Anaemia Flashcards
Define anaemia
Reduction in amount of Hb in a given volume of blood
BELOW
what would be expected in comparison with a healthy subject of the same age and gender
What is normally reduced in anaemia?
Hb
RBC and Hct/PCV are also usually reduced
What can often lead to anaemia but is NOT the case in a healthy person?
o reduction is ABSOLUTE amount of Hb in the blood stream
Could also occasionally result from an INCREASE in PLASMA VOLUME (rather than a decrease in Hb)
- this would NOT persist however because the body would be able to remove excess fluid
Mechanisms of anaemia?
o Reduced production of RBC/Hb in the bone marrow
o Loss of blood from the body
o Reduced survival of RBCs in circulation
o Pooling of RBCs in the spleen (splenomegaly)
In regards to the MECHANISM of anaemia, how is this different to the CAUSES of anaemia
MECHANISM:
- might be due to reduced synthesis of Hb in the bone marrow
CAUSE:
- could be due to a condition causing:
o reduced synthesis of haem (iron deficiency)
o reduced synthesis of globin (beta-thalassaemia)
Classification of anaemia based on cell size?
Microcytic (usually also hypochromic)
Normocytic (usually also normochromic)
Macrocytic (usually normochromic)
Common causes of microcytic anaemia?
o Defect in haem synthesis
- iron deficiency
- anaemia of chronic disease
o Defect in globin synthesis (thalassaemia)
- defect in alpha-chain synthesis (alpha thalassaemia)
- defect in beta-chain (beta thalassaemia)
Why does macrocytic anaemia usually occur?
Due to abnormal haemopoiesis:
- RBC precursors continue to synthesise Hb and other cellular proteins
BUT
- fail to divide normally
Therefore RBC end up larger than normal
2 causes of macrocytic?
- Megaloblastic erythropoiesis
2. Premature release of cells
Explain megaloblastic erythropoiesis
One of the causes of MACROcytic anaemia
Delay in the maturation of the nucleus
BUT
the cytoplasm continues to mature = cell continues to grow
What is a megaloblast?
Abnormal bone marrow erythrocyte - it is:
o larger than normal
o shows nucleocytoplasmic dissociation
What is required to reach a diagnosis of megablastic erythropoiesis?
Possible from peripheral blood features
BUT
requires bone marrow examination
Explain premature release of cells from the bone marrow
One of the causes of macrocytic anaemia
Young RBCs are 20% larger than normal RBCs so more young cells = MCV will be increased
Common causes of macrocytic anaemia?
o Megaloblastic anaemia - as a result of lack of:
- vitamin B12
OR
- folic acid
o DNA synthesis interfering drugs
o Liver disease & ethanol toxicity
o Recent major blood loss with adequate iron stores (reticulocyte no. increases as bone marrow tries to compensate)
o haemolytic anaemia (reticulocytes no. increase as RBCs lost (lyse in blood stream)
Mechanisms that cause normocytic (normochromic) anaemia?
o Recent blood loss
o Failure of production RBCs
o Pooling of RBCs in the spleen
Causes of normocytic (normochromic) anaemia?
o Peptic ulcers, oseophageal varices, trauma ( for blood loss)
o Early stages of iron deficiency, renal failure, bone marrow failure (for failure of RBC production)
o Hypersplenism e.g. portal cirrhosis (for pooling of RBC in the spleen)
What is haemolytic anaemia and what can it arise from?
Shortened survival of RBCs in the circulation
Can result from either:
o INTRINSIC abnormality of the RBCs
o EXTRINSIC factors acting on the normal RBCs
EXTRINSIC factors can also interact with RBCs that have an intrinsic abnormality
Haemolytic anaemia can be further classified - explain this (i.e. I & A)
Can be classified as either:
o INHERITED
o ACQUIRED
INHERITED:
- arise due to abnormalities in the cell membrane, Hb OR enzymes in the RBC
ACQUIRED:
- arise due to extrinsic factors such as micro-organisms, chemicals or drugs that damage the RBC
Haemolytic anaemia can be further classified - explain this (i.e. I & E)
Can be classified as either:
o INTRAvascular haemolysis
o EXTRAvascular haemolysis
INTRAvascular:
- occurs if there is acute damage to the RBC
EXTRSvascular:
- occurs when defective RBCs are removed by the spleen
Haemolysis is often partly both of these!
Examples of INHERITED factors resulting in Haemolytic anaemia?
ONENOTE!!
o abnormal RB cell membrane e.g. spherocytosis
o abnormal Hb e.g. sickle cell anaemia
o defect in glycolytic pathway e.g. pyruvate kinase deficiency
Examples of ACQUIRED factors resulting in Haemolytic anaemia?
