Embryology

Although an intact pulmonary system is not required for intrauterine viability, the prenatal development of the respiratory system is integral to ex utero life and survival. To allow successful transition to neonatal life, fetal lungs must proceed through both structural and functional maturation processes, which occur from the early embryonic period and continue after birth. During structural development, there is branching of the airways and development of alveolar spaces, allowing gas exchange to occur once the first breath is taken at delivery. Functional development results in the creation of a surfactant system. This system is composed of phospholipids that decrease alveolar surface tension, inhibiting alveolar collapse during exhalation. The surfactant system develops in the third trimester and is typically mature at 36 weeks’ gestation. Birth prior to the development of the surfactant system or completed pulmonary development results in neonatal respiratory compromise.

The respiratory diverticulum (lung bud) appears as an outgrowth of the ventral wall of the foregut. The epithelium of the internal lining of the larynx, trachea, bronchi, and lungs is entirely of endodermal origin. The cartilaginous, smooth muscle, and connective tissues of the trachea and lungs are derived from splanchnic mesoderm that surrounds the tubular framework. The lung bud is in open communication with the foregut. The diverticulum develops in a craniocaudal direction, leading to development of the upper respiratory structures (nose and pharynx) prior to the lower structures. Two tracheoesophageal ridges separate the diverticulum from the foregut. The dorsal portion of the foregut divides into the esophagus and the ventral portion into the trachea and lung buds.

The pulmonary circulation is a highly specialized vascular network, connecting the interdependent heart and lungs ( Fig. 12-1 ). The vascular bed parallels the airways and links the arterial and venous poles of the heart. The pulmonary vasculature has been described as appearing de novo within the mesoderm ventral and lateral to the foregut endoderm, suggesting that this mesoderm pool gives rise to the future pulmonary vasculature as lung develops from the foregut. The lungs have two sets of lymphatic vessels, a superficial set located beneath the pleura and a deep set which follows the blood vessels and extends along the bronchi. Both sets end within the bronchial glands. Efferent lymphatic vessels travel up the trachea, ending at the left-sided thoracic duct or the right-sided lymphatic duct. The fetal lungs play a key role in amniotic fluid volume maintenance: 15 mL/kg of body weight in fluid is produced by the lungs and flows out via the trachea and mouth, circulating and contributing to the amniotic fluid that is swallowed.

The pulmonary circulation. The right and left pulmonary veins and arteries and the branching capillaries are illustrated.

(From Brashers VL: Structure and function of the pulmonary system. In McCance KL, Huether SE [eds]: Pathophysiology: The Biologic Basis for Disease in Adults and Children. St. Louis, Elsevier, Mosby, 2006.)

The basic structure of the diaphragm is also established early in gestation. Initially, the septum transversum develops, lying caudal to the heart and rostral to the umbilicus, in a position that eventually divides the intraembryonic cavity into the pleuropericardial cavity and the peritoneal cavity. The diaphragm subsequently undergoes programmed muscularization; this represents the final stage in the formation of the basic foundation of the diaphragm and is completed by 14 weeks’ gestation.

Fetal lung development occurs in five stages: embryonic, pseudoglandular, canalicular, saccular, and alveolar ( Fig. 12-2 ). The timing of these phases is approximate. Transitions between stages are gradual, with overlap from one stage to the next.

A, The five stages of normal fetal lung development. B, Histologic sections illustrating progressive stages of lung development. 1. Pseudoglandular period (about 8 weeks). 2. Late canalicular period (about 24 weeks). 3. Early terminal sac period (about 26 weeks). 4. Early alveolar period (newborn infant). Note that the alveolocapillary membrane is thin and that some of the capillaries have begun to bulge into the primordial alveoli.

(A from Pringle KC: Human fetal lung development and related animal models. Clin Obstet Gynecol 3:502, 1986; B from Moore KL, Persaud TVN, Shiota K [eds]: Color Atlas of Clinical Embryology, 2nd ed. Philadelphia, WB Saunders, 2000.)

