The Controller and Acid-Base Physiology: An Introduction to a Complex Process

Carbon Dioxide-Carbonic Acid-Bicarbonate Buffer System

As noted, the primary extracellular buffer is bicarbonate via its role in the carbon dioxide-carbonic acid-bicarbonate system. In its gaseous form, carbon dioxide dissolves in the aqueous portion of blood to form carbonic acid. The amount of carbon dioxide that dissolves in the blood is proportional to the partial pressure of carbon dioxide in solution, that is, the P_aCO₂, which in a normal person is the same as the alveolar PCO₂. At normal body temperature (37°C), the amount of carbon dioxide that dissolves in blood is:

Assuming a normal arterial PCO₂:

Some of the dissolved carbon dioxide combines with water to form carbonic acid. Given the chemical equilibrium between dissolved carbon dioxide and carbonic acid:

You can use the dissolved carbon dioxide as a marker for the amount of carbonic acid in the blood.

The Henderson-Hasselbalch equation defines the dissociation relationship for weak acids:

For the carbon dioxide-carbonic acid system, this can be written:

Note that in this equation, the relationship for dissolved CO₂ is used where the concentration of acid is found. This convention is used because the concentration of carbonic acid is difficult to measure, and PCO₂, which is easily measured, is in equilibrium with carbonic acid. The ratio of dissolved CO₂ to carbonic acid at body temperature is approximately 400 to 1. The pKa of carbonic acid is 3.5. When adjusted for the use of dissolved CO₂ as a marker for carbonic acid, the relationship becomes:

To achieve a normal pH in blood, the ratio of [HCO₃^-] to the amount of dissolved carbon dioxide in the blood must equal 20 (log of 20 = 1.3). A normal bicarbonate concentration is 24 meq/L, and a normal P_aCO₂ is 40 mm Hg, which results in a ratio of 20.

In the end, we have a gas, carbon dioxide, which, while not an acid itself, leads to the production of carbonic acid once dissolved in water. Problems that lead to an increase in P_aCO₂ result in the accumulation of acid. Conversely, as acid builds up in the system and is buffered by bicarbonate to form carbonic acid, the respiratory system offers an incredibly fast and efficient system for eliminating the acid. By hyperventilating and lowering P_aCO₂, the body causes the equilibrium to shift to the left, allowing further buffering to occur. This response is made possible because of the physiology of the controller, as discussed in Chapter 6. The increase in hydrogen ion concentration stimulates the chemoreceptors, which trigger an increase in ventilation. Whereas nonbicarbonate buffers are limited by the quantity of the buffer and the pH, the capacity of the carbon dioxide-carbonic acid-bicarbonate system is determined primarily by the concentration of bicarbonate. The ability to modify pH by changing ventilation thus enhances the effectiveness of this buffering system.