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FUNCTIILE CELULELOR PROFESIONALE Sunt: CHEMOTACTISMUL, FAGOCITOZA si CITOTOXICITATEA OXIGEN DEPENDENTA Aceste functii se exercit nu! i " ni#e" tisu" r,$u% ce ceste ce"u"e u f&st tr se si cti# te !et '&"ic $e & serie $e !e$i t&ri s&"u'i"i e"i'er ti :$ifu( si in c ntit ti re$use in c&n$) fi(i&" s u "&c " si in c ntit ti crescute in c&n$) % t A)CHEMOTACTISMUL *e%re(int %r&%riet te fun$ !ent " ce"u"e"&r %r&inf" ! t&rii $e se $e%" s $e " ni#) %erete"ui # sc),un$e u re$ t,% n in centru" f&c ru"ui inf" ! t&r,$e%" s re ce se f ce strict $e+ "un,u" unui ,r $ient $e su'st) c-e!& tr ct nte ce tr ,, cti#e ( !et '&"ic si $irecti&ne ( $e%"s re ce")%r&inf" ! t&rii) In functie $e !&!entu" $e % ritue " su'st nte"&r c-e!& tr ct nte se c" sific in: .Subst.chemoatractante de linia I / & serie $e c&!%&nente "e c&!%"e!entu"ui cti# t:C0 1C2 3 n fi" t&xin . C2'1C41C5+ s !'" te intr+un c&!%"ex Tri!&"ecu" r '.Substante chemoatractante de linia aII-a / "euc&triene 3LT 67., PAF3f ct&ru" $e cti# re %" c-et r ., !e$i t&ri re(u"t ti $in cti# re c& ,u" rii38 "i8rein ,fi'rin&%e%ti$u" 0., $iferite cit&8ine3ce ! i %uternic este IL9., $iferiti c&!%usi re(u"t ti $in !et '&"is!u" ' cteri n3ex)FLM/f&r!i"+!eti"+"euci" %e%ti$u"., $iferite %e%ti$e re(u"t te $in $e,r $ re "&c " un&r %r&teine %r&%rii, "i%&%&"i( - ri$e De%" s re $irect ce"u"e"&r %r&inf" ! t&rii c tre centru" f&c ru"ui %resu%une : %r&cese si!u"t ne: e!itere $e %seu$&%&$e si cti# re 3in c $ru" cti# rii !et '&"ice ,ener "e ce"). c&ntr cti"it tii ctin&+!i&(inice cit&sc-e"etu"ui ce"u"e"&r f ,&cit re). ;.EMITE*EA DE PSEUDOPODE Are " ' ( %&"i!eri( re !&"ecu"e"&r $e ctin ,"&'u" r su' f&r! unui ,e" $e ctin 3 ctin fi" !ent& s .)Prin ce st se creste c&nc) %r&teic intr+& nu!it (&n ce"u" r ) Acest ,e" se # i!'i' cu % /< ii # creste %resine c&"&i$&s!&tic /<ii # creste #&"u+ !u"/<exercit re s%re !') ce") unei f&rte %r&%"usi#e ce st " ' ( e!iterii %seu$&%&$u"ui) F&r! re ,e"u"ui este c&ntr&" t $e in$uct&ri si in-i'it&ri: Profilina / %r&tein ' (ic cu "&c "i( re su'!') si cu ,reut te !&"ec) $e :=>$ , re %r&%riet te $e "e, , c %t , tr ns%&rt si $e ce$ !&n&!erii $e ctin " "&cusuri"e $e %&"i!eri( re situ te " ni#)su'!')Are & cti#it te cic"ic :este cti# c n$ se cti#e ( !et '&"ic, %e c "e PLC/<se %er!ite stfe" f&r! re ,e"u"ui)C n$ ce"u" este in re% &s %r&fi"in este in cti# ) Gelsolina / %r&tein ' (ic cu ,rut te !&"ec)$e 9=>$ ,cu "&c "i( re cit&%" s!) re efecte in#erse %r&fi"inei/<se &%une %&"i!) Actinei sif #&ri(e ( $e%&"i!) fi" !ente"&r $e? f&r! te, re cti#it te cic"ic in#ers %r&fi"inei ABP(actine binding protein) = %r&tein cu "&c "i( re su'!')ce se c&!%&rt c %uncte n&$ "e un$e se inser fi" !ente"e $e ctin f&r! te in t& te $irectii"e,inc t ,e"u" $e ctin este in fin " structur t c & rete 0D E!itere $e %seu$&%&$e este se! n t& re cu ur! t& re"e fen&!ene: .re%&(iti&n re rece%t&ri"&r !') %t) su'st nte"e c-e!& tr ct nte: c n$ ce") F&,&cit re #in in c&nt ct cu su'st)c-e!& tr ct nte se %r&$uce & !isc re $e tr ns" tie rece%t&ri"&r !'), cesti c&ncentr n$u+se in (&n !') ce #ine in c&nt ct cu surs $e f ct&ri c-e!& tr ct nti/fen&!en $e c&%%in,3se c&nstituie & c "&t $e rece%t&ri %t) f ct&rii c-e!& tr ct nti. +%er!ite c ce") f ,&cit r s sesi(e(e c&nc) extre! $e !ici $e f ct&ri c-e!& tr ct nt) C&ncentr ti $e rece%t&ri %e & nu!it (&n !') f ce c $u% fix re f ct&ri"&r c-e!& tr ct nti %e rece%t&rii res%ecti#i s se %r&$uc niste !&$ific ri c&nf&r! ti&n "e in str) cest&r rece%t&ri ce sunt trns!ise %rin se,!)"&r intr !') % n " PLC "&c " 3PLC $in (&n $i cent c "&tei $e rece%t&ri./<se cti#e ( & PLC "&c "i( t intr+un nu!it %unct %e !' $e cee ,e"u" $e ctin se # f&r! strict "&c "i( t ,in (&n !') ce #enit in c&nct ct cu ,r $ient $e f ct&ri c-e!& tr ct nti) '.fix re %seu$&%&$e"&r e!ise , $e $iferite structuri tri@tetr %e%ti$ice $in c&!%&(iti c&" ,enu"ui tisu" r+ %seu$&%&$e"e u %e !') "&r inte,rin ALA 7 %rin c re se fixe ( %e tri%e%ti$e c Ar,+G"B+As%,s u %e tetr %e%ti$e c Ar,+G"B+As%+Ser+ ce st fix re in structuri"e tisu" re s&ci t cu c&ntr cti"it te ctin&!i&(inic f ,&citu"ui f ce c %seu$&%&$u" s se , te succesi# /<f ,&citu" se $e%" se ( succesi# s%re c&nc) ! xi! f ct&ri"&r tr ct nti B)FAGOCITOZA Are 0 su'e %e: A. CAPTA*EA: Se c %te ( : ce"u"e strine 3' cterii,#irusuri., ce"u"e s&! tice%r&%rii "ter te structur "@functi&n ") Aceste sunt c %t te $e& rece f ,&citu" $etine rece%t&ri !') c re recun&sc si "e , & serie $e f ct&ri s&"u'ii" c re s+ u $e%&(it t %e $iferite % rticu"e Acesti f ct&ri s&"u'i"i $e%&(it tise nu!esc OPSONINE+ce"e ! i i!%&rt nte sunt: +Componentul C b: Se f&r!e ( si in c&n$itii n&r! "e ,$ r in c ntit ti re$use,%rin functi&n re c&ntinu c ii "terne c&!%"e!entu"ui Are c % cit te $e se fix %e $iferite !') ce"u" re $e& rece in str) "ui exist & ,ru% re ti&"+esteric e"ectr&n&fi" : ce st ,ru% re se " e, f& rte us&r $e ,ru% ri"e nuc"e&fi"e3c re ce$e ( e"ectr&ni.,r) NH : "e %r&t)!' ,r)OH "e str)

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,"uc !' Se "e , $e !') nu! i $ c ce"u" nu $etine !ec nis!e s u rece%t&ri c re s se &%un cestei "e, ri)Ce"u"e"e ' cteriene si #ir "e nu u se!ene !ec nis!ne)Ce"u"e"e s&! tice %re(int rece%t&ri ce se &%un fix rii C0') C n$ c "u" este "ter t cesti rece%t&ri:fie nu se sinteti( e( fie nu se ex%ri! " su%r f t !' fie %re(int n&! "ii) P rticu" res%ecti# este c %t t " su%r f t ce") f ,&citer %rin) inter!e$iu" C0' $e& rece re %rece%t&ri %t) cest 3C*0 si C*7 ce % rtin : inte,rine"&r.) +IgG: *ecun& ste si se "e , $e nu!ite structuri A,) %re(ente " su%r f t !') 6 cteriene @ #ir "e . *ecun& ste si se"e , $e nu!ite structuri A, "e !') unei ce" s&! tice ex%use $ t&rit "ter ri"&r ce"u" re structur "e@functi&n "e) Se "e , $e A, !') %rin se,!ente"e F ') C %t re %rticu"e"&r &%s&ni( te cu I,G " su%r f t ce" f ,&cit re se f ce cu ?ut&ru" unr rece%t&ri !') c re "e , fr ,!entu" Fc " I,G)Fix re % rticu"e"&r &%s&ni( te $e * !') %r&$uce !&$ific ri c&nf&r! ti&n "e ce se tr ns!it %rin se,) Intr !') " cestui *) % n " PLC/< cti# re f ,&citu"ui se f ce su%"ui!ent r si %e cest c "e) ) 6. ENDOCITA*EA PA*TICULELO* CAPTATE : Se re "i(e ( %rin !ici in# ,in ri "e !') ce in,"&'e ( % rticu"e"e c %t te, su' f&r! un&r #e(icu"e/FAGOZOMI M i !u"ti f ,&(&!i se unesc intr+& #e(icu" /ENDOZOM En$&(&!ii sunt initi " %eriferici, # ns n$ %r&,resi# ,in ti!%, c tre centru" cit) un$e #&r fu(i&n cu "i(&(&!ii/<ENDOLIZOZOMI *&"u" en$&(&!i"&r: ;. si,ur tr sn%&rtu" ! t) c %t t " su%r f t ce") % n " ni#) "i(&(&!i"&r ce c&ntin $if) en(i!e i!%"ic te in $i,estie :. si,ur & %re"ucr re nes%ecific si s" ' ! teri "u"ui c&ntinut1 cest %re"ucr re se $ t&re ( %H ci$ $in cit&%" s! f ,&citi"ui@en$&(&!u"ui1 %H ci$ re()$e& rece in c $ru" cti# rii !et '&"ice ,ener "e este sti!u" t ,"ic&"i( /< c) " ctic ce se cu!u"e ( ) O$ t cu fu(iune en$&(&!+"i(&(&! re "&c $e#ers re c&ntinutu"ui "i(&(&! " in en$&s&!/<et % III+ f ,&cit&(ei) C. P*ELUC*A*EA MATE*IALULUI ENDOCITAT En(i!e"e "i(&(&! "e,ce sunt c&ntinute in ,r nu"e"e %ri! re3 (ur&fi"e. "e f ,&cite"&r sunt cti# te nes%ecific $e %H+u" ci$ " en$&(&!i"&r . En(i!e"e %r&te&"itice scin$e ( $iferite "e,) Pr&teice) Hi$r&" (e"e ci$e scin$e ( $iferite "e,) %rin -i$r&"i( Micr&%er&xi$ (e"e $esc&!%un %er&xi(ii, Pr&teine"e c ti&nice u %r&%riet ti $e $eter,ent /< t c str) "i%i$ice "e ! teri ""ui en$&cit t) Li(&(i!u" re ctiune nti' cteri n ) F t $e ceste en(i!e !&n&cite"e si ! cr&f ,e"e %&se$ in "i(&(&!ii "&r: Nuc"e (e, G"ic&(i$ (e, Su"f t (e, F&sf t (e) Pre"ucr re en(i! tic ! teri "u"ui este s%ecific %e $iferite str)'i&c-) Ce") f ,&cit re $etin si ,r nu" tii secun$ re3ce nu sunt "i(&(&! "e. /$e%&(ite $e rece%t&ri3ex)ce%)%t)C*0siC*7. s u $e%)%t)un nu!it c&!%&nent " NADPH&xi$ (ei3c&!%)ce "c) cit)6:=2. En(i!e"e "i(&(&! "e $e# rs te in c ntit te suficient $e ! re c&n$uc " fect re ce"u"ei f ,&cit re/<"i( ei si e"i'er re cest&ir en(i!e in ext)/< % riti !icr&"e(iuni"&r str) in#ecin te 3te&retic.) Pr ctic in f&c r % r & serie $e %r&teinen(i!e ce se &%un cest&r en(i!e "i(&(&! "e:ex) nti%r&te (e ce '"&c-e( efecte"e en(i!e"&r %r&te&"itice ;+ ntitri%sin si :+! cr&,"&'u"in ?un, $in s n,e in f&c r $e& rece ici %er!e 'i"it te # sc)este f& rte crescut C) CITOTOXICITATEA OXIGEN DEPENDENTA Are " ' ( f&r! re $e c tre ce") f ,&cit re cti# te un&r r $ic "i "i' ri i O : ce c&ncur in !&$ nes%ecific " $e,r $ re intr ce") str) c-i!ice "e ! teri "u"ui f ,&cit t,ins in ce" s ti!% u "&c si scur,eri "e cest&r r $ic "i in fr ce") f ,&cit re ,inc t exist %&si'i"it te $e % ririe $e "ter ri tisu" re %rin cesti r $ic "i "i'eri)D r, " ni#) tisu" r ?un, $in circu" tie,%rin crestere %er!e 'i"it tii "&c ", & serie $e f ct&ri '"&c nti i r $) "i'eri $e O :3$e n t) en(i! tic ./<nu se %er!ite extin$ere "i(iunii) Cu%rin$e 0 !ec nis!e %rinci% "e: ;. cti# re NADPH+&xi$ (ei :. cti# re !ie"&%r&xi$ (ei 0.,ener re un&r r $ic "i "i' ri i O: si N:) ;.Acti!area "A#P$-o%ida&ei: / en(i! cu "&c "i( re !')3" ni#e"u" !') ce") $ r si " ni#e"u" !')en$&te"i"e este "c $in 2 su'unit ti1in functie $e siture f t $e !') ceste se i!% rt in: +c&!%&nente !e!'r n re 3in nr) $e :. re%re(ent te $e su'unit te si su'unit te ,ce "c tuiesc cit)6:=2, su'unit te re & ,reut te $e :;>$ , su'unit te re & r,eut te $e C;>$ si %re(int : situsuri $e "e, re: un %t) FAD un %t) NADPH: + c&!%&nente su'!e!'r n re 3in nr) $e 0. GP) 45 ce se t se ( $e su'unit te GP)75 ce se t se ( $e su'unit te *AC 3c&!%&nent s&ci ti# r s%unsu"ui. T& te ceste c&!%&nente sunt se% r te c n$ ce" f ,&cit r este in re% &s1c n$ e este se cti#e ( %e c "e PLC cest en(i! cti#e ( t& te ceste su'c&!%&nenete ce se # r s !'" re "i( n$ c&!%"exu" en(i! tic/NADPH+&xi$ ( Pri!e"e c&!%&nenete ce se se!'" e( sunt ce"e !e!'r n re: su'unit ti"e si sunt $e%&(it te,in re% &s, in ,r nu" tii"e secun$ re 1&$ t cti# t PLC, ce st # cti# & %r&tein /ci'escin c re %rei su'unit ti"e si $in ,r nu" tii"e sec) Si "e tr ns%&rt si "e "e , %&i " ni#)!')1in ce" s ti!% PLC cti#e ( si ceste c&!%&nente ce se #&r s !'" " ni#)!') O$ t t cu s !'" re ce"&r 2 unit ti se cti#e ( situsuri"e % FAD si NADPH: "e su'unit tii /NADPH: re(u"t $in crestere cti#it tii ,"ic&"i(ei3$in suntu" %ent&(& f&sf ti"&r.: c n$ ce"u" este cti# creste si cti#it te !it&c&n$ri " 3cic"u" >re's./<$e " ni# " ntu"ui res%ir t&r !it&nc&n$ri " % r scur,eri $e e"ectr&ni c re sunt %re"u ti $e NADPH :

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fix t %e su'unit te , %&i sunt ce$ ti FAD+u"ui situ t t&t %e su'unit te , %&i tr nsfer ti su'unit tii /<tr nsf&r! re O: t&!ic ,ener n$u+se %ri!u" r $ic " "i'er / i&nu" su%er&xi$ , c re este extre! $e re cti# $e& rece re e"ectr&n nei!%erec-e t, cest cti#it te !et '&"ic f ,&citu"ui cu c&nsu! crescut $e &xi,en si %r&$ucere $e r $ic "i "i'eri se nu!este EXPLOZIE OXIDATIAA A FAGOCITULUI De " i&nu" su%er&xi$ se #&r e"i'er si "tii:HO+ ,H :O:,%er&xi(i,s) ) :. Acti!area mielopero%ida&ei' en(i! "i(&(&! " ce intr in ctiune &$ t cu # rs re c&ntinutu"ui "i(&(&! " in en$&(&!, $esc&!%une %er&xi(ii f&r! ti %e c "e NADPH+&xi$ (ei,in%re(ent C" + cu f&r! re un&r c&!%usi si ! i cit&t&xici si nu!e: c"&r !ine, c) -i%&c"&r&s3HOC". 0. Generarea unor radicali liberi ai ( ) si ") ' se refer " f&r! re r $ic "u"ui !&n&xi$ $e (&t3NO)., se f&r!e ( cu %rec $ere " ni#) Ce" en$&te"i "e %e c "e en(i!ei NO+sintet ( ce este sti!u" t "&c " $e & serie $e cit&8ine:IL;1TNF1"i%&%&"i( - ri$e"e ' cteriene, re %r&%riet ti # s&$i" t t& re "&c "e, inter#ine c r $) "i'er in $e,r $ re extr ce") A $iferite"&r % rticu"e, cu%" re O:+ cu NO)/<ONOO+3PE*OXINIT*IT.ce este !u"t ! i re cti#)) MEDIATORII SOLUBILI AI INFLAMATIEI Au c %r&%riet ti: tr , ce"u"e"e %r&inf" ! t&rii in f&c ru" inf" ! t&r,"e cti#e ( !et '&"ic, unii $intre ei u & seire $e efecte # scu" re: # s&$i" t tie@crestere %er!e 'i"it tii # scu" re u : c r ctere c&!une: sunt nes%ecifici si % r in # "uri succesi#e, in functie $e !&!entu" $e % ritie exist ur! t& re"e c te,&rii $e !e$) s&"u'i"i: !e$i t&ri $e "ini I/< re%re(ent ti $e:+ siste!u" c&!%"e!ent 3-ist !in siste!u" cti# rii $e c&nt ct : siste!u" c& ,u" (e"&r siste!u" 8inine"&r., !e$i t&ri $e "ini II+ /<re%re(ent ti $e & serie $e f ct&ri "i%i$ici 'i& cti#i: PAF, PG, LT, cit&8ine"e MEDIATO*I SOLU6ILI DE LINIA INTII

A) Sistemul c m!leme"t# c t&ti !e$i t&rii $e "inie intii,este %ref&r! t,nu! i c tre'uie cti# t %t) +si re "i( efecte"e 'i&"&,ice cti# re : se f ce in in c (u" un&r ,enti se%tici@ se%tici c u(e se%tice3' cterii, #irusuri.+sunt &%s&ni( te $e C0' si $e I,G) C0' c re &%s&ni( t ,este c % 'i" s cti# (e c&!%"e!entu" %e c "e "t ern ) I,G c re &%s&ni( t ,este c % 'i" s cti#e(e c&!%"e!entu" %e c "e c" sic 3%rin C;s. Prin cti# re c&!%"e!entu"ui se ?un,e " ei'er re un&r c&!%&nenete cti#e: C0 ,C2 + n fi" t&xine3 u efect c-e!&t ctic. + u efecte # s&$i" t t& re@cresc %re!e 'i"it te # sc) cti&ne ( %re$&!in nt in$irect $e& rece se fixe ( %e *) $e %e ! st&cite@' (&fi"e,%r&$uc n$ $e,r nu" re /< e"i'er re $e -ist !in ce e ins si re efecte # s&$i" t& re@%er!e 'i"i( t& re # sc) C2',C4,C5+ u efect %uternic c-e!& tr ct nt) C;s+ cti#e ( siste!u" $e c& ,u" re)C u(e se%tice 3f ct&ri !ec nici,c-i!ici,r $i tii. + se ?un, " "e(iuni ce"u" re, ce"u"e"e "ter te sunt &%s&ni( te $e C0' %e c "e "tern $e I,G+ c "e c" sic n fi" t&xine B)Hist$mi"$# este $e se!ene %ref&r! t , este $e%&(it t in ,r nu" tii"e ! st&cite"&r@' (&fi"e"&r1$e,r nu" re cest&r se %& te f ce su' ctiune un&r: f ct&ri s%ecifici:+ n fi" t&xine"e C0 si C2 : fix re I,G %e *) $e %e ! st&cite@' (&fi"e, H*F3-ist !in re"e sin, f ct&r. e"i'er t, $in "i!f&cite"e@! cr&f ,e"e cti# te, IL01IL2 e"i'er te $in "i!f&cite"e cti# te su'st nt P/neur&tr s!it t&r ce se , seste in ter!) ner#& se %eric %i" re, f ct&ri nes%ecifici: !ec nici, ter!ici, r $i tii, c-inici, Are 0 c te,&rii $e %r&%riet ti : a) Proprietati proinflamatorii(proflagistic)' %r&#&c n$ # s&$i" t tie "&c " $eter!in sc $ere f"uxu"ui s n,#in in c %i" ru" res%ecti#/<%er!ite "euc&cite"&r circu" nte s $ere ! i !u"t/< recrut re ! i ! re $e "euc&cite in f&c r ,cu t& te efecte"e "&r) Se re "i(e ( %rin *) $e ti% H; si H: $e%e ce") nuscu" re nete$e ce se #&r re" x stfe" $e& rece e sti!) $esc rc re $e su'st) P $in TN %eri# sc "&c "e, c re " r n$u" ei %r&$uce $e,r nu" re "t&r ! st&cite cu & n&u e"i'er re $e -ist !in b)Proprietatea de a regla anumita !erigi din rectia inflamatoare : cerste %er!e 'i"it te # sc)D%rin %ece%t&ri H: $e %e ce")en$&te"i "e/< c&ntr cti "&r/<$esc-i$ere ?&nctiuni"&r $intre e"e/< %rin ceste trec $in sin,e in interstitiu & serie $e %r&teine/<creste %resinue c&"&i$&s!&tic in interstitiu/< tr ,ere $e % $in # s in interstitiu/<e$e!u" inf" ! t&r) Efecte:$i"utie % rticu"e"&r $in f&c ru" inf" ! t&r $e $e#in stfe" ! i us&r c %t 'i"e %e su%r f t f ,&cite"&r %er!ite intr re retr&,r $ un&r su'st nte ntiinf" ! t&rii) Sti!u"e ( neutr&fi"e"e +++ %rin inter!e$iu" *) H; $e %e neutr&fi"e /<-ist !in "e sti!u"e ( neutr&fi"e"&r c-e!&t ctis!u", cit&t&xicit te , ex%resi $e * )%t f ct&rii c-e!&t ctici, %r&$ucti $e IL, sti!u"e ( e&(in&fi"e"e+++ %rin rece%rt&rii $e ti% H: $e %e ceste /<-ist !in "e sti!u"e ( e&(in&fi"e"&r: c-e!&t ctis!u", cit&t&xicit te , ex%resi %e su%r f t "&r *) %t c&!%"e!ent3ins%eci " *) %t) C0'. c) Proprietati anti inflamatorii(antiflagistice)' %rin sti!u" re *) $e ti% H: $e %e $iferite ce"u"e tunci c n$ c ntit te $e -ist !in este f& rte ! re 3rece%t&rii H: sunt ! i %utin sensi'i"i.) /<-ist !in : exercit efecte in-i'it&rii su%r ' (&fi"e"&r,

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sc $e c-e!&t ctis!u"@ cti# re !et '&"ic neutr&fi"e"&r, sti!u"e ( rece%t&rii H: si Li!)Ts %e c re "e cti#e ( re$uce r s%unsu" i!un s&ci t inf" ! tiei, in-i' cti#it te "i!) N>/<sc $e riscu" % ritiei un&r "e(iuni ce"u" re )i) ceste #&r

C) Sistemul $cti%$&ii 'e c "t$ct# cu%rin$e 7 f ct&ri: f ct&ru" XII " c& ,u" rii,f ct&ru" XI " c& ,u" rii, %re8 "irein , HE>>3-e #B Fei,-t !&"ecu" r 8inin&,en. *) +actorul ,II' O !&"ecu" %r&teic f&r! t $intr+un sin,ur " nt %&"i%e%ti$ic, c re " n, c % tu" +COOH ter!in " %re(int & 'uc" $isu"fi$ic , " +NH: ter!in " %re(int & s c#ent $e " , re intens e"ectr&%&(iti# ,f&r! t $in: His), LBs),G"B)1%rin ce st sec#ent se t se ( $e $iferite str)e"ectr&ne, ti#e ,$e ex)c&" , nu" # scu" r ex%us c ur! re "e(iunii en$&te"i "e) Si!%" t s re F)XII " c&" ,en i" cti#e ( ,ins s" ')Acti# re s intens se re ")%rintr+& scin$ re " ntu"ui %&"i%e%ti$ic: fie in (&n %untii $isu"fi$ice/<fr ,!entu" F)XII , fie %rin scin$ re cestui " nt in f r %untii $isu"fi$ice /<fr ,!entu" F)XII) F)XII este ce" ! i %uternic cti# t&r " siste!u"ui $e c& ,u" re,!u"t ! i %uternic $ec t F)XII ) Scin$ re " ntu"ui %&"i%e%eti$ic in (&n "e,)S+S se re ")su' inf"uent 8 "icreinei s u %" s!inei) Scin$ re " ntu"ui in f r "e,) S+S se re ")su' ctiune c&!%&nentei C;s c ii c" sice c&!%"e!entu"ui) :. $-./ Este & ! "ecu" %r&teic sint ti( t $e fic t si c re se f" in circu" tie) L ntu" s u %&"i%e%ti$ic,unic, re f&r! $e 'uc" 1in (&ne"e s "e ter!in "e ce st 'uc" este su$ t %rin :+0 %unti S+S1in %&rtiune centr " re & s c#ent $e "e, re intens %&(iti# ,%rin c re se t se ( $e su%r f te ne, ti#e,$e ex) c&" ,enu" # sc ex%us in ur! "e(iunii en$&te"i "e) C n$ cest se t s e( sufer & !&$ific re c&nf&r! ti&n " ce %r&$uce $esc&%erire un&r situsuri: unu" %t)F XII si "tu" %t) 8 "icrein ACTIAA*EA SISTEMULUI ACTIAA*II DE CONTACT: Le(iune en$&te"i " /< t s re : HEM> /<" , FXI si %re8 "icrein /< t s re F)XII/< cti# re s s" ' ,$ r suficient %t) c s tr nsf&r!e %re8 "icrein ,fix t %e HEM>,in 8 "icrein c re u"teri&r # cti&n %e F)XII t s t,scin$ n$u+" in (&n %untii S+S/< fr ,!entu" F)XII 3!u"t ! i cti#.c re: # cti# F XI/< cti# re c sc $ei c& ,u" rii si # cti# "te !&"ecu"e $e %re8 "icrein /< !%"ific re fen&!enu"ui C&nsecinte"e cti# rii F)XII: ;.F&r! re " ni#e"u" "e(iunii en$&te"i "e un&r !icr&tr&!'usuri fi'rin&%" c-et re t&t " ni# "u" "e(iunii en$&te"i "e re "&c si & $er r @ ,re, re tr&!'&cit r "&c " %rin cti# re c& ,u" rii/<tr&!'in /<tr nsf&r! re fi'rin ,enu"ui in fi'rin !icr&tr&!'usuri"e t %ete ( "e(iunie" # scu" re $in f&c ru" inf" ! t&r/< stfe" se e#it s n,er re 1$e se!ene u r&"u" $e circu!scrie f&c ru" inf" ! t&r %rintr+&G ' rier H $e fi'rin /< stfe" se e#it extin$ere %r&cesu"ui inf" ! t&r) :.F&r! re un&r %r&$usi inter!e$i ri %e c "e c& ,u" rii 3f&r! re tr&!'inei, fi'rin&%e%ti$u"ui 6.1 cesti u efecte c-e!& tr cti#e : sti!u"e ( x%ri! re %e S) ce"u"e"&r en$&t) A se"ectine"&r P /<sti!u"e ( $er re "e&c&cite"&r " en$&te"iu sti!u"e ( ," ni#) ce") en$&t), %r&$ucti $e: PG)I:3%r&st cic"in .+ re efecte # s&$i" t t&rii, creste %er!e 'i"it te # scu" r , %e tr!'&cite re efect nti ,re, nt3se &%une ctiunii TX A: e"i'er t $in %" c-ete,ce re ctiune %r& ,re , nt si # s&c&nstirct&rie.) Ec-i"i'ru" PG)I:@TX A: %re#ine % riti tr&!'&(e"&r3este us&r $e%" s t in f #& re TX A:. PDGF cu r&" in fen $e re% r re tisu" r 0.Inter#enti s in initiere cti# rii siste!u"ui c&!%"e!ent %e c "e c "sic 3 cti#e ( C;s. Efecte"e 8 "icreinei: Are %r&%riet te $e scin$ " ntu" %&"i%e%ti$ic " HEM> si stfe" ce"e : fr ,!ente r ! se c % t c % cit te crescut $e "e, re %re8 "icreinei si F)XII) Acti&ne ( su%r 'r $i8inin&,enu"ui %"s! tic, %e c re i" tr nsf&r! "&c " in 'r $i8inin c re re c efecte: # s&$i" t tie, crestere %er! e'i"it tii # sc) "&c "e sti!u" re "&c " ter!in tii"&r ner#& se %t) $urere) P& te scin$ nes%ecific c&!%&nent C2 c&!%"e!entu"ui/<creste stfe" %r&$ucti $e C2 si C2' MEDIATO*I SOLU6ILI DE LINIA II

Princi% "ii re%re(ent nti sunt "i%i$e"e 'i&"&,ic cti#e re%re(ent te $e: PAF %r&st ," n$e "euc&triene)Aceste su'st nte ! i sunt $enu!ite si ut c&i(i 3 ut& !%"ific ti&n ce"" eic&s&n&i(i. PA+' Este e"i'er t ! i "es $in ce"u"e"e en$&te"i "e cti# te su' ctiune IL;,TNF si "t&r cit&8ine si $e se!ene $in f ,&cite"e cti# te in f&c ru" inf" ! t&r) Are i!%) efecte %r&inf" ! t&rii: efecte %uternice -i%er%er!e 'i"i( t& re # scu" re 3este $e ;== x ! i %uternic $ec t -ist !in ., sti!u"e ( " ni#)neutr&fi"e"&r si e&(ine"&r ce"e 0 functii ! ?&re3c-e!&t ctis!u",f ,&cit&( si cit&txicit te &xi,en $e%en$ent . re si c % cit te $e sti!u" $%$# !et '&"ic "euc&cite"e si $e cti# , tr&!'&cite"e $er te " "&cu" "e(iunii en$&te"i "e

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P0(S1AG2A"#I"323 SI 234C(10I"323(3IC(SA"(I5II P0(P0I4-5ISI.:Sunt sinteti( ti in f& rte !u"te ti%uri $e ce"u"e: "i!f&cite, ! st&cite, ce")en$&te"i "e, fi'r&'" sti) Met '&"is!u" "&r este si %"urice"u" r $ r si tr nce"u" r/une"e ce") c re nu u c % cit te $e sisnteti( nu!itic&!%usi inter!e$i ri neces ri sint) PG) si LT), ii c %te ( $e " "te ce"u"e si ii !et '&"i(e ( in "ti c&!%usi ,%e c re nici un $in ce"e : ti%uri $e ce"u"e nu "+ r fi %utut sinteti( $e un sin,ur ) In ,ener " t t %e c "e PG)c t si %e c "e LT) se %&rneste $e " un %recurs&r c&!un/ c) r -i$&nic O$ t cu cti# sre $if rite"&r ti%uri $e ce"u"e,este sti!u" t si en(i! PL+A:1 ces t $es%rin$e $in PL !e!'r n re cest c),r s %&"ines tur t) De " e", in %re(ent : . cic"&&xi,en (ei/<PG)G: $in c re se f&r!e ( %&i PG)H:/<se f&r!) %&i PG)A:1 PG)E:1 PG)D1 PG)F:1 TX A:3nu! i in tr&!'&cite ,in%re(ent tr&'&x&nsintet (ei.1PG I:3nu! i in ce") en$&te"i " in %re(ent %r&st cic"insint t (e.) PG )F::+ re ctiune # s&c&nstrict& re, ctiune c re ins nu se f ce resi!tit $ t&rit %re%&n$erentei $e f ct&ri # s&$i" t t&ri) '. "i%&&xi,en (ei/<2HPETE/<2HETE LT)A7 LT)67 +%uternic efect c-e!&t ctic +in-i' % rti "," ni#)ce")en$&t) f&r! re PG)I:/<in c&n$itii"e inf" ! tiei ec-i"i'ru" PG)I:@TX) A: este $e%" s t in f #& re TX A:/< f&r! re !icr&tr&'usuri"&r ce t %ete( en$&te"iu" "e( t LT)C7 !estecu" "&r f&r!)S*SA LT)D7 3s"&F re cti#e su'st nce &f LT)E7 n fi" xis. cu n fi" t&xine"e C0 si C2 %r&#& c $e,r nu" + re ! st&cite"&r si fi"e"&r "&c "e /< e"i' r re $e -ist !in

2HETE este %re"u t De "te ce"u"e si %re"ucr t " 2,;:+HETE si " ;:,:=+HETE, ce u %r&%riet ti si!i" re LT) ,$ r !u"t ! i s" 'e) MEDIATO*I DE LINIA III+

Sunt re%re(ent ti $e CITO>INE : IL.(:+este e"i'er t ! i "es $in "i!f&cite"e cti# te,$ r si $in ! cr&f ,e"e cti# te)Efecte: # s&$i" t t&rii+exercit te ! i "es in$irect, %rin sti!u" re en$&te"i " $e PG)I:,si ! i %utin $irect, c-e!&t ctice i!%&rt nte, sti!u"e ( $er re "euc&cite"&r " en$&te"iu" # sc) $e& rece sti!u"e ( , ex%ri! re se"ectine"&r E, inter#in in sti!u" re ex%ri! rii inte,rine"&r@ICAM+uri"&r, in-i' ex%resi %e ce") en$&te"i "e tr&!'&!&$u"inei3/*) " ce")en$&t, ce inter#ine in re," re c ,u" rii,&%un n $u+se c& ,u" rii intense, # n$ c % cit te $e " , tr&!'in si $e & in cti# .si %rin ce st f #&ri( n$ f&r! re "&c " $e !icr&tr&!'usuri, sti!u"e ( %r&$ucti $e c tre ce")en$&te"i "e f ct&ru"ui #&nEi""e'r n$, sti!u"e ( %r&$)$e PAF, in circu" tie cti&ne ( su%r centru"ui -i%&t " !ic " ter!&re," rii $ec" ns n$ re cti fe'ri" , inter#ine in re% r ti tisu" r in f&c r $e& r ce re %r&%riet ter $e tr ,e si cti# in f&c r fi'r&'" stii TNF: + este e"i'er t t t $e "i!f&cite"e cti# te c t si $e ! cr&f ,e)Efecte: c-e!&t ctice, sti!u"e ( $er re "euc&cite"&r " en$&te"iu" # sc) $e& rece sti!u"e ( ex%ri! re $e se"ectine,inte,rine,ICAM+uri, cti#e ( ce"e 0 functii ! ?&re "e f ,&cite"&r si ! i "es cit&t&xicit te &xi,en $e%en$ent c si IL I, inter#ine in re%er ti tisu" r in$irect $e& r ce tr ,e si cti#e ( "&c " fi'r&'" stii IL )III: +este e"i'er t ! i "es $e ce"u"e"e en$&te"i "e sti!u" te %rin IL I si TNF) Are i!%&rt nte efecte c-e!&t ctice si cti# t& re ,! i "es %t) Neutr&fi"e) Inter#ine si in sti!u" re ex%resiei $e inte,rine IL )I: +este e"i'er t ! i "es $in: "i!f&cite"e T-, ce")en$&te"i "e, fi'r&'" stii cti# ti, f ,&cite cti# te 3in ! sur ! i !ic . Princi% " ctiune/&$ t ?uns in circu" tie sti!u"e ( " ni#) -e% tic sinte( %r&teine"&r re cti#e $e f ( cut 3cu r&" ntiinf" ! t&r.$e ex) fi'rin&,enu"1 ntritri%sine"e) Sti!u"e ( si xu" -i%&t " !&+-i%&fi(&+suIr ren "i n /<creste %r&$ucti $e ,"uc&c&rtic&i(i/H) cu efecte ntiinf" ! t&rii $e& rece st 'i"i(e ( !' "i(&(&! "e,i!%ie$ic n$ stfe" $e,r nu" re ' (&fi"e"&r si ! st&cite"&r si c&nsecuti#, e"i'er re $e -iste!in )

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REPARATIA TISULARA Are 0 et %e ,in$iferent $e n t)tesutu"ui: ETAPA DE FI6*OPLAZIE, ANGIOGENEZA, ETAPA DE *EMODELA*E CICAT*ICIALA () ETAPA DE FIBROPLAZIE: se re ") su' ctiune fi'r&'" sti"&r, in c&n$itii n&r! "e fi'r&'" stii inter#in in %er! nentu" turn+&#er " tes)c&n?)$in ! tri ce extre ce"u" r %rin : %r&cese : + recun&sc si $e,r $e ( tes) C&n?)i!' tr nit,cu ?ut&ru" en(i!e"&r %r&te&"itice + sinteti(e ( t t c&!%&nent !&rf tes) C&n?),c t si %e ce fi'ri" r 3f') $e c&" ,en,reticu"in ,e"stin . In c&n$itii % t&"&,ice fi'r&'" stii u r&"u" $e rec&nstrui ! trice extr ce"u" r , %uternic fect t $e ctiune ,)eti&"&,ic se $esf s& r in 0 f (e: ;.!i,r re fi'r&'" sti"&r $in rii"e tisu" re # cine, s n t& se in centru" f&c ru"ui: se $esf s& r intr+un cic"u ,%rin ce"e si !ec nis!e c si ce"e $e !i,r re "e f ,&cite"&r 3e!itere $e %seu$&%&$e@fix re %se$&%&$e"&r $e tri si tetr %e%ti$e"e $in str)tes)c&n?,si nu!e:Ar,+As%+G"B 1Ar,+As%+G"B+Ser fix re %seu$&%&$e"&r se f ce %rin inter!e$iu" rece%t&ri"&r ALA7,%re(enti si %e !')fi'r&'" ste"&r. :. cti# re c&!%"et si %r&"ifer re cest&r fi'r&'" sti 0.sint ( c&!%&nenetei !&rfe si fi'ri" re "e tes) C&n?uncti#) Fi'r&'" stii sunt tr si si cti# ti % rti " t t $e f ct&ri nes%ecifici 3fr ,!ente $en tur te $e tes) C&n?uncti# $in f&c r.,$ r si $e f ct&ri s%ecifici, c IL;,TNF s u FGF3fi'r&'" stic ,r&Ftf ct&r+e"i'er t $e ! cr&f ,e.,PDGF 3e"i' r t $e ce") en$&te"i "e.) P % n " ! r,ine f&c ru"ui inf" ! t&r, fi'r&'" ste"e !i,re ( us&r $ t&rit existentei $e tesut c&n?uncti# n&r! ", ce &fer ,$in 'un$ent situsuri $e , t re %t)%seu$&%&$e) In f&c r, un$e tes) C&n? este fr ,!ent t,$is%ers t $ t&rit e$e!u"ui inf" ! t&r,nu ! i exist su%&rt $e !i,r re c&res%un( t& re /<fi'r&'" stii se #&r &%ri " ! r,ine f&c ru"ui,un$e su' ctiune f ct&ri"&r !ent&in ti se cti#e ( !et '&"ic ! i %uternic /<ince% s %r&$uc & ! trice / ! trice $e !i,r re,cu c re se inc&?& r 3este un ru$i!ent $e tes)c&n?)ce &fer su%&rt $e fix re. /<#&r !i,r %e ce st ! trice,% n " ! r,ine ei,un$e ne! i # n$ su%&rt $e fix re ,#&r e" '&r $in n&u & ! trice $e !i,r re,s) )!)$) % n ?un, in centru" f&c ru"ui O$ t ?unse in centru" f&c ru"ui,su' ctiune TGF 3tr nsf&r!in, ,r&Ft- f ct&r . isi $e,initi#e ( cti#it te si ince%e s secrete c&" ,enu /<ince%e ! tur re ! tricei $e !i,r re,ce se $esf&s& r in sens in#ers 3$e " centru s%re %eriferie.) L ince%ut c&" ,enu" n&u f&r! t este # scu" r / tesut $e ,r nu" tie i! tur) F&r! re c&" ,enu"ui ! i este f #) De f %tu" c in f&c r u f&ct in cti# te en(i!e"e %r&te&"itice,%r&#enite $in "i(&(&!i,%rin nti%r&te (e) D c c&" ,enu" se sinteti(e ( in c ntit te < $ec t este neces r /< fi'r&( (&nei res%ecti#e Acest "ucru este i!%ie$ic t, $e& rece $in fi'r&'" stii cti# ti se e"i'ere ( !ici c ntit ti $e c&" ,en ( ce in-i' e"i' r re $e TGF) *)ANGIOGENEZA: Presu%une & ne&# scu" ri( tie in f&c r) Tesutu" c&n?uncti# n&u f&r! t c % t # se / tesut $e ,r nu" tie ! tur)Ne&# sc)%&rneste$e " ni#) Ce") en$&te"i "e in$e!n ,#ecine f&c ru"ui)Aceste sunt cti# te !et '&"ic su' ctiune un&r cit&8ine 3IL ;,TNF .,$ r si su' ctiune un&r GF 3TGF ,AEGF+# scu" r en$&te"i " ,r&Ft- f ct&r .) Prin cti# re ceste unce% s %r&$uc %r&c&" ,en ( ,ce cti&ne ( su%r %" s!in&,enu"ui,tr nsf&r! n$u+" "&c " in %" s!in , c re " r n$u" ei tr nsf&r! %&rc " ,en ( in c " ,en ( cti# , c re "i(e ( !')' ( " c %i" ri"ui, cu f&r! re un&r !ici fenestr tii %rin c re ce") en$&te"i "e e!it %seu$&%&$e s%re tesut) Ce"u"e"e en$&t) cti# te sunt tr se c tre f&c r,e"e !i,r n$ su' ctiune GF+"&r 3FGF,PD+ECGF %" Juet $eri#e$ en$&te"i " ,r&Ft- f ct&r.,%rin e!itere $e %seu$&%&$e si fix re "&r %e situsuri"e c&res%un( t& re $e %e tes) N&u f&r! t /< c&r$& ne $e ce"u"e en$&te"i "e c re c&n#er, c tre centru" f&c ru"ui1u"teri&r ceste c&r$& ne se tr nsf&r! in str) tu'u" re %rin : %r&cese: # cu&"i( re ce"u"e"&r en$&te"i "e %&%t&( ce") en$&te"i "e $in centru" cest&r c&r$& ne) +)REMODELAREA CICATRICIALA# O$ t cu cti# re c&!%"et fi'r&'" sti"&r ce u in# $ t f&c ru", cesti $e#in ! i su'tiri,! i efi" ti, "e sc $e *E si %)G&",i,in sc-i!' "e creste sinte( $e ctin si !i&(in /<se tr nsf&r! in !i&fi'r&'" sti Mi&fi'r&'" stii cti#i u c % cit te c&ntr cti" /<c&ntr cti "&r $et) C&ntr cti tes)c&n? n&u f&r! t ,$e c re sunt fix ti /< stfe" r n se inc-i$e tre%t t si stfe" #in$ec re /$ensit te tesutu"ui re% r t se %r&%ie $e $ensit te n&r! " ) ETAPE SUPLIMENTA*E: PT) TESUTU*ILE CU ST*AT EPITELIAL: Et % $e ref cere e%ite"i " +ce") e%ite"i " " ( t e"i'ere ( EGF ce sti!u"e ( si cti#e ( ce") e%ite"i "e #ecine ,ce ince% s %r&"ifere(e) *EFACE*EA CEL)SOMATICE SPECIFICE UNUI TESUT: *ef cere % renc-i!u"ui -e% tic+%rin e"i' r re HGF ce cti#e ( -e% t&cite"e #ecine /< %r&"ifer re /< re,ener re) FIZIOPATOLOGIA INFLEMATIEI

