The acid-base balance in the body is influenced by the cellular metabolism of various dietary components. For instance, sulfur-containing amino acids like cysteine and methionine produce sulfuric acid when they are metabolized, while lysine, arginine, and histidine metabolism results in the production of hydrochloric acid. Aspartate and glutamate metabolism generates HCO3 −, which helps counterbalance the nonvolatile acid load. On average, the metabolism of dietary amino acids leads to a net production of nonvolatile acid. The metabolism of certain organic anions, such as citrate, also contributes to the production of HCO3 −, partially offsetting the nonvolatile acid production. Overall, individuals who consume a meat-containing diet produce more acid than HCO3 −. On the other hand, a vegetarian diet produces less nonvolatile acid. Additionally, the foods we eat contain acid and alkali components. For instance, phosphate (H2PO4 −) in ingested food increases the dietary acid load. During digestion, some HCO3 − is normally lost in feces, which adds nonvolatile acid to the body. In individuals who consume a meat-containing diet, the combination of dietary intake, cellular metabolism, and fecal HCO3 − loss leads to the 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, known as net endogenous acid production (NEAP), results in a corresponding loss of HCO3 − that needs to be replaced.

When insulin levels are normal, carbohydrates and fats are fully metabolized into CO2+ H2O. However, if insulin levels are abnormally low, such as in diabetes mellitus, cellular metabolism produces various organic ketoacids from fatty acids, including β-hydroxybutyric acid and acetoacetic acid. In the absence of sufficient O2 levels (hypoxia), anaerobic metabolism by cells can also lead to the production of organic acids, like lactic acid, instead of CO2+ H2O. This often occurs in normal individuals during intense exercise. Poor tissue perfusion, as observed with reduced cardiac output, can also result in anaerobic metabolism by cells, leading to acidosis. In these conditions, organic acids accumulate, causing a decrease in the pH of body fluids (acidosis). Treatment, such as insulin administration in the case of diabetes, or improved delivery of adequate O2 levels to tissues, as in the case of poor tissue perfusion, helps convert these organic acids into CO2+ H2O. This process consumes H+ and aids in correcting the acid-base disorder.

Nonvolatile acids do not circulate throughout the body but are immediately neutralized by the HCO3 − in extracellular fluid (ECF). This neutralization process produces the Na+ salts of the strong acids and removes HCO3 − from the ECF. Thus, HCO3 − limits the impact of these strong acids on the pH of ECF. As mentioned earlier, ECF typically contains around 350 mEq of HCO3 −. If this HCO3 − were not replenished, the daily production of nonvolatile acids (approximately 70 mEq/day) would deplete the ECF of HCO3 − within 5 days. To maintain acid-base balance, the kidneys must replenish the HCO3 − lost through neutralization of the nonvolatile acids, a process called renal net acid excretion (RNAE).
Net Acid Excretion by the Kidneys
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