The bicarbonate buffer system is an acid-base homeostatic mechanism involving the balance of carbonic acid (H2CO3), bicarbonate ion (HCO), and carbon dioxide (CO2) in order to maintain pH in the blood and duodenum, among other tissues, to support proper metabolic function. Catalyzed by carbonic anhydrase, carbon dioxide (CO2) reacts with water (H2O) to form carbonic acid (H2CO3), which in turn rapidly dissociates to form a bicarbonate ion (HCO ) and a hydrogen ion (H+) as shown in the following reaction: As with any buffer system, the pH is balanced by the presence of both a weak acid (for example, H2CO3) and its conjugate base (for example, HCO) so that any excess acid or base introduced to the system is neutralized. Failure of this system to function properly results in acid-base imbalance, such as acidemia (pH < 7.35) and alkalemia (pH > 7.45) in the blood. In systemic acid–base balance In tissue, cellular respiration produces carbon dioxide as a waste product; as one of the primary roles of the cardiovascular system, most of this CO2 is rapidly removed from the tissues by its hydration to bicarbonate ion. The bicarbonate ion present in the blood plasma is transported to the lungs, where it is dehydrated back into CO2 and released during exhalation. These hydration and dehydration conversions of CO2 and H2CO3, which are normally very slow, are facilitated by carbonic anhydrase in both the blood and duodenum. While in the blood, bicarbonate ion serves to neutralize acid introduced to the blood through other metabolic processes (e.g. lactic acid, ketone bodies); likewise, any bases (e.g. urea from the catabolism of proteins) are neutralized by carbonic acid (H2CO3). Regulation As calculated by the Henderson–Hasselbalch equation, in order to maintain a normal pH of 7.4 in the blood (whereby the pKa of carbonic acid is 6.1 at physiological temperature), a 20:1 ratio of bicarbonate to carbonic acid must constantly be maintained; this homeostasis is mainly mediated by pH sensors in the medulla oblongata of the brain and probably in the kidneys, linked via negative feedback loops to effectors in the respiratory and renal systems. In the blood of most animals, the bicarbonate buffer system is coupled to the lungs via respiratory compensation, the process by which the rate and/or depth of breathing changes to compensate for changes in the blood concentration of CO2. By Le Chatelier's principle, the release of CO2 from the lungs pushes