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INFLAMATIA e & re ctie tisu" r $e % r re nes%ecific , cu c r cter "&c ", $ r cu % rtici% re intre,u"ui &r, nis!) / n s !'"u $e !&$ific ri # scu" re, ce"u" re, u!&r "e ce u c sc&% : In" tur re efecte"&r ne, ti#e %r&$use $e $iferiti ,enti ce u % truns in tesut si #in$ec re "e(iuni"&r) In re cti inf" ! t&rie se $ec" nse ( si re ctie $e -e!&st ( $ r si in#ers /<*EACTIE 6IDI*ECTIONALA) *e cti $e % r re: in %ri! f ( "i!ite ( efecte"e, in ""+ f ( inter#ine in fen&!enu" $e re% r tie, este in %erfect $ %ti'i"it te in r %&rt cu intin$ere si se#erit te "e(iunii este in %erfect $ %t 'i"it te c "it ti# si c ntit ti# ) Exist si exce%tii: rr)inf" ! t&rii c re ins&tesc fen&!ene"e ut&i!!une)*e cti inf" ! t&rie: re: c r cter "&c " %t) c se $esf s& r cu intensit te ! x " "&cu" $e % trun$ere " ,entu"ui /<e"i!in re efecte"&r n&ci#e " %& rt $e intr re este nes%ecific %t) c re ce"e si et %e in$ifferent $e n tur ,entu"ui) A,entii eti&"&,ici:6i&"&,ici + ' cterii, #irusuri, fun,i /< inf" ! tie $e n tur se%tic , Fi(ici K !ec nici /< !icr&L! cr&)tr u! tis!e + Ec "&ric s u + * $i tii K i&ni( nte @ nei&ni( nte, C-i!ici+ex&,eni: ci(i L ' (e %uternice, +en$&,eni: ci(i 'i"i ri) In$iferent $e ,),t&%&,r fi este i$entic ":+in centru necr&( +" %eriferie i!%&rt nte "ter ri functi&n "e ce"u" re) Exist si inf" ! tie f r "e(iuni tisu" re ex)re cti "er,ic ETAPELE DE DESFASU*A*E ALE *)INFLAMATO*II # et % # scu" r , et % ce"u" r , et % $e re% r tie tisu" r 1 ETAPA )ASCULARA: Se c r ct) Printr+un f"ux ! si# $e ce""u"e %r&inf" ! t&rii " ni#) %erete"ui # sc) $in ri tisu" r fect t : neutr&fi"e, !&n&cite, ! cr&f ,e, e&(in&fi"e 3%rici% "e"e ce") %r&inf" ! t&rii.) *ecrut re cest&r " ni#) %erete"ui # sc) se re "i(e ( su' ctiune un&r !e$i t&ri s&"u'i"i e"i'er ti $in ce"u"e"e f&c ru"ui inf" ! t&r) cesti !e$i t&ri s&"u'i"i u c %r&%riet ti: tr , ce") s ,#ine %r&inf" ! t&rii si "e cti#e ( !et '&"ic, efecte # scu" re "&c "e:+# s&$i" t tie,+crestere %er!e 'i"it tii # sc), in$uc ex%resi un&r rece%t&ri $e $e(iune t t %e su%r f t ce")%r&inf" ! t&rii c t si %e ce"&r en$&te"i "e/<ce"u"e"e %r&inf" ! t&rii #&r $er "&c " ETAPA CELULARA # Cu%rin$e cti#it te !et '&"ic ce")%r&inf" ! t&rii $er te " en$&t) # scu" r si sti!u" re functii"&r cest&r ce")%r&inf" ! t&rii: c-e!&c-ine(ie / cti#it te ce"u"e"&r $e !i,r $in # s+<centru" f&c ru"ui inf" ! t&r, sti!u" re %r&cesu"ui $e f ,&cit&( , cit&t xicit te &xi,en $e%en$ent ) T& te ceste #i(e ( s n re f&c ru"ui inf" ! t&r ETAPA DE REPARATIE TISULARA Cu%rin$e: et % $e fi'r&%" (ie/ref cere "&c " ! tricei extr ce", et % $e n,i&,ene( /ref cere "&c " str) # sc)"e( te, ref cere ,in functie $e tesutu" fect t, str)e%i"e"i " 3$i,esti# res%ir t&r,intestin ",te,u!ent. s u str)ce"u" re %r&%rii unui nu!it tesut 3-e% t&cite"e., %r&cesu" $e re!&$e" re tisu" r 3re!&$e" re cic trici " . CLASIFICA*EA CELULELO* P*OINFLAMATO*II: A)C32423 P0(+3SI("A23 P0(I"+2A.A1(0II : *e%re(ent te $e :neutr&fi"e, !&n&cite+! cr&f ,e, e&(in&fi"e) Sunt $&t te cu :c % cit te $e f ,&cit&( , cit&t&xicit te &xi,en $e%en$ent ) Functii"e "&r sunt %erfect ut&n&!e $ r, cti#it te "&r $e%in$e si $e % rtici% re un&r ce") cu r&" cces&r:ce")en$&te"i "e, tr&!'&cite, ! st&cite, ' (&fi"e 6)C32423 P0(+3SI("A23 C3 I"1306I" I" 03PA0A1IA 1IS42A0A : Fi'r&'" sti 3Inter#in in ref cere ! tricei extr ce"). Ce") En$&te"i "e 3inter#in in n,i&,ene( . Ce") E%ite"i "e 3inter#in in ref cere srt) e%ite"i "e. Functii"e cest&r $e%) $e 'un functi&n re ce")%r&fesi&n "e %r&in f" ! t&rii /< re% r ti tisu" r este $e%) De c "it te ce"u"e"&r %r&fesi&n "e %r&inf" ! t&rii)

SECTOA*ELE DE DIST*I6UTIE A CELULELO* P*OFESIONALE P*OINFLAMATO*II : A)SECTORUL MEDULAR + %t)seri neutr&fi"e"&r si !&n&cit r ) Cu%rin$e: c&!% rti!entu" $e $iferentiere, c&!% rti!entu" $e ! tur re, c&!% rti!entu" $e !u"ti%"ic re) In $iferentiere ce" ste! %"uri%&tente 3c % $e "inie. %t) neutr&fi"e un r&" i!%&rt nt re#ine nu!it&r cit&8ine, secret te $e ! cr&f ,e,"i!f&cite: IL); ,IL0 ,IL4 si G+CSF 3f ct&ru" sti!u" nt " c&"&nii"&r $e ,r nu "&cite. Aceste cit&8ine se e"i'ere ( in tesuturi :" un ni#e" ' ( "+in c&n$ fi(i&"&,ice si in c ntit ti crescute+in c&n$itii"e existentei unui f&c r inf" ! t&r, c re #&r !%"ific %r&$ucti !e$u" r $e neutr&fi"e si $e !&n&cite) Neutr&fi"e"e % r sesc ! $u# c&!%"et ! tur te,in ti!% ce ! tu r re !&n&cite"&r se $efiniti#e ( in tesuturi &$ t cu tr nsf&r! re "&r in ! cr&f ,e) B)SECTORUL CIRCULANT Cu%rin$e: c&!% rti!entu" xi "+ce"u"e"e situte in !i?"&cu" t&rentu"ui circu" t&r c&!% rti!entu" ! r,in "+ce"u"e"e ce $er " en$&te"iu" # scu" r / ! r,in tie "euc&cit r 3%r&cess $e $e(iune !e$i t %rin rece%t&ri.

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Ce" ! i i!%&rt nt este c&!% rti!entu" ! r,in ") A$er re "euc&cite"&r " en$&te"iu" # scu" r se $esf s& r in 0 et %e: et % $er rii re#ersi'i"e, et % $er rii ire#ersi'i"e, et % ce"u"e"&r %e c "e $e $i %e$e( *) 31APA A#30A0II 03630SIBI23 = 0(22I"G 234C(CI1A0 C&nst in st 'i"ire un&r c&nt cte %er! nente !&'i"e si " x intre "euc&cite"e ! r,in "e si en$&te"iu" # scu" r Este un %r&cess % si# "euc&cite"e fiin$ ntren te $e f&rt t&rentu"ui s n,#in Afecte ( t& t su%r f t ent&te"i " Are "&c si in c&n$itii $e n&r! "it te *e "i( re cest&r c&nt cte se f ce %rin rece%t&ri $e $e(iune / se"ectine *&"uri:;)%rin $er re "uec&cite"&r si,ur & su%r #e,-ere c&ntinu tesuturi"&r %t e#entu " $e%ist re unui f&c r inf" ! t&r :)%rin $er re " en$&te"iu,"euc&cite"e se %&t cti# !et '&"ic,%rin $ifu(iune !e$i t&ri"&r s&"u'i"i,e"i'er ti " un ni#e" ' ( " in c&n$)n&r! "e, res%ecti#e " un ni#e" ri$ic t in c&n$itii"e existentei f&c ru"ui inf" ! t&r) )) 31APA A#30A0II I03630SIBI23 Presu%une st 'i"ire un&r "e, turi !u"t n i str nse intre "euc&cite"e $er te si en$&te"iu c re se re "i(e ( %rin nu!iti rece%t&ri $e $e(iune c re se nu!esc INTEG*INE , %re(enti %e !') Leuc&cit r , si res%ecti#e & serie $e !&"ecu"e $e $e(iune %re(ente %e !') En$&te"i " / ICAM) ICAM % rtine su%erf !i"iei i!un&,"&'u"ine"&r /< rece%t&ri $e $e(iune cu str) se! n t& re I,) Acesti rece%t&ri $e $e(iune sunt %re(enti " ni#e"u" !e!'r n r t t in c n$itii n&r! "e3" un ni#e" ' ( ".,c t si in c (u" unui f&c r inf" ! t&r3in c ntit ti ri$ic te.) Este neces r c et % %re!er, t& re trecerii "euc&cite"&r in tesuturi,$e& rece ceste c % t stfe" unH%unct $e s%ri?inH) ) 31APA C324232(0 P3 CA23 #3 #IAP3#35A Presu%une & cti# re t&t " "euc&cite"&r $er te Din e"e se e"i'ere ( un f ct&r cu %r&%riet te $e sti!u" $esc-i$ere ?&nctiuni"&r interen$&te"i "e,%recu! si !ici c ntit ti $e c&" ,en ( ce "i(e ( % rti " !') ' ( " en$&te"iu"ui) RECEPTORI DE ADEZIUNE IMPLICATI IN ADERAREA RE)ERSIBILA SI IRE)ERSIBILA # a) receptori implicati in aderarea re!ersibila / SELECTINELE Sunt GP)tr ns!')ce %re(int 0 se,!ente: extr ce"u" r, tr ns!e!'r n r si intr ce"u" r Pt) st 'i"ire c&nt cte"&r este i!%&rt nt s,)extr ce")c re in c (u" se"ectine"&r este "c)$in 0 $&!enii 3$ins%re ext+<int.: D&!eniu" "ectinic ;. D&!eniu" EGF+"i8e :. D&!eniu" !ici"&r sec#ente ) re%etiti#e) Lectine"e recun&sc si st 'i"esc "e, turi cu str) ,"uci$ice ce intr in "c) un&r GP)%re(ente %e !') "t&r ce""u"e,GP) c re u ur! t& re"e % rticu" rit ti: sunt in "t ,"ic&(i" te si si "i te si u c&ntinut crescut $e Ser) si Tre) D t&rit cest&r % rticu" rit ti sunt $enu!ite SIALOMUCINE) E"e unt c&ntr "i, n(ii "ectine"&r) Selecti"$ L + %re(ent %e :neutr&fi"e,!&n&cite,"i!f&cite,etc) +$&!eniu" s u "ectinic se "e , $e nu!ite str) ,"uci$ice: G"B+ CAM;3%e ce"u" en$&te"i " ., "e, tur L+G"B+CAM; este res%&ns 'i" %t) %r&cesu" $e r&""in, "euc&cit r A!'e"e ti%uri $e rece%t&ri 3se"ectin L,res%ecti#e G"B+CAM;. sunt %re(ente in !&$ c&nstituti#e %e su%r fete"e !e!'r n re res%ecti#e) M Selecti"$ E + %re(ent %e !') ce") en$&te"i "e,$ r nu in !&$ c nstituti#, e se ex%ri! " su%r f t !') su' ctiune un&r nu!iti f ct&ri:IL,TMF 3tu!&r necr&sBs f ct&r., "i%&%r&teine ' ct) Are ! i !u"ti c&ntr "i, n(i %e su%r f t "euc&cit r : &"i,&( - ri$u" LEEIS, ES+L3"i, n$u" %t) se"ectin L., N+ ceti"+G " ceti" t ) Este rece%t&r intr ce"), $e%&(it t intr cit&%" s! tic in ,r nu"e"e EEI6EL+PALADE) C n$ se $esc rc cit&8ine"e ce") en$&t se $e,r nu"e ( /<se"ectin E este $us " su%r f t en$&te"i " ) S%re $e&se'ire $e se"ectin L,cei nter#ine in r&""in,, Se"ectin E este & sectin G$e " r! H) Secti"$ P + este %re(ent si %e su%r f t en$&te"i " , ex%resi ei se f ce su' ctiune un&r f ct&ri f&r! ti 3%" c-ete. s u e"i'er ti in c $ru" unui f&c r inf" ! t&r 3tr&!'in , -ist !in , 'r $i8inin , "euc&triene., c&ntr "i, n$u":PSGL3"i, n$ ,r nu" r %t se"ectin P. b) receptori implicati in aderarea ire!ersibila / INTEG*INE 3%e su%r f t "euc&cite"&r. / ICAM 3%e su%r f t en$&te"i " . Sunt rece%t&ri nec&nstituti#i) INTEG*INELE + %r&teine -eter&$i!erice,n&t te si , sunt # ri 'i"e c structur ," ntu" # n$ & & rec re c&nst nt /<c" sific re $u% " ntu" : ex);, :, 0 3i!%&rt nte %t) r) inf" ! t&rie . AA*IANTE DE :INTEG*INE: D c " ntu" : se s&ci ( cu :+ /<rece%t&ru" LFA;3A,) s&ci t functiei "euc&cit re.)C&ntr "i, n$u" s u este ICAM) D c " ntu" : se s&ci ( cu :+' /< rece%t&ru" C*03rece%t&r %t) c&!%"e!ent.)Are r&" in c %t re " su%r f t ce")f ,&cit re $iferite"&r % rticu"e ce ur!e ( fi f ,&cit te3&%s&ni( te nteri&r cu C0'.) D c " ntu" : se s&ci ( cu :+c /<rece%t&ru" C*7) AA*IANTE DE ; INTEG*INE: ALA7 3#erB " te A7. +functi&n " nu! i $u% cti# re c&!%"et ce"u"ei c&ntr "i, n$:!ici %e%ti$e 3tri,tetr . %re(ente in srtuct c&" ,enu"ui:Ar,+As%+G"B, Ar,+As%+G"B+Ser &$ t cti# t , ce")f ,&cit r e!ite %seu$&%&$e:" su%r f t !') % re ALA7 cu c re se , t $e 0+7 %e%ti$e $in str) C&" ,enu"ui /< stfe" # nse ( % n in f&c r /< un$e # f ,&cit )*OLU*I:in $e(iune ire#ersi'i" " en$&te"iu ce" f ,&cit re, in c %t re si f ,&cit re un&r % rticu"e, in "&c&!&ti ce" f ,&cit re C) SECTORUL TISULAR# Ne&tr&fi"e"e si !&n&cite"e % trun$ in tesuturi: s" ' si $ifu(, in c&n$itii fi(i&"&,ice,c n$ f ct&rii ttr ct nt se secret " un ni#e" ' ( " in c ntit ti ! ri si strict "&c "i( t,in c&n$itii $e existent unui f&c r inf" ! t&r)

C
*&"uri: recun& stere si in$e% rt re ce"u"e"&r !& rte, in" tur re tutur&r $etritusuri"&r existente, % rtici% re " %r&cesu" $e re% r tie tisu" r MECANISMUL GENE*AL DE ACTIAA*E A CELULELO* P*OFESIONALE P*OINFLAMATO*II Se re "i(e ( su' ctiune un&r f ct&ri / FACTO*I CHEMOAT*ACTANTI) Acesti sunt f&r! ti si e"i'er ti " ni#e" tisu" r:$ifu( in c&n$)n&r! "e intens " ni#)f&c ru"ui inf" ! t&r $iferite c&!%&nente "e c&!%"e!entu"ui: %e%ti$e N+f&r!i" te $e n tur ' cteri n , "i%&%&"i( - ri$e ' cteriene, une"e "euc&triene, une"e cit&8ine:IL;, IL9, TNF, %r&teine %r&%rii $en tur te, s) ) Pe su%r f t ce") $er te exist rece%t&ri s%ecifici %t) fiec re $in cesti f ct&ri tr ct nti , "c)$in:se,!)extr !'), se,!) tr ns!') se,!)intr ce") Fix re f ct&ri"&r c-e!& tr ct nti %e cesti rece%t&ri este ur! t $e & !&$ific re c&nf&r! ti&n " str) cest&r , !&$ific re ce se tr ns!ite %rin se,!) intr % n " !es ,eru" sec)/%r&tein G, c re se cti#e ( /< cti#e ( PL+C/<tr nsf&r! PIP : in DAG si IP0) 3+3C1323 #AG:+ cti#e ( P>C,c re f&sf&ri"e ( si cti#e ( & , ! " r, $e en(B!e "euc&cit re i!%"ic te in $i,esti c&ntinutu"ui f ,&cit t cti#e ( & serie $e %r&t&&nc&,ene res%&ns 'i"e $e sinte( $e cit&8ine/< !%"ific efectu" initi ", cti#e ( & GP) *es%&ns 'i" $e sti!u" re NADPH+,&xi$ (ei i!%"ic t in cit&t&xicit te &xi,en $e%en$ent 3+3C1323 IP :+sti!u"e ( e"i'er re $e C :L $in *E /< IC :LM %" s! /< cti#it te en(i! tic / MLC>3!B&sin+ "i8e c- in 8in se. /< cti# re %r&teinei/P*OFILINA ce st " ' ( %&"i!eri( rii !&"ec) $e ctin /<,e" $e ctin ,i!%"ic t in e!itere $e %seu$&%&$e, /<sti!u" re !i&(inei "euc&cit re/<sti!u" re c&ntr ctiei cti&n+!i&(inic cit&sc-e"etu"ui EFECTELE ACTIAA*II META6OLICE ALE CELULELO* FAGOCITA*E A. CHEMO>INEZIA / !i,r re $e " ni#e"u" %erete"ui # scu" r in f&c r 6. STIMULA*EA CAPACITATII DE FAGOCITOZA C. STIMULA*EA CITOTOXICITATII OXIGEN DEPENDENTE T& te ceste st u " ' ( %r&cesu"ui $e s n re f&c ru"ui inf" ! t&r) FIZIOPATOLOGIA HEMOSTAZEI He!&st ( fi(i&"&,ic 3s%&nt n . re%re(int !ec nis!u" $e % r re "&c " $ec" ns t $e %r&$ucere unei "e(iuni # scu" re ce i!%iete ( inte,rit te si c&ntinuit te %erete"ui # su"ui si re c sc&% %r&$ucere unui $&% fi'rin&+%" c-et r ce stu% 'res # scu" r ) Eficient s se ! nifest in c (u" "e(iuni"&r # scu" re ce fecte ( # se"e $e c "i'ru !ic si !i?"&ciu, in c (u" "e( rii # se"&r $e c "i'ru ! re fiin$ neces r sutur c-irur,ic " ) He!&st (ei fi(i&"&,ice i se &%une fi'rin&"i( fi(i&"&,ic , !ec nis! cu r&" in rest 'i"ire er!e 'i"it tii "u!enu"ui # su"ui nteri&r "e( t) Ace st se re "i(e ( %rin $istru,ere en(i! tic tr&!'u"ui nteri&r f&r! t, $ r nu! i $u% #in$ec re c&!%"et "e(iunii %erete"ui # scu" r) He!&st ( fi(i&"&,ic se $esf s& r in 0 et %e: A. He!&st ( %ri! r 3ti!%u" # scu"&+%" c-et r. in c re inter#in f ct&rii # scu" ri si % c-et ri1 6.He!&st ( secun$ r 3ti!%u" %" s! ticNc& ,u" re .1 C.F ( $e retr ctie c-e ,u"ui 3ti!%u" tr&!'&$in !ic. Din %unct $e #e$ere " interesu"ui fi(i&% t&"&,ic %re(int interes %ri!e"e : et %e) A) HEMOSTAZA PRIMARA Ace st et % re c sc&% f&r! re nunui $&% strict %" c-et r, in c&n$itii"e un&r !&$ific ri -e!&$in !ice "&c "e f #&r 'i"e si c re este c % 'i" s &%re sc %e !&!ent s n,er re ) Acest $&% nu re%re(int & s&"utie $efiniti# $e& rece e" es te $estu" $e s" ' t s t " "&cu" 'resei # scu" re si %& te fi !entinut t t ti!% c t %ersist # s&c&nstricti # su"ui "e( t) O$ t cu $is% riti # s&c&nstrictiei, f"uxu" s n,uin $e#ine ! i %uternic si %& te %r&$uce $is"&c re $&%u"ui %" c-et r si re"u re s n,er rii, $ r cest "ucru este %re#enit %rin inter#enti ce"ei $e II+ f (e -e!&st (ei ce+" nc&re ( ! i fer! " %erete"e # su"ui %rintr+& rete $e fi'rin ) In $esf sur re -e!&st (ei %ri! re se $e&se'esc 7 f (e: ;.f ( !&$ific ri"&r -e!&$in !ice "&c "e 3r-e&"&,ice. f"uxu"ui s n,uin: :. $er re %" c-et r " "&cu" "e(iunii # scu" re1 0. ,re, re %" c-et r 1 7.!et !&rf&( # sc& s %" c-ete"&r ,re, te) 1)MODIFICARILE HEMODINAMICE LOCALE:

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Aceste c&nst u in %r&$ucere unei # s&c&nstrictii # su"ui "e( t, re "i( t %rin ref"ex $e x&n, $ec" ns t "&c " %rin ctiune f ct&ru"ui "e(i&n ") E este !entinut un & rec re ti!% $ t&rit e"i'er rii $in %" c-ete"e $er te $e Tx A : , ser&t&nin s u e%inefrin 3 $ren "in .) *&"u" cest&r este $i!inu re "&c " f"uxu"ui s n,uin, in une"e situ tii %ut n$u+se ?un,e " sist re s 3# se $e c "i'ru f)!ic., cee ce re%re(int & c&n$itie esenti " %entru 'un $esf sur re ur! t& re"&r et %e) O "t !&$ific re -e!&$in !ic & re%re(int $esc-i$ere c&" ter "e"&r # scu" re $i cente # su"ui "e( t ce %rei u s n,e"e ce in !&$ n&r! " str ' te # su" "e( t) 2)ADERAREA PLACHETARA *e%er(int %r&cesu" $e t s re " unui nr) $e tr&!'&cite " %erete"e # scu" r ex%us in ur! $enu$ rii en$&te"i "e) Este un fen&!en % si# ce nu necesit c&nsu! $e ener,ie si se re "i(e ( %rin inter!e$iu" f ct&ru"ui #&n Ei""e'r n$, & %r&tein ce se sinteti(e ( in ce"u"e"e en$&te"i "e si intr+& ! i !ic ! sur in -e% t&cite si !e, c ri&cite) Acest nu re $& r r&" in $er re, e re%re(ent n$ si tr ns%&rt&ru" f ct&ru"ui AIII " c& ,u" rii 3f)#)E)/ c&!%&nent %r&c& ,u" nt f)AIII.) 3Of)AIII este un c&!%"ex tri!&"ecu" r "c tuit $in f)#)E), c&!%&nent %r&c& ,u" nt / AIIIc si & c&!%&nent nti,enic ) In !&!entu" in c re exist & "e(iune en$&te"i " , f)#)E) se fixe ( %e ree%t&ri s%ecifici f" ti in structur c&" ,enu"ui # scu" r1 cesti u un c&ntinut in HO+LBs si HO+Pr&) Fix re f)#)E) " c&" ,enu" # scu" r %r&$uce !&$ific ri c&nf&r! ti&n "e in structur s ce $eter!in " ce" " "t c % t !&$ific ri ce %er!it f)#)E) s se t se(e si cu ce" $e+ " II+"e c % t $e rece%t&ri s%ecifici %re(enti %e !e!'r n tr&!'&citu"ui) Astfe" tr&!'&citu" $er %rin f)#)E) " "&cu" "e(iunii # scu" re) *ece%t&ru" tr&!'&cit r %entru f)#)E) este & ,"ic&%r&tein ;' ce f ce % rte $intr+un c&!%"ex ,"ic&%r&teic !e!'r n r " turi $e GP IX, $e c re este "e, t c&# "ent) Acest c&!%"ex se nu!este ,"ic&c "icin ) GP ;' este f&r! t $in : " nturi %&"i%e%ti$ice $iferite: + c re este ! i "un,1 + c re este ! i scurt si c re re r&" $& r structur " 3nu c& ,u" t&r.) L ntu" re in se,!entu" extr !e!'r n r un $&!eniu f&r! t $in 5 sec#ente ) re%etiti#e ce re%re(int situsu" $e "e, re " f)#)E) Fix re f)#)E) %e se,!)extr !') " GP);' ii $eter!in cestui & serie $e !&$ific ri c&nf&r! ti&n "e ce se tr ns!it %rin se,!) tr ns!')si %rin ce" cit&%" s! tic % n " $iferite siste!e en(i! tice ce se cti#e ( )$e " ni#e"u" se,!)tr ns!') se tr nsite !&$ific re c&nf&r! ti&n " si GP) $i cente 3GP)XI .,ce stfe" $e#ine c % 'i" s fixe(e $in circu" tie F XI " c& ,u" rii) +)AGREGAREA PLACHETARA: C&nst in st 'i"ire un&r c&nt cte !u"ti%"e si %unctif&r!e intre tr&!'&cite"e $er te) Are " ' ( e!itere $e %seu$&%&$e,$e c tre tr&!'&cite, c&nect te intre e"e %rin inter!e$iu" un&r %unti $e fi'rin&,en) Pr&cesu" $e $er re, c&n$uce %ri! se,!)intr cit&%" s! tic " GP;'," cti# re un&r siste!e en(i! tice, ! i i!%&rt nte fiin$: .siste!u" PLA:PLA: cti# t $es%rin$e $in PL) !e!'r n re c) r -i$&nic, $in c re %e c "e CO/<TxS TxA:3sinteti( t $e n&#&. tr&!'&citu" si ne cti# t c&ntine TxA: in ,r nu"e"e s "e $ense $e n&#& este ins "i'er " ni#) Cit&%" s! tic si re %r&%riet te $e !&'i"i( C $e%&(it t t&t in TxA: ,r nu"e"e $ense '.siste!u" PLCPLC cti# t cti&ne ( %e PL !e!e'r n re $ec" nsin$ c sc $ PI/<IP0LDAG IP0 re %r&%riet te $e %r&$uce !&'i"i( re $e C $in ,r nu"e"e $ense 3c re u rece%t&ri %t)IP0. DAG cti#e ( & "t en(i! c-eie / %r&tein8in ( C) CONSECINTELE ACTIAA*II META6OLICE A LE T*OM6OCITELO* : .creste c&nc) cit&%" s! tic C /< cti# re unei %r&teine c&ntr cti"e / tr&!'&stenin ce este % rte c&!%&nent cit&sc-e"etu"ui tr&!'&cit r in %re(ent C si ATP , tr&!'&stenin se c&ntr ct , $eter!in n$ e!itere $e %seu$&%&$e) '. cti# re PLC c re cti#e ( %rin f&sf&ri" re rece%t&rii !')i!%"ic ti in ,re, re, res%ecti# GP II' @ GP III , ce sunt "e, te c&# "ent su' f&r! unui c&!%"ex !') 3f&sf&ri" re se,! intr cit&%" s! tic " GP II' . /<se %r&$uce & !&$ific re c&nf&r! ti&n " ce se tr ns!ite % n " GP III ce $e#ine stfe" c % 'i" s fixe(e fi'rin&,enu" 3*) %t) fi'rin&,en.) Aceste GP) I!%"ic te in ,re, se , sesc inc"usi# %e !') %seu$&%&$e"&r) Pseu$&%&$e"e sunt s&"i$) intre e"e $e& rece fi'rin&,enu" se fixe ( cu un c % t " " ntu"ui %e rece%t&ru" III ,i r cu "t " nt se fixe ( %e ce" si ti% $e rece%t&r " unui tr!'&cit #ecin) Acest %r&ces $e ,re, r este ut& !%"ific t) O$ t cu c&ntr cti tr&!'&steninei se %r&$uce si e"i'er re in exteri&r c&ntinutu"ui $iferite"&r ,r nu"e tr&!'&cit re / re ctie $e e"i'er re) Me$i t&rii sunt uti"i t t %t) !%"ific re fen&!enu"ui $e ,re, re, $ r unii sunt uti"i 3in$is%ens 'i"i. si in c& ,u" re 3ex) f ct&ru" %" c-et r III . A"ti!e$i t&ri e"i'er ti 3ex) TXA:,ADP, e%inefrin . se fixe ( " su%r f t exteri& r !') tr&!'&cit re %e rece%t&ri s%ecifici c re %rin se,!ente"e "&r intr ce"u" re #&r cti# su%"i!ent r ce"e : sist !e en(i! tice) Prin c&nsecinte"e cti# rii su%"i!ent re /<AMPLIFICA*EA)

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c. se f&r!e ( un $&% %" c-et r ce nu este inc %erfect -e!&st tic, $e& rece %unti"e $e fi'rin&,e $intre tr&!'icite sunt fri 'i"e, intre %seu$&%&$e"e tr&!'&cite"&r ,re, te exist s% tii %rin c re s n,e"e nu %& te circu" )%entru c $&%u" %" c-et r s $e#in -e!&st tic este neces r et % 7 ,)METAMORFOZA )ASCOASA A PLACHETELOR AGREGATE# In % r "e" cu -e!&st ( %ri! r se cti#e ( si c sc $ c& ,u" rii $in c re re(u"t tr&!'in , ce cti&ne ( nu nu! i in tr nsf&r! re fi'rin&,en, fi'rin ,$ r si %e su%r f t tr&!'&cit re si nu!e se fixe ( $e rece%t&rii tr&!'&cit ri re%re(ent ti $e GP A) Ace st fix re c&n$uce " & crestere %er!e 'i"it tii !') %t) i&nii $e N ) Pe ' ( ,r $ientu"ui $e c&ncentr tie,N intr $in s%)extr ce" in tr&!'&cit1 cest tr ,e &s!&tic c ntit ti su%"i!ent re $e % /< -i%er-i$r t re /< crestere #&"u!u"ui tr&!'&citu"ui /< se inc-i$ &c-iuri"e $intre %seu$&%&$e /<$&%u" %" c-et r $e#ine -e!&st tic) In %"us ,%unti"e $e fi'rin&,en s+ u tr nsf&r! t in fi'rin /<$&%u" $e#enit !u"t ! i %uternic $er t $e& rece c&" ,enu" # scu" r c&ntine si rece%t&ri %t) fi'rin ) PATOLOGIA HEMOSTAZEI P*IMA*E He!&st ( %ri! r %& te fi fect t in trei circu!st nte: # scu"&% tii, tr&!'&% tii, tr&!'&cit&%enii Tu"'ur re -e!&st (ei %ri! re se ! nifest %rin sin$r& !e -e!&r ,i% re,! nifest te " ni#e" Kcut n t %rin : %ur%ur , %etesii, ec-i!&(e !uc& se"&r %rin s n, r ri: ,in,i#&r ,ii, e%ist xis, !e"en , -e! te!e( , -e!&%ti(ie, -e! turie, s n,er ri ,enit "e etc Aceste ! nifest ri -e!&r ,ice ce %&t #e "&c si in !&$ s%&nt n,f r %re(ent !icr& si ! cr& tr u! tis!e"&r,$e& rece si in c&n$itii fi(i&"&,ice % r !icr&fisuri en$&te"i "e su' ctiune !ec nic f"uxu"ui s n,#in 3in (&ne"e cu re,i! %resi&n " ri$ic t.) D c in ceste c&n$itii ni inter#in # s&c&nstricti si !icr& ,re, re %" c-et r % r s n,er ri s%&nt ne) ;. AASCULOPATIILE : NU PE*MIT O AASOCONST*ICTIE CO*ESPUNZATOA*E, NU PE*MIT O ADE*A*E T*OM6OCITA*A EFICIENTA LA COLAGENUL AASCULA*, AASCULA* ESTE FOA*TE F*IA6IL A scu"&% tii"e sunt $e $&u c te,&rii : D&' n$ite si Ere$it re A.AASCULOPATIILE DO6ANDITE : $) PURPURA ANAFILACTICA -&eum$t i'$) HENOCH.SCHOLEIN# Est & # scu"&% tie ce fecte ( in s%eci " c&%ii si c re % re ! i frec#ent " c&%ii in cursu" un&r infectii stre%t&c&cice 3 !i,$ "it stre%t&c&cic s u *AA.) Mec nis!u" este $e n tur i!un ) In %re(ent unui exces $e A, stre%t&/<c&!%"exe i!une $e t "ie ce %&t trece %rin %erete"e c %i" r %rinn nu!ite (&ne %referenti "e 3(&ne"e in c re exist un f"ux c %i" r tur'u"ent s u in c re exist re,i! %resi&n " ! re s u in c re c %i" re"e sunt $ %t te %t) fi"tr re Kex) " ni#) Cut n t , in %erete"e intestin ", " ni#) Sin&#i "ei rticu" re , in c %i" re"e ,"&!eru" re ren "e . A?unse %eric %i" r, c&!%"exe"e i!une $ec" nse ( fen) Inf" ! t&rii /)c %i" rit : c&!%"exe"e %&t cti# c&!%"e!entu" /< n fi" t&xine"e C0 si C2 /< .$e,r nu" re ! st&cite"&r/<e"i'er re -ist !inei /<crestere %er!e 'i"it tii /<crestere c ntit tii $e c&!%"exe i!une %eri# scu" re Efect c-e!&t ctic /< tr ,ere "euc&cite"&r ce e"i'ere ( %r&$usii ce #&r $eter!in "e(iuni "e %erete"e # scu" r /< !icr&s n,er ri, %recu! si "e ce"u"e"&r s&! tice)In f&r!e"e ,r #e, "e(iuni"e se#ere "e c %i" re"&r ,"&!eru" re, $ec" nse ( intr ,"&!eru" r fen&!ene f) intense $e -e!&st ( /< tr&!'usuri ce '"&c-e ( fi"tr re /<I)*)A) Fen&!ene"e inf" ! t&rii $e ti%u" c %i" ritei, ex%"ic $ureri"e rticu" re 3sin&#it .si '$&!in "e) /) SCORBUTUL -$%it$mi" 0$ C )# Ait !in C inter#ine in sinte( c&" ,enu"ui # scu" r) In "i%s ei ,c&" ,enu" re & sinte(e $eficit r 3se sinteti(e ( %utin si $efectu&s ./<# se fri 'i"e ,ce %&t %re(ent fisuri s%&nt ne) C&" ,enu" n&r! " nu %er!ite t s re f ct&ru"ui #&nEILE*6*AND /< "ter re -e!&st (ei) c) PURPURA SIMPLEX# A% re " une"e fe!ei ce u un ni#e" estr&,enic crescut) Nu se cun& ste !ec nis!u", $ r se % re c excesu" $e estr&,eni tu"'ur f&r! re c&" ,enu"ui # scu" r/<fr ,i"it te # scu" r ) ') PURPURA MACANICA# A% re " ni#e"u" !') inf), " %ers& ne"e ce u & str) # scu" r ! i fr ,i" ,in c&n$itii"e unui &rt&st tis! %re"un,it, ce $eter!in st ( # scu" r in !') inf) si %rin f&rt -i$r&st tic se exercit %resiune %e %eretii # scu" ri fr ,i"i) e) PURPURA SENILA# A% re " %ers& ne"e ! i in # rst ," c re !&$ific ri"e $e,ener ti#e fecte ( si str) %ereti"&r # scu" ri,ce $e#in fri 'i"i) 1) PURPURA HORMONALA# A% re in c (u" unui exces $e -&r!&ni ,"&c&c&rtic&i(i si tir&i$ieni, c re "tere ( !et '&"is!u" %r&teic, in sensu" incetinirii sinte(e"&r %r&teice si cce"er rii c t '&"is!u"ui %r&teic /<este fect t str) %r&teic 3c&" ,enic . %erete"ui # scu" r)

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2) PURPURA HIPERGLOBULINEMICA# A% re in c&ntextu" un&r '&"i ut&i!une, in c re se %&t f&r! ut&Ac in$re%t ti i!%&tri# un&r I, n&r! "e 3ex) %&"i rtrit reu! tis! t&i$ .) Se f&r!e ( c&!%"exe i!une circu" nte, c re $ c sunt $e t "ie !ic %&t ?un,e %eri# scu" r /<inf" ! tie 3#e(i . 6. AASCULOPATIILE E*EDITA*E: $) SIDROMUL EHLERS.DANLOS: C r cteri( t %rin tu"'ur re %r&fun$ $%$# c ntit ti# si c "it ti# sint (ei $e c&" ,en) Princi% "e"e c r cteristici sunt:+-i%ersensi'i"it te rticu" r $ t&r t unei -i%er" xit ti "i, !ent re,+-i%ere" sticit te te,u!ent r cu %"iuri cut n te f) ! ri, + n&! "ii "e str) c&" ,enu"ui # scu" r Exist ;; # ri nte "e cestui sin$r&!, $intre c re : ! i i!%&rt nte: Ti%u" IA Keste fect t sint ( c&" ,enu"ui III, ce intr in c&!%&(iti %erete"ui &rtic si intestin "/< sunt f) su'tiri, fri 'i"e, fr ,i"e si %&t %re(ent $i" t tii ne#ris! "e ce se %&t ru%e us&r in c (u" &rtei/<-e!&r ,ii c t c"is!ice 3!&rt "e. in c (u" intestinu"ui % r -e!&r ,ii L %erit&nite -e!&r ,ice si se%tice Ti%u" AI+este $efect c&n,enit " " en(i!ei "isi"+-i$r&xi" ( $ t&rit c rui nu se ! i f&r!e ( in str) c&" ,enu"ui ce"e str) '&, te in -i$r&xi+"isin ce re%re(int rece%t&ru" c&" ,enic %t) f ct&ru" #&nEILE*6*AND/<este fect t %r&cesu" $e $er re) /)TELANGIECTAZIA EREDITARA HEMORAGICA-/ $l$ RANDU.OESLER)# 6& " tr ns!is ut&s&! " $&!in n t, c r cteri( t %rintr+un $efect $e n,i&,ene( # se"&r !ici ,in s%eci " #enu"e"&r) Aceste # se !ici %re(int $in "&c in "&c n&! "ii c : +"i%s tunicii !uscu" re $e c&" ,en + une&ri %erete"e este f&r! t nu! i $in str t en$&te"i ") In ceste (&ne % r !ici $i" t tii /ect (ii ce se %&t ru%e f) us&r " !ici ef&rturi 3tuse ./<-e!&r ,ii $e su%r f t si " ni#e"u" &r, ne"&r) Aceste se $&t) Si f %tu"ui c "i%s tunicii !uscu" re nu %& te f ce# s&c&nstrictie in c ( $e "e(iune si ne # n$ str) $e c&" ,en nu se %r&$uce $er re tr&!'&cite"&r " "&cu" "e(iunii) :.T*OM6OPATIILE: Presu%une & fect re $)%)$)#) c "it ti# Tr&!'&% tii"e sunt $e $&u c te,&rii : ere$it re $&' n$ite A. T*OM6OPATIILE E*EDITA*E : $) DISTROFIA TROMBOCITARA HEMORAGICA - SINDROMUL BERNARD.SOULIER)# Afectiune este tr ns!is ut&s&! " recesi#) Tr&!'&cite"e re(int n&! "ii c : $eficit @% n " 'sent GP I' 3rece%t&ru" %t) F#E.functi $e $er re este ce ! i fect t $eficit $e tr&!'&stenin c&nsecinte:+e!itere $e %seu$&%&$e $eficit r re cti $e e"i'er re@ex%u"(ie !e$i t&ri"&r $in ,r nu" tii inc"usi# ce"&r cu r&" $e ! %"ific re ,r, rii,$eficit r , +$eficit $e GP A 3rece%t&r tr&!'&cit r %t) tr&!'in . este fect t !et !&rf&( # sc& s , +$eficit $e GP IX Crece%t&r %t)f ct&ru" XI " c& ,u" rii.f ct&ru" XI $e#enit cti#, nun i $u% fix re % IX) *)BOALA % " 3ILLEBRAND# Se s&cie ( si cu $eficit " c&!%&nenetei %r&c& ,u" nte f ct&ru"ui AIII fect re -e!&st (ei %ri! re si s cun$ re) Deficitu" -e!&st (ei %ri! re se $ t&re ( $efectu"ui $e $ er re tr&!'&cit r /<nu este & tr&!'&% tie %r&%riu+(is ) +)PSEUDOBOALA % " 3ILLERBRAND# Se c r cteri(e ( %rintr+un nr) f ! re $e rece%t&ri tr&!'&cit ri %t)F#E 3GP I' . se %&r$uce & fix re n&r! " F#E,int i %e tr&!'&cit 3e" # n$ & finit te !u"t crescut %t) F#E.si ii sc $e finit te , " ce" " "t c % t, %t) c&" ,enu" # scu" r) ,)TROMBASTENIA GLANTZMANN# Presu%une un $efect ! ?&r $e ,re, re %" c-et r ,$efectu" tr&!'&cit r c&nst n$ intr+un nr) f& rte !ic $e rece%t&ri i!%"ic ti in ,re, re II'+III ,%e c re7 sef&r!e ( %unti"e $e ,"ic&,en) P& te exist si & $eficient ,"ic&"i(ei tr&!'&cit re $ t) unui $eficit $&u en(i!e c-eie "e ,"ic&"i(ei: %iru# t8in ( si ,"icer "$e-i$+0P $e-i$r&,en ( )Deficitu" $e ,"ic&"i( f ce c %r&$ucti $e ADP s fie sc (ut %r&cese"e $e%en$ente $e ener,ie #&r #e $e suf&rit 3c&ntr cti tr&!'&steninei .) Se ! i %& te s&ci cu un $eficit $e GP A fect re !et !&rf&(ei # sc& se) 4)DEFICITUL EREDITAR AL REACTIEI DE ELIBERARE# Are $&u # ri nte : 'sent ,r nu"e"&r tr&!'&cit re, $eficit $e ex%u"(ie un&r !e$i t&ri . A'sent ,r nu"e"&r tr&!'&cit re: re $&u # ri nte: I. 'sent ,r nu"e"&r 3c" re.: Gr nu"e"e c&ntin in !&$ n&r! ":+PF III neces r %r) C& ,u" re, +PF IA cu ctiune nti-e% rini c 3%&rc& ,u" nt ., +!ici c ntit ti $e fi'rin&,en,+!ici c ntit ti $e F#E) A'sent "&r un & rec re $eficit $e $er re , "ter re c& ,u" rii %rin PF III ) 6& " este frec#ent s&ci t si cu n&! "ii "e rec) II'+III II. 'sent ,r nu"e"&r 3$ense.: Gr ni"e"e c&ntin C si !%"ific t&ri i c& ,i" rii: TX, ADP, e%inefrin , ser&t&nin ) Li%s "&r $et) Tu"'ur ri $e ,re, re tr&!'&cite"&r, nu! ru" "&r fiin$ re" ti# n&r! ")

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'.Deficit $e ex%u"(ie un&r !e$i t&ri: n&! "ii"e # (e ( $iferite $eficite ce % rtin fie : $e c "e c) r -i$&nic fie $e c "e PL+C I. $eficite ce % rtin $ c "e c) r -i$&nic: $eficit $e PL+C, $eficit $e CO, $eficit $e TS, $esi exist ,r nu"e , ceste nu u suficient TX A:/< fect re %r&c) De c& ,u" re) II.$eficite ce % rtin $e c "e PL+C: D)%)$)#) !et '&"ic c "e PL+C este n&r! " ,ins ,r nu"e"e nu u rece%t&ri %t)IP0IP0 nu %& te %r&#&c ex%u"(i $e C ) 6. T*OM6OPATIILE DO6ANDITE: ()TROMBOPATIA DIN IRC# Se $ t&re ( un&r c&!%usi t&xici ce nu se ! i %&t e"i!in %e c "e ren " , ce %ertur' inc"usi# functii"e tr&!'&cite"&r 3ex) c ,u ni $in succinic.) *)TROMBOCITEMIILE: Sunt %r&"ifer ri ! "i,ne "e serieie !e, c ri&cit re,in c re nr) $e tr&!'&cite in %eriferie este ! i! re $e ;======@!!0)Desi crescute nu!eric , u tu"'ur ri c "it ti#e Tr&!'&cite!i esenti " / %r&"ifer re seriei !e, c ri&cit re s&ci t cu "euce!ie ,r ni"&cit r cr&nic si cu %r&"if r re seriei r&sii 3%&"icite!i #er .) +)TROMBOPATIA DIN UNELE BOLI AUTOIMUNE : P&t % re ut&Ac in$re%t ti i!%&tri# un&r rece%t&ri !e!'r n ri tr&!'&cit ri:GP I', GP A, GP II'+III , GP IX "ter re functii"&r %" c-et re ,)TROMBOPATIA INDUSA DE DOZELE CRESCUTE DE ALCOOL: A% r $ t&rit efecte"&r t&xuce "e "c&&"u"ui su%r tr&!'&cite"&r) 4)TROMBOPATIA MEDICAMENTOASA# As%irin in-i' CO$eficit $e TX A: 0. T*OM6OCITOPENIILE: /sc $ere nr) $e tr&!'&cite su' ;2====@!!0 " # "&ri ! i !ici $e 52===@!!0 % re sin$r&!u" -e!&r ,ic sunt $e $&u c te,&rii: .tr&!'&cit&%enii ere$it re: sunt $e n tur centr " 3%rin fect re ! $u#ei. ex). ! " $i F nc&ni: / "ter re ,enetic ce") ste! %"uri%&tente ,ce # fect t& te ce"e" "te "inii /<PANCITOPENIE se s&ci ( cu n&! "ii c r$i&+# scu" re, ren "e, sc-e"etice)C&%ii tr iesc f) %utin '.tr&!'&cit&%enii $&' n$ite: %&t % re %rin $&u !ec nis!e: + %rin fect re centr " : ;) tr&!'&cit&%enii c u( te $e $iferite int&xic tii cu : 'en(en+ce "etere ( str)ADN+u"ui si str) "i%i$ic !') ce")ste!) !e$ic !ente+c"&r nfenic&", $iuretice ti (i$ice, feni"'ut (&n , cit&st tice "c&&"+sc $e c % cit te $e ! tur re %recurs&ri"&r) :) tr&!'&cit&%enii c u( te $e r $) i&ni( nte + in $&(e ! ri $uc " % ncit&%enie 0) tr&!'&cit&%enii c u( te $e in"&cuire @in# $ re tes) !e$u" r %rin $iferite %r&cese % t&"&,ice cu ce") !et st tice ,"euce!ice,tes) fi'r&s 7) tr&!'&cit&%enii $ te $e % riti un&r ut&Ac in une"e '&"i ut&i!une + %rin fect re sect&ru"ui s n,#in %eriferic: *. prin mecanism imunologic + tr&!'&cit&%eni ut&i!un 3/%ur%ur tr&!'&cit&%enic ut&i!un . se c r cteri(e ( %rin existent in s n,e"e %eriferic un&r Ac ntitr&!'&cit ri) In f ( cut : % re $es " c&%ii ,in %eri& $ $e c&n# "escent $u% ru'e&" , ru?e&" , MNI ex%"ic tie :exist & ! re se! n re intre A, #ir " si une"e A, $e %e !') tr&!'&citu"ui /<I,G se fixe ( %e !') tr&!'&citu"ui si cti#e ( C /<"i( $ r & stfe" $e "i( re "&c si intr s%"enic, %t) c intr # scu" r 1 ! cr&f ,e"e recun&sc I, se( te %e !') tr&!'&citu"ui f ( cr&nic : % re $es " fe!ei,fie c & '& " ut&i!un $ec" ns t $e !&$ific ri "e A, tr&!'&cit re ce nu ! i sunt recun&scute nc Gse"fH,fie in c $ru" "t&r '&"i ut&i!une in c re A, tr&!'&cit re nu s ufer !&$ific ri, $ r sc $e t&"er nt ,ener " si stfe" se %&t f&r! ut&Ac3ex) "u%us,tir&i$it ut&i!un . + tr&!'&cit&%eni !e$ic !ent& s : % re frec#ent " c-inin , c-ini$in !ec nis!:nu in$uc e"e sin,ure, ci se fixe ( %e $if) c&!%&nenete !e!'r n re "e tr&!'&citu"ui s u %e %r&teine"e %" s! tice "e cestui /)c&!%"exe ce in$uc f&r! re $e ntic&r%i /<se c&!%&rt c - %tene ) OT*OM6OCITELE AU *ECEPTO*I PT) I, SI AU AFINITATE PT) COMPLEXE) tr&!'&cit&%eni %rin ut&i!uni( re: ut&i!uni( re se %r&$uce: %&sttr nsfu(i&n " fet&+! tern !ec nis!: %este C=P $in in$i#i(i %re(int %e su%r f) tr&!'&cite"&r A, %" ,-et r A;1 ;=P $in in$i#i(i nu i" u1$ c un in$i#i$ %ri!este s n,e cu A, %" ,-et r A;, i r tr&!'&cite"e s "e nu %re(int cet

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A,, se f&r!e ( Ac1 " :+ tr nsfu(ie cu A, %" c-et rA; se # cti# C/<cit&"i( 1 t&t&$ t se e"i'ere ( c&!%"exe i!une ce se %&t fix %e tr&!'&cite"e n&r! "e "e %ri!it&ru"ui1 i$e! se %r&$uce si in c (u" fet&+! tern :) prin sechestrarea intrasplenica a trombocitelor: c u(e: -i%ertensiune %&rt " /<sc $e circu" ti s n,e"ui in s%"in /< st ( s%"enic /< % ncit&%enie 3HIPE*SPLENISM. infi"tr re s%"inei cu $if) ce") c ncer& se, inf" ! t&rii, int "nit in '&"i "e siste!u"ui "i!f&i$ 3'& " H&$?8in,"i!f& !e./<s%"en&!e, "ieL st ( # sc)/<% ncit&%enie) 0) prin consum crescut de trombocite Ksin$r&!u" CID

FIZIOPATOLOGIA COAGULARII COAGULA*EA / tr nsf&r! re fi'rin&,enu"ui in fi'rin su' ctiune tr&!'inei )i) se nc&re ( ! i 'ine $&%u" %" c-et r CALEA EXTRINSECA + re & intensit te ! i !ic , se re "i(e ( in #ecin tete $&%u"ui %" c-et r, c ntit te $e fi'rin f&r! t inter#ine in tr nsf&r! re %ri!e"&r %unti $e fi'rin&,en in fi'rin , este $ec" ns t $e e"i'er re f ct&ru"ui III $in c "u" "e( t /< e" se uneste cu F AII /<un c&!%"ex c % 'i" s cti#e(e "&c " F X/< ici %&rneste c "e c&!un : F X L F A L su'st)"i%i$ic $e3cef "in . /c&!%"ex tri!&"ecu" r+%r&tr&!'in ( , ce cti&ne ( %e F II /< tr&!'in stfe" f&r! t initi ( tr nsf&r! re ) CALEA INTRINSECA + este ! i "un, , c ntit te $e tr&!'in f&r! t este ! i ! re, cest fiin$ res%&ns 'i" $e tr nsf&r! re P ce" ! i , re $e fi'rin&,en, se $esf s& r %e !') tr&!'&cit re: F#E %rin$e tr&!'&cite"e $e en$&te"ui, %&i cti#e ( F AIII c re # fix F IX1 tr&!'&cite"e fixe ( , cu ?ut&ru" GP IX, f ct&ru" XI1 cef "in fixe ( F 0,ce fixe ( F A si %&i F X1F XII ct) %e F XI /<F XI ce ct) %e F IX /<F IX L F AIII/< c&!%"ex ce cti#e ( F X /< F X F A L F0 / %r&tr&!'in ( ce ct) %e %r&tr&!'in /< tr&!'in Sf) c& ,u" rii c&inci$e cu cti# re !et '&"ic tr&!'&cit r COAGULOPATII: + se ! nifest %rin s n,er re in $&i ti!%i: ;. s n,er re s%&nt n @$u% & "e(iune /<se f&r!e ( un $&% $e fi'rin ce tine t t ti!% c t #e! # s&c&nstrictie :. c n$ f"uxu" s n,#in creste,$&%u" %ri! r nefiin$ 'ine nc&r t, # fi $is"&c t $e c tre t&rentu" s n,#in /< re % re -e! r,) + sunt : c te,&rii: .%rin $eficite i(&" te sunt ere$it re 3%rin fectere ,enei . He!&fi"ii"e / $efecte $e f ct&ri $in c "e intrinsec 5em 1ili$ A / $eficit $e sinte( c&!%&nentei AIIIc +,en este sit) % cr&!&(&!u" X /<'& " se ! nifest " ' r' ti + -e!&st ( %ri! r nu este fect t ) +exist 0 f&r!e:se#er / c&ncentr ti $e AIIIc Q;P $in ce n&r! " 1! nifest ri"e % r $e " n stere, u"teri&r ! nifest ri"e % r si s%&nt n, $ r ! i "es c n$ in# t s !e r, /<ec,-i!&(e, s n,er ri intr rticu" re,$ c se re%et %&t $uce " $e ,ener ri /< nc-i"&(e !e$ie / c&nc)$e AIIIeste cu%rins intre2+9P $in n&r! "1 ! nifest ri"e sun $e intensit te inter!e$i r us& r / c&nc) $e AIIIc este <2P $ rQ:=P $in # ") n&r! " 1-e!&r ,ii"e s%&nt ne "i%sesc,$ r s n,er ri"e sunt %re"un,ite / $l$ % "3ille/&$"' / $eficit $e sint) F#E: + ,en este sit) % cr&!&(&!u" ;:1 + exist sincr&ni( re intre sint ( $e F#E si ce AIIIc,+ initi " F#E este sinteti( t c !&n&!er 3e" re c % cit te $e sti!u" ,en %t) AIIIc. ce se s !'"e ( /< %&"i!er 3F#E ! tur.) + exist 0 ti%uri $e '& " : ti%u" ; /sinte( n&r! " $e F#E si $e AIIIc,$ r nu %&t fi e"i'er ti in circu" tie /< fect re -e!&st (ei I si II ti%u" :: . / se sinteti(e ( !&n&!eri ,$ r csti nu se s !'"e ( /<$eficit $e F#E ! tur /< fect re -e!&st I, './se sinteti(e ( !&n&!eri,$ r c re se s !'"e ( inc&rect /<F#E ineficient /<tu"'ur re -e!&st (ei I ti%u" 0 / $eficit ,r # $e sinte( !&n&!eri"&r /<tu"'ur re -e!&st I L II 5em 1ili$ B / $eficit $e F IX1 re ! nifest ri se! n t& re -e!&fi"iei A 5em 1ili$ C / $eficit $e F XI1 re ! nifest&ri se! n t& re -e!&fi"iei A 5em 1ili$ H$2em$"" /$eficit $e F XII1 nu re ! nifest ri -e!&r ,ice P$&$5em 1ilii /$eficite $e f ct&ri $in c "e extrinsec L c&!un 1 u ! nifest ri si!i" re cu -e!&fi"ii"e !$&$5em 1ili$ Ale6$"'e& / $eficit $e F AII !$&$5em 1ili$ Ou6e" / $eficit $e F A !$&$5em 1ili$ Stu$&t.B 7e& / $eficit $e F X $1i/&i" 2e"i$ c "2e"it$l$ / $eficit $e F I '.%rin $eficite s&ci te:

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$%it$mi" 0$ 8 : + #it !)> inter#ine in sint) F II, AII, IX, X 3" c % tu" +NH: u sec#ent cu c) ,"ut !ic., in fic t #it)> este cti# %rin e%&xi$ re /<#it)> cti#e ( c r'&xi" (e ce inser ,r) KCOOH in %&(iti "e resturi"&r $e c) ,"ut !ic1 ceste r,) fixe ( us&r C , )i) f ct&rii %&t st 'i"i "e, turi cu "ti f ct&ri i c& ,u" rii %rin %unti $e C , ex :F XI tre'uie s se "e,e $e F IX %t + " cti# , F IX se "e , $e AIIIc %rin %unti $e C , F X se "e , $e F A, F X se "e , $e %r&tr&!'in ) Ait)> re 7 s%ecte "e circu" tiei in &r, nis!: ;.exist : #it)>:>; $in "i! #e,et "e si >:1 e"e $ifer in functie $e %&rtu" $e HL "e, $e #it)8 3str) $e ' ( .+>; re c) fitic , i r >: re $if rn (i"ic :. 's&rti $e%) $e & 'un $i,estie "i%i$e"&r 0.tr ns%&rtu" %rin #en %&rt 7.uti"i( re : + #it !in&( > % re %rin $eficit $e %&rt / '& " -e!&r ,ic n&u+n scutu"ui 3 re %utin #it)8.1 %rin $eficit $e 's)/ sin$r) $e ! " 's) "i%s s ruri"&r 'i"i re % ncre tit cr&nice se #e$e %rin $eficit $e tr ns%&rt / -i%ertensiune %&rt " %rin $eficit $e uti"i( re / "ter ri %r&fun $e "e -e% t&cite"&r 3cir&( -e% tic , f&r!e ,r #e $e -e% tit #ir " . i"su1icie"t$ 5e!$tic$ m$"i1est$&i 5em &$2ice '$t &$te: ;. HT%&rt "e, c n$ se $i" t (&ne $e n st&!&(e intre %&rt si c # /<# rice es&f ,iene :. HT%&rt " c n$ #e! st ( s%I"enic 0. sc $ere sinte(ei %r&teice 7. inc % cit te fic tu"ui $e cti# #it)8 2. -i%erfi'rin&"i( 3fic tu" sinteti(e ( f ct&ri ce in-i' %" s!in @%" s!in&,enu" : ;+ nti%" s!in , :! cr&,"&'u"in , ;+ ntitri%sin ,PAI, stfe" c&ntr&"e ( fi'rin&"i( . 4. %" s!in in exces /< ! nifest ri -e!&r ,ice %rin "i( re r %i$ %unti"&r $e fi'rin f&r! te/<c&nsu! $e f ct&ri $e c& ,u" re /<c& ,u"&% tie $e c&nsu! /< PDF 3%r&$usi $e $e,re $ re i fi'rin&,enu"ui. ce in-i' tr&!'in

CID# este un sin$r&! %"urieti&"&,ic/ -i%er cti#it te c& ,u" rii in !icr&circu" tie /< fect re tutur&r # se"&r !ici /<i!e$i t % r tr&!'usuri %e # se ce "e %&t '"&c 1 c&"& un$e #e! '"&c ? se $e(#&"t n&xie L necr&( tisu" r /<insuficient $e &r, n) L f&r! re cest&r tr&!'usuri % rtici% tr&!'&ci&te /< tr&!'&cit&%enie $e c&nsu!1 c n$ $&%u" nu re ") & &'structie c&!%"et , s n,e"e trece c %rintr+& sit si %&t % re $istru,eri $e e"e!ente fi,ur te /< ne!ie -e!&"itic !icr& n,i&% tic ) Iin fin " se $e(#&"t un se#er sin$r&! -e!&r ,ic $ t) c&nsu!u"ui $e f ct&ri $e c& ,u" re,tr&!'&cit&%eniei $e c&nsu! si $ec" ns re secun$ r sin$r&!u"ui fi'rin&"itic,%t) c tr&!'in in exces sti!u"e ( tr nsf&r! re %" s!in&,enu"ui in %" s!in CID+u" % re:;. $ t)"e(iuni"&r en$&te"i "e intinse 3ex)s&c -i%&#&"e!ic, s&c t&xic&se%tic. :. f r "e(iuni en$&te"i "e intinse 3ex)insitu tii in c re creste c ntit te $e tr&!'&%" stin , cu! r fi c&!%"ic tii"e &'stretic "e,c ncere.)

FIZIOPATOLOGIA METABOLISMULUI HIDROSALIN SI AL POTASIULUI FIZIOPATOLOGIA META6OLISMULUI HID*OSALIN 3H:O si N . H:O t&t " + re%re(int 4=+42P $in ,reut te c&r%&r " , este re% rti( t in $&u sect& re -i$rice ! ri: sect&ru" intr ce"u" r++ <7=+72P $in ,reut te c&r%, sect&ru" extr ce"u" r++<:=P $in ,reut te c&r% + c&ntine : su'sect& re : intr # scu" r++< 2P $in ,reut te c&r% si interstiti " ++<;2P $in ,reut te c&r% Crestere cest&r # "&ri se!nific st ri $e -i%er-i$r t re ce %&t fi $e 0 ti%uri: -i%er-i$ret re ce"u" r , -i%er-i$r t re extr ce"u" r , -i%er-i$r t re ,"&' " ) Sc $ere %r&centu"ui $e H:O su' # "& re n&r! " se!nific & st re $e $es-i$r t re ce %& te fi $e trei ti%uri: $es-i$r tere ce"u" r , $es-i$r tre extr ce"u" r , $es-i$r t re ,"&' " Exist tu"'ur ri -i$rice !ixte : -i%er-i$r t re intr+un sect&r si $es-i$r t re in ce" " "t) Mentinere n&r! " H:O $in &r, nis! $e%in$e $e ,r $ientu" $e %resiune &s!&tic $intre ceste $&u sect& re) Presiune &s!&tic unei s&") in ,ener " este $ t $e % rticu"e"e c&"&i$e $in ce s&")3nu c&nter ( # "ent ,inc rc tur e"ectric .)De ex) : un i&n $e N c re este f) !ic exercit cee si %resiune &s!&tic c si & ! cr&!&"ecu" %r&teic 3!u" ! i ! re .) Intre sect&ru" extr ce"u"" r si ce" intr ce"u" r exist un ec-i"i'ru si $ t) cestui nu exist $e%" s ri -i$rice intre ce"e $u& sect& re)

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G*ADIENT DE P*ESIUNE OSMOTICA / f&rt exercit t $e & % rte si $e "t unei !') se!i%er!e 'i"e 3!') ce"). ce se% r $&u c&!% rti!ente "ic-i$iene in, " '&, te in % rticu"e)Pe ' ( cestei f&rte H :O se # $e%" s s%re c&!% rti!entu" un$e ,r $ientu" $e %resiune este ! i ! re)Ac st $e%" s re se f ce % n c n$ ,r $ientu" &s!&tic se e, "i(e ( ) Presiune &s!&tic n&r! " sect&ru"ui extr ce"u" r este $e 0==+0;= !&s!&"i@")Din cest # "& re %&n$ere ce ! i ! rte & re i&nu" $e N 3% rticu" ce ! i 'ine re%re(ent t ,nu!eric, $in sect&ru" extr ce"u" r. E exercit 2=P $in %resiune, ;2= !&s!&"i@")De cee &rice # ri tii % t&"&,ice "e I N Mextr ce"u" r # ru%e ec-i"i'ru" &s!&tic cu sect&ru" ce"u" r /<$e%" s ri -i$rice intre ce"e $&u sect& re,ins%re sect&ru" cu %resiune &s!&tic ce ! i ! re) Pe "&cu" : se f" C", res%&ns 'i" $e ;==!&s!&"i@")In% tB&"&,ie # ri tii"e extr ce") "e I C"M sunt f) str ns "e, te $e ce"e "e IN M 3N si C" se 's&r' i!%reun " ni# intestin ".) Pe "&cu" 0 se f" HCO+0 , res%&ns 'i" $e :5!&s!&"i@") A"ti c&!%usi sunt: ,"uc&( + 2!&s!&"i@") uree + 2!&s!&"i@") %r&teine %" s! tice + :!&s!&"i@" P*ESIUNEA COLOID+OSMOTICA 3 . / %resiune &ferit $& r $e %r&teine) N si ,"uc&( sunt in !&$ n&r! " ! i c&nc) in sect&ru" extr ce"u" r f t $e ce" intr ce"u" r)E"e u un ,r $ient $e c&nc) si i!%"icit #&r #e si un ,r $ient &s!&tic)Cu t& te ceste nu exist in c&n$itii fi(i&"&,ice & $e%" s re $in ce") s%re sect&ru" extr ce",$e& rece cestui tr nsfer -i$ric i se &%une > intr ce"u" r,ce re%re(int %rinci% "u" sc-e"et " ce"u"ei 3este !u"t ! i c&ncentr t in ce"u" f t $e sect&ru" extr ce")M&$ific ri "e IN M si IG"uM in sect&ru" extr ce")$uce " ru%ere ec-i"i'ru"ui &s!&tic /<$e%" s ri -i$rice s%re sect&ru" cu %resiune &s!&tic crescut ) P rticu"e &s!&tic cti#e sunt N si ,"uc&( )Uree , $e exe!%"u,nu este & % rticu" &s!&tic cti# 3nu e i!%"ic t in $e%" s ri"e -i$rice . %t) c e us&r $ifu(i'i" si se re% rti(e ( unif&r! /< nu re ,r $ient $e c&nc) si ,r $ient &s!&tic) Presiune &s!&tic c&nferit $e % rticu"e"e &s!&tic cti#e / %resiune &s!&tic eficient /TONICITATE) S&"utie n&r!&t&n @ i(&t&n / re cee si t&nicit te cu ce %" s!ei n&r! "e 3t&nicit te %" s!ei / t&nicit te s%) interstiti " /t&nicit te intre,u"ui sect&r extr ce"u" r.) S&"utie -i%ert&n / re & t&nicit te < c %" s!ei n&r! "e S&"utie -i%&t&n / re & t&nicit te Q c %" s! i n&r! "e Misc ri"e -i$rice intre # s si interstitiu $e%in$ $e: ;.* %&rtu" $intre ,r $ientu" $e %res) -i$r&st tic " ni#) c %i" r si ,r$ientu" $e %resiune c&"&i$ &s!&tic R" c % tu" rteri&" r " c %i" ru"ui, %resiune -i$r&st tic $in # s este $e :2!!H,, i r %resiune -i$r&st tic interstiti " este $e 5!!H,) Diferent este $e 0:!!H, / ,r $ientu" $e %resiune -i$r&st tic ) A% tin$e s i s $in # s si s intre in interstitiu) Acest ten$int este infr n t $e c tre ctiune %resiunii c&"&i$+ &s!&tice) # s / :9!!H,) interstitiu / 7)2!!H,)Diferent /,r $ientu" $e %resiune c&"&$+&s!&tic / :0!!H, ,tin$e s ! ntin % in # s) L c % tu" rteri&" r ies $in # s % si s&"#iti) R" c % tu" #enu" r ,%resiune -i$r&st tic $in c %i" r / C!!H,, i r %resiune -i$r&st tic $in interstitiu / +5!!H, /<,r $ientu" este $e ;4!!H,,i r ,r $ientu" $e %resiune c&"&i$+&s!&tic este $e:0!!H,)Pe ' ( cest&r f&rte &s!&tice, % este retr s in # s) :.$ren ?u" "i!f tic " %ei interstiti "e R%rin siste!u" "i!f tic, % ?un,e t&t in siste!u" # n&s) 0.%er!e 'i"it te %erete"ui c %i" r Rcrestere %er!e 'i"it tii /<#&r trece si %r&teine, ) i) ,r $ientu" $e %resiune c&"&i$+&s!&tic sc $e/<# %re$&!in net ,r $ientu" $e %resiune -i$r&st tic /< % intr in interstitii si nu ! i %& te fi recu%er t ) Exist $&u ! ri c te,&rii $e tu"'ur ri -i$rice: A. s&ci te cu !&$ific re t&nicit tii &s!&tic %" s! tice 3extr ce"u" re. R!&$ific re i!%"ic ru%ere ec-i"i'ru"ui &s!&tic cu sect&ru" ce"u" r /< % riti $e $e%" s ri -i$rice) ;.Hi%ert&ni &s!&tic extr ce"u" r %& te fi %r&$us %rin: .crestere IN Mextr ce") / -i%ert&ni %rin -i%ern tre!ie : %resu%une crestere IN M " # "&ri %este ;75!E,@" exist $&u fe"uri $e -i%ern tre!ie: 's&"ut + se!nific & crestere IN M in %"s! %r&$us %rin crestere c %it "u"ui $e N $in cest sect&r, se %&r$uce %rin cu!u" re $e H:O si %re$&!in nt $e N in sect&ru" extr ce") c u(e: in,esti un&r c ntit ti se!nific ti#e $e H:O $e ! re, $!inistr re ,resit un&r s&") %erfu( 'i"e -i%ert&ne " % cienti cu insuficient ren " in f ( $e &"i,urie -i%er "$&ster&nis!u" 3cu c&n$iti c s nu fie & f&r! se#er .1 "$&ster&nu" sti!u"e ( re 's&rti $e N /< $et si & re 's&rtie crescut $e H:O1 c n$ este & f&r! f) se#er , re 's&rti $e N < re 's&rti $e H:O 1 In -i%ert&ni &s!&tic extr ce"u" r este tr s & % rte $in % ce"u" r in sect&ru" extr ce") /<t&nicit te !ixt ) Hi%er-i$r t re extr ce"u" r $et crestere #&"e!iei /<crestere $e'itu"ui c r$i c /<cerestere TA /<crestere riscu"ui $e AAC, ICS, EPA re" ti# + re%re(int crestere IN M%" s! tic, $ r nu %rin crestere c %it """u"ui $e N , ci %irn %ier$ere $in sect&ru" extrce") %re$&!in n t %ei f t $e N /<N se rec&ncentre ( )C u(e: %ier$eri $e "ic-i$e -i%&t&ne1 cest "ucru se %& te re "i( %e ! i !u"te c i: $i,esti# : # rs turi, sin$r) $i reice, fistu"e

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$i,esti#e, s%ir tii si s% " turi , strice re%et te, ren " : %&"iurii 3insuficient ren " cr&n) $ t&rit "ter rii !ec) ,ener " $e c&nc) urinii., %&"iuri $in $i ') ( - r t 3este &s!&tic $ t) e"i! crescute $e ,"uc&( ce tr ,e $u% e & c ntit te crescut $e % ., %&"iuri $in $i 'etu" insi%i$, cut n t : tr ns%ir tii 'un$ente $in c $ru" st ri"&r fe'ri"e, -i%ertter!ii"&r, res%ir t&rie 3su' f&r! $e # %&ri .: -i%er#enti" ti $in st ri"e $e ci$&( , $in st ri"e fe'ri"e, "ter ri"e centri"&r res%ir t&ri $ te $e tu!&ri In$ucere %&rtu"ui sc (ut $ % %& te fi in$us %rin: "i%s %ei, "i%s sen( tiei $e sete 3'&"n #ii c&! t&si, '&"n #ii %si-ic., tu"'ur re in,estiei $e % 3%" ,i '&c&+! xi"&+f ci "e, sten&(e esf ,iene f) str nse., -i$r&f&'i $in r 'ie T& te ceste $uc " $es-i$r t re -i%ert&n ) A% ce") este tr s in sect&ru" extr ce") /<$es-i$r tere $e#),"&' " ) Des-i$r t re extr ce" %r&$uce tu"'ur ri "e, te $e cti#it te c r$i&+# scu" r : sc $ere $e'itu"ui c r$i c /< sc $ere TA /< sc $ere %erfu(iei tisu" re /< % riti ! nifest ri"&r -i%&xice,une&ri % r n$ s&cu" -i%&#&"e!ic s u c-i r !& rte ) '.crestere IG"uMextrce"): fiec re crestere ,"iceniei cu ;9!,P ri$ic %resiune &s!&tic extr ce")cu ;!&s!&"@, cresteri f) ! ri "e ,"ice!iei 3in f&r!e f) se#ere $e $i 'et ( - r t. cresc t&nicit te &s!&tic extr ce"), i r crestere $e t&nicit te extr ce")%r&#& c & $e%" s re -i$ric $ins%re sect&ru" ce") s%re ce" extr ce" /<ten$int " $es-i$r t re este ,"&' " )D t&rit %&"iuriei, -i%ert&ni &s!&tic este si -i%ern tre!ic si -i%er,"ice!ic 3se # $iscut " c&! $i 'etic -i%er&s!&" r . c.!ec nis! !ixt :.Hi%&t&ni &s!&tic extr ce"u" r : este %r&#&c t $e sc $ere c&nc) $e N $in sect) extr ce") te&retic -i%&t&nie %& te %r&#&c si sc $ere c&nc) ,"uc&(ei extr ce") %r ctic ce st se $ t) nu! i -i%&n tre!iei, " # "&ri "e cestei $e %&x);05!E,@") exist $&u fe"ui $e -i%&n tre!ie: 's&"ut +++re%re(int sc $ere c %it "u"ui $e N $in sect) extr ce" %rin %ier$eri $e % si %re$&!in n t $e N 1 c u(e:Rnefrit 3$efect ere$it r @ $&' n$it " !ec) $e re 's) tu'u" r N ., -i%er "$&ster&nis!u" secer 3i!%"ic & sc $ere re 's) f) i!%)., tr t !enrtu" 'u(i# cu $iuretice) Iin t& te ceste situ tii , %ier$ere $e % si %re$&!in n t $e N in$uce & $es-ir t re extr ce")-i%&t&n ) A %re$&!in stfe" %resiune &s!&tic intr ce") /< % # intr in sect) ce" /<-i%er-i$r t re ce"u" r intr re $ % in ce" 3intr re ! si# .este %ericu"& s %t) creier /<%& te %r&#&c crestere tensiunii intr cr niene/<,r #e tu"'ur ri % n " c&! si !& rte, $e cee -i%&t&ni &s!&tic tre'uie c&rect t r %i$ re" ti# + re%re(int $i"uti extr ce") N in c &$it) cunu" rii in sect) extr ce") %re$&!in n t %ei) C u(e: $!inistr re ,resit un&r s&") s "ine i(&t&ne " % cientii cu insuficient ren " f" ti in f ( $e &"i,urie, nere$ucere c&res%un( t& re %&rtu"ui $e % " '&"n #ii cu insuf) ren " , secretie in $ec# t $e ADH 3secreti < $ec t n&r! " /< re 's) $e % e crescut /< cu!u" re %re$&!in n t -i$ric ., stfe" se ?un,e " -i%er-i$r t re, % extr ce"u" r 3& % rte. intr in sect) ce"/<-i%er-i$r t re ,"&' " 6. F r !&$ific ri "e t&nicit tii &s!&tice extr ce"u" re: ;. Des-i$r t re extrece"u" r n&r!&t&n Se %r&$uce %rin %ier$ere %ei si N in c ntit ti %r&%&rti&n "e, $in sect) extr ce"u" r : %rin -e!&r ,ii cute @ cr&nice, %rin %" s!&r ,ii 3" ni#) su%r f) rse., in -i%& "$&sterini !, t t ti!% c t nu este se#er) M nifest ri : se $ t&re ( -i%&#&"e!iei, sunt re%re(ent te in ,ener " $e e$e!e / -i%er-i$r t ri, extr ce") !&r!&t&ne %re$&!in n t in c&!% rti!entu" interstiti " Mec nis!e ,ener "e $e %r&$ucere e$e!u"ui: . crestere %resiunii -i$r&st tice " ni#) c %i" ru"ui, %r&$us $e : retenti urin r -i$r&s "in %rin -i%er "$&ster&nis! int "nit in insuf) c rfi c st,), insuf) -e% tic , sin$r&! nefr&tic, %rin st ( #en& s retr&,r $ 3 $e ex) in insuf c r$i c $r), $ t&rit AD ce nu %& te %re"u c ntit te n&r! " $e s n,e, se ?un,e " crestere %resiunii #en& se % n " ni#) c %i" re"&r un$e %resiune -i$r&st tic # creste1in insuf) #en& s cr&nic !') inf),%rin "ter re # "#e"&r #ene"&r si i!%"ic & crestere $e %resiune -i$r&st tic /<e$e! " !') inf) '. sc $ere %resiune c&"&i$+&s!&tice $et) $e -i%&%r&tiene!ii, ! i "es -i%& "'u!ine!ii, ce %&t fi %r&$use %rin: $eficit $e sinte( 3insuf) -e% tic ., %ier$ere ren " 3sin$r&! nefr&tic., %ier$ere $i,esti# 3, str&enter&% tie exu$ ti# ., sc $ere $r stic %&rtu"ui 3! "nutritie. c. sc $ere $ren ?u"ui "i!f tic " %ei interstiti "e re c r cter re,i&n ", se %r&$uce %rin '"&c re un&r st tii , n,"i&n re cu ce"u"e inf" ! t&rii, !et st tice, "euce!ice, %rin % r (iti 3fi" rii., cest ti% $e e$e! / "i!fe$e! In % t&"&,ie %& te % re & sc$ere $ren ?u"ui "i!f tic $e ex) in insuf) c r$i c $r) creste f) !u"t %resiune # n& s centr " )i) ,&"ire c n "u"ui t%&r cic in siste!u" #en&s centr " $e#ine $eficit r /<sc $ere $ren ?u"ui "i!f tic /<e$e! siste!ic) $. crestere %er!e 'i"it tii c %i" re int "nit " ni#) f&c re"&r inf" ! t&rii 3-ist !in , 'r $i8inin , %r&st ," n$ine. %& te fi cu c r cter siste!ic 3in s&cu" n fi" ctic c n$ se e"i'ere ( c ntit ti ! ri $e -ist !in ., in s&cu" -i%&#&"e!ic se e"i'ere ( !e$i t&ri cu %r&%riet ti -i%er%er!e 'i"i( nte Cl$si1ic$&e$ e'emel & i" 1u"ctie 'e su!&$1$t$ $1ect$t$# A. edeme generali&ate 7 sistemice +%r&$use %rin: crestere ,ener "i( t %resiunii -i$r&st tice intr c %i" re: %rin retentie ren " -i$r&s "in s u %rin st ( #en& s retr&,r $ , sc $ere %resiunii c&"&i$+&s!&tice %" s! tice)Necesit ctiune c&nc&!itent ce" %utin $&i f ct&ri % t&,eni cu %re$&!in nt unui , $eter!in & ten$int sc $erii #&"e!iei /<sti!u" re secr)$e ADH /< cti#) secr) $e renin , exces $e "$&ster&n si $e ADH ce #&r ! ri re 's ren "

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6. edeme regionale' e$e!u" !') inf) $in insuf) #en& s , "i!fe$e!e"e, scit +%& te fi c&nsi$er t e$e! re,i&n ", in %r&$ucere ei c&ncur @ c&ntri'uie: crestere %res) -i$r&s t tice " ni# c %i" r, -i%&%r&teine!i , sc $ere $ren ?u"ui "i!f tic %rin c %i" re %erit&ne "e si -e% tice t&t $ t) cresterii %resiunii " ni# siste!u"ui #enei %&rte C. edeme locale / e$e!e inf" ! t&rii, !ec nis!u" este re%re(ent t $e crestere %er!e 'i"it tii c %i" re "&c "e :. Hi%er-i$r t re extrece"u" r n&r!&t&n FIZIOPATOLOGIA META6OLISMULUI IONULUI DE POTASIU > este %rinci% "u" e"ectr&"it intr ce"u" r) C&ncentr ti s intr ce"u" r / ;4= !E,@",C&ncentr ti s extr ce"u" r / 0,2 K 2,2 !E,@" *&"uri: > re%r (int %rinci% "u" c&!%&nent &s!&" r " sect&ru"ui intr ce"u" r1 %e ' ( ,r $ientu"ui $e c&ncentr tie, > re ten$int $e iesi $in ce"u" 1 !entinere c&ncentr tiei n&r! "e intr ce"u" re N si > este re "i( t $e c tre %&!%e"e !') ce reintr&$uc > in ce"u" si sc&t N $iferent $e c&ncentr tie intre N si > st " ' ( %r&cesu"ui e"ectr&,enic $e c re $e%in$e cti#it te e"ectr&fi(i&"&,ic ce") !uscu" re si ner#& se /< > inter#ine in re%&" ri( re ce"u" r 1 &rice # ri tie intr ce"u" r c&ncentr tiei > # "ter ,r $ientu" $e c&ncentr tie Ic @ Extr ce" /< se # "ter excit 'i"it te neur&+!uscu" r > inter#ine in sinte( : insu"inei, ,"uc ,&nu"ui, STH+u"ui si in ,"ic&,rn&,ene( > % rtici% " ec-i"i'ru" ci$&+' (ic 3 %r&tein t $e > c re c&ncur cu HL %t) N " ni#e" ren ". Hi!e&! t$semi$# c&nc extr ce" < 2,2 !E,@" !ec nis!: ;. %&rt rescut $e > in nu!ite c&n$itii: $!inistr re %e c "e % renter " $e > in c ntit ti !&$er te, $ t in ti!% scurt /< -i%er8+e!ie $e& rece rinic-iu" necesit ti!% %t) e"i!in re, s u %t) c functi ren " este fect t %&rt %rin >C" f&"&sit in "i!ent tie %t in"&cui N C" %&rt %rin $!inistr re $e ! $ic !ente cu > 3 %enici"in G. %&rt %rin tr nsfu(ii cu s n,e c&nser# t, in c re c&ntinutu" in > este ! i ! re $ t) "i(ei un&r -e! tii %&rt %rin f&"&sire in "i!ent tie un&r c ntit ti ! ri $e fructe si "e,u!e :. sc $ere e"i!in ri"&r ren "e: I* cut @ cri&nic -i%& "$&ster&nis! /< sc $e re 's&rti $e N /< sc $e sc-i!'u" N @ > f&"&sire 'u(i# !e$ic !ent "&r nti "$&ster&nice $eficit ere$it r " !ec nis!u"ui secret&r $e > " ni#) TCD 0. iesire ! si# > $in ce"u"e: $istru,eri ce"u" re ! ri 3 tr u! tis!e, necr&(e, -e!&"i(e, rsuri, tr t !ent nti"euce!ic. st re $e ci$&( $ec&!%ens t f&"&sire 'u(i# un&r !e$ic !ente %recu! $i,it tice"e ce in-i' %&!%e"e N +> s u succini"c&"in ce ! reste %er!e 'i"it te !') -i%ert&ni &s!&tic extr ce"u" r ce $et) tre,ere %ei $in ce"u"e, $ r si > % r "i(i %eri&$ic f !i"i r 3ere$it r . / $isfunctie %&!%ei N @ > $e " ni#e"u" !usc-i"&r sc-e"etici C&nsecinte"e -i%er%&t se!iei: tu"'ur ri $e excit 'i"it te stenie !uscu" r , cre !%e !uscu" re /< % re(e !uscu" re /< % r "i(ii "e extre!it ti"&r steni !uscu" turii res%ir t&rii /< insuficient res%ir t&rie steni !uscu" turii nete$e /< % r "i(i functi&n " !uscu" turii , str&intestin "e ref"exe &ste&ten$in& se $i!inu te s u '&"ite tu"'ur ri $e c&!%&rt !ent $ t&rit fect rii ner#& se Hi! ! t$semi$# c&nc extr ce"u" r Q 0,2 !E,@" !ec nis!: ; . re$ucere %&rtu"ui: in nitie, ! " 's&rtie, exc"u$ere t&t " fructe"&r si "e,u!e"&r $in "i!ent tie : . crestere e"i!in rii $i,esti#e: # rs turi, $i ree, tu!&ri secret nte $e > fistu"e, 'u( $e " x ti#e 0 . crestere e"i!in rii ren "e: -i%er "$&ster&nis!, nefrit cu %ier$eri $e > 3ere$it r . : c&nst in crestere excesi# secretiei $e >, exces $e ,"uc&c&rtic&i(i, %&"iurii: initi " #e! -i%er%&t se!ie $ t&rit cresterii e"i!in rii $e % 1 $ c c&rect re se f ce cu % f r > /< $i"utie /< -i%&%&t se!ie , ci$&( tu'u" r $ist " /< in "i%s HL, se sc& te > %t) recu%er N f&"&sire 'u(i# un&r $iuretice ce in-i' re 's&rti N in se,!entu" su%eri&r 3 fur&se!i$, $iuretice ti (i$ice., cet& ci$&( $i 'etic 3 cet& ci(ii se e"i!in c s ruri $e N si >.

