Metabolic alkalosis is a primary acid-base disorder characterized by an elevated serum bicarbonate (HCO3−) concentration above the normal range of 22 to 26 mEq/L, often exceeding 30 mEq/L in clinically significant cases, resulting in an increase in blood pH above 7.45, which places the body in an alkaline state. This condition is one of the most frequently encountered acid-base disturbances, particularly in critically ill patients, such as those in intensive care units (ICUs). The rise in bicarbonate levels can occur due to a variety of underlying causes, and understanding the etiology and maintenance mechanisms of metabolic alkalosis is crucial for accurate diagnosis and effective treatment.
The disorder often arises as a result of processes that either generate excess bicarbonate or result in a loss of hydrogen ions (H+), such as excessive vomiting, diuretic use, or mineralocorticoid excess. Regardless of the cause, the increase in bicarbonate lowers the arterial hydrogen ion concentration, raising the pH into the alkaline range; this is the primary disturbance, not a compensation. Clinically it helps to separate the process that generates the alkalosis (acid loss, alkali gain, or chloride loss) from the renal process that maintains it, because a normal kidney would otherwise excrete the excess bicarbonate within hours.
Respiratory Compensation
As with other metabolic acid-base disorders, the body attempts to compensate for metabolic alkalosis through the respiratory system. In this case, the compensation occurs via hypoventilation, which leads to an elevation in partial pressure of carbon dioxide (pCO2) in the blood. This hypoventilatory response is designed to retain CO2, which, when combined with water, forms carbonic acid (H2CO3) to help reduce pH. While this compensatory mechanism can reduce the severity of alkalosis, the pH typically remains above 7.45 in uncomplicated cases. The expected response is a rise in PaCO2 of about 0.7 mmHg for each 1 mEq/L rise in serum bicarbonate; it is limited by the hypoxemia that hypoventilation produces, so PaCO2 rarely climbs above 55 to 60 mmHg, and full compensation is never achieved. Pain, anxiety, hypoxemia, sepsis, or a ventilator set to a normal minute ventilation blunt or override this response in perioperative patients, and a patient weaned after a period of alkalosis may hypoventilate to protect the pH.
Chloride and Metabolic Alkalosis
The serum chloride (Cl−) concentration plays an important role in the evaluation of metabolic alkalosis. Typically, a decrease in chloride concentration accompanies the increase in bicarbonate levels, which is independent of sodium (Na+) levels. This reciprocal relationship between bicarbonate and chloride reflects the body's efforts to maintain electrical neutrality. A low serum chloride by itself does not identify the disorder: the kidney also excretes chloride while it retains bicarbonate to compensate for chronic respiratory acidosis, so both conditions present with a high bicarbonate and a low chloride. The pH separates them. In metabolic alkalosis the blood pH is high or at the alkaline end of normal, whereas in compensated chronic respiratory acidosis it is low or at the acidic end of normal with a raised PaCO2. Where the chloride is decisive is in classifying the alkalosis itself: the urine chloride concentration, covered in the companion module, tells chloride-depletion (chloride-responsive) alkalosis apart from the chloride-resistant forms.
