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Mucosal Restitution and Repair

29.1 What Is Restitution? The epithelial lining of the mammalian small intestine and colon is a rapidly renewing population forming a single-cell barrier along the entire length of the lower gastrointestinal (GI) tract. Ulcerated wounds in the epithelium are typically repaired by coordinated molecular, cellular, and tissue processes that serve to reestablish the epithelial sheet continuity and normal cellular phenotypes. Conceptually, the repair process can be…

Chemosensing in the Colon

28.1 Introduction For centuries, it has been known that ingestion of foods rich in indigestible carbohydrates, sugars, bitter substances, and fats elicits specific cellular responses, such as releasing hormones that alter gastrointestinal (GI) function. It has been only in the past few years that the mechanisms underlying these host responses to ingested, endogenous, and microbially produced substances have been unraveled. In this chapter, we will describe…

Gut Barrier: Innate Immunity

Acknowledgments The authors greatly appreciate support from NIH including AI AI079145 (PE), DK DK107585 (SD), and DK061769 (SEC). Support has also been provided by the Wayne and Gladys Valley Foundation and the Chiba University – UC San Diego Program in Mucosal Immunology, Allergy and Vaccines. PE holds a joint appointment in the Department of Pathology, Microbiology, and Immunology, UC Davis School of Veterinary Medicine and the…

Gut Barrier: Adaptive Immunity

26.1 The Evolution of the Adaptive Immune Response The immune system can be viewed as a process evolving over 1000 million years ( Fig. 26.1 ). The classic immune system can be divided into an innate immune system that evolved early and an adaptive immune system that has evolved over the past ~ 500 million years. Immunocompetence was observed in its basic form in the prokaryotes…

Tight Junctions and the Intestinal Barrier

Abbreviations APC adenomatous polyposis coli protein Bves blood vessel epicardial substance CAR coxsackievirus and adenovirus receptor CD Crohn’s disease CFTR cystic fibrosis transmembrane conductance regulator Crb3 crumbs protein homolog 3 EGFP enhanced green fluorescent protein ENAC epithelial sodium channel ERK extracellular signal-regulated kinase H + K + ATPase hydrogen potassium ATPase IBD inflammatory bowel disease IFN interferon IL interleukin JAM junctional adhesion molecule JNK c-Jun N-terminal…

Neuromuscular Physiology of the Pelvic Floor

Acknowledgments The author thanks Dale Bjorling, DVM, MS, Professor and Chair, Department of Veterinary Surgical Sciences, University of Wisconsin for his review and helpful comments about the original manuscript published in the 5th edition of this textbook and Dannielle Dirienzo for her expert assistance in the preparation of the manuscript. 24.1 Introduction The neuromuscular function of the pelvic floor is critically important to the appropriate function…

Neurophysiologic Mechanisms of Human Large Intestinal Motility

Acknowledgment This study was supported in part by USPHS NIH Grants RO1 DK68055 (AEB) from the National Institutes of Health. 23.1 Introduction The human colon absorbs water and electrolytes and stores contents until elimination is socially convenient. It also scavenges nutrients produced by bacterial metabolism of undigested carbohydrates. The colon works slowly, taking an average of 65 h to transfer contents from the cecum to the…

Clinical and Translational Aspects of Normal and Abnormal Motility in the Esophagus, Small Intestine and Colon

22.1 Introduction Motility is the process of moving luminal contents through the gastrointestinal (GI) tract. However, motility encompasses many complex processes and is influenced by many internal and external factors. While there is intrinsic or enteric nervous system, motility is also influenced by the central nervous system and the sympathetic and parasympathetic nervous systems, by the hormonal milieu by receptors throughout the GI tract, by luminal…

Physiology of Gastric Motility Patterns

21.1 Overview The stomach is perhaps the most paradoxical organ of the gastrointestinal (GI) tract, accomplishing extensive and often rapid expansion to accommodate ingested food at low pressure in the proximal stomach while simultaneously generating propagating contractions in the distal stomach that can generate substantial pressures that breakdown and empty food. These disparate regions of the stomach are continuous with each other; there are no specialized…

Neuromuscular Function in the Biliary Tract

20.1 Introduction The prevalence of gallbladder disease makes the goal of understanding gallbladder function a clinically significant one. Gallstone disease in the United States afflicts some 6.3 million men and 14.2 million women aged 20–74 years. In other words, ~ 10%–15% of the adult US population has gallstones or have had a cholecystectomy. The direct costs associated with biliary disease (~$5.5–6.5 billion/year in the United States)…