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7 . intr re > in ce"u"e: "c "&( $ec&!%ens t , secretie crescut $e insu"in s u $!inistr re $e insu"in L ,"uc&( in c ntit ti ! ri 3 insu"in sti!u"e ( % trun$ere ,"uc&(ei ince"u"e /< tren re %ei L N L >1 t&t insu"in sti!u"e ( %&!%e"e N @ >., % r "i(i -i%&8 "e!ic % r&xistic / $efect " %&!%e"&r N @H $e" ni#e"u" !uscu" turii sc-e"etice C&nsecinte: si!i" re cu -i%er8 "e!i , $ t&rit fect rii excit 'i"it tii, cti#it te c r$i c este tu"'ur t %rin % riti $e extr sist&"e tri "e, n&$ "e, t -ic r$ie, f"utter si fi'ri" tie #entricu" re /< !& rte) FIZIOPATOLOGIA *EGLA*II META6OLISMULUI HID*OSALIN ALDOSTE*ONUL, ADH+u" PEPTIDELE, NAT*IU*ETICE Tu"'ur ri"e re," rii se re "i(e ( $ t&rit fect rii secretiei "$&ster&nu"ui si ADH+u"ui) A) P$t l 2i$ $l' ste& "ului# ;. Excesu" $e !iner "&c&rtic&i(i: + Excesu" $e "$&ster&n / -i%er "$&ster&nis!: + Hi%er "$&ster&nis!u" %ri! r $eter!in t $e & c u( $in interi&ru" CS*, re%re(ent t $e un $en&! -i%ersecret nt, ! i r r $e un c rcin&!) $eter!in crestere re 's) $e N si % /< retentie -i$r&s "in , sti!u"e ( excreti $e HL si > /< -i%&8 "e!ie L ci$&( !et '&"ic /< si"'& mul c$&'i %$scul$&: crestere TA $ t&rit -i%er#&"e!iei tu"'ur re cti#it tii c r$i ce $ t -i%&8 "e!iei, si"'& m "eu &muscul$&: stenie !uscu" r , %ere(e @ % r "i(ii, '&"ire ref"exe"&r &ste&ten$in& se, $ t&rit -i%&8 "e!iei se %& te ?u!,e " nu!er& se cri(e $e tet nie $ t&rit ci$&(ei, si"'& m ! liu&ic: se %ier$e c % cit te $e c&ncentr re urinii, nu se %&r$uc e$e!e siste!ice E $eter!in t $e un f ct&r extrinsec CS* / -i%ersecretie $e renin : $et) $e sc $ere f"uxu"ui in rteri&" fere nt ex). -i%&#&"e!ie $ t&r t %ier$erii -i$r&s "ine -i%&#&"e!ie $ t&r t -e!&r ,ii"&r @ %" s!&r ,ii"&r ten$int $e -i%&#&"e!ie $ t) e$e!u"ui ,ener " c u( t $e IC s u IH sc $ere #&"u!u"ui efecti# circu" nt 3 IAS, sec-estr re s n,e"ui $in HT %&rt " ., &'structi rterei ren "e, !&$ific ri intr ren "e cu c r cter c&!%resi#, in c $ru" -i%er%" (iei % r tu"ui ?ust ,"&!eru" r Hi%er "$&ster&nis!u" secun$ r C&nsecint -i%er "$&ster&nis!u"ui %ri! r @ secun$ r c&nst in HTA, $ r c re nu % re int&t$e un ) . Excesu" $e %recurs&ri "$&ster&nici: % re $ t&rit $eficite"&r ere$it re $&u en(i!e: ;;+-i$r&xi" ( si ;5+ -i$r&xi" ( + $eficitu" $e ;;+ -i$r&xi" ( sc $e ni#e"u" c&rti(&"u"ui /< sti!u"e ( secre tie $e ACTH /< creste DOC1 sin,ur c "e ne fect t $e cest $eficit este ce sinte(ei H sexu "i /< #iri"it te %rec&ce + $eficitu" $e ;5+-i$r&xi" ( sc $e ni#e"u" $e c&rti(&n /< sti!u"e ( secre ti $e ACTH /< creste DOC L "$&ster&n, $ r u"teri&r #&! #e $& r exces $e DOC1 ceste $eficit fecte ( si c "e H sexu "i) '. Deficitu" $e !iner "&c rtic&i(i: ;. $eficit %ri! r %rin "ter re cut @ cr&nic : !ec nis! . sc $ere ! sei $e tesut ," n$u" r CS*: cut / insuficient CS* cut cu $eficite %e t& te ce"e trei "inii"e, / sin$r&!u" E ter-&use K Frie$ric-sen, / ,resiuni infecti& se ! i "es " c&%ii, c&!%"ic te cu CID3 se%tice!ii ,r #e ! i "es cu!enin,&c&c., / in$e% rt re c-irur,ic " CS* $ t&rit un&r tu!&ri ! "i,ne cr&nic / insuficient CS* cr&nic 3 '& " A$$is&n. $ t&rit T6C ," n$u" r s u re ctii"&r ut&i!une, ! i r r infectii"&r s u tu!&ri"&r '. nu!ite $eficiente ere$it re $e en(i!e i!%"ic te in sinte( !iner "&c&rtic&i(i"&r ex). $eficit $e :;+-i$r&xi" ( /< sc $e %r&$ucti $e !iner "&c&rtic&i(i, ce %r&#& c %ier$ere -i$r&s "in , -i%er8 "e!ie, ci$&( !et '&"ic 1 cest $eficit fecte ( si "ini ,"uc&c&rtic&i$ /< creste secreti $e ACTH ce # sti!u" c "e sexu " /< %u'ert te %rec&ce :. $eficit secun$ r %rin sc $ere cti#it tii *AA: este $ef %t $eficit secun$ r $ t&rit sc $erii secretiei $e renin + $eficit secun$ r cu HTA: ex). $eficit $e ;5+-ir&xi" ( sin$r&! Arn&"$ + He "B / re 's&rtie %r&xi! " $e N ex ,er t /< -i%er#&"e!ie /< sc $ere secretiei $e renien -i%& "$&ster&nis! + $eficit secun$ r f r HTA: ex). f&"&sire 'u(i# $e -e% rin s u $e su'st) -e% rin+"i8e, ce $e%ri! sensi'i"it te ce"u"ei ," n$u" re " AT II "ter re % r tu"ui ?ust ,"&!eru" r !&$ific re $e,ener ti# t&nusu"ui !uscu" r ner#&s si!% tic cec&ntr&"e ( secreti $e renin f&"&sire 'u(i# si %e ter!en "un, !e$ic !ente"&r ce sc $ secretie $e renin 3 +'"&c nte. s u ce in-i' tr nsf&r! re AT I +++< AT II 3 c %t&%ri". P$t l 2i$ ADH# E"i'er re ADH se f ce in c&n$itii $e -i%&#&"e!ie si -i%er&s!&" rit te ce"u" r ) Excesu" $e ADH: + -i%er+ADH c&!%ens t&r / c n$ #e! sti!u"i fi(i&"&,ici /< creste re 's&r'ti $e % /< c&rectere -i%&#&"e!iei @ -i%er&s!&" rit tii + -i%er+ADH % t&"&,ic / ADH crescut in c&n$itii"e c n$ nu este neces r re 's&rti $e % /< secretie in $ec# t , ce este %&r$us %rin sti!u"i ne-i%&#&"e!ici @ ne-i%er&s!&tici1 ex). $ere," re sinte(ei $e ADH in sensu" cresterii %rin "e(iuni cere'r "e f&"&sire $e !e$ic !ente ce sti!u"e ( nuc"eii su%r &%tic si % r #entricu" r, ne&%" s!e %u"!&n re ce %&t sint ti( si e"i'er

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c&!%usi se! n t&ri cu ADH, $ureri f) intense %&t c&n$uce " sti!u" re ref"ex -i%&t&n , %&i -i%er-i$r t re ,"&' " nuc"ei"&r /< -i%er-i$r t re extr ce"u" r

Deficitu" $e ADH: - sin$r&!u" %&"iuric $ t) nere 's&r'tiei %ei / $i 'et insi%i$: - DI ti%I / neur&,en, $ t&r t sc $erii e"i' r rii neur&-i%&fi( re ADH, $ t&rit un&r "e(iuni -i%&t " !ice @ -i%&fi( re 3 tr u! tis!e, tu!&ri, 'cese. - DI ti% II / nefr&,en, in c re c&ncentr ti $e ADH este n&r! " , $ r nu ! i exist sensi'i"it te tu'i"&r %t ADH $ t&rit re$ucerii nr) $e * %t) ADH, %rin $efect ere$it r s u $&' n$it 3%ie"&nefrit cr&nic se#er , !i"&i$&( , !ie"&! !u"ti%"u, int&xic tie cu c r$&n t $e Li s u f"&ruri. /< $es-i$r t re extr ce"u" r -i%ert&n , %&i $es-i$r t re ,"&' " &r, nis!u" re !ec nis!e $e c&!%ens re / %&"i$i%sie 3sti!u" re centru"ui setei . 1 cest nu functi&ne ( in $esert s u " c&! t&si) DIABETUL ZAHARAT Di 'etu" ( - r t este & '& " $e !et '&"is! cu e#&"utie cr&nic , c r cteri( t $)%)$)#) 'i&"&,ic %rin %ertur' re !et '&"is!u"ui ,"uci$ic 3e#i$enti t %rin -i%er,"ice!ie ' ( " %er! nent s u nu! i %rin sc $ere t&"er ntei " ,"uc&( . " c re se s&ci ( si %ertur' ri "e !et '&"is!u"ui "i%i$ic si %r&ti$ic, t& te $ t&rit $eficitu"ui 's&"ut s u re" ti# $e insu"in ) C" sific re eti&+% t&"&,ic : I. C" se c"inice + cu%rin$ ur! t& re"e c te,&rii: A. Di'etu" ( - r t c"inic ! nifest: c r cteristic este c ,"ice!i ' ( " este %este "i!ite1 e n&r! "e in !&$ %er! nent, inc"u$e ur! t& re"e ti%uri: ; . DZ I 3insu"iun&+$e%en$ent.: $eficit f) se#er 3 's&"ut. $e insu"in , ! ?&rit r re $eter!inis! ,enetic ere$it r, !ec nis!u" % t&,enic este ut&i!un, $e'ut in c&%i" rie @ $&"escent /<DZ ?u#eni" : . DZ II 3insu"in&+in$e%en$ent.: $eficit insu"inic ! i %utin se#er, re $eter!inis! ,enetic, nu este i!%"ic t !ec i!un, se s&ci ( frc#ent cu &'e(it te , $e'ut $u% 7=+72 $e ni /<DZ $e ! turit te 3 " $u"tu"ui. ; . L : . / DZ %ri! re 3cu $eter!inis! ,enetic. 0. DZ secun$ r / DZ s&cit cu "te c&n$itii % t&"&,ice %rici% "e"e c&n$itii % t&"&,ice ce %&t in$uce DZ $unt: $iferite fectiuni en$&crine cu $esc rc re $e -&r!&ni nt ,&nisti insu"inei 3-i%ertir&i$is!, -i%erc&rticis!., tr t !ente 'u(i#e $e "un, $ur t si cu $&(e ! ri $e !e$ic !ente ce sc $ secreti $e insu"in , s u sc $ efectu" insu"inei " ni#) tisu" r 3 cresc re(istent tisu" r " ctiune insu"inei. / !e$ic !ente cu %&tenti " $i 'et&,en 3%re% r te c&rti(&nice, %e ' ( $e -&r! tir&i$ieni, $iuretice ti (i$ice, +'"&c nte, ntic&nce% ti&n "e &r "e., % ncre tite se#ere ce se %&t extin$e si " % ncre su" en$&crin cu fect re tesutu"ui % ncre tic,secret&r $e insu"in 6. DZ c r cteri( t %rin sc $ere t&"er ntei " ,"uc&( +in f&r! us& r ,"ice!i ' ( " este n&r! " /<in c&n$itii ' ( "e re(er#& re"e $e insu"in sunt suficiente) +in su%r s&"icit ri "e secretiei % cre tice $e insu"in , re(er#e"e functi&n "e $e insu"in nu sunt suficiente /< ,"ice!i creste cu !u" ! i !u"t $ec t " &!u" s n t&s /<t&"er nt " ,"uc&( sc (ut ) +su%r s&"icit ri: -i%er,"ice!i %&st%r n$i " , -i%er,"ice!i %&st ,resi# 3$u% infectii se#ere @ tr u! tis!e. +in %r ctic , " un % cient sus%ici&n t $e stfe" $e DZ i se f ce un GOTT 3,"uc&se &r " t&"er nce test. +%rinci%iu" GOTT: se $!) ,"uc&( si se $et ,"ice!i ti!% $e :- " inter# "e $iferite $e ti!% C. DZ ,est ti&n " - % re " une"e ,r #i$e si $e &'ucei $is% re cu ter!in re s rcinii - %& te #e & f&r! us& r c r ct) %rin sc $ere t&"er ntei, s u c-i r f&r!e c"inic ! nifeste) II. C" se cu risc st tistic crescut cu%rin$ ce"e c te,&rii $e in$i#i(i ce #&r f ce, cu %r&' 'i"it te crescut , in #iit&r un DZ c r cteri( t %rin sc $ere t&"er ntei @c"inic ! nifest, %entru c intrunesc f ct&ri $e risc: ntece$ente ere$ut re $e DZ 3ti% I LII ., &'e(i 3ti% II ., en$&crin&% tii cu $esc rc re $e -&r!&ni nt ,&nisti i insu"inei, c&nsu! t&ri cr&nici $e !e$ic !ente cu %&tenti " $i 'et&,en DIBETUL ZAHARAT ti! I Se c r cteri(e ( %rintr+un $eficit 's&"ut $e insu"in ) Se %r ctic tr t !entu" $e su'stitutie cu insu"in /<DZ I / DZ insu"in&$e%) De'ute ( in c&%i" rie @ $&"escent ) In "i%s tr t !entu"ui se c&!%"ic cu cet&+ ci$&( $i 'etic ce %& te !er,e % n " c&! $i 'etic cet&+ ci$&tic /< !& rte) Se c r cteri(e ( %rin tri $ si!%t&! tic c" sic : %&"iurie, %&"if ,ie, %&"i$i%sie Deficitu" $e insu"in $uce " t&%ire tesutu"ui $i%&s, tesutu"ui !uscu" r sc-e"etic /< in$i#i(i f) s" 'i /<DZ s" ' 3DZ II / DZ ,r s .

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Mec nis!u" % t&,enic este i!un) D)%)$)#) -ist&"&,ic se c r cteri(e ( %rintr+& infi"tr re "i!f&%" s!&cit r in % ncresu"ui en$&crin) De se!ene sunt i!%"ic ti si f ct&ri ,enetici si !u"t ! i %utini f ct&ri $e !e$iu) Dintre f ct&rii ,enetici: existent un&r ,ene ce c&nfer %re$is%&(itie " $istru,ere ut&i!un ce" % ncre tice secret& re $e insu"in )Aceste ,ene % rtin siste!u"ui HLA, f" t %e cr&!&(&!u"4 3i!%"ic t in sint) c&!%"exe"&r ! ?&re $e -ist&c&!% ti'i"it te I si II)MCH+I este un c&!%"ex %re(ent %e !')tutur&rce")nuc"e te)MCH+I si MCH+II sunt unice %t) un in$i#i$) Siste!u" i!unit r rec) MCH+I " ce"u"e"&r /<& recun& ste stfe" c SSELFH si nu & t c )MCH+II exist %e su%r f t APC)In$i#i(ii %re$is%usi, u in c&nfi,ur ti "&r ,enetic nu!ite ,ene %re$is%&( nte: HLA+69, HLA+6;2, HLA+A;, HLA+D*:, HLA+DD0, HLZ+DE:, HLA+DE5, HLA+DE9, HLA+DT)S nse"e cresc cu c t re ! i !u"te stfe" $e ,ene %re$is%&( nte) Existent cest&e ,ene in$uce & serie $e !&$ific ri in str) MCH+I si MCH+II)C&ncret: MCH+I $e %e su%r f t ce" % ncre tice recun&sc si "e , in !&$ n&r! " A, % ncretic %e cere "e ex%un ce") i!un&c&!%etente intr+& f&r! i!un&,en , nu t&"er&,en )Existent ,ene"&r in$uce %re(ent %e su%r f t ce" MCH+II n&r! " /< ce") % ncre tice se c&!%&rt c APC) MCH+II n&r! ", "e , si ex%une " su%r f)A, % ncre tice,ce"u"e"&r i!un&c&!%etente) MCH+II n&r! " %& te exist si " ni# ! cr&f ,e"&r, stfe" ceste %&t recun& ste si "e,e ut&A, % ncre tice)Se %& te $ec" ns t t *IU 3/< ut&Ac+ nti% ncre tici., c t si *IC 3cu cti# re LTc ce in# $e ( si $istru, tesutu" % ncre tic.)Distru,ere este %r&,resi# /<t&t " /< $eficit 's&"ut) * r in $ec" ns re DZ I % r si f ct&rii $e !e$iu 3si in 'sent susce%ti'i"it tii ,enetice., si nu!e #irusuri ce tr&%is! % ncre tic 3C&xs 8ie, ru'e&"ic, ur"i n.)Aceste %r&$uc "ter ri "e ce") % ncre tice /<ex%inere nu!it&r ut&A, 3in !&$ nn&r! " ! sc te. /<ce") nu ! i sunt rec) c se"f /< e" '&r re $e Ac+ nti ce") % ncre tice)Une&ri exist se! n ri intre c&!%) !' #ir "e si "e !') ce") % ncre tice /<Ac+ nti#ir "i %&t ct) incrucis t: #irus L ce" % ncre tice, %e cere "e $istru,) DIABETUL ZAHARAT ti! II Se c r cteri(e ( %rintr+un $eficit $e insu"in ! i %utin s #er) De cee tr t) cu insu"in nu este &'"i, t&riu /< DZ II / DZ insu"in&in$e%en$ent) Are un $etre!inis! ,enetic ! i %utin 'ine $eter!in t) De &'icei nu se c&!%"ic cu cet&+ ci$&( ) Mec nis!u" % t&,enic nu este i!un&"&,ic) D)%)$)#) -it&% t&"&,ic nu exist infi"tr re "i!f&%" s!&cit r ) Se s&ci ( frec#ent cu &'e(it te )In &'e(it te, $ t) un& f ct&ri ne%reci( ti sc $e c % cit te ce") $i%& se, -i%ertr&fi te si -i%er%" (i te, $e c %t ,"uc&( )Astfe" ni#) ,"ice!iei creste /< sti!u" re secretiei % ncre tice $e insu"in ) L ince%ut, DZ II re c-i r -i%erinsu"inis!)Excesu" $e insu"in , tre%t t, %rin feee$+' c8 ne,)3 $&Fn+re,u" ti&n. $et) sc $ere f&r! re $e rece%t&ri tisu" ri %t) insu"in )Astfe", insu"in este in c ntit te crescut , $ r nu+si %& te re "i( efecte"e /< crestere si ! i !u"t ,"ic !iei /<& st!u" re si ! i %ut) secretiei $e insu"in /<se cre ( stfe" un cerc #ici&s) Tre%t t % re e%ui( re secret&rie $e insu"in /< -i%&insu"inis!u", c r cteristic DZ) Tesuturi"e c % t re(istent " ct) insu"inei) * r, cre stere re(istentei tisu" re " insu"in se %& te re ") si %rin $efecte "e rec) tisu" ri %t) insu"in , s u in %re(ent rece%t&ri"&r n&r! "i, $ r cu $efecte " ni#) !es ,eri"&r secun(i, s u in c n$itii"e secretiei unei insu"ine n&r! "e 3 re finit te sc (ut %t rec), c&n#ersi inc&!%"et %r&insu"inei in insu"in , %r&insu"in re 2P $in cti#it te 'i&"&,ic insu"inei.) DIABETUL ZAHARAT GESTATIONAL Pe ! sur # ns rii unei s rcini in !&$ n&r! ", % r !&$ific ri -&r!&n "e ce fecte ( si -&!e&st (i ) Creste secrettti $e insu"in $in c u( -i%er%" (iei ce" % ncre tice $ t $e c ntit ti"e crescute $e estr&,eni si %r&,ester&n) Creste re(istent tisu" r " ct) insu"inei $ t&rit ni#e"e"&r crescute "e -&r!&ni"&r nt ,&nisti insu"inei, ce c&ntr c re ( ct) cestei 3,"&c&c&rtic&i(ii, " ct&,enii %" cent ri.) IN !&$ &'isnuit, t&tusi se % stre ( un ec-i"i'ru) Exist sit) r re c n$ crestere re(istentei este %r&%&rti&n " ! i ! re $ec t crestere secretiei $e insu"in /< se inst "e ( $i 'etu" ,est ti&n ") De &'icei, $u% ter!in re s rcinii, cest ti% $e DZ $is% re) MECANISMELE DE ACTIUNE INT*ATISULA*E ALE INSULINEI Pre " 'i" re "&c fix re $e rece%t&ri s%ecifici !e!'r n ri) Tesuturi"e ce u & $ensit te crescut $e rec) insu"inici / tesuturi insu"in&$e%en$ente 3tes) $i%&s, tes) !uscu" r sc-e"etic, tes) -e% tic.) Du% fix re, c&!%"exu" insu"in + rece%t&r este intern "i( t 3#e(icu"e., i r insu"in isi exercit ef) t t ti!% c t exist "e, tur $inre e si rec)Tre%t t, c&!%"exe"e #in in c&nt ct cu "i(&(&!i, en(i!e"e %r&te&"itice "e cest&r $et se ( insu"in $e rece%t&r,& $e,r $e ( , i r rec) este re$ t !')

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Fix re insu"inei $e rec) s u este c % 'i" s in$uc cti# re ,u ni" tcic" (ei /< creste c ntit te $e GMPc 3!ese,er secun$. /< cti# re en(i!e"&r i!%"ic te in sinte(e / sintet (e 3 ,"ic&,en+sint t ( , sintet (e"e "i%i$ice si %e ce"e %r&ti$ice. /<insu"in este un -&r!&n n '&"i( nt)GMPc cti#e ( %r&tein+8in (e i!%"ic te in f&sf&ri" re @ $ef&sf&ri" re un&r en(i!e /< cti# re @ in-i' re en(i! tic ) Fix re insu"inei $e rec) sti!) e"i'erere $e C $e %e $iferite str)!'), i r crestere IC Mcit&%") in-i' $eni" tcic" ( /< sc $e r%&$ucti $e AMPc /< insu"in in-i' en(i!e"e AMPc/$e%en$ente 3f&sf&ri" ( "e. /<in-i' ,"ic&,en&"i( , "i%&"i( ) De se!ene insu"in sti!u"e ( si %&!% !') $e N @ >) De se!ene cti#e ( si & %r&te ( s&ci t !') ce $es%rin$e $in str) %r&teic !'), %e%ti$e ce %&t functi&n c !es ,eri secun(i i insu"inei) INSULINA SI META6OLISMUL GLUCIDIC IN DIA6ETUL ZAHA*AT Efecte"e sunt ! i "es " ni#e" -e% tic si !uscu" r) In c&n$itii fi(i&"&,ice, insu"in re %e !et ' ,"uci$ic ur! t&ere"e efecte: . sti!u"e ( % trun$ere intr ce"u" r ,"uc&(ei,%rin cti# re ex&8in (e"&r ce f&sf&ri"e ( ,"uc&( /< G+4+P ce %& te tr #ers !')ce") 3" ni# -e% tic cti#e ( ,"uc&+8in ( . '. sti!u"e ( c&nsu!u" intr ce"u" r $e ,"uc&( , %rin sti!u" re ,"ic&"i(ei $ t&rit cti# rii en(i!e"&r c-eie "e s "e 3f&sf&+fruct&+8in ( , %iru# t+8in ( . /<se !%"ific si suntu" %ent&(&+f&sf ti"&r /< ri'&( neces r sint $e c) nuc"eici LNADPH neces r sint $e c) ,r si si c&"ester&"u"ui, si cic"u"ui >re's $ t&rit cti# rii en(i!e"&r s "e c-eie 3%iru# t+$e-i$r&,en ( , citr t+ sint t ( , ! " t+$e-i$r&,en ( .) c. " ni#)tes) !uscu" r, insu"in sti!u"e ( $e%unere sur%"usu"ui $e ,"uc&( su' f&r! $e ,"ic&,en,%ri sti!u" re ,"ic&,en+sintet (ei $. in-i' ,"ic&,en&"i( in in-i' re cti#it tii f&sf&ri" (e"&r) e. " ni#) -e% tic, in-i' ,"uc&ne&,ene( ,%t) c in-i' ce"e 7 en(i!e c-eie: %iru# t+$ec&r'&xi" ( , f&sf&+en&"+%iru# t+ c r'&xi+8in ( , ;,4+$if&sf t ( , G+4+f&sf t ( ) TOATE ACESTE EFECTE CONDUC IN FINAL LA HIPOGLICEMIE In DZ, $ t) $eficitu"ui $e insu"in , ceste 2 !ec nis!e sunt %ertur' te /< efecte c&ntr rii /< HIPE*GLICEMIE) C n$ ,"ice!i este !i ! re $e ;9=!,P,c ntit te $e ,"uc&( fi"tr t ,"&!eru" r $e#ine !u"t %re ! re /<este $e% sit c % cit te ! xi! tu'u" r $e re 's&rtie ren " ,"uc&(ei /<c ntit te exce$ent r este e"i!in t %ri urin /<GLICOZU*IA) D r, cu! ,"uc&( re ef) &s!&tic, e"i!in re ren " $e ,"uc&( # ntren si & e"i!in re crescut $e % /< POLIU*IA) P&"iuri $et) $es-i$r t re extr ce") -i%ert&n 3creste IN M si IG"uM . /< -i%ert&ni extr , % $in sect&ru"intr ce" /< %rie$ere c&ntinu /< ten$int " $es-i$r t re ,"&' " /< sti!u" re !ec nis!u"ui setei /< in,esti $e c ntit) crescute $e % /< POLIDIPSIA) Sc $ere % trun$erii ,"uc&(ei in neur&nii $in centru" f& !ei /< sen( tir %er! nent $e f& !e /< POLIFAGIA 3neur&nii centru"ui f& !ei sunt sin,urii neur&ni insu"in&$e%en$enti.) I"S42I"A SI .31AB(2IS.42 P0(1I#IC I" #IAB3142 5A$A0A1 Fi(i&"&,ic, insu"in re ur! t& re"e ctiuni %e !et ' %r&ti$ic: . sti!u"e ( sinte( $e %r&teine %rin: + cti# re $e ADN si A*N+%&"i!er (e /< sti!u"e ( sinte( $e c nuc"eici + f #&ri(e ( "e, turi"e %e%ti$ice intre ) ) + sti!u"e ( f ct&rii $e tr nscri%tie + furni(e ( ener,i nec sint) %r&teice, %rin sti!u" re cic"u"ui >re's '. "i!ite ( c t '&"is!u" %r&teic, in-i' n$ & serie $e en(i!e "i(&(&! "e %r&te&"itice ce $e,re$e( $iferite %r&teine) In DZ I,cu $eficit se#er $e insu"in , sinte( $e %r&teine sc $e f) !u"t si %re$&!in c t '&"is!u" %r&teic 3 stfe" se ex%"ic t&%ire %r&,resi# ! se"&r !uscu" re, #in$ecere ne#&i& s "e(iuni"&r tisu" re si f&c re"&r inf" ! t&rii ,riscu" crescut %t) c&!%"ic tii infecti& se, %rin fect re sint) $e I,G, ni#e"e"e circu" t&rii crescute "e c t '&"iti"&r %r&ti$ici: uree, c) uric, cre tinin .) I"S42I"A SI .31AB(2IS.42 2IPI#IC I" #IAB3142 5A$A0A1 N&r! ", insu"in re ur! t& re"e efecte %e !et '&"is!u" "i%i$ic, $e " ni#) -e% tic si $i%&s: . sti!u" re sinte(ei $e c) ,r si, $ t&rit cti# rii en(i!ei c-eie: ceti"+C&A+c r'&xi" ( '. sti!u" re sint (ei $e TG $in c) ,r si si ,"icer&", $ t&rit cti# rii en(i!ei c-eie: TG+sint t ( c. sti!u" re sinte(ei $e c&"ester&", %rin cti# re en(i!ei -i$r&xi+ !eti"+,"ut !i"+C&A+re$uct ( $. in-i' "i%&"i( , %ri in-i' re "i% (ei e. in-i' !et '&"i( re &xi$ ti# AG $e " ni# -e% tic,%rin in-i' re en(i!ei ci"+ c rniti"+tr nsfer (

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f. sti!u"e ( f&r! re , " ni#) -e%tic, $e "i%&%r&teine / f&r! $e tr ns%&rt in circu" tie fr ctiuni"&r "i%i$ice1 $& rece sunt ne!isci'i"e in s n,e, sunt in#e"it $e %&+%r&teine cu c r cter -i$rfi" /<tr ns%&rt ,. sti!u" re " ni#) -e% tic sinte(ei $e ! t "i%i$ic1t&tusi ni#e"u" cest&r %r&$usi nu creste ,$e& rece este sti!u" t si !et ' tisu" r " cest&r 1$e ex);. sti!u" re en() en$&te"i "e "i%&+%r&tein+"i% ( /< -i$r&"i( TG /< AG L ,"icer&" /<% trun$ in ce") $i%& se uin$e rec&nstituie TG1 ex):. sti!u" re $e rec) %t "i%&%r&tine"e '&, te in c&"ester&" 3LDL. /<c %t re ! i 'un si f&"&sire c&"ester&"u"ui %t str)!' si su'!') In DZ : + sinte(e"e "i%i$ice se re$uc "i%&"i( nu este in-i' t , c-i r este %uternic sti!u" t /<e"i'er re in circu" tie un&r c ntit ti crescute $e AG /<" ni#) -e% tic 3in "i%s insu"inei. cesti sunt !et ' %e c "e &xi$ ti# /< creste c ntit te $e ceti"+ C&A)D t&rit $eficitu"ui se#er $e insu"in , ceti"+C&A nu %& te intr c&res% in 0 c i !et '&"ice i!%&rt nte,$e%en$ente $e insu"in : >re's, sinte( $e AG si sinte( $e c&"ester&"1 /< ceti"+C&A # ur! "t c "e, insu"in&in$e%en$ent / sint ( -e% tic c&r%i"&r cet&nici/< CETOGENEZA 3 c) -i$r&xi+'utiric, cet&n , c)cet& cetic. Sinteti( ti in c ntit ti crescute,este $e% ssit c % cit te $e uti"i( re tisu" r /< cu!u" re "&r in &r,) /< ci$&( !et '&"ic / cet& ci$&( $i 'etic ) In c (u" $eficitu"ui se#er, este si ! i !u"t sc (ut sint $e "i%&%r&teine, este si ! i crescut ni#e"u"circu" nt, $e& rec sc $e si !et '&"is!u" %eriferic /<risc crescut " c&!%"ic tii ter&! t& se) C-i r si in st $ii"e initi "e "e DZ II, ni#) "i%i$e"&r este crescut, %t) c excesu" $e insu"in sti!u"e ( f&r!ere $e "i%&%r&teine cu c&ntinut ! re $e TG) COMPLICATIILE DIA6ETULUI ZAHA*AT : Di 'etu" ( - r t se ins&teste $e c&!%"ic tii cute si cr&nice C(.P2ICA1II23 AC413' sunt re%re(ent te $e: ;. cet $ci' 0$ 'i$/etic$9 cu 1 $m$ s$ e6t&em$. c m$ 'i$/etic$ $ci' tic$# - c&!%"ic tie frec#ent DZ I,c r cteri( t $e $eficit se#er $e insu"in - " un % cient cu DZ I exist c&n$itii % t&"&,ice c re, su%r %use %este f&n$u" $eficientei se#ere $e insu"in , %r&$uc & ccentu re cestei , si %rin ce st %&t fi fect&ri $ec" ns t&ri i c t& ci$&(ei si res%ecti# i c&!ei $i 'etice cet& ci$&tice) - %rinci% "e"e c&n$itii % t&"&,ice su%r %use $eficientei $e insu"in sunt: . $iferite"e c&n$itii ,res&,ene+$e& rece in c $ru" re ctiei siste!ice %&st resi#e se e"i'ere ( c ntit ti ! ri $e -&r!&ni $e stres $in cre f) !u"ti u %r&%riet ti nt ,&niste insu"inei ex).+ cci$ente"e # scu" re 3AAC, cci$ente"e c&r&n riene cu IMA., tr u! tis!e"e f) se#ere, infectii"e se#ere 3'r&n-&%neu!&nii ,r #e, se%tice!ii, s&cu" t&xic&se%tic., rsuri"e intinse si %r&fun$e, '$&!enu" cut 3&c"u(ie intestin " , -e!&r ,ie $i,esti# , % ncre tite cute., %ier$eri #&"e!ice f) ccentu te 3%ier$eri e"ectr&"itice, # rs turi, sin$rt& !e $i reice, -e!&r ,ii se#ere., inter#entii"e c-irur,ic "e f) !%"e '. s rcin +$e& rece in s rcin cresc ni#e"uri"e in&r -&r!&ni nt ,&nisti insu"inei 3ex) ,"uc&c&rtic&i(ii, -&r!&nu" " ct&,en %" cent r. c. f&"&sire in !&$ 'u(i# un&r !e$ic !ente c re re$uc ccentu t secreti $e insu"in s u ! resc re(istent tisu" r " ctiune ei 3ex) %re% r te c&rti(&nice, $iuretice"e ti (i$ice, +'"&c nte, $i (&xi$. $. e!&tii"e f) %uternice, tr u!e"e %si-ice+$e& rece se ins&tesc $e $esc rc re in c ntit ti crescute -&r!&ni"&r $e stres ce sunt nt ,&nisti insu"inei e. intreru%ere tr t !entu"ui cu insu"in , s u efectu" unui tr t !ent inc&rect cu insu"in 3$&(e nes tisf c t& re. f. neres%ect re re,i!u"ui -i%&,"uci$ic + t& te ceste c&n$itii, %e f&n$u" unui DZ I $uc " ccentu re -i%&insu"ine!iei /< sti!u" re cet&,ene(ei /< cet& ci$&( + s t re $e cet& ci$&( es te initi " c&!%&ns t %ri !ec)c" sice: . t !%&n re excesu"ui $e HL 3%r&#enit $in $is&ciere cet& ci(i"&r., $e c tre 'e(e"e t !%&n intr ce"u" re 3N HCO 0 . si extr ce"u" re 3%r&tein tu" $e >. '. -i%er#enti" tie $eter!in t $e sti!u" re centru"ui res%ir t&r $e cetre excesu" $e H L $in s n,e /< se e"i!in & c ntit te crescut $e CO: /< "c "&( res%ir tirie secun$ r cu c r cter c&!%ens t&r1%e ! sur ce se ,r # e ( ci$&( , res%ir ti i s%ectu" res%ir tiei ci$&tice >us! u" / ins%ir f) %r&fun$ ur!et $e & scurt % u( , $u% c re sur#ine & ex%ir tie f) scurt si cic"u" se rei 1 "e, t $e res%ir ti $in cet& ci$&( , ce st re un !ir&s $e !ere %utre$e$ t&rit cet&nei / c&!%us #&" ti" cese e"i!in %rin res%ir tie) c. inter#enti rinic-iu"ui, ce isi ! reste secreti si excreti $e HL , inc"usi# su' f&r! $e !&ni&,ene( , in % r "e" cu crestere re,ener rii si recu% r rii N HCO0 in s n,e) - $ t&rit f %tu"ui c $eficitu" $e insu"in este f) %uternic si $esf sur rii cet&,ene(ei intr+un rit! cce"er t, !ec nis!e"e c&!%ens t&rii sunt $e% site $e c tre -i%er%r&$ucti $e c&r%i cet&nici /< creste f) !u"t cet&ne!i si cet&(uri /< $ec&!%ens re / P-+u" sc $e su' "i!it "e n&r! "e) - st re $e $ec&!%ens re se c r cteri(e ( %rin efecte"e n&ci#e ce st u " ' ( suferintei cere'r "e, $uc n$ in fin " " inst " re c&!ei cet& ci$&tice) - & ci$&( ,r # : sc $e r s%unsu" # scu" r " sti!u"ii # s&c&nstrict&ri # s&$i" t tie %eriferic /< sc $ere TA, $e%ri! c&!tr cti"it te !i&c r$ic /< sc $e DC, sc $ere TA si DC $uce " -i%&%erfu(ie tisu" r , inc"usi# cere'r " si in fin " " -i%&xie cere'r " , $e%ri! cti#it te !u"t&r siste!e en(i! tice, inc"usi#, " ni#e" neur&ne" centr " /< ,r # re %ertur' ri"&r !et '&"ice cere'r "e /< ,r # re suferintei cere'r " , $e%ri! cti#it te %&!%e"&r !') $e N si > /<, ! "$istri'uti c&nsecuti# N si > /< "ter re %r&cesu"ui e"ectr&,enic n&r! ")

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- in ,ener " st re $e c&! $i 'etic cet& ci$&tic se inst "e ( c n$ %H+u" sc $e su' 5,:=) - " inst " re c&!ei % rtici% si "ti f ct&ri, "e, ti $irect @ in$irect $e $eficitu" se#er $e insu"in : R-i%er,"ice!i ! rc t $ t&rit $eficitu"ui se#er $e insu"in , ,"ice!i tin,e # "&ri < 7==+2==!,P, % re stfe" si & ,"ic (urie f) ! re, c re " r n$u" ei $eter!in ntren re unei %ier$eri i!%&rt nte $e % , %ier$eri"e $e % %rin %&"iurie sunt ,r # te si %rin cee c t re se#er $et) irit re !uc& sei , stice, ?un, n$u+se " # rs turi 'un$ente) t& te %ier$eri"e -i$rice nu ! i %&t fi c&!%ens te %rin !ec nis!u" setei si %&"i$i%siei /< ten$int " $es-i$r t re se tr nsf&r! intr+& $es -i$r t re ! nifest , ce ccentue ( suferint cere'r " ,) un & re c re ti!%, creieru" este %r&te? t i!%&ti# $es-i$r t rii $e& rece neur&nii c&ntin su'st) &s!&tic cti#e / &s!&"i i$i&,eni, ce !entin % intr ce"u" r, c n$ %resiune &s!&tic in sect&ru" extr ce") este f) ! re 3$ t&rit -i%er,"ice!iei extre!e si -i%ern tre+ !iei re" ti#e., c % cit te &s!&"i"&r i$i&,eni este $e% sit /<$es-i$ret re cere'r " , ce ccentue ( tu"'ur ri"e !et '&"ice neur&n "e Rtu"'ur ri i&nice 3 in s%eci " "e N si >. >: +se %ier$e in c ntit ti f) ! ri %e ce"e urin r $ t&rit :%&"iuriei &s!&tice in$us $e ,"ic&(urie -i%er "$&ster&nis!u"ui secun$ r3$et) $e $es-i$r t re extr ce") si -i%&# "e!iei ren "e ce sti!u"e ( secreti $e renin ., f&r! rii s ruri"&r $e > cu ci$u" cet& cetic si +-i$r&xi+'utiric,ce se e"i!in in c ntit ti f) ! ri in st re $e cet& ci$&( ) In st re $e cet& ci$&( , initi " >+e!i este f) ! re $e& rece iesiri"e $e > $in ce"u"e sunt sti!u" te %rin f %tu" c t !%&n re excesu"ui $e H L $e c tre %r&tein tu" $e > $uce " cre re unui ,r $ient $e c&ncentr tie intre ce" si s% t) extr ce",,r$'ient ce # !&'i"i( stfe" > $in ce"u" , >+e!i este e#i$ent $e& rece sunt in-i' te %&!%e"e !') $e N @ > /<> iesit $in ce"u" nu ! i %& te fi recu%er t) %ier$eri"e $e > %rin urin c&!tinu , $ r se f c %e se ! > intr ce") /< c %it "u" intr ce") $e > se re$uce $r stic /< >+e!i %e se ! iesirii nu ! i este !entinut /< sc $ere >+e!iei /< -i%&%&t se!ie, -i%er @ -i%&>+e!i sunt n&ci#e, ccentu n$ in !&$ $irect @ in$irect suferint cere'r " , in !&$ in$irect, cti&ne ( %rin %r&$ucere $e tu"'ur ri ,r #e $e rit! c r$i c /< sc $ere DC/<sc $ere %erfu(iei cere'r "e) in !&$ $irect, cti&ne ( %rin "ter re %r&cesu"ui $e e"ectr&,ene( " ni#) neur&n ") . N Kiniti " ,in c t& ci$&( , re & # ") crescut " ni#) %" s! tic,$e& rece %rin %&"iuri i!%&rt nt se %ier$e %re%&n$erent % si nu N /< -i%erN +e!ie re" ti# , ce c&ncur " -i%er&s!&" rit te extr ce") /< f ct&r $et) in $es-i$r t re ce"u" r , %e ! sur ce cet& ci$&( se ,r #e ( , N tin$e s se re$)/< -i%&N +e!ie), !ec nis!e"e %rin c re sc $e N : %ier$ere un&r ! ri c ntit ti $e N su' f&r! $e s ruri "e c) cet& cetic si +-i$r&xi+'utiric, stere $e ci$&( se#er in-i'e %&!%e"e !') $e N @ > /< N ce intr in ce") nu # ! i %ute fi ex%u"( t /<N +e!i se re$uce %rin sec-estr re N in sect&ru" ce"u" r, tu"'ur ri"e N c&ncur " "ter re %r&cesu"ui $e e"ectr&,ene( , %e ! sur ce sc $e N +e!i ,-i%er&s!&" rit te extr ce") $i!inu /< tr ,ere %ei c tre sect&ru" extr ce") Di!inu , tu"'ur ri -i$r&&s!&" re c&nsecuti#e O$ t inst " t c&! %rin t& te ceste !ec nis!e, in "i%s tr t !entu"ui $ec# t, st re $e $es -i$r t re se ,r #e ( &$ t cu $is% riti !ec nis!u"ui setei, %e ! sur ccentu rii c&!ei, sur#ine % r "i(i centir"&r #it "i cu EXITUS) *) c m$ 'i$/etic$ 5i!e& sm l$&$ 1$&$ cet $ci' 0$. - c&!%"ic tie cut ce sur#ine %e f&n$u" unui DZ II - se c recteri(e (e $)%)$)#) 'i&"&,ic %rin:R-i%er,"ice!ie <7==!,P, -i%er&s!&" rit te %" s! tic cu # "&ri <07=!&s!&"i@", $es-i$r t re %r&fun$ , 'sent cet& ci$&(ei) A'sent cet& ci$&(ei se ex%"ic $e& rece $eficitu" $e insu"in nu este t t $e se#er, c in DZ I, $ r t&tusi suficient $e ! re %t) %r&$uce & -i%er,"ice!ie ccentu t , ur! t $e ,"ic&(urie si %&"iurie! rc t si c&nsecuti# cestei , & $es-i$r t re se#er ce st " ' ( suferintei cere'r "e) L un % cient cu DZ II, c re, $ t) -i%er,"ice!iei si ,"ic&(uriei, re ten$int " $es-i$r t re ,"&' " , $ c % r f ct&ri ce %&t ccentu %ier$eri"e -i$rice, !ec nis!u" setei si %&"i$i%si nu ! i sunt suficiente %t) c&%eri %ier$eri"e /<ten$int se tr nsf&r! in $es-i$r t re ! nifest ) Du% !&$u" in c re cti&ne ( , f ct&rii ce %r&$uc in !&$ su%"i!ent r %ier$eri $e % %&t fi ,ru% ti stfe": ;. f ct&ri ce cti&ne ( in$irect: 3,"ice!i /< ,"ic&(uri /< %&"iuri . . f ct&ri ce ccentue ( -i%er,"ice!i %rin sc $ere su%"i!ent r secretiei $e insu"in ex).+% ncre tite cute ce fecte ( si tesutu" +% ncre tic, intr ru%ere tr t !entu"ui cu nti$i 'etice &r "e, f&"&sire un&r !e$ic !ete c : +'"&c nte, $iuretice, ti (i$ice, $ifeni-i$ nti&n ,$i (&xi$ '. crestere %r&$uctiei $e ,"uc&( $ t) sti!u" rii ,"uc&ne&,ene(ei -e% tice, fie %rintr+un exces $e n tur en$&,en $e c&rtic&ster&i(i 3ex) -i%erc&rticis!., fie %rintr+un excesex&,en $e %re% r te c&rti(&nice 3 ceste cresc ,"uc&ne&,ene( si sc $ c tiune insu"inei " ni#) tisu" r.)+ c. sc $ere uti"i( rii ,"uc&(ei $e c tre tesuturi ex).in st ri"e $e -i%&ter!ie $. %&rt crescut $e ,"uc&( %rin neres%ect re re,i!u"ui -i%&,"ice!ic :. f ct&ri ce cti&ne ( $irect: . f&"&sire 'u(i# $e $iuretice '. '&"i fe'ri"e cu %&"i%nee @ tr ns%ir tii c. , str&enterite cute $. rsuri intinse e. -e!&r ,ii - %rin t&ti cesti f ct&ri st re $e $es-i$r t re $e#) ! nifest %rin $e% sire !ec nis!u"ui sete+%&"i$i%sie)

