Megaloblastic anaemia

Question 1

What is Megaloblastic anaemia?

Answer 1

Anaemia where the bone marrow produces large, structurally abnormal, immature RBCs. It occurs as a result of B12 or folate deficiency.

Question 2

Why is vitamin B12 required?

Answer 2

1. Methylation of homocysteine to methionine (DNA production)
2. Methylmalonyl-CoA isomerisation (breakdown of fatty acids/proteins

Question 3

What are the daily requirements and possible sources of vitamin B12?

Answer 3

Normal requirement is 1microgram per day.
Dietary sources - Synthesised solely by microorganisms. Found in meat, and small amounts in dairy products

Question 4

Explain the process of B12 absorption

Answer 4

Proteins are broken down by gastric acid and enzymes to release B12 in the stomach and duodenum. Parietal gastric cells release intrinsic factor which B12 binds too. Once the IF-B12 complex forms it can then bind to cubulin, a receptor in the ileum, and it is then transported into the bloodstream where B12 binds to transcobalamin.

Question 5

How long is B12 stored for?

Answer 5

3-4 years so it takes a long time to become vitamin B12 deficient. Lose around 1-2ug per day in stool and urine

Question 6

What are the sources of folate and how long is it stored for?

Answer 6

Dietary sources - Leafy green veg (however can be destroyed by cooking)
Absorption - mainly in the small bowel.
Stores - Only last for a few days so can very quickly become deficient

Question 7

What is the role of folate?

Answer 7

It forms methyl-THF (tetrahydrofolate) which is involved in DNA synthesis

Question 8

What occurs to DNA synthesis with a B12/folate deficiency?

Answer 8

Causes insufficient supply of one of the four deoxyribonucleoside triphosphate (dNTPs) precursors.
Dissociation between nuclear and cytoplasmic development and ineffective erythropoiesis causing death of mature cells whilst in marrow. This causes raised bilirubin and raised LDH

Question 9

What tissues are affected by a B12/folate def?

Answer 9

All rapidly growing, DNA synthesising cells. Such as bone marrow, epithelial surfaces (mouth, stomach, small intestines, urinary tracts and female genital tracts)

Question 10

What are the clinical features of a B12 deficiency?

Answer 10

Blood abnormalities - Megaloblastic anaemia which can lead to leucopenia and thrombocytopenia.
Neurological abnormalities - Bilateral peripheral neuropathy or demyelination of the posterior and pyramidal spinal cord tracts (loss of JPS)

Question 11

What are the clinical features of a folate deficiency?

Answer 11

Blood abnormalities - Megaloblastic anaemia (leuopenia and thrombocytopenia)
- Can cause neural tube defects in a growing foetus in the 1st 12 weeks.

Question 12

What are the symptoms of a B12/folate def?

Answer 12

Anaemia symptoms - Tiredness (common) and easy bruising as a result of the thrombocytopenia (rare).
Mild Jaundice - Due to increased haemolysis.
Neurological problems - Nerve disturbance with B12

Question 13

What are some causes of a B12 deficiency?

Answer 13

• Dietar,
• Pernicious anaemia (autoimmune attack on intrinsic factor)
• Gastrectomy/achlorhydria (lack of acid to breakdown proteins)
• Issues at terminal ileum (Crohn’s disease or resection)

Question 14

What are some causes of a folate deficiency?

Answer 14

• Dietary (main cause)
• Small bowel disease such as coeliac’s or Crohns,
• Increase cell turn over (haemolysis, severe skin disorders and pregnancy)

Question 15

What are some other causes of a macrocytosis?

Answer 15

• Alcohol
• Liver disease
• Hypothyroidism
• Pregnancy
• Reticulocytosis
• Myelodysplasia
• Cytotoxics