Reabsorption of Bicarbonate in the Proximal Tubule

The apical membranes of the tubule cells (facing the lumen) are impermeable to bicarbonate. The reabsorption of bicarbonate must therefore occur indirectly. When the urine is acidic, HCO3-combines with H+ to form carbonic acid. Carbonic acid in the filtrate is then converted to CO2 and H2O in a reaction catalyzed by carbonic anhydrase. This enzyme is located in the apical cell membrane of the proximal tubule in contact with the filtrate.

Notice that the reaction that occurs in the filtrate is the same one that occurs within red blood cells in pulmonary capillaries (as discussed in chapter 16).

The tubule cell cytoplasm also contains carbonic anhydrase. As CO2 concentrations increase in the filtrate, the CO2 diffuses into the tubule cells. Within the tubule cell cytoplasm, carbonic anhydrase catalyzes the reaction in which CO2 and H2O form carbonic acid. The carbonic acid then dissociates to HCO3- and H+ within the tubule cells. (These are the same events that occur in the red blood cells of tissue capillaries.) The bicarbonate within the tubule cell can then diffuse through the basolateral membrane and enter the blood (fig. 17.28). When conditions are normal, the same amount of HCO3- passes into the blood as was removed from the filtrate. The H+, which was produced at the same time as HCO3- in the cytoplasm of the tubule cell, can either pass back into the filtrate or pass into the blood. Under acidotic conditions, almost all of the H+ goes back into the filtrate and is used to help reabsorb all of the filtered bicarbonate.

During alkalosis, less H+ is secreted into the filtrate. Since the reabsorption of filtered bicarbonate requires that HCO3-combine with H+ to form carbonic acid, less bicarbonate is reabsorbed. This results in urinary excretion of bicarbonate, which helps to partially compensate for the alkalosis.

By these mechanisms, disturbances in acid-base balance caused by respiratory problems can be partially compensated for



Table 17.7

Categories of Disturbances in Acid-Base Balance

Bicarbonate (mEq/L)*

Pco2 (mmHg)

Less than 21


More than 26

More than 4S

Combined metabolic and respiratory acidosis

Respiratory acidosis

Metabolic alkalosis and respiratory acidosis


Metabolic acidosis


Metabolic alkalosis

Less than 3S

Metabolic acidosis and respiratory alkalosis

Respiratory alkalosis

Combined metabolic and respiratory alkalosis

* mEq/L = milliequivalents per liter. This is the millimolar concentration of HCO3- multiplied by its valence (xl).

* mEq/L = milliequivalents per liter. This is the millimolar concentration of HCO3- multiplied by its valence (xl).

by changes in plasma bicarbonate concentrations. Metabolic acidosis or alkalosis—in which changes in bicarbonate concentrations occur as the primary disturbance—similarly can be partially compensated for by changes in ventilation. These interactions of the respiratory and metabolic components of acid-base balance are summarized in table 17.7.

When people go to the high elevations of the mountains, they hyperventilate (as discussed in chapter 16). q This lowers the arterial Pco2 an£l produces a respiratory alkalosis. The kidneys participate in this acclimatization by excreting a larger amount of bicarbonate. This helps to compensate for the alkalosis and bring the blood pH back down toward normal. It is interesting in this regard that the drug acetazo-lamide, which inhibits renal carbonic anhydrase, is often used to treat acute mountain sickness (see page 515). The inhibition of renal carbonic anhydrase causes the loss of bicarbonate and water in the urine, producing a metabolic acidosis and diuresis that help to alleviate the symptoms.

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