Maximizing net acid excretion occurs when there is minimal or no excretion of HCO3 − in the urine. Typically, very little HCO3 − is found in the urine as it is freely filtered at the glomerulus and then reabsorbed in the nephrons, with approximately 4320 mEq/day being delivered. The proximal tubule plays a significant role in reabsorbing the largest portion of the filtered load of HCO3 −. H+ secretion across the apical membrane of the cell happens through a Na+/H+ antiporter and H+-ATPase (V-type), with the Na+/H+ antiporter (NHE3) being the main pathway for H+ secretion and accounting for about two-thirds of HCO3 − reabsorption. This process utilizes the lumen-to-cell [Na+] gradient to drive the secretion. Fig. 37.2 illustrates the segmental reabsorption of HCO3 − by the various segments of the nephron, where normally the entire filtered load of HCO3 − is reabsorbed and little to no HCO3 − appears in the urine. In terms of the cellular mechanism for reabsorption of filtered HCO3 − by cells of the proximal tubule, H+ and HCO3 − are produced within the cell through a reaction catalyzed by carbonic anhydrase (CA-II). The H+ is secreted into the tubular fluid, while the HCO3 − exits the cell through the basolateral membrane and returns to the peritubular blood. The movement of HCO3 − out of the cell across the basolateral membrane is coupled with other ions, primarily through a symporter that couples the efflux of Na+ with HCO3 − (sodium bicarbonate symporter, NBC1). Some HCO3 − may exit the cell through other transporters, but their importance is not as significant as the Na+/HCO3 − symporter. Carbonic anhydrase (CA-IV) is present in both the brush border and basolateral membrane of the cell, where it facilitates the dehydration of H2CO3 in the luminal fluid and the exit of HCO3 − from the cell. CO2 movement into and out of the cell occurs through AQP1, which is localized to both the luminal and basolateral membranes. The cellular mechanism for HCO3 − reabsorption in the thick ascending limb (TAL) of the loop of Henle is similar to that in the proximal tubule. H+ is secreted through a Na+/H+ antiporter and H+-ATPase, with the Na+/H+ antiporter (NHE3) being the primary pathway for H+ secretion. HCO3 − exit from the cell involves both a Na+/HCO3 − symporter (NBC1) and a Cl−/HCO3 − antiporter (anion exchanger, AE-2), and some HCO3 − may also exit the cell through Cl− channels in the basolateral membrane.
Eq. 37.7 , net acid excretion is maximized when little or no HCO3 − is excreted in urine. Indeed, under most circumstances, very little HCO3 − appears in urine. Because HCO3 − is freely filtered at the glomerulus, approximately 4320 mEq/day is delivered to the nephrons and is then reabsorbed.
Fig. 37.2 summarizes the contribution of each nephron segment to reabsorption of filtered HCO3 − .
The proximal tubule reabsorbs the largest portion of the filtered load of HCO3 − .
Fig. 37.3 summarizes the primary cThis equation ignores the small amount of free H+ excreted in urine. As already noted, urine with a pH = 4.0 contains only 0.1 mEq/L of H+ .
transport processes involved. H+ secretion across the apical membrane of the cell occurs by both a Na+/H+ antiporter and H+-ATPase (V-type). The Na+/H+ antiporter (NHE3) is the predominant pathway for H+ secretion (accounts for ≈ two-thirds of HCO3 − reabsorption) and uses the lumen-to-cell [Na+] gradient to drive this process (i.e., •Fig. 37.2 SegmentalreabsorptionofHCO3− .ThefractionofthefilteredloadofHCO3− reabsorbedbythevarioussegmentsofthenephronisshown.NormallytheentirefilteredloadofHCO3− isreabsorbedandlittleornoHCO3− appearsintheurine.CCD,corticalcollectingduct;DT,distaltubule;IMCD,innermedullarycollectingduct;PT,proximaltubule;TAL,thickascendinglimb.
•Fig. 37.3 CellularmechanismforreabsorptionoffilteredHCO3− bycellsoftheproximaltubule.OnlytheprimaryH+ andHCO3− transportersareshown.ATP,adenosinetriphosphate;CA,carbonicanhydrase.
secondary active secretion of H+). Within the cell, H+ and HCO3 − are produced in a reaction catalyzed by carbonic anhydrase (CA-II). The H+ is secreted into the tubular fluid, whereas the HCO3 − exits the cell across the basolateral membrane and returns to the peritubular blood. HCO3 − movement out of the cell across the basolateral membrane is coupled to other ions. The majority of HCO3 − exits via a symporter that couples the efflux of Na+ with HCO3 − (sodium bicarbonate symporter, NBC1). Some HCO3 − exits the cell by other transporters, but they are not as important as the Na+/HCO3 − symporter. As noted in
Fig. 37.3 , carbonic anhydrase (CA-IV) is also present in the brush border and basolateral membrane of the cell. The brush border enzyme catalyzes dehydration of H2CO3 in the luminal fluid, whereas the enzyme localized to basolateral membrane facilitates HCO3 − exit from the cell. The movement of CO2 into and out of the cell occurs via AQP1, which is localized to both the luminal and basolateral membranes.
The cellular mechanism for HCO3 − reabsorption by the thick ascending limb (TAL) of the loop of Henle is very similar to that in the proximal tubule. H+ is secreted by a Na+/H+ antiporter and H+-ATPase. Like in the proximal tubule, the Na+/H+ antiporter (NHE3) is the predominant pathway for H+ secretion. HCO3 − exit from the cell involves both a Na+/HCO3 − symporter (NBC1) and a Cl−/HCO3 − antiporter (anion exchanger, AE-2). Some HCO3 − may also exit the cell through Cl− channels present in the basolateral membrane.