Flashcards in Cystic Fibrosis Vignette Deck (15)
1. Describe the genetics and underlying protein defect in Cystic Fibrosis (CF).
2. Describe current understanding of pathophysiology underlying CF lung disease.
3. Describe the diagnostic and therapeutic approaches in CF.
Cystic Fibrosis (CF) is an ______ condition that results in a syndrome of chronic sinopulmonary infections and nutritional abnormalities secondary to malabsorption.
CF is caused by a defect in an ATP-binding cassette transporter gene on chromosome 7 that encodes for the CF Transmembrane Conductance Regulator (CFTR) protein. The most common mutation is the:
F508del, although approximately 1500 other disease-causing mutations in the CF gene have been identified. CF gene is a large gene on chromosome 7
Types of CF mutations:
Types of CF mutations:
I - No synthesis (nonsense mutation)
II - Block in processing (F508 deletion)
III - Block in regulation (missense)
IV - Altered conductance (missense)
V - Reduced synthesis (missense)
Typical features of CF:
Greasy, bulky, malodorous stools; failure to thrive due to exocrine pancreatic insufficiency
Recurrent respiratory infections with opportunistic bacteria (e.g. Staphylococcus aureus,
Pseudomonas aeruginosa and Burkholderia cepacia)
Chronic sinus infections
Digital clubbing on examination.
Sweat chloride > 60 mmol/L.
CF newborn screening Immunoreactive trypsinogen
false negative rate ranges from 1-5%) may present with clinical symptoms later in life.
Pancreatic insufficiency occurs in more than ___% of persons with CF.
Approximately 15% of newborns with CF present at birth with _____.
[a severe intestinal obstruction resulting from inspissation of tenacious meconium in the terminal ileum.]
From a respiratory standpoint, clinical manifestations include
productive cough, wheezing, chronic bronchitis and recurrent pneumonias, progressive obstructive airways disease, exercise intolerance, dyspnea, and hemoptysis.
Chronic airway infection with bacteria, including ____ and _____, often begins in the first few months of life, even in asymptomatic infants. Eventually, _____ becomes the predominant pathogen.
S aureus and H influenzae; Pseudomonas aeruginosa
[Acquisition of the characteristic mucoid Pseudomonas is associated with a more rapid decline in pulmonary function. Chronic infection leads to airflow obstruction and progressive airway and lung destruction resulting in bronchiectasis.]
Treatment: pancreatic insufficiency
High fat/protein/calorie diet
Daily salt supplement
Inhaled antibiotics (tobramycin (TOBI) aztreonam(Cayston)
Recombinant human DNAse (Pulmozyme - mucolytic agent)
Inhaled hypertonic saline
Ivacaftor (CFTR potentiator)
G551D mutation or gating mutation. Must be older than 6