Physical Address

304 North Cardinal St.
Dorchester Center, MA 02124

Functional Development of the Kidney in Utero

Introduction The mature and differentiated mammalian kidney assumes a number of diverse, complex, and related functions in the postnatal environment. These functions include glomerular filtration, salt and water reabsorption, acid-base homeostasis, regulation of blood pressure, tubular secretion, and endocrine functions including vitamin D, calcium and phosphate metabolism, erythropoiesis, immune regulation, and circulating drug and toxin metabolism, among others. Most of these important postnatal physiologic functions that…

Development of the Kidney: Morphology and Mechanisms

Introduction The development of the mammalian kidney has been extensively studied for the past 60 to 70 years, and our understanding of renal development and molecular regulation is perhaps better understood than that of any other organ. This chapter provides an overview of the development of the three mammalian excretory organs (pronephroi, mesonephroi, and metanephroi) but explores metanephric development in detail. The processes of ureteric budding,…

Mechanistic Aspects of Phototherapy for Neonatal Hyperbilirubinemia

Acknowledgments This chapter was supported in part by the Ahlfors Center for Unbound Bilirubin Research & Development and the Kaplan-Goldstein Family Foundation. No commercial financial assistance was received in support of this chapter. We would also like to thank Angelo A. Lamola, PhD, for his contributions in the original chapter. Introduction The pathways by which light reduces levels of circulating bilirubin and how these mechanisms decrease…

Hereditary Contributions to Neonatal Hyperbilirubinemia

Introduction Neonatal jaundice is a common phenomenon, noted in more than 80% of otherwise healthy, term newborns. , In the majority of cases, the jaundice is transient, usually resolving by the end of the first postnatal week, and serum total bilirubin (STB) concentrations are not harmful. In some infants, severe hyperbilirubinemia may develop with the potential for acute bilirubin encephalopathy. , Some of these cases may…

Fetal and Neonatal Bilirubin Metabolism

Introduction Bilirubin, a neurotoxic pigment, is the end product of heme catabolism in mammals. In adults, bilirubin is extensively metabolized by hepatic UDP-glucuronosyltransferase (UGT) 1A1 and thereby cleared from the body almost immediately. Expression and function of UGT1A1 is much less in the neonatal liver, allowing accumulation of unconjugated bilirubin in the body. Mild hyperbilirubinemia is commonly observed in human neonates. However, neonates who develop severe…

Bile Acid Metabolism During Development

Introduction Bile acids have long been understood to be physiologic detergent molecules synthesized from cholesterol and critical for the absorption of intestinal lipids. More recently we have come to comprehend their broader role as signaling molecules in a variety of metabolic processes such as glucose homeostasis, immune cell function, and regulation of cell growth and proliferation. Thus, it is not surprising that bile acid physiology is…

Organogenesis and Histologic Development of the Liver

Introduction The liver is the largest internal organ of the body, compromising approximately 6% to 7% of the total weight of an adult. The organ is unique in that it receives dual supply, including venous inflow via the portal vein—predominantly from the intestines, pancreas, and spleen—and arterial inflow from the aorta via the hepatic artery. Together these sources provide the delivery of nutrients, hormones, toxins, and…

The Developing Microbiome of the Fetus and Neonate: A Multiomic Approach

Introduction In the past two decades, DNA-based technologies have identified a myriad of difficult-to-culture microbes in the human body, including the gastrointestinal tract, skin, vaginal tract, urethra, and reproductive tract. In addition to the DNA-based technologies, newly developed bioinformatics are being developed that integrate microbial metagenomes, genomics, transcriptomes, proteomes, and metabolomes (or multi-omics) into system-based schema that more clearly illustrate the pathophysiology of diseases. Problems seen…

Digestive-Absorptive Functions in Fetuses, Infants, and Children

Introduction The developing gastrointestinal (GI) tract is the largest and most active immune organ of the body and supports important endocrine and exocrine roles in addition to its role for digestion. It encompasses a large mass of neural tissue that interacts closely with the developing central nervous system. In addition to intestinal tissue that is derived from the human sperm and egg, the intestinal microbiome is…

Development of the Endocrine and Exocrine Pancreas

Acknowledgment Some content was based on a previous chapter by Steven L. Werlin, MD, and Alan N. Mayer, MD. Embryology and Histogenesis of the Human Pancreas The pancreas is a multifunctional organ consisting of three major tissues: exocrine tissue, endocrine islets, and epithelial ducts ( Fig. 85.1 ). The exocrine compartment contains the largest proportion of cells within the adult pancreas and is composed of acinar…

