Anaemia and Microcytic Anaemias Flashcards
What is anaemia?
Reduced total red cell mass
Is it easy to measure total red cell mass?
NO - so this is not routinely done
As total red cell mass is difficult to measure, what can be done measured instead?
- Haemoglobin
* Haematocrit
Outline the Hb and haematocrit levels to diagnose anaemia in adult males.
- Hb <130g/L
* Hct 0.38-0.52
Outline the Hb and haematocrit levels to diagnose anaemia in adult females.
- Hb <120g/L
* Hct 0.37-0.47
Where does red blood cell production take place?
Bone marrow
What type of method is used to measure haemoglobin concentration?
Spectrophotometric method
Outline the steps in the method of measuring haemoglobin concentration.
- Burst (lyse) the red cells to create Hb solution
- Stabilise the Hb molecules (cyan-metHb)
- Measure the optical density (OD) at 540nm
- OD Proportional to the concentration (Beer’s Law)
- Hb concentration calculated against known reference standard cyan-metHb concentration solution
How is haematocrit measured?
The ratio (also commonly expressed as the percentage) of the whole blood that is red cells if the sample was left to settle
In rare situations, haemoglobin/haematocrit are not good indicators of anaemia e.g a rapid bleed and haemodilution
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In what situations are Hb/haematocrit not good indicators of anaemia?
- Rapid bleed
* Haemodilution
Describe why measuring Hb/haematocrit in a rapid bleed is not a good indicator of anaemia.
If 50% of blood volume is lost, the patient will obviously be anaemic as their red cell mass will have dropped by 50%
However, as both blood volume and red cell mass are decreased in proportion to eachother, the concentration of Hb will initially remain the same
True red cell mass is only apparent after a few days once fluid shifts have occurred
If you take measurements too early, you will not see a decrease of Hb
Describe why measuring Hb/haematocrit in haemodilution is not a good indicator of anaemia.
For example, later in pregnancy, plasma volume increases, making Hb concentration lower despite red cell mass being the same
What is increased red cell production known as?
Reticulocytosis
What is a reticulocyte?
A reticulocyte is a young red blood cell, just after it has left the bone marrow
Describe the appearance of a reticulocyte.
- Larger than the average cell
- Contains RNA
- Stains deep purple/red
- Polychromatic
Up regulation of reticulocyte production by the bone marrow in response to anaemia takes a few days
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What can automated analysis of RBC’s tell us about RBC’s?
- Cell size
- Cell count
- Light-scattering properties
Outline the 3 measured indices of a red cell.
- The haemoglobin concentration
- The number of red cell (concentration)
- The size of the red cells (mean cell volume or MCV)
Outline the 3 calculated indices of a red cell.
- Haematocrit
- Mean cell haemoglobin
- Mean cell haemoglobin concentration
What does reticulocyte count assess?
Bone marrow response
By which 2 methods is anaemia classified?
- Pathophysiology
* Morphological characteristics
In terms of pathophysiology, anaemia can be classified as either __________ ____ or __________ __________
- Increased loss
2. Decreased production
What 2 things can decreased production be due to?
- Hypo-proliferation – reduced amount of erythropoiesis
* Maturation abnormality – erythropoiesis is present but ineffective
What are the 2 most common causes of a maturation abnormality, which causes decreased production of red cells?
- Cytoplasmic defects – impaired haemoglobinisation
* Nuclear defects – impaired cell division
Microcytic anaemia has a ____ MCV
LOW
Macrocytic anaemia has a ____ MCV
HIGH
LOW RETICULOCYTE COUNT is seen when?
In a decreased production of red cells
HIGH RETICULOCYTE COUNT is seen when?
In increased loss or destruction of red cells
Where is haemoglobin synthesised?
Cytoplasm
What 2 things are needed to make haemoglobin?
- Globins
* Haem – porphyrin ring + Iron (Fe2+)
What does a shortage of globins or haem do?
Shortage of these components results in small red cells with low haemoglobin count
Describe the cells seen in microcytic anaemia.
The cells are microcytic (small) and hypochromic (lacking in colour)
What is colour of RBC’s measured by?
MCH (mean cell haemoglobin)
What are the 2 main groups of causes of Hypochromic, Microcytic Anaemias?
