Macrocytosis and macrocytic anaemia Flashcards
What is macrocytic anaemia?
Anaemia in which the red cells have a larger than normal volume
What is used to measure cell size?
MCV - mean cellular volume
What do normal red cell precursors have that mature RBCs don’t, excluding reticulocytes?
A nucleus and are normally marrow based
What happens as erythroblasts develop?
They accumulate Hb, reduce in size and stop dividing (lost nucleus) once Hb content is optimal
What is a megaloblast?
An abnormally large nucleated red cell precursor with an immature nucleus
What characterises megaloblastic anaemias?
Predominant defects in DNA synthesis and nuclear maturation but RNA synthesis and Hb synthesis are preserved so the precursor cell is bigger with an immature nucleus i.e. a megaloblast
Once Hb level in the cell is optimal, the nucleus is extruded, leaving behind a bigger-than-normal red cell i.e. a macrocyte. This explains the megaloblastic part of megaloblastic anaemia but why are they actually anaemic?
There are too few macrocytes being produced, hence anaemia
What is the larger cell size in megaloblastic anaemia due to?
Not due to an increase in the size of the developing cell but a failure to become smaller
What are the main causes of megaloblastic anaemia?
B12 deficiency, folate deficiency
Why does lack of B12 or folate cause megaloblastic anaemia?
B12 and folate are essential co-factors for nuclear maturation. They enable chemical reactions for DNA synthesis and gene activity
Name the cycle that is important for nucleoside synthesis
Folate cycle
Name the cycle that is important for producing a methyl donor called S-adenosyl methionine
Methionine cycle - impact on DNA, RNA, proteins, lipids, folate intermediates
What can be used to measure B12 and folate deficiency?
Homocysteine
What foods provide vitamin B12?
Animal products - meat, fish, eggs
What protects vitamin B12 from digestion in the the stomach and duodenum respectively?
Haptocorrin and intrinsic factor
Where is vitamin B12 absorbed?
Terminal ileum
Name some causes of vitamin B12 deficiency
Vegan diet, atrophic gastritis, PPIs, gastrectomy (stomach), coeliac disease, bacterial overgrowth (jejunum), resection, Crohn’s (duodenum)
What is pernicious anaemia?
Autoimmune condition with resulting destruction of gastric parietal cells. Results in IF deficiency with B12 malabsorption and deficiency
What is pernicious anaemia associated with?
Atrophic gastritis, autoimmune disorders e.g. hypothyroidism, vitiligo, Addison’s disease
How is folate absorbed?
Dietary folates converted to monoglutamate, absorbed in jejunum
Name some causes of folate deficiency
Dietary cause e.g. alcoholics, coeliac disease, crohn’s disease, haemolysis, pregnancy, malginancy, anticonvulsants
What are the common clinical features of B12/folate deficiency?
Fatigue, weight loss, diarrhoea, infertility, glottitis, jaundice, developmental problems. Neurological problems with B12 deficiency - dorsal column abnormalities, neuropathy, dementia - subacute combined degeneration of the cord!!
What is pancytopenia?
ALL cells are low
How is megaloblastic anaemia diagnosed in the lab?
- Low RBC count
- Pancytopenia in some patients
- Blood film shows macrovalocytes and hypersegmented neutrophils - normally 3-5 nuclear segments
- Assay B12 and folate levels in serum
- Check for auto-antibodies - anti-IF and anti-GPC
- Bone marrow exam
How is megaloblastic anaemia treated?
Treat the cause Vitamin B12 injections for life in pernicious anaemia Folic acid tablets If potentially life-threatening anaemia, transfuse red cells
What are the causes of non-megaloblastic macrocytosis?
Alcohol, liver disease, hypothyroidism - these may not be associated with anaemia Marrow failure - myelodysplasia, myeloma, aplastic anaemia - associated with anaemia
What is spurious/false macrocytosis?
The volume of the mature red cell is normal, but the MCV is measured as high
What can cause spurious macrocytosis?
1) Reticulocytosis - rise in reticulocytes occurs as a marrow response to acute blood loss or red cell breakdown (haemolysis) Reticulocytes are bigger than mature RBCs and are analysed along with these for the MCV measurement 2) Cold agglutinins - clumps of agglutinated RBCs are registered as 1 giant cell
What is the approach to finding the cause of macrocytic anaemia? (roughly)
See flow chart
