Anaemia Flashcards
what is anaemia?
reduction in absolute Hb in given volume of blood
can also be due to an increase in plasma volume instead (but does not persist as it will be removed)
RBC and Hct also reduced as a result
4 mechanisms of anaemia
1- reduced RBC production in bone marrow
2- loss of blood
3- reduced RBC survival (Haemolysis)
4- pooling of RBC in the enlarged spleen (splenomegaly)
mechanism vs cause
mechanism: reduced Hb synthesis
cause: reduced haem or globin synthesis i.e. iron deficiency or thalassaemia
causes of anaemia in terms of causing reduced Hb production
As Hb as a whole unit is affected, its haem and globin components must be impacted:
1) reduced haem production due to iron deficiency
2) reduced globin production due to thalassaemia (inherited)
how is anaemia classified based on cell size?
when mechanism is not clear, its based on size:
- microcytic:
- normocytic
- macrocytic
what is macrocytic anaemia?
red cells larger than normal
high MCV
megaloblastic erythropoiesis
causes macrocytic anaemia
- delay in maturation of the nucleus while the cytoplasm continues to mature, cell continues to grow, therein nucleocytoplasmic dissociation
- does not require bone marrow examination
how does the premature release of cells increase MCV?
young cells (precursors) are 20% bigger than mature RBC and therefore increase the MCV
what are the most common causes of macrocytic anaemia
1) megoblastic: lack of vit b12 or folic acid
2) DNA synthesis interfering drugs
3) liver disease, ethanol toxicity
4) recent major blood loss
5) haemolytic anaemeia (with chronic macrocytosis, reticulocytes increase)
6) hypothyroidism
mechanisms of normocytic anaemia
- recent blood loss (peptic ulcer, trauma)
- failure to produce red cells i.e. iron def, renal failure, bone marrow failure/suppression, bone marrow infiltration, stem cell failure
- pooling RBCs in the spleen i.e. hypersplenism due to portal cirrhosis
how does haemolytic anaemia affect RBCs?
shortened survival of RBCs i.e. <120 days
what causes haemolysis?
intrinsically abnormal cells (cell defect) or
extrinsic agents acting on normal cells (defect outside of cells)
classifications of haemolytic anaemia?
inherited- abnormalities in cell membrane, Hb or enzymes in RBC
or
acquired- extrinsic factors like microorganisms, drugs or chemicals
intravascular- within blood vessels
or
extravascular- in the spleen
what is the alternative classification of haemolytic anaemia?
- intravascular: occurs due to acute damage to RBC
- extravascular: defective RBCs removed by spleen
haemolytic can be a mix of both
when would you suspect haemolytic anaemia?
-when there is otherwise unexplainable anaemia which is normochromic (MCHC is normal) and usually either normocytic or macrocytic
- abnormal cell
- increased RBC breakdown
- increased bone marrow activity
- they have irregularly contracted cells
- hereditary elliptocytosis
- poilkilocytosis
- or sickle cell disease
- polychromic anaemia
why may an HA patient have gall stones
high excretion of bilirubin in chronic HA
why may an HA patient have jaundice?
sickle cells- rapid breakdown of RBCs
what does a defective membrane lead to?
(hereditary) spherocytosis
what does a defect in Hb indicate?
sickle cell anaemia
what happens in inherited spherocytosis
RBCs become less flexible and are removed by the spleen prematurely causing extravascular haemolysis
how does the bone marrow respond to haemolysis?
increased output
shown by :
- polychromasia (immature red cells)
- reticulocytosis (premature cells)
- increased bilirubin, jaundice and gallstones
when are spherocytes more prone to haemolysis?
when osmotic pressure is reduced
how do you treat hereditary spherocytosis?
cause of extravascular haemolysis (in the spleen) therefore:
- splenectomy (only effective treatment)
- good diet
- folic acid tablets
what is G6PD?
an enzyme in the pentose shunt
important in protection of RBCs from oxidant damage
what is the effect of a G6PD deficiency?
oxidants generated in the blood affect RBCs (come from foods like broad beans , chemicals like naphthalene, or drugs like dapsone and primaquine)
origin of extrinsic oxidants that affect the RBCS
come from foods like broad beans , chemicals like naphthalene, or drugs like dapsone and primaquine
inheritance of G6PDD
located on chromosome X so it usually affects males but can affect homozygous females
how does G6PD def cause intermittent severe intravascular haemolysis?
infection or exposure to exogenous oxidant
G6PD reduces oxidant damage to RBCs normally
what are the associated blood films features with episodes of intravascular haemolytic?
appearance of irregular contracted cells
these are Heinz Bodies (like that seen in G6PD def)
how are Heinz bodies formed?
