In summary, NaCl reabsorption across the thick ascending limb occurs via transcellular and paracellular pathways. Fifty percent of NaCl reabsorption is transcellular, and 50% is paracellular. Because the thick ascending limb does not reabsorb water, owing to a lack of water channels (i.e., AQPs), reabsorption of NaCl and other solutes reduces the osmolality of tubular fluid to less than 150 mOsm/ kg H2O. Thus because the thick ascending limb of Henle’s loop produces a fluid that is dilute relative to plasma, this segment and the adjacent distal tubule (as discussed next) are often collectively referred to as the “diluting segments.”
The distal tubule and collecting duct reabsorb approximately 8% of the filtered NaCl, secrete variable amounts of K+ and H+ , and reabsorb a variable amount of water (≈8%–17%). The initial segment of the distal tubule (early distal tubule) reabsorbs Na+, Cl−, and Ca++ and is impermeable to water (
Fig. 34.8 ). Entry of NaCl into the cell across the apical membrane is mediated by a Na+/Cl− symporter,
Chapter 2, epithelial cells are joined at their apical surfaces by tight junctions (zonula occludens). A number of proteins have now been identified as components of the tight junction, including proteins that span the membrane of one cell and link to the extracellular portion of the same molecule in the adjacent cell (e.g., occludin and claudins), as well as cytoplasmic linker proteins (e.g., ZO-1, ZO-2, and ZO-3) that link the membrane-spanning proteins to the cytoskeleton of the cell. Of these junctional proteins, claudins appear to be major determinants of the permeability characteristics of tight junctions. For example, claudin-16 and claudin-19 are critical determinants of divalent cation permeability of the tight junctions in the thick ascending limb of Henle’s loop. Mutations in human claudin-16 and claudin19 cause familial hypomagnesemia (i.e., low plasma [Mg++]) with hypercalciuria (i.e., increased Ca++ in the urine) and nephrocalcinosis (i.e., calcification of the kidney). Claudin-2 is permeable to water and may be responsible for paracellular water reabsorption across the proximal tubule. Claudin-4 has been shown in cultured kidney cells to control the permeability of the tight junction to Na+ , whereas claudin-15 determines whether a tight junction is permeable to cations or anions. Thus the permeability characteristics of the tight junctions in different nephron segments are determined at least in part by the specific claudins expressed by the cells in that segment.
AVP, water is reabsorbed. By contrast, in the absence of AVP the late distal tubule and collecting duct reabsorb little
Bartter syndrome is a set of autosomal recessive genetic diseases characterized by hypokalemia, metabolic alkalosis, and hyperaldosteronism (see
Table 34.3 ). Inactivating mutations in the gene coding for the 1Na+/1K+/2Cl− symporter (NKCC2), the apical K+ channel (ROMK), or the basolateral Cl− channel (ClCNKB) decrease both NaCl reabsorption and K+ reabsorption by the ascending thick limb, which in turn causes hypokalemia (i.e., low plasma [K+]) and a decrease in ECFV. The fall in ECFV stimulates aldosterone secretion, which in turn stimulates NaCl reabsorption and H+ secretion by the distal tubule and collecting duct.