Red Blood Cells

RBC Anatomy

Red blood cells lack nuclei and have a biconcave shape.

Learning Objectives

Diagram the anatomy of an erythrocyte (red blood cell, or RBC)

Key Takeaways

Key Points

  • The biconcave shape allows RBCs to bend and flow smoothly through the body’s capillaries. It also facilitates oxygen transport.
  • Red blood cells are considered cells, but they lack a nucleus, DNA, and organelles like the endoplasmic reticulum or mitochondria.
  • Red blood cells cannot divide or replicate like other bodily cells. They cannot independently synthesize proteins.
  • The blood’s red color is due to the spectral properties of the hemic iron ions in hemoglobin.
  • Each human red blood cell contains approximately 270 million hemoglobin biomolecules, each carrying four heme groups to which oxygen binds.

Key Terms

  • iron: A metallic chemical element with atomic number 26 and symbol Fe. Iron-containing enzymes and proteins, often containing heme prosthetic groups, participate in many biological oxidations and in transport.
  • hemoglobin: The iron-containing substance in RBCs that transports oxygen from the lungs to the rest of the body. It consists of a protein (globulin) and haem (a porphyrin ring with an atom of iron at its center).

Human erythrocytes or red blood cells (RBCs) are the primary cellular component of blood. They are involved in oxygen transport through the body and have features that distinguish them from every other type of human cell. Adult humans have roughly 20-30 trillion RBCs at any given time, comprising approximately one quarter of the total number of human cells.

External Structure


Red blood cells: Human red blood cells (6–8μm)

RBCs are disc-shaped with a flatter, concave center. This biconcave shape allows the cells to flow smoothly through the narrowest blood vessels. Gas exchange with tissues occurs in capillaries, tiny blood vessels that are only as wide as one cell. Many RBCs are wider than capillaries, but their shape provides the needed flexibility to squeeze through.

A typical human RBC has a disk diameter of 6–8 micrometers and a thickness of 2 micrometers, much smaller than most other human cells. These cells have an average volume of about 90 femtoliters (fL) with a surface area of about 136 square micrometers. They can swell up to a sphere shape containing 150 fL without bursting their cell membrane. When the shape does change, it inhibits their ability to carry oxygen or participate in gas exchange. This occurs in people with spherocytic (sphere-shaped) anemia or sickle-cell anemia.

Internal Structure

Although RBCs are considered cells, they lack a nucleus, nuclear DNA, and most organelles, including the endoplasmic reticulum and mitochondria. RBCs therefore cannot divide or replicate like other labile cells of the body. They also lack the components to express genes and synthesize proteins. While most cells have chemotaxic ways to travel through the body, RBCs are carried through the body by blood flow and pressure alone.

Hemoglobin molecules are the most important component of RBCs. Hemoglobin is a specialized protein that contains a binding site for the transport of oxygen and other molecules. The RBCs’ distinctive red color is due to the spectral properties of the binding of hemic iron ions in hemoglobin. Each human red blood cell contains approximately 270 million of these hemoglobin biomolecules, each carrying four heme groups (individual proteins). Hemoglobin comprises about a third of the total RBC volume. This protein is responsible for the transport of more than 98% of the oxygen, while the rest travels as dissolved molecules through the plasma.

RBC Physiology

The primary functions of red blood cells (RBCs) include carrying oxygen to all parts of the body, binding to hemoglobin, and removing carbon dioxide.

Learning Objectives

Discuss the primary function of erythrocytes (red blood cells)

Key Takeaways

Key Points

  • Red blood cells contain hemoglobin,which contains four iron-binding heme groups.
  • Oxygen binds the heme groups of hemoglobin. Each hemoglobin molecule can bind four oxygen molecules.
  • The binding affinity of hemoglobin for oxygen is cooperative. It is increased by the oxygen saturation of the molecule. Binding of an initial oxygen molecule influences the shape of the other binding sites. This makes binding more favorable for additional oxygen molecules.
  • Each hemoglobin molecule contains four iron-binding heme groups which are the site of oxygen binding. Oxygen-bound hemoglobin is called oxyhemoglobin.
  • Red blood cells alter blood pH by catalyzing the reversible carbon dioxide to carbonic acid reaction through the enzyme carbonic anhydrase.
  • pH is also controlled by carbon dioxide binding to hemoglobin instead of being converted to carbonic acid.

