anaemia Flashcards
what is anaemia *
- a reduction in the amount of Hb in a given vol of blood, below what would be expected in comparision with a healthy subject of the same gender and age
- The Hb is reduced
- The RBC and Hct normally reduced
- usually becasue of a reduction in the absolute amount of Hb in the blood stream
- occaisionally because of an increase in plasma vol - can’t persist because extra vol would be excreted in the urine
what are the mechanisms of anaemia *
reduced production of RBC/Hb in marrow
loss of blood
reduced survival of red cells in the circulation - and marrow cant keep up
pooling of red cells in the spleen - amount in circulation decreases
what is a cause of reduced synthesis of haem
iron deficiency
what is a condition where there is an inherited defect leading to reduced synth of globin
thalassaemia
what are the 3 classifications of anaemia based on cell size *
microcytic - smaller than normal - not making enough Hb therefore reduced Hb in cells - usually hypochromic
normocytic - usually normochromic
macrocytic - normally normochromic - defect is not in the synth of Hb
what are the causes of microcytic anaemia *
defect in haem synth - iron deficiency or anaemia of chronic disease/inflammation (eg TB or rheumatoid arthritis - starts off normocytic but as disease continues -> microcytic and hypochromic, this is because iron is trapped in macrophages as haemosiderin and not mobilised into the circulation)
defect in globin synth - thalassaemia a/B thalassaemia affecting a/B chain respectively (foetus gamma chains)
describe macrocytic anaemia *
because of abnormal haemopoeisis - the RBC precursers still make Hb but fail to divide = larger cells
one cause of macrocytic anaemia is megaloblastic anaemia
another cause is premature release of cells from the bone marrow - young red cells larger so if there is an increased proportion of retiulocytes in circ the MCV will increase
another causes - liver disease
cause - excess alcohol intake
what is megaloblastic anaemia *
there is a delay in maturation of the nucleus (defect in DNA synth) while the cytoplasm matures normally and cell grown
a megaloblast is an abnormal bone marrow erythroblast - larger than normal and has nucleo-cytoplasmic dissociation - ie cytoplasm is mature and nucleus is not
how can you diagnose megaloblastic anaemia *
suspect it from peripheral blood film - anaemia, macrocytosis, oval and teardrop red cells, hypersegmentation of neutraphils ie right shift
can do bone marrow examination
in practice measure folic acid and B12 - if one is low it is diagnostic of megaloblastic anaemia
image of bone marrow cells - diserythropoeisis - nucleus has 3 lobes, also v pink cytoplasm (mature) but nucleus not condensed
what are the causes of macrocytic anaemia *
megaloblastic because of B12 or folic acid deficiency
drugs interfere with DNA synth - interfere with the action of folic acid - eg cancer treatment = megaloblastic
liver disease and ethanol toxicity - large cells with abundant memebrane
major blood loss with adequate iron stores = increased reticulocyte count
haemolytic anaemia - reticulocytes are increased to compensate
what are the mechanisms of normocytic anaemia *
recent blood loss - bone marrow hasnt responded = reduced number of cells but look normal
failure of production of red cells - because of haem stem cell failure
pooling of red cells in the spleen - wont alter the size in circulation
causes of normocytic anaemia *
blood loss - peptic ulcer, oesophageal varices, trauma
failure of production of red cells - early stages of iron deficiency or anaemia of chronic disease, renal failure, bone amrrow failure or suppression by drugs, bonme marrow infiltration by cancer
pooling in spleen - cirrhosis of liver, splenic sequestration (condition in children with sickle cell, red cells in spleen)
what is haemolytic anaemia *
anaemia because of shortened survival of red cells in circulation
can be because of intrinisic abnormality of red cells, or extrinsic factors acting on normal red cells
can be classifies as inherited or acquired
classified as intravascular haemolysis or extravascular
describe inherited haemolytic anaemia *
because of abnormalities in the cell membrane (heredity spherocytosis or elliptocytosis),
Hb (sickle),
or the enzymes in the red cell (either in glycolysis meaning cell not getting enough ATP eg pyruvate kinase deficiency, or abnormality in the pentose shunt meaning cell doesnt have enough reduction capacity to defend itself against oxident damage eg G6PD deficiency)
describe acquired haemolytic anaemia *
usually because of extrinsic factors eg microorganisms, chemicals or drugs that damage red cells
causes:
damage to red cell membrane leads to haemolysis eg autoimmune haemolytic anaemia or snake bite
damage to whole red cell eg microangiopathic haemolytic anaemia
oxident exposure damge to the red cell membrane and Hb - Hb oxidised into metHb - non-functional. eg dapsone or primaquine - to treat malaria
describe autoimmune haemolytic anaemia *
body have auto Ab against Ag on red cell membrane or may fix to complement
Ig recognised by spleen = cells removed or some of membrane is removed = spherocytosis
spleen removees the red cells because of the Ig and the cells ahve become more rigid so get stuck in the spleen
describe microangiopathic haemolytic anaemia *
deposition of fibrin strands in small bv - damage red blood cells and cause them to tear into pieces
or damage to endothelium - RBC stick to endo - so are torn and ruptured
describe the relationship between red cells prone to pentose shunt enzyme defects and oxidant exposure *
these red cells are prone to red cell exposure - they lack the enzyme to protect the cell
if you have this condition need to be careful about drugs and diet eg avoid broad beans
