Death by water intake - a look at osmosis and water balance

Many of you have probably already heard about Jennifer Strange, the woman who recently died while attempting to win a free Wii in a water-drinking contest. If you haven't, Orac has two posts that provide lots of background. Death from excessive water intake is not unheard of; for example, long-distance runners can die if they drink too much water in an attempt to stay hydrated (see here). Given water's relatively innocuous reputation, I thought it would be useful to look at a bit of the physiology behind what happens when a person drinks too much water.

Since much of the physiology of water balance depends on osmosis, I'm going to start by reviewing osmosis before getting into the physiology. If you're familiar with osmosis, feel free to skip the osmosis section (quiz to see if you can skip the osmosis section: which direction will water flow if a cell containing a 300 mOsm solution is placed in a beaker with a 150 mOsm solution?¹)

An introduction to osmosis

A key concept to understand when looking at water intake (and water balance) in organisms is osmosis. Osmosis is the tendency of water to move so that it ends up in equal concentrations on both sides of a semipermeable membrane. As an example, if you have a cell full of saltwater that's surrounded with pure water on the outside, the concentration of water inside the cell will be lower than that of the water outside (the salt inside the cell can be thought of as diluting the water), and thus water will move by osmosis from outside the cell to inside the cell. If you were to flip the concentrations (put pure water inside a cell that's surrounded with salty water), water would move the opposite direction (water would leave the cell). While osmosis may sound complicated, it's nothing more than the diffusion of water across a semipermeable membrane.

We can measure the likelihood that water will move into a solution via osmosis; we call this a solution's osmolarity (or osmotic pressure; units are mOsm). The osmolarity of a pure water solution is defined as having an osmolarity of 0 mOsm; the osmolarity of a solution is increased by adding solutes (salt, amino acids, glucose, or whatever else you want) to it. The higher the osmolarity of a solution, the more likely water is to osmose into it. So, to return to the salt and pure water example above, the pure water solution outside the cell has an osmolarity of 0 mOsm, while the salt solution inside the cell has a higher osmolarity (let's call it 100 mOsm, but at the least we know it's greater than 0), and thus water will move from the lower to the higher osmolarity solution (water will move into the cell).

We use osmosis in our bodies for many things. Osmotic gradients lead to water flowing into our bodies through tiny gaps between the cells of our small intestines (our guts are regulated so that the osmolarity of the gut contents is lower than that of the surrounding cells and interstitial spaces); this bulk flow of water brings along with it digested nutrients, and this is one of the mechanisms of nutrient absorption in our gut. Our kidneys use osmotic gradients to concentrate (or dilute) urine as it's being produced; to make concentrated urine the kidneys pass "pre urine" through an area of high osmotic pressure (high salt and urea concentration), thus causing water to osmose out of the urine (making the urine more concentrated).

Most regions of our body have the same osmolarity (~290 mOsm), and thus osmosis doesn't normally cause a net movement of water into or out of them. However, if we change the osmolarity of one component of the body (say, the blood plasma), then water will start moving from one region of the body to another. So, for instance, if you drank a lot of water, that water will be absorbed into your blood, and your blood plasma's osmolarity will be lowered (as the extra water dilutes the solutes). Once your blood osmolarity drops (say from 290 mOsm to 280 mOsm), water would start moving by osmosis from your blood into the other tissues of your body (as water would move from the lower osmolarity region in the blood plasma to the higher osmolarity region in your body tissues).

The physiology of drinking too much water

Now that we've gotten the general idea of osmosis and water movement, let's take a look at what happens when a person drinks too much water. Before I get into too much detail, however, I want to mention that my chemistry and physiology here will be filled with simplifying assumptions², and that I'm not a doctor and thus nothing I say should be taken as medical advice.

Jennifer Strange is reported to have consumed approximately 2 gallons (~7.5 liters) of water during the contest (data from Orac's post and this article). To put that volume into context, we need to look at how much water is in the human body.

