Sunday 19 July 2009

Is There Really A Liquid Lining Of The Lung?

A remarkable phenomenon has occurred in recent years in pulmonary physiology that may tell us something about the survival of orthodoxy despite ever more aggressive peer review. We refer to the widespread persistence of the notion that the pulmonary alveoli are normally lined with liquid. This notion persists in the scientific community in the face of a simple law of physics that shows it to be impossible. The law, appreciable by schoolchildren who blow soap bubbles, is that the only stable liquid–gas interface has the shape of a sphere, unless gravity upsets things badly. As a pulmonary alveolus is not a spherical structure, its epithelium cannot support a continuous thin lining with liquid that follows the non-spherical contour of its surface. It requires some explanation, therefore, why both the specialist medical literature, and school and university biology and physiology texts, are dominated by the view that the ‘alveolar surface is lined with liquid, which forms an air–liquid interface with alveolar gas’.1 To physicists this is inconceivable.2

The discovery by Brown and colleagues in 1959, that extracts from lung display a surface tension–area hysteresis on a Langmuir trough that looks a bit like the pressure– volume hysteresis seen in excised lungs,5 set the scene for an assumption that the alveoli themselves constitute a trough of liquid, albeit one with a complicated geometry. This assumption has pervaded the literature on lung mechanics for over 40 yr, and established itself firmly. Respiratory physiology texts speak with one voice about the liquid lining of the lung, assuming, or explicitly stating, that the whole alveolar surface is covered with a liquid.

The most vociferous opponent of alveolar wetness has made two fundamental errors in his otherwise challenging critique of established dogma.23 The first is the claim that a hydrophobic surface is required to prevent water from spreading within a polygonal structure. In fact, according to our earlier reasoning, even a hydrophilic surface can only sustain a continuous liquid lining if a sufficient volume of liquid is present on that surface to immerse irregularities beneath a spherical liquid–gas interface. This phenomenon is demonstrated in the micrographs of protein-rich pulmonary oedema published by Bachofen and colleagues.21 Hills’ second error, uncorrected even in a publication well after extensive new findings in the field,24 is the claim that passive forces alone account for the absorption of liquid from the corners of alveoli. His model of the ‘corner pump’, in which a liquid globule presents a convex surface to alveolar gas, and is emptied into lung interstitium by surface tension raising the pressure within the globule above that of alveolar gas and interstitial liquid, contrasts strikingly with the model that arises from the work of Basset and colleagues.25 26 In this model of adult lung, type II epithelial pneumocytes (the ones that secrete surfactant on to the alveolar surface) utilize fuel (ATP) actively to pump sodium, and with it glucose and water, from any collections of water that bathe the apical surface of the cells, into the interstitium.27 Matthay and colleagues have extensively characterized this process of liquid absorption in animals and humans,28 and there is some evidence that without active sodium transport fatal alveolar flooding would occur. Interestingly, however, the presence of aquaporins (water transport channels) in alveolar epithelium makes no measurable contribution to recovery from a wide variety of forms of lung injury associated with alveolar oedema.30

If the detectives on the case appear to be reluctant to make use of this fascinating new evidence of vigorous transport activity down in the alveoli, they appear even more reluctant to incorporate the most remarkable claims emanating from the laboratory of Scarpelli,31 who offers a whole ‘new anatomy’ of the alveolar surface. On the basis of studies that are claimed to preserve surface structures destroyed by the customary methods of histological preparation, Scarpelli has proposed that the alveolar ducts are normally filled with foam surfactant, within which each alveolus can be identified as a separate and complete bubble. Thus, astonishingly, the gas within each alveolus is not free to flow by convection, at least not continuously throughout the whole of the respiratory cycle as has been normally supposed. In this model, the entrances to alveoli are spanned by extremely thin bilayers of surfactant that are presumed usually to contain no ‘hypophase’ liquid, and consequently take the form of ‘Newtonian black films’.
http://bja.oxfordjournals.org/cgi/content/full/86/5/614

No comments: