Cystic Fibrosis Flashcards

Flashcards about Cystic Fibrosis, its genetic mechanism, disease function, and treatments.

What is Cystic Fibrosis (CF)?

An inherited life-threatening disorder that primarily affects the lungs and digestive systems.

What is the estimated prevalence of CF?

One in every 2500 live births

What causes CF?

Mutations in the cystic fibrosis transmembrane regulator (CFTR) gene.

What are the characteristics of CF disease?

Chronic respiratory diseases and infections, pancreatic insufficiency, elevated sweat electrolytes, and male infertility.

What is the function of the CFTR protein?

A regulated chloride ion channel located in the apical epithelial membrane of epithelial cells.

What happens when there is a loss of function in the CFTR gene?

It disrupts chloride ion transport, leading to abnormal fluids and mucus secretions.

What are the five major structural domains of the CFTR protein?

Membrane-spanning domains, nucleotide-binding domains, and a regulatory domain.

What happens in Class 1 CFTR mutations?

No proteins are produced, leading to the most severe form of the disease.

What happens in Class 2 CFTR mutations?

The CFTR protein is produced but misfolded, preventing it from reaching the cell surface.

What happens in Class 3 CFTR mutations?

The protein is produced and reaches the cell surface but is nonfunctional, preventing chloride ion transport.

What happens in Class 4 CFTR mutations?

Functional CFTR protein is produced but has reduced function, resulting in a small amount of chloride ion transport.

What happens in Class 5 CFTR mutations?

Functional CFTR protein is produced but at a reduced number, decreasing chloride ion transport.

What happens in Class 6 CFTR mutations?

Less stable CFTR proteins reach the cell surface and actively transport, but due to instability, they have reduced chloride ion transport.

What does 'delta F508' mean in the context of CF mutations?

Deletion of the amino acid phenylalanine at residue position 508.

Why is the delta F508 mutation so important in CF?

It's a Class 2 mutation resulting in a misfolded protein that cannot escape the endoplasmic reticulum.

What are the two major classes of pathogenicity associated with CF?

Pancreatic dysfunction and abnormal mucus secretion.

How does pancreatic dysfunction manifest in CF patients?

It leads to maldigestion and a lack of secreted digestive enzymes, resulting in poor growth.

How does defective CFTR protein lead to abnormal mucus secretion?

Due to a buildup of chloride ions inside epithelial cells, hypersecretion of sodium ions occurs, leading to increased salt concentration.

What is the result of increased salt concentration inside the cell?

It leads to a dehydrated mucus environment, resulting in thick, sticky mucus obstructing the lungs, causing bacterial infections and inflammation.

What role do cilia play in a healthy lung?

The cilia, which are hair-like filaments on lung cells, clear and remove mucus from the lungs.

How does surfing or saltwater help CF patients?

Salt water is concentrated sodium chloride, which helps rehydrate the mucus in the lungs.

How do antibiotics help treat CF lung disease?

Antibiotics, particularly inhaled antibiotics like Tobramycin, help reduce bacterial burdens in the lung.

What is the common theme among most CF treatments?

They are all preventative, aimed at controlling and reducing pulmonary infection and preventing mucus buildup.

What are Vertex's two small molecule drugs that target genetic diseases like CF?

Ivacaftor and Lumacaftor

What is Ivacaftor, and how does it work?

A CFTR potentiator which interacts with the CFTR protein, allowing a pore to open, thereby increasing chloride ion transport.

Which drug specifically improves the conformational stability of delta F508 homozygous mutations?

Lumacaftor

How does Lumacaftor affect the CFTR protein?

It allows it to refold into its proper confirmation, thereby escaping the endoplasmic reticulum and making its way to the cell surface.

What is the combination treatment of Lumacaftor and Ivacaftor marketed as?

Orkambi

What is a key learning objective regarding CF?

Understanding the function of the CFTR protein and how its disruption leads to progressive lung disease and infection.