Cystic Fibrosis Flashcards
What is CF
Cystic fibrosis (CF) is an inherited, autosomal recessive, multi-system disease affecting mucus glands.
Respiratory problems most prominent, as well as pancreatic insufficiency.
Epidemiology of CF
Cystic fibrosis is the most common inherited condition in the Caucasian population, affecting 1/2500 births, whilst 1/25 of the population are carriers
RFs of CF
- Family history of cystic fibrosis
- Known parental carriers: if both parents are known carriers, the child has a 1 in 4 chance of having cystic fibrosis
- Caucasian ethnicity
What is CF due to?
mutations in the CF transmembrane conductance regulator (CFTR) on chromosome 7
Most common CF mutation?
Δ-F508 is the most common mutation, where the codon for phenylalanine (F) in the CFTR gene is deleted, resulting in proteolytic degradation.
What is the CFTR protein?
channel protein that pumps chloride ions into various secretions, those chloride ions help draw water into the secretions, which ends up thinning them out.
Pathophysiology of CFTR protein with ∆F508 mutation
- CFTR Protein gets misfolded and can’t migrate from the endoplasmic reticulum to the cell membrane
- meaning there’s a lack of CFTR protein on the epithelial surface, and this means that it can’t pump chloride ions out
- means water doesn’t get drawn in, and the secretions are left overly thick.
Respiratory effects of CF
- Dry airways and impaired mucociliary clearance: results in cough, dyspnoea and recurrent pneumonia
- Low volume thick airway secretions that reduce airway clearance, resulting in bacterial colonisation and susceptibility to airway infections,
- Bronchiectasis
- Resp failure
What bacteria cause infiltrate?
- Pseudomonas aeruginosa
- Staphylococcus aureus
- Haemophilus influenza
- Klebsiella pneumoniae
- Escherichia coli
- Burkholderia cepacia
- Aspergillus
GI effects of CF
Thickened secretions within small and large bowel: presents with failure to pass meconium (stool) and can cause bowel obstruction
Pancreatic effects of CF
- Thick pancreatic and biliary secretions that cause blockage of the ducts, result in a lack of digestive enzymes such as pancreatic lipase in the digestive tract - results in malabsorption.
- Pancreatitis may develop as the pancreas gets damaged, because backed-up digestive enzymes degrade the cells lining the pancreatic ducts
- Destruction of pancreatic tissue can also compromise the endocrine function of the pancreas, causing insulin-dependent diabetes.
Liver cirrhosis and Right HF due to CF
Thickened biliary secretions: may block the bile ducts resulting in liver fibrosis, cirrhosis and portal hypertension
HF: Occurs due to pulmonary hypertension, resulting in cor pulmonale
Other issues of CF
- Congenital bilateral absence of the vas deferens in males: patients generally have healthy sperm, but the sperm have no way of getting from the testes to the ejaculate, resulting in male infertility
- Females able to conceive but often develop secondary amenorrhea (absence of menstruation) as disease progresses
Signs of CF
- Low weight or height on growth charts
- Nasal polyps
- Finger clubbing
- Crackles and wheezes on auscultation
- Abdominal distention
Symptoms of CF
-
Chronic cough
- Can be haemoptysis if inflammation erodes into a blood vessel
- Thick sputum production
- Recurrent respiratory tract infections
- Loose, greasy stools (steatorrhoea) due to a lack of fat digesting lipase enzymes
- Abdominal pain and bloating
- Parents may report the child tastes particularlysaltywhen they kiss them, due to the concentrated salt in the sweat
- Poor weight and height gain (failure to thrive)
Antenatal + neonatal presentation based on age
- Antenatal: Hyperechogenic bowel (appears brighter than usual) on ultrasound
- Neonatal: - Prolonged jaundice
- Meconium ileus: first stool passed is thick and sticky and obstructs the bowel
Childhood presentations
- recurrent chest infections (40%)
- Failure to thrive despite a voracious appetite
- Malabsorption: diarrhoea and steatorrhea (30%)
- Nasal polyps and chronic sinusitis
- Delayed puberty and short stature
- Other features: pancreatitis, rectal prolapse, portal hypertension (5-10%)
Adulthood in CF symptoms
- Recurrent chest infections
- Atypical asthma
- Diabetes mellitus
- Male infertility: absence of vas deferens
- Female subfertility
Primary investigations for CF
- Guthrie test: heel-prick test for serum immunoreactive trypsinogen (released into foetal blood when there is pancreatic damage)
- Sweat test:
- Genetic testing:Genetic testing for CFTR gene mutation can be performed during pregnancy by amniocentesis or chorionic villous sampling, or as a blood test after birth. Also offered to close relatives of people with cystic fibrosis.
GS test for CF
Sweat test
- gold standard test; induce sweating followed by analysis of sweat to check Cl- concentration
A result of****> 60 mmol/L (sweat chloride) is positive and requires referral to a cystic fibrosis specialist (normal value < 40 mmol/Ll)
Other investigations you can do are
Lung function tests
Sputum sample
Faecal elastase
Chest X-ray
Primary resp management
- Airway clearance techniques:minimum 2 times per day. Chest physiotherapy and postural drainage.
- Bronchodilator: inhaledsalbutamolfor exacerbations and prior to airway clearance techniques
Mucoactive agents used for CF
- First-line: rhDNase e.g. dornase alfa / recombinant human deoxyribonuclease
- Nebulised DNase is an enzyme that can break down DNA material in respiratory secretions, making secretions less viscous and easier to clear
- Second-line:hypertonic sodium chloride+/- mannitol dry powder (for inhalation)**+/- rhDNase
- Third-line:Lumacaftor/Ivacaftor(Orkambi)
What do we give to patients with deteriorating lung function or pulmonary exacerbations despite treatment
- First-line:azathioprine
- Second-line:oral corticosteroids
Antibiotics in CF
- Antibiotic choice is based on the isolated organism on sputum or blood cultures.
- Pseudomonas colonisation can be treated with long term nebulised antibiotics such as tobramycin or oral ciprofloxacin.
- Patients with cystic fibrosis take long term prophylactic flucloxacillin to prevent staph aureus infection.
Vaccinations for CF
including pneumococcal, influenza and varicella
Nutrition for CF
- High calorie, high-fat diet
- Fat-soluble vitamin supplementation: vitamins A, D, E, and K for pancreatic insufficiency
- Oral pancreatic enzyme replacement(Creon): to digest fats in patients with pancreatic insufficiency
- Proton pump inhibitor(PPI): aids the absorption of pancreatic enzyme replacement
Liver dysfunction in CF treatment
- Ursodeoxycholic acid: makes bile more soluble so it can flow through the liver easily
- Liver transplant if liver failure
Monitoring of CF
Patients with cystic fibrosis are managed and followed up in specialist clinics, typically every 6 months.
They require regular monitoring of their sputum for colonisation of bacteria like pseudomonas.
They also need monitoring and screening for diabetes, osteoporosis, vitamin D deficiency and liver failure.
