B12 Absorption & Pernicious Anaemia Notes

  • Vitamin B12 is crucial for several vital functions in the body, involved in the methylation pathway. It is essential for DNA synthesis, which is fundamental for cell division and replication. Additionally, it plays a significant role in the formation of red blood cells and the maintenance of the nervous system, making its absorption vital for overall health.

  • is stored in liver, so low daily intake required

Reasons for Low B12

  • Insufficient intake: Diet lacking animal-origin foods (meat, fish, eggs, cheese).

  • Insufficient absorption:

    • Abnormal acid secretion.

    • Abnormal intrinsic factor.

    • Abnormal pancreatic secretion.

    • Abnormal ileal absorptive function.


      Most at risk for deficiency = vegans/strict vegetarians, older people with poor appetites, metformin (medication for diabetes)


Macrocytic anaemia

  • B12 + folate = important for the production of new cells

  • B12 deficient RBC’s are larger and abnormal shaped, leading to high mean cell volume + low haemoglobin + low reticulocytes

  • Symptoms may include fatigue, weakness, shortness of breath, and neuropathy such as numbness or tingling in extremities.

B12 Absorption Process

  • HCl from parietal cells releases B12 from protein

  • Free B12 binds to R binder (in stomach)

  • B12+R binder broken down by proteases from pancreas in duodenum

  • Free B12 binds to Intrinsic Factor (from parietal cells in the stomach).

  • B12 + IF binds to terminal ileal cells and is absorbed.

  • B12 + R binder goes into blood to liver (50%) and other cells.


Gastric vs. Small Intestinal Problems

  • Stomach:

    • Lack of intrinsic factor (e.g., pernicious anaemia).

    • Not enough intrinsic factor to bind to B12

  • Small Intestine:

    • B12 binds to intrinsic factor but isn't absorbed in ileum

    • e.g., surgery removing terminal ileum, Crohn’s disease causing inflammation in terminal ileum.

Diagnosing Pernicious Anaemia

  • Autoimmune disorder where the individual develops auto-antibodies against intrinsic factor and parietal cells

  • Autoantibodies on blood test:

    • Antibodies to parietal cell = sensitive, so if -ve = No P.A

    • Antibodies to intrinsic factor = specific, so if +ve = P.A

  • Evidence of autoimmune gastritis:

    • Gastric biopsies.

    • Raised plasma gastrin (low acid output).

    • People with pernicious anaemia develop autoimmune gastritis = atrophy of the stomach lining (no rugae). Results in:

      Low acid output. And because of that the body attempts to make more acid (which the body can't do) by releasing more gastrin. Can also test for gastrin levels in blood - if high + no rugal folds = likely pernicious anaemia

Treatment for B12 Deficiency

  • High doses to replace: 1000 mcg every week for 4-6 weeks, then maintenance of 1000 mcg every 3 months.

  • Parenteral (intramuscular) administration due to impaired GI absorption.

  • Monitor response:

    • Check B12 levels.

    • Increase in haemoglobin/reticulocyte response.

    • Resolution of neurological symptoms.


Low B12 After Partial Gastrectomy

  • No antrum, no G cells low gastrin. leads to

    • Reduced gastric acid secretion.

      • Low acid - difficulty releasing B12 from food

    • Reduced pancreatic secretion stimulated by gastrin

  • No pylorus - Bile reflux causing atrophic gastritis = loss of parietal cells, therefore loss of intrinsic factor.

Effects of Terminal Ileal Resection on B12

  • Loss of specialized receptors.

    • Failure to absorb B12.

    • Failure to reabsorb bile salts.

  • Bile salts lost through the colon, causing secretory diarrhoea.

  • Impaired fat absorption due to reduced bile salts.


Other Causes of Low B12 (Not Covered)

  • Terminal ileal inflammation (e.g., Crohn’s).

  • Bacterial overgrowth.

  • Chronic pancreatitis.

  • Total gastrectomy/weight-loss procedures.

  • Certain drugs (omeprazole, metformin).

Low B12 in Coeliac Disease

  • Loss of small bowel villi, in severe cases: damage from duodenum to ileum.

  • Loss of endocrine cells secreting secretin and cholecystokinin (involved in stimulating pancreatic enzymes).