Cystic Fibrosis Flashcards
Definition
Autosomal recessive disorder. Increased viscosity of secretions (e.g. lungs + pancreas) due to defect in the cystic fibrosis transmembrane conductance regulator gene (CFTR) = Delta F508 mutation on the long arm of chromosome 7.
Organisms which may colonise CF patients
MOST PROBLEMATIC =
Staphylococcus aureus (gram +ve) - Patients take FLUCLOXACILLIN to prevent staph aureus
Pseudomonas aeruginosa (gram -ve)
Others =
Burkholderia cepacia
Aspergillus
Epidemiology
CAUCASIAN
Risk factors
Family history
Known to parenteral carriers
Aetiology
Autosomal recessive condition with 80% of cases being due to the delta F508 gene deficit where the codon for phenylalanine (F) in the CFTR gene is deleted
Pathophysiology
Normally the CFTR channel pumps Cl- into secretions which attracts water into the secretions = thins out secretions
The F508 mutation means the CFTR protein gets misfolded and cant migrate from the endoplasmic reticulum to the cell membrane.
This means there is lack of CFTR protein on the epithelial surface = can’t pump Cl- out so water cant drown in = THICK SECRETIONS
Results in both respiratory and gastrointestinal manifestations
Respiratory system manifestations
- Dry airways and impaired mucociliary clearance: results in cough, dyspnoea and recurrent pneumonia
- Normally the cillia in the lungs waft mucus containing debris + bacteria up into the pharynx (mucocilliary escalator), in CF the mucus is harder to clear so bacteria can colonise the lungs leading to chest infections especially with:
1. Pseudomonas aeruginosa
2. Staphylococcus aureus
3. Burkholderia cepacia
4. Aspergillus
Inflammation: chronic inflammatory response leads to bronchiectasis + worsening pulmonary function. - Right heart failure = occurs due to pulmonary hypertension, resulting in cor pulmonale
Gastrointestinal system manifestations
- Thickened secretions within small and large bowel = presents with failure to pass meconium and can cause bowel obstruction
- Pancreatic insufficiency = defects in ion transport impede the secretion of crucial enzymes: results in malabsorption
- Liver cirrhosis = thickened biliary secretions: may block the bile ducts resulting in liver fibrosis, cirrhosis and portal hypertension
Most common age of diagnosis
Most cases of cystic fibrosis are diagnosed in the neonatal period on screening following the Guthrie test. For a small number of patients, the disease is not detected until age 18 or older. These individuals often have a milder form of the disease.
Age related presentation + diagnosis: Antenatal
Hyperechogenic bowel on USS
Diagnosis: Chorionic villus sampling or amniocentesis
Age related presentation + diagnosis: Neonatal
Prolonged jaundice
Meconium ileus = the meconium is too thick + sticky which leads to no stool passing in 24 hours, vomiting, distended abdomen = SURGICAL EMERGANCY
Diagnosis: Guthrie heel-prick test
Age related presentation + diagnosis: Childhood
- Recurrent chest infections
- Failure to thrive despite a voracious appetite
- Malabsorption: diarrhoea and steatorrhea
- Nasal polyps and chronic sinusitis
- Delayed puberty and short stature
- Other features: pancreatitis, rectal prolapse, portal hypertension
Diagnosis: sweat test
Age related presentation + diagnosis: In Adults
- Recurrent chest infections = chronic wet cough
- Atypical asthma = crackles/wheeze on auscultation
- Diabetes mellitus
- Male infertility: absence of vas deferens so although there is healthy sperm, there’s no way for the sperm to get from the testes to the urethra
- Female subfertility
- Liver cirrhosis: due to thickened billiary secretions which may block the bile ducts causing portal HTN
- RSHF = Portal HTN -> Cor Pulmonale = finger clubbing
- Nasal polyps
Diagnosis: Sweat test
Investigations
FIRST LINE = New born blood spot test
- Done for all UK babies
- Blood is checked for a pancreatic enzyme called IRT (immunoreactive trypsinogen) = released into the blood when the pancreas is damaged
GOLD STANDARD = Sweat test
- Pilocarpine is applied to the skin to promote sweating
- Chloride conc more than 60mmol/L is diagnostic
Genetic testing for CFTR gene = can be done by amniocentesis or chorionic vivous sampling or even after birth
Faecal elastase: to test for pancreatic insufficiency
Resp management
Airway clearance techniques: minimum 2 times per day
- Chest physiotherapy and postural drainage
- Bronchodilator BEFORE airway clearance (SALBUTAMOL)
Mucoactive agents: Used to treat CF patients who are homozygous for the Δ-F508 mutation
- First-line: rhDNase e.g. dornase alfa / recombinant human deoxyribonuclease
- Second-line: hypertonic sodium chloride +/- mannitol dry powder (for inhalation) +/- rhDNase
- Third-line: Lumacaftor/Ivacaftor (Orkambi)
Immunomodulation =
- First-line: azathioprine
- Second-line: oral corticosteroids
Antibiotics: for the treatment of pneumonia
Lung or heart-lung transplantation: last-line for end-stage cardiorespiratory disease
