Enteroendocrine and neuronal mechanisms in pathophysiology of acute infectious diarrhea.

BACKGROUND: While enterocyte secretion is the predominant mechanism considered responsible for secretory diarrhea in response to acute enteric infections, there are several lines of evidence that support alternative mechanisms controlling fluid and electrolyte secretion in diarrhea. AIM: To review enteroendocrine and neuronal mechanisms that participate in the development of acute infectious diarrhea. RECENT ADVANCES: Acute infectious diarrheas due to bacterial toxins (e.g., cholera, E. coli heat-stable enterotoxin, C. difficile) and rotavirus are all associated with secretion of transmitters from enteroendocrine cells (e.g., 5-HT) and activation of afferent neurons that stimulate submucosal secretomotor neurons. The latter secrete acetylcholine (which binds to muscarinic receptors on epithelial cells) and VIP. Involvement of nerves was demonstrated by inhibition of bacterial toxin-induced secretion by hexamethonium (nicotinic), tetrodotoxin (Na(+) channel blocker), and lidocaine (visceral/mucosal afferents). Nicotinic receptors are present on secretomotoneurons and these are activated by release of acetylcholine from enteric interneurons or extrinsic efferent fibers. Specific organisms also modify other mechanisms that may contribute to development of acute diarrhea. Thus, mucin secretion, activation of motor mechanisms, increased mucosal permeability and inhibition of bile acid absorption have been reported in specific types of acute infectious diarrhea. CONCLUSION: New therapies targeting neural and transmitter mediation including 5-HT, VIP, NPY, as well as toxin receptors and channels activated during acute infectious diarrhea could usher in a novel approach to enhancing glucose-electrolyte solutions used in the treatment of acute diarrhea.

Regional colon transit in patients with dys-synergic defaecation or slow transit in patients with constipation.

OBJECTIVE: To differentiate dys-synergic defaecation (DD) from normal function and slow transit constipation (STC). METHODS: The medical records of 1411 patients evaluated by a single gastroenterologist over a 16-year period at a tertiary medical centre were reviewed. DD was characterised by anorectal manometry and balloon expulsion test. There were 390 patients with DD, and 61 with STC without DD. Transit data from 211 healthy individuals served as controls. The primary endpoints were overall colonic transit (geometric centre) at 24 h and 48 h (GC24 and GC48). Regional transit was measured as ascending colon half-emptying time (AC t(1/2)) and residual content in descending rectosigmoid colon and stool (DRS). RESULTS: Age and body mass index were similar in the STC and DD groups. DD was associated with smaller perineal descent and a greater difference in rectoanal pressure than STC. Both STC and DD were associated with lower GC24 and GC48 and slower AC t(1/2) than controls. GC48 differentiated DD from healthy controls (p<0.001) and DD from STC (p=0.007). AC t(1/2) values differentiated healthy controls from DD (p=0.006) and STC (p<0.001) and were associated with constipation (DD vs STC, p=0.007). The regional content of DRS at 48 h discriminated DD from STC (AUC=0.82) and stool content at 48 h, increasing the odds for DD over STC (OR per 5% in stool 2.4, 95% CI 1.1 to 5.5, p=0.03). CONCLUSIONS: DD is associated with delayed overall colonic transit at 48 h and AC t(1/2) compared with healthy controls. Regional scintigraphic transit profiles differentiate DD from STC and facilitate identification of a subgroup of patients with constipation.