Hematology & immune disorders


Vitamin B12 deficiency

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Last staff update: 4 October 2023

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PubMed Search: Vitamin B12 deficiency [title]

R. Amita, M.D.
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Cite this page: Amita R. Vitamin B12 deficiency. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/hematologyvitaminb12deficiency.html. Accessed May 19th, 2024.
Definition / general
  • Vitamin B12 deficiency, also known as hypocobalaminemia, refers to low blood levels of vitamin B12
  • 6% of those under age 60 and 20% over age 60
  • Rates may be as high as 80% in parts of Africa and Asia
  • Total amount of vitamin B12 stored in the body is between 2 - 5 mg in adults
    • Of this, 50% is stored in the liver, 0.1% is lost each day as secretions into the gut
    • Most of the vitamin B12 excreted into the bile is recycled via enterohepatic circulation
    • Because of this mechanism, the liver can store three to five years’ worth of vitamin B12 under normal conditions and functioning
  • Deficiency of Vitamin B12 affects the metabolic pathway in 2 critical points:
    • Homocysteine to methionine, catalyzed by methionine synthase needs cyanocobalamin as a cofactor; resulting hyperhomocysteinemia may lead to a prothrombotic state
      • The end product methionine aids in purine and thymidine synthesis, myelin production, protein / neurotransmitters / fatty acid / phospholipid production and DNA methylation, which becomes deficient in these individuals
    • Methylmalonyl-CoA to succinyl-CoA also requires Vitamin B12 as a cofactor
  • Poor absorption from the stomach or intestines
    • Pernicious anemia
    • Surgical removal of the stomach
    • Chronic inflammation of the pancreas
    • Intestinal parasites, certain medications
    • Some genetic disorders
  • Decreased intake
    • Vegan diet
    • Malnutrition
  • Increased requirements
    • HIV / AIDS
    • Rapid red blood cell breakdown
Clinical features
  • Extreme tiredness
  • Lack of energy
  • Pins and needles (paraesthesia)
  • Sore and red tongue
  • Mouth ulcers
  • Muscle weakness
  • Disturbed vision
  • Psychological problems, which may include depression and confusion
  • Problems with memory, understanding and judgement
  • Rarely hyperpigmentation (Indian J Endocrinol Metab 2013;17:S254)
  • Vitamin B12 levels in blood below 120 – 180 picomol/L in adults
  • Elevated methylmalonic acid levels (values > 0.4 micromol/L)
  • Hyperhomocysteinuria is a non-specific marker of deficiency
  • Hyperhomocysteinuria is a non-specific marker of deficiency
  • Methylmalonic acid is a more specific test of B12 deficiency
Case reports
  • Oral or parenteral supplements (J Hum Nutr Food Sci 2013;1: 1008)
  • When large doses (1 - 2 mg) are given by mouth, its absorption does not rely on the presence of intrinsic factor or an intact ileum - the free crystalline B12 is absorbed along the entire intestine by passive diffusion
Clinical images

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Hyperpigmentation before treatment

Microscopic (histologic) description
  • Individuals with autoimmune gastritis may develop pernicious anemia because of extensive loss of parietal cell mass and anti-intrinsic factor antibodies
  • Autoimmune gastritis is usually restricted to the gastric corpus and fundus; lymphocytes infiltrate the gastric mucosa, destroy epithelial cells and cause gastric atrophy
Microscopic (histologic) images

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Atrophic gastritis with intestinal metaplasia

Peripheral smear description
  • Decreased red blood cell (RBC) count and hemoglobin levels
  • Increased mean corpuscular volume (MCV > 100 fL) and mean corpuscular hemoglobin (MCH)
  • Reticulocyte count is decreased due to destruction of fragile and abnormal megaloblastic erythroid precursor
  • Platelet count may be reduced
  • Neutrophil granulocytes may have hypersegmented nuclei
  • Anisocytosis (increased variation in RBC size) and poikilocytosis (abnormally shaped RBCs)
  • Macrocytes (larger than normal RBCs) are present
  • Ovalocytes (oval-shaped RBCs) are present
  • Howell-Jolly bodies (chromosomal remnant) also present
Peripheral smear images

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Hypersegmented neutrophil

Macrocytes, macro-ovalocytes,
nucleated RBCs and hypersegmented neutrophils

Differential diagnosis
Additional references
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