Vitamin B12

Question 1

Reticulocytes are?

Answer 1

Immature RBC that sometimes increase in the circulation in response to anaemia (produced by bone marrow)

Question 2

Low haemoglobin indicates?

Answer 2

Anaemia

Question 3

What is required for normal erythropoeisis?

Answer 3

-iron, folate, B12

Question 4

Macrocytosis? Potential cause?

Answer 4

Larger the normal RBC, can be caused my ‘megoblastic anaemia’

Question 5

What is required to absorb B12?

Answer 5

• normal acid secretion
• normal pancreatic secretion
• normal IF*
• normal terminal ileal absorptive function *

Question 6

How is B12 actually absorbed?

Answer 6

1) gastric acid/pepsin releases food-bound B12
2) R-binders (saliva & stomach) bind to B12 in the stomach
3) Pancreatic enzymes can then help release B12 from R-binders to allow for binding to IF in SI
4) B12 has to bind to IF for absorption by specialised receptors in the terminal ileum

Question 7

If the B12 deficiency is a stomach issue, what is wrong?

Answer 7

Lack of IF due to pernicious anaemia, and autoimmune disease (ABs against IF and parietal cell)
- not enough IF to bind to B12, impaired absorbtion

Question 8

If the B12 deficiency is a small intestinal issue, what is wrong?

Answer 8

Surgery to remove terminal ilem or Crohns disease (IBD).

-B12 binds to IF but isn’t absorbed by SI

Question 9

What is the ‘schillings test’?

Answer 9

radioisotope test, used to determine if the patient has a lack of IF

Question 10

Why is the schillings test now rarely used clinically?

Answer 10

• time consuming
• involves radioisotopes
• urine collection
• can be difficult to interpret

Question 11

What are the steps of the Schilling’s test?

Answer 11

1) Oral radioactive B12 given
2) then i.m of non-radioactive B12 to saturate B12 binding
3) urine collected for 24hrs
normal person will excrete >10% in urine

Question 12

From the Schilling’s test, how much B12 will a normal person excrete in the urine?

Answer 12

> 10%

Question 13

Schilling’s test: if it is

Answer 13

Repeat test with addition of oral IF

if now normal: pernicious anaemia or gastrectomy

if still abnormal: lesion in terminal ileum or bacterial overgrowth

Question 14

Schilling’s Test: Why is an i.m injection of non-radioisotope B12 part of the test?

Answer 14

To saturate binders, stopping their interference, so you get the ‘true value’ of B12 bound to IF and absorbed

Question 15

What is autoimmune gastritis?

Answer 15

an inherited autoimmune disease that attacks parietal cells, resulting in decreased production of intrinsic factor. Consequences include atrophic gastritis, B12 malabsorption, and, frequently, pernicious anemia.

Question 16

How would you look for evidence of autoimmune gastritis?

Answer 16

1) AB blood test (parietal cells and IF)

2) Biopsy with endoscopy

Question 17

You’ve done an AB blood test to look for autoimmune gastritis, and you find AB against parietal cells. What does this mean?

Answer 17

Finding AB against parietal cells is helpful as it occurs in many people with AG,
BUT it is also present in some healthy people!
- = no pernicious anaemia
+ = inconclusive

Question 18

You’ve done an AB blood test to look for autoimmune gastritis, and you find AB against intrinsic factor. What does this mean?

Answer 18

This is a very specific test, if you have these antibodies you DEFINITELY have pernicious anaemia
BUT some people with pernicious anaemia don’t have this AB

Question 19

What could you potentially see for a endoscopic biopsy for autoimmune gastritis?

Answer 19

• Evidence of AG
• Evidence of low acid output (raised plasma gastrin)
• Evidence of other autoimmune diseases (thyroid disease)

Question 20

How long do our depleted B12 reserves take to ‘run out’

Answer 20

3-5 years

Question 21

Treatment of AG?

Answer 21

High replacement doses of B12 - 1000mcg every week for 4-6wks

then 1000mcg every 3 months

this is parenteral (intramuscular) due to impaired GI tract absorption, supplements wont work

Monitor response (B12 levels, haemoglobin/reticulocyte response, neurological symptoms)

Question 22

What are the effects of terminal ileal resection

Answer 22

Loss of specialised receptors leading to

• failure to absorb B12
• failure to reabsorb bile salts, instead they are lost through the colon. This has an irritant effect of the colon > excessive fluid > diarrhoea
• impaired absorption of fats bc of reduced bile salts (high faecal fat)

Question 23

Billroth 1 & 2 of distal gastrectomy

Answer 23

1) Antrum duodenum removed and rejoined ‘end-to-end’

2) same antrum and duodenal removal, but duodenum end sown up, and instead jejunum is connected to the stomach

Question 24

Why would you have low B12 after a partial gastrectomy?

Answer 24

No antrum > no G cells > low gastrin (reduced gastric acid secretion > hard to release B12 from food)(reduced pancreatic secretions)

No pylorus - bile can reflux back into stomach from duodenum (atrophic gastritis)

Question 25

Atrophic gastritis

Answer 25

Body of stomach becomes inflamed and mucosa atrophies (degenerates)

-loss of parietal cells - loss of IF secretion

Question 26

Some other causes of low B12 are?

Answer 26

Coeliac disease
Crohn's disease
bacterial overgrowth 
Chronic Pancreatitis 
Total gastrectomy
Some drugs

Question 27

Both B12 and folate are involved in? They are activated when

Answer 27

methylation pathway / DNA synthesis

Activated when B12 removes methyl group from flat

Question 28

Sources of B12. therefore whos at risk? What are they made by?

Answer 28

meat and dairy
also eggs

vegans and vegetarians at risk
made by bacteria

Question 29

another name for vitamin B12

Answer 29

cobalamin

Question 30

B12 Stored in ____ with the ____ for _____. How is it recycled

Answer 30

stored in the liver with R-binders for 2-3years. Recycled through bile.

Question 31

Vitamin B12 absorption

Answer 31

1) vitB12/cobalamin is injested and needs to be seperated from the protein-food it comes in
2) this is done in the stomach by pepsin and HCl, Cbl released
3) R-proteins or hepatochorin (HC) from the saliva or stomach bind to the Cbl forming a HC.Cbl complex that travels to the duodenum
4) In the duodenum pancreatic proteases release Cbl from the HC.
5) Intrinsic factor present (from P cells) binds and forms a IF.Cbl complex that travels to the terminal ileum and is absorbed in the enterocytebrush border
6) travels to cells for DNA synthesis

Question 32

Vitamin B12 deficiency results in

Answer 32

Pernicious (megoblastic) anaemia. Larger irregular BCs