Life Span Of Red Blood Cells And Erythropoiesis Process

Early stage of RBC formation

Life span of red blood cell/erythrocyte:

The life span of RBC is about 120 days. Such short life span of RBC is seen due to their inability to divide and replaced old ruptured cells with new cells. Hence, due to short life span, the process of erythropoiesis is a necessary for maintaining the number of RBC in human body. Erythropoiesis is the process by which red blood cells are formed from bone marrow cells.

Early stage: RBCs are first produced in the yolk sac during the first two month of intrauterine life. In the hepatic stage (third month of intrauterine life), liver and spleen organs performs erythropoiesis. Finally, in the last three months, the bone marrow takes over the process of erythropoiesis.

Differentiation stage: RBCs first exist in the form of hemocytoblast, which is a pluripotent hematopoieic stem cell. The maturation and full development of hemocytoblast into a mature RBC occurs through eight stages. These include the stepwise formation of multipotent stem cells, unipotent stem cells, pronormoblast, early normoblast, intermediate normoblast, late normoblast, reticulocyte and matured erythrocyte.

Regulation: RBCs circulate in the body and performs its function for 100-120 days.

Death: RBC are phagocytized by macrophages after undergoing changes in its plasma membrane. In this way, old and defective RBC cells degrade and they are finally removed from circulation. The aging and death of mature RBC is also known as eryptosis (Franco 2012).

Figure 1: Different stages in the formation of RBC. Source: (Unger et al. 2010)

There are four stages in erythropoiesis. Proethythroblast is first cell that is derived from stem cells and it multiplies several times to form the early normoblast cells involved in third stage of erythropoiesis. By this step, hemoglobic is not formed, however its formation initiates in the next phase when intermediate normoblast is formed. Chromatin network condenses in the intermediate normoblast and hemoglobic starts appearing. By the late normoblast stage, hemoglobin starts accumulating and the disintegration of nucleus occurs to form the reticulocytes. Reticulocyte is the immature form of RBC and the formation of RBC occurs after the reticular networks in reticulocyte disappear (Unger et al. 2010). Hence, the synthesis of RBC from proethroblast takes place in 7 days.

Structure and function of the red blood cells:

Red blood cells (RBC) have a flexible disc shaped or biconcave structure that provides maximum surface area for gas exchange.  The thickness of the disc is about 6-0 micrometers and its thickness is around 2 micrometers. It does not have a nuclei. This kind of structure supports RBC in gas exchange and allowing oxygen and carbon-dioxide to pass easily through the cell. RBC plays a role in transporting oxygen to body cells and delivering carbon dioxide to the lungs. By having a concave shape, RBC gets the opportunity to pass through tiny blood vessels and transport oxygen to body tissues and organs. The biconcave structures also support the RBC in easily circulating through narrow capillary openings. RBC contains hemoglobin that binds with oxygen molecule to transfer it into different organs and tissues (Volkers, Mechioukhi and Coste, 2015).

1. Three types of leucocytes seen in the diagram are monocytes, eosinophils and neutrophils.
2. The structure of each type of leucocytes are as follows:

Differentiation stage of RBCs

Monocytes: Monocytes are largest type of leucocytes or white blood cells, having amoeboid structure along with a granulated cytoplasm. It consist of 2-10 % of leucocytes and plays a role in immune function. Their function and biochemistry is also dependent on the environment in which they mature (Parihar, Eubank and Doseff 2010).

Eosinophils: Eosinophil consists of about 1-6% of the total WBC in human body. Eosinophols have a bilobed structure with a nucleus. The cell is filled with cytoplasm containing different enzymes and proteins (Muniz et al. 2012).

Neutrophils: Neutrophils comprise 40-75% of total leucocytes and it performs antimicrobial function by the process of phagocytosis. Neurophil has a complex lobulated nucleus and it cytoplasm contains many granules (Rosales et al. 2016).

