MO. Coloraie cu albastru de toluidin. n stnga, ob. 20x proliferare endocapilar intens ocupnd n ntregime lumenul anselor capilare.Hipercelularitate mezangial i infiltrat cu polimorfonucleare (anse capilare, mezangiu i interstiiu)

n dreapta, ob 100x, depozite subepiteliale (sgei), polimorfonucleare n vecintatea depozitelor(PMN); Pod podocit. Sindromul nefritic acut

Imunofluorescen ob 20x depozite granulare (C3) n mezangiu i conturnd ansele capilare (aspect de ghirlande).Sindromul nefritic acut

Microscopie electronicaDepozit (H humps) pe versantul extern al membranei bazale glomerulare (MBG). tergerea proceselor pediculate ale podocitului (P). Granulocit n interiorul capilarului glomerular (PMN).Sindromul nefritic acut

Manifestrile sindromului nefritic acut se instaleaz n ore, zile.

Se pot instala att la persoane fr afectare renal anterioar ct i la persoane cu o glomerulopatie cunoscut.

n ambele situaii, trebuie considerat urgen medical.Sindromul nefritic acut

Sindromul nefritic acut

Sindroame clinice glomerulare

2. Sindrom nefritic rapid progresiv - Definitie - sindrom caracterizat prin:- debut acut sau insidios- hematurie - proteinurie- oligo - anurie- anemie- insuficienta renala rapid progresiva

Sindroame Renale

Sindroame Renale

Anatomie patologica

Microscopie optica:Sindroame Renale

Anatomie patologica

Microscopie optica:Sindroame Renale

Anatomie patologica

Microscopie optica:Sindroame Renale

Anatomie patologica

Microscopie optica:Sindroame Renale

Anatomie patologica

Microscopie optica:Sindroame Renale

Anatomie patologicaMicroscopie optica:Sindroame Renale

Anatomie patologica

Imunofluorescenta:Sindroame Renale

Sindroame Renale

Sindroame Renale

Sindroame clinice glomerulare

3. Sindrom nefritic cronic - Definitie - sindrom caracterizat prin:- Proteinurie > 1 g/ 24h (dar < 3.5 g/ 24h)- hematurie cu hematii dismorfe- insuficienta renala lent progresiva- HTASindroame Renale

Sindroame clinice glomerulare

- Aspect histologic:- Glomerulonefrita mezangio-proliferativa IgA Berger- Boala membranelor bazale subtiri- Glomerulonefrita difuza membrano-proliferativa- Glomerulopatia membranoasa- Glomeruloscleroza focal segmentala- LES- Glomeruloscleroza diabetica- Amiloidoza- S. Alport- GMP fibrilara- Microangiopatie tromboticaSindroame Renale

Sindroame Renale

Sindroame Renale

SINDROMUL NEFROTIC

Sindrom nefrotic este definit prin asocierea dintre o proteinurie > 3,5g/zi i hipoalbuminemie (sub 3g/dL) i eventual hipoproteinemie (sub 6/dL), determinate de alterarea permeabilitii barierei de filtrare glomerular.Sindroame Renale

Membrana de filtrare glomerular (ME x60.000)Sindroame Renale

SUBSTRATUL I CAUZELE SINDROMULUI NEFROTICSindromul nefrotic este considerat primitiv, atunci cand nu este identificata o cauza a acestuia . Sindromul nefrotic primitiv este de dou ori mai frecvent dect cel secundar (70%).Are ca substrat glomerulopatii primitive, frecvent nefropatia membranoas (NM), nefropatia cu leziuni glomerulare minime (NLGM) i glomeruloscleroza focal i segmentar, mai rar glomerulonefrita membrano-proliferativ (GNMP) i nefropatia cu depozite mezanagiale de IgA (NIgA). Sindroame Renale

Sindroame Renale

Sindroame Renale

Hipoalbuminemia

- sinteza proteica hepatica = 12-14 g/zi - creste normal de 6 8 ori, dar este limitata de:- varsta- stare de nutritie- boli hepatice asociate- stimul: presiunea oncotica hepatocit- valori ale albuminemiei < 3 g/dlBolile Renale

