title: Disturbances in acid-base balance during hypophosphatemia and phosphate depletion.
abstract: Phosphate depletion leads to bone resorption, resulting in the accession of alkali to the blood and urine. There may also be a release of lactic acid from liver, resulting from ATP depletion and intracellular alkalosis. In general, the net result of these tissue effects is an alkali load discharged into the extracellular fluid. In the kidneys, phosphate depletion causes impaired proximal tubular reabsorption of bicarbonate, and perhaps other substrates, owing in all likelihood to both intracellular alkalosis and depletion of ATP. This impaired proximal capacity to reclaim bicarbonate results in hyperchloremic acidosis. The distal nephron may contribute to acidosis by virtue of inability to produce titratable acid (phosphate-free urine) and perhaps impaired ammonia production. Severe phosphate depletion, therefore, tends to produce hyperchloremic acidosis as a result of a diminished capacity for bicarbonate reclamation in the proximal tubule and probably some impairment of bicarbonate regeneration in the distal nephron. These effects, when marked, ultimately outweigh the contribution of alkali coming from bone breakdown. In the liver, phosphate depletion may stimulate lactic acid production by reducing hepatic ATP stores (Pasteur effect) and producing intracellular alkalosis. ATP depletion may also limit hepatic uptake of lactate. Finally, in muscle cells ATP depletion, resulting from either profound hypophosphatemia or the metabolism of massive fructose loads, may eventuate in frank rhabdomyolysis.
mesh_terms: D000137:Acid-Base Imbalance / Q000209:etiology*; D000468:Alkalies / Q000378:metabolism; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D005632:Fructose / Q000378:metabolism; D006801:Humans; D007015:Hypophosphatemia, Familial / Q000150:complications* / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D010710:Phosphates / Q000172:deficiency* / Q000378:metabolism
chemical_list: D000468:Alkalies; D010710:Phosphates; D005632:Fructose