Cystic Fibrosis Flashcards
1
Q
What is CF?
A
- Multi system disorder with significantly shortened life expectancy
- Autosomal recessive genetic condition
- Most common life threatening genetic disorder in Caucasians
2
Q
How is CF diagnosed in Australia?
A
- Historically: Failure to thrive, unexplained chronic respiratory disease
- New born screening program: Screen for most common 22 genotypes
3
Q
What are the implications for children diagnosed after newborn screening?
A
Higher mean FEV1 & BMI than those clinically diagnosed
4
Q
What are the genetic causal factors of CF?
A
- 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
5
Q
What happens when the CFTR protein is malfunctioning?
A
H2O and Cl- ions cannot flow out of the cell due to a blocked channel
6
Q
What is the effect of CFTR dysfunction?
A
- 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
7
Q
What are the mutation classes in CF?
A
I: No synthesis II: Block in processing III: Block in regulation IV: Altered conductance V: Reduced synthesis
8
Q
What organs are affected in CF?
A
- Respiratory System
- Digestive System
- Reproductive System
- Sweat Glands
- Sinuses
9
Q
What occurs in the lungs in CF?
A
- 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
10
Q
Why do repeated infections (neutrophil bronchiolitis) occur in CF?
A
- Neutrophils cannot destroy the micro organisms that have chronically infected the small airways
- They break down and release peptides – neutrophil elastase – destroy lung tissue
11
Q
What is the pathophysiology cycle of CF?
A
- 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
12
Q
What are the respiratory features of CF?
A
- 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
13
Q
How are lung volumes affected in CF?
A
- 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)
14
Q
How is the GI system affected in CF?
A
- 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
15
Q
What is meconium ileus?
A
- 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
