coexist with deficiencies of cardiac septation. They can also be found
of the common carotid artery into internal and external carotid arteries
with discordant connections at the atrioventricular junctions, produc-
occurs at the level of the upper border of the thyroid cartilage, in both
ing congenitally corrected transposition. The developmental history of
neonate and adult, the thyroid cartilage is relatively higher in the neo-
discordant connections remains unknown.
natal neck than it is in the adult. The renal arteries also arise higher in
Double outlet ventricle exists when the greater parts of both arterial
the neonate, often between T12 and L1, whereas they arise at the upper
valves are attached within the same ventricle, almost always the right.
border of L2 in the adult. The abdominal aorta bifurcates into common
For the circulation to continue, it is then necessary for the ventricular
iliac arteries at the upper border of L4, rather than at the lower border
septum to be deficient, although the septal defect can rarely close as a
of L4, as occurs in the adult.
secondary event. The position of the septal defect serves for subclassi-
fication. It is usually beneath the aorta or the pulmonary trunk, but can
Central venous catheterization
be doubly committed or even non-committed.
Either the systemic or pulmonary veins can be anomalously con-
nected. Right and left superior vena cavae are present in some animals Small-bore catheters can be fed into large central veins or into the right
and occasionally persist in mankind. The most common systemic atrium via needles or catheters inserted in the peripheral veins. Typi-
anomaly is a persistent left superior vena cava draining into the right cally, the median cubital or basilic veins are used in the upper limb, the
atrium through the enlarged orifice of the coronary sinus. More rarely, long saphenous vein at the medial malleolus in the lower limb and the
the persisting left-sided vena cava may connect directly with the supe- superficial temporal vein in the scalp. The tip of the catheter is sited at
rior aspect of the left atrium, usually associated with so-called ‘unroof- the entrance to the right atrium. The required catheter length is assessed


ing’ of the coronary sinus, so that the orifice of the sinus functions as from direct measurement of the distance between the point of surface
an interatrial communication. The most common lesion of the inferior entry in the limb to the right atrium, estimated at mid-sternal level. For
vena cava is when its abdominal course is interrupted, with drainage to details of umbilical catheterization, see Chapter 60.
the heart via the azygos or hemiazygos venous system. This lesion is
found most frequently with isomerism of the left atrial appendages. The
RESPIRATORY TREE
pulmonary veins can be connected to an anomalous site individually
or in combination. Totally anomalous connection is of most signifi-
cance. Usually, the veins form a confluence behind the left atrium, The development of the respiratory system can be conceptualized as the
which then connects to the superior vena cava, the coronary sinus or growth of six intertwined trees: the bronchial tree of conducting airways
the portal venous system after traversing the diaphragm. and terminal gas-exchanging sacs; the systemic arterial and venous trees
A right aortic arch is found most frequently with Fallot’s tetralogy or that perfuse and drain the airways, respectively; the pulmonary arterial
with a common arterial trunk. It can also exist, together with a left arch, and venous trees that supply and drain the alveolar membrane, respec-
in various combinations known as arterial rings, which compress the tively, and anastomose with the systemic and venous trees (and are


Development of the thorax
924.e1
25
retpahC
A
LV MV
RV
LA
TV RA
B
LV
RV LA
RA
Fig. 52.24 A, A normal four-chamber view at 22 weeks’ gestation.
B, The ventricular inflow with colour flow. Flow (seen in red) is seen from
each atrium to each ventricle. Abbreviations: LA, left atrium; LV, left
ventricle; MV, mitral valve; RA, right atrium; RV, right ventricle; TV,
tricuspid valve. (Courtesy of Gurleen Sharland, Evelina London Children’s
Hospital.)


respiratory tree
925
25
retpahC
pivotal to the provision of blood oxygenation and carbon dioxide excre-
tion after birth); and the lymphatic tree. Development of each tree is A B
related to the other and all proceed in proximal to distal growth and
expansion. Uniquely, the lung develops while not fulfilling its postnatal Primitive
Respiratory
function, and must function efficiently immediately after birth or else foregut
diverticulum
the baby will require respiratory support and may die of respiratory Laryngotracheal
failure. Current knowledge of the molecular basis of lung development Trachea groove will close
is based on growth in vitro of human and animal explants (usually Laryngo- from caudal to cranial
mouse and rat), and studies using knockout and transgenic mice (Her- tracheal
Oesophagus
riges et al 2012). Anomalies of lung development make an important groove
contribution to the development of airway diseases such as asthma and
chronic obstructive pulmonary disease (COPD) (Bush 2008). The
reader is referred to recent studies of lung developmental biology for Lung buds passing
dorsally around
more information (Roth-Kleiner and Post 2005, Kimura and Deutsch
oesophagus
2007, Maeda et al 2007, Bhaskaran et al 2009, Kho et al 2010, Morrisey
and Hogan 2010, Sgantzis et al 2011, Ornitz and Yin 2012).
C
The development of the respiratory diverticulum can first be seen at
stage 12 (approximately 26 days), when there is a sharp onset of epi-
thelial proliferation within the foregut at regions of the endoderm tube
destined to become the lungs, stomach, liver and dorsal pancreas. The
specialist respiratory epithelium forms from the endoderm, whereas the
Lobar bronchi are
other elements of the airway wall are of mesenchymal origin. The future
surrounded by
respiratory epithelium bulges ventrally into the investing splanchno- splanchnopleuric
pleuric mesenchyme, then grows caudally as a bulb-shaped tube (Fig. mesenchyme


52.25; see Figs 52.1C, 60.3, 60.5). By stage 13, the caudal end of the
tube has divided asymmetrically to form the future primary bronchi;
with growth, the right primary bronchus becomes orientated more
caudally, whereas the left extends more transversely. The trachea is
clearly recognizable at stage 14. From this time, the origin of the trachea
remains close to its site of evagination from the future oesophagus;
however, longitudinal growth of the trachea causes the region of the
future carina to descend, ultimately to lie within the thorax. Failure of
complete separation between trachea and oesophagus will result in the
baby being born with one of the variants of tracheo-oesophageal fistula
(see below). D Pericardioperitoneal canals
There is a sexual dimorphism in lung development. Androgens delay Lung buds
fetal lung maturation while stimulating fetal lung growth; in males, type Midgut
II cells are less mature than in females, as they develop during the Trachea
canalicular phase, perhaps because androgens block the effects of cor-
Laryngotracheal
tisol on fibroblast–pneumocyte factor concentrations. It is possible that, groove Peritoneal
cavity
in male fetuses, surfactant production is delayed. The clinical counter-
part is the observation that preterm males may have worse respiratory Hindgut
distress than females after control for other risk factors, such as degree
of prematurity.
Foregut
TRACHEA Pericardial cavity
Yolk sac
Septum transversum
The trachea starts to develop at stage 12, as a ventral outgrowth from
mesenchyme
the endodermal foregut into the mesenchyme that surrounds the sinus
venosus and inflow tract of the heart (see Figs 52.1C, 60.3, 60.5). The
point at which the original respiratory diverticulum buds from the Fig. 52.25 Development of the respiratory tree and diaphragm.
foregut, the laryngotracheal groove, remains at a constant level during A–C, Development of the endodermal respiratory tree. D, Major epithelial


the embryonic period, and the trachea lengthens distally as the bifurca- populations in the early embryo from a left dorsolateral view. The lung
tion point descends. The respiratory diverticulum generally becomes buds are bulging into the laterally placed pericardioperitoneal canals.
surrounded by angiogenic mesenchyme that connects to the developing
sixth aortic arch artery and is essential for airway branching. By stage
17, the mesenchyme around the trachea is beginning to condense to matrix molecule found commonly in basal laminae, is found in the
form cartilage. clefts and along the sides of the developing bronchi, but not on the
Initially, the tracheal mesenchyme is continuous with that surround- budding and distal tips. It is likely that, after the first generation,
ing the ventral wall of the oesophagus (see Fig. 52.3). Progressive branching morphogenesis is not rigidly prespecified, but adapts to the
lengthening and continued division of the tracheal bud, together with space available within the mesenchyme (Blanc et al 2012).
deviation of the lung buds dorsally, isolates the oesophagus and trachea The control of the branching pattern of the respiratory tree resides
within tissue-specific mesenchyme and facilitates regional differentia- with the splanchnopleuric mesenchyme. Experimental recombination
tion, not only between trachea and lungs, but also within the lungs of tracheal mesenchyme with bronchial respiratory endoderm results
themselves, i.e. the number of lobes, or the degree of growth and matu- in inhibition of bronchial branching, whereas recombination of bron-
rity of a particular lung. Each lung develops by a process of dichoto- chial mesenchyme with tracheal epithelium will induce bronchial out-
mous branching. For branching to occur, a cleft must develop in the tip growths from the trachea. Experimental exposure of rat fetal airway to
(or side) of the epithelial tube. The epithelium then evaginates each chick mesenchyme produces a chick airway branching pattern. Broadly,
side of the cleft, forming new branches that lengthen, and the process receptor tyrosine kinases and their ligands positively modulate growth


is then repeated (see Fig. 11.3). At the tips of the developing epithelial and branching morphogenesis, while transforming growth factor beta
buds, the mesenchyme is flattened and densely packed, whereas it (TGF-β) family members have an inhibitory effect.
forms an ordered row of cuboidal cells along the side of the bud and Interestingly, even at this early stage, airway smooth muscle is inner-
in the clefts. Cells in both arrangements send processes towards the vated and contractile (Tollet et al 2002). Phasic contraction and relaxa-
epithelial basal lamina, which is thicker in the clefts, but so attenuated tion of airways is important in growth factor release. Smooth muscle
as to be almost indistinguishable on the tips of the buds where the and nerves are found outside the airways at this developmental stage.
epithelium and mesenchymal cells form intimate contacts. Tenascin, an Glial-derived neurotrophic factor (GDNF) is important in this process.
extracellular matrix molecule, is present in the budding and distal tip In the normal neonate, the trachea is relatively small in relation to
regions, but absent in the clefts. Conversely, fibronectin, an extracellular the larynx (see Fig. 14.6B). The walls of the trachea are relatively thick


