Lecture 10

Question 1

What is another name for Vitamin B12?

Answer 1

Cobalamin

Question 2

What is the structure of cobalamin?

Answer 2

• Consists of a Corrinoid ring (4 pyrrole rings)

- Cobalt atom in the middle

Question 3

Describe how B12 and folate work together

Answer 3

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.

Question 4

What are the dietary sources of vitamin B12?

Answer 4

Milk products, eggs, animal flesh, shellfish, fortified grain

Question 5

What makes Vitamin B12?

Answer 5

Bacteria

Question 6

What is the RDI for B12?

Answer 6

2.4 micrograms per day

Question 7

Why are such small amounts of B12 needed?

Answer 7

Because it is stored in the liver for about 7 years.

Question 8

What does B12 deficiency have a similar blood film to?

Answer 8

Folate deficiency

Question 9

What does B12 deficiency lead to?

Answer 9

• 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.

Question 10

What leads to microcytic anaemia?

Answer 10

Iron deficiency

Question 11

Give an example of a malabsorption syndromes of B12. What is it usually treated with?

Answer 11

Pernicious anaemia

Treated with intra-muscular injections

Question 12

What does a low haemoglobin level indicate?

Answer 12

Anaemia

Question 13

What does elevated mean cell volume indicate?

Answer 13

Macrocytic anaemia (B12 or folate deficiency

Question 14

What can reticulocyte numbers increase in response to? If the numbers are low, what does this imply?

Answer 14

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.

Question 15

Describe the blood film of a person wth B12 deficiency

Answer 15

Hypersegmented neutrophils present

Question 16

What is required for normal eythropoeisis?

Answer 16

Iron, folate, B12

Question 17

What are the symptoms of B12 deficiency?

Answer 17

Shortness of breath, tiredness, tingling in fingers, concentration problems, raised mean cell volume, macrocytosis

Question 18

What are the causes of low B12?

Answer 18

Diet

Failure of absorption

Question 19

What are the requirements for B12 absorption?

Answer 19

• Acid to release food-bound cobalamin
• Secretion of intrinsic factors from healthy parietal cells *
• Normal pancreatic secretion
• Normal ileal function*

Question 20

What are the steps of B12 absorption?

Answer 20

• 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

Question 21

What does the Schilling test involve?

Answer 21

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

Question 22

What are the disadvantages of the Schilling test?

Answer 22

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

Question 23

What is the evidence for auto-immune gastritis?

Answer 23

• 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)

Question 24

How is pernicious anaemia related to autoimmune gastritis treated?

Answer 24

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.

Question 25

What is a right hemicolectomy?

Answer 25

Removal of the right side of the colon

Question 26

What is the explanation for low B12 after terminal ileal resection?

Answer 26

Loss of specialised receptors on terminal ileum leads to failure to absorb B12.

Question 27

What is the explanation for diarrhoea and increased faecal fat after terminal ileal resection?

Answer 27

Failure to reabsorb bile salts leads to irritant effect on colon and impaired absorption of fat

Question 28

Describe Bilroth 1

Answer 28

Antrum and first part of duodenum removed. Two ends brought together directly

Question 29

Describe Bilroth 2

Answer 29

Distal antrum and first part of duodenum removed. Duodenum sown shut. Jejunum sown onto stomach.

Question 30

Explain why low B12 occurs after partial gastrectomy.

Answer 30

- No antrum means no G cells and low gastrin. This reduces the gastric acid secretion. Low acid levels cause difficulty in releasing B12 from food. Low gastrin also causes less pancreatic secretion. Failure of mixing pancreatic juices with food. - No pylorus leads to bile reflux. This results in atrophic gastritis. Results in loss of parietal cells and loss of IF secretion.

Question 31

Why does coeliac disease lead to low B12?

Answer 31

- Loss of small bowel villi (mainly jujenal, some ileal) - Loss of endocrine cells that secrete secretin and cholecystokinin, which stimulate pancreatic secretion - Fewer ileal receptors in severe cases

Question 32

What are the causes of B12 deficiency?

Answer 32

- Diet - Autoimmune gastritis - Terminal ileal resection - Partial/total gastrectomy - Coeliac disease - Terminal ileal disease (Crohn's disease) - Bacterial overgrowth - Chronic pancreatitis - Some drugs - omeprazole, metformin

Question 33

How does bacterial overgrowth lead to low B12?

Answer 33

B12/B12 IF complex is utilised by intestinal bacteria