Complicatiile sindromului nefrotic

- edeme, anasarca- hipovolemia; colaps; soc hipovolemic- insuficienta renala acuta- dislipidemia- cardiopatia ischemica- evenimente trombo-embolice- infectii- insuf. tubulara proximala (S. Fanconi)- deficienta de oligometale: Fe, Cu, Zn- hipovit.D- malnutritia protein-caloricaSindromul nefrotic

Sindroame Renale

Edemele

Sindromul nefrotic

Edemele

Edemul reflect creterea coninutului n sodiu al organismului, scopul tratamentului este de a negativa balana sodiului, care poate fi realizat prin:Reducerea aportului sub 50mmol/zi (3g sare de buctrie);Creterea eliminrii pe cale renal prin administrarea de diuretice. Sindromul nefrotic

Edemele

In sindromul nefrotic exist rezisten la tratamentul cu diuretice, determinat de o serie de factori. :factori care in de pacient:eficiena tratamentului diuretic scade atunci cnd aportul de sodiu este mare administrarea concomitenta de medicamente care limiteaz aciunea diureticelor (Ex. antiinflamatoarele non-steroidiene)factori care tin de sdr. Nefrotic:

Sindromul nefrotic

Edemele

In sindromul nefrotic exist rezisten la tratamentul cu diuretice, determinat de o serie de factori:factori care tin de sdr. Nefrotic: edemul peretelui intestinal reduce absorbia diureticelor administrate pe cale oralfurosemidul este transportat legat de albumin:albumina aflat n lumenul tubular leag furosemidul i i limiteaz accesul spre pompe,

Sindromul nefrotic

Edemele

In sindromul nefrotic exist rezisten la tratamentul cu diuretice, determinat de o serie de factori. :factori care tin de sdr. Nefrotic: reabsorbia sodiului este crescut n tubii colectori, ceea ce limiteaz efectul diureticelor natriuretice care acioneaz la nivelul tubului contort (tiazidice) sau al ansei Henle (furosemid)Sindromul nefrotic

Edemele

Monitorizarea tratamentului diuretic include: diurezavariaia masei corporalepresiunea arterial (msurat inclusiv n ortostatism)monitorizarea sodiu, potasiului, ureei i creatininei serice la 3 zileSindromul nefrotic

Sindromul nefroticEdemele

Sindromul nefroticComplicatiile tromboembolice

A)(SN nephrotic syndrome; PG general population, LES - lupus)B)

Sindromul nefrotic

Risk of Thrombotic Events in NS

Anti-TromboticPro-TromboticHypercoagulability

CoagulareN/ Factor XI (GM 160kDa) N/ Factor II (GM 69kDa)N/ Factor IX (GM 56kDa)N/ Factor X (GM 56kDa) Proteinei C (GM 62kDa) Fibrinogen (GM 340 kDa) Factor V (GM 330 kDa) Factor VIII (GM 330 kDa)N/ Proteinei S(GM 69kDa) Antitrombina III (GM 60 KDa)Fibrinoliz 1-AT (GM 54kDa) tPA (GM 72kDa) PAI (GM 52kDa) Plasminogen (GM 92 KDa) Lp(a)(GM 500 kDa) 2-M(GM 725 kDa)

Sindromul nefroticInfectiile

Infectiile

- infecii severe sunt raportate la 14% dintre copii (jumtate, peritonite spontane cu Streptoccocus pnemoniae) i 19% la aduli (cel mai frecvent cu germeni nosocomiali) - Incidena infeciilor a fost asociat cu severitatea sindromului nefrotic - mecanisme:hipogamaglobulinemiepierderea unor fraciuni ale complementului (factorul B al cii alterne)deficitul de zinctratamentul imunosupresor i corticoizii

Sindromul nefrotic

Infectiile

- Tratament:utilitatea vaccinrii anti-pneumococ profilaxia antibiotic de rutin Sindromul nefrotic

Sindromul nefroticHiperlipemia

Hiperlipemia

- hipercolesterolemia (90%) - hipertrigliceridemia (70%) - invers corelata albuminemiei Sindromul nefrotic

Hiperlipemia

- mecanisme:Scaderea activitatii HMG-CoA reductazeiCresterea activitatii colesterol 17 reductazeiSupraexpresia acetil CoA transferazei enzima care esterifica colesterolul intracelularScaderea populatiei de receptori ai LDL Sindromul nefrotic

