Open AccessAlkalosis-induced hypoventilation in cystic fibrosis: The importance of efficient renal adaptation
Author(s) -
Peder Berg,
J.F. Andersen,
Mads Vaarby Sørensen,
Tobias Wang,
Hans Malte,
Jens Leipziger
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2116836119
Subject(s) - metabolic alkalosis , medicine , cystic fibrosis , cystic fibrosis transmembrane conductance regulator , endocrinology , base excess , hypoventilation , ventilation (architecture) , respiratory system , mechanical engineering , engineering
Significance In conditions when our blood experiences alkalosis, a pronounced kidney response is initiated causing a marked increase of urine base excretion. We recently discovered the cellular physiology of this, which employs fast activation of the base-secreting β-intercalated cells of the collecting duct. This function is fully dependent on the cystic fibrosis transmembrane conductance regulator (CFTR), the anion channel defective in CF. Hence, CF patients and mice cannot efficiently excrete an acute base load. Here, we find that the inability of fast urinary base removal in the CF mouse model causes a marked inhibition of ventilation. This study provides physiological insights into acid–base regulation and may have important implications for CF patients who are already burdened with reduced lung function.