In recent months, I’ve made a new CF friend on Twitter, @nanosmakemepuke, who just so happens to be a chemist with a Tumblr blog with a name that immediately gave me a source to go to for an expert answer to my ongoing query. I got the bright idea this week, “Who better to ask for an explanation of why cystic fibrosis patients need more salt than normal people than Amanda? She’s got a PhD in chemistry!” So I did, and she obliged with a pretty detailed reason in layman’s terms that I think you’ll find as fantastic as I did. Many, many thanks for such a great piece that will live on for a very long time to help educate others looking for the answer to the same question that has been bugging me for years.
Amanda: Salt is the combination of sodium and chloride. The biochemical processes that go on in our bodies are such that only a very narrow range of salinity (concentration of salt in our body’s fluids) is acceptable. Too little or too much is literally a matter of life and death. Fortunately, our bodies are really good at ensuring that it contains the ideal concentration of salt by adjusting the volume of fluid in our blood and tissue so that the salinity is always in the ideal range. If you have too much salt you become thirsty, causing you to drink water, which dilutes the too-high concentration of salt in your body. If you have too little, you usually crave and eat something salty.
In cystic fibrosis, improper transport of chloride (a component of salt) causes all the horrible symptoms and manifestations of this disease. CF bodies don’t fully regulate the concentration of salt within the cells that line our airways, digestive tract, and skin, causing the concentrations to be a bit out of whack—either too low or too high, depending on which side of the cell you’re looking at. In the case of the cells that create sweat in a CF patient’s sweat glands, they leave too much chloride inside the “sweat reservoir,” which must in turn be balanced with an equivalent amount of sodium (wherever chloride goes, sodium follows), making the super-salty sweat characteristic of cystic fibrosis.
Every time a CF person sweats, their body loses up to 10 times the amount of salt a normal healthy person would in the same amount of sweat. That means excessive sweating (as might happen in the summer or when exercising) puts people with CF at a much higher risk of dehydration than other people. Because of this salt loss, people with CF must be very diligent to replace lost salt whenever they sweat, otherwise there is a risk of suffering from dehydration.
Generally speaking, people with CF need to include salt as a regular part of their diet to compensate for abnormal amounts of salt lost through sweat. The usual reason doctors recommend a low-salt diet for non-CF people is so that they don’t develop high blood pressure, which causes your body to retain more fluid in your blood to compensate for the excessively high concentration. If you have CF and have high blood pressure, obviously the amount of salt in your diet is something you need to discuss with your doctor.
Bottom line: it’s important for people with CF to add a little extra salt into their diet in order to avoid dehydration in warm weather and when exercising. Also, always make sure you consume something salty with plenty of fluids so your body can process it properly.
This certainly explains things in a way that is easy to understand. Thank you Amanda and thank you Fatboy for posting it. 🙂
You're welcome – and yes, she wrote it VERY well. My hats off to you, and
thank you for allowing me to place it here for my readers for their
convenience. I hope you see a terrific readership increase as a result,
because you deserve it for this caliber of writing.
Thanks, Sean and Jesse! You flatter me. Thanks for inviting me to write on your blog.
The pleasure was mine, for sure. I was glad to finally get an answer I
understood and to be able to share it with all of my new friends.
Amanda: So, I'm trying to understand why the lungs get clogged. Is there too much salt stuck in the lungs, or can the salt not get into the lungs?
It’s really a complicated issue. There are various theories out there as to what’s the deal going on in the lungs, because it’s essentially the opposite of what’s going on with the sweat glands. The key to the whole problem is which way the one-way CFTR chloride pump is facing within a cell membrane. In the sweat glands, the pump is trying to pump chloride out of the sweat reservoir and back into the skin cells, but since it malfunctions and cannot pump, all the chloride stays outside the skin. Normally, CFTR would help pump chloride back into the body so you could reabsorb it. Another protein pump usually works alongside CFTR controlling the sodium flow into and out of cells. Because chloride is stuck outside the skin cells, it pumps enough sodium to balance it out, making the CF sweat super-salty. (In actuality, it is the sodium that makes the salty taste; if you’ve ever tasted the salt substitude component potassium chloride, you’ll realize that it doesn’t taste salty at all, but sort of sour/bitter.)
