It is often assumed that the pulmonary system’s most immediate role is to maintain arterial oxygen, but this is not the case. The primary homeostatic role of the lung is to maintain a constant arterial PCO₂, and the control of breathing in humans is much more directed at this than the maintenance of arterial oxygen.

The reason control of arterial CO₂ is so critical is that it influences arterial pH. Too much CO₂ in the blood and acidosis arises, while too little raises pH to produce an alkalosis. Any deviation from a set point pH of around 7.4 can be highly dangerous as changes in pH rapidly generate changes in protein shape and function. As enzymes, membrane transporters, channels, and more start to lose function, then cellular and systemic function rapidly deteriorates. With its high metabolic rate and critical need to maintain control over its membrane potential, the nervous system is usually the first to suffer when pH changes.

So we now need to look at the relationships between CO₂, arterial pH, and alveolar ventilation. Before starting this chapter you should be completely happy that you have an understanding of pH and what constitutes a weak or a strong acid and reversible reactions.

The Influence of CO₂ on pH

Active cells produce CO₂ through their anerobic and aerobic metabolic pathways. This CO₂ rapidly combines with water in the cytoplasm or plasma to produce carbonic acid. Carbonic acid is a weak acid, meaning that some but not all of it dissociates onto a hydrogen ion and bicarbonate ion. Both these molecules are critical players in the maintenance of pH, and this equation explains why CO₂ influences arterial pH.

Equation 11.1

[latex]CO_2 + H_2O \Leftrightarrow H_2CO_3 \Leftrightarrow H^+ + HCO^-_3[/latex]

It is well worth committing this equation to memory and ensuring you have a good understanding of it as it is not only crucial in pulmonary pH regulation, but you will also see this equation again in renal physiology, gastrointestinal physiology, and other systems. I would argue that this is the most important equation in physiology. But let us look at it in terms of respiratory gases and the pulmonary system.

It is critical to understand that this equation is reversible, so it really describes a balance. If CO₂ at the tissue rises, the reaction is driven to the right, and consequently the amount of hydrogen ion is increased and pH falls. Conversely, if CO₂ falls, then the reaction is driven to the left, so hydrogen ion concentration falls and pH rises. Because the lung has the ability to control the expulsion rate of CO₂ from blood, the lung also has the ability to influence pH.

Physiological Context

Let us look at the most common physiological scenario: a rise in metabolic rate causes an increase in the production of CO₂ by the tissue. This, of course, pushes our equation to the right, and more hydrogen ions are produced. Because of buffering and the way CO₂ is transported in the blood (discussed later on), the rise of PCO₂ and fall of pH in venous blood is usually minimal, but both of these factors are enough to stimulate an increase in ventilation.

This increase in ventilation (more specifically, alveolar ventilation) reduces the alveolar PCO₂. This, along with a raised level of CO₂ in the venous blood, steepens the diffusion gradient from blood to alveolus. Consequently more CO₂ is transferred to the airways and expelled. This lowers blood CO₂, driving our equation back toward the left, lowering hydrogen ion concentration and returning pH back to normal.

Because of the importance of maintaining normal CO₂ (and thereby pH), alveolar ventilation exponentially increases with decreasing pH. Put simply, the ventilation control mechanisms use negative feedback reflexes to generate the appropriate level of ventilation to keep CO₂ and pH constant. Put even more simply, CO₂ is a source of acid, and the more you breathe the more CO₂ you lose, so pH rises with increased ventilation.

Summary

So now you should be able to predict what will happen to blood pH with a change in PCO₂, and what the ventilatory response should be to maintain pH at a constant level.

These basic principles form the foundation to understanding common and serious clinical situations of metabolic and respiratory acidosis and alkalosis, and how compensation normally prevents deviation from a safe but narrow pH range.