Hman In Vb Studies

Colonic Motility

Studies on colonic motility in IBD patients date back decades and provide conflicting results. The discrep ancies reflect differences of study design, pressure sensors and patients selection [5]. Diarrhea may partly be explained by changes in mucosal secretory and absorptive functions, but some authors also suggest that alterations in colonic motility may also contribute to increased urgency and frequency of defecation in patients with ulcerative colitis. The cause of diarrhea could be identified in an excessive propulsive activity [6, 7], or in rectosigmoid inflammation rather than by rapid transit [8]. The disease is often associated with right-sided constipation and left-sided diarrhea [9], reflecting proximal colonic stasis with rapid transit through the rectosigmoid region [8]. The paradoxical slowing of transit in the small intestine and proximal colon seem to be consequential to an increased sensitivity to normal colonic contents which delays transit [10]. Clinical studies suggest that active inflammation is accompanied by a reduction in contractile activity in the diseased area and it seems that a decrease in segmental contraction, which normally slows down movement of colonic contents, would exacerbate diarrhea by allowing rapid forward movement of the bowel content. Prolonged recordings of colonic motility show a circadian variation characterized by a marked reduction of contractile activity at night [11, 12] and increased non-propagating contractions after eating [13] in healthy subjects. Different studies in patients with UC reported either a reduced or an exaggerated postprandial colonic response [14]. A simultaneous study of postprandial colonic motility and transit measured by scintigraphy in patients with UC showed a decreased contractility and an increased low-amplitude propagating contractions in patients compared to healthy controls, while transit had a variable pattern [10]. A diminished colonic contractile response to meals has been recently confirmed by a study that examined the effect of ulcerative proc-tosigmoiditis on motor functions of an uninflamed segment of descending colon, whereas fasting motility was increased [15]. Colonic compliance was unaffected by these changes, suggesting that modifications occur in physiological responses, and not in intrinsic wall properties. Moreover, the same authors assessed the effect of nicotine on colonic motor functions, without drawing any conclusion on a beneficial role of nicotine on motility, since low doses did not have any effect on transit or motor function. To overcome the limits of short-time period studies, other authors evaluated colonic motor activity by means of 24-h manometry [16] in patients with active UC, diarrhea-predominant irritable bowel syndrome (IBS) patients and healthy controls. Patients with IBD and IBS had increased high and low-amplitude propagated activity, suggesting that an increased propulsive contractility is responsible for diarrheal states. Most of the studies published in literature have been performed in patients with UC, since studies in patients with CD are limited by the access in the small intestine. There is evidence of altered interdigestive motility in the small intestine in the majority of patients studied with inactive and uncomplicated disease [2]. This may result in changes in orocecal transit that could lead to the bacterial overgrowth [17] present in 23% of unselected patients with CD, which is associated with a prolongation of orocecal transit time (OCTT). Other authors describe a delayed OCTT in 75% of patients: both delayed OCTT and small-bowel bacterial overgrowth may be clinically relevant in CD, not only because of the contribution to symptoms but also because of the possible negative influence on the releasing of the drug in slow-release drug formulations. Small-intestinal transit time is significantly shorter in ileocecal-resected patients, which might influence small-intestinal pH and transit time. An ileocecal resection might, therefore, affect the delivery of active drugs from tablets with pH-dependent delivery [18].

Gallbladder motility has also been evaluated since patients with CD have an increased risk of developing gallstones. Fasting gallbladder volume is decreased in patients with large-bowel involvement or after ileocecal resection, whereas postprandial motility seems to be unaffected [19]. Impaired gastric emptying was found in a subgroup of CD patients who complained of mild upper gut symptoms such as bloating, early satiety and abdominal distention and in those with localization restricted to the colon [3]. The impact of psychological, physical, and immuno-logical stressors on gastrointestinal secretion, motili-ty, epithelial permeability, and inflammation is now thoroughly documented, and stress has a major influence on digestive diseases [20]. Psychological stress is one environmental factor which has long been reported as having a relationship with activity in IBD. Psychological (dichotomous listening tests, stressful interviews) and physical (cold hand immersion) stress modulates gut function by enhancing colonic motor activity [21]. Dichotomous listening tests and cold pain stress have also been shown to increase jejunal water and sodium and chloride ion secretion [22].

Data suggest that stress-induced alterations in gastrointestinal inflammation may be mediated through changes in the hypothalamic-pituitary-adre-nal axis function and alterations in bacterial-mucos-al interactions, and via mucosal mast cells and mediators such as corticotrophin releasing factor. A recent report indicates that the intestine produces the same stress peptides that are present in the central nervous system [23]. In particular, a bacterial toxin that is the principal cause of antibiotic-induced colitis and diarrhea, results in the local generation of stress peptides that regulate the transit of digested material through the intestine under normal conditions and mediate inflammation without involving the central nervous system. This intrinsic stress response mechanism may contribute to disorders such as IBD and IBS, for which stress exacerbates the symptoms. For a more comprehensive review, the reader is referred to a detailed paper review that explores the recent advances on the pathogenic role of psychological stress in IBD [24].

