curs 2015 oct
DESCRIPTION
cTRANSCRIPT
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Obezitate, sdm metabolic,
dislipidemie
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Ce tb sa stie studentul dupa acest curs?
• Prediabet=sdm metabolic=inflamatie +rezistenta la insulina=risc dublu de boalacardiovasculara=de obicei, prezent la subiectii
cu circumferinta mare a taliei (obezitate mar)• Criteriile pentru diagnosticul sdm metabolic• Alte modificari metab asociate prediabetului• a recunoasca pe caz clinic pacientul cu sdm
metabolic• e poate preveni evolutia prediabetului la diabet
in peste !"# din cazuri, aplicand trat adecvat
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Ce tb sa stie studentul dupa acest curs?
• $ecanismele patogene care e%plica&relatiile obezitate'inflamatie (sliduri ,
*,*)relatiile obezitate'rezistenta la insulina(sliduri , *,*)
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Ce tb sa stie studentul dupa acest curs?
Profilul lipidic consta in determinarea pe ser sau pe plasma a
valorilor pentru: colesterolul total, HDL-c, trigliceride,
toate fasting ( a jeun)
• Formula Friedewald:
• LDL-c=ol t-HDL-c - !"#$ (toate e%primate in mg#dL)&
cand !"' mg#dL formula nu se mai aplica
*al apo+HDL, iar val apo .LDL-c
/ndici de aterosclero0a:ol t#HDL-c'1,$, sau LDL#HDL'2,$inseamna risc crescut de aterosclero0a
apoB:apoA1=0,4 e bun, dar >1,4 e rau (aterosc severa)
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Ce tb sa stie studentul dupa acest curs?
• $edicatia ipolipemianta&-tatine (inibitori de .$/coA reductaza),
care⇓
⇓
010'c,⇓
2/*-3ibratii (activeaza 0P0aza),care ⇓ 010'c si ⇓ ⇓2/
4-Celatori de saruri biliare Acid nicotinic ⇓0p(a)
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Ce tb sa stie studentul dupa acest curs?
• 2ipul de dislipidemie din prediabet si diabet&.10'c mic si 2/ mari⇒ dislipidemie foarteaterogena cu 010 mici si dense
• 5ezistenta la insulina ($atte6s fomula forhomeostatic model assessment- vezi wikipedia )
=iperinsulinemie cu normoglicemie sauiperinsulinemie cu iperglicemie
=glucoza nu intra in tes insulinodep (musci s7,tesut adipos ), gluconeogeneza ep nu esteinibata
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Ce tb sa stie studentul dupa acest curs?
• a calculeze riscul de boala C8 (pe "ani) conform algoritmului 3ramingam (manual, sliduri), conform AC81 ris7
estimator (google)• a calculeze riscul de moarte cardiovasc
(in urmatorii " ani) conform algoritmului
CO59 (slide)• /idul veci si gidul nou (ACC:A.A din*"4)pentru tratamentul dislipidemiilor
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Aspecte veci si noi in patologie
1ieta deficitara=risc mare de infectii9%cesul caloric=sdm- metabolic:diabet
zaarat
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0egatura sistemelor metabolice cucele imune
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2riggeri diferiti (iperglicemia,2;3alfa) cai
comune prin radicali liberi, efecte diferite
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RELAŢIA OBEI!"ŢII #$ I%&LA'AŢIA IREI!E%ŢA LA I%$LI%"
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indromul metabolic
= prediabet=<;30A$A2<9 + 59<29;2A 0A
<;>0<;A=asociat obezitatii
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<nfiltrarea cu macrofage a tesutului adipos laobezi este crescuta
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9fectul e%cesului de substrate laobezi=stress o%idativ crescut
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ubstrate*e (ac+++ -ras+ s+ -*ucoa) a.*ate +ne/ces deter+na s+ +ntret+n +n.*aat+a, +n
obe+tate
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/5A<$9A 8<C95A0A
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OBEI!A!EA ABO'I%ALA vs2 !E$!$L AI3O$B#$!A%A!
