hipertenziis paTogenezi da morfologia
Pirveli rigis faqtorebi
· dieta da hiperlipidemia (hiperqolesterinemia, hipertrigliceridemia)
· hipertenzia
· Tambaqos moweva
· Saqriani diabeti
Meore rigis faqtorebi
· simsuqne
· dabali fizikuri aqtivoba
· mamrobiTi sqesi
· asakis mateba
· genetikuri ganwyoba
· stresi (“A tipis” pirovneba)
· oraluri kontraceptivebi
· naxSirwylebis didi raodenobiT moxmareba
hipelipidemia
hiperqolesterinemia da cximovani cvlis sxva cvlilebebi warmoadgens aTerosklerozis ganviTarebis pirveli rigis risk faqtors. hiperqolesterinemiisa da aTerosklerozis urTierTkavSirs mravalgvari gamoixatuleba gaaCnia:
· aTerosklerozuli folaqi mdidaria sisxlis lipoproteinebisagan warmoiqmnili qolesteriniTa da qolesterinis eTerebiT.
· sacdeli cxovelebis, maT Soris adamianismagvari primatebis, specialuri dietiT (sisxlis plazmaSi qolesterinis raodenobis momatebis xelSemwyobi) kvebis Sedegad, aTerosklerozuli cvlilebebi yalibdeba eqsperimentis TiTqmis yvela SemTxvevaSi.
· mniSvnelovan hiperqolesterinemias iwvevs genetikuri faqtorebi (maRali simkvrivis lipoproteinebis receptorebis, an maRali simkvrivis lipoproteinebis Tandayolili ukmarisoba). aRniSnuli adreuli aTerosklerozis ganviTarebis mizezia da mcirewlovanebSi, miuxedavad sxva risk faqtorebis uqonlobisa, xSirad fatalurad mTavrdeba. hiperqolesterinemiis gamomwvevi SeZenili avadmyofobebi (nefrozuli sindromi da hipoTireoidizmi) aseve zrdis gulis iSemiuri avadmyofobis risks.
· iSviaTi gamonaklisis garda, mosaxleobis im nawilSi, romelsac sisxlSi aReniSneba qolesterinis momatebuli raodenoba, aseve maRalia gulis iSemiuri avadmyofobiT gamowveuli sikvdiloba.
· gvirgvinovani arteriebis dazianebis SesaZlo prevenciis gamokvleviT dakavebuli lipidebis cvlis Semswavleli samecniero klinikebis monacemebiT, hiperqolesterinemiis niSniT SerCeul pacientTa mier dietis dacva da qolesterinis raodenobis Semamcirebeli samkurnalo saSualebebiT mkurnaloba, iwvevs gul-sisxlZarRvTa avadmyofobaTa mizeziT sikvdilobis Semcirebas. SemTxveviTobis principiT SerCeul ojaxebs, romelTac aReniSneboda hiperqolesterinemia, aRwerili mkurnalobisas gvirgvinovani arteriebis dazianebebi ganicdida ukuganviTarebas, rogorc mamakacebSi, ise qalebSi.
sisxlis plazmaSi qolesterinis erTjeradi momateba ar niSnavs aTerosklerozis riskis gazrdas. rac ufro stabilurad maRalia qolesterinis raodenoba, miT metia riskic, magram 200 mg/dl-ze meti (5,2 mmoli/l) erTjeradi momatebac iwvevs riskis gazrdas. yvelaze mniSvnelovania urTierTkavSiri qolesteriniT mdidari dabali simkvrivis lipoproteinebis donis matebasa da aTerosklerozs Soris. hipertrigliceridemia, Zlier dabali simkvrivis lipoproteinebis koncentraciis momatebiT, aseve iwvevs riskis momatebas. gansxvavebiT aRniSnulisagan, sisxlis plazmis maRali simkvrivis lipoproteinebis momateba ukuproporciul damokidebulebaSia riskTan – rac metia misi raodenoba, miT naklebia riskic. aRniSnulidan gamomdinare, maRali simkvrivis lipoproteinebs xSirad marTebulad uwodeben “karg qolesterins”.
