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
For practical purposes, anaemia can therefore be regarded as a resulting from a decrease of the absolute amount of haemoglobin in the circulation
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.
Problem with Haem synthesis
Iron deficiency
Anaemia of chronic disease: anaemia is associated to some chronic inflammatory diseases like rheumatoid arthritis/tb
Problem with globin synthesis –thalassaemia
Alpha thalassemia (alpha chain defect)
Beta thalassemia (beta chain defect)
What mechanism usually causes macrocytic anaemia?
Name the causes of 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
- Megaloblastic eryhropoiesis
- reticulocyte mechanism
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.– 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
Drugs interfering with DNA synthesis
Liver disease and ethanol toxicity
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 three 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= Hypersplenism –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
INTRINSIC OR EXTRINSIC – HAEMOLYSIS RESULTS FROM INTRINSIC ABNORMALITY OF RBC VV
Extrinsic factors can interact with red cells that have an intrinsic abnormality that make the more susceptible
State two different classifications of haemolytic anaemia.
- INHERITED OR ACQUIRED
- 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
often haemolysis is partly intravascular and partly extravascular
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)-- ALSO VERY SUSCEPTIBLE OXIDANT DAMAGE THEREFORE LINK BETWEEN INHERIITED AND ACQUIRED
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