Original episode & show notes | Raw transcript
This document explores the critical mechanisms of oxygen transport, from its entry into the lungs to its delivery to muscle tissue, and how these processes are influenced by endurance training. We will dissect the concepts presented in the podcast, providing a detailed, scientific framework for understanding VO2 max and athletic performance.
The primary function of the lungs is gas exchange: bringing oxygen (O2) into the body and expelling carbon dioxide (CO2). While this sounds simple, the efficiency of this process is a marvel of biological engineering.
The respiratory tract is not a simple bag but a highly branched structure, starting with the trachea and dividing repeatedly into smaller bronchi and bronchioles. This branching terminates in microscopic air sacs called alveoli. These alveoli are the “business end” of the lungs.
The reason for this intricate structure is to maximize surface area. The podcast uses the “fractal problem” or the “coastline paradox” as an analogy: the more detailed your measurement, the longer a coastline appears. Similarly, by dividing the lung volume into approximately 300-500 million tiny alveoli, the human body creates an enormous surface area for gas exchange—roughly 50 to 75 square meters, about the size of a tennis court.
If the lungs were a single 4-liter sphere, the surface area would be a mere 0.1 m2. By dividing that volume into millions of tiny spheres (the alveoli), the surface area is amplified over 500-fold. This vast area is crucial because it allows a massive volume of gas to be exchanged in a very short amount of time.
Gas exchange operates on the principle of diffusion, governed by differences in partial pressure. Gases naturally move from an area of higher partial pressure to an area of lower partial pressure.
Atmospheric Air: Total pressure is ~760 mmHg (or Torr). Oxygen makes up about 21% of this, so its partial pressure (PO2) is roughly 160 mmHg.
Venous Blood: Blood returning to the lungs from the body is depleted of oxygen. Its PO2 is low, around 40 mmHg.
This large pressure gradient (160 mmHg in the alveoli vs. 40 mmHg in the capillaries) drives oxygen to diffuse rapidly from the air in the lungs into the blood. The walls of the alveoli and the surrounding capillaries are incredibly thin, minimizing the distance the oxygen must travel.
A common misconception is that the oxygen we exhale comes from our blood. This is incorrect. The oxygen in exhaled breath is primarily from two sources:
Anatomical Dead Space: Air that fills the trachea and bronchi but never reaches the alveoli for gas exchange.
Unused Alveolar Air: The diffusion process is so efficient that blood passing through the lungs becomes almost fully saturated with oxygen very quickly. The remaining oxygen in the alveoli is simply exhaled.
Once oxygen enters the blood, it doesn’t simply dissolve in the plasma. Over 98% of it is bound to hemoglobin (Hb), a protein contained within red blood cells. Hemoglobin is not just a passive carrier; it’s a sophisticated molecular machine.
Hemoglobin is a large protein composed of four separate polypeptide chains (subunits): two alpha and two beta. Each subunit cradles a heme group, which is a ring-like structure with an iron atom (Fe2+) at its center. It is this iron atom that reversibly binds one molecule of oxygen. Thus, a single hemoglobin molecule can carry up to four oxygen molecules.
The genius of hemoglobin lies in its cooperative kinetics. Unlike myoglobin (an oxygen-storage protein in muscle with only one heme group), hemoglobin’s affinity for oxygen changes as it binds more oxygen. This behavior results in a distinctive sigmoidal (S-shaped) oxygen-binding curve.
Low Affinity (Taut State): In its deoxygenated form, hemoglobin is in a “taut” (T) state. It has a relatively low affinity for oxygen.
High Affinity (Relaxed State): When the first oxygen molecule binds, it induces a conformational (shape) change in that subunit. This change is transmitted to the adjacent subunits, causing them to shift into a “relaxed” (R) state. This R state has a much higher affinity for oxygen.
The effect: Binding the first O2 is difficult, but it makes binding the second, third, and fourth O2 molecules progressively easier. Conversely, when one O2 molecule is released in the tissues, the affinity of the remaining sites decreases, making it easier to release the rest.
