Lecture 10

Question 1

What does Vitamin B12 (cobalamin) consist of (structure)?

Answer 1

Corrinoid ring (4 pyrrole rings).

Question 2

How does B12 become activated and release folate?

Answer 2

1. In the cells, folate is trapped in its inactive form.
2. To activate folate, vitamin B12 removes and keep the methyl group, this activates Vit B12.
3. Both the folate coenzyme and the vitamin B12 coenzyme are now active and available for DNA synthesis.

Question 3

Where does B12 come from?

Answer 3

Only produced by bacteria. neither fauna of lora can produce it. Tend to get it from contamination sources e.g. any products from cows.

Question 4

What is the RDI for B12?

Answer 4

2.4 micrograms a day. Tiny amounts, due to humans good at conserving B12.

Question 5

What are the natural sources of B12?

Answer 5

Eggs, meat, poultry, selfish, milk and milk products.

Question 6

B12 is added to what else?

Answer 6

Fortified grain products such as cereals.

Question 7

Where is B12 stored?

Answer 7

In our liver.

Question 8

Who are people at risk of primary B12 deficiency?

Answer 8

People who don’t consume meat or dairy products e.g. Vegan diets and strict vegetarian diets.

Question 9

Describe the 1st and 2nd step of Vitamin B12 absorption?

Answer 9

Eating our food rich in cobalamin. When we chew and start breaking it down, down oesophagus. Need to release cobalamin from protein. Pepsin and HCl start to break up the protein and from that B12 is released.

Question 10

Describe the 3rd step of Vitamin B12 absorption?

Answer 10

Cobalamin has to be attached to an R-protein: haptocorrin (HC) - HC is secreted from Gastric parietal cells. HC complexed with Cobalamin.

Question 11

Describe the 4th step of Vitamin B12 absorption?

Answer 11

HC.CbI travel to the duodenum. Once in the duodenum the pancreatic protease degrade and release the CbI from HC. Also Intrinsic Factor (IF) is produced by the parietal cells in the stomach.

N.B. CbI has to be bound to IF to be absorbed.

Question 12

Describe the 5th step of Vitamin B12 absorption?

Answer 12

IF.CbI has to travel to the terminal Ileum to be absorbed. They are absorbed through brush border receptors for Intrinsic Factors on the enterocyte of the terminal ileum. B12 (CbI) passes through the enterocyte and IF is released from it.

Question 13

Describe the 6th step of Vitamin B12 absorption?

Answer 13

CbI travels to all the cells. And taken up for DNA synthesis and cells with high turnover (RBC, gut cells).

Question 14

Describe the 7th step of Vitamin B12 absorption?

Answer 14

80& of CbI is stored with HC and stored in the liver. Where you can store for 2-3 years.

Question 15

Where do we loose B12?

Answer 15

From the liver into our intestine as bile. We can recycle it as well.

Question 16

What are the type of anaemia’s?

Answer 16

Megaloblastic or macrocytic anaemia.

Question 17

Describe the blood cells in pernicious anaemia?

Answer 17

RBC cells are larger than normal RBC and their shapes are irregular.

Question 18

what is the neuropathy that occurs with B12 deficiencies?

Answer 18

Sub-acute combined degeneration of the spinal cord. This could be due to build up of SAM. Not seen in folate deficiency.

Question 19

Describe supplementation for people who have B12 deficiencies?

Answer 19

Malabsorption syndroms e.g. pernicious anaemia are usually treated with intra-muscular injections.

Question 20

Describe Case 1?

Answer 20

• 45yo teacher presents with tiredness, difficulty concentrating over 6 months.
• weight loss and diarrhoea.
• Increasing shortness of breath on exertion.

Question 21

Describe the abnormalities of the blood tests?

Answer 21

Hb = 45g/L (normal 125-170).
Mean cell volume = 115 (80-100).

Low Hb indicates anaemia, and anaemia also indicates larger RBC.

Question 22

What is another indicator of anaemia in blood tests?