Hiperlipemia

- mecanisme:Pierderea urinara a LCAT (GM 63 kDa): scade preluarea excesului de colesterol de catre HDLScadere a populatiei de receptori ai HDLScade activitatea lipoproteinlipazei: scaderea lipolizei chilomicronilor si VLDL.Scaderea populatiei de receptori ai VLDLSindromul nefrotic

Sindromul nefrotic

MO: particule HDL colesterol (Lumina polarizata)

Hiperlipemia

- mecanisme:Pierderea urinara a LCAT (GM 63 kDa): scade preluarea excesului de colesterol de catre HDLScadere a populatiei de receptori ai HDLScade activitatea lipoproteinlipazei: scaderea lipolizei chilomicronilor si VLDL.Scaderea populatiei de receptori ai VLDLSindromul nefrotic

Consecinele hiperlipemiei secundare sindromului nefrotic

- riscul de infarct miocardic a fost de peste 5 X, dect n populaia general riscul de deces de cauz coronarian, de aproape 3 X, dect n populaia general progresia declinului funcional renal accentuat astenie, reducerea capacitii de efort fizicinterfer cu agregabilitatea plachetar, iar Lipoproteina (a) inhib fibrinoliza i poate contribui la accentuarea tulburrilor de coagulare. Sindromul nefrotic

Hiperlipemia

Tratament: - reducerea proteinuriei (scderea proteinuriei cu antagoniti ai sistemului renin angiotensin aldosteron poate ameliora anomaliile lipidice)dieta hipolipidic i creterea activitii fizice sunt deobicei ineficiente i trebuie asociate cu statine sau fibrai. fracia liber a statinelor este mai mare n sindromul nefrotic, cu un risc de rabdomioliz i de hepatotoxicitate mai mare, ceea ce impune monitorizarea enzimelor care reflect citoliza i adaptarea dozelor. Sindromul nefrotic

Sindromul nefroticInsuficienta renala acuta

Insuficienta renala acuta

- inciden de 20-30% - mecanism prerenal, eventual accentuat de hipovolemia indus de diuretice - obstrucia tubular: - colmatarea tubilor cu proteine - edem interstiial importantmodificri hemodinamice induse de medicamente (AINS, sau inhibitori ai sistemului renin angiotensin aldosteron)nefrit interstiial alergic (AINS, diuretice, antibiotice etc)suprapunerea unui alt mecanism patogenic (ANCA, anticorpi anti-membran bazal glomerular, mai ales n sindromul nefrotic din nefropatia membranoas).Sindromul nefrotic

Insuficienta renala acuta

- prognostic buncorectarea hipovolemieiEvitarea medicatiei nefrotoxiceSindromul nefrotic

- pierderea urinar crescut a proteinelor transportoare, rezultnd niveluri plasmatice reduse ale unor oligoelemente: - transferina - Fe - ceruloplasmina cupru - zinc - albumina - vitamin D binding protein - vitamina D - thyroid binding globulin - hormoni tiroidieni - cortisol binding protein - hormoni steroizi - relevana clinic a acestor anomali este incertSindromul nefrotic

Slide 2Moxonidine (4-chloro-N-(imidazolidine-2-ylidene)-6-methoxy-2-methyl-5-pyrimidinamine) is a centrally acting antihypertensive drug.

The blood pressure-lowering effect of moxonidine is due to a highly selective action in the rostral ventrolateral medulla, which leads to a reduction in overactivity of the sympathetic nervous system.

n sens morfopatologic, termenul de glomerulonefrit desemneaz leziuni inflamatorii (proliferative) ale corpusculului renal , n timp ce acela de nefropatie glomerular, leziunile non-inflamatorii ale corpusculului renala. n ambele situaii, exist i leziuni ale ale tubilor, interstiiului i ale vaselor renale. Glomerulonefritele i nefropatiile glomerulare pot fi ncadrate ca glomerulopatii.Slide 2Moxonidine (4-chloro-N-(imidazolidine-2-ylidene)-6-methoxy-2-methyl-5-pyrimidinamine) is a centrally acting antihypertensive drug.

