Objectives


  1. Describe the major blood cell types and outline their functions and expected numbers.
  2. Describe how these various types of blood cells are derived from a common progenitor cell (haemopoiesis).
  3. Discuss how red blood cells are produced in the body (erythropoiesis), at the molecular and cellular levels.
  4. Describe what is meant by a blood transfusion; why and when it is given and why cross-matching matters.
  5. Discuss the right of a patient to refuse treatment.


Blood



Major Cell types and Function


See Block 1 Scenario 3



Expected Numbers



Male

Female

Hematocrit (%)
45-60

39-51
The hematocrit is the % of RBCs in blood by volume.
Hb (g.dl^-1)
13-18

11.5-15.5
The mass of Haemoglobin per decilitre.
Mean Corpuscle Volume (MCV) (fl)

78-96

The total volume occupied by RBCs/ the no. of RBSc in the sample... ie. the average RBC volume.
White Cell Count (x10^9/L)

4.0-11.0

The white cell count is composed of Neutrophils, Lymphocytes, Macrophages, Eosinophils and Basophils.
Platelets (x10^9/L)

150-400

The platelet count per Litre.
Reticulocytes (%)

0.2-2.0

The % of immature RBCs in full blood. This rises in times of great blood need. ie. haemmorhage.





Erythropoeisis

Erythropoeisis: production of red blood cells

  • occurs in bone marrow
  • initiated by erythropoeitin, a hormone

When hypoxia occurs, kidneys release an enzyme called renal erythropoeitic factor.

Renal erythropoeitic factor catalyzes the conversion of a plasma globulin precursor into erythropoeitin.
This precursor protein is produced in the liver.



Erythropoeitin acts to:
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increase the number of developing precursor cells.

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increase the rate of red cell maturation.

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increase the rate of red cell release from the bone marrow.

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increase rate of hemoglobin synthesis within the red cell




Alternative PBL


It is the different number of different blood cells in a known volume of blood. Usually it’s a number per liter of blood. This is used for recognizing and investigating about blood diseases.
The indices like mean corpuscular value can be derived from these values; the white cell count gives the values of the total number of circulating leukocytes. Normally less than 2% of the red cells are reticulocytes and they give the erythoid activity in the bone marrow. Increased activity can be due to hemorrhage or haemolysis. A low count can mean can be present in anemia due to inappropriate response of the bone marrow.

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Normal Values for Blood
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Male
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Female
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Hemoglobin (Hb)
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13.5-17.5
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11.5-16
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Packed Cell Volume (PCV haematocrit; L/L)
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0.4-0.54
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0.37-0.47
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Red Cell Count (RCC 1012 /L)
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4.5-6.0
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3.9-5.0
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Mean Corpuscular Volume (MCV fl)
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80-96
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Mean Corpuscular Hemoglobin (MCH pg)
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27-32
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Mean Corpuscular Hemoglobin Concentration MCHC (g/dL)
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32-36
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White Blood Count (WBC 109/L)
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4.0-11.0
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Platelets
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150-400
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ESR
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<20
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Reticulocytes.
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0.5-2.5% (50-100 x 109 /L)
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Erythrocyte sedimentation rate
This is the rate of fall of red cells in a column of blood and is measure of acute-response to the pathological process maybe immunological, infective, ishaemic, malignant or traumatic. A raised ESR reflects an increase in the plasma concentration of large proteins such as fibrinogen and immunoglobulins. These are responsible for formation of cell clumps. It is high in patients with high anaemia.

Plasma viscosity
This is used instead of ESR in many laboratories. This is important if large concentrations of fibrinogens or immunoglobulins are present. There is no difference found between concentration found in males and females and as viscosity increases minor in elderly people. And is not affected by the level of Hb and the results can be obtained within 15 minutes.

C - reactive protein
C-reactive protein is a pentraxin, one of the proteins produced in the acute-phase response. This is only made in the liver and rises within 6 hours if the need is there after an acute event. They rise after fever and in inflammatory conditions and after trauma. The measurement is easy and quick to perform and high levels can predict future cardiovascular diseases.


How and where are RBC made?

Erythropoietin
Embryonic red blood cells are three weeks olds and then they start to divide rapidly so they can increase exponentially, the embryonic yolk saw are the main site of blood formation for the first eight weeks of development. As other organs appear some of the embryonic red blood cells move out of the blood stream and into the liver, spleen, thymus and bone marrow. These embryonic cells differentiate into stem cells whose division produces blood cells. The liver and spleen are the primary sites of hemopoiesis from the second to fifth months of development, but as the skeleton enlarges, the bone marrow becomes increasingly important. In adults, red bone marrow is the only site of red blood cell production, as well as the primary site of white/red blood cell formation.


Red Blood Cells Formation
  • Erythropoiesis occurs in red bone marrow or myeloid tissue; they are located in the vertebra, sternum, ribs, skull, scapulae, pelvis and proximal limb bones.
  • Under extreme stimulation yellow bone marrow can convert into red bone marrow and increase red blood cell formation.
Stages

· Division of hemocytoblasts or pluripotent stem cells in bone marrow produce myeloid stem cells which further differentiate to produce red blood cells
· After each stage more and more RNA is lost and eventually in red blood cells there is no nucleus left whatsoever.
· Reticulocytes stay inside the bone marrow for about 1 or 2 days and lose their RNA and become mature red blood cells and can not be distinguished from normal red cells.
· Erythropoetin (EPO) is a hormone (glycoprotein) which controls eryhtropeisis and hence is important for red blood cell formation. In case of hypoxia the EPO production is increased.

