Acid-base homeostasis pathway

Acid-base homeostasis is a critical physiological process that maintains the pH of extracellular fluid within a narrow range, typically 7.35 to 7.45, to ensure optimal protein function and cellular metabolism (StatPearls, 2023). This pathway is regulated by three primary mechanisms: chemical buffering systems (primarily the bicarbonate/CO2 buffer), respiratory compensation via CO2 excretion, and renal compensation through the secretion of hydrogen ions and reabsorption of bicarbonate (NIH, 2022). Key molecular players include the carbonic anhydrase (CA) enzyme family, which facilitates the interconversion of CO2 and water into carbonic acid, and various membrane transporters like the SLC4 family of bicarbonate transporters and the SLC9 family of sodium-hydrogen exchangers (NHE) (PubMed, 2021). Dysregulation of this pathway results in acid-base disturbances such as metabolic or respiratory acidosis and alkalosis, which are often associated with chronic kidney disease, respiratory failure, or metabolic disorders (StatPearls, 2023). Therapeutic strategies targeting this pathway involve the use of CA inhibitors like acetazolamide for glaucoma and altitude sickness, or diuretics that influence ion transport in the nephron to correct systemic pH imbalances (PubChem, 2024).

Other names

pH regulationAcid-base balanceAcid-base regulation system

Pharmacological agents interact with this pathway by inhibiting carbonic anhydrase enzymes to prevent bicarbonate reabsorption or by blocking sodium-hydrogen exchangers and other ion transporters to modulate the secretion of protons and bicarbonate in the kidneys and other tissues (StatPearls, 2023; PubChem, 2024).