Rough physiological formulas indicate that about 60% of our body mass is water (Berne et al. 1998). About 2/3 of that water is contained inside our cells, and is called intracellular fluid (Berne et al. 1998). The remaining 1/3 is contained outside our cells, and is called extracellular fluid (Berne et al. 1998). About 1/4 of the water contained outside of our cells is blood plasma; the rest is contained in the interstitial spaces around our cells (Berne et al. 1998). So, if we assume that Jennifer Strange was 165 pounds (the average weight of adult females in the US³; I have no idea what her weight was), we get the following amounts of water:

• Body mass: 165 lb (~75 kg)
• Total body water content: 45 L (75 kg * 0.6 * 1 L/kg)
• Total intracellular fluid: 30 L (45 L * 2/3)
• Total extracellular fluid (including blood plasma): 15 L (45 L * 1/3)
• Total blood plasma: 3.75 L (15 L * 1/4)

While those numbers are clearly just approximations, we can now see how large a volume of water 2 gallons (7.5 L) is: it's double the volume of water in the average female's blood plasma, and half the total water content of the average female's extracellular fluid. Adding that much water to a solution can clearly alter its osmolarity (by diluting the ions in solution), and thus will have a strong effect on osmotic movement of water in the body.

Of course we have kidneys, and one of their functions is to excrete excess water. So, a person could safely drink 2 gallons of water, as long as they could excrete those 2 gallons as quickly as they absorbed them. Unfortunately, the kidneys are limited in how fast they can excrete water; Orac cites data that the kidneys of a healthy adult can excrete a maximum of about 1 L of water per hour.

So, to fully understand what happens when a person drinks a large volume of water, we must look at this as a dynamic process. Water is being ingested at a specific rate, is then absorbed into the body (first stop: the blood plasma), is circulated around the body (where it is exposed to the various tissues of the body), and is then excreted from the body by the kidneys.

Based on the newspaper reports, contestants were given 0.25 L of water every 12 minutes, which is about 1.25 L per hour⁴. However, at some point in the contest the ingestion rate was increased, as contestants are reported as being given a "larger bottle." I don't have specific information on the duration of the contest, but to simplify things lets assume that contestants drank 1.25 L of water each hour for the first two hours, and then drank the remainder of the water in the next 2 hours (4 hours total seems like a good estimate for the duration of a radio show contest). Here's the net balance:

• Intake:
• First 2 hours: 2.5 L
  
• Last 2 hours: 5 L
• Total intake: 7.5 L
  
• Kidney filtration:
• First 2 hours: 2 L
• Last 2 hours: 2 L
• Total excretion: 4 L
  
• Net balance:
• Gain of 3.5 L of water

Note that this assumes both that all the water ingested was absorbed immediately (an incorrect assumption, as osmosis of water from the gut into the body will take time), and that all of the kidney filtration occurred immediately (again an incorrect assumption, especially as the contestants were prevented from urinating during the contest). However, lets hope that the delayed absorption of water in the gut is canceled out by the delayed (and possibly inhibited) filtration of water by the kidneys, and keep things simple by ignoring both.

The osmolarity of blood plasma is determined largely by the concentration of sodium in the plasma (typically 145 mmEq/L, which leads to a net blood plasma osmolarity of ~290mOsm; Berne et al. 1998). Given a starting blood plasma volume of 3.75 L (with 145 mmEq/L Na), and a final volume of 7.25 L (3.75 L starting + 3.5 L gain), the sodium concentration of the blood at the end of the contest (assuming no input of sodium from other body stores) would drop to 75 mmEq/L (3.75 L * 145 mmEq/L Na * 1/(7.25 L)). Orac specifies that a sudden drop in blood plasma sodium concentration from normal levels to below 120 mmEq is often fatal, so this drop in sodium concentration would be fatal.

As the sodium concentration of the blood plasma drops, the blood plasma's osmolarity will also drop (75 mmEq/L Na would lead to a blood plasma osmolarity of ~150 mOsm). This drop in plasma osmolarity would create an osmotic gradient between the blood plasma and extracellular fluid (the extracellular fluid would be 290 mOsm initially, as it is generally isotonic to the blood plasma under normal conditions). Thus, once some water is absorbed into the plasma, it will osmose from the blood plasma to the extracellular fluid.

