CYSTIC FIBROSIS
Thick mucus disease
CF is a genetic condition that causes dangerously thick mucus in Caucasian kids. It’s autosomal recessive. It famously causes chronic lung problems, but it can affect many other organs as well.
What gene is mutated?
The Cystic Fibrosis Transmembrane Regulator (CFTR) gene on c7 is mutated. This is a big gene -- CF can be caused by numerous different mutations. But the most common mutation is a 3-base deletion of the 508th amino acid, which happens to code for phenylalanine. In shorthand, the mutation is called ∆F508 (∆ means deletion, F means phenylalanine).
What protein is mutated?
The Cystic Fibrosis Transmembrane Regulator (CFTR) protein is abnormal. The CFTR directly moves around Chloride ions. Although the CFTR can be found in different parts of the body, ultimately CFTR makes secretions more watery! The CFTR is an ion pump that uses ATP for energy. In the lung, it moves Cl- from the cells to the airways. The whole point of that is to raise the osmotic gradient to draw more water into mucus. The CFTR has a secondary function in the sweat glands. It removes Cl- from sweat, so although the Cl- is moving in the opposite direction, we can still say that CFTR makes secretions more watery.
Why is thick mucus dangerous? That seems like an exaggeration.
Mucus is secreted into tubes. If the mucus is too viscous it can clog up the tube (like pouring cement into a didgeridoo). Obstruction results in stagnant flow, and THAT is what can really fuck you up.
Which organs have CFTRs?
Lungs, Bile Duct, Pancreas, Nose, Testes and Sweat glands.
What are the lung symptoms?
They basically have incredibly severe chronic bronchitis. The thick mucus clogs up the airways. The cilia aren’t strong enough to push the mucus up. So it sits. Then it gets infected, usually with Pseudomonas in adults or Staph aureus in kids. Recurrent bacterial infections will cause Bronchiectasis after a few years.
What are the pancreas symptoms?
The thick mucus clogs up the exocrine pancreas ducts. The pancreatic juice is full of digestive enzymes. So when it backs up, the juice starts digesting the pancreas itself. That’s called pancreatitis. If the Islets of Langerhan get eaten, type 1 diabetes ensues. And since the pancreatic juices aren’t being delivered to the intestines, they get fat malabsorption (stinky greasy voluminous floating poops). The bile ducts can also get clogged up, and that’s why cirrhosis is the 3rd most common cause of death in CF.
Other random symptoms?
Nasal polyps are a great test question (the other cause is aspirin-induced asthma). They’re also infertile (95%) due to a clogged vas deferens.
What are some clues when it comes to spotting undiagnosed CF in a baby?
Suspect CF in a baby who has recurrent lung infections, recurrent sinus infections, a meconium ileus or failure to thrive (from the fat malabsorption). A meconium ileus is when a baby doesn’t poop on its first day of life.
How do you diagnose CF?
The sweat chloride test is the best first test (it’s cheap). It’s kinda complicated though. You need a lot of sweat to make the diagnosis, but CF patients are babies with lung disease, so obviously we can’t force them to exercise. Some brilliant bastard figured out a way to induce sweating using Pilocarpine-soaked gauze and an electrode sensor. A high chloride level suggests CF. DNA testing will confirm the diagnosis.
Treatment?
There is no cure for CF. Symptoms can be controlled, but these guys require a lot of medical attention. And once they get Bronchiectasis, they’ll need a lung transplant. The average lifespan is 37 years (but this is rising rapidly). Death usually occurs from lung complications. There are a few (mediocre) ways to thin out lung secretions. An inhaled drug called Dornase Alfa chops up DNA, and that cleans up the thick neutrophil NETs. Inhaled saline thins it out too, which makes sense. NAC, the tylenol overdose antidote, is an old treatment that’s not frequently used. Periodic lung infections are controlled with antibiotics. They benefit greatly from vaccines. In kids with G551D mutations, Ivacaftor tablets will increase their ion flux and improve the source of the problem. They require oral pancreatic enzyme replacements and ADEK vitamin supplements.
Note that Kartagener Syndrome looks a lot like CF. But instead of a broken chloride transporter, it’s caused by broken cilia. It’s discussed elsewhere in this book.