5.1 Alveolar Gas Exchange

Alveolar gas exchange is the process where oxygen enters the bloodstream and carbon dioxide exits. This exchange occurs in tiny air sacs called alveoli, where a thin respiratory membrane separates air from blood, allowing gases to diffuse down their concentration gradients. Understanding the factors that govern this exchange helps explain how lung diseases impair breathing and why certain clinical signs appear when things go wrong.

Diffusion in Alveolar Gas Exchange

Concentration Gradient Drives Diffusion

Gases move from areas of high concentration to areas of low concentration. No energy is required for this process; it's entirely passive.

In the lungs, the concentration gradients work in opposite directions for the two main respiratory gases:

• Oxygen diffuses from the alveoli (high concentration) into the pulmonary capillary blood (low concentration)
• Carbon dioxide diffuses from the blood (high concentration) into the alveoli (low concentration)

These two exchanges happen simultaneously across the same alveolar-capillary membrane, which is only about 0.5 µm thick. That thinness is what makes rapid diffusion possible.

Factors Influencing Diffusion Rate

Fick's law of diffusion describes the variables that determine how quickly a gas crosses a membrane:

• Surface area: More membrane area means more room for gas molecules to cross. The lungs provide roughly 70 m² of alveolar surface area, about half a tennis court.
• Membrane thickness (diffusion distance): A thinner barrier means gases cross faster. Diffusion rate is inversely proportional to thickness.
• Concentration gradient (partial pressure difference): A steeper gradient pushes gas across more quickly.

So anything that shrinks surface area, thickens the membrane, or reduces the pressure gradient will slow gas exchange.

Factors Influencing Gas Exchange Efficiency

Alveolar Surface Area and Membrane Thickness

A larger alveolar surface area allows more gas molecules to cross at the same time, increasing overall exchange. A thinner membrane shortens the path each molecule must travel.

• In emphysema, alveolar walls break down and merge into larger, fewer air sacs. This destroys surface area and dramatically reduces gas exchange efficiency.
• In pulmonary fibrosis, scar tissue thickens the alveolar-capillary membrane, increasing diffusion distance and slowing gas transfer.

Concentration Gradient and Blood Flow

The partial pressure difference between alveolar air and capillary blood is what drives diffusion. If that gradient shrinks, exchange slows.

Adequate pulmonary blood flow is essential for maintaining the gradient. As blood flows past the alveoli, it continuously picks up oxygen and drops off carbon dioxide. Without that flow, the gradient would quickly equalize and diffusion would stop.

• In pulmonary edema, fluid accumulates in the interstitial space or alveoli themselves. This increases the diffusion distance and can also reduce the effective concentration gradient, impairing gas exchange.

Ventilation and Alveolar Gas Replenishment

Ventilation, the movement of air in and out of the lungs, keeps alveolar oxygen levels high and carbon dioxide levels low. Without fresh air cycling through, alveolar oxygen would be consumed and carbon dioxide would accumulate, collapsing the gradients.

• Shallow breathing (low tidal volume) reduces the amount of fresh air reaching the alveoli with each breath. This is sometimes called reduced alveolar ventilation, and it directly impairs gas exchange by weakening the concentration gradient.

Partial Pressures in Alveolar Gas Exchange

Partial Pressures of Oxygen and Carbon Dioxide

Partial pressure is the pressure exerted by a single gas within a mixture. In a gas mix like air, each gas contributes to the total pressure in proportion to its concentration. Partial pressure differences are what actually drive diffusion across the respiratory membrane.

Here are the key values to know:

• The oxygen gradient is 100 − 40 = 60 mmHg, which drives oxygen into the blood.
• The carbon dioxide gradient is 45 − 40 = 5 mmHg, which drives carbon dioxide into the alveoli.

Notice that the $CO_2$ gradient is much smaller than the $O_2$ gradient. Carbon dioxide still diffuses efficiently because it is about 20 times more soluble in the respiratory membrane than oxygen.

Factors Influencing Alveolar Partial Pressures

The partial pressures of gases in the alveoli depend on:

• Atmospheric pressure: At sea level (~760 mmHg), there's more total pressure pushing oxygen into the alveoli than at altitude.
• Alveolar ventilation: Faster or deeper breathing raises alveolar $P_{O_2}$ and lowers $P_{CO_2}$.
• Composition of inspired air: Supplemental oxygen increases inspired $P_{O_2}$; breathing in a closed space with depleted oxygen decreases it.

The alveolar gas equation estimates $P_{A_{O_2}}$ by accounting for atmospheric pressure, water vapor pressure (47 mmHg at body temperature), and the respiratory exchange ratio (normally ~0.8).

At high altitude, atmospheric pressure drops. For example, at 3,000 m elevation, atmospheric pressure is roughly 525 mmHg instead of 760 mmHg. This lowers alveolar $P_{O_2}$, reducing the gradient and making gas exchange less efficient. That's why people experience shortness of breath and fatigue at altitude.

Ventilation-Perfusion Matching for Effective Gas Exchange

Concept of Ventilation-Perfusion (V/Q) Matching

V/Q matching refers to the balance between alveolar ventilation (V) and pulmonary capillary blood flow, or perfusion (Q), in different regions of the lung. For gas exchange to work well, ventilated alveoli need blood flowing past them, and perfused capillaries need air in the adjacent alveoli.

The ideal V/Q ratio is about 1.0, meaning ventilation and perfusion are perfectly matched. In reality, V/Q varies across the lung (it's higher at the apex and lower at the base in an upright person), but the overall matching stays close enough for effective exchange.

When V/Q becomes significantly mismatched, gas exchange suffers and hypoxemia (low blood oxygen) results.

Types of V/Q Mismatch

• Dead space ventilation (high V, low Q): Alveoli receive air but little or no blood flow. The ventilation is "wasted" because there's no blood to pick up the oxygen.
  • Example: A pulmonary embolism blocks blood flow to a region of the lung. Those alveoli are ventilated but not perfused.
• Shunt (low V, high Q): Blood flows past alveoli that aren't receiving adequate air. That blood passes through without being oxygenated and mixes with oxygenated blood, lowering overall arterial $P_{O_2}$.
  • Example: In pneumonia, fluid or pus fills alveoli, blocking ventilation while blood flow to that region continues.

Minimizing V/Q Mismatch

The body's primary compensation mechanism is hypoxic pulmonary vasoconstriction (HPV). When alveolar $P_{O_2}$ drops in a particular region, the local pulmonary arterioles constrict. This redirects blood away from poorly ventilated areas toward better-ventilated regions, improving overall V/Q matching.

This response is unique to pulmonary vessels. Systemic arterioles do the opposite: they dilate in response to low oxygen to increase local blood flow.

Several lung diseases cause significant, sustained V/Q mismatch:

• COPD: Airway obstruction and alveolar destruction create both dead space and shunt regions
• Pulmonary embolism: Creates dead space by blocking perfusion
• Pneumonia: Creates shunt by blocking ventilation