Key Features for Assessment

Complete assessment of the thoracic structures includes evaluation of lung structure and appearance. The lung fields should appear homogeneous with no fluid collections present ( Fig. 12-3 ). The size of the thorax relative to the fetal abdomen and the overall chest size relative to the size of the heart structures are nonspecific but are important components of evaluation. The cardiac circumference should be approximately 50% of the thoracic circumference. When the heart is large relative to thoracic size, further evaluation will determine if the chest is too small (potential pulmonary hypoplasia) or whether cardiomegaly is present. Abnormal cardiac axis or abnormal position within the chest may be a marker for displacement by a chest mass or a missing portion of the lung. Any abnormal cardiac position should prompt thorough evaluation of the lung fields. In addition to the homogeneous appearance of lung fields, the echogenicity of the lungs should also be assessed, with normal echogenicity being slightly greater than that of the fetal liver.

Normal transaxial image of the fetal chest with four-chamber view of the heart. Normal cardiac position and axis. The bilateral lung tissue appears homogeneous.

Adequate evaluation of the diaphragm requires sweeping side to side to assess continuity of the structure. The diaphragm will appear echolucent on ultrasound images ( Fig. 12-4 ). Shadowing from the ribs may present a challenge to visualization of the entire diaphragm. Particular care should be taken to examine the posterolateral portions, where most defects will occur. It is important that diaphragm continuity is confirmed and not just assumed based on other organs that are not appreciated in the chest. The contour of the diaphragm should also be assessed, as some abnormalities may be associated with eversion of the diaphragm downward.

Sagittal section through the fetal chest showing the echolucent diaphragm ( arrow ). Note the convex shape of the diaphragm.

Pulmonary Hypoplasia

Pulmonary hypoplasia occurs as a spectrum characterized by incomplete development of unilateral or bilateral lung tissue. Clinically, it presents as respiratory compromise, with the severity reflecting the degree of reduction in lung size or in the number of lung cells, alveoli, or degree of bronchial branching. The severity is related to the timing of the insult in relation to the stage of embryologic development. Normal lung development requires adequate thoracic space as well as sufficient distention of the lungs through fluid exchange. Hypoplasia may therefore be caused by restriction or compression of developing fetal lung as well as by lack of amniotic fluid. Space-occupying lesions within the hemithorax, such as CDH, CPAM, massive cardiomegaly, and pleural effusion, can all cause pulmonary hypoplasia through mass effect, inhibiting normal formation of the pulmonary airways and alveoli. Thoracic musculoskeletal abnormalities, such as skeletal dysplasias and neuromuscular disorders, prohibit full expansion of the thoracic cage, with the restriction of chest size leading to hypoplasia. Additionally, oligohydramnios associated with renal or urinary tract abnormalities or preterm premature rupture of membranes during crucial embryologic stages reduces the development of normal pulmonary components. The mechanism by which lack of amniotic fluid inhibits lung growth is unknown. However, inhibition of fetal breathing movements or increased loss of fetal lung fluid into the amniotic space have been suggested as two possible mechanisms for pulmonary hypoplasia in the setting of oligohydramnios. The incidence of neonatal pulmonary hypoplasia with premature rupture of membranes between 18 and 26 weeks’ gestation ranges from 9% to 28%.

