Anaemia Flashcards
What is anaemia?
a reduction in the amount of haemoglobin in a given volume of blood below what would be expected in comparison with a healthy subject of the same age and gender.
- The Hb is therefore reduced but often the RBC and PCV/Hct is also usually reduced.
Anaemia is usually due to a reduction of the absolute amount of Hb but can also result from an increase in volume of plasma rather than a decrease in amount of Hb.
- This cause would not persist though due to the body’s ability to remove excess fluid
What are the mechanisms of anaemia?
- Reduced production of RBCs/Hb in the bone marrow.
- the mechanism of anaemia is reduced synthesis of Hb in the bone marrow but the cause could be a condition causing:
i. Reduced synthesis of haem – i.e. iron deficiency.
ii. Reduced synthesis of globin – i.e. beta-thalassaemia. - Loss of blood from the body.
- Reduced survival of RBCs in the body.
- Pooling of RBCs in the spleen (splenomegaly).
What are causes of microcytic anaemia?
- usually hypochromic as well
Defect in haem synthesis; iron deficiency or anaemia of chronic disease
Defect in globin synthesis; thalassaemia (alpha chain or beta chain)
What are causes of macrocytic anaemia?
- ususally normochromic
Usually a result of abnormal haemopoiesis – RBC precursors continue to synthesise Hb and other cellular proteins but fail to divide properly -> end up larger than usual.
Causes:
- Megablastic erythropoiesis – delay in maturation of the nucleus while the cytoplasm continues to mature and the cell continues to grow.
- Megaloblast – abnormal bone marrow erythroblast. It is larger than normal and shows nucleocytoplasmic dissociation.
- Possible to suspect from peripheral blood features but does require bone marrow examination.
* as a result of lack of vitamin B12 or folic acid - Premature release of cells from the bone marrow.
- Young red cells are 20% larger than normal RBCs so more young cells mean the MCV will be increased in the blood stream. - DNA synthesis interfering drugs.
- Liver disease and ethanol toxicity.
- Recent major blood loss with adequate iron stores (reticulocyte numbers increase) – body pumps more out.
- Haemolytic anaemia (reticulocyte numbers increase) – RBCs lyse in blood stream.
What are common causes of normocytic anaemia?
- Recent blood loss – i.e. peptic ulcer, trauma.
- Failure of production of red cells – i.e. beginning of iron deficiency, renal failure, bone marrow failure or suppression, bone marrow infiltration.
- Pooling of red blood cells in the spleen – i.e. hypersplenism from portal cirrhosis.
What is haemolytic anaemia?
What acn it be classed as?
shortened survival of RBCs in circulation.
Haemolysis can be classed as:
- Intrinsic - intrinsic abnormality of red cells.
- Extrinsic - extrinsicfactors acting on normal red cells.
- Inherited – abnormalities in cell membrane, Hb or in enzymes of the RBC.
- Acquired – extrinsic factors such as micro-organisms, drugs or chemicals.
- Intravascular – occurs due to acute damage to RBC.
- Extravascular – defective RBCs removed by spleen.
- Often haemolysis is a mix of the both intravascular and extravascular
When would you expect haemolytic anaemia?
There is an otherwise unexplainable anaemia, which is normochromic (MCHC is normal) and usually either normocytic or macrocytic
Evidence of morphologically abnormal cells
Evidence of increased RBC breakdown
Evidence of increased bone marrow activity
*suspect if patient has irregularly contracted cells, hereditary elliptocytosis, Poikilocytosis or Sickle Cell disease
You may also suspect HA if a patient has gall stones (chronic HA means high excretion of bilirubin so they get higher incidence of gall stones) or jaundice (sickle cell – RBCs are breaking down quickly).
Also suspect HA if a patient has polychromic anaemia – antibodies remove membranes of Spherocytes and lyse cells
What are some examples of inherited haemolytic anaemias?
What are their sites of defect?
hereditary spherocytosis - membrane
sickle cell anaemia - haemoglobin
pyruvate kinase defciciency - glycolytic pathway
glucose-6-phosphate dehydrogenase deficiency - pentose shunt
What are some examples of acquired haemolytic anaemias?
What are their target sites?
autoimmune haemolytic anaemia - membrane (immune)
microangiopathic haemolytic anaemia - whole red cell (mechanical)
drugs and chemicals - whole red cell (oxidant)
malaria - whole red cell (microbiological)
What happens in hereditary spherocytosis?
What is the treatment?
HA or chronic compensated haemolysis resulting from an inherited intrinsic defect in the RBC membrane.
Red cells become less flexible and so are removed by the spleen prematurely causing extravascular (occurs in the spleen) haemolysis.
The bone marrow then responds to haemolysis with increased output leading to polychromasia (immature red cells in blood) and reticulocytosis (premature cells).
The haemolysis leads to increased bilirubin, jaundice and gall stones.
Spherocytes are more prone to haemolyse when osmotic pressure is reduced.
Treatment:
- Splenectomy – the only effective treatment.
- Good diet or folic acid tablets – so folic acid deficiency does not occur
What happens in G6P dehydrogenase deficiency?
G6PD is an important enzyme in the pentose-phosphate shunt and is essential for protection of RBCs from oxidant damage.
Oxidants may be generated in the blood stream and so a G6PDD may intrinsically affect the RBCs tending the system to HA.
- Extrinsic oxidants include foodstuffs (e.g. broad beans) and chemicals (e.g. mothballs/naphthalene) or drugs (e.g. dapsone or primaquine).
- The G6PD gene is on the X-chromosome so usually affects hemizygous males but can affect homozygous females
G6PDD usually causes intermittent SEVERE INTRAVASCULAR (not in spleen) haemolysis as a result of infection or exposure to an exogenous oxidant
Usually these episodes of intravascular haemolysis are associated with appearance of considerable numbers of irregularly contracted cells.
Haemoglobin becomes denatured and forms round-balls known as Heinz bodies which are detected by a test.
Heinz bodies are removed by the spleen that leaves a defect in the cell
What happens in autoimmune haemolytic anaemia?
How is it diagnosed and treated?
Autoimmune HA results from production of autoantibodies directed at RBC antigens -> splenic macrophage recognises antibody and removes parts of the RBC membrane leading to spherocytosis (seen on left).
The Spherocytes are less flexible and so this combined with antigen recognition on RBC leads to removal of RBCs from circulation.
Diagnosis:
- Spherocytes and increased reticulocyte count on film.
- Detecting immunoglobulin on red cell surface.
- Detecting antibodies to RBC antigens.
Treatment:
- Corticosteroids (or other immunosuppressive).
- Splenectomy for severe cases.
How do you treat microangiopathic haemolytic anaemia?
removing cause e.g treating severe hypertension or stopping causative drug
plasma exchange when it is caused by an antibody in the plasma that is leading indirectly to fibrin deposition