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GNA ????

Munger KA in B&R The Kidney - 2012Nefronul

Glomerul unitate filtranta

Nielsen S in Brenner & Rector The Kidney 9th ed 2012Perico N, Remuzzi in Brenner & Rector The Kidney 9th ed 2012Glomerular endothelial layer the fenestrated filterThe pore area 20% to 50% of the cell surface the pores - 60nmNegative electric charge - glycoproteins, glycosaminoglycans, and glycocalyx Glycocalyx expression is affected by fluid shear stress - shear stress increases albumin passageVEGF formed by the podocytes increases endothelial cell permeability and induces the formation of endothelial fenestrations

GBMNielsen S in Brenner & Rector The Kidney 9th ed 2012

Size-selective and a charge-selective barrier.Composed of collagen IV, laminin, entactin, sulfated proteoglycans (perlecan, collagen XVIII, and agrin)

The strongest evidence for a specific role of the GBM in the filtration barrier is the finding that mice deficient in laminin-2, a major component of the GBM, developmassive proteinuria

Nielsen S in Brenner & Rector The Kidney 9th ed 2012Perico N, Remuzzi in Brenner & Rector The Kidney 9th ed 2012The epithelial (podocyte) layer Slit layerHypothetical model of the podocyte slit diaphragmThe epithelial filtration slit has a zipper-like structure, with a rectangular opening of 4 by 14 nmAlbumin concentration in Bowmans capsule is about 60 g/mL At a GF of 120ml/min - 172000ml filtered in 24h - 10368000g albumin filtered in 24h 10,368g/24hGLOMERULONEFRITEDEFINITIE(GN) sau nefrite glomerulare grup afectiuni caracterizate de leziuni (inflamatorii sau neinflamatorii) ale filtrului glomerular manifestate clinic prin :Sindrom nefriticSindrom nefroticManifestari urinare minoreProteinurie izolataHematurie izolataCLASIFICAREPatogenetica proliferative si neproliferativeClinica acuta si cronicaEtiologica primara sau secundaraGNSINDROMNEFROTICSINDROMNEFRITICPROTEINURIE SAU HEMATURIE IZOLATAMANIFESTARI CLINICEAcuteCronicePrimareSecundareProliferativeNeproliferativeP. Urie> 3,5g/1,73m2/24h < 3,5g/1,73m2/24h 150mg/24h) GMm

Normal

Microalbuminuria

AlbuminuriaProteinuria

Proteine

/ 24h

< 300mg/24hAv 50mg/24h

-

>300mg/24h

Dipstick

< 30mg/dl

-

>30mg/dl

First urineP/Cr

200mg/g

Albumine

/ 24h

< 30mg/24hMed 10mg/24h

30 300 mg/24h

>300mg/24h

Dipstick albumin specific

3mg/dl

-

First urineA/Cr

M 300 Fiziologica < 150mg/24h GMmPatologicaPROTEINURIA Glomerulara ( >150mg/24h) GM mica + mareHEMATURIA Glomerulara - dismorfica Postglomerular - eumorfica

