Metabolic acidosis is characterized by an increase in [H⁺], a decrease in serum [] and blood pH, and a secondary decrease in Pco₂ as a result of secondary hyperventilation. The expected decrease in Pco₂ in dogs with metabolic acidosis may be estimated as 0.7 mm Hg for each 1-mEq/L decrease in [].¹⁶ Cats with experimentally induced metabolic acidosis consistently show a lack of ventilatory compensation. In one study in which cats were chronically fed a diet containing NH₄Cl, significant decreases in pH and [] were observed, but there was no change in Pco₂.⁹ Similar results were obtained in another study also adding NH₄Cl to the diet³¹ and with dietary phosphoric acid supplementation.¹⁹ Contrary to what happens in dogs and humans, the feline kidney apparently is unable to adapt to metabolic acidosis and does not increase production of ammonia or glucose from glutamine during acidosis.³¹ Based on these studies, cats may not compensate for metabolic acidosis to the same extent (if at all) as do dogs and humans. Thus formulas for dogs or humans should not be extrapolated for use in cats. The clinical finding of metabolic acidosis and normal Pco₂ in a cat should not be interpreted as evidence of a mixed process until more data are available about respiratory compensation in cats.

Metabolic alkalosis is characterized by a decrease in [H⁺], an increase in serum [] and blood pH, and a secondary increase in Pco₂ as a result of compensatory hypoventilation. As a rule of thumb, a 1.0-mEq/L increase in plasma [] is expected to be associated with an adaptive 0.7-mm Hg increase in Pco₂ in dogs with metabolic alkalosis.¹⁶ Little is known about respiratory compensation in cats with metabolic alkalosis. In one study with 12- to 14-week-old kittens made alkalotic by selective dietary chloride depletion, a 1.0-mEq/L increase in plasma [] concentration was associated with a 0.7-mm Hg increase in Pco₂.⁶² This value is remarkably similar to that observed in humans and dogs, but care should be exercised when extrapolating data from normal kittens to sick adult cats.

Time is an important consideration when assessing compensation. Even in the experimental setting in which sudden changes in [] can be achieved, the respiratory response to acute metabolic acidosis in dogs occurs slowly, and it often takes 17 to 24 hours for maximal respiratory compensation to develop.¹⁶ Thus using the formulas within the first 24 hours of onset of metabolic acidosis may lead to an underestimation of the ventilatory response and the erroneous assumption that a mixed metabolic and respiratory disorder is present.

Metabolic compensation in respiratory processes

Respiratory acidosis is that acid-base disorder resulting from a primary increase in carbon dioxide tension (Pco₂) in the blood. It is synonymous with primary hypercapnia and is characterized by increased Pco₂, increased [H⁺], decreased pH, and a compensatory increase in [] in blood. Respiratory alkalosis is that acid-base disorder resulting from a primary decrease in Pco₂ in the blood. It is synonymous with the term primary hypocapnia and is characterized by decreased Pco₂, decreased [H⁺], increased pH, and a compensatory decrease in [] in blood.

Adaptive changes in plasma [] occur in two phases. In respiratory acidosis, the first phase represents titration of nonbicarbonate buffers, whereas in respiratory alkalosis, the first phase represents release of H⁺ from nonbicarbonate buffers within cells. This response is completed within 15 minutes (see Chapter 11). The second phase reflects renal adaptation and consists of increased net acid excretion and increased reabsorption (decreased Cl⁻ reabsorption) in respiratory acidosis and a decrease in net acid excretion in respiratory alkalosis. Experimentally, renal adaptation requires 2 to 5 days for a chronic steady state to be established.^21,^46,⁵¹

During acute respiratory acidosis, a compensatory increase of 0.15 mEq/L in [] for each 1-mm Hg increase in Pco₂ should be expected in dogs.¹⁶ There is a lack of data for compensation in cats with acute respiratory acid-base disorders, but values appear to be similar to those observed in dogs. In anesthetized, artificially ventilated cats made hypercapnic by exposure to increasing CO₂ levels, the average compensatory increase in [] was 0.07 to 0.1 mEq/L for each 1-mm Hg increase in Pco₂.^24,⁵⁴ In three awake cats exposed to an FIco₂ of 4%,⁵³ [] increased 0.16 mEq/L for each 1-mm Hg increase in Pco₂, a value very similar to the one observed in dogs. During acute respiratory alkalosis, a compensatory decrease of 0.25 mEq/L in [] for each 1-mm Hg decrease in Pco₂ should be expected in dogs.¹⁶ Compensation to hyperventilation has only been studied in anesthetized cats. The [] decreased an average 0.26 mEq/L for each 1-mm Hg decrease in Pco₂, a value similar to that obtained in dogs.²⁴

In dogs with chronic respiratory alkalosis, a decrease of 0.55 mEq/L in [] is expected for each 1-mm Hg decrease in Pco₂.^2,¹⁶ It is interesting to note that even in severe chronic respiratory alkalosis, the pH usually is normal. However, the normalization of pH in a clinical setting may take longer than 5 to 7 days. In humans with sustained respiratory alkalosis, the pH may not return to normal for 2 or more weeks.⁴⁰ Cats chronically exposed to a hypoxic environment (FIo₂ = 10%) for 28 days also were able to maintain a normal arterial pH.⁴ Expected compensation in cats cannot be inferred from this study, but based on the ability to maintain a normal pH, it may be reasonable to assume that cats can compensate for chronic respiratory alkalosis as well as dogs and humans. In dogs with chronic respiratory acidosis, serum [] increases 0.35 mEq/L for each 1-mm Hg increase in Pco₂.¹⁶ Similar rules have been used in humans with chronic respiratory acidosis, but these rules have been shown to work well in unstable, but not in stable, patients with long-standing respiratory acidosis.³⁵ In this latter group of patients, a 0.51-mEq/L increase in [] is expected for each 1-mm Hg increase in Pco₂.³⁵ Thus arterial pH appears to remain near reference ranges in human patients with long-standing respiratory acidosis.³ Similar results have been observed in dogs with chronic respiratory acidosis and no other identifiable reason for increased [] concentration other than renal compensation.^22,²⁵ Increases of 0.45²⁵ to 0.57 mEq/L²² [] for each 1-mm Hg increase in Pco₂ have been observed in dogs with chronic respiratory acidosis, suggesting that renal compensation in dogs with long-standing respiratory acidosis may return arterial pH to normal in stable patients.