The cellular metabolism of other dietary constituents also has an impact on acid-base balance. For example, cysteine and methionine, sulfur-containing amino acids, yield sulfuric acid when metabolized, whereas hydrochloric acid results from metabolism of lysine, arginine, and histidine. A portion of this nonvolatile acid load is offset by production of HCO3 − through metabolism of the amino acids aspartate and glutamate. On average the metabolism of dietary amino acids yields net nonvolatile acid production. Metabolism of certain organic anions (e.g., citrate) results in production of HCO3 − , which offsets nonvolatile acid production to some degree. Overall in individuals ingesting a meat-containing diet, acid production exceeds HCO3 − production. In contrast, a vegetarian diet produces less nonvolatile acid. In addition to the metabolically derived acids and alkalis, the foods ingested contain acid and alkali. For example, the presence of phosphate (H2PO4 −) in ingested food increases the dietary acid load. Finally, during digestion, some HCO3 − is normally lost in feces. This loss is equivalent to the addition of nonvolatile acid to the body. In an individual ingesting a meat-containing diet, dietary intake, cellular metabolism, and fecal HCO3 − loss result in addition of approximately 0.7 to 1.0 mEq/kg body weight of nonvolatile acid to the body each day (50–100 mEq/day for most adults). This acid, referred to as net endogenous acid production (NEAP), results in an equivalent loss of HCO3 − from the body that must be replaced.
Wheninsulinlevelsarenormal,carbohydratesandfatsarecompletelymetabolizedtoCO2+ H2O.However,ifinsulinlevelsareabnormallylow(e.g.,diabetesmellitus),cellularmetabolismleadstoproductionofseveralorganicketoacids(e.g.,β-hydroxybutyricacidandacetoaceticacidfromfattyacids).
IntheabsenceofadequatelevelsofO2(hypoxia),anaerobicmetabolismbycellscanalsoleadtoproductionoforganicacids(e.g.,lacticacid)ratherthanCO2+ H2O.Thisfrequentlyoccursinnormalindividualsduringvigorousexercise.Poortissueperfusion,suchasoccurswithreducedcardiacoutput,canalsoleadtoanaerobicmetabolismbycellsandthustoacidosis.IntheseconditionstheorganicacidsaccumulateandthepHofbodyfluidsdecreases(acidosis).Treatment(e.g.,administrationofinsulininthecaseofdiabetes)orimproveddeliveryofadequatelevelsofO2totissues(e.g.,inthecaseofpoortissueperfusion)resultsinthemetabolismoftheseorganicacidstoCO2+ H2O,whichconsumesH+ andtherebyhelpscorrecttheacid-basedisorder.
Nonvolatile acids do not circulate throughout the body but are immediately neutralized by the HCO3 − in ECF.
Equation 37.5
Equation 37.6
This neutralization process yields the Na+ salts of the strong acids and removes HCO3 − from the ECF. Thus HCO3 − minimizes the effect of these strong acids on the pH of ECF. As noted previously, ECF contains approximately 350 mEq of HCO3 − . If this HCO3 − were not replenished, the daily production of nonvolatile acids (≈70 mEq/day) would deplete the ECF of HCO3 − within 5 days. To maintain acid-base balance the kidneys must replenish the HCO3 − lost by neutralization of the nonvolatile acids, a process termed renal net acid excretion (RNAE).
Net Acid Excretion by the Kidneys