Cystic Fibrosis Flashcards
What is the name of the gene disorder that causes cystic fibrosis?
Cystic fibrosis transmembrane conductance regulator
What are the systems affected by CF?
Upper and lower respiratory tract
Pancreas
Gastrointestinal tract
Female/Male reproductive tract
What criteria must be met in order to diagnose cystic fibrosis?
Clinical symptoms consistent with CF in at least one organ system
Clinical evidence of CFTR dysfunction
Describe the ethnic distribution of CF
Most prevalent in caucasians by a wide margin
Least prevalent in asians
No fucking clue why
Being pasty as fuck may be a contributing factor
When are most cases of CF diagnosed?
Most are caught at birth via standard testing
Mutations on which chromosome are responsible for CF?
7
How many different mutations can cause CF?
According to steves slides, 2400. According to steves other slides, 24000. According to google, over 2000
CF is an autosomal recessive gene disorder. What is the significance of this
In order to be affected by the disease, both parents have to have the disease causing mutation, even if neither parent has the disease. Both parents can be carriers, but not be affected by the mutation since it is recessive
T/F: CF is a classical autosomal dominant gene disorder
False. CF is a classical autosomal recessive gene disorder
If one parent is a carrier, and one parent has CF, what are the chances that their children will be affected by the mutation?
50% chance of being affected
50% chance of being an unaffected carrier
If both parents are carriers, what are the chances that their offspring will be affected by the mutation?
25% unaffected
50% unaffected carrier
25% chance affected
If one parent is a non carrier, and one parent has CF, what are the chances their children will be affected by the mutation?
100% chance unaffected carrier
If one parent is a non-carrier, and one parent is an unaffected carrier, what are the chances that their children will be affected by the mutation
50% unaffected
50% unaffected carrier
What physiologic process does the CFTR gene regulate?
It regulates the conductance of chloride ions across the membrane
What effect does a mutation of the CFTR gene have?
It interferes with the production of the CFTR gene in a way that either completely halts the creation of the protein, completely or partially inhibits its ability to conduct ion transport, causes production of the protein to be significantly less than normal, or causes the protein to deteriorate at an advanced rate
What are the primary organs/areas that experience issues as a result of CFTR dysfunction?
Lining of of bronchial airways
Intestines
Pancreas
Liver ducts
Sweat glands
Describe the primary effect a mutation of the CFTR gene has on the respiratory tract
The mutation interferes with chloride transport in the bronchial airways. This in turn interferes with how fluid moves across the membrane from the mucus into the epithelium. As a result, there is a very low concentration of ions in the mucus resulting in fluid moving out of the mucus and into the epithelium creating a very tenacious mucus that is very difficult to clear
Describe how CF can affect infants before they are born
The mutation results in the infants meconium becoming dehydrated and sticky. This material is very difficult to pass and can create an ileus (blockage) in the intestines
What percentage of infants with CF are affected by meconium ileus?
About 20%
At birth, an infant with CF may have lungs that appear normal, however structural changes can develop quickly. What are examples of these structural changes?
Bronchial gland hypertrophy
Metaplasia of goblet cells
Infants with CF might exhibit what problems aside from meconium ileus?
Poor weight gain
Failure to thrive
Multiple respiratory infections per year
Consistent cough with sputum production
Pancreatic insufficiency
T/F: CF has obstructive and restrictive characteristics
True
CF results in mucus that is incredibly hard for individuals to clear. Besides airway restrictions, describe what other effects this incredibly thick mucous can have on patients
The mucus traps bacteria, however because patients are not able to clear this bacteria via normal means, the trapped bacteria becomes a food source for retained bacteria in the airway such as staph, haemophilus and pseudomonas
What are restrictive characteristics of CF?
Total obstruction of airways
Atelectasis
Bronchiectasis
What are obstructive characteristics of CF?
Partial obstruction of the airway
Overdistention of the alveoli
What are some bacteria that tend to be distinctively found in CF patients?
Stenotrophomonas maltophilia
Burkholderia cepacia complex
What are the results of respiratory infection in a patient with CF?
Increased mucus production (same as healthy individuals) but it remains thick, hard to clear, and continues to compromise mucociliary transport
What disease processes are common in patients with advanced CF?
Recurrent PNA
Chronic bronchitis
Bronchiectasis
Lung abscesses
Patient with CF often have digestive problems. Describe why they have these problems and what can happen as a result
Thick viscous mucous also accumulates in the passageways of the pancreas which prevents enzymes from being able to leave the pancreas and enter the intestines. This causes digestive issues (ie cant digest fat) and can lead to patients developing CF-associated diabetes mellitus
Describe the effects CF has on the pancreas and how that can affect individuals suffering from CF in relation to their nutrition
Loss of pancreatic enzymes inhibits digestion of fats and proteins
Inability to digest fats leads to deficiencies in fat soluble vitamins, ADEK
Diarrhea
Malnutrition
Failure to thrive
How does CF affect the bones?
Patients with CF have a significant decrease in bone density due to not being able to absorb vitamin D (fat soluble) which increased their risk of bone fractures and kyphoscoliosis
How can CF affect the upper airways and liver?
Upper airways = Sinusitis, nasal polyps
Liver = cirrhosis and neonatal jaundice
Describe how CF affects patients reproductive systems
In women, it results in accumulation of thick, viscous mucous at the cervix
In men, in results in azoospermia (no sperm) and a missing or underdeveloped vas deferens (sperm transport?)
How can CF affect the gallbladder and salivary glands?
Gallbladder = cholelithiasis
Salivary glands = altered electrolyte concentrations
What are the 2 assays used to test newborns for CF?
Serum immunoreactive trypsinogen (IRT)
DNA analysis for mutations in CFTR
Describe immunoreactive trypsinogen testing
MOST infants with CF have elevated levels of immunoreactive trypsinogen
Its a blood test
Catches 90% of infants with CF
If an infant tests positive for IRT, what test will likely follow?
DNA analysis to identify the specific gene mutation
What is the gold standard for CF testing?
Sweat chloride testing
Reliably identifies CF in about 98% of cases
Describe the sweat produced by CF patients
The sweat glands and amount of sweat produced will be normal, but the concentration of sodium and chloride will be more than 4x the normal amount
Describe how the sweat chloride test is administered
Pilocarpine (sweat producing chemical) is placed on the skin and an electrode is attached to the chemically prepared area. A mild electric current is then applied to simulate sweat production
The test is normally applied twice
In infants, what would a result of between 30-50 mmol/L mean?
CF possible, further testing required
In infants, what would a result of less than or equal to 29 mmol/L mean?
Normal
In infants, what would a result of greater than or equal to 60 mmol/L mean?
This level is sufficient to diagnose CF
In infants >6 months, children and adults what would a result of less than or equal to 39 mmol/L mean?
CF unlikely
In infants >6 months, children and adults what would a result of between 40-50 mmol/L mean?
CF possible
In infants >6 months, children and adults what would a result of equal to or greater than 60 mmol/L mean?
Diagnosis of CF
When testing for CF, what patient populations generally receive the sweat chloride test?
Infants with positive CF newborn screening adults
Infants with symptoms suggestive of CF ie meconium ileus
Adolescents and adults with symptoms suggestive of CF
Sibling with confirmed CF…why would they test again?
How is the nasal potential difference performed?
A voltmeter is used to measure charge
Nasal passages bathed with different salts
Different salts should provoke predictable ion movement across the epithelial membrane
Abnormalities in this ion movement suggest a dysfunction of the CFTR
What is the nasal potential difference test?
CF patients obviously suffer from impaired sodium and chloride transport. This results in changes in the electrical potential difference in the nasal passages
What does the stool fecal fat test evaluate?
The stool fecal fat test evaluates the function of the liver, gallbladder pancreas and intestines
An elevated stool fecal fat value shows a defect in digestive functioning
Who receives the nasal potential difference test?
Patients with clinical features of CF who have a borderline or normal sweat test values and nondiagnostic CF genotyping
Why is the stool fecal fat test used?
Individuals with CF have trouble digesting fat and as a result their stools will carry more fat than the stools of normal people
Besides fat content, how else can stool be used to support a CF diagnosis?
Individuals (or infants, according to the book) will have decreased amount of the fecal elastase 1 enzyme that gives information about pancreatic function
This is however, not CF specific
What tests can be performed prenatally to determine whether or not a fetus may have CF?
Test amniotic fluid after first trimester
This can only test for at most 85 of the 2400 mutations that cause CF
What happens to the FVC and FEV1 of patients with CF?
Decreased FVC and FEV1
Decreased FEV1/FVC ratio
Decreased flow measurements across the board
Describe the lung volume and capacity findings of a patient with CF
Increased or Normal VT, TLC
Normal or decreased IRV, ERV, IC
Increased RV and FRC
Describe the ABG of a patient with cystic fibrosis
Can present as acute respiratory alkalosis in mild to moderate stages of the disease
Can also present as compensated respiratory acidosis in the later severe stages
‘Which oxygenation indices are significantly impacted by the CF disease process?
Delivery of oxygen is decreased significantly
Describe the effect CF has on the hemodynamic indices
Inc CVP
Inc RAP
In PA
N PCWP
Inc PVR
N SVR
What would a CBC of a CF patient look like?
