22.5 Transport of Gases

Oxygen Transport in the Blood

Oxygen transport in blood

Oxygen travels through your blood in two forms:

• Dissolved in plasma (~1.5%): The amount dissolved is directly proportional to the partial pressure of oxygen ($PO_2$). This small fraction is what's actually measured when you see a $PO_2$ value on a blood gas report.
• Bound to hemoglobin (~98.5%): Each hemoglobin molecule can bind up to four oxygen molecules. Because hemoglobin carries the vast majority of oxygen, even a small drop in hemoglobin levels (like in anemia) significantly reduces oxygen delivery to tissues.

Oxygen binding to hemoglobin is cooperative, meaning that once the first oxygen molecule binds, the remaining binding sites pick up oxygen more easily. This produces the characteristic sigmoidal (S-shaped) oxygen-hemoglobin dissociation curve rather than a straight line.

The Bohr effect describes how increased $CO_2$ and decreased pH (more acidic conditions) shift the dissociation curve to the right. A right shift means hemoglobin releases oxygen more readily. This is exactly what you want at active tissues: metabolically active cells produce $CO_2$ and acid, which causes hemoglobin to "let go" of oxygen right where it's needed most.

Hemoglobin structure and function

Hemoglobin is a protein made of four subunits: two alpha ($\alpha$) and two beta ($\beta$) subunits. Each subunit contains a heme group, which is an iron-containing porphyrin ring. The iron atom at the center of each heme group is the actual binding site for one oxygen molecule.

How hemoglobin works as an oxygen carrier:

• In the lungs, $PO_2$ is high (~104 mmHg), so hemoglobin readily binds oxygen and becomes oxyhemoglobin.
• In systemic tissues, $PO_2$ is lower (~40 mmHg), so hemoglobin releases oxygen and becomes deoxyhemoglobin.
• Several factors influence how tightly hemoglobin holds onto oxygen:
  • $PO_2$ (the primary driver)
  • pH (lower pH promotes release)
  • Temperature (higher temperature promotes release)
  • 2,3-bisphosphoglycerate (2,3-BPG): This molecule, produced by red blood cells during glycolysis, binds to deoxyhemoglobin and reduces its oxygen affinity, promoting oxygen unloading at tissues.

Fetal vs. adult hemoglobin

Fetal hemoglobin (HbF) and adult hemoglobin (HbA) differ in their subunit composition:

• HbF: Two $\alpha$ subunits + two gamma ($\gamma$) subunits
• HbA: Two $\alpha$ subunits + two $\beta$ subunits

HbF has a higher oxygen affinity than HbA. The reason comes down to 2,3-BPG: the $\gamma$ subunits in HbF bind 2,3-BPG less effectively than the $\beta$ subunits in HbA. Since 2,3-BPG normally reduces oxygen affinity, less 2,3-BPG interaction means HbF holds onto oxygen more tightly.

Why does this matter? The fetus gets oxygen from the mother's blood across the placenta. For oxygen to move from maternal hemoglobin to fetal hemoglobin, the fetal hemoglobin must have a stronger "pull" on oxygen. On the oxygen-hemoglobin dissociation curve, HbF is left-shifted compared to HbA, meaning it picks up oxygen at lower $PO_2$ values. This ensures adequate oxygen delivery to the developing fetus even though placental $PO_2$ is relatively low.

Carbon Dioxide Transport in the Blood

Carbon dioxide transport mechanisms

Carbon dioxide travels in the blood in three forms:

1. Dissolved $CO_2$ (~7–10%):

   • Carried as dissolved gas directly in the plasma.
   • The amount is proportional to the partial pressure of carbon dioxide ($PCO_2$).

2. Bicarbonate ions, $HCO_3^-$ (~70–80%): This is the dominant transport method. Here's the process:

   1. $CO_2$ diffuses from tissues into red blood cells.
   2. Inside the RBC, the enzyme carbonic anhydrase catalyzes the reaction: $CO_2 + H_2O \rightarrow H_2CO_3$ (carbonic acid).
   3. Carbonic acid quickly dissociates: $H_2CO_3 \rightarrow H^+ + HCO_3^-$.
   4. The $HCO_3^-$ ions diffuse out of the RBC into the plasma. To maintain electrical neutrality, chloride ions ($Cl^-$) move into the RBC. This exchange is called the chloride shift (also known as the Hamburger phenomenon).
   5. The $H^+$ ions left behind are buffered by binding to deoxyhemoglobin, preventing dangerous drops in blood pH.

3. Carbaminohemoglobin (~10–20%):

   • $CO_2$ binds directly to the amino groups on hemoglobin (not to the heme group) to form carbaminohemoglobin.
   • The Haldane effect explains why this works well at tissues: deoxyhemoglobin (hemoglobin that has already released its oxygen) has a greater affinity for $CO_2$ than oxyhemoglobin does. So at the tissues, where hemoglobin is unloading oxygen, it simultaneously picks up $CO_2$ more effectively.

Gas Exchange Process

Pulmonary gas exchange

Gas exchange occurs in the alveoli of the lungs, where the thin respiratory membrane (only ~0.5 µm thick) separates alveolar air from blood in the pulmonary capillaries.

The driving force is partial pressure gradients:

• Oxygen moves from alveolar air ($PO_2$ ~104 mmHg) into the blood ($PO_2$ ~40 mmHg in deoxygenated blood arriving at the lungs).
• Carbon dioxide moves from the blood ($PCO_2$ ~45 mmHg) into alveolar air ($PCO_2$ ~40 mmHg). Even though this gradient is smaller than the oxygen gradient, $CO_2$ diffuses about 20 times more readily than $O_2$ because of its higher solubility, so the exchange is still efficient.

Two processes must be coordinated for effective gas exchange:

• Ventilation: The movement of air into and out of the alveoli, which maintains the concentration gradients by continuously refreshing alveolar gas.
• Perfusion: Blood flow through the pulmonary capillaries, which carries deoxygenated blood to the alveoli and transports freshly oxygenated blood away.

When ventilation and perfusion are well-matched (a normal V/Q ratio of about 0.8), gas exchange is most efficient. Mismatches, such as a blocked airway (reduced ventilation) or a blood clot in a pulmonary vessel (reduced perfusion), impair gas exchange and can lead to hypoxemia.