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- suferint cere'r " se $ t&re ( : $es-i$r t rii extr ce"u" re, sc $erii %erfu(iei cere'r "e, $es-i$r t rii neur&n "e, c re % re $& r tunci c n$ este $e% sit c % cit te &s!&"i"&r i$i&,eni cere'r "i %rin -i%er&s!&" rit te extr ce" $ t $e -i%erN + e!ie si -i%er,"icenie - si in ce st c&! % rtici% si tu"'ur ri"e $e N si >: . > + " fe" c " c&! 'i 'etic cet& ci$&tic + sin,ur $iferent este ce > iese cu tr nfer $e % ce"u" r c tre sect&ru" extr ce"u" r) N K r ! ne " & # ") crescut in s n,e, s%re $e&se'ire $e c&! cet& ci$&tic 3in c re tin$e s sc $ ., $e& rece: nu exist %ier$eri su%"i!ent re $e N %e c "e ren " su' f&r! $e s ruri nu exist ten$int " sec-estr re N in sect&ru" intr ce", $e& rece %&!%e"e !') nu sunt fect te 3$e cee &s!&" rit te este !u" ! i ! re. C(.P2ICA1II C0("IC3' Sunt re%re(ent te $e: ;. ! cr& n,i&% ti $i 'etic , :. !icr& n,i&% ti $i 'etic 3 n,i&% ti $i 'etic / "ter re %erete"ui # scu" r, c&nsecuti# i!%&rt nte"&r tu"'ur ri !et '&"ice in$use $e $eficitu" $e insu"in ). () M$c& $"2i !$ti$ 'i$/etic$ - $ese!ne ( fect re # se"&r $e c "i$ru ! re si !i?"&ciu,in s%eci " rtere"&r) - %rinci% "e !ec nis!e sunt: ;. "ter re !et '&"is!u"ui "i%i$ic R % riti unei -i%er"i%e!ii,$ t&rit ni#e"u"ui crescut $e "i%&%r&teine circu" nte)3cresc t t ce"e '&, te in c&"ester&"+ LDL+ c t si ce"e '&, te in TG en$&,ene+ALDL+ si ex&,ene+ c-i"&!icr&ni.1 R$ t&rit ni#e"u"ui ! re $e c&"ester&", % re tre%t t & inc rc re cu c&"ester&" !') ce"u" re en$&te"i "e /< ceste isi %ier$ f"exi'i"it te si %e !') $e#enit stfe" ! i ri,i$ %&t % re !u"t ! i us&r "e(iuni su' ctiune F !ec nice f"uxu"ui s ,#) R&$ t cu % riti cest&r !icr&"e(iuni, se $ec" nse ( & retr ctie ce" en$&te"i "e cu ! rire ?&nctiuni"&r interen$&te"i "e /< creste %er!e 'i"it te en$&te"iu"ui reteri "1 R"e(iuni"e en$&te"i "e sun cc) si $e c ntit ti"e crescute $e "i(&"ecitine c re %r&#in $in !et '&"is!u" %eriferic " "i%&%r&teine"&r '&, te in TG, ce u %&tenti " cit&t&xic R$ t&rit "e(iuni"&r en$&te"i "e se sti!u"e ( ," "&cu" cest&r $er re si ,r , re %" c-et r /< !icr&tr&!'usuri1 R cest %r&ces tr&!'&,enetic este % rte %r&cesu"ui $e ter&sc"e+ r&( ,initi t $e excesu" $e "i%i$e $in circu" tie) R%rin crestere %er!e 'i"it tii en$&te"i "e trec $in s n,e in s% tiu" su'en$&te"i " c ntit ti ! ri $e ! t) "i%i$ic, %rintrec re si LDL,'&, te in c&"ester&"1 R! cr&f ,e"e # scu" re $in %erete, u rece%t&ri %t) LDL, "e c %te ( si se cti#e ( !et '&"ic /< ince% s e" '&re(e: cit&c-ine, GF 3ce sti!u"e ( -i%ertr&fi tunicii !uscu" re # scu" re., f ct&ri c-e!et ctici ce tr , t tr&!'&cite 3 ccentu n$ %r&cesu" tr&!'&,enic. c t si !&n&cite 3ce se #&r tr nsf) in ! cr&f ,e, !%"ific n$ %r&cesu"., s%ecii re cti#e $e &xi,en c re " r n$u" "&r ccentue ( "e(iuni"e en$&te"i "e1 ceste s%ecii re cti#e &xi$e ( LDL su'en$&te"i "1 LDL &xi$ te sunt ! i us&r c %t te $e ! cr&f ,e,ce stfe" se #&r cti# ! i us&r fen&!ene inf" ! t&rii in %erete"e # scu" r %rin c re se ut&intretin si se ,r #e ( "e(iuni"e # scu" re) cu!u" re $e ! t)"i%i$icin %erete"e # scu" r, -i%ertr&fi tunicii !uscu" re si %r&cesu" tr&!'&,enic $eter!in in,r&s re %erete"ui # scu" r: /< $i!inu re "u!enu"ui # scu" r /<tu'ur ri $e n tur isc-e!ic in $iferite terit&rii/<crestere ri,i$it tii # scu" re /< crestere re(istentei # scu" re %eriferice /< HTA/< ccentu re "e( en$&te"i "e) :. G"ic&(i" re %r&teine"&r $in %erete"e #s cu" r: - re "&c ,"ic&i(i" re in s%eci " c&" ,enu"ui # cu" r 3re ctie neen(i! tic intre ,"uc&( si ,r) !in& $in str) " ntu"ui %&"i%e%ti$ic.) + ni#e"u" ,"ice!iei fiin$ ri$ic t, ,"ic&(i" re este ccentu t ) - c&" ,enu" # scu" r ,"ic&(i" t isi sc $e s&"u'i"it te /< $e#ine ri,i$ /< %erete"e # sc $e#ine ri,i$) - %r&cesu" $e ,"ic&(i" re se s&ci ( si cu re ctii $e &xi$ re, $et) $e e"i'er re $e r $ic "i "i'eri i &xi,enu"ui /<c&!'in ti ,"ic&(i" re+&xi$ re / ,"ic&xi$ re) - c-i r si LDL su'en$&te"i " este su%us ,"ic&xi$ rii /< ceste se c&r t s f us&r $e str) # sc) 3str)c&" ,enu"ui fiin$ e in s si ,"ic&xi$ t . /<creste ri,i$it te # su"ui si %e cest c "e) - LDL ,"ic&xi$ te u efect c-e!&t ctic 3 /< in$irect intretin %r&cesu" inf" ! t&r. si sti!u"e ( ,re, 'i"it te %" c-et r 3/<sti!u"e ( %r&cesu" tr&!'&,enic $e " ni# "e() ter&sc"er& se) 0. !et '&"i( re ,"uc&(ei, $e c tre ce"u"e"e $in %erete"e # se"&r %e c i insu"in&in$e%en$ente, in c&n$itii"e $eficitu"ui $e insu"in - % trun$ere ,"uc&(ei in ce"u"e"e # sc) nu este $e%en$ent $e insu"in , $e cee e este f) !u"t ! rit ) - !et '&"i( re ei %e c "e ,"ic%"i(ei si cic"u"ui >re's e0ste ins $e%en$ent $e insu"in ) - in c&n$itii"e unui $eficit $e insu"in , c ntit ti"e ! ri $e ,"uc&( ce u % truns in ce"u"e"e # sc) #&r f&rt "te c i !et '&"ice insu"in&in$e%en$entesi nu!e:

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. c$le$ ! li l: %r&$uce $&i "c&&"i %&"icic"ici: s&r'it&" fruct&(&+;+P, en(i!e"e sunt: "$&(&re$uct ( , s&r'it&"$e-i$r&,en ( 1 ce st ce"e este -i%er cti# nu! i in tesuturi"e ce %re(int ceste en(i!e:+ce"u"e"e $in %eretii # se"&r ! ri, ce"u"e"e $in te c Sc-F n, ce"u"e"e $in crist "in +s&r'it&"u" si fruct&(&+;+P sunt c&!%usi ,reu $ifu(i'i"i /< se cu!u"e ( in ce"u"e"e res%ecti#e, si fiin$ in ce" si ti!% si &s!&tic cti#i, $eter!in cu!u" re -i$ric i!%&rt nt in ce"u"e"e res%ecti#e /<-i%er-i$r + t re % n " $e,enerescent -i$ric cest&r ce"u"e tu!efiere -i$ric ce"u"e"&r # scu" rec&ntri'uie " in,r&s re %erete"ui # scu" r /<$i!inu re si ! i cc) "u!enu"ui, %recu! si s%&rire ri,i$it tii # su"ui) +$e,enerescent -i$ric este res%&ns 'i" $e & % rte neur&% tiei $i 'etice 3 fect re tecii Sc-F n.si c t r ctei $i 'etice 3 fect re crist "inu"ui. '. c$le$ $ci'ului 2lucu& "ic: c ntit ti ! ri $e ,"uc&( sunt tr nsf&r! te excesi# in c) ,"ucur&nic, c re $uce " cu!u" re excesi# $e !uc&%&"i( - ri$e in %erete"e # sc) c re #&r s%&ri in,r&s re cestui , $uc n$ " & si ! i ccentu t $i!inu re "u!enu"ui, si & ! i s%&rit ri,i$it te %erete"ui # scu" r - ! nifest ri"e ! cr& n,i&% tiei $i 'etice $eri# $in: sc $ere "u!enu"ui # scu" r, crestere re(istentei # scu" re %eriferice cu %&r$ucere HTA - %rinci% "e"e ! nifest ri sunt: c r$i&% ti isc-e!ic , % n " ICI si cci$ent inc-e!ic, AAC, ce %& te fi $e n tur inc-e!ic -e!&r ,ic , HTA cc) %rin F !ec nic %r&cesu"ui ter&sc"er&tic nefr& n,i&sc"er&( /<insuf) *en " , AAC, IC, sin$r&! $e isc-e!ie %eriferic ++++se $ t&re ( fect rii !') inferi& re, % n " necr&( /<, n,ren /< !%ut tie *) Mic& $"2i !$ti$ 'i$/etic$# - $ese!ne ( fect re # se"&r $e c "i'ru !ic, in s%eci " rteri&"e"&r si c %i" re"&r) - !ec nis!e: . f&"&sire $e c tre ce"u"e"e $in %erete"e # se"&r unei c i $e !et '&"i( re ,"uc&(ei,insu"in&in$e%en$ent , si nu!e, c "e c) ,"ucur&nic /< cu!u" re $e !uc&%&"i( - ri$e in %&erete"e # scu" r /< sc $ere "u!enu"ui # scu" r si crestere ri,i$it tii %erete"ui # scu" r1 cu! %erete"e # se"&r !ici este in !&$ n&r! " ! i ri,i$, ccentu re cestei ri,i$it ti # $eter!in & #u"ner 'i"it te crescut cestui terit&riu # scu" r " % riti $e !i&cr&"e(iuni /< % riti $e !icr&tr&!'usuri /< &'structi c&!%"et "u!enu"ui /< fen&!ene $e necr&( ) '.,"ic&(i" re c&" ,enu"ui $in %erete"e # scu" r 3#e(i ! cr& n,i&% ti . /< sc $ere s&"u'i"it tii c&" ,enu"ui /< crestere ri,i$it tii %erete"ui # scu" r) c. ,"ic&(i" re H' /< creste finit te ei %t) &xi,en /< i" ce$e ( ! i ,reu " ni#) tisu" r /< -i%&xie tisu" r ) $.sti!u" re ,"ic&"i(ei n er&'e in tesuturi"e insu"in&in$e%en$ente /< creste %r&$ucti $e c) " ctic /<sc $e # "& re %H+ u"ui /< % re & c %i" r&$i" t tie in % r "e" cu crestere %er!e 'i"it tii c %i" re /< sc $e #ite( $e circu" tie s n,e"ui in c %i" re"e res%ecti#e1 crestere %er!e 'i"it tii c %i" re %er!ite extr #& ( re -i$ric c tre interstitii /< creste # sc&(it te s n,e"ui /<#ite( $e circu" tie s n,e"ui in c %i" re se re$) si ! i !u"t /) s t( c %i" r , c re cc) fen&!ene"e -i%&xice ce %&t %r&#&c "e(iuni en$&te"i "e %e su%r f t c r&r se $e(&"t !icr&tr&!'usuri /< &'tur re "u!enu"ui /< necr&( terit&riu"ui $eser#it $e c %i" ru" res%ecti#) - %rinci% "e"e ! nifest ri "e !icr& n,i&% tiei sunt: retin&% ti $i 'etic /<&r'ire ,"&!eru"&sc"er&( $i 'etic 3 fect re c %) ,"&!eru" re. /< sc $ere c&nsi$er 'i" fi"tr rii ,"&!eru" re /< insuficient ren " fect re rteri&"ei ferente /< sc $ere %erfu(iei ren " /< si!u" re S*AA /< sti!u" re retentiei $e N @ H :O /< ,r # re HTA neur&% ti $i 'etic 3 fec tre ner#i"&r %rin !icr& n,i&% ti # ssei ner#&ru!.1 este t t s&! tic c t si #e,et ti# 1 neur&% ti s&! tic $e ti% sen(iti# 3se %ier$e ! i "es sensi'i"it te %r&%ri&ce%ti# ., neur&% ti s&! tic $e ti% !&t&r 3se ! nifest %rin sc $ere f&rte !uscu" re si %rin '&"ire ref"exe"&r &ste&ten$in& se. neur&% ti #e,et ti# : + %e %" n c r$i&# scu" r: t -ic r$ie c&nst nt -i%&tensiune &rt&st tic 3 fect re ' r&rece%t&ri"&r. + %e %" n $i,esti#: st ( , stric si intestin " ce f #&ri(e ( # rs turi"e + %e %" n ur&,enit ": sc $ere !&ti"it tii #e(ic "e cu e# cu re inc&!%"et s t ( urin r ce f #&ri(e ( infectii"e urin re " ' r' ti $et) i!%&tent sex) + " ni#) te,u!ent r: sc $ere secretiei su$&ri% re te,u!ente"e $e# usc te fisuri te,u!ent re ce se %&t su%r infect /< , n,ren

FIZIOPATOLOGIA REACTIEI SITEMICE POSTAGRESI)E SI A STARILOR DE SOC *)S)P)A) / re ctie ,ener " $e n tur neur&en$&crin&!et '&"ic , cu c r cter $e % r re nes%rcific si c re se $e(#&"t in c (u" unei ,resiuni cu sc&%u" $e reec-i"i'r $)%)$)#) functi&n " &r, nis!u", $ r si $e cre %re!ise"e %t) "i!it re , c&re" re si e"i!i&n re tutur&r efecte"&r ,resiunii)

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*)P)S)A) re 0 f (e $e e#&"utie: + f ( $e $e(ec-i"i'ru i!e$i t + f ( c t '&"ic + f ( n '&"ic 3 % re $& r c n$ f ( c t '&"ic nu reusit reec-i"i'r re functi&n " &r, ni!u"ui, ! i reec-i"i'r re -e!&$in !ic 1 $ c in ceste c&n$itii f ( n '&"ic nu % re se inst "e ( st re $e s&c).

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() F$0$ 'e 'e0ec5ili/&u ime'i$t A,entii eti&"&,ici ce u c % cit te % t&,en ! re, cti&n n$ "&c " 3tr u! tis!e ! ri, inter#entii c-iru,ic "e inse!n te. s u cti&ne ( siste!ic 3-e!&r ,ii, se%tice!ii. %&t %r&$uce "e(iuni tisu" re $iferite si $e ! i ! ri $i!ensiuni, $ r ei %&t !&$ific si & serie $e c&nst nte s n,#ine 3-&!e&st tice. /< %& te % re HTA, -i%&xe!ie, !&$ific ri $e &s!&" tit te) In ur! "e(iuni"&r ! ri tisu" re si !&$ific rii c&nst nte"&r, se sti!u"e ( # ri ti * tisu" ri si * s%eci "i( ti, ce exist in (&ne str te,ice "e siste!u"ui c r$i&# sci" r 3#&"&+*, ' r&+*, &s!&+*, c-e!&+*.)De " ce"e $&u ti%uri $e * %"e c & c ntit te ! re $e i!%u"su"ri %e c "e s&! tic si # ,et ti# , s%re centrii ner#&si su%ei&ri) Ce ! i ! re % rte i!%u"suri"&r sti!u"e ( intens centrii neur&en$&crini i -i%&t " !usu"ui 3re"eu" en$&crin.)O !ic % rte i!%u"suri"&r $e% sesc et ?u" su'c&rtic ", ?un, n$ " ni#e" c&rtic ", $eter!in n $ sen( tii: $e nxiet te, $e fric 1 ceste %&t $ec" ns " r n$u" "&r, %e c i ref"exe "te tu"'ur ri neur&#e,et ti#e /< re%re(int f ct&ri % t&,enici i!%&rt nti %t) intretinere si ,r # re tu"'ur ri"&r c r cteristice *)S)P)A) si re ctiei $e s&c) Sti!u" re et ?u"ui su'c&rtic " %e c i ner#& se si u!&r "e: . centrii -i%&t " !ici sunt sti!u" ti %rin !&$ific re %r&%riet ti"&r s n, "ui3te!%er tur , %O:, %CO:, &s!&" rit te . %t) c -i%&t " !usu" $etine * s%eci "i( ti 3ter!&+*, c-e!&+*, &s!&+*. '.-i%&t " !usu" %& te fi sti!u" t %rin exist nt in s n,e un&r c ntit ti crescute $e cit&c-ine, !e$i t&ri e"i'er ti $in tesuturi"e "e( te, $e ,er!eni,en$&t&xine ' cteriene) Sti!u" re ! re -i%&t " !usu"ui $ec" ns e( initi " & re ctie , ner " cu c re cter $e%res&,en $e ti% % r si!% tic, cu &ri,ine in c entrii % r si!% tici $in -i%&t " !usu" nt)3%ri!u" ce se su%r cti#e ( , centrii "ui fiin$ cei ! i sensi'i"i.)*e cti $e%res&,en se ! nifest ! i "es %e siste!u" c r$i&# scu" r: Rsc $e frec#ent c rci c /< 'r $ic r$ie /<6AA/< st&% c r$i c) A s&$i" t tie%eriferic ! re )i) se %r&$uce & s t ( r " ti# in %eriferie, ur! t $e sc $ere int& rcerii #en& se " ini! /<sc $ere u!%"erii c r$i ce /< sc $ere $e'itu"ui c r$i c) C-i r $ c ,resiune nu este ins&tit $e " ince%it $e %ier$eri #&"e!ice, % re & sc $ere #&") efecti# circu" nt $ t&rit st (ei)T&t $ t&rit # s&$i" t tiei re "&c si sc $ere re(istentei # scu" re %eriferice ce $uce " -i%&tensiune) Sc $ere #&"u!u"ui circu" nt si -i%&tensiune sunt %rinci% "ii sti!u"ui ce excit ' r&+* si #&"&+* c r$i&# cu" ri si $in -i%&t " !us,$ec" ns n$ i!%u"suri ce $ec" nse ( $&u f ( *)S)P)A) *) F$0$ c$t$/ lic$ Se c r cteri(e ( %rintr+& sti!u" re si!% t& $rener,ic si %rintr+& re ctie en$&crin cu e"i'er re $e -&r!&ni cu efect c t '&"i( nt) A. STIMULA*EA SIMPATOAD*ENE*GICA: - re &ri,ine in nuc"eii -i%&t " !ici %&steri&ri - %e c i $escen$ente se cti#e ( stfe" SNS %eriferic /< se $esc rc in circu" tiec ntit ti ! ri $e c tec&" !ine, ce se e"i'ere ( $in f') si!% tice %&st,,") $in $iferite tesuturi3 ceste e"i'ere ( N&rA. si $in !e$u"&su%r re n " 3iner# t %rin nn) s%" c-nici1 e"i'ere ( ! i "es A, $ r si N&rA si $&% !in .) - c&nsecint "e $esc rc rii $e c tec&" !ine+efect 'enefic %t) re$res re -e!&$in !ic : . sti!u"e re frec#entei si f&rtei c r$i ce %rin rece%t&rii ; /< crestere $e'itu"ui c re$i c / efect c&!%ens t&r i!%) ce re$rese ( sc $ere $e'itu"ui $in f ( ;.) '.# s&c&nstricti %eriferic $e ti% se"ecti# 3$& r in terit&rii ce u & $ensit te ! re $e rece%t&ri ;: tesut cut n t, tesut $i%&s, rinic-i, #iscere '$&!in "e ! i "es TGI. /< s n,e"e este re$istri'uit c tre "te terit&rii, ce nu u rece%t&ri ;, ! i "e c tre c&r$ si creier, )i) in c&n$itii %&st ,resi#e ceste $&u &r, ne s fie %r&te? te $e ten$int $e sc $ere #&"u!u"ui efecti# circu" nt)Acest fen&!en se nu!este centr "i( re circu" tiei) T&t # s&c&nstricti c&recte ( ten$int $e sc $ere TA $in f ( ;.) De se!ene # s&c&nstricti fecte ( si terit&riu" #en&s te,i!ent r, -e% tic, s%"enic 3re(er#& re"e s n,#ine. /<e"i'er re unei c ntit ti ! ri $e s n,e ce % rtici% " re$res re #&"u!u"ui efecti# circu" nt) c. sti!u" re site!u"ui *AA, %rin crestere secre tiei $e renin %rin $&u !ec nis!e: % r tu" ?usr ,"&!eru" r $etine *+ $rener,ici ce sunt sti!u" ti: # s&c&nstricti # se"&r ren "e $uce " sc $ere %erfu(iei rteri&"ei eferente /< si!u" re ' r& si c-e!&+* 3!ec nis! in$irect. cti# re site!u"ui *AA $uce " % riti -i%er "$&ster&nis!u"ui , ce sti!u"e ( " ni# TCD re 's&rti $e N si H:O/< sc $ e"i!in ri"e -i$rice ren "e, !ec nis! i!%&rt nt %t) re$res re #&"e!ic $. sti!u" re $rener,ic re efecte !et '&"ice c t 'i"ice1 ceste efecte c t '&"ice cresc $is%&ni'i"u" $e su'st) ener,etice f& rte neces re %t) crestere %r&$uctiei $e ener,ie neces r %t) functi&n re &%ti! !i?"& ce"&r $e % r re) ;.%e !et ') ,"uci$ic, c tec&" !ine"e sti!u"e ( ,"ic&"i( -e% tic si !uscu" r , %rin cti# re f&sf&ri" (e"&r)L ni#e"u" fic tu"ui, ,"ic&( ce re(u"t $in ,"ic&,en&"i( este e"i'er t in circu" tie %t) c fic tu" re ,"uc&(&+4+f&sf t ( ce e"i'ere ( ,"uc&(&+4+f&sf tu" su' f&r! $e ,"uc&( in circu" tie /< creste ,"ice!i /< -i%e,"ice!ie %&st ,resi# 1Mi&c r$u", creieru", %&t

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%r&$uce ! i !u8t ener,ie %ri r$ere ,"uc&(ei1Din ,"ic&,en&"i( !uscu" r re(u"t ,"uc&( c re nu %& te trece in circu" tie3nu exist ,"uc&(&i+4+f&sf t ( . /< se cti#e ( ,"ic&"i( /< creste %r&$ucti $e c) " ctic /<!usc-iu" e"i'ere ( in circu" tie c) " ctic, c re c t ti!% ni#e"u" s u nu este %re ! re %& te fi c&nsu! t, ! i "es $e c tre c&r$ %t) %r&$ucere $e ener,ie si $e fic t %t) ,"uc&ne&,ene( $in c re re(u"t $in nu& ,"uc&( %e c re fic tu" & e"i'ere ( in circu" tie) :.%e !et '&"is!u" "i%i$ic, ! i "es $ren "in , creste "i%&"i( " ni#) tes) $i%&s, cti# n$ "i% ( /< se e"i'ere ( AG ce %&t fi uti"i( ti $e c&r$ c su'str t ener,etic) 0.%e !et '&"is!u" %r&teic, c tec&" !ine"e cresc c t '&"is!u" %r&teine"&r /< se e"i'ere ( in circu" tie c ntit ti c&res%un( t& re $e ) ),c re sunt uti"i( ti " ni#e" -e% tic %t) ,"uc&ne&,ene( /< ,"uc&( ce este e"i'er t in circu" tie) e. re cti $e tre(ire / cti# re $ifu( sc& rtei %rin S*AA1 ce st se ut&intretine %rin circuite c&rtic&reti&cu"&c&rtic&-i%&t " !ice, !entin n$u+se st re $e "ert c&rtic " neces r %t) c&&r$&n re re ctiei neur&en$&crine %&st ,resi#e) 6. *EACTIA ENDOC*INA A FAZEI CATA6OLICE: - c&nst in e"&'er re un&r c ntit ti ! ri $e -&r!&ini cu efecte c t '&"ice ce inter#in in crestere re(ist ntei &r, nis!u"ui " ,resiune) ;. AC1$ si hormonii glucocorticoi&i, D D t&rit ur! t&ru"ui !ec nis!:-i%&t " !usu" %&steri&r sti!u" t re si nuc"ei en$&crini ce secret C*F ce ?un,e %e c "e siste!u"ui %&rt -i%&t " !&-i%&fi( r in -i%&fi( nteri& r un$e sti!u"e ( sinte( $e ACTH, ce se e"i'ere ( in circu" tie si sti!u"e ( C*S si "ini ,"uc&cc&rtic&i$ ! i "es) ACTH re * %e su%r f t ce"u"e"&r secret& re $in C*S)Fix re "ui %e * $uce " cti# re siste!u"ui $eni" tcic" ( + AMPc) Su' inf"uent AMPc, creste inc&r%&r re $e c&"ester&" in !it&c&n$rii"e cest&r ce"u"e si c&n#ersi "ui in %re,nen&"&n , c re este %recurs&ru" trei "inii -&r!&n "e:,"uc&c&rtic&i$ , !iner "&i$ si -&r!&ni"&r sexu "i) ACTH sti!u"e ( "ini ,"uc&c&rtic&i$ , ! i "es c&rti(&"u"ui /< creste c&rti(&" !i c re %rin fee$+' c8 ne, ti# sc $e secre ti $e ACTH 3 cest "ucru este # " 'i" in c&n$itii fi(i&" &,ice.1%&st ,resi# nu sc $e secreti $e ACTH ci r ! ne " # "&ri crescute1 ACTH c&ntinu s se secreete %t) c sti!u" re -i%&t " !ic $uce in c&ntnu re " e"i'er re $e C*F) G"uc&c&rtic&i(ii 3c&rti(&"u". u c efecte !et '&"ice: . !et ') ,"uci$ic : " ni#) -e% tic sti!u" re ,"uc&ne&,ene( 1 c&ntr c re ( fecte"e insu"inei " ni#e"u" tesuturi"&r insu"in&$e%en$ente /< sc $e inre re ,"uc&(ei ince"u"e /< -i%er,"ice!ie %&st ,resi# ) '.!et ') "i%i$ic: sti!u"e ( "i% ( /< creste e"i'er re in circu" tie AG) c. !et ') %r&teic:creste c t '&"is!u" %r&teic /< creste e"i'er re $e ) ) f&"&siti in ,"uc&ne&,ene( -e% tic ) G"uc&c&rtic&i(ii %&tente ( efecte"e c r$i&# scu" re "e c tec&" !ine"&r, %&tente ( efectu" ntiinf" ! t&r " ni#) tes "e( te, sc $e extin$ere "e(iuni"&r inf" ! t&rii 3ex) st 'i"i(e ( !') "i(&(&! "e, sc $e e"i'er re en(i!e"&r %r&te&"itice, st 'i"i(e ( ,r nu"e"e ! st&cit re, sc $e e"i'er re $e -ist !in ., creste %r&$ucti $e tr&!'&cite " ni#) ! $u#ei -e! t&"&,ice si $e ,r nu"&cite, fen&!en i!%) in ,resiuni"e se%tice si -e!&r ,ice) G"uc&c&rtic&i(ii sunt " turi $e c tec&" !ine, %rinci% "ii -&r!&ni $e stres) )) Aldosteronul si A#$ 'A"$&ster&nu" cti&ne ( " ni# ce" TCD, fix n$u+se %e * s%ecifici intr cit&%" s! tici) c&!%"exu" H+* !i,r n$ in nuc"eu un$e sti!u"e ( nu!iti f ct&ri $e tr nscri%tie ce sti!u"e ( f&r! re $e A*N! neces r %t) sint) unei %r&tein (e c re inter#ine in crestere re 's&'tiei N %t) c " ni#) %&"u"ui tu'u" r " ce"u"ei creste %er!e 'i"it te !') %t) N , i r " ni#e"u" %&"u"ui s n,#in sti!u"e ( & %&!% !') ce tr nsfer N $in ce"u" tu'u" r in c %i" ru" %eritu'u" r /< creste re ') N /< creste re 's&rti H:O /< re$res re #&"e!ic ) Hi%er "$&ster&nis!u" crteste secreti tu'u" r " sc-i!' cu H si >1 /< crestere e"i!in rii $e H "i!ite ( ten$int $e ci$&( !et&'&"ic $et) $e -i%&%erfu(i tisu" r 3$ t&r t& sc $erii #&"u!u"ui $e s n,e circu" nt si # s&c&nstrictiei. /< crestere secretiei $e > "i!ite ( ten$int $e -i%&%&t se!ie ce % re %rin e"i'er re crescut > $in ce"u"e"e "ter te $e " ni#) su%r fetei "e( te) ADH: sinte( s se re "i(e ( in nuc"eii su%r &%tic si % r #entricu" r $in -i%&t " !usu" %&steri&r1 e" este tr ns%&rt t %e c "e x&n " in -i%&fi( %&steri& r $e un$e e e"i'er t in circu" tie su' ctiune un&r f ct&ri: sc $ere #&"u!u"ui circu" nt 3! i "es., !e$ic !ente $!) %t) c&!' tere $urerii s u fricii 3!&rfin s u ' r'iturice., $urere i!%&rt nt , ce $et) in !&$ ref"ex %rin sti!u"ui sc) $e " ni#) (&nei "e( te si $esc $e " sc& rt ) L ni#e" ren " ADH se fixe ( %e * s%ecifici ce exist %e !') %&"u"ui c %i" r " ce" tu'u" re $ist "e si " ce") tu'i"&r c&"ect&ri /) cti# re siste!u"ui $eni" tcic" ( +AMPc si unei %r&tein8in (e ce creste %er!e 'i"it te !') tu'u" re %t) H:O)/< % este tres c tre intestitiu" ren " un$e exist & t&niucit te ! i ! re c in tu' /< $in interstiitu trece in c %i" ru" %eritu'u" r /< re$res re #&"e!ic ) In c ntit te ! re , ADH re si efecte # s&c&nstrict& re /< # s&c&nstrictie %eriferic ) 0. $ormonii tiroidieni (1 si 18. Se $esc rc in c ntit ti ! ri si u efecte !et '&"ice c t '&"ice: . !et ') ,"uci$ic: cresc ,"ic&,en&"i( '. !et ') %r&teic: cresc c t '&"is!u" r%&teine"&r /< ) ) f&"&siti " ,"uc&ne&,ene( c. !et ') "i%i$ic: cresc "i%&"i( " ni#) tes) $i%&s /< creste e"i'er re $e TG

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//<crteste $is%&ni'i"u" $e su'st ener,etice) Screti -&r!&ni"&r tir&i$iei este crescut %rin ur! t&ru" !ec nis!: nuc"eii -i%&t " !ici sti!u" ti e"i'ere ( T*F c re ?un,e %e c "e sist) %&rt -i%&t " !&-i%&fi( r in -i%&fi( nteri& r si sti!u"e ( secreti $e TSH c re $esc rc t in circu" ti s n,#in , ?un,e " ni# ,") tir&i$e un$e creste sinte( si s creti $e -&r!&ni tir&i$ieni) 8) $ormonii pancreatici G"uc ,&nu" se e"i'ere ( in c ntit ti crescute $ t&rit $esc rc rii crescute $e c tec&" !ine 3tesutu" +% ncre tic re rece%t&ri + $rener,ici) G"uc ,&nu" re efecte c t '&"ice: . !et ') ,"uci$ic: creste ,"ic&,en&"i( si ,"uc&ne&,ene( '.!et ') "i%i$ic: creste "i%&"i( !et ') %r&teic: creste c t '&"is!u" /< creste e"i'er re ) ) G"uc ,&nu" in c&nc) ! ri sti!u"e ( c&ntr cti"it te !i&c r$ic 3%rin rece%t&ri s%ecifici !i&c r$ici. /< creste $e'itu" c r$i c Insu"in se $esc rc in c ntit ti crescute $ t&rit -i%er,"ice!iei) Pt) c %re$&!in -&r!&nii nt ,&nisti insu"inei 3c t&c&" !ine, ,"uc&c&rtic&i(i, ,"uc ,&n, tir&i$ieni., se cre ( un $eficit re" ti# $e insu"in )Tesuturi"e insu"in&$e%en$ente u re(istent crescut " insu"in /< creste ,"ice!i ) F ( c t '&"ic , %rin !&$ific ri"e -e!&$in !ice si !et '&"ice ince rc s reec-iu"i'r re -e!&$in !ic si ener,etic , cre n$ c&n$itii %t) "i!it re efecte"&r "e(i&n "e "e ,resiunii) E#&"uti f (ei c t '&"ice: - $ c intensit te ,resiunii nu este f) ! re si $ c re cti#it te &r, nis!u"ui este 'un , %e ! sur re$res rii -e!&$in !ice, $is% r sti!u"ii ce excit u -i%&t " !usu" )i) %r&,resi#, %rin sc $ere intensit tii sti!u"i"&r, f ( c t '&"ic $is% re, " s "&c unei %re$&!in nte -i%&t " !usu"ui nteri&r) A% re & f ( fin " *)S)P)A)cu &ri,ine in -i%&t " !usu" nteri&r si c re este c recteri( t %rintr+& us& r %re$&!in nt % r si!% tic si $esc rc re $e -&r!&ni cu efect n '&"ic) %re$&!in nt % r si!% tic ex%"ic us& r 'r $ic r$ie si -i%&tensiune1 t&t e $uce " crestere secretiei $e insu"in 3 ce" + % ncre tice u rece%t&ri % r si!% tici.1 cu! -i%erinsu"ine!i nu ! i este c&ntr c r t $e -&r!&nii nt ,&nisti i insu"inei ce u re#enit " # "&ri"e n&r! "e /< efecte"e n '&"ice "e insu"inei: se ref c st&curi"e ener,etice c&nsu! te, creste ,"ic&,en&,ene( , "i%&,ene( , sinte( $e %r&teine neces re %t) re%er ti tesuturi"&r "e( te) + se e"i'ere ( si "ti -&r!&ni n '&"i( nti STH + $in -i%&t " !usu" nteri&r se e"i'ere ( un f ct&r ce sti!u"e ( " ni#e"u" -i%&fi(ei nt) secreti $e STH1 e" sti!u"e ( sint (e"e %r&teice F ct&ru" sti!u" t&r %t) -&r!&nii ,&n $&tr&%i $in -i%&fi( nteri& r , e"i'er t $in -i%&t " !usu" nteri&r1 e" creste secreti $e -&r!&ni sexu "i c re u efecte n '&"i( nte: sti!u"e ( sint ( %r&teic ) - $ c ,resiune f& t f) ! re s u re cti#it te &r, nis!u"ui este re$us 3 nteri&r #ut& '& " cr&nic ce sc (ut % r re : IH, I*, IC, #it !in&(e, $eficite i!unit re, DZ, # rst inint t ., f ( c t '&"ic nu reuseste s reec-i"i're(e $)%)$)#) functi&n " &r, nis!u", ! i "es -e!&$in !ic, f ( n '&"ic nu se $e(#&"t 1 in' "&cu" ei se inst "e ( st re $e s&c) S&cu" este c"inic&+fi(i&% t&"&,ic, c r cteri( t %rin sc $ere %erfu(iei tisu" re su' & "i!it !ini! c&!% ti'i" cu & cti#it te !et '&"ic s tisf c t& re) Sc $ere %erfu(iei $uce " ,r # tu"'ur ri !et '&"ice ce ,r #e ( tu"'ur ri"e -e!&$in !ice) CLASIFICA*EA TIPU*ILO* DE SOC: SOCUL HIPOAOLEMIC: re%er(int sc $ere %erfu(iei tisu" re su' "i!it !ini! $ t&rit sc $erii $e'itu"ui c r$i c, in ur! unei -i%&#&"e!ii! rcete ce %r&$uce sc $ere u!%"erii c r$i ce SOCUL CA*DIOGEN : re%re(int sc $ere %erfu(iei tisu" re $ t&rit fect rii ,r #e functiei $e %&!% ini!ii 3ex)sc $ere su%r fetei c&ntr cti"e in ur! unui IM intens. SOCUL TOXIC: re%er(int $e(ec-i"i'ru" intre %&rtu" $e O: " ni# tisu" r si neces ru" cestui in c&n$itii"e unei %erfu(ii &%ti!e $ r unui neces r $e O: crescut %rin !ec) -ist&t&xic) FIZIOPATOLOGIA SOCULUI HIPOAOLEMIC St re $e s&c se c r cteri(e ( %ri sc $ere %erfu(iei tisu" re su' & "i!it su' c re cti#it te !et '&"ic tisu" r nu ! i este nici ! c r s tisf c t& re) In s&cu" -i%&#&"e!ic 3S-A., sc $ere %erfu(iei tisu" re se $ t&re ( re$ucerii se#ere $e'itu"ui c r$i c $ t fiin$ u!%"ere #entricu" r extre! $e !ic in c&n$itii"e unei -A i!%&rt nte) ETIOLOGIA SOCULUI HIPOAOLEMIC: Sc $eri"e se#ere $e #&"u! %&t fi 's&"ute s u re" ti#e ) I. HIPOAOLEMIILE A6SOLUTE Se %r&$uc %rin %ier$eri extre# scu" re $e s n!,e s u %" s! s u nu! i $e "ic-i$e e"ectr&"itice) Sc $e nu nu! i #&"u!u" efecti# circu" nt, ci si #&"e!i t&t " ) P&t fi %r&$use ! i frec#ent $e ur! t& re"e c&n$itii % t&"&,ice: A) 5em &$2ii 2&$%e ce ! t 1i !& 'use !&i"#

