Macrocytic Anaemia Flashcards
what is macrocytic anaemia?
red cells have a larger than normal volume
what is false macrocytic anaemia?
the volume of mature red cell is normal, but the MCV is measured as high
what are the two classifications of macrocytic anameia?
o Megaloblastic
o Non-megaloblastic
what are the causes megaloblastic anaemia?
B12 Deficiency
Folate Deficiency
Others – drugs, rare inherited abnormalities
what are the causes of non-megaloblastic anaemia?
Alcohol
Liver Disease
Hypothyroidism Marrow Failure – myelodysplasia, myeloma, aplastic anaemia
what are the blood count features of macrocytic anaemia?
Hb (low), RBC (low), MCV (high)
what are the blood count features of macrocytosis?
Hb (normal), RBC (normal), MCV (high)
what are the features of macrocytic anaemia on blood film?
o >100fl
o Macrocytic red blood cells greater in size than nucleus of Lymphocyte
what are the causes of normocytic anaemia?
- Acute blood loss
- Anaemia of chronic disease (or ↓MCV)
- Bone marrow failure
- Renal failure
- Hypothyroidism (or ↑MCV)
- Haemolysis (or ↑MCV)
- Pregnancy
what are the causes of megaloblastic anaemia?
B12/ Folate deficiency
– Drugs (hydroxycarbamide/ hydroxyurea
what are the causes of Vit B12 deficiency anaemia?
Diet - vegan
Impaired absorption: Pernicious anaemia, Gastrectomy, illeal disease/resection, coeliac disease.
what are the causes of pernicious anaemia?
Autoimmune condition where there is atrophy of the gastric mucosa, with failure of Intrinsic Factor (and acid production)→ B12↓ absorption.
what are the causes of folate deficiency anaemia?
Poor Intake - old age, poverty, alcohol excess, anorexia
Malabsorption - coeliac, tropical sprue
Excess utilization
– pregnancy, lacatation, prematurity, chronic haemolytic anaemia, malignant and inflammatory diseases, dialysis
what are the clinical features of megaloblastic anaemia?
Usually asymptomatic
what are the clinical features of vit B12 deficiency anaemia?
Peripheral neuropathy – dorsal column degen.
Rarely – dementia
what are the general clinical features of pernicious anaemia?
Glossitis, Angular stomatitis, Mild jaundice, weakness + tiredness, Dysponea, Diarrhoea, grey hair, Mild Splenomegaly, Fever
what are the clinical features of folate deficiency anaemia?
Anaemia
what is the management of Vit B12 deficiency anaemia?
Treat cause
IM B12 injections
what is the management of pernicious anaemia?
IM Hydroxocobalamin
what is the management of folate deficiency anaemia?
– Tx of underlying conditon.
– Oral folic acid 5mg daily for 4 months
what is the pathophysiology of megaloblastic anaemia?
delayed nuclear maturation relative to that of the cytoplasm.
what are the neurological clinical features of pernicious anaemia?
Polyneuropathy– weakness, ataxia, paraplegia
Optic atrophy – dementia, visual disturbances.
what are the features on blood film of megaloblastic anaemia?
hypersegmented polymorphs (B12 ↓),
what is the characteristic feature of pernicious anaemia?
Parietal cell antibodies 90%
IF antibodies 50%.
what are the blood test features in pernicious anaemia?
– Hb ↓ – WCC + Platelets ↓ – Serum B12 ↓ < 50ng – Red cell folate ↓ – Serum Bilirubin ↑
what are the blood tests features for folate deficiency anaemia?
– Red cell folate ↓
– Serum folate ↓
what doe the red blood cells look like in megaloblastic anaemia?
abnormally large nucleated red cell precursor with an immature nucleus (primitive)
what normally happens to erythroblast DNA?
stop diving and lose nucleus once Hb content is optimal
what is the main mechanism of megaloblastic anameia?
defects in DNA synthesis and nuclear maturation but RNA and haemoglobin synthesis are preserved.
Proerythroblasts expand but in maturing erythroblasts, division is reduced and apoptosis increases.
what is the the process of megaloblastic cell formation?
- Cytoplasmic development and haemoglobin accumulation occur normally, and so the precursor cell is bigger with an immature nucleus, i.e. a ‘megaloblast’.
- Once haemoglobin level in the cell is optimal, the nucleus is extruded, leaving behind a bigger-than-normal red cell
what are the roles of B12 and folate?
Enable chemical reactions for
DNA synthesis
Gene activity
what is the role of the folate cycle?
nucleoside
synthesis (eg uridine to thymidine
conversion).
what is the role of the methionine cycle?
producing
a methyl donor called ‘S-adenosyl
methionine’ (impact on DNA, RNA, proteins,
lipids, folate intermediates)
what is the role of R protein?
Binds to B12 for transport
what cells release intrinsic factor?
gastric cells in response to food
what is the role of intrinsic factor?
Acid in stomach frees B12 which binds to intrinsic factor
bound form travels to terminal bowel to be absorbed
what are the sources of B12?
animal
what are the sources of folate?
liver, leafy veg, fortified cereals
how long does the body store B12?
2-4 years
how long does the body store Folate?
4 months
where is B12 absorbed?
ileum
where is folate absorbed?
duodenum and jejunum
what is the daily requirement of B12?
1.5micrograms/day
what is the daily requirement of folate?
200micrograms/day
what are the causes of megaloblastic anaemia?
B12 Deficiency
Folate Deficiency
Others – drugs, rare inherited abnormalities
what is the consequence of both vitB12 and folate deficiney?
microcytic anaemia (cancel each other out)
what are the causes of B12 deficiency?
Diet – vegans
Pancreas - Chronic pancreatitis
Stomach – PA, Atrophic gastritis, PPIs/H2-receptor antganoists, Gastrectomy/Bypass
Small Bowel - Jejunum: bacterial overgrowth, coeliac disease - Duodenum: resection, crohns disease
Cubulin Receptors – inherited deficiency
Pernicious Anaemia
what are the causes of folate deficiency?
Inadequate intake -
Malabsorption - Coeliac disease, Crohn’s disease
Excess utilisation – Haemolysis, Exfoliating dermatitis, Pregnancy, Malignancy, Drugs, anticonvulsants
what are the clinical features of megaloblastic anaemia?
o Symptoms/signs of anaemia
o weight loss, diarrhoea, infertility
o Sore tongue, jaundice
o Developmental problems
what symptoms are specific to vit B12 deficiency?
Neurological problems** – posterior/dorsal column abnormalities, neuropathy, dementia, psychiatric manifestations
how is megaloblastic anaemia diagnosed?
FBC Blood film B12 and folate levels Autoantibodies Schillings test Bone Marrow Exam
what will FBC in megaloblastic anaemia show?
low red cells
Sometimes pancytopenia
What will the blood film in megaloblastic anaemia show?
macrovalocytes and hypersegmented neutrophils (3-5 nuclear segments)
what is the management of megaloblastic anaemia?
Treat cause
Vitamin B12 (hydroxycobalamin) injections for life in pernicious anaemia
Folic acid tablets (5mg per day) orally
