Embryology18 Dr.Ban The respiratory system Respiratory system development is a highly coordinated and complex process it’s development is tightly associated with the digestive system from the beginning.The respiratory tract is divided anatomically into 2 main parts: A-upper respiratory tract, consisting of the nose, nasal cavity and the pharynx B-lower respiratory tract consisting of the larynx, trachea, bronchi and the lungs. The pharynx is the part of the throat behind the mouth and nasal cavity, and above the esophagus and larynx. In humans, the pharynx is part of the digestive system and the conducting zone of the respiratory system. The conducting zone which also includes the nostrils of the nose, the larynx, trachea, bronchi, and bronchioles filters, warms and moistens air and conducts it into the lungs). The human pharynx is divided into three sections: . nasopharynx . oropharynx . laryngopharynx 1 Embryology18 Dr.Ban The larynx The internal lining of the larynx originates from endoderm, but the cartilages and muscles originate from mesenchyme of the 4th and 6th pharyngeal arches. As a result of rapid proliferation of this mesenchyme, the laryngeal orifice changes in appearance from a sagital slit to a T-shaped opening. When the mesenchyme of the two arches transforms into the thyroid, cricoid and arytenoid cartilages the adult shape of the laryngeal orifice can be recognized. The laryngeal epithelium proliferates rapidly, resulting in a temporary occlusion of the lumen. Subsequently, vacuolization and recanalization produces a pair of lateral recesses, the laryngeal ventricles that are bounded by folds of tissue that differentiate into the false and true vocal cords. Since musculature of the larynx is derived from mesenchyme of the 4th and 6th pharyngeal arches, all laryngeal muscles are innervated by branches of vagus nerve (the superior laryngeal nerve innervates derivatives of the fourth pharyngeal arch and the recurrent nerve innervates derivatives of the sixth laryngeal arch). 2 Embryology18 Dr.Ban Formation of the lung buds When the embryo is approximately 4 weeks old , the respiratory diverticulum (lung bud) appears as an outgrowth from the ventral wall of the foregut. Initially, the respiratory diverticulum is continuous with the foregut then tracheoesophageal folds develop on either side and join to form a tracheoesophageal septum that separates it from the rest of the foregut. This divides the foregut into the laryngotracheal tube (ventral) and the esophagus (dorsal). The caudal end of the laryngotracheal diverticulum enlarges to form the lung bud, which is surrounded by splanchnic mesenchyme. A, B, and C. Successive stages in development of the respiratory diverticulum showing the esophagotracheal ridges and formation of the septum, splitting the foregut into esophagus and trachea with lung buds Trachea, bronchi and lungs Phases of development Embryonic phase The development of the lungs begins with the appearance of a respiratory diverticulum (lung bud).During its separation from the foregut, the lung bud forms the trachea and two bronchial buds. At the beginning of the 5th week, each of these buds enlarges and form right and left main bronchi. The right main bronchi gives rise to three secondary bronchi and the left main bronchi forms two secondary bronchi. During further development, secondary bronchi 3 Embryology18 Dr.Ban divide repeatedly, forming ten tertiary bronchi in the right lung and eight in the left, demarcating the end of the embryonic phase. Terminal bronchiole (anterior view) Canalicular phase Each terminal bronchioles further divide into respiratory bronchioles, with increase in vascularization. Subsequently, the lumens of the respiratory bronchioles become enlarged as a result of the thinning of their epithelial walls. Saccular phase The respiratory bronchioles give rise to a final generation of terminal branches. These branches become invested in a dense network of capillaries, forming the terminal sacs (primitive alveoli) that are lined with type I and type II alveolar cells. Type I alveolar cells are branched cells which are the gas exchange surface in the alveolus. Type II alveolar cells act as the ‘caretaker’ by responding to damage of the type I cells. Type II alveolar cells do this by dividing and acting as a progenitor cell for both type I and type II cells. 