5.2 Oxygen and Carbon Dioxide Transport in Blood

Hemoglobin's Role in Oxygen Transport

Structure and Function of Hemoglobin

Hemoglobin (Hb) is the oxygen-carrying protein packed inside red blood cells. Its job is to pick up oxygen in the lungs and deliver it to every tissue in the body.

Each hemoglobin molecule has four subunits, and each subunit contains a heme group with a central iron ($Fe^{2+}$) atom. That iron atom is the actual binding site for oxygen. Since there are four heme groups, a single hemoglobin molecule can carry up to four oxygen molecules (written as $O_2$).

• In the lungs, the partial pressure of oxygen ($PO_2$) is high (~104 mmHg), so hemoglobin binds oxygen readily.
• In the tissues, $PO_2$ drops (~40 mmHg at rest), and hemoglobin's affinity for oxygen decreases. This is what allows oxygen to be released where cells actually need it.

Cooperative Binding of Oxygen

Oxygen binding to hemoglobin is cooperative, meaning the first $O_2$ molecule that binds makes it easier for the next ones to attach. After the first oxygen binds, it causes a conformational (shape) change in hemoglobin that increases the affinity of the remaining heme groups.

This cooperative behavior is the reason the oxygen-hemoglobin dissociation curve is sigmoidal (S-shaped) rather than a straight line. The practical result: hemoglobin loads oxygen very efficiently in the lungs and unloads it effectively in the tissues. Without cooperative binding, hemoglobin would be far less responsive to the difference in $PO_2$ between lungs and tissues.

Oxygen-Hemoglobin Dissociation Curve

Characteristics of the Curve

The oxygen-hemoglobin dissociation curve plots $PO_2$ (x-axis) against % hemoglobin saturation (y-axis). It tells you how much of the hemoglobin is loaded with oxygen at any given $PO_2$.

• Steep portion ($PO_2$ ~10–40 mmHg): Small changes in $PO_2$ cause large changes in saturation. This is the tissue range, where oxygen is being unloaded.
• Plateau portion ($PO_2$ ~70–104 mmHg): Hemoglobin is nearly fully saturated. Even if $PO_2$ drops a bit, Hb still holds onto most of its oxygen. This is the lung range, and the plateau acts as a safety buffer, ensuring you stay well-oxygenated even if lung function dips slightly.

At a normal alveolar $PO_2$ of ~104 mmHg, hemoglobin is about 98% saturated. At a typical resting tissue $PO_2$ of ~40 mmHg, saturation drops to about 75%, meaning roughly 25% of the oxygen is offloaded to the tissues at rest.

Factors That Shift the Curve

Several factors shift the curve right or left, changing how readily hemoglobin releases or holds onto oxygen.

Right shift (decreased O₂ affinity, promotes unloading in tissues):

• Increased temperature
• Increased $CO_2$ (Bohr effect)
• Decreased pH (more acidic)
• Increased 2,3-bisphosphoglycerate (2,3-BPG) levels

Left shift (increased O₂ affinity, promotes loading in lungs):

• Decreased temperature
• Decreased $CO_2$
• Increased pH (more alkaline)
• Decreased 2,3-BPG levels

A helpful way to remember right shifts: think about what happens in actively exercising muscle. Temperature rises, $CO_2$ production increases, and pH drops. All of these push the curve right, forcing hemoglobin to dump more oxygen exactly where demand is highest.

Left shifts occur in conditions like the lungs, where $CO_2$ is being exhaled and pH is slightly higher, helping hemoglobin grab onto oxygen tightly for transport.

2,3-BPG is produced by red blood cells during glycolysis and increases during chronic hypoxia (e.g., at high altitude), shifting the curve right so tissues can extract more oxygen even when overall $PO_2$ is lower.

Carbon Dioxide Transport in Blood

Three Forms of CO₂ Transport

Carbon dioxide is a waste product of cellular respiration that must travel from the tissues back to the lungs for elimination. It's transported in three forms:

• Dissolved in plasma (~7–10%): A small fraction of $CO_2$ simply dissolves in the blood plasma.
• Bound to hemoglobin (~20%): $CO_2$ binds to the amino groups on hemoglobin's protein chains (not to the heme iron), forming carbaminohemoglobin. Deoxygenated hemoglobin binds $CO_2$ more readily than oxygenated hemoglobin.
• As bicarbonate ions (~70%): This is the dominant form. Inside red blood cells, the enzyme carbonic anhydrase catalyzes a rapid reaction:

$CO_2 + H_2O \rightarrow H_2CO_3 \rightarrow HCO_3^- + H^+$

Carbonic acid ($H_2CO_3$) forms first, then immediately dissociates into a bicarbonate ion ($HCO_3^-$) and a hydrogen ion ($H^+$).

Bicarbonate Transport and the Chloride Shift

Once bicarbonate ions are produced inside the red blood cell, they're shuttled out into the plasma through a membrane transporter called the band 3 protein (also called the chloride-bicarbonate exchanger). For every $HCO_3^-$ that leaves, one chloride ion ($Cl^-$) enters the red blood cell. This swap is the chloride shift, and it maintains electrical neutrality across the red blood cell membrane.

The $H^+$ ions left behind inside the red blood cell are buffered by binding to deoxygenated hemoglobin, which prevents blood pH from dropping too sharply.

In the lungs, the entire process reverses:

1. $HCO_3^-$ re-enters the red blood cell ($Cl^-$ exits).
2. $HCO_3^-$ combines with $H^+$ to form $H_2CO_3$.
3. Carbonic anhydrase converts $H_2CO_3$ back into $CO_2$ and $H_2O$.
4. $CO_2$ diffuses into the alveoli and is exhaled.

This bicarbonate system does double duty: it transports $CO_2$ and acts as the body's major blood pH buffer.

Bohr Effect and Oxygen Delivery

Mechanism of the Bohr Effect

The Bohr effect describes how $CO_2$ and pH influence hemoglobin's affinity for oxygen. Here's the chain of events in metabolically active tissue (like exercising skeletal muscle):

1. Cells produce large amounts of $CO_2$ through aerobic respiration.
2. $CO_2$ diffuses into the blood and into red blood cells, where carbonic anhydrase converts it to $H_2CO_3$, then $HCO_3^-$ and $H^+$.
3. The rising $H^+$ concentration lowers local pH.
4. Both the elevated $CO_2$ and the lower pH bind to hemoglobin and change its shape, reducing its affinity for $O_2$.
5. The dissociation curve shifts right, and hemoglobin releases more oxygen to the tissue.

The tissues that are working hardest produce the most $CO_2$ and acid, so they automatically receive the most oxygen. It's a built-in demand-matching system.

Physiological Significance of the Bohr Effect

In the lungs, the opposite conditions exist. As $CO_2$ is exhaled, blood $CO_2$ drops and pH rises. This shifts the curve left, increasing hemoglobin's affinity for oxygen and promoting efficient loading.

The Bohr effect means that oxygen loading and unloading are coupled to $CO_2$ levels. The two gases essentially regulate each other's transport:

• Where $CO_2$ is high (tissues), $O_2$ is released.
• Where $CO_2$ is low (lungs), $O_2$ is picked up.

This coupling is critical during exercise, when muscle $O_2$ demand can increase dramatically. It's also vital for organs like the brain and heart that have continuous high metabolic rates and cannot tolerate oxygen deprivation. The Bohr effect ensures these tissues receive priority oxygen delivery proportional to their metabolic activity.