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Cellular Growth and Neoplasia

Normal cellular proliferation and differentiation are essential to tissue homeostasis in all organs, including the digestive tract. The neoplastic process involves a fundamental disruption of these mechanisms, which can give rise to cancer development and metastasis with the additional acquisition of other hallmarks of cancer. As a group, malignancies of the GI tract are the leading cause of cancer-associated mortality, and it is therefore essential to…

Pathophysiology of Diarrhea and Its Clinical Implications

Acknowledgment NIH grant R01DK041274 is acknowledged for financial support. 68.1 Introduction Diarrhea is a global health concern ranked second only to respiratory diseases in worldwide occurrence. In 2015, UNICEF estimated that half a million deaths per year from diarrhea occur among children under 5 years of age worldwide, which corresponds to 1400 childhood deaths every day. It is especially prevalent in the developing world, where mortality…

Neuropathophysiology of the Irritable Bowel Syndrome

67.1 Irritable Bowel Syndrome The irritable bowel syndrome (IBS) is a functional disorder present in 10%–20% of worldwide population. A functional disorder is the one for which no abnormal physical or metabolic process can be found to explain patienťs symptoms. Predominant symptoms of IBS are abnormal defecation and abdominal pain, both of which may be exacerbated by emotional stress. Abnormal defecation can be diarrhea, constipation or…

Mechanisms of Gastrointestinal Malignancies

Gastrointestinal cancers represent a heterogeneous, complex array of disorders and diseases. They may be divided into rare inherited forms and more frequent sporadic forms. There is a critical interplay of genetic and environmental factors that foster the conversion of normal tissue to precursor, premalignant lesions, and eventually to frank malignancy. While it is apparent that certain genetic mechanisms are better appreciated in a cell-type and tissue-type…

Recruitment of Inflammatory and Immune Cells in the Gut

65.1 Introduction The intestinal mucosa is unique among other tissues of the human body, as it exists in close proximity to an enormous number of microorganisms and their products. Such factors constitute a potential trigger for proinflammatory responses by the gut-associated lymphoid tissue (GALT) and a constant challenge to mucosal homeostasis. The latter is typically preserved by the function of a dense network of diverse, although…

Host-Pathogen Interactions in Pathophysiology of Diarrheal Disorders

64.1 Introduction Gastric acid is one of the most important host defenses against infectious agents that enter the gastrointestinal tract (GIT). At pH < 3, gastric juice can kill bacteria within 15 min and hypochlorhydria (caused by drugs that inhibit acid secretion, atrophic gastritis, or gastric surgery) increases the risk of enteric infections. GI motility also provides host defense by reducing the adherence of pathogenic microbes…

Mechanisms of Helicobacter pylori -Induced Gastric Inflammation

63.1 Introduction Helicobacter pylori is a Gram-negative bacterial species that selectively colonizes gastric mucosa, and virtually all persons colonized by this organism develop coexisting gastritis. A signature feature of the inflammatory response to H. pylori is its capacity to persist for decades, which is in marked contrast to inflammatory reactions induced by other Gram-negative enteric pathogens, such as Salmonella , that either resolve within days or…

The Gastrointestinal Tract and Control of Food Intake

Control of food intake and body weight involves multiple pathways and body systems. The traditional view of energy balance proposes that input from the gastrointestinal (GI) tract is largely involved in short-term regulation of food intake associated with signals arising before, during, and after meals. Other signals related to metabolic state indicate the degree of stored or available energy; these two systems ultimately regulate overall energy…

Trace Metal Absorption and Transport

Acknowledgments Research from the author’s laboratory as cited here is the result of support from the National Institutes of Health. Figs. 61.2–61.4 were produced by AASarts.com . 61.1 General Properties of Trace Metal Absorption The trace metals are roughly divided into the “trace” metals and the “ultratrace” metals. The latter term comprises a group of elements, which includes chromium, for which there are various degrees of…

Mechanisms and Regulation of Intestinal Iron Transport

60.1 Introduction 60.1.1 The Essentiality of Iron and Overview of Intestinal Iron Homeostasis Iron is abundant in the Earth's soils and as such, it is ubiquitously present in life forms on this planet. Most species, including humans, require iron for numerous biological functions, yet iron in excess is toxic; as such, iron levels must be precisely managed. Iron is necessary for several critical physiological functions, including…

Molecular Mechanisms of Intestinal Transport of Calcium, Phosphate, and Magnesium

59.1 Introduction Calcium, phosphorus, and magnesium belong to a group of essential chemical elements required to support a variety of biochemical processes by serving structural and functional roles. Although sophisticated homeostatic mechanisms have evolved to maintain serum levels, intracellular levels, and optimal mineral content in bone, disorders of mineral metabolism, including abnormalities of calcium, phosphorus, and magnesium homeostasis, are not uncommon. The homeostatic mechanisms affect primarily…

