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Cell Death

Acknowledgment Thanks to Micah Iticovici for helping with figure development. In this chapter, we will focus on the morphologic and biochemical events in three mechanisms of cell death: apoptosis, autophagy, and necroptosis. The importance of these mechanisms in intestinal homeostasis and wound repair will be addressed. The intestinal barrier is established by a single layer of polarized intestinal epithelial cells (IECs) separating bacteria in the intestinal…

The Cell Cycle

Acknowledgment This work was in part supported by grants from the National Institutes of Health (DK052230, DK093680, CA084197, and CA172113). 8.1 Components of the Cell Cycle A typical eukaryotic cell cycle contains several distinct phases, which progress in an orderly fashion—a phase cannot commence without completion of the previous one. The four phases of the cell cycle are G 1 (G for gap), S (synthesis), G…

WNT Signaling in the Intestine: Development, Homeostasis, Disease

7.1 Introduction The gastrointestinal (GI) tract must maintain a barrier to food antigens and the microbial communities within the gut, while continually producing an array of specialized cell types to carry out digestive, absorptive, and regulatory functions unique to each regional segment. To fulfil this diversity of roles, the intestinal epithelium has evolved to maximize epithelial surface area through the formation of villi, which are finger-like…

Notch Pathway Regulation of Intestinal Cell Fate

6.1 Notch Pathway Overview The Notch pathway is an evolutionarily conserved signaling pathway present in all metazoans that influences a wide range of developmental and physiological processes, including the maintenance of self-renewing adult cells and tissues. Since Notch is a critical regulator of proliferation and differentiation in both development and tissue homeostasis, it is not surprising that dysregulation of Notch activity or mutations within the Notch…

The Role of Hippo Signaling in Intestinal Homeostasis

Conflict of Interests The authors declare no conflict of interest. 5.1 Hippo Pathway The Hippo pathway was first described in Drosophila melanogaster and core proteins in the kinase cascade and coactivators are highly conserved in mammalian cells. The Hippo pathway consists of regulatory kinases that modulate transcriptional output including STE-20 like protein kinase 1 and 2 (MST1/2; homolog of Drosophila Hippo), Salvador family WW domain-containing protein…

Hedgehog Signaling in Gastrointestinal Morphogenesis and Morphostasis

Abbreviations BMP bone morphogenetic protein Disp dispatched d.p.c. days post coitum Fgf fibroblast growth factor Fu fused Hh Hedgehog Hhip Hedgehog interacting protein HSC hepatic stellate cell IFT intraflagellar transport PanIN pancreatic intraepithelial neoplasia PDAC pancreatic ductal adenocarcinomas Ptch patched Smo smoothened Sufu suppressor of fused Tgfβ transforming growth factor β 4.1 Patterning We are built from hundreds of specialized cell types that make up our…

Growth Factors in the Intestinal Tract

Acknowledgments The authors would like to thank the contributions of authors of previous editions of this chapter to the development of this text: John A. Barnard and Kirk M. McHugh (4th ed.), and John F. Kuemmerle (5th ed.). 3.1 Introduction Gastrointestinal (GI) tissues express a multitude of growth factors, broadly defined as naturally occurring polypeptides that elicit cellular growth, proliferation, or differentiation following binding to surface…

Gastrointestinal Hormones

2.1 Introduction The intestinal tract secretes a number of hormones that coordinate local, peripheral, and central responses to food intake. Hormones produced in the stomach are regulated rapidly after food ingestion and are largely involved in the control of acid and enzyme secretion. As food reaches the small intestine, it triggers the secretion of a range of hormones that serve to match the release of digestive…

Transcription and Epigenetic Regulation

Acknowledgment The work was supported by Public Health Service NIH Grant R01-DK55732 and R37-DK45729 to JLM. With the human genome sequencing project completed in 2001, perhaps the most important piece of information that we have learned is that the clues to our genetic destiny are contained in more than just the primary sequence of DNA encoding 20,500 proteins. Apparently, what distinguishes man from other life forms…

Fecal Transplant

Introduction * Just prior to publication, the FDA reported on invasive infections in two immunocompromised patients who received a fecal transplant from a donor found to be infected with extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (E.coli). One of the subjects died. The stool was not tested for ESBL prior to the fecal transplant. The FDA now requires testing of donor stool for multi-drug resistant organisms (MDROs), including…