Development of the Enteric Nervous System and Gastrointestinal Motility

Introduction A critical modulator of gastrointestinal (GI) motility and secretion is the enteric nervous system (ENS). The ENS is a highly unique integrated neuronal circuitry, which, in contrast to other components of the peripheral nervous system, can and often does mediate reflex activity independent of the central nervous system (CNS). The ENS consists of two major plexuses ( Fig. 84.1 ): the myenteric plexus (Auerbach plexus),…

Development of Gastric Secretory Function

Introduction The stomach plays a number of roles in the digestive process and in host defense. Not only does the stomach serve as a reservoir for ingested foods and an important site of digestion; it is also exposed to a wide variety of swallowed bacteria, fungi, viruses, and parasites, and as such, it has a role in both innate and adaptive immunity. These functions are performed,…

Organogenesis of the Gastrointestinal Tract

Introduction Development of the gastrointestinal tract involves crucial processes, including endoderm formation and patterning along the anterior-to-posterior, dorsoventral, and left-right axis; gut tube morphogenesis into the foregut, midgut, and hindgut domains; assembly of mesenchyme, epithelial morphogenesis, and cytodifferentiation. The organogenesis of the gut tube and its derivatives starts around the third week of gestation from a primitive abdominal tube. From the initiation of gut tube formation…

Trophic Factors and Regulation of Gastrointestinal Tract and Liver Development

Acknowledgments This work is a publication of the U.S. Department of Agriculture/Agricultural Research Service, Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine and Texas Children’s Hospital, Houston, Texas. The work was supported in part by federal funds from the U.S. Department of Agriculture/Agricultural Research Service, cooperative agreement no. 58-6258-6001, and by the National Institutes of Health (R01 HD33920 and DK094616). The contents of…

Genetics and Physiology of Surfactant Protein Deficiencies

Acknowledgments The authors thank Jeffrey A. Whitsett, MD, Darrell Kotton, MD, Timothy Weaver, PhD, Aaron Hamvas, MD, F. Sessions Cole, MD, Frances V. White, MD, Lisa Young, MD, Robin Deterding, MD, Alicia Casey, MD, Martha Fishman, MD, Susan Guttentag, MD, Michael Beers, MD, Surafel Mulugeta, PhD, and Elizabeth Fiorino, MD, for their collaboration, along with Susan Wert, PhD, who also provided photographs of immunostained lung tissue.…

Surfactant Treatment

Historical Background A brief history of surfactant for the treatment of respiratory distress syndrome (RDS) provides perspective on this major therapeutic advance. In 1959, not long after surfactant had been identified as critical to maintaining lung inflation at low transpulmonary pressures, , Avery and Mead reported that saline extracts from the lungs of preterm infants with RDS lacked the low surface tension characteristics of pulmonary surfactant.…

Antenatal Hormonal Therapy for Prevention of Respiratory Distress Syndrome

Introduction The use of antenatal hormone therapy to accelerate fetal maturation and decrease the incidence of respiratory distress syndrome (RDS) and other neonatal problems has been one of the great success stories of perinatal medicine. Here we describe the actions of glucocorticoids and other hormones on the lung and other tissues. We then review the evidence for the clinical use of antenatal glucocorticoids, including current recommendations…

Regulation of Surfactant-Associated Phospholipid Synthesis and Secretion

Introductory Remarks on Mammalian Surfactant Phospholipid Analysis and Functions Application of the Young-Laplace Equation (1805) by van Neergard in 1929 substantially promoted the understanding of lung physiology, showing that pulmonary retraction is primarily based on surface tension. It took three decades to emphasize its clinical relevance and start the exploration of pulmonary surface active agent (“surfactant”). , 1,2-Dipalmitoyl-glycero-3-phosphocholine, also named 1,2-dipalmitoyl-phosphatidylcholine , DPPC, or PC16:0/16:0 (the…

Structure and Development of Alveolar Epithelial Cells

Introduction The ultimate temporal and morphologic stage of lung development is the formation of millions of gas exchange units, the alveoli. Life is possible without the alveolus; there are few in very premature infants. However, without expansion and maturation of the alveolar population, respiratory function and even survival are likely to be compromised. In this chapter, the development and unique features of AT1 and AT2 cells…

Surfactant Homeostasis: Composition and Function of Pulmonary Surfactant Lipids and Proteins

Introduction In vertebrates, adaptation to a nonaqueous respiratory environment was achieved by the development of lungs, which provide an extensive surface area for gas exchange. The unique physicochemical boundary between respiratory gases and the alveolar epithelium creates a region of high surface tension, generated by the unequal distribution of molecular forces on water molecules at the air-liquid interface. Unopposed, this surface tension creates collapsing forces that…