The alveolar surface network: a new anatomy and its physiological significance

It is generally held that the terminal lung unit (TLU) is an agglomeration of alveoli that opens into the branching air spaces of respiratory bronchioles, alveolar ducts, and alveolar sacs and that these structures are covered by a continuous thin liquid layer bearing a monomolecular film of surfactants at the open gas-liquid interface. The inherent structural and functional instability given TLUs by a broad liquid surface layer of this nature has been mitigated by the discovery that the TLU surface is in fact an agglomeration of bubbles, a foam (the alveolar surface network) that fills the TLU space and forms ultrathin foam films that 1) impart infrastructural stability to sustain aeration, 2) modulate circulation of surface liquid, both in series and in parallel, throughout the TLU and between TLUs and the liquid surface of conducting airways, 3) modulate surface liquid volume and exchange with interstitial liquid, and 4) sustain gas transfer between conducting airways and pulmonary capillaries throughout the respiratory cycle. The experimental evidence, from discovery to the present, is addressed in this report. Lungs were examined in thorax by stereomicroscopy immediately from the in vivo state at volumes ranging from functional residual capacity to maximal volume (Vmax). Lungs were then excised; bubble topography of all anterior and anterolateral surfaces was reaffirmed and also confirmed for all posterior and posterolateral surfaces. The following additional criteria verify the ubiquitous presence of normal intraalveolar bubbles. 1) Bubbles are absent in conducting airways. 2) Bubbles are stable and stationary in TLUs but can be moved individually by gentle microprobe pressure. 3) Adjoining bubbles move into the external medium through subpleural microincisions; there is no free gas, and vacated spaces are rendered airless. Adjacent bubbles may shift position in situ, while more distal bubbles remain stationary. 4) The position and movement of “large” bubbles identifies them as intraductal bubbles. 5) Transection of the lung reveals analogous bubble occurrence and history in central lung regions. 6) Bubbles become fixed in place and change shape when the lung is dried in air; the original shape and movement are restored when the lung is rewet. 7) All exteriorized bubbles are stable with lamellar (film) surface tension near zero. 8) Intact lungs prepared and processed by the new double-embedding technique reveal the intact TLU bubbles and bubble films. Lungs were also monitored directly by stereomicroscopy to establish their presence, transformations, and apparent function from birth through adulthood, as summarized in the following section. Anatomy: Intraalveolar bubbles and bubble films (the unit structures of the alveolar surface network) have been found in all mammalian species examined to date, including lambs, kids, and rabbit pups and adult mice, rats, rabbits, cats, and pigs. Rabbits were used for the definitive studies. 1) A unit bubble occupies each alveolus and branching airway of the TLU; unit bubbles in clusters correspond with alveolar clusters. 2) The appositions of unit bubble lamellae (films) form a network of liquid channels within the TLUs. The appositions are bubble to bubble (near alveolar entrances, at pores of Kohn, and between ductal bubbles), bubble to epithelial cell surface, and bubble to surface liquid of conducting airways. They rapidly form stable Newtonian black foam films (∼7 nm thick) under hydrodynamic conditions expected in vivo. 3) Lamellae of the foam films and bubbles tend to exclude bulk liquid and thus maintain near-zero surface tension. At the same time, the foam film formations—abetted by the constant but small retractive force of tissue recoil—stabilize unit bubble position within the network. 4) Unit bubble mobility in response to applied force increases as liquid accumulates within the network (e.g., in excised lungs or (in extremis) pulmonary edema) to produce reversible foam film transformations (Newtonian black ⇄ common ⇄ thin liquid). 5) Free (bulk) liquid is normally present at Plateau borders of the foam films and over crevices in the epithelial cell surface (the pressure points). 6) Thus, the network is both a continuous liquid circulation within foam film channels and a gas phase within the lamellae of unit bubbles. 7) Both foam films and their constituent bubble films are deformed and destroyed by the usual laboratory methods of lung degassing and tissue processing for light and electron microscopy. However, they can be preserved in the fresh lung by aldehyde fixation alone and by a new double-embedding method. Physiology: 1) Bubble formation and lamellar appositions originate in previously airless units to form, re-form, and repair the network. Formation mechanisms include gas dispersion in liquid and liquid drainage from microdroplets. 2) The essential substrates are components of the lung surfactant system. 3) Both unit and collective (i.e., network) bubbles provide the infrastructural support that sustains alveolar and ductal aeration. 4) Network formation is the indispensable process for transition from the fetal aqueous to the neonatal aerial environment. Surfactant-poor, bubble-free immature lungs fail this transition without therapy (e.g., instillation or aerosol delivery of surfactant to induce bubble formation). 5) The network, from birth to adulthood, modulates gas, liquid, and solute balance at the TLU surfaces. It minimizes liquid content of the gas-permeable lamellae (black films) in the path of respiratory gas exchanges. At the pressure points, it is a reservoir for liquid and solute exchanges within the network and with the septal interstitium and liquid surface of conducting airways. 6) Fluidity of unit structures of the network is a fundamental characteristic of TLU mechanics that underlies the independence of unit structure and consequent local modulation of gas and liquid transfers, the modest force requirement to effect volume change in the normal breathing range, the virtual exclusion of liquid from interfacial lamellae to establish near-zero surface tension in this range, the reentry of liquid at high volumes (>∼80% Vmax), the formation of surpellic films that resist collapse at the lowest volumes, the formation of new bubbles in previously airless units, the formation of new bubbles in units with preexisting bubbles, and the virtually frictionless movement of newly formed bubbles to establish/reestablish the TLU space-filling topography of the network. Anat. Rec. 251:491–527, 1998. © 1998 Wiley-Liss, Inc.