PhronesisSweat glands reveal the canonical structure of epithelial transport in cystic fibrosis: a two-stage system of secretion followed by recapture, where CFTR mediates the recapture stage. We generalize this structure to all CFTR-expressing epithelia, introducing intertissue sweating as the framework concept for controlled solute transport across epithelial boundaries. In healthy tissue, every such boundary operates as a managed displacement interface: solutes are exported from one compartment and recaptured before they escape the regulated zone.
CFTR is the mechanism of recapture. Its loss does not merely reduce chloride secretion --- it eliminates recapture capacity at every epithelial surface simultaneously, converting controlled intertissue sweating into uncompensated leakage. We formalize this with a two-compartment transport model, show that the displacement cost of uncompensated sweating accumulates across all CFTR-expressing surfaces, and derive the systemic nature of CF pathophysiology from first principles.
The model explains why CF is not a lung disease with complications, but a total-body intertissue sweating disorder in which the lungs are simply the most displacement-sensitive surface.