The cystic fibrosis transmembrane conductance regulator

JR Riordan - Annual review of physiology, 1993 - annualreviews.org
JR Riordan
Annual review of physiology, 1993annualreviews.org
Cystic fibrosis (CF) is a fatal genetic disease with an especially high incidence in Caucasian
populations, where it has a frequency of approximately one in 2500 live births (11). There is
dysfunction at wet epithelial surfaces of a range of tissues, but most significantly those of the
gastrointestinal and respiratory tracts. It is widely accepted that as a consequence of an
aberrant control of salt and water movement across these surfaces, macromolecular
secretions have an altered physical state and cannot be normally cleared (27). This results …
Cystic fibrosis (CF) is a fatal genetic disease with an especially high incidence in Caucasian populations, where it has a frequency of approximately one in 2500 live births (11). There is dysfunction at wet epithelial surfaces of a range of tissues, but most significantly those of the gastrointestinal and respiratory tracts. It is widely accepted that as a consequence of an aberrant control of salt and water movement across these surfaces, macromolecular secretions have an altered physical state and cannot be normally cleared (27). This results in blockage of small diameter tubes such as pancreatic ductules and small airways. In the pancreas, this leads to fibrosis and obliteration of the exocrine ductular system, which results in a reduction or absence of delivery of digestive enzymes to the small intestine. The ensuing malabsorption and malnutrition can be severe, although nowadays, the ingestion of capsules containing pancreatic enzymes is a reasonably effective therapy. In addition to the impact of the pancreatic deficiency, there is aberrant fluid balance in the intestine per se. In the lung, an inability to clear excessively viscous mucus has much more severe consequences. Recurrent infections with a variety of microorganisms, the establishment of encapsulated antibiotic-resistant strains, and repeated bouts of inflammation cause progressive tissue deterioration. This loss of lung function is almost always the cause of death. Other tissues are also affected including the reproductive tracts in both
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