- Haem deficiency
* Globin deficiency
Iron deficiency is the commonest cause of microcytic anaemia worldwide
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What is the most common cause of a globin deficiency?
Thalassaemia (trait, intermedia, major) – globin chain defect
List 3 causes of a haem deficiency.
- Lack of iron for erythropoiesis
- Problems with porphyrin synthesis e.g lead poisoning - ‘Pyridoxine responsive anaemias’
- Congenital Sideroblastic Anaemia (very rare)
What 2 things is iron essential for?
- Oxygen transport – haemoglobin and myoglobin
* Electron transport – mitochondrial production of ATP
Iron is potentially toxic and needs to be handled safely by the body – generates free radicals
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Describe the structure of adult haemoglobin.
4 globin (protein) sub-units, each containing a single haem group
Each haem group has a Fe2+ ion and porphyrin ring
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1 haem group binds to one O2 molecule
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How much iron to we absorb per day?
1mg/day of iron
How can the amount of iron in the blood be roughly calculated?
The amount of iron in the blood can be roughly calculated by halving the volume of blood
Iron is stored in the liver as a molecule known as ferritin
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How is iron stored?
Iron is stored in the liver as a molecule known as ferritin
Most of the iron in the body is in haemoglobin
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Where is most of the iron in the body?
Most of the iron in the body is in haemoglobin
We are only able to absorb small amounts of iron !!
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Circulating iron is bound to transferrin
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What is circulating iron bound to?
Transferrin
Iron is transferred to the bone marrow macrophages that ‘feed it’ to red cell precursors
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List all the ways we can assess iron status.
Functional Iron
- Haemoglobin
Transported Iron
- Serum iron
- Transferrin
- Transferrin saturation
Storage Iron
- Serum ferritin
Describe the structure of transferrin.
A protein with two binding sites for iron atoms
When might transferrin levels be reduced?
- Reduced in anaemia of chronic disease
When might transferrin levels be increased?
- Increased in genetic haemachromatosis
What does transferrin tell us about?
Tells us about the availability of iron, rather than the amount of iron in the system
What is the normal range of transferrin?
30-50%
What is ferritin?
A large intracellular protein
Spherical protein stores up to 4000 ferric ions
What does ferritin reflect?
Reflects intracellular ferritin synthesis in response to iron status of the host
Serum ferritin is an easily measured indirect measure of storage iron
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Low ferritin means iron deficiency
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Ferritin is one of the acute phase proteins. What does this mean?
It can therefore be high in acute illness, but patient may actually be iron deficient
Iron deficiency can be confirmed by a combination of anaemia (decreased functional iron) and reduced storage iron (low serum ferritin)
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List 3 causes of chronic blood loss.
- Menorrhagia
- Gastrointestinal – tumours, ulcers, NSAID’s
- Haematuria
____________ is the most common cause of chronic blood loss worldwide
Menorrhagia
Outline 4 consequences of negative iron balance.
- Exhaustion of iron stores
- Iron deficient erythropoiesis - falling red cell MCV
- Microcytic anaemia
- Epithelial changes - skin, koilonychia
What are the 3 main causes of iron deficiency.
- Reduced diet consumption
- Losing iron
- Reduced absorption of iron
What 3 things can reduce the absorption of iron?
- Malabsorption (relatively uncommon)
- Coeliac disease
- Achlorhydria (no acid in stomach)
How can someone lose iron?
Blood loss (usually gastrointestinal)
Outline the 2 types of reduced diet intake of iron.
- Relative Deficiency – especially women of child bearing age and children
- Absolute Deficiency – vegetarian and vegan diets
If you have heavy periods/blood loss, what can you lose the ability to do?
Absorb iron
What is heavy menstrual blood loss defined as?
> 60ml – so >30mg iron/month
What is average menstrual blood loss?
- Average 30-40ml/month
* Equivalent to 15-20mg/month
Describe occult blood loss.
A small volume gastrointestinal blood loss can occur without any symptoms or signs of bleeding
It can outstrip the maximum dietary iron absorption of iron, and result in anaemia
How can you treat iron deficiency?
Iron absorption can be increased by iron supplements