ANAEMIA Flashcards
what is the definition of anaemia
reduced total red cell mass
which markers are used to assess for anaemia
haemoglobin concentration and haematocrit
what are the normal levels of Hb concentration and haematocrit for males and females
males Hb 130-180 Hct 0.38-0.55 females Hb 120-180 Hct 0.37-0.47
how is Hb concentration measured
burst red cells to create Hb solution stabilise the Hb molecules with cyanide measure the optical density density is proportional to density concentration is calculated against a known standard solution
what does Beer’s law state
optical density is proportional to concentration
what is the haematocrit
ration of the whole blood that is red cells if the sample was left to settle
in what situation might Hb/Hct not be an accurate marker
directly after an acute rapid bleed (falsely reassuring)
after harm-dilution with fluids (falsely worrying)
how do reticulocytes differ from mature RBCs
larger than average RBCs
still have remnants of protein making machinery (RNA)
stains purple/deeper red due to presence of RNA
what is a polychromatic blood film
shows different colours
presence of reticulocytes
what is the normal reactive response to anaemia
reticulocytosis
increased production of reticulocytes by the bone marrow
measured red cell indices
Hb concentration
number of red cells
MCV
calculated red cell indices
haematocrit
mean cell Hb
(mean cell Hb concentration)
pathophysiological classifications of anaemia
decreased production (low reticulocyte count)
- hypo proliferative
- maturation abnormality
increased loss/destruction of red cells (high reticulocyte count)
- bleeding
- haemolysis
what types of maturation abnormality can occur
cytoplasmic defects (impaired haemoglobinisation) nuclear defects (impaired cell division)
how can the MCV be used to distinguish maturation abnormalities
low MCV consider problems with haemoglobinisation (cytoplasmic)
high MCV consider problems with cell division (nuclear)
define microcytic and macrocytic
microcytic = low MCV
macrocytic = high MCV
microscopic features of microcytic anaemias
low Hb content
small cells
hypo chromic (lacking in colour)
what is the deficiency in hypo chromic, microcytic anaemia
deficient haemoglobin synthesis (cytoplasmic defect)
what is the commonest cause of microcytic anaemia
iron deficiency
what is thalassaemia and what type of anaemia is it
globin deficiency
hypochromic microcytic
causes of hypo chromic microcytic anaemia
haem deficiency
- lack of iron
- anaemia of chronic disease (lack of available iron)
- problems with porphyrin synthesis
globin deficiency
- thalassaemia
what is iron needed for
oxygen transport
electron transport
what is the structure of Hb
four globin subunit
each globin contains one haem molecule
each haem molecule contains on Fe2+ ion
which molecule transfers iron from liver stored to the erythroid
transferrin
what is the name of the molecule that iron is stored as
ferritin
where is the main iron store in the body
liver
how can ferritin be used to assess iron stores
it goes up when iron replete and down when iron deficient
how to assess iron status
Hb (functional iron) transported iron - serum iron - transferrin - transferrin saturation storage iron - serum ferritin
ow many binding sites are there in a molecule of transferrin
2
what does the % saturation of transferrin with iron measure
iron supply
in what situations might % saturation of transferrin with iron be abnormal
reduced in iron deficiency
reduced in anaemia of chronic disease
increased in genetic haemachromatosis
what does low serum ferritin mean
iron deficiency
causes of iron deficiency
not eating enough
losing too much (bleeding)
not absorbing enough
what is the difference between relative deficiency and absolute deficiency of iron
relative deficiency = still eating a normal amount but physiological increased demand eg child bearing age woman and children
absolute deficiency = not eating a normal amount eg vegetarian diet
what is achlorhydria
deficiency of HCl resulting in impaired absorption of non-haem iron
common causes of chronic blood loss
menorrhagia
GI tumours/ulcers
haematuria
what is the equivalent iron loss due to menstrual bleeding per month
15-20 mg/month
what happens if there is an iron deficiency
exhaustion of iron stores
iron deficient erythropoiesis (falling red cell MCV)
microcytic anaemia
epithelial changes (skin, koilonychia)
why is occult blood loss a risk factor for microcytic anaemia
a small volume of GI blood loss can occur without symptoms
this can outstrip the maximum dietary iron absorption of iron
signs of macrocytic anaemia on FBC
Hb low
RBC low
MCV high
how can you tell if RBCs are normocytic on a blood film
size of the nucleus of a normal small lymphocyte should correspond to the size of RBC
