Cystic Fibrosis Vignette Flashcards
- Describe the genetics and underlying protein defect in Cystic Fibrosis (CF).
Cystic Fibrosis:
- Auto recessive condition
- chronic sinopulmonary infections
- nutritional abnormalities
- lung disease (major cause of mortality).
- Avg. life expectancy = 37 year.
-CF caused by a defect in ATP-binding cassette transporter gene on chromosome 7 –> encodes CFTR Cl- channel.
-Most common mutation = F508del, but there are >1500 more.
Mutation causes problems in salt and water movement across cell membranes –> abnormally thick secretions that alters host defense in the lung.
-Now we’ve implemented an NBS program.
- Describe current understanding of pathophysiology underlying CF lung disease.
- Molecular consequences of mutation = no protein synthesis (I), block in processing of protein (II, causing no F508), block in protein regulation (III), altered conductance (IV), and reduced protein synthesis (V).
- Types IV and V are milder.
Features of CF =
- greasy, bulky, malodorous stool
- exocrine pancreatic insufficiency
- respiratory infections (particularly via pseudomonas aeruginosa)
- chronic sinus infection
- digital clubbing
- bronchiectasis
- high levels of sweat chloride
- Most common presentation of CF = failure to thrive.
-Particularly because pancreas isn’t making the digestive enzymes necessary to breakdown food and absorb nutrients. (85%)
Can present with:
- hypoproteinemia (+/- edema)
- anemia
- deficiency of Vitamins DAKE
- dehydration
- alkalosis
- bronchiectasis
- rectal prolapse
- nasal polyps
- chronic sinusitis
-15% newborns have meconium ileus – which is an intestinal obstruction due to inspissation of meconium in terminal ileum.
Clinical manifestations:
- productive cough,
- wheezing,
- bronchitis,
- pneumonia,
- airway diseases, etc.
- Infections = decline in pulmonary function –> airflow obstruction and airway/lung destruction = bronchiectasis.
- Acute changes in respiratory signs = pulmonary exacerbation –> give antibiotics and augmented airway clearance; probably requires hospitalization.
- Describe the diagnostic and therapeutic approaches in CF.
Manage pancreatic insufficiency with:
- enzyme supplementation
- high calorie, high protein, and high fat diet.
- Need to take fat-soluble vitamin supplements.
- Salt supplement to compensate for salt loss in sweat.
Airway clearance treatment:
- daily percussive therapy (chest PT, vest)
- DNAse = inhaled mucolytic agent
- inhaled hypertonic saline
- bronchodilators
Antibiotic therapy
-inhaled TOBI or aztreonam;
-oral or intravenous
Anti-inflammatory treatment = ibuprofen or azithromycin
-CFTR potentiator = ivacaftor (only for patients with G551D mutation) –> improves CFTR function
-If you have abnormal genes, hoping for gene therapy and modifier genes.
-If abnormal CFTR protein –> hoping for protein rescue with correction/potentiation to make it work better.
-If altered ion transport –> deliver the proper ion transporter.
-If infection/inflammation/tissue destruction = try drugs or transplant.
