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Urinary Acidification

Introduction The functions of the fetal kidney in utero remain little understood. Prior to delivery, the placenta regulates fetal homeostasis of salt and water, and fetal acid-base balance in the context of the acid load generated by intrauterine metabolism and growth. The fetal kidney in utero generates the amniotic fluid that contributes to fetal pulmonary development and provides mechanical protection to the enlarging fetus. Parturition marks…

Concentration and Dilution of Urine

Acknowledgments We acknowledge with great sadness the passing of Dr. Michael Linshaw, the renowned pediatric nephrologist who contributed the “Concentration and Dilution of Urine” chapter to this textbook for several editions. He was a beloved teacher and mentor who enjoyed solving the mysteries of the kidneys. His passion and tenacity for doing so improved the lives of many children and their families. Physiology of the Urinary…

Organic Anion Transport in the Developing Kidney

Acknowledgments This work was partly supported by NIH grant U54 HD090259. Introduction Rapid and complex changes in physiology occur when the fetus transitions from an intrauterine to an extrauterine environment. From dependency on the maternal circulation via the placenta for nutrition, oxygen, and waste excretion, the infant shifts to reliance on its own organ systems for vital functions. These organ systems include the pulmonary system for…

Transport of Amino Acids in the Fetus and Neonate

Introduction Amino acids are the building blocks for proteins and are critical for growth. In addition, they are involved in many metabolic processes within mammalian cells. Thus, regulating their circulating concentrations in the bloodstream is very important for many metabolic processes, including protein synthesis, which results in the growth and development of the fetus and neonate. This chapter reviews the regulation of amino acid transport in…

Role of the Kidney in Calcium and Phosphorus Homeostasis

Acknowledgments We acknowledge the coauthors of this chapter in the previous edition: Drs. Abhijeet Pal, Juhi Kumar, Craig B. Woda, Robert P. Woroniecki, and Susan E. Mulroney. Introduction Calcium and phosphate serve many complex and vital functions. They are key components of the cartilage and skeleton systems. Calcium is an important cofactor in many complex enzymatic reactions and a main messenger in signaling pathways in excitability…

Potassium Homeostasis in the Fetus and Neonate

Introduction Potassium is the most abundant intracellular cation. Maintenance of a high intracellular potassium concentration (100 to 140 mEq/L) is essential for many basic cellular processes, including cell growth and division, DNA and protein synthesis, conservation of cell volume and pH, and optimal enzyme function. The steep gradient between potassium concentration in the cell and that in the extracellular fluid, maintained by the ubiquitous sodium-potassium adenosine…

Renal Transport of Sodium During Development

Introduction The kidney is responsible for maintaining a constant composition and volume of the extracellular fluid. This steady state is achieved by the remarkable capacity of the kidney to maintain sodium balance between what is absorbed in the intestine and what is excreted in the urine. To achieve this, the adult kidney filters approximately 150 L of an ultrafiltrate of plasma from which the tubules reabsorb…

Postnatal Development of Glomerular Filtration Rate in Neonates

Introduction The production of urine begins with the formation of an ultrafiltrate of plasma by the glomerulus. The function of the tubule is to modify this ultrafiltrate to allow an efficient excretion of waste products and the retention of those substances required to maintain constant body fluid volume and homeostasis. Glomerular filtration is also essential for the elimination of drugs. Alterations in glomerular filtration rate (GFR)…

Development and Regulation of Renal Blood Flow in the Neonate

Introduction Newborn mammals, including humans, exhibit lower renal blood flow than their adult counterparts. The low fetal and neonatal renal blood flows are maintained by a high renal vascular resistance and establish the newborn’s unique renal functional state, which is characterized by a low glomerular filtration rate. The unique renal hemodynamic state at birth affects the clinical management of the newborn. The low renal blood flow…

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),…