NEAP must be equal to RNAE in order to maintain acid-base balance under steady-state conditions. Although NEAP varies between individuals and from day to day in each individual, it is not regulated. Instead, the kidneys regulate RNAE to match NEAP and replenish the lost HCO3- (new HCO3-) resulting from the neutralization of nonvolatile acids. Additionally, the kidneys must prevent the loss of HCO3- in urine, which is quantitatively more significant due to the higher filtered load of HCO3- (approximately 4320 mEq/day) compared to the 50 to 100 mEq/day required to balance NEAP.

The nephrons accomplish both the reabsorption of filtered HCO3- and the excretion of acid through H+ secretion. As a result, the nephrons must secrete approximately 4390 mEq of H+ into the tubular fluid within a day. Most of the secreted H+ serves to reabsorb the filtered load of HCO3-. Only 50 to 100 mEq of H+, equivalent to NEAP, is excreted in urine. Consequently, urine is normally acidic due to this acid excretion.

The kidneys are unable to excrete urine more acidic than pH 4.0 to 4.5. Even at a pH of 4.0, only 0.1 mEq/L of H+ can be excreted. Therefore, in order to excrete sufficient acid, the kidneys excrete H+ with urinary buffers such as phosphate (Pi). Other constituents of urine can also act as buffers, although their role is less significant than Pi. The various urinary buffers are collectively referred to as titratable acid, as they are quantitated in the laboratory by adding alkali (OH-) to a urine sample to titrate its pH to that of plasma (7.4). The amount of alkali added represents the H+ titrated by these urine buffers and is known as titratable acid.

Excretion of H+ as titratable acid alone is not sufficient to balance NEAP. An important additional mechanism by which the kidneys contribute to acid-base balance is through the synthesis and excretion of ammonium (NH4+). The details of the mechanisms involved in this process will be discussed later in this chapter. Each NH4+ excreted in urine leads to the return of one HCO3- to the systemic circulation, replenishing the HCO3- lost during the neutralization of nonvolatile acids. Thus, the production and excretion of NH4+, similar to the excretion of titratable acid, is equivalent to acid excretion by the kidneys.

In summary, the kidneys contribute to acid-base homeostasis by reabsorbing the filtered load of HCO3- and excreting an amount of acid equivalent to NEAP. This process can be quantitated as shown in Equation 37.7, where (UNH4+ × V˜) and (UTA × V˜) represent the rates of NH4+ and titratable acid (TA) excretion (mEq/day), and (UHCO3- × V˜) represents the amount of HCO3- lost in urine (equivalent to adding H+ to the body).

Maintaining acid-base balance means that net acid excretion must be equal to nonvolatile acid production. In most conditions, only a small amount of HCO3- is excreted in urine. As a result, net acid excretion mainly reflects the excretion of titratable acid and NH4+, with titratable acid accounting for approximately one-third and NH4+ for two-thirds of RNAE.

Reabsorption of HCO3- Along the Nephron
Under steady-state conditions, NEAP must equal RNAE to maintain acid-base balance. Although NEAP varies from individual to individual and from day to day in anyone individual, it is not regulated. Instead the kidneys regulate RNAE to match NEAP and in so doing replenish the HCO3 − (new HCO3 −) lost by neutralization of nonvolatile acids. In addition the kidneys must prevent the loss of HCO3 − in urine. This latter task is quantitatively more important because the filtered load of HCO3 − is approximately 4320 mEq/day (24 mEq/L × 180 L/day = 4320 mEq/day), compared with only 50 to 100 mEq/day needed to balance NEAP.
Both reabsorption of filtered HCO3 − and excretion of acid are accomplished via H+ secretion by the nephrons. Thus in a single day the nephrons must secrete approximately 4390 mEq of H+ into the tubular fluid. Most of the secreted serves to reabsorb the filtered load of HCO3 . Only 50 to 100mEq of H+ , an amount equivalent to NEAP, is excreted in urine. As a result of this acid excretion, urine is normally acidic.
The kidneys cannot excrete urine more acidic than pH 4.0 to 4.5. Even at a pH of 4.0, only 0.1 mEq/L of H+ can be excreted. Therefore to excrete sufficient acid, the kidneys excrete H+ with urinary buffers such as phosphate (Pi).
Other constituents of urine can also serve as buffers (e.g., creatinine), although their role is less important than Pi. Collectively the various urinary buffers are termed titratable acid. This term is derived from the method by which these buffers are quantitated in the laboratory. Typically, alkali (OH−) is added to a urine sample to titrate its pH to that of plasma (i.e., 7.4). The amount of alkali added is equal to the H+ titrated by these urine buffers and is termed titratable acid.
Excretion of H+ as a titratable acid is insufficient to balance NEAP. An additional and important mechanism by which the kidneys contribute to maintenance of acid-base balance is through synthesis and excretion of ammonium (NH4 +). The mechanisms involved in this process are discussed in more detail later in this chapter. With regard to renal regulation of acid-base balance, each NH4 + excreted in urine results in the return of one HCO3 − to the systemic circulation, which replenishes the HCO3 − lost during neutralization of the nonvolatile acids. Thus production and excretion of NH4 + , like excretion of titratable acid, is equivalent to excretion of acid by the kidneys.
In brief the kidneys contribute to acid-base homeostasis by reabsorbing the filtered load of HCO3 − and excreting an bThe titration reaction is: HPO42−+ H+↔ H2PO4 − . This reaction has a pK of approximately 6.8.
amount of acid equivalent to NEAP. This process can be quantitated as follows:
Equation 37.7 where (UNH4+× V˜ ) and (UTA × V˜ ) are the rates of excretion (mEq/day) of NH4 + and titratable acid (TA), and (UHCO3−× V˜ ) is the amount of HCO3 − lost in urine (equivalent to adding H+ to the body).
Again, maintenance of acid-base balance means that net acid excretion must equal nonvolatile acid production. Under most conditions, very little HCO3 − is excreted in urine. Thus net acid excretion essentially reflects titratable acid and NH4 + excretion. Quantitatively, titratable acid accounts for approximately one-third and NH4 + for two-thirds of RNAE.
HCO3 − Reabsorption Along the Nephron