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This Concept Map, created with IHMC CmapTools, has information related to: Glomerular Diseases, Glomerular Diseases Nephrotic Syndrome MEMBRANOUS GLOMERULONEPHRITIS (MEMBRANOUS NEPHROPATHY) -autoimmure (Heymann model) -most common cause of nephrotic syn -diffusely thickened cap wall -subEPITHELIAL Ig/comp-rich deposits -in GBM -85% idiopathic Can be 2ndary to: Drugs (PCNamine, gold), NSAIDs, malignant tumors, SLE, infx(HBV, HCV syphilis, schisto, malaria), metabolic Can->sclerosis of caps (deposits impinge) Hyaline droplets in epith cells of proxtub (protein reabsorption) CLINICAL-insidious onset of glom syn -15% non-nephrotic -hematuria, mild HTN -NONSELECTIVE proteinuria -little response to corticosteroids ->increased BUN, LESS proteinuria Spontaneous remissions in: WOMEN, non-nephrotic, mild changes, Glomerular Diseases Progressive Renal Failure: 2 Major Histologic Characteristics TUBULOINTERSTITIAL DMG -tub dmg, interstitial inflam -degree correlates w/ decline in renal fcn -ppting factors-ischemia, immune rxns, phosphate, ammonia retention, possible impt role of proteinuria, Glomerular Diseases In Situ Immune Complex Deposition via drugs, endotoxin, GVHD HEYMANN NEPHRITIS -granular, interrupted staining -AB:Ag on basal surface of epith cells -Heymann Ag=megalin -like human memb glom'itis, Glomerular Diseases Nephrotic Syndrome MEMBRANOPROLIFERATIVE GLOM'ITIS (MESANGIOCAP GN) -Altered GBM, glom cell prolif, WBCs -5-10% of idio nephrotic in kids/young adults Primary MPGN -large, hypercellular gloms from inc. mesan (PAS+) -also from WBCs, epith crescents -LOBULAR-like gloms -thick GBM-'TRAM-TRACK'-'duplication' -mesan-monocyte interposition Type I-2/3 chronic dz- SUBENDOTH/MESAN deposits -C3 in dense deposits, C1-C4,IgG present -?via classic/alt complement pathway Type II-1/3 autoimmune- ribbon-like LAM DENSA -DEPOSITION INTO GBM PROPER -"dense-deposit dz"-continuous deposit -pseudo-linear IF deposits -C3 NOT in deposits-either side of GBM -in granular-linear deposits, mesangium -DECREASED SERUM C3, properdin, factor B -C3 nephritic factor (C3NeF)-auto-AB C3bBb -IgG, C1-C4 absent (C3bBb=C3 convertase) -?via alternative complement pathway -some pts w/ partial lipodystrophy Type III-BOTH subendoth & subepith deposits -GBM disruption, reduplication Secondary MPGN-from other systemic d/os -chonic immune (SLE(IV), HBV, HCV, endocarditis, HIV, schisto), lipodystrophy, a1-Antitrypsin def, CLL, lymphoma, melanoma, comp def states CLINICAL-older children, young adults -nephritic w/ hematuria, mild proteinuria Txs not very effective -high recurrence in xplant pts, Glomerular Diseases Nephrotic Syndrome FOCAL (PROLIFERATIVE AND NECROTIZING) GLOM'ITIS -NOT sclerotic lesions 3 circumstances: 1.Early/mild global systemic dz SLE, PAN, H-S purpura, Goodpasture, subacute bac endocarditis, Wegener's 2. Part of other glom dz-eg IgA neph 3. Primary idiopathic-exclude all others CLINICAL-mild, recurrend hematuria, non-nephrotic proteinuria -sometimes nephrotic, Glomerular Diseases Hereditary Nephritis THIN MEMBRANE (GBM) DZ (BENIGN FAM HEMATURIA) -familial (-)Sx hematuria -diffuse