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A primer on diuretics

Below is an excerpt of a chapter I’m writing on diuretics for my new book on steroids. And yes, the book will be written in English. I’ve taken the references out, because I’m too lazy to include them right now (they will be available in the book of course).

Diuretics

I’m not sure about which subject drug coaches go most potato: the AAS or the diuretics. Either way, going potato with diuretics is by far more dangerous than going potato with AAS. Diuretics are so dangerous that they can get you hospitalized within hours if you don’t know what you’re doing. Even worse, it can get you into a coffin. Perhaps these drug coaches hold shares in coffin companies, I don’t know.

Either way, I feel almost obliged to give a good and comprehensive explanation of how the human body regulates its fluids and how diuretics tie in to that. Hopefully this chapter will get rid of at least some of the dangerous practices I see with drug coaches advising about diuretics. Their advises being dangerous because of a total misunderstanding of how they work.

First, I’ll provide an explanation about how body fluid is distributed into a number of compartments. Not all fluids entering or leaving the body have the same effect on fluid distribution. This concept is at the center of what most bodybuilders are after. They want to look dry on-stage. Obviously, they’re not after losing fluids from their muscle cells. This will make their muscles shrink, since they lose volume and it will not aid at all in obtaining a dry look. So the first section of this chapter will cover fluid distribution and which forces act on it and can thereby cause shifts in it.

Second, I’ll go over how your kidneys work, because this organ takes center stage when it’s about fluid regulation. It’s the sole organ of the human body which is able to directly regulate the total amount of water (and electrolytes) you’re carrying around.

Finally, it’s the organ which is targeted by diuretics and which will be the topic of the third section of this chapter. All diuretics have in common that they make you lose water. However, various classes of diuretics exists and they differ in their mechanism of action. As a consequence, they also differ in side-effects and their effect on body fluid distribution. Importantly, they also strongly differ in how dangerous they are!

Fluid distribution and changes in the body

The human body contains an awful lot of water, in fact, the majority of your body mass is just that. Water. The blood flowing through your veins, the saliva running through your mouth when you opened this book for the first time, those digestive juices secreted in your gastrointestinal tract after you ate that chicken breast, etc. Fluid is running everywhere through your body.

Physiology textbooks make a distinction between fluid contained within cells and that outside of cells. The total body water within cells is called the intracellular fluid (ICF) and the total body fluid outside of cells is called the extracellular fluid (ECF). The ECF is then further subdivided into interstitial fluid (the fluid between the cells where they bath in) and the blood plasma, which runs through your veins. This distinction is not an arbitrary one, as we will discover in this section. It’s one of high relevance physiologically.

What’s important about these body compartments is that they are physically separated from each other by what is called a semipermeable membrane. The ICF is separated from the ECF by cell membrane, whereas the interstitial fluid and blood plasma is separated by endothelial membrane (the membrane lining of the blood vessels). But what is that exactly, a semipermeable membrane? Simply put, it’s a membrane which selectively lets through some substances, but not others. As a consequence, different amounts of different substances can be found at each side of such a membrane. When considering a cell, the composition of substances dissolved in its intracellular fluid is vastly different from that of the interstitial fluid surrounding it. For example, sodium (Na+) is found in a relatively high concentration (roughly 140 mM) extracellularly compared to intracellularly (around 10 mM in most cells). This concentration difference is the result of the cell membrane. Ions such as Na+, but also chloride (Cl) and potassium (K+), among others, cannot freely diffuse across it.

This brings me to a process which will probably remind you of your biology classes in high school, namely, osmosis. In contrast to the ions I just mentioned, water can always freely diffuse across a cells membrane. The net flow with which this happens is dependent on the tonicity of either side. It’s the number of solutes in a solvent, commonly expressed as milliosmoles per kg of solvent, which cannot freely pass the membrane. If the tonicity on both sides of the membrane is equal (and ignoring other forces), there will be no net water movement between both sides. However, if there’s a higher tonicity on one side of the membrane than the other (again, ignoring other forces), then there will be net water movement from the lower tonicity side to the higher tonicity side, until an equilibrium is reached. When you add more water to a side with higher tonicity, as is the case when water flows to it, it’s tonicity will drop. This is because the amount of solutes does not change while the amount of solvent is increased. So in summary, when the tonicity on both sides is equal, the net water movement will stop. This flow of water across the membrane which is driven by this difference in tonicity on either side is called osmosis.

