Structure and function of the thin limbs of the loop of Henle.

The thin limbs of the loop of Henle, which comprise the intermediate segment, connect the proximal tubule to the distal tubule and lie entirely within the renal medulla. The descending thin limb consists of at least two or three morphologically and functionally distinct subsegments and participates in transepithelial transport of NaCl, urea, and water. Only one functionally distinct segment is recognized for the ascending thin limb, which carries out transepithelial transport of NaCl and urea in the reabsorptive and/or secretory directions. Membrane transporters involved with passive transcellular Cl, urea, and water fluxes have been characterized for thin limbs; however, these pathways do not account for all transepithelial fluid and solute fluxes that have been measured in vivo. The paracellular pathway has been proposed to play an important role in transepithelial Na and urea fluxes in defined thin-limb subsegments. As the transport pathways become clearer, the overall function of the thin limbs is becoming better understood. Primary and secondary signaling pathways and protein-protein interactions are increasingly recognized as important modulators of thin-limb cell function and cell metabolism. These functions must be investigated under diverse extracellular conditions, particularly for those cells of the deep inner medulla that function in an environment of wide variation in hyperosmolality. Transgenic mouse models of several key water and solute transport proteins have provided significant insights into thin-limb function. An understanding of the overall architecture of the medulla, including juxtapositions of thin limbs with collecting ducts, thick ascending limbs, and vasa recta, is essential for understanding the role of the kidney in maintaining Na and water homeostasis, and for understanding the urine concentrating mechanism. 2012 American Physiological Society. Compr Physiol 2:2037-2061, 2012.