Regulation of hydrogen ionsA simple modelResponse to acidosisResponse to alkalosis

Regulation of hydrogen ions (H+)

Most of the acid in the body is buffered by the carbon dioxide/bicarbonate (CO2/HC03-) system:

The partial pressure of CO2 (PaCO2) is regulated by the lungs and changes in alveolar ventilation, whereas the plasma concentration of HC03- is regulated by the kidneys. Indeed, the pH of blood is simply a constant plus the ratio of HC03- to PaCO2. More simply, we can think of pH varying in proportion to this ratio, or more simply what the kidneys are doing relative to the lungs.

regulation of blood ph

What matters is the ratio, not the absolute values of HC03- and PaCO2. The body may compensate for a disturbance in one with an alteration in the other. So, you may encounter a patient with very odd HC03-, but an equally odd PaCO2 and a relatively normal pH. What is going on here is compensation – there is an unresolved acid-base irregularity but the body is managing to compensate.

A simple model

When we are thinking about the overall role of the kidney in acid-base regulation, we can simplify the work of all the component parts into a simple model that ignores the complex anatomy and different functional components of this organ. Such a model is not helpful in understanding diseases of the kidney, but is satisfactory for our needs here. The way the kidney regulates H+ ions is by regulating whether HC03- is added to blood or allowed to be excreted into the urine. So:

1. In acidaemia, urine is acid, not because H+ has been secreted into the urine, but because filtered HC03- has been removed.
2. In alkalaemia, urine is basic, because filtered HC03- has been allowed to stay in the urine, not because H+ has been removed.

Neither of these is truly an active response to the change in pH of blood, but rather what happens to the existing mechanics of the regulation of HC03- when the concentration of plasma H+ ions changes. In either case though, the change in HC03- regulation helps compensate for the acid-base disturbance. The way the kidneys actively regulate HC03- is by altering metabolism of glutamine, which is broken down into NH4+ and HC03-; this new HC03- is pumped back into the blood. The enzyme responsible for glutamine metabolism (glutaminase) is induced by chronic acidosis, which provides additional renal compensation in this acid-base disturbance.

The three processes (although the first two are quite similar) by which the kidney regulates plasma HC03- are summarised in Figure 1 (below). Remember, this is an oversimplification of total renal function and does not consider the many different mechanisms by which ions may enter or leave cells, nor which parts of the kidney these mechanisms occur in.

renal acid base

Figure 1: Summary of the three main ways that the kidney can regulate plasma bicarbonate, and hence plasma [H+]. Important note: these three mechanisms occur in various parts of the kidney and this figure serves as a simple overview of total kidney function only. (A). Carbonic anhydrase (CA) catalyses the formation of H+ and HC03- from water and CO2. HC03- is transported into the blood and H+ is transported into the urine where it is partially buffered by filtered HC03-. Note, the mechanisms for transporting H+ out of the cell are manifold and depend on the specific region of this kidney under consideration. (B). New HC03- is also produced if the supply of filtered HC03- is exhausted in the tubules by complete reabsorption. HC03- and H+ are produced in the same was as in panel (A), it’s just that the transported H+ is combined with filtered HPO42- and excreted. (C). Finally, tubular epithelial cells metabolise glutamine into NH4+ and HC03-. This reaction is catalysed by the enzyme glutaminase, the levels of which are regulated according to acid-base balance. Glutaminase is induced by chronic acidosis to assist in HC03- production (mainly in the proximal tubule). (Redrawn with minor adaptation from Vander’s Physiology).

Renal response to acidosis

If there is an increased concentration of H+ in plasma, then sufficient H+ will be secreted into the tubules (Panel A) to allow complete reabsorption of all of the filtered HC03-, increasing plasma HC03-. Any additional H+ will be excreted bound to non-bicarbonate buffers such as HPO42- (Panel B). Finally, if acidosis persists, glutaminase expression will be induced to produce further HC03- (and NH4+; Panel C). The result will be increase acidification of the urine and increased plasma HC03- to buffer H+.

Renal response to alkalosis

If there is a decreased concentration of H+ in plasma, then insufficient H+ will be secreted into the tubules and excess HCO3- and other buffers will be left in urine, meaning less is reabsorbed into plasma (Panels A & B). Glutaminase is not induced, so further HC03- production is reduced (Panel C). Overall, plasma HC03- levels are reduced and the urine is allowed to become alkaline.

ALL this becomes more complicated if the kidney is the cause of the acid-base disturbance!

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