Anaemia and Polycythaemia 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
Other than a reduction in the absolute amount of haemoglobin in the blood stream, what else could cause anaemia?
An increase in the plasma volume can decrease the haemoglobin concentration
Why would anaemia where excess plasma only be transient in a healthy individual?
The excess fluid would be excreted in a healthy individual
Broadly speaking, state four 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 (haemolytic)
Pooling of red blood cells in a very large spleen
For each type of anaemia, state whether they are usually hypochromic, normochromic or hyperchromic.
Microcytic – hypochromic
Normocytic – normochromic
Macrocytic - normochromic
State the common causes of microcytic anaemia.
Problem with Haem synthesis
Problem with globin synthesis
What mechanism usually causes macrocytic anaemia?
It usually results from abnormal haemopoiesis
The cells fail to divide properly
What is megaloblastic erythropoiesis? Describe the appearance of a megaloblast.
Megaloblastic erythropoiesis refers to a delay in the maturation of the nucleus while the cytoplasm continued to mature and the cell continues to grow
A megaloblast is an abnormal bone marrow erythroblast
They are large and show nucleo-cytoplasmic dissociation
What is an alternative mechanism of macrocytosis?
You can get premature release of cells from the bone marrow
Reticulocytes are about 20% larger than mature red cells so reticulocytosis would increase the MCV
State the two most common causes of megaloblastic anaemia.
B12 deficiency
Folate deficiency
State some common causes of macrocytic anaemia.
Megaloblastic anaemia
Haemolytic anaemia
Blood loss with adequate iron stores
Ethanol toxicity
State three mechanisms of normocytic normochromic anaemia.
Recent blood loss
Failure to produce red blood cells
Pooling of red blood cells in the spleen
Define haemolytic anaemia.
Anaemia resulting from shortened survival of red blood cells in the circulation
State some inherited abnormalities that can cause haemolytic anaemia.
Abnormal red cell membrane
Abnormal haemoglobin
Defect in the glycolytic pathway
Defect in the enzymes of the pentose shuttle
State some acquired abnormalities that cause haemolytic anaemia.
Damage to the red cell membrane
Damage to the whole red cell
Oxidant exposure
Explain how G6PD Deficiency can cause haemolytic anaemia.
G6PD is part of the pentose phosphate pathway
This is the only source of reduced glutathione in red blood cells
Because of the oxygen-carrying role of red blood cells, they are at constant risk of oxidant damage
So people with G6PD deficiency are at risk of haemolytic anaemia in states of oxidative stress
When would you suspect haemolytic anaemia?
Otherwise unexplained anaemia that is normochromic and usually either normocytic or macrocytic
Evidence of morphologically abnormal red cells
Evidence of increased red blood cell turnover
Evidence of increased bone marrow activity
What does the presence of fragments in the blood film suggest?
This suggests that red blood cells are being broken down within the circulation (in the small circulation)
What condition causes breakdown of red blood cells in small blood vessels?
Microangiopathic haemolytic anaemia
State some important signs of haemolytic anaemia.
Jaundice – because of the increased break down of red blood cells there is an increase in bilirubin
The increase in bilirubin can also increase the risk of getting gallstones
What are the features of red cells in hereditary spherocytosis?
They are LARGE and ROUND and have an increased MCHC
How does the bone marrow respond to the increased extravascular haemolysis in hereditary spherocytosis?
It increases the output of red cells leading to polychromasia and reticulocytosis
What is an effective treatment for hereditary spherocytosis?
Splenectomy
Why is a good diet important in patients with hereditary spherocytosis?
They have increased bone marrow activity and erythropoiesis so they need a supply of B12, folate and iron to keep producing red blood cells
What can G6PD deficiency cause?
Intermittent, severe intravascular haemolysis as a result of infection or exposure to an exogenous oxidant
What causes acute haemolytic anaemia?
Results from the production of antibodies against red cell antigens
This is very sudden and dramatic. An AUTOIMMUNE disease
Describe how acute haemolytic anaemia can lead to spherocytosis.
The immunoglobulin bound to the red cell is recognised by splenic macrophages, which remove parts of the cell membrane leading to spherocytosis
State two causes of spherocytosis.
Hereditary spherocytosis
Autoimmune haemolytic anaemia
Describe the diagnosis of acute haemolytic anaemia.
Finding spherocytes
Detecting immunoglobulin on the red cell surface Detecting antibodies to red cell antigens or other antibodies in the plasma
Which red blood cell parameters are increased in polycythaemia?
RBC
Hct
Hb
What is the term given to a condition where these parameters are increased but the absolute amount of haemoglobin is not increased?
Pseudopolycythaemia (or apparent polycythaemia)
This is due to a decrease in plasma volume
What are the consequences of polycythaemia?
Hyperviscosity of the blood
This can lead to vascular obstruction
Cause of defect in haem group
Fe deficiency
Anaemia of chronic disease
Cause of defect in globin group
A and b thalassaemia
Common causes of blood loss in normocytic anaemia
Peptic ulcer
Esophageal varices
Trauma
Causes of failing to produce RBCs in normocytic anaemia
Bone marrow failure
Renal failure (EPO)
Anaemia of chronic disease early stages
Causes of pooling of red blood cells in spleen
Hypersplenism
3 ways to classify haemolytic anaemia
Intrinsic/external factors
Hereditary/acquired
Intra/extravascular
Ways acquired haemolytic anaemia can damage RBC
Cell membrane
Whole cell
Causes of damage to RBC membrane in haemolytic anaemia
Autoimmune haemolytic anaemia
Snake venom
Causes of damage to whole cell in haemolytic anaemia
Oxidant damage
Malaria infection
Microangiopathic haemolytic anaemia
Ways inherited haemolytic anaemia can damage RBCs
Cell membrane defect
Hb defect
Glycolytic pathway defect
Pentose shunt enzymes defect
Cause of cell membrane damage in inherited haemolytic anaemia
Hereditary spherocytosis
Cause of Hb defect in inherited haemolytic anaemia
SCD
Cause of glycolytic pathway defect in inherited haemolytic anaemia
Pyruvate kinase deficiency
Cause of pentonse shunt pathway defect in inherited haemolytic anaemia
G6P deficiency
3 causes physiological causes of polycythaemia
Too much blood
Increased erythropoietin
Polycythaemia vera
Cause of too much blood polycythaemia
Doping
Medical negligence
Cause of too much erythropoeitin polycythaemia
Hypoxia-
Doping
Renal tumour
What is polycythaemia vera
Myeloproliferative neoplasm producing too many RBCs independent of EPO
Treatment for polycythaemia
Remove blood
Drugs to reduce bone marrow activity
Cause of polycythaemia in these instances Healthy athlete Breathless and cyanosis Abdominal mass Splenomegaly
Doping
Hypoxia
Renal tumour
Polycythaemia vera
