Airways

The neonatal airway is composed of the nose, pharynx, larynx, trachea, and bronchi. The nasal structures, which are derived from ectoderm, begin developing during the fourth week of gestation.3,4 The olfactory placodes, which are evident as early as the third fetal week, eventually become the nasal pits, which separate into paired medial and lateral boundaries of the nasal walls. The medial portion of the nasal wall fuses during the formation of the nasal septum and central upper lip. The medial and lateral nasal processes fuse with the maxillary processes of the mandibular arch. The nasal cavity extends posteriorly, thinning the oronasal membrane, which eventually ruptures to form the choanae. Persistence of the oronasal membrane leads to choanal atresia.^3,5

Incomplete closure of the foramen caecum during the third week of fetal development leads to the formation of gliomas or nasal encephaloceles. Neural tissue remains attached to epidermal elements, preventing normal migration of mesenchymal elements that will form the cartilaginous structures of the midface. This process leads to the presence of a bony defect through which brain tissue may herniate (e-Fig. 48-1). Gliomas have lost their central nervous system attachment, although 15% have a fibrous stalk connecting to the subarachnoid space. Encephaloceles maintain their central nervous system connection.⁵

Nasal dermoid cysts are benign masses with ectodermal and mesodermal elements. They present as masses on the dorsum of the nose and may have a fistulous opening on the skin or a sinus tract extending into the deep nasal elements. Nasal dermoid cysts are the result of faulty closure of the foramen caecum with invagination of dermal tissue between the developing nasal bones and cartilage.⁵

The larynx, trachea, and bronchi embryologically arise from a ventromedial diverticulum of the foregut that is known as the laryngotracheal groove. The proliferation of the laryngeal mesenchyme results in the arytenoid swellings that grow toward the tongue, converting the primordial glottis into a T-shaped laryngeal inlet. By 8 weeks, the larynx is usually sufficiently formed. In the infant, the larynx is high in location, with its inferior border located at the C4 level. During childhood, the lower border of the larynx descends and eventually reaches its adult location at the C6-C7 level by age 15 years. Functions of the larynx include breathing, phonation, and protection of the lower airway against aspiration.4,6,7

The laryngotracheal groove grows caudally, forming the trachea. It lies ventral and parallel to the dorsal foregut, which eventually becomes the esophagus. The separation of the trachea and esophagus progresses cranially and is complete by 6 weeks’ gestation. The endodermal lining will produce the epithelium and glandular structures of the trachea, whereas the connective tissue, cartilage, and smooth muscle come from the surrounding splanchnic mesenchyme.4,6,7 Faulty separation of the trachea and esophagus gives rise to esophageal atresia/tracheoesophageal fistula. Disproportionate growth of the esophagus at the expense of the trachea may give rise to tracheal stenosis or, in the most severe form, tracheal agenesis.

Lungs

The lung bud arises from the caudal end of the laryngotracheal groove by the end of the fourth week and soon divides into two bronchial buds.4,8,9 The bronchial buds grow laterally into the pericardioperitoneal canals. Early in the fifth week, the connection of the bronchial buds to the trachea enlarges to form the main stem bronchi. The right main stem bronchus bifurcates into a superior secondary bronchus, supplying the right upper lobe and an inferior secondary bronchus. The inferior bronchus subdivides into two bronchi, supplying the right middle and lower lobes. The left main stem bronchus divides into two secondary bronchi that supply the upper and lower lobes of the left lung. The bronchi continue to divide, and all airway divisions are complete by 16 weeks’ gestation (Fig. 48-2). Cartilage appears at 10 weeks in the trachea and is found in the segmental bronchi by 16 weeks. Unequal growth of the lung buds can lead to the development of unilateral pulmonary agenesis or hypoplasia. Prolonged oligohydramnios or space-occupying thoracic lesions are associated with pulmonary hypoplasia.^4,8

Lung development has been divided into five stages (Table 48-1). The embryonic (26 to 52 days) and pseudoglandular (52 days to 16 weeks) stages have been described previously. During the canalicular stage (17 to 28 weeks), the bronchi and terminal bronchioles become larger. The capillary bed begins to approximate the future air spaces, and gas exchange is possible. Type I and type II pneumocytes can be identified in the fetal lung by 20 to 22 weeks, but the capillary-alveolar interface is not adequate for extrauterine survival until 23 to 24 weeks of gestation.^4,8,9 The saccular stage (29 to 36 weeks) is characterized by the development of terminal air sacs with flattening of the epithelium in the distal air spaces. The type II pneumocytes produce surfactant, which is stored as lamellar bodies. During the alveolar stage (36 weeks to infancy), the size and number of alveoli increase. When birth occurs at full term, it is estimated that 50 million alveoli are present. Alveolar development continues postnatally, and the mature human lung ultimately has 300 million alveoli (Table 48-2).

