Cystic Fibrosis Vignette Flashcards
What is a typical presentation of CF?
Childhood presentation (Case 2&1/2 yo)
Normal birthweight and full term
Intermittent diarrhea with foul smelling stools
Failure to thrive (Case persistently under third percentile)
Lower Respiratory Infections (1st pneumonia at 7 months old, 4 subsequent LRIs)
Chronic cough (case was O2 dependent)
Non-ambulatory, poor speech, poor muscle tone & coord.
Family history of CF (2nd or 3rd degree)
Physcial exam findings in CF
Vital signs: RR 30, O2Sat 87% on room air
Physical Exam: Malnourished appearance, Tachypnea and retractions at rest, Poor aeration and diffuse crackles on R, Distended abdomen, Palpable liver 4-5cm below RCM, Clubbing Sweat test: 107mmol/L (>60 = CF) Mut: F508
What is bronchiectasis and how is it diagnosed?
Bronchiectasis is the breakdown and scarring of lung tissue. Airways that are larger than their associated blood vessels are diagnostic for bronchiectasis. Enlarged walls of airways in bronchiectasis decrease the lungs’ ability to clear mucus, compounding problems of CF and leading to more bronchiectasis.
What is cystic fibrosis?
CF is a syndrome of chronic sinopulmonary infections, malabsorption and nutritional abnormalities. Incidence is 1:3500 caucasians (most frequent genetic disease in caucasian population). Caused by mutations in the CFTR gene (F508 most common, 1500 mut known). Affects salt and H2O movement into and out of cells.
What organ systems or structures does CF primarily impact?
Sinuses, lungs, pancreas, intestines, liver, vas deferens, sweat glands
What are the most significant problems arising from CF?
Bronchiectasis, Exocrine deficiency (causes malnutrition and diarrhea/foul stools), CF related Diabetes (not type 1 or 2), Meconium ileum (failure to pass first stool, can be fatal), DIOS, Male infertility (due to lack of Vas Deferens, still produce sperm), Dehydration due to salt loss in sweat.
How common is the F508 mutation?
80-90% of CF patients have one copy of F508
40% of CF patients are homozygous F508
What are the five possible mechanisms for CF mutations to affect patients?
1) No synthesis of CFTR at all
2) Synthesis of mutant CFTR that is never expressed (F508)
3) Synthesis of mutant CFTR that locates to surface but does not function (G551D; 4% of patients)
4) Altered conductance, expressed but less effective
5) Altered expression, expressed in insufficient amounts
How might CF manifest in a less severe manner?
Through altered conductance or altered expression, the CFTR channel is still present but is less effective. Many of the patients with these mutations do not have the pancreatic problems and may absorb their food without enzymes, but still have lung problems.
What is the pathogenesis of CF?
Abnormal CFTR -> Impaired mucociliary clearance -> Infection and inflammation -> Bronchiectasis & lung damage -> functional airway impairment
What are the details of the CFTR protein?
CFTR is a member of the ATP Binding Cassette (ABC) superfamily. It is expressed in epithelial cells lining exocrine glands. It has 2 six-span membrane spanning domains (MSD) and 2 nucleotide binding domains (NBD), as well as a highly charged regulatory (R) domain.
How does CF lead to dehydration?
With mutant CFTR channels Cl- cannot exit the cell, thus Na+ is retained and the extra ions attract more H2O from surrounding fluids, leading to the dehydration of the lumen. This leads to a thickening of the normal mucous which inhibits the cilia from performing their normal function of clearing the lungs.
What is tested in newborn screening for CF?
IRT Immunoreactive trypsinogine (emitted from the pancrease if it is damaged) is tested twice and if it is elevated both times genetic tests are conducted. The genetic tests cover the 30 most common mutations. Sweat chloride is also tested. Testing has about a 3% false negative rate.
What are the traditional treatments for CF?
Pancreatic enzymes, airway clearance - inhaled medications for mucous clearance and infections (inhaled antibiotics), coughing techniques
What are the newest treatments for CF?
Ivacattor: potentiator that increases the activity of poorly functioning CFTRs.
Lumacattor: Promotes the localization of F508 CFTR to the cell membrane. Works in conjunction with ivacattor.