The blood pressure-lowering effect of moxonidine is due to a highly selective action in the rostral ventrolateral medulla, which leads to a reduction in overactivity of the sympathetic nervous system.

Slide 2Moxonidine (4-chloro-N-(imidazolidine-2-ylidene)-6-methoxy-2-methyl-5-pyrimidinamine) is a centrally acting antihypertensive drug.

The blood pressure-lowering effect of moxonidine is due to a highly selective action in the rostral ventrolateral medulla, which leads to a reduction in overactivity of the sympathetic nervous system.

Sdr nefritic acut este o urgenta medicalaOliguria cu urini modificate la aspect, la un pacient cu oligurie, eventual cu edeme i HTA, rapid instalate, impune testarea urinei cu bandelet indicatoare.Slide 2Moxonidine (4-chloro-N-(imidazolidine-2-ylidene)-6-methoxy-2-methyl-5-pyrimidinamine) is a centrally acting antihypertensive drug.

The blood pressure-lowering effect of moxonidine is due to a highly selective action in the rostral ventrolateral medulla, which leads to a reduction in overactivity of the sympathetic nervous system.

Slide 2Moxonidine (4-chloro-N-(imidazolidine-2-ylidene)-6-methoxy-2-methyl-5-pyrimidinamine) is a centrally acting antihypertensive drug.

The blood pressure-lowering effect of moxonidine is due to a highly selective action in the rostral ventrolateral medulla, which leads to a reduction in overactivity of the sympathetic nervous system.

Slide 2Moxonidine (4-chloro-N-(imidazolidine-2-ylidene)-6-methoxy-2-methyl-5-pyrimidinamine) is a centrally acting antihypertensive drug.

The blood pressure-lowering effect of moxonidine is due to a highly selective action in the rostral ventrolateral medulla, which leads to a reduction in overactivity of the sympathetic nervous system.

Slide 2Moxonidine (4-chloro-N-(imidazolidine-2-ylidene)-6-methoxy-2-methyl-5-pyrimidinamine) is a centrally acting antihypertensive drug.

The blood pressure-lowering effect of moxonidine is due to a highly selective action in the rostral ventrolateral medulla, which leads to a reduction in overactivity of the sympathetic nervous system.

Slide 2Moxonidine (4-chloro-N-(imidazolidine-2-ylidene)-6-methoxy-2-methyl-5-pyrimidinamine) is a centrally acting antihypertensive drug.

The blood pressure-lowering effect of moxonidine is due to a highly selective action in the rostral ventrolateral medulla, which leads to a reduction in overactivity of the sympathetic nervous system.

Slide 2Moxonidine (4-chloro-N-(imidazolidine-2-ylidene)-6-methoxy-2-methyl-5-pyrimidinamine) is a centrally acting antihypertensive drug.

The blood pressure-lowering effect of moxonidine is due to a highly selective action in the rostral ventrolateral medulla, which leads to a reduction in overactivity of the sympathetic nervous system.

Slide 2Moxonidine (4-chloro-N-(imidazolidine-2-ylidene)-6-methoxy-2-methyl-5-pyrimidinamine) is a centrally acting antihypertensive drug.

The blood pressure-lowering effect of moxonidine is due to a highly selective action in the rostral ventrolateral medulla, which leads to a reduction in overactivity of the sympathetic nervous system.

Slide 2Moxonidine (4-chloro-N-(imidazolidine-2-ylidene)-6-methoxy-2-methyl-5-pyrimidinamine) is a centrally acting antihypertensive drug.

The blood pressure-lowering effect of moxonidine is due to a highly selective action in the rostral ventrolateral medulla, which leads to a reduction in overactivity of the sympathetic nervous system.

Slide 2Moxonidine (4-chloro-N-(imidazolidine-2-ylidene)-6-methoxy-2-methyl-5-pyrimidinamine) is a centrally acting antihypertensive drug.

The blood pressure-lowering effect of moxonidine is due to a highly selective action in the rostral ventrolateral medulla, which leads to a reduction in overactivity of the sympathetic nervous system.

Slide 2Moxonidine (4-chloro-N-(imidazolidine-2-ylidene)-6-methoxy-2-methyl-5-pyrimidinamine) is a centrally acting antihypertensive drug.

