03-11-22 – Cystic Fibrosis Flashcards
Learning outcomes
- Understand the Pathophysiology of Cystic Fibrosis.
- Have a basic understanding of the management of patients with Cystic Fibrosis.
What is cystic fibrosis (CF)?
How is it caused?
What is the CFTR?
How many mutations are associated with cystic fibrosis?
What are 6 different outcomes of CF mutations on the CFTR?
- Cystic fibrosis is the commonest autosomal (non-sex chromosome) recessive condition
- It is caused by a defect in gene coding for Cystic Fibrosis Transmembrane Regulator (CFTR) located on chromosome 7
- This leads to proteins for the CFTR being made incorrectly, or not being made at all
- The CFTR is an energy dependent chloride channel
- There are currently 2110 mutations listed that are associated with cystic fibrosis
6 different outcomes of CF mutations on the CFTR:
1) Premature stop codon
2) Folding/trafficking defect
3) Gating defect
4) Narrow channel
5) Splicing defect
6) Decreased stability
What type of epithelium is respiratory epithelium?
Where are CFTRs found in the lungs?
How do both of these normally function together?
How is this altered in CF?
How does this lead to infection?
- Respiratory epithelium is pseudostratified ciliated columnar epithelium with goblet cells for mucous secretion
- In the lungs, CFTRs are found on the apical membrane of the respiratory epithelium
- In physiology, Cl- ions will move out of the surface membrane of respiratory epithelium via CFTRs, which will also drag along Na+, which will drag along water
- This ‘salty water’ will combine with mucous secreted by goblet cells to form a gel like layer on top of the cilia
- In CF, the CFTR Cl- pump doesn’t function properly, leading to the gel becoming sticky
- This squishes the cilia on the respiratory epithelium, making it difficult for the cilia to clear mucous
- This results in bacteria and other microorganisms here not being cleared effectively, leading to infection
- This is why those with CF get frequent chest infections
What are the 5 different organ systems CF can affect?
Which 2 are the most commonly affected?
- 5 different organ systems CF can affect:
1) Lungs
2) GI tract
3) Pancreas
4) Liver
5) Reproductive organs - The lungs and the GI tract are the most commonly affected
What is the most common organ in the GI tract to be affected by CF
What are the 2 primary functions of the pancreas?
How does CF affect exocrine function?
How does this affect stool formation?
How can this prevent weight gain in CF patients?
How can endocrine functions be affected later in life?
- The pancreas is the most common organ in the GI tract to be affected by the sticky mucous in CF, with the pancreatic ducts being affected first
- The 2 primary functions of the pancreas are exocrine functions (digestive enzymes) and endocrine functions (hormones)
- CF can block exocrine functions through sticky mucous blocking pancreatic ducts and preventing digestive enzymes from being secreted into the gut
- Lipases that break down fat are the digestive enzymes most exclusive to the pancreas
- This leads to fats not being digested in the stomach and passing through to the intestines, where they can act as an osmotic substrates and absorb water
- This leads to stools being loose and oily and also gas production
- Without absorbing enough fat, this can lead to CF patients struggling to reach their calorie requirements needed, which makes it hard for them to gain weight
- CF patients already have a higher calorie requirement due to fighting chest infections constantly
- Later on in life, the endocrine functions of the pancreas can be affected
- This can lead to insulin not being produced by the pancreas, which will cause diabetes
How can CF affect the liver?
- Initially in CF, the liver is unaffected
- Over time the hepatic ducts of the liver can start getting occluded., making patients with CF more prone to gallstones and gallbladder disease
How can CF affect reproductive organs in men and women?
- Certain mutations in CF can affect the reproductive organs in men and women
- In men, the vas deference can become occluded by sticky secretions, leading to semen becoming deficient in sperm
- Sperm is still being produced, but the duct that carries it is (vas deferens) is blocked off
- This leads to 95% of men with CF being infertile
- In women, the thick mucus can block the fallopian tubes, which can cause menstruation issues and ectopic pregnancies
- Poor nutrition in those with CF can also cause menstrual cycle problems
What are 10 common symptoms seen in CF?
