Cystic fibrosis – causes, symptoms, diagnosis, treatment, pathology

Cystic fibrosis – causes, symptoms, diagnosis, treatment, pathology

Learning medicine is hard work! Osmosis makes it easy. It takes your lectures and notes to create
a personalized study plan with exclusive videos, practice questions and flashcards, and so
much more. Try it free today! You’re probably aware that cystic fibrosis,
or CF, is a genetic disorder that affects the lungs, but that’s only part of the story. In fact, the name “cystic fibrosis,” refers
to the disease’s effects on the pancreas, where it can lead to cysts, which are fluid-filled
sacs wrapped in a membrane and fibrosis—excess deposition of connective tissue that can replace
or infiltrate normal tissue in an organ. CF is an autosomal recessive disorder involving
the CFTR gene, which stands for “cystic fibrosis transmembrane conductance regulator,”
and this gene codes for the CFTR protein. CF develops when there’s a mutation in the
CFTR gene, but because it’s autosomal recessive, you need to inherit two mutated CFTR genes,
one from mom and one from dad. Now if mom and dad both have one copy of the
mutated gene and one normal gene, they’re considered carriers and don’t have the disease. Inheriting CF is more common in people of
European descent. The CFTR protein is a channel protein that
pumps chloride ions into various secretions, those chloride ions help draw water into the
secretions, which ends up thinning them out. The most common mutation is the “∆F508”
mutation. Delta means a deletion, and the F (which can
also be written as “Phe”) is short for phenylalanine, and the 508 is the five hundred
and 8th amino acid in the CFTR protein. So, the ∆F508 mutation is where the 508th
amino acid out of 1480, phenylalanine, is deleted and missing. This CFTR protein with the ∆F508 mutation
gets misfolded and can’t migrate from the endoplasmic reticulum to the cell membrane,
meaning there’s a lack of CFTR protein on the epithelial surface, and this means that
it can’t pump chloride ions out, which means water doesn’t get drawn in, and the secretions
are left overly thick. In a newborn, thick secretions can affect
the baby’s meconium, or first stool, or, which can get so thick and sticky that it
might get stuck in the baby’s intestines and not come out, and this is called a meconium
ileus and is a surgical emergency. In early childhood, pancreatic insufficiency
is the most prominent effect of CF. This happens because thick secretions jam
up the pancreatic ducts, not allowing digestive enzymes to make it to the small intestine. Without those pancreatic enzymes, protein
and fat aren’t absorbed. And over time this can lead to poor weight
gain and failure to thrive. Fat malabsorption can lead to steatorrhea,
or fat-containing stools. Eventually the pancreas gets damaged, because
backed-up digestive enzymes degrade the cells lining the pancreatic ducts, causing local
inflammation. This can lead to acute pancreatitis and—with
repeated episodes—chronic pancreatitis, with the development of cysts and fibrosis
like we talked about, giving the disease it’s name. Finally, the destruction of pancreatic tissue
can also compromise of the endocrine function of the pancreas, causing insulin-dependent
diabetes. It’s usually not until later in childhood
that lung problems start to crop up. Normally the cilia, these hair-like projections
lining the airways, do a pretty good job of keep the them clean by moving mucus, which
catches things like debris and bacteria, toward the pharynx, called mucociliary action. With thick mucus, though, it gets a lot harder
to clear and the mucociliary action becomes defective, which means bacteria is allowed
to chronically colonize the lungs. If the bacterial load suddenly increases,
it causes symptoms like cough and fever, a decrease in lung function, and sometimes changes
on a chest X-ray, and this is called a CF exacerbation and usually prompts a round of
antibiotics. Pneumonia is one example of a CF exacerbation
which requires antibiotic treatment. Examples of problematic bacteria include gram
positive bacteria like Staphylococcus aureus, which is gram positive, and Pseudomonas aeruginosa,
which is gram negative, both of which can be hard to treat if they are resistant to
typical antibiotics. In addition, the bacteria usually form a biofilm
where individual bacterial cells are fixed in a matrix of slime which protects them from
the immune system as well as antibiotics. Chronic bacterial infection and inflammation
can lead to bronchiectasis, which is airway wall damage causing permanent dilation of
the bronchi. Occasionally, if inflammation erodes into
a blood vessel, there can even be hemoptysis, or coughing up of blood. Over time, the repeated CF exacerbations can
ultimately lead to respiratory failure, the leading cause of death with CF. Other CF-related issues include infertility
in men who commonly lack the vas deferens which are the tubes that transport the sperm
from the testes to the urethra in the penis. Men and women can also have digital clubbing
where the fingernails begin to spoon around the fingertips, nasal polyps which are tissue
growths in the nose, and allergic bronchopulmonary Aspergillosus (or ABPA), which is a hypersensitivity
reaction to the fungus Aspergillus fumigatus which can live in a sinus or lung cavity. For diagnosis, it’s possible to screen for
CF in newborns, something that is done in some countries where CF is common and that
helps treatment get started earlier. The newborn screen detects a pancreatic enzyme
called IRT, or immunoreactive trypsinogen, which is released into the fetal blood when
there is pancreatic damage from CF. And then if a sweat test then detects high
levels of chloride in the sweat—CF is confirmed. Unlike in the lungs and pancreas where chloride
can’t go out, when CFTR’s not working in the sweat glands, chloride can’t come
in, or be reabsorbed, so there’s actually high chloride in the sweat. In fact, parents of children with CF sometimes
notice that, when kissing their baby, the baby tastes salty. In terms of treatment, a major goal is around
nutrition and healthy weight gain. Fortunately, fat-soluble vitamins (ADEK),
extra calories, and replacement pancreatic enzymes, can all be supplemented to help boost
nutrition and help the patient absorb nutrients. In terms of pulmonary treatment, there’s
chest physiotherapy, which to loosens the mucous by literally banging on the chest,
as well as inhalers. There are also medications like N-acetylcysteine
which cleaves disulfide bonds in the mucus glycoproteins and dornase alfa which is a
nuclease that cuts up nucleic acids in the mucus to thin it out. CF lung disease is obstructive (like asthma
and COPD), so pulmonary function tests are regularly used to monitor the disease. Finally, because of the chronic infections
and loss of pulmonary function over time, a lung transplant is sometimes needed. A new hope for patients with CF has been the
development of personalized treatments that target specific CFTR mutation types. For example, lumacaftor is a chaperone that
can bring the mutated ∆F508 CFTR to the cell membrane and is given in combination
with ivacaftor. Ivacaftor was originally designed against
G551D mutations, but also improves function of mutated ∆F508 CFTR. Even though this isn’t a cure, these drugs
are a good example of the potential of personalized medicine. In addition, there are new genetic technologies
on the horizon aimed at correcting specific gene mutations. Alright! Time for a quick recap: cystic fibrosis is
an autosomal recessive disorder involving the CFTR gene, which most notably causes issues
with the lungs and the pancreas, but can also affect other organs.

