Hiperuricemia

atunci cnd exist concentraii mari de acid uric n snge.

Concentraiile serice de acid uric >7mg/dL (n

mod normal, 2.4-6mg/dL la femei; 3.4-7mg/dL la

brbai)

La un astfel de nivel ridicat, acid uric tinde s

cristale agregate i forma.

Hiperuricemia primar: o eroare innascuta in metabolismul

purinelor i / sau excreiei de acid uric

Hiperuricemia secundar: o concentraie crescut de

Source: Rubin R, Strayer DS. 2007. Rubins Pathology:

Clinicopathologic Foundations of Medicine. 5th ed. USA: Lippincott
Williams & Wilkins; p 1142

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

rinichi ; 1/3 via tractul GI

Urat: forma protonat a acidului

uric

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%):

Exogen (diet bogat n purine)
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

Activitatea crescut a PRPP sintetazei

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

HGPRT (hipoxantin guanin fosforibozil transferaza)

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)

Source: http://seqcore.brcf.med.umich.edu/mcb500/nucsyl/nucmetab.html

IMP

Reducerea excreiei de acid uric (90%):

Cele mai multe cauze de

hiperuricemie
Normal:

98 - 100% a acidului uric se

resoarbe n regiunea proximal a
tubului contort

50% din cantitatea iniial este

secretat n poriunea distale a
tubului contort proximal, dar
ulterior se resoarbe 40 - 44% i
6 - 12% din filtratul glomerular n
cele din urm excretat

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

Transportorii de acid uric :

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 fructozo1 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

ribozo-5-fosfate + ATP ------------------------------ PRPP + AMP

Gut
Litiaz renal
Sindromul Lesch-Nyhan
Source: http://en.wikipedia.org/wiki/Gout

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.

Diagnosticul este

confirmat de evidenierea
de cristale de acid uric n
lichidul sinovial cristalele
sunt sub form de ac
Source: http://www.nlm.nih.gov/medlineplus/ency/imagepages/1222.htm

Litiaza renal
O acumulare de acid uric

Simptomatologie
La nceput -asimptomatic
Durere, hematurie, polakiurie i febr
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

Este important a determina

cauza hiperuricemie,
pentru a o trata

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.

Source: Golan DE. 2007. Physiology of Purine

Metabolism. Principles of Pharmacology: The
Pathophysiologic Basis of Drug Therapy.
Therapy. 2nd Edition.
Lippincott Williams & Wilkins

Inhibitori de xantin oxidaz

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

Source: Golan DE. 2007. Physiology of Purine

Metabolism. Principles of Pharmacology: The
Pathophysiologic Basis of Drug Therapy.
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

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