Ventilation: Metabolism's Gateway

One of the oldest methods to gauge exercise intensity, that many still swear by today, is the talk test. If you can have a conversation while exercising, you’re in Zone 2. If you can only get out a few words, you’re in Zone 4. In reality, the talk test is simply a low-tech way of measuring ventilation – that is, the volume of air flowing in and out of your lungs.

The talk test works because there is a strong correlation between ventilation and exercise intensity. When the work is light, so is ventilatory drive, which means you can easily get out full sentences in between breaths. As work increases, so does ventilation, making it harder to find spaces to speak. And at the highest intensities, it can become virtually impossible to control your breath long enough to utter a single word, as the neural drive to inhale and exhale dominates.

This is all due to ventilation’s role as the gateway to both the beginning and end of the metabolic cycle that produces the energy needed for exercise. You breathe in oxygen required by the muscles to produce ATP and you exhale carbon dioxide as a byproduct of the energy production process – if you stop either of these processes you cannot go on. Given this, ventilation has been used by researchers to assess exercise intensity since the mid 19^th century. And since the main function of VTCheck is to automatically and objectively quantify and analyze ventilation, understanding the primary drivers of breathing during exercise can help users interpret the data they get from their training.

Primary drivers of ventilation

The primary drivers of ventilation can be broadly categorized in two buckets – (1) Direct Metabolic Triggers and (2) Indirect Metabolic Triggers.

Direct Metabolic Triggers

Although ventilation controls the flow of both oxygen and CO₂, it is the need to expel CO₂ that drives breathing in most scenarios. There are specialized sensors throughout the body that detect the level of CO₂ in the blood which send signals to the brain to stimulate ventilation when CO₂ levels are elevated. This is a critical mechanism because CO₂ regulation is the primary way the body maintains pH balance.

Many bodily functions depend on the body keeping blood pH within a narrow band, normally 7.35 to 7.45. This delicate balance is primarily achieved by shifting the equilibrium that naturally occurs in the body between (a) carbon dioxide (CO₂) and water (H₂O), on the one hand, and (b) hydrogen ions (H⁺) and bicarbonate (HCO₃⁻), on the other hand.

Two ponds connected by a stream illustrate shifts between CO₂ plus water and H⁺ plus bicarbonate. — The above diagram visualizes the process of how the body maintains pH balance. Because the two ponds are connected by a stream, they have a natural inertia to stabilize at the same water level. When the body accelerates CO₂ production (represented by the rain over Pond A), Pond A overflows to Pond B, increasing H⁺, and vice-versa. And when the body accelerates CO₂ removal via increased ventilation (represented by the drain under Pond A), Pond B overflows to Pond A, decreasing H⁺, and vice-versa. Note: The kidneys also support pH balance by excreting acid and conserving bicarbonate, but their slower response contributes relatively little to the rapid pH adjustments needed during exercise.

The operative molecule that alters pH balance is H⁺, which is an acid. When H⁺ accumulates, pH goes down. When H⁺ dissipates, pH goes up. And the main way the body modulates H⁺ levels is by controlling the amount of CO₂ in the body through ventilation. When pH gets too low, the brain stimulates ventilation to expel more CO₂, which in turn causes H⁺ and bicarbonate to convert to CO₂ and water to maintain an equilibrium, which raises pH. And if pH gets too high, breathing slows down, causing CO₂ to accumulate, which then combines with water and is converted to H⁺ and bicarbonate, lowering pH.

So what does this have to do with exercise?

When the body initiates movement for exercise it requires energy, in the form of ATP, to contract muscles. ATP is primarily produced by breaking down fats and carbs, either aerobically (i.e. with oxygen) in the mitochondria, or, with respect to carbs, anaerobically (i.e. without oxygen) outside the mitochondria. These processes produce CO₂ and H⁺ as byproducts and being able to balance the two is essential for endurance exercise because, as mentioned earlier, many bodily functions can only optimally operate within a narrow band of pH. This includes enzymes, which are needed for metabolic function, and muscles, where acidity can inhibit both activation and contraction.

CO₂ Accumulation: The end products of the oxidation of fats or carbs within the mitochondria are ATP (energy), CO₂ (byproduct) and water (byproduct). If the brain didn’t stimulate ventilation to expel this additional CO₂, the CO₂ would accumulate above resting levels. That accumulation of CO₂ would then cause H⁺ to rise due to the natural equilibrium that occurs between these two molecules as we just discussed. And because H⁺ is an acid, this in turn would cause pH to drop. To avoid this, the brain increases ventilation alongside rising energy demand, helping expel the additional CO₂ before it accumulates.

Glucose passes through glycolysis and mitochondrial metabolism. The diagram identifies ATP formation, CO₂ release, oxygen reduction to water, and H⁺ released with ATP use. — Glucose Aerobic Pathway: (1) Glucose is broken down into pyruvate through glycolysis, generating ATP. (2) Pyruvate enters the mitochondria and is converted into acetyl-CoA, releasing CO₂. (3) Acetyl-CoA enters the Krebs cycle, generating ATP, releasing CO₂, and transferring hydrogen and electrons to carriers. (4) These carriers deliver electrons to the electron transport chain. The movement of electrons along the chain provides the energy to pump H⁺ across the membrane; H⁺ then flows back through ATP synthase, powering ATP production. At the end of the chain, oxygen combines with electrons and H⁺ to form water. Fat enters the same downstream mitochondrial pathway as acetyl-CoA.

