Thoracic Cavity

The thoracic cavity is encased by the thoracic walls and houses thoracic viscera (lungs, heart, esophagus, and trachea) and associated neurovascular structures. The space can be divided into two independent pleural cavities and a centralized mediastinum. Within the mediastinum is the pericardia! cavity, which contains the heart and roots of the great vessels. The thoracic cavity is partitioned off from the abdominal cavity by the muscular diaphragm.
A. Embryology
The intraembryonic coelom is a single continuous cavity that forms when spaces coalesce within the lateral mesoderm and form a horseshoe-shaped space that opens into the chorionic cavity (extraembryonic coelom) on the right and left sides. The intraembryonic coelom provides the needed room for the growth of various organs in the thorax and abdomen. The intraembryonic coelom gets partitioned during development into the definitive adult body cavities called the pleural cavity, pericardia! cavity, and peritoneal cavity (Fig. 1). How does the embryo divide one continuous cavity (i.e.,the intraembryonic coelom) into three separate adult cavities (i.e., pleural, pericardia!, and peritoneal)? The answer is that the embryo forms two partitions called the paired pleuropericardial membranes and the diaphragm.

Figure 1: Embryology of the body cavities and diaphragm. A, Formation of intraembryonic coelom. B, Formation of the pleuropericardial membranes. C, Formation of the diaphragm. A= aorta, E = esophagus, GI = gastrointestinal, IVG = inferior vena cava.
1. Paired pleuropericardial membranes: These sheets of somatic mesoderm separate the pericardia! cavity from the pleural cavities. These membranes develop into the definitive fibrous pericardium surrounding the heart.

2. Diaphragm: The diaphragm separates the pleural cavities from the peritoneal cavity.
a. Position: By week 8, an apparent descent of the diaphragm to L 1 occurs because of the rapid growth of the neural tube. The phrenic nerves are carried along with the "descending diaphragm," which explains their unusually long length in the adult.
b. Formation: The diaphragm is formed through the fusion of tissue from four different sources.
[1] Septum transversum: This thick mass of mesoderm is located between the primitive heart tube and the developing liver. The septum transversum is the primordium of the central tendon of the diaphragm in the adult.
[2] Paired pleuroperitoneal membranes: These appear to develop from the dorsal and dorsolateral body wall by an unknown mechanism.

[3] Dorsal mesentery of the esophagus: Invaded by myoblasts, this forms the crura of the diaphragm in the adult.
[4] Body wall: This contributes muscle to the peripheral portions of the definitive diaphragm.
B. Pleurae
The thoracic cavity houses a right and left pleural sac, each containing the right or left lung, respectively (Fig. 2). These pleural sacs are formed by a continuous serous membrane that lines either the inner surface of the thoracic cavity (parietal pleura) or the surface and fissures of the lung (visceral pleura).

Figure 2: Pleurae and pleural cavity. Layers of pleura lining lung (visceral) and thoracic cage (parietal) surfaces. Lower left corner illustrates the balloon analogy.

1. Anatomy: Pleural layers are continuous with one another at the root of the lungs, forming pleural reflections that assist in anchoring respiratory viscera. The space between the parietal and visceral pleura is the pleural cavity. This space contains a small amount of serous fluid to allow for smooth movement during respiration.
a. Parietal pleura: Parietal pleura is described based on the surface it is covering-costal, mediastinal, diaphragmatic, and cervical (around apex of lung). A thin layer of connective tissueendothoracic fascia-separates the costal parietal pleura from the internal surface of the thoracic cage (ribs and intercostal muscles).
b. Visceral pleura: Visceral pleura lines the lungs and follows lung fissures along their entirety.
c. Pleural recesses: These are spaces that occur at the limits of the pleural cavity where regions of parietal pleura are continuous.
The costodiaphragmatic recess is located where the inferior margin of the costal parietal pleura meets the outer margin of the diaphragmatic parietal pleura. The costomediastinal recess occurs where the anterior costal parietal pleura and mediastinal pleura meet. During inspiration and expiration, lung tissue moves in and out of these spaces. These spaces are clinically important, as they can be accessed without risk of lung tissue damage .
2. Vasculature: Arteries that supply the thoracic wall and diaphragm also supply the parietal pleurae, including intercostal, internal thoracic, and musculophrenic arteries. Venous drainage of parietal pleurae occurs by way of veins that accompany the above arteries. Visceral pleura is supplied by bronchial arteries; however, venous return occurs by way of pulmonary veins rather than bronchial veins. This small amount of deoxygenated blood has no effect on the oxygenated pulmonary blood returning to the heart.
3. Innervation: Sensory innervation from parietal pleurae is mediated by the phrenic (diaphragmatic part) and intercostal nerves. Parietal pleura is pain sensitive, often referring pain over intercostal spaces proximal to the injury. Sensory innervation from visceral pleura is mediated by sympathetic and parasympathetic autonomic (general visceral afferent [GVA]) fibers of the pulmonary plexus. Visceral pleura is pain insensitive.
4. Lymphatics: Lymph from parietal pleurae drains into thoracic wall nodes, including intercostal, mediastinal, parasternal, and phrenic. Lymph from visceral pleura drains into the superficial lymphatic plexus just deep to the visceral pleura. Lymph then travels to bronchopulmonary nodes in the lung hilum before draining into tracheobronchial lymph nodes at the tracheal bifurcation. 
C. Trachea and lungs
Lungs are the main respiratory viscera, responsible for oxygenation of blood at the interface of alveoli and pulmonary capillaries. Each lung (right and left) is contained within a pleural sac. These sacs are separated from each other by the mediastinum and, therefore, do not communicate. Although the respiratory tract begins in the head, it continues into the thoracic cavity as the trachea and bronchial tree associated with each lung.
1. Embryology: The respiratory diverticulum initially is in open communication with the foregut, which means that the respiratory system and the digestive system are in open communication in early embryologic development. This open communication is closed off by indentations of visceral mesoderm called the tracheoesophageal folds. When the tracheoesophageal folds fuse in the midline to form the tracheoesophageal septum, the foregut is divided into the trachea anteriorly and esophagus posteriorly.
a. Respiratory diverticulum: During week 4, the respiratory diverticulum, which consists of endoderm, forms in the anterior wall (or floor) of the primitive foregut and is the first sign in the development of the respiratory system (Fig. 3). The respiratory diverticulum protrudes into the surrounding visceral mesoderm. The distal end of the respiratory diverticulum enlarges to form the lung bud, which is also surrounded by visceral mesoderm. The lung bud divides into two bronchial buds that are also surrounded by visceral mesoderm. The bronchial buds branch into airway channels that progressively decrease in size.

