Doctor world

Along with the lungs, the kidneys are particularly involved in keeping the pH value of the
extracellular fluid constant (see p. 288). The contributionmade by the kidneys particularly
involves resorbing HCO3 – and actively excreting protons.
A. Proton excretion _
The renal tubule cells are capable of secreting protons (H+) from the blood into the urine
against a concentration gradient, despite the fact that the H+ concentration in the urine is
up to a thousand times higher than in the blood. To achieve this, carbon dioxide (CO2)
is taken up fromthe blood and—togetherwith water (H2O) and with the help of carbonate
dehydratase (carbonic anhydrase, [1])—converted into hydrogen carbonate (“bicarbonate,” HCO3 –) and oneH+. Formally, this yields carbonic acid H2CO3 as an intermediate, but it is not released during the reaction. The hydrogen carbonate formed in carbonic anhydrase returns to the plasma, where it contributes to the blood’s base reserve.
The proton is exported into the urine by secondary active transport in antiport for Na+ (bottom right). The driving force for proton excretion, as in other secondary active processes, is the Na+ gradient established by the ATPase involved in the Na+/K+ exchange (“Na+/K+ ATPase”, see p. 220). This integral membrane protein on the basal side (towards the blood) of tubule cells keeps the Na+ concentration in the tubule cell low, thereby maintaining Na+ inflow. In addition to this secondary active H+ transport mechanism, there is a V-type H+- transporting ATPase in the distal tubule and
collecting duct (see p. 220). An important function of the secreted H+ ions is to promote HCO3 - resorption (top right). Hydrogen carbonate, the most important buffering base in the blood, passes into the primary urine quantitatively, like all ions. In the primary urine, HCO3 – reacts with H+ ions to form water and CO2, which returns by free diffusion to the tubule cells and from there into the blood.



In this way, the kidneys also influence the CO2/HCO3 – buffering balance in the plasma. B. Ammonia excretion _ Approximately 60 mmol of protons are excreted with the urine every day. Buffering systems in the urine catch a large proportion of the H+ ions, so that the urine only becomes weakly acidic (down to about pH 4.8). An important buffer in the urine is the hydrogen phosphate/dihydrogen phosphate system (HPO4 2–/H2PO4 –). In addition, ammonia also makes a vital contribution to buffering the secreted protons. Since plasma concentrations of free ammonia are low, the kidneys release NH3 from glutamine and other amino acids. At 0.5–0.7 mM, glutamine is the most important amino acid in the plasma and is the preferred form for ammonia transport in the blood. The kidneys take up glutamine, and with the help of glutaminase [4], initially release NH3 from the amide bond hydrolytically.
From the glutamate formed, a secondmolecule of NH3 can be obtained by oxidative deamination with the help of glutamate dehydrogenase [5] (see p. 178). The resulting 2-oxoglutarate is further metabolized in the tricarboxylic acid cycle. Several other amino acids—alanine in particular, as well as serine, glycine, and aspartate—can also serve as suppliers of ammonia. Ammonia can diffuse freely into the urine through the tubule membrane, while the ammonium ions that are formed in the urine are charged and can no longer return to the cell. Acidic urine therefore promotes ammonia excretion, which is normally 30–50 mmol per day. In metabolic acidosis (e. g., during fasting or in diabetes mellitus), after a certain time increased induction of glutaminase occurs in the kidneys, resulting in increased NH3 excretion. This in turn promotes H+ release and thus counteracts the acidosis. By contrast, when the plasma pH value shifts towards alkaline values (alkalosis), renal excretion of ammonia is reduced.