Lecture 10 Flashcards
What is another name for Vitamin B12?
Cobalamin
What is the structure of cobalamin?
- Consists of a Corrinoid ring (4 pyrrole rings)
- Cobalt atom in the middle
Describe how B12 and folate work together
B12 and folate work synergistically in the methylation pathway. B12 (coenzyme) helps attachment of methyl group. Allows conversion of homocysteine to methionine and back. In cells, folate is trapped in its inactive form. To activate folate, vitamin B12 removes and keeps the methyl group, which activates B12. Both the folate coenzyme and the vitamin B12 coenzyme are now active and available for DNA synthesis.
What are the dietary sources of vitamin B12?
Milk products, eggs, animal flesh, shellfish, fortified grain
What makes Vitamin B12?
Bacteria
What is the RDI for B12?
2.4 micrograms per day
Why are such small amounts of B12 needed?
Because it is stored in the liver for about 7 years.
What does B12 deficiency have a similar blood film to?
Folate deficiency
What does B12 deficiency lead to?
- Megaloblastic/macrocytic anaemia: enlarged RBC’s irregular due to poor production of DNA
- Neuropathy: sub-acute combined degeneration of the spinal cord. Not seen in folate deficiency.
What leads to microcytic anaemia?
Iron deficiency
Give an example of a malabsorption syndromes of B12. What is it usually treated with?
Pernicious anaemia
Treated with intra-muscular injections
What does a low haemoglobin level indicate?
Anaemia
What does elevated mean cell volume indicate?
Macrocytic anaemia (B12 or folate deficiency
What can reticulocyte numbers increase in response to? If the numbers are low, what does this imply?
Reticulocytes can increase in response to anaemia because the body responds to low blood count by producing more reticulocytes. If low, implies that the bone marrow is unable to respond to the usual stimulus of anaemia.
Describe the blood film of a person wth B12 deficiency
Hypersegmented neutrophils present
What is required for normal eythropoeisis?
Iron, folate, B12
What are the symptoms of B12 deficiency?
Shortness of breath, tiredness, tingling in fingers, concentration problems, raised mean cell volume, macrocytosis
What are the causes of low B12?
Diet
Failure of absorption
What are the requirements for B12 absorption?
- Acid to release food-bound cobalamin
- Secretion of intrinsic factors from healthy parietal cells *
- Normal pancreatic secretion
- Normal ileal function*
What are the steps of B12 absorption?
- Gastric acid releases food-bound B12
- R-binders secreted in saliva and stomach bind to B12 in the stomach
- Pancreatic enzymes then help release B12 from R-binders to allow binding with IF in small bowel.
- IF binding to B12 critical for absorption by specialised receptors in terminal ileum
What does the Schilling test involve?
Used to determine if patient has lack of IF. Oral radioactive B12 is given. Intramuscular injection of non-radioactive B12 to saturate B12 binding proteins and to flush out radioactive B12. Urine is collected for 24 hours. Normal person will excrete more than 10% of oral dose. If
What are the disadvantages of the Schilling test?
Time consuming, involves radio-isotopes, requires collection of urine, results difficult to interpret as the distinction between ileal and gastric disease is not clear-cut
What is the evidence for auto-immune gastritis?
- Antibodies to parietal cells
- Antibodies to IF
- Evidence of other auto-immune disease (thyroid disease)
- Evidence of autoimmune gastritis on gastric biopsies
- Evidence of low acid output (raised plasma gastrin)
How is pernicious anaemia related to autoimmune gastritis treated?
B12 replacement. Depleted reserves have taken years to run out. Need high doses to replace - 1000 micrograms intramuscularly (due to impaired absorption) every week for 4-6 weeks then maintenance of 1000 micrograms every 3 weeks. Monitor response to B12 replacement.
