Urinary Concentrating Mechanism: The Role of the Inner Medulla

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Title: Urinary Concentrating Mechanism: The Role of the Inner Medulla
Authors: Chou, Chung-Lin; Knepper, Mark; Layton, H. E.
Publisher: Seminars in Nephrology
Date Published: March 01, 1993
Reference Number: 355
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Translation

This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)

Humans and animals can maintain body water balance because they can concentrate their urine. The urine concentrating process involves the main working unit of the kidney: the nephron. There are about one million nephrons in each kidney. Each consists of a filter, called a glomerulus, and a tiny tube called the tubule.

The tubule has different segments: the proximal tubule is that segment of the tubule closest to the glomerulus. The distal tubule is that segment furthest from the glomerulus. It connects with a part of the nephron called the kidney collecting duct. Inbetween the proximal and distal tubule is a segment called the Loop of Henle. The Loop of Henle has a descending thin limb, a descending thick limb, an ascending thin and thick limb. The nephrons located in the inner medulla (the innermost part of the kidney) have a long Loop of Henle which turns within the inner medulla.)

Urine is concentrated with relative little expenditure of metabolic energy thanks to a complex interaction between the Loops of Henle, the medullary interstitium (the kidney's inner tissue) and the collecting tubule. The different nephron segments have different degrees of cell membrane permeability. This allows the body fluid moving through the nephron to be reabsorbed into interstitium according to the osmotic conditions at play between the interstitium and the different segments.

Osmosis is the process that allows the reabsorption of body fluid, and hence, the concentration of urine, to take place. It involves the passage of a solvent on one side of a membrane through to the solution on the other side of the membrane. (A solution is comprised of solvent, the liquid part, and solutes, the particle part. For example, the body fluid filtered through the glomerulus is a solution comprised of water (solvent) and solutes such as sodium and calcium.) The solvent flows across the membrane from the solution with the lesser solute concentration to the solution with the greater solute concentration. The solvent flow stops when the solutions on both sides of the membrane are of equal solute concentration.

Body fluid enters the nephron via the glomerulus, which filters it. About two-thirds of this fluid is reabsorbed along the proximal tubule. The remaining fluid then enters the descending limb of Henle having the same osmotic pressure as the plasma in the interstitium. As this fluid enters the descending limb near where Henle's Loop bends, it becomes concentrated with osmotically active particles. By the time the fluid reaches the early portion of the distal tubules, it is always less concentrated than plasma surrounding it because more solute than water is being reabsorbed in the Loop of Henle. This is thought to occur between the bend of Henle's Loop and the early distal tubule. Finally, the fluid flows into the collecting duct where much of the remaining fluid is reabsorbed, leaving behind concentrated urine that is shunted to the bladder and later voided.

This report by Chou, et al., focuses on the mechanisms that are involved in the solute reabsorption that takes place between the bend of Henle's Loop and the early distal tubule, either the thin or thick ascending limb or both. The modern concept of urinary concentration is based on the theory of countercurrent multiplication that states the Loop of Henle can take the small osmotic difference in concentration of particles that exist between a limb of the Loop of Henle and the interstitium adjacent to it (This difference is called the "single effect".) and amplify that difference many-fold so that both fluid and solutes can be reabsorbed to leave behind concentrated urine.

Many researchers believed that the counterflow in the descending and ascending limbs of the Loop of Henle, i.e. that the fluid flows in opposite directions -- down the descending limbs and up the ascending limbs -- multiplies the single effect, i.e. osmotic difference many-fold. Originally, a passive model of countercurrent multiplication was proposed whereby the single effect could be generated in the absence of active transport in the ascending limb. However, research uncovered a mass of data that indicate the passive model may not be valid. Alternatives to the passive model have been introduced (i.e. a dynamic mechanism for generation of the single effect) but none have been generally accepted.

The authors urge researchers to carefully determine whether their in vivo and in vitro measurements taken during relevant experiments faithfully represent the function of the Loop of Henle and the interstitium of the inner medulla. If they do, and if the experimental results still fail to support the passive model for countercurrent multiplication, then the authors suggest considering a dynamic model. They believe a dynamic mechanism, driven by the peristalsis of the pelvic wall, might provide the essential single effect for the inner medullary concentrating mechanism.