qolesteriniTa da gajerebuli cximebiT datvirTuli sakvebis miReba, magaliTad, frinvelis kvercxis guli, cxoveluri cximebi da karaqi iwvevs sisxlis plazmaSi qolesterinis raodenobis momatebas. xolo, mcire raodenobis qolesterinisa da gaujerebeli cximebis Semcveli sakvebi sisxlis plazmaSi amcirebs qolesterinis Semcvelobas. paradoqsia, magram grenlandiaSi mcxovreb eskimosTa Soris, romlebic sakvebSi didi raodenobiT moixmaren cximebs, gulis iSemiuri avadmyofobiT avadoba dabalia. iTvleba, rom aRniSnulis mizezia maT racionSi didi raodenobiT cximovani mJavebis (-3) Semcveloba, romelic aseve didi raodenobiTaa Tevzsa da Tevzis qonSi. amgvarad, cximovan mJavebs gaaCnia mravali antiaTerogenuli Tviseba da maT Soris sisxlis plazmaSi dabali simkvrivis lipoproteinebis raodenobis Semcirebis da maRali simkvrivis lipoproteinebis momatebis unari.
hipertonia
miuxedavad imisa, rom hipertonuli avadmyofobiT ganpirobebuli aTerosklerozis ganviTarebis meqanizmi bolomde garkveuli ar aris, sisxlis wnevis momateba mainc aCqarebs aTerogenezs da zrdis gulisa da Tavis tvinis sisxlZarRvebis dazianebiT gamowveuli avadmyofobebis raodenobas. rac stabilurad maRalia sisxlis wneva, miT metia riskic. damazianebelad moqmedebs, rogorc diastoluri, ise sistoluri hipertonia. 45 wlis asakis zemoT, hipertonia ufro Zlieri risk-faqtoria, vidre hiperqolesterinemia. antihipertenziuli mkurnaloba amcirebs gulis iSemiuri avadmyofobebisa da insultis warmoqmnis sixSires.
Tambaqos moweva
sayovelTaod cnobilia, rom Tambaqos weva aTeroskleroziT gamowveuli avadmyofobebis risk-faqtors warmoadgens. Tambaqos wevis mavne Cveva iwvevs – qalebSi gulis iSemiuri avadmyofobis raodenobis momatebas; zrdis gulis Setevebis dros uecari sikvdilobis raodenobas da autofsiis dros aRmoCenili aortisa da gvirgvinovani arteriebis aTerosklerozis SemTxvevebs. maRali riskis jgufSi myofi pirebis mier Tambaqos wevis Tavis danebeba ramdenime wlis ganmavlobaSi amcirebs gulis iSemiuri avadmyofobiT gamowveuli sikvdilis risks.
Saqriani diabeti
miokardiumis infarqtis, Tavis tvinis sisxlZarRvebis Trombozisa da infarqtebis riski gaormagebulia Saqriani diabetiT daavadebulebSi, amasTan 18-jer imatebs qvemo kidurebis gangrenis ganviTarebis riski.
meore rigis risk-faqtorebs umniSvnelos, an “rbil” risk-faqtorebs uwodeben imis gamo, rom maTi kavSiri aTerosklerozTan nakleb SesamCnevia da riskis xarisxis gansazRvrac rTulia. pirveli rigis yovel risk-faqtors marto SeuZlia gamoiwvios klinikurad gamoxatuli aTerosklerozi, magram orive rigis risk-faqtorTa erToblioba iwvevs sinergiul (mets vidre damatebiTs) efeqts. miuxedavad aRniSnulisa, aTerosklerozTan dakavSirebuli avadmyofobebiT daavadebul zogierT pacients ar gaaCnia gamokveTili riskis faqtorebi.
ATerosklerozis morfologia
aTerosklerozis ZiriTad morfologiur gamovlinebas warmoadgens sisxlZarRvis kedlis intimis adgilobrivi gasqeleba, masSi cximovani nivTierebebis dagroveba da damaxasiaTebeli aTeromuli folaqiswarmoqmna. rogorc aRniSnuli iyo, aTerosklerozi warmoadgens arteriis yvelaze mZime dazianebis – misi sanaTuris Seviwroebis mTavar mizezs.
cximovani laqebi zedapiridan TiTqmis ar wamoiweva da Sesabamisad, ar warmoadgens xelSemSlel faqtors sisxlis dinebisaTvis. maTi gaCena iwyeba mravlobiTi 1 mm diametris brtyeli warmonaqmnebis saxiT, romlebic mogvianebiT erTiandeba 10 mm-sa da ufro didi zomis mogrZo laqebad. cximovani laqebi Sedgeba lipidebiT gadavsebuli qafiani ujredebisagan. cximovan laqebSi T-limfocitebi da ujredgareTa cximi warmodgenilia naklebi raodenobiT, vidre folaqSi, xolo proteoglikanebi, kolageni da elastikuri boWkoebi aRiniSneba sxvadasxva raodenobiT.
miuxedavad geografiuli adgilmdebareobis, erovnebis, sqesisa da garemo pirobebisa, cximovani laqebi warmoiqmneba erT wlamde asakis zogierT da aT welze ufrosi asakis yvela bavSvis aortaSi. gvirgvinovan arteriebSi cximovani laqebi naklebi raodenobiTaa, vidre aortaSi. axalgazrda asakSi warmoqmnili cximovani laqebi anatomiurad Seesabameba mogvianebiT ganviTarebuli folaqebis lokalizacias. aTerosklerozuli folaqebis raodenobis zrdis Sesabamisad, cximovani laqebis raodenoba droTa ganmavlobaSi mcirdeba.
cximovan laqebsa da aTerosklerozul folaqebs Soris calsaxa kavSiri ar arsebobs. rogorc aRniSnuli iyo, cximovani laqebi warmoiqmneba cxovrebis dasawyisSi, magram xSirad im sisxlZarRvebSi, romlebSic mogvianebiT ar warmoqmneba damaxasiaTebeli aTeromebi. garda amisa, aTeromebi xSirad warmoiqmneba mosaxleobis im geografiul populaciaSi, romelTaTvisac aTerosklerozuli folaqis Camoyalibeba uCveuloa. amgvarad, yvela cximovani zoli ar gardaiqmneba fibrozul folaqad, an sisxlZarRvebis sanaTuriskena zedapiris ufro mZime dazianebad. miuxedavad aRniSnulisa, cximovani laqebi mozrdilebSi ukavSirdeba aTerosklerozis warmoqmnis risks (sisxlis plazmaSi lipoprotein-qolesterinis gazrdili koncentracia da Tambaqos weva). samecniero eqsperimentebis zogierTi Sedegi cximovani laqebis folaqebad evoluciuri gardaqmnis SesaZleblobaze miuTiTebs. amgvarad, miuxedavad cximovani laqebis specifikuri rolisa, cxovrebis dasawyisSi maTi gavrceleba aortasa da gvirgvinovan arteriebSi naTlad warmoaCens, rom aTerosklerozuli procesebi iwyeba sicocxlis dasawyisidanve.
aTeromul folaqs agreTve uwodeben boWkovan, fibrozul-cximovan, cximovan, an fibrozul-lipidur folaqs, romelic warmoiqmneba arteriis sanaTuriskena zedapirze – TeTridan, moTeTro-yviTeli feris laqis saxiT. misi diametri 3-15 mm-s farglebSia, magram zogjer isini erTiandebian da qmnian farTo warmonaqmnebs. seqciis Catarebis procesSi aRmoCenili sisxlZarRvis sanaTuriskena mxares warmoqmnili amgvari ubnis zedapiri mkvrivi konsistenciisa da TeTri ferisaa (fibrozuli saxuravi), xolo siRrmeSi yviTeli, an moTeTro-yviTeli feris da rbili konsistenciis. didi zomis folaqebis centri SeiZleba Seicavdes yviTel, fafismagvar narCenebs, romelsac aTeroma (berZnulad “fafa”) ewodeba. adamianTa sisxlZarRvebSi aTerosklerozul folaqebs gaaCnia damaxasiaTebeli gavrceleba. muclis aorta ufro metad ziandeba, vidre gulmkerdis aorta, amasTan ufro meti dazianebis tendenciiT gamoirCeva misi ZiriTadi gantotebis mimdebare ubani.
muclis aortis Semdeg dazianebas yvelaze metad eqvemdebareba gvirgvinovani arteriebi, Semdeg daRmavali TanmimdevrobiT – muxlqveSa arteria, gulmkerdis daRmavali aorta, SigniTa saZile arteriebi da viliziis wris sisxlZarRvebi. zeda kidurebis sisxlZarRvebi Cveulebriv naklebad ziandeba iseve, rogorc jorjlisa da Tirkmelebis arteriebi, garda maTi saTaveebisa. amasTan, yovel konkretul SemTxvevaSi, erTi arteriis mZime aTerosklerozi ar gansazRvravs mis simZimes sxva arteriaSi. aTerosklerozuli dazianeba Cveulebriv moicavs arteriis kedlis mxolod nawils – igulisxmeba sisxlZarRvis garSemowerilobis nawili (“eqscentruli” dazianeba), xolo sisxlZarRvebis mTel sigrZeze ki aRiniSneba sxvadasxva xarisxis polimorfuli dazianebebi.
aTerosklerozuli folaqi Sedgeba sami mTavari komponentisagan:
1. ujredebisagan – gluvkunTovani ujredebi, makrofagebi da sxva leikocitebi;
2. SemaerTebeli qsovilis eqstraceluluri matriqsisagan – kolageni, elastikuri boWkoebi da proteoglikanebi;
3. ujredSida da ujredgareTa cximovani danaleqi.
