CFTR, bicarbonate, and the pathophysiology of cystic fibrosis. (3rd September 2015)

• Record Type: Journal Article
• Authors: Borowitz, Drucy
• Other Names: Murphy Thomas guestEditor.; Noah Terry guestEditor.; Ratjen Felix guestEditor.; Tiddens Harm guestEditor.
• Is Part Of: Pediatric pulmonology. Volume 50(2015:Sep.)Supplement 40
• Page Start: 2S4
• Page End: S30
• Publication Date: 2015-09-03
• Subjects: cystic fibrosis (CF); Pediatric respiratory diseases -- Periodicals; Pediatrics -- Periodicals; 618.922
• DOI: 10.1002/ppul.23247
• Languages: English
• ISSNs: 8755-6863

Abstract

Summary: The gene that encodes for the cystic fibrosis transmembrane regulator protein (CFTR) was identified in 1989, yet major pathophysiologic questions remain unanswered. There is emerging evidence that CFTR is a bicarbonate channel, a driver of chloride‐bicarbonate exchange and through its action on local pH, a regulator of other ion channels and of proteins that function optimally in a neutral environment. In both the respiratory and gastrointestinal (GI) tracts, bicarbonate drives ionic content and fluid on epithelial surfaces, allows mucins to unfold and become slippery, and contributes to innate immunity. In the GI tract bicarbonate neutralizes gastric acid to support digestion and absorption. When CFTR is dysfunctional, lack of bicarbonate secretion disrupts these normal processes and thus leads directly to the clinical symptoms and signs of CF. This article synthesizes evidence from cell, animal, and human investigations that support these concepts. Bicarbonate secretion does not seem to be the same in all tissues and varies with physiologic demand. Thus, tissue type and whether conditions are baseline or stimulated needs to be taken into account when evaluating the evidence concerning the role of bicarbonate in the pathophysiology of CF as a regulator of local pH. Basic and applied research that focuses on the role of CFTR‐mediated bicarbonate secretion helps explain many of the diverse clinical manifestations that are CF.Pediatr Pulmonol. 2015; 50:2S4–S30. © 2015 Wiley Periodicals, Inc.