Red Blood Cells

Red Blood Cells (RBCs), also known as erythrocytes, are the most abundant cellular components of human blood and play a crucial role in transporting oxygen from the lungs to body tissues and carrying carbon dioxide back to the lungs for exhalation. Their specialised structure and composition enable them to perform this essential function efficiently, making them indispensable to life and physiological balance.

Structure and Morphology

Red blood cells are biconcave, disc-shaped cells with a diameter of approximately 7–8 micrometres and a thickness of about 2 micrometres. This unique shape increases their surface area-to-volume ratio, facilitating the rapid exchange of gases.
Key structural features include:

• Lack of a nucleus and organelles: Mature RBCs in mammals lack a nucleus, mitochondria, and endoplasmic reticulum. This absence allows more space for the main oxygen-carrying molecule, haemoglobin.
• Flexible membrane: Their elastic cell membrane enables RBCs to deform as they pass through narrow capillaries.
• Haemoglobin content: Each RBC contains about 270 million molecules of haemoglobin, a conjugated protein consisting of the pigment haem (iron-containing) and globin (protein component).

The haem group binds oxygen in the lungs, forming oxyhaemoglobin, and releases it in tissues where oxygen concentration is low, reverting to deoxyhaemoglobin. This reversible binding process is central to respiratory gas transport.

Formation and Life Cycle

The production of red blood cells, known as erythropoiesis, occurs in the red bone marrow of long bones such as the femur, ribs, and sternum.
The stages of erythropoiesis are as follows:

1. Haemocytoblast (stem cell): The pluripotent stem cell differentiates into a committed erythroid progenitor.
2. Proerythroblast → Erythroblast → Reticulocyte: Through successive stages, the cell synthesises haemoglobin, loses its nucleus, and becomes a reticulocyte, an immature RBC.
3. Maturation: Reticulocytes enter the bloodstream and mature into fully functional erythrocytes within 1–2 days.

The hormone erythropoietin (EPO), produced mainly by the kidneys (and to a lesser extent by the liver), regulates erythropoiesis. Low oxygen levels (hypoxia) stimulate EPO secretion, enhancing RBC production.
The average lifespan of an RBC is about 120 days, after which old or damaged cells are removed by macrophages in the spleen, liver, and bone marrow—a process known as haemolysis. The iron from haemoglobin is recycled for new RBC formation, while the remaining haem portion is converted to bilirubin, which is excreted in bile.

Composition and Chemical Properties

Red blood cells are composed primarily of:

• Water (approximately 64%)
• Haemoglobin (about 34%)
• Membrane lipids and proteins (2%)

The average haemoglobin concentration in blood is around 13–18 g/dL in males and 12–16 g/dL in females.
The normal RBC count varies according to sex and altitude:

• Males: approximately 5.4 million cells/mm³
• Females: approximately 4.8 million cells/mm³

At high altitudes, where oxygen levels are lower, the body compensates by increasing RBC production to enhance oxygen-carrying capacity.

Function

The primary function of red blood cells is gas transport:

• Oxygen Transport:
  • Oxygen binds reversibly to the iron in haemoglobin in the lungs, forming oxyhaemoglobin.
  • In tissues, oxygen dissociates where it is needed for cellular respiration.
• Carbon Dioxide Transport:
  • About 20–25% of carbon dioxide is carried by haemoglobin as carbaminohaemoglobin.
  • The rest is dissolved in plasma or converted to bicarbonate ions (HCO₃⁻) by the enzyme carbonic anhydrase within RBCs.

Additionally, RBCs help maintain acid–base balance by regulating hydrogen ion concentration through the bicarbonate buffer system.

Types and Abnormalities

While the normal erythrocyte maintains a consistent morphology, variations in size (anisocytosis) or shape (poikilocytosis) may indicate disease. Common abnormalities include:

• Anaemia: A reduction in the number of RBCs or haemoglobin concentration, leading to fatigue and pallor.
  • Iron-deficiency anaemia: Due to inadequate iron intake or absorption.
  • Megaloblastic anaemia: Caused by vitamin B₁₂ or folate deficiency.
  • Aplastic anaemia: Resulting from bone marrow failure.
  • Haemolytic anaemia: Premature destruction of RBCs due to genetic or autoimmune causes.
• Polycythaemia: An abnormal increase in RBC count, which may occur as a physiological response to high altitude or as a pathological condition (polycythaemia vera).
• Sickle Cell Disease: A genetic disorder where defective haemoglobin (HbS) causes RBCs to become rigid and sickle-shaped, leading to vascular blockages and tissue damage.
• Thalassaemia: Inherited conditions affecting haemoglobin synthesis, resulting in fragile and short-lived RBCs.

Blood Typing and Antigens

Red blood cells carry surface antigens that determine blood groups, the most important being the ABO and Rh systems.

• ABO System: Determined by the presence of A and B antigens on the RBC surface.
  • Type A: A antigen present, anti-B antibody in plasma.
  • Type B: B antigen present, anti-A antibody in plasma.
  • Type AB: Both A and B antigens, no antibodies (universal recipient).
  • Type O: No antigens, both antibodies (universal donor).
• Rh Factor: Based on the presence or absence of the Rh (D) antigen. Rh-positive blood has the antigen; Rh-negative blood lacks it.

These antigens are critical for safe blood transfusions and pregnancy management (to prevent haemolytic disease of the newborn in Rh incompatibility).

Clinical and Diagnostic Importance

The condition and number of red blood cells are vital indicators of overall health. Common diagnostic tests include:

• Complete Blood Count (CBC): Measures RBC count, haemoglobin, haematocrit, and indices such as Mean Corpuscular Volume (MCV) and Mean Corpuscular Haemoglobin Concentration (MCHC).
• Blood Smear Examination: Evaluates cell morphology to detect anaemia or parasitic infections like malaria.
• Reticulocyte Count: Assesses bone marrow activity in producing new RBCs.

These investigations are essential for diagnosing haematological disorders, infections, and systemic diseases.

Evolutionary and Comparative Perspective

In most vertebrates, red blood cells are nucleated, except in mammals, where the absence of a nucleus enhances haemoglobin content and gas transport efficiency. In birds and reptiles, RBCs are oval and retain their nuclei. The adaptation of anucleate RBCs in mammals is considered an evolutionary advancement to support higher metabolic demands.

Lifespan and Breakdown

After approximately 120 days, senescent RBCs lose membrane flexibility and are engulfed by macrophages in the spleen, liver, and bone marrow. The iron component from haemoglobin is stored as ferritin or haemosiderin and reused, while the haem is converted to bilirubin, transported to the liver, and excreted via bile into the intestines.
Disruptions in this process can lead to conditions such as jaundice, characterised by the accumulation of bilirubin in the blood.

Physiological Adaptations

RBC production and oxygen affinity can adapt to various physiological conditions:

• High altitudes: Increased erythropoietin secretion enhances RBC count to compensate for low oxygen.
• Pregnancy: Plasma volume expands, slightly lowering haematocrit but maintaining oxygen delivery.
• Physical training: Endurance athletes may have increased RBC mass, improving oxygen transport capacity.