SM 170a - Cystic Fibrosis Flashcards
Besides the respiratory tract, what other organ systems have primary effects due to cystic fibrosis?
- GI Tract
- Pancreatic insufficiency
- Malabsorption
- Constipation
- Obstruction
- Liver
- Obstructive jaundice
- Cirrhosis
- Galstones
- Reproductive tract
- Obliteration of the Vas Deferens (males)
- Increaesed viscocity of cervical and vaginal mucus (females)
- Increas frequency of anovulatory menstrual cycles (females)
- Sweat glands
- Metabolic alkalosis
- Dehydration
Class _____ CFTR mutations affect the channel itself; chloride conduction through the channel is decreased
Class IV CFTR mutations affect the channel itself; chloride conduction through the channel is decreased
A drug targeting the _____ mutation is likley to have the most profound overlal effect on the CF population.
Why?
A drug targeting the F508 deletion mutation is likley to have the most profound overlal effect on the CF population.
90% of patients with CF have at least one copy of this mutation, and this mutation is sever compared to other possible mutations
Genotype is most predictive of CF phenotype in which systems?
Genital tract > GI tract > Respiratory tract
Respiratory manifestations depend largely on the environment
Class _____ CFTR mutations are caused by retention of a misfolded protien in the ER, resulting in degradation of the protein in the proteasome. It never makes it to the plasma membrane
Class II CFTR mutations are caused by retention of a misfolded protien in the ER, resulting in degradation of the protein in the proteasome. It never makes it to the plasma membrane
Class II CFTR gene mutations result from…
Retention of misfolded protein in the ER, leading ot degradation in the proteasome
The protein does not make it to the plasma membrane.
Class II mutations include the ΔF508
List the available diagnostic tests for CF
Diagnostic for cystic fibrosis:
- Genetic
- Sweat test
- Nasal potential difference (rarely done)
Pancreatic insufficiency:
- Low fecal elastase
Class I CFTR gene mutations result from…
A premature stop codon -> no protein production
What is the most common CFTR mutation?
ΔF508 = deletion of phenylalanine 508
A class II mutation; results in a misfolded protein that is degraded in the proteasome
Describe the 3 components of the CFTR protein
- Transmembrane component
- Creates an anion channel
- Nucleotide binding fold
- Regulates the opening and closing of the channel
- R-domain
- Can be phosphorylated or dephosphorylated to regulate channel opening
Class V CFTR gene mutations result from…
A splicing abnormality
This causes decreased mRNA, CFTR protein, or both
Class _____ CFTR mutations are the result of a splicing abnormality, resulting in decreased mRNA, CFTR protein, or both.
Class V CFTR mutations are the result of a splicing abnormality, resulting in decreased mRNA, CFTR protein, or both.
What is the most commonly used newborn screening test for CF?
How are the results confirmed?
IRT (immunoreactive trypsin)
If IRT is elevated, repeat the test or run the genotype
If IRT is still elevated or a CFTR mutation is found, confirm with a sweat test
What is Ivacaftor?
Who should recieve it?
Ivacaftor is a potentiator drug used to treat CF
It increases Cl- movement through the CFTR channel
- Ivacaftor monotherapy
- Patients with class III, IV, and V mutations
- Includes G551D (class III)
- Ivacaftor + Tazacaftor + Elexacaftor
- Patients with F508 deletion
The _________ is the best initial diagnostic test for cystic fibrosis.
The sweat test is the best initial diagnostic test for cystic fibrosis
Run the test if CF is suspected;
Cl- ≥ 60 mmol/L => CF likely
Cl- 40-59 mmol/L => Additional testing needed
Cl- mmol/L => CF unlikely
