Red Blood Cells and Their Journey - Essay Example

RED BLOOD CELLS AND THEIR JOURNEY Introduction and functions of Red Blood cells Red blood cell (RBC) or erythrocyte is the simplest cell among allhuman cells. Mature RBC lacks the specialised cellular organelles including the nucleus, mitochondria and endoplasmic reticulum (Goodman, Kurdia, Ammann, Kakhniashvili, & Daescu, 2007). The cell membrane is the key in determining the properties of the erythrocyte. The cell membrane also consists of certain cytoplasmic enzyme that helps in maintaining the flexibility of the cell membrane, transport of ions and also prevents the oxidation of proteins in the red blood cells. A spectrin network which is attached to the lipid bilayer is composed of several organic proteins, phospholipids, sphingolipids and cholesterol. It is vital to note that this type of attachment increases the stiffness of the RBC. Moreover, this sort of spectrin protein allows the free diffusion of vital component from extracellular fluid to intracellular fluid. (Li & Lykotrafittis, 2012). The journey of red blood cells (erythrocytes) usually begins in the circulatory system. During their passage through the blood vessels the erythrocytes undergo several important changes in shape and structure particularly when needed to pass through the narrow passages in the circulatory system. An erythrocyte is a biconcave disc of a diameter ranging between 6-8 microns, with mean thickness of 2.5 micrometres at the periphery and approximately 1 micrometre towards the centre of the cell (Guyton & Hall, 2006). It is clear that transporting of oxygen from lung to various other organs is the function of the RBCs during their journey in the human circulatory system. Importantly, this oxygen available for the functioning of organs is stored into the haemoglobin of RBC and when it reaches its particular destination, oxygen is liberated from haemoglobin and it moves through the cellular passive diffusion. Furthermore, carbon dioxide (CO2) that is released after cellular activities is then again fused with haemoglobin of RBC. This deoxygenated blood due to presence of CO2 into the haemoglobin then enters into the heart, and is finally diffused to the lungs. It was reported that in some lower animals (some invertebrates), Hb is present as a free protein in plasma and it is not bound to the RBCs like in human beings. The total life span of each erythrocyte in the circulation is 120 days (Dean, 2005). But during this period if any of them gets damaged, then they could be eliminated from the circulatory system with the help of macrophages which is usually present in the bone marrow, spleen or in the liver (Premkumar, 2004). It is reported, a normal man has an average of 5,200,000 red blood cells (RBC) per cubic millimetre and a normal woman has an average of 4,700,000 RBCs per cubic millimetre (Guyton & Hall, 2006). It is also demonstrated that around 3 million red blood cells (RBC) enter the circulation each second (Starr & McMillan, 2012). Haemoglobin is usually concentrated in the red blood cells (RBC); the metabolic limit of haemoglobin-forming mechanism of the body allows only a maximum concentration of 34grams of Haemoglobin in each 100 millilitres of cells (Guyton & Hall, 2006). In any normal and healthy individual, the haemoglobin (Hb) concentration remains at this maximum permitted level. 2. Bone marrow, Journey and Production of erythrocytes: Production of the erythrocytes from the bone marrow is called erythropoiesis (Schlossberg & Zuiderna, 1997). Apart from bone marrow, red blood cells are also produced by various other organs during the early development of human body. Yolk Sac is the primary site of the production of RBCs during the early embryonic period (Guyton & Hall, 2006, p. 421). Liver serves as the main organ for RBC production during the middle trimester of gestation while lymph nodes and spleen also produce an amount of RBCs during this stage of development (Guyton & Hall, 2006, p. 421). Bone marrow is an important part of human body for the production of red blood cells (RBC) during the last month of gestation and soon after the birth (Guyton & Hall, 2006). Particularly, in bone marrow the stem cells take part in their development. These stem cells are undifferentiated and pluripotent in nature which enables them to differentiate into different types of blood cells (Guyton & Hall, 2006, p. 421). The pluripotent bone marrow stem cells differentiate to form erythrocytes. The rate and the amount of production of erythrocytes decrease with increase in age (Guyton & Hall, 2006, p. 421). Until the age of 5, marrow of all bones have the ability to produce erythrocytes whereas the marrow of long bones excluding proximal portions