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

Thomas L. Pannabecker

10.1002/cphy.c110019

Source: Volume 2, Issue 3, July 2012

Published online: July 2012

Full Article on Wiley Online Library



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. © 2012 American Physiological Society. Compr Physiol 2:2063‐2086, 2012.

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Figure 1. Figure 1.

Segmentation of thin limbs of the loop of Henle. The short‐loop nephron (right, belonging to a superficial glomerulus) has a descending thick limb (pars recta of proximal tubule; hatched), a descending thin limb (DTL) (turning back near the outer medullary‐inner medullary boundary), and a thick ascending limb (cross hatched), which passes into the distal convoluted tubule a short distance beyond the macula densa (shown in black). The long‐loop nephron (second from right, belonging to a juxtamedullary glomerulus) contains a DTL subdivided into two parts, type 2 and type 3 epithelium; and an ascending thin limb (ATL), type 4 epithelium; the bend is located in the inner medulla. Two additional long‐loop nephrons (incompletely drawn) demonstrate heterogeneity among long‐loop nephrons, which turn back at different levels within the inner medulla. Numbers 1‐4 refer to type of epithelium encountered in corresponding thin limb part: type 1, DTL of short loops; type 2, upper part of DTL of long loops; type 3, lower part of DTL of long loops; type 4 (beginning short distance before bend), ATL. Aquaporin 1 (AQP1)‐negative segments/yellow; AQP1‐positive segments/red; ClC‐K1‐positive segments/green. Figure based on data adapted, with permission, from references 27,63,125, and 185.
Figure 2. Figure 2.

Segmentation of C57/BL/6J mouse short‐loop and long‐loop nephrons. Tortuous descending thin limb (DTL) of long‐loop nephron (LLN; large arrow); winding course of thick ascending limb (red arrowhead) of short‐loop nephron (SLN) and CD (black arrowhead); a piece of TAL inserted in the DTL of LLN (LLNt; small arrow), which forms its bend just beneath the “transitional zone” within the inner medulla; and three different types of SLN bends (SLN1, SLN2, and SLN3). Outer stripe of outer medulla (OSOM), inner stripe of outer medulla (ISOM), and inner medulla (IM). Figure adapted, with permission, from reference 184.
Figure 3. Figure 3.

Immunolocalization of wide‐bend thin limbs of loops of Henle (arrows), ascending thin limb (ATLs), and CDs in Munich‐Wistar rat papilla. ATLs and wide‐bend loops/ClC‐K1/green (structure/immunogen/color), and CDs/aquaporin 2 (AQP2)/blue in a transverse section that lies 70 μm above the tip of the papilla. Scale bar, 100 μm. Figure adapted, with permission, from reference 130.
Figure 4. Figure 4.

Type 1 epithelium of rat short‐loop descending thin limb (DTL). (A) Overview of cross‐sectional profile, x ∼ 4000. (B) Simple type 1 epithelium, x ∼ 12,000. (C) Complex tight junction in freeze‐fracture replica, x ∼ 71000. Intramembrane particle clusters (*) seen on P‐face of basolateral membrane correspond to desmosomes. Figure modified, with permission, from reference 63.
Figure 5. Figure 5.

Type 2 epithelium of rat long‐loop descending thin limb (DTL) (DTLupper). (A) Overview of tubular profile; note many tight junctions (arrows), x ∼ 4000. (B) Longitudinal section through epithelium; numerous tight junctions (arrows) indicate extensive cellular interdigitation. Note basolateral “labyrinth,” x ∼ 18,000. (C) Flat section through epithelium showing star‐like shape of epithelial cells responsible for cellular interdigitation. Note microfilament bundles (*) in basal epithelium, x ∼ 13,500. Figure modified, with permission, from reference 63.
Figure 6. Figure 6.

Type 3 epithelium of rat long‐loop descending thin limb (DTL) (DTLlower). (A) Overview of cross‐sectional profile. Only two tight junctions (arrows) are encountered, x ∼ 3750. (B) Simple type 3 epithelium, x ∼ 16,500. (C) Freeze‐fracture electron microscopy shows complex tight junction, x ∼ 52,000. Figure modified, with permission, from reference 63.
Figure 7. Figure 7.