Pulmonary Vasculature/Circulation

The fetal lung is the only organ that does not perform its postnatal function before birth. No reason exists for cardiac output to go to the fetal lungs because all gas exchange occurs via the placenta. Oxygenated blood returns to the fetus via the umbilical vein to the inferior vena cava (IVC) and right atrium (RA). Approximately two thirds of the IVC return entering the right atrium crosses the foramen ovale into the left atrium. The remaining one third of the IVC return and all of the superior vena cava (SVC) return enter the right ventricle. Most of the right ventricle output crosses the ductus arteriosus (DA) into the aorta. These shunts at the foramen ovale and DA result in most of the fetal cardiac output bypassing the lungs (Fig. 48-4).¹⁴

At delivery, the pulmonary circulation undergoes dramatic changes. The lungs expand with air, the partial pressure of oxygen rises, and the umbilical cord is clamped. These changes result in a decrease in pulmonary vascular resistance, ductal constriction, and functional closure of the foramen ovale. The fetal shunts are functionally closed and all of the blood entering the RA passes through the lungs. In term and near-term infants, this process may go awry with the persistence of high pulmonary vascular resistance and continued shunting of blood away from the lungs via the foramen ovale and DA. This mechanism results in hypoxemia and is known as persistent pulmonary hypertension of the newborn. It usually is seen in infants with underlying respiratory disease or infection or in infants with perinatal stresses such as asphyxia or hypoglycemia. Management of persistent pulmonary hypertension of the newborn currently is aimed at treating the underlying disease and dilatation of the pulmonary vasculature. Inhalation of nitric oxide often results in relaxation of the pulmonary vasculature with improved oxygenation. Infants who do not respond to conventional treatment or administration of nitric oxide frequently require extracorporeal membrane oxygenation.

The Diaphragm

The diaphragm is derived from four embryonic components: the septum transversum, the pleuroperitoneal membranes, the dorsal mesentery of the esophagus, and the lateral body walls (Fig. 48-5).^15,16 The septum transversum is the precursor of the central tendon of the diaphragm. The septum transversum grows from the ventrolateral body wall and forms a semicircular shelf that separates the heart from the liver and partially separates the pericardial cavity from the peritoneal cavity.

The pleuroperitoneal folds develop as the result of progressive narrowing of the opening between the pleural cavities and the pericardium. These pleuroperitoneal folds become pleuroperitoneal membranes. The pleuroperitoneal membranes extend ventromedially until they fuse with the septum transversum and the dorsal mesentery of the esophagus, separating the pleural and peritoneal cavities. This fusion obliterates the pleuroperitoneal canals that are present on each side of the esophagus. The right pleuroperitoneal canal closes earlier than does the left.

Between the ninth and twelfth weeks of gestation, the enlarging lungs and pleural cavities “burrow” into the body walls. This process forms the muscular and costal components of the diaphragm.

Airways

Basic airway anatomy to the level of the terminal bronchiole (the last purely conducting, i.e., nonalveolated, airway) is not substantially different in children compared with adults except in size. The right lung has three lobes, and the left lung has two lobes (Fig. 48-6). The pleural fissures separating the lobes of the lungs often are anatomically incomplete. Portions of the fissures occasionally are radiographically visualized as fine lines in healthy infants. The lungs are subdivided further into 8 to 10 segments on the left and 10 on the right, each served by a segmental bronchus (Figs. 48-7 and 48-8).^17–19

The trachea, which is the largest of the conducting airways, is a fibromuscular tube lined principally by ciliated columnar epithelium and mucous cells. The trachea is supported by 16 to 20 cartilaginous rings, which are incomplete posteriorly, where the tracheal wall is composed of fibrous, muscular, and elastic tissue. The trachea extends from the cricoid cartilage at the C4 level to the carina near the T4 level at birth and at a lower level with age. The right main bronchus originates from the trachea at an angle of 32 ± 5.5 degrees and the left at an angle of 51 ± 9.5 degrees from birth to 2 years of age. A tracheal cross-sectional area has been analyzed by computed tomography (CT) and grows predictably with age.20,21 The cross-sectional shape may vary considerably in the normal population and depending on the phase of respiration.²²

The bronchi are conducting airways that consist of the first 11 branching generations after the carina. The first four bronchial generations (through the segmental branches) are strongly supported by cartilaginous plates that aid in keeping the bronchi patent. The smaller cartilaginous bronchial branches, from the fifth to the eleventh generation, double in number with each branching generation and decrease in size down to approximately 1 mm in diameter (Fig. 48-9).²³ They are in a common fibrous sheath with an accompanying pulmonary arterial branch.