1. Function of different types of leucocytes in relation to immune system are as follows:

Monocytes: In relation to immune system, monocytes play a significant role in defending against diverse pathogens. It undergoes spontaneous apoptosis contributing to accumulation of macrophages and increase in inflammatory response. Hence, monocytes and macrophages function to initiate inflammation through phagocytosis, release of inflammatory cytokines and and activation of the immune system (Parihar, Eubank and Doseff 2010).

Eosinophils: Eosinophils plays a major role in modulating inflammatory response and killing bactericidal activity in cells. In relation to damaging parasitic pathogen in helminth infection, eosinophils perform cytotoxic effector function. The immune response of eosinophils is seen due to its capacity to store and release cytokines, chemokines and growth factors during immune response. The accumulaton of eosinophil is responsible for causing symptoms of allergic asthma and allergic diseases (Shamri, Xenakis and Spencer 2011).

Neutrophils: Neutrophils mainly have bactericidal properties. With neutrophils acting as a the most abundant leucocytes in the blood, it acts the bodies first line of defense against foreign invaders like bacteria. Neutrophils are also known as granulocyte as the cytoplasm of the cell contains many granules, which performs major function of the cell. These granules are composed of antimicrobial effectors and they engulf microbes to kill them (Rosales et al. 2016).

Flow diagram for blood clotting process:

Injured tissue    +     blood platelets

Figure 2: Flow diagram for blood clotting process.

The above diagrams shows that clotting mechanism initiates when tissues are injured and platelets in the blood are disintegrated and release thromboplastin. The prothrombin acts to convert inactivated prothrombin into activated thrombin. The thrombin in turn plays a role in converting fibrinogen into fibrin, an insoluble form of damages cells. The fibrin fibres forms mesh like network as red blood cells and platelets pass through it. This ultimately results in forming blood clot and preventing bleeding after injuries (Whelihan et al. 2012).

1. Prothrombin is produced in the liver and converst into thrombin to initiate blood clotting
2. Within the clotting process, the most important element is thrombin and calcium.. Calcium is required in almost all the steps and  thrombin is the clotting factor that initiates other reactions like formation of fibrin from fibrinogen and finally forming blood clot.
3. Blood clotting does not occurs normally because heparin, an anticoagulant is present inside the blood vessels that prevents blood clotting.  When cell wall is damaged, heparin is released and coagulation cascade is initiated.  The collagen layer in the damaged endothelium initiates coagulation cascade and several coagulation factors are needed for the initiation of reaction. Coagulation factors circulate in the blood and initiate the coagulation cascade when blood vessel is injured (Ternström et al. 2010).
4. The last stage of coagulating cascade involves the formation of fibrinogen into fibrin. Fibrinogen is a soluble plasma protein. The soluble protein is cleaved into non-soluble plasma protein. This process of fibrinolysis is influenced by clot structure and morphological formations of fibrinolysis. Fibrinogen is a 340-kDa protein and it consists of sets of disulfide linked polypeptide chains and fibrin monomer. When thrombin reacts with fibrinogen, it removed N-terminal fibrinopeptides A and B and converts fibrinogen into monomers of fibrin (Chapin and Hajjar 2015).