Development of the thorax
926
7
noItCeS
and the tracheal cartilages are relatively closer together than in the arise from the sixth aortic arch arteries, and the pulmonary veins
adult. The trachea begins at the upper border of the sixth cervical ver- develop from a solitary channel derived from the dorsal mesocardium,
tebra, a relationship that is conserved with growth, and it bifurcates at which, by branching morphogenesis, establishes continuity with the
the level of the third or fourth thoracic vertebra. vascular plexus formed in the mediastinal mesenchyme. The pulmonary
veins become surrounded by myocardium to the level of the second
Endotracheal intubation in the neonate bifurcation. The veins themselves expand and are incorporated into the
roof of the left atrium; cardiac muscle is, therefore, found in the central
branches of the pulmonary venous tree (Hislop 2005).
The insertion of an endotracheal tube is a procedure that may be
The lung buds on each side of the oesophagus project dorsally into
required to resuscitate the newborn at birth and, subsequently, to
the pericardioperitoneal canals at stage 15. After this stage, the coelomic
enable artificial ventilation. Initially, the tube is usually introduced
epithelium at the perimeter of the lung surface follows a differentiation
orally and it is then guided through the vocal cords under direct vision
pathway to form the visceral pleura. Lobar or secondary bronchi can be
using a laryngoscope. The length of the trachea in the neonate can be
seen at stage 16, and the bronchopulmonary segments are present at
as short as 3 cm in premature infants, and the distance from T1 to
stage 17 (see Fig. 60.3). Later stages of respiratory development involve
carina ranges from 1.4 cm in babies weighing 500–1000 g to 1.8 cm in
the repeated division of the bronchial tree to form the subsegmental
those weighing 3001–3500 g. Once in place, the tip of the tube should
bronchi.
be in the mid-trachea, well above the carina.
The required length of the tube can be estimated according to birth


weight. If a shouldered tube is used, only the distal, tapered portion of Pseudoglandular phase (5–17 weeks:
the tube is inserted beyond the vocal cords, and the shoulders should development of airways and blood vessels
prevent the tube being advanced too far. Confirmation of correct posi- to level of acinus)
tioning of the endotracheal tube is obtained from a chest X-ray. The
anatomical reference points used for the X-ray to assess the position of
By stage 17 (late sixth to early seventh week), the separation of the lungs
the endotracheal tube are the clavicles, the bodies of the vertebrae and
from the digestive system is complete and the pseudoglandular phase
the carina (although the last of these is not always visible on X-ray).
of pulmonary development, which includes the development of the
Previously, it was advised that the tip of the endotracheal tube should
lower conducting airways and the appearance of the acinar structures,
be placed just below the clavicles, at the level of the first rib or 1–2 cm
can be identified. During this period, virtually the complete branching
above the carina. Recently, this has been revised because positioning of
structure of the future bronchial tree is laid down, giving rise to 20
the clavicles can vary according to angulation and placement of the
generations.
baby, and the carina cannot always be identified. It is now suggested
The growth and branching of the endoderm epithelium is controlled
that the body of the first thoracic vertebra (T1) is a more stable reference
by the local investing splanchnopleuric mesenchyme. The airways begin
point as the target for the tip of the endotracheal tube.
to differentiate during this stage. Primitive ciliated cells appear at about
week 7, initially in the region of the membranous trachea, and in the
LUNGS cartilaginous region by week 12. Ciliary biology and ciliopathy are an
increasing focus of study (Bush and Hogg 2012). There are three known
types of cilia. Best known are motile cilia, which propel mucus along
Branching of the conducting airways is generally complete by week 16.
epithelial surfaces, or are responsible for motility of unicellular organ-


Airways subsequently increase in size but not in number. Alveolar devel-
isms, but also probably have some cell signalling role; these are abnor-
opment is largely (but not completely) a postnatal phenomenon. The
mal in primary ciliary dyskinesia (PCD, Kartagener’s syndrome). Nodal
development of pre-acinar blood vessels follows the conducting airway
cilia are also motile and are responsible for determining organ situs in
development, the airways acting as a template for blood vessel develop-
the developing embryo (Nonaka et al 2002). Primary cilia are non-
ment by de novo vasculogenesis driven by epithelial-derived vascular
motile, are ubiquitous throughout the body, and have a wide range of
endothelial growth factor (VEGF), whereas development of intra-acinar
signalling functions during development (Goetz and Anderson 2010).
blood vessels follows the development of the alveolar ducts and alveo-
The exact in utero function of these early ciliated cells in the trachea is
lar sacs. Lung development is described histologically as progressing
obscure. It is unclear whether airway ciliated cells develop from an
through embryonic, pseudoglandular, canalicular, saccular and alveolar
undifferentiated precursor or through the further development of a
phases. (For further details, see Bush (2005).)
population of secretory cells. The epithelium differentiates into ciliated
and goblet cells. The proximal airways develop basal cells from week
Embryonic phase (0–7 weeks: appearance of
11, and ciliogenesis is complete at birth in humans. Mucous glands
lung buds and main pulmonary arteries)
develop by 12 weeks and enlarge in the submucosa; secretory activity
has been identified in the trachea at 14 weeks. The splanchnopleuric
The lung buds grow dorsally, passing each side of the relatively smaller mesenchyme condenses around the epithelium and differentiates into
oesophagus, and bulge into the medial walls of the laterally situated connective tissue cell types and smooth muscle, which differentiates
pericardioperitoneal canals (see Figs 52.25, 60.5A). The investing proximal to the tips of the developing airways as they develop, from


splanchnopleuric mesenchyme surrounding the lung buds contains a week 6 onwards. Smooth muscle cells are innervated from as early as
mixed population of cells. Further mesenchymal cells will differentiate week 8 (see below). First-trimester human tracheal smooth muscle cells
into the smooth muscle cells that surround both the respiratory tubes have a fluctuating resting membrane potential that is associated with
and the blood vessels. In stage 13 embryos, proliferation of the adjacent the spontaneous development of tone and peristalsis-like contractions
splanchnopleuric coelomic epithelium (of the primary pleural cavities) of the airway of a myogenic nature, probably modified by neurohu-
is especially evident. The proliferative activity decreases in stage 14, and moral factors. These contractions are important in moving fluid from
the mesenchyme becomes arranged in zones around the developing distal to proximal within the airways, which is essential for normal lung
endoderm. Key molecules in airway branching include the fibroblast development and may also stimulate mediator release. Clara cells
growth factors (FGFs), especially FGF-10, and their four receptors. There develop in the peripheral airways during the pseudoglandular period.
is almost certainly redundancy in the system, since mice null for either They produce a 10 kDa protein (CC10) with immunomodulatory and
FGF-1 or FGF-7 exhibit normal lung development, despite the potent anti-inflammatory activities, as well as producing a surfactant apopro-
in vitro effects of these mediators. The key receptor appears to be tein. Cartilage also develops during this period, and is found in the
FGFR2IIIb, and those ligands that bind it. Sonic hedgehog is important airways in an adult distribution by 24 weeks. By the end of this period,
in lung development; it is tightly regulated and over-expression leads the airway branching and the pre-acinar vascular patterns are fully
to the formation of excessive lung mesenchyme. The three members of mature. A normal airway ‘template’ is essential for normal alveolar
the gli family of transcription factors are implicated in Sonic hedgehog formation; in conditions characterized by an abnormal airway branch-
signalling. Sonic hedgehog produced in distal epithelial cells appears ing pattern (e.g. both ipsilateral and contralateral to a diaphragmatic


to act on mesenchymal cells to suppress FGF-10 to limit budding. Other hernia), a degree of pulmonary alveolar hypoplasia is inevitable.
signals interacting with this process include bone morphogenetic Endothelial development is also seen in the pseudoglandular phase
protein 4 and TGF-β1. when capillary networks form around the developing lung buds. These
At stage 15, angiogenetic mesenchyme is apparent around the networks will become capillary anastomoses around the future alveoli.
primary bronchi. It forms an extensive capillary network around each The mesenchyme produces both the endothelium and the smooth
lung bud, receiving blood from the developing sixth aortic arch artery muscle cells of the tunica media of the vessels. Vimentin occurs in the
and draining it into an anastomosis connected to the dorsal surface of cells around developing vessels in the pseudoglandular stage, but is
the left atrium in the mediastinal mesenchyme. The pulmonary arteries replaced by desmin in the saccular phase.


respiratory tree
927
25
retpahC
Canalicular phase (17–27 weeks: formation enriched mixtures is probably irreversible and, indeed, may be the basis
of respiratory airways and thinning of blood– of ‘new’ bronchopulmonary dysplasia.
Elastin gene expression, possibly modulated through retinoic acid,
gas barrier)
appears to be of pivotal importance in alveolar budding. Retinoic acid
treatment of rats increases alveolarization, and salvages some alveoli in
During the canalicular phase, about two to three generations of branch- an experimental model, whereas mice with a deletion in the retinoic
ing take place, after which the amount of mesenchyme around the acid receptor γ have impaired alveolarization. Retinoic acid regulates
branching tips of the dividing respiratory tree decreases and the distal the expression of a number of growth signalling molecules, homeobox
airspaces widen. At 23 weeks, longitudinal sections of the future distal genes and lung epithelial genes; other gene groups involved in alveo-
regions show a sawtooth margin, which may indicate the site of further larization probably include TGF-β, platelet-derived and fibroblast
acini. Peripheral growth is accompanied by an increase in the capillary growth factors. (For further reading on the control of alveogenesis, see
network around the distal airspaces. In many places, the capillaries are Galambos and DeMello (2008) and Hind et al (2009).)
in close contact with the respiratory cuboidal epithelium. The primitive
cuboidal cells, which hitherto predominated in this part of the lung,
Development of the intrapulmonary
differentiate into type 2 epithelial cells (pneumocytes), containing
lamellar bodies that form the intracellular storage bodies of surfactant, vasculature and lymphatics
and type 1 epithelial cells (pneumocytes). Type II pneumocytes are
believed to be the stem cells of the alveolar epithelium. Apposition of In an adult lung, the pulmonary arteries accompany the airways. The
the capillary networks to the thin pneumocytes (type 1), and reduction pulmonary veins have a similar number of branches but are separated
of the interstitial tissue of the lung, are prerequisites for future effective from the airways by the alveoli; they have a different embryological


gas exchange. By 24 weeks of gestation, the histological characteristics origin, being derived from the mediastinal mesenchyme proximally
of the airways, including cartilage distribution, are the same as in rather than from the splanchnopleuric mesenchyme around the bifur-
the adult. cating respiratory tree. New vessels are formed by either vasculogenesis
(the formation in situ of new blood vessels) or angiogenesis (out-
Saccular/alveolar phase (28 weeks to term: sprouting from existing vessels). Failure of separation of pulmonary
first appearance of alveoli in humans) veins from the arterial–airway bundle is a feature of the alveolar–
capillary dysplasia spectrum (alveolar–capillary dysplasia with mis-
alignment of the pulmonary veins), and may be caused by FOXF1 or
Thin-walled terminal saccules are apparent at the saccular stage and will
STRA6 mutations (Bishop et al 2011). The mesenchyme around the
become alveolar ducts as development proceeds. The expansion of the
single lung bud contains a number of cells that stain positively for the
prospective respiratory airspaces that occurs during this period is
endothelial cell markers CD34 and CD31. The earliest pulmonary
accompanied by a further decrease in the amount of interstitial tissue,
vessels form in the mesenchyme by vasculogenesis; the capillaries
and the capillary networks become ever more closely opposed to the
coalesce to form small blood vessels alongside the airways. By 34 days
pneumocyte epithelium. Invaginations (secondary crests) develop from
of gestation, blood circulates from the aortic sac via pulmonary arteries
the saccule walls. As a crest protrudes into a saccule, part of the capillary
into a capillary plexus around the two lung buds and drains to the
network becomes drawn into it. After the later expansion of the saccules
developing atrium. As each new airway forms in the mesenchyme, a
on each side of the crest, a double capillary layer becomes annexed
new plexus forms as a halo around it and coalesces with the vessels
between what are now alveolar walls. During the saccular stage, elastin
already alongside the previous airway. In this way, addition of the newly


is deposited beneath the epithelium (an important step for future alveo-
formed tubules to the existing vessels is sustained; the airways act as a
lar formation), and surfactant production from type 2 pneumocytes
template for the development of blood vessels. Vessel formation occurs
(essential for the survival of a preterm neonate) matures.
at least until the end of the pseudoglandular stage and is probably
Maturation of the blood–gas barrier is an essential part of normal
controlled by production of VEGF from the epithelial cells of the
human development but the molecular basis of this is little understood.
peripheral lung buds. As the arteries increase in size, they acquire a
Mechanical stretch drives type 2 to type 1 cell differentiation. VEGF is
muscular wall. Initially, this arterial tunica media is derived from the
a key mediator; it is upregulated by hypoxia, in late gestation, by cyclic
bronchial smooth muscle of the adjacent airways, but as the vessels
stretch and by the transcription factor HIF2α. Type 2 cell maturation
progressively enlarge, cells derived from the splanchnopleuric mesen-
and capillary development fail in HIF2α−/− mice. VEGF also drives sur-
chyme differentiate around the wall to form layers of smooth muscle
factant production from glycogen in type 2 cells.
cells. The muscular wall is thick relative to the lumen and this, in part,
increases resistance to blood flow, although only 10% of blood flow
Alveolar phase
goes through the pulmonary circulation of the lung during intrauterine
life. None the less, this small blood flow is important in normal lung
Exactly when the saccular structure of the lung can be termed alveolar development (see below). At 20 weeks, the structure of the pulmonary
is not yet clear: estimates range from 28 to 32 weeks. The distal airspaces vessels is the same as it is in the adult. Vascular innervation follows
expand during late gestation and continue to do so after birth. The muscularization; the vasoactive peptides in the nerves are predomi-
number of alveoli present at birth (variously estimated as between none nantly vasoconstrictor.
and 5 × 107) is controversial but the numbers probably increase particu- As the pulmonary veins enlarge, they become separated from the


larly rapidly over the first 6 months of life. This process is accompanied airways by lymphatic vessels lying within connective tissue. At around
by fusion of adjacent capillary nets, so that, shortly after birth, there is week 12, the peripheral veins develop a single layer of smooth muscle
an extensive double capillary net. Fusion of these layers is apparent at cells in their walls. This layer is derived only from the splanchnopleuric
28 days postnatally, extensive at 1.5 years and probably complete by 5 mesenchyme and not from bronchial smooth muscle (as occurs in the
years. The alveolar stage is now considered to continue beyond infancy arteries). The lumen of each vein is relatively large and the wall is rela-
and to last throughout childhood (see below). Interestingly, in rats and tively thin at all levels. Arteries and veins continue to develop in the
mice, formation of alveoli is entirely postnatal. canalicular phase, probably by angiogenesis; dividing cells are seen in
The formation of millions of alveoli is accomplished by a complex the peripheral capillaries. The epithelium of the most peripheral con-
process of folding and division. Existing walls of distal airspaces become ducting airways flattens when the developing capillaries come to lie
thinner as pneumocyte epithelial cells flatten, and some cells undergo immediately subjacent to it during this phase. (For a review of the
apoptosis. Ridges subsequently grow out from the sides of the saccule development of the pulmonary circulation, see Hislop (2005).)
walls, forming primitive alveoli. The secondary septa contain a double Lymphatic capillaries and vessels run within bronchovascular
capillary layer and further new alveoli form by the infolding of one of bundles. Lymphatic channels develop from outgrowths of vascular
these layers, further subdividing the airspaces. The double capillary endothelial cells; the molecular trigger for lymphatic sprouting is
networks then undergo remodelling to form the familiar single capillary VEGF-C and D, acting through the VEGF receptor 3 (Janér et al 2006).
sheet around each alveolus. Conducting airways also undergo profound (See Kulkarni et al (2011) for a review of lymphatic development in the
postnatal changes and exhibit increased smooth muscle and broncho- lung.)


constrictor responsiveness. The precise molecular signalling for these As well as developing a pulmonary circulation, the lung also devel-
processes has yet to be established. However, they are clearly tightly ops a bronchial supply from the systemic circulation. Two or three
regulated developmentally; hyperoxia or dexamethasone treatment of bronchial arteries grow from the descending aorta from week 8 onwards,
rats during the alveolarization period permanently abrogates alveolar entering the lung at the hilum. These arteries extend down the intrapul-
development. This experimental finding implies that iatrogenic damage monary airways, eventually forming subepithelial and adventitial plex-
to the developing alveoli when ventilating a preterm baby with oxygen- uses, which, by birth, have reached the distal portions of the bronchioli.


Development of the thorax
928
7
noItCeS
The bronchial veins from the periphery of the lungs drain into the ized by persistence of bombesin-positive neuroendocrine cells. Persist-
pulmonary veins. Bronchial arteries also supply the pleura near the ence of glycogen-containing cells results in pulmonary interstitial
hilum, and form vasa vasorum in the adventitia of the large arteries and glycogenosis (PIG), which is not related to any of the systemic glycogen
veins. Postnatally, inflammatory lung conditions, such as asthma, cystic storage diseases. Both conditions tend to remit over time, and in neither
fibrosis and bronchiectasis, cause hypertrophy of the bronchial circula- case is it known whether the abnormal cells are of pathophysiological
tion and these vessels may bleed, sometimes giving rise to massive significance or are merely markers of another process.
haemoptysis (see McCullagh et al (2010)).
Adverse effects on intrauterine
lung development
Intrauterine maturation of the lungs
There is increasing evidence from epidemiological studies that ante-
There are more than 30 different cell types within the adult lung that
natal factors have effects on lung development that are long-lasting. The
mature during development. Only a few important changes relevant to
earliest major effect is congenital diaphragmatic hernia, which leads to
human disease will be highlighted here.
both ipsilateral and contralateral anomalies in branching pattern in
Pulmonary surfactant is produced by type 2 alveolar epithelial cells
the first 16 weeks of gestation that cannot be corrected subsequently,
and stored in lamellar bodies. Surfactant proteins (Sp) B and C are
even by intrauterine tracheal balloon occlusion. Inevitably, abnormal
surface-active, whereas A and D are part of the collectin family of
branching leads to abnormal alveolarization in this condition. The
pattern recognition receptors. Surfactant is crucial for maintaining the
most important later influence is maternal smoking but there is evi-
functional integrity of alveoli; the main morbidity of extreme prematu-
dence that maternal exposure to pollution is also important (Latzin
rity reflects surfactant deficiency causing neonatal respiratory distress
et al 2009). Animal studies have confirmed that antenatal nicotine
(treatment of these babies has been transformed by the availability of


exposure leads to structural changes in the fetal lung (Elliot et al 2001,
exogenous surfactant). Mutations in the genes encoding SpB and SpC,
Sekhon et al 2002, Fu et al 2011). Other factors that may be important
ABCA3 (responsible for surfactant processing) and the transcription
include maternal hypertension in pregnancy, and maternal antibiotic
factor TTF-1 (controlling SpB, SpC and ABCA3 expression) can all
and paracetamol usage.
present in the newborn period in term babies with relentlessly progres-
sive respiratory distress, with diffuse ground-glass shadowing on
Ultrasound antenatal imaging of the lungs
imaging studies (Bush and Nicholson 2008, Galambos et al 2010). Fetal
breathing movements appear to be important in surfactant synthesis:
the functional maturation of the surfactant system can be accelerated Pulmonary hypoplasia, an absolute decrease in lung volume and weight
therapeutically by the administration of steroids to the mother. for gestational age, may be identified but cannot be confirmed. It is
Normal lung development requires sufficient intrathoracic space, normally associated with oligohydramnios and renal agenesis. Unilat-
normal fetal breathing movements and sufficient amniotic fluid. There eral hypoplasia may be suggested by rotation and displacement of
is evidence that perturbation of fetal lung blood flow also affects lung the heart on ultrasound examination. In bilateral pulmonary hypopla-
growth, even though most of the right ventricular output of the heart sia, the heart appears relatively large with reduced chest volume. How-
is shunted away from the lungs through the ductus arteriosus; pulmo- ever, intrauterine growth retardation may also cause similar findings.
nary valve stenosis is associated with pulmonary hypoplasia. Increased echogenicity of the lungs indicates conditions that prevent
Although many fetal organs are able to grow to normal proportions the normal circulation of lung fluid (for further details, consult Coady
even if they are in abnormal locations, this is not the case for the lungs. and Bower (2015)). Details of prenatal lung anomalies and their detec-
Lung growth becomes impaired by restricted expansion, and distension tion are given in Epelman et al (2013).
of the developing lung may provide a major stimulus to growth during