Anorectal Motility

Most of the studies on anorectal motility yielded different results, depending on the activity of disease, especially in the rectums of patients with ulcerative colitis. Reduction of anal sphincter pressures in active colitis may contribute to episodes of fecal incontinence in some patients; however, overall, resting and squeeze pressures are similar in patients, irrespective of disease activity [9]. Rectal inflammation seems to be responsible for the augmented sensitivity to air-filled balloon distention [7, 26] or to rectal saline infusion [5], as well as decreased rectal compliance and higher contractility, suggesting that symptoms of urgency of defecation and fecal incontinence may be due to a hypersensitive, hyperactive, and poorly compliant rectum [9]. The role of acute inflammation on rectal motility and sensory perception are corroborated by data showing that, despite decreased rectal compliance in active and quiescent disease [7], only patients with active UC are hypersensitive to distention compared to controls and patients during remission [9]. The increased rectal sensitivity in active colitis is associated with a marked decrease in rectal compliance, which is reduced in active disease, suggesting that reduced rectal size is due to loss of distensibility. Moreover, in patients, lower rectal volumes are required for initiating sustained anal relaxation than in controls and continence is threatened in the absence of a strong external anal sphincter contraction that counterbalances the prolonged sphincter relaxation. From these conflicting data, it is not clear whether rectal inflammation or decreased compliance are responsible for augmented sensation, or whether symptoms (e.g., abdominal pain) commonly present during flares depend on the inflammation grade of the mucosa. In order to shed light on this, some authors evaluated the rectosigmoid perception to balloon distention in patients with mild UC, patients with IBS and controls [27]. They found that despite mild rectal mucosa inflammation and similar mechanoelastic properties, patients with UC were hyposensitive to balloon distension compared to the other groups. Another interesting point was that repeated rectosigmoid stimulation induced hypoalgesia in more than 50% of the UC patients, as compared to the hyperalgesia detected in IBS patients [28]. The authors concluded that persistent peripheral irritation is associated with activation of counter-regulatory antinociceptive mechanisms which produce endogenous analgesia, and that acute symptoms during disease exacerbation are partially related to transient inflammatory mucosal events resulting in sensitization of visceral afferent pathways.

The different perceptual responses to rectosig-moid stimuli between mild chronic inflammatory and functional disease are confirmed by different regional activation (i.e., greater activation of lim-bic/paralimbic circuits in IBS and inhibition of these circuits by the right lateral frontal cortex in UC and controls) in cerebral PET studies [29].

Alterations of anorectal functions are not confined to UC, but are also recognizable in CD. A linear relationship between the degree of proctitis and the rectal maximal tolerated volume is observed in patients with CD involving the rectum [30]. Impairment of anorectal functions (i.e., lower anal resting and squeeze pressures, lower wave amplitude and frequency, altered perception and reduced compliance) is documented not only in simultaneous endoscopic and histologic lesions of the disease, but also in patients with sole microscopic lesion [31]. Moreover, in the absence of macroscopic anorectal disease, some alterations, specifically absence of rectoanal inhibitory reflex and hyposensitivity to rectal balloon distension, could be due to alterations in the enteric nervous system [32].

Another study evaluating visceral sensitivity in patients with ileal Crohn's disease presented evidence for reduced pain sensitivity, possibly related to descending bulbospinal inhibition of sacral dorsal horn neurons in response to chronic intestinal tissue irritation [33]. The presence of a hyposensitive rectum in CD was already observed by some authors years ago, where almost half of patients with a nor mal looking rectum could tolerate higher volumes of distension without reporting discomfort as opposed to healthy controls [30]. It is likely that a certain type of inflammation may reduce pain sensitivity by the production of endorphins at the seat of the injury [34]. In contrast to previously reported results, some data indicate that patients with CD limited to the ileum or colon, exhibit increased resting pressures in conjunction with rectal hypersensitivity, indicative of a potential role in the pathogenesis of fissures [35].

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Constipation Prescription

Constipation Prescription

Did you ever think feeling angry and irritable could be a symptom of constipation? A horrible fullness and pressing sharp pains against the bladders can’t help but affect your mood. Sometimes you just want everyone to leave you alone and sleep to escape the pain. It is virtually impossible to be constipated and keep a sunny disposition. Follow the steps in this guide to alleviate constipation and lead a happier healthy life.

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