Although it is relatively uncommon, the high mortality rate associated with pulmonary hypoplasia makes prenatal prediction critical for appropriate counseling. Subjective ultrasound assessment of relative chest size is helpful only in extreme cases ( Fig. 12-5 ). Two-dimensional ultrasound measurements of fetal thoracic circumference, thoracic length, and the thoracic circumference to abdominal circumference (TC/AC) ratio have all been established ( Table 12-1 ) but also have limited predictive value except at the extremes. The use of the lung-to-head ratio (LHR) and lung volume measurements has been described more frequently with CDH (see later discussion under “ Congenital Diaphragmatic Hernia ”). Other methods, such as the quantitative lung index (QLI), have been employed in attempts to mathematically quantify lung volumes. This index, which is obtained by calculating lung area/(head circumference/10) , has been described as a calculation that is fetal age independent. It has been reported to have minimal variation throughout pregnancy, with near constant parameters. Recent studies have provided reference ranges for normal 20- to 36-week fetal lung areas and LHRs (using the longest diameter and area tracing methods). Unfortunately, these indirect measurements of lung volumes do not reliably and uniformly predict pulmonary hypoplasia, lung function, or likelihood of survival. The use of three-dimensional ultrasound to obtain volume measurements either directly or through the VOCAL technique (Virtual Organ Computer-Aided Analysis, General Electric Medical Systems) would seem more promising but have not been shown to be superior. MRI has also been used to calculate lung volumes ( Fig. 12-6 ). The risk for pulmonary hypoplasia is assessed by comparing lung volumes measured by MRI with normal reference values based on the gestational age. MRI has the advantage of more clearly delineating lung tissue from mediastinal structures and is not compromised by some of the limitations of ultrasound in the presence of oligohydramnios or high maternal body mass index (BMI). However, the ability of MRI to predict prognosis and survival has also been inconsistent, and the superiority of MRI in this regard remains controversial.

Axial view through the chest in a fetus with pulmonary hypoplasia. Note the heart occupying nearly the entire thorax.

Magnetic resonance imaging (MRI) obtained in a 29-year-old pregnant woman at 30 weeks’ gestation in whom detailed prenatal ultrasound depicted a normal fetal chest and fetal abdomen; MRI was performed because placenta accreta was suspected. Coronal single-shot rapid acquisition with relaxation enhancement (T2-weighted MR image 8/90, 4-mm section) of the fetal chest and fetal abdomen shows lungs ( arrows ) with high signal intensity. Use of this sequence facilitated easy identification of the lungs and planimetry.

(From Williams G, Coakley FV, Qayyum A, et al: Fetal relative lung volume: quantification by using prenatal MR imaging lung volumetry. Radiology 233:457, 2004.)

Pulmonary hypoplasia is associated with a need for prolonged respiratory support and can even result in infant death despite aggressive postnatal management. It is important to understand that neither sonography nor MRI uniformly predicts hypoplasia except in extreme cases. Despite the limitations, measurements obtained from both modalities may assist with predicted range of disease severity, allowing for appropriate counseling of families while sharing the limitations.

Congenital Pulmonary Airway Malformation

Fetal chest masses include CPAM (formerly referred to as congenital cystic adenomatoid malformation [CCAM]) and bronchopulmonary sequestration (BPS). CPAMs are the most common lung lesions identified by fetal ultrasound imaging. On occasion, hybrid lesions are found, with imaging and pathologic features of both CPAM and BPS. Historically, CPAMs were thought to be infrequent, with reported incidence between 1 in 25,000 and 1 in 35,000 live births. With ongoing improvements in ultrasound resolution, smaller CPAMs are now being diagnosed with increasing frequency, and the incidence of CPAM is now reported to be as high as 1 in 12,000 live births, accounting for 30% to 47% of fetal thoracic lung lesions. These lesions are most often unilateral (95%) and are rarely bilateral. The right and left lungs are involved with equal frequency, with the lower lobes more commonly affected. Current theories of pathogenesis suggest maturational arrest in bronchopulmonary development, resulting in dysplastic tissue distal to this segment.

CPAMs have best been described as hamartomatous malformations of the lung characterized by abnormal branching of immature bronchioles. They communicate with the normal tracheobronchial tree and derive their blood supply from normal pulmonary circulation. These lesions develop during the pseudoglandular period, at 7 to 16 weeks. Stocker and associates initially classified the most common types of CPAMs into three categories. Type 1 is described as a lesion with a dominant cyst (3-10 cm in diameter); type 2 comprises multiple small cysts (0.5-2.0 cm diameter) that are distributed evenly and blend in with adjacent normal tissue; and type 3 is the small microcyst or what appears to be solid type of cyst on sonographic images ( Fig. 12-7 ). Recently, Stocker added two subtypes: type 0 (acinar dysplasia) and type 4 (large peripheral cyst of the distal acinus lined with alveolar cells), expanding the classification of CPAMs into five subtypes. However, this categorization was intended to be applied to resected lung specimens, rather than sonographic diagnoses. As the various types of CPAMs have little clinical significance, and the size and presence of larger cysts have more prognostic importance, the most common current practice is to describe the CPAM lesion as microcystic or macrocystic and to report its size.