Figure 3: Embryologic formation of the respiratory system. A-C, Relationship between developing trachea and esophagus. D-G, Stages of lung development.

These airway channels include the main (primary), lobar (secondary), segmental (tertiary), subsegmental bronchi, and all the smaller airway channels. This means that the respiratory system forms from both endoderm and mesoderm.
b. Trachea: The epithelium that lines the trachea and the tracheal glands are derived from endoderm associated with the foregut. The tracheal smooth muscle, connective tissue, and C-shaped cartilage rings are derived from the surrounding visceral mesoderm.
c. Bronchi: In week 5, the bronchial buds enlarge to form the main (primary) bronchi. These subdivide into lobar (secondary) bronchi {three on the right side and two on the left side, corresponding to the lobes of the adult lung). The lobar bronchi further subdivide into segmental (tertiary) bronchi (10 on the right side and 9 on the left side), which further subdivide into subsegmental bronchi. The segmental bronchi are the primordia of the bronchopulmonary segments, which are morphologically and functionally separate respiratory units of the lung. The bronchial epithelium and glands are derived from endoderm. The bronchial smooth muscle, connective tissue, and cartilage are derived from visceral mesoderm.
d. Primitive pleural cavity: As the bronchi continue to grow and develop, the lungs expand laterally and caudally into a space known as the primitive pleural cavity. The visceral mesoderm covering the outside of the lungs develops into visceral pleura, and the somatic mesoderm covering the inside of the body wall develops into parietal pleura. The space between the visceral and parietal pleura is called the pleural cavity.

e. Lungs: The fetal and postnatal development of the lungs is divided into four periods.

[1] Pseudoglandular period (weeks 7-16): During this period, the developing lung resembles an exocrine gland. The numerous endodermal tubules are lined by simple columnar epithelium and are surrounded by visceral mesoderm containing a modest capillary network. Each endodermal tubule branches into a number of terminal bronchioles. At this point, respiration is not possible, and premature infants cannot survive.
[2] Canalicular period (weeks 16-24): During this period, the terminal bronchioles branch into a number of respiratory bronchioles that subsequently branch into a number of alveolar ducts. The terminal bronchioles, respiratory bronchioles, and alveolar ducts are now lined by a simple cuboidal epithelium and are surrounded by visceral mesoderm containing a prominent capillary network. Premature infants born before week 20 rarely survive.
[3] Terminal sac period (weeks 24 to birth): During this period, terminal sacs bud off the alveolar ducts and then dilate and expand into the surrounding mesoderm. The terminal sacs are separated from each other by connective tissue called primary septa. The simple cuboidal epithelium within the terminal sacs differentiates into type I pneumocytes (thin, flat cells that make up part of the blood-air barrier) and type II pneumocytes (which produce surfactant). The terminal sacs are surrounded by mesoderm containing a rapidly proliferating capillary network. The capillaries make intimate contact with the terminal sacs and thereby establish a blood-air barrier with the type I pneumocytes. Premature infants born between week 25 and week 28 can survive with intensive care.

[4] Alveolar period (week 32-8 years of age): During this period, terminal sacs are partitioned by connective tissue called secondary septa to form adult alveoli. About 20-70 million alveoli are present at birth. About 300-400 million alveoli are present by age 8 years. The major mechanism for the increase in the number of alveoli is formation of secondary septa that partition existing alveoli. After birth, the increase in the size of the lung is due to an increase in the number of respiratory bronchioles.
2. Lung anatomy: The lungs are housed in the thorax, each within a separate pleural sac. Recall that visceral pleura covers the external surface of the lung, including into the fissures.
a. Common features: In general, each lung has the following features (Fig. 4).

Figure 4: Lung features. A, In situ with mediastinal structures. B, Cadaveric specimens (lungs removed from body). A = anterior, LBCV = left brachiocephalic vein, SVC = superior vena cava, T = trachea, P = posterior.

[1] Surfaces: Each lung has a costal, mediastinal, and diaphragmatic (base) surface.
[2] Borders: Each lung has an anterior, inferior, and posterior border.
[3] Apex: The superior portion of each lung extends into the root of the neck, forming the apex.
[4] Hilum: This is the medial point of entry/exit for bronchi, vessels, and nerves (Fig. 5).
[5] Root: The root of each lung is a collection of structures entering/exiting the lung at the hilum. It is the structural junction of visceral and parietal pleurae.
b. Unique features: Separately, the right and left lungs have the following unique features (Fig. 6).

Figure 5: Hilum of lungs and impressions.

Figure 6: Bronchopulmonary segments. Segments indicated by lines within each lobe. Pink = upper lobes, yellow = middle lobe, blue = lower lobes, LLL = left lower lobe, LUL = left upper lobe, RLL = right lower lobe, RML = right middle lobe, RUL = right upper lobe.
[1] Right lung: The right lung has three lobes: superior, inferior, and middle. It has two fissures-horizontal and oblique. Impressions of the right lung include cardiac, superior vena cava (SVC), arch of the azygos vein, azygos vein, and the esophagus.
[2] Left lung: The left lung has just two lobes, superior and inferior, and one oblique fissure. Its impressions are cardiac,arch of the aorta, and the descending aorta. The left lung also has two notches, a cardiac notch and a lingual notch (homologue to middle right lobe).