normal development. Absence or impairment of fetal breathing move-
FUNCTIONAL CHANGES IN THE LUNG AROUND THE
ments, and anomalies affecting diaphragmatic activity, are all associated
with pulmonary hypoplasia. It is believed that normal fetal breathing TIME OF BIRTH
movements increase the lung volume and stimulate growth of the distal
airspaces. These movements involve rhythmic activation of the dia- Just prior to birth, the placenta is the organ of respiration. Virtually all
phragm and the muscles of the upper respiratory tract; even though the venous return to the right heart is shunted away from the lungs
they are necessarily very small compared with those seen after birth through the foramen ovale and the ductus arteriosus. Pulmonary vas-
(because the fetal airways are filled with lung fluid), there is evidence cular resistance (PVR) is maintained at a very high level by the muscular
that these phasic movements are important in the release of growth precapillary pulmonary vessels. At birth, the umbilical cord is tied and
factors. (The role of fetal breathing movements has been reviewed in cut; within seconds, the lungs must take over all respiratory function in
Inanlou et al (2005).) order to maintain life. They also must convert from secreting fluid to
During development, the mucous glands of the trachea and bronchi absorbing it. The mechanisms that mediate these dramatic changes are
secrete a chloride-rich fluid, which usually passes up the respiratory obscure. However, it is clear that the first breath results in vasodilation
tract to mix with the amniotic fluid. The relationship between lung fluid by at least two mechanisms. First, there is the mechanical effect of trac-
and amniotic fluid is far more complex than was previously believed. tion on the vasculature: as the chest wall expands, it pulls open the
Pulmonary hypoplasia at birth may be associated with severe congenital pulmonary vessels. Second, oxygen entering the lungs for the first time
urinary obstruction and oligohydramnios (Potter’s syndrome). In renal produces pulmonary vasodilation. The experimental demonstration
agenesis, reduced bronchial branching occurs as early as 12–14 weeks that PVR falls, even if the fetus is delivered into an atmosphere of pure


of gestation (i.e. at a time before amniotic fluid is produced by the nitrogen, implies that other mediators, including cyclo-oxygenase
kidneys), which suggests that a direct renal factor supports lung devel- metabolites, are important. The gene for cyclo-oxygenase 1 (but not 2)
opment. Later, the presence of amniotic fluid is necessary for normal in endothelium and vascular smooth muscle shows enhanced expres-
fetal lung development. The fetal lung is a net fluid secretor, the output sion in late fetal and early postnatal life. Endothelin receptor expression
of fluid reaching as high as 5 ml/kg shortly before birth (see p. 179). increases around the time of birth, implying a role for this system in
Most of the fluid produced within the lungs remains there because of postnatal adaptation (Levy et al 2005). The role of nitric oxide in post-
the mechanical effect exerted by amniotic fluid pressure and, normally, natal adaptation is controversial and there are likely to be important
only a small amount of this fluid contributes to the amniotic fluid. The species differences. Nitric oxide synthase (NOS) is more abundant in
normal functioning of the kidneys regulates the volume and pressure young compared with mature animals, and smooth muscle sensitivity
of the lung airway fluid and may, in turn, provide the pressure needed to nitric oxide may be greater at birth than in older animals. The effects
for expansion and enlargement of the bronchial and pulmonary of mediators may differ ante- and postnatally, e.g. endothelin (ET)-1
systems. Interestingly, obstruction to the fetal airway causes accelerated causes vasodilation in fetal sheep, but vasoconstriction postnatally in
maturation of alveoli; this approach has been used therapeutically in lambs. Immediately after birth, and before structural remodelling has
congenital diaphragmatic hernia, where intermittent inflation and taken place, PVR may rise steeply if the baby becomes even minimally
deflation of an intratracheal balloon in a lamb model resulted in better hypoxic or acidaemic. The fetal shunts (foramen ovale and ductus arte-
lung growth and maturation (Nelson et al 2005). riosus) reopen and right to left shunting causes profound hypoxaemia


Two other cell types that are part of normal lung development, and ‘persistent fetal circulation’.
neuroendocrine cells and glycogen-containing cells, are implicated in To summarize, at birth, the lung volume is small but related to body
postnatal paediatric interstitial lung disease, with early onset of respira- weight; all airways are present and differentiated (cartilage, glands,
tory distress. Neuroendocrine cells are found in the normal developing muscle, nerves); the one-third to one-half of the adult complement of
airway. Neuroendocrine cell hyperplasia of infancy (NEHI) is character- alveoli present at birth give sufficient surface area for gas exchange; the


respiratory tree
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25
retpahC
morphology of the blood–gas barrier is the same as in adults; and most
arteries and veins are present.
Newborn
POSTNATAL LUNG DEVELOPMENT
The amount and type of connective tissue in the lung change after birth. Newborn
The neonatal lung has abundant type III and type IV collagen, but little
type I collagen. Types III and IV collagen are not mechanically strong,
suggesting that the neonatal lung has a phenotype that facilitates
2–4 hours
the changes in cell shape and orientation that characterize adaptation
to extrauterine life. It is probable that the rapid deposition of type
I collagen postnatally contributes structural stiffness to the blood
8–12 hours
vessel walls.
Lung volume increases most rapidly during the first year of life and
also increases more rapidly than airway calibre during this time, a
finding consistent with the concept of dysanaptic lung growth, i.e. a 12–24 hours
dissociation between the growth of the lung parenchyma and the
airways. Until recently, it was thought that most of the alveoli were
formed by 2 years of age, and that subsequent lung growth primarily 24 hours
resulted from an increase in the size of individual alveoli. However,
recent work measuring alveolar size throughout childhood and adoles-
cence using hyperpolarized helium has shown that neo-alveolarization,
3 days
as well as increase in alveolar size, continues through childhood and
adolescence (Narayanan et al 2012). This has important implications Endothelial cell
for diseases characterized by neonatal arrest of alveolarization, e.g. after
ventilation of the extreme preterm baby. Forced vital capacity is reported 3 weeks
to be the same in male and female infants and very young children Endothelial cell
(Jones et al 2000), which is consistent with postmortem morphometric Elastin
measurements. By the second year of life, the rate of increase in forced Smooth muscle
vital capacity is similar to that reported in older children. Fig. 52.26 En face views (left) and transverse sections (right) showing the
During childhood, lung volumes and flow rates increase linearly changes in the endothelial and smooth muscle cells of small muscular
with height, with a greater intercept and more positive slope in boys pulmonary arteries accompanying terminal bronchi from the neonatal


compared to girls (Stanojevic et al 2008). The linearity of these changes period to 3 weeks after birth. (With permission from Haworth SG 1992
is interrupted by puberty (Rosenthal et al 1993a, 1993b, Rosenthal and Pathophysiological and metabolic manifestations of pulmonary vascular
Bush 2002), when important shape changes occur in the thorax, par- disease in children. Herz 17(40:254–261).)
ticularly in boys; these are mirrored by changes in the size of the under-
lying lung (and, in particular, the alveoli), as manifested by an abrupt
increase in vital capacity, forced expired volume in 1 second, and total
lung capacity. Thereafter, the change in lung size again proceeds in a positions. At birth, the internal elastic lamina of the small muscular
linear fashion. High-resolution computed tomographic scanning has arteries consists only of amorphous elastin in a basal lamina-like
been used to measure airway dimensions (de Jong et al 2006), although matrix. By 3 weeks of age, a definitive elastic lamina is evident, although
this technique should be used with caution because of the radiation it is heavily fenestrated, permitting contact between the endothelial
exposure. cells and the smooth muscle cells.
There is little in the way of structural data to set alongside epidemiol-
ogy. The reticular basement membrane (lamina reticularis) is first Stage three This continues into adulthood. The intrapulmonary
detected at about 30 weeks’ gestation, thickens throughout childhood arteries increase in size and their walls increase in thickness. However,
and adolescence, and plateaus, or possibly declines, in thickness with the maturation of all of the pulmonary vascular smooth muscle cells,
age (Tsartsali et al 2011). In terms of airway smooth muscle, autopsy from the hilum to the precapillary bed, is not advanced until 2 years.
data suggest that it increases over the first 2 years of life; limited data As the distal airspaces expand, the capillary nets fuse from one alveolus
from endobronchial biopsies suggested that it did not change from age to another, forming, for a period, an extensive double capillary net; this


3 years throughout childhood (O’Reilly et al 2013). Goblet cells also process can be seen from postnatal day 28, becomes more extensive by
increase over the same timeframe (Hislop and Haworth 1989). 1.5 years, and is believed to be complete by 5 years.
Adverse effects on postnatal
Normal postnatal pulmonary lung development
arterial development The long-term effects of preterm birth and its treatment are changing
over the years. Current extremely premature babies, who are treated
Immediately after birth, dramatic remodelling of the pulmonary vascu- with surfactant and ventilated using low pressure, high-risk strategies,
lature occurs, to effect an abrupt reduction of pulmonary vascular resist- have arrest of alveolar development and pulmonary hypoplasia. Survi-
ance. This process continues at a rapid rate throughout the first 1–2 vors from the pre-surfactant era have disease dominated by airflow
months, while the lungs adapt to extrauterine life, and then more slowly obstruction. Importantly, even so-called ‘late pre-term’ babies (born at
throughout childhood. Failure to remodel in the presence of an ana- 33–34 weeks’ gestation) have persistent airflow obstruction (Kotecha
tomically normal heart leads to persistent pulmonary hypertension. et al 2012). Postnatal lung development is also impaired by exposure
Normal postnatal pulmonary arterial development in the full-term to tobacco smoke, and there is increasing evidence that air pollution
neonate can be divided into three stages. (Schultz et al 2012) and early sensitization to aeroallergens (Illi et al
2006) also have an adverse impact on normal lung growth. The first
Stage one This lasts from birth to about postnatal day 4 and concerns 4–6 years of life seem to be a key time window, after which there is no
the immediate adaptation to extrauterine life. At birth, the endothelial catch-up growth in lung function (Oswald et al 1997, Morgan et al
cells of the precapillary arteries are squat and have narrow bases on the 2005, Stern et al 2007); early effects on lung growth have lifelong
subendothelium, a low surface to volume ratio and many surface pro- implications.
jections. Five minutes after birth, the endothelial cells are thinner and


gradually show less cell overlap, the surface to volume ratio increases,
CONGENITAL MALFORMATIONS OF THE TRACHEA,
few cell projections are seen, the vessel wall becomes thinner and the
luminal diameter increases (Fig. 52.26). The smooth muscle cells show BRONCHI AND LUNGS
a significant reduction in diameter during this time.
This is an enormous topic and only a small number of anomalies can
Stage two This lasts from around day 4 to 3–4 weeks and is the time be mentioned here (for further information, see Abel et al (2012)). The
when the cells deposit matrix around themselves to fix their new concept of the lung as six ‘trees’ has been mentioned earlier; all but the