Hb becomes denatured and forms round-balls
can be detected by a test
spleen partially removes Heinz bodies leaving a defect
what happens in autoimmune haemolytic anaemia?
antibodies mediating splenic removal:
antibodies are produced and directed at RBC antigens
splenic macrophages recognise this and removes the cell membrane of the RBC leading to spherocytosis
diagnosis of autoimmune haemolytic anaemia?
spherocytes and increased reticulocytes on film
Ig detected on RBC surface
antibodies attached to antigens
how is autoimmune haemolytic anaemia treated?
- corticosteroids (plus other immunosuppressives)
- splenectomy (for severe cases)
what are the blood film features of megaloblastic anaemia?
- macrocytic
- nucleo-cytoplasmic dislocation
- hypersegmented neutrophils
- anisocytosis
where is unconjugated Bilirubin found?
pre-hepatically
what are the signs of splenomegaly?
- high bilirubin (due to high RBC turnover)
- jaundice
- polychromasia
- koilonychias
- spherocytes
what do microcytic cells look like?
small, hypochromic (pale)
what are the common causes of microcytosis?
REDUCTIONS
- iron deficiency anaemia (reduction in haem)
- anaemia of chronic disease (reduction in haem)
- thalassaemia (reduction of globin)
result of reduced haemoglobin synthesis caused by either reduction in haem synthesis or reduction in globin synthesis
what does an elevated MCV indicate?
macrocytic anaemia
what are the causes of macrocytosis?
1) megaloblastic anaemia (due to B12 or folic def)
2) liver disease
3) excess alcohol intake
4) increase release of immature cells from bone marrow
what are the causes of normocytic anaemia
1) early stage of iron deficiency
2) early stage of anaemic of chronic disease
3) renal failure
4) recent blood loss
5) bone marrow failure or infiltration
describe how one may get haemolytic anaemia
inherited or acquired
what are the 2 main mechanisms of haemolytic anaemia
1) defective red cells
e. g. hereditary spherocytosis
2) defect outside the red cells
e. g. fragmentation by fibrin strands deposited in capillaries (microangiopathic haemolytic anaemia)
how is haemolytic anaemia classified in terms of location?
1) extravascular
- RBC removal by splenic macrophages in hereditary spherocytosis
2) intravascular
e. g. incompatible blood transfusion in which ABs destroy the RBCs
what are the causes inherited haemolytic anaemia?
cells themselves:
- abnormal red cell membrane e.g. hereditary spherocytosis
- abnormal Hb
enzymes:
- defect in glycolytic pathway (pyruvate kinase def)
- defect in enzyme in the pentose shunt (G6PD def)
what are the causes of acquired haemolytic anaemia?
Acquired damages to RBC:
- damage to RBC membrane
e.g AIHA or snake bite
- damage to whole red cell
- oxidant exposure damages membrane and Hb
this precipitates episodic haemolysis in individuals with enzyme deficiency
what is Polychromasia?
blue tinge caused by ribosomal RNA in young cells
there is also the pink colouring of the Hb
what is the reticulocytosis a response to?
- haemolytic anaemia
- recent blood loss
- treatment to iron, b12 or folic def
when is a decrease in reticulocytes seen?
when there is a reduced output from bone marrow
what will help make a haemolytic anaemia diagnosis?
- defective cells: abnormal cells like spherocytes, eliptocytes and fragments
- evidence of increased red cell breakdown (increased unconjugated BR and LDH)
- evidence of increased bone marrow response (reticulocytosis and polychromasia)
what shows that there is increased RBC breakdown happening? especially extravascular
- increased unconjugated bilirubin
- increased lactate dehydrogenase
- haemoglobin in plasma
what is polycythaemia?
too many RBCs produced
Hb conc is too high
what are the 4 types of polycythaemia (causes)?
1) physiological e.g. newborn baby
2) appropriate erythropoietin secretion e.g. living at high altitude, hypoxia
3) inappropriate erythropoietin secretion e.g. EPO abuse, tumour secretion
4) intrinsic bone disease e.g. polycythaemia vera
(independent of erythropoietin)