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. secti&n ri cci$ent "e @ tr u! tice "e # se"&r $e c "i'ru ! re 3 rtere@#ene. '. er&$ ri % t&"&,ice "e un&r # se /<-e!&r ,ii $i,esti#e 3!e"ene@-e! te!e(e. s u -e!&r ,ii %u"!&n re 3-e!&%ti(ii. c. ru%tur un&r ne#ris!e $. $iferit c&!%"ic tii &'stetric "e /<s rcin extr uterin ru%t , #&rt inc&!%"et, ru%turi uterine, $ec&" ri "e %" centei e. $eficite se#ere "e -e!&st (ei Pt) inst " re st rii $e S-A, %ier$ere $e ! s s n,#in este / 0=P $in ! s t&t " ) I!%&rt nt nu este nu! i ! s $e s n,e ci si #ite( cu c re cest se %ier$e1 $ ce #it ( este f& rte ! re, !ec nis!e"e c&!%ens t&rii nu %&t inter#enii eficient,!u"te $intre e"e necesit n$ ti!% %t inter#eni1 stfe", %ier$eri r %i$e $e s n,e $uc " inst " re st rii $e S-A " # "&ri Q0=P $in ! s t&t " ) B) !l$sm &$2iile se%e&e ce ! t 1i c$u0$te !&i"# . rsuri"e intinse si %r&fun$e+++ " ni#e"u" su%r fete"&r rse creste f) !u"t %er!e 'i"it te %erete"ui # sc) t t %rin "e(iuni"e se#ere %r&$use $e f ct&ru" ter!ic, $ r si %rin & serie $e !e$i t&ri # s& cti#i e"i'er ti $in tesuturi"e rse 3"e( te. /< extr #& ( re %" s!ei / %" s!ex&$ieG(e!uire G (&ne"&r rse) '. % ncre tite"e necr&tice 3 f&r!e f) se#ere $e inf" ! tie t sutu"ui % ncr tic, cu $istru,ere t&t " cestui tesut., se e"i'ere ( & c ntit te crescut $e su'st) %r&te&"itice c t si & c ntit te crescut $e !e$i t&ri # s& cti#i, c r&r %re(ent $uc " creste re %er!e 'i"it tii, nu nu! i " ni #e"u" "&?ei % ncre tice, ci si in tes) in#ecin te /< %" !ex&$ie/<-i%&#&"e!ie se#er c. %erit&nite"e ,r #e 3inf" ! tii se#ere " e %erit&neu"ui, ce" ! i frec#ent %r&#&c te $e %ef&r re unui se,!ent " TD. inf" !) este initi " $e n t) C-i!ic @ irit ti# , u"teri&r c % t n$ si & c uc u( se%tic %rin su%r infectie %e su%r fete %erit&ne "e ! ri se e"i'ere ( c ntit ti i!%&rt nte $e f ct&ri # s& cti#i /< creste %er!e 'i"it te # scu" r ) sin$r&!u" $e stri#ire 36BF ters. /< % re " %ers& ne"e %rinse su' $ r ! turi, " c re c&!%resi %uternic ! se"&r !uscu" re $et) isc-e!i (&nei res%ecti#e/<"e(iuni $e n t -i%&xic ce fecte ( si %eretii # scu" ri1 &$ t cu in" tur re f&rtei c&!%resi#e, %rin "e(iuni"e res%) %" s extr #& (e ( f) !u"t 3 c %rintr+& sit . /< -i%&#&"e!ie se#er C) !ie&'e&e$ m$si%$ 'e lic5i'e elec& litice !&i"# . # rs turi@sin$r& !e $i reice ,r #e si %re"un,ite '. %&"iurii"e f ! ri, in c&nt xtu" in c re !ec nis!u" setei nu ! i functi&ne ( 3ex) c&! $i 'etic cet& ci$&tic ., s u in c (u" $i 'etu"ui insi%i$) c. &c"u(ii"e intestin "e c&!%"ete, in "te, $e $iferite eti&"&,ii /< cu!u" re %r&,resi# $e % si e"ectr&"iti ce sunt sustr se 's) intestin "e L s t ( $in !&nte $e ' r ? /< # rs turi /< ccentu re %ier$eri"&r -i$rice1 %e ! sur ce %erete"e $i,esti# se $i" t $ t&rit st (ei, tensiune intr % riet " creste /< f ct&r c&!%resi# %e # se"e %erete"ui intestin " / isc-e!ie L "ter ri ce"u" re -i%&xice ce%&t c&n$uce " e"i' r re $e !e$i t&ri # s& cti#i /< creste %er!e 'i"it te /< extr #& ( re -i$ric , c-i r %" s!ex&$ie ce inf"&uente ( (&n res%ecti# ) II. HIPOAOLEMIILE *ELATIAE Sunt %r&$use %rin sec-estr ri s n,#ine ! ri in $iferit terit&rii # scu" re) Nu sunt %ier$eri %r&%riu+(ise extr # scu" re) Sc $e #&"u!u" efecti# circu" nt, $ r #&"e!i t&t " r ! ne " # "&ri n&r! "e) P&t % re in ur! t& re"e c&n$itii: In c (u" un&r secti&n ri "e ! $u#ei s%in "e 3s&cu" s%in ". /<# se"e s n,#ine $e%en$ente $e iner# ti &ri,in r in se,!) !e$u" r su'i cet sectiunii isi %ier$ t&t " t&nusu", % r n$ & # s&$i" t tie extre! L st ( s n,#in in cest terit&riu) In c (u" unei int&xic tii cute cu !e$ic !ente $e%res& re ner#& se3' r'iturice, fen&ti (inice, $i ( %ine. /< % re stfe" & re$ucere $r stic t&nusu"ui # cu" r, ur! t $e # s&$i" t tie L st ( s n,#in F&"&sire 'u(i# $e , n,"i&%"e,ice in $&(e f) ! ri In c (u" s&cu"ui n fi" ctic /<se e"i'ere ( in ceste c&n$itii & c ntit te crescut $e -ist !in c ur! re c&nf"ictu"ui i!un&"&,ic1 -it !in creste %er!e 'i"i t te # scu" r /< % re extr #& ( re s n,#in ) /<in c (u" s&cu"ui n fi" ctic #e! & c&!'in tie $e -i%&#&"e!ie re" ti# cu -i%&#&"e!ie 's&"ut ) TUL6U*A*ILE HEMODINAMICE DIN SOCUL HIPOAOLEMIC In S-A se $escriu : c te,&rii $e tu"'ur ri:I. tu"'ur ri circu" t&rii II. tu"'ur ri c r$i ce I) TULBURARILE CIRCULATORII DIN SOCUL HIPO)OLEMIC Inc"u$ ur! t& re"e fen&!ene: A. *e$ucere % tu"ui # scu" r++++se re "i(e ( %rin : !ec nis!e: ;. # s&c&nstircti 3$eter!in t in s%eci " $e %uternic sti!u" re si!% t&+ rener,ic . - este in ! re % rte se"ecti# 3(&ne"e cu $ensit te ! re rece%t&ri"&r ; $rener,ici: tes) !uscu" r sc-e"etic, tesutu" $i%&s, rinic-i, TGI, #iscere '$). - re%re(int un !ec nis! c&!%ens t&r, $e& rece s n,e"e $in terit&riu" # s&c&nstricti&n t este re$risti'uit c tre terit&rii f r # s&c&nstrictie 3c&r$ si creier.) - c&nsecinte : + in %ri!e"e st $ii "e s&cu"uui ini! si creieru" %ri!esc & c ntit te c&res%un( t& re $e s n,e sunt %r&te? te $e isc-e!ie, re$res re TA %rin ! rire re(ist ntei # scu" re %eriferice

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+ fecte ( si terit&rii #en& se1 #en&c&nstricti un&r terit&rii ce re%re(int re(er#& re $e s n,e re c efect !&'i"i( re un&r c ntit ti su%"i!ent re $e s n,e ce ince rc s ref c #&"u!u" circu" nt) :. $esc-i$ere un&r sunturi rteri&+#enu" re " ni#e"u" !icr&circu" tiei un&r tesuturi 3!ec nis! ! i %ut) si ! i eficient $ec t # s&c&nstricti .) - in c&n$itii fi(i&"&,ice, sunturi"e sunt inc-ise) - " ni#e"u" c % tu"ui ter!in " " rter&i"ei, in inte $e rete u c %i" r , exist & c&ncentr re $e f') !uscu" re nete$e, ce re "i(e ( $)%)$)#) functi&n " un $e# r t sfincter / sfincter %rec %i" r - " ni#e"u" c % tu"ui %r&xi! " " #enu"ei, $u% rete u c %i" r , exi t $e se!ene & c&ncentr re $e f') !uscu" re n te$e ce re " si " cest ni#) un sfincter functi&n " / sfincteru" %&stc %i" r) - c "e $&u sfinctere u & $ensit te si!i" r $e rece%t&ri + $ren r,ici /< sti!u" re si!% t& $rener,ic f) intens %r&$uce c&nstricti ce"&r $&u sfinnctere /< f"uxu" s n,#in intr in c nti te !ic in rete u c %i" r /< creste %resiune %rec %i" r ce f&rte ( $esc-i$ere n st&!&(e"&r rt&ri&+#enu" re /< s n,e"e &c&"este rete u c %i" r ) - %rin exc"u$ere unui nr) crescut $e rete"e c %i" re, $i!ensiuni"e % tu"ui # scu" r se re$uc f) !u"t) Princi% "u" # nt ? " re$ucerii % tu"ui # scu" r este ce" $e rest 'i"i r %&rtu" c % cit te # scu" r @ #&"u! circu" nt /< i!%ie$ic re te!%&r r %r 'usirii TA) 6. incerc re &r, nis!u"ui $e ref cere , ce" %utin % rti " , #&"u!u"ui circu" nt)3#e(i re cti siste!ic %&st ,resi# . . -i%er "$&ster&nis!u" secun$ r - este $et) $e cti# re siste!u"ui S*AA) - crestere secretiei $e renin se $ t&re ( in %rinci% " ctiunii $irecte sti!u" rii $rener,ice %e % r tu" ?ust ,"&!eru" r,c t si ctiunii in$irecte # s&c&nstrictiei ren "e ce %r&$uce sc $ere %erfu(iei s n,uine in rteri&"e"e ferente - creste stfe" re 's&rti $e N " ni#) TCD /< efect &s!&tic /< ntren re %ei) '. ADH - in c&n$itii %&st ,rs&,ene creste sinte( si secreti "ui) - cti&ne ( " ni#e"u" TD L TC, $eter!in n $ crestere re 's&rti $e % - in c&ncentr tii crescute, ADH 3c si "ti -&r!&ni ce %&t exercit efecte"e tisu" re "e c t&c&" !ine"&r., re & c&ntri'utie " # s&c&nstricti $in st re $e s&c) c. !&'i"i( re un&r c ntit ti $e s n,e $in $e%&(ite"e #en& se 3$eter!in t $e sti!u" re si!% t&+ rener,ic .) $. intr #& ( re $e % interstiti " - se $ t&re ( in %rinci% " re$ucerii $r stice %resiunii -i$r&st tice $in c %i" re, c&nsecuti# -i%&#&"e!iei) - ec-i"i'ru" %resiune -i$r&st tic @%resiune c&"&i$&s!&tic este net in f #& re %resiunii c&"&i$&s!&tice /< tr , re %ei interstiti "e in # s) D c nu se in" tur f ct&ru" eti&"&,ic " S-A, nu se reuseste re$res re #&"e!ic ) Prin %ersistent s , -i%&%erfu(i tisu" r se ,r #e ( )Astfe" -i%&xi tisu" r $e#ine $in ce in ce ! i intens , %r&#&c n$ fen&!ene ce $uc " un "t ,en $e tu"'ur ri,cu! r fi : C. crestere $i!ensiunii % tu"ui # scu" r /< re " ' ( & rteri&"&$i" t tie extre! , cu intr re ! si# $e s n,e in rete"e"e $e c %i" re, un$e se %r&$uce sec-e tr re cestei ! se s n,#ine) /< este %r&$us %rin ctiune ! i !u"t&r f ct&ri: . ci$&( : +sc $e t&nusu" !uscu" r %rin sc $ere sinte(ei $e %r&teine c&ntr cti"e1 este ur! re -i%&xiei tisu" re i!%&rt nte1 '. -ist !in : +se e"i'ere ( $in ! st&cit "e %eri# sc "ter te -i%&xic) c. 8inine"e: +%r&#in $in %recurs&ri 38inin&,en. c re se , sesc t t in circu" tie c t si " ni#e" tis) in c&n$itii"e "ter ri ce"u" re -i%&xice, se e"i'ere ( c&ntinutu""i(&(&! " " ce"u"e "&r fect te, c&ntinut c re %e " n, en() %r&te&"itice, $is%une si $e & %r&en(i! / %re8 "i8rein 1 +su' ctiune !e$iu"ui ci$, %re8 "i8rein se tr nsf) in 8 "i8rein cti# c re tr nsf&r ! 8inin&,enu" in 8inine1 tr nsf&r! re ce st %& te fi f cut si nes%ecific $e c tre %r&teinen(i!e"e res%ecti#e e"i'er te $in "i(&(&!ii "ter ti1 $e se!ene %& te fi f cut si $e c tre f ct&ru" XII " c& ,u" rii1 8inine"e u %r&%riet ti # s&$i" t t& re si $e crestere %er!e 'i"it tii # scu" re1 '.PG: + se sinteti(e ( si e"i'ere ( in c ntit ti ! ri $e " ni#e"u" (&nei -i%&xice, in s%eci " ce"e $in seri A si E cu %r&%riet ti # s&$i" t si $e crestere %er!e 'i"it tii # scu" re1 sinte( "&r %&rneste $e " c) r -i$&nic, %rin PL+A : ce in c&n$itii $e -i%&xie tisu" r este cti# t ! i "es $e crestere c&nc) $e C intr ce") 3$ t&rit sc $erii ATP %&!% !') $e C nu ! i functi&ne ( .1 c. feritin : +se , seste in c "u"e"e siste!u"ui reticu"&-isti&cit r, isc-e!i "&r $uce " e"i' r re $e feritin in circu" tie si %r&$ucere $e # s&$i" t tie %rin '"&c re ctiunii C in %r&cesu" c&ntr cti" $. en$&rfine"e:+neur&tr ns!it t&ri f) i!%&rt nti in c&!' tere sti!u"i"&r $urer&si1 se e"i'ere ( in c&n$itii %&st ,res&,ene $in (&n -i%&t " !&-i%&fi( r 1 !u"te sect& re # scu" re cu rece%t&ri %t+en$&rfine r s%in$ %rin # s&$i" t tie " ctiune cest&r 1 e. en$&t&xine"e ' cteriene: + u c&ntri'utie in # s&$i" t tie, $ t&rite "e(iuni"&r !uc& sei, %&t trece $in "u!enu" TD in circu" tie, in c ntit) suficient $e ! ri1 $ t&rit -i%&xiei crescute ce fecte ( si fic tu", en$&t&xine"e nu ! i sunt neutr "i( te si trec ! i $e% rte, ?un, n$ " ni#) tisu" r un$e, %e " n, "e(iuni"e res%ecti#e, '"&c-e ( cti#it te en(i!e"&r cic"u"ui >re's si

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sti!u"e ( cti#it te en(i!e"&r ,"ic&"i(ei n er&'e /< se ccentue ( $e(ec-i"i'ru" n er&'i&( @ er&'i&( /< creste %r&$ucti $e c) L ctic, ci$&( ) T&ti cesti f ct&ri %r&$uc $i" t re sfincteru"ui %rec %i" r " un !&!ent$ t, in ti!% ce sfincteru" %&stc %i" r 3!u"t ! i re(istent " ctiune cest&r f ct&ri. r ! ne inc % rti " c&ntr ct t /) in rete u c %i" r intr & c ntit te $e s n,e 3% t # scu" r ! rit., $ r r ! ne s c-estr t ici %rin %ersistent inc-i$erii sfincteru"ui %&stc %i" r) Ace st sec-estr re $uce " sc $ere int& rcerii #en& se /< cti#it te c r$i c ince%e s sufere) De& rece !u"te $in sus'st nte"e $escreise u ctiune -i%er%er!e 'i"i( t& re % re extr #& ( re -i$ric " ni#) c %i" r, c tre interstitii /<sc $e int& rcere #en& s si ! i !u"t, %rin sc $ere #&"e!ic ) Extr #& ( re s n,e"ui $et) crestere # sc&(it tii s "e /< fen&!enu" $e GSLUGGED 6LOODH /< sc $e #ite( $e circu" tie /< sc $e int& rcere #en& s L f #&ri( re ccentu rii -i%&xiei /< % r %e rii extinse "e(iunien$&te"i "e -i%&xice) Le(iuni"e en$&te"i "e L crestere # sc&(it tii s n,e"ui, f #&ri(e ( fen&!ene"e $e $er re @ ,re, re s n,#in L c& ,u" re /<sc $ere ccentu t int& rcerii #en& se /< sc $ere ccentu t DC ) CID in s&c este un f ct&r $e ire#ersi'i"it te) Secun$ r "ui CID se cti#e ( si fi'rin&"i( @ -i%erfi'rin&"i( secun$ r , ce re " ' ( e"i'er re ! si# , $in en$&te"iu" "e( t, un&r cti# t&ri tisu" ri $e %" s!in&,en /< -i%er%" s!ine!ie /< % riti unui ,r # sin$r&! -e!&r ,ic) D t&rit "e( rii f ct&ri"&r $e c& ,u" re I, A, AII, % re ,r # re c& ,u"&% tiei $e c&nsu!) Li( r %i$ c-e ,uri"&r, in inte $e #in$ec re "e(iuni"&r # scu" re, $uce " ,r # re sin$r&!u"ui -e!&r ,ic)Fi'rin&"i(&%e%ti(i c re in-i' tr&!'in , $e%ri! si ! i !u"t c& ,u" re ) II) TULBURARILE CARDIACE DIN SOCUL HIPO)OLEMIC In s t $ii"e initi "e, ini! nu sufer fen&!enu" $e centr "i( re circu" tiei) Prin sti!u" re si!% t& $ren r,ic , cti#it te c r$i c este c-i crescut /< creste D C / f ct&r c&!%ens t&r i!%&rt nt in re "i( re #&"u!u"ui efecti# circu" nt) Ini! isi %& te creste %r&$ucti $e ener,ie, $ t fiin$ $is%&ni'i"u" crescut $e ,"uc&( , c) ,r si 3f ( c t '&"ic re ctiei %&st ,resi#e.) Pe ! sur ce % re sec-estr re s n,#in in !icr&circu" tie si int& rcere #en& s se re$uce, u!%"ere #entricu"ui st n, sc $e /< sc $e DC )Din cest !&!ent % re si -i%&%erfu(i cere'r " si c&r&n ri n )Mi&c r$u" ince%es %re(int tu"'ur ti -i%&xe!ice @ isc-e!ice /< sc $e c ntit te $e ATP /< sc $e c&ntr cti"it te !i&c r$ic ) C n$ ci$&( $e#in se#er si e re & c&ntri'utie i!%&rt nt " sc $ere c&ntr cti"it tii) In st $ii"e # ns te $e s&c, se secret un nu!it f ct&r ,r # nt, $in tesutu" % ncre tic isc-e!ic / %&"i%e%ti$e $e ,enu" MDF c re re %r&%riet te $e sc $e c&ntr cti"it te !i&c r$ic ) In st $ii"e se#ere % re & -i%er>+e!ie, $eter!in t t t $e iesire > $in ce"u"e"e "ter te in c&n$itii $e ci$&( 3$i("&cuire %r&tein tu"ui $e >., c t si nerecu%er rii > in sect&ru" ce"u" r $e& rece %&!% $e NA @ > $e%en$ent $e ATP, nu ! i functi&ne ( $ t&rit $eficitu"ui $e ATP si in-i' rii ei $e c tre ci$it te)Hi%er>+e!i $et) %ertur' ri ,r #e $e rit! c r$i c /< sc $ere D C ) In fin " se ?un,e " insuficient c&tr cti" ener,&$in !ic in %rinci% " %rin $efect $e ener,&,ene( ce este unu" $in f ct&rii ! ?&ri i ire#ersi'i"it tii s&cu"ui) In S-A, s%re $e&se'ire $e s&cu" c r$i&,en, suferint c r$i c este secun$ r tu"'ur ri"&r -e!&$in !ice) SOCUL CA*DIOGEN *e%re(int sc $ere %erfu(iei tisu" re su' "i!it !ini! $ t&rit sc $erii D C $ r nu secun$ r unei -i%&#&"e!ii se#ere, ci in !&$ %ri! r, %rin fect re functiei $e %&!% ini!ii) Fen&!ene"e -e!&$in !ice sunt se! n t& re cu ce"e $in S-A: /<re$ucere #&"u!u"ui circu" nt, $etere!in sti!u" re intens si!% t& $rener,ic , cu re$ucere $i!ensiunii % tu"ui circu" t&r /< -i%&xie se#er /< crestere $i!ensiunii % tu"ui # scu" r /< sec-estr re s n,#in /< s&c -i%&#&"e!ic) Princi% "ii f ct&ri eti&"&,ici sunt: ;. IMA extins - (&n necr&( t nu ! i este c&ntr cti" - $ c $e% seste 7=P $in su%r f t c&ntr cti" AS , functi s $e %&!% este $r stic fect t /< s&c c r$i&,en :. Tu"'ur ri ,r #e $e rit! cu frec#ent f) in "t si %re"un,ite in ti!% - $ t&rit frec#entei c r$i ce !u" %re ! ri, sc $e $i st&" /< sc $e u!%"ere #entricu" r / -i%&$i st&"ie, c re in f&r!e ,r #e %& te !er,e % n " sc $ere $e'itu"ui siste!ic/< s&c c r$i&,en 0. T !%&n $ c r$i c 3/ cu!u" re ! si# "ic-i$i n in c #it te %eric r$ic , $e n tur -e!&r ,ic s u ne-e!&r ,ic . %r&$uce c&!%resi extrinsec !i&c r$u"ui $e& rece %eric r$u" este %utin $istensi'i" /< se re$uce c % cit te $e u!%"ere #entricu" r /< sc $e $e'itu" c r$i c /< s&c c r$i&,en 7. E!'&"ii"e %u"!&n re ! si#e 3in s%eci " %e trunc-iu" c&!u" " rterei %u"!&n re, s u %e un $in ce"e : rtere %u"!&n re, $re %t s u st n, .

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+ %&t fi $e n tur tr&!'&tic @ ,r s& s @ , (& s @ s u cu ce"u"e tu!&r "e) - in s% te"e ' r ?u"ui e!'&"ic, circu" ti %u"!&n r $e#ine f) re$us /< int& rcere s n,e"ui " c&r$ %rin #ene"e %u"!&n re sc $e /< sc $e u!%"ere AS /< sc $e DC /< s&c c r$i&,en SOCUL TOXICOSEPTIC Este & c&!%"ic tie ,r # un&r $iferite infectii se#ere) In s&cu" t&xic&se%tic 3Sts., in %ri!e"e st $ii, %erfu(i tisu" r este n&r! " c ntit ti#, $ r este t&t " insuficient in r %&rt cu n cesit ti"e $e &xi,en, !u"t %re ! ri, "e tesuturi"&r)Aceste necesit ti se $ t&re ( ctiunii -ist&t&xice $iferite"&r t&xine su%r cti#it tii tisu" re res%ecti#e) In %rinci% " %rin $e%ri! re cti#it tii !et '&"ice &xi$ ti#e si sti!u" re ,"ic&"i(ei n er&'e, ceste en$&t&xine c&ncur " inst " re unei ci$&(e se#ere, inc $e " ince%ut) Prin cu!u" re $e c) " ctic si % riti st rii $e ci$&( , sc $e t&nusu" # scu" r % n " st ( in !icrcircu" tie /< ,r # re -i%&xiei /< e"i'er re $e !e$i t&ri # s& cti#i 3#e(i ce"e" "te s&curi.) Princi% "ii f ct&ri eti&"&,ici sunt: ;.%erit&nite"e 3in s%eci " ce"e %rin ru%turi $e se,!ente $i,esti#e si &r, ne ,enit "e.) :.infectii"e , n,ren& se cu ' ci"i n er&'i 0. rsuri"e intinse c&!%"ic te cu su%r infectii f&r!e"e su%r cute "e un&r '&"i infecti& se 3t&xiinfectii "i!ent re, st fi"&c&cii, stre%t&c&cii, $ifterie.) 7.$iferite ! ne#re $e ex%"&r re % r c"inic @ inter#entii c-irur,ic "e efectu te in c&n$itii $e re" ti# se%sie, ! i "es ce"e %r ctic t %e tr ctu" urin r inferi&r) 2. $!inistr re un&r %erfu(ii cu $iferite s&"utii nec&ntr&" te si c&nt !in te ' cteri n 4.tr nsfu(ii cu s n,e nec&ntr&" t si c&nt !in t) TUL6U*A*ILE META6OLICE IN SOC In s&cu" circu" tt&r 3ex) s&cu" -i%&#&"e!ic, s&cu" c r$i&,en. initi " % r tu"'ur ri -e!&$in !ice,i r secun$ r -i%&functiei % r si tu"'ur ri"e !et '&"ice) In s&cu" t&xic&se%tic, $ t&rit % trun$erii ! si#e $e ,er!eni si en$&t&xine," ni#e" tisu" r % r int i tu"'ur ri !et '&"ice si secun$ r tu"'ur ri -e!&$in !ice) In$iferent $e ti%u"s&cu"ui, in f (e # ns te tu"'ure ri"e !et '&"ice si -e!&$in !ice se intre% trun$) Tu"'ur ri"e !et '&"ice $in s&cu" -i%&#&"e!ic A. Tu"'ur ri"e !et '&"is!u"ui ,"uci$ic:

. $in %ri!e"e !&!ente "e inst " rii s&cu"ui -i%&#&"e!ic se inre,istre( & -i%er,"ice!ie %&st ,resi# , f& rte i!%&rt nt %t)
c %rin crestere $is%&ni'i"u"ui $e ,"uc&( c tre tesuturi 3! i "es %t) ini! si creier. se !%"ific %r&$ucti $e ener,ie neces r %&st ,resi# %t) functi&n re " c % cit te ! xi! $iferite"&r &r, ne) . !ec nis!u" -i%er,"ice!iei %&st ,resi#e: ;. G"ic&,en&"i( -e% tic este sti!u" t $e c&ncentr tii"e crescute "e -&r!&ni"&r: $ren "in , ,"uc ,&n, AT II,-&r!&nii tir&i$ieni, ADH1 -&r!&nii se fixe ( %e * s%ecifici -e% t&cit ri cti# n$ siste!u" $eni" tcic" ( +AMPc /< AMPc sti!u"e ( & f&sf&8in ( ce cti#e ( f&sf&ri" (e"e /< $esf cere ,"ic&,enu"ui 3,"ic&,en&"i( . /< G+;+Pc re este tr nsf&r! t $e f&sf&,"uc&!ut ( in G+4+P c re cu ?ut&ru" G+4+f&sf t (ei este e"i'er t $in ce"u" -e% tic in circu" tie /< -i%er,"ice!ie Si !usc-iu" re ,"ic&,en %e c re in $e,r $e ( %rin ,"ic&,en&"i( , $ r ne # n$ G+4+P nu %& te e"i'er in circu" tie ,"uc&( stfe" &'tinut 1 in sc-i!' creste c ntit te $e G+4+P in ce"u" !uscu" r /< se cti#e ( ,"ic&"i( /< creste c ntit te $e c " ctic c re se # e"i'er in circu" tie, $ r nu # % re ci$&( $e& r ce c) " ctic este uti"i( t $e fic t %t ,"uc&ne&,ene( /< ,"uc&( %e c re fic tu" & e"i'ere ( in circu" tie /< -i%er,"ice!ie :. Sti!u" re ,"uc&ne&,ene(ei -e% tice1 ,"uc&ne&,ene( se $esf s& r %rin re ctii in#erse c ii ,"ic&"itice ce $uc " &'tinere $e G+4+P $in c re ,"uc&( # fi e"i'er t cu ?ut&ru" G+4+f&sf t (ei) G"uc&ne&,ene( este sti!u" t %&st ,resi# $e nu!iti -&r!&ni: ,"uc&c&rtic&i(i, ,"uc ,&n1 cesti -&r!&ni cresc in$ucti sint) en() i!%"ic te in ,"uc&ne&,ene( ) Mu"te c i "e ,"ic&"i(ei nu sunt re#ersi'i"e1 sunt $eci neces re c i !et '&"ice ce sunte ( ceste et %e s u sunt neces re "e en(i!e) G+4+P F+4+P $i-i$r&xi cet&nf&sf t F+;,4$iP ,"icer "$e-i$trif&sf t

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f&sf&en&"%iru# t %iru# t ceti"+C&A

.,"uc&ne&,ene( $in c) " ctic

. c " ctic %r&#ine ! i "es $in !%"ific re ,"ic&"i(ei !uscu" re . in$i#i$u" in s&c nu este -i%&xe!i t /< c) " ctic este tr nsf&r! t in c) %iru#ic su' inf"uent LDH1
c)" ctic c)%iru#ic c)&x "& cetic f&sf&en&"%iru# t F+;,4,$iP F+4+P G+4+P Ce"e 7 en(i!e c-eie "e ,"uc&ne&,ene(eisunt: . %iru# tc r'&xi" ( . f&sf&en&"%iru# tc r'&xi" ( . fruct&(&;,4$if&sf t ( . i(&!er ( E"e sunt cti# te $e -&r!&nii ,"uc&c&rtic&i(i si $e ,"uc ,&n) '. ,"uc&ne&,ene( $in ,"icer&" . ,"icer&"u" %r&#ine $in sti!u" re "i%&"i(ei " ni#e"u" tes $i%&s $e c tre -&r!&ni cu efect c t '&"ic) . -i$r&"i( TG /< AG L ,"icer&" ce sunt $esc rc ti in s n,e $e un$e ,"icer&"u" este %re"u t $e c tre fic t su' ctiune unei ,"icer&8in (e c re in tr nsf) in ,"icer&"+P TG AG L ,"i,er&" ,"icer&"+P $i-i$r&xi cet&n+P F+;,4$iP F+4+P G+4+P c. ,"uc&ne&,ene( $in !in& ci(i . $is%&ni'i"u" crescut %&st ,resi# se $ t&re ( sti!u"1 rii c t '&"is!u"ui %r&teic $e c tre -&r!&nii c t '&"i( nti ) ) re(u"t ti sunt $e( !in ti /< & % rte sunt tr nsf) in c) %iru#ic ce # ur! c "e ,"uc&ne&,ene(e(ei/< & % rte sunt tr nsf) in c&nstit) i cic"u"ui >re's: c)&x "& cetic, c)fu! ric, c) succinic1 cesti #&r % rcur,e cic"u" 8re's: c) &x "& cetic ,"uc&ne&,ene( 0. *e$ucere intr rii ,"uc&(ei in tesuturi"e insu"in&$e%en$ente1 . in f (e"e # ns te "e s&cu"ui, ,"ice!i sc $e %r&,resi# /< -i%&,"ice!ie ,r # / f ct&r $e ire#ersi'i"it te s&cu"ui 3creieru" nu %& te f&"&si $ec t ,"uc&( .

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02 . ce st -i%&,"ice!ie se $ t&re ( : e%ui( rii re(er#e"&r $e ,"ic&,en, in-i' rii t&t "e ,"uc&ne&,ene(ei c n$ fic tu" sufer & -i%&xie ! r c t 3en(i!e"e ,"uc&ne&,ene(ei necesit ATP1 in c&n$) -i%&xice cic"u" 8re's nu ! i functi&ne ( 'ine/<sc $e %r&$ucti $e ATP.
6.Tu"'ur ri"e !et '&"is!u"ui "i%i$ic . $in f ( c t '&"ic *)S)P)A se cti#e ( "i%&"i( $ t&rit un&r -&r!&ni: $en "in , ,"uc&c&rtic&i(i, ,"uc ,&n, -&r!&ni tir&i$ieni1 . cesti -&r!&ni cti&ne ( %rin sti!u" re siste!u"ui $eni" tcic" ( +AMPc $e " ni#e"8 $i%&cit r1 . AMPc sti!u"e ( & %r&tein8in ( c re cti#e ( & "i% ( su' ctiu!e c rei re "&c -i$r&"i( TG /< AG L ,"icer&" . ,"icer&"u" # ser#i ,"uc&ne&,ene(ei . AG / surs ener,etic i!%&rt nt , sunt %re"u ti $e tesuturi ce sufer %utin $ t&rit # s&c&ntrictiei 3!i&c r$, fic t., sunt $e,r $ ti &xi$ ti# % n " CO: si H:O . $e,r $ re &xi$ ti# AG / +&xi$ re, %r&ces $in c re re(u"t ener,ie) . +&xi$ re AG: re "&c in !it&c&n$rii, $u% ce AG sunt %re"u ti $e ci"c rniti"tr nsfer ( %&i re"&c scin$ re succesi# " ntu"ui $e AG, cu e"i'er re $e fr ,!) $e : t&!i $e C su' f&r! $e ceti"+C&A1 c&nc&!it nt cu c est %r&ces re "&c si un %r&ces $e $e-i$r&,en re cest&r fr ,!ente, -i$r&,enu" re(u"t t fiin$ %re"u t $e NAD /< NADH ceti"+C&A re(u"t t intr in cic"u" >re's 3 "c) $in re ctii $e $e-i$r&,enere1 -i$r&,enu" re(u"t t fiin$ %re"u t $e NAD/<NADH t&!ii $e -i$r&,en $e %e NADH+u" re(u"t t $in cic"u" >re's si $in et % initi " sun %&i "u ti $e cit&cr&!i si tr nsfer ti succesi# % n " c %u" " ntu"ui res%ir t&r, c n$ #&r fi ce$ ti O: f&r! n$ H:O1 cest tr nsfer $e, ? & c ntit te ! re $e ener,ie ce este in! , (in t in ATP) . c n$ fic tu" nu este -i%&xi t, cic"u" >re's functi&ne ( , %rei -i$r&,enu" $e %e NADH /< n&i !&"ecu"e $e NAD %t + &xi$ re si cic"u" >re's . in st $ii # ns te "e s&cu"ui, -i%&xi este ! rc t /< $ t&rit "i%sei $e O: ni ! i functi&ne ( " ntu" res%ir t&r /< -i$r&,enu" nu ! i este %re,u t $e %e NADH /<$eficit $e NAD /< +&xi$ re este '"&c t /< $is% re & surs i!%&rt n t $e ener,ie / ! t '&"i( re &xi$ ti# AG /< AG s&siti " fic t sunt &rient ti c tre sinte( $e TG . $ c ,r $u" $e-i%&xie este ! rc t TG nu ! i sunt int ,r te in "i%&%r&teine /< inc rc re ,r s -e% t&cite"&r /< insuficient -e% t&ce"u" r . % n " -i%&xie se#er , +&xi$ re este f #&r 'i" si %t) sti!u" re ,"uc&ne&,ene(ei: creste $is%&ni'i"u" $e ceti+C&A c re in-i' %iru# t$e-i$r&,en ( /< in-i' re tr nsf&r! rii %iru# tu"ui in ceti"+C&A /< %iru# tu" este &rient t c tre ,"uc&ne&,ene( 1 $e se!ene excesu" $e ceti"+C&A creste sinte( $e c&r%i cet&nici /< %e " n, ten$int $e ci$&( " ctic 3c t&rit -i%&xiei. e este ,r # t si $e sin) c&r%i"&r cet&nici) C.Tu"'ur ri"e !et '&"is!u"ui %r&teic . $esc rc re crescut $e -&r!&ni c t '&"i( nti creste si c t '&"is!u" %r&teic /< se $is%&ni'i"i(e ( & c ntit te ! re $e ) ), c re t t ti!% c t nu exist -i%&xie -e% tic sunt uti"i( ti %t) ,"uc&ne&,ene( ,ni#e"u" "&r %"s! tic necresc n$) . crestere ni#e"u"ui %" s! tic " ) ) % re in f (e"e # ns te: in insuficient -e% tic , c n$ nu ! i sunt f&"&siti in ,"uc&ne&,ene( si nici in sinte(e %r&teice, $e se!ene e"i!in re "&r ren " fiin$ $i!inu t in ce st f ( t r$i# 3sc $ere %erfu(iei ren "e / I*. . $ t&rit c t '&"is!u"ui %r&teic crtesc si ni#e"uri"e "t&r c&!%usi $e c t '&"is! %r&teic: c) uric, $in c t '&"is!u" nuc"e&%r&teine"&r, cre tinin $in c t '&"is!u" f&sf&cre tinei !uscu" re, uree , f&r! t " ni#) -e%) $in NH0 re(u"t t $in $e( !in re ) ) . %e ! sur ce sc $e functi ren " , ureee nu se ! i e"i!in ren "/) creste ure!i si $e%ri! ur&,ene( -e% tic /< sc $e ni#e"u" ureei in s n,e, $ r se cu!u"e ( NH0 /< creste %ericu"&s !&ne!i 3NH0 t&xic ! i "es %t) tes) ner#&s. . &$ t cu ,r # re -i%&xe!iei % r "ter ri ce"u" re i!%&rt nte /< !') "i(&(&! " se $istru,e /< e"i'er re in tesuturi $e en(i!e "i(&(&! "e1 !u"te $ie e"e sunt %r&te (e c re se cti#e ( f) us&r in !e$iu ci$ si t c $iferite str) %r&teice tisu" re /< i u n stere $iferite %eti$e n&ci#e in st re $e s&c: MDF3f ct&ru" $e $e%ri! re !i&c r$ic . f ct&ru" $e "e( re %u"!&n r 3"e( re e%ite"iu"ui "#e&" r si en$&te"iu"ui c %i" r %u"!&n r. f ct&r ntisurf ct nt3t&xic %t) %neu!&cite"e II ce secret surf ct ntu". L*F / sti!u"e ( e"i'er re en(i!e"&r "i(&(&! "e1 ceste en(i!e %&t cti# nes%ecific 0 siste!e cu r&" f) i!%&rt nt in e#&"uti ne, ti# s&cu"ui: ;. cti#e ( siste!u" 8inine"&r

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:. cti#e ( c& ,u" re /< CID 0. cti#e ( siste!u" fi'rin&"itic /< -i%erfi'rin&"i( /< sin$r&! -e!&r ,ic) D.Tu"'ur ri"e !et '&"is!u"ui -i$r&r"rctr&"itic .N :

. c&nser# t %rin restr n,ere "i!i) ren "e, %rin -ie%rsecreti $e "$&ster&n . sre efect &s!&tic /< re 's) H:O /< re$res re #&"e!ic . &$ t cu # ns re s&cu"ui % re ten$int $e -i%&n tre!iere $ t&rit intr rii N in ce"u"e 3in !&$ n&r! " e" este ex%u"( t
$e c tre %&!% N @ >.1 in s&c ce st %&!% este $eficit r L ci$&( in-i' %&!%e"e /< cu!u" re N intr ce" /< cu!u" re H:O intr ce") /< -i%er-i$ret re ce"u" r /< cce"er re $istru,erii ce"u" re /< !& rte ce"u" r . -i%er-i$r t re tesutu"ui ner#&s $eter!in c&!%resi centri"&r ner#&si '.>: . $in %ri!e"e f (e "e s&cu"ui, creste >+e!i $ t&rit e"i'er rii > $in ce"u"e"e $istruse, i r %t) c ci$&( si $efici&tu" $e ATP in-i' %&!%e"e !') /< > nu ! i este recu%er t $e c tre ce"u"e) . efecte"e $ef #&r 'i"e: tu"'ur ri $e rit! c r$i c /< sc $ere $e'itu"ui c r$i c /< sc $ere %erfu(iei tisu" re 3cere'r "e. "ter re e"ectr,ene ei 3suferint cere'r " . c.C :

. re ten$int $e cu!u" re ce") &$ t cu $eficitu" $e ATP,%rin in-i' re %&!%ei !') $e C . efecte"e $ef #&r 'i"e:
in-i' re $eni" tcic" (ei si %r&$ucereii $e AMPc / !es ,er secun$ i!%&rt nt %t) ctiune un&r -&r!&ni ce sti!u"e ( ,"ic&"i( , ,"ic&,en&"i( i!%ie$ic tr ns"&c re nuc"e&ti$e"&r $in !') !it&c&n$ri " : este in-i' t e"i'er re $e ATO $in !it) in cit) cti#e ( niste en$&nuc"e (e ce initi ( !& rte ce"1u" r %rin %&%t&( cti#e ( en(i!e ce $uc " "i( &r, nit "&r /< necr&( ce"u" r ) $.H:O: . $u% &rice ctiune i!%&rt t , e"i!in re %ei $in &r, nis! esFte restircti&n t %rin crestere re 's) $e %e su' ctiune ADH si "$&str&nu"ui) . in % r "e cu restricti&n re e"i!in rii $e % , $ t&rit cresterii c t '&"is!u"ui, creste si f&r! re $e % en$&,en " ni#e"u" ce"u" r /< efect $i"uti&n " " %ei /< sc $e &s!&" rit te intr ce" /< tre,ere $e % ce"u" r c tre interstitii /< % trece $in interstiti in c %i" re % rtici% n$ " ref c re #&"e!ic si $et) sc $ere %resiunii c %i" re /< %resiune c&"&i$&s!&tic %" s!ei este ! i ! re /< tre,ere $e % . in ,resiuni"e cu %ier$eri ! ri $e % , initi " se %r&$uce & -i%er&s!&" rit te extr ce" %ri -i%erN +e!ie /< % intr in # s . in f ( "e # ns te cest tr nsfer este in#ers t, % trece c tre ce"u"e /< sc $e #&"u!u" circu" nt L tu!efiere -i$ric ce") /< $istructie ce"u" r . !ec nis!e"e ce f #&ri(e ( intr re %ei $in # s in interstitiu +<ce"u"e c n$ se $esc-i$e sf) %rec %i" r $ r ce" %&stc %i" r r ! ne inc-is, intr re s n,e"ui in rete"e"e %&stc %i" re creste %resiune -i$r&st tic /< tr nsfer c tre interstitiu -i%&xi tisu" r $et) $esc rc re !e$i t&ri"&r ce cresc %er!e 'i"it te c %i" r /< creste tr nsferu" c tre interstitii fectere cti#it tii %&!%e"&r !') $eter !in cu!u" re N intr ce"u" r cec tre,e % in s&cu" t&xic&se%tic, existent in tes) $e ,er!eni si en$&t&xine $ec" nse ( fen&!ene inf" ! t&rii siste!ic /< se e"i' re ( cit&8in , IL, f ct&ric-e!&t ctici, se cti#e ( c&!%"e!entu" c re " r n$u" s u $et % riti "t&r f ct&ri c-e!&t ctici si # s& cti#i1 cesti f ct&ri tu"'ur !et '&"is!u" tisu" r: cit&8ine"e si IL $et) # s&$i" t tie /< st ( in !icr&circu" tie, $e se!ene ?un, n$ " centri" $e ter!&re," re $et re cti fe'ri" ce c&nsu! !ut ener,ie /< cce"er re e%ui( rii re(er#e"&r ener,etice1 f ct&rii c-e!&t ctici cti#e ( en(i!e"e f ,&cit re /< en(i!e, s%ecii $e &xi,en cti#e /< "e(iuni tisu" re E.Tu"'ur ri"e ec-i"i'ru"ui ci$&+ ' (ic: . $ t&rit sc $erii #&") efecti# circu" nt si # s&c&nstrictiei in nu!ite terit&rii /< -i%&xie /< creste c ntit te $e c) " ctic /< ci$&( " ctic . $ t&rit sti!u" rii cet&,ene(ei /< ci$&( . i!%ei$ic re ci$&(ei !ec nis!e"&r c&!%ens t&rii:

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-i%&xi si ci$&( sti!u"e ( centru" res%ir t&r /< -i%er#enti" tie c re c&!%ense ( -i%&xi si ci$&( 3 creste e"i!in re $e CO:. /< "c "&( res%ir t&rie %erfi(i ren " inc %re(ent /< creste e"i!in re $e %r&t&ni si recu%er re $e 'ic r'&n t ' (e t !%&n extre si intr ce"u" re . %e !esur ce -i%&xi creste /< creste %r&$ucti $e c) " ctic /< !ec nis!e"e c&!%ens t&rii sunt $e% site /< ci$&( $ec&!%ens t /< !%"ific re I* si sec-estr re s n,e"ui in !icr&circu" rti %eriferic ce $uce " "ter re sc-i!'uri"&r , (& se /< nu se ! i e"i!in CO: /< -i%erc %nie . efecte n&ci#e: !et ') ci$&' (ic CONSECINTELE TUL6U*A*ILO* META6OLICE In cti#it te &r, ne"&r % r G&r, ne $e s&cH In f (e"e # ns te % r insuficiente $e &r, n, !u"ti%"e / f ct&ri $e ire#ersi'i"it te s&cu"ui P" ! nu" $e s&c: initi " -i%er#enti" tie c re c&!%ense ( ci$&( si -i%&xi ,r # re tu"'ur ri"&r s&cu"ui /< sc $ere sc-i!'uri"&r , (& se /< ,re# re -i%&xiei si -i%erc %niei se $esc-i$ sunturi"e rteri&c %i" re /< c %i" re"e %u"!&n re sunt sunt te /< sc $e sc-i!'u" , (&s s t ( in !icr&circu" ti %u"!&n r /< '"&c re cu f&r! re $e tr&!'i 3Q/ CID. /< extr #& ( re -i$ric c tre interstitiu 3crestere %er!e 'i"it tii c %i" re $ t&rit un&r !e$i t&ri. /< e$e! %u"!&n r nec r$i&,en ce creste $int nt intre %erete"e "#) si ce" c %i" r /< in,reun re $ifu(iunii , (e"&r %rin !' res%ir t&rie e$e!u" se nu!este $etres res%ir t&rie $u"tu"ui sut fect te sc-i!'uri"e , (& se si $ t&rit c&" ' rii "#) $ t&rit $istructiei surf ct ntu"ui 3 ct&ru" ntisurf ct nt.1 !u"te "#) sunt &'stru te %rin $escu ! re c "u""&r "#) $ t&rit "e() -i%&xice si $ t&rit f ct&ri"&r $e "e( re %u"!&n r Fic tu" $e s&c: initi " creste %r&$ucti $e ener,ie si ni#e"u" $e ,"uc&( $in s n,e in f (e"e # ns te -i%&xi fecte ( functii"e -e% tice functi $e sint ( %r&teine"&r: sc $ere sint (ei f ct&ri"&r $e c& ,u" re, sc$ere %r&$uctiei $e in cti# t&ri i %" s!inei /< creste c&nsu!u" $e f ct&ri $e c& ,u" re /< creste fi'rin&"i( $is% re ,"&c&ne&,ene( functi ntit&xic : t&xi"e"e si en$&t&xine"e cresc si in tesuturi functi $e !et '&"i( re %i,!enti"&r 'i"i ri: creste 6*+e!i c re este c r$i& $e%ri! nt Tr ctu" , str&intestin ": sufer # Js&c&nstrictie inc $e " ince%ut /< "e(iuni si u"cer tii " e !uc& sei , strice /< % r -e!&r ,ii $i,esti#e /< sc $ere #&"e!ic u"cer tii"e sunt f #&ri( te $e sc $ere %r&$uctiei $e !ucus $ t&rit cresterii ni#e"u"ui $e ,"uc&c&rtic&i(i " ni#e"u" intestinu"ui, $ t&rit "e(iuni"&r isc-e!ice /< trecere %rin !uc& s "e( t in circu" tie in&r en$&t&xine %e c re fic tu" ne! i%utunt in cti# #&r ?un,e " tesuturi *inic-iu": sc $e f"uxu" ren " /< sc $e %resiune $e fi"tr re /< nu" re ,r $ientu"ui $e fi"tr re /< I* functi&n " %i& se ,r #e ( -i%&%erfu(i /< "e(iuni ren " ! i "es tu'u" re, $i" cer ri "e !') ' ( "e / tu'u"&re(is1 ceste "e(iuni, %rin $escu ! re ce") in "u!en $et: ;.&'structie tu'u" r :.se %er!ite re 's) c&!%"et u"tr fi"tr tu"ui /< nurie /< I* &r, nic I* se inst "e ( %rin 0 !ec nis!e: ;. '&"ire fi"tr rii ,"&!eru" re :. &'structi tu'u" r 0. retr&s&r'ti u"tr fi"tr tu"ui STADIALIZA*EA STA*II DE SOC () St $iu" initi " : st $iu" $e -i%&tensiune c&!%ens t %rin sc $ere % tu"ui # scu" r se c&!%ense ( ten$int " %r 'usire TA *) si,ur +) ,) St $iu" in c re ince%e st ( s n,uin in !icr&circu" tie sc $e int& rcere #en& s " ini! /< % re & inc % cit te $e & %erfu(ie suficient %t &r, ne"e #it "e St $iu" in c re % r, $ t&rit -i%&xiei, "ter ri"e structur "e "e ce"u"e"&r ce e#&"ue ( c tre f ( ur! t& re St $iu" $e ire#ersi'i"it te s&cu"ui F ct&rii $e ire#ersi'i"it te s&cu"ui sunt:

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-i%&,"ice!i ci$&( CID insuficient !u"ti%" $e &r, n FIZIOPATOLOGIA INSUFICIENTEI CARDIACE Insuficient c r$i c / st re % t&"&,ic c r cteri( t %rin "ter re functiei $e %&!% ini!ii, ini! fiin$ in %t s %rei si@ s u s ex%u"(e(e & c ntit te $e s n,e $ec# t necesit ti"&r !et '&"ice, cu "te cu#inte, $e'itu" c r$i c este in $ec# t f t $e necesit ti"e &r, ne"&r) In ! re ! ?&rit te c (uri"&r $e IC Dc este sc (ut, exce%tie fiin$ IC ce $e'ute ( %e f&n$u" unui Dc crescut, $ r t&tusi insuficient cu necesit ti"e tisu" re !u"t crescute $e O:1 cest % re c n$ exist c&n$itii % t&"&,ice %re " 'i"e ce cresc Dc %rin crestere int& rcerii #en& se, s u %rin re(istent # scu" r %eriferic , cu! r fi: . fistu"e rteri&+#en& se nu!er& se /< creste int& rcere #en& s '. ne!ii i!%&rt nte /< re(istent # scu" r sc (ut 3s n,e cu $ensit te sc (ut . L" tesuturi ?un,e & c ntit te sc (ut $e O: 3$ t&rit c ntit tii sc (ute $e H'. /< -i%&xie /< cu!u" re $e c) " ctic /< ci$&( /< sc $ere t&nusu"ui # scu" r %eriferic c. -i%ertir&i$is! /< efct c "&ri,en /< sc $ere t&nusu"ui # sc) %eriferic /< sc $ere re(istentei # sc) %eriferice In ceste c&n$itii % t&"&,ice, $esi Dc este crescut % re & IC $e& rece cest Dc este t&tusi ineficient: - in ne!ii este neces r & c ntit te ! re $e O: - -i%ertir&i$is!u" creste necesit ti"e !et '&"ice - fistu"e"e rteri&+ #en& se %r&$uc -i%&xie tisu" r /< neces r $e O: crescut A,r # re cestei IC se ! nifest %rin sc $ere c&ntr cti"it tii !i&c r$ice /< tre%t t # sc $e si Dc /< se # tr nsf) intr+& IC ti%ic cu Dc sc (ut CLASIFICA*EA INSUFICIENTELO* CA*DIACE: () INSUFICIENTA CARDIACA LATENTA: - este IC in c re sc $ere Dc este !ini! )i) nu % r ! nifest ri c"inice *) INSUFICIENTA CARDIACA ACUTA# - este IC 'rut " inst " t ce nu %er!ite intr re in functie tutur&r !ec nis!e"&r c&!%ens t&rii +) INSUFICIENTA CARDIACA CRONICA# - este IC inst " t %r&,resi#, "ent ce %er!ite intr re in functiune tutur&r !ec) c&!%ens t&rii, )i) tu"'ur ri"e fi(i&% t&"&,ice si c"inice se $ t) IC %r&%riu+(ise si !ec) c&!%ens t&rii ,) INSUFICIENTA CARDIACA RETROGRADA - este IC in c re ! ?&rit te tu"'ur ri"&r fi(i&% t&"&,ice si c"inice se $ t) st (ei #en& se in %&i #entricu"u"ui ce este insuficient: st ( #en& s retr&,r $ As /< st ( #en& s %u"!&n r , st ( retr&,r $ A$ /< st ( #en& s siste!ic 3 %e #ene"e c #e. 4) INSUFICIENTA CARDIACA ANTEROGRADA - este IC " c re !e?&rit te tu"'ur ri"&r fi(i&% t&"&,ice si c"inice se $ t&re ( sc $erii ex%u"(iei #entricu" re :) INSUFICIENTA CARDIACA RETROGRADA SI ANTEROGRADA - este IC in c re ce" si '&"n # %re(int un nu!it ,r $ $e IC retr&,r $ c t si un nu!it ,r $ $e IC nter&,r $ , in %r&%&rtii $iferit , un $in e"e %re$&!in n$ s u in %r&%&rtii e,e"e) ;) INSUFICIENTA CARDIACA STANGA - se ! nifest nter&,r $, retr&,r $ s u !ixt <) INSUFICIENTA CARDIACA DREAPTA - se ! nifest %re$&!in nt retr&,r $ =) INSUFICIENTA CARDIACA GLOBALA - % re %rin extin$ere IAS " A$ - ! i r r % re c t re $e " ince%ut 3 !i&c r$ite, c r$i&!i&% tii. (>) CORDUL PULMONAR ACUT? CRONIC - IC$r cut @ cr&nic $et) $e su%r s&"icit re A$ %rin HTP $et) $e $iferite fectiuni %u"!&n re (() INSUFICIENTA CARDIACA CONGESTI)A - este IC in c re se!ne"e si si!%t&!e"e se $ t) st (ei #en& se retr&,r $e - st ( %u"!&n r /< IAS : $is%nee, r "uri - st ( in #ene"e c #e /< IAD: tur,escent ?u,u" re"&r, -e% t&!e, "ie, e$e!e "e !' inferi& re (*) INSUFICIENTA CARDIACA REFRACTARA - este IC ter!in " , c re nu %& te fi c&ntr&" t ter %eutic, $e#enin$ ire$ucti'i"

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CLASIFICA*EA ETIOPATOGENICA A INSUFICIENTEI CA*DIACE Afect re functiei $e %&!% ini!ii se %& te fr ce %rin fect re : . !ec nis!u"ui $i st&"ic / fect re functiei $e u!%"ere '. !ec nis!u"ui sist&"ic / fect re functiei $e e?ectie In functie $e !ec nis!u" "ter t $e f ct&rii eti&% t&"&,ici se $intin, 0 f&r!e $e IC, : $ t&r te fect rii e?ectiei si ; $ t&r t fect rii u!%"erii) ;. INSUFICIENTA CA*DIACA DISDIMAMICA - este $ t&r t su%r s&"icit rii $e re(istent 3%resiune. s u $e #&"u! su%r #entricu"i"&r - su%r s&"icit ri"e $e %resiune s u $e #&"u! cr&nice $uc secun$ r " $e%ri! re tre%t t c&ntr cti"it tii !i&c r$ice /< sc $e e?ecti #entricu" r - su%r s&"icit ri"e $e %resiune si $e #&"u! cut %&t $et) sc $ere ex%u"(iei c-i r $ c c&ntr cti"it te , c %r&%riet te intrinsec !i&c r$u"ui nu este fect t - e!'&"i %u"!&n r ! si# $et) su%r s&"icit re %resi&n " ! re su%r A$ /< A$ se $i" t c&!%ens t&r, c&ntr cti"it te s nu este fect t , $ r $ t&rit cresterii %resi&n "e e?ecti s nu se ! i f ce c&res%un( t&r) . su%r s&"icit re $e %resiune: c u(e c r$i ce: - $efecte $e !ec nic # "#u" r : sten&( str ns $e # "# - c r$i&!i&% ti &'structi# cr&nic : -i%ertr&fie ! re fetei st,) se%tu"ui #entricu" r ex ct in(&n c n "u"ui $e e# cu re As /< (&n se &'strue ( /< ' r ? in c "e e?ectiei c u(e extr c r$i ce: - HTA esenti " 3 %t) As. - HTP 3 %t) A$. - crestere # sc&(it tii s n,e"ui 3%&"i,"&'u"ii. /< su%r s&"icit re t t As c t si A$ '. su%r s&"icit re $e #&"u!: c u(e c r$i ce: - $efecte i!%&rt nte $e !ec nic # "#u" r : insuficient # "#u" r 3ex)IA&: $u% ex%u"(i As s n,e"e re,ur,ite ( $in A& in As, in $i st&" " cest s n,e se $ u, ce" $in As /< " ur! t& re sist&" As # ex%u"( & c ntit te ! i ! re $e s n,e - DSA : ce" $&i #entricu"i c&!unic /< in sist&" & % rte $in s n,e"e As ?un,e in A$ /< A$ # fi su%r s&"icit t $e #&"u! c u(e extr c r$i ce: - -i%er#&"e!ii 3int& rcere #en& s ! i ! re. - fistu"e rteri&+#en& se /< creste int& rcere #en& s :. INSUFICIENTA CA*DIACA P*IN AFECTA*EA P*IMA*A A CONT*ACTILITATII MIOCA*DICE SAU @ SI SCADE*II EFICIENTEI CONT*ACTIEI MIOCA*DICE A. Sc $ere %ri! r c&ntr cti"it tii 3c si sc $ere sec) c&ntr cti"it tii. $et) "ter re !ec nis!u"ui sist&"ic / sc $ere e?ectiei ex). !i&c r$ite"e t&xice s u infecti& se 3 !i&c r$it $ifteric . !i&c r$ite"e !et '&"ice s u nutriti&n "e 3!i&c r$it %rin #it !in&( 6;, !i&c r$it "c&&"ic . !i&c r$ite"e i!un& "er,ice 3 !i&c r$it reu! tis! " . c r$i&!i&% ti %ri!iti# @ secun$ r $i" t ti# isc-e!i !i&c r$ic se!nific ti# 3 sc $e %r&$ucere $e ener,ie neces r c&ntr ctiei. %" ,i !i&c r$ice, tr u! tis!e !i&c r$ice 6. Sc $ere eficientei !i&c r$ice 3 r n$ !entu" c&ntr ctiei este ! i !ic. ;. sc $ere ! sei !uscu" re #entricu" re c&ntr cti"e ex). inf rct ! re /< (&n necr&( t nu ! i este c&ntr cti" :. n&! "ii $e ! c nic si ,e&!etrie #entricu" r . $i" t ti #entricu" r /< $et $i" t re &rificiu"ui tri&+#entricu" r /< % r tu" # "#u" r nu ! i %& te inc-i$e et ns &rificiu" /< re,ur,it re s n,e"ui $in #entricu" in trii in sist&" '. sincr&nii !ec nice # ntricu" re : (&ne"e necr&tice %&stinf rct sunt -i%&8inetice 3 c&ntr ctie ! i s" ' si ! i t r$i# . /< e?ectie sc (ut cu eficient sc (ut c. $isc-ine(ii #entricu" re : & % rte %erete"ui se c&ntr ct , i r ce " "t % rte se re" xe ( ex). ne#ris!u" #entricu" r: une&ri (&n %&stinf rct se re!&"este /< in sist&" #entricu" r ce st (&n se $i" t , se u!%"e cu s n,e c & $i" t tie s cif&r! , & % rte $in s n,e"e ce tre'uie e?ect t se str n,e ici

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0. INSUFICIENTA CA*DIACA P*IN ALTE*A*EA UMPLE*II AENT*ICULA*E DE CAUZA CA*DIACA A.F ct&ri !i&c r$ici: . sc $ere c&!%"i ntei #entricu" re: '&"i !i&c r$ice infi"tr ti#e fi'r&( !i&c r$ic s&ci t unei -i%ertr&fii !i&c r$ice cic trici !i&c r$ice !u"ti%"e '. sc $ere c&ntr cti"it tii !i&c r$ice /< in$irect sc $e u!%"ere 1 in c&ntr cti #entricu" r , f') !i&c r$ice se scurte ( cu!u" n$ in e"e & f&et e" stic / f&rt $e res&rt intern1 c n$ s+ ter!in t sist&" , cest f&rt se e"i'ere ( 'rusc /< %e ' ( ener,iei e" stice se %r&$uce & re" x re ener,ic ce $ n stere unei f&rte / f&rt e suctiune s n,e"ui $in trii ce f #&ri(e ( u!%"ere 1 &$ t cu sc $ere c&ntr cti"it tii sc $e si f&rt $e res&rt &$ t cu c re sc $e si f&rt $e suctiune /< sc $e u!%"ere #entricu" r 6. F ct&ri %eric r$ici: %eric r$ite c&nstricti#e t !%&n $ c r$i c efectu" c&nstricti# su%r !i&c $u"ui ii sc $e c % cit te $e u!%"ere C. F ct&ri en$&c r$ici: sten&(e # "#u" re AA str nse existent $e tr&!'i s u tu!&ri in c #it te #entricu" r D. F ct&ri c r$i ci functi&n "i: tu"'ur ri $e rit! cu frec#ent crescut 3 se scurte ( $i st&" /< se scurte ( u!%"ere #entricu" r . TUL6U*A*I NEU*OENDOC*INE IN INSUFICIENTA CA*DIACA Initi " ceste tu"'ur ri sur#in in c&!%ens re $e'itu"ui, ins , cu ti!%u", %e ! sur ce $e#in excesi#e, ,r #e ( tu"'ur ri"e c r$i ce) TUL6U*A*EA ACTIAITATII SNS Inc $in %ri!e"e st $ii "e IC sunt cti# ti intens centrii #e,et ti#i si!% tici) Punctu" $e %"ec re " cti# rii este sc $ere $e'itu"ui siste!ic /< !ec n&, #&"&, ' r&* sin&c r&ti$ieni nu ! i sunt sti!u" ti suficient /< nu ! i tri!it i!%u"suri in-i'it& re c tre centrii si!% tici /< cesti se cti#e ( Sc $ere e?ectiei #entricu" re /< crestere #&") te"e$i st&"ic : $u% fiec re sist&" r ! ne in #entricu" & c ntit te $e s n,e re(i$u " " c re se $ u, in $i st&" s n,e $in triu /< #&"u!u" te"e$i st&"ic #entricu" r este ! i ! re /< $istensi %ereti"&r #entricu" ri /< sti!u" re nu!iti"&r !ec n&rece%t&ri $e $istensie $e " c re %"e c i!%u"suri c cti#e ( centrii si!% tici) In e#&"uti IC %rin inter#enti un&r !ec nis!e 3 # sic&nstricti %eriferic , retenti -i$ric ., TA si #&"u!u" circu" t&r se re$rese ( 1 in ti!% se ?un,e c-i r " -i%er#&"e!ie /< !ec n&) #&"&, ' r&* r tre'ui s re#in " cti#it te n&r! " , $ec" ns n$ i!%u"suri in-i'it& re %t) centrii si!% tici1 $ r cesti * c&ntri'uie in c&ntinu re " -i%er cti# re centri"&r si!% tici, $e& rece in ti!% $ t&rit cresterii #&"e!ice, !ec n&* isi %ier$ sensi'i"it te , %erete"e tri " , un$e se , sesc cesti , $e#ine ! i ri,i$ 3 $ t&rit retentiei -i$rice /< e$e! $e %erete. )i) crestere #&"e!ic tre'uie s fie f& rte ! re )i) !ec n&* s fie sti!u" ti Efecte"e cti# rii SNS: ;. L ni#e"u" c&$u"ui: . efecte fe#&r 'i"e: - cresctere frec#entei si c&ntr cti"it tii c r$i ce, $ t&rit e"i'er rii $e N&rA $in ter!in tii"e ner#& se si% tice intr !i&c r$ice1 N&rA se fixe ( %e *; !i&c r$ici /<creste AMPc /< efecte - ceste efecte !&"i&re ( $e'itu" c r$i c - %e ! sur ce IC e#&"ue ( , c&ntr cti"it te sc $e, sin,uru" su%&rt " cresterii $e'itu"ui fiin$ t -ic r$i - excesu" $e N&rA sti!u"e ( -i%ertr&fi !i&c r$ic /< !e"i&r re c&ntr cti"it tii in ti!%1 $ c -i%ertr&fi este excesi# sc $e %erf&r! nt c r$i c ) '. efecte $ef #&r 'i"e: - in ti!% c&ncentr ti intr !i&c) $e N&rA sc $e %t) c : +G$i"uti H ter!in tii"&r ner#& se intr+& ! s !uscu" r -i%ertr&fi t + e%ui( re c % cit tii secret&rii ter!in tii"&r ner#& se intr !i&c r$ice sti!u"te in$e"un, + sc $ere cti#i ttii tir&(in-ir&xi" (ei +recu%er re insuficient $e $&% !in in #e(icu"e"e secret&rii "e ter!in tii"&r ner#& se intr !i&c r$ice - sti!u" re ex ,er t $e N&rA frec#entei si c&ntr cti"it tii !i&c r$ice creste c&nsu!u" $e O:1 $ r un !i&c r$ insuficient nu %& te creste $e'itu" c&r&n ri n /< creste si !ei !u"t neces ru" $e O: /< $e(ec-i"i'ru intre neces r si %&rt $e O: /< ic-e!ie !i&c r$ic ce sc $e c&ntr cti"it te !i&c r$ic

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- sti!u" re $rener,ic cti#e ( " ni# c r$i&!i&cite"&r ,"ic&"i( /< crescte c ntit te $e c) " ctic /< ci$&( cu efecte ne, ti#e : sc $ere finit tii %r&teine"&r c&ntr cti"e %t) C /< sc $ere c&ntr cti"it tii !i&c r$ice - sti!u" re $rener,ic f #&ri(e ( crestere excit 'i"it tii /< tu"&'ur ri $e rit! cu crestere frec#entei !i&c r$ice /< crestere neces ru"ui $e O: si sc $ere eficientei c&ntr cti"it tii) - excesu" initi " $e N&rA este c r$i&!i&cit&t&xic %rin : !ec): . N&rA %r&$uce r%&$usi $e &xi$ re in %re(ent s%ecii"&r $e O: cu efect $irect '. excesu" $e N&rA su%r cti#e ( siste!u" $eni" tcic" ( +AMPc /< AMPc c&ncur " $esc-i$ere un&r c n "e tr ns!') $e C #&"t ?$e%en$ente /< creste c&nc) intr ce" $e C /< cti# re en$&nuc"e (ei si un&r en(i!e ce $ec") !& rte ce") %rin %&%t&( si necr&( 1 $)%)$)#)-ist&"&,ic ce"e : f&r!e $e !& rte ce") $ifer %rin: + necr&( ce") %resu%une "i( &r, nite"&r, e$e! ce"u" r, e%ui( re re(er#e"&r $e ATP, fr ,!ent re !') si $e#ers re c&ntinutu"ui ce"u" r in tesuturi: se e"i'ere ( cit&8ine, en(i!e "i(&(&! "e, f ct&ri $e crestere ce initi ( un %r&ces inf" ! t&r1 fr ,!) ce") !& rte %rin necr&( sunt f ,&cit te $e ! cr&f ,e /< ! cr&f ,e"e se cti#e ( /< e"i'er re $e "te cit&8ine, en(i!e, s%ecii $e O: cti#e /< inf" ! ti %&stnecr&tic se !%"ific ) + %&%t&( ce") %resu%une sc $ere #&") ce"), c&n$ens re cr&! tinei nuc"e re " %eriferi nuc"eu"ui si f "$uri "e ce"u"ei1 &r, nite"e sunt int cte, ce"u" nu se fr ,!ente ( 1 %rin sc $ere #&"u!u"ui ce") se f&r!e ( c&r%i %&%t&tici c re sunt f ,&cit ti $e ! cr&f ,e, $ r nu % re inf" ! ti $e& rece c&r%ii %&%t&tici in-i' cti#it te ! cr&f ,e"&r %rin TNF si IL;.) Sti!u"u" %rinci% " %t) necr&( este isc-e!i ) A%&%t&( %& te fi $ec" 's t t t $e isc-e!ie, $e $istensi c r$i&!i&cite"&r 3 su%r s&"icit re $e %resiune si $e #&"u!.c t si $e f ct&ri neur&-&r!&n "i in exces: N&rA, AT II, en$&te"in ) Cit&8ine"e, s%ecii"e $e O:, e"i'er te in inf" ! tii"e %&stnecr&tice $ec" nse ( %&%t&( ) A%&%t&( re un !ec nis! c&!%"ex, c&ntr&" t ,enetic: exist ,ene cti# t& re si ,ene in-i'it& re1 in !&$ n&r! " exist un ec-i"i'ru intre ceste ,ene) In IC %&%t&( este crescut c & c&nsecint un&r f ct&ri 3exces $e -&r!&ni,$istensi ,isc-e!i intr !i&c r$ic ., $ r %& te fi si $eter!in t ,enetic, initiin$ fen&!ene"e % t&"&,ice $in IC) :. L ni#e"u" circu" tiei %eriferice: . efecte f #&r 'i"e: - # s&c&nstrictie se"ecti# /< $i'itu" siste!ic se c $istri'ui %referenti " c tre !i&c r$ si creier - # s&c&nstric ti %eriferic i!%ie$ic sc $ere TA c&nsecuti# sc $erii $e'itu"i c r$i c, )i) %resiune $e %erfu(ie in tesuturi cce%t 'i" - # s&c&nstrictie #en& s 3s%"enic , fic t, te,u!ent. !&'i"i( re in circu" tie $e c ntit ti su%"i!ent re $e s,) ce !e"i&re ( $e'itu" c r$i c si %erfu(i tisu" r '. efecte $ef #&r 'i"e: - creste re(istent %eriferic initi t $e # s&c&nstrictie se %er! nenti(e ( %rin f %ru" c excesu" $e N&rA si $e "ti -&r!&ni $et) & -i%ertr&fie tunicii !uscu" re rteri "e1 re(istent %eriferic creste si ! i !u"t %rin e$e!u" %eretu"ui $ t) retentiei -i$r&s "ine1 crestere re(istentei %eriferice $uce " crestere %&sts rcinii /< su%r s&"icit re $e %resiune si #&"u! #entricu"u"ui /< se ,r 'este $ec&!%ens re #entricu" r - crestere %&sts rcinii $et crestere c&nsu!u"ui $e O:, neces ru" $e O: nu %& te fi s tisf cut /< $e(ec-i"i'ru intre neces r si %&rt $e O: /) isc-e!ie /< sc $ere c&ntr cti"it tii) :.SISTEMUL *ENINA+ANGIOTENSINA+ALDOSTE*ON 3S*AA.: .An,i&tensin : - in IC se %r&$uce & cti# re i!%&rt nt S*AA - sti!u"u" %rinci% " este $ t $e sc $ere f"uxu"ui in rteri&"e"e ferente $ t&rit : + sc $erii $e'itu"ui c r$i c si ren "+ # s&c&nstrictiei $rener,ice) - crestere secretiei $e renin $eter!in f&r! re in circu" tie un&r c ntit ti ! ri $e AT I 3renin /%r&tein ce tr nsf&r! n,i&tensin&,enu" in AT I. - AT I este tr nsf&r! t in AT II su' inf"uent en(i!ei $e c&n#ersie existent " ni#e"u" en$&te"iu"ui # scu" r ! i "es " ni#e"u" # se"&r %u"!&n re1 exist si & en(i! $e c&n#ersie tisu" r in rinic-i, creier, S*) - $e se!ene exist si %&si'i"it te tr nsf&r! rii $irecte n,i&tensin&,enu"ui in AT II in nu!ite tesuturi, $e exe!%"u: in rinic-i exist te&nin 3en(i! res%&ns 'i" $e ce st tr nsf&r! re. in $#entice ) ) c&r&n re exist : en(i!e: 8in ( c r$i c si CAGE 3c-B!&st tin+ n,i&tensin II ,ener tin, en(i!e.1 in IC cti#it te cest&r en(i!e este crescut - in IC ni#) $e AT II nu se $ t&re ( $& r cti# rii S*AA ci si %r&$uctiei crescute intr !i&c r$ice %rin tr nsf) $irect - ni#e"u" crescut $e AT II $in IC re ce efcte:

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efect # s&c&nstrict&r /< AT II inter#ine in !entinere unei TA si unei %resiuni $e %erfu(ie cce%t 'i"e in c&n$itii"e sc $erii $e'itu"ui c r$i c $e( # nt ?: cresctere re(istentei %eriferice /) crescte %&sts rcin /< su%r s&"icit re %resi&n " %t) As sti!u"e ( -i%ertr&fi tunicii !uscu" re /< inter#ine in ccentu re cresterii re(istentei %eriferice inter#ine in !entinere unei fi"tr i ,"&!eru" re 'une in c&n$itii"e sc $erii $e'itu"ui c r$i c si ren " %rin ur! t&ru" !ec nis!: sc $ere $e'itu"ui c r$i c $et) sc $ere %resiunii $e fi"tr re, $ r AT II %r&$uce & # s&c&nstrictie ! i ! re %e rteri&" eferent 3$ensit te $e * %t) AT II ! i ! re " cest ni#e". /< in ,"&!eru" creste %resiune $e fi"tr re /< se i!'un t teste fi"tr re efecte c r$i ce: +sti!u"e ( c&ntr cti"it te 3 ef) f #). +$et -i%ertr&fi !i&c r$ic 3 ef) $ef #. creste f&rte $e c&ntr ctie1 %e ! sur ce -i%ertr&fi $e#ine excesi# , $et) sc $ere %erf&r! ntei c r$i ce sti!u"e ( %&%t&( !i&cite"&r s&ci t cu -i%ertr&fi !i&cite"&r /< re!&$e" re c r$i c 3 ef) $ef #). +creste excit 'i"it te /< fe#&ri(e ( tu"'ur ri"e $e rit! 3ef) $ef #). creste neces ru" $e O: se scurte ( $i st&" +f #&ri(e ( # s&c&nstricti c&r&n ri n %rin efect $irect c t si in$irect 3 AT II sti!u"e ( e"i'er re $e en$&te"in / ce" ! i %uternic # s&c&nstrict&r n tur ", $in ce") en$&te"i "e. f #&ri( re isc-e!iei !i&c r$ice si!u"e ( secreti $e ADH inter#ine in cti# re SNS inter#ine in sti!u" re s cretiei $e "$&ster&n - t& te ceste efecte sunt ! $i te $e c tre * s%ecifici /< !es ,eri secun(i intr ce"u" ri si c sc $ f&sf ti$i"+in&(it&") '. A"$&ster&nu": - c&ncentr ti s creste in s n,e su' ctiune excesu"ui $e AT II - efectu" s u %rinci% " este sti!u" re re 's&rtiei tu'u" re $e N si H:O - retenti -i$r&s "in inter#ine initi " c !ec nis! c&!%ens t&r: crestere re 's&rtiei -i$r&s "ine $etr) crestere int& rcerii #en& se /< crestere u!%"erii #entricu" re /< crestere $e'itu"ui c r$i c - %e ! sur ce retenti $e#ine excesi# , % r $e( # nt ?e: -i%er#&"e!ie cu su%r s&"icit re $e #&"u! si %resiune ce"&r $&i #entricu"i f #&ri( re e$e!e"&r inc"usi# EPA i!'i'iti %erete"ui rteri " /< crestere re(istentei # csu" re /< creste %&sts rcin 0. ADH+u": - c&ncentr ti s este crescut in IC - f ct&ru" ce $ec" nse ( secreti crescut $e ADH este re%re(ent t $e sc $ere #&"u!u"ui efecti# circu" nt, $ t&rit sc $erii $e'itu"ui c r$i c, se!n "i( t , $e #&"& si ' r&* rteri "i, c tre (&n retr&-i%&fi( r $e un$e se # s cret in c ntit ti crescute ADH) - efectu" s u este crestere re 's&rtiei $e % cu ref cere #&") circu" nt - %e ! sur ce #&"u!u" circu" nt se ref ce %rin inter#enti ADH, #&"& si ' r&* r tre'uii s re#in " & sti!u" re n&r! " 1 $ r c-i r si in c (u" -i%er#&"e!iei, ni#e"u" ADH $in circu" tie c&ntinu s fie ri$ic t1 cest "ucru se ex%"ic %rin: . %e ! sur ce % re -i%er#%"e!i s %r&$uce & $istensie %ereti"&r rteri "i /< #&"& si ' r&* isi %ier$ sensi'i"it te 1 $ t&rit retentiei -i$ris "ine % re i!'i'iti %erete"ui /< ri,i$it te %erete"ui1 %t) c * s se!n "i(e(e crestere #&"e!iei, %erete"e rteri " r tre'ui s fie f"exi'i" )i) %rin $istensie s se!n "i(e(e *, $ r cu! cest s+ ri,i$i( t, se!n "i( re nu se ! i f ce c&res%un( t&r /< $e " ni#e"u" * %"e c inf) inc&recte1 centrii si!% tici si (&n retr&-i%&fi( r %ri!in$ inf) inc&recte, secreti $e ADH se !entine crescut '. ni#e"u" crescut $e AT II sti!u"e ( $irect (&n retr&-i%&fi( r 7. PEPTIDELE NAT*IU*ETICE: - sunt f ct&ri ce cresc n triure( 3 cresc e"i!in re ren " $e N /< cresc e"i!in re ren " $e H:O %rin efectu" &s!&tic " N . /< cresc $iure( - u ctiune # s&$i" t t& re ! i "es %rin efect $irect 3 sti!u"e ( ,u ni" tcic" ( si %r&$ucti $e GMPc in ce"u" !uscu" r # scu" r . si in$irect 3 in-i' efectu" # s&c&nstrict&r " c tec&" !ine"&r, AT II, en$&te"inei si # s&%resinei. - in-i' %r&"ifer re ce"u" r !uscu" r # scu" r /< se &%une -i%ertr&fiei tunicii !uscu" re - !i&c r$u" tri " si #entricu" r u ce"u"e ,r nu" te ce secret ! i !u"te ti%uriu $e %e%ti$e n triuretice, ce" ! i i!%&rt nt ANP 3%e%ti$ n triuretic tri ". ce f&st i(&" t %ri! & r $in triu $ r exist si in#entricu"e, %e%ti$u" n triuretic cere'r ", %e%ti$u" n triuretic $e ti% C, secret t in !i&c r$ - sti!u"u" %t) e"i'er re "&r $in !i&c r$ este $istensi %erete"ui tri " @ #entricu" r

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- in IC cest e"i'er re este crescut $ t&rit $istensiei #entricu" re in$us $e crestere #&"u!u"ui te"e$i st&"ic1 $istensi este %erce%ut $e c tre !ec n&* $e %e !') ce") ,r nu" re ce secret %e%ti$e"e netriuretice - $ t&rit ni#e"u"ui ! re $e %e%ti$e netriuretice $in IC r tre'ui s i'e efecte f #&r 'i"e: s se &%une unei retentii -i$r&s "ine excesi#e si unei # s&c&nstrictii %er&ferice ce r creste %&sts rcin 1 $ r ceste efecte 'enefice nu se f c resin!tite $e& rece: . $istensi cr&nic %erete"ui c&n$uce " %ier$ere sensi'i"it tii !ec n&*, )i) ce") ,r nu" re secret & c ntit te ! re $e %e%ti$e c re ins este insuficient %t) % riti efecte"&r f #&r 'i"e '. $ t&rit ni#e"u"ui ! re $e %e%ti$e n triuretice $in circu" tie se %r&$uce sc $ere nr) $e * # scu" ri si ren "i %t) %e%ti$e"e n triuretice, %rin $&Fn+re,u" ti&n c. nu se cun& ste $e ce !i&c r$u" insuficient r secret %e%ti$e n triuretice 'i&"&,ic in cti#e - efecte"e "&r nef c n$u+se resin!tite se ,r #e ( retenti -i$r&s "in si # s&c&nstricti %eriferic 2. ENDOTELINA: - %e%ti$ sinteti( t ! i "es " ni#e"u" ce") en$&te"i "e - ce" ! i %uternic # s&c&nstrict&r 3 ! i %uternic $ec t N&rA s u AT II $e (ece &ri. - $ t&rit # s&c&nstrictiei %eriferice ,%e c re & $eter!in , en$&te"in re in IC t t efecte fe#&r 'i"e c t si nef #&r 'i"e - sti!u"u" ce $eter!in cresctere secretiei $e en$&te"in in IC este sc $ere f&rtei !ec nice f"uxu"ui s n,#in $ t&rit sc $erii $e'itu"ui : ce"u" en$&te"i " re !ec n&* ce sesi(e ( sc $ere f&rtei !ec nice f"uxu"ui s n,#in si r%in !es ,eri secun(i se!n "i(e ( e"i'er re crescut $e en$&te"in - e"i'er re crescut se $ t&re ( si ni#e"u"ui crescut $e N&rA, AT II , ADH, ce"u" en$&te"i " # n$ rece%t&ri %t) cesti - inter#ine in sti!u" re -i%ertr&fiei !i&c r$ice si tunicii !uscu" re # scu" re /< creste %&sts rcin - sti!u"e ( %&%t&( c r$i&!i&cite"&r /) re!&$e" re #entricu" r cu sc $ere %erf&r! ntei c r$i ce - %rin #s&c&nstricti c&r&n ri n $et) isc-e!ie !i&c r$ic /< $eficit ener,etic %rin %&rt sc (ut $e O: /< sc $e c&ntr cti"it te !i&c r$ic 4. HO*MONUL SOMATOT*OP: - in IC c&ncentr ti s este crescut , $ r nu se stiu ! c nis!e"e - initi " excesu" $e STH re efecte f #&r 'i"e, sti!u" n$ -i%ertr&fi !i&c r$ic /< crescte f&rt c&ntr ctiei - u"teri&r, $ t&rit -i%ertr&fiei excesi#e %erf&r! nt c r$i c sc $e - efecte"e "ui sunt !e$i te $e f ct&ri $e crestere $e " ni#e"u" ce") !i&c r$ice: IGF 3 insu"in+"i8e ,r&Ft- f ct&r. 5. TNF: - cit&8in siteti( t ! i "es in, $ r f&st e#i$enti t si in c r$i&!i&cite si in ce"u"e"e !uscu" re # scu" re - inIC cti# re necr&(ei c r$i&!i&cite"&r $et) e"i'er re in !i&c r$ $e c ntit ti ! ri $e TNF - fr ,!ente"e $e ce"u"e necr&( te sunt f ,&cit te $e ! crif ,e c re se cti#e ( !et '&"ic/< e"i'ere ( "te c ntit ti $e cit&8ine %rintre c re si TNF - " fe", in ce"u" !uscu" r # scu" r - /< creste c ntit te $e TNF in circu" tie, in ce"u" !i&c r$ic si in ce"u" !uscu" r # scu" r - efecte nef #&r 'i"e: TNF sti!u"e ( %&%t&( !i&c r$ic /< se %ier$e ! s !uscu" r /< sc $e f&rt $e c&ntr ctie TNF sti!u"e ( " ni#e"u" ce") en$&te"i "e "e # se"&r !i&c ri$ce, & NO+sint te( in$ucti'i" /< creste %r&$ucti $e NO c re $e%ri! c&!tr cti"it te 9. DISFUNCTIA ENDOTELIALA: - in IC, crestere re(istentei %eriferice re " 'e( & # s&c&nstrictie &!%&rt nt " c re c&ntri'uie si $isfuncti en$&te"i " / " ni#e"u" en$&te"iu"ui sc $e f&r! re $e f ct&ri $i" t t&ri 3NO. si creste %r&$ucti $e f ct&ri # s&c&nstrict&ri 3 en$&te"in . Mec nis!u" $isfunctiei en$&te"i "e: ;. sc $ere %r&$uctiei $e NO: - fi(i&"&,ic, %r&$ucti $e en$&te"i " $e NO este re," t $e f&ert f"uxu"ui s n,#in) %rin inter!e$iu" un&r !ec n&* en$&te"i "i1 c n$ f&rt f"uxu"ui s n,#in creste , se %r&$uce "&c " & crestere %r&$uctiei $e NO c re %rin # s&$i" t tie creste c "i'ru" # se"&r c re se $ %te ( stfe" f"uxu"ui crescut - $u% sti!u" re !ec n&*, crestere %r&$uctiei $e NO se f ce %e : c i: $e " !ec n&* %rin ! s ,eri secun(i se %&r$uce cti# re un&r f ct&ri $e tr nscri%tie ce cresc tr nscri%ti inf&r! tiei ,enetice uti"e %t) sinte( NO+sintet (ei ti% III, en(i! ce si,ur f&r! re NO in c&n$itii fi(i&"&,ice $e " !ex n&* %rin ! s ,eri secun(i se cti#e ( tir&(inin ( c re %rin f&sf&ri" re cti#e ( NO+sintet ( ti% III