Key Terms

  • carbonic anhydrase: The enzyme found in RBCs that catalyzes the reaction between carbonic acid and carbon dioxide and water.
  • cooperative binding: In binding in which multiple molecules can potentially bind to multiple binding sites, when a first molecule is bound to a binding site, the same molecule is favored for the rest of the binding sites through increased binding affinity.

Red blood cells (RBCs) perform a number of human respiratory and cardiovascular system functions. Most of these functions are attributed to hemoglobin content. The main RBC functions are facilitating gas exchange and regulating blood pH.

Gas Exchange


Heme: This is a diagram of the molecular structure of heme.

RBCs facilitate gas exchange through a protein called hemoglobin. The word hemoglobin comes from “hemo” meaning blood and “globin” meaning protein. Hemoglobin is a quaternary structure protein consisting of many smaller tertiary structure proteins composed of amino acid polypeptide chains. Each hemoglobin molecule contains four iron-binding heme groups, which are the site of oxygen (O2) binding. Oxygen bound hemoglobin is called oxyhemoglobin.

The binding of oxygen is a cooperative process. Hemoglobin bound oxygen causes a gradual increase in oxygen-binding affinity until all binding sites on the hemoglobin molecule are filled. As a result, the oxygen-binding curve of hemoglobin (also called the oxygen saturation or dissociation curve) is sigmoidal, or S-shaped, as opposed to the normal hyperbolic curve associated with noncooperative binding. This curve shows the saturation of oxygen bound to hemoglobin compared to the partial pressure of oxygen (concentration) in blood.

This line graph shows PO2 on the X-axis and oxyhemoglobin on the Y access. The lines indicate that the oxygen saturation curve is S-shaped as a result of the cooperative binding process described in the previous paragraph.

Oxygen saturation curve: Due to cooperative binding, the oxygen saturation curve is S-shaped.

pH Control

RBCs control blood pH by changing the form of carbon dioxide within the blood. Carbon dioxide is associated with blood acidity. That’s because most carbon dioxide travels through the blood as a bicarbonate ion, which is the dissociated form of carbonic acid in solution. The respiratory system regulates blood pH by changing the rate at which carbon dioxide is exhaled from the body, which involves the RBC’s molecular activity. RBCs alter blood pH in a few different ways.


Quaternary structure: hemoglobin: Hemoglobin is a globular protein composed of four polypeptide subunits (two alpha chains, in blue, and two beta pleated sheets, in red). The heme groups are the green structures nestled among the alpha and beta.

RBCs secrete the enzyme carbonic anhydrase, which catalyzes the conversion of carbon dioxide and water to carbonic acid. This dissociates in solution into bicarbonate and hydrogen ions, the driving force of pH in the blood. This reaction is reversible by the same enzyme. Carbonic anhydrase also removes water from carbonic acid to turn it back into carbon dioxide and water. This process is essential so carbon dioxide can exist as a gas during gas exchange in the alveolar capillaries. As carbon dioxide is converted from its dissolved acid form and exhaled through the lungs, blood pH becomes less acidic. This reaction can occur without the presence of RBCs or carbonic anhydrase, but at a much slower rate. With the catalyst activity of carbonic anhydrase, this reaction is one of the fastest in the human body.

Hemoglobin can also bind to carbon dioxide, which creates carbamino-hemoglobin. When carbon dioxide binds to hemoglobin, it doesn’t exist in the form of carbonic acid, which makes the blood less acidic and increases blood pH. However, because of allosteric effects on the hemoglobin molecule, the binding of carbon dioxide decreases the amount of oxygen bound for a given partial pressure of oxygen. This decrease in hemoglobin’s affinity for oxygen by the binding of carbon dioxide is known as the Bohr effect, which results in a rightward shift to the O2-saturation curve. Conversely, when the carbon dioxide levels in the blood decrease (i.e., in the lung capillaries), carbon dioxide and hydrogen ions are released from hemoglobin, increasing the oxygen affinity of the protein. A reduction in the total binding capacity of hemoglobin to oxygen (i.e. shifting the curve down, not just to the right) due to reduced pH is called the Haldane effect.

