6 Retinoic Acid Signaling and Development of the Respiratory System
153
Introduction
Mature Respiratory Systems
The mature mammalian respiratory system consists of the diaphragm and respiratory muscles, the trachea and airways, and the lung. The lung is the principal gas
exchanger, providing the primary interface between air and blood to facilitate the
exchange of oxygen and carbon dioxide (Schittny 2017; Warburton et al. 2000). The
mammalian lung is actively ventilated by the diaphragm and the intercostal muscles.
Inhalation occurs when the diaphragm contracts to create negative intrathoracic pressure, causing the air to rush in through the trachea and airways and fill the alveoli
where gas exchange takes place. Exhalation occurs passively due to the relaxation
of the diaphragm and the elastic recoil in the alveoli units.
The avian respiratory system differs from the mammalian system. The respiratory
apparatus is separated into two parts, the ventilators (air sacs) and a gas exchanger (the
parabronchial lung). Synchronized bellows-like movement of the air sacs ventilates
the lung continuously and unidirectionally, which allows oxygenation of blood even
during exhalation. The avian lung is anchored by the ribs, the vertebrae, and the
horizontal septum making it essentially rigid and noncollapsible (Maina 2006). The
avian respiratory system is considered to be the most efficient respiratory system of
the vertebrates. Compared to mammals of equivalent body mass, the avian lung’s
respiratory surface area is approximately 15% greater, the blood-gas barrier is about
62% thinner, though its volume is approximately 26% smaller (Hsia et al. 2013). In
addition, the avian respiratory system utilizes unidirection air flow, as opposed to
the bidirectional air flow seen in mammalian systems, allowing for oxygenation of
blood throughout the respiratory cycle, not just during inhalation (Hsia et al. 2013;
Maina 2006).
In comparison with other major organ systems, the respiratory system of vertebrates is unique in that it is not required until birth. In fact, the whole of respiratory
system development in utero is designed to prepare the neonate for its first breath at
the time of birth.
Embryonic Development of the Mammalian Lung
Historical studies have divided mammalian lung development into five overlapping phases: embryonic, pseudoglandular, canalicular, saccular, and alveolar (Pringle
1986) that encompass both prenatal and postnatal life, depending upon species (Table
6.1 and Fig. 6.1). In humans, monkeys, sheep, and rabbits, the alveolarization stage
begins in late gestation and continues in postnatal life. In rodents, however, the pups
are born during the saccular stage, and the alveolar phase does not begin until a
few days after birth. Each developmental stage is characterized by complex cell–cell
interactions between the endodermal and mesodermal tissues in a highly regulated
153
Introduction
Mature Respiratory Systems
The mature mammalian respiratory system consists of the diaphragm and respiratory muscles, the trachea and airways, and the lung. The lung is the principal gas
exchanger, providing the primary interface between air and blood to facilitate the
exchange of oxygen and carbon dioxide (Schittny 2017; Warburton et al. 2000). The
mammalian lung is actively ventilated by the diaphragm and the intercostal muscles.
Inhalation occurs when the diaphragm contracts to create negative intrathoracic pressure, causing the air to rush in through the trachea and airways and fill the alveoli
where gas exchange takes place. Exhalation occurs passively due to the relaxation
of the diaphragm and the elastic recoil in the alveoli units.
The avian respiratory system differs from the mammalian system. The respiratory
apparatus is separated into two parts, the ventilators (air sacs) and a gas exchanger (the
parabronchial lung). Synchronized bellows-like movement of the air sacs ventilates
the lung continuously and unidirectionally, which allows oxygenation of blood even
during exhalation. The avian lung is anchored by the ribs, the vertebrae, and the
horizontal septum making it essentially rigid and noncollapsible (Maina 2006). The
avian respiratory system is considered to be the most efficient respiratory system of
the vertebrates. Compared to mammals of equivalent body mass, the avian lung’s
respiratory surface area is approximately 15% greater, the blood-gas barrier is about
62% thinner, though its volume is approximately 26% smaller (Hsia et al. 2013). In
addition, the avian respiratory system utilizes unidirection air flow, as opposed to
the bidirectional air flow seen in mammalian systems, allowing for oxygenation of
blood throughout the respiratory cycle, not just during inhalation (Hsia et al. 2013;
Maina 2006).
In comparison with other major organ systems, the respiratory system of vertebrates is unique in that it is not required until birth. In fact, the whole of respiratory
system development in utero is designed to prepare the neonate for its first breath at
the time of birth.
Embryonic Development of the Mammalian Lung
Historical studies have divided mammalian lung development into five overlapping phases: embryonic, pseudoglandular, canalicular, saccular, and alveolar (Pringle
1986) that encompass both prenatal and postnatal life, depending upon species (Table
6.1 and Fig. 6.1). In humans, monkeys, sheep, and rabbits, the alveolarization stage
begins in late gestation and continues in postnatal life. In rodents, however, the pups
are born during the saccular stage, and the alveolar phase does not begin until a
few days after birth. Each developmental stage is characterized by complex cell–cell
interactions between the endodermal and mesodermal tissues in a highly regulated