macrocytosis andmacrocytic anaemia Flashcards
macrocytosis?
big cells, increase in number of cells
macrocytic anaemia
anaemia in which red cells have a larger than normal volume
units of MCV?
femtolitres
normal MCV?
80-100
over 100 is macrocytic
blast =
with a nucleus
what is a megalosbast?
abnormally large nucleated red cell precurosor with an immature nucleus
megaloblastic anaemias are characterised by predominent defects in ?
DNA synthesis and nuclear maturation, with relative preservation of RNA and haemoglobin synthesis
preservation of ?
RNA and haemoglobin synthesis
while cytoplasm has developed and become mature (big enough to divide), the nucleus is still immature and lagging behind
leads to bigger than normal red precursor
cell can sense it has enough haemoglobin and doesnt need to divide anymore
end result = microcytic cells
larger cell in megaloblastic anarmia due to?
a failure to become smaller, not an increase in cell size
causes of megaloblastic anaemia
b12 deficiency
folate deficiency
others - drugs or rare inherited anomalies
what are b12 and folate essential co factors for?
nuclear maturation
what do they enable?
chemical reactions that provide enough nucleosides for DNA SYNTHESIS
2 cycles ?
methionine and folate cycle
b12 and folate biochemical reactions are interlinked .
what does the methionine cycle produce?
s-adenosyl methionine
y
what is s-adenosyl methionine?
a methyl donor to DNA and folate intermediates
folate cycle important for nucleoside synthesis
eg uridine to thymidine conversion
what is b12 bound to in the stomach ?
haptocorrin
ditches haptocorrin and binds with ?
IF
absorbed across which receptors?
cubulin
where is b12 absorbed?
ileum
dietary folates converted into?
monoglutamate
where is folate absorbed?
jejunum
where do you get vitamin b12 from?
animal
folate?
leafy geren veg - destroyed by cooking
how long does body store vitamin b12?
2-4 years
folate?
4 months
B12 ilium
bilium
Folate at Duodenum and Jejunm
.
causes of folate deficiency?
dietary causes more likely than b12 due to lesser stores. malabsorption (coeliac, crohns)
when can you get excess utilisation of folate?
haemolysis, exfoliating dermatitis, pregnancy, malignancy
which type of drugs cause folate deficiency?
anti convulsants
clinical features of B12 and folate deficiency?
symptoms/signs of anaemia, weight loss, diarrhoea, sore tongue, jaundice
if you have vitamin b 12 problems only, can get neurologica problems i.e. neuropathy, dementia, psychiatric manifestations
y
autoimmune condition resulting in destruction of gastric parietal cells?
pernicious anaemia
associated with atrophic gastritis and personal or family history of other autoimmune disorders
eg hypothyroidism, addisons
perniciooud anaemia also known as ?
b12 defiency anaemia
why do you get a shortage of b12?
autoimmune attack against gastric parietal cells, which produce intrinsic factor
what would blood film show?
macrovalocytes and hypersegmented neutrophils (usually 3-5 nuclear segments)
pancytopaenia in some patients
y
diagnosis…?
anti GPC (gastric parietal cell) and anti intrinsic factor (anti IF)
which one is sensitive and non specific?
ant GPC
which one is specific and non sensitive?
anti IF
can also do?
assay b12 and folate levels in serum
treatment of megaloblastic anaemia?
treat the cause
folic acid tablets orally
treatment for p anemia?
b12 injections for life
causes of non megaloblastic macrocytosis? (big cells, increased number)
LAHM - liver disease, alcohol, hypothyroidism, marrow failuer
spurrious macrocytosis
reticulocytes bigger than mature red blood cells
what does reticulocytosis indicate?
marrow response to loss of red cells either through acute bleeding or haemolysis
in cold agglutinated disease, what happens?
analyser gets confused as clumps of agglutinated red cells go through and are registered as 1 big cell
why can patients with pernicious anaemia appear mildly jaundiced?
due to intramedullary haemolysis
why do you get jaundice in pernicious anaemia?
defective red cells broken down. ham converted to bilirubin
can get pancytopenia due to b12 folate deficiency
nuclear maturation defects can affect all lineages
