✅
Cystic fibrosis
a genetic, multisystemic disorder
characteristics:
recurrent airway dysfunction
pancreatic exocrine insufficiency
intestinal dysfunction
sweat gland dysfunction
urogenital dysfunction
pathogenesis
autosomal recessive disease — involving gene is CFTR
CF transmembrane conductance regulator gene - located on chromosome 7
function of CFTR - chloride channel and regulator of other ion channels
location of CFTR - apical membrane of epithelium lining airway, sweat gland
ducts, intestines, biliary duct, pancreatic ducts.
dysfunctions due to CFTR loss in Sweat glands: loss of absorption of Cl- from sweat and thereby prevents
absorption of Na+ ⇒ results into high Na and Cl concentration in sweat
(baby tastes salty when kissed)
in Exocrine Pancreas: absent CFTR causes lack of secretion of Na and
HCO3 and Water into the duct ⇒ retention of enzymes in pancreas ⇒
destruction of pancreas
in Liver: absent CFTR causes disruption in Na and Water balance in small
biliary ducts ⇒ obstruction in the biliary tract
Cystic fibrosis
1
in Genital tract (esp males): causes obstruction of small ducts ⇒ leads to
atrophy, fibrosis of vas deferens, epididymis and seminal vesicles etc.
in Ileum: disruption of salt and water secretion ⇒ thick dehydrated wastes
in bowel ⇒ causes obstruction of bowel
in Airways:
high NaCl concentration in mucosa ⇒ reduced mucociliary clearance
⇒ impairment of local defence mechanisms (defective phagocytosis of
pathogens) ⇒ repeated airway infections
thick, viscous, purulent sputum ⇒ obstructs airways ⇒ leads to
bronchiectasis
clinical features:
Newborn patients meconium ileus
failure to thrive in infants - due to fat and protein malabsorption
steatorrhea
generalised edema - due to hypoproteinemia
Adult patients recurrent LRTI
recurrent cough, persisting longer
thick, purulent, foul-smelling, blood tinged Sputum
green-colored sputum → suspect Pseudomonas infection
may develop presentation of bronchiectasis
infertility
cholelithiasis
obstructive jaundice presentation
investigations:
Cystic fibrosis
2
Sweat Chloride levels if concentration of Cl- is ≥60 mEq/L ⇒ suggests CF
Genetic testing for presence of CFTR gene
Nasal transepithelial potential difference is raised
Sputum examination, culture and AST
Chest X-ray
CT chest
PFT
treatment:
Antibiotic therapy lasting for 2-3 weeks
to be prescribed based on AST results of sputum cultures
in case of Pseudomonas - Aminoglycoside + Beta-Lactam
Chest physiotherapy chest percussion
Postural drainage - helpful in bronchiectatic patient
Bronchodilators prescribed only during exacerbations
DEOXY-RIBO-NUCLEASE
nebulised recombinant human DNase - Dornase alpha
neutrophils in the lesions release DNA which forms long fibrils
these fibrils cause increased viscosity of the sputum
DNase can cleave DNA and thereby reduce sputum viscosity
nebulised Hypertonic saline inhalation
increases hydration of airway surface
Cystic fibrosis
3
improves lung function
reduces recurrent pulmonary exacerbations
for patients with FEV1< 30% → LUNG TRANSPLANTATION
oral Pancreatic enzymes and Vitamin supplements
includes Lipase and trypsin
given at meal times
vitamin A, D, E are given along with it
Vitamin K is given as per prothrombin time
in case of development of diabetes, patients must be started on Insulin
therapy
Ivacaftor/ Lumacaftor/ Tezacaftor
corrects the deletion mutations in the abnormal CFTR gene
improves lung function
reduced pulmonary exacerbations
reduces concentration of sweat chloride
Supportive measure:
intake of salt is increased to make up for the NaCl lost in sweat
immunise against influenza and pneumococcus
avoid smoking
complications:
Cystic fibrosis
4