Haem 3 Flashcards
Define 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
Hb reduced, The RBC and the PCV/Hct are usually also reduced
2 conceptual causes of anaemia
usually due to a reduction of the absolute amount of haemoglobin in the blood stream
Occasionally it results from an increase in the volume of plasma rather than a decrease in the amount of haemoglobin
In healthy person, can anaemia be from an increase in plasma volume?
NO- increase in plasma volume cannot persist because the excess fluid in the circulation is excreted
(anaemia can therefore be regarded as a resulting from a decrease of the absolute amount of haemoglobin in the circulation)
4 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
This is really critical for framework... think Production reduces Pooling in spleen Blood loss Lifespan reduces
Differentiate mechanism and 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
Classification of anaemia on cell size, and whether each type is hyperchromic or hypochromic or normochromic
Microcytic (usually also hypochromic)
Normocytic (usually also normochromic)
Macrocytic (usually also normochromic)
Common cause of microcytic anaemia
- Defect in haem synthesis
(Iron deficiency or
Anaemia of chronic disease) - Defect in globin synthesis (thalassaemia)
Defect in α chain synthesis (α thalassaemia)
Defect in β chain synthesis (β thalassaemia)
2 mechanisms of macrocytic anaemia
- usually result from abnormal haemopoiesis so that the red cell precursors continue to synthesize haemoglobin and other cellular proteins but fail to divide normally
e. g. megaloblastic erythropoiesis - 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 is megaloblastic erythropoiesis
A specific type of macrocytic anaemia, in which there is delay in maturation of the nucleus while the cytoplasm continues to mature and the cell continues to grow (nothing wrong with ribosomes but DNA synthesis wrong) shows nucleo-cytoplasmic dissociation
What might imply megaloblastic anaemia without needing to do bone marrow test
Hypersegmented neutrophil and oval macrophages in perpheral blood
Outline premature release of cells from bone marrow as a cause of macrocytic anaemia
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
List 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)
Mechanism of normocytic normochromic anaemia
Recent blood loss
Failure of production of red cells
Pooling of red cells in the spleen
(note… soon after lots of blood loss you’ll get macrocytic anaemia)
Causes of normochromic anamia (distinct from mechanism)
Blood loss (mech): Peptic ulcer, oesophageal varices, trauma
Failure of production: 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
anaemia resulting from shortened survival of red cells in the circulation
2 causes of haemolytic anaemia
intrinsic abnormality of the red cells
extrinsic factors acting on normal red cells
Inherited and acquired cause of haemolytic anaemia
inherited:
1. abnormalities in the cell membrane (e.g hereditary spherocytosis),
- abnormalities in the Hb (e.g. sickle cell)
- enzyme defect (G6PD deficiency) in the red cell
- defect in glycolytic pathway (pyruvate kinase deficiency)
Acquired:
- Damage to whole red cell
- microangiopathic haemolytic anaemia, see end - Oxidant exposure (such as?), damage to red cell membrane and Hb this will lead to episodic haemolysis in inviduals with G6PD deficiency
- Damage to cell membrane (autoimmune haemolytic anaemia or snake bite)
EXTRINSIC FACTORS can interact with INHERENTLY ABNORMAL RED CELLS TOO
How else can haemolytic anamia be classified
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
When to suspect haemolytic anaemia
Otherwise unexplained anaemia, which is normochromic and usually either normocytic or macrocytic (reticulocytes increased in haemolysis)
Evidence of increased bone marrow activity increased reticulocte count/polychromasia)
Evidence of morphologically abnormal red cells
Evidence of increased red cell breakdown (unconjgated bilirubin)
Why would jaundice in child imply haemolytic anaemia?
Because break down of red blood cells exceeds the amount lliver can process
Outline 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
Consequences of hereditary spherocytosis and the type of anaemia this is
Red cells become less flexible and are removed prematurely by the spleen – extravascular haemolysis
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
So haemolytic anaemia
OSMOTIC FRAGILITY TEST
Treatment of Hereditary spherocytosis
only effective treatment is splenectomy (only in severe cases) due to the extravascular haemolysis
good diet is important so that a secondary folic acid deficiency does not occur (otherwise this can lead to megaloblastic crisis –> due to not enough vitamins)
or 1 folic acid tablet daily
Function fo G6PD
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
important enzyme in pentose phosphate shunt in normal carb metabolism
