Respiratory: Cystic Fibrosis Flashcards
In which population is cystic fibrosis more common in?
White population
How does cystic fibrosis occur?
- Mutation in a gene that encodes Cystic Fibrosis Transmembrane conductance Regulator (CTFR)
- It’s the chloride channel expressed in epithelial cells and other type of cells
What is the cystic fibrosis clinical manifestation of pulmonary disease?
- Persistent Cough
- Copious sputum production
- Chronic airway infection: S. aureus
- Inflammation and tissue damage
What is the cystic fibrosis clinical manifestation of pancreatic dysfunction and gastrointestinal symptoms?
- Impaired enzyme secretion from pancreas (pancreatic insufficiency)
- Plugging of small ducts, obstruction and progressive damage to the pancreas
- CF related diabetes mellitus in older patients over over 25
Where is the Cystic Fibrosis Transmembrane conductance Regulator (CTFR) located?
- The apical membrane of secretory and absorptive epithelial cells of the pancreas
- Intestine and liver
- Airway, vas deferens and sweat glands
What are other cystic fibrosis clinical manifestations?
- Meconium ileus: intestinal obstruction in newborn child, leads to thickening of meconium
- Thickened intestinal secretion, malabsorption, malnutrition, decreased gut motility
- Salty tasting skin
- Interfertility
What can mutations do in cystic fibrosis?
- Reduce CTFR transcription or translation
- Affects trafficking or acceleration of protein turn over
- Causes loss of protein function
- Delta F508 class 2 mutation which means that CTFR does not reach the apical membrane where it’s meant to work
How do you test of cystic fibrosis?
- Blood test: Look at the most common gene alterations that cause CF
- Sweat test: Sweat levels with higher salt levels than normal
How does CTFR dysfunction lead to the phenotypic disease of cystic fibrosis?
- CTFR gene defect
- Defective ion transport
- Decrease chloride transport
- Increase sodium transport
- Increase H2O absorption - Airway surface liquid depletion
- Defective mucocillary clearance
- Mucus obstruction
- Infection leads to inflammation and mucus obstruction again
What do mucolytics do and give an example of some and how they work?
Reduce viscosity of bronchial secretion
Examples:
- Hypertonic saline (7%)
- Water into airways
- Rehydration of pericillary layer
- Improved mucocillary clearance - Inhaled recombinant human DNase I
- Degrades large amount of free DNA within CF mucus
- Improves the viscoelastic properties of airway secretion and promotes airway clearance
What is chest physiotherapy and give an example of how it’s done?
Augment clearance of tenacious airway secretions
Example:
1. Person gets in varied position to drain mucus
- Chest is clapped and vibrated- dislodge mucus to large airways
How else can people clear the tenacious airway secretions during chest physiotherapy?
- Mucolytics and beta agonists before phyio
- Airway oscillating devices- person wears vibrating vest
- Active cycle of breathing technique
How can you manage cystic fibrosis with life style changes and other clinical methods?
- Respiratory infections: Antibiotics
- Pancreatic enzymes: ensures proper digestion
- Good nutrition
- High caloric food
- Fat soluble vitamin supplementation
How does a healthy lung cell work compared to an unhealthy one?
Healthy
- Cillia sweep mucus out of the lungs and allow chloride ions to pass through freely through CTFR protein
Unhealthy:
- Mucus build up flattens cilia which means that the CTFR protein is made but cannot reach cell surface
Explain how the common cystic fibrosis DF508 occurs? in first nuclear binding domain?
- The first nuclear binding domain is affected and results in delation and loss of phenylalanine.
- This causes protein trafficking defect
