glomerulopati

GLOMERULAR DISEASESBagian Patologi AnatomiFK-UISU2011Glomerular DiseasesPrimary Glomerular Diseases Minimal-change disease Focal and segmental glomerulosclerosis Membranous nephropathy Acute postinfectious GN Membranoproliferative GN IgA nephropathy Chronic GNGlomerulopathies Secondary to Systemic Diseases Lupus nephritis (systemic lupus erythematosus) Diabetic nephropathy Amyloidosis GN secondary to lymphoplasmacytic disorders Goodpasture syndrome Microscopic polyangiitis Wegener's granulomatosis Henoch-Schnlein purpura Bacterial endocarditis-related GN GN secondary to extrarenal infection Thrombotic microangiopathyHereditary Disorders Alport syndrome Fabry disease Podocyte/slit-diaphragm protein mutationsCLINICAL MANIFESTATIONSACUTE NEPHROTIC SYNDROMERAPIDLY PROGRESSIVE GLOMERULONEPHRITISNEPHROTIC SYNDROMECHRONIC RENAL FAILUREASYMPTOMATIC HEMATURIA or PROTEINURIA3PATHOLOGIC MANIFESTATIONSCELLULAR PROLIFERATIONMesangialEndothelialLEUKOCYTE INFILTRATIONCRESCENTS (RAPIDLY progressive)BASEMENT MEMBRANE THICKENINGHYALINIZATIONSCLEROSIS4PATHOGENESISAntibodies against inherent GBMAntibodies against planted antigensTrapping of Ag-Ab complexesAntibodies against glomerular cells, e.g., mesangial cells, podocytes, etc.Cell mediated immunity, i.e., sensitized T-cells as in TB5

Antibody-mediated glomerular injury. Injury can result either from the deposition of circulating immune complexes or from formation in situ of complexes. A, Deposition of circulating immune complexes gives a granular immunofluorescence pattern. B, Anti-GBM antibody GN is characterized by a linear immunofluorescence pattern. C, Antibodies against some glomerular components deposit in a granular patternPathogenesisMEDIATORSNEUTROPHILS, MONOCYTESMACROPHAGES, T-CELLS, NK CELLSPLATELETSMESANGIAL CELLS

SOLUBLE: CYTOKINES, CHEMOKINES, COAGULATION FACTORS7ACUTE GLOMERULONEPHRITISHematuria, Azotemia, Oliguria, in children following a strep infectionPOSTSTREPTOCOCCAL (old term)HYPERCELLULAR GLOMERULIINCREASED ENDOTHELIUM AND MESANGIUMIgG, IgM, C3 along GMB FOCALLY95% full recovery8

Why is the pic on the left classic for glomerulonephritis? Ans: Inflammatory cell infiltrates in the glomeruli9RAPIDLY PROGRESSIVE GLOMERULONEPHRITISClinical definition, NOT a specific pathologic oneCRESCENTICAnti-GBM AbIMMUN CPLXAnti-Neut. Ab

Recent studies have suggested that crescents are primarily of monocytic origin. They are signs that ANY glomerulonephritis may be severe or rapidly progressing.10NEPHROTIC SYNDROMEMASSIVE PROTEINURIAHYPOALBUMINEMIAEDEMALIPIDEMIA/LIPIDURIANUMEROUS CAUSES:MEMBRANOUS, MINIMAL CHANGE, FOCAL SEGMTL.DIABETES, AMYLOID, SLE, DRUGSTo make a long story short, the NEPHROTIC SYMDROME is usually a sign of a glomerulonephropathy.11MEMBRANOUS GLOMERULONEPHRITISDrugs, Tumors, SLE, InfectionsDeposition of Ag-Ab complexesIndolent, but >60% persistent proteinuria15% go on to nephrotic syndromeWhat does indolent mean?Causing little or no pain; inactive or relatively benign

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13MINIMAL CHANGE GLOM.(LIPOID NEPHROSIS)MOST COMMON CAUSE of NEPHROTIC SYNDROME in CHILDRENEFFACEMENT of FOOT PROCESSES

The ability to recognize the BM as being rather uniform in thickness and density is so critically important14FOCAL SEGMENTAL GLOMERULO-SCLEROSISJust like its nameFocalSegmentalGlomerulo-SCLEROSIS (NOT itis)HIV, Heroine, Sickle Cell, ObesityMost common cause of ADULT nephrotic syndrome

15MEMBRANOPROLIFERATIVEGLOMERULONEPHRITISMPGN can be idiopathic or 2 to chronic immune diseases Hep-C, alpha-1-antitrypsin, HIV, MalignanciesGBM alterations, subendo.Leukocyte infiltrationsPredominant MESANGIAL involvement

16IgA NEPHROPATHY(BERGER DISEASE)Mild hematuriaMild proteinuriaIgA deposits in mesangium

17HEREDITARY HEMATURIA SYNDROMESALPORT SYNDROMEProgressive Renal FailureNerve DeafnessVARIOUS eye disorderDEFECTIVE COLLAGEN TYPE IV

THIN GBM (Glomerular Basement Membrane) Disease, i.e., about HALF as uniformly thin as it should be18CHRONICGLOMERULONEPHRITISCan result from just about ANY of the previously described acute onesTHIN CORTEXHYALINIZED (fibrotic) GLOMERULIOFTEN SEEN IN DIALYSIS PATIENTS19SECONDARY (2) GLUMERULONEPHROPATHIESSLEHenoch-Schonlein Purpura (IgA-NEPH)BACTERIAL ENDOCARDITISDIABETES (Nodular Glomerulosclerosis, or K-W Kidney)AMYLOIDOSISGOODPASTUREWEGENERMYELOMA

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