Gn csbrp

Editor's Notes

• #10: FIGURE 20-1  A, Low-power electron micrograph of renal glomerulus. CL, capillary lumen; EP, visceral epithelial cells with foot processes; END, endothelium; MES, mesangium. B, Schematic representation of a glomerular lobe.  (A, Courtesy of Dr. Vicki Kelley, Brigham and Women's Hospital, Boston, MA.)
• #12: Arrows= 20nm Filtration slits with thin diaphragm
• #13: FIGURE 20-2  Glomerular filter consisting, from bottom to top, of fenestrated endothelium, basement membrane, and foot processes of epithelial cells. Note the filtration slits (arrows) and diaphragm situated between the foot processes. Note also that the basement membrane consists of a central lamina densa, sandwiched between two looser layers, the lamina rara interna and lamina rara externa.  (Courtesy of Dr. Helmut Rennke, Brigham and Women's Hospital, Boston, MA.)
• #14: FIGURE 20-3  A simplified schematic diagram of some of the best-studied proteins of the glomerular slit diaphragm. CD2AP, CD2-associated protein
• #18: There is little confusion in the terminology. Best and easy to remember is Fixed and Planted Ags. Fixed = already present in the glomerulus. Planted = not normally present in the glomerulus but are planted there.
• #22: FIGURE 20-5  Localization of immune complexes in the glomerulus: (1) subepithelial humps, as in acute glomerulonephritis; (2) epimembranous deposits, as in membranous nephropathy and Heymann glomerulonephritis; (3) subendothelial deposits, as in lupus nephritis and membranoproliferative glomerulonephritis; (4) mesangial deposits, as in IgA nephropathy; (5) basement membrane. EN, endothelium; EP, epithelium; LD, lamina densa; LRE, lamina rara externa; LRI, lamina rara interna; MC, mesangial cell; MM, mesangial matrix.  (Modified from Couser WG: Mediation of immune glomerular injury. J Am Soc Nephrol 1:13, 1990.)
• #27: FIGURE 20-6  Epithelial cell injury. The postulated sequence is a consequence of antibodies specific to epithelial cell antigens, toxins, cytokines, or other factors causing injury; this results in foot process effacement and sometimes detachment of epithelial cells and protein leakage through defective GBM and filtration slits.
• #29: FIGURE 20-7  Mediators of immune glomerular injury including cells and soluble mediators
• #32: Post Streptococcal GN (Old term)
• #33: Post Streptococcal GN (Old term)
• #34: Post Streptococcal GN (Old term)
• #35: Recollect the terms we used in the previous lectures: Diffuse / Focal Global / Segmental
• #36: FIGURE 20-9  Acute proliferative glomerulonephritis. A, Normal glomerulus. B, Glomerular hypercellularity is due to intracapillary leukocytes and proliferation of intrinsic glomerular cells. C, Typical electron-dense subepithelial “hump” and a neutrophil in the lumen. D, Immunofluorescent stain demonstrates discrete, coarsly granular deposits of complement protein C3, corresponding to “humps” illustrated in part C.  (A–C, courtesy of Dr. H. Rennke, Brigham and Women's Hospital, Boston, MA. D, courtesy of D. J. Kowaleska, University of Washington, Seattle, WA.)
• #46: FIGURE 20-10  Crescentic glomerulonephritis (PAS stain). Note the collapsed glomerular tufts and the crescent-shaped mass of proliferating parietal epithelial cells and leukocytes internal to Bowman capsule.  (Courtesy of Dr. M.A. Venkatachalam, University of Texas Health Sciences Center, San Antonio, TX.)
• #47: FIGURE 20-11  Crescentic glomerulonephritis. Electron micrograph showing characteristic wrinkling of GBM with focal disruptions (arrows).
• #48: FIGURE 20-11  Crescentic glomerulonephritis. Electron micrograph showing characteristic wrinkling of GBM with focal disruptions (arrows).
• #49: FIGURE 20-12  Membranous nephropathy. A, Silver methenamine stain. Note the marked diffuse thickening of the capillary walls without an increase in the number of cells. There are prominent “spikes” of silver-staining matrix (arrow) projecting from the basement membrane lamina densa toward the urinary space, which separate and surround deposited immune complexes that lack affinity for the silver stain. B, Electron micrograph showing electron-dense deposits (arrow) along the epithelial side of the basement membrane (B). Note the effacement of foot processes overlying deposits. CL, capillary lumen; End, endothelium; Ep, epithelium. C, Characteristic granular immunofluorescent deposits of IgG along GBM. D, Diagrammatic representation of membranous nephropathy.  (A, Courtesy of Dr. Charles Lassman, UCLA School of Medicine, Los Angeles, CA.)