Answer 22

Abnormal count of reticulocytes (immature red cells). Increase in the circulation as response to anaemia. Bone marrow response to low blood count by making reticulocytes.

Question 23

What is severe anaemia?

Answer 23

Shortness of breath and tiredness.

Question 24

What do low reticulocytes imply?

Answer 24

That the bone marrow is unable to respond to the usual stimulus of anaemia.

Question 25

What are the requirements for normal eythropoeisis?

Answer 25

Iron, folate and B12.

If serum B12 is very low it will explain tingling in fingers, concentration problems and raised MCV (macrocytosis).

Question 26

What are the requirements to absorb B12?

Answer 26

Normal acid secretion.
Normal intrinsic factor. *
Normal pancreatic secretion.
Normal ill absorptive function. *

• = most important factors

Question 27

Describe the features of a stomach problem causing lack of IF?

Answer 27

1. Lack of IF due to anaemia.
2. Autoimmune disorder with antibodies against IF and parietal cells.
3. Not enough IF to bind to B12, which means B12 cannot be absorbed later on in the small intestine.

Question 28

Describe the features of a small intestine problem causing lack of IF?

Answer 28

1. B12 binds to IF normally but is not absorbed in the small intestine.
2. e.g. surgery to remove terminal lei, Crohn’s disease causing inflammation in the terminal ileum.

Question 29

What is a schilling test and what is it used to determine?

Answer 29

Radioisotope test, used to determine if a patient has lack of IF.

Question 30

Describe the principles of schilling’s test?

Answer 30

1. An oral radioactive B12 is given.
2. Then and intra-muscular injection of non-radioactive B12 to saturate B12 binding proteins and to flush out ‘Co-B12’.
3. The urine is collected for 24 hours.
4. Normal person will excrete > 10% of the oral dose.
5. If

Question 31

What are the disadvantages of the Schilling’s test?

Answer 31

1. Time consuming.
2. Involves radioisotopes.
3. Requires collection of urine.
4. Results can be difficult to interpret yet the distinction between ill and gastric disease not clear-cut.

Question 32

What is evidence of autoimmune gastritis?

Answer 32

Antibodies to parietal cells.
Antibodies to IF.
Evidence of autoimmune gastritis on gastric biopsies.
Evidence of low acid output (raised plasma gastrin).
Evidence of other autoimmune disease (e.g. thyroid disease).

Question 33

What do people who are B12 deficient have?

Answer 33

Depleted reserves of B12. These reserves that normally take 3-5 years to run out, have gone pretty quickly.

Question 34

What do people who are B12 deficient need to do?

Answer 34

Need high does to replace the B12 - 1000 micrograms every week for 4-6 weeks then maintenance of 1000 micrograms every 3 months.

Question 35

What are the treatments for B12 deficiencies?

Answer 35

Parenteral (intramuscular) - because of impaired absorption by GI tract.
Monitor response to B12 replacement - check B12 levels; increase in Hb/reticulocyte response; resolution of neurological symptoms.

Question 36

What are the effects of a distal ill resection?

Answer 36

Loss of specialised receptors on terminal ileum leads to: failure to reabsorb B12 and bile salts.

Bile salts are instead lost through the colon. This causes an irritant effect of bile salts on the colon (secretory diarrhoea) and impaired absorption of fat because of reduced bile salts.

Question 37

What happens when the antrum is removed?

Answer 37

No G cells means, low gastrin secretion.

Question 38

What will low gastrin lead to?

Answer 38

reduced gastric acid secretion - Low acid, therefore difficulty to release B12 from food.

reduced pancreatic secretion - gastrin stimulates pancreatic enzymes.

Question 39

What will no pylorus cause?

Answer 39

bile refuses from the small intestine.

Question 40

What will bile reflux cause?

Answer 40

Atrophic gastritis i.e. body of stomach becomes inflamed due to irritation of bile. This will lead to degeneration of mucosa, so loss of parietal cells able to release IF.