3. Tracheal and bronchial tree anatomy: The trachea begins in the neck at the inferior boundary of the larynx and extends into the thorax anterior to the esophagus, through the superior thoracic aperture (Fig. 7). The skeleton of the trachea is composed of C-shaped cartilaginous rings that are open posteriorly, maintaining patency while permitting some flexibility.
a. Primary bronchi: At the sternal angle, the trachea bifurcates into right and left primary (main) bronchi (see Fig. 7). The right primary bronchus is oriented in a more vertical position and is wider and shorter than the left. The left primary bronchus passes anterior to the esophagus and inferior to the aortic arch in a more horizontal orientation. Primary bronchi enter their respective lungs at the hilum, along with pulmonary arteries and veins, lymphatic vessels, and bronchial arteries. The carina is a ridge of cartilage that serves as an important visual landmark at the tracheal bifurcation.

Figure 7: Trachea and bronchial tree. A, Distal trachea and bronchial tree. B, Cadaveric specimen of trachea and primary bronchi.
b. Secondary and tertiary bronchi and terminal bronchioles: Branching of the bronchial tree continues at the hilum of the lung. Primary bronchi divide into multiple secondary {lobar) bronchi corresponding to the number of lobes-three on the right, two on the left. Branching continues into tertiary (segmental) bronchi to supply each bronchopulmonary segment and continues down to the level of terminal bronchioles.
4. Vasculature: The lungs receive poorly oxygenated blood from two large pulmonary arteries that arise from the pulmonary trunk (Fig. 8). Pulmonary arteries are contained within the root of the lung and branch into lobar and segmental arteries, traveling adjacent to bronchial tree branches. Paired pulmonary veins (superior and inferior) carry oxygen-rich blood from each lung to the left atrium of the heart. These veins originate at the capillary level and join to eventually form intersegmental veins that unite to form the pulmonary veins. Bronchial arteries supply lung parenchyma and root structures, while bronchial veins drain the structures supplied by the bronchial arteries near the root of the lung. The remaining deoxygenated blood is removed by the pulmonary veins.

Figure 8: Respiratory blood supply. Pulmonary and segmental vessels.

5. Innervation: Respiratory structures receive autonomic innervation (general visceral efferent, GVA) from the pulmonary plexus (Fig. 9). This plexus lies anterior and posterior to the root of each lung. The anterior pulmonary plexus is located anterior to the tracheal bifurcation and is continuous with the deep cardiac plexus anteriorly and the posterior pulmonary plexus posteriorly. Sympathetic and parasympathetic fibers contribute to the formation of the pulmonary plexus.

Figure 9: Pulmonary plexus. Autonomic innervation of respiratory structures.

a. Sympathetic fibers: Postganglionic fibers arise from the cardiac plexus and thoracic sympathetic trunk ganglia (T1-T6). Sympathetic stimulation causes bronchodilation and decreased mucous secretions.
b. Parasympathetic fibers: Preganglionic fibers arise from the cardiac plexus and direct branches of the right and left vagus nerves (cranial nerve X). Parasympathetic stimulation causes bronchoconstriction and increased mucous secretions. Postganglionic parasympathetic neurons are in the walls of the viscera.
6. Lymphatics: The lymphatics of the lung are clinically important in terms of lung cancer metastasis (Fig. 10). The lymphatic system in the lung is divided into continuous superficial and deep plexuses.

Figure 10: Lymphatic drainage of lungs.
a. Superficial plexus: The superficial plexus lies deep to visceral pleura. It drains lung parenchyma and visceral pleura first into bronchopulmonary lymph nodes at the hilum of the lung.
b. Deep plexus: The deep plexus is located in submucosa of bronchi and surrounding connective tissue. It drains primarily lung root structures first through pulmonary lymph nodes before draining into bronchopulmonary lymph nodes.
c. Lymph flow: Lymph from bronchopulmonary lymph nodes drains to superior and inferior tracheobronchial lymph nodes situated around the tracheal bifurcation. Lymphatic vessels coalesce into right and left bronchomediastinal trunks that ultimately drain into the venous system at the junction between subclavian and jugular veins (venous angle).

7. Tracheal histology: The trachea is organized into a mucosa, submucosa, and adventitia (Fig. 11).

Figure 11: Histology of the respiratory system. A, Trachea. B, Bronchus. C, Respiratory epithelium. D, Bronchiole. E, Cystic fibrosis. Plain film radiograph shows hyperinflation bilaterally, reduced heart size due to pulmonary compression, cyst formation, and atelectasis (collapsed alveoli) bilaterally.
a. Mucosa: The mucosa of the trachea consists of an epithelium and the lamina propria. The epithelium is a pseudostratified ciliated columnar epithelium and, for simplicity, is generally called respiratory epithelium. The lamina propria of the trachea consists of loose connective tissue with collagen and elastic fibers and diffuse lymphatic tissue referred to as bronchusassociated lymphatic tissue (BALT).

b. Submucosa: The submucosa of the trachea consists of loose connective tissue with collagen and elastic fibers, seromucous glands, and BALT.
c. Adventitia: The adventitia of the trachea consists of dense, irregular connective tissue with collagen and elastic fibers, C-shaped hyaline cartilage rings, and the trachealis muscle (smooth muscle) that spans the dorsal ends of the C-shaped cartilage rings.
8. Bronchial histology: A bronchus is organized into a mucosa, smooth muscle layer, submucosa, and adventitia.
a. Mucosa: The mucosa of a bronchus consists of an epithelium and the lamina propria. The epithelium is a pseudostratified ciliated columnar epithelium and, for simplicity, is generally called respiratory epithelium. The lamina propria of a bronchus consists of loose connective tissue with collagen and elastic fibers and BALT.

b. Smooth muscle layer: The smooth muscle layer of a bronchus consists of a prominent circular layer of smooth muscle. The submucosa of a bronchus consists of loose connective tissue with collagen and elastic fibers, seromucous glands, and BALT.
c. Adventitia: The adventitia of a bronchus consists of dense, irregular connective tissue with collagen and elastic fibers and discontinuous plates of hyaline cartilage.
9. Bronchiole histology: A bronchiole is organized into a mucosa and a smooth muscle layer.
a. Mucosa: The mucosa of a bronchiole consists of an epithelium and the lamina propria. The epithelium in a large bronchiole is a simple ciliated columnar epithelium with goblet cells. The lamina propria of a bronchiole consists of loose connective tissue with collagen and elastic fibers and BALT.

b. Smooth muscle layer: The smooth muscle layer of a bronchiole consists of a prominent circular layer of smooth muscle.