Type 4 epithelium of rat long‐loop ascending thin limb (ATL). (A) Overview of cross‐sectional profile, x ∼ 3000. Note many tight junctions (arrows). (B) Longitudinal section through epithelium showing high degree of cellular interdigitation (junctions marked by arrows), x ∼ 11,500. (C) Freeze‐fracture electron micrograph showing luminal aspect of two interdigitating cells, x ∼ 12,000. Note two different types of intramembrane textures. Figure modified, with permission, from reference 63.
Figure 8. Figure 8.

Photomicrographs of Munich‐Wistar rat thin limbs of the loop of Henle from the inner medullary outer zone (OZ; see Fig. 13), viewed with differential interference contrast optics. (A) Type 2 epithelium [descending thin limb (DTLupper)] and (B) type 4 epithelium [ascending thin limb (ATL)]. Note cells with nuclei protruding into lumen in type 2 epithelium and cells with large, round, flat nuclei in type 4 epithelium. Scale bar, 100 μm. Figure adapted, with permission, from 127.
Figure 9. Figure 9.

Immunolocalization of tubules and vessels in the inner stripe of the Munich‐Wistar rat outer medulla. CDs/aquaporin 2 (AQP2)/yellow; long‐loop descending thin limb (DTL)/aquaporin 1 (AQP1)/white; short‐loop DTL/UT‐A2/blue; thick ascending limb/ClC‐K2/orange; descending vasa recta/UT‐B/green. Ascending vasa recta, capillaries, and AQP1‐negative long‐loop DTLs are not shown. Overlay of two adjacent transverse sections, 1 μm apart. Scale bar, 250 μm. Unpublished figure, Thomas Pannabecker.
Figure 10. Figure 10.

Immunolocalization of CDs and associated thin limbs of the loop of Henle in the Munich‐Wistar rat inner medulla. The “intracluster” region is bounded by the red borders, the “intercluster” region lies between the red and white borders. Transverse section is from about 400 μm below the outer medullary‐inner medullary boundary (outer zone 1; see Fig. 13). Five primary CD clusters are outlined by white borders; borders were determined by the Euclidean distant map technique (132). These five primary clusters make up a single secondary CD cluster that consists of 31 CDs near the outer medullary‐inner medullary boundary. Descending thin limb (DTL)/aquaporin 1 (AQP1)/red, CD/aquaporin 2 (AQP2)/blue, ascending thin limb (ATL)/ClC‐K1/green. Scale bar, 100 μm. Figure modified, with permission, from reference 132.
Figure 11. Figure 11.

Immunolocalization of thin limbs of the loop of Henle in the Munich‐Wistar rat inner medulla. Transverse sections showing (A) nonuniform distribution of aquaporin 1 (AQP1)‐positive descending thin limb (DTL)/AQP1/red and (B) near uniform distribution of prebend segments and ascending thin limb (ATL)/ClC‐K1/green. Sections lie within 1300 μm below the outer medullary‐inner medullary boundary (outer zone 2, see Fig. 13). AQP1‐negative DTLs are not shown. Scale bars, 100 μm. Figure modified, with permission, from reference 129.
Figure 12. Figure 12.

Three‐dimensional reconstruction of a primary CD cluster and associated tubules and vessels in the Munich‐Wistar rat inner medulla. (A) Descending thin limbs (DTLs) and descending vasa recta that are associated with a primary CD cluster lie at the periphery of or outside of the cluster along the entire axial length of the cluster. Aquaporin 1 (AQP1)‐positive DTLs/AQP1/red; AQP1‐negative DTLs/α‐B crystalline/gray; descending vasa recta/UT‐B/green; CDs/aquaporin 2 (AQP2)/blue. (B) Ascending thin limbs (ATLs) and prebend segments associated with a primary CD cluster lie at the periphery of, outside of, or amongst the CDs along the entire axial length of the cluster. ATLs and prebend segments/ClCK/green; CDs/AQP2/blue. The upper edge of the image is positioned near the outer medullary‐inner medullary boundary. Scale bars, 250 μm; inset scale bars, 500 μm. Figure modified, with permission, from references 128 and 129.
Figure 13. Figure 13.

