Cystic fibrosis- epidem, pathophysiology, clinical features

epidemiology
1. commonest life-limiting autosomal recessive condition in Caucasians
2. incidence
  1. 1 in 2500 live births
3. carrier rate
  1. 1 in 25
4. average life expectancy
  1. in the 40s
5. defective protein
  1. cystic fibrosis transmembrane conductance regulator
    1. cAMP-dependent Cl- channel
    2. on cell membranes
    3. gene on chromosome 7
    4. most freq mutation in UK
      1. delta F508
        need to ID gene mutation in a family
        to allow prenatal diag
        to allow carrier detection in wider family
6. correlation btw genotype & phenotype
  1. stronger
    1. CF gastrointestinal disease
  2. weaker
    1. CF lung disease
  3. other factors important to determine severity
    1. different microbial pathogens
    2. passive smoking
    3. social deprivation
    4. other modifier genes
Pathophysiology
1. multisystem disorder
2. abnormal ion transport across epithelial cells
  1. -> reduction in airway surface layer
    1. -> impaired ciliary function
      1. retention of mucopurulent secretions
        ->chronic endobronchial infection
        caused by e.g. Pseudomonas aeruginosa
  2. dysregulation of
    1. inflammation
    2. defence vs infection
  3. instestine
    1. production of thick, viscid meconium
      1. ->meconium ileus
        10-20% of CF infants
    2. blockage of pancreatic ducts
      1. -> pancreatic enzyme deficiency
        -> malabsorption
  4. abnormal sweat gland function
    1. too high [Na] & [Cl-] in sweat
clinical features
1. presentation
  1. on Guthrie test
    1. heel-prick blood spot biochem screen
  2. poor growth
  3. malabsorption
  4. recurrent chest infections
  5. chronic infection
    1. bacteria
      1. initially Staph aureus
        subsequently
        P.aeruginosa
        Burkholderia spp.
    2. due to viscid mucus in smaller airways
    3. ->
      1. bronchial wall damage
      2. bronchiectasis
      3. abscess formation
2. Sx
  1. persistent loose cough
    1. productive of purulent sputum
3. on examination
  1. hyperinflation of chest
    1. due to air trapping
  2. coarse inspiratory creps (crackles)
    1. +/- expiratory wheeze
  3. finger clubbing
    1. with established disease
4. death due to respiratory failure
  1. 95% of pts
5. pancreatic exocrine insufficiency
  1. -> maldigestion & malabsorption
    1. steatorrhoea
      1. freq large, pale, offensive & greasy stools
  2. -> failure to thrive if untreated
  3. diag by demonstrating low elastase in faeces
  4. lipase, amylase and proteases lacking
6. neonatal period
  1. meconium ileus
    1. 10-20% of CF pts
    2. inspissated meconium->
      1. instestinal obstruction
        vomiting
        abdo distension
        failure to pass meconium in 1st few days of life
    3. Rx
      1. gastrografan enemas initially
      2. surgery

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Cystic fibrosis- epidem, pathophysiology, clinical features

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	Erstellt von v.djabatey vor fast 11 Jahre