10. Terminal and respiratory bronchiole histology: Both terminal and respiratory bronchioles are organized into a mucosa and a smooth muscle layer (Fig. 12).

Figure 12: Histology of the respiratory system. Terminal bronchiole, respiratory bronchiole, and alveolar duct.
a. Mucosa: The mucosa consists of an epithelium and lamina propria. The epithelium is a simple ciliated cuboidal epithelium with Clara cells. The lamina propria consists of loose connective tissue with collagen and elastic fibers.
b. Smooth muscle layer: The smooth muscle layer consists of an incomplete circular layer of smooth muscle.

11. Alveolar duct histology: An alveolar duct is organized into a mucosa and a smooth muscle layer. The mucosa of an alveolar duct consists of an epithelium and lamina propria. The epithelium of an alveolar duct is a simple squamous epithelium. The lamina propria of an alveolar duct consists of loose connective tissue with collagen and elastic fibers.
The smooth muscle layer of an alveolar duct consists of smooth muscle "knobs" because numerous alveoli perforate its wall.

12. Alveolar histology: An alveolus is organized into a mucosa only (Fig. 13). The mucosa of an alveolus consists of an epithelium and the lamina propria. The epithelium of an alveolus is composed of a type I pneumocyte, type II pneumocyte, and an alveolar macrophage. The lamina propria of an alveolus consists of loose connective tissue with collagen and elastic fibers that comprises the alveolar septum.

Figure 13: Histology of the respiratory system. A, Alveolus. B, Alveolar macrophage. C, Collagen fibers. D, Elastin fibers.

a. Type I pneumocyte: The type I pneumocyte is a simple squamous epithelial cell that lines the alveolus. It has no mitotic capacity. Adjacent type I pneumocytes are joined by zonula occludens (tight junctions).
b. Type II pneumocyte: The type II pneumocyte is a cuboidal-shaped cell with a round-shaped nucleus. Its cytoplasm contains rough endoplasmic reticulum, polyribosomes, a Golgi complex, smooth endoplasmic reticulum, mitochondria, and distinctive lamellar bodies that store surfactant. Type II pneumocytes have a high mitotic capacity, thereby functioning as stem cells to regenerate the alveolar lining. Hyperplasia of type II pneumocytes is an important marker of alveolar injury and repair of alveoli. Type II pneumocytes secrete surfactant.

c. Alveolar macrophage: Alveolar macrophages are found within the alveolar septum or within the alveolus where they phagocytize inhaled dust, bacteria (e.g., Mycobacterium tuberculosis), degraded surfactant, or red blood cells that may enter the alveolus in heart failure (i.e., hemosiderin-laden "heart failure cells"). Alveolar macrophages within alveoli may pass upward along the bronchial tree toward the pharynx where they are expectorated or swallowed.
d. Blood-air barrier: This is where diffusion of 0 2 and CO2 occurs (Fig. 14). The components of the blood-air barrier include surfactant, type I pneumocyte cytoplasm, basal lamina, and endothelium cytoplasm lining a continuous capillary.

Figure 14: Histology of the respiratory system. Blood-air barrier.

D. Mediastinum
As shown in Figure 15, the mediastinum lies centrally in the thoracic cavity, between the two pleural cavities (lateral), the sternum and thoracic vertebral bodies (anterior/posterior), and the superior thoracic aperture and diaphragm (superior/inferior). The mediastinum contains thoracic viscera and associated neurovascular and lymphatic structures, except for the lungs. For descriptive purposes, this region is divided into superior and inferior compartments. The inferior mediastinum is further divided into anterior, middle, and posterior sections. As previously mentioned, the sternal angle is a palpable landmark on the anterior thoracic wall, marking the junction between the manubrium and body of the sternum. This junction also marks the imaginary dividing line between the superior and inferior mediastinal compartments.

Figure 15: Mediastinum. A, Division between superior and inferior mediastinal
compartments at sternal angle. B, Mediastinal subdivisions. IVC = inferior vena cava; red= posterior, yellow= middle, blue = anterior, brown = superior.
1. Superior mediastinum: The superior mediastinum extends from the superior thoracic aperture to the imaginary horizontal plane between the sternal angle and T4/T5 intervertebral disc (Figs. 16 and 17). The superior mediastinum is continuous with the retropharyngeal space of the neck. The contents of the superior mediastinum are as follows:
a. Thymus: This lymphoid gland is typically more prominent in children.
b. Brachiocephalic veins (right and left): These are formed by the junction of Internal jugular and subclavian veins on the right and left sides.
c. Superior vena cava: The SVC is formed by the junction of right and left brachiocephalic veins and delivers blood to the right atrium.
d. Arch of the azygos vein: The SVC receives the arch of the azygos vein.
e. Aortic arch with branches (brachiocephalic trunk, left common carotid, left subclavian arteries): Aortic arch branches supply head, neck and upper limbs structures. The obliterated ductus arteriosus (ligamentous arteriosus) connects the inferior surface of the arch to the superior surface of the pulmonary trunk and is closely associated with the left recurrent branch of the vagus nerve.
f. Vagus nerve: These pass posterior to the root of each lung, and right and left recurrent branches are found just inferior to the right subclavian artery and arch of the aorta, respectively. This inconsistency is due to changes that occur during embryologic
development of major vessels.

Figure 16: Superior mediastinum (with heart/lungs). Cadaveric specimen. BCA = brachiocephalic artery, LBCV = left brachiocephalic vein.

Figure 17 : Superior mediastinum (heart/lungs removed). SVC = superior vena cava.
g. Phrenic nerves (C3-C5): These pass anterior to the root of each lung.
h. Trachea: The trachea extends into the thorax from the neck through the superior thoracic aperture, just anterior to the esophagus.
i. Esophagus: The esophagus is located posterior to the trachea and anterior to thoracic vertebral bodies.
j. Thoracic duct: This large lymphatic vessel lies between the esophagus and left vagus nerve ("duck between two gooses").

