Macrocytosis and Macrocytic Anaemia Flashcards
what is macrocytic anaemia
low levels of RBCs of a high volume
how is RBC size measured
Mean cell volume
causes of macrocytosis
genuine/true
- megaloblastic
- non-megaloblastic
how do red cells develop
start with large cell
gains Hb
looses nucleus
shrinks
stages of erythropoiesis
pronormoblast early normoblast intermediate normoblast late normoblast reticulocyte mature red cell
what is megaloblastic anaemia
RBC come from megaloblasts
an abnormally large nucleated red cell precursor with an immature nucleus
how are megaloblastic anaemias characterised
lack of red cells due to defects in DNA synthesis and nuclear maturation
RNA, cytoplasm and haemoglobin synthesis preserved so the precursor cell is v big
what happens to megaloblasts after they have got all the Hb they need
nucleus is extruded leaving behind a bigger than normal red cell
overall fewer macrocytes than normal RBCs hence anaemia
what happens after a megaloblast looses its nucleus
megaloblast becomes a macrocyte - large RBC
due to failure of them to get smaller at the right time
causes of megaloblastic anaemia
B12 deficiency Folate deficiency Others -drugs -rare inherited abnormalities
why do B12 and folate deficiency impact RBC production
they are important in DNA synthesis and nuclear maturation
also causes nervous system problems due to DNA modification and gene activity
where is B12 in the diet
meat
eggs
(cobalamine = B12)
physiology of B12 absorption
released from meat in stomach
binds to haptocorrin protein
causes release of intrinsic factor from parietal cells
pancreatic secretions into the small intestine causes PH to get more alkaline so B12 and haptocorrin release each other
THEN B12 is free to bind to the Intrinsic Factor (IF)
goes through the whole intestinal system as B12IF
in the ilial epithelium in the distal gut the B12 is released from IF and absorbed
binds to protein called transcobalamin into the blood
where are iron, calcium and B12 absorbed
iron and calcium in proximal gut
B12 in distal gut
causes of B12 deficiency anaemia
Diet Stomach problems -pernicious anaemia -atrophic gastritis -PPIs, H2 receptor antagonists -Gastrectomy/bypass
small bowel problems -jejunum bacterial overgrowth coeliac disease -duodenum resection crohns disease
distal bowel problems
-inherited receptor deficiency
absorbed in the ilium
what is pernicious anaemia
autoimmune destruction of gastric parietal cells, preventing the release of IF leading to B12 deficient anaemia
where is folate absorbed
duodenum and jejunum
dietry folate is converted to monoglutamate
where do you get folate from
liver
leafy veg
fortified cereals
where do you get B12 from
animal products
how long are the body stored from B12 and folate
B12 - 2-4 years
Folate - 4 months
causes of folate deficiency
dietary causes malabsorption (coeliac, crohn's) excess utilisation -haemolysis -exfoliating dermatitis -pregnancy -malignancy
drugs
-anticonvulsants
clinical features common to both B12 and folate deficiency
anaemia weight loss diarrhoea infertility sore tongue jaundice developmental problems
clinical features of B12 deficiency
Neurological problems
- posterior column abnormalities
- neuropathy
- dementia
- psychiatric manifestations
what are the blood film features of B12 deficiency
large oval shaped RBCs (macrovalocytes)
Hypersegmentated neutrophils (number of nuclear segments increases from 3-5 to much more)
what other lab signs point to B12 deficiency
macrocytic anaemia
pancytopenia (all cells are low)
investigations for B12 deficiency
assay B12 and folate serum levels
check for autoantibodies (anti-intrinsic factor and anti-gastric parietal cell)
Treatment of megaloblastic anemia
treat cause
vitamin B12 injections for life in pernicious anaemia
folic acid tablets orally
one if potentially life threatening - transfuse red cells
what are non-megaloblastic causes of genuine macrocytosis
alcohol (macrocytosis in the absence of anaemia)
liver disease
hypothyroidism
marrow failure - always associated with anaemia
-myelodysplasia
-myeloma
-anaplastic anaemia
what is false macrocytosis
volume of MCV is normal but tests read it as being raised
causes of false macrocytosis
an increase in reticulocyte numbers as a marrow response to acute blood loss
-because reticulocytes are larger in tests it looks like RBCs are larger
Cold-agglutinins
- abnormal proteins only active at room temp not body temp
- cause clumping of red cells and confuses the machine giving v high MCV values which aren’t possible
why do people with pernicious anaemia appear mildly jaundice
red cells die prematurely in the marrow
intramedullary haemolysis - so the bilirubin is just released
this can also occur in B12 and folate deficiency?