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- in IC $ t&rit f"uxu"ui sc (ut,secun$ r $e'itu"ui sce(ut, !ec n&* nu ! i sunt sti!u" ti suficient /< sc $e sinte( NO+ sintet (ei si cti# re ei /< sc $e %r&$ucti $e NO :. $e,r $ re ex ,er t NO f&r! t: - %e " n,e NO+sintet ( ti% III in f&r! re NO inter#ine si NO+sintet ( ti% II1 ce st este & en(i! in$ucti'i" - NO+sintet ( ti% II nu este fi(i&"&,ic cti# t 1 cti# re eise f ce in nu!ite c&n$itii, $e c tre cit&8ine, "i%&%&"i( - ri$e ' cteriene - in IC TNF cti#e ( sinte( NO+sintet (ei ti% II /< creste %r&$ucti $e n& %e ce st c "e - $ r ni#e"u" ,ener " $e NO $in en$&te"iu este sc (ut $ t&rit sti!u" rii $e,r $ rii NO su' ctiune ,ener rii crescute $e s%ecii re cti#e $e O: in %erete"e # scu" r - ni#e"u" crescut $e AT II sti!u"e ( " ni#e"u" %erete"ui # scu" r & NADPH+&xi$ ( $in c rei cti#it te re(u"t s%ecii re cti#e $e O: - s%eci re cti# $e O: c re inter#ine in $e,r $ re NO este ni&nu" su%er&xi$ c re f&r!e ( cu NO ni&nu" %er&xinitrit ce nu re efect # s&$i" t t&r ci re efect cit&t&xic 0. crestere %r&$uctiei en$&te"i "e $e f ct&ri # s&c&nstrict&ri: - su' inf"uent ni#e"u"ui crescut $e en$&te"in se sinteti(e ( TX A: c re re efect # s&c&nstrict&r, %recu! si PG H: c re in !&$ n&r! " este ni-i" t $e c tre NO, $ rcu! c ntit te $e NO este sc (ut /< PG H: isi exercit efectu" # s&c&nstrict&r) ANOMALIILE META6OLISMULUI HID*OSALIN IN INSUFICIENTA CA*DIACA Initi ", retenti -i$r&s "in re efecte 'enefice, u"teri&r # n$ efecte nef #&r 'i"e) Mec ni!e ce $eter!in retenti -i$r&s "in : ;. !&$ifc ri in cti#it te S*AA, ADH+u", %e%ti$e"e n triuretice :. !&$ific ri $e -e!&$in !ic intr ren " $eter!in te $e excesu" $e f ct&ri # s&c&nstrict&ri In IC se %&r$uce & intens # s&c&nstrictie ren " ce fecte ( %re$&!in nt rteri&" eferent c re re & $ensit te ! re $e * %t) f ct&rii # s&c&nstrict&ri1 A s&c&nstricti s%&rit %e rteri&" eferent si,ur !entinere unei fi"tr ri ,"&!eru" re 'une in c&n$itii"e in c re %resiune $e fi"tr re tin$e s sc $ $ t&rit sc $erii $e'itu"ui c r$i c si ren "1 Fi"tr re se !entine " c&te &%ti!e /< fr ctie $e fi"tr re se ! reste1 Fr cti $e fi"tr re / r %&rtu" fi"tr t ,"&!eru" r @ f"ux %" s!tic ren " x ;== r t ce P $in c ntit te $e s ',e ce iri, rinic-iu" @ !inut este fi"tr t in !&$ n&r! " re # "& re $e :=P in IC nu f& rte # ns t FF este crescut $ t&rit unei fi"tr ri ,"&!eru" re %er nefr&n ! i 'un si sc $erii f"uxu"ui %" s! tic ren " crestere FF /) & c ntit te ! i ! re $e % este fi"tr t ?un, n$ in tu' /< in rteri&" eferent c ntit te $e % este ! i !ic $ec t in !&$ n&r! ", %r&teine"e nefiin$ fi"tr te /<creste %resiune c&"&i$+&s!&tic in rteri&" eferent /< creste re 's&ti %ei $in tu' T&ti f ct&rii # s&c&nstrict&ri %r&$uc # s&c&nstrictie ! i ! re in c&rtic " ren " f t $e !e$u" r /< s n,e"e este re$istri'uit %referenti " c tre !e$u" r Nefr&nii ?ust !e$u" ri u & %resiune -i$r&st tic ! i ! re /< u & c % cit te ! i ! re $e re 's&r'i % si N /< %rin iri, re "&r %referenti " ei re 's&r' si ! i !u"t % si N Mec nis!e"e $e %r&$ucere e$e!e"&r siste!ice: ;. retenti ren " -i$r&s "in /< crestere #&"e!iei /< crestere f&rtei -i$r&st tice $in c %i" r /< tr nsfer c tre interstitii si c tre ser& se 3 %"eur , %eric r$ %erit&neu. :. st ( #en& s siste!ic retr&,r $ $in IAD si ICG ce $uce " crestere %resiunii #en& se centr "e ce se r sfr n,e retr&,r $ in c %i" re un$re creste f&rt -i$r&st tic 1 $ c se s&ci ( si IAS, %resiune #en& s creste si ! i !u"t: -i%er#&"e!i %rin retentie c&n$uce " i!'i'iti %ereti"&r # scu" ri /< crestere ri,i$it tii %ereti"&r /< sc $e c&!%"i nt #en& s /< # s&c&nstricti fecte ( si siste!u" #en&s) 0. -i%&%r&teine!i $uce " sc $ere %resiunii c&"&i$+&s!&tice %" s! tice1-i%&%r&teine!i %& te fi $i"uti&n " $ t&rit retentiei -i$r&s "ine s u %& te fi re " , 's&"ut , inc $ru" ICD $ t&rit st (ei #en& se ce fecte ( fic tu" /< "ter re -e% t&cit r si c-i r cir&( c r$i c /< sc $ere sint (e"&r %r&teice,s u @ si fect rii terit&riu"ui %&rt /< st ( #en& s %e # se"e intestin "e /< sc $ere 's&rtiei %rinci%ii"&r "i!ent re si !in& ci(i"&r /< sc $ere sinte(e"&r %r&teice 7. sc $ere $ren ?u"ui "i!f tic " %ei interstiti "e: in ICD, $ t&rit cresterii %resiunii #en& se %rin st ( #en& s centr " , $e#ers re "i!fei $in c n "u" t&r cic in #ene"e c #e este in,reun t /< st ( retr&,r $ %e # se"e "i!f tice tri'ut re c n "u"ui t&r cic /< sc $ere $ren ?u"ui "i!f tic interstiti " 2. crestere %er!e 'i"it tii c %i" re, !ec nis! ce % re ! i "es in IC ,r #e cu -i%&#&"e!ie extre! ce $et) $istensi c %i" re"&r i r ?&nctiuni"e $intre ce"u"e"e en$&te"i "e se " t,esc /< creste %er!e 'i"it te c %i" r /) se %er!ite extr #& ( re

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"ic-i$e"&r c tre interstitii1 nu se cun&sc!ec nis!e"e , $ r cest !ec nis! re "&c ! i "es " ni#e"u" %"eurei) %eric r$u"ui si %erit&neu"ui, f #&ri( n$ cu!u" re "ic-i$e"&r in ceste c #it ti) MECANISMELE COMPENSATO*II IN INSUFICIENAT CA*DIACA O$ t cu % r&ti unei n&! "ii structur "e s u functi&n "e c&r$u"ui, ini! &nce%e s se c&!&$e( e %rin !&'i"i( re !ec nis!e"&r c&!%ens t&rii, ce u c sc&% i!'un t tire $e'itu"ui c r$i c si %erfu(iei tisu" re) O %eri& $ $e ti!%, !ec nis!e"e c&!%ens t&rii sunt eficiente, $ r &$ t ce $e#in excesi#e, % r $e( # !t ?e ce c&ntri'uie %r&,resi# " sc $ere %erfu(iei c r$i ce /< $ec&!%ens re IC) Sunt i!%"ic te : c te,&rii $e !ec nis!e c&!%ens t&rii: ;) Mec nis!e c&!%ens t&rii centr "e 3ce tin c-i r $e ini! . ;); $i" t ti c r$i c 3 !ec nis! $i st&"ic. ;): crestere cti#it ti si!% tice " ni#e"u" c&r$u"ui ;)0 -i%ertr&fi !i&c r$ic ;);.si ;):. %&t intr in functie i!e$i t /) sunt !&'i"i( te in IC cut ;)0. necesit ti!% %t) intr re in functiune /< este int "nit in IC cr&nic :) :); :): :)0 :)7 Mec nis!e c&!%ens t&rii %eriferice 3extr c r$i ce.: re$istri'uire $e'itu"ui As %rintr+& # s&c&nstrictie %eriferic se"ecti# crestere $es tur rii H'O " ni#e" tisu" r f&"&sire unui !et '&"is! %re$&!in nt n er&' c&"& un$e este %&si'i" retenti ren " -i$r&s "in %rin c re0 creste int& rcere #en& s /< creste $e'itu" c r$i c)

;)MECANISMELE COMPENSATO*II CENT*ALE ;); Di" t ti c r$i c 3 !ec nis!u" $i st&"ic.: re " ' ( crestere #&"u!u"ui te"e$i t&"ic #entricu" r c ur! re sc $erii e?ectiei #entricu" re este ne#&ie si $e & u!%"ere #entricu" r $i s&"ic 'un %t c AFTD s %r&$uc $i" t re c&r$u"ui %r&$uce $istensi %erete"ui #entricu" r /< : efecte f #&r 'i"e: . "un,ire unit ti"&r c&ntr cti"e !i&c r$ice c re s%&reste f&rt e" stic cu!u" t in !i&fi'ri"e, c re &$ t $e, ? t , ! reste f&rt $e c&ntr ctie Le,e Fr n8+St r"in,: "un,ire unit ti"&r s rc&!erice se f ce % n " & # ") ! x), &%ti! , $e :,:+:,0 & e"&n, tie ! i ! re $e :,0 nu se %& te re "i( $e& rec s cu" %er&c r$ic, inextensi'i", ni %er!ite & $i" t tie c r$i c extre! $e ! re $ c te&retic, s+ r %ute %r&$ece & e"&n, tie %este ce st # ") ! x, f&rt $e c&ntr ctie s+ r !ics&r $ t&rit $e( n, ? rii %unti"&r ct&+!i&(inice cest !ec nis! intr in functiune i!e$i t in c (u" su%r s&"icit ri"&r cute $e %resiune @ #&"u! 3 ICA. cu c&n$iti c #entricu"ii s fie $istensi'i"i1 cest "ucru nu se %& te re "i( in c $ru" unei t !%&n $e c r$i ce, %eric r$ite c&nstricti#e in c re c&!%"i nt #entricu" r este sc (ut si in c $ru" ICC exist un & rec re ,r $ $e $i" t re #entricu" r in c $ru" ICC, $i" t re c r$i c nu se f ce %rin e"&n, re unit ti"&r s rc&!erice, ci %rin sinte( $e n&i unit ti s rc&!rice, $isuse in serie f t $e ce"e initi "e /< $i" t re c r$i c $in ICC este ec-i# "e nt unei -i%ertr&fii excesi#e Mec nis!u" $i st&"ic re si $e( # nt ?e: ;. %e ! sur ce %erete"e #entricu" r se $estin$e, creste T intr % riet " /< se ,enere ( & f&rt ce se &%une c&ntr ctiei /< i!%"ic un c&nsu! ener,etic ! i ! re %t) c&ntr ctie /< creste tr # "iu" c r$i c /) creste c&nsu!u" $e O: :. %e ! sur ce %erete"e #entricu" r se ! reste, se ! reste si ine"u" AA /< cest nu ! i %& te fi et ns t &%ti! $e c tre % r tu" # "#u" r AA /< s n,e"e re,ur,ite ( /< sc $e eficient c&ntr ctiei 0. creste #&"u!u" te"e$i t&"ic #entricu" r $e%) si $e & u!%"ere $i t&"ic &%ti! 1 $e !u"te &ri, in IC u!%"ere #entricu" r $i st&"ic este $eficit r ) U!%"ere #entricu" r $eficit re se %& te $ t&r : A. sc $erii c&!%"i ntei #entricu" re c u( te $e: ;) re" x re !uscu" r inc&!%"et c u( t $e: ;); sc $ere %r&cesu"ui $e in cti# re c&ntr ctiei in re% us !uscu" r, situsu" rece%t&r " ctinei %t) !i&(in este c&%erit $e & %r&tein re," t& re / tr&%&!i&(in $e c re est t s t & "t %r&tein / tr&%&nin C

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i!%u"su" ner#&s $et) $esc-i$ere c n "e"&r !') $e C si e"i'er re $e C $in *E /< creste c&ncentr ti $e C intr cit&%" s! tic /<fix re C %e tr&%&nin C /< !&$ific re steric cest ie # $uce " e"i'er re situsu"ui rece%t&r %t) %unte !i&(inic /< %rin c&!%"e!ent rit te ce st se t se ( $e ctin /< c&ntr ctie in %r&cesu" $e re "x re, inter#in %&!%e"e s rc&%" s!ice $e C ce $es%rin$ C $e %e tr&%&nin si i" intr&$uc in $e%&(ite"e ce"1 $e se!ene inter#ine si &%&!% !') ce sc& te C $in cit&%" s! in !e$) extr ce" /<tr&%&nin C re#ine " c&nf&r! ti steric initi " /< in" tur %unte !i&(inic si c&%er situsu" rece%t&r) in IC sc $ere in cti# rii c&ntr ctiei re ! i !u"te !ec nis!e: ;);); & $eficient %&!%ei s rc&%" s!ice $e C , ce nu ! i %& te $es%rin$e C $e %e tr&%&nin C ;);): nu se ! i intr&$uce intr , c ntit te $e C in *E, %e ti!%u" $i st&"ei %ersist n$ & c ntit te crescut $e C intr cit&%" s! tic ;);)0 finit te crescut tr&%&ninei C f t $e C ;);)7 finit te crescut %untii !i&(inice %t) situsu" s u rece%t&r $e %e ctin , in$e%en$ent $e cti#it te tr&%&!i&(inei si tr&%&ninei C ;): !&$ific re un&r f&rte ce cti&ne ( i!e$i t in inte $ r si in ti!%u" re" x rii $i st&"ice #entricu" re: ;):); crestere re(istentei " e?ectie, c re se $ t&re ( cresterii re(istentei # scu" re %eriferice sec) # s&c&nstrictiei %eriferice $in IC1 un #entricu" ce int !%in & re(istent crescut " e?ectie tre'uie s se c&ntr cte ! i %uternic /< creste T intr % riet " " sf rsitu" sist&"ei, c re " r n$u" ei # i!%ie$ic %r&cesu" $e re" x re /< ce st tensiune tre'uie ! i int i in#ins si %&i se %&r$uce re" x re %r&%ri+(is f') !uscu" re ;):): in ICC 3 re$ucere c&ntr ctiei !i&c r$ice. sc $e f&rt $e res&rt intern #entricu"u"ui /< re" x re # fi in,reun t ;):)0 sc $ere #ite(ei si ,r $u"ui $e u!%"re % tu"ui c&r&n ri n1 u!%"ere %&stsist&"ic % tu"ui c&r&n ri n ?ut re" x re $i st&"ic 1 u!%"ere % tu"ui c&r&n ri n $e%in$e $e ,r $ientu" $e %resiune $intre c&r&n re si c #it te #entricu" r 1 in IC cest ,r) este re$us /) u!%"ere c&r&n ri n $eficit r 3 "ent si ! i !ic . $e& rece creste !u"t %resiune intr c #it r %rin crestere AFTD 3 c&nsecint sc $erii e?ectiei . si %resiune $in A& $e& rece $e'itu" As este sc (ut ;):)7 tensiune % riet " $e " ince%utu" u!%"erii #entricu" re / este $ t f&rt ,ener t $e s n,e"e existent in #entricu" in !&!entu" ince%erii u!%"erii #entricu" re, ce ?ut " re" x re #entricu" r 1c&nf&r! "e,ii "ui L %" ce: Tintr % tiet " / % intr c #it r x r @ :- , un$e - / ,r&si!e %erete"ui #entricu" r + in ICC s&cit t cu -i%ertr&fi !i&c r$ic , T % riet " in inte $e u!%"ere #entricu" r este ! i !ic $ec t in !&$ n&r! " /< f&rt exercit t $e s n,e"e ce intr in c #it te este ! i !ic /< re" x re !uscu" r este fect t 1 + nu! r t&ru" r %&rtu"ui creste $ c creste %resiune intr c #it r secun$ r cresterii #&"u!u"ui te"e$i st&"ic si@ s u creste r ( c #it tii secun$ r cresterii #&"u!u"ui te"e$i st&"ic1 + nu!it&ru" creste in %r&%&rtie ! i ! re $ec t nu! r t&ru" /< # ") r %&rtu"ui sc $e1 + in su%r s&"icit ri cute $e #&"u! @ %resiune creste nu! r turu" 3 creste %, creste r. si nu ! i exist -i%ertr&fie /< r %&tu" creste /< ?ut re" x re ;)0 $e -i%ertr&fie f ct&ri extr c r$i ci ce exercit c&!%resie: t !%&n $ c r$i c , %eric r$it c&nstricti#

6. Sc $ere %resiunii $e u!%"ere AA $eter!in t $e: ;) %re(ent in c #) #entricu" r unei ! se $e s n,e re(i$u "e $u% fiec re sist&" /< ,r $ientu" $e %resiune tri&+#entricu" r sc $e :) sc $ere f&rtei $e succtiune %e c re un #entric&" & re su%r triu"ui 0) $is% riti %&!%ei tri "e ex). fi'ri" ti tri " 7) f ct&ri extr !i&c r$ici: & int& rcere #en& s insuficient 3 $es-i$r t ri, -e!&r ,ii i!%&rt nte. retenti ren " $e N @ H:O nu este eficient 3 'u(u" $e $iuretice. C. Pre(ent $e &'st c&"e !ec nice @ functi&n "e in c "e u!%"erii #entric ;) sten&(e AA :) %re(ent in c #it te #entricu" r un&r tr&!'i, tu!&ri 0) c u(e functi&n "e 3 t -ic r$ie cu frec#ent c r$i c ! re c re scurte ( $i st&" . D. sc $erii %resiunii $e u!%"ere AA E. %re(entei un&r e#entu "e &'st c&"e &r, nice s u functi&n "e ;):crestere cti#it tii si!% tice " ni#e"u" c&r$u"ui 3 #e(i c %) tu"'ur ri neur&en$&crine in IC. ;)0-i%ertr&fi !i&c r$ic : ini! se HT $ c este su%us ti!% in$e"un, t unei su%r s&"icit ri su%r s&"icit re %& te fi re%re(ent t $e: . su%r s&"icit re cr&nic $e #&"u!

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'.su%r s&"icit re cr&nic $e %resiune c. %re"u re s rcinii un&r f') !uscu" re "ter te @ $istruse $e c tre f') !uscu" re r ! se, in$e!ne $.sc $ere unif&r! c&ntr cti"it tii %e t& te f') !uscu" re /< ef&rt ! i ! re %e fiec re f') in % rte - c" sific re HT: HT %ri! r / s&ci t sc $eri %ri! re c&ntr cti"it tii 3ex) in !i&c r$ite. HT secun$ r / $e(#&"t t c ur! re un&r su%r s&"icit ri cr&nice $e %resiune @ #&"u! - HT re un s,) # nt ? / creste f&rt $e c&ntr ctie !i&c r$u"ui - HT re " ' ( & sinte( crescut $e %r&teine c&ntr cti"e 3 unit ti src&!erice. - sti!u"u" %rinci% " " HT sunt re%re(ent ti $e: . crestere T intr % riet "e: %& te fi & crestere sist&"ic T intr % riet "e 3 in su%r s&"icit ri"e $e %resiune. %& te fi & crestere $i st&"ic T intr % riet "e 3 in su%r s&"icit ri"e $e #&"u!. in crestere sist&"ic T intr % riet "e este sti!u" t sinte( $e n&i unit ti c&ntr ti"e si $is%unere "&r in % r "e" f t $e ce"e %reexistente /< HT c&ncentric in crestere $i st&"ic T intr % riet "e este sti!u" t sint) $e n&i unit ti c&ntr cti"e, i r $is%&(iti "&r este in serie cu ce"e $e? existente /< # creste ! i !u"t $i !etru" /< $i" t tie #entricu" r in ICC " crestere #entricu" r inter#ine t t & -i%ertr&fie c t si & $i" t tie '. crestere c&ncentr tiei un&r f ct&ri neur&en$&crini, $intre c re ce" ! i i!%) este AT II : - HT se $e(#&"t % n c n$ T intr % riet " este re $us " n&r! " / $is% re sti!u"u" $e& rece cresc n$ nr) $e unit ti s rc&!erice # "& re T re% rti( te %e fiec re f') in % rte sc $e - in su%r s&"icit ri"e $e #&"u! @ %resiune exist & re") $irect intre T intr % riet " si ,r&si!e %erete"ui #entricu" r 3 "e,e L %" ce. - in su%r s&"icit ri"e $e %resiune: %resine intr c #it r creste f) !u"t /< T creste f) !u"t /< sti!u"u" %t) HT este intens /< ,r&si!e %erete"ui # creste f !u"t - in su%r s&"icit ri"e $e #&"u!, & !ic crestere r (ei c #it tii #entricu" re este c % 'i" s nu"e( crestere $e %resiune /< %er ns !'"u %r&$usu" % x r nu creste se!nific ti# /< T nu creste se!nific ti# /< sti!u"u" %t HT nu este %uternic /< HT excentric este ! i !ic in sc $ere %ri! r c&ntr cti"it ti, HT se $e(#&"t %rin $is%&(iti in serie si in% r "e" n&i"&r unit ti sinteti( te Mec nis!u" -i%ertr&fiei: . stresu" tensi&n " " c r$i&!i&citu"ui $et) $esc-i$ere un&r c n "e "ente $e C s nsi'i"e " $intensie / c n "e strec- /< % re un inf"ux crescut $e C /< creste C intr cit)/< cti# re unei serii $e %r&tein8in (e /< cti# re un&r f ct&ri $e tr nscri%tie /< sti!u" re tr nscri&erii ,ene"&r res%&ns 'i"e $e sinte( un&r $iferiti f ct&ri $e crestere ce")3ex) PDGF, FGF, TGF, EGF, ILGF. '. r&"u" f ct&ri"&r en$&crinici: un r&" %rinci% " i" re AT II c re re un ni#e" %" s! tic ri$ic t in IC1 AT II ct) %e c r$i&cit %rin fix re *;1 !ec nis!u" %rin c re AT II sti!u"e ( sinte( $e n&i unit ti c&ntr cti"e: - fix re AT II %e * $et) cti# re unei %r&teine !') / Gs, c re $et ! rire finit tii %t) GTP unui su'c&!%&nent " cestei / su'c&!%&nentu" GJ II - c&!%"exu" GTP+GJ II cti#e ( PL+C c re cti#e ( c sc $ PI /< IP0 L DAG - IP0 sti!u"e ( e"i'er re C $in *E - C e"i'er t $in *E L DAG /< cti# re %r&tein8in (e"&r, $intre c re i!%) este P>+C - P>+C cti#e ( & serie $e %r&teine c re inter#in in crestere sinte(ei un&r f ct&ri $e tr nscri%tie un&r ,ene i!%"ic te in sinte( un&r f ct&ri $e crestere - $u% fix re %e * t&t %rin P>, cti#e ( & serie $e %r&t&&nc&,ene ce !eresc r s%unsu" ce"u" r " ctiune f ct&ri"&r $e crestere - t&t %rin P>, ! reste ex%resi ,ene"&r %t f ct&rii $e crestere - ! ?&rit te cest&r f ct&ri $e crestere sti!u"e ( nu nu !i HT ci si -i%er%" (i c r$i&!i&cite"&r - $ t&rit cresterii FGF, se cti#e ( fi'r&'" stii $in !i&c r$ /< creste %r&$ucti $e c&" ,en /< % re fi'r&( intr !i&c r$ic /< sc $e c&!%"i nt !i&c r$ic - %e " n, AT II ! i inter#in si excesu" $e N&rA si $e en$&te"in ) $e& rece !'e"e cresc c&ntinutu" intr ce"u" r in C - crestere C intr ce"u" r cti#e ( si %&%t&( c r$i&!i&cite"&r 3 #e(i N&rA. - fen&!ene"e $e -i%ertr&fie @ -i%er%" (ie, fi'r&( !i&c r$ic si %&%t&( !i&c r$ic , $uc in ti!% " re!&$e" re #entricu" r ce isi %ier$e c r cteru" $e !ec nis! $ %t t&r si c % t nu!er& se $e( # nt ?e /< sc $e %erf&r! nt c r$i c ) De( # nt ?e"e -i%ertr&fiei @ re!&$e" rii #entricu" re excesi#e:

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() Ht c r$i&!i&citu"ui se re "i(e ( %rintr+& $is%&r%r&tie #&"u!u"ui ce"u" r in r %&rt cu su%r f t ce"u" r 3 "&cu" $e %&rt " ce"u"ei cu O:, su'st) nutriti#e. /< %&rtu" $e su'st) ener,etice " & ce"u" cu neces r crescut este $eficut r /< sc $e %r&$ucti $e ener,ie /< sc $e c&ntr cti"it te *) & HT f) i!%&rt nt 3 ex) ce c&ncentric . %& te exercit un efect c&!%resi# %e # se"e intr % riet "e /< fen&!ene isc-e!ice /< sc $ere ener,iei c&ntr ctiei /< sc $ere c&ntr ctiei +) %rin HT c r$i&!i&citu"ui se ! reste $ist nt $intre c %i" ru" s n,#in si centru" ce"u"ei 3 un$e !it&c&n$rii"e %r&$uc ener,ie. /< in,reun re $ifu(iunii O: c tre !it&c&n$rii /< $eficit $e O: /< sc $e ener,i /< sc $e c&ntr cti"it te ,) HT necesit ener,ie 4) $e(#&"t re % tu"ui c&r&n ri n nu se %& te f ce sincr&n cu $e(#&"t re !i&c r$ic 1 $ c se $e% seste "i!it critic iri, tiei /< %&r$ucti $e ener,ie $e#ine ineficient /< sinte( $e n&i unit ti nu !i %& te c&ntinu 1 t&tusi %ersist sti!u"u" %t HT / T intr % riet " c re se ! reste in c&ntinu re $in ce in ce ! i !u"t /< este si ! i !u"t in,reun t c&ntr cti , ener,i neces r c&ntr ctiei $e? re$us se ir&seste $in ce in ce ! i !u"t %t) in#in,ere T si 'i $u% cee $ c ! i r ! ne ce# %t $et) c&ntr cti :) $ t&rit fi'r&(ei intr !i&c r$ice sc $e c&!%"i nt #entricu" r /) sc $e u!%"ere #entricu" r /< sc $e AFTD /) sc $e $e'itu" c r$i c ;) crestere C intr cit) i!%ie$ic in cti# re c&ntr ctiei /< sc $e c&!%"i nt #entricu" r si %e ce st c "e <) c n$ HT nu ! i %& te c&!tinu , %re$&!in fen&!ene"e $e %&%t&( , %rin c re sc $e ! s c&ntr cti" ) MECANISMELE COMPENSAT*O*II PE*IFE*ICE DIN INSUFICIENTA CA*DIACA ;) *e$istri'uire $e'itu"ui As %rintr+& # s&c&nstictie %eriferic se"ecti# : - in ICS se %r&$uce & # s&c&ntrictie se"ecti# # n$ " ' ( sti!u" re si!% t&+ $rener,ic - # nt ?e: inter#ine in !entinere unei %erfu(ii s n,#ine " ni#e" cere'r " si c r$i c c-i r in c&n$iti cu $e'it siste!ic !ic 3 iri, re %referenti " . !entinere TA si %resiunii $e %erfu(ie tesuturi"&r c re u ten$int $e sc $ere &$ t cu sc$ere $e'itu"ui siste!ic - $e( # nt ?e: crestere re(istentei # scu" re %eriferice /< crestere %&sts rcinii /< inter#ine in su%r s&"icit re %resi&n " AS in terit&riu" un$e se %r&$uce # s&c&nstricti %&rtu" $e O: este !u"t re$us /< tesuturi"e res%ecti#e $e#in -i%&xice ) :) Crestere $es tur rii H'O " ni#e" tisu" r: - in ICS extr cti $e O: $e %e H'O " ni#e" tisu" r este ! i ! re c&!% r ti# cu n&r! "u" si %rin ce st se c&ntr c re ( in 'un ! sur %&rtu" sc (ut $e O: c&nsecuti# sc $erii $e'itu"ui siste!ic - extr cti rescut $e O: " ni#) tis) /< in ICS $iferent rteri&+#en& s %resiunii % rti "e O: se ! reste f t $e n&r! " - extr cti c&nst intr+& ce$ re ! i us& r O: s%re tesuturi %rin sc $ere finit tii H' %t) O: si %rintr+un c&nt ct ! i %re"un,it " -e! tii"&r cu %erete"e c %i" r, $ t&rit incetinirii f"uxu"ui s n,#in c&nsecuti# sc $erii $e'itu"ui siste!ic - sc $ere finit tii H6 %t) O: se ex%"ic %rin : !ec nis!e: crestere %r&$uctiei intr eritr&cit re $e c) :,0+'isf&sf&,"iceric / c&!%us ce $is"&c O: $e %e H'O1 cest re(u"t %rintr+& c "e ,"ic&"i(ei cti# t $e crestere %H+u"ui intr eritr&cit r in c&n$itii $e -i%&xie +crestere %H+u"ui cti#e ( f) !u"t en(i!e $in c "e ,"ic&"i(ei - crestere %H+u"ui se $ t&re ( sc $erii %&rtu"ui $e O: c tre tesuturi: sc $ere %&rtu"ui $e O: " ni#) * sin&c r&ti$ieni /< $ersc rc re $e i!%u"suri ce sti!u"e ( centru" res%ir t&r /< -i%er#enti" tie /< e"i!in re unei c ntit ti crescute $e CO: /< -i%&c %nie /< eritr&citu" # #e un $is%&ni'i" ! i !ic $e CO: /< sc $e f&r! re $e H:CO0 si ,ener re $e HL /) creste %H+u" intr eritr&cit r) ci$&( $e " ni#e" tisu" r / ur! re cu!u" rii $e c) " ctic $ t&rit %re$&!in ntei ,"ic&"i(ei n er&'e in tesuturi"e -i%&xice 0. F&"&sire $e c tre tesurturi unui ,et '&"is! %re$&!in nt n er&': - ! ?&rit te tesuturi"&r %&t f&"&si " ne#&ie !et '&"is!u" n er&' /< ec&n&!iesire O: %t) creier si ini! - cest ti% $e !et '&"is! %re$&!in si " ni#e"u" tesuturi"&r un$e s+ %r&$us # s&c&nstrictie) - $e( # nt ?: cu!u" re %r&,resi# $e c) " ctic $et) tre%t t & ci$&( siste!ic n&ci# %t) !i&c r$ /<sc $e finit te f') c&ntr cti"e %t) C /< sc $e cti#it te c&ntr cti" 1 $e se!ene # % re si sc $ere tre%t t t&nusu"ui # scu" r /< re$istri'uire $e'itu"ui AS) 7. *etenti -i$r&s "in : - inter#ine initi " c !ec nis! c&!%ens t&r : se ! reste int& rcere #en& s c tre ini! /< $e'itu" se !e"i&re ( - cu ti!%u" $e#ine excesi# %t) c %ersist un ni#e" f) crescut $e ADH, "$&ster&n, ce intretin retenti -i$r&s "in c-i r $ c #&"u!u" circu" nt s+ ref cut /< -i%er#&"e!ie c re $et: su%r s&"icit re #entricu" r $e #&"u!

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crestere %resiunii in site!u" rteri " /< su%r s&"icit re %resi&n " #entricu" r , initi " %t) AS i!'i'iti -i$ric %erete"ui rteri " $ t&rit e$e!u"ui /< creste re(istent # scu" r %eriferic /< su%r s&"icit re %resi&n " su%"i!ent r %t) As - ICS L ICD L st ( #en& s retr&,r $ in siste!u" c # /< retenti -i$r&s "in c&ntri'uie " crestere %resiunii in siste!u" c # /) f #&ri(e ( % riti e$e!e"&r siste!ice - in ICS 3 $& r e . retenti -i$r&s "in $eter!in crestere %resiunii -i$r&st tice " ni#e"u" rete"e"&r c %i" re f #&ri(e ( % riti $e e$e!e siste!ice, EPA

MECANISMELE INTIME MOLECULA*+ CELULA*E ALE SCADE*II CONT*ACTILITATII MIOCA*DICE IN SUFICIENTA CA*DIACA Aceste !ec nis!e sunt cun&scute intr+& ! sur f) !ic D te"e ex%eri!ent "e r t c sunt !ec nis!e cu r&" secun$ r ce inter#in in ,r # re IC, nefiin$ !ec nis!e %ri! re c re s ex%"ice ince%ut" $e%ri! rii c&ntr cti"it tii) Sunt : ! ri c te,&rii: A. M&$ific ri"e u"tr structur "e $e " ni#e"u" c r$i&!i&cite"&r 6. An&! "ii"e 'i&c-i!ice $e " ni#e"u" c r$i&!i&cite"&r A) M 'i1ic$&ile ult&$st&uctu&$le 'e l$ "i%elul c$&'i mi citel & Initi " exist i%&te( c , in ICA $ r si in ICC, %rin su%r s&"icit re $e #&"u!, sc $ere c&ntr cti"it tii s+ r $ t&r unei e"&n, ri excesi#e unit ti"&r s rc&!erice1 $ ( n, ? re %unti"&r ct&+!i&(inice nu u f&st %us in e#i$ent in %r ctic , $e& rece s cu" %eric r$ic, inextensi'i" nu %er!ite & e"&n, re t t $e ! re inc t %unti"e s se $( n, ?e(e) Ace st i%&te( nu %& te ex%"ic sc $ere c&ntr cti"it tii $in ICC, c re este !u"t ! i ccentu t $ec t in ICA) A"te i%&te(e: sc $ere su%r fetei !i&fi" !ente"&r su%t f t n&r! " !i&fi" !ente"&r) $ r e"e u & !&$ific re c "it ti# / "ter re " nturi"&r %&"i%e%ti$ice sc $ere nr) $e !it&c&n$rii $in c r$i&!i&cite /< %&si'i"it te re$us $e %r&$uctie ener,iei, inc"usi# ce"ei neces re c&ntr ctiei) B) M 'i1ic$&ile /i c5imice . Cu%" ?u" excit tie K c&ntr ctie f&st , sit c&nst nt "ter t in IC /< s+ u c&nst t t efecte"e e"i'er rii un&r c ntit ti suficient $e C neces r %r&cesu"ui c&ntr cti", in % r "e" cu $efecte "e %&!% rii in %&i C " sf rsitu" %eri& $ei c&ntr cti"e) Aceste $efecte u " ' ( & "ter re $in !&ti#e necun&scute cti#it tii %&! %ei s rc&%" s!ice $e C /< " sf rsitu" %eri& $ei c&ntr cti"e C nu ! i este suficient intr&$us in%&i in *E) L c r$i&!i&cit ?un,e PA /< c r$i&!i&citu" nu # %ute e"i'er & c ntit te suficient $e C $e& rece *E nu ! i este inc rc t suficient cu CA /< c&ntr cti $i!inu In cit&%" s! , $i% c&ntr ctie # r ! ne & c ntit te crescut $e C c re i!%ie$ic in cti# re c&ntr ctiei /< re" x re nu este suficient /< u!%"ere #entricu" r sc $e /< c&ntr cti ur! t& re este s" ' ) Ni#e"u" $e C $in $e%&(ite"e intr ce"u" re %& te fi &%eri& $ sustinut %t) c !it&c&n$rii"e %&t %re"u $e " *E ce st functie, se %&t inc rc cu C 1 %e ! sur ce !it) se inc rc excesi# se $ecu%"e ( f&sf&ri" re &xi$ ti# !it&c&n$ri " /< sc $e %r&$ucti $e ener,ie /< sc $e c&ntr cti"it te ) Ni#e"u" $e C $in c r$i&!i&cit $e%) $e cti#it te unei %&!%e !')/ sc-i!' t&r @ nti%&rt $e N si C / GP !' cu creut te !&"ecu" r $e 9: D , e functi&ne ( e"ectr&,enic: %t) fiec re i&n $e N intr t in c r$i&!i&cit, sunt ex%u"( ti $in cit) : i&ni $e C i!%&tri# unui ,r $ient $e c&ncentr tie, cu c&nsu! $e ener,ie ce este furni( t $e ATP) Ni#e"u" $e C $in c r$i&!i&cit este inf"uent t in$irect $e cti#it te %&!%ei !') $e N si >1 in IC ce st %&!% re & cti#it te crescut f t $e n&r! " /< ex%u"(i $e N este %re ! re /< $eter!in & ten$int $e reintr re N in ce"u" /< sti!u" re nti%&rtu"ui N @ C /< ni#e"u" $e C in cit este ! i !ic $ec t ce" neces r Me$ic !ente"e t&nic r$i ce in-i' %&!%e"e ce u cti#it te crescut , $eter!in n$: sc $ere ex%u"(iei $e N /< ,r $ientu" $e c&ncentr tie " N se re$uce /< sc $e ten$int $e intr re N /) se i!'un t teste ni#e"u" $e C $in c r$i&!i&cit creste ni#e"u" $e N $in c r$i&!i&cit /< sti!u" re sc-i!' t&ru"ui N @ C $in !it&c&n$rie /< C iese $in !it) in cit) /< creste C cit&%" s! tic neces r c&ntr ctiei) '. Uti"i( re ener,iei neces re c&ntr ctiei este ! i re$us in IC in f (e"e ! i # ns te) Ener,i neces r c&ntr ctiei este furni( t $e ATP su' ctiune unei ATP+ (e re%re(ent t c-i r $e !i&(in si nu!e $e un $&!eniu structur " " " ntu"ui ,reu " !i&(inei)

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In IC, in f (e"e ! i # ns t , % r nu!ite !&$ific ri structur "e "e " ntu"ui ,reu " !i&(inei, ce $uc " & sc $ere functiei ATP+ (ice /< e"i'er re sc (ut ener,iei $in ATP) L &!, su' ctiune $iferite"&r s&"icit ri %resi&n "e @ $e #&"u!, !i&c r$u" sinteti(e ( & !i&(in cu c % cit te ATP+ (ic ! i ! re, tre%t t se !&$ific $&!eniu" ,reu cu %ier$ere functiei $e ATP+ ( /< ,r # re IC nu ,enere ( sc $ere c&ntr cti"it tii) c. Pr&$ucti $e ener,ie in IC este sc (ut in f (e"e # ns te) Sc $ere %r&$uctiei $e ener,ie se $ t&re ( : $ecu%" rii f&sf&ri" rii &xi$ ti#e $ t&rit inc rc rii excesi#e !it&c&n$rii"&r cu C sc $erii tre%t te %&rtu"ui $e O: " ni#e"u" !it&c&n$rii"&r $in c r$i&!i&cite, t t $ t&rit HT c&ncentrice , ce exercit un efect c&!%resi# %e # se"e intr !i&c r$ice, c t si %rin sc $ere u!%"erii % tu"ui c&r&n ri n ce $e%in$e $e $iferent $e %resiune intre A& si c #it te #entricu" r /< isc-e!ie !i&c r$ic res%&ns 'i" $e sc $ere %r&$uctiei $e ener,ie in inte $e % riti fen&!ene"&r isc-e!ice, $e $ecu%" re f&sf&ri" rii &xi$ ti#e, este sc (ut eficient uti"i( rii ener,iei /< un !i&c r$ ineficient tre'uie s se c&ntr cte ! i %uternic %t) ex%i"( ce" s #&"u! s n,#in /< creste T intr % riet " ce ! reste neces ru" $e ener,ie !u"t f t $e c % cit te s $e furni( re) $. Extr cti $e O: si su'str turi"e ener,etice $in s n,e"e c&r&n ri n sunt n&r! "e in IC t t ti!% c t nu % r fen&!ene"e isc-e!ice IN f&r!e"e $e IC cu fen&!ene isc-e!ice %ri! re 3 %rin trer&sc"er&( # se"&r c&r&n riene. extr ,ere O: @ unit te $e ! s !i&c r$ic este $e " ince%ut sc (ut ) e. St&c re ener,iei su' f&r! $e c&!%usi f&sf t+ ! cr&er,ici este n&r! " , cu exce%ti IC $et) $e $eficient &r, nis!u"ui in f&sf ti)

FIZIOPATOLOGIA EDEMULUI PULMONA* ACUT CA*DIOGEN EPA c r$i&,en este & c&!%"ic tie ,r # insuficientei c&ntr cti"e As) Se c r cteri(e ( $)%)$)#) fi(i&% t&"&,ic %rin crestere %resiunii -i$r&s tice in c %i" re"e %u"!&n re, ur! t $e extr #& ( re "ic-i$i n in interstitiu" %u"!&n r1 c n$ interstitiu" s+ s tur t,%resiune interstiti " in#in,e %resiune intr "#e&" r , ?&nctiuni"e $intre "#e&"e se " r,esc /< inun$ re "#e&" r % n " !& rte %rin suf&c re '&"n #u"ui) F ct&ru" $eter!in nt " %r&$u#erii EPA c r$i&,en este st ( #en& s %u"!&n r in %&i As insuficient, st ( c re se tr ns!ite % n " ni#e"u" rete"ei c %i" re %u"!&n re, un$e $et) crestere %resiunii -i$r&st tice) C&ntri'utie " crestere %resiunii -i$r&st tice in c %i" re"e %u"!&n re & re si retenti -i$r&s "in ) EPA c r$i&,en se instituie !u"t ! i us&r $ c A$ re & c % cit te c&ntr cti" n&r! " , %&!% re c&re%un( t& re s n,e"ui in circu" tie %u"!&n r $et) & crestere si ! i ! re st (ei) D c " ICS s s&ci ( si ICD, %resiune -i$r&st tic in c %i" re"e %u"!&n re sc $e /< EPA se !e"i&re ( ) A"ti f ct&ri uxi"i ri c re % rtici% " c&nstituire EPA c r$i&,en: . sc $ere %resiunii c&"&i$+&s!&tice %" s! tice in ICS sc $ere %resiunii &s!&tice %" s! tice se f ce %rin $i"uti s n,#in secun$ r retentiei -i$&s "ine in ICD cu s t ( -e% tic %re"un,it L cir&( -e% tic /< sc $ere sinte(e"&r -e% tice $e %r&teine, in %ri!u" r n$ $e "'u!ine '.sc $ere $ren ?u"ui "i!f tic " %ei $in interstitiu" %u"!&n r n&r! " cic"u" ins%ir+ ex%ir ec-i# "e ( cu & %&!% res%ir t&rie ce ?ut f) !u"t $ren ?u" "i!f tic in %" ! n in ICS, $ t&rit st (ei %u"!&n re, %" ! nu" se inc rc cu s n,e /< excursii"e s "e res%ir t&rii isi !ics&re ( !%"itu$ine /< nu ! i ?ut $ren ?u" "i!f tic %u"!&n r In ICD L s t( #en& s in site!u" c # , sc $e in %"us $ren ?u" "i!f tic " %ei interstiti "e in t&t &r, nis!u" $ t&rit sc $erii $e#ers rii "i!fei in c n "u" t&r cic) c. crestere %er!e 'i"it tii c %i" re %u"!&n re se $ t&re ( -i%&xiei se#ere L ci$&(ei se#ere $in f&r!e"e f ,r #e "e ICS Mec nis!e"e ce f #&ri(e ( ,r # re -i%&xiei in EPA c r$i&,en Inu$ re un&r "#e&"e /< efect $e sunt $re %t + st n, / s n,e"e ce #ine in c %i" re"e ce $eser#esc "#e&"e"e inun$ te nu ! i %& te fi &xi,en t /) se int& rce ne&xi,en t in ini! st,) /< c&nt !in re s,) siste!ic rteri " cu s n,e #en&s /< ,r # re -i%&xiei) Inun$ re unui nr) n i ! re @ !ic $e "#e&"e $et crestere %resiunii %rti "e O: in eru" "#e&" r /< $eter!in ref"ex # s&c&nstrict&r " rteri&"ei %u"!&n re / ref"ex #&nEn"er1 ce st rteri&"&c&nstrictie %u"!&n r , nese" cti# , fecte ( si rteri&"e"e ce $eser#esc si "#e&"e neinun$ te inc /< sc $e %O: in ceste "#e&"e /< sc $e %&si'i"it te $e inc rc re s n,e"ui cu O:) Arteri&"&c&nstricti %u"!&n r $et) crestere %resiunii in rteri&"e /< f&rt re $esc-i$erii un&r n st&!&(e rteri&+#enu" re /< s n,e"e # &c&"i terit&riu" c %i" r /< ccentu re fen&!enu"ui $e sunt $r+st,)

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C t ti!% exist un nu! r $e "#e&"e neinun$ te, se %r&$uce $& r -i%&xe!ie, nu % re -i%erc %nie, $e& rece CO: re & $ifu(i'i"it te !u"t ! i ! re %rin !') "#e&"&+c %i" r , %ut n$ fi e"i!in t %rin -i%er#enti" tie)

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