Macrocytic Anaemia Flashcards
What is macrocytosis
macro= big
cytosis= an increase in cell numbers
What is macrocytic anaemia
anaemia in which the red cells have a larger than normal volume
How is size expressed ? (2)
MCV: Mean Corpuscular (Cellular) Volume
Units: femtolitres (1 femtolitre is equal to 10-15L )
Measurement of MCV
Modern analysers use the light scatter properties of red cells to measure the MCV
Recognising macrocytes on blood film (2)
80-100fl= Normal
> 100fl= Macrocytic
Causes of macrocytosis (2)
megaloblastic
non-megaloblastic
Megaloblastic
- larger than normal, nucleated red cell precursor (mother cell) with an immature nucleus
-
Where is megaloblastic based
bone marrow in adults
Red cell development (2)
- a mature red cell= membrane surrounding soluble proteins and electrolytes
-norm red cell precursors (exclude reticulocyte) have a nucleus (erythroblasts or normoblasts) + marrow based
What happens in megaloblastic anaemia? (5)
lack of red cells due to predominant defects/ problem in DNA synthesis and nuclear maturation in developing precursor cells in the marrow
due to DNA defects cell division is reduced and apoptosis increases
in surviving cells cytoplasmic development and Hb accum continues norm so the precursor cell is bigger
Hb level in cell optimal, nucleus removed leaving bigger than norm red cell- a ‘macrocyte’
overall fewer microcytes and hence anaemia
megaloblastic anaemia
characterised by larger precursor cells with an immature nucleus leading to macrocytic anaemia
Causes of megaloblastic anaemia (4)
B12 deficiency
Folate deficiency
Others=
-Drugs
-inherited abnormalities
Why are B12 and folate important? (4)
they are essential co factors in linked biochemistry reactions regulating=
-DNA synthesis and nuclear maturation- blood cell effect
-DNA modification , gene activity- nervous system
-B12 deficiency may effect lipid synthesis impacting on myelin (protective sheath around nerve fibres)
DNA synthesis and nuclear maturation (3)
uracil (deoxyuridine monophosphate) > thymine (deoxythymide monophosphate)
by thymidylate synthase
DNA modification and gene activity (3)
homocysteine> methionine
by methionine synthase
Causes of Vitamin B12 deficiency (7)
vegans
pancreas=
-chronic pancreatitis
small bowel =
- jej- bact overgrowth, coeliac
-duodenum- crohns, resection (distal)
stomach =
-prenicous anaemia- gastritis
-PPIs/ H2 receptors
-gastrectomy/ bypass
What is pernicious anaemia? (3)
autoimmune - destruction of gastric parietal cells
results in intrinsic factor deficiency with B12 malabsorption + deficiency
assoc atrophic gastritis, hypothyroidism, vitiligo, addisons
Folate absorption (2)
dietary dilates converted to monoglutamate
absorbed in jejunum- diffusion and actively
Causes of folate deficiency (7)
inadequate intake- diet cause! more likely than B12 due to lesser stores
malabsorption- coeliac, crohns
excess utilisation=
-haemolysis
-pregnancy
-exfoliating dermatitis
-malignancy
-drugs=
Clinical features of B12/ folate deficiency (9)
Both
- symps/ signs anaemia
- weight loss, jaundice!! , diahorrea
- sore tongue, infertility
- developmental problems
B12
-neurological manifestations- irreversible in some patients
Lab diagnosis B12/ folate deficiency - 1 (3)
macrocytic anaemia- red cell count LOW
pancytopenia- all cells LOW in some
blood fills show macrovalocytes + hypersegmented neutrophils - (3-5 nuclear segments)
Lab diagnosis B12/ folate deficiency - 2 (5)
Assay b12/ folate levels
-low levels may not always indicate deficiency ( pregnancy/ birth control)
Check autoantibodies=
-anti gastric partietal (GPC)- sensitive not specific
-anti intrinsic factor (IF)- sensitive not specific
Lab diagnosis B12/ folate deficiency - 3 (4)
schillings test- for B12
bone marrow exam- not required usually
measure metabolites + holotranscobalamin- not standard
trial of therapy
Treatment megaloblastic anaemia
treat causes where possible-
Vit B12 injections
Folic acid tablets
