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Source: Rubin R, Strayer DS. 2007. Rubins Pathology: Clinicopathologic Foundations of Medicine. 5th ed. USA: Lippincott Williams & Wilkins; p 1142
Hiperuricemia secundar: o concentraie crescut de acid uric din cauza medicamente / afeciuni medicale, cum ar fi cetoacidoz diabetic, psoriazis, saturnism cronic Acid uric se pot acumula ca urmare a: Supraproductia de nucleotide purinice Creterii turnover celular( degradarea purinelor Reducerea cii de salvare a purinelor Reducerea excreiei de acid uric
Predispoziia la numeroase boli Oamenii pot avea valori crescute ale acidului uric, fr a se confrunt cu nici un simptom de boal
Acid Uric
Acidul uric este produsul final al
metabolismului purinelor
Excreia de acid uric ndeprteaz deeuri de azot din organism. Antioxidant eficient a SRO poate la fel de eficient ca vitamina C
2/3 of uric acid este excretat via
Metabolismul purinelor: Calea De novo : sinteza purinelor din precursori nonpurine Calea de cruare a purinelor : purinele sunt transformate n nucleotidul corespunztor
Source: http://www.med.unibs.it/~marchesi/nucmetab.html
Cauzale hiperuricemiei
1. Producie crescut acid uric (10%):
Endogen (catabolismul crescut a purinelor): a) proliferare celular intensa ( turnover)(leucemie, anemia hemolitic) b) moartea celular (terapia n neoplazii) Activitatea enzimatic:
Un procent mic poate fi din cauza deficit enzimatic sau mutaii care sunt determinate genetic : PRPP sinthetaz i HGPRT
Anomalie X-linked Concentraia intracelular a 5fosforibozil-1-pirofosfate(PRPP) este principala etap limitant n in sinteza acidului uric Creterea activitii PRPP sintetazei duce la o supraproduciei de PRPP, care accelereaz biosinteza bazelor purinice (i degradarea ulterioar), care va determina o supraproducie acid uric Source: http://seqcore.brcf.med.umich.edu/mcb500/nucsyl/nucmetab.html
Source: http://www.macaulay.ac.uk/IFRU/iaeacd/html/techdoc/html/02_2.htm
Deficit enzimatic transmis prin mecanism legat de sex HGPRT catalizeaz conversia hipoxantinei la inozin monofosfate (IMP), unde PRPP este donor de fosfat Deficitul enzimatic de HGPRT conduce la acumularea de PRPP, rezult accelerarea biosintezei bazelor purinice i ulterior creterea concentraiei de acid uric
(HGPRT)
IMP
Source: http://seqcore.brcf.med.umich.edu/mcb500/nucsyl/nucmetab.html
Acid Uric neexcretat : Insuficiena funciei renale = reducerea clearance-lui sau reducerea excreiei fracionate renale Rezultat -scderea filtrrii glomerulare, scderea secreiei tubulare sau creterea reabsoriei tubulare
URAT1 = transportor de acid uric 1 hOAT1 = transportor anion organic uman (inhibat de medicaia uricozuric UAT = transportor de acid uric - care faciliteaz efluxul celular de urai Aceti transportori pot fi considerai pentru reabsorbia renal i excreia de acid uric.
Reducerea secreie de urai apare la pacienii cu acidoz (acidocetoza diabetic ,intoxicaie cu etanol) din cauza acizilor organici care se
acumuleaz n aceste condiii i intr n competiie cu eliminrile de acid uric.
Consumul de alcool
Alcoolul:
Crete degradarea adenin nucleotidelor Crete concentraia hipoxantinei = hiperuricemie Crete concentraia acidului lactic Scade excreia acidului uric Acidul lactic intr n competiie cu eliminrile de acid uric.
Deficien de Aldolaz-B
Aldolaza B este responsabil pt.formarea dihidroxiaceton-P i glideraldehidei din fructozo-1 fosfat n calea glicolitic Deficiena Aldolazei B duce la acumularea de fructozo-1 fosfat , crete fosfatul, ceea ce face imposibil formarea ATP din ADP i acumularea AMP . AMP n exces este degradat la acid uric.
Source: http://www.macaulay.ac.uk/IFRU/iaeacd/html/techdoc/html/02_2.htm
AMP Inozin Hipoxantin Xantin acid uric GMP Guanozin Guanin Xantin acid uric
Deficien de Glucozo -6-fosfataz Glicogenoza tip 1,boala von Gierke Scade secreia renal de acid uric consecin a acidozei lactice Crete sinteza de novo a purinelor din cauza formrii n exces a ribozo-5-fosfatului (excesul de glucozo-6-fosfat trece pe calea suntului hexozomonofosfatic) Crete degradarea ATP ; hiperuricemie
PRPP Sintetaz
Gut
Dureri articulare
Simptomatologie Localizarea predilect - haluce ( >90% ) Alte localizri articulaiile glezn,genunchi ,degete . Prezint semnele unui proces inflamator . Cauza Cristale de urat monosodic care se depune la nivelul sinovialei articulare. Ca urmare apare un rspuns inflamator imun.