40 Replies to “Cystic fibrosis – causes, symptoms, diagnosis, treatment, pathology”

  1. Since it will lead to respi. Failure is there a need or is it necessary to put the patient on Mechanical vent.?.

  2. oh yss this also affect other organs……….{cyst in URINARY BLADDER}……which is commonly called in India

  3. DIOS is also another issue with CF. It's called Distal Intestinal Obstructive Syndrome and treatment is usually a laxative (Golytely) but this is important to know because sometimes the symptoms aren't always clearly indicated and they are at risk for intestinal issues like perforation, etc if left untreated.

  4. I’ve got Cystic Fibrosis and it’s a complex disease which people don’t see everything we go though as it’s an invisible illness, we look ok on the outside but inside we do struggle! Great video to spread awareness! I wish I could explain it this well on my channel.

  5. Its better if you put full video in youtube rather than post a few full and few are can get more subscribers more than you are having right now..better having mind and intention of sharing knowledge and get rewards by adding ads at least..rather than prioritize of finding money via sharing knowledge..these 2 are very different in term of intention..tq i hope this could be in your consideration of changing back your channel like before..

  6. This is a second to none explanation. i really have to admit that this account is amazing. i used to suffer from uncomprehending especially because i couldnt imagine it, but now its much better….. thanks a lot.

  7. first of all, thanks for this video. But there is a question. In some references is written that loss of Phenylalanine is by ATP connected unit of Chanel proteins ( just by one side of them) which are connected to regulatory units . For this reason closed the regulatory unit the Chanel and this is the reason which leads to stoping the transportation of Chloride ion! it means the Chanle protein is already in membrane! would you mind clarifying this for me?

  8. Studying for Mild to Moderate Praxis Exam, need to understand many disabilities, how to teach, understand and relate to children living with them. Love your vids!! They really help to break ailments down.

  9. I came to this because my 3 year old son might have this but if it can be detected at newborn stage why wasn't it then pray that he doesn't have it heard its life threatening

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