The body's acid–base balance is tightly regulated. Several buffering agents exist which reversibly bind hydrogen ions and impede any change in pH. Extracellular buffers include bicarbonate and ammonia, while proteins and phosphate act as intracellular buffers. The bicarbonate buffering system is especially key, as carbon dioxide (CO) can be shifted through carbonic acid (HCO) to hydrogen ions and bicarbonate (HCO) as shown below.
Acid–base imbalances that overcome the buffer system can be compensated in the short term by changing the rate of ventilation. This alters the concentration of carbon dioxide in the blood, shifting the above reaction according to Le Chateliers principle, which in turn alters the pH. For instance, if the blood pH drops too low (acidemia), the body will compensate by increasing breathing, expelling CO, and shifting the reaction above to the right such that fewer hydrogen ions are free–thus the pH will rise back to normal. For alkalemia', the opposite occurs.
The kidneys are slower to compensate, but renal physiology has several powerful mechanisms to control pH by the excretion of excess acid or base. In responses to acidosis, tubular cells reabsorb more bicarbonate from the tubular fluid, collecting duct cells secrete more hydrogen and generate more bicarbonate, and ammoniagenesis leads to increased formation of the NH buffer. In responses to alkalosis, the kidney may excrete more bicarbonate by decreasing hydrogen ion secretion from the tubular epithelial cells, and lowering rates of glutamine metabolism and ammonia excretion.