Download - 6.1curs Studenti 2009 Gmn Excrescen Semilun
![Page 1: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/1.jpg)
Glomerulopatia cu excrescente semilunare
Prof. Dr. M. Voiculescu
Centrul de Medicina Interna – Nefrologie Fundeni
![Page 2: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/2.jpg)
Glomerulopatia rapid progresivaDefinitie
- entitate morfologica - etiologie variata- caracterizata prin leziuni inflamatorii si fibroase glomerulare severe cu aspect de semilune
- instalarea rapida a insuficientei renale
GMN cu excrescente semilunare
![Page 3: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/3.jpg)
Epidemiologie
- F > B
- tineri > varstnici
GMN cu excrescente semilunare
![Page 4: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/4.jpg)
Etiologie (1)
1. Primare
A. GMP proliferativa mezangiocapilaraB. GMP focala si segmentalaC. GMP membranoasa
GMN cu excrescente semilunare
![Page 5: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/5.jpg)
Etiologie (2)
GMN cu excrescente semilunare
2. Secundare (I)
A. Infectioase poststerptococice endocardite stari septice de
diverse etiologii
B. Vasculite LES sclerodermie sistemica PAN b. Wegener crioglobulinemie purpura Henoch-Schonlein GMP ANCA + GMP IgA Berger
![Page 6: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/6.jpg)
Etiologie (3)
2. Secundare (II)
C. Medicamentoase alopurinol rifampicina
D. neoplazii
GMN cu excrescente semilunare
![Page 7: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/7.jpg)
Anatomie patologica
- elementul histologic caracteristic este reprezentat de formarea excrescentelor cu aspect semilunar
excrescentele sunt formate din: celule
- epiteliale rezidente din capsula Bowman- mononucleare sistemice macrofage epitelioide
material acelular
- fibrina- colagen
GMN cu excrescente semilunare
![Page 8: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/8.jpg)
MO: Excrescente
GMN cu excrescente semilunare
![Page 9: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/9.jpg)
GMN cu excrescente semilunare
![Page 10: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/10.jpg)
Anatomie patologica
- In raport cu mecanismul patogenic se descriu trasaturi histologice specifice:
GMP mediate de CIC predomina: hipercelularitate influx leucocitar crescut peretii capilari ingrosati
GMP mediata de ANCA si de Ac. anti-MBG: necroza fibrinoida bine exprimata
GMN cu excrescente semilunare
![Page 11: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/11.jpg)
Anatomie patologica
Microscopie optica:
GMN cu excrescente semilunare
![Page 12: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/12.jpg)
Anatomie patologica
Microscopie optica:
GMN cu excrescente semilunare
![Page 13: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/13.jpg)
Anatomie patologica
Microscopie optica:
GMN cu excrescente semilunare
![Page 14: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/14.jpg)
Anatomie patologica
Microscopie optica:
GMN cu excrescente semilunare
![Page 15: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/15.jpg)
Anatomie patologica
Microscopie optica:
GMN cu excrescente semilunare
![Page 16: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/16.jpg)
Anatomie patologica
Microscopie optica:
GMN cu excrescente semilunare
![Page 17: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/17.jpg)
Anatomie patologica
Microscopie optica:
GMN cu excrescente semilunare
![Page 18: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/18.jpg)
Anatomie patologica
Imunofluorescenta:
GMN cu excrescente semilunare
![Page 19: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/19.jpg)
Anatomie patologica
Imunofluorescenta:
GMN cu excrescente semilunare
![Page 20: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/20.jpg)
Anatomie patologica
Imunofluorescenta:
GMN cu excrescente semilunare
![Page 21: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/21.jpg)
Anatomie patologica
Microscopie electronica:
GMN cu excrescente semilunare
![Page 22: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/22.jpg)
Clasificarea patogenica
- Tipul I: Ac. anti MBG- Tipul II: CI- Tipul III: ANCA (necrotizanta, pauciimuna)- Tipul IV: ANCA + Ac. anti MBG- Tipul V: primitiva (fara ANCA sau Ac. anti MBG)
GMN cu excrescente semilunare
![Page 23: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/23.jpg)
Patogeneza
- Debutul: leziuni capilare glomerulare necrotizante severe
GMN cu excrescente semilunare
![Page 24: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/24.jpg)
Patogeneza
- Evolutia:
leziune necrotizanta capilara
extravazare sangvina
depunere de fibrina, acumulare celulara
excrescente celulare +/- ruperea capsulei Bowman
excrescente fibrocelulare
excrescente fibroase
scleroza
GMN cu excrescente semilunare
![Page 25: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/25.jpg)
Structura excrescentelor celulare
- macrofage- limfocite T
Mediatori:
- complement seric- oxigen reactiv- proteinaze- substante procoagulare si fibrinoliza- TNF- IL-1
GMN cu excrescente semilunare
![Page 26: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/26.jpg)
IL-1 si TNF
Sursa: macrofageleIL-1 amplifica formarea excrescentelor
Th1
IL-2, INF-
formarea de excrescente
react DTH
Th2
IL-4, IL-10
GMN cu excrescente semilunare
![Page 27: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/27.jpg)
- Clasificare nonhistologica:
GMN cu anticorpi anti-MBG:
2 – 20% aspect IF: neted anticorpi anti-lant alfa 5 a fibrelor de colagen tip IV
GMN rapid progresiva
![Page 28: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/28.jpg)
IF: IgM anti MBG cu dispozitie lineara (S. Goodpasture)
GMN cu excrescente semilunare
![Page 29: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/29.jpg)
MO: S Goodpasture
GMN cu excrescente semilunare
![Page 30: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/30.jpg)
GMN rapid progresiva
- Clasificare nonhistologica:
GMN cu complexe imune: 15 – 50% secundare: aspect IF: granular anticorpi: Ag; C primare
- LES - nefropatii postinfectioase- nefropatia IgA- purpura Henoch- Schonlein,
GMN cu excrescente semilunare
![Page 31: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/31.jpg)
MO: LES
GMN cu excrescente semilunare
![Page 32: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/32.jpg)
LES excrescente glomerulare
GMN cu excrescente semilunare
![Page 33: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/33.jpg)
GMN rapid progresiva
- Clasificare nonhistologica:
GMN pauci imuna:
40 – 80% aspect IF: fara sau minim de depozite singura manifestare in cadrul unei vasculite necrotizante
GMN cu excrescente semilunare
![Page 34: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/34.jpg)
Patogeneza
CIC Ac. anti MBG ANCA Ruperea peretelui capilar
Transvazeaza in spatiul Bowman polimorfonucleare
monocite trombocite
proteine plasmatice complement seric
GMN cu excrescente semilunare
![Page 35: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/35.jpg)
Eliberarea din: celule rezidente (endoteliale si
mezangiale) celule sistemice (PMN, monocite,
trombocite) citokine (TGF.TNF-)
prostaglandine leukotriene
molecule de adeziune celulara
Imobilizare Hyalunoninat Cytokine Chemotactism
fixare polimerizare proliferare infiltrare PMN FBG in fibrina celulara leucocitara
Proliferare epiteliala + invazie monocitara
Compresie glomerulara si inhibitia filtrarii
GMN cu excrescente semilunare
![Page 36: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/36.jpg)
AcECAcEC
nPMN
Recrurare de celule mononucleare
nEC
AcPMN(a)
(c)
(b)
Instalarea leziunilor vasculitice in vasele mici de catre citokinele ANCA activatoare primed neutofile
intr-un loc si moment nepotrivit
![Page 37: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/37.jpg)
Vasculitele ANCA +
![Page 38: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/38.jpg)
Vasculitele ANCA +
![Page 39: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/39.jpg)
Vasculitele ANCA +
![Page 40: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/40.jpg)
Vasculitele ANCA +
![Page 41: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/41.jpg)
Vasculitele ANCA +
![Page 42: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/42.jpg)
Vasculitele ANCA +
![Page 43: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/43.jpg)
Vasculitele ANCA +
![Page 44: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/44.jpg)
Tratament
- planul terapeutic este determinat de:1. cauza2. stagiu3. severitate
- tratament agresiv:- GMP ANCA (+)- GMP anti - MBG- LES- b. Wegener- purpura Henoch-Schonlein
Supravietuirea: 50% la 6 luni 70% la 5 ani
GMN cu excrescente semilunare
![Page 45: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/45.jpg)
Tratament
A. Pulse therapy
- metiprednisolon 1g/zi, iv – 3 (5) zile consecutiv urmat de 60mg/zi oral, 6 luni
asociat cu
- ciclofosfamida 0,6 -0,8 g/m2/luna, iv, 3-6 luni sau 2 mg/zi oral
GMN cu excrescente semilunare
![Page 46: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/46.jpg)
Tratament
B. Plasmafereza
- Introdusa de Lockwood (1976)- studiul lui Pusey (1991):
- beneficiaza de plasmafereza: GMP cu anticorpi anti-MBG (S. Goodpasture) GMP ANCA+ GMP severe cu excrescente > 70%
- obligatoriu asociata cu tratament imunosupresiv- efecte adverse:
infectii moarte subita
GMN cu excrescente semilunare
![Page 47: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/47.jpg)
Tratament
C. Alte tratamente
- anticorpi monoclonali anti – TNF - imunoglobuline
GMN cu excrescente semilunare
![Page 48: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/48.jpg)
Raspunsul terapeutic
- 70-80% raspund- independent de % excrescentelor- prezenta oliguriei
- dependent de indicele de cronicitate- indice mic: 85-92%- indice ridicat: 36-71%
GMN cu excrescente semilunare
![Page 49: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/49.jpg)
Raspunsul terapeutic
- dozele vor fi mai mici la- varstnici- IRCr avansata
- efecte adverse- toxicitate medulara- infectii- cistita hemoragica
GMN cu excrescente semilunare
![Page 50: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/50.jpg)
Istoric + ex. Obiectiv
Teste hematologice, chimice, serologice
PBR Altele
AlteleGN crescentica
ac.Anti MBGANCA- ANCA+
Creatinina serica ac.Anti MBG ac.Anti MBG
< 6 mg/dL< 50%SEMILUNE
> 6 mg/dL> 50%SEMILUNE
Dependent dializa
- tratament suportiv- pulster. Steroizi / schimb plasma- transplant
- prednison- CFA
- schimp plasma- prednison- CFA
GMN cu excrescente semilunare
![Page 51: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/51.jpg)
GMN cu excrescente semilunare
![Page 52: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/52.jpg)
GMN cu excrescente semilunare
![Page 53: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/53.jpg)
GMN cu excrescente semilunare
![Page 54: 6.1curs Studenti 2009 Gmn Excrescen Semilun](https://reader036.vdocumente.com/reader036/viewer/2022062515/55cf99f8550346d0339ff015/html5/thumbnails/54.jpg)
GMN cu excrescente semilunare