טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentWeisbord Michal
SubjectInvestigation of Interstitial Fluid Flow of Alveolar Primary
Septa after Pneumonectomy
DepartmentDepartment of Mechanical Engineering
Supervisor Professor Emeritus Shimon Haber


Abstract

Neoalveolation is known to occur in the remaining lung after a pneumonectomy. While compensatory lung growth is a complex process, stretching of the lung tissue appears to be crucial for tissue remodeling. Even a minute shear stress exerted on fibroblasts in the interstitial space is known to trigger cell differentiation into myofibroblasts that are essential to building new tissues.

We hypothesized that the non-uniform motion of the primary septa due to their heterogeneous mechanical properties under tidal breathing and/ or operation of an external pressure gradient induces a spatially unique interstitial flow and shear stress distribution in the interstitial space. This may, in turn, trigger pulmonary fibroblast differentiation and neoalveolation.

In this study, we developed a theoretical basis for how cyclic motion of the primary septal walls with heterogeneous mechanical properties and/ or the application of an external pressure gradient affects the interstitial flow and shear stress distribution.

In the first part of the research, the velocity field of the interstitial fluid was expressed by a Fourier (complex) series and its leading term was accounted for. In the second part of the research, the velocity field of the interstitial flow was obtained according to the assumption of homogeneous mechanical properties of the primary septa. In the third part of the research, the velocity field of the interstitial fluid was assumed to be sinusoidal and included a component of the primary septa's heterogeneous mechanical properties.

From the velocity field (for the various cases explained above), we found the spatial stress distribution exerted on the primary septal walls and the location of maximal shear stresses was obtained. We hypothesized that from the latter one can infer where the walls of new lung alveoli will be formed.

In the last part we include an additional factor to the analysis - the application of an external pressure gradient - and investigated the relative importance of these two factors (i.e. external pressure gradient and non-uniform primary septal wall motion) in determining the interstitial flow and shear stress distribution in the interstitial space of the primary septa.

The analysis showed that whereas the basic pattern of non-uniform shear stress distribution is created during the cyclic motion of the primary septal walls, the external pressure gradient plays an important role in modifying this pattern. A non-dimensional parameter, , defines the relative importance of the pressure gradient vis-a-vis the heterogeneity parameters of the primary septa, and for which different results are obtained:

For   we expect that new alveoli are half the size of the original ones;

For  we expect that new alveoli are of the same size as the original ones but be shifted from their original location. The analysis yielded an estimate of    

In summary, alteration of mechanical properties of the primary septa caused by a pneumonectomy can develop a new interstitial flow field, which alters the shear stress distribution. This may trigger the differentiation of resident fibroblasts, which may, in turn, induce spatially unique neoalveolation in the remaining lung.