Pleural Anatomy

Pleural Embryonic Development

Once the embryonic disc has been formed in the trilaminar phase, which contains three germ layers, namely, ectoderm, mesoderm, and endoderm, the embryo will experience morphological changes following a basic body structuring plan, based on:

\(a)\ Craniocaudal differentiation gradient with the formation of the notochord, and the neural plate.

\(b)\ Body regular and transversal segmentation pattern, which evokes the evolutionary phases of the phylogenetic past ( sh, reptiles, etc.).

\(c)\ Body lateral folding, approaching the midline, converting its fat, trilaminar shape into a cylindrical structure with the ectoderm on the outside, the endoderm on the inside, and the mesoderm between the two.

It is precisely from the mesoderm that the pleura derives, among other embryo intermediate structures, forming a serous membrane that along with the peritoneum, internally covers the future coelomic cavity (parietal serosa), as well as

J. A. Moya Amorós (*)

Thoracic Surgery Department, Bellvitge University Hospital, Barcelona, Spain

e-mail: juan.moya@bellvitgehospital.cat

externally covers the organs and viscera. contained inside that cavity (visceral serosa).

The rst pleural vestige appears in the 22–23-­ day embryo, when it has already acquired three blastoderm sheets: ectoderm, mesoderm, and endoderm [1]. From this moment on, in the fat embryo thickness, the mesoderm (hereinafter mesenchyme) in turn undergoes fragmentation changes in three territories:

\1.\ Medial territory or chordamesoderm, from which the notochord will derive.

\2.\ Two lateral masses or lateral mesoderms, on each side of the embryo, from which they derive:

\(a)\ The somites, precursors of muscles, and bones.

\(b)\ The gononephrotome, precursor of the kidney, and the gonads.

\(c)\ The somatic mesoderm or somatopleura (future parietal pleura), and the splanchnic mesoderm or splanchnopleura (visceral pleura precursor) (Fig. 29.1).

The somatopleura is con gured by the somatic mesoderm fusion with the ectoderm internal part, so that the “coalescence” of both structures will end up forming the parietal pleura, which will internally cover the ribs and the intercostal space elements (costal pleura), with which it is kept separated by the endothoracic fascia.

The splanchnopleura, however, is produced by the fusion of the splanchnic mesoderm with the endoderm external part, so that the serosa resulting from this fusion will be the visceral pleura that will intimately surround the lung mesenchyme (lung parenchyma).

Approximately at the fourth week [2], the embryo has already evolved from having a fat shape to progressively acquiring a tubular-­

Fig. 29.1  Diagram of a 23-day embryo with 8 somites, at the neural canal stage in the lateral and ventral folding phas. (1) Ectoderm, (2) Neural canal, (3) Notochord, (4) Somite, (5) Gononephrotome, (6) Somatopleura, (7) Splacnopleura, (8) Endoderm

cylindrical shape due to a folding process of its lateral walls, both in the cranial-caudal and lateral-­medial directions. The cause still does not have a coherent explanation, although as a consequence­ of it, there is an approximation and fusion in all the embryonic leaves midline, except at the point where the omphalo-mesenteric duct or future umbilical cord emerges.

From this development moment, the embryo will have a closed body or trunk with a single cavity inside or coelomic cavity, which contains the future viscera (Fig. 29.2).

In parallel, embryonic changes have also been taking place at the level of the endoderm foregut anterior face. Immediately below the III to IV pharyngeal pouch, an endodermal cells outgrowth appears in the form of a laryngo-tracheo-­bronchial bud [3] that progressively and after 24 divisions comes to constitute both adult lungs tracheobronchial tree. In this sense, the lung can be considered as an enormous gland that, from the endodermal duct, invaginates towards the mesenchyme depth, maintaining communication with the outside through the embryo primitive mouth (stomodeum).

Fig. 29.2  Embryo of 25 days with 8–10 somites in the initial stage of tubular closure.