thinning of GBM (1/2) -NL renal fcn, Px excellent -can have mild-mod proteinuria DDx -skin Bx-type IV coll alpha5 (unlike Alport), Glomerular Diseases Nephrotic Syndrome IgA NEPHROPATHY (BERGER DZ) -Prominent IgA deposits in mesang -similar deposits in H-S purpura -recurrent gross, uscopic hematuria PATHOGENESIS-genetic influence -IgA ICs in mesang+fibronectin -no C1q or C4 (no alternative C) -increased serum IgA->glom ->activate complement -increased in CELIAC DZ -and in LIVER DZ (can't clear ICs) -CROHN DZ, CHRONIC BRONCH MORPH-variable-NL-mesangioprolif -can be focal/diffuse prolif GN -can be crescentic rarely, necrosis -IgA, properdin, C3 deposits EM-densities in mesang -lumpy-bumpy deposits -aa hyaline thickening->HTN->CRF CLINICAL-15-30yo MALE>fm -gross hematuria after infx (ᡪ%) (resp, GI, urinary) +/-proteinuria, uscopic hematuria -hematuria every few months ->CRF in 20 yrs in 25-50% -recurs in xplanted kidneys, Glomerular Diseases In Situ Immune Complex Deposition via drugs, endotoxin, GVHD ANTI-GBM NEPHRITIS ɝ% glom'itis -ABs against fixed Ags (NL GBM) -linear staining pattern (Masugi expt model) Goodpasture's-NC1 of collagen type IV=Ag -anti-GBM also react w/ lung BM ->sever glom dmg -> rapidly progressive renal failure, Glomerular Diseases Progressive Renal Failure: 2 Major Histologic Characteristics FOCAL SEGMENTAL GLO'SCLEROSIS -proteinuria -adaptive change -compensatory hypertrophy of gloms ->total glom sclerosis, uremia DUE TO increased GFR, blood flow, cap HTN, systemic HTN -proteins accum in mesan matrix -fibrin deposition, endoth/epith cell injury ->mesang cells prolif, ECM deposits -chronic inflam, fibrosis -TGFbeta->sclerosis ACE inhibitors slow progression, Glomerular Diseases Acute Glomerulonephritis ACUTE PROLIF GLOM'ITIS -diffuse prolif of glom cells+WBCs -via ICs POSTSTREPTOCOCCAL-most common -1-4 wks after strep throat, impetigo -M-types 12, 4, 1 -low serum complement levels -elevated AB titers (ASO) MORPH-diffusely hypercellular, WBCs -fibrin deposits in caps, CASTS -granular IgG, IgM, C3 deposits in mesang and along GBM -IF-'starry-sky', 'garland' pattern -subepithelial deposits in HUMPS CLINICAL-kids-acute malaise, fever, oliguria, hematuria, nausea -RBC casts in urine, mild proteinuria, periorbital edema, mild-mod HTN -adults-atypical presentation -elevated antistrep ABs (anti-cationic proteinase, anti-DNAse B) -dec. serum C3, present cryoglobulins Px better in kids than adults -some -> crescentic or chronic NONSTREPTOCOCCAL -staph. endocarditis, pneumococcal pneumo, meningococ -HBV, HCV, mumps, HIV, VZV, mono -malaria, toxoplasmosis MORPH-granular IF deposits, HUMPS, Glomerular Diseases Related to Systemic Dzs ESSENTIAL MIXED CRYOGLOBULINEMIA -rare -cryoglobulin deposits (IgG-IgM complexes) ->cutaneous vasculitis, synovitis, focal or diffuse proliferative GN -if 2ndary to infx (HCV)->MPGN PLASMA CELL DYSCRASIAS Multiple Myeloma: ->Amyloidosis ->monoclonal cryoglobulin deposition ->nonfibrillar light chain deposition -LIGHT-CHAIN GLOMERULOPATHY -looks like diabetic nodules, MPGN -lobular, mesangial hypercellularity, Glomerular Diseases CIRCULATING IMMUNE COMPLEX DEPOSITION Trapped ICs (from