Four subsections, or zones, of the rat inner medulla; based on data from the Munich‐Wistar rat (132): (1) an outer‐most zone (OZ1) of about 1 mm thickness, just below the outer medulla, in which loops expressing negligible or no inner medullary aquaporin 1 (AQP‐1) have their bends; (2) a larger outer zone (OZ2), just below the outermost zone, 2 to 2.5 mm in thickness, which contains well‐organized CD clusters in which tubules and vessels are tightly packed and in which loops bend within the central portions of the clusters; (3) an outer inner zone (IZ1) in which the organization of the CD clusters is diminishing and nearly all vasa recta are fenestrated; and (4) an innermost zone (IZ2) in which CD clusters can no longer be distinguished, the CDs appear to dominate all other structures, nearly all vasa recta are fenestrated, and a large fraction of loops have transversely running segments. The two inner zones make up approximately 1.5 to 2 mm of the papilla. CD clusters/blue coalesce into single CDs. AQP1‐positive DTLs/red, AQP1‐negative descending thin limbs (DTLs)/yellow, and ascending thin limbs (ATLs) and prebend segments/green. Scale bar, 1 mm along the axial dimension; lateral dimensions are not to scale. Figure adapted, with permission, from reference 90.
Figure 14. Figure 14.

Organization of a primary CD cluster and thin limbs of the loop of Henle in the Munich‐Wistar rat inner medulla. (A, B) A single transverse section from near the outer medullary‐inner medullary boundary (outer zone 1; see Fig. 13) showing profiles of CDs and associated thin limbs. Aquaporin 1 (AQP1)‐positive descending thin limbs (DTLs)/AQP1/filled red; AQP1‐negative DTLs/α‐B crystallin/unfilled red; ATLs and prebend segments/ClCK/green and white; CDs associated with the primary cluster/aquaporin 2 (AQP2)/dark blue; CDs not associated with the primary cluster are shown in light blue. (A) Thin limbs of short long‐loop nephrons associated with the CD cluster. These thin limbs form their bends within 1 mm below the outer medullary‐inner medullary boundary. AQP1‐negative DTLs lie at the edge of the CD cluster and their connecting prebend segments and ATLs lie in the intracluster region. (B) Thin limbs of long long‐loop nephrons associated with the CD cluster. These thin limbs form their bends between approximately 2 to 3 mm below the outer medullary‐inner medullary boundary. AQP1‐positive DTLs and their connecting ascending thin limbs (ATLs) lie in the intercluster region, distant from CDs. (C‐F) Three‐dimensional reconstruction of primary cluster CDs and associated thin limbs that are shown in A and B. AQP1‐positive/red; AQP1‐negative/yellow; ATLs and prebend segments/green; CDs/blue. The outer medullary‐inner medullary boundary lies near the top edge of the figure. (C) DTLs of nephrons that form their bends within 1 mm below the outer medullary‐inner medullary boundary. (D) DTLs of nephrons that form their bends between approximately 2 to 3 mm below the outer medullary‐inner medullary boundary. (E) ATLs of nephrons that form their bends within 1 mm below the outer medullary‐inner medullary boundary, and (F) ATLs of nephrons that form their bends between approximately 2 to 3 mm below the outer medullary‐inner medullary boundary. Scale bars, 100 μm. Figure modified, with permission, from reference 128.
Figure 15. Figure 15.

Three‐dimensional reconstruction of Munich‐Wistar rat thin limbs of the loop of Henle that form bends at four different levels below the outer medullary‐inner medullary boundary. (A) Thin limbs that form bends within the first mm below the outer medullary‐inner medullary boundary. Descending thin limbs (DTLs) lack detectable aquaporin 1 (AQP1). ClC‐K1 is expressed continuously along the prebend segment and the ascending thin limb (ATL). (B‐D) Thin limbs that form bends below the first millimeter of the inner medulla. AQP1 is expressed along the initial 40% of each DTL (type 2 epithelium), and is absent from the terminal 60% (type 3 epithelium). ClC‐K1 is expressed continuously along the prebend segment and the ATL. Boxed area is enlarged in E. (E) Enlargement of near‐bend regions of four thin limbs from box in D. ClC‐K1 expression begins, on average, approximately 170 μm before the bend (arrows). AQP1‐positive DTLs/AQP1/red; AQP1‐negative DTLs/α‐B crystallin/gray; ATLs and prebend segments/ClCK/green. Scale bars, (A‐D) 500 μm; (E) 100 μm. Figure modified, with permission, from reference 91.
Figure 16. Figure 16.

