Urinary Concentration The Loop of Henle

The challenge of any model of urine formation is to see how concentrating and diluting mechanisms work together to determine the composition of the urine and to regulate the interstitial contents, and then to account quantitatively for the concentrating ability of particular species. The challenge is substantial. For example, for humans, the maximal urine concentrating ability is 1200 mOsm/liter, while some desert animals, such as the Australian hopping mouse, can concentrate urine to as high as 10,000 mOsm/liter. It is not understood how such high urine concentrations can be obtained. It is also necessary that the kidney be able to produce a dilute urine under conditions of high fluid intake.

A normal 70 kg human must excrete about 600 mOsm of solute (waste products of metabolism and ingested ions) every day. The minimal amount of urine to transport these solutes, called the obligatory urine volume is total solute/day obligatory volume =-:-=-:---:— (20.13)

maximal urine concentration

600 mOsm/day

1200 mOsm/L J

This explains why severe dehydration occurs from drinking seawater. The concentration of salt in the oceans averages 3% sodium chloride, with osmolarity between 2000 and 2400 mOsm/liter. Drinking 1 liter of water with a concentration of 2400 mOsm/liter provides 2400 mOsm of solute that must be excreted. If the maximal urine concentration is 1200 mOsm/liter, then 2 liters of urine are required to rid the body of this ingested solute, a deficit of 1 liter, which must be drawn from the interstitial fluid. This explains why shipwreck victims who drink seawater are rapidly dehydrated, while (as Guyton and Hall have kindly pointed out) the victim's pet Australian hopping mouse can drink all the seawater it wants with impunity.

Urinary concentration or dilution is accomplished primarily in the loop of Henle. After leaving Bowman's capsule, the glomerular filtrate flows into a tubule having five sections: the proximal tubule, the descending limb of the loop of Henle, the ascending limb of the loop of Henle, the distal tubule, and, finally, the collecting duct. These tubules are surrounded by capillaries, called the peritubular capillaries, that reabsorb the fluid that has been extracted from the tubules. In Fig. 20.9 are shown the relative concentrations of various substances at different locations along the tubular system.

The purpose of the proximal tubule is to extract much of the water and dissolved chemicals (electrolytes, glucose, various amino acids, etc.) to be reabsorbed into the bloodstream while concentrating the waste products of metabolism. It is this concentrate that eventually flows as urine into the bladder. The proximal tubular cells to to to 585 140 125

to to to 585 140 125

Hopping Mouse Loop Henle

tubule Henle tubule tubule

Figure 20.9 Relative concentrations of various substances as functions of distance along the renal tubule system. (Guyton and Hall, 1996, Fig. 27-11, p. 341.)

tubule Henle tubule tubule

Figure 20.9 Relative concentrations of various substances as functions of distance along the renal tubule system. (Guyton and Hall, 1996, Fig. 27-11, p. 341.)

have large numbers of mitochondria to support rapid active transport processes. Indeed, about 65 percent of the glomerular filtrate is reabsorbed before reaching the descending limb of the loop of Henle. Furthermore, glucose, proteins, amino acids, ace-toacetate ions, and the vitamins are almost completely reabsorbed by active cotransport processes through the epithelial cells that line the proximal tubule.

Any substance that is reabsorbed into the bloodstream must first pass through the tubular membrane into the interstitium and then into peritubular capillaries. There are three primary mechanisms by which this transport takes place, all of which we have filtration

Peritubular Capillary

Tubular Cells


Peritubular Capillary

Loop Henle Cell Types


—Passive (Diffusioi



—Passive (Diffusioi


Paraceltular Path

Transcellular Path

^Z; Solutes

Paraceltular Path

Transcellular Path jflEABSORFTION

Figure 20.10 Schematic diagram of the reabsorption of water and solutes in the proximal tubule. (Guyton and Hall, 1996, Fig. 27-1, p. 332.)

seen before (Fig. 20.10). First, there is active transport of Na+ from the interior of the epithelial cells into the interstitium, mediated by a Na+-K+ ATPase pump. Although this pump actively pumps K+ into the cell from the interstitium, both sides of the tubular epithelial cells are so permeable to K+ that virtually all of the K+ leaks back out of the cell almost immediately.

