The unique architecture and physiology of the mammalian intestine, together with a tightly coordinated regulatory system, allows for the handling and absorption of as much as 9 L of fluid a day with 98% or greater efficiency. Advances in the past 40 years have made inroads into revealing the intricacies and interplay of numerous ion transporters and their modulators that are responsible for intestinal electrolyte and water transport. Studies of two devastating diseases, the virulent infectious disease cholera and the autosomal recessive disease cystic fibrosis, were largely responsible for this information explosion. These advances have been critical in the development of new therapeutic strategies to combat life-threatening diseases of varying etiologies ranging from enteric infections to cystic fibrosis and inflammatory bowel diseases. Yet, the story is far from complete, and progress needs to continue on translating information gained from reductionistic cell and tissue culture models, in vivo models, and ultimately human studies and on improving therapeutic approaches. This book reviews the current status of our knowledge of fluid transport across the intestine, including the complexities of transcellular and paracellular ion transport down the length of the intestine and how aberrations of normal physiological processes lead to disease. Table of Contents: Overview / Epithelial Cell and Tissue Architecture / Principles of Transepithelial Electrolyte and Water Movement / Intestinal Architecture and Electrolyte Transport / Electrolyte Transporters--Pumps, Carriers, and Channels / Water Transport / Regulation / Intestinal Disorders and Advances Toward Better Treatment of Intestinal Disorders / Conclusion / References

Three distinct types of contractions perform colonic motility functions. Rhythmic phasic contractions (RPCs) cause slow net distal propulsion with extensive mixing/turning over. Infrequently occurring giant migrating contractions (GMCs) produce mass movements. Tonic contractions aid RPCs in their motor function. The spatiotemporal patterns of these contractions differ markedly. The amplitude and distance of propagation of a GMC are several-fold larger than those of an RPC. The enteric neurons and smooth muscle cells are the core regulators of all three types of contractions. The regulation of contractions by these mechanisms is modifiable by extrinsic factors: CNS, autonomic neurons, hormones, inflammatory mediators, and stress mediators. Only the GMCs produce descending inhibition, which accommodates the large bolus being propelled without increasing muscle tone. The strong compression of the colon wall generates afferent signals that are below nociceptive threshold in healthy subjects. However, these signals become nociceptive; if the amplitudes of GMCs increase, afferent nerves become hypersensitive, or descending inhibition is impaired. The GMCs also provide the force for rapid propulsion of feces and descending inhibition to relax the internal anal sphincter during defecation. The dysregulation of GMCs is a major factor in colonic motility disorders: irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and diverticular disease (DD). Frequent mass movements by GMCs cause diarrhea in diarrhea predominant IBS, IBD, and DD, while a decrease in the frequency of GMCs causes constipation. The GMCs generate the afferent signals for intermittent short-lived episodes of abdominal cramping in these disorders. Epigenetic dysregulation due to adverse events in early life is one of the major factors in generating the symptoms of IBS in adulthood.

Studies on the colon not only serve medical interest or clinical purposes, but are also a highly interesting subject of comparative physiology, from which we can learn much about the basic principles in physiology. Presented here are examples of research on colonic ion transport of each vertebrate group, including the classical models of epithelia, rat and rabbit, and also on the special and unique features in fish, amphibians, reptiles, birds, and selected mammals such as the guinea pig. Physiology and pathophysiology of ion transport in the human large intestine are as well covered as the use of colonic cell cultures as model systems for crypt cell properties.

The functional and organic alterations of the colon constitute one of the leading reasons why patients consult gastroenterologists. The irritable colon is one of the most com mon causes of discomfort in human beings. The organic pathology of the large bowel (malignancy and chronic inflammatory disease) contributes, particularly among Occi dental peoples, to discouragingly high levels of morbidity and mortality. One realizes the importance of having a thorough physiologic knowledge of the colon in order to scientifically plan the functional treatment of organic colonic dis eases. If we consider the large amount of material published on the physiology of the esophagus, stomach, small bowel, pancreas, and liver, we realize that the colon has been relatively neglected. The chapters in this book have been written by people who have done their utmost to alter this imbalance. I want to thank all the contributors for their generous collaboration that allows me to present in one volume virtually all the information known about the structure and function of the colon, and to record my deep graditude to Dr. Howard Spiro for his willingness to include this volume in his series. I would also like to express my sincere appreciation to Plenum Publishing Corporation for making this book possible. A spe cial thanks goes to Dr.