The bronchioles are the conducting airways that extend to the sixteenth generation and lack cartilage in their walls. They are dependent for their patency on the support of the surrounding lung parenchyma. As the lung expands, the bronchioles dilate. The last purely conducting branch of the airway is the terminal bronchiole, which gives rise to three generations of respiratory bronchioles, each giving rise to progressively greater numbers of alveoli. The alveoli and the alveolar ducts and sacs that give rise to them constitute the pure gas-exchange portion of the lung (see Fig. 48-9).

The Respiratory Portion of the Lungs

The number of alveoli rapidly increases after birth by a process of septation of the primary saccules distal to the terminal bronchioles. Most alveoli are formed in the first 2 years of life, and the process is complete by 8 years of age, after which the lungs continue to grow by enlarging the dimensions of all lung structures.

The two subunits of the peripheral airspaces that are most important to the radiologist are the acinus and the secondary lobule. The alveolus, which in an adult averages approximately 200 to 300 mm in diameter, is just below the limits of visibility. The acinus is the unit of lung peripheral to the terminal bronchiole and consists of a cluster of 50 to 400 alveoli. It occasionally is visible in the pediatric lung and typically ranges in diameter from 1 to 2 mm in infants younger than 1 year old to 7 to 9 mm in adolescents and adults (Fig. 48-10 and e-Fig. 48-11).²⁴

The secondary pulmonary lobule is a cluster of about 3 to 24 acini that are separated from other lobules by interlobular septa composed of fibrous tissue. The secondary lobules and their septa are much better developed in the periphery of the lung than in the center. The mean diameter of the secondary lobule at birth is 3 mm, and by 12 years it measures 15 mm (see e-Fig. 48-11).²⁴ The pulmonary veins and lymphatics course through the interlobular septa, and the PAs and bronchioles are positioned centrally within the lobule (see Fig. 48-10). Thickened septa are visible in chest radiographs as Kerley B lines and on high-resolution CT (Fig. 48-12).

Multiple imaging modalities have been used to determine prenatal and postnatal lung volumes and growth. Accurate prenatal lung volumetry is currently possible using three-dimensional ultrasonography25–27 and magnetic resonance imaging (MRI).^28,29 Total lung capacity and its subcomponents (i.e., tidal volume, vital capacity, functional residual capacity, and residual volume) increase with age. Linear or planometric measures from posteroanterior and lateral chest radiographs of children^30,31 obtained in inspiration may reliably estimate total lung capacity in children. In recent years, computerized automatic lung volume measurement tools available in most three-dimensional workstations can provide accurate volumetric measurement of lung volume from an axial CT dataset obtained with multidetector CT.^32–34

A study of 50 subjects (birth to 17 years) undergoing CT with carefully controlled breath holding found substantial variability in lung expansion between subjects, but the size of the airway wall and lumen, as well as arterial areas, were exponentially related to the subject’s height.³³ In a study of normal lung volume ranges as a function of age and sex in 1050 boys and girls with normal chest CT scans obtained during quiet breathing (e-Fig. 48-13), it was found that children younger than 8 years had a relatively narrow lung volume range.³² The ranges broadened considerably in older children, likely reflecting a considerable variation in response to breath-holding instructions. Mean CT density decreases with age and increases in an anterior to posterior gradient in a quietly breathing supine child.³⁵ Patient age, anterior versus posterior location, and apical versus basal location are significant predictors of regional lung density at inspiratory and expiratory volumes.³⁶

Collateral ventilation can occur across pulmonary segments because no pleurae separate them. It also may occur between lobes when fissures are incomplete. There are three routes of collateral ventilation: (1) alveolar pores of Kohn (2- to 10-mm circular apertures in the alveolar walls); (2) canals of Lambert (epithelial-lined tubular structures between preterminal, terminal, or respiratory bronchioles and the alveoli surrounding them); and (3) direct small airway anastomoses.¹⁸ Collateral ventilatory pathways are less well developed in young infants than in older children and adults.

