Macro and Micro Structure of the Lung

Chapter 1 Macro and Micro Structure of the Lung*

Lung Development

The emergence of a normal, functioning respiratory system requires simultaneous development of the conducting airway system and the vascular system. Of interest, the mechanisms that drive this process also hold true for other branched-structure organ systems, such as the kidney and breast. Lung development, beginning with organogenesis, is divided into several stages, as indicated in Table 1-1. However, considerable overlap of the signaling cascades between the various stages is recognized.

The earliest stage of lung development is known as the embryonic stage—that of organogenesis—and continues to approximately week 7. The primary lung buds arise from the ventral wall of the anterior foregut at approximately day 28. The trachea develops independently as a foregut tube anterior to the lung buds. Although it initially also includes the esophagus, the tube subsequently separates into two parts, with the ventral aspect forming the trachea, which then connects to the lung buds. The lung bud–tracheal domain is characterized by expression of Nkx2-1 (also called Titf1 [thyroid transcription factor 1]). Signal proteins from the mesenchyme, including bone morphogenetic proteins (BMPs), Noggin, fibroblast growth factors (FGFs), and Wnts, influence patterning, and deficiencies in some of these proteins result in failure of foregut separation with or without abnormal differentiation of epithelium and mesenchyma. Retinoic acid also plays an important role in lung morphogenesis during primary bud formation. Canonical Wnt signaling appears to be important in the regulation of cell proliferation and differentiation and also plays a role in lung branching. Beta-catenin phosphorylation is an integral portion of this pathway, with subsequent translocation to the cell nucleus and activation of T cell factor/lymphoid enhancer factor (TCF/LEF) target genes. Epigenetic changes, including methylation of DNA or histones, may influence developmental processes.

Vasculogenesis is initiated at the same time as that for development of the foregut bud. The vascular endothelial growth factor (VEGF) signaling cascade is integral to lung development and is necessary for endothelial proliferation and continued maintenance of the maturing vessels. The VEGF signaling event may be downstream from the Fgf signaling pathway.

The pseudoglandular stage generally is considered to encompass weeks 5 to 17, during which the lung has the appearance of a tubular gland. Continuing development of the lung buds is dependent on expression of FGF10 in the mesoderm and FGF receptor 2 (FGF2) in the endoderm. Branching is controlled by expression of Br1 (Branchless), a ligand of FGF, in small clusters of endodermal and mesodermal cells. Patterning genes determine the position of the clusters. The signaling network involved in this stage is complex, with feedback loops that significantly influence the morphogenetic signals.

In the canalicular stage (weeks 16 to 26) and extending into the saccular stage (weeks 24 to 38), the endoderm differentiates to form type I and II epithelial cells, and the air-blood barrier forms as capillaries remodel and become applied to the type I cells. The saccular stage is characterized by formation of saccules, the precursors of the alveoli. Matrix proteins assemble into a scaffold configuration at this time and also act as a reservoir for growth proteins such as transforming growth factor-β (TGF-β). Multiple signaling pathways are involved, with the Fgf pathway appearing to have a critical role in alveolar development.

The postnatal stage is characterized by rapid alveolarization and microvascular maturation, with an approximate 20-fold multiplication of surface area and an increase from approximately 50 million to 300 million alveoli. New alveoli arise from septa containing a double capillary network, or new septa are formed from mature septa, with induced formation of capillary network. Myofibroblasts and collagen and elastic fibers appear to be necessary for continued septation, and platelet-derived growth factor (PDGF) is necessary in this process, whereas VEGF is necessary for capillary maturation and maintenance.

Normal Lung Anatomy

The lungs can move freely within the thorax, attached normally only at the hila. The lungs are covered by a serosal membrane known as the visceral pleura. This membrane is then reflected as the parietal pleura over the hilum to cover the mediastinum, chest wall, and diaphragm. The serosal space is a theoretic space between the two pleural layers; normally, only a thin layer of pleural fluid separates the two layers. The pleura itself is formed as a layer of mesothelial cells supported by an elastic fiber network, which in turn is supported by a loose fibroconnective tissue layer. Mesothelial cells are characterized by their long microvilli.

As shown in Table 1-2 and Figure 1-1, A to D, the lungs are asymmetrically paired. The right lung is divided by major and minor fissures into three lobes: the upper, lower, and middle lobes. By contrast, the left lung has a single fissure dividing it into upper (superior) and lower (inferior) lobes. In the left lung, the homologue of the right lung’s middle lobe is the lingula, made up of the anterior and inferior portions of the upper lobe. In some persons there may be an incomplete fissure separating the lingula from the upper lobe. Bronchopulmonary segments are subunits of the lobes that derive from the first generation of bronchi below the lobar bronchi. These also are asymmetric between lungs; Table 1-1 shows the nomenclature.

Table 1-2 Segments of Lung

Right Lung Left Lung
Upper Lobe Upper Lobe
 1. Apical  1, 2. Apical-posterior
 2. Posterior  
 3. Anterior  3. Anterior
Middle Lobe Lingula
 4. Lateral  4. Superior
 5. Medial  5. Inferior
Lower Lobe Lower Lobe
 6. Superior  6. Superior
 7. Medial basal  
 8. Anterior basal  8. Anterior basal
 9. Lateral basal  9. Lateral basal
10. Posterior basal 10. Posterior basal

The next-smallest unit of the lung below the gross level of definition is the pulmonary lobule, also known as the secondary lobule of Miller. On the pleural surface, the secondary lobule is outlined by connective septa and has a roughly polygonal shape, measuring between 1 and 2 cm in diameter. Examination of the cut surface of lung again shows the interlobular septa demarcating the edges of the lobule (Figures 1-2

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Jun 12, 2016 | Posted by in RESPIRATORY | Comments Off on Macro and Micro Structure of the Lung

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