Nutrition and Feeding for Children With Developmental Disabilities

Children with neurologic motor disorders such as cerebral palsy (CP) and muscular dystrophies are a challenging, diverse population of patients who require an innovative approach to nutritional management. These children and their families experience unique and daunting challenges. Medical expenses in children with CP are 10 times those of other children. In addition to the family’s increased financial burden, caregivers spend many hours a week providing…

Effects of Digestive Diseases on Bone Metabolism

Introduction The skeleton has a variety of functions, including mechanical support, protection of soft tissues, locomotion, hematopoiesis, energy homeostasis, and acid–base buffering. The skeleton is the largest reservoir for calcium and phosphate in the body. Chronic gastrointestinal (GI) and liver disorders can affect skeletal mass, size, and structure through perturbation of bone cell function. Bone-forming cells (osteoblasts) and bone-resorbing cells (osteoclasts) regulate bone mass, the most…

Management of Diarrhea

Hippocrates was the first to define the term “diarrhea” literally from the Greek “rhea” (to flow) and “dia” (through). Diarrhea is defined as the passage of at least three loose or watery stools in a 24-hour period. It is further classified as either acute, which lasts less than 7 days, or chronic, which lasts more than 14 days. Acute diarrhea is most often the consequence of…

Enteral Nutrition

The preferred route for the nutritional support of a sick child is via the alimentary canal. The first option is always to determine if a palatable oral diet that meets the patient’s nutritional needs can be absorbed and tolerated. When this is not possible an alternative method for repleting and maintaining the nutritional state of pediatric patients who have adequately functioning gastrointestinal tracts is the goal.…

Parenteral Nutrition

Parenteral nutrition (PN) is the intravenous administration of nutrients necessary for the maintenance of life. The nutrient components of PN include dextrose, amino acids, fat, electrolytes, multivitamins, and trace elements. Clinicians who are caring for infants and children should pay close attention to the changing nutrient requirements with age, specialized needs of children, vascular access, and the sometimes-limited ability of infants, children, and the critically ill…

Tubes for Enteric Access

Tubes are an integral part of gastroenterology practice and have been used in clinical care as well as in research for more than a century. A multitude of tubes are available to allow access to the gastrointestinal (GI) tract. They vary by composition, inner and outer diameter, presence or absence of weighted tip, tip size and shape, and location and number of access and egress ports.…

Nutritional Assessment

Normal Growth and Body Composition in Children Age-appropriate growth is the hallmark of adequate nutrition; children with abnormal growth patterns should be evaluated for diet adequacy, organic disease, and access to food. Universally, growth can be measured objectively, but growth characterization must be interpreted in the context of a clinical assessment. , Length in infants increases about 2.5 cm per month for the first 6 months…

Infant and Toddler Nutrition

Introduction Infancy, considered as the time of birth until erect posture is assumed, is a highly vulnerable period of life, especially where nutrition is concerned. Infants have high nutrient requirements, are unable to secure food for themselves, and have immature digestive and absorptive functions. In the narrow sense, the focus of nutrition is on meeting nutritional needs to assure health of the infant. In fact, growth…

Pancreatic Neuroendocrine Tumors

Pancreatic neuroendocrine tumors (PNETs) are a rare group of neoplasms, especially in children and adolescents, with an estimated incidence of 0.18 cases per million in individuals younger than 19 years of age, approximately one-tenth of that observed in adults. As a subset of pancreatic tumors, however, PNETs represent an important clinical entity in the pediatric population, comprising approximately 13% to 25% of all pediatric pancreatic neoplasms.…

Total Pancreatectomy With Islet Autotransplantation

Total Pancreatectomy with Islet Autotransplantation Chronic pancreatitis represents irreversible morphologic and functional changes in the pancreas from persistent or recurrent inflammation. Although an uncommon disease in childhood and adolescence, with an incidence of 4 to 13 cases per 100,000, the incidence is comparable with that seen in adults. The general concepts regarding presentation and management are well covered in Chapter 82. The clinical presentation and course…