The differentiation process in red blood cells is as follows:
1. Pluripotent Stem cell
2. Proeryhtroblasts
3. Erythroblasts
4. Normoblasts
5. Reticulocyte after 4 days (this contains 80% of the Hb)

· There is still some RNA which is left inside the reticulocytes, so they enter the blood stream after two days however they mature after 24 hours and can not be distinguished from red blood cells.

Erythropoiesis

For the red blood cell formation Iron, Vitamins B12, B6 and folic acid is required for protein synthesis these vitamins can be obtained from dairy products or meat however different factors are required like fat so these nutrients can be absorbed. Vitamin B12 can cause pernicious anemia.
EPO is stimulated by different hormones like thyroxin, androgens and growth hormones; however estrogen does not account for the difference in the haematocrit in values in males and females.
EPO is produced when low oxygen is present especially the kidney, this is also known as hypoxia. EPO is released during anaemia, when blood flow to the kidney decreases, when oxygen content of air in the lung declines e.g. disease or high altitude, when the respiratory surfaces in the lungs are damaged. When EPO enters the blood stream it goes to the red bone marrow and stimulates the RBC stimulation.

EPO has two major effects on the body, first increase of red cell production in erythroblasts, as well as the faster maturation of RBC and this can be an increase by 1000%, which are about 30 mill cells per second.
This is important for after a person has lost a lot of blood has been lost, however if EPO is administered to athletes it can be seen as doping, but this may cause problems in some cases as the blood viscosity is increased and the heart need to carry out more tasks. Blood tests are made to look for different illness or internal bleeding, and these values can be compared to the values above.

Blood Types

Bloods are categorized on the basis which antigens and antibodies they have, and the main system for categorizing is the ABO-system. Antigens trigger the reaction for the defense mechanism of the body, most of the antigens are made of proteins, however they can be made of organic molecules as well, the antigens on our own blood cells are normal for our body and hence not foreign so they are not attacked, however different blood groups have different antigens or in case of O, no antigens at all.
Overall the presence of surface antigens as well as the presence of antibodies determines the blood type. The most important ones are A, B and RH+ (D), however the blood type is based on the presence of these antigens Blood group A has antigens A on them, Blood group has antigens B on them and AB has both A and B antigens however O has none of them. The average distribution in the UK is as follows. O 44%, A 45%, B 8%, AB 3.
The term Rh positive indicates the presence of Rh surface antigens, sometimes called the Rhesus factor; hence the absence of it can be seen as rhesus negative. When the whole blood type is recorded and the blood is usually described as O negative, a positive and so on. Rhesus factors differ in ethnic groups and by region. Surface antigens are also known as agglutinogens. However antibodies are also known as agglutinin these will attack foreign cells and will agglutinate, this term is called agglutination. This can be seen in the following example; Blood Group A has A antigens; however Group B antibodies, if they come in contact with Blood Group B the antigens of B will be attacked by the antibodies of Group A. A person with O has no antigens (well not the most important ones) however both antibodies, but a person with AB has both antigens but no Antibodies. These antibodies and antigens are present regardless of exposure to foreign RBCs.
However a Rh-negative person has no Rh-antibodies present and they only develop if exposure to Rh-positive blood has been done either during transfusion or pregnancy.

Cross Reactions

Cross reaction occurs if a antibody of a specific type of blood reacts with its corresponding antigen on a different Blood cell, this agglutination is called cross reaction. This test can be used for finding out about donors if a blood transfusion is required in case of blood loss due to a wound or operation. Usually Blood Group O- is used as they lack A, B and Rh antigens and hence can be used as universal donors, however they can only receive blood from O as they have both antibodies. Blood group AB on the other side can only receive Blood from any other blood group but can not be used as a good donor as their blood will react with A and B as AB has both surface antigens. The surface antigens of the donor are more important than the antibodies of the donor, as the agglutination will occur due to the antibodies of the recipient but the donors antibodies will be diluted to such a minor concentration, so the blood clots formed will not be as harmful as the blood clots formed due to the antigens of the recipient as high concentration of the antibodies are much higher.
In extreme cases like a person who has a severe gunshot wound and loss of 5 liters, he might need a transfusion without taking a cross matching beforehand, so in these cases O- will be used as it is lacking the most important surface antigens, there are more antigens but these are the most important ones as O- will clot really rarely.


What is Blood transfusion and why is it needed?

Blood transfusion is the injection of blood from a healthy donor into the circulation of a patient (the recipient); the patient might need the blood either due to a illness which causes the blood to have a low quality, or due to low quantity of blood through a wound. Direct transfusion is carried out rarely and is not wise as it might lead to patient’s death as no cross reaction is carried out. The Blood for transfusion is usually kept in blood banks and they can be used if a necessity arises. The blood is being tested for several diseases like HIV, hepatitis and syphilis.