Lesions in glomerular architecture include mesangial expansion, capillary ballooning, capillary unfolding and microaneurysm formation. Such lesions appear to develop in response to mechanical overextension. A frequent pathway to segmental glomerulosclerosis starts from capillary ballooning and unfolding. Podocytes supporting those deranged capillaries are exposed to increased mechanical stress. This may lead to podocyte injury terminating in detachments from the GBM. Naked GBM areas at peripheral capillary loops allow the attachment of parietal cells to the GBM, i.e. the formation of a tuft adhesion to Bowman’s capsule. An adhesion has a strong tendency to progress to segmental sclerosis.
We present a structural analysis of the ability of the biomechanical unit consisting of mesangium and glomerular basement membrane to maintain normal capillary architecture in the face of mechanical challenges due to high intraglomerular pressures. Capillary support function may be considered in terms of the stabilization of local form (development of wall tension against capillary dilation) and global form (centripetal fixation of capillary loops to maintain higher order form). The pathologic consequences of the loss of this support are illustrated by way of experimental models of mechanical mesangial failure. Such failure may express itself as mesangial widening, increased transmesangial macromolecule "traffic," ballooning of capillary segments, and unfolding of capillary loops. Mechanisms are described by which these structural changes may lead to segmental glomerular sclerosis.
The goal of this study has been to characterize the process of glomerular microaneurysm formation and to separate it from capillary ballooning. In the Habu venom model glomerular capillary ballooning and glomerular microaneurysm formation are seen regularly. The sequence of glomerular lesions leading to a glomerular microaneurysm has been examined and it is clear that the process starts with local mesangiolysis. This may proceed to mesangial expansion and/or ballooning of glomerular capillaries but in contrast to ballooning the formation of a glomerular microaneurysm is based on endothelial defects. The process occurs as follows: once initiated by mesangial failure lesions extend along the mesangial axis. As long as the extension of the lesion encroaches on divergent capillary branches, capillary ballooning by "coalescence" is the result. This process comes to an end when convergent capillary branching is reached and two capillaries join. At this point endothelial disruptions occur, blood and mesangial spaces merge and a glomerular microaneurysm is established. Further growth of the microaneurysm occurs following damage spreading along the lobular axis. The entire process has been reconstructed and is presented in a three-dimensional model.
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