22.4 Gas Exchange

Composition and Mechanisms of Gas Exchange

Gas exchange is the core purpose of the respiratory system. Every breath you take brings oxygen into your blood and removes carbon dioxide, a waste product of cellular metabolism. This exchange depends on differences in gas concentrations between your lungs and blood, and it happens across the incredibly thin walls of the alveoli.

Atmospheric vs. Alveolar Air Composition

The air you breathe in from the atmosphere is not the same as the air sitting in your alveoli. By the time air reaches the alveoli, gas exchange has already altered its makeup.

• Atmospheric air: ~78% nitrogen, ~21% oxygen, ~0.04% carbon dioxide, and variable water vapor
• Alveolar air: ~74% nitrogen, ~14% oxygen, ~5% carbon dioxide, and fully saturated water vapor

Why the difference? Oxygen is constantly being absorbed into the blood, so alveolar $O_2$ drops. Carbon dioxide is constantly being dumped from the blood into the alveoli, so alveolar $CO_2$ rises. The air is also humidified as it passes through the airways, which dilutes the other gases slightly.

Mechanisms of Lung Gas Exchange

Gas exchange across the alveolar-capillary membrane relies on a few key principles:

• Diffusion: Gases move passively from areas of high concentration to low concentration. No energy is required. The alveolar-capillary membrane is extremely thin (about 0.5 µm), which keeps diffusion distances short.
• Partial pressure gradients: Each gas has its own partial pressure, and that gradient is what drives its movement. Oxygen moves from high $P_{O_2}$ in the alveoli (~104 mmHg) to low $P_{O_2}$ in the pulmonary capillary blood (~40 mmHg). Carbon dioxide moves the opposite direction, from high $P_{CO_2}$ in the blood (~45 mmHg) to low $P_{CO_2}$ in the alveoli (~40 mmHg). Notice that the $CO_2$ gradient is much smaller than the $O_2$ gradient, yet $CO_2$ still exchanges efficiently because it's about 20 times more soluble in water than oxygen.
• Moist membrane surface: The alveolar lining is coated with a thin layer of fluid. Gases must dissolve into this fluid before crossing the membrane, so moisture is essential.
• Surfactant: A phospholipid mixture produced by type II alveolar cells that reduces surface tension in the alveoli. Without surfactant, smaller alveoli would collapse, drastically reducing the surface area available for gas exchange.

Ventilation, Perfusion, and Respiration

Ventilation-Perfusion Matching

For gas exchange to work well, airflow (ventilation) and blood flow (perfusion) need to be matched in each region of the lung. The ventilation-perfusion ratio (V/Q) describes this balance.

• An ideal V/Q ratio means that well-ventilated alveoli receive proportional blood flow, and poorly ventilated areas receive less.
• Hypoxic vasoconstriction is the body's main mechanism for maintaining V/Q balance. When alveolar $O_2$ drops in a particular region (say, due to a mucus plug blocking airflow), the local pulmonary arterioles constrict. This diverts blood away from that poorly ventilated area and toward alveoli that are receiving fresh air. This is the opposite of what happens in systemic circulation, where low oxygen causes vasodilation.
• Alveolar recruitment and distension: During exercise or other high-demand states, collapsed alveoli open up (recruitment) and already-open alveoli stretch (distension). Both increase the total surface area for gas exchange.
• Pulmonary compliance refers to how easily the lungs expand. High compliance means the lungs stretch easily; low compliance (as in pulmonary fibrosis) means more effort is needed to inflate them, which can impair gas exchange.

External Respiration

External respiration is the gas exchange that occurs between the alveoli and the pulmonary capillaries. Here's how it works step by step:

1. Oxygen diffuses from the alveoli ($P_{O_2}$ ~104 mmHg) into the pulmonary capillary blood ($P_{O_2}$ ~40 mmHg) across the alveolar-capillary membrane.
2. Oxygen binds to hemoglobin in red blood cells, forming oxyhemoglobin. Each hemoglobin molecule can carry up to four oxygen molecules.
3. Carbon dioxide diffuses from the blood ($P_{CO_2}$ ~45 mmHg) into the alveoli ($P_{CO_2}$ ~40 mmHg).
4. The carbon dioxide is then exhaled during the next breath, removing it from the body.

By the time blood leaves the pulmonary capillaries, its $P_{O_2}$ has risen to ~104 mmHg and its $P_{CO_2}$ has dropped to ~40 mmHg, matching alveolar values.

Internal Respiration and Tissue Exchange

Internal respiration is the gas exchange that happens between the systemic capillaries and the body's tissues. It's essentially the reverse of external respiration.

• Oxygen unloading: Oxygen dissociates from hemoglobin and diffuses from the blood (high $P_{O_2}$) into the tissues (low $P_{O_2}$), where cells use it for aerobic metabolism and ATP production.
• Carbon dioxide loading: Tissues produce $CO_2$ as a metabolic waste product. It diffuses from the tissues (high $P_{CO_2}$) into the blood (low $P_{CO_2}$), where it enters red blood cells.

Once inside red blood cells, $CO_2$ is transported back to the lungs in three forms:

1. Dissolved in plasma (~7-10% of total $CO_2$)
2. As bicarbonate ions (~70%): The enzyme carbonic anhydrase catalyzes the reaction $CO_2 + H_2O \rightarrow H_2CO_3$, and carbonic acid quickly dissociates into $HCO_3^-$ (bicarbonate) and $H^+$ (hydrogen ions). The bicarbonate is shuttled out of the red blood cell into the plasma.
3. As carbamino compounds (~20-23%): $CO_2$ binds directly to hemoglobin and other blood proteins.

The Bohr effect is a key concept here. When tissues are metabolically active, they produce more $CO_2$ and $H^+$, which lowers local pH. This lower pH causes hemoglobin to release oxygen more readily. So the tissues that need oxygen the most (because they're working the hardest) get the most oxygen delivered. It's an elegant feedback mechanism.

Ventilation Dynamics

Ventilation Measurements

These measurements quantify how effectively air moves through the respiratory system:

• Tidal volume (TV): The volume of air inhaled or exhaled in a single normal breath, typically about 500 mL in an average adult.
• Minute ventilation: The total volume of air moved in and out of the lungs per minute. It's calculated as $\text{Minute Ventilation} = \text{Tidal Volume} \times \text{Respiratory Rate}$. For example, at a tidal volume of 500 mL and a rate of 12 breaths/min, minute ventilation is 6,000 mL/min (6 L/min).
• Dead space: The volume of air that fills the conducting airways (nose, trachea, bronchi) but never reaches the alveoli, so it doesn't participate in gas exchange. Anatomical dead space is roughly 150 mL. This means that of each 500 mL tidal breath, only about 350 mL actually reaches the alveoli for gas exchange.