Macrocytic Anaemia Flashcards
What is macrocytosis?
An increase in cell volume (MCV)
What is macrocytic anaemia
Anaemia in which the red cells have a larger than normal volume
What is mean corpuscular volume measured in
femtolitres (1 = 10 to the -15)
What is a normal MCV
80-100fl
more than 100 = macrocytic
What does megaloblastic mean?
An abnormally large nucleated re cell precursor with an immature nucleus
What are the predominant defects in megaloblastic anaemia
DNA synthesis and nuclear maturation
RNA and Hb synthesis is preserved
What is the mechanism that leads to the formation of megaloblastic cells?
While the cytoplasm has developed appropriately and is mature enough to divide (it is large) the nucleus is still immature so after enucleation you end up with larger than normal cells.
IMPORTANT- the larger cell size is not due to an uncrea in the size of the developing cell but a failure to become smaller
What are the causes of megaloblastic anaemia
B12
Folate
Others - drugs, rare inherited abnormalities
Why does B12 or folate deficiency cause megaloblastic anaemiea
B12 and folate are both essential co factors for nuclear maturation.
They enable chemical reaction that provide enough nucleosides for dNA synthesis.
What two biochemical cycles are B12 and folate involved in
methionine and folate cycle- these are interlinked cycles
How do the methionine and folate cycles interine
Methionin cycle produces s-adenosyl methionine, a methyl donor to DNA and folate intermediates.
What is the folate cycle important for
nucleoside synthesis
What are the various causes of B12 deficiency
Dietary deficiency Atrophic gastritis PPIs Gastrectomy/bypass Chronic pancreatitis Bacterial overgrowith Coeliac Bowel resection Crohn's
Where is folate absorbed in the gut
the jejunum and duodenum
How long can your body rely on your B12 stores vs folate stored
2-4 yrs for B12
4 mths for folate
Become deficient in folate much quicker
Where is B12 absorbed
Ileum
What is your daily requirement of B12 vs folate
B12 much less - 1-3ug/day
Folate - 100ug per day
What are the causes of folate deficiecy
Inadequate dietary intake- more likely than B12
Malabsoption - coeliac, crohns
Excess utilisation- haemolysis, exfoliating dermatitis, pregnancy, malignancy
Drugs- anticonvulsants, methotrexate
What are the symptoms of B12 and/or folate deficiency
Symptoms of anaemia
Weight loss, diarrhoea, infertility
Glossitis, jaundice
developmental problems
What symptom/sign is specific to B12 deficiency
neurological problems- neuropathy, dementia, psychiatric
What is pernicious anaemia
Autoimmune condition resulting in destruction of gastric parietal cells
What is associated with pernicious anaemia
FHx of autoimmune conditions
Atrophic gastritis
What are the features of the cells in pernicious anaemia
Macrocytic
can be pancytopenia
Macrovalocytes and hypersegmented neutrophils on blood film
what test can be done to diagnose macrocytic megaloblastic anaemias
serum B12 and folate levels- not perfect!
Auto- antibodies= anti intrinsic factors and anti gastric parietal cells
Schillings test - not used anymore
Bone marrow examination - not usually required
What are the disadvantages to antibody testing
Anti GPC = sensitive, not specific
Anti- IF= more specific, not sensitive
How is pernicious anaemia treated
B12 injections for life
Folic acid 5mg per day also lifelong
What are the causes of non megaloblastic anaemia
Alcohol, Liver disease, Hypothyroid –> may not have anaemia
Marrow failure e.g. Myelodysplasia, myeloma, aplastic anaemia —) associated with anaemia
What is the problem in anaemia due to alcohol, liver disease and hypothyroid
Due to red cell membrane changes
What are the causes of spurious macrocytosis
reticulocytosis
Cold agglutinin disease
What is reticulocytosis and what is it caused by
increased no of reticulocytes (which are bigger than mature red cells hence macrocytosis)
Caused by acute bleed or haemolysis
what is cold agglutinin disease
Cold agglutinin disease is an autoimmune disease characterized by the presence of high concentrations of circulating antibodies, usually IgM, directed against red blood cells.
Why does the analyser register cold agglutinin disease as macrocytic
the agglutinated red cells clump together and appear as one large cell
What important symptom my patients with pernicious anaemia have
Jaundice
Why do patients with pernicious anaemia get jaundice
Red cells die in marrow –> Hb and LDH are released –> Hb converted to bilirubin
