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Host Defense Mechanisms Against Fungi

Acknowledgments The authors wish to thank Richard B. Johnston, Jr., MD, PhD, who remarkably contributed to this chapter in previous editions of Fetal and Neonatal Physiology . Introduction Fungal infections are commonly classified as either endemic or opportunistic. An endemic fungal infection may occur in any individual living in a geographic area that is the natural habitat of that fungus. Histoplasmosis, coccidioidomycosis, and blastomycosis, which are…

Host Defense Mechanisms Against Bacteria

Introduction Globally, infections cause an estimated 1 million neonatal deaths annually, representing over 40% of all neonatal deaths. , Overwhelming host response to a microbial infection, or neonatal sepsis, is defined as infection in the first 28 days of life; for preterm infants, this period includes up to 4 weeks after the expected due date. This is further subdivided into early-onset neonatal sepsis (EOS), with an…

Platelet–Vessel Wall Interactions

Introduction Platelets are the sentinels of the circulatory system; they recognize and rapidly respond to a disruption in vascular integrity, thereby preventing significant blood loss. This is achieved through the formation of a primary hemostatic plug, which requires platelets to undergo a highly regulated series of events including the adhesion, activation, generation, and release of thrombogenic agents and ultimately aggregation. The importance of these processes is…

Developmental Hemostasis

Introduction The presence of a complex hemostatic system is fundamental to all multicellular organisms with a blood circulatory system. Blood must remain in a fluid form to flow, and for survival, organisms must be able to stop that flow at sites of local injury, through the process of physiologic thrombus formation. However, under certain conditions, thrombus formation can become pathologic. In the mid-1800s Rudolf Virchow described…

Developmental Megakaryopoiesis

Introduction Megakaryocytes (MKs), among the rarest and most unusual hematopoietic cells in the human bone marrow, comprise 0.02% to 0.1% of the total nucleated marrow cells. , Over the past decades, the study of these cells lagged behind that of other hematopoietic lineages, partly because of the rarity and fragility of MKs in the bone marrow, and partly because of the lack of a potent thrombopoietic…

Developmental Erythropoiesis

Acknowledgments Parts of this chapter were adapted from sections of Chapter 134 by authors James A. Stockman III and Pedro A. DeAlarcon in the first edition of this book. We thank Erin Adair for assistance with illustrations. Erythrocyte Kinetics Sites and Stages of Fetal Red Blood Cell Production Extraembryonic Erythropoiesis Extraembryonic erythropoiesis begins in the fetal yolk sac by 14 days’ gestation. Small nests of nucleated…

Neutrophil Granulopoiesis and Homeostasis

Introduction From their initial emergence in the yolk sac at the beginning stages of embryogenesis to their vast proliferation in the bone marrow at the end of term gestation, the differentiation of the pluripotent hematopoietic stem cell into a mature, segmented neutrophil is a tightly controlled process where the transcriptional regulators C/EBP-α and C/EBP-ε have essential roles. Despite their relatively short life span, these intriguing cells…

Developmental Biology of Hematopoietic Stem Cells

Introduction The hematopoietic system is made up of all of the blood cells, including red blood cells, platelets, myeloid cells such as granulocytes, monocyte-macrophages, and dendritic cells (DC), and lymphoid cells such as T, B, and natural killer (NK) cells. Together, these cells function to provide oxygen-carrying capacity, hemostasis, innate and adaptive immune function, and tissue regeneration and repair. Hematopoiesis is the process by which these…

Regulation of Acid-Base Balance in the Fetus and Neonate

Introduction The majority of the existing information on the regulation of acid-base homeostasis in mammals and humans was obtained from studies in adult subjects. Revolution in micromethodology and advances in developmental physiology and molecular biology provided additional insights and improved our understanding of the key mechanisms of fetal and neonatal regulation of acid-base balance. In general, acid-base homeostasis is tightly regulated by extracellular and intracellular buffer…

Fluid Distribution in the Fetusand Neonate

Introduction The human body is composed of fluids and solids (proteins, fat, and minerals). Total body water (TBW) is inversely related to body fat content because fat has very low water content. Body water also contains an array of dissolved substances. Water is the largest single constituent of body composition. TBW is divided into two compartments: intracellular fluid (ICF) and extracellular fluid (ECF). ECF is further…

Response to Nephron Loss in Early Development

Acknowledgments The authors are supported by the following funding: PG: NICHD, Pediatric Scientist Development Program (PSDP) and K12-HD000850. FL: R01DK118140, R01DK107653. JC: R01DK110622, R01DK111861, U34DK117128. Introduction Glomerular endowment is highly variable in humans. Although each kidney contains approximately 1 million nephrons, glomerular number ranges from 210,000 to 2,700,000 per kidney representing a 10-fold difference. , Both environmental and genetic factors influence nephrogenesis, a complex developmental program…

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…