Definition

The acid-base status of the body is carefully regulated to maintain the arterial pH between 7.35 and 7.45 and the intracellular pH between 7.0 and 7.3. This regulation occurs in the setting of continuous production of acidic metabolites and is accomplished by intracellular and extracellular buffering processes in conjunction with respiratory and renal regulatory mechanisms. This chapter reviews the normal physiology of acid-base homeostasis.

Net Acid Production

Both acid and alkali are generated from the diet. Lipid and carbohydrate metabolism results in production of carbon dioxide (CO₂₎, a volatile acid, at the rate of approximately 15,000 mmol/day. Protein metabolism yields amino acids, which can be metabolized to form nonvolatile acid and alkali. Amino acids such as lysine and arginine yield acid on metabolism, whereas the amino acids glutamate and aspartate as well as organic anions such as acetate and citrate generate alkali. Sulfur-containing amino acids (methionine, cysteine) are metabolized to sulfuric acid (H₂SO₄), and organophosphates are metabolized to phosphoric acid (H₃PO₄). In general, animal foods are high in proteins and organophosphates, thereby providing a net acid diet; plant foods are higher in organic anions and provide a net alkaline load. In addition to acid and alkali generated from the diet, there is a small daily production of organic acids, including acetic acid, lactic acid, and pyruvic acid. Also, a small amount of acid is generated by the excretion of alkali into the stool. Under normal circumstances, daily net nonvolatile acid production is approximately 1 millimole (mmol) of hydrogen ions (H⁺) per kilogram (kg) of body weight (Fig. 11-1).

Respiratory System in Regulation of pH

Removal of acid or alkali from the body is accomplished by the lungs and kidneys. The lungs regulate the CO₂ tension (Pco₂), and the kidneys regulate the serum bicarbonate concentration, [HCO₃⁻]. Although the HCO₃⁻-CO₂ buffer system is not the only buffer system, all extracellular buffer systems are in equilibrium. Because serum [HCO₃⁻] is much greater than that of other buffers, changes in the HCO₃⁻-CO₂ buffer pair can easily titrate other buffer systems and thus set pH. The following Henderson-Hasselbalch equation explains how the lungs and kidneys function in concert:

As can be seen, pH is determined by the ratio of HCO₃⁻ to CO₂. Conditions associated with similar fractional changes in [HCO₃⁻] and [CO₂], such as when both are halved, will not change blood pH.

The lungs defend pH by altering alveolar ventilation, which alters the CO₂ excretion rate and thereby controls the arterial CO₂ tension (Paco₂) of body fluids. Systemic acidosis stimulates the respiratory center, resulting in increased respiratory drive that lowers the Paco₂. As a result, the fall in blood pH is less than would have occurred in the absence of respiratory compensation. If the fractional change in Pco₂ were similar to that in serum [HCO₃⁻], blood pH would not change. However, respiratory compensation rarely normalizes blood pH, and thus the fractional change in Pco₂ is less than the change in serum [HCO₃⁻]. Quantitatively, the normal respiratory response in metabolic acidosis is a 1.2 mm Hg decrease in Paco₂ for every 1 mmol/l decrease in HCO₃⁻; the increase in Paco₂ in response to metabolic alkalosis averages 0.7 mm Hg for every 1 mmol/l increase in HCO₃⁻ above baseline.¹

Renal Regulation of pH

Buffer systems and respiratory excretion of CO₂ help maintain normal acid-base balance, but the kidneys provide a critical role in acid-base homeostasis. The kidneys normally generate sufficient net acid excretion (NAE) to balance nonvolatile acid produced from normal metabolism. NAE has three components, titratable acids, ammonium (NH₄⁺), and bicarbonate, and is calculated by the following formula:

NAE=UAmV+UTAV−UHCO3−V

where U_AmV is the rate of NH₄⁺ excretion, U_TAV is the rate of titratable acid excretion, and U_HCO3⁻V is the rate of HCO₃⁻ excretion. Under basal conditions, approximately 40% of NAE is in the form of titratable acids and 60% is in the form of ammonia (NH₃); urinary bicarbonate concentrations and excretion are essentially zero under normal conditions. When acid production increases, the increase in acid excretion is almost entirely caused by an increase in excretion of NH₄⁺.