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
RBC and Hct are usually also reduced
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 this type of anaemia 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 or eg into the stools)
Reduced survival of red blood cells (haemolytic)
Pooling of red blood cells in a very large spleen
For each type of anaemia(microcytic, normocytic and macrocytic), state whether they are usually hypochromic, normochromic or hyperchromic.
Microcytic – hypochromic as both are usually caused by defect in Hb synthesis
Normocytic – normochromic
Macrocytic - normochromic, macrocytosis is usually caused by other defects rather than Hb synthesis so Hb conc would be normal
State the common causes of microcytic anaemia.
In general, it is caused by problems in Hb synthesis.
Problem with Haem synthesis
Iron deficiency
Anaemia of chronic disease: anaemia is associated to some chronic inflammatory diseases like rheumatoid arthritis
Problem with globin synthesis
Alpha thalassemia (alpha chain defect)
Beta thalassemia (beta chain defect)
What mechanism usually causes 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 megaloblastic erythropoiesis? Describe the appearance of a megaloblast.
Megaloblastic erythropoiesis is a mechanism for MACROCYTIC ANAEMIA.
A megaloblast is an abnormal bone marrow erythroblast
The nucleus is delayed but the rest of the cell continues to grow. Cannot produce DNA quickly enough to divide at the right time and thus grow too large before division
They are large and show nucleo-cytoplasmic dissociation (nucleus more primitive compared to the rest of the cell)
What is an alternative mechanism of macrocytosis?
Reticulocyte mechanism.
NB two mechanisms for macrocytic anaemia:
- reticulocyte
- megaloblastic
You can get premature release of cells from the bone marrow (reticulocytes)
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 causes for the 2 mechanisms of macrocytic anaemia:
- megaloblastic mechanism
- Reticulocyte mechanism
Megaloblastic: B12 deficiency Folate deficiency Drugs that interfere with DNA synthesis (e.g. chemotherapy) Liver disease Ethanol toxicity
Haemolytic:
Recent major blood loss with adequate iron stores (reticulocytes increased). Bone marrow tries to spit out reticulocytes to compensate for the blood loss
Haemolytic anaemia (reticulocytes increased). Breakdown of RBC causing bone marrow to spit out reticulocyte which are bigger than normal RBC, hence causing macrocytic anaemia
State three mechanisms of normocytic normochromic anaemia.
Recent blood loss
Failure to produce red blood cells
Pooling of red blood cells in the spleen
State five causes of normocytic normochromic anaemia.
- Mechanism=Recent blood loss, caused by eg:
Peptic ulcer
Oesophageal varices
Trauma
2.Mechanism=Failure of production of red blood cells, caused by:
Early stages of iron deficiency and Anaemia of CD
Renal failure (drop in EPO)
Bone marrow failure (reduced no of stem cells or bone marrow suppression by cancer drugs)
Bone marrow infiltration by eg cancer cells
- Mechanism= Pooling of RBC in spleen, caused by PORTAL CIRRHOSIS (cirrhosis of liver)
Define haemolytic anaemia.
Anaemia resulting from shortened survival of red blood cells in the circulation
State two different classifications of haemolytic anaemia.
INHERITED OR ACQUIRED
OR
INTRAVASCULAR OR EXTRAVASCULAR
Haemolysis can be inherited (resulting from abnormalities of the cell membrane, haemoglobin or the enzymes in the red blood cell)
It can be acquired usually resulting from extrinsic factors such as micro-organisms, chemicals or drugs
Haemolytic anaemia can also be described as intravascular if there is very acute damage to the red cell
It can also be classified as extravascular when the spleen removes defective red cells too quickly
State some inherited abnormalities that can cause haemolytic anaemia.
Abnormal red cell membrane eg hereditary spherocytosis Abnormal haemoglobin (Sickle cell) Defect in the glycolytic pathway (pyruvate kinase deficiency) Defect in the enzymes of the pentose shuttle (eg G6PD deficiency)
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.
slide 27
G6PD is part of the pentose phosphate pathway, this pathway produces a lot of NADPH which helps to REDUCE OXIDATIVE STRESS. Without this pathway, cell would be more prone to oxidative stress.
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 via 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 (increased bilirubin and lactate dehydrogenase, LDH is released when cells are destroyed)
- 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
Caused by overactive coagulation system, leading to fibrin mesh formation, these are protein networks that CUT RBC into schistocytes.
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
State examples of inherited diseases causing haemolytic anaemia that have defects at the following sites:
a. Membrane
b. Haemoglobin
c. Glycolytic Pathway
d. Pentose Shunt
a. Membrane Hereditary spherocytosis b. Haemoglobin Sickle cell anaemia c. Glycolytic Pathway Pyruvate kinase deficiency d. Pentose Shunt G6PD deficiency
State examples of acquires disease causing haemolytic anaemia that have defects at the following sites:
a. Membrane - immune
b. Whole red cell - mechanical
c. Whole red cell - oxidant
d. Whole red cell - microbiological
a. Membrane – immune Autoimmune haemolytic anaemia b. Whole red cell –mechanical Microangiopathic haemolytic anaemia c. Whole red cell – oxidant Drugs and chemicals d. Whole red cell – microbiological Malaria
What is hereditary spherocytosis?
This is haemolytic anaemia or chronic compensated haemolysis resulting from an intrinsic inherited defect of the red cell membrane
After entering the circulation, the cells lose membrane in the spleen and become spherocytic
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
Describe the pattern of inheritance of G6PD deficiency.
X linked recessive
What can G6PD deficiency cause?
Intermittent, severe intravascular haemolysis as a result of infection or exposure to an exogenous oxidant
What tends to appear in blood films during these episodes of severe intravascular haemolysis?
Irregularly contracted cells
What happens to the haemoglobin during these episodes?
It becomes denatured and forms round inclusions called Heinz bodies
NOTE: you can get more than one Heinz body per cell unlike Howell-Jolly bodies
What causes autoimmune haemolytic anaemia?
Results from the production of antibodies against red cell antigens
This is very sudden and dramatic
Describe how autoimmune haemolytic anaemia can lead to spherocytosis.
The immunoglobulin bound to the red cell is recognised (Fc part) 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 autoimmune haemolytic anaemia.
Finding spherocytes
Increased reticulocyte count
Detecting immunoglobulin±complement on the red cell surface
Detecting autoantibodies to red cell antigens or other autoantibodies in the plasma
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What is the treatment for autoimmune haemolytic anaemia?
Corticosteroids or other immunosuppressive agents Splenectomy in severe cases
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
State some causes of polycythaemia.
Blood doping
Elevation of EPO when at altitude
Tumour (renal or other tumour that can secrete high amounts of EPO)
Abnormal function of bone marrow – it can result from inappropriately increased erythropoiesis that is independent of EPO, this is an intrinsic bone marrow disorder called polycythaemia vera
It is a chronic myeloproliferative neoplasm
What are the consequences of polycythaemia?
Hyperviscosity of the blood
This can lead to vascular obstruction