what is intravascular haemolysis *
if there is very acute damage to the red cell in the circulation
what is extravascular haemolysis *
occurs when defective red cells are removed by the spleen
when would you expect haemolytic anaemia *
when there is otherwise unexplained anaemia - normochromic and wither normocytic/macrocytic (macrocytic if reticulocyte count has increased)
evidence of morphologically abnormal red cells eg fragments (MAHA), sickle cell, spherocytes, elliptocytes
evidence of increased red cell breakdown - high lactate dehydrogenase (normally a lot in red cells), high unconjugated bilirubin (liver cant cope with the increased red cell break down)
evidence of high bone marrow activity - eg increased reticulocyte count
Hb is also released from cells = Hb in plasma which binds to haptoglobin and the complex is cleared in the liver = low haptoglobin. whenall haptoglobin is saturated, free Hb is filtered by kidney = Hb and haeomosiderin in urine
what is the effect off inheriting HbC from 1 parent and HbS from another
forms Hb crystals - square
how can you see clinically that there is excess bilirubin *
jaundice
BR gallstones - show dark on scan (-ve image)
example of inherited haemolytic anaemia that affect membrane *
hereditory spherocytosis
example of inherited haemolytic anaemia that affect Hb *
sickle cell
example of inherited haemolytic anaemia that affect gycolytic pathway *
pyruvate kinase deficiency
example of inherited haemolytic anaemia that affect pentose shunt *
glucose-6-phosphate dehydrogenase deficiency
example of acquired haemolytic anaemia that affects membrane *
autoimmune haemolytic anaemia - either isolated or part of another autoimmune condotion
example of acquired haemolytic anaemia that affects red cell (mechanical) *
MAHA
example of acquired haemolytic anaemia that affects red ccell (oxidant) *
drugs and chemicals
example of acquired haemolytic anaemia that affects red cell (micorbiological) *
malaria - cells have parasites and so are destroyed by macrophages
describe hereditory sphherocytosis *
either caused by haemolytic anaemia or by chronic haemolysis from an inherited intrinsic defect of mem that is compensated by the marrow (tethering of lipid bilayer to the the cytoskeleton is defective - buts of membrane are loose)
after entering the circulation some membrane is removed by the spleen -> cells spherocytic
spleen remove cells becasue they are rigid and so get stuck in spleen (extravascular haemolysis)
marrow responds by increased output of red cells= polychromasia and reticulocytosis
how can you test for spherocytes *
they are more osmotically fragile so burts more easily when osmotic pressure is reduced
this the osmotic fragility test and is not used very often
what is the treatment for hereditory spherocytosis *
only effective treatment - splenectomy - wait until age 5-6 and only in severe cases - has risks
need good diet so that secondary folic acid deficiency doesnt occur because marrow v active - or take 1 folic acid tablet daily (no SE and cheap)
describe G6PD defiency *
G6PD essential for protection against oxidents
extrinsic oxidents may be in food (broad beans), chemicals (naphtalene) drugs (dapsone, primaquine)
gene for G6PD deficiency is on X chromosome so mainly affects males but occaisionally homozygous females/some cells deficeint in heterozygous females
it causes intermittent severe intravascular haemolysis as a result of infection or exposure - cause appearance of many irregularly contracted cells - membrane is damaged and Hb denatured so it is condensed and deposited in red cells (Heinz bodies)
spleen removes Heinz body or destroys all cell
if removes Heinz body it leaves bite cell/keratocyte
treatment of G6PD deficiency *
acute haemolysis requires blood transfusion
prevention is importanmt - diet and drugs
how can you tell the difference between hereditory spherocytosis and AIHA *
people with AIHA would have been previously well then suddenly have this condition
how do you diagnose AIHA *
finding spherocytes and an increased reticulocyte count
detect Ig and complement on red cell surface - antigolbulin test
detecting Ab to red cell antigens or other autoAb in plasma
treatment of autoimmune haemolytic anaemia *
corticosteroids (prednisolone) and immunosuppressive agents (if chronic to avoid SE from prednisolone)
treatment of microangiopathic haemolytic anaemia *
remove the cause - treat the hypertension or stop drug
plasma exchange when it is caused by an Ab that is leading to fibrin deposition which causes thrombocytopenic purpura -> thrombosis/thrombocytopenia
describe haemolytic ureamic syndrome *
caused by c difficile - damages the red cell membrane
have diarrhoea, haemolysis and renal failure
marrow working fine - have polychromasia, high reticulocyte count
have red cell fragments - suggest cells being broken down - haemolysis - this is haemolytic anaemia (not the diagnosis, it is the cause of the diagnosis)
high liver func tests - LDH raised because in red cells so released when they are broken down, alt and alp raised
BR also raised because of red cell turnover = pre-hepatic jaundice
high creatine - show that there is renal failure- because free hb released from red cells is toxic
treatment: supportive, hydrate and maybe transfusion
what are principles of diagnosis of haemolytic anaemia, ie what is ot helped by *
see if there is a raised reticulocyte count - altough can also be seen when Fe or b12 are given
The detection of morphologically abnormal red cells, e.g. spherocytes, elliptocytes, fragments.
Evidence of increased red cell breakdown, e.g. increased serum bilirubin (unconjugated) and lactate dehydrogenase (LDH).
Evidence of an increased bone marrow response, e.g. polychromasia and an increased reticulocyte count.
