Macrocytosis and Macrocytic anaemia Flashcards
what is a macrocytic anaemia
anaemia where the red cells have a larger than normal volume
what are the units for MCV
femolitres
what will MCV be like in macrocytic anaemia
high
what will FBC be like in macrocytosis
MCV raised
Hb and RBC normal
how is MCV measured
light scatter properties of red cells
when is a red cell macrocytic
> 100fl
what are erythroblasts/ normoblasts
red cell precursors
have a nucleus and are usually marrow based
what triggers developing erythroblasts to stop dividing and loss their nucleus (enucleation)
when Hb accumulates to a certain level
what is a megoblast
an abnormally large nucleated red cell precursor with an immature nucleus
what are megablastic anaemia characterised by
lack of red cells due to predominant defects in DNA synthesis and nuclear maturation
(RNA and Hb synthesis are preserved)
(proerythroblasts expand but in maturing erythroblasts division is reduced and apoptosis increases)
what happens to cytoplasmic development and Hb accumulation in megablostic anaemias
normal - why the precursor cell is bigger (as has immature nucleus that isnt dividing= a megaloblast)
how is a macrocyte formed
when megaloblast (abnormally large precursor cell with immature nucleus) reaches specific level of Hb then nucleus is extruded leaving behind abnormally large red cell
are there more or less red cell in a macrocytic anaemia
less they are just bigger
less as reduced cell division and apoptosis
when is a cell macrocytic
when >100fl
what is a macrocyte
abnormally large mature red cell
why are cells large in megaloblatic anaemia
not because cell getting bigger but not able to become smaller during cell divisions
what does megaloblastic anaemia result in
larger precursor cells with immature nuclei leading to a macrocytic anaemia
what causes megaloblastic anaemia
B12 deficiency
folate deficiency
drugs
rare inherited abnormalities
why are B12 and folate important
essential co factors in:
- DNA synthesis and nuclear maturation (blood cell effect)
- DNA modification and gene activity (nerve system)
how is B12 absorbed
when first consumed binds to R-binder to prevent it getting broken down with food in the stomach
in response to food being in the stomach parietal cells secrete intrinsic factor which binds to B12 and releases it from food
pancreatic secretion raise the pH in the fluid in the small intestine to further separate it
IS ABSORBED IN THE ILEUM
taken into cells bound to transcobalamin
where is iron and calcium absorbed
proximal gut (duodenum- affected by crohns)
what can cause B12 deficiency
diet (vegans)
stomach:
- pernicious anaemia
- atrophic gastritis
- PPIs/H2-receptor antagonists
- gastrectomy/ by-pass
pancreas:
- chronic pancreatitis
small bowel:
- jejunum: bacterial overgrowth, coeliac disease
- Duodenum: resection, crohns disease
cubulin receptors: inherited deficiency
what is pernicious anaemia
autoimmune condition with resulting destruction of gastric parietal cells
results in intrinsic factor deficiency= B12 malabsorption and deficiency
what is pernicious anaemia associated with
atrophic gastritis
personal/ FHx of other autoimmune disorders (hypothyroidism, vitiligo, addisons)
how is folate absorbed
dietary folates converted to monoglutamate
absorbed in the jejunum and duodenum (diffusion and actively)
what are sources of B12
animal produce
what is the requirement for B12
1.5 micrograms a day
stores last 2-4 years
what is the requirement for folate
200 micrograms a day
body stores last 4 months
what causes folate deficiency
inadequate intake: diet (esp in alcoholics)
malabsorption: coeliac disease, crohns
excess utilisation (using folate to make DNA very quickly): haemolysis, exfoliating dermatitis, pregnancy, malignancy
drugs: anticonvulsants (enhance folic acid metabolism)
what are the features of B12 and folate deficiency
symptoms/ signs of anaemia
weight loss, diarrhoea, infertility
sore tongue, jaundice
development (motor delay) problems
for B12 especially: neurological problems- dorsal column abnormalities, neuropathy, dementia, psych manifestations (these can be irreversible)
how is megalobastic anaemia diagnosed
red cell count is low
(pancytopenia in some patients)
blood film shows macrovalocytes and hypersegmented neutrophils (3-5 nuclear segments)
assay B12 and folate levels in serum
check for auto-antibodies:
-anti-intrinsic factor IF
-anti gastric parietal GPC
what are the types of causes of macrocytosis
megaloblastic (B12 or folate deficiency) non megaloblastic (alcohol, liver disease, hypothyroidism, marrow failure)
spurious (false)
what is the treatment for megaloblastic anaemia
treat the cause where possible
B12 injections for life if pernicious anaemia
folic acid 5mg tablets per day
if potentially life threatening transfuse red cells
what can cause non megaloblastic macrocytosis
alcohol, liver disease, hypothyrioidism (these may not be associated with anaemia)
marrow failure: myelodysplasia, myeloma, aplastic anaemia (these all associated with anaemia)
what is spurious macrocytosis
when the volume of the red cell is normal but the MCV is recorded as high: false diagnosis
what can cause spurious macrocytosis
reticulocytosis
cold agglutinins
what is reticulocytosis
an increase in reticulocyte numbers (bigger than mature cells) occurs a marrow response to acute blood loss/ red cell breakdown (haemolysis)
what should you think in a macrocytic anaemia with raised reticulocyte count
haemorrhage/ haemolysis causing reticulocytosis
what other symptoms might people with pernicious anaemia have
mild jaundice due to intramedullary haemolysis (released but not mature) and pallor due to anaemia
what is released from dead red blood cells
lactate dehydrogenase and Hb
what can complicate severe megaloblastic anaemia
pancytopenia
