Urine Concentration and Dilution

The kidney can generate a urine as dilute as 40 mOsm (one seventh of plasma osmolality) or as concentrated as 1200 mOsm (four times plasma osmolality)

In the steady state, water intake and output must be equal ( Table 38-1 ). The body's three major sources of water are (1) ingested water, (2) water contained in the foods eaten, and (3) water produced by aerobic metabolism as mitochondria convert foodstuffs and O ₂ to CO ₂ and H ₂ O (see p. 1185 ).

The major route of water loss is usually through the kidneys, the organs that play the central role in regulating water balance. The feces are usually a minor route of water output (see p. 901 ). Although the production of sweat can increase markedly during exercise or at high temperatures, sweat production is geared to help regulate body core temperature (see p. 1201 ), not body water balance. Water also evaporates from the skin and is lost in the humidified air exhaled from the lungs and air passages. The figures summarized in Table 38-1 will obviously vary, depending on diet, physical activity, and the environment (e.g., temperature and humidity).

The kidney adjusts its water output to compensate for either abnormally high or abnormally low water intake, or for abnormally high water losses via other routes. The kidney excretes a variable amount of solute, depending especially on salt intake. However, with consumption of a normal diet, the excreted solute is ~600 milliosmoles/day. For average conditions of water and solute intake and output, these 600 milliosmoles are dissolved in a daily urine output of 1500 mL. A key principle is that, regardless of the volume of water they excrete, the kidneys must excrete ~600 milliosmoles/day. Stated somewhat differently, the product of urine osmolality and urine output is approximately constant:

Therefore, to excrete a wide range of water volumes, the human kidney must produce urine having a wide range of osmolalities. For example, when the kidney excretes the 600 milliosmoles dissolved in 1500 mL of urine each day, urine osmolality must be 400 milliosmolar (i.e., 400 mOsm):

When the intake of water is especially high, the human kidney can generate urine having an osmolality as low as ~40 mOsm. Because the kidneys must still excrete 600 milliosmoles of solutes, the urine volume in an extreme water diuresis would be as high as ~15 L/day.

However, when it is necessary to conserve water (e.g., with restricted water intake or excessive loss by sweat or stool), the kidney is capable of generating urine with an osmolality as high as ~1200 mOsm. Therefore, with an average solute load, the minimal urine volume can be as low as ~0.5 L/day:

Therefore, the kidney is capable of diluting the urine ~7-fold with respect to blood plasma, but it is capable of concentrating the urine only ~4-fold. Renal failure reduces both the concentrating and diluting ability.

Free-water clearance ( ) is positive if the kidney produces urine that is less concentrated than plasma and negative if the kidney produces urine that is more concentrated than plasma

A urine sample can be thought of as consisting of two moieties: (1) the volume that would be necessary to dissolve all the excreted solutes at a concentration that is isosmotic with blood plasma, and (2) the volume of pure or solute-free water —or, simply, free water —that one must add (or subtract) to the previous volume to account for the entire urine volume. As discussed below, the kidney generates free water in the tubule lumen by reabsorbing solutes, mainly NaCl, in excess of water along nephron segments with low water permeability. When the kidney generates free water, the urine becomes dilute (hypo-osmotic). Conversely, when the kidney removes water from an isosmotic fluid, the urine becomes concentrated (hyperosmotic). When the kidney neither adds nor subtracts free water from the isosmotic moiety, the urine is isosmotic with blood plasma.

The urine output is the sum of the rate at which the kidney excretes the isosmotic moiety of urine (osmolal clearance, C _Osm ) and the rate at which it excretes free water— free-water clearance ( ):

Of course,
is negative (i.e., excretion of negative free water) if the kidney removes free water and produces a concentrated urine. We compute C _Osm in the same way we would compute the clearance of any substance from the blood (see p. 731 ):

P _Osm is the osmolality of blood plasma. The osmolal clear­ance is the hypothetical volume of blood that the kid­neys fully clear of solutes (or osmoles) per unit time. For example, if the daily solute excretion (U _Osm ⋅
) is fixed at 600 milliosmoles/day, and P _Osm is 300 milliosmoles/L, then Equation 38-6 tells us that C _Osm has a fixed value of 2 L/day.

We can obtain the only by subtraction:

Indeed,
does not conform to the usual definition of “clearance” because
is not
. Never­theless, this apparent misnomer has been accepted by renal physiologists and nephrologists.
N38-1

N38-1

“Effective Osmolal-less” versus “Osmolal-less” Water Clearance

In the text, we define free-water clearance as the clearance of water that is devoid of all solutes. However, if you were interested in how a gain or loss of water would affect cell volume, you would really be interested in the clearance of water that is devoid of impermeant or effective solutes (see discussion of effective osmolality on pp. 132–133 ). These effective osmoles do not include urea because cells are generally highly permeable to urea, owing to the presence of transport pathways for urea (see p. 770 ). Therefore, it may be useful to consider the clearance of water that is devoid of all effective osmoles. We will—tongue in cheek—define this as effective osmolal-less water clearance, to distinguish it from classical free-water clearance, which is osmolal-less water clearance.

