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Updated: 03/11/08 02:32 PM |
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| HOME | HEAL | EDUCATE | RESEARCH | DIRECTORY | OUTREACH |
Authors: D.R. Saunders, C.E. Rubin, and J.D. Ostrow
Download Chapter ♦ Download Lecture Slides & Notes
Download Chapter ♦ Download Lecture Slides & Notes
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H. Water & Electrolyte Malabsorption
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You can appreciate that minute changes of 2-3 % in overall fluid and electrolyte balance will increase fecal water, and will be associated with diarrhea (the passage of liquid stools). Most diarrheas are caused by multiple mechanisms (rapid intestinal transit, increased intestinal secretion, impaired absorption). Some examples of deranged physiology will be discussed.
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1. Hypersecretory Diarrhea
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Profuse diarrhea can lead to hypokalemia, and metabolic acidosis. Oral electrolyte solutions save many lives. They are often underutilized. |
Enterotoxigenic organisms cause hypersecretion by inhibiting Na+ and Cl- absorption, and by stimulating Cl- secretion. Cholera toxin binds to a specific ganglioside receptor on the luminal membrane of enterocytes and it irreversibly activates adenylate cyclase. The increase in cAMP activates protein kinases which phosphorylate proteins that activate Cl- secretion. The toxin’s effect is lost only after the enterocyte dies in several days. Afflicted persons can have profuse diarrhea (sometimes 10-40 L per day!), and can die of dehydration and electrolyte imbalance. The more profuse the output of stools, the more the electrolyte composition of the stools becomes similar to that of plasma so that patients are losing large amounts of HCO-3 and K+. Oral replacement with NaCl and water is ineffective because cholera toxin also inhibits Na+/H+ exchange. Fortunately, Na+ - co transporters with glucose, and amino acids are unaffected by increased intracellular cAMP so that oral replacement of water and Na+ is possible by providing nutrients such as glucose in oral electrolyte solutions. If glucose is unavailable, soluble starches of rice, or table sugar (sucrose) can be substituted.
Small intestinal absorption of Na+ with glucose is unaffected by most enterotoxins so that the world traveler can prepare to meet the challenge of watery diarrhea with a concoction of readily available ingredients: |
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2. Diarrhea Associated with Mucosal Injury and Inflammation
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Oral electrolyte solutions may worsen diarrhea if the mucosa is damaged |
Small bowel mucosa can be injured by infection (invasive E. coli, enteroviruses), by certain laxatives (castor oil), by antimetabolites (methotrexate), by radiation, and by immune attack (celiac disease).
Structural injury to enterocytes or to membranes can harm pumps, carrier proteins, and enzyme systems. Cytoskeletal alterations may affect the intercellular junctions to increase permeability. Infiltrating inflammatory cells may secrete immune substances and cytokines which stimulate intestinal secretion. Many of these mediators can activate enteric nerves which in turn can enhance intestinal propulsion. |
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3. Diarrhea Caused by Luminal Hyperosmolarity
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| Gut contents become isotonic with plasma ~290 mosmols/kg Intestinal mucosa is a semi-permeable membrane |
Hyperosmolarity of the small intestinal contents may result from rapid emptying of hypertonic foods from the stomach, and from ingesting poorly absorbed osmotically active substances such as magnesium salts, or as sugars such as lactulose. Water and NaCl crosses from blood to intestinal lumen to restore isotonicity with plasma. Diarrhea may result if propulsion is stimulated and if the colon is unable to cope with the extra volume of isotonic fluid.
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4. Diarrhea Due to Increased Hydrostatic Pressure
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Increased interstitial pressure in the intestinal wall decreases absorption, and enhances secretion; it helps to explain the diarrhea which can occur in patients with partial intestinal obstruction or with venous congestion (portal hypertension, or severe heart failure).
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Next Section (I): Normal Bile Salt Absorption » |
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