The nephron, the kidney’s basic structural and functional unit, is responsible for the purification and filtration of the blood. During filtration, bicarbonates leave the blood and become part of nephron filtrate, including water, electrolytes, glucose, amino acids, vitamins, small proteins, creatinine, and urea. As these substances pass through the nephron, many of them are selectively reabsorbed and returned to the blood, including sodium and bicarbonate ions.   Other substances are secreted into the filtrate from the surrounding cells and capillaries, such as hydrogen and ammonium ions. Carbon dioxide plays the key role both in the return of bicarbonates from the filtrate back into the blood, and the synthesis of new bicarbonates lost through the buffering of unutilized hydrogen ions, generated during protein metabolism.

Carbon dioxide and H₂O, in the filtrate, diffuse into the tubular cells that surround the filtrate, to form carbonic acid:

CO₂ + H₂O ↔ H₂CO₃.   Just as in the case of red blood cells, carbonic acid dissociates into hydrogen and bicarbonate ions: H₂CO₃ ↔ H⁺ + HCO₃‾. The bicarbonates in tubular cells are transported into the surrounding capillaries, and are thus fully reclaimed for general circulation (bicarbonate reclamation). The hydrogen ions in these cells are transported into the filtrate in exchange for sodium ions. Sodium ions in the tubular cells, together with the bicarbonate ions, are co-transported to the capillaries, and thus returned to general circulation.   And, the hydrogen ions, now in the filtrate, combine with more bicarbonate ions in the filtrate to form carbonic acid: H⁺ + HCO₃‾ ↔ H₂CO₃.   The carbonic acid in the filtrate dehydrates into CO₂ and H₂O, which then diffuse into the same tubular cells, where once again they form carbonic acid in the tubular cells, and the cycle begins anew. A nearly identical process, also requiring CO₂, provides for the synthesis of new bicarbonates that replace the ones lost in the buffering of acids generated during protein metabolism (bicarbonate regeneration). In this case, however, H⁺ in the filtrate is combined with sodium phosphate and excreted, rather than being utilized in the formation of H₂O reabsorbed by tubular cells.

Overbreathing results in CO₂ deficit in the kidneys, which means that less bicarbonate is recovered from the filtrate, and new bicarbonate is no longer formed. This may mean that bicarbonate ions, crucial to the buffering of metabolic acids, such as lactic acid produced during exercise, are depleted. The consequences may include (1) compromised physical endurance in sports and fitness enthusiasts, and (2) the appearance of fatigue symptoms associated with chronic stress, where adequate buffering of even small amounts of lactic acid is compromised. The exchange of hydrogen ions for sodium ions is also reduced, and may contribute to development of sodium deficiency and its associated symptoms.

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