Urea can be one of the major contributors to urine osmolality (U _Osm ) and thus an important contributor to osmolal clearance (C _Osm ):

Equation NE 38-1 above is also Equation 38-6 . Because urea equilibrates freely across cell membranes, it does not influence the effective plasma osmolality (P _{effective-Osm} ) nor the distribution of water between cells and the extracellular fluid. Thus, we could convert Equation NE 38-1 to an expression for effective osmolal clearance by substituting U _{effective-Osm} for U _Osm and P _{effective-Osm} for P _Osm in Equation NE 38-1 . The resulting new expression for effective osmolal clearance (C _{effective-Osm} ) is

$C_{\text{effective-Osm}}=\frac{U_{\text{effective-Osm}}\cdot \dot{V}}{P_{\text{effective-Osm}}}$

Note that in both the numerator and the denominator, we are considering only the effective osmoles in urine and plasma.

By analogy to Equation 38-7 , the effective osmolal-less water clearance is

$\begin{array}{c}{C}_{H_{2}O}^{*}=\dot{V}-C_{\text{effective-Osm}}\\ \text{or}\\ C_{H_{2}O}^{*}=\dot{V}-\frac{U_{\text{effective-Osm}}\cdot \dot{V}}{P_{\text{effective-Osm}}}\end{array}$

Because plasma levels of urea are generally quite low (i.e., P _{effective-Osm} ≅ P _Osm ), the important issue is the extent to which urea contributes to the total osmolality of the urine (i.e., the extent to which U _Osm exceeds U _{effective-Osm} ).

The range of values for the human kidney is related to the extremes in urine osmolality, as shown in the three examples that follow.

Isosmotic Urine

If the osmolalities of the urine and plasma are the same (U _Osm = P _Osm ), then osmolal clearance equals urine flow:

Therefore, Equation 38-7 tells us that the
must be zero.

Dilute Urine

If the urine is more dilute than plasma ( > C _Osm ), the difference between and C _Osm is the positive . When the kidney maximally dilutes the urine to ~40 mOsm, the total urine flow ( ) must be ~15 L/day, and is a positive 13 L/day (see Equation 38-3 ):

Concentrated Urine

If the urine is more concentrated than plasma ( < C _Osm ), then the difference between and C _Osm is a negative number, the negative . When the kidney maximally concentrates the urine to 1200 mOsm, the total urine flow must be 0.5 L/day, and is a negative 1.5 L/day (see Equation 38-4 ):

Thus, the kidneys can generate a
of as much as +13 L/day under maximally diluting conditions, or as little as −1.5 L/day under maximally concentrating conditions. This wide range of
represents the kidneys' attempt to stabilize the osmolality of extracellular fluid in the face of changing loads of solutes or water.

The kidney concentrates urine by driving water via osmosis from the tubule lumen into a hyperosmotic interstitium

The kidney generates dilute urine by pumping salts out of the lumen of tubule segments that are relatively impermeable to water. What is left behind is tubule fluid that is hypo-osmotic (dilute) with respect to the blood.

How does the kidney generate concentrated urine? One approach could be to pump water actively out of the tubule lumen. However, water pumps do not exist (see pp. 127–128 ). Instead, the kidney uses osmosis as the driving force to concentrate the contents of the tubule lumen. The kidney generates the osmotic gradient by creating a hyperosmotic interstitial fluid in a confined compartment, the renal medulla. The final step for making a hyperosmotic urine—controlled by regulated water permeability—is allowing the lumen of the medullary collecting duct (MCD) to equilibrate with the hyperosmotic interstitium, resulting in a concentrated urine.

Although net absorption of H ₂ O occurs all along the nephron, not all segments alter the osmolality of the tubule fluid. The proximal tubule, regardless of the final osmolality of the urine, reabsorbs two thirds of the filtered fluid isosmotically (i.e., the fluid reabsorbed has nearly the same osmolality as plasma). The loop of Henle and the distal convoluted tubule (DCT) reabsorb salt in excess of water, so that the tubule fluid leaving the DCT is hypo-osmotic. Whether the final urine is dilute or concentrated depends on whether water reabsorption occurs in more distal segments: the initial and cortical collecting tubules (ICT and CCT) and the outer and inner medullary collecting ducts (OMCD and IMCD). Arginine vasopressin (AVP) —also called antidiuretic hormone (ADH) —regulates the variable fraction of water reabsorption in these four nephron segments. Figure 13-9 shows the structure of AVP.