In the lung cells, there was a bit of scientific debate as to what was going on for awhile. I’m not super-well-studied in the subject, but I’m pretty sure the working hypothesis now for CFTR research is the “dehydration model” which essentially is that mucus in the lungs is dehydrated. It is dehydrated because the CFTR protein which is supposed to transport chloride from inside the lung cells to the outside is not working. Therefore, no chloride is transported to the outside surface of the cells (which contain the airway surface liquid). Because no chloride is transported out of the cells, the sodium pump pumps sodium to the inside of the lung cells to balance out the chloride inside the cells. Because the body (especially the lungs; not so critical with sweat) requires a very specific salt-to-water ratio within the cells, when the body sees that there is too much salt inside the lung cells, it compensates by letting water diffuse inside the cells to create this ideal concentration of salt water. The water that diffuses inside is unfortunately from the airway surface liquid layer (which covers the lung’s cilia that are supposed to be completely submersed in this liquid so they can clear mucus, dirt, bacteria, etc. out of the lungs), leaving the airway surface liquid layer entirely too shallow and a little too sticky. The cilia are no longer completely submersed in the airway surface liquid, so they can’t wiggle around to clear out the mucus, allowing it to grow bacteria.
So basically, to answer your question…there is too much salt on the inside of the lung cells, but it’s trapped and can’t get to the outside surface of the cells (which is where a normally thin layer of easy to clear mucus should reside). Instead the thin, easy to clear mucus is dehydrated and sticky on the outside surface of the lung cells. If the salt were able to get out of the cells and to the outside surface, it would bring enough water with it to thin out the sticky mucus and there would be no problem. When you use nebulized hypertonic saline, this artificially puts an overabundance of salt outside the lung cells, causing the body to pull water from other places (maybe from inside the lung cells, maybe from the blood, maybe from inside other tissues; I’m not really sure where it comes from and I don’t think scientists are either) to achieve the magic salt-to-water ratio and effectively rehydrate the airway surface liquid layer so it can be easily cleared out.
Hope this is helpful and not too science-heavy. This is sort of a simplified idea of what’s going on, because there are other molecules/ions at work besides sodium and chloride, but essentially this is the crux of the problem with CF. Scientists studying this aren’t even 100% sure what’s going on in and around the lung cells.
As for treatment, Vertex’s drug VX-770 has been shown to fix the CFTR protein so that it can work and pump chloride out of the lung cells. It works on people with certain CF mutations where the CFTR is already in its proper position at the cell surface; the CFTR just doesn’t open/close properly. The problem with the deltaF508 mutation (which is what I think Jesse has? I have two of these genes) is that the CFTR protein is so messed up early on in its production inside the cell that it’s marked as garbage and never makes it to its spot on the cell surface. So that’s where VX-809 comes in. I’m fuzzy on the details as to how, but somehow it helps the bad CFTR protein fold itself correctly (even if it can’t pump properly) so that it’s not flagged as garbage by the cells and actually gets positioned at the cell surface. Then maybe VX-770 can make it pump properly…hopefully.
Let me know if you have any more questions. I’m by no means an expert, but I am more than happy to help any way I can.
It's really a complicated issue. There are various theories out there as to what's the deal going on in the lungs, because it's essentially the opposite of what's going on with the sweat glands. The key to the whole problem is which way the one-way CFTR chloride pump is facing within a cell membrane. In the sweat glands, the pump is trying to pump chloride out of the sweat reservoir and back into the skin cells, but since it malfunctions and cannot pump, all the chloride stays outside the skin. Normally, CFTR would help pump chloride back into the body so you could reabsorb it. Another protein pump usually works alongside CFTR controlling the sodium flow into and out of cells. Because chloride is stuck outside the skin cells, it pumps enough sodium to balance it out, making the CF sweat super-salty. (In actuality, it is the sodium that makes the salty taste; if you've ever tasted the salt substitude component potassium chloride, you'll realize that it doesn't taste salty at all, but sort of sour/bitter.)
