Renal handling of an acid load

Acid is constantly generated by metabolism.

Volatile acids (i.e. carbonic acid) can be exhaled, but fixed acids, while they can be buffered or respiratory compensation can occur, must be excreted by the kidney.

3 mechanisms allow the kidneys to acidify urine (alkalinise the body), all 3 upregulated by acidosis:

Ammoniagenesis - quantitatively most important

1. Ammonia symthesized from glutamine in PCT, immediately binds \(H^+\). Renal systhesis can \(\uparrow\) up to 10x in acidosis.
2. NH4 secreted in PCT, then reabsorbed in ascending limb of Loop of Henle via NKCC2 (masquerading as potassium)
3. Concentrated ammonium in medulla then excreted in medullary collecting duct, along with equimolar amount of chloride \(\to\) widens SID \(\to\) alkalinization

Reabsorption of filtered bicarbonate

80% in PCT

1. \(H^+\) apically secreted via antiport with Na; this is secondary active transport powered by basolateral Na/K ATPase
2. \(H^+\) + HCO3 in tubule \(\xrightarrow{\text{apical carbonic anhydrase}}\)CO2 + H2O \(\to\) CO2 diffuses back into cell
3. In cell, CO2 \(\xrightarrow{\text{carbonic anhydrase}}\) HCO3 + \(H^+\)
4. New HCO3 is symported basolaterally with sodium
5. Process continues until tubular HCO3 is exhausted

Does little to help with an acid load; it does not generate new bicarbonate and under normal circumstances 100% of filtered bicarbonate is already reabsorbed

Excretion of titratable acids

Phosphate, creatinine, and other organic weak bases are buffer molecules. Phosphate most important (pKa 6.8)

In PCT, \(H^+\) apically secreted via antiport with Na (secondary active with basolateral Na/K ATPase)

In DCT, \(H^+\) apically secreted via active antiport with K in \(alpha\)-intercalated cells.

This \(H^+\) is buffered by phosphate et al and the buffers are excreted as conjugate acids.

Limited by amount of buffer present.