• e asociaza cu grasimea ectopica• .iperinsulinismul creste secretia de
cortisol, accentuand aspectul cusingoid• <nfiltrarea cu macrofage are locpreferential in grasimea omentala
• 9ste mai usor mobilizabila (concentratiade acizi grasi liberi in sange e mare)
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Circumferinta taliei'elementimportant in sdm metabolic
• >n inc mai mult la circumferinta talieidetermina modificari& "#2A (creste) .10 @# (scade) 2/ @# (creste) 5isc dm metabolic @# (creste)
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9%cesul de acizi cu lant lung (long cainacids'0CA) favorizeaza rezistenta la insulina
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<<<- A029 modificari metab inobezitate si sdm metabolic
• -1islipidemia&.10'C scazut asociat cu 2/crescute= 010 mici, dense
• *- 3icat gras• 4- tare protrombotica& cresc fibrinogenul, PA<• .omocisteinemie, ipouricemie
• 1isfunctie erectila• Adiponectina cu valori scazute
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1ef- ;C9P' A2P a sdm metabolic4 criterii din
• #+rcu.er+nta ta*+e+&"*cm la B si @@ cm la 3
• !6 ≥ "mg:dl
• 7L8# " mg:dl la B si " mg:dl la 3• !A ≥ 4":@ mm.g• 6*+ce+a ≥ " mg:dl
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193- <13'sdm metabolic
• Circumferinta taliei& Dcm B, @" cm 3 @ cm B, D" cm 3
2/≥ "mg:dl.10'C " mg:dl B, " mg:dl 3
2A ≥ 4" mm:@ mm.g
/licemia ≥ ""mg:dl
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Caz clinic Are sdm metabolic?
• 3emeie En varsta de ! ani, asimptomaticF, nu face tratamentmedicamentos
• A.C de diabet zaarat tip*- 2atFl Gi unciul din partea tatFlui audiabet zaarat tip * care este controlat prin dietF Gi medicaHie oralF-
• >ltimul control medical a fost fFcut En urmF cu un an-Atunci,
2A = 4": @"mm .g, <$C *I7g:mJ• 0ipidograma En urmF cu *ani& colesterol, D mg:d0 .10'C=" mg:d0'010'C=*" mg:d0'2/=*" mg:d0-
• 0a controlul prezent, 2A este *:@" mm .g Gi <$C is *D 7g:mJ-Profilul lipidic actual& colesterol total=**" mg:d0K 010'C=4" mg:d0K.10'C= " mg:d0, iar trigliceridele= mg:d0- /licemia a Leuneste de " mg:d0, iar circumferinHa taliei este de ID cm-
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1upa ! luni
• ;u urmeaza recomandarile medicului• <a in greutate 7g , circumf taliei @ cm,
lipide nemodificate, 2A 4:D" mm.g,glicemia " mg:dl-
• 1/;?
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Ce recomanda medicul?9fectele compliatei pacientei
• 1ieta mediteraniana, sport, metformin• 1upa * ani&
• <$C *! 7g:mJ, circumferinta taliei ID cm,2A *:@" mm .g, glicemia D '""mg:d0
• <ar pt valorile persistent mari de 4" mg:dlale 010'C primeste statine si fibrati
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Caz *
• 3emeie, !* ani, fumatoare pacet:zi, circtaliei D cm, <$C=4,* 7g:m*, 2A":IImm.g sub <9C, glicemia mg:dl,
dislipidemie cu colesterol **I mg:dl, 010'C=4" mg:dl, .10 " mg:dl, non .10@Img:dl, 2/=*@ mg:dl, risc
3ramingam *#• 1/;? 5ecomandari-
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1>PA 4 luni
• 3umeaza M pacet tigari, <$C 4,@ 7g:m*,D4 cm, glicemia 4* mg:dl, 2A=4":@"mm.g, colesterol @ mg:dl, .10
colesterol * mg:dl, 2/=*@mg:dl• 1gn, tratament ?
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Caz 4 si caz
• 3emeie, nefumatoare, ! ani, talia D cm,glicemia mg:dl, 2A=:@@ mm.g, col*@" mg:dl, .10'C 4 mg:dl, 2/ 4"" mg:dl
1gn, 010'C, tratament?3emeie, fumatoare M p,menopauza,
sedentara, talie D" cm, 2A 4!:@! mm.g,
glicemie D mg:dl, col *4 mg:dl, .10'C! mg, 2/**" mg:dl1gn, 010'C, tratament?