RBC Life Cycle

Human erythrocytes are produced through a process called erythropoiesis. They take about seven days to mature.

Learning Objectives

Outline the life cycle of erythrocytes (red blood cells, or RBCs)

Key Takeaways

Key Points

  • After about 100-120 days, RBCs are removed from circulation through a process called eryptosis.
  • Erythropoiesis is the process by which human erythrocytes are produced. It is triggered by erythropoietin, a kidney hormone produced during hypoxia.
  • Erythropoiesis takes place in the bone marrow, where hemopoietic stem cells differentiate and eventually shed their nuclei to become reticulocytes. Iron, vitamin B12, and folic acid are required for hemoglobin synthesis and normal RBC maturation.
  • Reticulocytes mature into normal, functional RBCs after 24 hours in the bloodstream.
  • Following eryptosis, the liver breaks down old hemoglobin into biliverdin and iron. The iron is taken back to the bone marrow for reuse by transferrins, while biliverdin is broken down into bilirubin and excreted through digestive system bile.

Key Terms

  • erythropoietin: A hormone produced by the kidneys in response to hypoxia, which stimulates erythropoiesis.
  • bilirubin: A bile pigment that arises when biliverdin is separated from the iron of old hemoglobin molecules in the liver. Bilirubin becomes part of bile salts in the digestive system and is excreted, while the iron content is reused.

Human erythrocytes are produced through a process called erythropoiesis, developing from committed stem cells to mature erythrocytes in about seven days. When matured, these cells circulate in the blood for about 100 to 120 days, performing their normal function of molecule transport. At the end of their lifespan, they degrade and are removed from circulation.


Scanning electron micrograph of blood cells: Shown on the left, the erythrocyte, or red blood cell, has a round, donut-like shape.


Erythropoiesis is the process in which new erythrocytes are produced, which takes about seven days. Erythrocytes are continuously produced in the red bone marrow of large bones at a rate of about 2 million cells per second in a healthy adult. Erythrocytes differentiate from erythrotropietic bone marrow cells, a type of hemopoietic stem cell found in bone marrow. Unlike mature RBCs, bone marrow cells contain a nucleus. In the embryo, the liver is the main site of red blood cell production and bears similar types of stem cells at this stage of development.

Erythropoiesis can be stimulated by the hormone erythropoietin, which is synthesized by the kidney in response to hypoxia (systemic oxygen deficiency). In the last stages of development, the immature RBCs absorb iron, Vitamin B12, and folic acid. These dietary nutrients that are necessary for proper synthesis of hemoglobin (iron) and normal RBC development (B12 and folic acid). Deficiency of any of these nutrients may cause anemia, a condition in which there aren’t enough fully functional RBCs carrying oxygen in the bloodstream. Just before and after leaving the bone marrow, the developing cells are known as reticulocytes. These immature RBCs that have shed their nuclei following initial differentiation. After 24 hours in the bloodstream, reticulocytes mature into functional RBCs.


Eryptosis, a form of apoptosis (programmed cell death), is the aging and death of mature RBCs. As an RBC ages, it undergoes changes in its plasma membrane that make it susceptible to selective recognition by macrophages and subsequent phagocytosis in the reticuloendothelial system (spleen, liver, and bone marrow). This process removes old and defective cells and continually purges the blood. Eryptosis normally occurs at the same rate as erythropoiesis, keeping the total circulating red blood cell count in a state of equilibrium. Many diseases that involve damage to RBCs (hemolytic anemias, sepsis, malaria, pernicious or nutritional anemias) or normal cellular processes that cause cellular damage (oxidative stress) may increase the rate of eryptosis. Conversely, erythropotein and nitric oxide (a vasodilator) will inhibit eryptosis.

Following eryptosis, the hemoglobin content within the RBC is broken down and recirculated throughout the body. The heme components of hemoglobin are broken down into iron ions and a green bile pigment called biliverdin. The biliverdin is reduced to the yellow bile pigment bilirubin, which is released into the plasma and recirculated to the liver, then bound to albumin and stored in the gallbladder. The bilirubin is excreted through the digestive system in the form of bile, while some of the iron is released into the plasma to be recirculated back into the bone marrow by a carrier protein called transferrin.  This iron is then reused for erythropoiesis, but additional dietary iron is needed to support healthy RBC life cycles.