Gas Exchange and Transport: From the Atmosphere to the Cell

The longest short trip

An oxygen molecule in the air outside your window is less than a metre from your nose. To reach a mitochondrion in your big toe, it must cross two cell layers in the lungs, ride a red blood cell through the heart and over a metre of arteries, leave the blood through a capillary wall and cross a cell membrane. All of that takes less than a minute. This lesson explains every step, using one idea: gases diffuse from higher partial pressure to lower partial pressure.

Partial pressure

Air is a mixture. Each gas in the mixture contributes part of the total pressure, its partial pressure (written PO₂, PCO₂). Dalton's law says the partial pressures add up to the total. At sea level the total is about 760 mm Hg, and air is about 21% oxygen, so:

PO₂ = 0.21 × 760 mm Hg ≈ 160 mm Hg

Air is only about 0.04% CO₂, so PCO₂ in the air is tiny (about 0.3 mm Hg).

A gas dissolved in blood or tissue fluid also has a partial pressure. Each gas diffuses down its own partial-pressure gradient, regardless of the other gases.

Alveolar air is not the same as outside air. It mixes with the residual air left in the lungs, is saturated with water vapour, and keeps losing O₂ to the blood and gaining CO₂. So alveolar PO₂ is about 104 mm Hg and PCO₂ about 40 mm Hg.

External and internal respiration

External respiration happens in the lungs. Blood arriving in the lung capillaries has PO₂ ≈ 40 and PCO₂ ≈ 46 mm Hg. Alveolar air has PO₂ ≈ 104 and PCO₂ ≈ 40. So O₂ diffuses into the blood and CO₂ diffuses out. Within a fraction of a second, the blood nearly matches the alveolar air.

Internal respiration happens in the tissues. Cells use O₂ in cellular respiration, keeping their PO₂ low (about 40 mm Hg at rest, lower in working muscle) and their PCO₂ high. So O₂ diffuses out of the blood into the cells and CO₂ diffuses in.

(Don't confuse these with cellular respiration, the chemical reaction in mitochondria. External and internal respiration are just diffusion.)

Hemoglobin: the oxygen carrier

Oxygen does not dissolve well in water. If blood carried only dissolved O₂, you would need many times more blood. Instead, about 98.5% of the O₂ in blood is carried by hemoglobin, and only about 1.5% is dissolved in plasma.

• Hemoglobin is a protein made of four polypeptide chains. Each chain holds a heme group with an iron (Fe) atom at its centre, and each iron can bind one O₂. So one hemoglobin carries up to four O₂ molecules.
• Each red blood cell contains roughly 250 to 300 million hemoglobin molecules.
• Hemoglobin with O₂ attached is oxyhemoglobin, bright red. Without O₂ it is a darker red. (Blood is never blue. Veins look bluish through skin because of how skin absorbs and scatters light.)

The oxygen–hemoglobin dissociation curve shows how saturated hemoglobin is at each PO₂. Its S shape is the key:

• At the lungs (PO₂ ≈ 100), Hb is about 97 to 98% saturated. The curve is flat here, so even if alveolar PO₂ drops somewhat (for example, at moderate altitude), Hb still loads almost fully.
• At resting tissues (PO₂ ≈ 40), Hb is still about 75% saturated: it has released only about a quarter of its oxygen, leaving a large reserve.
• On the steep part (PO₂ 10 to 40), a small drop in PO₂ makes Hb release a lot of O₂. Working muscle has very low PO₂, so it gets much more oxygen exactly when it needs it.

The Bohr effect: more CO₂, more acid (lower pH) and higher temperature all lower hemoglobin's grip on oxygen, shifting the curve to the right. Active muscles produce all three, so Hb unloads even more O₂ there.

How carbon dioxide travels

CO₂ is carried in three ways:

1. About 70% as bicarbonate ions (HCO₃⁻). CO₂ enters red blood cells, where the enzyme carbonic anhydrase quickly combines it with water to make carbonic acid (H₂CO₃), which splits into H⁺ and HCO₃⁻. The bicarbonate moves into the plasma. Hemoglobin picks up much of the H⁺, which helps keep blood pH steady (about 7.4).
2. About 23% bound to hemoglobin (on the protein part, not the iron), as carbaminohemoglobin.
3. About 7% dissolved in plasma.

In the lungs, everything runs in reverse: HCO₃⁻ and H⁺ recombine into H₂CO₃, carbonic anhydrase splits it into CO₂ and water, and the CO₂ diffuses into the alveoli.

Who decides how fast you breathe?

Breathing is controlled automatically by the respiratory centre in the medulla oblongata of the brainstem, which sends rhythmic nerve signals to the diaphragm and intercostal muscles.

• Central chemoreceptors in the medulla detect changes in the acidity of the fluid around the brain, which rises when blood CO₂ rises. This is the main signal: a small rise in CO₂ strongly increases breathing rate and depth.
• Peripheral chemoreceptors in the carotid bodies (in the neck) and aortic bodies (near the heart) detect CO₂, H⁺ and low O₂. Low O₂ becomes a strong signal only when PO₂ falls a lot, for example at high altitude.
• Stretch receptors in the lungs help prevent over-inflation.
• You can override the rhythm voluntarily (to talk, sing or hold your breath), but rising CO₂ eventually forces you to breathe.

Safety: never hyperventilate (breathe very fast and deep) before swimming underwater. It lowers CO₂, so the urge to breathe comes too late, and a swimmer can black out from low oxygen without warning.

Carbon monoxide and altitude

• Carbon monoxide (CO), from car exhaust, faulty furnaces, gas stoves or fires, binds to hemoglobin's iron about 200 times more strongly than oxygen does. Even small amounts in the air block hemoglobin from carrying O₂. CO has no colour or smell, which is why Ontario law requires CO alarms in homes with a fuel-burning appliance, fireplace or attached garage.
• At high altitude, total air pressure is lower, so PO₂ is lower even though air is still 21% oxygen. The body responds over days and weeks: the kidneys release the hormone EPO, which stimulates the bone marrow to make more red blood cells.