Abnormal passive chloride absorption in cystic fibrosis jejunum functionally opposes the classic chloride secretory defect
Michael A. Russo, … , Michael Emmett, John S. Fordtran
Michael A. Russo, … , Michael Emmett, John S. Fordtran
Published July 1, 2003
Citation Information: J Clin Invest. 2003;112(1):118-125. https://doi.org/10.1172/JCI17667.
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Abnormal passive chloride absorption in cystic fibrosis jejunum functionally opposes the classic chloride secretory defect

Abstract

Due to genetic defects in apical membrane chloride channels, the cystic fibrosis (CF) intestine does not secrete chloride normally. Depressed chloride secretion leaves CF intestinal absorptive processes unopposed, which results in net fluid hyperabsorption, dehydration of intestinal contents, and a propensity to inspissated intestinal obstruction. This theory is based primarily on in vitro studies of jejunal mucosa. To determine if CF patients actually hyperabsorb fluid in vivo, we measured electrolyte and water absorption during steady-state perfusion of the jejunum. As expected, chloride secretion was abnormally low in CF, but surprisingly, there was no net hyperabsorption of sodium or water during perfusion of a balanced electrolyte solution. This suggested that fluid absorption processes are reduced in CF jejunum, and further studies revealed that this was due to a marked depression of passive chloride absorption. Although Na+-glucose cotransport was normal in the CF jejunum, absence of passive chloride absorption completely blocked glucose-stimulated net sodium absorption and reduced glucose-stimulated water absorption 66%. This chloride absorptive abnormality acts in physiological opposition to the classic chloride secretory defect in the CF intestine. By increasing the fluidity of intraluminal contents, absence of passive chloride absorption may reduce the incidence and severity of intestinal disease in patients with CF.

Authors

Michael A. Russo, Christoph Högenauer, Stephen W. Coates Jr., Carol A. Santa Ana, Jack L. Porter, Randall L. Rosenblatt, Michael Emmett, John S. Fordtran

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Conventional models of normal electrolyte absorption by the human jejunu...
Conventional models of normal electrolyte absorption by the human jejunum and a possible explanation for chloride malabsorption in cystic fibrosis. The illustrations represent epithelial cells and the adjacent tight-junction paracellular pathways. The apical membrane is on the left and the basolateral membrane is on the right side of each cell. A Na+, K+-ATPase on the basolateral membrane pumps Na+ out of the cell, into the subepithelial space. For convenience, water absorption is depicted as occurring exclusively through paracellular spaces, although it may also occur through the cell. Since these are models of electrolyte absorption, the transporters and channels that mediate active chloride secretion are not depicted. Detailed explanations of the models for normal absorption and a proposed explanation for passive chloride malabsorption in cystic fibrosis are provided within the Results and Discussion sections, respectively.