Megaloblastic Anaemia

Question 1

Describe the requirements for normal RBC production

Answer 1

• drive for erythropoiesis (erythropoietin production by kidney)
• genetic coding for erythropoiesis
• essential components (iron, B12, folate, minerals)
• a functioning marrow

Question 2

Describe the role of B12/folate metabolism

Answer 2

• essential for DNA synthesis and maturation
• required by all dividing cells (deficiency affects red cells first)
• deficiency will eventually affect other organs

Question 3

What 2 processes is B12 necessary for?

Answer 3

Processes involved in DNA synthesis and fatty acid/protein breakdown
- methylation of homocysteine to methionine
- isomerisation

Question 4

What are the requirements and excretion volume of B12?

Answer 4

• requirement of 1 microgram a day (in meat mostly)
• loss is 1-2 micrograms a day (urine/faeces)
• stores last 3-4 years

Question 5

Describe the process of B12 absorption

Answer 5

• B12 ingested
• gastric parietal cells in stomach produce intrinsic factor
• acid in stomach release B12 from protein ingested
• B12 binds to intrinsic factor
• complex travels to ileum where it is absorbed into the blood and binds to transcobalamin

Question 6

Where do we get folate from, how is it absorbed and how long do stores last?

Answer 6

• absorbed from dietary sources (green veg - but destroyed in cooking)
• absorption occurs in small bowel (no carrier molecule required)
• stores last a few days so higher demand than B12

Question 7

Describe the mechanism of folate absorption

Answer 7

• dietary folates ingested and absorbed across small intestine into plasma
• B12 needed for DNA synthesis

Question 8

Describe the pathophysiology behind Megaloblastic anaemia

Answer 8

• disparity in the rate of synthesis of precursors of DNA due to deficiency in folate
• abnormality of cell division

Question 9

Describe the cellular effect of Megaloblastic anaemia

Answer 9

• production of abnormal cells with big nuclei which should have matured but is failing to
• oval in shape
• can affect other blood cells (eg. Increased nuclei in neutrophils)
• dissociation between nuclear and cytoplasmic development
• ineffective erythropoiesis (bone marrow recognises there is a problem and tries to break down red cells to start again - increase in bilirubin + LDH)

Question 10

Describe the clinical manifestations of Megaloblastic anaemia

Answer 10

• tissues affected (bone marrow and epithelial surfaces)
• blood abnormalities (leukopenia, thrombocytopenia)
• neurological manifestations (rare + present in advanced disease): demyelination of dorsal and lateral columns

Question 11

What is the clinical relevance of folic acid in pregnancy?

Answer 11

Folate deficiency can cause neural tube defects of the developing foetus

Question 12

Describe the possible patient presentation of Megaloblastic anaemia

Answer 12

• tired
• easy bruising (from thrombocytopenia - late complication)
• mild jaundice (due to haemolysis)
• neurological problems (gait, JPS etc.)

Question 13

What are the indirect causes of B12 deficiency?

Answer 13

• problems with intrinsic factor production (pernicious anaemia)
• gastrectomy (lack ability to break down B12)
• problems with terminal ileum (eg. Crohn’s) which can impair absorption

Question 14

What are the main causes of folate deficiency?

Answer 14

• deficiency in dietary intake
• extensive bowel disease (eg. Coeliac)
• increased cell turnover (haemolysis)
• severe skin disorders (eg. Psoriasis)
• pregnancy (run out of folate quicker)

Question 15

What are other causes of macrocytosis?

Answer 15

• reticulocytosis (immature red cells are larger than average mature red cells): in individuals making a lot of new cells resulting in change in overall MCV
• cell wall abnormality (lipids): alcohol, liver disease, hypothyroidism
• with anaemia = bone marrow syndromes