Red Blood Cell (Erythrocyte) - Structure & Physiology

Shape and Size

The mature RBC is a biconcave disc - flattened in the center and thicker at the rim. Key dimensions:

Parameter	Value
Diameter	~7.8 µm
Thickness (rim)	~2.5 µm
Thickness (center)	~1 µm
Volume	90-95 µm³
Surface area	~140 µm²

Scanning electron micrograph showing the characteristic biconcave disc shape:

SEM of RBCs showing biconcave disc shape

The biconcave shape is not just geometric elegance - it has clear functional purposes:

Maximizes surface area relative to volume, improving gas exchange efficiency
Creates excess membrane (140 µm² actual vs 98 µm² needed for a sphere), allowing deformation without rupture
Enables the cell to fold and squeeze through capillaries and splenic sinusoids as narrow as ~3 µm in diameter
Guyton and Hall Textbook of Medical Physiology, p. 441
Basic Medical Biochemistry - A Clinical Approach, 6e, p. 1530

Normal Counts and Hemoglobin Content

Parameter	Men	Women
RBC count	~5.2 million/mm³	~4.7 million/mm³
Hemoglobin	~15 g/100 mL blood	~14 g/100 mL blood
Hematocrit	40-45%	40-45%
Max Hb concentration in cell	34 g/100 mL cells	same

Each gram of hemoglobin carries 1.34 mL O₂ at full saturation, giving ~20 mL O₂/100 mL blood in men.

Guyton and Hall, p. 441

The Mature RBC is "Stripped Down"

The mature erythrocyte has ejected its nucleus and lost most organelles (mitochondria, ribosomes, Golgi) during maturation. Consequences:

No oxidative phosphorylation - relies entirely on anaerobic glycolysis for ATP
Cannot synthesize new proteins - membrane proteins cannot be replaced
Cannot divide
Lifespan ~120 days, after which senescent cells are cleared by splenic macrophages

Membrane Architecture

The RBC membrane has two components: a lipid bilayer with integral proteins, and an internal cytoskeletal lattice.

Integral Membrane Proteins

Protein	Function
Band 3	Anion exchanger (Cl⁻/HCO₃⁻); most abundant (~1.2 million copies/cell); anchors cytoskeleton via ankyrin; aging marker
Glycophorin A	Carries MN blood group antigens; provides negative surface charge (sialic acid)
Glycophorin C	Anchors band 4.1 complex to membrane

The Cytoskeleton

The internal meshwork gives the RBC its deformability. The diagram below shows the key connections:

Erythrocyte membrane cytoskeleton showing spectrin, ankyrin, band 3, glycophorin A/C, and actin

Key cytoskeletal proteins:

Spectrin (bands 1 & 2 = α and β chains) - the dominant scaffold protein. α and β chains intertwine antiparallel to form ~100 nm dimers, which head-to-head associate into ~200 nm tetramers. Forms the underlying mesh.
Ankyrin (band 2.1) - pyramid-shaped linker that binds β-spectrin AND band 3, anchoring the mesh to the membrane
Band 4.2 - stabilizes the ankyrin-band 3 connection
Actin (band 5) - short F-actin filaments serve as nodes where multiple spectrin tetramers converge
Band 4.1 - links spectrin-actin complex to glycophorin C (and glycophorin A), providing a second membrane anchor point
Adducin, tropomyosin - accessory proteins that regulate actin filament length

When the cell is mechanically stressed, spectrin molecules uncoil and extend or compress, changing cell shape without changing surface area. This is the molecular basis of RBC deformability.

Defects in any of these proteins (especially spectrin or ankyrin) cause hereditary spherocytosis (autosomal dominant; ~1:5,000 Northern Europeans) or hereditary elliptocytosis.

Harper's Illustrated Biochemistry, 32nd Ed, p. 671
Basic Medical Biochemistry - A Clinical Approach, 6e, p. 1531-1532

Metabolism

Because the RBC has no mitochondria, it depends on two main metabolic pathways:

1. Embden-Meyerhof Pathway (Glycolysis)

Source of ATP - used for Na⁺/K⁺-ATPase (cation pump) and membrane maintenance
Generates NADH - used by methemoglobin reductase to keep hemoglobin iron in the ferrous (Fe²⁺) state (ferric = methemoglobin = cannot carry O₂)

2. Hexose Monophosphate Shunt (Pentose Phosphate Pathway)

Generates NADPH - reduces glutathione via glutathione reductase
Reduced glutathione (GSH) protects the cell against oxidative stress
G6PD (glucose-6-phosphate dehydrogenase) is the rate-limiting enzyme; G6PD deficiency is the most common RBC enzyme deficiency worldwide

3. Rapoport-Luebering Shunt

Produces 2,3-bisphosphoglycerate (2,3-BPG)
2,3-BPG binds the central cavity of deoxyhemoglobin, reducing O₂ affinity (right-shifts the O₂-Hb dissociation curve), promoting O₂ delivery to tissues
Harrison's Principles of Internal Medicine 22E (2025), p. 835

Lifespan and Destruction

Normal RBC lifespan: ~120 days
Senescent RBCs accumulate damage; band 3 proteins cluster on the surface and become recognized by natural anti-band 3 IgG antibodies
Opsonized cells are phagocytosed by macrophages in the spleen, liver, and bone marrow (extravascular hemolysis)
Hemoglobin is broken down: globin → amino acids (recycled); heme → bilirubin → conjugated in liver → excreted in bile → urobilinogen/stercobilin in feces

Summary Table

Feature	Detail
Shape	Biconcave disc
Diameter	~7.8 µm
Lifespan	~120 days
Nucleus	Absent (ejected during maturation)
Organelles	None (no mitochondria)
Energy source	Anaerobic glycolysis only
Main protein	Hemoglobin (34 g/100 mL cell)
Key scaffold	Spectrin-ankyrin-actin cytoskeleton
O₂ affinity regulator	2,3-BPG
Oxidant defense	G6PD → NADPH → reduced glutathione
Clearance site	Spleen (primarily)

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