An overview of the pathogenesis of cystic fibrosis lung disease.
The pathogenesis of cystic fibrosis (CF) lung disease is reviewed, focusing on an overview of the physiologic mechanisms that regulate mucus transport. A major emphasis is placed on the active transport systems that regulate the airway surface liquid (ASL) volume and, particularly, regulate the volume of the periciliary liquid (PCL) layer. A sequence is developed for CF whereby there is a depletion of the PCL that reflects the combined dysfunctions of accelerated Na(+)-dependent volume absorption and failure to secrete Cl(-). Both dysfunctions are a direct consequence of missing cystic fibrosis transmembrane conductance regulator (CFTR) at the apical membrane of airway epithelial cells. PCL depletion leads to failure of mucus transport, which is associated with persistent mucin secretion and formation of adherent mucus plaques and plugs. These plugs become the nidus for persistent bacterial airway infections that ultimately lead to a markedly anaerobic luminal environment.
Boucher
R C
RC
Cystic Fibrosis/Pulmonary Research and Treatment Center, 7011 Thurston-Bowles Building, CB# 7248, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. rboucher@med.unc.edu
D001424:Bacterial Infections / Q000150:complications; D003550:Cystic Fibrosis / Q000209:etiology / Q000235:genetics / Q000473:pathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D004848:Epithelium / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D017136:Ion Transport; D008168:Lung / Q000382:microbiology / Q000473:pathology* / Q000503:physiopathology; D009093:Mucus / Q000378:metabolism
C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator