1. Copyright © 2017 American Academy of Pediatrics.
From: Renal Tubular Acidosis
American Academy of Pediatrics Textbook of Pediatric Care, 2nd Edition, 2017
Figure Legend:
Ammonium excretion is a 4-step process. Step 1 is the generation of ammonium (NH4+) from glutamine in the mitochondria of cells of the proximal tubule. NH4+ exits the cell of the proximal tubule after binding to the H+ site of the apical Na+, H+ exchanger (NHE3, Figure 322-1). The broad arrow in the figure labeled with the numeral 1 denotes a packet of NH4+ leaving the proximal tubule and entering the descending thin limb of the loop of Henle (DTL). There is further net addition of NH4+ to this packet as the DTL courses through deeper strata of the renal medulla and encounters the high concentration of interstitial NH4+ produced by the reabsorption of NH4+ in the thick ascending limb loop of Henle (TALH) (step 2). The mechanism of transport of interstitial NH4+ into the lumen of the DTL is not known. The broad arrow labeled with the numeral 2 represents a packet of NH4+ arriving at the TALH. Step 2 is the reabsorption of NH4+ in the TALH by binding to the K+ site of the apical Na+, K+, 2Cl− cotransporter (NKCC2, Figure 322-4). Step 3 is the interstitial accumulation of NH4+. After absorption, NH4+ exits the cells of the TALH by possibly binding to the H+ site of a basolateral Na+, H+ exchanger (not depicted in Figure 322-4). The net effect of this recycling of NH4+ is to populate the medullary interstitium with a pool of NH4+, which “feeds” the uptake of NH3 from the interstitium by the type A intercalated cell, TAIC (also see Figure 322-2) via a basolateral RhCG transporter. The cytosolic NH3 is then shuttled to the apical RhCG transporter for secretion into the lumen of the medullary collecting duct, CD (also see Figure 322-2). Although not depicted in the above figure, RhCG transporters are also found in principal cells (PRNC) of the CD (also see Figure 322-2). Step 4 is the protonation of NH3 and “ion trapping” of NH4+ in the lumen of the collecting duct. As NH4+ (and the NH3, which is in equilibrium with NH4+) are removed by excretion, a gradient for continuing transport of NH3 from the medullary interstitium is maintained (broad, dotted arrow). The shading of the vertical arrow labeled osmolality denotes the increasing concentration of NH4+ and other solutes in successively deeper layers of the medulla. CD, medullary collecting duct; DTL, descending thin limb of loop of Henle; PRNC, principal cell; PROX, proximal tubule; TAIC, type A intercalated cell; TALH, thick ascending limb of loop of Henle.
Date of download: 11/9/2017
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