Acid-base homeostasis is essential for maintaining normal physiological activities in humans. The pH of various body fluids is strictly regulated because it is critical for the optimal activity of enzymes involved in metabolic reactions. Enzymes are basically proteins, so, any significant change in pH can affect their structure and activity. In humans, pH is regulated using three primary mechanisms— chemical buffer systems, respiratory regulation, and renal regulation.

Respiratory Regulation of pH

CO₂ reacts with water in the blood plasma and body fluids to form carbonic acid— a weak acid that further dissociates into H⁺ and HCO₃⁻ ions. Usually, the levels of CO₂ and carbonic acids are in equilibrium. But when the CO₂ surpasses the normal level, more carbonic acid is produced, making the blood pH acidic. Under such conditions, the brain's respiratory control center prompts the lungs to increase respiration rate, expelling surplus CO₂. This loss of CO₂ lowers blood carbonic acid levels and aids in bringing pH levels back to normal.

In contrast, when the blood pH becomes more alkaline due to an increase in HCO₃⁻ ions, the respiratory center lowers the respiration rate increasing blood CO₂ levels. This further increases the concentration of H⁺ ions, restoring the blood pH to normal level.

Renal Regulation of pH

The kidneys regulate pH through the excretion of waste products in the urine. During acidosis, meaning when the blood pH is acidic, kidneys secrete excess H⁺ ions into the urine. The kidneys then promote the reabsorption of HCO₃⁻ ions in the blood that binds to H⁺ ions producing H₂CO₃ and restoring normal pH. During alkalosis or when the blood pH is alkaline, kidneys release fewer H⁺ ions through urine and limits the reabsorption of HCO₃⁻ ions in the blood. In addition, kidneys remove more ammonia through the urine during alkalosis.