This cooperativity makes hemoglobin a perfect transport molecule:
In the Lungs: Where PO2 is high (~100-160 mmHg), hemoglobin rapidly binds oxygen and becomes nearly 100% saturated.
In the Tissues: Where PO2 is low (~20-40 mmHg), hemoglobin readily releases its oxygen cargo. The steepest part of the S-curve falls precisely within the range of tissue PO2, allowing for significant oxygen unloading in response to small changes in local oxygen pressure.
Hemoglobin’s oxygen delivery is further fine-tuned by local metabolic conditions. This is known as the Bohr effect. Actively respiring tissues produce acid (protons, H+) and carbon dioxide (CO2).
Increased Acidity (Lower pH): Protons can bind to hemoglobin, stabilizing its T-state (low affinity). This causes the S-shaped curve to shift to the right, meaning hemoglobin releases oxygen more easily at any given PO2.
Increased CO2: Carbon dioxide can also bind directly to hemoglobin (forming carbaminohemoglobin), which also promotes a rightward shift. Furthermore, the enzyme carbonic anhydrase in red blood cells rapidly converts CO2 and water into bicarbonate and a proton, further increasing acidity and enhancing the Bohr effect.
This is an elegant feedback system: the tissues that are working the hardest (and thus need the most oxygen) automatically trigger hemoglobin to release its cargo more readily. Other factors like increased temperature and 2,3-Bisphosphoglycerate (a byproduct of glycolysis) also cause a rightward shift, further enhancing oxygen delivery during exercise.
While hemoglobin’s function is critical at the molecular level, the total amount of blood and its composition are critical at the systemic level.
Total Hemoglobin Mass: The absolute amount of hemoglobin in the body is strongly correlated with VO2 max (r ≈ 0.75). More hemoglobin means a higher total oxygen-carrying capacity.
Hematocrit: This is a measure of concentration—the percentage of blood volume occupied by red blood cells. Counterintuitively, hematocrit has a very poor correlation with VO2 max (r ≈ 0.1).
This distinction is crucial. An athlete can increase their fitness without changing their hematocrit, and vice-versa. Relying on hematocrit alone is misleading. For instance, early in a training program, an athlete’s plasma volume often increases faster than their red blood cell volume. This leads to a drop in hematocrit (a condition sometimes called “sports anemia”), yet their performance and VO2 max are improving.
The problem with excessively high hematocrit (>50%) is that it increases blood viscosity. The blood becomes thick and sludge-like, making it harder for the heart to pump and impairing its flow through narrow capillaries.
A seminal 1986 study by Coyle, Hemmert, and Coggan powerfully illustrates these concepts.
Protocol: They took highly trained cyclists, tested their VO2 max, and then had them completely stop training for 2-4 weeks. They were tested again in their detrained state. Finally, they were re-tested after an infusion of saline solution to restore their plasma volume to its trained level.
Results:
Detraining: VO2 max dropped by ~6%. This was accompanied by a 9% drop in total blood volume, primarily from plasma loss, but also a ~6% loss in red cell volume. Paradoxically, their hematocrit went up as they lost more plasma than red cells.
Plasma Reinfusion: When the lost plasma volume was restored in the detrained athletes, their VO2 max was restored by about half, returning to only ~3% below their trained peak. This occurred even though their red blood cell count remained low and their hematocrit was now lower than in their trained state.
Conclusion: This study demonstrates that blood volume, particularly plasma volume, plays a direct and critical role in cardiovascular performance, independent of red cell count. The extra plasma volume is thought to increase the filling pressure of the heart, leading to a more forceful contraction and a higher stroke volume (the amount of blood pumped per beat)—a concept known as the Frank-Starling mechanism. This increased stroke volume allows the cardiovascular system to compensate for a lower oxygen concentration (lower hematocrit) by simply pumping more blood per minute.