Megaloblastic anaemia

Question 1

What is required for normal red cell production?

Answer 1

• Drive for erythropoiesis (erythropoietin)
• Genes coding erythropoiesis
• Essential components for erythropoiesis: Iron, B12, folate and minerals
• Functioning bone marrow

Question 2

In very generalised terms, explain anaemia

Answer 2

Reduced production of red cells or increased destruction of red cells

Question 3

In very generalised terms, explain polycythaemia

Answer 3

Increased red cell production or decreased red cell destruction/loss

Question 4

What are vitamin B12 and Folate needed for?

Answer 4

DNA synthesis and nuclear maturation, they are required in all dividing cells

Question 5

In which cells is the deficiency of B12/folate first noted?

Answer 5

Red cells

Question 6

What is the result of a deficiency of B12/folate?

Answer 6

Megaloblastic (abnormally large red cells) anaemia, it will eventually effect other organs

Question 7

What 2 process is B12 necessary for?

Answer 7

• Methylation of homocysteine to methionine (involved in DNA production)
• Methylmalonyl-CoA isomerisation (involved in the breakdown of fatty acids/proteins)

Question 8

What are the sources of B12?

Answer 8

Dietary sources:
•Synthesised soley by microorganisms
•Meat (especially liver and kidney)
•Small amount in dairy products

Question 9

What is the daily requirement of B12?

Answer 9

1 microgram a day

Question 10

Describe the absorption of B12

Answer 10

• B12 ingested in form of animal protein
• Gastric parietal cells produce intrinsic factor
• B12 is released by enzymes and acid in the stomach and duodenum
• Intrinsic factor binds to B12
• The intrinsic factor- B12 complex binds to cubulin (a specific receptor in the ileum)
• B12 is absorbed into the blood and binds to transcobalamin

Question 11

What makes intrinsic factor?

Answer 11

Gastric parietal cells in the fungus/body of the stomach

Question 12

What is the daily loss of B12?

Answer 12

1-2 micrograms are lost each day in the urine/faeces

Question 13

How long do the stores of B12 last?

Answer 13

3-4 years

Question 14

What are the sources of folate?

Answer 14

Green veg (but the folate is destroyed by cooking)

Question 15

Describe the absorption of folate

Answer 15

Mostly in the small bowel, no carrier molecule is required

Question 16

How long do the stores of folate last?

Answer 16

A few days - quickly used up if there is increased demand e.g. increased cell turnover

Question 17

Explain what happens if there is not enough folate or B12

Answer 17

• Disparity in the rate of synthesis of the precursors of DNA (deoxyribonucleoside triphosphates)
• Abnormality of cell division
• If no dietary folate, no methyl THF
• If no B12, Methyl THF can’t be converted to THF

Question 18

Explain the blood film of someone with a B12/folate deficiency

Answer 18

• Dissociation between nuclear and cytoplasmic development (nucleus not mature)
• Abnormal cells e.g. too many lobes in a neutrophil due to failure of division
• Microcytic red cells, often oval shaped

Question 19

Why may there be increased bilirubin or LDH with megaloblastic anaemia?

Answer 19

Because of ineffective erythropoiesis, there is death of mature cells whilst still in the bone marrow as they are abnormal. This breakdown results in raised bilirubin and lactate dehydrogenase

Question 20

Describe the tissues affected in B12 or folate deficiency

Answer 20

All rapidly growing, DNA synthesising cells, especially therefore the bone marrow and epithelial surfaces (mouth, stomach, small intestine, urinary and female genital tracts)

Question 21

What are the blood abnormalities in a B12 deficiency?

Answer 21

Megaloblastic anaemia with leucopenia and thrombocytopenia

Question 22

What is leucopenia

Answer 22

Low white blood cell count

Question 23

What is thrombocytopenia?

Answer 23

Low platelet count

Question 24

What are the neurological manifestations of B12 deficiency?

Answer 24

Bilateral peripheral neuropathy or demyelination of the posterior and pyramidal tracts of the spinal cord

Question 25

What are the blood abnormalities of folate deficiency?

Answer 25

Megaloblastic anaemia, potentially leucopenia and thrombocytopenia

Question 26

What is the effect of folate deficiency on a growing foetus?

Answer 26

If in the first 12 weeks, deficiency can cause neural tube defects

Question 27

How do patients with a folate or B12 deficiency present?

Answer 27

• Symptoms of anaemia/cytopenia: tired, easy bruising (due to thrombocytopenia (rare))
• Mild jaundice “lemon yellow tint” due to haemolysis
• Neurological problems with gait and vibration sense due to B12 deficiency (subacute combined degeneration of cord

Question 28

What are the causes of B12 deficiency?

Answer 28

• Dietary - B12 not ingested
• Pernicious anaemia
• Gastrectomy/ achlorhydria
• Terminal ileum problem e.g. Chron’s, resection

Question 29

Explain how pernicious anaemia leads to B12 deficiency

Answer 29

Autoimmune reaction to the gastric parietal cells, resulting in less intrinsic factor so no binding to B12 so it cannot be absorbed into the blood

Question 30

Explain how a gastrectomy/achlorhydria leads to B12 deficiency

Answer 30

Removal of the stomach, therefore lacks the acid and therefore ability to release B12

Question 31

What are the causes of folate deficiency?

Answer 31

• Dietary (majority)
• Extenisve small bowel disease e.g. coeliac/chrons
• Increased cell turnover e.g. haemolysis or severe skin disorders such as psoriasis

Question 32

Other than folate/B12 deficiency (megaloblastic anaemia), what are the other causes of macrocytosis?

Answer 32

• Reticulocytosis
• Red cell membrane abnormality (made of lipids) due to alcohol/liver disease/ hypothyroidism
• In anaemia with bone marrow failure syndromes - congenital or myelodysplasia