Reviews for Primary Care - Fall 2007 - (Page 15) Chronic Constipation and Functional Bowel Disorders observed in IBS and slow-transit physiology are equally common and overlap frequently in constipated patients. The Role of the Central Nervous System, Enteric Nervous System, and Gastrointestinal Function in Constipation Normal gastrointestinal function relies on the brain-gut axis to coordinate afferent and efferent information and transmission of stimuli among the central nervous system (CNS), the autonomic nervous system, and the enteric nervous system (ENS).13 The ENS has, in part, independent function from the CNS. Because of the complex interaction between these systems, any interruption or miscommunication can lead to altered sensory processing and characteristic symptoms of dysmotility common to IBS and other gastrointestinal motility disorders. Over the last several decades, multiple neurotransmitters and other substances involved in gastrointestinal motility, sensation, and secretion have been identified and their roles clarified (Table 1),14-18 but the workings of the brain-gut axis and ENS remain largely undefined. Slow-Transit Constipation STC primarily presents in young women with very infrequent (ie, less than once per week to once every couple of weeks) defecation.11 Several neurologic abnormalities have been identified in patients with STC, the most important of which appears to be dysfunction or loss of the interstitial cells of Cajal, which function as the pacemakers of the gut.19,20 The history of very infrequent defecation has been suggested to be an important characteristic that may be suggestive of STC, but this assertion remains to be validated. Dyssynergic Defecation Dyssynergic defecation results in an incomplete evacuation of fecal material from the rectum due to the inability to appropriately coordinate the muscles of the pelvic floor and abdomen involved in successful defecation.9,11 This discoordination most typically takes the form of paradoxical contraction of the external anal sphincter and/or failure to relax pelvic floor muscles when straining to defecate. Up to 50% of patients with dyssynergic defecation may also have slow colonic transit.21 Dyssynergic defecation is thought by most experts to be a learned behavioral disorder because of the lack of associated morphologic or neurologic abnormalities identified via histopathology examination or provocative neurologic testing.9 Some individuals with dyssynergic defecation can develop megarectum with a loss of sensation to rectal distention and an inappropriate sphincter contraction during defecation. The Role of Chloride and Bicarbonate Secretion: Alternative Physiological Considerations in Constipation Chloride and bicarbonate secretion provide 5 major physiological functions in the digestive tract22: • Provides aqueous phase for digestion and absorption of meals • Hydrates mucus, and in its absence (eg, cystic fibrosis), it presents a clinical problem • Facilitates the delivery of antibodies and cryptins, which are antimicrobial ligands, into the gut lumen • Helps to purge intestinal pathogens and noxious agents • Adjusts luminal pH to optimize nutrient digestion and absorption The actual physical process of chloride secretion is illustrated in Figure 4.22 Figure 4 depicts the standard chloride secretion model. On the right side of the cell, or the basolateral side, are transporters that enable chloride secretion. The Na , K -ATPase pump lowers the concentration of sodium within the cell and makes the cell electronegative.22 This allows the Na , K , 2Cl cotransporter to build intracellular chloride concentrations to above its electrochemical equilibrium. In this state, the cell is primed for chloride secretion. When chloride channels in the luminal or apical membrane open, active chloride secretion occurs. One of these channels is the cystic fibrosis transmembrane regulator (CFTR), which is highly regulated by Table 1 Neuroactive Compounds Involved in Gastrointestinal Function Motility Serotonin (5-HT) Acetylcholine Nitric oxide Substance P Vasoactive intestinal peptide Cholecystokinin Adapted from Gershon MD and Tack J; Grider JR et al; Kim D-Y and Camilleri M; Crowell MD; Lacy BE and Yu S.14-18 Visceral Sensitivity Serotonin (5-HT) Tachykinin Calcitonin gene-related peptide Neurokinin A Enkephalins Secretion Vasoactive intestinal peptide Acetylcholine Serotonin (5-HT) VOL. 1 NO. 1 2007 REVIEWS FOR PRIMARY CARE 15
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