Cystic Fibrosis Flashcards
What is CF?
- Multi system disorder with significantly shortened life expectancy
- Autosomal recessive genetic condition
- Most common life threatening genetic disorder in Caucasians
How is CF diagnosed in Australia?
- Historically: Failure to thrive, unexplained chronic respiratory disease
- New born screening program: Screen for most common 22 genotypes
What are the implications for children diagnosed after newborn screening?
Higher mean FEV1 & BMI than those clinically diagnosed
What are the genetic causal factors of CF?
- Basic defect on chromosome 7
- Faulty gene codes for CFTR
- CFTR protein is a channel protein that controls flow of H2O and Cl- ions into & out of cells
What happens when the CFTR protein is malfunctioning?
H2O and Cl- ions cannot flow out of the cell due to a blocked channel
What is the effect of CFTR dysfunction?
- Airway surface dehydration
- Reduced fluid layer at the
top of the cilia
- Fluid movement back into cell produces mucus with higher viscosity
- MCC compromised - Reduced airway surface liquid pH
- Triggers mucus plugging, chronic inflammation & impaired antibacterial host defence in CF airways
What are the mutation classes in CF?
I: No synthesis II: Block in processing III: Block in regulation IV: Altered conductance V: Reduced synthesis
What organs are affected in CF?
- Respiratory System
- Digestive System
- Reproductive System
- Sweat Glands
- Sinuses
What occurs in the lungs in CF?
- Lungs close to normal structurally at birth
- Cilia become damaged, fused & flattened
- By 12 months abnormal inflammation & infection seen on bronchoscopy
- Infection stimulates further mucus production
- Repeated infections - neutrophil bronchiolitis
- Cycle of infection & inflammation impairs ciliary function & reduces MCC further
- Bronchiectasis
Why do repeated infections (neutrophil bronchiolitis) occur in CF?
- Neutrophils cannot destroy the micro organisms that have chronically infected the small airways
- They break down and release peptides – neutrophil elastase – destroy lung tissue
What is the pathophysiology cycle of CF?
- Abnormal CFTR
- Abnormal chloride & water transport through the cell
- Thick & dry mucous & compressed cells
- Release of proteases & DNA
- Inflammation
- Infection & defective immune response
- Bronchial obstruction
- Progressive airway damage
What are the respiratory features of CF?
- Airway collapse, air trapping, hyperinflation
- Lung function (FEV1%) drops a small amount further below the average for a child of the same age and sex each year
- Chronic Hypoxia – pulmonary hypertension
How are lung volumes affected in CF?
- FRC increases (gas trapping)
- Higher closing volume: Point at which airways close during
expiration (obstruction & reduced elasticity) - Chest wall kept more expanded
- Flattened diaphragm (inefficient, more easily fatigued)
- Inspiratory muscles work harder (fatigue, shorter & tighter, altered length-tension)
How is the GI system affected in CF?
- 90% are pancreatic exocrine & endocrine insufficient
- Accumulation of mucus in small pancreatic ducts
- Reduction of enzymes leads to malabsorption of fat from small intestine
- Pancreatic enzyme replacement therapy can achieve energy losses of <10% of intake
What is meconium ileus?
- 25% of patients with CF plugs of mucus also have plugs in the small intestine causing a bowel obstruction (Meconium Ileus)
- Can be the first indication of CF in the neonatal period
- Poor prognostic sign
What are the characteristics of growth & development in CF?
- Low BMI associated with poor clinical outcome
- Delayed growth related to balance between absorbed nutrient intake & energy requirement
- Improvement in growth & weight status associated with decreased hospitalisations & antibiotic courses & increase pulmonary function
What are the characteristics of gastroesophageal reflux in CF?
- 35% - 81% people with CF are affected
- Contributing factors: chronic cough, hyperinflation, chest physio
- LFTs found to be worse compared to those without significant reflux
- Upright PEP therapy considered most appropriate
airways clearance technique for those with GOR
How is the liver affected by CF?
- 5% have liver bile canaliculi plugged by mucus
- Leads to biliary cirrhosis
- Coagulopathy
- May require transplant
- Salivary gland can also be affected
How is the reproductive system affected by CF?
Males
- 95-99% infertile
- Blocked or absent vas deferens
Females
- Viscous cervical secretions may block sperm entry
- Success with IVF
What are the cornerstones of management for CF?
- Medical & Nursing
- Physiotherapy
- Nutrition
- Psychosocial role expanding all the time
What does the medical management of CF involve?
- Early aggressive use of antibiotics for any sign of respiratory illness
- Nutritional intake (120-150% average requirement)
- Pulmozyme, hypertonic saline, saline nebs
What is the aim of infection control for CF?
- Respiratory pathogens heavily influence morbidity & mortality
- Aim to prevent transmission
What are some of the respiratory pathogens in CF?
- Burkholderia Cepacia: Isolation, associated with rapid decline in late 80s
- Pseudomonas aeruginosa: Requires IV or neb antibiotics
- Staph aureus
What are the CFTR modulators?
- Ivacaftor/kalydeco
- Orkambi (lumacaftor/ivacaftor)
What are the features of ivacaftor/kalydeco?
- CFTR potentiator approved for patients with G551D mutation
- Improved lung function & weight
- Sweat chloride normalised
What are the features of Orkambi (lumacaftor/ivacaftor)
- Delta F508 mutation
- Lumacaftor helps move defective CFTR to correct location at the cell surface
- Ivacaftor increases activity of CFTR
- Increased flow of salt & fluids, reduces thick mucus buildup
When are CF patients considered for lung transplant in Australia?
- When life expectancy is two years or less
- Complex decision making regarding timing of transplant