• #50: FIGURE 20-12  Membranous nephropathy. A, Silver methenamine stain. Note the marked diffuse thickening of the capillary walls without an increase in the number of cells. There are prominent “spikes” of silver-staining matrix (arrow) projecting from the basement membrane lamina densa toward the urinary space, which separate and surround deposited immune complexes that lack affinity for the silver stain. B, Electron micrograph showing electron-dense deposits (arrow) along the epithelial side of the basement membrane (B). Note the effacement of foot processes overlying deposits. CL, capillary lumen; End, endothelium; Ep, epithelium. C, Characteristic granular immunofluorescent deposits of IgG along GBM. D, Diagrammatic representation of membranous nephropathy.  (A, Courtesy of Dr. Charles Lassman, UCLA School of Medicine, Los Angeles, CA.)
• #51: FIGURE 20-12  Membranous nephropathy. A, Silver methenamine stain. Note the marked diffuse thickening of the capillary walls without an increase in the number of cells. There are prominent “spikes” of silver-staining matrix (arrow) projecting from the basement membrane lamina densa toward the urinary space, which separate and surround deposited immune complexes that lack affinity for the silver stain. B, Electron micrograph showing electron-dense deposits (arrow) along the epithelial side of the basement membrane (B). Note the effacement of foot processes overlying deposits. CL, capillary lumen; End, endothelium; Ep, epithelium. C, Characteristic granular immunofluorescent deposits of IgG along GBM. D, Diagrammatic representation of membranous nephropathy.  (A, Courtesy of Dr. Charles Lassman, UCLA School of Medicine, Los Angeles, CA.)
• #58: FIGURE 20-13  Minimal-change disease. A, Glomerulus stained with PAS. Note normal basement membranes and absence of proliferation. B, Ultrastructural characteristics of minimal-change disease include effacement of foot processes (arrows) and absence of deposits. CL, capillary lumen; M, mesangium; P, podocyte cell body.
• #62: Recollect the terms we used in the previous lectures: Diffuse / Focal Global / Segmental
• #64: The hyalinosis and sclerosis stem from entrapment of plasma proteins in extremely hyperpermeable foci and increased ECM deposition
• #65: The hyalinosis and sclerosis stem from entrapment of plasma proteins in extremely hyperpermeable foci and increased ECM deposition
• #66: The hyalinosis and sclerosis stem from entrapment of plasma proteins in extremely hyperpermeable foci and increased ECM deposition
• #67: The hyalinosis and sclerosis stem from entrapment of plasma proteins in extremely hyperpermeable foci and increased ECM deposition
• #68: FIGURE 20-14  Focal segmental glomerulosclerosis, PAS stain. A, Low-power view showing segmental sclerosis in one of three glomeruli (at 3 o'clock). B, High-power view showing hyaline insudation and lipid (small vacuoles) in sclerotic area
• #69: FIGURE 20-15  Collapsing glomerulopathy. Visible are retraction of the glomerular tuft, narrowing of capillary lumens, proliferation and swelling of visceral epithelial cells, and prominent accumulation of intracellular protein absorption droplets in the visceral epithelial cells. The appearance is identical in cases wherein the etiology is idiopathic to cases associated with HIV infection. Silver methenamine stain.  (Courtesy of Dr. Jolanta Kowalewska, University of Washington, Seattle, WA.)
• #71: FIGURE 20-8  Focal segmental glomerulosclerosis associated with loss of renal mass. The adaptive changes in glomeruli (hypertrophy and glomerular capillary hypertension), as well as systemic hypertension, cause epithelial and endothelial injury and resultant proteinuria. The mesangial response, involving mesangial cell proliferation and ECM production together with intraglomerular coagulation, causes the glomerulosclerosis. This results in further loss of functioning nephrons and a vicious circle of progressive glomerulosclerosis.
