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Normal Human KidneyNormal Human KidneyNormal Human KidneyNormal Human KidneyNormal Human KidneyNormal Human KidneyNormal Human KidneyNormal Human KidneyPodocytes in minimal change NS The electron micrograph is from a patient with minimal change glomerulopathy and shows almost complete effacement of the visceral epithelial foot processes.There is condensation of the epithelial cytoskeleton near the basement membrane.Normal podocytes Podocytes in minimal change NS FSGSFSGSFSGSFSGSFSGSFSGSFSGSFSGSFSGSFSGSFSGSMoving from urinary space to capillary limen there is the urinary space,effaced foot processes,the lamina lucida externa,lamina densa,the subendothelial electron dense deposits which are lying adjacent to the little fingers of mesangial cytoplasm that have extended into the subendothelial zone,new basement membrane material,and endothelial cell with pores.This electron micrograph shows the urinary space,the effaced foot processes,the original basement membrane,and conspicuous subendothelial deposits.Immunofluorescence microscopy(slide 47)typically demonstrates peripheral granular or band-like staining that may outline the hypersegmentation.In many patients with type I MPGN,C3 will be the most conspicuous component in the deposits,especially in the idiopathic childhood variant.Patients with MPGN often have hypocomplementemia and a circulating autoantibody called C3 nephritic factor,which binds to the C3 convertase of the alternative pathway.Hepatitis C infection is a common cause for type I membranoproliferative glomerulonephritis,especially if it is accompanied by mixed cryoglobulinemia.When mixed cryoglobulinemia is present,sometimes as shown in,there will be globular accumulations of cryoglobulin in the capillary lumens.These can be seen by light microscopy as hyaline thrombi.Sometimes,when the immune complexes are derived from cryoglobulins,there will be tubular arrays in the deposits that have about a 30-40 nanometer diameter.When these immunotactoids are present in the absence of cryoglobulinemia,the appropriate diagnostic term is immunotactoid glomerulopathy This is an uncommon disease that is sometimes accompanied by a B-cell neoplasms.Immunotactoid glomerulopathy should not be confused with the more common disease called fibrillary glomerulonephritis,which is characterized ultrastructurally by approximately 20 nm diameter fibrils The PAS(on left)and H&E-stained sections in slide 52 demonstrates thickening of the basement membrane and capillary wall,respectively.The diagram in illustrates the dense transformation of the basement membrane that causes the thickening.The electron micrograph shows the urinary space,an expanded mesangial region with a little bit of dense material in the increased matrix,and capillary basement membrane with stretches of normal lamina densa and zones of dense transformation.shows GBM as well as mesangial deposits.These dense deposits are not subepithelial or subendothelial,but rather are within the basement membrane.there is intense staining for C3,typically with almost no staining for immunoglobulin.The capillary wall staining is usually linear or bilinear.There often are spherical or ring-shaped mesangial deposits that correspond to the mesangial dense deposits observed by electron microscopy.StageProteinuriaGlemerular filtrationPathologyInormalnormal-hyperfiltrationnormal-mild diffuse lesionIImicroalbuminurianormal-hyperfiltrationnormal-moderate diffuse lesionwith occasional nodular lesionIIIApersistentnormalmoderate diffuse lesionwith frequent nodular lesionIIIBpersistent(1g=day)low(=60 ml/min)severe diffuse lesionwith frequent nodular lesionIVpersistentvery lowend-stage kidneyVHemodialysisDiabetic NephropathyDiabetic NephropathyDiabetic NephropathyDiabetic NephropathyDiabetic NephropathyDiabetic NephropathyDiabetic NephropathyDiabetic NephropathyDiabetic Nephropathy
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