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<<- Profil lipidic normal adulti
e cer la laborator&• 2C @" mg:d0 (*"")• 2/ "'" mg:d0• .10 ≥ " mg:d0 la B, ≥" mg:d0 la 3• NNNNNNNNNNNNNNNNNN-• e calculeaza&• 010'C 4" mg:d0• ;on .10'C !" mg:d0
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<<- 1efinitie dislipidemie
• anomalie cantitativF Gi calitativF alipoproteinelor-
• 9%emple de dislipidemii& colesterolemiecrescutF sau trigliceridemie crescutF sauambele crescute, sau .10 scFzut
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von 9c7ardstein, 9ur .eart , *"", 4
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#*as+.+carea &reder+cson ad+s*+p+de++*or .a+*+a*e
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#*as+.+carea &reder+cson ad+s*+p+de++*or .a+*+a*e
• Clasa < =9+perc9+*o+crone+e • Clasa <<a=LL crescute • Clasa <<b=LL s+ LL crescute • Clasa <<<=IL crescute (!6 crescute s+
co*estero* u*t crescut)• Clasa <8=8010 crescute (!6 u*t
crescute ;+ co*estero* crescut )• Clasa 8=9+perc9+*o+crone+e ;+ cu
LL crescute (2/ crescute)
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#*+n+ca* B+oc9e+str<8 an I**ustrated #o*our !e/t, sec ed+t+on
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#*+n+ca* B+oc9e+str<8 an I**ustrated #o*our!e/t, sec ed+t+on
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Ce trebuie sa stie studentul?
• Ce analize trebuie cerute pentru profil lipidic?Cand trebuie cerute?
• 1e ce .10 trasporta colesterolul Bun?
• 1e ce 010 transporta colesterolul 5au?• Ce rol are enzima C92P(colesterol ester
transport protein)?
• Ce inseamna transportul invers al colesterolului?• Ce sunt lipoproteinele restante si daca suntaterogene?
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Ce trebuie sa stie studentul?
• Ce rol are lipaza epatica?• Ce rol are lipoprotein lipaza?• .10'subtipuri, modificari cantitative si calitative,
factori care influenteaza valoarea .10• Care este legatura dintre consumul crescut de
zaar si dislipidemie? Care este legatura dintre
consumul crescut de zaar si uricemie?• Ce riscuri aduce dislipidemia?
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Ce trebuie sa stie studentul?
• .ipertrigliceridemia primara, secundara,riscuri
• .ipertrigliceridemia postprandiala'riscuri• Ce este 0p(a)?• 1islipidemia la copii
• 2ratamentul dislipidemiei
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9fecte .10
• 2ransporta colesterolul la organul deeliminare, ficat
• Antio%idante• Antiinflamatoare• Anticoagulante
• <mbunatatesc functia endocrina
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von 9c7ardstein, 9ur .eart , *"",4
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von 9c7ardstein, 9ur .eart , *""
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939C29 .10'C CA>2
• Boli cardiovasculare• Prediabet, diabet zaarat
• <nfectii• Cancere ( plaman, san, colon)
3 t ii i i i fl t
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3actorii primari care influenteazaval .10'colesterolului
• 9tnia(.10 scazut la arabi, ispanici si crescut la
Laponezi si europeni)• e%ul3emeile au .10'C mai mare
• $utatiile (apo'A)
3 t ii d i i fl t
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3actorii secundari care influenteazaval .10'colesterolului
• Alcoolul, sportul, estrogenii, fibratiicresc .10'C
• 3umatul, sedentarismul,androgenii, ipertrigliceridemiascad .10'C
1i li id i i l it ii d b l
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1islipidemia si algoritmii de boalacardiovasculara
Parametrii lipidici inclusi in algoritm&Colesterolul total seric
.10'c
gor mu ram ng am
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gor mu ram ng am
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Cand dam statine?
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Cand dam statine?
• 19P<;19QQQ 1e cati factori de risc arepacientulQ
• 5aport colesterol t: .10'c !