• #72: In summary, a pathologic diagnosis of MPGN requires not merely light microscopic recognition of an appropriate pattern of glomerular injury, but, more importantly, specific ultrastructural changes that are the diagnostic features of these diseases. Many types of glomerular disease can produce light microscopic patterns of glomerular injury that mimic MPGN, but the diagnostic term MPGN should be reserved for the specific types of disease just described, and should be further qualified as MPGN type I, MPGN type II or MPGN type III. Otherwise, a diagnosis of MPGN would be of no value for predicting prognosis, identifying possible causes and directing therapy.
• #73: Type-I Planted antigens: HCV, HBV When the deposits in the subepithelial zone are as numerous as in membranous glomerulopathy, the glomerulonephritis may be designated type III membranoproliferative glomerulonephritis or mixed membranous and proliferative glomerulonephritis (although the term type III MPGN also has been used for another patterns of glomerular injury characterized by irregular electron-lucent thickening of glomerular basement membranes).
• #74: FIGURE 20-16  The alternative complement pathway in MPGN. Note that C3NeF, an antibody present in the serum of individuals with membranoproliferative glomerulonephritis, acts at the same step as properdin, serving to stabilize the alternative pathway C3 convertase, thus enhancing C3 activation and consumption, causing hypocomplementemia.
• #75: Type-I Planted antigens: HCV, HBV
• #77: FIGURE 20-18  A, Membranoproliferative glomerulonephritis, type I. Note discrete electron-dense deposits (arrows) incorporated into the glomerular capillary wall between duplicated (split) basement membranes (double arrows), and in mesangial regions (M); CL, capillary lumen. B, Dense-deposit disease (type II membranoproliferative glomerulonephritis). There are markedly dense homogeneous deposits within the basement membrane proper. CL, capillary lumen. In both, mesangial interposition gives the appearance of split basement membranes when viewed in the light microscope. C, Schematic representation of patterns in the two types of membranoproliferative GN. In type I there are subendothelial deposits; type II is characterized by intramembranous dense deposits (dense-deposit disease). In both, mesangial interposition gives the appearance of split basement membranes when viewed in the light microscope.  (A, Courtesy of Dr. Jolanta Kowalewska, University of Washington, Seattle, WA.)
• #78: FIGURE 20-18  A, Membranoproliferative glomerulonephritis, type I. Note discrete electron-dense deposits (arrows) incorporated into the glomerular capillary wall between duplicated (split) basement membranes (double arrows), and in mesangial regions (M); CL, capillary lumen. B, Dense-deposit disease (type II membranoproliferative glomerulonephritis). There are markedly dense homogeneous deposits within the basement membrane proper. CL, capillary lumen. In both, mesangial interposition gives the appearance of split basement membranes when viewed in the light microscope. C, Schematic representation of patterns in the two types of membranoproliferative GN. In type I there are subendothelial deposits; type II is characterized by intramembranous dense deposits (dense-deposit disease). In both, mesangial interposition gives the appearance of split basement membranes when viewed in the light microscope.  (A, Courtesy of Dr. Jolanta Kowalewska, University of Washington, Seattle, WA.)
• #79: FIGURE 20-17  Membranoproliferative glomerulonephritis, showing mesangial cell proliferation, increased mesangial matrix (staining black with silver stain), basement membrane thickening with segmental splitting, accentuation of lobular architecture, swelling of cells lining peripheral capillaries, and influx of leukocytes (endocapillary proliferation).
• #80: FIGURE 20-18  A, Membranoproliferative glomerulonephritis, type I. Note discrete electron-dense deposits (arrows) incorporated into the glomerular capillary wall between duplicated (split) basement membranes (double arrows), and in mesangial regions (M); CL, capillary lumen. B, Dense-deposit disease (type II membranoproliferative glomerulonephritis). There are markedly dense homogeneous deposits within the basement membrane proper. CL, capillary lumen. In both, mesangial interposition gives the appearance of split basement membranes when viewed in the light microscope. C, Schematic representation of patterns in the two types of membranoproliferative GN. In type I there are subendothelial deposits; type II is characterized by intramembranous dense deposits (dense-deposit disease). In both, mesangial interposition gives the appearance of split basement membranes when viewed in the light microscope.  (A, Courtesy of Dr. Jolanta Kowalewska, University of Washington, Seattle, WA.)
