Macrocytic anaemia Flashcards
What is macrocytosis
increase in number of big cells
usually refers to RBC’s
What is macrocytic anaemia
anaemia in which the red cells have a larger than normal volume
How is size of the cell expressed or detected
MCV (mean cell volume)
units are femtolitres
give size (in fl) of normal and macrocytic red blood cells
normal = 80-100 fl
macrocytic = >100 fl
What are the types of macrocytic anaemia
True: megalobastic and non-megaloblastic
false (spurious) =
What is a megaloblast?
erythroblast = normal red cell precursor with nucleus
megaloblast = abnormally large nucleated red cell precursor
what is megaloblastic anaemia?
defect in DNA synthesis and nuclear maturation with sparing of RNA and haemoglobin synthesis
cytoplasm = normal nucleus = lags, immature
What is the cellular consequence of this defect in DNA and nuclear maturation?
cytoplasm develops normally and is large enough to divide but the nucleus isnt and lags behind. This results in an abnormally large cell
What are some causes of megaloblastic anaemia?
B12 deficiency
folate deficiency
other: drug, inherited
Why are B12 and folate deficiency causes of megaloblastic anaemia?
B12 and folate are essential for nuclear maturation as they provide chemical reactions that provide nucleosides for DNA synthesis and replication
what is required to absorb B12 in the gut?
intrinsic factor is required
what cells secrete intrinsic factor?
parietal cells in the stomach
Where in the small bowel is B12 absorbed into the blood stream??
terminal ileum
patients with terminal ileum resection will malabsorb B12
What are some causes of B12 deficiency?
inadequate intake in diet (vegans) absorption defect (pernicious anaemia, gastrectomy, tape worm)
What are dietry folates converted to?
monoglutamate
where are folates absorbed in the small bowel?
duodenum and jejunum
What foods provide B12 and folate?
B12 - meat
folate - leafy veg, yeast (destroyed by cooking)
What are some causes of folate deficiency?
inadequate dietary intake
inadequate absorption (coeliac, crohns)
excess utilisation - haemolysis, pregnancy, malignancy, dermatitis
drugs - anticonvulsants
What are symptoms and signs of B12 and folate deficiency?
signs and symptoms of anaemia
weight loss, diarrhoea, sore tongue, jaundice
What can happen with B12 deficiency?
neurological signs as B12 affects myelin sheath
dorsal column signs, dementia, neuropathy
What is pernicious anaemia?
autoimmune destruction of gastric parietal cells
no secretion of IF so no absorption of B12
What is pernicious anaemia associated with?
atrophic gastritis and other autoimmune conditions like addisons, vitiligo, hypothyroidism
What cell mediates the autoimmunity of pernicious anaemia
CD4
How do you diagnose pernicious anaemia in laboratory?
macrocytic anaemia
pancytopaenia (reduction in number of all cells)
hypersegmented neutrophils
macrovalocytes (enlarged oval shaped erythrocyte)
How else can you diagnose pernicious anaemia in the lab?
assay B12 and folate levels
check for autoantibodies: anti gastric-parietal cell (anti-GPC)
anti intrinsic factor (anti-IF)
schillings test
How do you treat megaloblastic anaemia
treat cause
give B12 injection
folic acid tablets
transfuse red cells if life threatening
What are some causes of non-megaloblastic macrocytosis
alcohol
liver disease
hypothyroidism
(these may not be associated with anaemia and are due to red cell membrane changes)
marrow failure
- myeloma
- myelodysplasia
- aplastic anaemia
what are some types of spurious (false) macrocytosis
reticulocytosis
cold agglutinins
what is reticulocytosis
formation of reticulocytes in response to decreased erythrocytes (haemolysis / bleed)
Why is reticulocytosis confused with macrocytosis
reticulocytes are the precursor to RBC’s and are larger than mature red blood cells
How is cold agglutinins confused with macrocytosis
red blood cells clump together and appear to be one abnormally large red cell