2. Inferior mediastinum: The inferior mediastinum extends from the imaginary horizontal plane between the sternal angle and T4/T5 intervertebral disc inferiorly to the superior surface of the diaphragm. It is subdivided into anterior, middle, and posterior mediastinal regions.
a. Anterior: The smallest of the inferior compartments sits just posterior to the body of the sternum, anterior to the pericardia! cavity. In children, the thymus extends into this compartment. The internal thoracic vessels are the main contents of the anterior mediastinum.
b. Middle: This compartment contains the pericardium, heart, and roots of the great vessels entering/leaving the heart (Fig. 18). c. Posterior: This compartment lies posterior to the pericardia! cavity and anterior to the thoracic vertebral bodies T5-T12 (Fig. 19). The posterior mediastinum is continuous with the superior mediastinum and contains the following.

Figure 18: Middle mediastinum, including heart wall and pericardium layers.

Figure 19:Posterior mediastinum. A, Blue-dotted line indicates upper limit of posterior mediastinum. Esophagus removed. B, Cadaveric specimen showing mediastinal (*) and posterior thoracic wall structures.
[1] Esophagus: The esophagus travels posterior to the pericardia sac to reach the abdomen through the diaphragm at T10 vertebral level (Fig. 20). The esophagus receives postganglionic sympathetic innervation from thoracic levels along its course and preganglionic parasympathetic innervation from vagus nerves.

Figure 20: Esophageal plexus. Esophagus and aorta pass through diaphragm at indicated vertebral levels.
[2] Azygos venous system: The azygos vein receives posterior intercostal veins to drain the right posterior thoracic wall. On the left, the accessory hemiazygos and hemiazygos veins receive tributaries from the left upper and middle portions of the posterior thoracic wall, respectively. Venous blood from the left side typically crosses to reach the azygos vein at vertebral levels TB and T9.
[3] Descending aorta: This gives off posterior intercostal arteries and travels through the aortic hiatus in the diaphragm at vertebral level T12 to enter the abdomen.
[4] Thoracic duct: This receives lymph at the level of the diaphragm from the cisterna chyli.
[5] Vagus nerves: Right and left vagus nerves travel posterior to the root of the lungs, giving off branches to the cardiac and pulmonary plexuses . Right and left vagus nerves become plexiform at the mid to lower esophagus before reconjoining to form the anterior (left vagus nerve) and posterior (right vagus nerve) trunks. The transition of right and left vagus nerves into posterior and anterior vagal trunks, respectively, occurs as a result of foregut rotation during development. Vagal trunks travel with the esophagus through the diaphragm to enter the abdominal cavity.
[6] Splanchnic nerves: Thoracic splanchnic nerves are preganglionic sympathetic nerves that arise from spinal levels T6-T9 (greater splanchnic nerve), T10-T11 (lesser splanchnic nerve), and T12 (least splanchnic nerve). Thoracic splanchnic nerves provide sympathetic innervation to abdominal viscera and vasculature.

3. Adjacent structures: Select structures in the thoracic cavity are not contained within the mediastinum. For example, the phrenic nerves and pericardiacophrenic vessels run along between the mediastinal pleurae and pericardium; however, they are not considered a part of the middle mediastinum. The IVC enters the thoracic cavity through the diaphragm (at the TB level) to join the right atrium of the heart, but it is not considered in the middle mediastinum.
Finally, the thoracic sympathetic trunks lie on either side of the thoracic vertebral bodies and are, therefore, outside the posterior mediastinal boundary. However, the splanchnic nerves that arise from the sympathetic trunks course anteriorly over the vertebral bodies of T5-T12; thus, these nervous structures are contained within the posterior mediastinum.
E. Heart
As previously mentioned, the heart and the roots of its great vessels are contained within a pericardia! sac in the middle mediastinum. The heart is the principle cardiac organ that functions to circulate deoxygenated blood to the lungs and oxygenated blood throughout the body. The heart develops from a single heart tube before transitioning into a four-chambered organ, consisting of right and left atria and ventricles.
1. Embryology: The heart is the first organ to function, beginning to beat at day 21 and beginning to pump blood at day 25. Conceding that the embryologic formation of the heart is extremely complex, we can establish a basic understanding of heart formation by addressing the following three key formation events.
a. Formation of the heart tube: During gastrulation, precardiac mesoderm emerges from the upper third of the primitive streak and migrates in a cranial-lateral direction (Fig. 21). The precardiac mesoderm becomes localized to the lateral plate mesoderm in the cranial region on both sides of the embryo and extends across the midline forming a crescent-shaped area.

Figure 21: Heart tube formation. A, Dorsal view. Band C. Sagittal views. D-G. Cross-sectional views. HFRs = heart-forming regions, VEGF = vascular endothelial growth factor.
[1] Pericardia! cavity and heart-forming regions: The lateral plate mesoderm located in the cranial region of the embryo splits into a somatic layer and splanchnic layer, thus forming the pericardia! cavity. The precardiac mesoderm preferentially migrates into the splanchnic layer and forms the heart-forming regions (HFRs). As lateral folding of the embryo occurs, the HFRs and the pericardia! cavities fuse in the midline and form a continuous sheet of mesoderm surrounded by a single pericardia cavity.
[2] Endocardium, myocardium, and epicardium: Hypertrophied foregut endoderm secretes vascular endothelial growth factor, which induces the sheet of mesoderm to form discontinuous vascular channels that remodel into a single endocardial tube (i.e., the endocardium). The mesoderm that surrounds the endocardium forms the myocardium, which secretes a layer of extracellular matrix proteins called the cardiac jelly. The mesoderm that lines the coelomic wall near the liver migrates into the cardiac region and forms the epicardium.
b. Formation of the heart dilations and dextral looping: The five dilations that form along the length of the heart tube are called the: 1) truncus arteriosus, 2) bulbus cordis, 3) primitive ventricle, 4) primitive atrium, and 5) sinus venosus (Fig. 22).

