The pathogenicity of bubbles is described later, but it is interesting to reflect on what happens to a notional bubble in tissue over time if only to discuss the concept of the so-called oxygen window because this will arise again in several subject areas.
We must begin by assuming that when a diver surfaces from a dive, a bubble forms from dissolved supersaturated nitrogen in a tissue. While the tissue remains supersaturated with nitrogen the bubble will grow, but eventually the PN2 in the tissue will come to equilibrium with that in the blood and alveoli for an air breathing subject at 1 atm. The bubble will not grow any more, and one may then ask ‘What is to stop the bubble, once formed, from simply sitting in the tissue unresolved for long periods?’ There are two reasons.
First, the pressure inside a spherical bubble is always likely to be greater than 1 atm, creating a driving force for the inert gas contained therein to diffuse into tissue, thence to blood and alveolus. This is because some pressure will be generated by surface tension at the bubble–tissue fluid interface and because some pressure will be generated by surrounding tissue that has been displaced by the bubble. These factors are summarized by the following equation, whose middle term describes pressure resulting from surface tension and whose final term describes pressure resulting from tissue displacement:
where Pbub is the pressure inside the bubble, Pamb is the ambient pressure, σ is the surface tension of the fluid, r is the bubble radius, Vtis is the volume of tissue affected by bubble displacement, and B is a term describing the bulk modulus of elasticity of the tissue.
Second, even during air breathing, there is a small partial pressure gradient for nitrogen diffusion from bubble to tissue created by the oxygen window. This arises primarily because of the solubility difference between the oxygen consumed and the carbon dioxide (CO2) produced by metabolism. The partial pressure of oxygen (PO2) in alveolar gas during air breathing is approximately 100 mm Hg, and after exchange with the blood, the PO2 in arterial blood is about 95 mm Hg. Oxygen is carried to the tissues, where a given number of molecules are consumed through metabolism and replaced with a similar number of molecules of CO2. Removal of these oxygen molecules drops the PO2 from 95 mm Hg in arterial blood to 40 mm Hg in venous blood. However, because CO2 is much more soluble, the addition of the same number of molecules of CO2 to the venous blood only raises its partial pressure to 46 mm Hg (from 40 mm Hg in arterial blood). The PO2 in the tissues where the oxygen is actually being consumed is slightly lower than the venous PO2, but this is difficult to measure, so we have to speculate a little. Relevant data are summarized in Table 10.2.
Note from Table 10.2 that for the purposes of this discussion it is assumed that a tissue bubble has an internal pressure equivalent to ambient (760 mm Hg). As discussed earlier, the typical internal pressure of a bubble in tissue is probably higher, which would actually enhance the effect described here, but for the purposes of illustrating the oxygen window, we will assume that the internal pressure is same as ambient. The gas contained within the bubble will be composed of water vapour at a pressure equivalent to the saturated vapour pressure for water at 37°C (47 mm Hg), and oxygen and CO2 in equilibrium with the tissue pressures of those gases. The balance of the bubble gas must be nitrogen, and by Dalton’s Law of partial pressures, the PbubN2 must be given by this equation:
where PbubN2 is the pressure of nitrogen inside the bubble, Pbub is the pressure inside the bubble that in this example we are considering to be the same as ambient pressure (760 mm Hg), PbubO2 is the partial pressure of oxygen in the bubble, PbubCO2 is the partial pressure of CO2 in the bubble, and PH2O is the saturated vapour pressure for water at 37°C.
Table 10.2 shows that this resolves to a PN2 of approximately 637 mm Hg which is about 64 mm Hg greater than the PN2 in the tissue, venous blood and alveoli (573 mm Hg). This difference, which creates a gradient for diffusion of nitrogen from the bubble to the tissue, is referred to as the ‘oxygen window’. We reiterate that it is created by the dissolved gas partial pressure difference that arises from removing relatively insoluble oxygen from solution and replacing it with very soluble CO2.
As discussed again later, the oxygen window could be further enhanced by breathing oxygen. Although this markedly elevates the alveolar and arterial PO2, it has a much smaller effect on venous and tissue PO2 because the small amount of extra oxygen dissolved in the arterial blood will be preferentially removed and metabolized, thereby dramatically dropping the PO2 back down to near normal levels. The venous PO2 (and therefore the venous oxygen saturation) may be marginally elevated. Because the same amount of oxygen is consumed and the same number of molecules of CO2 is produced, there will be virtually no effect on tissue or venous PCO2. Thus, the PbubN2 as calculated earlier will change very little, while at the same time the alveolar, arterial and tissue PN2 will fall markedly; potentially to zero if 100 per cent oxygen is breathed for long enough. The difference in PN2 between bubble and surrounding tissue will be correspondingly exaggerated, and nitrogen will diffuse out of the bubble more quickly. The same is true if the bubble is compressed. In this case, the Pbub in the foregoing equation is elevated, whereas bubble oxygen, CO2 and water vapour are little affected, even if oxygen is breathed during the compression.
The existence of the oxygen window, even during air breathing at 1 atm, at least partly explains why bubbles of nitrogen cannot exist in a stable condition in tissues. It also explains why bubbles involute even more quickly during oxygen breathing, especially when combined with recompression.