Anaemia Flashcards
What is anaemia
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
What in a FBC is reduced in anaemia
Hb
Usually RBC and Hct
Describe the general pathogenesis of anaemia
Reduction in the absolute amount of haemoglobin in the blood stream
Occasionally due to an increase in volume plasma (cannot persist as excess fluid is excreted)
Give an latrogenic cause of anaemia
giving too much IV fluid too fast
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 are the causes of microcytic anaemia
Defect in haem synthesis
- iron deficiency
- anaemia of chronic disease
Defect in global synthesis (thalassaemia)
- Defect in α chain synthesis
- Defect in β chain synthesis
What is macrocytic anaemia
Average cell size is increased
Describe the general pathogenesis of macrocytic anaemia
Usually abnormal haemopoiesis
The red cell precursors continue to synthesise haemoglobin and other cellular proteins but fail to divide normally
What are the two types of causes of macrocytic anaemia
Premature release of RBCs from bone marrow
Megaloblastic erythropoiesis
Describe the premature release of RBCs in macrocytic anaemia and what might cause it
Reticulocytes are 20% larger than mature RBCs
Excess haemolysis
Recent major haemorrhage (if the body has plentiful iron stores)
What is a megaloblast
Abnormal bone marrow erythroblast (RBC precursors)
Larger than normal
What occurs in megaloblastic erythropoiesis
Maturation of the nucleus is delayed but the cell keeps on growing and synthesising protein in the meantime (nuclei-cytoplasmic dissociation)
What are the common causes of megaloblastic anaemia
Vitamin B12 or folic acid deficiency
Drugs interfering with DNA synthesis
Liver disease
Ethanol/alcohol toxicity
What are the mechanisms of normocytic anaemia
Recent blood loss
Failure of production of red cells
Pooling of red cells in the spleen
What can cause haemorrhage that causes normocytic anaemia
- trauma
- peptic ulcer
- oesophageal varices
What can cause failure of RBC production (normocytic anaemia)
Renal failure - lack of erythropoietin
Early stage iron deficiency or anaemia of chronic disease (ACD)
Bone marrow suppression
What can cause pooling of RBCs in the spleen
portal hypertension
Hypersplenism e.g. portal cirrhosis
What is haemolytic anaemia and what can it be due to
Anaemia resulting from shortened survival of red cells in the circulation
May be due to intrinsic abnormality of the red cells or extrinsic factors acting on normal red cells
What is the difference between inherited and acquired haemolytic anaemia
Inherited - can result from abnormalities in the cell membrane, haemoglobin or enzymes in the red cell
Acquired - usually results from extrinsic factors such as micro-organisms, chemicals or drugs that damage the red cell
What is the difference between intravascular and extravascular haemolysis
Haemolysis is partly intravascular and partly extravascular
Intravascular - if there is very acute damage to the red cell
Extravascular - Defective red cells are removed by the spleen
Give examples of causes of inherited haemolytic anaemia
Defective:
Cell membrane - Hereditary spherocytosis
Haemoglobin - Sickle cell
Glycolysis - pyruvate kinase deficiency
Enzymes of pentose shunt - G6PD deficiency
Give examples of causes of acquired haemolytic anaemia
Damage to:
Cell membrane - Autoimmune haemolytic anaemia or snake bite
Whole cell - Microangiopathic haemolytic anaemia, malaria
Damage caused by:
Oxidant exposure - dapsone or primaquine
microorganisms - malaria
What is the role of glucose-6-phosphate dehydrogenase
G-6-P dehydrogenase is an important enzyme in the pentose phosphate shunt
It is crucial for protecting the RBC from oxidative damage
What can cause oxidant damage
Broad beans, naphthalene (in moth balls)
Dapsone or primaquine (drugs).
What does a deficiency in glucose-6-phosphate dehydrogenase lead to
Increases vulnerability to oxidants
It causes intermittent, severe intravascular haemolysis due to infection or oxidant exposure.
What kind of cells may be found in the blood in glucose-6-phosphate dehydrogenase deficiency
Irregularly contracted cells
Hb is denatured and forms around inclusions called Heinz bodies which can be detected
The spleen removes Heinz bodies, leaving defective RBCs.
Which sex does glucose-6-phosphate dehydrogenase deficiency affect more and why
The G6PD gene is on the X chromosome, so men are more frequently affected than women.
What does autoimmune haemolytic anaemia result from
Autoantibodies specific to RBC antigens
Explain how the presence autoantibodies for RBC antigens lead to anaemia
Splenic macrophages recognise the antigen-antibody complex and remove it along with part of the cell membrane, leading to spherocytosis.
The spherocytes then get removed by the spleen, causing the anaemia.
How is autoimmune haemolytic anaemia diagnosed
Spherocytes found
Increased reticulocyte count
Immunoglobulin and complement on red cell surface detected
Antibodies to red cell antigens or other autoantibodies in the plasma detected
How is autoimmune haemolytic anaemia treated
Immunosuppression (e.g. with steroids)
Splenectomy for severe cases
Describe hereditary spherocytosis
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
How does hereditary spherocytosis lead to jaundice
Spherocytes are less flexible and are removed prematurely by the spleen (extravascular haemolysis)
The bone marrow responds nay increasing output of red cells, leading to polychromasia and reticulocytosis
Leads to increased bilirubin production, jaundice and gall stones
What is the osmotic fragility test
Spherocytes are more prone to haemolyse when osmotic pressure is reduced
How is hereditary spherocytosis treated
Splenectomy
Good diet so secondary folic acid deficiency does not occur
One folic acid tablet taken daily
