Pathophysiology of abnormal electrolyte transport in bacterial and viral diarrheas

(A) Bacterial diarrheas — Some bacteria secrete enterotoxins that increase intracellular cyclic nucleotides, resulting in chloride ion (Cl^–) secretion and inhibition of the NHE3 and sodium ion (Na⁺) absorption. Invasive bacteria cause a tissue inflammatory response involving recruitment of immune cells and release of cytokines, resulting in intracellular calcium ion (Ca²⁺) signaling.
(B) Viral diarrheas — The rotaviral protein NSP4 causes elevation of cytoplasmic Ca²⁺ concentration by binding to integrin-alpha(1)beta(2) and Gal, and/or by activation of enteric nerves. Rotaviral NSP4 also inhibits NHE3 and SGLT1.

E. coli: Escherichia coli; CFTR: cystic fibrosis transmembrane conductance regulator; DRA: downregulated in adenoma Cl^–/HCO₃ exchanger (SLC26A3); NHE3: sodium-hydrogen exchanger 3; CaCC: calcium-activated chloride channel; CT: cholera toxin; STa: heat-stable toxin; eNaC: epithelial Na⁺ channel; EC cells: enterochromaffin cells; cGMP: cyclic guanine monophosphate; cAMP: cyclic adenosine monophosphate; 5-HT: 5-hydroxytryptamine; VIP: vasoactive intestinal peptide; ENS: enteric nervous system; NKCC: Na⁺/K⁺/Cl^– symporter; IL-6: interleukin-6; IL-8: interleukin-8; TNF: tumor necrosis factor; SGLT1: sodium/glucose cotransporter (SLC5A1); NSP4: nonstructural protein 4; Gal: galanin; GALR1: galanin receptor 1.

Adapted by permission from Macmillan Publishers Ltd: Nature Reviews Gastroenterology & Hepatology. Thiagarajah JR, Donowitz M, Verkman AS. Secretory diarrhoea: mechanisms and emerging therapies. Nat Rev Gastroenterol Hepatol 2015; 12:446. Copyright © 2015. www.nature.com/nrgastro.

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Pathophysiology of abnormal electrolyte transport in bacterial and viral diarrheas