of the humerus and tibia produce erythrocytes till the age of 20years(Guyton & Hall, 2006, p. 421) Thereafter, the red blood cells (RBC) are produced in the marrow of membranous bone. Importantly, this growth and production of erythrocytes are regulated by certain proteins recognised as growth inducers. Interleukin- 3 is one of such inducer which mainly involves in production of red blood cells (RBC). The maturation of the RBCs begins in the bone marrow with the differentiation of primitive pro-erythroblast into basophil erythroblast. Upon maturation, the haemoglobin concentration increases to the 34 per cent (Guyton & Hall, 2006, p. 421). This results in the condensation of the nucleus and then it is eliminated. Now, the cell is in the reticulocyte form and consists of persistent cellular organelles including Golgi apparatus, mitochondria, cytoplasmic organelles. The reticulocytes formed during this stage enter into the circulatory system from the bone marrow by passing through the pores present in the capillary membrane. This movement of the reticulocyte is called as diapedesis. Once the other remnants of the red blood cell are eliminated in a span of 1 or 2days, the reticulocyte transforms into a mature erythrocyte. Fig. 1.2 (Guyton and Hall 2006, p 421) This process of production and the maturation of the red blood cell is called erythropoiesis. Furthermore, when there is insufficient amount of oxygen (hypoxia condition) the production of red blood cells abruptly increases and this process of development of erythrocytes is stimulated by specialised hormone called erythropoietin (Guyton & Hall, 2006). Erythropoietin produced in the kidney helps in the regulation of production of red blood cells with the help of other neurotransmitters like epinephrine, norepinephrine and prostaglandins. As it is reported, erythropoietin hormone is primarily produced into the liver before birth, and then into the kidney after the birth. In a normal person 90 percent of the erythropoietin is produced in the kidney while the remaning amount is predominantly produced in the liver. In conditions like severe hypoxia, there is an extreme increase in the production of erythropoietin upto 1000 fold. This hormone binds to the ‘receptors’ present in the circulation in order to stimulate the stem cells to produce more red blood cells (Ebert & Bunn, 1999). 3 Red Blood cell disorders: There are many diseases or disorders which occur due to abnormal or unregulated production of red blood cells. Patients with kidney failure may face reduced production of red blood cells (RBC) and suffer from anaemic conditions. A bone marrow failure also results in depleted production of red blood cells (RBC) and reduced oxygen supply to vital organs (Hazinski, 2013). 3.1 Polycythemia It is usually associated with increase in erythrocytes-count which increases haemoglobin and haematocrit level. Polycythemia vera presents with a value of 7-8millions red blood cells per cubic millmeter(Guyton & Hall, 2006, p. 428). The unusual development of hematopoietic stem cells is demonstrated to be the main factor resposible for the increase in number of red blood cells (RBC)(Fernandes-Luna, 1998). Polycythemia Vera (PV) is a condition of unknown aetiology usually occurring after the age of 50years (Greenberg, 2003).  Secondary Polycythemia is commonly seen in people living in high-altitudes and in people with diseases like renal diseases, congestive heart diseases, chronic pulmonary diseases and also other endocrine disorders (Greenberg, 2003, p. 430). 3.2 Anaemia A decrease in the amount of haemoglobin in red blood cells results in anaemia.(Ross, 2000). This disorder might be due to excessive loss of blood, reduced production of the red blood cells or due to increased breakdown of the red blood cells (Greenberg, 2003). This disorder is also related to iron deficiency anaemia, haemolytic anaemia, pernicious and folic acid deficiency. The shape of the RBCs (normocytic, microcytic and macrocytic) and the concentration of haemoglobin (hypochromic and normochromic) present in the RBCs are also used to classify anaemia (Greenberg, 2003, p. 430). Iron deficiency anaemia is the most common type of anaemia caused due to the excessive loss of blood which may be due to prolonged bleeding resulting in chronic blood loss in conditions like menstrual bleeding, parturition and bleeding malignant lesions of GIT (Greenberg, 2003). Inadequate intake and absorption of iron by the human body is also an important causative for iron deficiency anaemia. Haemolytic anaemia is caused due to decreased survival rate of the erythrocytes. Lab findings show decreased haemoglobin count and increased reticulocyte count as a result of bone marrow’s compensatory mechanism to produce erythrocytes (Greenberg, 2003, p. 432).Hereditary spherocytosis is a type of haemolytic anaemia that shows spherical and smaller red blood cell making them very fragile, a slight compression during their passage in vascular beds results in rupturing.