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Mechanics of Breathing

Introduction The human infant has at least two important advantages over the adult in the evaluation of respiratory mechanical function. First, the infant, like newborn mammals of many species, is often asleep and does not immediately react to gently performed maneuvers. Hence, a maneuver consisting of a very brief occlusion of the airways during spontaneous breathing is often used in the evaluation of the mechanical properties…

Functional Development of Respiratory Muscles

Introduction This chapter provides a snapshot of fetal and neonatal development of the diaphragm muscle (DIAm), the major inspiratory muscle in mammals, and partition between the thoracic and abdominal cavities. The DIAm appears rather late in evolution, being present only in mammals, while other vertebrates use different means of ventilation. The embryologic origin of the DIAm has been elucidated by studies using molecular markers of muscle…

Regulation of Lower Airway Function

Acknowledgment This chapter was prepared through the financial support of grant HL 56470 (R.J. Martin and Y.S. Prakash), HL138402 (P.M. MacFarlane), and HL 133459 (T.M. Raffay) from the National Institutes of Health. Introduction Significant progress has been made in elucidating the fetal and neonatal development of lower airway structures and regulation of their function. During early development, airway smooth muscle differentiates from the mesenchyme of the…

Upper Airway Structure: Function, Regulation, and Development

Introduction Although the conducting airways are formed well in advance of fetal viability, they undergo significant maturational changes in late gestation. Conducting airways are susceptible to damage until they acquire the characteristics of more mature airways. Controversy exists concerning the pathogenesis of bronchopulmonary dysplasia (BPD) in the neonate ; in any case, prolonged mechanical ventilation and oxygen toxicity appear to be major contributing factors. Serial evaluations…

Regulation of Liquid Secretion and Absorption by the Fetal and Neonatal Lung

Acknowledgment The editors wish to thank David P. Carlton for his excellent work on this chapter in the fifth edition. It has been republished here essentially unchanged. Introduction Before birth, the lung is filled with liquid secreted by the epithelia lining the potential air spaces of the fetal lung. The amount of liquid retained in the fetal lung is similar to the functional residual capacity of…

Molecular Mechanisms of Lung Development and Lung Branching Morphogenesis

The need to extract and utilize sufficient amounts of oxygen from the environment to sustain life has had an incredible impact on the evolution of the respiratory systems. In particular, breathing amphibians and mammals with their high metabolic rates have been forced to evolve a sophisticated organ to meet their oxygen requirements and get rid of carbon dioxide, the cellular waste of aerobic metabolism. We explore…

Physiologic Mechanisms of Normal and Altered Lung Growth Before and After Birth

Introduction Growth and development of the lung occurs both before and after birth and is a major determinant of respiratory health throughout postnatal life. Adequate lung growth before birth is necessary for the successful transition from fetal to postnatal life. Normal lung growth after birth is necessary to enable the lung to meet increasing metabolic demands during infancy and childhood and into adulthood. During its development,…

Regulation of Alveolarization

Introduction Lung development is a continuous process, starting very early in embryonic life with the differentiation of the tracheal bud from the ventral side of the primitive gut and ending in postnatal life with the multiplication of alveoli and the maturation of the pulmonary microvasculature. Alveoli represent the functional unit of the lung, the site at which oxygen and carbon dioxide are exchanged between inspired air…

Normal and Abnormal Structural Development of the Lung

Acknowledgments The author thanks Dr. Susan E. Wert for her writing of this chapter for the fifth edition, which is the foundation for this updated chapter. The author would also like to thank Dr. Jamie Verheyden for assistance with this manuscript. Introduction The respiratory system functions to provide oxygen from the external environment to the organism, while removing excess carbon dioxide from the blood. The respiratory…

Fetal and Placental Circulation During Labor

Physiologic Background A sufficient maternal blood supply to the placenta is of utmost importance to the fetus during pregnancy and labor. It has long been recognized that uterine contractions diminish uteroplacental blood flow. Contractions of myometrium compress the vessels traversing the uterine wall and increase intrauterine pressure, thus influencing the intervillous space pressure as well. The intrauterine pressure during labor usually ranges from 25 to 100…