• Cel mai bine, te orientezi dupa gidveci:nou
/id i i b lil di l i
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/id veci pt prevenirea bolilor cardiovasculare sipt medicatia ipolipemianta
• e urmareste obtinerea unei tinteterapeutice pentru lipoproteine
-2<;2A nr era 010'c R0OS95 te B92QTCat de Loasa tb sa fie valoarea? 1epinde de
riscul calculat conform algoritmi (veziurmatoarele sliduri)
*- 2<;2A nr * era non .10'c (cu 4" mg:dlpeste 010'c)
Adult 2reatment Panel (<<<)
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Adult 2reatment Panel (<<<)(A2P <<<) sau 3ramingam'gid veci
5isc Uinta 010'C (mg:dl)
$ai mare de *"# $ai mic de ""
"#'*"# ( mai mult de * factori derisc)
risc moderat crescut
$ai mic de ""
$ai puHin de "# (mai mult de *factori de risc) risc moderat
$ai mic de 4"
$ai puHin de "# ("' factori derisc cardiovasc)
$ai mic de !"
/id veci tinte terapeutice
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/id veci'tinte terapeuticederivate folosind algoritmul CO59• 1aca riscul CO59 este #, dar col t este ≥
D" mg:dl se recomanda stil de viata sanatos ,iar tinta 010'c este mg:dl
• 1aca riscul CO59 este ≥# si col t ≥ D"mg:d0 se rec pt 4 luni stil de viata sanatos- 1acadupa 4 luni de dieta si sport, col t ≥D"mg:d0sau 010'c mg:dl, dai statine- 1aca riscul
CO59 este inca ≥#, dai statine pt a obtinetinta de "" mg:d0 pt 010 si de I mg:d0 ptcol total
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2ratamentul cu statine'gid nou
• Boala cardiovasculara ateroscleroticadocumentatatatina potenta mare
• 010'C ≥D" mg:d0 tatina potenta mare
• "'I ani, cu 1 tatina potenta medie• nu boala cardiovasc, nu are 010 ≥D" mg:d0, nu
1, dar
risc de VI,# de boala cardiovasc tatinapotenta medie:mare
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!A!I%A #$ 3O!E%!A 'ARE • 1oza zilnica scade 010C cu V"#• Rosuvastat+n *" mg
• Atorvastat+n 40 -
• Pitavastatin 2–4 mg Simvastatin 10 mg• 3ravastat+n 100 -• Lovastat+n 0 -• luvastatin 20–40 mg• Pitavastatin 1 mg
!A!I%A #$ 3O!E%!A 'EIE
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!A!I%A #$ 3O!E%!A 'EIE
1oza zilnica scade 010C cu 4"# '"#
• Rosuvastat+n (! ) 10 -• +vastat+n 040 -W• 3ravastat+n 40 -• Lovastat+n 40 -
• luvastatin "# $0 mg• &*uvastat+n 40 - b+d•
!A!I%A #$ 3O!E%!A 'I#A
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!A!I%A #$ 3O!E%!A 'I#A • 1oza zilnica scade 010C cu 4"#• imvastatin " mg
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Concluzie trat dislipidemie
• 'evaluarea riscului de boalFcardiovascularF
• $odificarea stilului de viaHF ( practicarea
sportului, dieta)• Pentru scFderea 010 colesterolului se dau
statine, celatori de sFruri biliare,
ezetimib, niacina• Pentru scFderea 2/ se dau niacina,fibraHi, A/ Omega'4
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Caz clinic 'dislipidemie
• Barbat, 4 ani, cu obezitate centrala,nefumator, 2A :D mm.g, //24@><:0(; "'@ ><:0) are valori a Leun&
• Colesterol total 4*4mg:dl• 2/ D" mg:dl• /licemia I!mg:dl• Ce tip de dislipidemie are?
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caz'dislipidemie
• Pacientul are diabet zaarat• 9ste obez, cu grasime centrala, ceea ce
inseamna probabil rezistenta la insulina
• //2 crescut (fie ficat gras, fie consum etanol)• 1islipidemie cu valori mari col si 2/• 1islipidemie familiala tip <<< 3rederic7son (valori
anormale apo 9) sau tip <8
• 2b cerute& A.C, genotip apo9, verificat prezentaficat gras sau consum alcool, teste rezistenta lainsulina, se cauta %antoame palmare
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Caz *'dislipidemie
• Pacienta obeza, sedentara,consumatoarede multe fainoase, cu profilul lipidic&colesterol total *""mg:dl, 2/ *" mg:dl,
.10 * mg:dl- Ce tip de dislipidemie?2rat?