circ) in glom -can -> in situ formation No specificity fo glom, just big -endogenous-SLE -exo-HBsAg, HCV Ag/RNA, T. pallidum, P. falciparum, viruses ->WBCs into glom, prolif mesang/endoth -ICs mostly in mesangium, b/w endoth cells -membranoproliferative -can be degraded by monos, mesang cells -short course (eg post-strep) -continual in SLE, hep B or C -subendoth if (-) charge -subepith if (+) charge (get through (-) BM), End-stage-some w/ no antecedent -uremia Post-strep glom->rarely RPGN->if survive acute episode MGN, MPGN, IgA neph->slowly Focal sclerosis->rapidly MORPH-symmetrical, contracted kidneys -diffusely granular -thin cortex, more fat -gloms progress to hyaline obliteration -acellular eosinophilic mass -plasma proteins, matrix, GBM, coll -HTN->aa sclerosis -atrophy of tubs, interstit fibrosis -lymphocytic infilitration CLINICAL-insidious, slow death in uremia -years-decades -MOST PTS w/ HTN, CV, cerebral d/o -anorexia, vomiting, weakness, edema -proteinuria, HTN, azotemia on routine -if nephrotic-protein loss decreases Uremic Complications If dying: Uremic... Pericarditis Gastroenteritis 2ndary hyperparathyroidism -nephrocalcinosis, osteodystrophy LVH due to HTN Diffuse Alveolar Dmg (pneumonitis), Glomerular Diseases Nephrotic Syndrome FOCAL SEGMENTAL GLOM'SCLEROSIS -sclerosis of SOME gloms, SOME caps -w/ nephrotic syndrome or proteinuria TYPES: 1. w/ other conditions-HIV, heroin, Li, SCD, obesity 2. 2ndary after other glom'itis 3. in adaptive response in glom ablation nephropathy in adv'd renal d/os -Reflux nephropathy, Unilateral agenesis 4. Certain inherited, congen forms - Chrom 19q13 -near NEPHRIN 5. primary, idiopathic dz -10-15% of nephrotic syn in kids-adults Mediated by reduced renal mass, but initially NL Compared to min change dz: -Higher HEMATURIA, REDUCED GFR, HTN -nonselective proteinuria -can->chronic glom'itis (50%->ESRD in 10yrs) -deposits of IgM, C3 in sclerotic segment MORPH-SEGMENTAL (can be missed if bad Bx) -begin w/ JM glom, then generalize -collapse of GBM, increased matrix, HYALINOSIS -lipid droplets, foam cells, hyalinosis PAS+ -lose foot processes (like MCD), detachment from/denudation of GBM -ACCENTUATED MCD?? -hyaline thickening of afferent aa. ->spreading->tubular atrophy->interstit fibrosis CLINICAL-kids better Px than adults -variable response to steroids (unlike MCD) -20%-"malignant" course-renal failure w/in 2yr -recurrences in 25-50% of allografts, Glomerular Diseases In Situ Immune Complex Deposition via drugs, endotoxin, GVHD ABs AGAINST PLANTED Ags -planted Ags: cationin molecules, DNA, bac products, large proteins (Ig), immune complexes, Glomerular Diseases Related to Systemic Dzs SLE-all from deposition of DNA-anti-DNA ICs -formed in situ -deposits also in tubular BMs in 50% 5 Classes: NL by light uscope (class I)-rare Mesangial Lupus Nephritis (II)-ONLY mesangial -20% SLE - mild hema/proteinuria -increased mesangial matrix -granular Ig, complement deposits in mesang Focal Glomerulonephritis (III)-20% SLE អ% gloms, 2 portions of each glom ->hematuria, proteinuria; can -> IV -PMN infiltrate, fibrinoid deposits, thrombi -wire loops too (indicate active dz, poor