The average oral intake for an adult is 1.5 liters of fluid per day. Combined with salivary, gastric, biliary and pancreatic secretions 7 liters of 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 likely exceeds 50 liters of isotonic fluid each day, to aid in the absorption of digested dietary intake (4). This striking bidirectional electrolyte transport is driven by an active, ATP-dependent active sodium (Na) absorption pump located on the basolateral membranes of both intestinal crypt and villus tip cells (middle panel). 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 liters per 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 GMP (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.

In addition to the management of fluid and electrolyte imbalance, non-secretory or outbreak-related diarrhea may need further work-up for definitive etiologic diagnoses and pathogen-directed therapy. Depending on the epidemiologic setting involved and likely causes, specific diagnostic tests are suggested as discussed in the text. Specific bacteria such as Campylobacter, Shigella or Clostridium difficile and protozoa such as Cryptosporidium, Giardia, or Cylcospora may require specific antibacterial or antiparasitic agents, respectively. Empiric anti-microbial therapy, while awaiting laboratory test results, is usually appropriate for these pathogens. On the other hand, antibacterial treatment may worsen diarrhea secondary to EHEC (e.g. E. coli 0157:H7), which usually presents with non-inflammatory, bloody diarrhea.

For patients with diarrheal illnesses, it is important to first adequately assess the patient and determine the level of dehydration (panel 1). Important factors include: duration of illness; alertness, skin turgor, mucous membrane dryness, sunken eyes or fontanelles and postural hypotension all indicate moderate or severe hypovolemia and dehydration; signs of inflammation include fever, bloody stool and tenesmus. In cases of dehydration (panel 2), patients can be rehydrated by oral administration of fluids that contain glucose, sugar or starch and electrolytes, or patients can be given bismuth subsalicylate or loperamide if their diarrhea is not bloody (panel 2). If patients are unconscious or vomiting, fluids should be replaced intravenously. Pediatric can be given an oral rehydration solution made of sodium chloride, sodium bicarbonate, potassium chloride and glucose or glucose polymer (such as sucrose) in water. Or, table salt and sugar can be added to orange juice, and bananas can be added to provide potassium. There are a number of epidemiological and clinical clues that can be used to identify the infectious agent (panel 3). Epidemiological actors that should be considered include the food that patients have eaten (raw, undercooked meats, raw seafood), antibiotics taken (especially for C. difficile infection), sexual practices (men who have sex with men might have proctitis or colitis with sexually transmitted pathogens) and recent travel (indicate bacterial pathogens such as enterotoxigenic E. coli, SalmonellaShigella, and Campylobacter; persistant diarrhea can be caused by protozoans such as Giardia or Cryptosporidium). Outbreaks of viral-related (norovirus or rotavirus) disease or those caused by organisms with relatively low-infectious inocula that are spread by fecal oral contact, such as Shigella Giardia, and Cryptosporidium, are most commonly observed in daycare settings. Other epidemiological clues include immunoglobulin A deficiency, which predisposes to giardiasis, and immunosuppression (particularly in patients with AIDS), which can lead to protozoal infections, Mycobacterium avium complex, and intestinal cytomegalovirus infections. Clinical features can also be used to identify the infectious agent. Bloody diarrhea is associated with STEC, Shigella and E. histolytica infections; abdominal pain with Yersinia and some C. difficile infections; dysentery with Shigella or Campylobacter infection; wasting with Giardia or Cryptosporidium infection; and fecal inflammation with Shigella, Campylobacter Salmonella, and some E. coli and C. difficile infections.