Red blood cell

Concept of Red blood cell

Red blood cells, also called erythrocytes, are the most abundant elements in the blood. They are highly specialized cells whose function is to transport oxygen (O₂) from the lungs (or gills) to the cells and carbon dioxide (CO₂) in the opposite direction.

Morphology

Red blood cells may arise with different forms in different animals. In humans, they appear as anucleated cells without organelles, bi-concave disk-shaped and measure approximately 7.2 µm.

They have only a plasma membrane and an underlying cytoskeleton, glycolytic enzymes and haemoglobin, a red pigment that has as the function of transporting oxygen and that gives them a red colouring.

Erythrocyte membrane

The membrane of the red blood cells has the same composition of other cell membranes: 40% of phospholipids in a bilayer, 10% of carbohydrates and 50% of proteins. These consist mainly in:

Transmembrane proteins: Glycophorins, band 3 protein and aquaporins;

Peripheral proteins: The spectrin forms a hexagonal skeleton beneath the plasma membrane. Spectrin molecules are connected between them by junctional complexes composed by band 4.1 protein, actin, tropomyosin, adducin and glycophorin. The spectrin network connects, in turn, to band 3 protein with the help of ankyrin.

Properties and functions of the erythrocyte membrane

• The protein support network provides flexibility, stability and resistance to deformation forces that red blood cell requires during the passage through the microcirculation.
• The membrane holds organophosphates and other vital components and helps the elimination of metabolic waste.
• It maintains a surface that prevents the adherence of red cells to the endothelium and prevents their aggregation and the obstruction of the microcirculation.
• During erythropoiesis, the membrane responds to erythropoietin and captures the iron needed to get the synthesis of haemoglobin.
• The extracellular surface of the red blood cells membrane has proteins, glycoproteins or glycolipids that act as antigens. These are inherited and able to be recognized by the immune system. A given set of antigens form a system. In humans, it was identified more than 20 erythrocyte antigens systems, mainly ABO and Rh systems.

Function

• Transport of oxygen (O₂) from the lungs to the tissues. Oxygen binds to the haemoglobin (Hb) present in red blood cells to form oxyhaemoglobin (Hb (O₂)) and each molecule of haemoglobin can carry up to four oxygen molecules:

HB + 4 O₂  ↔ Hb (O₂) ₄

Carbon monoxide can also bind to haemoglobin preventing the binding of oxygen. Here lies the toxicity of carbon monoxide – prevented this connection, the oxygen don’t reach the cells in the amount needed and these fail to perform their functions.

• Regulation of blood pH and transport of carbon dioxide (CO₂) from the tissues to the lungs due to the presence of carbonic anhydrase (CA), an enzyme which catalyzes the rapid interconversion of the carbon dioxide and water into carbonic acid (H₂CO₃). Carbonic acid, on the other hand, dissociates forming bicarbonate (HCO₃^–), which acts as a buffer holding the blood pH within normal values, and protons in a reversible reaction:

Co₂ + H₂O ↔ H₂CO₃ ↔ HCO^3-+ H⁺

Life and death of red blood cells

– Erythropoiesis

Erythropoiesis, which designates the set of phenomena that leads to the formation of red blood cells, takes place in the bone marrow. This process begins with the differentiation of blasts colony-forming units – BFU-E (Erythroid burst-forming unit) in Erythroid colony-forming unit – CFU-E that, in turn, differentiate into:

• Proerythroblast – Rounded cell with a voluminous nucleus and 1 or 2 nucleoli, ribosome-rich and with the common organelles such as Golgi apparatus and mitochondria. After 20 hours of life, each proerythroblast originates, by mitosis, 2 basophilic erythroblasts ;
• Basophilic erythroblast – circular cell smaller than the proerythroblast and with a relatively large nucleus, basophilic cytoplasm (blue) and 1 nucleolus (not always visible). After an average lifespan of 40 hour, each basophilic erythroblast originates, by mitosis, 2 polychromatic erythroblasts ;
• Polychromatic erythroblast – Cell smaller than the previous one, with a central nucleus, dense chromatin, without nucleolus and a gray cytoplasm due to the appearance of haemoglobin. It presents an average lifespan of 24 hours, after which it differentiate into orthochromatic erythroblast;
• Orthochromatic erythroblast – This cell is characterized by the displacement of the nucleus to the periphery. It has a very dense chromatin and an abundant and acidophilic cytoplasm. After an average time of 24 hours and the loss of the nucleus, the orthochromatic erythroblast is called reticulocyte;
• Reticulocyte – Cell slightly larger than the red blood cell. It has a blue-gray coloration due to the presence of residual nuclear material and organelle residues with a bluish colour associated with the reddish colour of haemoglobin. Reticulocytes come out of the bone marrow by diapedesis, through pseudopodic movements, and pass to the circulation where they continue the maturation. They represent 1 to 2% of circulating red blood cells and they live 24 to 48 hours following which they lost the organelles residues and turn into red blood cells.

– Regulation of erythropoiesis

Erythropoiesis is regulated by the erythropoietin hormone secreted mainly by specialized cells of the kidney. This hormone stimulates maturation and proliferation of red blood cells. Erythropoietin synthesis is stimulated by hypoxia (decrease in availability of oxygen in the tissues) which may have several causes: reduction in the number of red blood cells or haemoglobin content, decreased blood flow or decrease in the input of oxygen from the lungs to the blood.

The necessary elements for erythropoiesis are:

• Iron: Crucial element in the formation of haemoglobin. It is where the oxygen is fixed. About 70% of the iron of the body is found in haemoglobin, the remainder is stored in the liver, spleen and bone marrow;
• Folic acid (vitamin B9): Essential vitamin for DNA synthesis and as such is necessary for the maturation of cells during the erythropoiesis;
• Vitamin B12: As the folic acid, it is necessary for the maturation of red blood cells. This vitamin is stored in large quantities in the liver.

Haemolysis

After an average lifespan of 120 days, aged red blood cells are destroyed by haemolysis via the action of macrophages present in the bone marrow, spleen and liver. The haemoglobin is decomposed into hemosiderin, bilirubin and globin. The hemosiderin pigment, which contains iron, is reused by the bone marrow for formation of new red blood cells; bilirubin is eliminated by the liver in bile and globin is metabolized by the liver.

Reference values

Hematocrit = Proportion of the volume of the blood sample occupied by red blood cells in %; M.C.V = Mean corpuscular volume expressed in femtolitres (fl or x10^-15); M.C.H = Mean corpuscular haemoglobin expressed in picograms (pg or x10^-12); M.C.H.C = Mean corpuscular haemoglobin concentration expressed in g/dL.

Erythrocyte anomalies

Erythrocyte anomalies can result in anaemia (reduced ability of the blood to transport oxygen which usually results in a reduction of the mass of circulating red blood cells below normal levels) or, less commonly, Polycythemia (increased number of red blood cells).

Anomalies associated to the accelerated destruction of red blood cells (haemolytic anaemia):

• Hereditary spherocytosis
• Sickle cell anaemia (Drepanocytosis)
• Thalassemias
• Immuno-hemolytic anaemia

Anaemia by diminished erythropoiesis:

• Iron deficiency anaemia
• Chronic disease anaemia
• Megaloblastic anaemia
• Aplastic anaemia
• Mielotisic anaemia

References:

• Gartner, L.P. and Hiatt, J.L . (2012). Histologia Essencial. Rio de Janeiro: Elsevier Brazil. p132-151.
• kierszenbaum, A.L. and Tres L.L. (2012). Histologia e Biologia Celular – Uma introdução à patologia. 3rd ed. Rio de Janeiro: Elsevier Brazil. p169-171.
• Nguyen, S. and Bourouina, R. (2008). Manuel d’anatomie et de physiologie. 4th ed. Paris: Editions Lamarre. p179-182.
• Widmaier, E.P. et al. (2003). Human Physiology – The mechanisms of body function. 9th ed. Boston: McGraw-Hill. p376; 450-454.