Development of the thorax
930
7
noItCeS
systemic venous tree may contribute to a congenital thoracic malforma-
Bonus e-book images and video
tion (CTM) (Bush 2009). In addition, congenital anomalies of the heart
and great vessels, and of the chest and abdominal walls, including
neuromuscular disease, may impact on lung development. It is some-
what artificial to describe airway malformations in isolation, and the Fig. 52.4 A Morgagni hernia in an 8-year-old boy, as displayed at
possibility of associated vascular anomalies must always be considered. laparotomy.
Moreover, descriptions of what is seen clinically should be kept separate
from speculations about the embryological origins of the anomaly. Fig. 52.5 A plain radiograph of the chest and abdomen in a
1-day-old neonate with left posterolateral congenital diaphragmatic
Disorders of the proximal airways hernia.
Fig. 52.24 A, A normal four-chamber view at 22 weeks’ gestation.
Available with the Gray’s Anatomy e-book B, The ventricular inflow with colour flow.
Fig. 52.27 Examples of tracheo-oesophageal fistulae and
Disorders of the distal airways
oesophageal atresia.
Video 52.1 Animation of the pattern of contraction of the early
Available with the Gray’s Anatomy e-book
heart tube.
KEY REFERENCES
Abel RM, Bush A, Chitty LS et al 2012 Congenital lung disease. In: Wilmott Nelson SM, Hajivassiliou CA, Haddock G et al 2005 Rescue of the hypo-
R, Boat T, Bush A et al (eds) Kendig and Chernick’s Disorders of the plastic lung by prenatal cyclical strain. Am J Respir Crit Care Med 171:
Respiratory Tract in Children, 8th ed, pp. 317–57. 1395–402.
A review of all aspects of the diagnosis, nomenclature and management of An explanation of how tracheal occlusion can be used in an animal model
congenital malformations of the airways, lung and chest wall. to improve lung growth and maturation.
Bush A 2005 Asthma research: the real action is in children. Paediatr Respir Ornitz DM, Yin Y 2012 Signalling networks regulating development of the


Rev 6:101–10. lower respiratory tract. Cold Spring Harb Perspect Biol 1;4. pii: a008318.
A review of how early problems with lung growth and development impact This paper presents a review of the signalling factors in lung development.
on later lung disease.
Roth-Kleiner M, Post M 2005 Similarities and dissimilarities of branching
Bush A 2009 Prenatal presentation and postnatal management of congenital and septation during lung development. Pediatr Pulmonol 40:113–34.
thoracic malformations. Early Human Dev 85:679–84. An account of the molecular mechanisms underlying normal lung
This paper presents an overview of congenital thoracic malformations. development.
Jesudason EC 2002 Challenging embryological theories on congenital dia- Sylva M, van den Hoff MJ, Moorman AF 2013 Development of the human
phragmatic hernia: future therapeutic implications for paediatric heart. Am J Med Genet A 164A:1347–71.
surgery. Ann R Coll Surg Engl 84:252–9. This paper presents the signalling factors in heart development.
This paper considers the evidence for anomalous lung development
Van Vonderen JJ, Roest AAW, Siew ML et al 2014 Measuring physiological
underpinning the development of diaphragmatic hernia.
changes during the transition to life after birth. Neonatology 105:
Morrisey EE, Hogan BL 2010 Preparing for the first breath: genetic and cel- 230–42.
lular mechanisms in lung development. Dev Cell 18:8–23. This paper presents an overview of the respiratory and haemodynamic
This paper presents an overview of the molecular mechanisms of lung transitions occurring at birth.
development.


Development of the thorax
930.e1
25
retpahC
Tracheomalacia and bronchomalacia Complete cartilage rings
Anomalies in cartilage development lead to the affected airways being The normal large-airway cartilages are horseshoe-shaped, and the ends
‘floppy’ and collapsing during inspiration or expiration, depending on of the horseshoes are bridged by the membranous part of the trachea.
whether they are outside or inside the bony thorax, respectively; these Complete cartilage rings may develop in the trachea and large airways,
anomalies are termed tracheomalacia when the trachea is affected, and and the posterior, membranous, part of the airway may be absent in a
bronchomalacia when the bronchi are involved. The anomaly may single cartilage or in long segments of the airway. This anomaly may be
involve a small, localized area or may be more generalized (e.g. associated with vascular anomalies such as pulmonary artery sling
Williams–Campbell syndrome, a congenital deficiency of the airway (where the left pulmonary artery originates from the right pulmonary
cartilage, in which there is diffuse bronchomalacia from the second to artery and not from the main pulmonary trunk). Extensive severe
the seventh generation of bronchi). Tracheobronchomalacia usually disease may present with neonatal respiratory distress; later presenta-
presents in early infancy with cough, tachypnoea, stridor and wheeze; tions include apparently steroid-resistant asthma. Tracheal transplanta-
it may also be associated with cardiac or respiratory anomalies, such as tion has been used to treat long-segment tracheal stenosis. Tracheal
absent pulmonary valve syndrome, or tracheo-oesophageal fistula, cartilage shape is abnormal in cystic fibrosis in both human infants and
respectively. Patients with significant obstruction and apnoea may be the experimental pig model, but the cartilages are not continuous rings
treated by the insertion of airway stents if the disease is localized, in this condition (Meyerholz et al 2010).
although there is only limited long-term experience in children with
Agenesis and aplasia of the lungs
stents; generalized disease may mandate respiratory support, either with
non-invasive mask ventilation during sleep, or via a tracheostomy, Agenesis and aplasia of the lungs are extremely rare congenital anoma-


depending on severity. Surgical treatment by aortopexy is controversial. lies, in which there may be unilateral or bilateral absence of the lung.
In agenesis, the airway stump is absent, i.e. the trachea is absent in
Tracheo-oesophageal fistulae
bilateral disease, or the primary bronchus is absent in unilateral disease.
Tracheo-oesophageal fistulae are the most common anomalies of the In aplasia, there is a rudimentary airway stump but no distal lung; the
lower respiratory tract and occur in about 1 in 3000 births. They usually contralateral lung is enlarged, with a greater number of alveoli, but has
present in the newborn with recurrent respiratory distress and choking a normal bronchial branching pattern. Individuals with aplasia may
spells, although late presentation in adult life has been described and present with recurrent infection, dyspnoea and reduced exercise capac-
may be associated with oesophageal atresia. Normally, the oesophagus ity, and there may be pooling of bronchial secretions, with secondary
lengthens with the rapid elongation of the embryo up to 7 weeks. The infection and overspill of infected secretions into the contralateral
rapid proliferation of the oesophageal lumen partially obliterates the normal lung.
mucosa and recanalization is not complete until 8 weeks. The cellular
Bronchogenic and other cysts
processes that lead to separation of the trachea and oesophagus occa-
sionally produce oesophageal atresia. Tracheo-oesophageal atresia is Cysts of various types, by order of frequency, may be found in the
rare, with an incidence of 1 in 3000 to 1 in 4500 births. Five types of carinal (51%), right paratracheal (19%), para-oesophageal (14%), hilar
tracheo-oesophageal fistulae may be recognized (Fig. 52.27). In almost (9%) and pericardial, retrosternal and paravertebral (7%) regions. Clin-
all cases, the oesophagus ends blindly and the stomach is connected to ically, they are part of the spectrum of congenital thoracic anomalies,
the lower end of the trachea. Because of this connection, the abdomen and can only be classified in more detail pathologically when the wall


becomes rapidly distended with air once the baby is delivered and starts of the cyst is examined; they may have a systemic blood supply and
breathing. Prenatally, polyhydramnios may be a clinical feature but may venous drainage. Multicystic anomalies, described as various types of
not be apparent until the third trimester. In two of the five types of congenital cystic adenomatous malformations (CCAM) and sequestra-
tracheo-oesophageal fistulae, there is no communication between the tions (intra- and extrapulmonary), are best considered generically as a
stomach and the upper gut. Such cases are identifiable on ultrasound CTM spectrum, at least until examined pathologically; even then, fea-
because the stomach should always be visible at a 20-week examina- tures of CCAM and sequestration may be found in the same anomaly,
tion; its absence on ultrasound should prompt further evaluation. rendering classification difficult. Presentation may involve a range of
Tracheo-oesophageal fistula is commonly associated with other con- problems, from intractable newborn respiratory distress to a chance
genital anomalies, including cardiovascular defects (30%), anorectal finding in adult life. If the infant is symptomatic, then surgical resection
anomalies (15%) and genitourinary anomalies (15%). These defects is indicated. Treatment of the asymptomatic anomaly is controversial;
may be combined in the VATER, VACTER and VACTERL associations, some centres would operate electively on all but the tiniest malforma-
which involve varying combinations of vertebral defects, anorectal tions, whereas others would manage even large, asymptomatic, cystic
atresia, cardiac anomalies, tracheo-oesophageal fistula and oesophageal malformations conservatively. Evidence is summarized in a recent
atresia, together with radial aplasia and other limb anomalies, renal meta-analysis (Stanton et al 2009).
anomalies and the presence of a single umbilical artery.
Fig. 52.27 Examples of tracheo-oesophageal fistulae and oesophageal atresia.


