The LoH is the site of action of loop diuretics, the most potent class of diuretic agents. Nephron Structure. Diseases and Cell Therapies Related to. Description description. External Description. Home Contact Us. Copyright LifeMap Sciences, Inc. This site does not provide medical advice and is for research use only.
The other classes of vertebrates, such as amphibians or any of the fish classes, secrete urine that is hypoosmolar relative to their plasma [6,7]. It makes evolutionary sense as to how animals that evolved to survive in drier habitats on land or in the air, such as many birds and mammals, would benefit from the ability to concentrate urine. As access to water becomes more limited, concentrating urine by increasing salt and water resorption in the kidney decreases unnecessary loss [6,7].
Yet the exact relationship between the loop of Henle and water retention in evolution is not as simple as it initially would seem. As the physical shape of the loop of Henle is vital to the creation and maintenance of the corticomedullary gradient, it would follow that longer loops would allow for steeper gradients and greater capacity to concentrate urine.
Indeed, this was supported by initial evolutionary studies that found that desert rodents had larger medullary thickness, a surrogate measurement for loop of Henle length, compared to rodents from environments with more moisture [8]. But this theory of longer loop length leading to greater concentration falls apart on closer evaluation.
Firstly, larger mammals have larger kidneys and therefore larger loops, but in actuality mammalian body mass has been shown to be generally inversely related to urine concentration [9]. Several theories have been proposed to attempt to reconcile this with our understanding of how the loop works. One such explanation points out that, within any given kidney, the nephrons are not all equal in terms of length.
Different species have different relative percentages of long vs. Thus, perhaps mammals with higher ratios of long loops to short loops would have greater ability to concentrate urine. This idea has not been found to be fully supported by reality, however. While species that have only the short-type nephrons in their kidneys, such as beavers, have been shown to have low urine concentration, the species that have only long-type nephrons have only average urine concentrating capability [10].
Other studies looked for different solutions to the discrepancy between loop length and ability to retain water. One study attempted to correct the thickness of the medulla for overall body mass and found that there was still a positive correlation between the relative medulla thickness of different mammals and urine concentration [12].
Another study looked at the biochemical profile of loop function; these researchers found that kangaroo rats from an arid environment had higher protein expression and activity of sodium-potassium ion transporters in the thick ascending limb than other rodent species [13].
This would suggest that cellular variables like genomic expression and protein function may add an additional effect to length of the loop alone. In addition, the apparent inconsistency between strict loop of Henle length and ability to concentrate urine may lie in the fact that our understanding of the loop remains limited to this day.
While the role of the thick ascending limb in sodium chloride transport and creating an osmotic gradient in the outer medulla has been well-described [3,4,5], the function of the thin portion of the ascending limb, which exists in the inner medulla, remains less clear. It has been established that the steep interstitial osmotic gradient exists in the inner medulla as well, which contributes to the concentration of filtrate as it moves through collecting tubules.
It is postulated that the thin ascending limb plays a role in establishing this deeper gradient [5]. The mechanism is less clear, however, as research has shown that the thin limbs do not participate in active transport of solute, unlike the thick ascending limb [14]. This section of the loop is thin because its epithelial cells are physically thin; they lack the dense mitochondria and energy consumption of the epithelium in the thick ascending limb [15].
Animal studies have suggested that the thin ascending limb is permeable to passive diffusion of sodium, chloride, and urea while being impermeable to water [14]. Researchers have created mathematical models as well to better describe the movement of solutes in this portion of the loop [16,17]. Ultimately, understanding this portion of the loop of Henle may be the key next step in elucidating the evolutionary connection between the loop and urine concentration.
For instance, it has been found that in mammals from mesic habitats, which have a moderate supply of moisture, the thickness of the inner medulla a marker for the length of the thin ascending limb is significantly positively associated with ability to concentrate urine [18].
And yet, in day-to-day patient care, different types of medicine are used to disrupt the processes of the kidney to treat disease. These drugs, which include furosemide, bumetanide, and torsemide, have their main site of action in the thick ascending limb of the loop of Henle [20].
These diuretics are secreted into the tubular lumen in the proximal tubule of the nephron before traveling to the thick ascending limb, where they block the electroneutral sodium-potassium-2 chloride pump NKCC [21].
The effect of this decreases solute transport from filtrate to interstitium, which disrupts the interstitial osmotic gradient and reduces water resorption as well. Thus, the loop diuretics can be used to treat conditions of sodium and water overload, such as ascites, congestive heart failure, and high blood pressure, diseases that are encountered nearly daily in internal medicine.
Jacob Henle first noted tubular loops that extended from the cortex to the medulla of the kidney years ago, but the mysteries of these loops continue to be researched today. The loop of Henle and the kidney represent one aspect of how animals have evolved to survive in different habitats, but the ability to retain salt and water is determined by more complicated factors than just the size or number of the loops.
Scientists and physicians have made use of loop diuretics to disrupt the function of the loop in our care of patients, but perhaps a deeper understanding of evolutionary aspects of the loop and its mechanisms will allow for better therapies to be created in the future. Jacob Henle: the kidney and beyond. Am J Nephrol. The loop of Henle, a turning-point in the history of kidney physiology.
Nephrol Dial Transplant. Greger R. Physiol Rev. Editorial: Physiologic role of the loop of Henle in urinary concentration. Kidney Int. Mammalian urine concentration: a review of renal medullary architecture and membrane transporters. J Comp Physiol B. Braun EJ. Comparative aspects of the urinary concentrating process.
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