A, Macrocystic congenital pulmonary airway malformation, type 1, with several sizable cysts in the left-sided chest mass. B, Echogenic congenital pulmonary airway malformation, type 2, within the chest, displacing the heart. Small peripheral cysts are seen. C, Displacement of the fetal heart toward the right facilitates identification of homogeneous left-sided mass. The solid-appearing mass is consistent with congenital pulmonary airway malformation, type 3. No discrete cysts are seen. Small amount of normal-appearing lung is present on the right. LT, left thorax; RT, right thorax.

BPS describes a mass of nonfunctioning lung tissue that does not communicate with the bronchial tree. These lesions have aberrant systemic arterial blood supply (which is how they can be differentiated from CPAM), commonly arising from the descending thoracic aorta ( Fig. 12-8 ). BPS may be intralobar, with the same pleural covering as normal lung tissue, or extralobar, with a distinct and separate pleural covering. Almost all prenatally diagnosed cases of BPS are extralobar, above the diaphragm, and most frequently in the lower left side of the chest. Extralobar lesions may occur within the abdomen, appearing as echogenic masses below the diaphragm ( Fig. 12-9 ).

Axial ( A ) and coronal ( B ) views through the fetal chest with homogeneous left-sided mass consistent with bronchopulmonary sequestration (BPS). Note rightward cardiomediastinal shift. Color ( C ) and spectral ( D ) Doppler sonographic images of left-sided BPS demonstrating anomalous arterial supply to the lesion arising from the descending aorta.

Axial sonographic image through the fetal upper abdomen demonstrating a subdiaphragmatic sequestration.

The identification of CPAM is often aided by shift in the location or axis of the fetal heart. The affected lung tissue will appear to have increased echogenicity with possible presence of discrete cysts (see Fig. 12-7 ). Sometimes the increased echogenicity is confined to a single lobe of the lung, most often a lower lung field ( Fig. 12-10 ). Polyhydramnios may be seen in the later stages of pregnancy and might be a consequence of decreased swallowing of amniotic fluid owing to mass effect by the lesion resulting in esophageal compression or increased fluid production by the abnormal lung ( Fig. 12-11 ). With larger masses, there is a risk of fetal hydrops.

Homogeneous, echogenic chest mass shown in axial ( A ) and sagittal ( B ) views, consistent with type 3 congenital pulmonary airway malformation.

Fetus with homogeneous echogenic lung mass and polyhydramnios.

The overall prognosis for CPAM lesions has improved considerably, in part owing to the diagnosis of smaller lesions but also because of prenatal therapy for larger masses. For the individual patient, the natural history and prognosis depend primarily on the size of the lesion, the presence of mediastinal shift, and fetal hemodynamic alterations. The presence of hydrops without therapy is associated with a poor outcome and is generally an indication for fetal intervention.

Because the outcome of CPAM is most closely related to the size of the mass, attempts have been made to quantify lesion size to provide prognosis. The CVR is one approach used for risk assessment and patient counseling. The volume of the chest mass is calculated by multiplying the maximal length, width, and depth dimensions (in cm) of the lesion: craniocaudal × anteroposterior × mediolateral dimensions). This product (in cm ³ ) is then multiplied by a correction factor of 0.52, resulting in a calculated lesion volume (formula for determining volume of a prolate ellipsoid). Then, to control for gestational age, this estimated volume is divided by the fetal head circumference (in cm) ( Fig. 12-12 ):

Stay updated, free articles. Join our Telegram channel

Join