Clin Med - CF Flashcards
General characteristics
- Most common cause of severe chronic lung disease in young adults
- Most common fatal hereditary disorder of whites in the United States
Inheritance pattern + characteristics
Autosomal recessive exocrinopathy - exocrine glands produce and secrete substances onto an epithelial surface via a duct.
–Sweat, salivary, mammary, ceruminous, lacrimal, sebaceous and mucous
What protein does CF affect?
Caused by abnormalities in a membrane chloride channel (the cystic fibrosis transmembrane conductance regulator [CFTR] protein)
CF results in…
altered chloride transport and water flux across the surface of epithelial cells (necessary for production of thin, freely flowing mucous)
CF Mutation
Mutation referred to as D F508 accounts for about 60% of cases of cystic fibrosis.
Effect on exocrine glands
Almost all exocrine glands produce abnormal mucus that obstructs glands and ducts and leads to tissue damage
Morbidity & Mortality associated with CF
- Attributed to respiratory compromise
- Characterized by copious hyperviscous and adherent pulmonary secretions that obstruct small and medium-sized airways
- Obstructive lung dz with chronic infection
Symptoms
- Cough
- Sputum production
- Decreased exercise tolerance
- Wheezing
- Recurrent pneumonia
- Dyspnea
- Recurrent hemoptysis
- Chronic rhinosinusitis
Clinical findings - pancreas
In the pancreas, the mucus prevents the release of digestive enzymes that allow the body to break down food and absorb vital nutrients
Clinical findings - digestion
- Chronic malabsorption, steatorrhea (fat in the stool), diarrhea, and abdominal pain.
- Poor growth in infants (failure to thrive)
- CF related diabetes (30%)
Clinical findings - male reproduction
Nearly all men with cystic fibrosis have congenital bilateral absence of the vas deferens with azoospermia
Clinical findings on exam
digital clubbing,increased anteroposterior chest diameter (”barrel chest”), hyper-resonance to percussion, and apical cracklesare noted on physical examination
Bacteria found in airway
- S. aureusandH. influenzae, often begins in the first few months of life.
- Eventually,Pseudomonas aeruginosaand other gram-negative bacteria become the predominant pathogens.
- -Burkholderia cepacia – Gram neg. that is very resistant to antibiotics
Chronic infection leads to…
airflow obstruction and progressive airway and lung destruction
Diagnosis - newborn screening
- measuring immunoreactive trypsin (IRT): a pancreatic enzyme in the blood.
- most infants with CF have elevated IRT in the newborn period, although false negative results are possible.
Diagnosis - next step in newborn screening
- in positive newborn screen, the diagnosis of CF must be confirmed by sweat testing, mutation analysis, or both
- Quantitativepilocarpineiontophoresis sweat testreveals elevated sodium and chloride levels (greater than 60 mEq/L) in the sweat of patients with cystic fibrosis
- Two tests on different days are required for accurate diagnosis
If there is high clinical suspicion, what other diagnostic tool should you use?
Genotyping
Treatment
Conventional treatment programs focus on:
- -Clearance and reduction of lower airway secretions
- -Reversal of bronchoconstriction
- -Treatment of respiratory tract infections and airway bacterial burden
- -Pancreatic enzyme replacement
- -Nutritional and psychosocial support
Chest Physiotherapy
- Postural drainage
- Chest percussion or vibration techniques
- Positive expiratory pressure (PEP) or flutter valve breathing devices
- Directed cough, and other breathing techniques
How do PEP and flutter valve work?
PEP: allow air behind mucus to help move it from lung and airway walls.
Flutter: creates vibrations to move mucus.
Medications
- inhaled recombinant human deoxyribonuclease (rhDNase, dornase alpha)- Pulmozyme
- inhalation of hypertonic (7%) saline twice daily
- inhaled bronchodilators
Antibiotics & CF
- Short-term antibioticsare used to treat active airway infections
- S. aureus(including methicillin-resistant strains),P aeruginosa andH influenza
-Long-term antibiotic therapyis helpful in slowing disease progression and reducing exacerbations in patients with sputum cultures positive forP. aeruginosa.
General CFTR modulator therapies MOA
Potentiator of the CFTR channel that works by increasing the time the channel remains open after being activated
What is definitive treatment?
Lung transplantation
Other treatments…
- Exogenous pancreatic enzymes
- Vaccinationagainst pneumococcal infection and annual influenza vaccination
- Screeningof family members and genetic counseling are suggested
How does death occur?
from pulmonary complications (eg, pneumonia, pneumothorax) or as a result of terminal chronic respiratory failure and cor pulmonale
- median age 39
- median survival following transplantation is 7-8 years
