12.1: Alveolar Ventilation and Arterial pH

With the help of the buffering systems and renal function, the pulmonary system plays an important role in pH homeostasis. In this chapter we will look at how the lungs contribute to the control of pH, and how failure of the pulmonary system or control of breathing can lead to dangerous deviations in pH.

CO₂ and pH

We will start by revisiting the equation dealt with in the previous chapter in the context of four different clinical scenarios.

Case #1, normal: In the normal situation an increase in tissue metabolism leads to a rise in arterial CO₂, pushing the equation to the right and causing a rise in hydrogen ion concentration and a consequent fall in pH. Both the rise in CO₂ and fall in pH stimulate breathing. This increase in alveolar ventilation leads to a fall in arterial CO₂, pushing the equation back left and lowering hydrogen ions back to normal.

\[\ce{CO2 + H2O <=> H2CO3 <=> H^{+} + HCO3^{-}} \label{eq1} \]

Case #2, metabolic acidosis: CO₂ is by no means the only source of hydrogen ions in the system. Most metabolic pathways result in acidic by-products, and the pulmonary, renal, and buffering systems are generally battling to raise blood and tissue pH back from their tendency to turn acidic. The rise in hydrogen ions resulting from metabolic processes is referred to as metabolic acidosis. The fall in pH stimulates an increase in respiration, which in turn causes a fall in CO₂, and the lower CO₂ drives the equation to the left, reducing the number of H⁺ and thereby raising pH back to normal. Here the pulmonary system has compensated for a metabolic process, and this is referred to as respiratory compensation of metabolic acidosis. The patient may now have a normal blood pH, but the CO₂ will be low. In summary, all the pulmonary system has done is get rid of one source of hydrogen ions (carbonic acid derived from dissolved CO₂) to compensate for another source of hydrogen ions it cannot do anything about (most metabolically driven acids are nonvolatile (i.e., do not vaporize into a gas the lungs can get rid of)).

The advantage of the pulmonary system being involved in pH regulation is that it is quick—a few larger breaths and arterial PCO₂ can be dropped significantly. So the pulmonary system is adept at minute-by-minute (or breath-by-breath) regulation of pH that copes admirably with short-term changes in pH. It is worth noting here that metabolic alkalosis can be reversed by reducing or even stopping breathing, allowing CO₂ to accumulate in the arterial blood and lowering pH back to normal.

The disadvantage to using the pulmonary system for compensation is that it can only mediate its effect via CO₂. So any metabolic acids are eventually dealt with by the renal system, which, although much slower, is capable of excreting any nonvolatile metabolic acids. So through a combination of rapid pulmonary CO₂ expulsion and slower but more versatile renal function, pH is normally maintained within a tight range even in the face of large metabolic changes. The kidney also has the advantage of being able to modify bicarbonate levels, which we will see the importance of when we look at the buffering systems in a moment.

Note

It is worth noting here, especially for the chemists and biochemists among you, that although Equation \ref{eq1} is a reversible reaction, it is open at both ends—the lung being able to expel or retain CO₂ at one end and the kidneys being able to retain or expel hydrogen ions and bicarbonate at the other.

Case #3, respiratory acidosis: Given its capability to influence pH, failure of the lung to expel an appropriate amount of CO₂ can lead to deviations in pH. Let us take a case of severe lung disease, say COPD, for example. The disease has diminished the ability of the lung to expel CO₂, so arterial PCO₂ rises, pushing the equation to the right and causing a fall in pH, referred to as respiratory acidosis. This acid must be immediately buffered until kidney function can be modified to begin secreting the excess hydrogen ions and even produce more bicarbonate to replenish the buffering system, a process referred to as metabolic compensation of respiratory acidosis.

Case #4, respiratory alkalosis: Likewise, if ventilation is inappropriately high with respect to CO₂ production, such as during a period of hyperventilation, then too much CO₂ will be lost and pH will fall. The alkalosis must be immediately buffered to avoid deleterious effects. Over the longer term the kidney can lower the raised pH by reabsorbing hydrogen ions and even excreting bicarbonate buffer—again this is termed metabolic compensation—but this time for an alkalosis caused by an inappropriate respiratory response.