(1)Closed neural tube,

(2)Notochord, (3) Dorsal aorta, (4) Endoderm connected toon (5) Extraembryonic coelom (yolk vesicle),

(6)Somite, (7) Somatopleura, (8) Splacnopleura

1

6

7

8

5

Between the fourth and ninth weeks, inside the coelomic cavity, a new transverse septation process is outlined at the expense of a mesoderm septum internal growth (transverse septum), which will form the future diaphragm. As a consequence of this septation the coelomic cavity, (until now the only one) it is divided into two interconnected cavities, one cranial or thoracic and caudal or abdominal.

Parallel to these embryonic movements, in the paraxial regions inside the thoracic cavity, some cardinal folds emerge that protrude towards the cavity interior, pushing the somatopleura [4] in a dorso-ventral and cranio-caudal direction, in

relation to vascular structures formation contained within. As a consequence of these folds progressive growth, the de nitive septation of the thoracic cavity results in three cavities: a central one or pericardial cavity and two lateral ones or pleural cavities [4, 5] (Fig. 29.3).

Pleural Molecular Biology During

Embryogenesis

Since 1990, molecular biology techniques application has made it possible to understand the correlation between the fundamental embryologic

morphological changes, and the molecular aspects involved in genes maintenance and conservation that direct or guide the body’s normal development.

Currently, molecular families that direct embryonic development are already recognized, and in this sense, genetic sequencing studies have shown a phylogenetic conservatism from the rudimentary species of worms to humans, so that there are very few changes in the developmental regulatory genes nucleotide bases. It is also known that the same gene can express different functions in the different ontogenesis phases, and can even act in different organs.

There is the possibility that the same speci c gene acts even differently both in the embryonic phase and after birth. To all this molecular complexity is added the fact that mutated genes presence can induce changes even to the point of converting a normal cell into tumoral cells (proto oncogenes). The fundamental molecular processes during this body structuring period are grouped into categories that act as:

\1.\ Transcription factors, which are proteins with domains that bind speci c genes DNA, or even act on RNA polymerase II and, consequently, regulate the amount of RNA-­ messenger that the gene produces. Speci cally in humans the 38 homologous genes are called Hox genes, POU genes, and Pax genes.

They belong to this group that are collectively called Homeobox:

•\ Basic protein helix-loop-helix. •\ Zinc nger proteins.

•\ Homeodomain proteins.

\2.\ Activation or signal factors, most of which are proteins that act as peptide growth factors. The rst one obtained in the 1950s was neural growth factor, later on TGF-β (transforming growth factor β), and FGF ( broblast growth factor), involved in mesenchymal cells broblastic proliferation capacity. Another important family of activation molecules are the

hedgehog proteins, of which the sonic hedgehog is the most peculiar in that it undergoes autoproteolysis that allows obtaining a peptide capable of stimulating the target cell to directly or indirectly produce new differentiation pathways.

Speci cally, the pleura, as a mesoderm derivative, is constituted as a morphogenetic eld that remains at the mercy of molecular signals infuenced from the ectoderm, neural tube, and notochord (Speman’s induction theory, 1938) [5]. These molecular signals cause very curious but necessary events such as the transformation of mesenchymal cells into epithelial cells, and vice versa.

Once the epithelial somites have formed, their ventromedial cells undergo the inductive stimulus of activation by sonic hedgehog [6] (which originates in the notochord and neural tube). The response to this induction is Pax-1 and Pax-91 expression inside the somite, and as a nal consequence, there is a cell adhesion molecule loss, speci cally N-cadherin6, which again favors the “transformation of epithelial cells into mesenchymal cells,” thus acquiring the ability to migrate towards the embryo midline after forming the secondary mesoderm.

Contrary to these events, the somite is exposed to the infuence of products secreted by neural tube Wnt gene [6], which establish a sonic hedgehog inhibitory action, and the somatic cells remain under Pax-3, Pax-7 and paraxis expression, obtaining dermatome and myotome morphogenesis.

On the other hand, under BMP-4 infuence from the ectoderm [6], lateral mesoderm cells also begin to produce it. This molecule has the ability to infuence the paraxial or lateral mesoderm to assume lateral mesoderm properties. All these biological facts together allow to establish a balance between the medializing forces coming from the neural tube and the notochord, against the lateralizing forces coming from the ectoderm (Fig. 29.4).