Normal intestinal physiology and alteration by pathogens and their toxins. The average oral intake for an adult is 1.5 L fluid/day. Combined with salivary, gastric, biliary, and pancreatic secretions 7 L fluid enter the upper small bowel each day, most of which is absorbed by the time it reaches the distal small bowel. However, this small bowel fluid is mixed with a remarkable bidirectional flux of water and electrolytes in the upper small bowel that probably exceeds 50 L isotonic fluid each day, to aid in the absorption of digested dietary intake. . This striking bidirectional electrolyte transport is driven by an active, adenosine triphosphate (ATP)–dependent active sodium (Na) absorption pump located on the basolateral membranes of both intestinal crypt and villus tip cells ( middle ). Because the chloride (Cl− ) channel is located on the luminal surface of the crypt cells, this Na pump mediates secretion of Cl− (along with Na and water) from the crypts and neutral NaCl absorption in the differentiated villus tip cells. Thus, a relatively slight shift in this large bidirectional flux can readily overload the colonic absorptive capacity, which rarely exceeds 2–3 L/day. Like cholera toxin (CT), E coli heat-labile toxin (LT) opens Cl− channels, leading to secretory watery diarrhea or traveler's diarrhea. The E coli heat-stable toxin (ST) activates guanylate cyclase to increase intracellular cyclic guanosine monophosphate (cGMP) levels, inhibiting NaCl absorption and leading to secretory diarrhea. Selective damage of absorptive villus tips, which occurs in viral, protozoal, and other villus-damaging or inflammatory processes, leaves unbalanced secretory crypts that are not offset by healthy villus tip absorption, also leading to watery diarrhea. Small bowel pathogens are presented in the right panels : those that produce secretory enterotoxins are in the red box , those that selectively disrupt absorptive villus tips are in the green box , and ileocolonic pathogens are in the tan box.