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Breaking the Seal

So you’re drinking, and you deliberately delay the evening’s first visit to the toilet, because you know that subsequent visits will be much more frequent. That first pee “breaks the seal.” Sound familiar?

Science is here to sweep in and deny our folk intuitions. There is no seal to break, either in a literal or metaphorical sense. Urine production isn’t regulated by how long you wait or how often you go. The water balance in our bodies, and subsequently the rate of urine production, is mostly regulated by our kidneys, which reabsorb fluid. Their fluid absorption, in turn, is regulated by a hormone known as vasopressin or antidiuretic hormone (ADH). Vasopressin is released when osmoreceptors—cells that sense water pressure—detect that there’s too little water in our bodies. Then ADH comes along to the kidneys and says, “Oy! Conserve some more water!” As we conserve water, less urine is produced.

Ethanol throws a wrench in the works by inhibiting the release of ADH. Thus the mere presence of alcohol in your body makes you produce more pee, for any given fluid intake. Of course, it doesn’t help that when drinking, especially when drinking lower-alcohol content beverages like beer, we tend to drink a lot more in a shorter timespan than we otherwise do. The reason the effect is delayed—the reason there is an illusion of a seal to break—is that it takes some time for the body to “use up” the vasopressin that’s already present in your body, and it takes a while for the full effect of alcohol’s diuretic properties to be felt. And of course, it takes some time for that beer to travel from the bottle, down your throat, through your stomach and kidneys and into your bladder as urine. Once your kidneys are working full tilt, it takes a while for them to ramp down production again.

The mechanism by which ADH regulates kidney water absorption was actually a Nobel-worthy discovery. In 2003, Peter Agre was awarded the Nobel Prize in Chemistry for his discovery of aquaporins. These are proteins that function as water channels and transport water molecules efficiently from one place in the cell to another, or between the inside and outside of a cell. They’re quite marvelous molecular machines:

In essence, the architecture of the channel allows water molecules to pass only in single file, and positively charged residues in the channel repel H3O+. Furthermore, the local electrostatic field generated by the protein switches polarity in the middle of the channel, forcing the passing water molecules to rotate in such a way that their dipole moments are oriented in opposite directions in the upper and the lower halves of the channel. This reorientation prevents the formation of a continuous network of hydrogen-bonded water molecules across the channel, and thus blocks the passage of protons via “proton hopping”…

Unique to the cells in the collecting ducts of the kidney, there is an aquaporin called AQP-CD. Recent findings indicate that these are usually found in the vesicles inside the cell. The vesicles are small bubbles inside the cell that have their own membrane. When ADH shows up, this stimulates exocytosis of vesicles—the vesicles merge with the cell’s outer membrane, so that the Aquaporins gain access to the outside of the cell and can start transporting water efficiently from the outside to the inside.

Recent studies have tried to cast doubt on the vasopressin-inhibition explanation for why alcohol makes us pee more. It remains the most complete explanation, however. One study attempted to see if alcohol had any direct effect on the kidney (not mediated by vasopressin). They did an experiment with isolated rat kidneys and alcohol, but couldn’t observe any effect, so that hypothesis is stillborn.

Whatever the complete explanation turns out to be, it’s unlikely to involve any sort of seal or the breaking thereof.