Macrocytosis and Macrocytic anaemia Flashcards
macrocytic anaemia definition
anaemia in which the red cells have a larger volume than normal
(so not enough of them, but big)
classification of macrocytosis
- megaloblastic
- non-megaloblastic
megaloblastic meaning
A larger than normal, nucleated red cell precursor (‘mother cell’), with an immature nucleus.
what triggers the normoblast (red cell precursor) to stop dividing and lose nucleus?
Hb content
Megaloblastic anaemias are characterised by a lack of ____ cells due to predominant defects in ____ _________ and nuclear maturation in developing precursor cells in the marrow.
red
DNA synthesis
megaloblastic anaemias - is the problem the cytoplasm or the nucleus
nuclear
what causes megaloblastic anaemia (_______ defects)
nuclear defects
causes of megaloblastic anaemia
B12 deficiency
Folate deficiency
Others
-Drugs
-Rare inherited abnormalities
why are B12 or folate important?
B12 and folate are essential co-factors in linked biochemical reactions regulating:
-DNA synthesis and nuclear maturation - (e.g. blood cell effect)
-DNA modification, gene activity – (e.g. nervous system)
B12/folate is needed to turn uracil to _______
thymine
what food does B12 come from
meat eggs fish
causes of B12 deficiency - what sort of diet
vegan
causes of B12 deficiency -stomach
- PA
- atrophic gastritis
- PPIs
- gastrectomy/bypass
causes of B12 deficiency - small bowel
jejunum
- bacterial overgrowth
- coeliac
duodenum
- resection
-crohns
what is pernicious anaemia
Autoimmune condition where antibodies target either the gastric parietal cells or intrinsic factor, resulting in a lack of intrinsic factor and a lack of absorption of vitamin B12
what other conditions is pernicious anaemia associated with
atrophic gastritis and personal or family history of other autoimmune disorders (eg. hypothyroidism, vitiligo, Addison’s disease)
where is folate absorbed
Absorbed in jejunum (diffusion and actively)
Dietary folates converted to ___________________
monoglutamate
causes of folate deficiency
Inadequate intake
Dietary cause more likely than B12 due to lesser stores (e.g. ‘alcoholic excess’)
Malabsorption
-Coeliac disease, Crohn’s disease
Excess utilisation
-Haemolysis
-Exfoliating dermatitis
-Pregnancy
-Malignancy
Drugs
- anticonvulsants
Clinical Features common to both B12 and folate deficiency
Symptoms/signs of anaemia
weight loss, diarrhoea, infertility
Sore tongue, jaundice
Developmental problems
clinical features more with vit B12 deficiency than folate
Neurological problems –dorsal/lateral column abnormalities, neuropathy, dementia, psychiatric manifestations
Laboratory diagnosis of B12/folate deficiency
Macrocytic anaemia (red cell count is low)
Pancytopenia (all cells low) in some patients
Blood film shows macrovalocytes and ‘hypersegmented’ neutrophils (normally 3-5 nuclear segments)
Assay B12 and folate levels in serum
Check for auto-antibodies
- anti gastric-parietal cell (GPC)
- anti-intrinsic factor (IF)
what might blood film show in B12 and folate deficiency
macrovalocytes and ‘hypersegmented’ neutrophils (normally 3-5 nuclear segments)
lab diagnosis of B12/folate deficiency - autoantibodies - which are sensitive and which are specific
anti gastric-parietal cell (GPC) - sensitive, not specific
anti-intrinsic factor (IF) – specific, not sensitive