Figure 22: Dilations and dextral looping. A, Coronal view. B, Adult derivative table. C, Dextral looping. D, Final adult placement of primitive atria and ventricles (no partitioning). AS = aortic sac, p = primitive.
These five dilations will eventually develop into the adult structures of the heart. In addition, dextral looping (i.e., bending to the right side) occurs concurrently as the dilations form, which brings the presumptive chambers of the future heart into their correct spatial relationship to each other.
c. Formation of the heart septa: By day 28, dextral looping is complete, and the heart is a one-chambered structure (i.e., if you cut the heart open, the lumen is one continuous space). The puzzle the embryo now needs to solve is how to partition one continuous space (i.e., a one-chambered heart) into four separate spaces (i.e., a four-chambered heart). The answer to the puzzle is the formation of four heart septa.
[1] Atrioventricular septum: The atrioventricular (AV) septum begins to form when the dorsal AV cushion and the ventral AV cushion enlarge and approach each other due to a proliferation of cells within the endocardium (Fig. 23).

Figure 23 : Atrioventricular (AV) septum formation (A-C).
The dorsal AV cushion and the ventral AV cushion eventually fuse with each other in the center of the heart to form the AV septum. The AV septum partitions the AV canal into the right AV canal and the left AV canal. The AV septum is important because the other three septa grow toward and fuse with the AV septum.
[2] Atrial septum: As shown in Figure 24, the atrial septum begins to form when the crescent-shaped septum primum develops in the roof of the primitive atrium and grows toward the AV cushions (or the future AV septum). The foramen primum (first opening) is located between the free edge of the septum prim um and the AV cushions and eventually closes when the septum prim um fuses with the AV cushions.
As the septum primum fuses with the AV cushions, small perforations in upper portion of the septum prim um coalesce to form the foramen secundum (second opening). A second crescent-shaped septum secundum develops in the roof of the primitive atrium to the right side of the septum prim um and also grows toward the AV cushions. The foramen ovale  (i.e., the opening in the septum secundum) is located in the lower portion of the septum secundum. Later in life, the septum primum and septum secundum anatomically fuse to complete the formation of the atrial septum and to obliterate the foramen ovale and foramen secundum. The fused portion of the septum is called the fossa ovale.

Figure 24 : Atrial septum formation (A-F). AV = atrioventricular.
[3] lnterventricular septum: As shown in Figure 25, the interventricular (IV) septum begins to form when the muscular IV septum develops in the floor of the primitive ventricle and grows toward the AV cushions (or the future AV septum).
The IV foramen is located between the free edge of the muscular IV septum and the AV cushions and allows for communication between the right ventricle and left ventricle.

Figure 25 :lnterventricular (IV) septum formation (A and B).
The IV foramen is closed by the membranous IV septum, which forms by the proliferation and fusion of tissue from the right and left bulbar ridges and the AV cushions.

[4] Aorticopulmonary septum: The aorticopulmonary (AP) septum begins to form when the truncal ridges (within the truncus arteriosus) and the bulbar ridges (within the bulbus cordis) develop due to a proliferation of cells within the endocardium (Fig. 26). Later, neural crest cells from the hindbrain region migrate into the truncal and bulbar ridges so that the ridges enlarge and approach each other. As the ridges do so, they twist around each other in a spiral manner and fuse to form the AP septum. The AP septum divides the truncus arteriosus and bulbus cordis (or the outflow tract) into the aorta and pulmonary trunk.

Figure 26: Aorticopulmonary (AP) septum formation (A-C).
d. Circulatory system: With a foundational understanding of the complexities of heart development, the nuances of fetal versus newborn circulation can be described. Fetal heart structures described above allow maternal blood to bypass developing fetal viscera (lungs and liver) in order to provide appropriate nutrients for growth in utero. Following birth, these fetal structures change to permit oxygenation and filtering of blood by the lungs and liver, respectively. Pulmonary trunk
[1] Fetal circulation: As shown in Figure 27, highly oxygenated and nutrient-enriched blood from the mother is distributed to the fetus from the placenta via the left umbilical vein. [Note: Highly oxygenated blood is carried by the left umbilical vein, not by an artery]. From the left umbilical vein, blood enters the liver, where most of the blood bypasses the hepatic sinusoids by coursing through the ductus venosus to enter the IVC. From the IVC, blood enters the right atrium, where most of the blood bypasses the right ventricle by coursing through the fora men ovale to enter the left atrium. From the left atrium, blood enters the left ventricle and is delivered to fetal tissues via the aorta. Poorly oxygenated and nutrientpoor fetal blood returns to the placenta via right and left umbilical arteries. Although most of the blood bypasses the right ventricle, some blood does enter the right ventricle.

Figure 27: Fetal circulation. A, Magnification of placental structures and arrangement. B, Circulatory anatomy of the fetus. Arrows indicate direction of blood flow between placenta and fetus.
The blood in the right ventricle enters the pulmonary trunk, but most of the blood bypasses the fetal lungs by coursing through the ductus arteriosus.

[2] Newborn circulation: The circulatory changes that occur at birth are facilitated by a decrease in right atrial pressure due  to occlusion of placental circulation and by an increase in left atrial pressure due to increased pulmonary venous return.
The circulatory changes include closure and formation of adult remnants of the following: left umbilical vein (/igamentum teres), ductus venosus (ligamentum venosum), foramen ovale (fossa ovate), right and left umbilical arteries (medial umbilical ligaments), and the ductus arteriosus Vigamentum arteriosum).
2. Anatomy: The heart is contained within a fibrous pericardia sac. a. Pericardium: The fibrous pericardium is continuous with the covering of the great vessel roots superiorly and is anchored inferiority to the central tendon of the diaphragm .
Mediastinal pleura covers the lateral outer surfaces of the fibrous sac, along with varying amounts of adipose. The phrenic nerves and pericardiacophrenic vessels course anterior to the root of the lung within the adipose and parietal pleura on way to the diaphragm. The inner surface of the fibrous pericardia sac is covered with a parietal serous pericardium, while a visceral serous pericardia! layer covers the heart's surface. The pericardia cavity is a potential space that occurs between these two serous layers and contains a small amount of serous fluid.

[1] Sinuses: At two locations, reflections of visceral serous pericardium are continuous with the parietal serous pericardium (Fig. 28). These reflections create sinuses. The transverse pericardia! sinus occurs where the aorta and pulmonary trunk emerge from the heart and is located posterior to these vessels and anterior to the SVC. The oblique pericardia sinus occurs posterior to the heart where the SVC, IVC, and pulmonary veins enter the heart.

