Tuesday, May 3, 2005

And You Thought the Age of Anatomic Discovery Was Over

Vivette D'Agati wins the award for most poetic kidney pathologist. Although some knowledge of renal microanatomy helps, you don't need to know anything about the podocyte to appreciate her writing. Brief excerpts from the editorial in JASN, "And You Thought the Age of Anatomic Discovery Was Over":

In this modern age of molecular biology, it is hard to imagine that any significant new discoveries remain to be made in the field of renal anatomy. Just thumb through any textbook of nephrology and you will find the classic references falling into predictable historical eras. Anatomic advances tend to cluster in the first half of the 20th century. The introduction of micropuncture in the 1960s set the stage for investigations into renal physiology. And since the 1980s, we have all witnessed a dizzying explosion of knowledge in molecular biology, molecular genetics, and their applications to nephrology...

Despite these trends, the application of electron microscopy to the study of glomerular structure has provided a window of discovery that continues to shed new and exciting insights... Not before the wondrous scanning electron microscopic images of the podocyte in the 1970s could the complex cytoarchitecture of this cell be fully appreciated...

The article by Neal et al. in this issue of the Journal of the American Society of Nephrology renews our faith in the power of structural observations as it explores new, as yet uncharted frontiers in the field of podocyte microanatomy...

The article... defines three structurally distinct compartments of the urinary (or Bowman's) space. The first is the one we are all familiar with: the large open space that forms a broad shell delimited by Bowman's capsule on the outside and the glomerular globe on the inside. The second is the interpodocyte space that forms an anastamosing, branching region between individual podocytes. Third is the subpodocyte space, defined as the space bounded by the glomerular basement membrane (GBM) and foot processes below, and by the underside of the podocyte cell bodies and their processes above. A sizeable area, some 60% of the total filtration surface of the glomerulus, is actually covered by podocyte cell bodies at any one time... In these regions, the glomerular filtrate cannot enter the open urinary space without passing through the more restricted subpodocyte space, which serial sections depict as a long, narrow, and tortuous space serviced by small exit pores... In other words, to reach Bowman's space, the filtrate entering into the subpodocyte space must pass through tiny exit pores that occupy only 4% of the corresponding glomerular filtration area. (This is an astounding statistic and one that any commuter into New York City who must cross the George Washington Bridge during the peak flow of morning rush hour can well appreciate...)

The cytoarchitecture of the podocyte is becoming ever more complex. The article by Neal et al. gives us new appreciation for the underbelly of the beast and the unique anatomic compartment that is the subpodocyte space.

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