My Clinical Notes

• A widespread disorder in epithelial transport affecting fluid secretion in the exocrine glands and the epithelial lining of the respiratory, gastrointestinal and reproductive tracts
• Clinical features are;
  • Chronic lung disease
  • Pancreatic insufficiency
  • Steatorrhoea
  • Malnutrition
  • Hepatic cirrhosis
  • Intestinal obstruction
  • Male infertility

 

• Incidence of 1 in 3200 live births making it the most common lethal genetic disease which affects Caucasians
• It is an autosomal recessive disease

 

Aetiology and Pathogenesis

• Disease results from abnormal function of an epithelial chloride channel protein encoded by the cystic fibrosis transmembrane conductance regulator (CFTR) encoded on chromosome 7
• CFTR is primarily a chloride channel
• The affects of the mutations are tissue specific;
• In the sweat duct epithelia, CFTR is required for reabsorpion of chloride and therefore in CF , inability to reabsorb chloride results in increased chloride concentration in the sweat and hence the basis of the chloride sweat test used in the diagnosis
• Conversely in the respiratory and GI tract, the CFTR is required for the secretion of chloride. The inability to secrete chloride causes water reabsorption from the lumen and dehydration of the mucus layer covering the mucosal cells
• This results in defective mucociliary action and accumulation of hyperviscous concentrated secretions

 

• CFTR has two transmembrane domains, two nucleotide binding domains and a regulatory domain that contains protein kinase phosphorylation sites
• Various mutations in the CF gene affect different regions of the CTFR
• There are at least 800 disease causing mutation of the CFTR that have been identified
• The most common mutation is a three nucleotide deletion normally encoding for phenylalanine at position 508 that results in defective intracellular processing, resulting in the degradation of CFTR before it reaches the cell surface

 

• A number of environmental factors play a role in the severity and progression of CF;
  • Infections
  • Smoking
  • Allergen exposure

 

Lung morphology

• Changes stem from the viscous mucus secretionsof the submucosal glands with secondary obstruction and infection of the air passages
• The mucus secreting cells hypertrophy and exhibit hyperplasia resulting in blockage and dilation of the bronchiole
• Superimposed infections can result in chronic bronchitis and abscess formations can occur
• The most common infections are;
  • Staph aureus
  • Haemophilus influenzae
  • Pseudomonas aeruginosa

 

Clinical

• Clinical manifestation is highly variable
• In classic CF, pancreatic insufficiency is universal associated with malabsorbtion and steatorrhoea
• Poor fat absorption results in deficiencies in the fat soluble vitamins A, D and K
• The most common cause of death are cardiopulmonary complications;
  • Persistent infections
  • Obstructive pulmonary disease
  • Cor pulmonale
• Median life expectance is 30 years

This entry was posted on Wednesday, February 20th, 2008 at 2:21 pm and is filed under Respiratory. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.