Lack of applicability of the Enterocyte Chloride ion secretion paradigm to the Pathology of Cystic Fibrosis

This historical approach to past CF research shows that the evidence for the mucus hydration view is slender and can be called into question as providing adequate proof. This approach also indicates that associated smooth muscle cell pathophysiology in CF has been overlooked but may prove to be the more productive hypothesis. Present views on the pathophysiology of cystic ibrotic lung function have drawn heavily on developments within the ield of intestinal secretion physiology, having assumed that the current paradigm of enterocyte secretion is, in almost all respects, the correct one for explaining how secretory diarrhoeal disease occurs. This model for secretion assumes that microbes and associated pathogens act on normally occurring luid secretion from the enterocytes by pathologically enhancing chloride ion secretion, which in turn due to osmotic imbalance at the brush border compels the movement of luid into the lumen. The enterocytes are purported to have a normally occurring chloride secretion mechanism, in addition to their undoubted ability to absorb luid. Within the brush border of the enterocyte is a chloride channel (the cystic ibrosis transmembrane regulator or CFTR protein) that participates in a putative chloride secretion process. As the CFTR channel is defective in CFTR patients, for various reasons to be discussed, aspects of cystic ibrosis pathology became inextricably intertwined with small intestinal secretory diseases because of the common chloride ion channel in the affected lung and intestinal cell types. Particular weight was given to the possibility that heterozygote advantage in cystic ibrosis could be explained by a defective CFTR Summary