CFTR & Cystic Fibrosis Flashcards
(16 cards)
What does the CFTR protein do at the cellular level?
CFTR functions as a chloride ion channel located in epithelial cell membranes. It regulates the transport of Cl⁻ ions out of the cell, indirectly influencing sodium and water movement to maintain hydration of mucus, sweat, and digestive secretions.
In which tissues is CFTR activity especially critical?
Lungs, pancreas, intestines, sweat glands, and reproductive tracts.
What is the structural classification of CFTR?
CFTR is an ATP-binding cassette (ABC) transporter-class protein, unique in that it functions as an ion channel rather than a transporter.
What type of genetic disorder is cystic fibrosis and how is it inherited?
CF is an autosomal recessive disorder caused by mutations in both copies of the CFTR gene on chromosome 7.
What is the structural classification of CFTR?
CFTR is an ATP-binding cassette (ABC) transporter-class protein, unique in that it functions as an ion channel rather than a transporter.
What is the ΔF508 mutation and what is its consequence?
ΔF508 is a deletion of phenylalanine at position 508. It causes CFTR misfolding and degradation before reaching the cell membrane, resulting in loss of function.
Why is heterozygous carriage of CFTR mutations clinically silent?
One functional copy of the gene produces sufficient CFTR protein to maintain ion balance in epithelial tissues.
How does defective CFTR protein lead to thick mucus?
Impaired chloride ion transport prevents water from following into the lumen, causing mucus to become dehydrated, thick, and sticky.
Name three systemic effects of cystic fibrosis and explain their cause.
Pulmonary: Obstructed airways → chronic infections
Gastrointestinal: Pancreatic duct blockage → enzyme insufficiency, malabsorption
Reproductive: Absence of vas deferens in males → infertility
Why is the sweat of CF patients abnormally salty?
CFTR normally reabsorbs Cl⁻ from sweat; its dysfunction prevents this, leaving high salt content in the final sweat product.
What is the gold standard diagnostic test for CF?
The sweat chloride test, which measures elevated Cl⁻ concentrations in sweat (>60 mmol/L suggests CF).
What is the role of CFTR modulators like Ivacaftor?
They enhance the function of defective CFTR proteins by improving gating activity or trafficking to the membrane, depending on mutation type.
When is a lung transplant indicated in CF patients?
In cases of severe lung damage and respiratory failure unresponsive to medical management.
How is CFTR involved in cross-regulation of sodium channels?
CFTR downregulates ENaC (epithelial sodium channel); loss of CFTR leads to unopposed Na⁺ absorption, worsening mucus dehydration.
What is the importance of newborn screening for CF?
Early diagnosis allows for timely intervention, improved growth, reduced pulmonary decline, and better prognosis.
Q: Describe the connection between CFTR mutation class and therapy strategy.
Class I–III mutations: Severe dysfunction → potential use of correctors (like Lumacaftor)
Class IV–V mutations: Residual function → potentiators (like Ivacaftor) may suffice
