curs 18-guta
Transcript of curs 18-guta
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HIPERURICEMIILE
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cresterea concentratiei sanguine a acidului uric si asarurilor lui (urati) cu depozitarea consecutiva ale acestorain tesuturi
5 forme clinice: - hiperuricemia asimptomatica uratilor > 6 mg% la si >7 mg% la ; factor de risc pentru celelalte forme clinice
- artrita acuta urica (guta clasica) mono - sau oligoartrita,unica sau recurenta, prin depunere intraarticulara de
cristale de urat de Na monohidrat- artrita gutoasa cronica (guta cronica tofacee) si tofii gutosi deformari articulare cronice datorita depunerilor intra - siperiarticulare de urati, resp. aparitia de tofi gutosi depuneri circumscrise de urati pe pavilionul urechii,tendoane, burse, viscere
- nefropatia urica (gutoasa) nefropatie interstitiala lentevolutiva sau IRA obstructiva prin precipitarea masiva deurati in tubii colectori
- litiaza renala urica formare de calculi de urati in aparatulurinar aceste forme se pot combina
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prevalenta hiperuricemiilor: 2-18%
prevalenta gutei: 0,13-0,37%net mai frecvent la , mai ales in decada 5.
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EtiopatogenezaProducerea de acid uric prin oxidarea
purinelor endo- si exogene; prin defectegenetice sau prin turnoverului inhemopatii maligne se poate exacerba
sinteza purinelor Eliminarea deficitara a acidului uric prin
RFG (IRC) sau reabsorbtiei si
secretiei tubulare (rinichi polichistic, ceto-acidoza, acidoza lactica, tratam. diuretic)De obicei, cele 2 mecanisme coexista
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Clasificare etiopatogenetica1. Prin cresterea producerii de ac. uric (metabolice)- primare: idiopatice (poligenice)
prin defecte genetice definite- secundare:
a) sintezei de novo a purinelor- glicogenoliza tip I (deficit de glucozo-6-fosfataza)- sindr. Lesch-Nyhan (deficit de hipoxantin-fosforibozil-transferaza)
b) turnoverului acizilor nucleici- sindr. mielo- si limfoproliferative- radio- si chimioterapie- aport alim. de purine
2. Prin reducerea eliminarii renale- primare- secundarea) IRCb) rinichi polichisticc) saturnismd) etilisme) medicamente (aspirina, diuretice, tbcstatice)f) sarcoidozag) acidozah) afectiuni endocrine (hiper- si hipoparatiroidism, hipotiroidism, insuf. CSR)i) infometare si suprasolicitare fizica
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Diagnostic- Hiperuricemia asimptomatica determ. ac. uric sanguin - Artrita ac. uricaclinic debut brusc, evt. dupa traumatism minim, frig,
masa copioasa, alcool; frecvent noaptea; de obiceimonoarticular, mai ales la prima articulatie metatarso-falangiana, dar si haluce, glezna, calcai, mana, cot; durere
lancinanta; semne celsiene; dureaza pana la 2 saptamaniparaclinic evid. cristalelor de urat Na in lichid sinovial (ex.in lumina polarizata); VSH, leucocitoza
dg. diferential pseudoguta (artrita cu pirofosfat Ca),tendinite, artrite septice, artrita psoriatica, artritareumatoida, artroze, LES
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- Artrita cr. gutoasa si tofii gutosi (guta cr. tofacee) pedegete, tendonul lui Achile, fata cubitala a antebratelor,pavilionul urechii; durere persistenta, mobilitate redusaprogresiv, evt. exulcerare
dg. diferential: PR- Nefropatia urica (gutoasa)a) Nefropatia urica interstitiala proteinurie, izostenurie,
evt. HTA
b) IRA obstructiva mai ales dupa chimioterapii agresive,rabdomioliza extinsa, favorizat de pH urinar acid- Litiaza urinara urica evt. colici paraclinic ex.ecografic, determ. ac. uric din urina, analiza
chimica a calculilor
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Tratamentobiective:
- tratam. hiperuricemiilor asimptomatice- remisia atacului ac. de artrita urica si
prevenirea recurentelor - prevenirea formarii depozitelor tisulare de uratisi celor existente - prevenirea calculilor urinari
mijloace de realizare:- dieta specifica si modif. stilului de viata- colchicina si antiinflam. nesteroid. si steroid.- uricozurice sau medicam. care sinteza de ac.uric- tratam. afectiunii generatoare in guta sec.
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Tratam. hiperuricemiilor asimpt. individualizat dieta saraca in purine (proteine anim.)
