Red Blood Cell

Red blood cells, commonly known as erythrocytes, are the most abundant cellular component of vertebrate blood and serve as the primary vehicle for transporting oxygen from respiratory organs to tissues throughout the body. Their distinctive structure, biochemical composition, and physiological behaviour render them uniquely suited to this essential function. In humans, these cells form a major proportion of total blood volume and play a vital role in sustaining aerobic metabolism and overall homeostasis.

Structure and Composition

Human erythrocytes possess a flexible biconcave disc shape that increases their surface-area-to-volume ratio, allowing efficient gas exchange. This morphology also enables them to deform readily as they pass through extremely narrow capillaries. The mature human red blood cell is notable for its absence of a nucleus and organelles, features lost during the final stages of erythropoiesis to create additional internal space for haemoglobin.
Haemoglobin, an iron-containing metalloprotein, constitutes roughly one-third of the erythrocyte’s total volume. Each red blood cell contains around 270 million haemoglobin molecules. The iron atoms within the haemoglobin’s heme groups bind reversibly with oxygen, conferring the characteristic red colour to both erythrocytes and blood. Oxygenated haemoglobin (oxyhaemoglobin) appears bright scarlet, whereas deoxygenated haemoglobin (deoxyhaemoglobin) appears a darker burgundy. Haemoglobin also binds limited amounts of carbon dioxide, although most carbon dioxide is transported as bicarbonate dissolved in plasma.
The erythrocyte membrane is a dynamic lipid–protein bilayer that confers both durability and deformability. Specific cytoskeletal proteins maintain membrane stability and shape while enabling the cell to bend without rupture. These properties are critical given the mechanical stresses erythrocytes encounter during continuous circulation.

Development and Lifespan

Erythrocytes originate in the bone marrow through a highly regulated process known as erythropoiesis. Immature precursors gradually synthesise haemoglobin before expelling their nucleus to form reticulocytes. These then mature into erythrocytes after losing residual organelles. Approximately 2.4 million new red blood cells are generated every second in a healthy adult.
Once released into the bloodstream, erythrocytes circulate for about 100–120 days. During their lifespan they complete one full circuit of the circulatory system roughly every minute. As cells age, they lose membrane flexibility and are ultimately removed from circulation by macrophages, particularly in the spleen and liver. Their components—including iron—are recycled for new red blood cell production.
Erythrocytes make up nearly half of total blood volume, a measurement known as the haematocrit. They also account for approximately 84 per cent of all human cells by number, reflecting their crucial biological role.

Erythrocytes in Vertebrates

Most vertebrates possess red blood cells containing haemoglobin, although there is considerable diversity in erythrocyte characteristics across species. A significant distinction between mammals and other vertebrates is the presence of a nucleus. Non-mammalian vertebrates—including birds, reptiles, amphibians, and most fish—retain nucleated red blood cells.
A notable exception exists in the crocodile icefish (family Channichthyidae), which completely lack red blood cells and haemoglobin. Living in extremely cold, oxygen-rich Antarctic waters, these fish transport oxygen dissolved directly in their plasma. Interestingly, remnants of haemoglobin genes persist in their genome, providing evidence of evolutionary loss.
Vertebrate erythrocytes vary significantly in size and shape. Many species display red blood cell diameters approximately 25 per cent larger than the capillaries they traverse, which may enhance oxygen delivery. Haemoglobin-related proteins such as myoglobin supplement oxygen storage and transport, particularly in muscle tissue.

Mammalian Erythrocyte Diversity

Mammalian red blood cells are typically biconcave discs, but several species present unusual shapes. Members of the Artiodactyla (even-toed ungulates) show remarkable variation:

• Llamas and camels possess small, highly ovoid erythrocytes.
• Mouse deer have tiny spherical cells.
• Deer and wapiti exhibit fusiform, lanceolate, and polygonal erythrocytes.

These distinct morphologies reveal alternative pathways of erythrocyte development within the mammalian lineage. Nevertheless, the defining feature of mammalian erythrocytes remains their enucleated state, which allows the cell to carry more haemoglobin and enhances gas transport capacity.
The spleen acts as a reservoir of red blood cells in many mammals, including dogs and horses. Rapid contraction of the spleen during physical exertion releases stored erythrocytes, temporarily increasing oxygen-carrying capacity. This capacity is far less pronounced in humans, whose spleen stores comparatively few erythrocytes.

Human Red Blood Cell Characteristics

In humans, a typical erythrocyte has:

• A diameter of approximately 7–8 micrometres.
• A maximum thickness of about 2.25 micrometres and a central thickness of roughly 0.8 micrometres.
• A cellular volume of around 90 femtolitres.
• A surface area of roughly 136 square micrometres.

These cells can swell to accommodate up to 150 femtolitres of fluid without rupturing, thanks to their flexible membrane. The body maintains a population of around 20–30 trillion erythrocytes at any time. Men typically have about 5–6 million red blood cells per microlitre of blood, while women average 4–5 million.
Red blood cells significantly outnumber the two other blood cell types:

• White blood cells: approximately 4,000–11,000 per microlitre.
• Platelets: approximately 150,000–400,000 per microlitre.

The iron content of haemoglobin means that erythrocytes collectively store about 2.5 grams of iron in the average adult male, representing the majority of the body’s total iron stores.

Microstructure and Nuclear Loss

The absence of a nucleus in mammalian red blood cells has both physiological and evolutionary significance. Anucleation increases intracellular space for haemoglobin and enhances the cell’s deformability. In contrast, nucleated red blood cells in other vertebrates must accommodate a nucleus, limiting internal volume and influencing cell rigidity.
A few exceptions among non-mammals exist. Some plethodontid salamanders and Maurolicus fish species have evolved varying degrees of red blood cell enucleation. These rare occurrences offer insights into the genomic and developmental mechanisms associated with nuclear loss.
The elimination of the nucleus during erythropoiesis has been linked to the C-value enigma, which concerns the wide variation in genome sizes among species. Efficient gas exchange requires red blood cells to remain small; thus, large genomes with extensive repetitive sequences would restrict nuclear elimination. This relationship provides a potential explanation for evolutionary genome size constraints in species with highly specialised erythrocytes.
Nucleated red blood cells in mammals appear primarily during development or under pathological conditions. Normal erythropoiesis progresses through nucleated precursors called normoblasts, while abnormal processes can produce unusually large nucleated precursors known as megaloblasts, typically associated with vitamin B₁₂ or folate deficiency.