Cystic Fibrosis Flashcards
What is cystic fibrosis?
genetic disease from abnormalities in cystic fibrosis transmembrane conductance regulator (CFTR gene)
What are the common clinical manifestations of cystic fibrosis?
- pancreatic dysfunction: calorie malabsorption
- lung disease: mucus retention, infection and inflammation
Describe the pathophysiology of cystic fibrosis
- mutations in CFTR causes abnormal salt transport by epithelial cells causing thick, sticky secretions
- in pancreas:
- blockage of exocrine ducts
- early activation of pancreatic enzymes
- autodestruction of exocrine pancreas
- in intestine: bulky stools that can lead to intestinal blockage
- in respiratory: mucus retention, chronic infection and inflammation that results in destruction of lung tissue
How are newborns screened for cystic fibrosis?
- dried heel-stick blood spot
- looking for serum immunoreactive trypsinogen
What are the possible presentations of cystic fibrosis?
- newborns: delayed passage of meconium
- infancy/early childhood: faltering growth
- infants/young children: prolonged/severe bronchiolitis/recurrent respiratory complaints
- adults: chronic/recurrent bronchitis/sinusitis/pancreatitis
What are findings in physical examination which can be signs of CF?
- appearance of malnutrition
- nasal polyps
- increased antero-posterior diameter of chest
- crackles at auscultation
- clubbing
- stool mass upon palpation of stomach
- enlarged liver/spleen
- males: bilateral absence of vas deferens
Describe the sweat test for CF
- small amount of pilocarpine put on skin of forearm to stimulate sweating
- area of skin stimulated by small current
- sweat collected in microcapillary tube and chloride content measured
What are the benefits of the sweat test?
- painless
- relatively inexpensive
- provides results in hours
- accurate if performed at qualified centre
Describe the outcomes of a sweat test
- negative test <30mmol/l of sweat chloride
- positive test >60mmol/l of sweat chloride
- if falls in intermediate range: needs further investigations
What is the other modes of investigation of CF other than the sweat test?
- genetic testing
- screen for most common CFTR mutations
- if not found, can sequence more of CFTR gene
- sinus x-ray (parasinusitis)
- deep throat swab after a gag (pathogens)
(not specific tests for CF)
Describe the management of CF
- if signs of respiratory disease: assisted mucociliary clearance techniques
- if signs of GI disease: supplemental, exogenous pancreatic enzymes used to support growth/nutrition
What is the management of CF if respiratory disease?
- augmented airway clearance to mobilise secretions from airway walls into lumen to be coughed out
- use of antibiotics to treat pulmonary infections
- manual chest physiotherapy
- active cycle of breathing high-frequency oscillatory vest device (VEST therapy)
- flutter valve
- positive expiratory mask
- non-invasive ventilation
Describe the inhaled therapy options for CF treatment
- short acting bronchodilators (salbutamol)
- mucolytics (dornase alfa): degrades DNA from inflammatory cells in airway
- hydrators (hypertonic saline)
- corticosteroids
- anti-inflammatory agents
Describe CFTR modulator therapies
- can partially restore function in mutated channels
- medicine only effective in people with specific mutations
- ivacaftor
- lumacaftor
- tezacaftor
- elexacaftor
What are the considerations for lung transplantation in patients with CF?
- severely decreased lung function
- requirement for supplemental oxygen
- evidence of hypercarbia (elevated CO2) with progressive worsening of disease
What are the absolute contraindications to lung transplant?
- sepsis
- mutli-organ dysfunction
- documented non-adherence to treatment
- patients with colonised burkholderia cepacia class III
- BMI 40 or above
- refractory gastro-oesophageal reflux
What are the relative contraindications to lung transplant?
- renal insufficiency
- exceedingly poor functional status, inability to consistently walk less than 600 feet
- history of pleurodesis
- severe malnutrition with BMI less than 16
- fungal infection
- poorly controlled diabetes
Describe the management of acute pulmonary exacerbation in patients with CF
- mild: oral antibiotic with or without inhaled tobramycin for 14 days
- oral antibiotics: amoxicillin/clavulanic acid
- moderate/severe: IV antibiotics
- tobramycin combined with one or two antibiotics with staphylococcus/pseudomonas coverage
Describe how pancreatic insufficiency is treated in CF patients?
- pancreatic enzyme replacement therapy and fat-soluble vitamin supplements
- enzyme replacements: lipase, protease, amylase
- vitamins: A, D, E and K
- H2 antagonists/PPIs to provide more alkaline environment for pancreatic enzyme supplement therapy
Describe liver disease in patients with CF and how its treated
- obstruction of biliary ducts leading to periportal inflammation and fibrosis
- can become multiobular cirrhosis associated with portal hypertension
- treated with administration of oral bile acids
Describe intestinal disease in patients with CF and how its treated
- abnormal salt and water balance leading to thickening of stool and intestinal mucus- intestinal obstruction in terminal ileum commonly
- risk of intussusception (when intestine slides in on itself)
- neonates: meconium ileus
- after neonatal period: distal intestinal obstruction syndrome
- surgery in some states
- water soluble enemas
- oral osmotic agents
How does CF affect the reproductive system?
Males:
- sperm duct blocked preventing movement of sperm
Females:
- levels of mucus in menstrual cycle change
- mucus can block cervix so sperm cannot reach
Describe the long term management of CF?
- seen by CF team every 3 months
- history and physical examination at each appointment
- spirometry
- annual blood work and CXR
- disease changes can result in changes in dosage of aminoglycoside medicine
- monitor serum aminoglycosides and levels of nephrotoxic antibiotics
- serum creatinine checked weekly and antibiotic dosage adjusted