In the lung cells, there was a bit of scientific debate as to what was going on for awhile. I'm not super-well-studied in the subject, but I'm pretty sure the working hypothesis now for CFTR research is the “dehydration model” which essentially is that mucus in the lungs is dehydrated. It is dehydrated because the CFTR protein which is supposed to transport chloride from inside the lung cells to the outside is not working. Therefore, no chloride is transported to the outside surface of the cells (which contain the airway surface liquid). Because no chloride is transported out of the cells, the sodium pump pumps sodium to the inside of the lung cells to balance out the chloride inside the cells. Because the body (especially the lungs; not so critical with sweat) requires a very specific salt-to-water ratio within the cells, when the body sees that there is too much salt inside the lung cells, it compensates by letting water diffuse inside the cells to create this ideal concentration of salt water. The water that diffuses inside is unfortunately from the airway surface liquid layer (which covers the lung's cilia that are supposed to be completely submersed in this liquid so they can clear mucus, dirt, bacteria, etc. out of the lungs), leaving the airway surface liquid layer entirely too shallow and a little too sticky. The cilia are no longer completely submersed in the airway surface liquid, so they can't wiggle around to clear out the mucus, allowing it to grow bacteria.
So basically, to answer your question…there is too much salt on the inside of the lung cells, but it's trapped and can't get to the outside surface of the cells (which is where a normally thin layer of easy to clear mucus should reside). Instead the thin, easy to clear mucus is dehydrated and sticky on the outside surface of the lung cells. If the salt were able to get out of the cells and to the outside surface, it would bring enough water with it to thin out the sticky mucus and there would be no problem. When you use nebulized hypertonic saline, this artificially puts an overabundance of salt outside the lung cells, causing the body to pull water from other places (maybe from inside the lung cells, maybe from the blood, maybe from inside other tissues; I'm not really sure where it comes from and I don't think scientists are either) to achieve the magic salt-to-water ratio and effectively rehydrate the airway surface liquid layer so it can be easily cleared out.
Hope this is helpful and not too science-heavy. This is sort of a simplified idea of what's going on, because there are other molecules/ions at work besides sodium and chloride, but essentially this is the crux of the problem with CF. Scientists studying this aren't even 100% sure what's going on in and around the lung cells.
As for treatment, Vertex's drug VX-770 has been shown to fix the CFTR protein so that it can work and pump chloride out of the lung cells. It works on people with certain CF mutations where the CFTR is already in its proper position at the cell surface; the CFTR just doesn't open/close properly. The problem with the deltaF508 mutation (which is what I think Jesse has? I have two of these genes) is that the CFTR protein is so messed up early on in its production inside the cell that it's marked as garbage and never makes it to its spot on the cell surface. So that's where VX-809 comes in. I'm fuzzy on the details as to how, but somehow it helps the bad CFTR protein fold itself correctly (even if it can't pump properly) so that it's not flagged as garbage by the cells and actually gets positioned at the cell surface. Then maybe VX-770 can make it pump properly…hopefully.
Let me know if you have any more questions. I'm by no means an expert, but I am more than happy to help any way I can.
Absolutely brilliant explanation, Amanda. Thanks! Yes, I'm ΔF508/ΔF508, so I'm waiting for the next round of VX-770 because my function was below 40% for the last trial. For now, I'm more than happy to be on Cayston and getting those benefits while VX-770 progresses. This also explains the purpose of the Hyper-Sal so eloquently, too, even though no one knows why the heck it works. 😉
Thanks Amanda!! You explained that very well. That makes a lot of sense why the saline aerosol helps.
Amazing how such a “simple” problem can cause such big problems.
This is very helpful! And understandable!!
Could it be possible that we CF-ers are all a little chronically dehydrated all the time? I once had a phlembotomist tell me that my veins were too small and hard to find because I was dehydrated but no matter how much water I drank, nothing helped. This could be a stupid question; just wondering.
I know I’m dehydrated more often than not, but I don’t personally have an issue getting hydrated and I have huge veins that can donate blood faster than a 200lb guy next to me. I think we might be pre-disposed to lose water faster because of the CTFR, but not sure about the in ability to be hydrated.
Interesting. Amanda’s new post might shed light on that. Pehaps each person gets water pulled from different areas to hydrate the lungs. Mine must be pulled from my blood.
I feel so much more well informed now with your blogs.