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After reading this chapter, you should be able to:

  • Outline the processes involved in the secretion of H+ into the tubules and discuss the significance of these processes in the regulation of acid-base balance.

  • Define acidosis and alkalosis, and give (in mEq/L and pH) the normal mean and the range of H+ concentrations in blood that are compatible with health.

  • Describe the changes in blood chemistry that occur during the development of metabolic acidosis and metabolic alkalosis, and the respiratory and renal compensations for these conditions.

  • Describe the changes in blood chemistry that occur during the development of respiratory acidosis and respiratory alkalosis, and the renal compensation for these conditions.


The kidneys play a key role in the maintenance of acid–base balance and to do this they must excrete acid in the amount equivalent to the production of nonvolatile acids in the body. The production of nonvolatile acids will vary with diet, metabolism, and disease. The kidneys must also filter and reabsorb plasma bicarbonate, and thus prevent the loss of bicarbonate in the urine. Both processes are linked physiologically, due to the nephron’s ability to secrete H+ ions into the filtrate.


The cells of the proximal and distal tubules and the collecting ducts secrete hydrogen ions. The transporter that is responsible for H+ secretion in the proximal tubules is the Na–H exchanger (primarily NHE3) (Figure 39–1). This is an example of secondary active transport; Na+ is moved from the inside of the cell to the interstitium by Na, K-ATPase on the basolateral membrane, which keeps intracellular Na+ low, thus establishing the drive for Na+ to enter the cell from the tubular lumen via the Na–H exchanger. The Na–H exchanger secretes H+ into the lumen in exchange for Na+. The secreted H+ combines with filtered HCO3 to form H2CO3; the presence of carbonic anhydrase on the apical membrane of the proximal tubule catalyzes the formation of H2O and CO2 from H2CO3. The apical membrane of epithelial cells lining the proximal tubule is permeable to CO2 and H2O, and they enter the tubule rapidly. Eighty percent of the filtered load of HCO3 is reabsorbed in the proximal tubule.


Secretion of acid and reabsorption of filtered bicarbonate by proximal tubular cells in the kidney. H+ is transported into the tubular lumen by NHE3 in exchange for Na+. Active transport by Na, K-ATPase is indicated by arrows. Dashed arrows indicate diffusion.

Inside the cell, carbonic anhydrase is also present and can catalyze the formation of H2CO3...

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