Fig. 7.3 ). However, the impact of this defect on transport function is tissue specific. The major function of the CFTR protein in the sweat gland ducts is to reabsorb luminal chloride ions and augment sodium reabsorption through the epithelial sodium channel (ENaC). Therefore, in the sweat ducts, loss of CFTR function leads to decreased reabsorption of sodium chloride and production of hyper-tonic (“salty”) sweat (
Fig. 7.3 , top). In contrast to sweat glands, CFTR in the respiratory and intestinal epithelium is one of the most important avenues for active luminal secretion of chloride. At these sites, CFTR mutations result in loss or reduction of chloride secretion into the lumen (
Fig. 7.3 , bottom). Active luminal sodium absorption through ENaCs also is increased, and both of these ion changes increase passive water reabsorption from the lumen, lowering the water content of the surface fluid layer coating mucosal cells. Thus, unlike the sweat ducts, there
Fig. 7.3 (Top) In CF, a chloride channel defect in the sweat duct causes increased chloride and sodium concentration in sweat. (Bottom) Patients with CF have decreased chloride secretion and increased sodium and water reabsorption in the airways, leading to dehydration of the mucus layer coating epithelial cells, defective mucociliary action, and mucous plugging. CFTR, Cystic fibrosis transmembrane conductance regulator; ENaC, epithelial sodium channel responsible for intracellular sodium conduction.
is no difference in the salt concentration of the surface fluid layer coating the respiratory and intestinal mucosal cells in normal persons and in those with CF. Instead, respiratory and intestinal complications in CF seem to stem from dehydration of surface fluid layer. In the lungs, this dehydration leads to defective mucociliary action and the accumulation of concentrated, viscid secretions that obstruct the air passages and predispose to recurrent pulmonary infections. In addition to chloride, CFTR also regulates secretion of bicarbonate ions. In fact, certain CFTR variants manifest only with abnormal bicarbonate transport while chloride ion transport is largely preserved. Pancreatic insufficiency, a feature of classic CF, is virtually always present in patients who carry CFTR mutations with abnormal bicarbonate conductance.