micro + macrocytic anaemia Flashcards
hypochromic microcytic anaemias
deficient haemoglobin synthesis, a cytoplasmic defect
something lacking in Hb synthesis -> nuclear machinery intact so cells keep dividing
- one of the signal to stop dividing is Hb accumulation
-> as a result the cells are small
and as they contain little Hb, they are hypochromic (lacking in colour)
causes of microcytic anaemia
TAILS
Thalassamia - globin
Anaemia of chrondisease - Fe (heme)
iron def - Fe (heme)
Lead poisoning - porphyrin
Sideroblastic anaemia - protoporphyrin (heme)
haem deficiency causes causing microcytic anaemia
lack of iron for erythropoiesis
- iron def
- AOCD - normal body iron but lack of available
problems with porphyrin synthesis
- lead poisoning
- congenital sideroblastic anaemias
(globin def = thalassaemia)
causes of macrocytic anaemia
megaloblastic anaemia
- B12 def
- folate def
normoblastic macrocytic anaemia
- alcohol
- reticulocytosis
- hypothyroidism
- liver disease
- drugs - azathioprine, methotrexate
megaloblastic
a larger than normal, nucleated red cell precursor, with an immature nucleus - usually based in the bone marrow
cytoplasmic development + Hb accumulation occur normally + so precursor cell is bigger with an immature nucleus
(stops replicating when reaches certain Hb content)
more apoptosis due to falty cells - big cells but less of them (anaemia)
causes of megaloblastic anaemia
B12 def (pernicious anaemia)
folate def
others - drugs, rare inherited stuff
treatment of megaloblastic anaemia
treat cause
- vit B12 injections (pernicious anaemia)
- folic acid tablets (5mg per day)
only if potentially lifethreatening anaemia - transfuse red cells
why are b12 + folate important?
essential co-factors in linked biochemical reactions which regulate -
- DNA synthesis + nuclear maturation - needed for conversion from uracil to thymine, def means too much uracil + initiating apoptosis
- DNA modification + gene activity - acts as a methyl donor to modify gene expression
blood film features of megaloblastic anaemia
hypersegemented neutrophils
pancytopenia
how is B12 absorbed?
intrinsic factor released by parietal cells in stomach forms a complex with B12 which is then absorbed in the distal ileum (end of small intest)
where does absorption of iron take place
occurs in duodenum + proximal jejunum (must be ferrous (Fe2+) state or bound to a protein such as heme
pernicious anaemia
autoimmune condition with resulting destruction of gastric parietal cells - results in intrinsic factor deficiency with B12 malaborption + deficiency
assoc with atrophic gastritis + history/FH of autoimmune disorders
symptoms often subtle - delayed diagnosis
other causes of b12 def - malnutrition, alcoholism
presentation of pernicious anaemia
Peripheral neuropathy with numbness or paraesthesia – “pins + needles”
Subacute combined degeneration of spinal cord – progressive weakness, ataxia, paresthesias
Loss of vibration sense or proprioception
Visual changes
- Mood or cognitive changes – memory loss, poor concentration, confusion, irritability
- Anaemia features – lethargy, pallor, dyspnoea
Mild jaundice – “lemon tinge” (combined with anaemia pallor)
Glossitis -sore tongue
pernicious anaemia investigations
testing for autoantibodies
- intrinsic factor antibody - 1st line
- gastic parietal cell antibody
(before)
FBC
- macrocytic anaemia (may be absent)
- hypersegmented polymorphs
- low WCC + platelets may also be seen
vit b12 + folate levels
management of pernicious anaemia
1mg IM vit B12 replacement (hydroxycobalamin) 3 times weekly for 2 weeks then every 3 months
- more intense regimes if neuro symptoms
if folate def too, treat B12 FIRST !!
- treating with folic acid with b12 def can lead to subacute combined degeneration of cord