• #81: FIGURE 20-18  A, Membranoproliferative glomerulonephritis, type I. Note discrete electron-dense deposits (arrows) incorporated into the glomerular capillary wall between duplicated (split) basement membranes (double arrows), and in mesangial regions (M); CL, capillary lumen. B, Dense-deposit disease (type II membranoproliferative glomerulonephritis). There are markedly dense homogeneous deposits within the basement membrane proper. CL, capillary lumen. In both, mesangial interposition gives the appearance of split basement membranes when viewed in the light microscope. C, Schematic representation of patterns in the two types of membranoproliferative GN. In type I there are subendothelial deposits; type II is characterized by intramembranous dense deposits (dense-deposit disease). In both, mesangial interposition gives the appearance of split basement membranes when viewed in the light microscope.  (A, Courtesy of Dr. Jolanta Kowalewska, University of Washington, Seattle, WA.)
• #84: FIGURE 20-19  IgA nephropathy. A, Light microscopy showing mesangial proliferation and matrix increase. B, Characteristic deposition of IgA, principally in mesangial regions, detected by immunofluorescence.
• #85: FIGURE 20-19  IgA nephropathy. A, Light microscopy showing mesangial proliferation and matrix increase. B, Characteristic deposition of IgA, principally in mesangial regions, detected by immunofluorescence.
• #86: FIGURE 20-19  IgA nephropathy. A, Light microscopy showing mesangial proliferation and matrix increase. B, Characteristic deposition of IgA, principally in mesangial regions, detected by immunofluorescence.
• #87: FIGURE 20-19  IgA nephropathy. A, Light microscopy showing mesangial proliferation and matrix increase. B, Characteristic deposition of IgA, principally in mesangial regions, detected by immunofluorescence.
• #88: FIGURE 20-19  IgA nephropathy. A, Light microscopy showing mesangial proliferation and matrix increase. B, Characteristic deposition of IgA, principally in mesangial regions, detected by immunofluorescence.
• #94: Normal GBM thickening is 300-4000nm.
• #96: FIGURE 20-21  Primary glomerular diseases leading to chronic glomerulonephritis (GN). The thickness of the arrows reflects the approximate proportion of patients in each group who progress to chronic GN: poststreptococcal (1% to 2%); rapidly progressive (crescentic) (90%), membranous (30% to 50%), focal segmental glomerulosclerosis (50% to 80%), membranoproliferative GN (50%), IgA nephropathy (IgAN, 30% to 50%).
• #102: FIGURE 20-22  Chronic glomerulonephritis. A Masson trichrome preparation shows complete replacement of virtually all glomeruli by blue-staining collagen.  (Courtesy of Dr. M.A. Venkatachalam, Department of Pathology, University of Texas Health Sciences Center, San Antonio, TX.)
• #118: Glomerular BM is diffusely thickenend throughout the entire length. (EM can detect this lesion very early before any changes can be appreciated in renal function).
• #129: Source: AFIP fascicle
• #130: Source: AFIP fascicle
• #131: Source: AFIP fascicle.
• #132: Source: AFIP fascicle.
• #133: Source: AFIP fascicle.
• #134: Source: AFIP fascicle.
• #135: Source: AFIP fascicle.
• #136: In the diagram in slide 2 are my conceptions of the major distinctions between the three major categories of FSGS. There is a perihilar predominance of sclerosis in one variant of FSGS, a glomerular tip location for a distinctive injury in the tip lesion variant of FSGS, and a particular type of collapsing pattern of destruction of capillaries and matrix expansion in the collapsing glomerulopathy variant of FSGS.
• #137: The diagram in Picture3  depicts perihilar segmental sclerosis, which is continuous with the afferent arteriole where the blood is coming into the glomerulus. A leading theory for the pathogenesis of this variant is single nephron hypertension, hyperperfusion, hyperfiltration. This is possibly analogous to a small local area of arteriosclerosis (arteriolosclerosis) where plasma constituents are exuding into the glomerular tuft much as plasma proteins exude into the walls of arterioles causing the hyaline arteriolosclerosis of hypertension. The PAS-stained section in Picture 4 shows the perihilar location of sclerosis with hyalinosis and lipids vacuolation and an adhesion to Bowman's capsule. These are very distinctive and characteristic features of focal segmental glomerulosclerosis, but they are not specific. These features should be present in the absence of any other cause of focal glomerular scarring in order to diagnose FSGS.