si alcooltratam. obezit.tratam. medicam. doar la AHC
incarcate, lit.ren., IRA, ac. uric urinar > 1,1mg/24h
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Tratam. atacului ac. de artrita urica:Colchicina 1 tb./2 ore (max. 6); daca
apare diareea iv. (2 mg, apoi inca 2 doze a 1 mg la 6h) Antiinflam. nesteroidice (indometacin,
diclofenac, ibuprofen, naproxen) alternativa pentru colchicina
Glucocorticoizi (prednison 20-30 mg/zicateva zile, apoi scazand doza)
Profilaxia recurentelor colchicina 1 -2tb/zi, celputin inca 1 an dupa normalizarea uricemieiregim dietetichipouricemiante
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Prevenirea formarii depozitelor tisularede urati si celor existente: hipouricemiante (probenecid, benemid,benurtil, sulfinpirazona efecturicozuric, 500 1000 mg/zi, seadministreaza cu lichide multe si cualcalinizarea urinii prin bicarbonat Na;benziodarona si efect de reducere a
sintezei, 100- 300 mg/zi; allopurinol reduce sinteza de ac. uric, 200 mg/zi;ac. orotic 1000 mg/zi)
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Tratam. nefropatiei urice si litiazeiurice:
- aport suplimentar de lichide- alcalinizarea urinii
- Allopurinol
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ProfilaxieMonitorizarea subiectilor cu risc: AHC,
obez., DZ, hiperlipidemii, HTA, sindr.metabolic)
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PORFIRIILE
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boli datorate unor defecte enzimatice
in biosinteza hemului, rezultand osupraproductie si acumulare de porfirina
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EtiopatogenezaBiosinteza hemului
succinilCoA + glicina ac. -aminolevulinic (ALA) porfobilinogen(PBG) hidroximetibilan (HMB) uroporfirinogen coproporfirinogen protoporfirinogen protoporfirin hem hemoglobina
Prin deficite enzimatice (ereditare sau dobandite) la diferite nivele seacumuleaza porfirinele respective:
- deficit de HMB- sintetaza acumulare de porfobilinogen porfirie ac.intermitenta
- deficit de urosintetaza acumulare de HMB porfirie eritropoieticacongen.
- deficit de urodecarboxilaza acumulare de uroporfirinogen porfiriecutanata tardiva
- deficit de coprooxidaza acumulare de coproporfirinogen coproporfirie ered.
- deficit de protooxidaza acumulare de protoporfirinogen porfirievariegata (mixta)- deficit de ferochelataza acumulare de protoporfirin protoporfirie
eritropoietica85% din hem este sintetizat in celulele eritroide, 15% in ficat porfirii
hepatice si eritropoietice
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Clasificarea porfiriilorPorfirii hepatice:- Deficienta de ALA-dehidraza- PAI- CPE- PV
- PCTPorfirii eritropoietice:- Anemie sideroblastica X-linkata- PEC- PPE
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Porfiria acuta intermitenta (PAI) mai frecventa in N -EUetiopatogeneza: transmisa autosomal dominant; activitatea HMB-
sintetazei redusa la jumatate; activata dupa droguri, corticoterapie, curede slabire, infectii, interv. chirurg.
clinic: foarte variabil; multi asimptomatici;- digest.: durere abdom. ferma, evt. sub forma de crampa, greata,
varsaturi, constipatie, chiar ileus;- neurolog.: hiperactiv. simpatica, resp. degenerare axonala
tahicardie, HTA, transpiratii abundente;dureri ale membrelor, capului, gatului, slabiciuni musculare, tremor,convulsii, chiar paralizii respiratorii si deces
- psihice: anxietate, depresie, halucinatii, paranoiedg.: ALA si PBG in sange si urina in timpul atacurilor; in peroada
asimptomatica pot fi normale, incat se determina HMB-sintetaza dineritrocite
tratament:- patogenetic: hem 3-4 mg iv. 4 zile(hematina, hem-albumina, hem-
arginat) inhiba prin feed -back negativ formarea de ALA;- simptomatic:analgezice narcotice pentru durerile abdom.,
fenotiazine pentru greata, varsaturi, anxietate
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Coproporfiria ereditara (CPE) mai ales la
etiopatogeneza: transmitere autosomal dominanta;prin deficit de coprooxidazaclinic:- latenta pana la pubertate- manifestari neuroviscerale ca in PAI- manifestari cutanate ca in PCTdg.: coproporfirinogen in urina si fecale
tratament: ca in PAI
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Porfiria variegata (PV)etiopatogeneza: transmitere autosomal
dominanta; deficit de protooxidazaclinic: ca in PAI si CPEdg.: proto- si coproporfirinele urinare
tratament: ca in PAIevitarea expunerii la soare
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Porfiria eritropoietica congenitala (PEC, b.Gunther)
etiopatogeneza: transmitere autosomal recesiva;
deficit de urosintetaza; aparitia de izomeri deuro- si coproporfirineclinic:- fotosensibilitate cutanata severa (prin
depozitarea porfirinelor) cu manifestari ca in
PCT- dintii prezinta fluorescenta rosie-purpurie lauv. (prin depozitare de porfirine)
- splenomegaliedg.: anemie hemolitica; izomerii de uro- si
coproporfirine in sange, urina si fecaletratament:- transfuzii pentru reprimarea eritropoiezei- splenectomie- evitarea expunerii la soare- -caroten
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Protoporfiria eritropoietica (PPE)etiopatogeneza: transmitere autosomal dominante;
deficit de ferochelataza
clinic: fotosensibilitate, fenomene asemanatoare cucele din angioedem, fara leziuni veziculare ingeneral, in schimb lichenificare, pseudovezicule
dg.: protoporfirina in sange si fecale; evt. leziunihepatice prin depozitare (fiind insolubila, formeazacristale)
tratament:- -caroten po.(creste toleranta la lumina soarelui)- colestiramina, carbune activat (absorbanti de
porfirine)- splenectomie- transfuzii, administrare de hem- transplant hepatic (in complicatii hepatice severe)