Maintaining a normal physiologic acid-base balance is essential for the functioning of every organ system in the body. The renal and pulmonary systems are the primary regulators of acid-base balance. There are four principal acid-base disorders: metabolic acidosis, metabolic alkalosis, respiratory acidosis, and respiratory alkalosis. A systematic approach to evaluation is critical to identify potential etiologies. A history, physical examination, metabolic profile, and arterial blood gas measurement provide a full assessment of acid-base status. However, availability of arterial blood gas measurements is usually limited outside of inpatient and emergency department settings. Calculation of an anion gap is a crucial first step for evaluating laboratory test results. Changes in serum pH, Pco2, serum bicarbonate concentration, and anion gap suggest the primary disorder, and predictable compensatory changes indicate whether a secondary acid-base disturbance is present. Mixed acid-base disorders involving the renal and pulmonary systems can occur, underscoring the importance of a systematic approach to evaluation. In the outpatient setting, primary care physicians play a vital role in identifying and treating these disorders based on initial evaluation. Prompt recognition and management of acid-base disorders can help prevent morbidity and mortality.
Regehr J. Acid-Base and Electrolyte Disorders: Acid-Base Disorders. FP Essent. 2026;565:23-29.
Case 3. CR is a 22-year-old patient with type 1 diabetes. She has had gastroenteritis for the past few days, with frequent episodes of vomiting and decreased oral intake. CR says she reduced the basal rate on her insulin pump because she was afraid of hypoglycemia. You take a careful history and perform a physical examination. CR appears lethargic and her breath has a fruity smell. You obtain blood samples for a metabolic profile and urinalysis to be performed at the office. Urinalysis results show 3+ ketones.
Physiology
Every organ system in the body relies on the physiologic maintenance of normal acid-base status to function.1,2 Serum pH is controlled within a tight range, and any deviation can have potentially fatal adverse effects.1
The renal and pulmonary systems regulate this process via the bicarbonate buffer system in the blood. Carbon dioxide is produced by normal cellular metabolism and a portion of it is eliminated via alveolar ventilation in the lungs.1 Carbon dioxide can be exhaled or retained to maintain a normal serum pH.3 In addition, the body produces a large amount of acid daily, which the kidneys excrete and buffer via ammonia production.4 The kidneys also produce, filter, and reabsorb bicarbonate to help maintain a normal serum pH.1
There are four principal acid-base disorders: metabolic acidosis, metabolic alkalosis, respiratory acidosis, and respiratory alkalosis.5 Acidosis refers to an increase in hydrogen ion concentration, while alkalosis refers to a decrease.
Acidemia refers to a low serum pH (ie, less than 7.35) and alkalemia a high serum pH (ie, greater than 7.45).2 Any disruption that results in a serum pH outside the normal range prompts a predictable compensatory response that does not usually return the serum pH to normal.2 However, the serum pH can be normal when a mixed acid-base disorder is present.6
Initial Evaluation
Evaluation of an acid-base disorder begins with a history and physical examination, which can provide clues to the underlying cause.2 Patient medications should be reviewed carefully because diuretics, laxatives, metformin, and salicylates can cause abnormalities in acid-base balance.7
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