what are the causes of macrocytosis
genuine
- megaloblastic
- non-megaloblastic
spurious
what are erythroblasts/normoblasts
normal red cell precursors with a nucleus
what are the steps of erythroblasts developing into RBCs
accumulate Hb
reduce in size
lose nucleus when Hb content optimal
at what point to red cell precursors stop dividing
late normoblast
what are the names of the cells as red cell precursors develop into mature red cells
pronormoblast early normoblast intermediate normoblast late normoblast reticulocyte RBC
define megaloblast
an abnormally large nucleated red cell precursor with an immature nucleus
how are megaloblastic anaemias characterised
predominant defects in DNA synthesis and nuclear maturation but RNA and HB synthesis are preserved
what is the result of megaloblastic development
reduced division
apoptosis
how does megaloblastic development result in anaemia
nuclear development is impaired but Hb accumulation is not
once Hb level is optimal, the immature nucleus is removed leaving a bigger than normal cell
the cells are bigger, but there are less of them because they were not able to divide
ANAEMIA
causes of megaloblastic anaemia
B12 deficiency folate deficiency (drugs, congenital abnormalities)
why do we need B12 and folate for effective RBC development
essential co-factors for nuclear maturation
enable chemical reaction for DNA synthesis and gene activity
what is the folate cycle important for
nucleoside synthesis
what is the methionine cycle important for
producing a methyl donor (s-adenosyl methionine) to switch genes on/off
causes of B12 deficiency
diet (vegans)
stomach (pernicious anaemia, atrophic gastritis, PPIs, gastrectomy)
small bowel (bacterial overgrowth, coeliac, Crohn’s, resection)
inherited deficiencies of things
what is pernicious anaemia
autoimmune destruction of gastric parietal cells
results in intrinsic factor deficiency with B12 malabsorption and deficiency
anaemic patient with family history of autoimmune conditions??
pernicious anaemia
dietary sources of B12 and folate
B12
animal products
folate
liver, leafy veg, fortified cereals
how long do B12 stores last
2-4 years
how long do folate stores last
4 months
causes of folate deficiency
inadequate intake
malabsorption
excess utilisation (haemolysis, increased skin turnover, pregnancy, malignancy)
drugs (anticonvulsants)
clinical features of B12 and folate deficiency
symptoms/signs of anaemia
weight loss, diarrhoea, infertility
sore tongue, jaundice
developmental problems
in which system is B12 deficiency more likely to cause symptoms that folate
neurological system posterior/dorsal column abnormalities neuropathy dementia psychiatric manifestations
what is pancytopenia
all cells low
red and white and platelets
what is a macrovalocyte
macrocytic RBC that is oval shaped
hyperhsegmented neutrophils are a sign of what
B12/folate deficiency
how to assess for B12/folate deficiency
blood films (for macrovalocytes) B12/folate levels antibody tests (pernicious anaemia)
which autoantibodies are useful for investigation of pernicious anaemia
anti-intrinsic factor (specific, not sensitive)
anti-gastric parietal cell (sensitive, not specific)
treatment of megaloblastic anaemia
treat the cause where possible
IM vitamin B12 injections
folic acid tablets
red cell transfusions if life threatening
causes of non-megaloblastic macrocytosis
alcohol
liver disease
hypothyroidism
marrow failure
red cell membrane changes
what is spurious macrocytosis
mature red cell volume is normal but the MCV is measured as high
causes of spurious macrocytosis
reticulocytosis
- increase in reticulocytes which are bigger than mature red cells
- the machine measures reticulocytes as RBCs so thinks the MCV is higher
cold agglutinations
- cold temperatures (25 degrees) makes RBCs clump together and be registered as a giant cell
why do patients with pernicious anaemia have jaundice
intramedullary haemolysis
big cells get stuck in the bone marrow and breakdown, forming bilirubin –> jaundice
investigations for anaemia
history/exam/clinical contet FBC retic count blood film ferritin/B12/folate bone marrow biopsy
what is reticulocyte count a marker of?
red cell production
causes of hypo proliferative anaemia
marrow failure hypo metabolic marrow infiltration (malignancy, fibrosis) renal impairment chronic disease
how does renal disease cause anaemia
kidneys can’t sense hypoxia and/or release epo to induce red cell production
pathophysiology of anaemia of chronic disease
inflammation causes macrophages to produce IL-6
unregulated hepcidin
hepcidin prevents iron release from tissue by degrading ferraportin
when is a retic count indicated
if there is evidence of haemolysis eg from history, polychromasia
