Non-GI Glands – Lower Gastrointestinal Secretion

00:00 Okay.

00:01 Now that we have how gallbladder releases bile into the small intestine, we need to discuss something called the cystic fibrosis transmembrane regulator.

00:14 And this process involves a very specialized transporter.

00:18 This transporter, although in pathophysiology, can be mutated.

00:24 And a mutated CFTR transporter can cause problems both in the pancreas, in the gallbladder, elsewhere in the GI tract.

00:34 So how do we know if the CFTR transporter is working properly or not? One way is to test in a gland that is easily accessed than the pancreas.

00:46 It’s hard to test this in the pancreas itself.

00:47 So we can test it in other glands.

00:50 So this is a sweat gland.

00:52 From a sweat gland, you will use the CFTR transporter to move chloride into the cells of the sweat gland duct and eventually across the basolateral membrane into the plasma or into the interstitial fluid and then plasma.

01:11 So it’s done through a two-stage process in where you reabsorb chloride.

01:17 So the solute that you will normally be able to reabsorb will then produce a hypotonic sweat.

01:25 How you can use this clinically is if the CFTR transporter is not working properly, chloride will not be able to be reabsorbed in the same way.

01:37 It will be left in the lumen of the sweat gland and sweat it out.

01:42 Interestingly, there’s a relationship between chloride and sodium.

01:47 If chloride is left in the luminal portion of the sweat gland, it prevents sodium from being reabsorbed as well.

01:56 So sodium is normally reabsorbed across an ENaC sodium channel, which is an endothelial sodium channel.

02:03 And then across the basolateral membrane with the sodium-potassium ATPase.

02:08 If the CFTR channel is not working properly and chloride is left in the luminal portion of the duct, then sodium will be also left in the luminal portion of the duct.

02:19 So let’s look at how this looks in terms of secretions.

02:24 This will cause an increase in the concentration of both sodium and chloride in sweat secretions.

02:31 How can you use this clinically? One way is you can test if the CFTR transmembrane regulatory is working correctly.

02:41 This shows and example of what a CFTR membrane, cystic fibrosis transmembrane regulator looks like.

02:50 And this is an ABC binding transporter.

02:53 So this needs ATP for it to function properly to have the chloride go from the cytosol into the interstitial space.

03:05 If we stimulate sweating, we should get a sweat rate along the X-axis and a concentration of sodium and chloride along the Y-axis.

03:17 This shows a normal individual who has a normal functioning CFTR.

03:22 If you contrast that with someone with cystic fibrosis, who has an abnormal CFTR transporter, they will have large amounts of sodium and chloride across any sweat rate.

03:38 How can you use this clinically? Is you can test someone who has cystic fibrosis, you can test the sweat glands.

03:50 And this is done through a quantitative pilocarpine iontophoresis test, which is abbreviated QPIT.

03:58 So what does this do? Well, pilocarpine is a cholinergic agonist, meaning that it acts like acetylcholine.

04:05 You use this particular type of transmembrane stimulus by using electrical current to pass the drug across the skin.

04:16 This then causes sweating to occur.

04:20 If the person has a low amount of chloride, then they’re unaffected by cystic fibrosis.

04:29 If they have in between 40 to 60 millimolars, it’s hard to tell.

04:34 They might have the disease, they might not.

04:37 Diagnostic for cystic fibrosis if you have more than 60 millimoles per liter.