Anaemia Flashcards
(33 cards)
what is anaemia?
Anaemia is 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
By definition, the Hb is reduced
The RBC and the Hct/PCV are usually also reduced
Anaemia is usually due to a reduction of the absolute amount of haemoglobin in the blood stream
what is the other possible cause of anaemia?
Occasionally it results from an increase in the volume of plasma rather than a decrease in the amount of haemoglobin
In a healthy person, anaemia resulting from an increase in plasma volume cannot persist because the excess fluid in the circulation is excreted
For practical purposes, anaemia can therefore be regarded as a resulting from a decrease of the absolute amount of haemoglobin in the circulation
what are the mechanisms of anaemia?
Reduced production of red cells/haemoglobin in the bone marrow
Loss of blood from the body
Reduced survival of red cells in the circulation
Pooling of red cells in a very large spleen
what is the difference between the mechanism and causes of anaemia?
We need to distinguish the mechanism of anaemia from the cause
The mechanism of the anaemia might be reduced synthesis of haemoglobin in the bone marrow
The cause of this could be either a condition causing reduced synthesis of haem or one causing reduced synthesis of globin
what is the classification of anaemia on the basis of cell size?
Microcytic (usually also hypochromic)
Normocytic (usually also normochromic)
Macrocytic (usually also normochromic)
what are the common causes of a microcytic anaemia?
Common causes of a microcytic anaemia
Defect in haem synthesis
- Iron deficiency
- Anaemia of chronic disease
Defect in globin synthesis (thalassaemia)
- Defect in α chain synthesis (α thalassaemia)
- Defect in β chain synthesis (β thalassaemia)
what is the mechanism behind macrocytic anaemia?
Macrocytic anaemias usually result from abnormal haemopoiesis so that the red cell precursors continue to synthesize haemoglobin and other cellular proteins but fail to divide normally
As a result, the red cells end up larger than normal
what is one cause of macrocytic anaemia?
A macrocytic anaemia is one in which average cell size is increased
One cause of this is megaloblastic erythropoiesis
This refers specifically to a delay in maturation of the nucleus while the cytoplasm continues to mature and the cell continues to grow
what is a megaloblast?
A megaloblast is an abnormal bone marrow erythroblast
It is larger than normal and shows nucleo-cytoplasmic dissociation
It is possible to suspect megaloblastic anaemia from the peripheral blood features but to be sure requires bone marrow examination
what is an alternative mechanism of macrocytosis?
An alternative mechanism of macrocytosis is premature release of cells from the bone marrow
Young red cells are about 20% larger than mature red cells so if there is an increased proportion of young red cells (reticulocytes) in the circulation, the average cell size (MCV) will be increased
what are the common causes of macrocytic anaemia?
- Megaloblastic anaemia as a result of lack of vitamin B12 or folic acid
- Use of drugs interfering with DNA synthesis
- Liver disease and ethanol toxicity
- Recent major blood loss with adequate iron stores (reticulocytes increased)
- Haemolytic anaemia (reticulocytes increased)
what might be the mechanism behind normocytic normochromic anaemia?
Recent blood loss
Failure of production of red cells
Pooling of red cells in the spleen
what are the causes behind normocytic normochromic anaemia?
-Peptic ulcer, oesophageal varices, trauma
-Failure of production of red cells
Early stages of iron deficiency or anaemia of chronic disease
Renal failure
Bone marrow failure or suppression
Bone marrow infiltration
Hypersplenism, e.g. portal cirrhosis
what is haemolytic anaemia?
Haemolytic anaemia is anaemia resulting from shortened survival of red cells in the circulation
Haemolysis can result from an intrinsic abnormality of the red cells
Haemolysis can result from extrinsic factors acting on normal red cells
haemolytic anaemia can be further divided into inherited or acquired- what does this mean?
what can extrinsic factors do?
Haemolytic anaemia can also be classified as inherited or acquired
Inherited haemolytic anaemia can result from abnormalities in the cell membrane, the haemoglobin or the enzymes in the red cell
Acquired haemolytic anaemia usually results from extrinsic factors such as micro-organisms, chemicals or drugs that damage the red cell
Extrinsic factors can interact with red cells that have an intrinsic abnormality
Haemolytic anaemia can also be classified into intravascular haemolysis and extravascular haemolysis- what does this mean?
Haemolytic anaemia can also be classified as intravascular or extravascular
Intravascular haemolysis occurs if there is very acute damage to the red cell
Extravascular haemolysis occurs when defective red cells are removed by the spleen
Often haemolysis is partly intravascular and partly extravascular
give examples of inherited anaemia
- abnormal red cell membrane eg hereditary spherocytosis
- abnormal Hb eg in sickle cell anaemia
- defect in glycolytic pathway eg pyruvate kinase deficiency
- defect in enzymes of pentose shunt eg G6PD deficiency
give examples of acquired anaemia
-damage to red cell membrane eg snake bite or autoimmune haemolytic anaemia
-damage to whole red cell eg malaria
-oxidant exposure damage to red cell membrane and Hb eg dapsone
(this can then lead to precipitation of episodic haemolysis in individuals with enzyme deficiency)
when would you suspect haemolytic anaemia?
Otherwise unexplained anaemia, which is normochromic and usually either normocytic or macrocytic
Evidence of morphologically abnormal red cells
Evidence of increased red cell breakdown
Evidence of increased bone marrow activity
what is hereditary spherocytosis? and what happens?
Haemolytic anaemia or chronic compensated haemolysis resulting from an inherited intrinsic defect of the red cell membrane
After entering the circulation the cells lose membrane in the spleen and thus become spherocytic
Red cells become less flexible and are removed prematurely by the spleen – extravascular haemolysis
The bone marrow responds to haemolysis by an increased output of red cells leading to polychromasia and reticulocytosis
Haemolysis leads to increased bilirubin production, jaundice and gallstones
what are spherocytes more prone to?
Spherocytes are also more prone to haemolyse when osmotic pressure is reduced
name some treatment options for hereditary spherocytosis?
The only effective treatment is splenectomy, but this has its own risks so is only done in severe cases
A good diet is important so that a secondary folic acid deficiency does not occur
Alternatively, one folic acid tablet can be taken daily
what occurs in glucose-6-phosphate dehydrogenase deficiency?
G6PD is an important enzyme in the pentose phosphate shunt
It is essential for the protection of the red cell from oxidant damage
Oxidants may be generated in the blood stream, e.g. during infection, or may be exogenous (Extrinsic oxidants may be foodstuffs (e.g. broad beans), chemicals (e.g. naphthalene) or drugs (e.g. dapsone, primaquine))
where is the gene for G6PD?
The gene for G6PD is on the X chromosome so affected individuals are usually hemizygous males (but occasionally homozygous females)