For example, lets say you have a glass of salty water. You put a membrane in the middle which is permeable for water, so it will let water freely cross it. And this membrane is not be permeable for table salt (Na+ and C), so it will not let Na+ and Cl cross it. First, the tonicity on either side will be equal (no different in the amount of solutes on either side). But then you add a bit more table salt on one side, but not the other. You’ll have more solutes now on that side, making it hypertonic compared to the other side (and the other side being hypotonic relative to it). As a result, there will be a net water movement from the side to which you didn’t add salt to, to the the hypertonic side, until an equilibrium is reached. However, some might think that the equilibrium is reached when the tonicity of either side is equal again (isotonic). But this is not the case, because there are other forces in play which drive the water flow. If you’ve ever been scuba diving, you probably noticed you have to ‘pop’ your ears when you go deeper and deeper. This is the weight of the water above you pressing on you and your ears. Similarly, in our example, when water is moving to the hypertonic side, the level of water will rise a bit in your glass, and more water will exert pressure on the membrane from that side. This force is called the hydrostatic pressure. This same force acting on the walls of the blood vessels is what we call blood pressure.

The ‘pressure’ exerted by the concentration of solutes is what is called osmotic pressure. The higher the concentration on one side versus the other, the higher the osmotic pressure is. In other words, hypertonic solutions exert a high osmotic pressure on the semipermeable membrane. As a result, water will diffuse across it to dilute the hypertonic solution.

To recap the above:

  • Water in the body is divided into three compartments, which are separated by semipermeable membranes. A semipermeable membrane selectively allows some solutes to cross it, but not others. The ICF is separated from the ECF by cell membrane. The ECF is subdivided into blood plasma and interstitial fluid, which are separated by the endothelial lining of the blood vessels.
  • Each body compartment has a different composition of the solutes it contains. For example, cells contain a low concentration of Na+ compared to the outside environment. If you consider the concentration of solutes which cannot readily cross the semipermeable membrane at each side, a relatively high concentration makes it hypertonic, a relatively low concentration makes it hypotonic and an equal concentration makes it isotonic.
  • If you ignore other forces acting on a semipermeable membrane, net flow of water will occur if there’s a difference in tonicity between either side. That is, one side is hypertonic (or hypotonic) compared to the other. This net flow will continue until an equilibrium is reached (isotonicity; again, ignoring other forces). So waterflow (osmosis) between compartments is dependent on the difference in concentration of solutes between them. This is the most important force in this regard.
  • There are other forces also in play which drive the water flow. One of them we discussed is hydrostatic pressure, which simply is the pressure of the weight of water put on it’s surrounding environment.

With the knowledge we’ve just gathered, let’s consider a somewhat simplified example. Let’s say you drink a glass of hypotonic glass of water. Note that when I not state relative to what a solution is hypotonic or hypertonic, I mean it’s hypotonic or hypertonic compared to a cell (specifically a red blood cell is used as the standard reference with this stuff). When you drink this glass of water, the water will be absorbed by your GI tract and will be added to your ECF. Since it was a hypotonic glass of water, it dilutes the ECF a bit. That means the concentration of solutes in the ECF decreases. If the ECF and ICF were in equilibrium, they aren’t now anymore. As a result, there will be a net flow of water from the ECF to the ICF to ‘correct’ this.

We can run the same example with an isotonic glass of water (a 0.9 % NaCl solution, also called saline, comes to mind). You drink it, the stuff gets absorbed and gets added to the ECF. Because it’s isotonic, the concentration of solutes in the ECF remains the same. So if the ICF and ECF were in equilibrium, they will remain in equilibrium. There will be no net flow of water between the ICF and ECF. So that isotonic glass of water you drank will only increase the amount of water in the ECF.

Now lets also consider sweating. I know there are a few coaches who recommend sweating your ass of towards a bodybuild competition to lose water. Is sweat hypertonic or hypotonic? It’s hypotonic. Where does it come from? The ECF. What happens with the concentration of effective solutes in the ECF when you lose hypotonic fluid from it? It increases. So the ECF itself will become slightly hypertonic. As a result, a net flow of water from the ICF to the ECF will occur. Water will be sucked out of the cells to compensate.

Similarly, lets consider the practice of carbohydrate (glycogen) loading or carbloading for short. Carbloading is commonly performed by endurance athletes to enhance their performance, whereas bodybuilders use it to increase their muscle volume for competition. Those oiled up tanned glutes just look better with some more glycogen in them. A regular carbloading protocol boils down to depleting muscle glycogen with torturing exercise, followed by eating a ton of carbohydrates for several days (roughly 10 g per kg bw). The result is that the muscles will store more glycogen than they usually do because of this overload of glucose supply. The part which is interesting for this chapter, is that glycogen is stored hydrated in the skeletal muscle. It draws water into the muscle cells. For each gram of glycogen roughly 3 gram of water is stored in concert. Part of this is due to osmosis (although likely most of it is not due to osmosis, but due to hydration of the hydroxyl groups of each glucose monomer). The glycogen is deposited inside the cells and thereby increases the osmotic pressure on the semipermeable membrane. This will lead to water being drawn into the muscle cells.

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