Cystic fibrosis Flashcards
what is the definition of cystic fibrosis?
Cystic fibrosis (CF) is a severely life-shortening genetic disease resulting from abnormalities in the cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel found in cells lining the lungs, intestines, pancreatic ducts, sweat glands, and reproductive organs. There are over 2000 known disease-causing mutations that interrupt various stages of CFTR synthesis and function.
what is the epidemiology of CF?
Higher incidence in white people
Incidence decreasing due to newborn screening
what is the aetiology of CF?
CF is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), an anion channel found in the apical membrane of epithelial cells. Patients may be either homozygous or heterozygous with respect to CFTR mutations. Carriers of one CFTR mutation and one normal CFTR allele usually do not demonstrate disease (autosomal recessive)
what are the risk factors for CF?
Family history
Known carrier status of both parents
Ethnicity
what is the pathophysiology of CF?
Mutations in CFTR result in abnormal salt transport by epithelial cells, resulting in thick, sticky secretions.
In the pancreas, this leads to blockage of exocrine ducts, early activation of pancreatic enzymes, and eventual autodestruction of the exocrine pancreas. Therefore, most patients require supplemental pancreatic enzymes.
In the intestine, bulky stools can lead to intestinal blockage.
In the respiratory system, the absence of CFTR function results in mucus retention, chronic infection, and inflammation that eventuate in the destruction of lung tissue. There are multiple hypotheses regarding the genesis of lung disease, each of which is supported by data in vitro and in vivo. Lung disease is the most common cause of morbidity and mortality.
what are the key presentations for CF?
Risk factors Positive newborn screening Failure to pass meconium Failure to thrive Voracious appetite Wet-sounding cough Recurrent infection Chronic sinusitis Genital abnormalities in males - absent vas deferens steatorrhea late puberty
what are the first line and gold standard investigations for CF?
Sweat test - positive (sweat chloride >60 mmol/L [≥60 mEq/L])
Immunoreactive trypsinogen test (newborn screening) - positive (value depends on units of measure and population norms)
Genetic testing - presence of two disease-causing mutations
what are the differential diagnoses for CF?
Primary ciliary dyskinesia
Primary immunodeficiency
Asthma
how is CF managed?
Neonate with meconium ileus:
lactulose: consult specialist for guidance on dose, surgery, nasogastric decompression
Complete interesting obstruction:
Surgery, nasogastric decompression
Acute resp infection:
Mild: Oral antibiotic (amoxicillin/clavulanate: children: 45-90 mg/kg/day orally given in divided doses every 12 hours; adults: 875 mg orally every 12 hours), chest pysio, inhaler, mucolytic inhaler, non invasive ventilation, tobramycin inhaler
Moderate: IV antibiotics (tobramycin: children and adults: 3.3 mg/kg intravenously every 8 hours, or 10 mg/kg intravenously every 24 hours and ticarcillin/clavulanic acid: children: 400 mg/kg/day intravenously given in divided doses every 6 hours; adults: 4000 mg intravenously every 6 hours) + as above
Ongoing resp:
Chest physio, inhalers, NSAIDs, inhaler corticosteroids, CFTR modulator, non-invasive ventilation, oxygen, bilateral lung transplant
Ongoing GI:
Optimising nutrition, pancreatic enzyme replacement. H2 antagonist, fat soluble vitamin supplements, ursodeoxycholic acid, CFTR modulator
how is CF monitored?
There is no cure, and therefore long-term care is a cornerstone of successful disease management. Patients should be seen by a CF care team at a CF centre at least once every 3 months.
what are the complications of CF?
Distal intestinal obstructive syndrome
Pneumothorax
Intussuscption
diabetes
what is the prognosis of CF?
Survival rising. Around 40 years old
which chromosome is the mutation on in CF?
7