Schematic diagram of Munich‐Wistar rat thin limb of loop of Henle architecture along the corticopapillary axis (124,131). In the outer medulla, vascular bundles can be considered to be the central organizing elements around which DTLS of long‐loop nephrons, TALs, CDs, and capillaries are systematically arranged; in the inner medulla, the CD clusters can be considered to be the central organizing elements. DTLs of nephrons that form their bends within 1 mm below the outer medullary‐inner medullary boundary express no detectable AQP1 in their inner medullary segments and lie near the interface of the intercluster and intracluster regions; their ATLs lie within the intracluster region (cf. Fig. 14). Descending thin limbs (DTLs) of loops that form their bends deeper than 1 mm below the outer medullary‐inner medullary boundary pass from the intercluster region into the intracluster region above the prebend segment, and their ascending thin limbs (ATLs) exit into the intercluster region above the equivalent postbend length. ATLs may be positioned either adjacent to or distant from their contiguous DTLs. The depicted symmetry between bundle and cluster regions of the outer medulla and inner medulla, respectively, has not been demonstrated.
Figure 17. Figure 17.

Number of Munich‐Wistar rat thin‐limb subsegments along the inner medullary corticopapillary axis. The plot shows the numbers of aquaporin 1 (AQP1)‐positive and AQP1‐negative descending thin limbs (DTLs) and contiguous ascending thin limbs (ATLs) associated with a single secondary CD cluster at successive transverse levels. Prebend segments were not included in the DTL count, and as a result, the number of ATLs exceeds the number of DTLs. The thin‐limb population declines with increasing depth below the outer medullary‐inner medullary boundary, at the exponential rate defined in previous studies (loop decay rate) (43,91,93). Inset: DTL and ATL segments for two inner medullary nephrons. AQP1‐positive DTL/red; AQP1‐negative DTL/yellow; prebend and ATL/green. Figure modified, with permission, from reference 132.
Figure 18. Figure 18.

Interstitial nodal spaces in Munich‐Wistar rat inner medulla, as seen with electron microscopy. Electron micrograph shows a transverse section from outer zone 2 (OZ2; see Fig. 13), showing ascending thin limbs (ATLs) and ascending vasa recta (AVR) arranged around a single CD. Interstitial nodal spaces are marked with X. Scale bar, 10 μm. Figure adapted, with permission, from reference 129.


Figure 1.

Segmentation of thin limbs of the loop of Henle. The short‐loop nephron (right, belonging to a superficial glomerulus) has a descending thick limb (pars recta of proximal tubule; hatched), a descending thin limb (DTL) (turning back near the outer medullary‐inner medullary boundary), and a thick ascending limb (cross hatched), which passes into the distal convoluted tubule a short distance beyond the macula densa (shown in black). The long‐loop nephron (second from right, belonging to a juxtamedullary glomerulus) contains a DTL subdivided into two parts, type 2 and type 3 epithelium; and an ascending thin limb (ATL), type 4 epithelium; the bend is located in the inner medulla. Two additional long‐loop nephrons (incompletely drawn) demonstrate heterogeneity among long‐loop nephrons, which turn back at different levels within the inner medulla. Numbers 1‐4 refer to type of epithelium encountered in corresponding thin limb part: type 1, DTL of short loops; type 2, upper part of DTL of long loops; type 3, lower part of DTL of long loops; type 4 (beginning short distance before bend), ATL. Aquaporin 1 (AQP1)‐negative segments/yellow; AQP1‐positive segments/red; ClC‐K1‐positive segments/green. Figure based on data adapted, with permission, from references 27,63,125, and 185.



Figure 2.

Segmentation of C57/BL/6J mouse short‐loop and long‐loop nephrons. Tortuous descending thin limb (DTL) of long‐loop nephron (LLN; large arrow); winding course of thick ascending limb (red arrowhead) of short‐loop nephron (SLN) and CD (black arrowhead); a piece of TAL inserted in the DTL of LLN (LLNt; small arrow), which forms its bend just beneath the “transitional zone” within the inner medulla; and three different types of SLN bends (SLN1, SLN2, and SLN3). Outer stripe of outer medulla (OSOM), inner stripe of outer medulla (ISOM), and inner medulla (IM). Figure adapted, with permission, from reference 184.



Figure 3.