ONENOTE!!
o damage to RB cell membrane e.g. AHA or snake bite
o Damage to WHOLE RBC e.g. MAHA
o Oxidant exposure damages RBC membrane and Hb e.g. dapsone or primaquine
Example of where an extrinsic factor can interact with RBCs that have an intrinsic abnormality?
(ONENOTE!!)
So people with G6PD deficiency are at risk of haemolytic anaemia in states of oxidative stress (LAZ!)
Defect in enzymes of the pentose shunt e.g. G6PD deficiency links with
Oxidant exposure damages RBC membrane
AS
causes precipitation of episodic haemolysis in individuals with enzyme deficiency
When to suspect haemolytic anaemia?
o when otherwise unexplainable anaemia which is normochromic and usually either normocytic OR macrocytic
Evidence of:
o morphologically abnormal RBCs
o increased RBC breakdown
o increased bone marrow activity
Certain conditions that the patient may have hence why would suspect haemolytic anaemia?
o Irregularly contracted cells
o Hereditary elliptocytosis (leads to haemolysis)
o Poikilocytosis
o Sickle cell disease
o Fragments - as not being broken down in spleen BUT within circulation (in small capillaries)
= MICROANGIOPATHIC HAEMOLYTIC ANAEMIA
o Gall stones - chronic HA means high excretion of bilirubin SO get higher incidence of gall stones
o Jaundice - sickle cell, RBC broken down quickly
Define Hereditary Spherocytosis
H.A or chronic compensated haemolysis
resulting from an
INHERITED INTRINSIC defect of the RB CELL MEMBRANE
What is the resulting end due to Hereditary Spherocytosis?
RBCs become less flexible SO are removed by the spleen prematurely
Known as EXTRAVASCULAR HAEMOLYSIS
What happens to the RBCs in Hereditary spherocytosis?
After entering the circulation, the RBCs lose their membrane in spleen = spherocytic
What often follows hereditary spherocytosis?
Extravascular haemolysis
The bone marrow responds by INCREASING output of RBCs. This leads to:
o polychromasia (immature RBCs in blood)
o reticulocytosis (premature cells)
Haemolysis also leads to increased bilirubin production = jaundice = gallstones
What are spherocytes prone to?
Haemolysis WHEN osmotic pressure is REDUCED
Treatment for hereditary spherocytosis?
o Splenectomy - ONLY effective treatment
o Good diet
- so that a 2o folic acid deficiency does not occur
G6PD?
Glucose-6-phosphate dehydrogenase
Why is G6PD important?
Important enzyme in the PENTOSE PHOSPHATE SHUNT - essential for:
o protection of RBCs from oxidant damage
What can G6PDD lead to?
Oxidants may be generated in the BS so G6PDD may intrinsically affect the RBCs leading to
HA (haemolysis anaemia)
Where do oxidants come from?
May be generated in the BS e.g.
o during infection
May be exogenous
o broad beans
o chemicals (mothballs/naphthalene)
o drugs (dapsone/primaquine)
Who is normally affected by G6PDD?
Gene for G6PD is on the X chromosome
SO normally males BUT females as well is homozygous
What does G6PDD usually end up causing?
Intermittent, severe INTRAvascular haemolysis
due to an exogenous oxidant
G6PDD ends up causing severe intravascular haemolysis - what are these associated with and what does it lead to the formation of?
The appearance of IRREGULARLY CONTRACTED CELLS
Hb is denatured and so forms round-balls knows as HEINZ BODIES
Can Heinz bodies be removed?
YES - by the spleen
BUT it leaves a defect in the RBC
Howell-Jolly Bodies vs. Heinz Bodies?
Can get MORE THAN ONE Heinz Body in a cell
Why does Autoimmune HA arise?
Due to the production of autoantibodies directed at RC antigens
What does AI HA lead to?
Recognised by splenic macrophages = removes parts of RBC membrane = spherocytosis
Complement components can also be bound to Ig molecule which can also be recognised by receptors on the splenic macrophages
Why are the RBCs formed in AI HA removed?
Form spherocytes which are less flexible - so combined with:
o cell rigidity
o recognition of Abs + complement on RB surface by splenic macrophages
LEADS to removal of these cells from the circulation by the spleen
How can AI HA be diagnosed?
o Finding spherocytes & an INCREASED reticulocyte count
o Detecting Ig +/- complement of RB surface
o Detecting Abs to RB antigens OR autoAbs in the plasma
Treatment for AI HA?
o Use CORTICOSTEROIDS and other immunosuppressive agents
o Splenectomy for severe cases
Treatment for Microangiopathic HA?
o Remove cause e.g. treat severe hypertension OR stopping causative drug
o Plasma exchange when it is caused by an Ab in the plasma (as this leads indirectly to fibrin deposition - i.e. the FRAGMENTS!)