Figure 29 :Pericardia! sinuses. Heart removed. IVC = inferior vena cava, LIPV = left inferior pulmonary vein, LPA = left pulmonary artery, LSPV = left superior pulmonary vein, RIPV = right inferior pulmonary vein, RPA = right pulmonary artery, RSPV = right superior pulmonary vein, SVC = superior vena cava.

[2] Blood supply: The pericardium receives blood supply mainly from pericardiacophrenic and musculophrenic arteries. Azygos and internal thoracic vein tributaries control venous return. It is innervated by the phrenic nerve and branches of the cardiac plexus, although the visceral serous pericardium is pain insensitive.
b. External features: The heart can be described as having four borders, an apex, and a base (Figs. 30 and 31). It is roughly pyramid shaped and oriented with its apex facing anterolaterally toward the left side of the body and base facing posteriorly.
[1] Borders: The borders of the heart are primarily made up of the right atrium (right and inferior), left ventricle (left), and the roots of the great vessels (superior).
[2] Apex and base: The apex of the heart is primarily made up of the left ventricle and the base the left atrium.

Figure 30: A. Posterior external features of the heart. B. Cadaveric specimen with vasculature visible.

Figure 31: Anterior external features of the heart. A, Blue boxes indicate borders/boundaries. B, Cadaveric specimen with vasculature visible.

[3] Sulci: Several sulci characterize the surface of the heart, including coronary and IV sulci.
[4] Auricles: Right and left auricles are ear-like appendages extending from the surface of the right and left atria, respectively. These vestigial structures represent portions of the primitive atria. Other than increasing the capacity of the atria, auricles have minimal functional significance in the adult heart.
[5] Surface: Along with visceral pericardium, the surface of the heart contains varying degrees of adipose tissue. Coronary arteries and cardiac veins course along the surface of the heart, giving rise to branches or receiving tributaries, respectively. These vessels often travel within sulci that correspond to partitions of underlying chambers.
c. Arterial supply: The heart receives blood from the right and left coronary arteries and their branches (see Figs. 30 and 31). Coronary arteries arise from aortic sinuses in the ascending aorta, just superior to the aortic value cusps. As oxygenated blood is expelled from the left ventricle to the aorta, a small portion of that blood is distributed to the structures of the heart by coronary arteries. Branching patterns can vary significantly.

[1] Right coronary: This artery begins at right aortic sinus and travels to the right in the coronary sulcus to the posterior surface of the heart. Major branches include sinoatrial (SA) nodal, right marginal (travels along inferior border), AV nodal, and posterior IV (travels in posterior IV sulcus) arteries.
[2] Left coronary: This artery begins at the left aortic sinus and travels a short distance to the left between the pulmonary trunk and left auricle before bifurcating into the circumflex artery, which travels around to the posterior surface of heart and anterior IV artery (left anterior descending), which travels in the anterior IV sulcus and gives rise to a left marginal branch.

d. Venous drainage: Venous blood from the heart is drained by a series of cardiac veins that travel with adjacent arteries (see Figs. 30 and 31). The great, middle, and small cardiac veins run with the anterior IV, posterior IV, and right marginal arteries, respectively. These veins drain into the coronary sinus, which returns venous blood to the right atrium. A collection of small anterior cardiac veins arises from the right ventricular wall and bypasses the coronary sinus to drain directly into the anterior wall of the right atrium.
e. Chambers: The four chambers of the heart are the right atrium, right ventricle, left atrium, and left ventricle. The right side of the heart receives deoxygenated systemic blood and distributes it to the lungs. The left side of the heart receives oxygenated blood from the lungs and distributes it to the head and body.
Valves and septa partition these four chambers, allowing unidirectional flow and sidedness, respectively. To better visualize the direction of blood flow and the structures associated with each chamber, imagine tracing a drop of blood from the right atrium to the thoracic aorta (Fig. 32).

Figure 32:Cardiac circulation. A, Internal view of heart chambers and valves. B, Direction of blood flow. External flow {white arrowheads); internal flow {black arrows). IVC = inferior vena cava, LA= left atrium, LV = left ventricle, PA = pulmonary artery, PV = pulmonary vein, RA= right atrium, RV= right ventricle, SVC = superior vena cava.

[1] Right atrium: This chamber receives blood from the SVC and IVC, coronary sinus, and anterior cardiac veins (Fig. 33). The inner surface has smooth (sinus venarum) and rough (pectinate muscle} portions, which as separated partially by a vertical ridge of tissue called the crista terminalis. Externally, this ridge is represented by the sulcus terminal is. Within the sinus venarum is a small oval depression called the fossa ovalis-a remnant of the once patent foramen ovale.

Figure 33 :Right internal heart structures

[2] Right ventricle: The inner surface is characterized by rough, trabeculae carne muscle and a set of papillary muscles that correspond to each value cusp (anterior, posterior, septal). Extending from the muscular portion of the IV septum to the anterior pupillary muscle is a ridge of tissue called the septomarginal trabeculae (moderator band), which transmits the right bundle branch of the heart's intrinsic conduction system. Two adjacent cusps are tethered to one papillary muscles by string-like structures called chordae tendineae. The smooth membranous portion of the IV septum-conus arteriosus-extends superiorly toward the pulmonary valve.

[3] Left atrium: Oxygenated Blood returns to the left atrium from the lungs although paired pulmonary veins (right and left superior and inferior). The left atrium makes up the base of the heart. The inner surface is primarily smooth, less the pectinate muscle inside the left auricle. The valve of the foramen ovale is also visible from the inside of the left atrium (Fig. 34).

Figure 34: Left internal heart structures.

[4] Left ventricle: The inner surface of the left ventricle is like that of the right ventricle, in terms of structures present-papillary muscles (anterior and posterior), trabeculae carneae, and chordae tendineae. The muscular walls of the ventricle are thicker than those of the right ventricle, which aids in overcoming systemic blood pressure during left ventricular contraction. A smooth area-aortic vestibule-is located superiorly, adjacent to the aortic valve.

f. Heart sounds: Contrary to popular belief, heart sounds are not produced by heart contractions, but rather the closure of valves during systolic stages of the cardiac cycle (Fig. 35). Clinically, heart sounds can be heard best with a stethoscope at predictable thoracic surface locations, as follows.

