Cystic Fibrosis

Write about Cystic Fibrosis here.


• One of the commonest life-threatening autosomal recessive conditions affecting Caucasians

• 1:2000 live births

• About 1 in 25 = carrier

• > 6250 patients with CF in UK

• Mutation in the  CF transmembrane conductance regulator )CFTR) gene on chromosome 7 (long arm) - 800+ mutations

• CTFR functions as a chloride channel in the membrane of epithelial cells and the primary physiological defect in CF is reduced chloride conductance at epithelial membranes, especially in the respiratory, gastrointestinal, pancreatic, hepatobiliary and reproductive tracts 

• Leads to combination of defective chloride secretion and increased sodium absorption across airway epithelium

• In sweat ducts, failure to reabsorb chloride ions results in elevated concentrations of chloride and sodium in the system - characteristic feature of the disease and the basis for the SWEAT TEST


• Lungs:

• Failure of chloride transport results in secretions of abnormal viscosity which interfere with mucociliary clearance and permit the adherence of bacteria to the mucosa

• The inflammatory response is unable to clear the infection and a vicious cycle of infection and inflammation occurs -> bronchiectasis, respiratory failure and death


• Gastrointestinal Tract:

• The abnormal ion transport results in the plugging and obstruction of ductules with progressive destruction of the gland

• Enzymes fail to reach the small intestine, leading to pancreatic insufficiency and fat malabsorption

• Progressive destruction may cause Diabetes mellitus

• Increased risk of gallstones and biliary cirrhosis

• Meconium ileus (neonatal intestinal obstruction) - 10% of babies with CF

• Distal intestinal obstruction syndrome (meconium ileus equivalent) in older children and adults


• Reproductive Tract:

• Nearly all male patients are infertile due to congenital bilateral absence of the vas deferens


• Other Complications:

CF arthropathy due to deposition of immune-complex in joints

• Vasculitic rashes

• Salt loss in high temperatures

• Osteoporosis and amyloidosis

• Sinusitis and nasal polyps


• Diagnosis:

Sweat test - sweat sodium and chloride = > 60 mmol/L; Cl usually > Na.  Induced by pilocarpine iontophoresis.

Genetics - DNA screening for common mutations


Treatment:

• Chest - physiotherapy

Abx - acute infective exacerbations and prophylatically (flucloxacillin or colomycin/tobramycin)

CF have increased renal clearance of Abx

Mucolytics (DNase) - sputum in CF has high levels of DNA which make it viscid

Bronchodilators

?NSAIDS/Steroids?

• GI - Pancreatic Enzyme Replacement

Fat soluble vitamin supplement (A, D, E and K)

Ursodeoxycholic acid for impaired liver function


• Prognosis:

Median survival is now > 30 years.