Red blood cells, also called erythrocytes, are specialised blood cells whose principal function is to transport oxygen from the lungs to tissues and to transport carbon dioxide from tissues towards the lungs. They are the most numerous cellular components of human blood and contain the oxygen binding protein haemoglobin. Mature human red blood cells have a distinctive biconcave disc shape, lack a nucleus and lack most organelles, including mitochondria.
These adaptations maximise the amount of haemoglobin that can be contained within each cell, increase surface area relative to volume and allow the cells to deform as they pass through extremely narrow capillaries. Red blood cells are produced through erythropoiesis in the red bone marrow and are eventually removed from circulation when they become old or damaged. Their specialised structure is closely linked to their role in gas transport.
Haemoglobin is the major functional protein inside red blood cells. It consists of four globin subunits, each associated with a haem group containing iron capable of binding oxygen reversibly. Adult haemoglobin is usually composed of two alpha and two beta globin chains. Each haem group can bind one oxygen molecule, allowing a haemoglobin molecule to carry up to four oxygen molecules when fully saturated.
Oxygen binding is cooperative, meaning that binding of one oxygen molecule changes haemoglobin's affinity for subsequent oxygen molecules. This produces the characteristic sigmoidal oxygen haemoglobin dissociation curve. Haemoglobin binds oxygen strongly in the lungs, where oxygen partial pressure is relatively high, and releases it in tissues where oxygen partial pressure is lower and conditions favour unloading.
The biconcave shape of red blood cells is important for efficient gas exchange and mechanical flexibility. The shape produces a relatively large surface area compared with cell volume and keeps most of the cell close to its membrane, facilitating diffusion of gases. Red blood cells must deform repeatedly as they pass through capillaries that can be narrower than the resting diameter of the cell. Their membrane and cytoskeleton provide sufficient flexibility to permit this deformation while maintaining structural integrity.
As red blood cells age, membrane properties gradually change and damaged or less flexible cells are more likely to be removed by macrophages, particularly in the spleen. The specialised shape is therefore not merely an anatomical characteristic but an adaptation that supports both gas transport and circulation through narrow vessels.
Red blood cells transport carbon dioxide as well as oxygen, although most carbon dioxide is not carried simply by binding directly to haemoglobin. A substantial proportion of carbon dioxide enters red blood cells and is converted by the enzyme carbonic anhydrase into carbonic acid, which dissociates into bicarbonate and hydrogen ions. Bicarbonate then contributes to transport of carbon dioxide in the plasma. Haemoglobin can also bind some carbon dioxide to globin groups, forming carbaminohaemoglobin.
The ability of red blood cells to participate in carbon dioxide transport is closely connected with acid base regulation. Haemoglobin also acts as an important buffer because it can bind hydrogen ions generated during carbon dioxide transport. These functions make red blood cells important participants in both respiratory gas transport and blood pH regulation.
Oxygen release by haemoglobin is influenced by several physiological conditions. Increased carbon dioxide concentration, increased acidity and increased temperature generally reduce haemoglobin's affinity for oxygen, promoting oxygen unloading in metabolically active tissues. This relationship is associated with the Bohr effect. The concentration of 2,3 bisphosphoglycerate inside red blood cells also influences haemoglobin oxygen affinity. These mechanisms allow oxygen delivery to adjust to tissue demand. In active tissues, metabolism increases carbon dioxide production and heat generation while reducing local oxygen availability, creating conditions that favour oxygen release. The blood can therefore transport oxygen efficiently without releasing all of it uniformly in every tissue.
Red blood cells are produced through erythropoiesis, a process in which haematopoietic stem cells differentiate through progressively specialised precursor stages. Erythropoietin, a hormone produced mainly by the kidneys in response to reduced oxygen availability, stimulates red blood cell production in the bone marrow. During maturation, erythroid cells synthesise haemoglobin and progressively reduce their cellular organelles before entering circulation as mature erythrocytes. Iron, vitamin B12, folate, amino acids and other nutrients are required for normal erythropoiesis. After approximately four months in circulation, old red blood cells are removed mainly by macrophages in the spleen, liver and bone marrow. Iron from haemoglobin is largely recycled, while the haem component is broken down through pathways that ultimately contribute to bilirubin production.
The concentration and characteristics of red blood cells have major physiological consequences. Anaemia refers broadly to a reduction in the blood's oxygen carrying capacity, often caused by reduced red cell number, reduced haemoglobin concentration or abnormal red cell properties. Causes include iron deficiency, vitamin deficiencies, blood loss, chronic disease, inherited disorders and impaired bone marrow function. Polycythaemia refers to an abnormally increased red cell concentration and can increase blood viscosity.
Inherited disorders such as sickle cell disease involve alterations in haemoglobin that can change red blood cell shape and behaviour under particular conditions. Thalassaemias involve impaired production of globin chains and can produce varying degrees of anaemia. These disorders demonstrate how strongly red blood cell structure and haemoglobin function influence health.
Red blood cells are adapted to a narrow physiological purpose and consequently sacrifice several features found in other cells. Their lack of a nucleus prevents them from producing new proteins through conventional gene expression once mature, and their lack of mitochondria means they do not consume the oxygen they carry through aerobic respiration. Instead, mature red blood cells generate ATP primarily through anaerobic glycolysis. This preserves their transported oxygen for delivery to tissues.
Their simple internal organisation provides more space for haemoglobin and reduces metabolic competition with the tissues they supply. Red blood cells therefore represent a striking example of cellular specialisation in which structural modifications, metabolism, membrane mechanics and protein composition are all adapted to maximise gas transport within the circulatory system.
