FIGURE 15–2 Apical membrane Na+/H+ exchange (via NHE3) and bicarbonate reabsorption in the proximal convoluted tubule cell. Na+/K+-ATPase is present in the basolateral membrane to maintain intracellular sodium and potassium levels within the normal range. Because of rapid equilibration, concentrations of the solutes are approximately equal in the interstitial fluid and the blood. Carbonic anhydrase (CA) is found in other locations in addition to the brush border of the luminal membrane. SGLT2, Na+/glucose transporter.
can be inhibited by acetazolamide and other carbonic anhydrase inhibitors.
More recently, inhibitors of the sodium-glucose cotransporter, isoform 2 (SGLT2; Figure 15–2) have been approved to treat diabetes mellitus. The sodium-glucose cotransporter is responsible for reabsorbing much of the glucose that is filtered by the glomeruli. Although not indicated as diuretic agents, these drugs have diuretic properties accompanied by increased sodium and glucose excretion (see below). The diuretic properties are thought to result from mainly osmotic diuresis.
Organic acid secretory systems are located in the middle third of the straight part of the proximal tubule (S2 segment). These systems secrete a variety of organic acids (uric acid, nonsteroidal anti-inflammatory drugs [NSAIDs], diuretics, antibiotics, etc) into the luminal fluid from the blood. These systems thus help deliver diuretics to the luminal side of the tubule, where most of them act. Organic base secretory systems (creatinine, choline, etc) are also present, in the early (S1) and middle (S2) segments of the proximal tubule.
At the boundary between the inner and outer stripes of the outer medulla, the proximal tubule empties into the thin descending limb of Henle’s loop. Water is extracted from the descending limb of this loop by osmotic forces found in the hypertonic medullary interstitium. As in the proximal tubule, impermeant luminal solutes such as mannitol oppose this water extraction and thus have aquaretic activity. The thin ascending limb is relatively water-impermeable but is permeable to some solutes.
Lumen-urine Thick ascending limb Interstitium-blood Na+ Na+ K+ K+ K+ K+ Cl – 2Cl– (+) Potential Mg2+, Ca2+ NKCC2 ATP FIGURE 15–3 Ion transport pathways across the luminal and basolateral membranes of the thick ascending limb cell. The lumen positive electrical potential created by K+ back diffusion drives divalent (and monovalent) cation reabsorption via the paracellular pathway. NKCC2 is the primary transporter in the luminal membrane.
The thick ascending limb (TAL), which follows the thin limb of Henle’s loop, actively reabsorbs NaCl from the lumen (about 25% of the filtered sodium), but unlike the proximal tubule and the thin descending limb of Henle’s loop, it is nearly impermeable to water. Salt reabsorption in the TAL therefore dilutes the tubular fluid, and for this reason, the TAL is called a diluting segment. Medullary portions of the TAL contribute to medullary hypertonicity and thereby also play an important role in concentration of urine by the collecting duct.