The blood pressure-lowering effect of moxonidine is due to a highly selective action in the rostral ventrolateral medulla, which leads to a reduction in overactivity of the sympathetic nervous system.

Slide 2Moxonidine (4-chloro-N-(imidazolidine-2-ylidene)-6-methoxy-2-methyl-5-pyrimidinamine) is a centrally acting antihypertensive drug.

The blood pressure-lowering effect of moxonidine is due to a highly selective action in the rostral ventrolateral medulla, which leads to a reduction in overactivity of the sympathetic nervous system.

Slide 2Moxonidine (4-chloro-N-(imidazolidine-2-ylidene)-6-methoxy-2-methyl-5-pyrimidinamine) is a centrally acting antihypertensive drug.

The blood pressure-lowering effect of moxonidine is due to a highly selective action in the rostral ventrolateral medulla, which leads to a reduction in overactivity of the sympathetic nervous system.

Slide 2Moxonidine (4-chloro-N-(imidazolidine-2-ylidene)-6-methoxy-2-methyl-5-pyrimidinamine) is a centrally acting antihypertensive drug.

The blood pressure-lowering effect of moxonidine is due to a highly selective action in the rostral ventrolateral medulla, which leads to a reduction in overactivity of the sympathetic nervous system.

In perioada de urmarire 29 (11.3%) dintre pacienti au dezvoltat un eveniment tromboembolic venos.

Rata incidenei a fost de 4,4 (95% CI 3.2-5.7) cazuri la 100 pacieni-an. Ceea indic o inciden de 30 de ori mai mare , comparativ cu cele raportate n populaia general , de 5 ori mai mare dect rata incidenei la pacienii cu LES si respectiv de 15 ori mai mare decat cea raportata in sarcina

*In patogeneza complicatiilor TE in SN sunt implicate numeroase mecanisme, insuficient clarificate printre care: unele comune oricarui pacient cu boala renala cum ar fi efectul medicatiei imunosupresoare si diuretice asupra coagularii, leziunile de perete vascular induse de necesitatea montarii cateterelor de dializa, predispozitia genetica, efectul inflamatiei asupra echilibrului fluido-coagulant, iar altele specifice reprezentat de pierderea preferentiala a proteinelor cu efect antitrombotic, cresterea sintezei hepatice de proteine procoagulante, etc.*Acest status de hipercoagulabilitate propriu SN este si cel mai puternic implicat in patogeneza EVT, la acesti pacienti inregistrandu-se un dezechilibru intre factorii anti-trombotici si cei Pro-trombotici.Pe de o parte in functie de crestere permeabilitatii membranei de filtrate glomerulara se pierd urinar factori ai coagularii cu GM mica cum ar fi factorii.In ceea ce priveste sistemul fibrinolitic se constata o scadere a nivelului seric a plasminogenului, acompaniata de *Studii mai vechi sau unele foarte recente au identificat o frecventa mai mare a complicatiilor tromboembolice in anumite tipuri de glomerulopatii cum ar fi GN membranoasa *Astfel analiza retrospectiva a unei cohorte de 1300 pacienti cu SN, a identificat la pacientii cu GNM un risc de 10 ori mai mare comparativ cu pacientii cu nefropatie IgA, iar la pacientii cu GSFS de 6 ori mai mare*Acest lucru a fost demonstrat de analiza retrospectiva a unei cohorte de 1300 pacienti cu SN, pacientii cu GNM inregistrand un risc de 10 ori mai mare comparativ cu pacientii cu nefropatie IgA, iar pacientii cu GSFS de 6 ori mai mare

*Slide 2Moxonidine (4-chloro-N-(imidazolidine-2-ylidene)-6-methoxy-2-methyl-5-pyrimidinamine) is a centrally acting antihypertensive drug.

The blood pressure-lowering effect of moxonidine is due to a highly selective action in the rostral ventrolateral medulla, which leads to a reduction in overactivity of the sympathetic nervous system.

Slide 2Moxonidine (4-chloro-N-(imidazolidine-2-ylidene)-6-methoxy-2-methyl-5-pyrimidinamine) is a centrally acting antihypertensive drug.