There are secondary transporters that use the gradient of Na+ ions (established by the ATPase) to transport other substances from the tubular lumen into the interior of the epithelial cell. The most important of these are cotransporters of glucose and amino acid ions, but the epithelial cells of the proximal tubule also contain transporters of phosphate, calcium, and magnesium ions. There is also a transporter that exchanges hydrogen ions for Na+ ions across the membrane of the epithelial cell membrane into the tubule. The third mechanism of transport is that of water across cell membranes, mediated by osmotic pressure (see Chapters 2 and 21).

The descending limb of the loop of Henle is lined with thin epithelial cells with few mitochondria, indicating minimal metabolic activity; it is highly permeable to water and moderately permeable to Na+, urea, and most ions. The ascending limb of the loop of Henle begins with a thin wall but then about halfway up becomes grossly thickened. In contrast to the descending limb, the ascending limb is highly impermeable to water and urea. The cells of the thick ascending limb are similar to those of the proximal tubule, suited for strong active transport of Na+ and Cl- ions from the tubular lumen into the interstitial fluid.

The thick segment travels back to the region of the glomerulus, where it passes between the afferent and efferent arterioles, forming the juxtaglomerular apparatus, where much of the feedback control of the flow rate takes places. Passing beyond this point, the tubule becomes the distal tubule, the function of which is similar to that of the ascending limb of the loop of Henle.

Finally, the flow enters the descending collecting duct, which gathers the flow from several nephrons and descends back through the cortex and into the outer and inner zones of the medulla. The flow from the collecting duct then flows out of the kidney through the ureter on the way to the bladder. The cells lining the collecting duct are sensitive to a number of hormones that act to regulate their function as well as the final chemical composition of the urine. Primary among these hormones are aldosterone and antidiuretic hormone (ADH). Aldosterone determines the rate at which Na+ ions are transported out of the tubular lumen, and ADH determines the permeability of the collecting duct to water, and thereby determines the final concentration of the urine. When there is no ADH present, the collecting duct is impermeable to water, but with ADH present, the permeability of the collecting duct allows water to be reabsorbed out of the collecting duct, leaving behind a more highly concentrated urine.

Putting this all together, we arrive at a qualitative summary of how a nephron operates. Along the ascending limb of the loop of Henle portion of the tubule, Na+ is absorbed into the interstitium, either passively (in the thin ascending limb) or actively (in the thick ascending limb). This creates a high Na+ concentration in the intersti-tium, which then serves to draw water out of the descending limb and allows Na+ to reenter the descending limb. Hence, fluid entering the descending limb is progressively concentrated until, at the turning point of the loop, the fluid osmolarity is about 1200 mOsm/liter (compared to the entering fluid, which is about 300 mOsm/liter). Clearly, because the fluid entering the ascending limb is so concentrated, Na+ extraction from the ascending limb is enhanced, which further enhances water extraction from the descending limb, and so on. This positive feedback process is at the heart of the coun-tercurrent mechanism, to be discussed in more detail below. As the fluid ascends the ascending limb, Na+ is continually extracted until, at the level of the juxtaglomerular apparatus, the fluid in the tubule is considerably more dilute than the original filtrate. However (and this is the crucial part), the dilution process results in a steep gradient of Na+ concentration in the interstitium, a gradient that can, when needed, concentrate the urine.

When there is no ADH present, the dilute urine formed by the loop of Henle proceeds through the collecting duct essentially unchanged, resulting in a large quantity of dilute urine. In the presence of large amounts of ADH, the collecting duct is highly permeable to water, so that by the time the filtrate reaches the level of the turning point of the loop of Henle, it is essentially at the same concentration as the interstitium, about 1200 mOsm/liter, thus giving a small quantity of concentrated urine.

It is important to emphasize that the principal functions of the loop of Henle are, first, the formation of dilute urine, which allows water to be excreted when necessary, and, second, the formation of the interstitial gradient in Na+ concentration, which allows for the formation of a concentrated urine when necessary. The importance of the loop of Henle in creating the interstitial gradient of Na+ concentration is underlined by the fact that although all vertebrates can produce dilute urine, only birds and mammals can produce hyperosmotic urine, and it is the kidneys of only these animals that contain loops of Henle.

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  • roma abel
    Can concentrate urine to as high?
    8 years ago

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