Cystic Fibrosis Flashcards
what type of inheritance is cystic fibrosis
autosomal recessive
mutation of what gene causes cystic fibrosis
CFTR gene (on long arm of chromosome 7)
what mutation is most common in CF and what does it cause?
∆F508
results in misfolding of CTFR protein
what role does the CFTR protein have?
CFTR protein is a channel protein the pumps chloride ions into various secretions
Chloride ions help draw water into secretion – thinning them out
how does the mutation impact physiology?
Misfolded protein – can’t migrate from endoplasmic reticulum to the cell membrane = lack of CFTR protein on the epithelial surface – can’t pump chloride ions out, water can’t get drawn in, secretions are thick
what is the diagnostic criteria of new-borns
failure to thrive, purulent sputum, meconium ileus
All of the above plus: extended period of neonatal jaundice and steatorrhea
how does meconium ileus occur?
Normally, after birth, pancreatic enzymes act on the meconium, and it is passed in the stools. In CF meconium is not broken down = obstruction
diagnostic criteria of CF in early childhood
same as newborn, plus pancreatic insufficiency
Bronchiectasis, Rectal prolapse, Nasal polyps, Sinusitis
how does pancreatic insufficiency occur in CF
Digestive pancreatic enzymes can’t make it to small enzymes
Fat and protein aren’t absorbed
Over time poor weight gain, failure to thrive, steatorrhea
Eventually pancreas damage – the backed up digestive enzymes degrade the pancreatic duct lining cells
what are the long term impacts of pancreatic insufficiency ?
acute pancreatitis
chronic pancreatitis = cysts and fibrosis
Endocrine dysfunction – insulin dependent diabetes
what are the diagnostic features of CF in late childhood?
As above, chronic lung infections plus cor pulmonale, diabetes (type 2), cirrhosis, distal intestinal obstruction, pneumothorax, haemoptysis, infertility, psychological disorders, cyanosis, clubbing, osteoporosis
what causes the lung exacerbations in CF?
Normally cilla clears mucous
With thick mucus – cilla becomes defective
Bacteria allowed to chronically colonise lungs
Increased bacterial load = symptoms (cough + fever) + changes on chest xray
This is an exacerbation of CF
what bacteria are common in CF exacerbations?
staph aureus, h influenza early, pseudomonas aeruginosa in later life
what are the consequences of chronic bacterial infection?
bronchiectasis, haemoptysis if inflammation into a blood vessel, repeated = resp failure
what are other consequences of CF?
Infertility in men – lack of vas deferens
Digital clubbing
Nasal polyps
Allergic bronchopulmonary aspergillosis
what common tests are used in the diagnosis of CF?
Guthrie test
Elastase in Faeces
Sweat Test
what are other tests that can be used in CF diagnosis?
GGT raised Vitamins A, D, E, K – low CXR – hyperinflation, bronchiectasis Abdominal US Spirometry - Obstructive PFTs Aspergillus skin test
What does the Guthri Test look for?
Immunoreactive Trypsin (raised in CF babies)
Elastase is
a pancreatic enzyme detected in faeces of CF patients
what indicates a positive sweat test
o Child – >60 mmol/L chloride – is abnormal
o Adult – >90mmol/L chloride is abnormal
what are the different parts of CF management?
Nutrition and healthy weight gain
Pulmonary treatment
Medications
Personalised Treatments
what treatment options are used to manage nutrition and healthy weight gain?
Fat soluble vitamins
Replacement pancreatic enzymes
Extra calories – aim for normal growth and percentiles
PPIs
What treatments options are sued for pulmonary treatment?
Chest physiotherapy – postural drainage Nebulised Saline Prophylaxis – flucloxacillin, azithromycin Home oxygen and CPAP Lung Transplant
what medications are used in the management of CF?
N-acetylcysteine
DNases
Ursodeoxycholic acid