EDEMULRENAL Glomerular Nefrotic Nefritic Hiperhidratare (din IR)PHPCoPIVCRAAL

Aparatul juxtaglomertularNa Adenozina VC Aaf Renina, RFGTubGlom Feed BackThe kidney is involved in the genesis of any type of hypertensionArthur C. Guyton 1919 - 2003RHTA> 80% of BCR, 13,5% in targetCaractere comune asociere frecventa cu o infectie semnele clinice precedate de un interval liber variabil debut brusc al simptomelor: HTA, edem, proteinurie, hematurie frecvent, scaderea filtrarii glomerulare frecvent, evolutie favorabila cu tendinta la vindecare GNAGNA PRIMARE GNPM, GN cu depozite de IgA, GNMC, GNRPGNA SECUNDARE1. INFECTIOASE Bacteriene - streptococice, stafilococi, pneumococi, meningococi - rar -brucella, leptospire Virale : Coxackie, ECHO, VHB, VHC, varicela, mononucleoza, parotidita, etc Protozoare - toxoplasme, plasmodii, histoplasme Paraziti - trichinellaETIOLOGIE2. BOLI DE SISTEM LES, Arterite, granulomatoza Wegener, Goodpasture, Purpura Henoch-Schonlein, SHU, Purpura trombotica trombocitopenica, Crioglobulinemia mixta, 3. IMUNOTERAPIE SI SEROTERAPIE Corine bacterium, BCG seroterapii diverseETIOLOGIEGNA POSTSTREPTOCOCICAGN PROLIFERATIVA ENDOCAPILARA Streptococul hemolitic de grup A - variantele nefritigene si mixte (nefritigene si reumatogene) - cel mai frecvent tip - tipul 12 Streptococii din grupul C - mai rar

Localizarea infectiei Expresia clinica a infectiei faringian - clinic manifesta dentar - fara manifestari clinice cutanatETIOLOGIE IMUNA Antigen necunoscut dar se suspicioneaza: endostreptozimul - evidentiat la nivel mezangial - Lange proteinaza cationica antigene streptococice extracelulare - evidentiate in complexele imune Mecanism : CIC - CIC in titru crescut la majoritatea bolnavilor - depozite de IgG si C3 subendotelial - ar corespunde cu ci CI in situ - antigen cationic cu fixare in MBGEvidentiabile uneori - crioglobulinePATOGENIEATGATCCIEndoEpiHumpsFenomene autoimune: ATC anti colagen, laminina, HS, Factor reumatoid PMN Citokine Coagulare ComplementEfectori imunitari Chemotactism Fagocitoza Leziuni membranare Inflamatie ProliferarePATOGENIEATCATGCIMO- Exudatie - infiltrat limfo-monocitar si neutrofilic- Proliferare endocapilara ( mai ales mezangiala )- Depozite eozinofile, neregulate pe versantul extern al MBGIF- C3 +/- IgG - granulare, de-a lungul capilarelor si in mezangiu, sau numai mezangialME- Depozite electronodense extramembranoase ( subepiteliale ) ANATOMIE PATOLOGICA

ANATOMIE PATOLOGICA

Depozite de C3 +/- IgG - aspect de cer instelatANATOMIE PATOLOGICA

HumpANATOMIE PATOLOGICAPREVALENTA predomina la copil si adolescent predomina la sexul masculin prevalenta scade cu varsta - foarte rara >50 ani1 - INFECTIA STREPTOCOCICAa.) inaparenta clinicb.) aparenta clinic- localizare - faringo-amigdaliana, cutanata (intertrigo, supuratie) abces dentar, etcTABLOU CLINIC2. PERIOADA DE LATENTA (Intervalul liber)- durata 14 - 21 zile- stare generala buna, fara simptomatologie clinica evidenta- foarte rar - proteinurie discreta sau microhematurieAbsenta intervalului liber sau un interval liber mai mic de 7 zile pledeaza impotriva GNA poststreptocociceTABLOU CLINIC3. PERIOADA DE STARE Sindrom nefritic HTA - Proteinurie subnefrotica ( rar nefrotica) - Hematurie microscopica sau macroscopica - Edem prin retentie hidrosalina indusa de dezechilibru glomerulo-tubular +/- complicatii +/- -Oligurie in perioada de instalare a edemelor -Durere lombara difuza, bilaterala -Retentie azotataTABLOU CLINIC Sindrom inflamator nespecific - VSH accelerat, - CRP cu titru crescut, - Fibrinogen cu concentratie crescuta - PDF crescut in ser si in urina Sindrom urinar - proteinurie sub nefrotica (rar nefrotica) - cilindrurie cilindri hialini - hematurie microscopica sau macroscopicaTABLOU CLINICLABORATOR Sindrom imunitar - CIC cu titru crescut - C3 cu titru scazut - Scade activitatea hemolitica a CH50