- 10 common symptoms seen in CF:
1) Meconium illeus
2) Recurrent chest infections
3) Diarrhoea/constipation
4) Growth faltering
5) Hypernatremic dehydration
6) Liver dysfunction
7) Intussusception
8) Pancreatitis
9) Diabetes
10) Infertility
What is one of the earliest symptoms of CF?
If babies are not born with GI problems, when can CF be suspected?
How do CFTR in sweat glands function in normal people?
How is this altered in CF?
What can this cause?
How do affected CFTRs in CF affect the kidneys?
- One of the earliest symptoms of CF is meconium ileus, which is a bowel obstruction that occurs when the meconium in the child’s intestine is even thicker and stickier than normal meconium
- Meconium is a new-borns first poop
- If a baby with CF isn’t born with gut problems, they may not show symptoms for weeks
- It will be suspected CF when the infant isn’t gaining weight, getting frequent chest infections, and is passing watery malabsorption stools that cause burning on the baby’s bottom, all of which can appear around weeks 5-8
- In normal people, the CFTR in sweat glands reabsorb water from sweat (same thing happens in kidney tubules)
- In CF, the CFTR is reversed, which can lead to profuse sweating (which is rich in salt)
- This loss of salt and water can cause an acute form of dehydration called hypernatremic dehydration, which can be a medical emergency
- Due to CFTRs also being reversed in kidneys, this can also lead to less water reabsorption in the kidney tubules, causing polyuria (excess urination)
As CF patients get older, what 4 other conditions might we see?
What is intussusception?
What things can it block off?
When might it be seen in CF?
- As CF patients get older, we may see:
1) Liver dysfunction
2) Pancreatitis
3) Diabetes
4) Infertility - Intussusception is a serious condition in which part of the intestine slides into an adjacent part of the intestine.
- This telescoping action often blocks food or fluid from passing through.
- Intussusception also cuts off the blood supply to the part of the intestine that’s affected, leading to bowel necrosis
- Intussusception can be seen in some children with CF that have heavy constipation, and constitutes a medical emergency
How are new-borns screened for CF?
How many CF mutations are screened for?
What is IRT?
How can it end up in the blood?
Describe the flowchart for Scottish Screen Protocol
- New-borns can be screened for CSF by taking a blood spot at day 5/6 and analysing the IRT concentration
- The 4 most common CF mutations are screened for, which account for 85% of CF cases
- IRT (immunoreactive trypsinogen) is an enzyme produced by the pancreas
- It is not normally present in the blood, but when the pancreatic duct is obstructed, the IRT is washed back into the blood where it can be detected
When is the sweat test for CF used?
What kind of technique is the sweat test?
How is it done?
- When we have a positive screening test, we use a sweat test to detect CF
- The sweat test is a Pilocarpine iontophoresis technique
- The minimum sweat volume is taken and the chloride concentration of the sweat is analysed
- Sweat chloride concentration > 60mmol/l – indicates CF
- 40-60mmol/l is borderline
- <40mmol/l is normal
After a positive screening test has been obtained, what 3 tests can be we use to detect CF?
- 3 tests used for detection of CF after positive screening test:
1) Sweat test
2) Stool elastase
3) Genetics
What health care professionals make up a CF multi-disciplinary team (MDT)?
What is another important aspect of the MDT?
- Health care professionals make up a CF multi-disciplinary team:
1) Doctors
* Respiratory
* GI/Liver
* Endocrine-diabetes
2) Specialist nurse
3) Physiotherapist
4) Dietician
5) Respiratory physiologist
6) Psychologist
7) Pharmacist
- Another important aspect of the MDT is family
What 5 things will make up treatment in the early years of CF?
- 5 things that will make up treatment in the early years of CF:
1) Airway clearance
* Mucolytic therapy delivered through nebulisers
2) Nutritional management
* Calories
* Vitamins
* Salt
3) Management of chest exacerbations
4) Regular MDT clinic
5) Ad-hoc reviews
A journey of CF
A journey of CF