Enteric Neural Regulation of Mucosal Secretion

Transport of water and salt across the gastrointestinal (GI) mucosa is essential for the survival of all mammals. In the proximal GI tract, secretion of water and electrolytes into the lumen provides an appropriate environment for the actions of digestive enzymes, solvent for water soluble nutrients allowing them to be absorbed, counter ions for nutrient transport and assists in neutralizing gastric acid. In the distal small…

Neuroimaging of Brain-Gut Interactions in Functional Gastrointestinal Disorders

Acknowledgments Thanks to Cathy Liu and Christine Canilao for assistance with manuscript preparation. Grant support: National Center for Complementary and Integrative Health R01 R01AT007137 (KT and BDN); NIDDKP50 DK064539 (EAM); NIDDK P30 DK041301. 18.1 Introduction While a variety of peripheral candidate biomarkers related to functional gastrointestinal disorders (FGIDs) continue to be investigated, none appear to account for a large proportion of the symptom variance in this…

Extrinsic Sensory Afferent Nerves Innervating the Gastrointestinal Tract in Health and Disease

Abbreviations 4-HNE 4-hydroxynonenal 5-HT-R 5-HT receptor ASIC1 acid sensing ion channel 1 ASIC2 acid sensing ion channel 2 ASIC3 acid sensing ion channel 3 CGRP calcitonin gene-related peptide CNS central nervous system CRD colorectal balloon distension CVH chronic visceral hypersensitivity CVP chronic visceral pain DH dorsal horn DRG dorsal root ganglia DSS dextran sodium sulfate GABA γ-aminobutyric acid GABA B γ-aminobutyric acid receptor B GPCR G-protein…

Brain Processing of Gastrointestinal Sensory Signaling

16.1 Introduction Visceral information reaches the brain through a diverse array of neural, humoral, and immune pathways, conveying an abundance of ascending visceral information that helps to maintain homeostasis within the gastrointestinal (GI) tract. While the vast majority of these physiological processes are subconscious, those that do enter the consciousness include sensations such as hunger, satiety, and the urge to defecate. Contrastingly, at the extreme of…

Enteric Nervous System: Brain-in-the-Gut

15.1 The Gut's Brain The enteric nervous system (ENS) was first referred to as “the brain-in-the-gut” in a 1981 issue of the Annual Review of Physiology. Its status as an independent integrative nervous system, which determines motility and secretory behavior of the digestive tract, has since become a widely accepted concept. There is strong implication that, like the central nervous system, neurophysiology of the ENS is…

Enteric Nervous System Structure and Neurochemistry Related to Function and Neuropathology

14.1 Introduction The gastrointestinal (GI) tract is the only internal organ with its own nervous system, known as the enteric nervous system (ENS), which is concealed entirely within the gut wall and can function fully independently of any neural inputs from the central nervous system (CNS). What is particularly unique about the ENS and the GI tract compared to all other organs is that it is…

The Physiology and Pathophysiology of Interstitial Cells of Cajal: Pacemaking, Innervation, and Stretch Sensation

Acknowledgments My research has been consistently funded by grants from the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada. This review is dedicated to all students, post docs, technicians, research assistants, and research scientists past and present in my laboratory with whom it has been and continues to be such a great pleasure to discover ICC structure and function.…

Enteric Neurogenesis

Abbreviations ENS enteric nervous system NSC neural stem cell CNS central nervous system NCSC neural crest stem cells ENP enteric neuronal progenitor ES cell embryonic stem cell ICC interstitial cells of Cajal iPS cell induced pluripotent stem cell LMMP longitudinal muscle layers with the adherent myenteric plexus PGP9.5 protein gene protein 9.5 nNOS neuronal nitric oxide synthase PNA peanut agglutinin HAS heat stable antigen HSCR Hirschsprung’s…

Development of the Enteric Nervous System

Acknowledgments LAS, MMH, and DFN are supported by NHMRC Australia grants 1079234, 1071153, and 1069757, respectively, and the research of TU and HE is supported by the Ministry of Education, Culture, Sports, Science, and Technology Science Research Funds Grant 2212005, Japan Society for the Promotion of Science Grant 25460279, and the Core Research for Evolutional Science and Technology, Japan Science and Technology Agency. We thank Annette…

Molecular Physiology of Gastrointestinal Function During Development

Acknowledgments Writing of this chapter was supported by National Institutes of Health grants R01-DK-412174 (F.K.G.), R01-DK-33209 (F.K.G.), and R01-DK-73638 (F.K.G. and H. Xu). The mammalian intestinal tract undergoes dramatic changes during the first few weeks of postnatal life. Genetic and neurohormonal regulators influence the changes in digestive and transport functions that mediate the development of the gut. In precocial species, such as rats and mice, gut…