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442 FLUID THERAPY
E. coli (heat-labile) exert their effects by increasing the intracellular concen-
PGs tration of cAMP in enterocytes. Norepinephrine,
VIP somatostatin, and opioids lower intracellular cAMP and
Vibrio cholerae
Salmonella calcium concentrations and stimulate neutral NaCl
Campylobacter jejuni absorption (see Figure 18-7).
Yersinia enterocolitica Secretin Volume status and intestinal blood flow also influence
E. coli (heat-stable) Glucagon
LUMEN ion transport. Systemic volume expansion results in an
increase in intestinal secretion, whereas volume contrac-
Na + tion results in adrenergic stimulation and increased
Cl – cGMP cAMP absorption. 20 Osmotic forces are also important in the
–
regulation of electrolyte and fluid transport. Luminal
Phosphorylation of osmolality is normally maintained close to plasma osmo-
apical membrane Protein kinase activity Ach lality. 20 After intake of hypertonic foods and liquids, rapid
proteins
5-HT equilibration is accomplished by movement of water into
+ NT the intestinal lumen. In particular, the duodenum and
Cl – Cl – Ca ++ Histamine upper jejunum are subject to major fluid shifts. As intes-
Substance P
Clostridium tinal chyme moves distally, absorptive processes steadily
þ
difficile decrease luminal Na ,Cl , and water. Osmotic diarrhea
Figure 18-7 Role of intracellular messengers cGMP, cAMP, and results if nonabsorbable solutes such as disaccharides
Ca 2þ on NaCl absorption and Cl secretion by small intestine remain in the lumen. Increased fluid absorption in the
epithelium. Increases in messenger-specific protein kinase activity colon can compensate to some extent for fluid lost into
result in phosphorylation of specific brush border membrane the lumen of the small bowel, but eventually colon
phosphoproteins that alter ion movement. PGs, prostaglandins; VIP, absorptive capacity is overwhelmed. Cations such as
vasoactive intestinal polypeptide; Ach, acetylcholine; 5-HT, serotonin;
NT, neurotensin. (From Moseley RH. Fluid and electrolyte disorders magnesium and anions such as sulfate are poorly
and gastrointestinal disease. In: Kokko JP, Tannen RL, editors. absorbed and can also lead to osmotic diarrhea.
Fluid and electrolytes. Philadelphia: WB Saunders, 1996: 681.) In response to inflammation, the number of immune
cells in the lamina propria increases. Inflammation can
lead to mucosal ulceration, exudation of protein, motility
dysfunction, and loss of absorptive surface area, all
acetate, propionate, and butyrate, which are the preferred of which can result in intestinal fluid loss. Many
metabolic substrates for colonic cells. They are known to secretagogues associated with inflammation have been
þ
þ
stimulate Na , water, and K absorption by the colon, identified. Adenosine, serotonin, and histamine have
but the exact mechanism of this process has not been both direct effects on epithelial cells and indirect effects
defined. 104 via neural pathways. Other secretagogues include
Intestinal secretion is a function of villus crypt cells. oxidants (e.g., superoxides, hydrogen peroxide, and
It is thought the electrogenic transport of Cl across OH released from neutrophils) that stimulate Cl secre-
the basolateral membrane into the enterocyte and Cl tion, cytokines (e.g., interleukin-1, interleukin-3),
efflux through Cl channels in the microvillus membrane arachidonic acid, platelet-activating factor, substance P,
into the intestinal lumen (Figure 18-7) cause intestinal kallikreins, and bradykinin. 120 Escherichia coli heat-labile
secretion. enterotoxin and enterotoxins produced by Vibrio
cholerae, Salmonella sp., Campylobacter jejuni, Pseudomo-
CONTROL OF ABSORPTION AND nas aeruginosa, and Shigella sp. activate adenylate cyclase,
SECRETION OF WATER AND producing cAMP and augmenting secretion in the intes-
ELECTROLYTES 44
tine (see Figure 18-7). The eicosanoids, especially the
Control of absorption and secretion is an autonomous lipoxygenase metabolites of arachidonic acid, are central
process that is regulated by the neurocrine systems to the secretory response associated with inflammation.
located in the submucosal plexus. 21,22,82,120 Acetylcho- Kinins stimulate secretion in both the small and large
line and vasoactive intestinal polypeptide (VIP) are the intestines, where they stimulate production of prosta-
major mediators of gastrointestinal secretion, whereas glandin E 2 . 85
norepinephrine, somatostatin, and opioids are the princi- Acid-base balance may also affect intestinal electrolyte
pal regulators of absorption. At the cellular level, acetyl- transport. In the rat, metabolic acidosis is a potent stim-
choline and VIP cause an increase in intracellular calcium ulus for ileal Na absorption (possibly in exchange for
þ
and cAMP that inhibits neutral NaCl absorption and H ), whereas metabolic alkalosis decreases Na absorp-
þ
þ
facilitates transcellular Cl efflux. Many bacterial agents tion but increases HCO 3 secretion. 20