(Greenberg, 2003, p. 427) Sickle Cell Anaemia is an autosomal recessive disorder characterised by patients with marked under-development and the survival age is often not more than 40 years (Greenberg, 2003, p. 432). Hypo-vascularity of the bone marrow because of increased haemolysis makes the bone prone to osteomyelitis. Here, an abnormality in the beta chain of the haemoglobin is present; valine is substituted with glutamic acid in position 6. This abnormal type of haemoglobin is called Haemoglobin-S. Sickling of cells is the main diagnostic factor in Sickle cell anaemia. The erythrocyte attains a sickle shape due to lowered oxygen in blood.  (Guyton and Hall. 2006) p 421 Thalassemia: A deficient synthesis in the alpha or beta chain of globin in the haemoglobin molecule results in this congenital disorder. They show different sizes and shapes. There are several side effects of this kind of disorder. For instance, retardation of growth, sexual maturation failure, jaundice, pallor, hepato-splenomegaly, changes in the bone marrow, etc. Beta Thalassemia is classified as Major, Minor and Intermediate. This condition is seen associated with other features like the molecular lesion seen encoded with the transcription factor TFIIH or in X –linked transcription factor GATA-1.Survival of the patients with this condition depends on the blood transfusions which help in replacement and deposition of iron necessary for the body tissues. It thereby helps in the correction of anaemia and suppression of erythropoiesis. A definitive treatment for patients with Thalassemia is Bone Marrow Transplantation (Galanello & Origa, 2010). Anaemia is also caused due to decreased production of red blood cells as in the case of megaloblastic anaemia, pernicious anaemia, folic acid deficiency anaemia and aplastic anaemia (Greenberg, 2003, p. 436). Megaloblastic anaemia is characterized by a morphologic pattern of the cells which show small immature nuclei and large mature cytoplasm and hence described as “Megaloblastic” (Greenberg, 2003, p. 432). Pernicious anaemia is due to the deficiency of Vitamin B12 and their impaired metabolism. The main cause for the failure of RBC maturation in this condition is due to the inability to absorb Vit B12 from the gastrointestinal tract (Guyton & Hall, 2006). Histological diagnosis is presented with macrocytic and normochromic red blood cells. Therapeutic Vitamins are used to treat the deficiency once the cause is identified. Folic acid is an essential constituent of some vegetables and fruits and hence folic acid deficiency is seen in patients who have fewer intakes of leafy vegetables in their daily diet. It is also presented as an adverse effect in certain anti-cancer drugs like methotrexate, azathioprine, 6-mercaptopurine etc (Greenberg, 2003, p. 437). Aplastic anaemia is caused as a result of bone marrow failure and also due to certain chemical substances and increased exposure to x-ray radiation (Greenberg, 2003, p. 437). A complete destruction of bone marrow is followed by severe anaemia after high exposure to gamma radiations.(Guyton & Hall, 2006) References Dean, L. (2005). Blood Groups and Red Cell Antigens. NCBI. Ebert, B. L., & Bunn, H. F. (1999). Feedback Loop Mechanism: For Regulation of Erythropoiesis. Blood Journal, 94, 1864-1877. Fernandes-Luna, e. a. (1998). Pathogenesis of polycythemiavera. Haematologiea, 83, 150-158. Galanello, R., & Origa, R. (2010). Beta-thalassemia. Journal of Rare Diseases, 5(11). Goodman, R. S., Kurdia, A., Ammann, L., Kakhniashvili, D., & Daescu, O. (2007). Experimental Biology and Medicine. RSM Journals, 232, 1391-1408. Greenberg, M. S. (2003). Burketts Oral medicine and radiology (10 ed.). BC Decker. Greenberg, M. S. (2003). Burketts Oral medicine and radiology (10 ed.). BC Decker. Guyton, A. C., & Hall, J. E. (2006). Guytons Physiology. Elsevier Saunders. Hazinski, M. F. (2013). Nursing Care of the Critically Ill Child (3 ed.). Li, H., & Lykotrafittis, G. (2012). Two Component Coarse-Grained Molecular-Dynamics Model for the Human Erythrocyte Membrane. Biophysical Journal, 102, 75-84. Premkumar, K. (2004). The Massage connection - Anatomy and Physiology. Lippincott. Ross, A. J. (2000). Anemia (1st ed.). Rosen Publishing Group. Schlossberg, L., & Zuiderna, G. D. (1997). The Johns Hopkins Atlas of Human Functional Anatomy (4 ed.). Johns Hopkins University press. Starr, C., & McMillan, B. (2012). Human Biology (9 ed.). 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