Macrocytosis and macrocytic anaemia Flashcards
macrocytic anaemia
red cells have a larger than normal volume
how is size expressed
MCV- mean corpuscular volume
expressed in units- femtolitres
MCV
average size of a red blood cell
reference ranges MCV
80-100fl - normal
> 100fl - macrocytic
causes of genuine macrocytosis
Megaloblastic Anemia (Defective DNA Synthesis)
Vitamin B12 deficiency
Folate deficiency
Drug-induced (e.g., methotrexate, hydroxyurea, zidovudine)
genuine macrocytosis
red blood cells are truly larger
false macrocytosis
increase in MCV on lab tests that doesnt correspond to a true increase in rbc size
causes of false macrocytosis
hypergylcaemia
leukocytosis
reticulocytosis
megaloblastic
larger than normal nucleated red cell with an immature nucleus in the bone marrow
megaloblastic anaemia characterisation
characterised by lack of red cells due to defect in dna synthesis and nuclear maturation in developing precursor cells in the marrow
due to this cell division is reduced and apoptosis increases
larger precursor cells with an immature nucleus leading to macrocytic anaemia
what do b12 and folate help in the conversion of
uracil to thymine
what reactions are b12 and folate co factors in
- DNA synthesis and nuclear maturation (e.g. blood cell effect)
- DNA modification and gene activity (e.g. nervous system)
where is b12 absorbed
ileum
where is folate absorbed
duodenum and jejenum
metabolism of folate
dietary folates converted to monoglutamate
absorbed in jejunum
metabolism of b12
- Vitamin B12 is liberated from protein complexes in food by gastric enzymes and then binds to a vitamin B12-binding protein (‘R’ binder)
- Vitamin B12 is released from the ‘R’ binder by pancreatic enzymes and then becomes bound to intrinsic factor
- Intrinsic factor is a glycoprotein secreted by gastric parietal cells; it combines with vitamin B12 and carries it to a specific receptor on the mucosa of the ileum
- Vitamin B12 enters the ileal cells and intrinsic factor remains in the lumen and is excreted
- Vitamin B12 is transported from the enterocytes to the bone marrow and other tissues by the glycoprotein transcobalamin II
pernicious anaemia
autoimmune condition with resulting destruction of gastric parietal cells
with does pernicious anaemia result in
intrinsic factor deficiency with b12 malabsorption and deficiency
causes of folate deficieny
Inadequate intake
Dietary cause more likely than B12 due to lesser stores
Malabsorption
Coeliac disease, Crohn’s disease
Excess utilisation
Haemolysis
Exfoliating dermatitis
Pregnancy
Malignancy
Drugs
anticonvulsants
clinical features of b12/ folate def
Symptoms/signs of anaemia
weight loss, diarrhoea, infertility
Sore tongue, jaundice
Developmental problems
what deficiency can cause neurological problems
b12 def
irreversable damage
lab diagnosis of b12/folate def
macrocytic anaemia- low red cell count
pancytopenia - all cells low
blood film shows macrovalocytes and hypersegmented neutrophils
auto antibodies in b12/ folate def
anti gastric parietal cell - sensitive not specific
anti intrinsic fcator - specific not sensitive
treatment of megaloblastic anaemia
diet/ oral supplementation
vit b12 injevtions for life in pernicous anaemia
folic acid tablets 5mg per day
life threatening anaemia treatment
transfuse red cells
causes of non megaloblastic macrocytosis
alcohol
liver disease
hypothyrodisim
marrow failure
ineffective erythropoiesis points
Red cells die prematurely in the marrow
Haemoglobin and lactate dehydrogenase (LDH) are released from dead red cells
Haemoglobin converted to bilirubin
can patients with pericious anaemia appear mildly jaundixed
yes due to intramedullary haemolysis
