Macrocytosis Flashcards
what is macrocytic anaemia
anaemia in which the red cells have a larger than normal volume
how is ‘size’ expressed
Mean Corpuscular Volume (MCV) in femtolitres 1 femtolitre=10-15
how is macrocytosis different to macrocytic anaemia
both have increased MCV but Hb is within normal range in macrocytosis but decreased in macrocytic anaemia
what are the 2 main categories of macrocytosis
genuine (true) and spurious (false)
what are the 2 types of genuine macrocytoiss
megaloblastic and non-megaloblastic
what is an erythroblast/normoblast
a normal red cell precursor with a nucleus
precursors of red cells usually originate from where
bone marrow
describe the features of the developing erythroid cells in the marrow
accumulate Hb
reduce in size
stop dividing and lose nucleus (regulated by Hb content)
what is the first step in erythropoiesis
pronormoblast
describe the stages of development of a red blood cell
pronormoblast basophilic/early normoblst polychromatic/intermediate normoblast orthochromatic/late normoblast reticulocyte mature red cell/erythrocyte
do reticulocytes have a nucleus
no
what is a megaloblast
an abnomrlaly large nucleated rec cell precursor with an immature nucleus
how are megaloblastic anaemias characterised
predominant defects in DNA synthesis and nuclear maturation with relative preservation of RNA and haemoglobin synthesis
what is the cellular consequence of this
cytoplasm has developed and is big enough to divde but the nucleus is still immature which leads to a bigger than normal red cell precursor
what is the larger cell size in megablobalstic anaemia therefore due to
a failure to become smaller (cell doesn’t divide)
what are the causes of megaloblastic anaemia
B12 deficiency, folate deficiency
others-drugs and rare inherited abnormalities
why does B12 and folate deficiency cause megaloblastic anaemia
they are essential co-factors for nuclear maturation
they enable chemical reactions that provide enough nucleosides for DNA synthesis
B12 is synthesised in what cycle
methionine cycel
what does the methionine cycle produce which is important
s-adenosyl methionine which is a methyl donor to DNA, RNA, proteins, lipids, folate intermediated
what does folate cycle produce
nucleoside synthesis (eg uridine to thymidine conversion)
what is B12 combine with in stomach
intrinsic facotr
where is B12 absorbed
distal ileum
how long can the bodys store of B12 last for
2-4 years
what is the daily requirement for B12
1-3 ug a day
where is folate absorbed
duodenum and jejunum
what are sources of folate
leafy veg, yeast, brown rice, chickpeas, nb destroyed by cooking
what is the daily requirement for folate
100ugs/day
what are the causes of folate deficiency
inadequate dietary intake is most common
malabsorption-coeliac disease, crohns disease
excess utilisation eg haemolysis, exfoliating dermatitis, pregnancy, malignancy, anticonvulsants
what are the clinical features of B12/folate deficiency
symptoms/signs of anaemia
weight loss, diarrhoea, infertility,
sore tongue, jaundice
developmental problems
what are dietary folates converted to
monoglutamate
what clinical feature is just due to B12 deficiency
neurological problems-posterior/dorsal column abnormalities, neuropathy, dementia, psychiatric problems
what is pernicious anaemia
autoimmune condition with resulting destruction of the gastic parietal cells
what is pernicious anaemia associated with
atrophic gastits, other autoimmune diseases eg hypothyroid, vitiligo, addisons disease
how is pernicious anaemia diagnosed
macrocytic anaemia
pancytopaenia in some patients
blood film shows macrovalocytes in hypersegmented neutrophils (normally 3-5 nuclear segents)
also -assay B12 and folate levels in serum but low levels may not indicate deficiency and normal may not indicate normalcy
check for auto-antibodies (anti-gastric-parietal cell (GPC) and anti-intrinsic factor (IF)
how is megaloblastic anaemia treated
treat the cause where possible
vitamin B12 injections for life in pernicious anaemia
folic acid tables (5mg per day orally)
only trandfuse red cells if life threatening anaemia
what are the causes of non-megaloblastic macrocytosis
alcohol, liver disease, hypothyroidism (may not be associated with anaemia due to red cell membrane changes)
marrow failure-associated with anaemia-myelodysplasia, myeloma, anaplastic anaemia
what is spurious macrocytosis
the size of the mature red cell is normal but the MCV is high
what are the causes of spurios macrocytosis
increase in reticulocyte numbers as a marrow response to acute blood loss or red cell breakdown (hameolysis)
cold agglutins-clumps of agglutinate red cells as registered as 1 giant cell
why can patients with pernicious anaemia appear mildly jaundice
intramedullary haemolysis
red cells die prematurely in the marrow, haemoglobin and lactate dehydrogenase LDH are released from dead cells, haemo converted to bilirubin
what can complicate sever megaloblastic anaemia
pancytopenia
