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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

http://www.lehrbuch-medizin.de:8080/biochemie/public/klinik/_images/klinik04.jpg

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http://images.google.ro/imgres?imgurl=http://www.fwiegleb.de/gicht02.gif&imgrefurl=http://www.fwiegleb.de/urica.htm&h=184&w=104&sz=15&hl=ro&start=6&tbnid=uVuDFTRz4YPsnM:&tbnh=102&tbnw=58&prev=/images%3Fq%3D%2Bgichtknoten%26gbv%3D2%26svnum%3D10%26hl%3Drohttp://www2.chemie.uni-erlangen.de/education/medchem/harnsteine/bilder/gicht2.jpghttp://www.sophie-scholl-schule.de/Seiten/projekte/ziv_krank/gicht/gicht.htm

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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

http://images.google.ro/url?q=http://www.rheumanet.org/bibliothek/images/gicht.jpg&usg=__BN4PoBtmgAp3ao8uert591iXb7o=

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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)