Cystic fibrosis Flashcards
Definition?
CF is a multisystem disorder caused by a genetic defect in the genes encoding the CF transmembrane conductance regulator (CFTR).
What is the CF transmembrane conductance regulator (CFTR)
A transmembrane regulator protein involved in chloride transport across epithelial cells via a complex channel e.g. passage of electrolytes and ions
(transmembrane proteins that cross phospholipid bilayer - plasma membrane)
What does loss of function of the CFTR lead to?
Excessively viscous mucus secretions and subsequent multiorgan dysfunction.
Aetiology of CF?
- common genetically transmitted disease
- is an autosomal recessive condition occurring in 1/2000 live births
- multiple genetic mutations have been identified as causing six distinct classes of CFTR
- the commonest mutation is a specific gene deletion in the codon for phenylalanine at position 508 in the amino acid sequence (ΔF508)
- in part, the different genetic mutations contribute to the range of phenotypic presentation of CF from severe to milder presentations
What occurs in normal cells lining the airways?
→ Passage of sodium which brings water with it into the airway
→ This water hydrates the mucus - can move through MCE normally
→ The charge chloride of ions moving through the transmembrane protein drives movement of sodium and water
What occurs in pathological cells lining the airways?
Water is not taken into the airway/lumen through the chloride channel.
Therefore, mucus is stickier and becomes infected by bacteria
Clinical features of CF in the lungs?
LUNGS → Loss of mucociliary clearance leads to mucus obstruction and bacterial colonisation and bronchiectasis develops by the age of 5 years.
Clinical features of CF in the liver?
LIVER → focal biliary cirrhosis occurs in 5%-10% and can cause liver failure (immune system attacks bile ducts)
Clinical features of CF for fertility?
males commonly infertile
Clinical features of CF for bones and joints?
→ low bone density and increased fractures caused by malabsorption of vitamin D and calcium
→ arthropathy is common and causes disabling joint pain
Clinical features of CF for gastrointestinal tract?
Viscid faecal material can cause distal intestinal obstruction commonly at the terminal ileum.
This is referred to as a meconium ileus in childhood and distal intestinal obstruction (DIOS) in adulthood
Diagnosis and investigations of CF?
Diagnosis is usally made during the neonatal and childhood period; however, milder phenotypes are being increasingly recognised in adulthood.
In the UK, all neonates are screened with the heel prick test for immunoreactive trypsinogen, promoting further investigation if positive.
Childhood symptoms of CF?
- failure to thrive
- meconium ileus
(a rare condition that occurs when a newborn’s first stool, called meconium, becomes very thick and blocks the small intestine) - cough
- recurrent chest infections
Diagnostic tests for CF?
- Sweat chloride test - a result of >60 mmol/L is suggestive of CF
- CFTR genetic mutation testing
Management for CF?
On a daily basis each patient may require:
→ Two hours of physiotherapy - airway clearance
→ Fifty tablets including pancreatic enzymes, vitamin supplements and antibiotics
→ Nebulised therapy up to four times a day
→ Intravenous antibiotics for exacerbations
→ Subcutaneous insulin for CF-related diabetes
What are modulator therapies for CF?
CF transmembrane conductance regulator modulator therapies are designed to correct the malfunctioning protein made by the CFTR gene.
Because different mutations cause different defects in the protein, the medications that have been developed so far are effective only in people with specific mutations.
Typical physiotherapy problems?
- retained secretions
- reduced exercise tolerance
- dyspnoea
Interventions for CF?
→ ACBT - all parts of it
→ acapella/ bubble pep / flutter
→ percussion
→ shaking
→ relaxation
→ pacing
→ mobilising
for children: exercise, don’t go out in the cold