Development of the thorax
930.e2
7
noItCeS
Bronchial atresia cases are asymptomatic and are revealed as incidental findings on chest
radiographs. However, many eventually become the seat of recurrent
Bronchial atresia is a congenital condition in which a major bronchus
infection and require operative removal. Some infants may show a
or segmental airway ends blindly or with a thin membrane. Pulmonary
congenital large hyperlucent pulmonary lobe (CLHL). This condition
development normally occurs distally and, over time, this tissue
is termed ‘congenital lobar emphysema’, although it has nothing to do
becomes distended with debris and mucus (bronchocele), with adja-
with adult emphysema. Presentation in severe cases is with newborn
cent over-inflated lung tissue. Typically, bronchial atresia affects the left
respiratory distress; in this case, early surgery is required. Otherwise, it
upper lobe (64% of cases); the chest radiographic findings are of a
may be a chance radiographic finding later in life; in this case, no action
perihilar ovoid density with strands projecting into a localized area of
is needed.
hyperlucent lung. The left lower lobe is affected in 14% of cases and
the right lower and right middle lobes in 8% of cases. The majority of


Development of the thorax
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retpahC
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20:1261–6. dren aged 4–19 years: II. Single breath analysis and plethysmography.
Thorax 48:803–8.
Janér J, Lassus P, Haglund C et al 2006 Pulmonary vascular endothelial
growth factor-C in development and lung injury in preterm infants. Am
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Rosenthal M, Bush A 2002 The growing lung: normal development, and the Stern DA, Morgan WJ, Wright AL et al 2007 Poor airway function in early
long-term effects of pre- and post-natal insults. In: Bush A, Zach M, infancy and lung function by age 22 years: a non-selective longitudinal
Carlsen K-H (eds) Growing up with lung disease: the lung in transition cohort study. Lancet 370:758–64.
to adult life. Eur Respir Monograph 7:1–24. Sylva M, van den Hoff MJ, Moorman AF 2013 Development of the human
Roth-Kleiner M, Post M 2005 Similarities and dissimilarities of branching heart. Am J Med Genet A 164A:1347–71.
and septation during lung development. Pediatr Pulmonol 40:113–34. This paper presents the signalling factors in heart development.
An account of the molecular mechanisms underlying normal lung
Tollet J, Everett AW, Sparrow MP 2002 Development of neural tissue and
development.
airway smooth muscle in fetal mouse lung explants: a role for glial-
Schultz ES, Gruzieva O, Bellander T et al 2012 Traffic-related air pollution derived neurotrophic factor in lung innervation. Am J Respir Cell Mol
and lung function in children at 8 years of age: a birth cohort study. Am Biol 26:420–9.
J Respir Crit Care Med 186:1286–91. Tsartsali L, Hislop AA, McKay K et al 2011 Development of the bronchial
Sekhon HS, Keller JA, Proskocil BJ et al 2002 Maternal nicotine exposure epithelial reticular basement membrane: relationship to epithelial
upregulates collagen gene expression in fetal monkey lung. Association height and age. Thorax 66:280–5.
with alpha7 nicotinic acetylcholine receptors. Am J Respir Cell Mol Biol Van Vonderen JJ, Roest AAW, Siew ML et al 2014 Measuring physiological
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branching morphogenesis and mesenchymal FGF networks. Dev Biol This paper presents an overview of the respiratory and haemodynamic
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253–60.
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J Pediatr Surg 44:1027–33.


CHAPTER
53
Chest wall and breast
The chest wall surrounds the thoracic cavity. The skin and soft tissue Innervation
cover a musculoskeletal frame consisting of twelve pairs of ribs, which
articulate with twelve thoracic vertebrae posteriorly and (except for the
The skin of the thorax is supplied by cutaneous branches of cervical and
last two pairs of ribs) with the sternum anteriorly, via their costal car-
thoracic nerves in consecutive, curved zones; the upper zones are almost
tilages; intrinsic muscles and muscles that connect the chest wall with
horizontal and the lower are oblique. On the upper anterior aspect of
the upper limb and the vertebral column; and numerous blood
the thorax, the areas innervated by the third and fourth cervical nerves
and lymphatic vessels and nerves that supply the components of the
adjoin those innervated by the first and second thoracic nerves because
musculoskeletal frame and the overlying skin and breast tissue.
the intervening nerves provide the sensory and motor supply to the
upper limb (Ladak et al 2014) (Fig. 53.3). There is a similar, but less
SKIN AND SOFT TISSUE extensive, posterior ‘gap’: most of the skin covering the posterior aspect
of the thorax is supplied by the dorsal rami of the thoracic nerves (see
Fig. 45.8). The subcostal margin is supplied by the seventh thoracic
SKIN
nerve.
The ventral rami of the first to the eleventh thoracic nerves pass into
Vascular supply
the appropriate intercostal space, giving off a lateral cutaneous branch
that arises beyond the angle of the rib and divides into anterior and
Arteries posterior branches, terminating near the sternum as an anterior cutane-
The skin of the thorax is supplied by a combination of direct cutaneous ous branch (see Fig. 53.21).
vessels and musculocutaneous perforators that reach the skin primarily Branches of the supraclavicular nerve, which originates from the
via the intercostal muscles, pectoralis major, latissimus dorsi and trape- third and fourth cervical nerve roots, supply the skin in the upper pec-
zius. The major contributing vessels are branches from the thoraco- toral region. Most of the first thoracic nerve joins the brachial plexus,


acromial axis, lateral and internal thoracic, anterior and posterior apart from a small inferior branch that becomes the first intercostal
intercostal, thoracodorsal, transverse cervical, dorsal scapular and cir- nerve. The lateral cutaneous branch of the second intercostal nerve sup-
cumflex scapular arteries (Figs 53.1–53.2; see Fig. 43.4). plies the skin of the axilla as the intercostobrachial nerve. The costal
The anterior aspect of the thoracic skin is supplied by the thoraco- margin is supplied by a branch from the seventh thoracic nerve. The
acromial axis, the internal thoracic arteries, perforating branches from seventh to eleventh thoracic nerves supply the skin of the thoracic wall
the intercostal arteries and branches from the lateral thoracic and super- as they pass anteriorly and inferiorly; they continue beyond the costal
ficial thoracic arteries. The thoraco-acromial axis supplies the skin pri- cartilages to supply the skin and subcutaneous tissues of the abdominal
marily via musculocutaneous perforators from its pectoral branch; they wall. The skin of the abdomen at the level of the umbilicus is supplied
reach the skin through pectoralis major. In addition, direct cutaneous by the tenth thoracic nerve. The subcostal nerve follows the inferior
branches arise from the acromial and deltoid branches. The internal border of the twelfth rib and supplies the skin of the lower abdominal
thoracic artery sends direct perforating branches to the skin of the upper wall (see Fig. 61.5).
six intercostal spaces, accompanied by the cutaneous branches of the
anterior intercostal nerves. The branches reach the skin after passing
SOFT TISSUE
through pectoralis major and travelling laterally in the subcutaneous
fat as direct cutaneous vessels. The second intercostal perforator is
Superficial fascia
usually the largest. The lateral aspect of the thoracic skin is supplied by
the lateral thoracic and superficial thoracic arteries and by lateral cuta-
neous branches of the intercostal arteries. The lateral thoracic artery The superficial fascia consists primarily of fat and is only loosely
gives off direct cutaneous branches to the lateral chest wall in addition attached to the skin, an arrangement that allows some movement of


to musculocutaneous branches that pass through pectoralis major. The the underlying structures. Small blood vessels and nerves perforate the
posterior aspect of the thoracic skin is supplied by the medial and superficial fascia to supply the skin. The breast lies within the superfi-
lateral dorsal cutaneous branches of the posterior intercostal arteries cial fascia, apart from a superolateral extension that pierces the deep
(via erector spinae and latissimus dorsi); musculocutaneous perforating fascia to form the axillary tail in the female. It is described later in this
branches from the superficial cervical, transverse cervical and dorsal chapter.
scapular arteries (via trapezius); musculocutaneous perforating branches
from the thoracodorsal artery and the intercostal arteries (via latissimus Deep fascia
dorsi); and direct cutaneous branches from the circumflex scapular
artery. Clavipectoral fascia
Veins The clavipectoral fascia is the cranial continuation of the deep lamina
of the pectoral fascia and the medial continuation of the parietal layer
The intercostal veins accompany the similarly named arteries in the
of the subscapular bursal fascia. It extends between the clavicle and
intercostal spaces (see Fig. 51.3). The small anterior intercostal veins are
pectoralis minor, surrounds subclavius and extends medially to the first
tributaries of the musculophrenic and internal thoracic veins, the latter
rib. It is described in detail on page 799.
draining into the appropriate brachiocephalic vein. The posterior inter-
costal veins drain backwards directly or indirectly into the azygos vein
on the right and the hemiazygos or accessory hemiazygos veins on the BONE AND CARTILAGE
left. The azygos veins exhibit great variation in their origin, course,
tributaries, anastomoses and termination (Ch. 56).
The twelve thoracic vertebrae and their associated intervertebral discs
are described in detail in Chapter 43.
Lymphatic drainage
Superficial lymphatic vessels of the thoracic wall ramify subcutaneously STERNUM
and converge on the axillary nodes (p. 834; see Figs 53.22, 53.24, 48.45).


