1.04 Macrocytosis and macrocytic anaemia Flashcards
what is a femtolitre?
1 femtolitre = 10^-18 m&3
or 10^-15L
macrocytosis
increased numbers of cells >100fL
What are the ABCDEF of macrocytic anaemia causes?
alcoholism- liver disease b12 deficiency compensatory reticulocytosis drugs- cytotoxic, AZT, dysplasia endocrine- hypothyroidism folate deficiency/fetus (pregnancy)
megaloblastic
erythroblast/normoblast- normal red cell precursor with a nucleus
megaloblast
an abnormally large nucleated red cell precursor
megaloblastic anaemia
defects in dna synthesis and nuclear maturation
preservation of RNA and haemoglobin synthesis
what happens in megaloblastic development of RBC?
cytoplasm development ahead of nuclear development; cell senses that it has enough haemoglobin and doesn’t need to divide anymore, but the cell is too big after enuclation
what are the 4 main causes of megaloblastic anaemia?
b12 deficiency
folate deficiency
drugs
rare inherited abnormalities
why do b12 and folate deficiencies cause megaloblastic anaemia?
these are essential cofactors for nuclear maturation. they enable chemical reaction that provide enough nucleosides for DNA synthesis.
in their absence, the nuclear maturation lags behind.
which nucleoside is affected in the impaired DNA replication of b-12 defieicies?
slow uracil to thymine conversion
where is b12 abnorbed?
terminal ileum
causes of b12 deficiency
vegan diet pernicious anaemia gastrectomy- no IF tropical sprue blind loop syndrome fish tapeworm
What is filate converted to?
monoglytamate
Where is folate absorbed?
in jejunum, active and by diffusion
Which has a smaller body store? b12 or folate?
folate- it would run out in 4 months.
there is also a greater daily requirement- 100 micrograms per day
what are the causes of folate deficiency?
dietary insufficiency of leafy greens, yeasts, destroyed by cooking
malabsorption- coeliac, crohn’s
excess use: haemolysis, exfoliating dermatitis, pregnancy, malignancy
drugs- anticonvulsants
B12/folate/or both deficient in: s/s of anaemia weight loss, diarrhoea sore tongue jaundice
common to both
b12 deficiency s/s only:
neurological problems posterior/dorsal column abnormalities neuropathy dementia psychiatric manifestations
myelin sheath
what other autoimmune disorders are associated with pernicious anaemia?
atrophic gastritis
hypothyroidism
vitiligo
addisons disease
what is the pathogenesis of atrophic gastritis in pernicious anaemia?
autoimmune attack by dendritic cells in stomach
they clear apoptotic parietalcells
they go to paragastric lypmh nodes to activate CD4+ cells that recognise the H+/K+ ATPase on gastric parietal cells
lab diagnosis of macrocytic anaemia
macrocytic anaemia
somtimes pancytopaenia
macroovalocytes
hypersegmented neutrophils- (>3-5 nuclear segments)
b12 and folate levels in serum ( but low may not mean deficiency, and normal may not mean normal)
autoantibodies- anti-gastric parietal cell(more sensitive) and anti-intrinsic factor (more specific)
Schilligs test
step 1- saturate cells with b12
step 2- give radiolabelled b12
step 3- measure b12 in urine
if high- the absorption mechanism is intact, and cells are refusing extra b-12
if low- there is no absorption of b12 in the gut, and thus impossible to get into urine
part 2
step 4- give oral intrinsic factor to see if more appears in urine. if yes there is insufficient intrinsic factor
part 3
repeat test after antibiotics because overgrowth can prevent b12-IF complex absorption
mx of megaloblastic anaemia
tx cause
b12 injections for life in pernicious anaemia
folic acid tablets 5mg/day orally
in life-threatening anaemia- transfuse red cells
causes of non-megaloblastic macrocytosis
may not be assocaited with anaemia (because due to cell membrane changes)
alcohol
liver disease
hypothyroidism
associated with anaemia:
-marrow failure- myelodysplasia, myeloma, asplastic anaemia
