Anaemia Flashcards
What is anaemia?
Reduction in amount of haemoglobin in a given volume of blood below what would be expected in comparison with a healthy subject of same age and gender
What else is also normally reduced during anaemia?
RBC and Hct
Why can anaemia in a healthy person not be due to increase in plasma volume?
Excess fluid in circulation will be excreted
What are the mechanisms of anaemia?
Reduced production of red blood cells/haemoglobin in the bone marrow
Loss of blood from the body (haemorrhage)
Reduced survival of red blood cells in circulation (haemolytic)
Pooling of red blood cells in a very large spleen
How is anaemia classified?
Cell size:
Microcytic- usually hypochromic
Normocytic- normochromic
Macrocytic- normochromic
What are the common causes of microcytic anaemia?
Defect in haem synthesis:
Iron deficiency
Anaemia of chronic disease
Defect in global synthesis (thalassaemia):
Defect in alpha chain synthesis (alpha thalassaemia)
Defect in beta chain synthesis (beta thalassaemia)
What does macrocytic anaemia usually result from?
Abnormal haemopoiesis so red cell precursors continue to synthesise haemoglobin and other cellular proteins but they fail to divide normally so much larger
What is megaloblastic erythropoiesis?
A delay in the maturation of the nucleus while the cytoplasm continues to mature and cell continues to grow
What is a megaloblast?
An abnormal bone marrow erythroblast
What are key features of megaloblasts?
Larger than normal and shows nucleo-cytoplasmic dissociation
What can megaloblastic erythropoiesis lead to?
Macrocytosis
What is an alternative mechanism for macrocytosis?
Premature release of cells from the bone marrow
How do reticulocytes compare in size to normal erythrocytes?
They are 20% bigger
What are 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 e.g. chemotherapy or azathioprine
Liver disease and ethanol toxicity
Recent major blood loss with adequate iron stores
Haemolytic anaemia
What are the mechanisms for normocytic normochromic anaemia?
MCV and MCH are normal so:
Recent blood loss
Failure to produce red blood cells
Pooling of red blood cells in the spleen
What causes normocytic normochromic anaemia?
Peptic ulcer Oesophageal varices Trauma Failure of production of red blood cells Early stages of iron deficiency or anaemia of chronic disease Renal failure Bone marrow failure or suppression Bone marrow infiltration Hypersplenism
What is haemolytic anaemia?
Anaemia resulting from shortened survival of red blood cells in the circulation
What can cause haemolysis?
Intrinsic abnormality of red cells or extrinsic factor acting on normal red cells
What is normal red cell survival?
120 days
What is the difference between intravascular and extravascular haemolysis?
Intravascular occurs if there is very acute damage to the red cell
Extravascular occurs when defective red cells are removed by the spleen
What other way can haemolytic anaemia be classified?
Inherited or acquired
What examples of inherited haemolytic anaemia are there?
Abnormalities of cell membrane, haemoglobin or enzymes in RBC
What examples of acquired haemolytic anaemia are there?
They usually result from extrinsic factors such as microorganisms, chemicals or drugs that damage the red cell
What will cause a red cell to burst?
Abnormal cell membrane
Abnormal haemoglobin
Defect in glycolytic pathway
What does G6PD stand for?
Glucose-6 phosphate dehydrogenase
What is G6PD?
Enzyme involved in pentose phosphate pathway
What is the pentose phosphate pathway?
Metabolic pathway parallel to glycolysis that generates NADPH and pentoses
What is the pentose phosphate pathway the only source of in red blood cells?
Reduced glutathione
What does G6PD protect you from?
Substantial risk of damage from oxidising free radicals due to the oxygen carrying role of red blood cells
What are people with G6PD deficiency at risk of?
Haemolytic anaemia in states of oxidative stress
What is pyruvate kinase involved with?
Last reaction of glycolysis
What will a deficiency in pyruvate kinase result in?
Red blood cells with decreased energy- Red blood cells can’t synthesise ATP so cellular death occurs
What would make you suspect haemolytic anaemia?
Unexplained anaemia that is normochromic and either normocytic or macrocytic
Evidence of morphologically abnormal red cells
Evidence of increased red cell breakdown
Evidence of increased bone marrow activity
What is microangiopathic haemolytic anaemia?
Red cells are being broken down within the circulation rather than the whole red cell being taken up and broken down in the spleen, they are being smashed up within the circulation
How can haemolytic anaemia lead to jaundice?
Increase in red blood cell breakdown leads to an increase in bilirubin leading to jaundice
What is hereditary spherocytosis?
Haemolytic anaemia or chronic compensated haemolysis resulting from an inherited intrinsic defect of the red cell membrane
How do spherocytes compare to normal erythrocytes?
Larger and rounder
Increased MCHC
Less flexible
What happens to spherocytes?
They are less flexible (can’t go through sinusoids) so removed prematurely in spleen- extravascular haemolysis
How does bone marrow respond to haemolysis?
Increased output of red cells leading to polychromasia and reticulocytosis
What is polychromasia?
The presence of certain blue red blood cells seen in blood films stained with Romanowsky stains as well as normal pink cells. Cells that appear blue are juvenile red blood cells
What is the only effective treatment for hereditary spherocytosis?
Splenectomy- only done in extreme situations
What is important for the diet of someone with hereditary spherocytosis?
To avoid vitamin deficiency due to the increased usage to make more red blood cells, vitamin B12, folic acid and iron
What examples of extrinsic oxidants are there?
Foodstuffs- broadbeans
Chemicals- naphthalene
Drugs- dapsone
Where is the gene for G6PD deficiency?
X chromosome
What sort of individuals are most commonly affected by G6PD deficiency?
Homozygous males
What does G6PD deficiency usually cause?
Intermittent, severe intravascular haemolysis as result of infection or exposure to an exogenous oxidant
What does acute haemolytic anaemia result from?
Production of antibodies against red cell antigens- immunoglobulin bound to red cell membrane is recognised by splenic macrophages which remove part of the cell membrane leading to spherocytosis
How do you diagnose spherocytosis?
Finding spherocytes and increased reticulocyte count
Detecting immunoglobulin on red cell surface
Detecting antibodies to red cell antigens or other antibodies in plasma
How do you treat spherocytosis?
Use of corticosteroids and other immunosuppressive agents
Splenectomy for severe cases
What is polycythaemia?
Too many red blood cells in the circulation
What is Hb, RBC and Hct like in polycythaemia?
All raised
What is pseudopolycythaemia?
High Hb, RBC and Hct from a decrease in plasma volume
What can cause polycythaemia?
Doping
Too much erythropoietin- potentially due to altitude
Tumour- renal or other tumour secreting too much EPO
Abnormal function of bone marrow-
Increased erythropoiesis
Intrinsic bone marrow disorder- polycythaemia vera
What can polycythaemia result in?
Vascular obstruction due to hyper viscosity of the blood
If there is no physiological reason for high haemoglobin or there is extreme hyperviscosity, what can be done?
Venesection- blood can be removed to thin the blood
How would you treat polycythaemia due to intrinsic bone marrow disease?
Drugs can be used to reduce the production of red blood cells by the bone marrow
