MECHANISMS OF TRANSPORT

In all portions of the nephron, basolateral Na⁺/K⁺ ATPases pump sodium from the tubular epithelial cells into the interstitium. As a result, intracellular sodium concentrations remain low, establishing a gradient for transcellular reabsorption.

Proximal Tubule. Throughout the proximal tubule, sodium crosses the apical membranes of tubular epithelial cells on Na⁺/H⁺ exchangers (NHE-3), causing proton secretion by secondary active transport. To a lesser extent, sodium crosses apical membranes on symporters that transport one or more sodium ions in combination with various substances, including glucose, amino acids, phosphate, lactate, and citrate. The reabsorption of sodium, irrespective of the mechanism, transiently establishes an osmotic transepithelial gradient that promotes the passive, isotonic reabsorption of water (see Plate 3-15).

As sodium and water are reabsorbed, chloride becomes increasingly concentrated in proximal tubular fluid. In addition, the initial segment of the proximal tubular lumen has a negative charge. Thus there are chemical and electrical gradients favoring chloride reabsorption, which occurs along a paracellular pathway. In later parts of the proximal tubule, the negative charge in the lumen dissipates, owing to extensive paracellular reabsorption of chloride. Instead, there is a positive charge, which creates an electrical gradient for the paracellular reabsorption of sodium. Despite this reversal, paracellular chloride reabsorption continues because of the strong chemical gradient in its favor. Some chloride also undergoes transcellular reabsorption via apical Cl⁻ -anion antiporters, which are coupled with basolateral Cl channels and K /Cl cotransporters (KCC-3 and -4).

Thin Limb. The descending thin limb is impermeable to solutes but permits reabsorption of water, as discussed on Plate 3-15. Tubular fluid thus becomes concentrated in this segment, which establishes a chemical gradient favoring the reabsorption of some sodium and chloride from the ascending thin limb. Sodium undergoes paracellular reabsorption, whereas chloride undergoes transcellular reabsorption through apical and basolateral CLC-NKA channels.