• It may take 2 years or more after absorptive failure before B₁₂ deficiency develops as the daily losses are small
• Vitamin B₁₂ is absorbed from the terminal ileum by its binding to intrinsic factor (IF)
• IF is secreted by gastric parietal cells

Causes of vitamin B₁₂ deficiency:

Low dietary intake:

• Vegans

Impaired absorption:

• Pernicious anaemia (most common)
• Gastrectomy
• Ileal disease/resection
• Bacterial overgrowth
• Tropical sprue

Abnormal metabolism:

• Nitrous oxide (inactivates B₁₂)

Pathogenesis of pernicious anaemia:

Pernicious anaemia (PA) is a condition in which there is atrophy of the gastric mucosa with consequent failure of IF production and B₁₂ malabsorption

• 1 in 8000 people over 60 years affected (females>males)
• Is an association with other autoimmune diseases (especially thyroid and Addison’s)
• Increased risk of gastric carcinoma
• There is associated achlorhydria

Clinical features of PA:

• Insidious onset
• Progressively increasing symptoms of anaemia
• Glossitis
• Angular stomatitis
• Lemon-yellow colour (owing to a combination of pallor and mild jaundice)
• Neurological changes (which can become irreversible if untreated):
• Symmetrical paraethesia in the fingers and toes
• Loss of vibration sense and proprioception
• Progressive weakness and ataxia
• Paraplegia may result
• Dementia can also occur

Investigations:

FBC:

• Shows a megaloblastic anaemia

Bone marrow:

• Shows the typical features of megaloblastic erythropoiesis

Serum bilirubin:

• May be raised (as a result of ineffective erythropoiesis)

Serum vitamin B₁₂:

• Usually well reduced

Serum folate level:

• Is normal or high
• The red cell folate is normal or reduced (owing to the inhibition of normal folate synthesis)

The Schilling test:

Part 1:

• Give 1μg radio-labelled B₁₂ orally to fasting patient
• Give 1000μg B₁₂ by IM injection to saturate B₁₂-binding proteins and to flush out the radio-labelled B₁₂
• Collect urine for 24 hours
• Normal subjects excrete more than 10% of the radioactive dose

Part 2:

• Repeat part 1 with oral IF capsules

Part 3:

• If excretion is now normal, diagnosis is PA or Gastrectomy
• If excretion is still abnormal, lesion is in the terminal ileum or there is bacterial overgrowth
• Vitamin B₁₂ malabsorption due to bacterial overgrowth may be corrected by antibiotic therapy

Treatment:

• Hydroxycobalamin 1000μg IM to a total of 5-6mg over the course of 3 weeks
• 1000μg is then necessary every 3 months for the rest of the patients life
• Clinical improvement may occur within 48 hours
• Improvement of the polyneuropathy may occur over 6-12 months (but longstanding spinal cord damage is irreversible)