Some runners consume water or hypotonic drinks during a race to stay hydrated. Water is also produced from the breakdown of glycogen and triglycerides used as energy by the muscles. However, if the amount of water ingested and produced exceeds the kidneys' ability to excrete or the amount lost through sweating, hyponatremia can occur. Severe hyponatremia can cause neurological symptoms.

The kidneys can excrete a maximum of 18 L of water per day, depending on the amount of solute excreted, which is influenced by food intake. For example, if urine is maximally diluted (Uosm = 50 mOsm/kg H2O), the maximum urine output of 18 L/day can be achieved if the solute excretion rate is 900 mmol/day. Elderly individuals with reduced food intake may have a decreased capacity to excrete water, leading to a lower maximum urine output.

To remove water from the tubular fluid without solute, the kidney generates a hyperosmotic compartment in the renal medulla. This allows passive water reabsorption from the tubular fluid. Henle's loop plays a critical role in establishing the hyperosmotic medullary interstitium, which drives water reabsorption from the collecting duct and urine concentration.

Fig. 35.6 summarizes the osmolality of the tubular fluid at different points along the nephron in the absence and presence of AVP. The tubular fluid entering the loop of Henle from the proximal tubule is isoosmotic with plasma, regardless of AVP. The tubular fluid leaving the thick ascending limb is hypoosmotic to plasma, both in the absence and presence of AVP. In the absence of AVP, the osmolality of the tubular fluid along the collecting duct is hypoosmotic to plasma, but it becomes progressively hyperosmotic from the cortex to the inner medulla in the presence of AVP.

The establishment and maintenance of the hyperosmotic medullary interstitium have been studied for over 50 years. However, the current model for how the medullary osmotic gradient is formed, especially in the inner medulla, is incomplete and not consistent with recent experimental findings on the transport properties of nephron segments in this kidney region.
This reflected the practice of some runners of ingesting water or other hypotonic drinks during the race to remain “well hydrated.” In addition, water is produced from the metabolism of glycogen and triglycerides used as fuels by the exercising muscle. Because over the course of the race they ingested (and generated through metabolism) more water than their kidneys were able to excrete or was lost by sweating, hyponatremia developed. In some racers the hyponatremia was severe enough to elicit the neurological symptoms described previously.
The maximum amount of water that can be excreted by the kidneys (e.g., 18 L/day) depends on the amount of solute excreted, which in turn depends on food intake. For example, with maximally dilute urine (Uosm = 50 mOsm/kg H2O), the maximum urine output of 18 L/day will be achieved only if the solute excretion rate is 900 mmol/day:
If solute excretion is reduced, as commonly occurs in the elderly with reduced food intake, the maximum urine output will decrease. For example, if solute excretion is only 400 mmol/day, a maximum urine output (at Uosm = 50 mOsm/kg H2O) of only 8 L/day can be achieved. Thus individuals with reduced food intake have a reduced capacity to excrete water.
dAlmond CS et al. Hyponatremia among runners in the Boston Marathon. N Engl J Med 2005;352:1150-1556.
involves removing water from the tubular fluid without solute. Because water movement is passive, driven by an osmotic gradient, the kidney must generate a hyperosmotic compartment into which water is reabsorbed, without solute, osmotically from the tubular fluid. The hyperosmotic compartment in the kidney that serves this function is the interstitium of the renal medulla. Henle’s loop is critical for generating the hyperosmotic medullary interstitium. Once established, this hyperosmotic compartment drives water reabsorption from the collecting duct and thereby concentrates urine.
Fig. 35.6 summarizes tubular fluid osmolality at several points along the nephron, both in the absence and presence
CHAPTER 35 Control of Body Fluid Osmolality and Volume of AVP. Note that tubular fluid entering the loop of Henle from the proximal tubule is isoosmotic with respect to plasma and is so regardless of the absence or presence of AVP. Also, tubular fluid leaving the thick ascending limb is hypoosmotic with respect to plasma, both in the absence and presence of AVP. The osmolality of tubular fluid along the collecting duct is hypoosmotic with respect to plasma in the absence of AVP and becomes progressively hyperosmotic (i.e., from cortex to inner medulla) in the presence of AVP.
Establishment and maintenance of the hyperosmotic medullary interstitium has been a subject of study for more than 50 years. Despite this intense study, the most accepted model for how the medullary osmotic gradient is established, especially within the inner medulla, is incomplete and not consistent with more recent experimental findings regarding the transport properties of the nephron segments in this region of the kidney. With the caveat that the current model needs refinement, it is presented here because it embodies some fundamental concepts that underlie the process.