genitourinary disorders
Overview of Nephrotic Syndrome
Pathophysiology of Nephrotic Syndrome
Proteinuria occurs because of changes to capillary endothelial cells, the glomerular basement membrane (GBM), or podocytes, which normally filter serum protein selectively by size and charge. The mechanism of damage to these structures is unknown in primary and secondary glomerular diseases, but evidence suggests that T cells may upregulate a circulating permeability factor or downregulate an inhibitor of permeability factor in response to unidentified immunogens and cytokines. Other possible factors include hereditary defects in proteins that are integral to the slit diaphragms of the glomeruli, activation of complement leading to damage of the glomerular epithelial cells and loss of the negatively charged groups attached to proteins of the GBM and glomerular epithelial cells. The disorder results in urinary loss of macromolecular proteins, primarilyalbuminbut also opsonins, immunoglobulins,erythropoietin, transferrin, hormone-binding proteins (including thyroid-binding globulin andvitamin D-binding protein), andantithrombin III. Deficiency of these and other proteins contribute to a number of complications (see table); other physiologic factors also play a role. 