Increased hematocrit
Increased white blood cell count
Describe what serial CXRs would show as a patient with CF ages
Toddler - pneumonias
Adolescent - hyperinflation and bronchial wall thickening
Teenager - progressing hyperinflation, bronchiectasis and enlargement of the hila
Late 20s - marked hyperinflation and barrel chest, severe bronchiectasis and tubular opacities consistent with mucus plugs
When would the application of bronchodilators be appropriate for individuals with CF?
When they have hyperreactive airways
Before treatment with medications such as hypertonic saline which cause irritation
Airway clearance is incredibly important for individuals with CF. What is the main way airway clearance is accomplished?
The vest
What are basic practices individuals with CF utilize in their every day lives to attempt to mitigate the risk of infection?
Physical distancing
Hand hygiene
Masking
Ceiling and disinfecting nebulizers
Not sharing personal items
Avoiding frequent contact with dust and dirt
What does dornase alpha do?
CF sputum is different than normal sputum as it is exceptionally thick and viscous. Bacteria will get trapped in this viscous sputum and neutrophils will move it to kill the bacteria, but die in the process as well leaving long strands of DNA which increase the viscosity of the sputum. Dornase alpha breaks up these strands of DNA and makes the sputum easier to clear
What is the main mucolytic drug utilized by individuals with CF?
Dornase alpha
Besides dornase alpha, what can be used to decrease the viscosity of mucus in patient suffering from CF?
Hypertonic saline
Note, for some reason steve didnt tell us, you should only give hypertonic saline to patients greater than 6 years old
Describe the differences in make-up between sputum found in a patient suffering from chronic bronchitis and a patient suffering from CF
The patient suffering from chronic bronchitis will have sputum that is primarily made up of mucin polymers which NAC can theoretically cleave. The patient suffering from CF will have sputum that is dominated by DNA polymers which will not be affected by NAC
Why is NAC not recommended for patients with CF?
NAC can cleave disulfide bonds that make secretions difficult to clear in non-CF patients, however it is markedly less effective in patients with CF while still causing airway irritation, potentially starting bronchospasm and inhibiting ciliar function
What concentrations are hypertonic saline administered in and how frequently?
3% and 7%
Administered BID
You have a CF patient that needs dornase alpha, alburterol and hypertonic saline. What order should you administer these medications and why?
Albuterol-mitigate potential airway hyperreactivity
Hypertonic saline to hydrate mucus
Dornase alpha to thin the mucus out
Note-dornase alpha is deactivated if combined with hypertonic saline
What are the primary antibiotics utilized by patients with CF to deal with respiratory tract infections?
Tobramycin (tobi)
Aztreonam (cayston)
Colistin/colistimethate sodium
An altera nebulizer system is used for what kind of medication
cayston(aztreonam)
aztreonam/cayston requires nebulization via what kind of nebulizer?
Altera nebulizer system
Individuals with CF are very susceptible to infections and therefore take a lot of antibiotics. What are some problems that could potentially result from this?
May develop antibiotic resistant bacteria
May result in fungal infections of the mouth, oral pharnyx and tracheobronchial tree
What common over the counter drug has been shown to impede the decline of the lung function in CF patients less than 18 years old?
Ibuprofen
Ibuprofen is common anti-inflammatory drug shown to help patients suffering from CF under 18, what is another antiinflammatory drug that is also recommended for CF patients?
Azithromycin
Should patients with CF be given inhaled corticosteroids for their condition?
Generally no. unless the patients have a history of airway reactivity or allergic bronchopulmonary aspergillosis
What inhaled anti-inflamatory drugs are generally not recommended for CF patients?
Leukotriene modifiers
NAC
Inhaled glutathione
Why are systemic glucocorticoids not recommend for children and adolescents with CF?
Growth retardation
Glucose metabolism
Development of CF-related diabetes
Cataract formation
Lung transplants can be very beneficial to CF patients who have very severe versions of the disease. However, despite recieving lungs that do not have CF, the transplant process in of itself creates more problems for the individual. Elaborate on the challenges a lung transplant can bring with it
Transplants require the individual to constantly take immunosuppressive medications in order to not reject the new organ. however, this cripples their already fragile immune system and makes them very vulnerable to bacterial infections such as pseudomonas or burkholderia
New medications are focused on correcting the function of the CFTR cells. Expound on the categories of these drugs and what they do
Correctors - help mutated CFTR reach epithelial surface
Potentiators - improve the function of CFTR protein that have reached the epithelial surface
What does ivacaftor do?
Improve function of CFTR proteins that have reached epithelial surface
Potentiator
What is orkambi?
Ivacaftor + lumacaftor
Promises to reduce the rate of exacerbations in qualified patients by 30-39%
What are the drug components of trikafta?
Elexacaftor+tezacaftor+ivacaftor
What are the drug components of symdeko?
Tezacaftor + ivacaftor
