Week 1- Introduction to anaemia and microcytic anaemias Flashcards
What is anaemia?
Reduced total red cell mass.
What markers are used to measure anaemia?
Haemoglobin and haematocrit are used as surrogate markers. However this assumes that haemoglobin mass equals red cell mass. Also assumes that there is a steady state in blood volume (haematocrit measures the proportion of red cells in total blood vol)
What should the adult male haemoglobin be?
<130g/L
What should the adult female haemoglobin be?
<120g/L
What should the adult male haematocrit be?
0.38-0.52
What should the adult female haematocrit be?
0.37-0.47
Where does red cell production take place?
Bone marrow
How would you measure haemoglobin using a spectrophotometric method?
Burst (lyse) the red cells to create a Hb solution
Stabilise the Hb molecules (cyan-met Hb)
Measure the optical density (this is how red the cells are)
Optical density is proportional to the density (Beers Law)
Hb concentration worked out using known reference standard cyan-met Hb.
How do you measure haematocrit? How do modern machines differ?
Ratio of the blood that is red cells if the blood was left to settle. Modern machines now by adding a calculated volume of the red cells it counts.
In what cases are haematocrit or haemoglobin not good markers of anaemia?
When someone becomes acutely unwell and loses blood, the total volume of blood reduces however the haemoglobin concentration will remain the same and so will the percentage of blood that is red cells.
Also in haemodilution. Plasma volume expands in pregnancy and therefore the haemoglobin concentration is reduced.
What is a reticulocyte?
Red cells that have just left the bone marrow, they are larger than normal red cells. It still has some traces of dark blue/purple RNA.
How does the body respond to anaemia?
Reticulocytosis (cytosine means excess (along with aphelia)). This is increased red cell production.
How long does the process of up regulation of reticulocyte formation take in response to anaemia?
A few days.
What do automated analysers measure and calculate?
They measure
- Hb conc
- Number of red cells
- Size of red cells
They calculate
- Haematocrit
- Mean cell haemoglobin (from number of red cells and Hb conc)
- Mean cell haemoglobin conc (this ensures all parameters are working correctly).
What parameters does a full blood count look for?
HGB- haemoglobin RBC- red blood cell HCT- haematocrit MCV- mean cell volume (how big the cells are) MCH- mean cell haemoglobin MCC- mean cell haemoglobin concentration RET- reticulocyte count And also white cells like neutrophils, lymphocytes, basophils, eosinophils.
What does a reticulocyte count allow you to assess?
The marrow response to the problem at hand.
What will a blood film allow you to look at?
The cellular morphology
How is anaemia classified?
By morphological characteristics or pathophysiology
How is pathophysiological classification of anaemia split?
Into decreased production (low reticulocyte count) or increased destruction (high reticulocyte count).
What are the two causes of decreased production in anaemia?
Hypoproliferative (reduced amount of erythropoiesis)
Maturation abnormality- erythropoiesis present but ineffective. This could be due to cytoplasmic (impaired haemoglobin generation) or nuclear defects (impaired cell division)
What are the two causes of increased destruction in anaemia?
Problems with bleeding or haemolysis (premature red cell destruction)
How can mean cell volume be used to classify anaemia?
Mean cell volume is basically how big the cell is. If the cell MCV is low (microcytic) there is likely to be a problem with haemoglobuilsation (haemoglobin production) making the cell smaller.
If MCV is high (macrocytic)- usually a problem with cell division.
Where does haemoglobin synthesis occur?
What do defects in its production cause?
In the cytoplasm of red blood cells.
Defects in production of haemoglobin result in a small cell.
What do you need to make Hb?
Globin (2 alpha chains, 2 beta chains)
Iron
Porphyrin ring
What does a shortage in any one of the building blocks of haemoglobin result in?
Small cells as they can’t make as much haemoglobin.
What do the RBC’s in microcytic anaemia look like?
Microcytic (small)
Hypochromic (lacking in colour)
If you have a microcytic, hypo chromic RBC, where is the defect likely to be?
Well the defect is in haemoglobulinsation which is a CYTOPLASMIC defect.
What are the causes of microcytic, hypo chromic anaemias?
Haem deficiency- lack of iron, chronic disease causing normal body iron but lack of available iron,
Porphyrin ring problems- all very rare. Lead poisoning or pyridoxine responsive anaemias.
Or global deficiency- thalassaemia
Do we absorb a lot of iron from our diet?
No, iron isn’t really lost so only 1mg is absorbed a day. Women lose more iron than men do.
Where will iron be found in the body?
Mostly found in the haemoglobin.
But also can be found in the nursing macrophages in the bone marrow, erthroid marrow and liver stores.
What form is iron stored in?
As ferritin.
What is circulating iron bound too?
Transferrin.
What is the job of bone marrow macrophages?
They ‘feed’ the iron to red cell precursors.
What available tests can assess how much iron is present?
Functional iron- iron in Hb
Transported iron- serum iron, transferrin, transferrin saturations
Stored iron-serum ferritin
Specifically, what does transferrin do?
Transports iron from donor sites (macrophages, intestinal cells, hepatocytes) to tissues expressing transferrin receptors (especially erythroid marrow)
When will % saturation of transferrin be reduced?
Reduced in iron deficiency and in anaemia of chronic diseases,
When will % saturation of transferrin be increased?
Increased in genetic haemachromatosis.
Describe the structure of ferritin?
Large intracellular protein. Its a spherical shape and stores up to 4000 ferric ions.
Although ferritin is the storage form of iron, where else can it be found and what is this indicative of?
Can be found in the serum. It reflects intracellular ferritin synthesis.
What is serum ferritin a good measure of?
Good indirect measure of storage iron.
What does low ferritin mean?
Iron deficiency
NOTE on ferritin
If you get an infection and need to get rid of it, you want to make your body an unfavourable environment. This means getting rid of iron. Therefore your ferritin will increase to mop up the iron. This is acutely.
How can iron deficiency be confirmed?
Confirmed by a combination of anaemia (decreased functional (Hb) iron) and reduced storage iron (low serum ferritin)
What causes iron deficiency?
Not eating enough- women in pregnancy (relative deficiency) or vegetarian diets (absolute deficiency)
Losing too much- blood loss
Not absorbing enough- malabsorption
- coeliac disease
- achlorhydria
Name some causes of chronic blood loss?
Menorrhagia
GI causes- tumours, ulcers, NSAIDs
Haematuria
How much iron is lost a month during menstruation?
15mg for about 30mls (normal women release this) of blood.
How much iron is lost in heavy menstrual bleeding?
Heavy menstrual bleeding can be about 60mls a month therefore a loss of 30mg of iron.
What are the consequences of having iron inbalances?
Exhaustion of iron stores
Iron deficient erythropoiesis (falling MCV)
Microcytic anaemia
Epithelial changes- to the skin, koilonychia.
NOTE
Iron deficiency anaemia is a symptom not a diagnosis. Iron supplements may relieve this however will not tackle the underlying issue. Investigations are essential.
