Structure and Function of the Thin Limbs of the Loop of Henle

Abstract

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.

Comparative physiology and architecture associated with the mammalian urine concentrating mechanism: role of inner medullary water and urea transport pathways in the rodent medulla

“…Similar subdivisions likely occur in other rodents (2,4,5,17,49,65,79). Structural characteristics of the outer and inner medullary zones and regions have been summarized in several reviews (80,104,109).…”

Targeted delivery of solutes and oxygen in the renal medulla: role of microvessel architecture

“…Ascending thin limbs combine with these segments to form well-defined interstitial compartments within the intracluster region, the so-called "interstitial nodal spaces" (21,55,56). Based on the preferential arrangements of collecting ducts (which reabsorb urea and water) and ascending thin limbs and prebend segments (which reabsorb NaCl but not water), we hypothesized that interstitial nodal spaces (and the intracluster region more generally) might be specialized sites for NaCl and urea mixing in the antidiuretic rat (30,32,53,56).…”

Pathophysiology, diagnosis and management of nephrogenic diabetes insipidus

“…4 Concentration of the tubular fluid in these innermost parts of the TDL might occur via passive sodium influx, 5 but no substantial sodium permeability has been observed. 6 Thus, the exact mechanism of urinary concentration in the innermost part of the medulla remains to be elucidated.…”