Regulation of normal pH (7.35-7.45) depends on both the lungs and kidneys (Fig. 1-5). By the Henderson-Hasselbalch equation, pH is a function of the ratio of HCO₃^- (regulated by the kidney) to PCO₂ (regulated by the lungs). The HCO₃/PCO₂ relationship is useful in classifying disorders of acid-base balance. Acidosis is due to gain of acid or loss of alkali; causes may be metabolic (fall in serum HCO₃^-) or respiratory (rise in PCO₂). Alkalosis is due to loss of acid or addition of base and is either metabolic (↑ serum [HCO₃^-]) or respiratory (↓ PCO₂).

To limit the change in pH, metabolic disorders evoke an immediate compensatory response in ventilation; full renal compensation for respiratory disorders is a slower process, such that “acute” compensations are of lesser magnitude than “chronic” compensations. Simple acid-base disorders consist of one primary disturbance and its compensatory response. In mixed disorders, a combination of primary disturbances is present.

The cause of simple acid-base disorders is usually obvious from history, physical examination, and/or basic laboratory tests. Initial laboratory evaluation depends on the dominant acid-base disorder, but for metabolic acidosis and alkalosis this should include electrolytes, BUN, creatinine, albumin, urinary pH, and urinary electrolytes. An arterial blood gas (ABG) is not always required for pts with a simple acid-base disorder, e.g., mild metabolic acidosis in the context of chronic renal failure. However, concomitant ABG and serum electrolytes are necessary to fully evaluate more complex acid-base disorders. The compensatory response should be estimated from the ABG; Winter's formula [PaCO₂ = (1.5 × [HCO₃^-]) + 8 ± 2] is particularly useful for assessing the respiratory response to metabolic acidosis. The anion gap should also be calculated; the anion gap = [Na⁺] - ([HCO₃^-] + [Cl^-]) = unmeasured anions - unmeasured cations. The anion gap should be adjusted for changes in the concentration of albumin, a dominant unmeasured anion; the “adjusted anion gap” = anion gap + ~2.5 × (4 - albumin mg/dL). Other supportive tests will elucidate the specific form of anion-gap acidosis (see below).