Pulmonary Vasculature/Circulation

The lung has a dual blood supply consisting of a pulmonary arterial and a systemic arterial supply. The main PA arises from the right ventricle distal to the pulmonic valve and forms a segment of the left heart border before it bifurcates at the level of the carina. The left PA curves superiorly and posteriorly to the left hilum anterior to the left main bronchus, where it divides into two branches. The lower branch is directed posteriorly and crosses over the left upper lobe bronchus, descending parallel with but lateral to the left lower lobe bronchus. This vessel gives branches to the lingual segment, to the superior segment of the lower lobe, and to the basilar segments. The smaller superior branch divides, and its branches parallel the bronchial divisions to the upper lobe. The right PA is almost horizontal and divides into its two major branches while still within the pericardium. It lies posterior to the ascending aorta and SVC and anterior to the right main bronchus. The main upper lobe branch, the truncus anterior, ascends anterior to the right upper lobe bronchus and subdivides into three branches that parallel the three segmental bronchi to the right upper lobe. The largest branch of the right PA is the interlobar artery, which passes anterior to the bronchus intermedius and descends lateral to it, giving branches, in order, to the middle lobe, the superior segment of the lower lobe, and four branches to the basilar segments of the right lower lobe.

In the lung parenchyma, the pulmonary arterial branches travel and divide with the bronchial branches, although they also give off unaccompanied supernumerary branches. There are approximately 23 divisions of airway branching and approximately 28 divisions of pulmonary arterial branching. These vessels can be visualized on high-resolution CT to about the level of the sixteenth generation, which is a few millimeters from the pleural surface and corresponds to the level of the terminal bronchioles, allowing identification of the secondary pulmonary lobule (the parenchyma supplied by three to five or more terminal bronchioles). The arterioles continue to divide until they form a dense capillary network surrounding the alveolus. This network consists of 280 billion capillary segments with a total blood volume of 140 mL; pulmonary blood volume can nearly double during exercise.³⁷

The primary role of the pulmonary circulation is to transport deoxygenated blood from the heart to the alveolar capillaries, where oxygenation occurs, and then transport oxygenated blood through the pulmonary veins back to the left atrium. The pressure in the pulmonary circuit is about one sixth that of the systemic circuit; total pulmonary blood flow is determined primarily by cardiac output, although the control of pulmonary blood flow is complex and also depends on the relative systemic and pulmonary pressures, gravity, and local pulmonary factors. Large numbers of lung capillaries normally are not perfused or are only minimally perfused, which allows for increased arterial flow without increased pulmonary arterial pressure. Gravity is an important determinant of regional pulmonary blood flow, with the more dependent regions receiving a greater volume of blood. The smaller, muscular, pulmonary arterial branches vasoconstrict under conditions of hypoxia in an attempt to maintain the ventilation-perfusion balance. When lung disease becomes severe enough, this protective mechanism is overwhelmed, and poorly ventilated alveoli are perfused, which results in right-to-left shunting and systemic desaturation. Hypoxemia and accompanying acidosis increase pulmonary vascular resistance, which leads to right ventricular hypertrophy and eventually to cor pulmonale.

The vast pulmonary capillary bed serves the function of gas exchange. Its endothelial cell lining has important metabolic functions and is quite sensitive to toxins, including high oxygen concentrations. When endothelial cells are damaged, increased permeability pulmonary edema often results.

The pulmonary venous radicles arise distal to the capillary meshwork and travel in the interlobular septa, which form the walls of the secondary pulmonary lobules; the veins do not accompany the PA and bronchial branches. They drain toward the hilum and gradually increase in size. Usually two large pulmonary veins are found on each side. The upper lobe veins are more vertical in orientation, and the lower ones are more horizontal before they enter the left atrium. The right superior vein is located posterior to the SVC and anterior to the right interlobar PA. The left superior pulmonary vein is located anterior to the left main PA and is just anterior to the left upper lobe bronchus. The right inferior branch enters the left atrium anterior to the right lower lobe bronchus, and the left inferior pulmonary vein enters the left atrium at a point just anterior to the descending aorta and posterior to the left lower lobe bronchus.

The systemic circulation to the lung is via two to four (most commonly one right and two left) bronchial arteries that are branches of the thoracic aorta. These vessels provide nourishment to the airways and central mediastinum. In the presence of PA obstruction, collateral circulation to the pulmonary capillaries can develop through precapillary anastomotic channels.

Lymphatics

Pulmonary lymphatics are essential to removal of initial fetal lung liquid and to the removal of protein and water outside the vascular space.38,39 This fluid is returned to the circulation via the right lymphatic duct and the thoracic duct. Lymphatic vessels travel beside blood vessels in the bronchovascular spaces and in the connective tissues of the pleura. No lymphatics are present within the alveolar walls, but juxta-alveolar lymphatics represent the initial part of the lung lymphatic system. Enlargement of lymphatic channels in secondary lobular septa may be visualized on chest radiography and with CT (see Fig. 48-12).

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