Arterial pH is slightly alkaline (7.4) despite the production of large amounts of acid on a daily basis. This acid production has two forms: volatile acid (carbon dioxide, CO2) and nonvolatile, or fixed, acid. Both volatile and fixed acids are produced in large quantities and present a challenge to the normally alkaline pH.
CO2, or volatile acid, is the end product of aerobic metabolism in the cells and is generated at a rate of 13,000 to 20,000 millimoles daily (mmol/day). CO2 itself is not an acid. However, when it reacts with water (H2O), it is converted to the weak acid carbonic acid, H2CO3:
The reactions show that CO2 combines reversibly with H2O to form H2CO3, catalyzed by the enzyme carbonic anhydrase. H2CO3 dissociates into H+ and HCO3−, and the H+ generated by this reaction must be buffered. Recall that CO2 produced by the cells is added to venous blood, converted to H+ and HCO3− within the red blood cells, and carried to the lungs. In the lungs, the reactions occur in reverse and CO2is regenerated and expired. (CO2 is therefore called a volatile acid.) Thus, buffering of the H+ that comes from CO2 is only a temporary problem for venous blood.
Catabolism of proteins and phospholipids results in the production of approximately 50 mmol/day of fixed acid. Proteins with the sulfur-containing amino acids (e.g., methionine, cysteine, cystine) generatesulfuric acid when they are metabolized, and phospholipids generate phosphoric acid. In contrast with CO2, which is volatile and will be expired by the lungs, sulfuric acid and phosphoric acid are notvolatile. Therefore, fixed acids first must be buffered in the body fluids until they can be excreted by the kidneys.
In addition to sulfuric and phosphoric acids, which are produced from normal catabolic processes, in certain pathophysiologic states, fixed acids can be produced in excessive quantities. These fixed acids include β-hydroxybutyric acid and acetoacetic acid, both ketoacids that are generated in untreated diabetes mellitus, and lactic acid, which may be generated during strenuous exercise or when the tissues are hypoxic. In addition, other fixed acids may be ingested, such as salicylic acid (from aspirin overdose), formic acid (from methanol ingestion), and glycolic and oxalic acids (from ethylene glycol ingestion). Overproduction or ingestion of fixed acids causes metabolic acidosis, as discussed later in the chapter.