Day 8, Lecture 3 (Aug 31): Clinical Correlation 2: Cystic Fibrosis Flashcards
Mode of transmission of Cystic fibrosis
- Autosomal recessive
- mutations of a gene located on chromosome 7 called the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)
- CFTR protein is a cAMP-regulated chloride channel that usually resides within the apical portion of mucosal epithelial cells
- Most common mutations- DeltaF508, G542X, G551D, W1282X, W1303K, and R 553X
___ mortality in CF is a result of lung disease
85%
THe CFTR gene is on what chromosome
Chromosome 7
A normal-functioning CFTR channel moves ______ while a mutant CFTR channel does not, thus causing ______
chloride ions to the outside of the cell while a mutant CFTR channel does not, causing sticky mucus to build up on the outside of the cell
Classes of cystic fibrosis-causing mutations
Newborn screen for CF
- A few drops of blood from a heel prick are placed on a special card, called a Guthrie card.
- IRT level: >65ng/dl
What steps are taken if a newborn has a hellp prick IRT level: >65 ng/dl
Why does the sweat test help determine CF
- Malfunction of CFTR in sweat glands leads to the inability to reabsorb water and thus dehydration
- this leads to sweat having a higher than normal concentration of sodium and chloride
What are the primary goals of CF
- Maintain lung function
- Reduce pulmonary exacerbations
- Improve nutritional status
What is the most prevalent bacterial infections for CF patients
- P. aeruginosa
What are the most difficult/complex bacterial infections to eradicate in CF patients
-
Ps. aeruginosa and B. cepacia
-
True infection, not “colonization”
- difficulty in eradicating due too:
- intrinsic antibiotic resistance
- Acquired antibiotic resistance
- Poor antibiotic penetration into secretions
- Alginate produced by mucoid Ps. (biofilms)
- CF-related defects in mucosal (but not systemic) defenses
- difficulty in eradicating due too:
-
True infection, not “colonization”
What is the most reconized hallmark in CF disease
- progressive obstructive lung disease
- early thickening of progressive mucus
- subsequent colonization with pathogenic bacteria
- Ultimately diffuse airway inflammation that destroys conducting airways and lung parenchyma
- Combination of:
- Dessicated mucosal suface, infection, and host’s inflammatory response leads to inspissation of airway debris and progressive endobronchial destruction
Symptoms of CF
- Couch, sputum production
- Tachypnea
- use of accessory muscles
- Increased AP diameter of chest
- Hypoxemia
- Exercise intolerance
- Coarse crackles
- Decreased or absent breath sounds/air movement
- Decreased pulmonary function
- Weight loss
What is the strongest predictor of mortality in CF
- FEV1 (forced expiratory volume)
The underlying cause of CF is
- loss of CFTR protein activity
- Reduced CFTR activity results in a loss of chloride transport causing abnormalities in tissues where CFTR protein is present
What causes infections in the airways of CF patients
What are some of the therapies that help combat the effects of neutrophils attacking bacterial infections in CF patients lungs
What are some therapies of CF that help with mucus clearing?
- Clearance techniques and vests are also used
What is Kalydeco/Ivacaftor used for in treatment of CF
- Re-establish Chloride transport via the CFTR protein.
- IVacaftor is aCFTR potentiator that facilitates increased chloride transport by potentiating the channel-open probability (or gating) of the CFTR protein at the cell at the surface
- thus resulting in more normal function of the cilia and mucus layer combined with physical removal of mucus form the airway relieves physical obstruction and helps clear bacteria form the airways
- Restoring CFTR function results in improved FEV
Therapies for the treatment of chronic airway infections in CF patients
*
do current therapies treat the underlying cause of CF
- No!
_____ treat the underlying cause of CF
- CFTR modulators
