Cystic Fibrosis Flashcards
What is cystic fibrosis?
Cystic Fibrosis (CF) is an inherited autosomal recessive disease that disrupts ion transport in epithelial-lined organs, including pulmonary airways, sweat ducts, pancreatic ducts and intestine
Where is the mutation for CF?
Long arm of chromosome 7 (Delta F508 deletion most common)
Which gene is associated with CF?
CFTR: Cystic Fibrosis Transmembrane Regulator
a cAMP regulated epithelial chloride channel in apical cell membranes
T or F: there are varying degrees of loss of function of the CFTR gene associated with five classes of mutations
T: I - no synthesis II - block in processing III - block in regulation IV - altred conductance V - reduced synthesis
Which class of mutation is more severe?
I to III more severe
What is the Delta F508 mutation?
Deletion of 3 nucleotides that encode phenylalanine in position 508
T or F: CF occurs in Caucasian and European descent more frequently than other groups
T
What is the pathophysiology of CF?
Abnormal chloride channels on the apical surface of epithelial cells ---> Depleted airway surface layer --> defective mucociliary transport and accumulation of mucus --> Clogged ducts Thick, sticky secretions --> Airways: -Sinus disease -Lung disease
GI tract
- Pancreatic disease
- Constipation/bloating
Liver and biliary disease
Male infertility
Salty sweat
What are the clinical hallmarks of CF?
Recurrent lung infections, often with unusual pathogens (funny bugs)
Obstructive airways disease – cough, thick sticky sputum, wheeze, dyspnea
Low BMI
Progression to lung disease
What is the classic CF phenotype [2 severe mutations]?
Early age of diagnosis
Pancreatic insufficient
Elevated sweat chloride
What is the atypical CF phenotype [ie. 1 mild mutation]?
Diagnosed at an older age
Pancreatic sufficient
Sweat chloride levels closer to normal
What are the upper airway conditions related to CF?
Sinusitis
Nasal polyps
What are the lower airway conditions related to CF?
Chronic productive cough Recurrent respiratory infections (Pulmonary exacerbations): - pseudomonas aeruginosa - staphylococcus aureus Hemoptysis Pneumothorax Exercise intolerance
What are radiographic findings for CF?
Bronchiectasis (permanent enlargement of parts of the airways of the lung)
Hyperinflation
Fibrosis
What is the common GI finding with CF?
DIOS (Distal intestinal obstruction syndrome)
What is the common pancreatic finding with CF?
pancreatic insufficiency
What is the common liver finding with CF?
Cholelithiasis
Cirrhosis
Portal HTN
What is other clinical features in CF?
Failure to thrive
Osteoporosis
Male infertility (CBAVD)
Clubbing (Shamroth sign)
How is CF diagnosed?
- Compatible clinical findings AND
- Biochemical or genetic confirmation
What are some biochemical and genetic tests for CF?
Sweat Chloride test*
Genotyping
Nasal potential difference
T or F: the newborn screen is useful as clinical finding
T
How does the newborn screening work for CF?
Immunoreactive Trypsinogen levels determined from cord blood or foot pad blood spot
Positive test result to further testing (ie. sweat and genetic)
What clinical clues would let you suspect of CF?
Meconium ileus (infant) Chronic Pulmonary Infection Failure to thrive Clubbing Upper Lobe Bronchiectasis Pseudomonas Aeruginosa in sputum Pancreatic Insufficiency Idiopathic pancreatitis Azospermia Positive family history
What is the gold standard test for CF?
Sweat chloride test
What is a positive sweat chloride test
positive > 60 meq/l
negative < 30 meq/l
indeterminate 30-60 meq/l
If the sweat chloride test is indeterminate, what is the next step?
Nasal Potential Difference – Physiologic test done in a few sites in Canada to evaluate indeterminate cases
What are the therapy needs for CF?
Correct underlying genetic abnormality:
- Gene therapy
- Correct underlying CFTR defect
Improve mucociliary transport, airway clearance:
- Chest physiotherapy – percussions, vibrations
- Mucolytics
- Hypertonic saline
Antibiotics
Oral, IV, inhaled routes
Lung transplant
Nasal secretion treatments:
- Rinses
- Steroid sprays
- Surgery
Nutritional supplementation:
Fat soluble vitamins
Caloric supplements
Enteric feeds
Treatment of DIOS/constipation
Bone density maintenance/treatment
Diabetic management
Exercise