Lymph vessels from the deeper tissues of the thoracic walls drain mainly The sternum is an elongated, flattened bone that forms the middle
to the parasternal, intercostal and diaphragmatic lymph nodes. portion of the anterior wall of the thorax. It articulates with the clavicles 931


Chest wall and breast
932
7
nOItCes
1
2
3
4
6
5 1
4
6 5
3
7
8
7 9
9 2
10
8 11
10
11
12
1 Circumflex scapular artery 5 Thoraco-acromial axis
1 Transverse cervical artery 7 Deep circumflex iliac artery
2 Musculocutaneous perforators 6 Internal thoracic artery
2 Direct cutaneous branch of the 8 Superficial circumflex iliac artery
through latissimus dorsi from
thoraco-acromial axis intercostal and lumbar arteries 7–11 Lateral cutaneous branches
9 Superficial inferior epigastric artery
from intercostal arteries
3 Anterior perforators from the
interior thoracic artery 10 Superficial external pudendal artery 3 Musculocutaneous perforators 12 Musculocutaneous perforators
through latissimus dorsi from
4 Superficial thoracic artery 11 Deep external pudendal artery thoracodorsal artery through external oblique from
intercostal arteries
5 Intercostal perforators 4 Cutaneous branches from
thoracodorsal and lateral
6 Musculocutaneous perforators thoracic arteries
from the superior and inferior
Fig. 53.2 Anatomical territories of cutaneous blood vessels on the lateral
deep epigastric arteries
trunk. (With permission from Cormack GC, Lamberty BGH 1994 The
Fig. 53.1 Anatomical territories of cutaneous blood vessels on the Arterial Anatomy of Skin Flaps, 2nd ed. Edinburgh: Churchill Livingstone.)
anterior trunk. (With permission from Cormack GC, Lamberty BGH 1994
The Arterial Anatomy of Skin Flaps, 2nd ed. Edinburgh: Churchill
Livingstone.) Manubrium
The manubrium is level with the third and fourth thoracic vertebrae. It
has a somewhat quadrangular form, being broad and thick above and
narrowing to its junction with the body. The anterior surface is smooth,
at the sternoclavicular joints (p. 808) and with the cartilages of the transversely convex and vertically concave, and the posterior surface is


first seven pairs of ribs. The sternum consists of a cranial manubrium, concave and smooth. The superior border is thick and contains a central
an intermediate body (mesosternum, gladiolus) and a caudal xiphoid jugular (suprasternal) notch between two oval fossae, the clavicular
process (Figs 53.4–53.5). Until puberty, the body consists of four notches, that are directed up and posterolaterally for articulation with
sternebrae, which are intersegmental. The average length of the adult the sternal ends of the clavicles. Fibres of the interclavicular ligament are
sternum is 17 cm; the ratio between manubrial and mesosternal lengths attached to the jugular notch. The inferior border, oval and rough, carries
differs between the sexes. Growth may continue beyond the third a thin layer of cartilage for articulation with the body. The lateral borders
decade and possibly throughout life. are marked above by a depression for the first costal cartilage and below
In natural stance, the sternum slopes down and slightly forwards. by a small articular demifacet, which articulates with part of the second
The bone is anteriorly convex and posteriorly concave, and broadest at costal cartilage. The narrow curved edge descends medially between
the junction with the first costal cartilages. It narrows at the manubrio- these facets. There is very little accessory movement at the manubrioster-
sternal joint, widens to its articulation with the fifth costal cartilages, nal joint, although pressure on either the body or the manubrium close
and then narrows again. The sternum contains highly vascular trabecu- to the joint will produce slight angling of the two sections.
lar bone enclosed by a compact layer that is thickest in the manubrium Unlike all the other sternocostal joints, the joint between the manu-
between the clavicular notches. Centrally, the bone is lightly constructed brium and the first costal cartilage is a fibrous synarthrosis. It lies 1 cm
whereas, laterally, the trabeculae are thicker and wider. The medulla below and 1 cm lateral to the medial end of the clavicle and is difficult
contains haemopoietic bone marrow. to palpate.


bone and cartilage
933
35
retPahC
Medial, intermediate
1 1
and lateral supraclavicular
nerves ( C3,4)
2 6
9
2
7 10
3
T2 8
3 T3 11
4
12
4 5 3 13
9
6
5
4
6 7 5
7 8 10 14
11 15
8 9 4
Lateral
9 10 cutaneous
11 branches of 6 16
Anterior cutaneous 10 thoracic nerves 12
branches of
thoracic nerves 11 Lateral cutaneous 7
branches of twelfth 17
Anterior cutaneous 12 thoracic nerve 8
branch of
iliohypogastric nerve L1 Lateral femoral 13 18
cutaneous nerve 5
Ilioinguinal nerve
A 14 B
Femoral branch
of genitofemoral
nerve Fig. 53.4 The sternum. A, Anterior aspect. Key: 1, jugular notch; 2,
attachment for sternocleidomastoid; 3, sternal angle and manubriosternal
joint; 4, attachment for pectoralis major; 5, seventh costal notch; 6,
clavicular notch; 7, first costal notch 8, manubrium; 9, second costal
notch; 10, third costal notch; 11, body of sternum; 12, fourth costal
notch; 13, sixth costal notch; 14, xiphisternal joint. B, Posterior aspect.
Key: 1, jugular notch; 2, attachment for sternohyoid; 3, attachment for
sternothyroid; 4, edge of area covered by left pleura; 5, edge of area
covered by right pleura; 6, attachment for transversus thoracis; 7, area in
Fig. 53.3 The approximate segmental distribution of the cutaneous nerves contact with pericardium; 8, attachment for transversus thoracis; 9,


on the anterior trunk. The contribution from the first thoracic spinal nerve clavicular notch; 10, first costal notch; 11, manubrium; 12, second costal
is not shown and the considerable overlap that occurs between adjacent notch; 13, sternal angle and manubriosternal joint; 14, third costal notch;
segments is not indicated. 15, body of sternum; 16, fourth costal notch; 17, fifth costal notch; 18,
seventh costal notch.
Body
The body is level with the fifth to ninth thoracic vertebrae. It is longer, Muscle attachments The sternal ends of pectoralis major and ster-
narrower and thinner than the manubrium, and is broadest near its nocleidomastoid are attached to the anterior surface of the manubrium.
lower end. The anterior surface, being nearly flat and facing slightly Sternothyroid is attached to the posterior surface, opposite the first
upwards, usually bears three variable transverse ridges that mark the costal cartilage, and the most medial fibres of sternohyoid are attached
levels of fusion of its four sternebrae. A sternal foramen, of varying size above sternothyroid. The articular capsules of the sternocostal joints
and form, may occur between the third and fourth sternebrae. The and sternal fibres of pectoralis major are attached to the anterior surface
posterior surface, slightly concave, also displays three less distinct trans- of the body. Transversus thoracis (sternocostalis) is attached to its pos-
verse lines. The oval upper end articulates with the manubrium at the terior surface. The external intercostal membranes are attached to the
level of the sternal angle (manubriosternal joint, angle of Louis), which borders of the body between the costal facets. The most medial fibres
lies opposite the inferior border of the fourth vertebral body and is of rectus abdominis and the aponeuroses of external and internal
marked by a posterior transverse groove. oblique are attached to the anterior surface of the xiphoid. The linea
Named after the French surgeon, Antoine Louis (1723–1792), the alba is attached to its lower end, and the aponeuroses of internal


Latin name, angulus Ludovici, is not infrequently mistranslated into oblique and transversus abdominis are attached to its borders. Slips of
English as ‘the angle of Ludwig’. the diaphragm are attached to its posterior aspect, and the sternum is
The lower end of the body is narrow and continuous with the here related to the liver.
xiphoid process. On each lateral border, at its superior angle, a small
notch articulates with part of the second costal cartilage (see Figs 53.4, Vascular supply The internal thoracic artery provides the main
53.5). Below this, four costal notches articulate with the third to sixth blood supply for the sternum via anterior and posterior networks of
costal cartilages. The inferior angle bears a small facet, which, together perforating arteries that directly penetrate the sternum at the level of
with the xiphoid process, articulates with the seventh costal cartilage. each intercostal space. These networks are particularly well devel-
Between these articular depressions, a series of curved edges diminish oped posteriorly and at the level of the fourth and fifth intercostal
in length downwards and form the anterior limits of the intercostal spaces.
spaces. The venous network is less developed. It is formed mainly by an
inframedullary network of sinuses in the bone that drain via transcorti-
Xiphoid process (xiphisternum)
cal veins either into the peripheral sternal networks or the internal
The xiphoid process is in the epigastrium. It is the smallest and most thoracic vein.
variable sternal element, and may be broad and thin, pointed, bifid,
perforated, curved or deflected. When elongated and curved forwards, Innervation The manubrium is supplied by the anterior branch of the
it may be mistaken for an epigastric mass. The xiphoid is cartilaginous supraclavicular nerve and the anterior cutaneous branch of the first
in youth but more or less ossified in adults. It is continuous with the intercostal nerve, whereas the body of the sternum is supplied largely
lower end of the body at the xiphisternal joint. Demifacets that articu- by anterior branches of the intercostal nerves. The anterior branch of


late with parts of the seventh costal cartilages occur anterior to its the phrenic nerve runs anteromedially from the diaphragm and sup-
superolateral angles (see Fig. 53.5). plies the lower portion of the sternum.


Chest wall and breast
934
7
nOItCes
Suprasternal ossicles, paired or single, sometimes occur. They may
fuse to the manubrium or articulate posteriorly at the lateral border of
Clavicular notch the jugular notch. When well formed, they are pyramidal, and their base
is articular. The ossicles are cartilaginous at birth and ossify during
adolescence.
Manubrium First costal notch
Pectus excavatum Pectus excavatum is the most common congeni-
tal deformity of the anterior chest, and is a depression of the sternum
and costal cartilage that is sometimes referred to as cobbler’s chest,
Sternal angle sunken chest, the crevasse or funnel chest. The lower costal cartilages
Second costal notch
and the body of the sternum are depressed and there is some asym-
metric curving of the ribs posteriorly. There is often an abnormal
posture with dorsal lordosis, sometimes with developing scoliosis. The
deformity is found either at birth (1 in 500 live births) or early in
Third costal notch life; in the majority of cases, the condition is manifest by 1 year but
may not develop until puberty. The aetiology is unknown but some
cases are associated with connective tissues diseases, such as Marfan’s
syndrome.
Fourth costal notch Pectus carinatum Pectus carinatum, often called ‘pigeon chest’, is
an overgrowth of cartilage that causes the sternum to protrude forwards.
Body It is less common than pectus excavatum and a quarter of cases are
familial. The condition may occur as a solitary congenital abnormality
Fifth costal notch or in association with other genetic disorders. Although present in early
childhood, pectus carinatum usually progresses during adolescence and
then remains unchanged throughout adulthood.
Sixth costal notch
CLAVICLE
Seventh costal notch
The clavicle is described in Chapter 48.
Xiphoid process
RIBS
The ribs are 12 pairs of elastic arches (Fig. 53.8), each consisting of
highly vascular trabecular bone containing large amounts of red
Fig. 53.5 The sternum, left lateral aspect. (With permission from Waschke marrow, enclosed in a thin layer of compact bone.