Figure 35 :Heart sounds. Letters indicate proper placement for heart auscultation sites
(blue circles). A = aortic valve, M = mitral (bicuspid) valve, P = pulmonary valve, T = tricuspid valve.
[1] Tricuspid valve: Sounds from the tricuspid valve can be heard at the fifth or sixth intercostal space near the left sternal border.
[2] Pulmonary valve: Sounds from the pulmonary valve can be heard at the second intercostal space, at the left sternal border.
[3] Bicuspid (mitral) valve: Sounds from the mitral valve can be heard at the fifth intercostal space in the left midclavicular line.
[4] Aortic valve: Sounds from the aortic valve can be heard at the second intercostal space, at the right sternal border.

g. Innervation: The heart has its own intrinsic conduction system, which is further regulated by the autonomic nervous system.
[1] Intrinsic conduction system: In the heart's conduction system, a wave of depolarization originates at the SA (sinoatrial} node, which is the intrinsic pacemaker of the heart (Fig. 36). The SA node is located in the wall of the right atrium, adjacent to the SVC. The initial impulse is spread through the atrial walls, causing coordinated contraction before reaching the AV (atrioventricular) node, which is located posteriorly between the atria and ventricles. From the AV node, the impulse travels through the AV bundle (bundle of His) located in the IV septum before bifurcating into right and left bundle branches, which distribute to right and left ventricles, respectively. Subendocardial branches distribute to papillary muscles and to the muscular myocardium to control valve closure and ventricular wall contraction, respectively.
[2] Autonomic regulation: Autonomic regulation of heart function occurs through sympathetic and parasympathetic components of the cardiac plexus (Fig. 37). The cardiac plexus is a mixed plexus, described as having superficial and deep components. Postganglionic sympathetic fibers arise from the sympathetic trunk at levels T1-T5 , while preganglionic parasympathetic fibers are supplied through the right and left vagus nerves (cardiac branches). In general, sympathetic stimulation will increase heart rate and force of contraction and cause vasodilation of coronary arteries. Parasympathetic stimulation decreases heart rate and force of contraction and causes vasoconstriction of coronary arteries.

Figure 36 :Steps in the heart conduction system. AV = atrioventricular, SA = sinoatrial.

Figure 37: Cardiac plexus.

h. Histology: The pericardia! cavity is surrounded by the fibrous pericardium, which is a dense connective tissue layer that is continuous with the tunica adventitia of the blood vessels entering and leaving the heart . The heart wall in all four chambers of the heart consists of three layers: endocardium, myocardium, and epicardium.
[1] Endocardium: The endocardium is the innermost layer of the heart wall and is thickest in the atria and thinnest in the ventricles. It is continuous with the tunica intima of the blood vessels entering and leaving the heart. It is composed of endothelium, a basal lamina, and a loose connective tissue layer (Fig. 38).

Figure 38 : Histology of the heart. A, Endocardium. B, Subendocardial layer.

(a) Endothelium: This simple squamous epithelium lines the inside of the heart chambers and abuts the blood.
(i) Subendocardium: The subendocardial layer is a layer of connective tissue that lies beneath the endocardium and contains blood vessels, autonomic nerve bundles, and Purkinje cells.
(ii) Purkinje cell: The Purkinje cell is a modified cardiac muscle cell that is specialized for conduction (not contraction). The Purkinje cell is not a neuron.
Purkinje cells comprise the AV bundle (bundle of His) and right and left bundle branches that travel in the subendocardium and then terminate as an intramural network of Purkinje cells within the myocardium. Purkinje cells are arranged end to end in long rows. They have irregular borders often with large extensions that protrude into a neighboring Purkinje cell that increases the surface area for cellto-cell contact. They are connected to each other by intercalated discs. The Purkinje cell has only scattered myofibrils, abundant mitochondria, and a high content of glycogen.
(b) Basal lamina: The basal lamina lies beneath the endothelium.
(c) Loose connective tissue layer: This layer consists of scattered fibroblasts, collagen fibers, and elastic fibers.
[2] Myocardium: The myocardium is the middle layer of the heart wall and is thickest in the ventricles and thinnest in the atria (Fig. 39). It is continuous with the tunica media of the blood vessels entering and leaving the heart. The myocardium contains a number of different cell types: cardiac muscle (most abundant), Purkinje, myocardial endocrine, and cardiac nodal cells.

Figure 39 : Histology of the heart. A, Myocardium. B, Epicardium.
(a) Cardiac muscle cell: The cardiac muscle cell is a branching, cylinder-shaped cell that ends in finger-like projections that interdigitate with neighboring cardiac muscle cells. In many cases, a cardiac muscle cell will branch and join two or more neighboring cardiac muscle cells.
The cardiac muscle cell is surrounded by a basal lamina and the endomysium. It has a single nucleus located at the center of the cell with a distinctive juxtanuclear region. It is characterized by striations (although not as prominent as in a skeletal muscle cell) that consist of A bands (dark), I bands (light), and Z discs. In addition, intercalated discs are conspicuous.

(b) Intercalated disc: This is a highly specialized attachment site that exits between neighboring cardiac muscle cells. It is located along the finger-like projections at the ends of a cardiac muscle cell that interdigitate with neighboring cardiac muscle cells. An intercalated disc consists of a fascia adherens, a macula adherens (desmosome), and a gap junction (nexus).
[3] Epicardium: The epicardium is the outermost layer of the heart wall. It consists of three components: mesothelium, simple squamous epithelium that lines the inside of the pericardia cavity and abuts the pericardia! fluid in the pericardia! cavity; basal lamina lying beneath the mesothelium; and a loose connective tissue layer consisting of scattered fibroblasts, numerous adipocytes, collagen fibers, and elastic fibers. The coronary arteries, cardiac veins, and autonomic nerve bundles travel within this connective tissue layer.