1. Patients who have type O Rh D negative blood type are universal donors. This is because individuals with type O bloods neither have A nor B surface antigens on the RBC. These antigens are required for evoking allergic response in bodies, who does not have antigens. Hence, type O blood can be easily donated to other type of patients (Fagherazzi et al. 2015)
2. Patient 2 had B negative blood type. However, it was found that blood was given to the wrong person by staff-nurse and the patient started having symptoms like fever, chills and headache on receiving blood. The blood group which could have initiated adverse reaction in patient 2 is the A and AB blood type. This is because a person with B negative blood has antigen B and no Rh antigen. However, Blood A type contains A antigen which can trigger immune reaction in patients. In addition, O blood type neither contains A nor B antigen. Hence, patient with B blood type has anti-A antibodies and it will reacts with A antigens thus leading to adverse reaction in patients. In addition, AB blood type contains both A and B antigens on the surface of blood. Hence, anti-A antibodies present in patient2 can react with A antigen to initiate adverse reaction.
3. Patient 4 is a patient with O negative blood type and anti-D injection was given to patient because patients with O negative blood group contains negative rhesus factor in blood. However, if their baby has positive blood type, then incompatibility issues may arise due to mixture of negative and positive blood types. Antibodies in the Rh-negative woman may attack the Rh-positive baby blood cells. Hence, anti-D injection is given to patient 4 to prevent the patient from developing antibodies in her blood stream. This would help to stop reaction of the antibody with baby’s antigen and prevent miscarriages. The anti-D injection neutralized any blood cells from Rh-positive babies before making antigens (Crowther, Middleton and McBain 2013). For this reason, pregnant women with O negative blood types are carefully examines as there Rh negative factors can stimulate adverse reactions in babies having positive blood types. Anti-D injection is a major preventive option to prevent miscarriage and sustain pregnancy.
4. Simulated blood typing is similar to actual human blood typing because in both case, antigen-antibody reaction is analyzed for each blood type.

References:

Chapin, J.C. and Hajjar, K.A., 2015. Fibrinolysis and the control of blood coagulation. Blood reviews, 29(1), pp.17-24.

Crowther, C.A., Middleton, P. and McBain, R.D., 2013. Anti-D administration in pregnancy for preventing rhesus alloimmunisation. Cochrane Database Syst Rev, 2.

Fagherazzi, G., Gusto, G., Clavel-Chapelon, F., Balkau, B. and Bonnet, F., 2015. ABO and Rhesus blood groups and risk of type 2 diabetes: evidence from the large E3N cohort study. Diabetologia, 58(3), pp.519-522.

Franco, R.S., 2012. Measurement of red cell lifespan and aging. Transfusion medicine and hemotherapy, 39(5), pp.302-307.

Muniz, V.S., Weller, P.F. and Neves, J.S., 2012. Eosinophil crystalloid granules: structure, function, and beyond. Journal of leukocyte biology, 92(2), pp.281-288.

Parihar, A., Eubank, T.D. and Doseff, A.I., 2010. Monocytes and macrophages regulate immunity through dynamic networks of survival and cell death. Journal of innate immunity, 2(3), pp.204-215.

Reid, M.E., Lomas-Francis, C. and Olsson, M.L., 2012. The blood group antigen factsbook. Academic Press.

Rosales, C., Demaurex, N., Lowell, C.A. and Uribe-Querol, E., 2016. Neutrophils: their role in innate and adaptive immunity. Journal of immunology research, 2016.

Shamri, R., Xenakis, J.J. and Spencer, L.A., 2011. Eosinophils in innate immunity: an evolving story. Cell and tissue research, 343(1), pp.57-83.

Ternström, L., Radulovic, V., Karlsson, M., Baghaei, F., Hyllner, M., Bylock, A., Hansson, K.M. and Jeppsson, A., 2010. Plasma activity of individual coagulation factors, hemodilution and blood loss after cardiac surgery: a prospective observational study. Thrombosis research, 126(2), pp.e128-e133.

Unger, E.F., Thompson, A.M., Blank, M.J. and Temple, R., 2010. Erythropoiesis-stimulating agents—time for a reevaluation. New England Journal of Medicine, 362(3), pp.189-192.

Volkers, L., Mechioukhi, Y. and Coste, B., 2015. Piezo channels: from structure to function. Pflügers Archiv-European Journal of Physiology, 467(1), pp.95-99.

Whelihan, M.F., Zachary, V., Orfeo, T. and Mann, K.G., 2012. Prothrombin activation in blood coagulation: the erythrocyte contribution to thrombin generation. Blood, 120(18), pp.3837-3845.