1 - macrocytic anaemia Flashcards
what is macrocytic anaemia?
red cells larger than normal
what is a comparison you can make to check size of RBCs?
normal RBC should be same size as nucleus of normal mature small lymphocyte
what is a megaloblast?
larger than a “normal nucleated red cell precursor (which is erythroblast)” with immature nucleus, they’re normally in bone marrow
what is megaloblastic anaemia?
lack of red blood cells, the ones that do exist are bigger than they should be with immature nuclei (megaloblasts)
- they’re caused by nuclear maturation defect from DNA synthesis defect which means DNA cell division is reduced and apoptosis increases
what are causes of megaloblastic anaemia?
- B12 deficiency
- folate deficiency
- also drugs or rare inherited conditions
how do B12 and folate deficiency cause megaloblastic anaemia?
B12 and folate both help conversion of uracil to thiamine which is what needed for DNA, so basically B12 & folate deficiency mean defect in DNA so nuclear abnormality so megaloblast made (large with immature nucleus)
what is physiology of B12, where do they travel and absorbed etc?
B12 travel to stomach, B12 dissociated from food in acidity of stomach, the haptocorrin (from mucous) helps prevent acid destroying B12. at same time gastric parietal cells secrete intrinsic factor which travels with B12 through small intestine. trypsin causes dissociation of B12 & haptocorrin so now B12 with intrinsic factor, now absorbed in distal small bowel (ileum)
what are causes of B12 deficiency?
- food from mouth = vegans
- pancreas = chronic pancreatitis
- stomach = gastritis, PPI
- small bowel = coeliac, crohn’s, bowel resection
what is pernicious anaemia?
= autoimmune condition where destruction of gastric parietal meaning intrinsic factor deficiency so B12 malabsorption & deficiency = type of megaloblastic anaemia
*it’s associated with atrophic gastritis & fam history of autoimmune
where is
a) folate
b) iron
c) b12
absorbed?
a) jejunum
b) duodenum/ proximal jejunum
c) ileum
what are causes of folate deficiency?
- inadequate diet (most important one, more likely than B12 deficiency from diet cause folate has worse stores than B12)
- malabsorption like coeliac or crohn’s (would present with loose stools)
- excess utilisation (when something happening in body meaning more blood cells being used so more folate required) = haemolysis, exfoliating dermatitis, pregnancy, malignancy
- drugs = anti-convulsants (not important)
what are clinical symptoms of B12 and folate deficiency? what is additional symptom that only B12 deficiency has?
- weight loss, diarrhoea, infertility
- sore tongue, jaundice
- developmental problems
- big beefy tongue or smooth red big tongue
B12 deficiency also has neurological problems since B12 helps convert to methionine which is for myelin sheath = this damage is irreversible so very important
what is buzzword on blood film for B12 and folate deficiency macrocytic anaemia?
macroovalocytes + hypersegmented neutrophils (normally 3-5 nuclear segments) - multiple nuclear lobes enlarged oval shaped erythrocytes
what auto-antibodies can be checked for megaloblastic macrocytic anaemia? why bad?
= not great as if find doesn’t necessarily mean they have it
- anti-gastric parietal cell
- anti-intrinsic factor
what are treatments of B12 and folate deficiency? (obvious)
very good to treat with B12 or folate as have very few side effects - much worse if don’t treat than if do
- vit B12 injections for life if pernicious anaemia, higher dose if neurological features
- folic acid 5mg per day
- only if life threatening anaemia transfuse red cells