Immunolocalization of wide‐bend thin limbs of loops of Henle (arrows), ascending thin limb (ATLs), and CDs in Munich‐Wistar rat papilla. ATLs and wide‐bend loops/ClC‐K1/green (structure/immunogen/color), and CDs/aquaporin 2 (AQP2)/blue in a transverse section that lies 70 μm above the tip of the papilla. Scale bar, 100 μm. Figure adapted, with permission, from reference 130.



Figure 4.

Type 1 epithelium of rat short‐loop descending thin limb (DTL). (A) Overview of cross‐sectional profile, x ∼ 4000. (B) Simple type 1 epithelium, x ∼ 12,000. (C) Complex tight junction in freeze‐fracture replica, x ∼ 71000. Intramembrane particle clusters (*) seen on P‐face of basolateral membrane correspond to desmosomes. Figure modified, with permission, from reference 63.



Figure 5.

Type 2 epithelium of rat long‐loop descending thin limb (DTL) (DTLupper). (A) Overview of tubular profile; note many tight junctions (arrows), x ∼ 4000. (B) Longitudinal section through epithelium; numerous tight junctions (arrows) indicate extensive cellular interdigitation. Note basolateral “labyrinth,” x ∼ 18,000. (C) Flat section through epithelium showing star‐like shape of epithelial cells responsible for cellular interdigitation. Note microfilament bundles (*) in basal epithelium, x ∼ 13,500. Figure modified, with permission, from reference 63.



Figure 6.

Type 3 epithelium of rat long‐loop descending thin limb (DTL) (DTLlower). (A) Overview of cross‐sectional profile. Only two tight junctions (arrows) are encountered, x ∼ 3750. (B) Simple type 3 epithelium, x ∼ 16,500. (C) Freeze‐fracture electron microscopy shows complex tight junction, x ∼ 52,000. Figure modified, with permission, from reference 63.



Figure 7.

Type 4 epithelium of rat long‐loop ascending thin limb (ATL). (A) Overview of cross‐sectional profile, x ∼ 3000. Note many tight junctions (arrows). (B) Longitudinal section through epithelium showing high degree of cellular interdigitation (junctions marked by arrows), x ∼ 11,500. (C) Freeze‐fracture electron micrograph showing luminal aspect of two interdigitating cells, x ∼ 12,000. Note two different types of intramembrane textures. Figure modified, with permission, from reference 63.



Figure 8.

Photomicrographs of Munich‐Wistar rat thin limbs of the loop of Henle from the inner medullary outer zone (OZ; see Fig. 13), viewed with differential interference contrast optics. (A) Type 2 epithelium [descending thin limb (DTLupper)] and (B) type 4 epithelium [ascending thin limb (ATL)]. Note cells with nuclei protruding into lumen in type 2 epithelium and cells with large, round, flat nuclei in type 4 epithelium. Scale bar, 100 μm. Figure adapted, with permission, from 127.



Figure 9.

Immunolocalization of tubules and vessels in the inner stripe of the Munich‐Wistar rat outer medulla. CDs/aquaporin 2 (AQP2)/yellow; long‐loop descending thin limb (DTL)/aquaporin 1 (AQP1)/white; short‐loop DTL/UT‐A2/blue; thick ascending limb/ClC‐K2/orange; descending vasa recta/UT‐B/green. Ascending vasa recta, capillaries, and AQP1‐negative long‐loop DTLs are not shown. Overlay of two adjacent transverse sections, 1 μm apart. Scale bar, 250 μm. Unpublished figure, Thomas Pannabecker.



Figure 10.

Immunolocalization of CDs and associated thin limbs of the loop of Henle in the Munich‐Wistar rat inner medulla. The “intracluster” region is bounded by the red borders, the “intercluster” region lies between the red and white borders. Transverse section is from about 400 μm below the outer medullary‐inner medullary boundary (outer zone 1; see Fig. 13). Five primary CD clusters are outlined by white borders; borders were determined by the Euclidean distant map technique (132). These five primary clusters make up a single secondary CD cluster that consists of 31 CDs near the outer medullary‐inner medullary boundary. Descending thin limb (DTL)/aquaporin 1 (AQP1)/red, CD/aquaporin 2 (AQP2)/blue, ascending thin limb (ATL)/ClC‐K1/green. Scale bar, 100 μm. Figure modified, with permission, from reference 132.



Figure 11.

