Pathophysiology of Chronic Constipation and Ibs*

The pathophysiology of chronic constipation and irritable bowel syndrome (IBS) involves consideration of disturbances in colonic sensorimotor activity, often resulting from disordered extrinsic and/or intrinsic innervations. The mechanisms by which normal colonic activity is altered to cause constipation or IBS are complex, as are the enteric neuropathologic changes that are present in some patients with slow-transit constipation and the serotoninergic disturbances in patients with IBS. Using normal colonic motor patterns and functions as a starting point, this article explores these processes in some detail. It also addresses the assessment of colonic sensorimotor function, the causes of slow-transit constipation, the role of high-amplitude propagated contractions and loss of interstitial cells of Cajal in constipation, the role of serotonin in the gut, and the serotoninergic disturbances in IBS. (Adv Stud Med. 2006;6(2A):S58-S66) T he pathophysiology of chronic constipation (CC) and irritable bowel syndrome (IBS) is complex, involving colonic motor activity, colonic and pelvic floor function, the sympathetic and parasympathetic nervous systems, and the serotoninergic system. To explore these processes in greater depth, particularly the physiology and pathophysiology of colonic motor and pelvic floor dysfunction, it is best to begin by addressing normal colonic motor patterns and functions, and then follow with a discussion of motor activity disturbances and enteric neuropathology in CC and serotoninergic disturbances in IBS. NORMAL COLONIC MOTOR PATTERNS AND FUNCTIONS The functions of the colon are to extract water and electrolytes from the lumen, digest dietary fiber and other nutrients that are not digested by enzymes, propel contents from the ileum to the rectum, and evacuate feces from the rectum in a controlled manner. Although the colon is generally regarded as a single organ, there are several distinct differences in anatomy, blood and nerve supply, and functions among the right colon, the left colon, and the rectosigmoid colon. The right colon functions primarily as a reservoir where water and electrolytes are absorbed and intestinal contents are mixed, while the left colon, under normal circumstances, functions primarily as a conduit. The rectosigmoid is involved in defecation. The average normal colonic transit time is 36 hours: 12 hours in the right colon, 12 hours in the left colon, and 12 hours in the rectosigmoid. The nerves supplying the colon are crucial to its normal functions. The intrinsic or enteric nerves primarily regulate colonic sensorimotor functions and the extrinsic nerves modulate colonic motility. With S58 Vol. 6 (2A) n February 2006 PROCEEDINGS PATHOPHYSIOLOGY OF CHRONIC CONSTIPATION AND IBS*