Macrocytic Anaemia Flashcards
What is macrocytic anaemia?
Anaemia where red cells volume is larger than normal (>100 MCV)
What causes macrocytic anaemia?
Genuine- Megaloblastic and Non-megaloblastic
Spurious- cold-agglutnins, reticulocytosis
What is megaloblastic anaemia?
Defects in DNA synthesis and nuclear maturation leading to lack in red cells
How do megaloblastic cells appear on blood film?
Larger than normal, nucleated red cell precursors (with an immature nucleus)
What causes megaloblastic anaemia?
B12 deficiency
Folate deficiency
Drugs ie methotrexate
How do megaloblasts come about forming?
In normal erythopoesis, normoblasts are marrow based and have nuclei, and Hb accumulation triggers them to stop dividing, lose the nucleus, and reduce in cell size
B12 and Folate deficiency impair the process of normal cell division
Precursor is a megaloblast due to nucleus presence, so upon full erythropoiesis there are less cells that are larger
Why are b12 and folate important?
B12 and folate convert uracil to thymine
Lack of thymine impairs proper DNA replication, inhibiting nuclear division and hence leaving erythrocytes too big
B12- where is it found and how is it absorbed?
Animal sources
Attached to R-binder in stomach which carries it through digestive system until pancreatic enzymes detach it from the binder, it is then bound to IF (secreted by gastric paretial cells) which carries it to its specific receptor for absorption in the ileum
Folate- where is it found and how is it absorbed?
Liver, leafy veg and fortified cereals
Converted to monoglutamate and absorbed in jejunum
What causes deficiency of b12 and folate?
B12:
Inadequate dietary intake eg veganism
Pernicious anaemia- autoimmune gastric paretial cell destruction -> IF deficiency -> malabsorption
Malabsorption due to stomach conditions
Folate:
Diet
Malabsorption
Haemolysis
Exfoliating dermatitis
Pregnancy
Malignancy
Anticonvulsant drugs
Excess urination
How does megaloblastic anaemia present?
General anaemia symptoms
Weight loss
Diarrhoea
Sore tongue
May be jaundiced- prematurely dead cells release their Hb which is converted to bilirubin
B12 deficiency may present neurological deficit
Investigations for megaloblastic anaemia
FBC- macrocytic anaemia, may show pancytopenia
Blood film- !macrovalocytes (oval shaped RBC), hypersegmented neutrophils!
Assess serum folate and B12 levels
Autoantibodies (for pernicious):
anti gastric paretial cell (not specific)
anti-IF autoantibodies (not sensitive)
Management for megaloblastic anaemia
Treat cause
For pernicious-
Lifelong b12 (Hydroxocobalamin) injections, with higher dose if neuro symptoms present
Folic acid tablets
Red cell transfusion in life threatening cases
What is non-megaloblastic anaemia?
Macrocytosis without megaloblastic changes
What causes non-megaloblastic anaemia?
Associated with anaemia-
Myelodysplasia
Myeloma
Aplastic anaemia
Not associated with anaemia-
Alcohol and liver disease
Hypothyroidism
Marrow failure
