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,…
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…
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…
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.…
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.…
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…
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…
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…
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…
Acknowledgments This work was supported by the Canadian Institutes of Health Research (CIHR), the German Research Foundation (Deutsche Forschungsgemeinschaft), the Ontario Institute for Regenerative Medicine (OIRM), the Stem Cell Network, the Heart and Stroke Foundation Canada, the Ontario Graduate Scholarship, and the Canadian Lung Association—Breathing as One Studentship. Abbreviations Abbreviation Meaning αSMA α-Smooth muscle actin ABCA3 ATP binding cassette subfamily A member 3 AcLDL Acetylated low-density…
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Introduction Throughout fetal life, the pulmonary circulation forms and establishes a hierarchical system that is essential for postnatal gas exchange. In humans, a continuity of the circulation between the heart and the capillary plexus of the lung appears at approximately 34 days of gestation. , There is no appreciable reactivity of pulmonary vessels at midterm gestation, but reactivity increases with advancing gestation thereafter, with increased pulmonary…
Spectrum of Lung Disease in Preterm Infants The normal fetal lung at 26 weeks gestation is in a late canalicular or early saccular stage of development and surfactant deficient. Surfactant treatment and the use of more gentle modes of assisted ventilation have resulted in populations of very preterm infants with a wide range of lung diseases not easily classifiable into the traditional categories of respiratory distress…
Acknowledgments Portions of this work were supported by NIH grants HL110002 (KHA), HL62875 (KHA), HL56401 (KHA; PL Ballard, P.I.), and AHA Grant-in-Aid 96014370 (KHA). Introduction Infants born as early as 22 weeks estimated gestational age may survive if supported by neonatal intensive care, which includes the routine use of antenatal steroids, postnatal surfactant-replacement therapy, and respiratory support. These and other therapies are required because the gas-exchange…
Introduction At birth, the term newborn lung is at the alveolar phase of lung development, with a smaller number of alveoli normalized to body weight than an adult has. The lung must make the rapid transition from a fluid-filled structure with low stretch frequency and low strain, to an air-filled structure subjected to high strain at variable frequency to support gas exchange. Spontaneous breathing efforts just…
Introduction The ability to measure lung function is essential for understanding lung growth and developmental physiology, diagnosing pathologic conditions, and assessing therapeutic interventions and management. Neonatal pulmonary function evaluation in the 21st century has achieved a remarkable level of sophistication, making use of new and emerging technologic innovations; these advances stand in stark contrast to very early lung function evaluation efforts that occurred in the 19th…
Introduction A large body of experimental work has been performed on oxygen sensing and on the cellular events that result from oxygen deprivation in a variety of cell types and organisms. Such comparative studies have contributed to our understanding of O 2 sensing and adaptation to hypoxia. As a result, a number of new concepts and mechanisms regarding O 2 sensing and hypoxia adaptation have emerged.…
Acknowledgment The late Dr. Henrique Rigatto was the original author of this chapter, which still contains parts of those original contributions. Introduction There are at least three important considerations regarding the study of the control of breathing during the fetal and neonatal periods. First, the fetus sleeps all the time and the neonate most of the time. This means that their control of breathing must be…
Acknowledgment This chapter is based on a previous contribution by Maria Delivoria-Papadopoulos and Jane E. McGowan. Introduction Because aerobic metabolism is critically dependent on a consistent and adequate supply of oxygen, oxygen is an essential fuel source for normal cellular metabolic function. Hence, control of oxygen uptake, transport, and release are essential functions. Although molecular oxygen participates in numerous oxidative reactions necessary for cellular metabolism (e.g.,…
Introduction Integral to the system of pulmonary gas exchange are mechanisms to maintain matching of pulmonary perfusion and alveolar ventilation, known as ventilation / perfusion matching . The goal is that alveolar oxygen and pulmonary capillary blood have intimate contact to optimize diffusion of O 2 and CO 2 . Requisite features of the efficient gas-exchange apparatus include sustained effective ventilation to replenish the oxygen stores…