How does glomerular epithelial cell injury contribute to progressive glomerular damage?
Glomerular visceral epithelial cells, unlike epithelial cells in other organs or in the more distal segments of the nephron, are highly differentiated, terminal cells that do not undergo cell division under physiological conditions in the postnatal period or during conditions that result in renal hypertrophy. Adjacent cells are connected to each other at the level of complex interdigitations or foot processes by filtration slit diaphragms. This particular arrangement contributes to the extremely high hydraulic conductivity of the normal glomerular capillary. Toxic and metabolic damage to the visceral epithelial cells or conditions of extreme glomerular hypertrophy result, in the short term, in diffuse or focal simplification and flattening of the foot processes. The areas of the capillary wall covered by such a simplified epithelium are likely to have a greatly reduced hydraulic conductivity which results from the greatly diminished surface area available for filtration. The rearrangement of foot processes also leads to focal areas of denudation of the basement membrane. Such denuded areas, however, are likely to result in an increase in local hydraulic flux, especially under conditions of capillary hypertension. Such defects have been shown to be the pathway of increased permeability to macromolecular markers and proteinuria. Large plasma proteins are retained in the subendothelium by the size-restrictive water-filled channels of the lamina densa and accumulate upstream in the form of hyaline which eventually occludes individual loops. More severe epithelial cell injury and denudation may also result in collapse of entire tuft segments.(ABSTRACT TRUNCATED AT 250 WORDS)
Rennke
H G
HG
Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
D000818:Animals; D004848:Epithelium / Q000473:pathology; D005923:Glomerulosclerosis, Focal Segmental / Q000209:etiology* / Q000473:pathology*; D006801:Humans; D007678:Kidney Glomerulus / Q000473:pathology*; D014781:Viscera / Q000473:pathology / Q000503:physiopathology