H⁺ Accumulation: In addition to H⁺ being produced via conversion from CO₂, H⁺ can also be produced in a few other ways during the energy production process, primarily through the breakdown of ATP, which releases H⁺. At lower intensities, this additional H⁺ is cleared relatively easily through a variety of mechanisms, including expelling CO₂ via increased ventilation (as we just discussed) and mitochondrial metabolism, which includes reactions that combine H⁺, O₂ and electrons to form water. However, at a certain point, commonly known as the first lactate threshold, the aerobic threshold or ventilatory threshold 1, the release of H⁺ from energy production begins to exceed your body’s mechanisms of clearance. This occurs, in significant part, because as energy demands increase, relative contribution to ATP from anaerobic glycolysis rises due to the slower pace of mitochondrial processing of fats and carbs. This results in a mismatch between (a) ATP breakdown, which accumulates H⁺, and (b) oxidation of fats/carbs in the mitochondria, which consumes H⁺. As discussed, when H⁺ accumulates, pH begins to drop and a signal is sent to the brain to stimulate ventilation further. This draws out more CO₂ from the blood thereby causing H⁺ and bicarbonate to be converted to CO₂ and water to maintain an equilibrium.

Glycolysis produces ATP, pyruvate and NADH. Conversion of pyruvate to lactate consumes H⁺ and converts NADH back to NAD⁺, which returns to glycolysis. ATP use is shown separately as a source of H⁺. — During harder exercise, glycolysis can generate pyruvate faster than the mitochondria can process pyruvate aerobically. Converting pyruvate to lactate allows glycolysis to continue generating ATP because glycolysis requires NAD⁺, which is converted to NADH during the conversion of glucose into pyruvate and then recycled back into NAD⁺ during the conversion of pyruvate into lactate. Lactate can then be shuttled to other muscle fibers or organs, where it is used aerobically to generate ATP.

Indirect Metabolic Triggers

Although ventilation is primarily driven by the need for the body to expel CO₂ from pH disturbances caused by the energy production process, ventilation can also be impacted by other factors that are indirectly related to, but not necessarily triggered by, metabolism.

Central Command: Ventilation, along with the muscular and cardiovascular systems, are controlled by the brain through a system commonly referred to as central command. This system allows for coordinated synchronization of all the activities/processes within the body that are needed for spontaneous movement. As a way of minimizing delay between the mind and body, the brain can trigger an increase in ventilation in anticipation of metabolic demand. Additionally, the brain can trigger elevated ventilation levels independent of metabolic demand, for example, when in pain or under significant stress.

Muscle Afferents: Muscle afferents are sensors located in skeletal muscle that monitor local stress levels in and around the muscles and report this information to the brain and spinal cord. This stress may include metabolic disturbances, such as pH imbalances discussed above, or mechanical stress/damage in the muscle itself. The signals sent by muscle afferents can directly stimulate breathing via the nervous system, helping match ventilation to the activity and conditions within the muscles, even without an increase in CO₂ production or acidity. In this way, muscle afferents represent “bottom up” control of breathing in contrast to central command’s “top down” control.

Heat: Similar to muscle afferents, there are sensors in the neck that can trigger increased ventilation via the nervous system when core temperature rises. And this effect can be exacerbated when the athlete is dehydrated due to reduced sweating, making it harder to shed heat. Although heat can increase ventilation independent of metabolic demand, it is connected to metabolism in several ways. For one, when ATP is broken down to create energy, some of that energy is lost through heat. So the more intense the exercise is, the more ATP that is broken down, which generates more heat, raising core temperature. And when core temperature is elevated, one of the ways the body cools itself down is by pushing blood to the skin, which allows some of that heat to escape into the air. This increases energy expenditure, for example, by increasing heart rate. It can also reduce aerobic energy production through the reduction of blood flow, and therefore O₂, to the muscles. The body has two compensatory mechanisms to mitigate this effect - (1) by increasing heart rate to push more total blood through the body to address both heat dissipation and the oxygen demands of exercise, and (2) by the muscles extracting additional O₂ from the blood. However, at higher intensities, these compensatory mechanisms may be insufficient to maintain O₂ uptake at the muscles, thereby limiting aerobic energy production.

Application

If you’ve made it this far, you may be wondering what the point is of knowing all these physiological processes if you just want to improve your endurance performance. Well, although we know that all the aforementioned factors can impact ventilation, what we don’t know is which of these factors are impacting the ventilation of a given athlete during a specific workout on a given day. Understanding the underlying physiological factors that drive ventilation can help the athlete interpret the data in the context of his recent training and unique characteristics. This will then allow the athlete to make reasonable inferences from the data to target desired adaptations, manage fatigue and assess condition. We will discuss specifically how to apply this physiological knowledge to interpret data from VTCheck in future blogs.