Cystic fibrosis pathophysiology

- [Voiceover] So the gene that's not working well in cystic fibrosis is called the "CFTCR" gene. So, my gosh, it's a long acronym and it stands for, let's write this quickly, Cystic Fibrosis, so they obviously named this after they named the disease. Cystic Fibrosis Transmembrane, which means it goes from one side of the membrane to the other. Conductance is letting things through, across a membrane, from one side to the other. And then Regulator. So it controls the movement of something, going cross a membrane. The two ions that are affected are chloride and sodium. But keep in mind that CFTCR is a chloride channel. So chloride is physically being blocked by this channel not working. And sodium is affected because it has a relationship with chloride, but sodium has its own channel, which is not affected in cystic fibrosis. This CFTCR gene is all over the body, and depending on where it is, the situation's a little different. But the common rule's the same, and to illustrate this, let's talk about the sweat gland. This is a place where this gene has a big role. And from this example, it's kinda the same thing, going across the body for cystic fibrosis symptoms. So if this is our sweat gland, it starts here. So what is secreted into here that's a channel, and then here is the surface to our skin. I'm gonna label this side "Skin". So when sweat is first secreted by this gland, it's a lot of sodium and chloride in it. For sodium, let's use blue. Notice that it has a plus charge. Sodium all over here. At the same time, there's also a lot of chloride in it. Chloride has a negative sign. As you can see in nature, positive and negative attract, right? So, sodium and chloride like to balance each other out. And they're friends. In other words, the body likes the amount of sodium chloride to be about balanced. So going along this sweat gland, going towards the skin, there's gonna be channels to reabsorb this chloride and sodium into the body. We don't want to secrete it all out. So for sodium, we have its own channels, and we use blue here. And then just dot it along the way. Of course, next to them there's the chloride channels. Now these channels are the ones that are affected by our CFTCR thing. I wanna label this, so CFTCR. In cystic fibrosis, these channels are not working. But let's look at this as a normal one. So, let's see, this is normal sweat gland. And normally, as the chloride flows down here, everything goes this way as it floats down here, it'll leave through these channels and go back into the body. So this face here, is the body. That's the skin, that's the outside. So these, as they go along, they go back into the body. And sodium does the same thing. Remember that we want to keep our amount of sodium and chloride pretty balanced. So as the chloride leaves, so does the sodium, through their channels. And they kinda keep an eye on each other to make sure that their numbers are about balanced. So when we get to the end here, let's say that there's, let's just say there're two sodium molecules left, and their buddies, two chloride ions. Now sodium chloride, this is table salt. So this is why our sweat tastes slightly salty on our skin. And this is normal, because not all of the sodium and chloride will be reabsorbed. Just as an aside, have you noticed that when you sweat a lot, it gets to be a little saltier, or the sweat has a stronger smell? That's because this is going through this channel faster, when you're sweating a lot, and there's less time for these reabsorptions, so there's more salt left. But that's still normal. Here, let's look at a channel with in a person with cystic fibrosis. So same channel, structurally everything's gonna be the same. And here I'm gonna label this one "CF". Now initially the sweat, the content of it being secreted into here is the same. So I'm gonna use the little dots instead of writing it out this time. You already know blue is sodium, and orange is chloride. So same channels for the sodium, and they're working just the same. So no problem with sodium channels. However, this time the CFTCR gene is not working, so the chloride channels are all messed up. So they look like this, it's not open. So as the chloride floats down this way, it can't leave. Do you see, it just has to stay in here, and it keeps going towards the skin. And sodium, at this point, it sees that the chloride is still in here. The negative and positive want to stay together, so even though the sodium channel is open, the sodium doesn't go either, because its buddy chloride is still in here. And the body won't just take the positive sodium ions, and leave the negative in here. It has to be balanced. So, same thing, the sodium gets trapped in here, too, pulled by the chloride. So in this person, when we get to the skin, it's almost the same content of sodium chloride as before. As you can see this is a lot more than just two of each. Now, I chose two as just an arbitrary number, but just to show you that this one is gonna have a lot more, and this is a lot saltier on the skin. So one of the symptoms of having CF is having salty skin, or even a baby we do a chloride test to see how much chloride is on the skin, and that can point to CF. But the pathophysiology of this channel is similar throughout the body. I just chose one organ here to show you. Now really quickly, in the lungs, the problem is secreting chloride across the epithelium to moisten the lungs. And since the chloride can't get secreted, the sodium also doesn't get secreted. And water follows sodium. So that's why the secretions are really thick, because they're lacking in water. And that's how you get the thick secretions in the lungs and in the pancreas. But here in the skin you get salty sweat.