Immunolocalization of thin limbs of the loop of Henle in the Munich‐Wistar rat inner medulla. Transverse sections showing (A) nonuniform distribution of aquaporin 1 (AQP1)‐positive descending thin limb (DTL)/AQP1/red and (B) near uniform distribution of prebend segments and ascending thin limb (ATL)/ClC‐K1/green. Sections lie within 1300 μm below the outer medullary‐inner medullary boundary (outer zone 2, see Fig. 13). AQP1‐negative DTLs are not shown. Scale bars, 100 μm. Figure modified, with permission, from reference 129.



Figure 12.

Three‐dimensional reconstruction of a primary CD cluster and associated tubules and vessels in the Munich‐Wistar rat inner medulla. (A) Descending thin limbs (DTLs) and descending vasa recta that are associated with a primary CD cluster lie at the periphery of or outside of the cluster along the entire axial length of the cluster. Aquaporin 1 (AQP1)‐positive DTLs/AQP1/red; AQP1‐negative DTLs/α‐B crystalline/gray; descending vasa recta/UT‐B/green; CDs/aquaporin 2 (AQP2)/blue. (B) Ascending thin limbs (ATLs) and prebend segments associated with a primary CD cluster lie at the periphery of, outside of, or amongst the CDs along the entire axial length of the cluster. ATLs and prebend segments/ClCK/green; CDs/AQP2/blue. The upper edge of the image is positioned near the outer medullary‐inner medullary boundary. Scale bars, 250 μm; inset scale bars, 500 μm. Figure modified, with permission, from references 128 and 129.



Figure 13.

Four subsections, or zones, of the rat inner medulla; based on data from the Munich‐Wistar rat (132): (1) an outer‐most zone (OZ1) of about 1 mm thickness, just below the outer medulla, in which loops expressing negligible or no inner medullary aquaporin 1 (AQP‐1) have their bends; (2) a larger outer zone (OZ2), just below the outermost zone, 2 to 2.5 mm in thickness, which contains well‐organized CD clusters in which tubules and vessels are tightly packed and in which loops bend within the central portions of the clusters; (3) an outer inner zone (IZ1) in which the organization of the CD clusters is diminishing and nearly all vasa recta are fenestrated; and (4) an innermost zone (IZ2) in which CD clusters can no longer be distinguished, the CDs appear to dominate all other structures, nearly all vasa recta are fenestrated, and a large fraction of loops have transversely running segments. The two inner zones make up approximately 1.5 to 2 mm of the papilla. CD clusters/blue coalesce into single CDs. AQP1‐positive DTLs/red, AQP1‐negative descending thin limbs (DTLs)/yellow, and ascending thin limbs (ATLs) and prebend segments/green. Scale bar, 1 mm along the axial dimension; lateral dimensions are not to scale. Figure adapted, with permission, from reference 90.



Figure 14.

Organization of a primary CD cluster and thin limbs of the loop of Henle in the Munich‐Wistar rat inner medulla. (A, B) A single transverse section from near the outer medullary‐inner medullary boundary (outer zone 1; see Fig. 13) showing profiles of CDs and associated thin limbs. Aquaporin 1 (AQP1)‐positive descending thin limbs (DTLs)/AQP1/filled red; AQP1‐negative DTLs/α‐B crystallin/unfilled red; ATLs and prebend segments/ClCK/green and white; CDs associated with the primary cluster/aquaporin 2 (AQP2)/dark blue; CDs not associated with the primary cluster are shown in light blue. (A) Thin limbs of short long‐loop nephrons associated with the CD cluster. These thin limbs form their bends within 1 mm below the outer medullary‐inner medullary boundary. AQP1‐negative DTLs lie at the edge of the CD cluster and their connecting prebend segments and ATLs lie in the intracluster region. (B) Thin limbs of long long‐loop nephrons associated with the CD cluster. These thin limbs form their bends between approximately 2 to 3 mm below the outer medullary‐inner medullary boundary. AQP1‐positive DTLs and their connecting ascending thin limbs (ATLs) lie in the intercluster region, distant from CDs. (C‐F) Three‐dimensional reconstruction of primary cluster CDs and associated thin limbs that are shown in A and B. AQP1‐positive/red; AQP1‐negative/yellow; ATLs and prebend segments/green; CDs/blue. The outer medullary‐inner medullary boundary lies near the top edge of the figure. (C) DTLs of nephrons that form their bends within 1 mm below the outer medullary‐inner medullary boundary. (D) DTLs of nephrons that form their bends between approximately 2 to 3 mm below the outer medullary‐inner medullary boundary. (E) ATLs of nephrons that form their bends within 1 mm below the outer medullary‐inner medullary boundary, and (F) ATLs of nephrons that form their bends between approximately 2 to 3 mm below the outer medullary‐inner medullary boundary. Scale bars, 100 μm. Figure modified, with permission, from reference 128.



