THE ALVEOLAR SURFACE NETWORK - A NEW ANATOMY AND ITS PHYSIOLOGICAL SIGNIFICANCE

It is generally held that the terminal lung unit (TLU) is an agglomera tion of alveoli that opens into the branching air spaces of respirator y bronchioles, alveolar ducts, and alveolar sacs and that these struct ures are covered by a continuous thin liquid layer bearing a monomolec ular film of surfactants at the open gas-liquid interface. The inheren t structural and functional instability given TLUs by a broad liquid s urface layer of this nature has been mitigated by the discovery that t he TLU surface is in fact an agglomeration of bubbles, a foam (the alv eolar surface network) that fills the TLU space and forms ultrathin fo am films that 1) impart infrastructural stability to sustain aeration, 2) modulate circulation of surface liquid, both in series and in para llel, throughout the TLU and between TLUs and the liquid surface of co nducting airways, 3) modulate surface liquid volume and exchange with interstitial liquid, and 4) sustain gas transfer between conducting ai rways 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 immedia tely from the in vivo state at volumes ranging from functional residua l capacity to maximal volume (Vmax). Lungs were then excised; bubble t opography of all anterior and anterolateral surfaces was reaffirmed an d also confirmed for all posterior and posterolateral surfaces. The fo llowing additional criteria verify the ubiquitous presence of normal i ntraalveolar bubbles. 1) Bubbles are absent in conducting airways. 2) Bubbles are stable and stationary in TLUs but can be moved individuall y by gentle microprobe pressure. 3) Adjoining bubbles move into the ex ternal medium through subpleural microincisions; there is no free gas, and vacated spaces are rendered airless. Adjacent bubbles may shift p osition in situ, while more distal bubbles remain stationary. 4) The p osition and movement of ''large'' bubbles identifies them as intraduct al bubbles. 5) Transection of the lung reveals analogous bubble occurr ence and history in central lung regions. 6) Bubbles become fixed in p lace and change shape when the lung is dried in air; the original shap e and movement are restored when the lung is rewet. 7) All exteriorize d bubbles are stable with lamellar (film) surface tension near zero. 8 ) Intact lungs prepared and processed by the new double-embedding tech nique reveal the intact TLU bubbles and bubble films. Lungs were also monitored directly by stereomicroscopy to establish their presence, tr ansformations, and apparent function from birth through adulthood, as summarized in the following section. Anatomy: Intraalveolar bubbles an d bubble films (the unit structures of the alveolar surface network) h ave been found in all mammalian species examined to date, including la mbs, kids, and rabbit pups and adult mice, rats, rabbits, cats, and pi gs. Rabbits were used for the definitive studies. 1) A unit bubble occ upies each alveolus and branching airway of the TLU; unit bubbles in c lusters correspond with alveolar clusters. 2) The appositions of unit bubble lamellae (films) form a network of liquid channels within the T LUs. 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 rap idly form stable Newtonian black foam films (similar to 7 nm thick) un der hydrodynamic conditions expected in vivo. 3) Lamellae of the foam films and bubbles tend to exclude bulk liquid and thus maintain near-z ero surface tension. At the same time, the foam film formations-abette d by the constant but small retractive force of tissue recoil-stabiliz e unit bubble position within the network. 4) Unit bubble mobility in response to applied force increases as Liquid accumulates within the n etwork (e.g., in excised lungs or tin extremis) pulmonary edema) to pr oduce reversible foam sim transformations (Newtonian black reversible arrow common reversible arrow thin liquid). 5) Free (bulk) Liquid is n ormally present at Plateau borders of the foam films and over crevices in the epithelial cell surface (the pressure points). 6) Thus, the ne twork is bath a continuous liquid circulation within foam film channel s and a gas phase within the lamellae of unit bubbles. 7) Both foam fi lms and their constituent bubble films are deformed and destroyed by t he usual laboratory methods of lung degassing and tissue processing fo r Light and electron microscopy. However, they can be preserved in the fresh lung by aldehyde fixation alone and by a new double-embedding m ethod. Physiology: 1) Bubble formation and lamellar appositions origin ate in previously airless units to form, re-form, and repair the netwo rk. Formation mechanisms include gas dispersion in liquid and liquid d rainage fi om microdroplets. 2) The essential substrates are component s of the lung surfactant system. 3) Both unit and collective (i.e., ne twork) bubbles provide the infrastructural support that sustains alveo lar and ductal aeration. 4) Network formation is the indispensable pro cess for transition from the fetal aqueous to the neonatal aerial envi ronment. Surfactant-poor, bubble-free immature lungs fail this transit ion without therapy (e.g., instillation or aerosol delivery of surfact ant to induce bubble formation). 5) The network, from birth to adultho od, modulates gas, liquid, and solute balance at the TLU surfaces. It minimizes liquid content of the gas-permeable lamellae (black films) i n the path of respiratory gas exchanges. At the pressure points, it is a reservoir for Liquid and solute exchanges within the network and wi th the septal interstitium and liquid surface of conducting airways. 6 ) Fluidity of unit structures of the network is a fundamental characte ristic of TLU mechanics that under lies the independence of unit struc ture and consequent local modulation of gas and liquid transfers, the modest force requirement to effect volume change in the nor mal breath ing range, the virtual exclusion of liquid from interfacial lamellae t o establish near-zero surface tension in this range, the reentry of Li quid at high volumes (> similar to 80% Vmax), the formation of surpell ic 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 frictio