So, let's assume that the extra 3.5 L of water isn't all stored in the blood plasma, but is also moved to the extracellular fluid that's in the interstitial spaces. In this case we start with 15L of extracellular fluid with a sodium concentration of 145 mmEq/L (extracellular fluid has about the same sodium concentration as blood plasma), and end with 18.5 L of extracellular fluid (15 L + 3.5 L gain). This scenario leads to a final extracellular fluid sodium concentration of 118 mmEq/L (~236 mOsm), again low enough to lead to death.

But what is actually causing death? While I'm not an expert here (and haven't been able to find a good reference for this quickly), one of the problems that the body runs into in this situation is that those 3.5 liters of water have to go somewhere. As we've seen above, that somewhere will initially be the blood plasma and extracellular fluid, which will be followed by movement of water into the intracellular fluid pool (i.e., inside cells, which are ~290 mOsm to begin with, and will thus begin absorbing water as soon as the osmolarity of the extracellular fluid drops). All of this water movement means that tissues throughout the body are going to be gaining water, and when tissues gain water they swell. This swelling can be tolerated to some extent in many tissues (e.g., your leg muscles), but can lead to extremely negative effects when it occurs in tissues that have only a limited ability to expand, such as your brain (which is mostly surrounded by bone). Swelling in the brain increases pressure on the tissues of the brain, which can lead to many problems, including reduced transport of nutrients from the capillaries in the brain to the cells of the brain⁵. Many of the symptoms of hyperhydration/hyponatremia are neurologic (fatigue, headache, loss of alertness, cognitive impairment; see here and here), and thus it seems likely that swelling in the brain is at least a contributing factor to why people die after drinking too much water⁶.

To end with a little taxonomic diversity, plants can actually tolerate this type of osmotic situation very easily (you water your plants with tapwater, right?) The difference is that plant cells are surrounded by a rigid cell wall, whereas animal cells have just a wimpy little plasma membrane (plant cells have a plasma membrane too). This cell wall restricts the ability of plant cells to expand (it's like a little suit of armor), and thus once the plant cell is full of water (turgid), the cell wall exerts a force (a pressure) that counteracts osmosis and prevents water from entering the cell. Thus, plant cells can have a higher osmolarity than their environment (e.g., be immersed in gallons of pure water), but not risk death due to excessive water intake⁷.


Reference

Berne, R. M., M. N. Levy, B. M. Koeppen, and B. A. Stanton. 1998. Physiology: 4th edition. Mosby, St. Louis.


¹ Water will flow into the cell.
² In addition to the assumptions stated in the rest of the article, I'm assuming (among other things) that all consumed water was absorbed into the body (it could have been vomited out, remained in the gut, or excreted with fecal material), that the water ingested was pure water (it wasn't; fresh water typically has an osmolarity around 70 mOsm), and that non-excretory sources of water loss (breathing, sweating, crying, etc.) were minimal. I'm also entirely ignoring the lymph system, which transports excess interstitial fluid back to the blood.
³ Data from the Wikipedia and this article.
⁴ Based on this quote "participants were given two minutes to drink an 8-ounce [~0.25 L] bottle of water and then given another bottle to drink after a 10-minute break," and then this quote "Sherrod said she managed to drink eight, eight-ounce bottles but became nauseated after drinking half of a larger bottle." (both quotes from here)
⁵ Nutrient delivery from capillaries to the surrounding tissues requires a pressure difference between the inside of the capillaries and the interstitial fluid surrounding them (the fluid in the capillaries is under higher pressure thanks to the heart; this higher pressure forces nutrient-filled fluid out of the capillaries). Increased pressure in the brain would negate this pressure difference, and could thus reduce (or eliminate) nutrient delivery.
⁶ Note, however, that I am not certain of this. Other factors could also play a role; for example, it seems at least feasible that the changes in ion concentrations might alter nerve and muscle resting membrane potentials enough to cause problems.
⁷ So why do terrestrial plants die from overwatering, you ask? It's actually because plant roots need oxygen to survive (they're an oxidatively metabolizing tissue; they can't do photosynthesis to generate oxygen or carbohydrates because it's rather dark in the soil), and when soil is saturated with water the roots can't obtain enough oxygen. Thus, overwatered plants functionally die by drowning.

[Updated to correct the name to Jennifer Strange.]
[Update 2, July 2007: The Georgetown Medical Center has a detailed article on water requirements during exercise here.]