Ion Channels of the Gastrointestinal Epithelial Cells

Electrolyte absorption and secretion mediated by ion channels of the epithelial cells play an important role in determining basal and active fluid movement (i.e., absorption or secretion) in the GI tract. Ion channels that are involved in regulating fluid movement include Na + , K + , and anion (Cl − and HCO 3 − ) channels. Active Na + absorption and active Cl − secretion…

Intestinal Anion Absorption

Acknowledgments Studies in the author’s laboratories were supported by NIDDK grants RO1 DK54016 (PKD), RO1 DK81858 (PKD), RO1 DK92441 (PKD), RO1 DK71596 (WAA), RO1 DK109709 (WAA) and Department of Veterans Affairs Merit Awards BX002011 (PKD), BX000152 (WAA), BX002687-01 (SS) and VA Senior Research Career Scientist Award (PKD), Research Career Scientist Award (WAA). 57.1 Mechanisms of Intestinal Chloride Absorption 57.1.1 Chloride Absorption in the Intestine Chloride is…

Na + /H + Exchange in Mammalian Digestive Tract

Acknowledgment NIH grant R01DK041274 is acknowledged for financial support. The first physiological observations suggesting the existence of a Na + /H + exchange mechanism in mammalian membranes were made by Mitchell and Moyle and by Brierley et al. in rat liver and cow heart mitochondria, respectively. These observations were soon followed by similar findings in prokaryotic plasma membrane by Harold and Papineau in Streptococcus faecalis and…

Water Transport in the Gastrointestinal Tract

55.1 Introduction Large quantities of fluid are transported across epithelial barriers in the gastrointestinal (GI) tract for secretion of saliva, gastric juice, bile and pancreatic fluid, and for fluid absorption in the intestine. The quantity of fluid transported in the GI tract is second only to kidney, where ~ 180 L of fluid per day are filtered by the glomerulus in humans and processed by various…

Intestinal Absorption of Water-Soluble Vitamins: Cellular and Molecular Mechanisms

Abbreviations AMV apical membrane vesicles AA ascorbic acid BLM basolateral membrane BLMV basolateral membrane vesicles BBM brush-border membrane BBMV brush-border membrane vesicles CaM Ca/calmodulin ChIP chromatin immunoprecipitation Cbl cobalamin cKO conditional Knockout DHAA dehydro- l -ascorbic acid DIDS 4,4′-diisothiocyano-2,2′-disulfonic acid stilbene EMSA electromobility shift assay EGFP enhanced green fluorescent protein EPEC enteropathogenic Escherichia coli ETEC enterotoxigenic Escherichia coli FAD flavin adenine dinucleotide FMN flavin mononucleotide Glut2…

Intestinal Absorption of Vitamin K: Cellular and Molecular Mechanisms

Abbreviations CD36 cluster determinant 36 GGCX γ-carboxyglutamyl carboxylase MK Vitamin K 2 [represented by members of the menaquinones (MK) family] NPC1L1 Niemann-Pick C1-like 1 Phylloquinone Vitamin K 1 SR-BI scavenger receptor class B-type I UBIAD1 UbiA prenyltransferase-containing domain 1 Acknowledgment Supported by grants from the Department of Veterans Affairs and the National Institutes of Health (DK56061, DK58057 and AA 018071). You’re Reading a Preview Become a…

Bioavailability of Vitamin E

Abbreviations ABCA1 ATP binding cassette A1; ABCG1 ATP binding cassette subfamily G member 1 ASBT apical sodium-bile acid transporter CD36 CD36 molecule NPC1L1 NPC1 like intracellular cholesterol transporter 1 SR-B1 scavenger receptor class B-type I SREBP2 sterol regulatory element binding protein 2 VE vitamin E Conflict of Interest The authors have declared that no conflict of interest exists. 52.1 Introduction The term vitamin E (VE) is…

The Vitamin D System: Biological and Molecular Actions in the Intestine and Colon

51.1 Introduction Studies of Mellanby, McCollum, Steenbock, Windaus, and others earlier in the 20th century resulted in the discovery and characterization of an important new bioactive substance termed vitamin D. Although this vitamin was found to be produced in the skin following exposure to sunlight, studies that rapidly followed indicated that the compound undergoes sequential hydroxylations in the liver to 25-hydroxyvitamin D 3 and then in…

Digestion and Intestinal Absorption of Dietary Carotenoids and Vitamin A ☆

Abbreviations ARAT acyl-CoA:retinol acyltransferase BCO1 β-carotene 15,15′-oxygenase BCO2 β-carotene 9′10′-oxygenase 2 CEL KO CEL knockout CEL carboxyl ester lipase CM chylomicrons CRBP cellular retinol-binding protein DGAT diacylglycerol acyltransferase KO knock out LRAT lecithin:retinol acyltransferase LUT lutein LYC lycopene OA oleic acid PLRP pancreatic lipase-related protein PTL pancreatic triglyceride lipase RA retinoic acid RAR retinoic acid receptors RE retinyl esters REH retinyl ester hydrolase RPE retinal pigment…