Figure 15.

Three‐dimensional reconstruction of Munich‐Wistar rat thin limbs of the loop of Henle that form bends at four different levels below the outer medullary‐inner medullary boundary. (A) Thin limbs that form bends within the first mm below the outer medullary‐inner medullary boundary. Descending thin limbs (DTLs) lack detectable aquaporin 1 (AQP1). ClC‐K1 is expressed continuously along the prebend segment and the ascending thin limb (ATL). (B‐D) Thin limbs that form bends below the first millimeter of the inner medulla. AQP1 is expressed along the initial 40% of each DTL (type 2 epithelium), and is absent from the terminal 60% (type 3 epithelium). ClC‐K1 is expressed continuously along the prebend segment and the ATL. Boxed area is enlarged in E. (E) Enlargement of near‐bend regions of four thin limbs from box in D. ClC‐K1 expression begins, on average, approximately 170 μm before the bend (arrows). AQP1‐positive DTLs/AQP1/red; AQP1‐negative DTLs/α‐B crystallin/gray; ATLs and prebend segments/ClCK/green. Scale bars, (A‐D) 500 μm; (E) 100 μm. Figure modified, with permission, from reference 91.



Figure 16.

Schematic diagram of Munich‐Wistar rat thin limb of loop of Henle architecture along the corticopapillary axis (124,131). In the outer medulla, vascular bundles can be considered to be the central organizing elements around which DTLS of long‐loop nephrons, TALs, CDs, and capillaries are systematically arranged; in the inner medulla, the CD clusters can be considered to be the central organizing elements. DTLs of nephrons that form their bends within 1 mm below the outer medullary‐inner medullary boundary express no detectable AQP1 in their inner medullary segments and lie near the interface of the intercluster and intracluster regions; their ATLs lie within the intracluster region (cf. Fig. 14). Descending thin limbs (DTLs) of loops that form their bends deeper than 1 mm below the outer medullary‐inner medullary boundary pass from the intercluster region into the intracluster region above the prebend segment, and their ascending thin limbs (ATLs) exit into the intercluster region above the equivalent postbend length. ATLs may be positioned either adjacent to or distant from their contiguous DTLs. The depicted symmetry between bundle and cluster regions of the outer medulla and inner medulla, respectively, has not been demonstrated.



Figure 17.

Number of Munich‐Wistar rat thin‐limb subsegments along the inner medullary corticopapillary axis. The plot shows the numbers of aquaporin 1 (AQP1)‐positive and AQP1‐negative descending thin limbs (DTLs) and contiguous ascending thin limbs (ATLs) associated with a single secondary CD cluster at successive transverse levels. Prebend segments were not included in the DTL count, and as a result, the number of ATLs exceeds the number of DTLs. The thin‐limb population declines with increasing depth below the outer medullary‐inner medullary boundary, at the exponential rate defined in previous studies (loop decay rate) (43,91,93). Inset: DTL and ATL segments for two inner medullary nephrons. AQP1‐positive DTL/red; AQP1‐negative DTL/yellow; prebend and ATL/green. Figure modified, with permission, from reference 132.



Figure 18.

Interstitial nodal spaces in Munich‐Wistar rat inner medulla, as seen with electron microscopy. Electron micrograph shows a transverse section from outer zone 2 (OZ2; see Fig. 13), showing ascending thin limbs (ATLs) and ascending vasa recta (AVR) arranged around a single CD. Interstitial nodal spaces are marked with X. Scale bar, 10 μm. Figure adapted, with permission, from reference 129.

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Article Title: Structure and Function of the Thin Limbs of the Loop of Henle
 

How to Cite

Thomas L. Pannabecker. Structure and Function of the Thin Limbs of the Loop of Henle. Compr Physiol 2012, 2: 2063-2086. doi: 10.1002/cphy.c110019