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
folate absorption
dietary folates converted to monoglutamate
- absorbed in jejunum - diffusion + actively
why can patients be jaundiced in pernicious anaemia?
B12 deficiency causes premature red cell destruction in the BONE MARROW
-> this results in excess bilirubin prodution
due to ineffective erythropoiesis
- red cells die prematurely in marrow
- Hb + lactate dehydrogenase (LDH) are released from dead red cells
- Hb converted to bilirubin
causes of folate deficiency
inadequate intake - dietary more likely than b12 due to lesser stores - eg alcoholics
malabsorption - coeliac, crohns
excessive utilisation
- haemolysis, exfoliating dermatitis, pregnancy, malignancy
drugs - anticonvulsants !!!! know for exam**
source, body store, site of absorption + daily requirement of b12
source = animal
body store = 2-4yrs (onset of def - years)
site of absorption = ileum
daily requirement = 1.5ug/day
source, body store, site of absorption + daily requirement of folate
source = liver, leafy veg, fortified cereals
body store = 4months (onset of def quicker - weeks)
site of absorption = duodenum + jejunum
daily requirement = 200ug/day
clinical features common to both b12 + folate deficiency
anaemia signs
weight loss
diarrhoea
infertility
sore tongue
jaundice !
developmental problems
clinical features more assoc with b12 def
neurological problems
- posterior/dorsal column abnormalities - subacute degeneration of cord (can be assoc with irreversible neurological damage - early recognition important)
- neuropathy
- dementia
- psychiatric manifestations
why does a b12/folate deficiency present as pancytopenia?
b12/folate required for DNA synthesis (uracil -> thymine)
defective DNA synthesis in haematopoitic precursors affected, so all haematopoeic cells lines after are affected
(also maybe haemolysis of faulty cells?)
blood findings in b12/folate deficiency
macrocytic anaemia
red cell count low
pancytopenia
blood film - macrovalocytes + hypersegmented neutrophils (neutrophils usually have 3-5segments)
autoantibodies
- antigastro-parietal cells - flaw sensitive not specific
- anti-intrinsic factor - flaw, specific not sensitive
spurious/false macrocytosis
volume of mature red cell is NORMAL, but MCV is measured as high
causes - reticulocytosis, cold-agglutinins
causes of spurious/false macrocytosis
reticulocytosis
- an increase in reticulocyte number occurs as a marrrow response to acute blood loss or red cell breakdown (haemolysis)
- reticulocytes are bigger than mature red cells + are analysed along with these for the MCV measurement
cold-agglutinins
- clumps of agglutinated red cells are registered as 1 giant cell - increases MCV
approach to investigating macrocytic anaemia
reticulocyte count
- raised - haemorrhage, haemolysis
- normal/decreased - blood film for hyperseg neutrophils
yes - serum b12/folate
no - liver disease, alcoholism, hypothyroidism - if no myelodysplasia, myeloma, aplastic anaemia -> bone marrow biopsy
causes of normocytic anaemia
3As + 2Hs
acute blood loss
anaemia of chronic disease
aplastic anaemia
haemolytic anaemia
hypothyroidism
what can cause a false anaemia?
haemodilution - excess fluid
what is the core difference between microcytic + macrocytic? other than the size obvs
microcytic - haemoglobin problem
macrocytic - maturation problem