Inconstant FR prezent in ser - Crioglobuline urinare prezenteLABORATOR Infectie streptococica - ASLO creste la 3 saptamani de la infectia streptococica si se normalizeaza in 6 luni ( ? infectiile cutanate anticorpi anti hialuronidaza, ATC anti AND polimeraza B, tulpini care nu sintetizeaza SLO ? ) - ATC anti streptozim - ATC anti proteinaza cationica - ATC anti proteina M

LABORATOR Rinichi mariti de volum bilateral ecografic si la urografia IV RFG uneori scazuta FPR frecvent normal PC uzual normala NU SE EFECTUEAZAIMAGISTICAPROBE FUNCTIONALE RENALEInfectie streptococica in antecedentele recenteInterval liber > 7 zileSindrom nefritic cu debut acut Sindrom inflamator nespecific Modificari imunitare CIC crescut, C3 scazutInfectie streptococica evidenta sau anamneza biologica a infectiei streptococice Paraclinic rinichi mari bilateralAbsenta unei boli de sistemPBR glomerulita proliferativa endocapilaraECUATIE DE DIAGNOSTIC (+)GNA cu oligo-anurieGNA cu RA care nu se normalizeaza in 4 saptamaniHTA nu se normalizeaza dupa 4 saptamaniProteinurie > 3,5g% cu durata > 4 saptamaniC3 scazut dupa 8 saptamani de la debutul boliiINDICATII DE PBRGNA PNA - clinic polaki-disurie + febra si absenta edemului si a HTA - leucocituria > hematuria, hematuria eumorfa - absenta semnelor de infectie streptococica si C3 normal

GNA GNC in puseu de acutizare - istoric de HTA si sau hematurie si sau proteinurie - interval liber < 7 zile - retinopatie hipertensiva - rinichi mici bilateral, egal contur regulatDIAGNOSTIC DIFERENTIALEtiologic al GNA GNA secundare - LES - Purpura H-S - Din endocardita bacteriana - Din poliarterita nodoasa GNA primitive - GN IgA - GN proliferativa focala - GNRPDIAGNOSTIC DIFERENTIALForma comuna- tablou clinic completForma cu semne extrarenale HTA + edemForme monosimptomatice HTA sau edem sau hematurieForma cu SNForma cu IRAForme fruste cu disparitia simptomelor in cateva zileRenale IRACardio-vasculare EPA, edemcerebral, encefalopatie hipertensiva, insuficienta cardiacaInfectioase ITU, infectii respiratoriiFORME CLINICECOMPLICATII Evolutie favorabila vindecare - 1 an - 70 80% copii, 50 60% adulti Cronicizare dupa 1 an de la debut GNRP cazuri rareEVOLUTIE - PROGNOSTIC Profilactic - profilaxia infectiei streptocociceCurativ - Penicilina G 400.000ui/6h IM - 14-21 zile apoi Moldamin 1200000ui/10 zile IM 6-12luniRegim igieno-dietetic - repaus la pat pana la disparitia edemelor apoi - evitarea eforturilor fizice si a expunerii la intemperii - hiposodat 4g NaCl/zi - hipoproteic 0,4g/kg/zi in caz de IRA TRATAMENT Tratamentul focarelor de infectie - la minimum 3 luni de la debutul bolii Tratament simptomatic - al edemelor diuretice de ansa Furosemid 80-160 mg/zi - al HTA se pot utilizaIEC sau BRABCCa - Amlodipin 2 x 5mg/ziClonidina 3 x 0,15mg/zi- al complicatiilorTRATAMENTSe contraindica: - Vaccinarea de orice tip 2 ani de la vindecarea bolii - Tratamentul corticoterapic - contraindicat - exceptie formele cu IRA si proliferare extracapilaraTRATAMENT