Introductory part:

A major homeostatic challenge is keeping the H+ concentration (pH) of body fluids at an appropriate level.
This maintenance of acid–base balance is of critical importance to normal cellular function.
Example; the three-dimensional shape of all body proteins, which enables them to perform specific
functions, is very sensitive to pH changes.

When the diet contains a large amount of protein, as is typical in North America, cellular metabolism
produces more acids than bases, which tends to acidify the blood.

Kidney excretion of H+. The slowest mechanism, but the only way to eliminate acids other than carbonic
acid, is through their excretion in urine

Metabolic reactions produce nonvolatile acids such as sulfuric acid at a rate of about 1 mEq of H ⁺ per day
for every kilogram of body mass. The only way to eliminate this huge acid load is to excrete H⁺ in the urine.
Given the magnitude of these contributions to acid–base balance, it's not surprising that renal failure can
quickly cause death.

Cells in both the proximal convoluted tubules (PCT) and the collecting ducts of the kidneys secrete
hydrogen ions into the tubular fluid. In the PCT, Na⁺–H⁺ antiporters secrete H⁺ as they reabsorb Na⁺. Even
more important for the regulation of pH of body fluids, however, are the intercalated cells of the collecting
duct. The apical membranes of some intercalated cells include proton pumps (H⁺ ATPases) that secrete H ⁺
into the tubular fluid. Intercalated cells can secrete H⁺ against a concentration gradient so effectively that
urine can be up to 1000 times (3 pH units) more acidic than blood. HCO₃⁻ produced by dissociation of
H₂CO₃ inside intercalated cells crosses the basolateral membrane by means of Cl⁻–HCO₃⁻ antiporters and
then diffuses into peritubular capillaries (Figure 27.8a). The HCO₃⁻ that enters the blood in this way is new
(not filtered). For this reason, blood leaving the kidney in the renal vein may have a higher HCO ₃⁻
concentration than blood entering the kidney in the renal artery.

Interestingly, a second type of intercalated cell has proton pumps in its basolateral membrane and Cl ⁻–
HCO₃⁻ antiporters in its apical membrane. These intercalated cells secrete HCO ₃⁻ and reabsorb H ⁺. Thus,
the two types of intercalated cells help maintain the pH of body fluids in two ways—by excreting excess H ⁺
when the pH of body fluids is too low and by excreting excess HCO₃⁻ when the pH is too high.

Some H⁺ secreted into the tubular fluid of the collecting duct is buffered, but not by HCO₃⁻, most of which
has been filtered and reabsorbed. Two other buffers combine with H⁺ in the collecting duct (Figure 27.8b).
The most plentiful buffer in the tubular fluid of the collecting duct is HPO₄²⁻ (monohydrogen phosphate
ion). In addition, a small amount of NH₃ (ammonia) is also present. H⁺ combines with HPO₄²⁻ to form
H₂PO₄⁻ (dihydrogen phosphate ion) and with NH₃ to form NH₄⁺ (ammonium ion). Because these ions
cannot diffuse back into tubule cells, they are excreted in the urine.