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Profil lipidic copii
• 2C I" mg:d0• 010'C " mg:d0• ;on .10'C *4 mg:d0• Apo B D" mg:d0• 2/ I mg:d0 pt "'D ani si D" mg:d0 pt
"'D ani
• .10 mg:d0• Apo A *" mg:d0
A;A0<9 la copiii obezi vs
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A;A0<9 la copiii obezi vsnormoponderali
• $ar7eri antropometrici crescuti & circumferintataliei, <$CK 2A in limite normale, darsemnificativ crescuta fata de normoponderali
• 1islipidemie& 2/ , 010, col total crescute si .10
mic• Analize uzuale& glicemia, A02, A2, creatinina inlimite normale, dar semnificativ crescute fata denormoponderali
• $ar7erii de inflamatie crescuti• Adipocito7inele dezecilibru adiponectina:leptina
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1$ metab la copii
• #+rcu.er+nta ta*+e+& ≥ D" percentile dinvaloarea medie (grafice)
• !6 ≥ "mg:dl
• 7L8# " mg:dl, "mg:d0• !A ≥ 4":@ mm.g ≥• 6*+ce+a ≥ D" percentile din valoarea
medie (grafice)• '!# dintre copiii obezi au sdm-metabolic
Profilul lipidic la copii se determina
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Profilul lipidic la copii se determina0a cine? (recomandari veci *"")
• A.C mama Bcv la ! ani, tata Bcv ani
• $ama sau tata cu colesterolemie peste*"mg:d0
• Copii obezi• Copii cu .2A• Cu ipotiroidism, <1A• Copii cu %antelasme
Profil lipidic se determina la copii
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Profil lipidic se determina la copiicand? (recomandari *")
• creening la D,", ani apoi dupa @ ani
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2ratamentul dislipidemiei la copii
• 0a copiii cu ipercolesterolemie familialF, formaeterozigotF, tratamentul constF En dietF GimedicaHie (statine), administratF dupF varsta de" ani
• 0a copiii cu ipercolesterolemie familialF formaomozigotF, tratamentul constF En dietF,tratament medicamentos (statine) GiplasmaferezF din momentul punerii
diagnosticului-• 0a copiii cu ipertrigliceridemie se dau A/
Omega4
9f A/ O 4 fi
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9fecte A/ Omega 4 pe ficat
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9fecte A/ Omega 4 pe tesut adipos
9f t A/ 4
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9fecte A/ omega4 pe mm
9f A/ O 4 i i
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9fecte A/ Omega4 via receptori
;A301
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;A301
• 3<CA2>0 /5A(steatoza)• 29A2O.9PA2<2A
;O;A0CO0<CA(steato epatita';A.)
• C<5OA ;O;A0COO0<CA
P t ;A301
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Patogeneza ;A301
Insulinorezistenţă
(hiperglicemie,
hiperinsulinemie)
Lipogeneză
Acizi graşi liberi
crescuţi în plasmă
şi intracelular
DAG!"c
$ecanisme patogene ;A301 'a doua etapF
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$ecanisme patogene ;A301 a doua etapF(steatoepatitF ;A., steatopancreatita ;AP)
Acizi graşi liberi
crescuţi în #icat şi
pancreas
!ero$i%are lipi%ică
crescută,
&$i%area proteinelor
Antio$i%anţi scăzuţi
G!$, catalaza scăzute
'A'A!
tres o$i%ati* crescut
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0<895 ultrasounds before and
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after treatment, in obese cildren
PA;C59A ultrasounds before and after
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C u t asou ds be o e a d a tetreatment, in obese cildren
C fi t
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Caz ficat gras
• Persoana sedentara, dieta bogata inglucide, sau cu rezistenta la insulina, A02la limita sup a normalului,ecografic=ficat
gras• 2rat'scimbare stil viata, 0iv *, acizi grasi
Omega 4
939C2909 benefice ale acizilor
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grasi O$9/A 4
• 9fecte antiinflamatoare• Corecteaza dislipidemia& scad mult 2/,
scad col- total si cresc usor .10'c
• Cresc sensibilitatea la insulina• 5ecomandate in ;A301
• cad valorile C<$2, prevenindateroscleroza
8X $>0Ț>$9CQ
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8X $>0Ț>$9CQ
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• calculator are available atttp&::mY-americaneart-org:cvris7calculator and
ttp&::666-cardiosource-org:science'and'ZualitY