Source: http://www.nlm.nih.gov/medlineplus/ency/imagepages/1222.htm
Litiaza renal
O acumulare de acid uric
Simptomatologie
La nceput -asimptomatic
Cauz
Atunci cnd acidul uric este n concentraie mare n snge, acesta poate precipita n parenchimul renal.Srurile formeaz calculi renali.
Litiaza renal
Source: http://www.nlm.nih.gov/medlineplus/ency/imagepages/17091.htm
Sindromul Lesch-Nyhan
O anomalie genetic ,se transmite printr-un mecanism legat de sex.
Siomptome
Deficien mintal, agresiune, cu tendin la autodistrugere Copii devin agresivi i i rod buzele i falangele .
Cause
Absena hipoxantin-guanin fosforiboziltransferazei duce la creterea
concentraiei de PRPP. Creterea sintezei purinelor, determin hiperuricemie.Explicaia pt comportament este necunoscut. Datorit hiperuricemiei guta i litiaza renal
Tratamentul hiperuricemiei
Combaterea efectelor nocive proinflamatorii ale depunerilor de urai n esuturi. Administrarea medicaiei antiinflamatorie
Medicaie uricozuric
probenecid (Benemid) and sulfinpirazon(Anturane) Blocheaz reabsorpia acidului uric n tubul contort proximal Contraindicat la pacieni cu litiaz renal.
Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy. 2nd Edition. Lippincott Williams & Wilkins
allopurinol Reduce producerea de acid uric Xantine oxidaza catalizeaz ultima etapa de degradare a purinelor la acid uric Blocheaz conversia xantinei la acid uric inhibnd xantin oxidaza
Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy. 2nd Edition. Lippincott Williams & Wilkins
Regim igieno-dietetic
Este recomandat o diet cu o concentraie sczut de purine A se evita cafeaua i alcoolul Alimente cu un coninut crescut de purine : Carne roie i organe meats (ficat) Bere spanac, fasole, conopid,ciuperci Alimente cu un coninut sczut de purine : Cereale , paste Lapte i produse din lapte ,ou Roii, legume verzi Alimente cu un coninut crescut de purine
References
Berg, J.M. et al. 2007. Disruptions in Nucleotide Metabolism Can Cause Pathological Conditions. Biochemistry. 7th Edition. W.H. Freeman and Company. College of Medicine. University of Illinois at Urbana-Champaign. Chapter 29: Nucleotide Metabolism. (https://www.med.uiuc.edu/m1/biochemistry/TA%20reviews/chap29.htm) Accessed March 12, 2008. Dellaripa, P.F. et al. 2003. Rheumatologic and Collagen Vascular Disorders in the Intensive Care Unit. Irwin & Rippe's Intensive Care Medicine. 5th Edition. Lippincott Williams & Wilkins Golan DE. 2007. Physiology of Purine Metabolism. Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy. 2nd Edition. Lippincott Williams & Wilkins Grahame-Smith, D.G. et al. 2002. Gout and Hyperuricaemia. Oxford Textbook of Clinical Pharmacology and Drug Therapy. 3rd Edition. Oxford University Press. Herfindal, Eric T. et al. 2000. Gout and Hyperuricemia. Textbook of Therapeutics. Drug and Disease Management. 7th Edition. Lippincott Williams & Wilkins. Hyperuricemia High Uric Acid Levels In Blood Chemocare.com Accessed: March 15, 2008 <http://www.chemocare.com/managing/hyperuricemia-high-uric-acid.asp> Kumar V, Cotran RS, Robbins SL. 2003. Robbins Basic Pathology. 7th ed. Philadelphia: Saunders; pp 774-777 Lyons, Dr. 2006. Nucleotide Metabolism. (http://seqcore.brcf.med.umich.edu/mcb500/nucsyl/nucmetab.html) Accessed March 16, 2008. Parent-Stevens, Louise. 1998. Hyperuricemia And Gout. PMPR652 Pharmacotherpeutics II. (http://www.uic.edu/classes/pmpr/pmpr652/Final/stevens/gout.html) Accessed March 6, 2008. Qazi, Yasir. Sep 21, 2007. Hyperuricemia. eMedicine (http://www.emedicine.com/med/TOPIC1112.HTM). Accessed March 15, 2008. Rubin R, Strayer DS. 2007. Rubins Pathology: Clinicopathologic Foundations of Medicine. 5th ed. USA: Lippincott Williams & Wilkins; p 1142 Shargel L, Mutnick AH, Souney PF, Swanson LN. 2006. Comprehensive Pharmacy Review. 6th ed. USA: Lippincott Williams & Wilkins; pp 1089-1098 Silberbreg, C. Kidney Stones. MedlinePlus Medical Encyclopedia. (http://www.nlm.nih.gov/medlineplus/ency/article/000458.htm) Accessed March 16, 2008. Taylor RB. 2003. Family Medicine Principles and Practive. 6th ed. USA: Springer; p 1061 Technical Manual Brief background of purine metabolism. (http://www.macaulay.ac.uk/IFRU/iaeacd/html/techdoc/html/02_2.htm). Accessed March 16, 2008.