The GI tract is responsible for handling approximately 8–10 L of fluid containing approximately 800 mmol of sodium (Na+), 700 mmol of chloride (Cl−), and 100 mmol of potassium (K+) that passes through the intestinal lumen every day.
Physiologically, chloride is absorbed from the intestinal lumen via three distinct mechanisms:
a. Paracellular (passive) pathway;
b. Electroneutral pathways which involve coupled Na+/H+ and Cl−/HCO3− exchange; and
c. HCO3−-dependent chloride absorption, which is not coupled to a parallel Na+/H+ exchange
Passive pathway is predominant in the small intestinal epithelium and depends on the transmural potential difference and downhill Cl− gradient.
In the upper part of the small intestine (duodenum and jejunum), chloride ion absorption is rapid and occurs mainly by diffusion— that is, absorption of sodium ions through the epithelium creates electronegativity in the chyme and electropositivity in the paracellular spaces between the epithelial cells. Then chloride ions move along this electrical gradient to “follow” the sodium ions.
The second, electroneutral exchange pathway is the main route of Cl− absorption in the ileum and colon. Electroneutral NaCl absorption and Cl- secretion by CFTR are oppositely regulated by the autonomic nerve system, the immune system, and the endocrine system via PKAα, PKCα, cGKII, and/or SGK1.
Precisely 90% of chloride is excreted in the urine and the other 10% are eliminated in stool and sweat.
Absorption of chloride