J, Paulsen F (eds), Sobotta Atlas of Human Anatomy, 15th ed, Elsevier, The ribs articulate posteriorly with the vertebral column and form
Urban & Fischer, 2013.) the greater part of the thoracic skeleton. Their number may be increased
by cervical or lumbar ribs or reduced by the absence of the twelfth pair.
The first seven ‘true’ ribs connect to the sternum by costal cartilages,
A Time of B Time of whilst the remaining lower five ‘false’ ribs either join the superjacent
appearance union
costal cartilage (8–10) or ‘float’ free at their anterior ends as relatively
small and delicate structures tipped with cartilage (11–12). The tenth
1 rib may also float: the incidence varies from 35% to 70%, depending
on ancestry.
Fifth fetal month
Usually remain The ribs are separated by the intercostal spaces, which are deeper in
non-united
front and between the upper ribs. The latter are less oblique than the
2
lower ribs; obliquity is maximal at the ninth rib. Ribs increase in length
Fifth to sixth fetal month Between puberty up to the seventh and thereafter diminish. They decrease in breadth
3 and the twenty-fifth
downwards; in the upper ten the greatest breadth is anterior. The first
year
two and the last three ribs present special features, whereas the remain-
4 der conform to a common plan.
Soon after puberty
Typical rib
5
About the fortieth
Unossified (cartilaginous) region 6 year A typical rib has a shaft with anterior and posterior ends (Fig. 53.9).
The anterior costal end has a small concave depression for the lateral
end of its cartilage. The shaft has an external convexity and is grooved
Fig. 53.6 The ossification of the sternum. A, Before birth. B, After birth.
internally near its lower border, which is sharp, whereas its upper
border is rounded. The posterior vertebral end has a head, neck and
Ossification The sternum is formed by fusion of two cartilaginous tubercle. The head presents two facets, separated by a transverse crest.
sternal plates flanking the median plane. The arrangement and number The lower and larger facet articulates with the body of the correspond-


of centres of ossification vary according to the level of completeness ing vertebra, its crest attaching to the intervertebral disc above it. The
and time of fusion of the sternal plates, and according to the width of neck is the flat part beyond the head, anterior to the corresponding
the adult bone. Incomplete fusion leaves a sternal foramen. The manu- transverse process. It is oblique and faces anterosuperiorly. Its postero-
brium is ossified from one to three centres appearing in the fifth fetal inferior surface is rough and pierced by foramina. Its upper border is
month. The first and second sternebrae usually ossify from single the sharp crest of the neck, its lower border rounded. The tubercle,
centres that appear at about the same time (Fig. 53.6A). Centres in the which is more prominent in upper ribs, is posteroexternal at the junc-
third and fourth sternebrae are commonly paired, and appear in the tion of the neck and shaft, and is divided into medial articular and
fifth and sixth months, respectively; one of either pair may be delayed lateral non-articular areas. The articular part bears a small, oval facet for
until the seventh or even eighth month, and the fourth sternebral centre the transverse process of the corresponding vertebra. The non-articular
may be absent. The xiphoid process begins to ossify in the third year area is roughened by ligaments. The shaft is thin and flat, and has
or later. In some sterna, all centres are single and median; in others, the external and internal surfaces, and superior and inferior borders. It is
manubrial centre is single and the sternebral centres are all paired, sym- curved, bent at the posterior angle (5–6 cm from the tubercle), and
metric or asymmetric. Union between mesosternal centres begins at twisted about its long axis. The part behind the angle inclines supero-
puberty and proceeds from below upwards; by the age of 25 years, they medially and so its external surface is posteroinferior. In front of the
are all united (Fig. 53.6B). angle, the rib faces slightly up. It is convex and smooth, and, near the


Chest wall and breast
934.e1
35
retPahC
The clinical significance of pectus excavatum may vary considerably Depressed sternum Right ventricle Left ventricle
(Fig. 53.7). Severe defects can lead to cardiopulmonary dysfunction,
whilst almost all patients will have some degree of cosmetic concern.
Back and chest pain may occur. Evaluation of the deformity demands
careful symptom assessment in addition to baseline radiological inves-
tigations (chest radiograph and computed tomography (CT)). Where
there are physiological restrictions, lung function tests, electrocardio-
grams (ECGs) and echocardiograms form part of the assessment before
specialist clinicians can determine the safety of any surgical interven-
tion. A classification system based on morphology using CT scanning
has been proposed (Park et al 2004) and is useful for standardizing the
results of surgical correction of the different subtypes.
Mild defects causing aesthetic concerns may be improved with cus-
tomized silicone implants (Masson et al 1970) or with soft tissue recon-
structive procedures (Raab et al 2009), to camouflage the concavity.
More severe defects often require correction of the underlying skeletal
deformity. Several techniques have been described. Open resection pro-
cedures were pioneered by Ravitch; however, more recently, minimally
invasive techniques have gained in popularity (Ravitch 1955, Nuss et al
1988).
Pectus carinatum occurs in three different ways, most commonly in
the 11–14-year-old pubertal male undergoing a growth spurt. Some
Right atrium Descending thoracic aorta Left atrium
parents report that their child’s pectus seemingly popped up ‘overnight’.
The second most common occurrence is from birth, when it is evident Fig. 53.7 Pectus excavatum.
in newborns as a rounded chest, becoming more prominent as the
child reaches 2 or 3 years old. The least common occurrence is as an
acquired condition after open heart surgery, when healing has been
aberrant. Pectus carinatum may be associated with Turner’s, Marfan’s,
Ehlers–Danlos, Morquio’s, Noonan’s, Sly’s or multiple lentigines syn-


dromes, trisomies 18 or 21, homocystinuria, osteogenesis imperfecta or
scoliosis.


bone and cartilage
935
35
retPahC
Scalenus medius
First thoracic vertebra
Serratus anterior, Facet for articulation with
first digitation clavicle
Scalenus anterior
Subclavius
Second rib
Sternal angle
Pectoralis major
Pectoralis minor
Serratus anterior
(remaining digitations)
Rectus abdominis
Twelfth thoracic
vertebra Levator
Twelfth rib costae
Fig. 53.8 The skeleton of the thorax, anterior aspect, showing muscle attachments.
tubercle, is crossed by a rough line, directed inferolaterally, towards the of external oblique and serratus anterior (or latissimus dorsi, in the case
posterior angle. The smooth internal surface is marked by a costal of the ninth and tenth ribs). The internal intercostal muscle is attached
groove, bounded below by the inferior border. The superior border of to the costal groove on the internal surface, and separates the bone and
the groove continues behind the lower border of the neck, but termi- the intercostal neurovascular bundle. At its vertebral end, the groove
nates anteriorly at the junction of the middle and anterior thirds of the faces down, its borders in the same plane. The shaft broadens near the
shaft, anterior to which the groove is absent. posterior angle, and the groove reaches its internal surface. The inner-
most intercostal is attached to the superior rim of the groove, and this
Attachments and relations A radiate ligament is attached along attachment occasionally extends to the anterior quarter of the rib. Pos-
the anterior border of the head and an intra-articular ligament is teriorly, the superior rim meets the lower border of the neck. The
attached along its crest. The anterior surface of the head is related to external intercostal muscle is attached to the sharp inferior costal
costal pleura and, in the more inferior ribs, to the sympathetic trunk. border. The superior border has two lips posteriorly: an inner and an
The anterior surface of the neck is divided by a faint transverse ridge for outer lip. The internal intercostal muscles and the innermost intercostal
the internal intercostal membrane and is continuous with the inner lip muscles are attached to the inner lip. The external intercostal muscle is


of the superior border of the shaft. The area above the ridge, which is attached to the outer lip.
more or less triangular, is separated from the membrane by fatty tissue
whilst the inferior smooth area is covered by costal pleura. The posterior Vascular supply and innervation Typical ribs receive their blood
surface of the neck gives attachment to the costotransverse ligament and supply anteriorly via branches from the internal thoracic artery (first six
is pierced by vascular foramina. The superior costotransverse ligament intercostal spaces) or musculophrenic artery (subsequent spaces), and
is attached to the crest of the neck, which extends laterally into the outer posteriorly from intercostal arteries derived directly from the aorta.
lip of the superior border of the shaft. The rounded inferior border of Venous drainage is into the corresponding intercostal vein and thence
the neck continues laterally into the upper border of the costal groove, into the azygos system. Typical ribs are innervated segmentally by
and gives attachment to the internal intercostal membrane. The articu- branches from their corresponding intercostal nerves.
lar area of the tubercle in the upper six ribs is convex and faces postero-
Cervical rib
medially. In the succeeding three or four ribs it is almost flat, and faces
down, back and slightly medially. The lateral costotransverse ligament
is attached to the non-articular area. A cervical rib, the costal element of the seventh cervical vertebra, may
The ridge on the external surface of the shaft (near its posterior be a mere epiphysis on its transverse process but more often it has a
angle) gives attachment to an upward continuation of the thoracolum- head, neck and tubercle. When a shaft is present, it is of variable length
bar fascia and lateral fibres of iliocostalis thoracis. From the second to and extends anterolaterally into the posterior triangle of the neck, where
the tenth ribs, the distance between angle and tubercle increases. Medial it may end freely or join the first rib, its costal cartilage or even the
to the angle, the external surface gives attachment to levator costae and sternum. A cervical rib may be partly fibrous but its effects are not


is covered by erector spinae. Near the sternal end of this surface, an related to the size of its osseous part. If it is long enough, its relations
indistinct oblique line, the anterior ‘angle’, separates the attachments are those of a first thoracic rib; the brachial plexus (usually lower trunk)