4 Embryology18 Dr.Ban In addition, they synthesize, store and release pulmonary surfactant which acts to optimise conditions for gas exchange. (surfactant production is essential to reduce surface tension in the alveolar , wall and thereby prevent collapse of the airway). In the absence of surfactant, the lung can maintain alveoli in an open state for only a very short time. Although gas exchange is possible at this point, it is very limited as the alveoli are still immature and few in number. In fact, the formation of the terminal sacs continues during fetal and postnatal life. Premature infants born at the beginning of this stage can survive, but will likely need ventilation assistance and administration of exogenous surfactant. Alveolar phase The alveolar phase is characterized by the maturation of the alveoli, a process that takes place during the end of fetal life and after birth for several weeks with the formation of secondary septa, which increase surface area for gas exchange. The first inhalation occurs within seconds after birth serves as the first inspiration, also acts to inflate the lungs. 5 Embryology18 Dr.Ban Alveolus (anterior view) A. The canalicular period ,cuboidal cells lining the respiratory bronchioli. B. The terminal sac period .Cuboidal cells become very thin and intimately associated Lung tissue in a newborn, thin squamous epithelial cells (also known as alveolar epithelial cells, type 1) and surrounding capillaries protruding into mature alveoli. 6 Embryology18 Dr.Ban Initial development of the lower respiratory tract 1. Foregut 2. Esophagotracheal septum 3. Respiratory diverticulum 1- Lung buds 2. Trachea 7 Embryology18 Dr.Ban 1. Pharynx 2. Lung buds 3. Trachea 4. Esophagus 1. Right upper lobe 2. Left upper lobe 3. Right lower lobe 4. Left lower lobe 5. Right middle lobe 6. Splanchnic mesoderm 7. Bronchial buds 8. Visceral pleura Congenital anomalies of respiratory system Congenital anomalies are the product of errors in embryogenesis (malformations) or the result of intrauterine events that affect embryonic and fetal growth (deformations and disruptions) . The more complex the formation of a structure, the more opportunities for malformation. Accurate identification of congenital anomalies often makes the difference between an infant's survival and death. Choanal atresia is a congenital disorder where the back of the nasal passage (choana) is blocked, usually by abnormal bony or soft tissue (membranous) due to failed recanalization of the nasal fossae during fetal development. It can be unilateral or bilateral. Arhinia also called nasal agenesis, is the congenital partial or complete absence of the nose at birth. It is an extremely rare condition 8 Embryology18 Dr.Ban Bilateral choanal atresia arhinia Laryngeal atresia is the most catastrophic anomaly of the airways in the newborn. This extremely rare lesion results from failed recanalization of the laryngeal orifice in utero. There is usually no specific cause identified Laryngocele A congenital anomalous air sac communicating with the cavity of the larynx, which may bulge outward on the neck. It may also be acquired, as seen in glassblowers, due to continual forced expiration producing increased pressures in the larynx which leads to dilatation of the laryngeal ventricle. It is also seen in people with chronic obstructive airway disease. Laryngocele Pulmonary hypoplasia is incomplete development of the lungs, resulting in an abnormally low number or size of bronchopulmonary segments or alveoli.It most often occurs secondary to other fetal abnormalities that interfere with 9 Embryology18 Dr.Ban normal development of the lungs. Primary (idiopathic) pulmonary hypoplasia is rare and usually not associated with other maternal or fetal abnormalities. Pulmonary hypoplasia Respiratory distress syndrome (RDS) is a common breathing disorder that affects newborns, RDS is more common in premature newborns because their lungs are not able to make enough surfactant. Surfactant is a foamy substance that keeps the lungs fully expanded so that newborns can breathe in air once they are born.Without enough surfactant, the lungs collapse and the newborn has to work hard to breathe. He or she might not be able to breathe in enough oxygen to support the body's organs. Most babies who develop RDS show signs of breathing problems and a lack of oxygen at birth or within the first few hours that follow. The lack of oxygen can damage the baby's brain and other organs if not treated promptly. 10 .