Px) Diffuse Prolif Glom'itis (IV)-40-50% SLE -MOST SERIOUS-most gloms, entire gloms -prolif of mesan, endoth, epith cells -can make ENDOTH CRESCENTS-fill bowman's -fibrinoid necrosis, hyaline thrombi-active dz -nephrotic syndrome in 50%, HTN, renal insuff -SUBENDOTHELIAL DEPOSITS->WIRE LOOP -resembles MPGN-NODULARITY Diffuse Membranous Glom'itis (V)-15% -like MEMBRANOUS GN -widespread thickened cap walls -like idiopathic memb glom'itis -severe proteinuria w/ nephrotic syndrome -SUBEPITHELIAL/mesan DEPOSITS-wire loops Advanced Sclerosing (VI)-90% sclerosed, Glomerular Diseases Related to Systemic Dzs HENOCH-SCHONLEIN PURPURA-any or all Sx -3-8yo kids -Purpuric skin lesions on extensor surfaces- -arms, legs, buttocks -subepidermal hemorrhages -necrotizing vasculitis of small vessels-IgA -also in GI tract -Abd-pain, vomiting, int bleeding -Non-migratory arthralgia -Renal-1/3 pts-worse in adults -hematuria, proteinuria, nephrotic syn -few adults->RPGN w/ crescents Pathogenesis-1/3pts w/ h/o atopy -onset follows URI MORPH-IgA deposits in mesan, like IgA neph'y -mild focal prolif to diffuse to crescentic GN -IF-IgA, sometimes IgG and C3 in mesang -lumpy-bumpy deposits CLINICAL-recurring hematuria for years Worse Px - diffuse lesions or Nephrotic Syn -renal failure in crescentic, Glomerular Diseases Related to Systemic Dzs DIABETIC GLOMERULOSCLEROSIS -ESRD in up to 40% type I, II -COD in 20% pts មyo 3 syndromes: -Non-nephrotic Proteinuria-microalbuminemia -Nephrotic Proteinuria->death/dialysis w/in 5yrs -Chronic renal failure -changes due to: non-enz glycosylation, hemodynamics MORPH- -Thickened cap BM-in all diabetics -Diffuse glom'sclerosis -increased mesan matrix, thick GBM -PAS(+) matrix depositions -Nodular glom'sclerosis-Kimmelsteil-Wilson dz -w/ laminated, hyaline masses(K-W nods) PAS+ ->compress caps->ischemia -PATHOGNOMONIC FOR DM -Linear IF-like anti-GBM AB CLINICAL-Microalbuminemia->overt protein loss -HTN increases risk ofDM nephropathy -less predictable course in DM-II Tx-many on dialysis- ACE-inhibitor beneficial, Glomerular Diseases Related to Systemic Dzs AMYLOIDOSIS -kidney involvement most common -usual COD for amyloidosis Gross-can be NL, large or small (ischemia) Histo-deposits in glom-thickened mesang ->also deposits along GBM (subendoth) ->vascular narrowing, obliteration -also deposits in vessels, interstitium -ultra-fine fibrils -late-deposit in tub BM, vasa recta, medulla ->tub fibrosis, atrophy CONGO RED STAIN-apple-green birefringence PAS(-), Silver stain (-) CLINICAL-heavy proteinuria, nephrotic syn -Die in uremia -tubular amyloid casts More on amyloid-peptides form beta-pleats, Glomerular Diseases Related to Systemic Dzs All-early-focal, segmental (necrotizing) GN -hematuria w/ mildly decreased GFR Severe-RPGN-extensive necrosis, fibrin deposits, crescents GOODPASTURE - anti-BM ABs RPGN+necrotizing, hemorrhagic interstit pneumonitis ->hemoptysis, rapidly prog Renal Failure ->COD-uremia -linear IgG, C3 in GBM -anti-GBM ABs cross-react w/ pulm ABM ->pulm hemorrhage -Ag: alpha3 of collagen type IV -?exposure via smoking, viruses, poisons MICROSCOPIC POLYANGIITIS WEGENER GRANULOMATOSIS -hemoptysis+renal