The blood pressure-lowering effect of moxonidine is due to a highly selective action in the rostral ventrolateral medulla, which leads to a reduction in overactivity of the sympathetic nervous system.

Cresterea sintezei hepatice de colest si scaderea clearence-ului LDL de catre hepatocit sinteza ambelor enzime este reglat de nivelul colesterolului liber din hepatocit, aceste anomalii ar putea fi explicate de supraexpresia ACAT-2 (acetil-CoA acetiltransferaza - enzima care esterific colesterolul intracelular) i de deficitul de receptori pentru LDL (calea pe care hepatocitul se aprovizioneaz cu colesterol).The blood pressure-lowering effect of moxonidine is due to a highly selective action in the rostral ventrolateral medulla, which leads to a reduction in overactivity of the sympathetic nervous system.

Slide 2Moxonidine (4-chloro-N-(imidazolidine-2-ylidene)-6-methoxy-2-methyl-5-pyrimidinamine) is a centrally acting antihypertensive drug.

The blood pressure-lowering effect of moxonidine is due to a highly selective action in the rostral ventrolateral medulla, which leads to a reduction in overactivity of the sympathetic nervous system.

Continutul crescut in colesterol esterificat al particolelor de HDL creaza in lumina polarizata un aspect specific.*Slide 2Moxonidine (4-chloro-N-(imidazolidine-2-ylidene)-6-methoxy-2-methyl-5-pyrimidinamine) is a centrally acting antihypertensive drug.

The blood pressure-lowering effect of moxonidine is due to a highly selective action in the rostral ventrolateral medulla, which leads to a reduction in overactivity of the sympathetic nervous system.

Hipertrigliceridemia apare secundar alterarii clerance-ului trigliceridelor din VLDL si chilomicroni, datorita inactivarii lipoprotein lipazei.*Lipoproteinlipaza este inactivata de catre o glicoproteina circulanta ANGPTL4, scazand astfel conversia trigliceridelor in acizi grasi liberi.Expresia ANGPTL 4 la nivelul t. muscular, adipos si al inimii este reglata de catre PPAR*ANGPTL4 este secretata in principal de catre: tesutul adipos, musculatura striata si inima.*Mutatie a aa 40/39 a ANGPTL4, pastreaza proprietatile antiproteinurice, fara sa induca inactivarea lipoproteinlipazei endoteliale*Slide 2Moxonidine (4-chloro-N-(imidazolidine-2-ylidene)-6-methoxy-2-methyl-5-pyrimidinamine) is a centrally acting antihypertensive drug.

The blood pressure-lowering effect of moxonidine is due to a highly selective action in the rostral ventrolateral medulla, which leads to a reduction in overactivity of the sympathetic nervous system.

Slide 2Moxonidine (4-chloro-N-(imidazolidine-2-ylidene)-6-methoxy-2-methyl-5-pyrimidinamine) is a centrally acting antihypertensive drug.

The blood pressure-lowering effect of moxonidine is due to a highly selective action in the rostral ventrolateral medulla, which leads to a reduction in overactivity of the sympathetic nervous system.

Slide 2Moxonidine (4-chloro-N-(imidazolidine-2-ylidene)-6-methoxy-2-methyl-5-pyrimidinamine) is a centrally acting antihypertensive drug.

The blood pressure-lowering effect of moxonidine is due to a highly selective action in the rostral ventrolateral medulla, which leads to a reduction in overactivity of the sympathetic nervous system.

Slide 2Moxonidine (4-chloro-N-(imidazolidine-2-ylidene)-6-methoxy-2-methyl-5-pyrimidinamine) is a centrally acting antihypertensive drug.

The blood pressure-lowering effect of moxonidine is due to a highly selective action in the rostral ventrolateral medulla, which leads to a reduction in overactivity of the sympathetic nervous system.

Slide 2Moxonidine (4-chloro-N-(imidazolidine-2-ylidene)-6-methoxy-2-methyl-5-pyrimidinamine) is a centrally acting antihypertensive drug.

The blood pressure-lowering effect of moxonidine is due to a highly selective action in the rostral ventrolateral medulla, which leads to a reduction in overactivity of the sympathetic nervous system.