Conserved Mechanisms in the Formation of the Airways and Alveoli of the Lung

Branching is an intrinsic property of respiratory epithelium that can be induced and modified by signals emerging from the mesenchyme. However, during stereotypic branching morphogenesis of the airway, the relatively thick upper respiratory epithelium extrudes through a mesenchymal orifice to form a new branch, whereas during alveologenesis the relatively thin lower respiratory epithelium extrudes to form sacs or bubbles. Thus, both branching morphogenesis of the upper airway and alveolarization in the lower airway seem to rely on the same fundamental physical process: epithelial extrusion through an orifice. Here I propose that it is the orientation and relative stiffness of the orifice boundary that determines the stereotypy of upper airway branching as well as the orientation of individual alveolar components of the gas exchange surface. The previously accepted dogma of the process of alveologenesis, largely based on 2D microscopy, is that alveoli arise by erection of finger-like interalveolar septae to form septal clefts that subdivide pre-existing saccules, a process for which the contractile properties of specialized alveolar myofibroblasts are necessary. Here I suggest that airway tip splitting and stereotypical side domain branching are actually conserved processes, but modified somewhat by evolution to achieve both airway tip splitting and side branching of the upper airway epithelium, as well as alveologenesis. Viewed in 3D it is clear that alveolar “septal tips” are in fact ring or purse string structures containing elastin and collagen that only appear as finger like projections in cross section. Therefore, I propose that airway branch orifices as well as alveolar mouth rings serve to delineate and stabilize the budding of both airway and alveolar epithelium, from the tips and sides of upper airways as well as from the sides and tips of alveolar ducts. Certainly, in the case of alveoli arising laterally and with radial symmetry from the sides of alveolar ducts, the mouth of each alveolus remains within the plane of the side of the ductal lumen. This suggests that the thin epithelium lining these lateral alveolar duct buds may extrude or “pop out” from the duct lumen through rings rather like soap or gum bubbles, whereas the thicker upper airway epithelium extrudes through a ring like toothpaste from a tube to form a new branch.

Visualizing the Flow Patterns in an Expanding and Contracting Pulmonary Alveolated Duct Based on Microcomputed Tomography Images

We visualized the flow patterns in an alveolated duct model with breathing-like expanding and contracting wall motions using particle image velocimetry, and then, we investigated the effect of acinar deformation on the flow patterns. We reconstructed a compliant, scaled-up model of an alveolated duct from synchrotron microcomputed tomography images of a mammalian lung. The alveolated duct did not include any bifurcation, and its entire surface was covered with alveoli. We embedded the alveolated duct in a sealed container that was filled with fluid. We oscillated the fluid in the duct and container simultaneously and independently to control the flow and duct volume. We examined the flow patterns in alveoli, with the Reynolds number (Re) at 0.03 or 0.22 and the acinar volume change at 0%, 20%, or 80%. At the same Re, the heterogeneous deformation induced different inspiration and expiration flow patterns, and the recirculating regions in alveoli changed during respiratory cycle. During a larger acinar deformation at Re = 0.03, the flow patterns tended to change from recirculating flow to radial flow during inspiration and vice versa during expiration. Additionally, the alveolar geometric characteristics, particularly the angle between the alveolar duct and mouth, affected these differences in flow patterns. At Re = 0.22, recirculating flow patterns tended to form during inspiration and expiration, regardless of the magnitude of the acinar deformation. Our in vitro experiments suggest that the alveolated flows with nonself-similar and heterogeneous wall motions may promote particle mixing and deposition.

The time-controlled adaptive ventilation protocol: mechanistic approach to reducing ventilator-induced lung injury

Airway pressure release ventilation (APRV) is a ventilator mode that has previously been considered a rescue mode, but has gained acceptance as a primary mode of ventilation. In clinical series and experimental animal models of extrapulmonary acute respiratory distress syndrome (ARDS), the early application of APRV was able to prevent the development of ARDS. Recent experimental evidence has suggested mechanisms by which APRV, using the time-controlled adaptive ventilation (TCAV) protocol, may reduce lung injury, including: 1) an improvement in alveolar recruitment and homogeneity; 2) reduction in alveolar and alveolar duct micro-strain and stress-risers; 3) reduction in alveolar tidal volumes; and 4) recruitment of the chest wall by combating increased intra-abdominal pressure. This review examines these studies and discusses our current understanding of the pleiotropic mechanisms by which TCAV protects the lung. APRV set according to the TCAV protocol has been misunderstood and this review serves to highlight the various protective physiological and mechanical effects it has on the lung, so that its clinical application may be broadened.

Variations in the path of the inferior alveolar canal. Review of the literature.

The knowledge and application of anatomy is essential for any professional involved in the evaluation, diagnosis, prognosis and treatment of the different alterations of the maxillofacial complex. The ignorance of the anatomical relationships of the inferior alveolar duct in the different surgical procedures can lacerate, compress or stretch the nerve generating lesions such as neuropraxia, axonotmesis and neurotmesis. The objective of this review is to describe the variations of the inferior alveolar duct course reported in the literature. There are 6 possible categories in which the variations of the CAI can be classified: 4 views in panoramic radiographs (two dimensions) and 2 views in computerized axial tomography (three dimensions). The inferior alveolar duct presents a great variability between patients and populations, which accentuate the product of tooth loss and alveolar reabsorption. Computed tomography of conic beam is the most suitable method for its evaluation.

Platelets play an essential role in murine lung development through Clec-2/podoplanin interaction

Key Points Association of platelet Clec-2 with lymphatic podoplanin regulates lung development by facilitating alveolar duct myofibroblast differentiation. Alveolar duct myofibroblast differentiation is regulated in part by transforming growth factor-β released from platelets activated by Clec-2/podoplanin interaction.