Red Blood Cells

Red blood cells (erythrocytes) provide the system for oxygen delivery from the lungs to the tissues and evolution has produced one of the most specialized cells for this purpose. The erythrocyte lacks organelles and a nucleus and instead is no more than a membrane enclosing a solution of protein and electrolytes. Over 95% of the protein is the oxygen transport protein haemoglobin, the remainder being enzymes required to maintain haemoglobin in a functional, reduced state and enzymes for glycolysis. The bi-concave shape of erythrocytes increases the surface area-to-volume ratio, making gas exchange more efficient and also makes the cell more deformable (compared with a sphere), therefore, more able to navigate the microvasculature. Under normal circumstances the average survival of erythrocytes is 120 days.

Haemopoiesis starts in the yolk sac in the 2-week-old embryo. At 6 weeks the liver, and to a lesser extent the spleen, start to produce haemopoietic cells and by 12-16 weeks the liver is the main haemopoietic tissue. The bone marrow starts to produce blood cells at 20 weeks. At birth haemopoietic (red) marrow occupies all bones. Fat gradually replaces the red marrow until in adults red marrow is confined to the axial skeleton only.

Manufacture of erythrocytes (erythropoiesis) occurs predominantly in the bone marrow from the seventh month of gestation. A homeostatic mechanism ensures that, under physiological conditions, the rate of production equals the rate of destruction but at the same time there is a capability to respond to demands such as hypoxia, haemorrhage or haemolysis by increasing production. Erythropoietin (EPO) is a glycoprotein produced mainly in the kidney but also in the liver, and is one of the most important erythropoietic stimuli. Specialized cells in the renal and hepatic parenchyma have been shown by in situ hybridization studies to manufacture EPO. In the kidney, the cells are located outside the tubular basement membrane mainly in the inner cortex and outer medulla. Serum levels increase in response to hypoxia, anaemia and increased metabolism (due to effects of corticosteriods, androgens, thyroxine and growth hormone). The bone marrow is among the most highly proliferative tissues in the body and, therefore, requires an uninterrupted supply of nutrients, those particularly needed for erythropoiesis include iron (for haem), vitamin Bn folate and pyridoxine (for DNA synthesis), riboflavin, vitamin E and copper.

Haemoglobin

Eighteen times more energy is available if glucose is metabolized aerobically than anaerobically. Hence, the transition to aerobic life was a major step in evolutionary terms. The acquisition of oxygen carrying molecules became necessary to overcome the relative insolubility of oxygen in water. The oxygen carriers in vertebrates are haemoglobin and myoglobin. Haemoglobin increases the oxygen carrying capacity of 1 litre blood > 50fold, it also is involved in the transport of CO2 and hydrogen ion (H+). Myoglobin is present in skeletal muscle and serves as an oxygen store, releasing oxygen when needed.

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