Umbilical Circulation

Introduction The fetoplacental circulation, also known as umbilical circuit, with its transport of nutrients, gases, and endocrine signaling, is critical for fetal development. A long tradition of animal experiments has given us indispensable insights into its physiology. However, the introduction of ultrasound techniques enabled studies of the human version of this physiology free from the surgical trauma hampering the experimental procedures. This chapter prioritizes human data…

Mechanisms Regulating Closure of the Ductus Arteriosus

Introduction a a Portions of this chapter are reprinted from Chapter 54 in Avery’s Diseases of the Newborn, 10e. The ductus arteriosus represents a persistence of the terminal portion of the sixth branchial arch. During fetal life, the ductus arteriosus serves to divert blood away from the fluid-filled lungs toward the descending aorta and placenta. After birth, constriction of the ductus arteriosus and obliteration of its…

Nutritional and Environmental Effects on the Fetal Circulation

Acknowledgments Preparation of this chapter was supported by grants from the British Heart Foundation, the Biotechnology and Biological Sciences Research Council, and Gerald Kerkut Trust. Introduction The fetus depends on its cardiovascular system for growth and development. Vascular growth is closely linked to tissue growth, and the fetal heart must develop in relation to the venous return (preload), primarily from the umbilical vein, and the similar…

Regulation of Cardiovascular Function During Fetal and Newborn Life

Introduction The regulation of cardiovascular function in the fetal and newborn periods is mediated through interacting neural, endocrine, and metabolic mechanisms acting at central, systemic, and local levels. The role of the central nervous system, in particular, is critical for cardiovascular homeostasis, including maintenance of blood pressure within normal limits. , Sympathetic outflow to the heart and blood vessels is continuously modulated by an array of…

Physiology of Congenital Heart Disease in the Neonate

† Deceased. Introduction Understanding the cardiovascular physiology of a neonate with a cardiac malformation requires consideration of many factors, including myocardial systolic and diastolic function; intravascular volume; cardiac and vascular transmural pressures; the pattern of intracardiac blood flow with shunting lesions; and arterial and pulmonary venous oxygen (O 2 ) content. Any description taking into account only these variables would be incomplete, however, because cardiac lesions…

Development of the Gastrointestinal Circulation in the Fetus and Newborn

Introduction The intestine is a complex series of tissues, each with a specific role in digestion and excretion. For a mature intestine to function properly, it must protect its component cells from other organisms, including bacteria, viruses, and parasites, as well as from toxic substances. In addition, the intestine, in partnership with the liver and pancreas, disassembles potential nutrients and presents them (sugars, fats, proteins, vitamins,…

Developmental Biology of the Pulmonary Vasculature

Introduction This chapter discusses the changing morphology of the developing fetal, neonatal, and postnatal pulmonary vascular bed. Studies have focused on structural and functional alterations in endothelial cells during postnatal development and have addressed the phenotypic heterogeneity of the vascular smooth muscle cells (SMCs) in the perinatal period. There are new insights into mechanisms regulating endothelial migration and angiogenesis, SMC proliferation, hypertrophy, and migration. These studies…

Developmental Electrophysiology in the Fetus and Neonate

Introduction In this chapter, the physiology of both impulse formation and conduction in the developing heart is discussed. Significant developmental or age-related changes in the ionic currents are responsible for the generation of cardiac action potential, as well as changes in the microscopic and macroscopic anatomic and neural substrates that govern the physiology of cardiac depolarization and repolarization during health and disease. Recently, important breakthroughs in…

Cardiovascular Development

Introduction The formation and subsequent development of the heart is a complex process that involves multiple cell populations, a plethora of molecular regulatory mechanisms, and intrinsic, complicated spatiotemporal remodeling events. When all the developmental steps have been properly concluded, the fully septated four-chambered heart will beat a few billion times during the individual’s life span, thereby sustaining three interdependent blood circulations (systemic, pulmonary, and coronary). Although…

Physiologic Development of the Skin

Introduction Human skin is a complex structure with unusual functional diversity. , Topologically, the skin is continuous with the lung and intestinal epithelia. The lung and gut are generally viewed as exchange surfaces for gases and nutrients; the skin is more commonly considered a barrier. , , The concept of an integumental barrier emphasizes the role of the skin as a protective boundary between an organism…