Vitamin B12

Question 1

Describe the mportance of Vitamin B12 and folate

Answer 1

Important in DNA synthesis and if you have a deficiency it can lead to severe anaemia which can be fatal. Vitamin B12 is integral to the nervous system and folate is involved in homocysteine metabolism

Both needed for deoxythymidine (dTMP), which is critical building block. Dietary folate is converted to methyl tetrahydrofolate (methyl-THF) as it is absorbed into the luminal cells. Vitamin B12 acts as a co factor for methionine synthetases for the conversion of homocysteine to methionine. (Homocysteine is important for DNA)

Question 2

Describe the clinical features of B12 and folate deficiency

Answer 2

1. Anaemic - tired, weak, short of breath
2. Jaundice - red cell breaks down - ineffective erythropoiesis - increased bilirubin
3. Glossitis and angular cheilosis - soreness in corner of the mouth
4. Weight loss and change in bowel habit - GI disturbances

Question 3

What are the other physiological associations to folate and vit b12

Answer 3

MCV is typically high: macrocytic anaemia and megaloblastic. Macrocytic is due to range (liver disease, hypothyroid, drugs, haem too) but megaloblastic is only due to vit B12 and folate and is associated to morphological changes within the bone marrow.

In megaloblastic change, no existing maturation of nucleus and cytoplasm so looks like a normablast and reticulocyte

Question 4

What are the causes of folate and vitamin B12 deficiency and its physiological effects

Answer 4

1. Not enough dietary folate absorbed.
2. Not absorbing enough folate

Not being able to have folate at cellular level leads to inability got methylation of nucleotide and affects DNA synthesis and so homocysteine accumulates because you can’t convert it to methionine without folate

Vitamin B12 not absorbed well and therefore vegans are at the greatest risk (no diary)

Question 5

Describe reasons why there would be an increased demand for folate

Answer 5

1. Physiological: rapid increase in growth, pregnancy, adolescence, premature babies.
2. Pathological: malignancy, erythrdema (skin rash), haemolytic anaemia (red cell production increase and folate increase)

Question 6

What are the diagnostic tests

Answer 6

FBC, blood film, blood folate level: useful as screening test and is affected by changes to the diet (diurnal variation). Red cell folate is confirmatory, if you have B12 deficiency = high serum folate and low red cell folate (because b12 is responsible for bringing folate into cell,

Vitamin B12: absent reflexes and upgoing plantar response - central and peripheral nerve damage.

Schilling test: first (drink radio labelled B12, measure excretion in urine (means not absorbed) then repeat test with addition of intrinsic factors and measure excretion in urine.

Question 7

What are the clinical consequences of the deficiency

Answer 7

Megaloblastic anaemia, neural tube defects (spina bifida/ anencephaly) and increased risk of venous thrombosis.

Homocysteine and thrmobosis: high homocysteine levels are associated with
Atherosclerosis and premature vascular disease. Mild homocysteine levels: CWD, areterial thrombosis, venous thrombosis

Vitamin B12 deficiency - neurological problems: affecting peripheral and central, subacute combined degeneration of the cord, optic atrophy and dementia.

Question 8

Describe the method of Vitamin B12 absorption and why it can be impaired

Answer 8

Occurs in small intestine - B12 is stored - then combines with intrinsic factors (made in the stomach - parietal cells) B12-IF binds to Ileal receptors

Impaired due to:

1. Post-grastectomy surgery
2. Inflammatory disease
3. Auto-immune disease - pernicious anaemia
4. Infections (H.pylori, fish tape worm)
5. Drugs (eg metformin, proton pump inhibitors, oral contraceptive pill).

Question 9

Describe the treatment for b12 deficiency

Answer 9

Injections (3x a week for 2 weeks)
Thereafter for 3 months

If neurological involvement: injection every other day up to 3 weeks and then thereafter every 2 months