aRniSnuli sami komponenti sxvadasxva folaqSi gansxvavebuli proporciiTaa warmodgenili da iZleva dazianebis mravalgvar speqtrs. fibrozuli saxuravi Sedgeba gluvkunTovani ujredebis, mcire raodenobiT leikocitebisa da SedarebiT mkvrivi SemaerTebeli qsovilisagan; saxuravis mxares da mis qvemoT ganTavsebuli ubani Sedgeba makrofagebis, gluvkunTovani ujredebisa da T-limfocitebis narevisagan; siRrmeSi myofi nekrozuli SigTavsi Sedgeba erTmaneTSi areuli lipidebis, qolesterinis kristalebis, ujredebis narCenebis, lipidebiT datvirTuli qafiani ujredebis, fibrinis, organizaciis sxvadasxva etapze myofi Trombebisa da sisxlis plazmis sxva cilebis narevisagan. lipidebi warmodgenilia upiratesad qolesteriniTa da qolesterinis eTerebiT. qafiani ujredebi upiratesad warmoiqmneba sisxlis monocitebis makrofagebad gardaqmnis Sedegad, amasTan sisxlZarRvebis gluvkunTovani ujredebi aseve ganicdian lipidebiT imbibicias (gaJRenTas) da gardaiqmnebian qafian ujredebad. dazianebis periferiis garSemo aRiniSneba mcire kalibris sisxlZarRvebis warmoqmna – neovaskulizacia.
folaqis histologiuri Senebis mravalferovnebis mizezia gluvkunTovani ujredebisa da makrofagebis, kolagenis ganawilebis, sxva eqstracelularuli matriqsisa da lipidebis raodenobis gansxvavebuli Sefardeba. tipiuri aTeroma Seicavs SedarebiT didi raodenobiT lipidebs. miuxedavad aRniSnulisa, mravali e.w. fibrozuli folaqi Sedgeba gluvkunTovani ujredebisa da fibrozuli qsovilisagan. xandazmuli aTerosklerozis mimdinareobaSi, progresuli fibrozis zemoqmedebiT, SesaZlebelia cximovani aTeroma gadaiqces fibrozul nawiburad.
aTeroskleroziT gamowveul dazianebaTa garTulebebs mniSvnelovani adgili ukavia avadmyofobis Semdgom ganviTarebaSi:
· xandazmuli avadmyofobisas, aTeroma TiTqmis yovelTvis ganicdis kerovan, an masobriv “kalcifikacias”. arteriebi gadaiqceva tixrul milebad da aortam SeiZleba SeiZinos kvercxis naWuWis simyife. kvlevis Tanamedrove teqnologiebi, rogoricaa intravaskuluri ultrabgeriTi, an kompiuteruli tomografiiT skanireba, kalcifikatebs iyenebs rogorc markers da arainvaziuri meTodis gamoyenebiT martivad axdens avadmyofobis diagnostikasa da Terapias.
· sisxlZarRvebis sanaTuriskena zedapirze aTeromuli folaqis mTlianobis adgilobrivi darRveva, an wylulis warmoqmna, an orive erTad maRali Trombogenuli Tvisebebis mqone nivTierebebis eqspoziciis mizezi xdeba da iwveven Trombebis warmoqmnas, an sisxlSi folaqis narCenebis gadasrolasa da mikroembolebis warmoqmnas (qolesterinis embolebi da aTeroembolebi).
· zemoTaRniSnulze TandarTuli Trombozi, xSirad saSiSi da mZime garTulebis mizezi xdeba. Cveulebriv Trombebi warmoiqmneba folaqis napralebSi, an dawylulebul ubnebSi. SesaZlebelia TrombebiT srulad, an nawilobriv daixSos sisxlZarRvebis sanaTuri; moxdes Trombuli masebis organizacia da maTi sruli mierTeba (inkorporacia) intimis folaqTan.
· ZiriTadad gvirgvinovan arteriebSi, SesaZlebelia ganviTardes sisxlCaqceva folaqis sxeulSi. sisxlCaqceva viTardeba fibrozuli saxuravis gaskdomis, an folaqis vaskulizaciis ganmapirobebeli Txelkedliani kapilarebidan. sisxlCaqcevam SesaZlebelia xeli Seuwyos folaqis gaglejas.
· miuxedavad imisa, rom aTerosklerozis mimdinareoba xasiaTdeba sisxlZarRvebis intimis upiratesi dazianebiT, mZime SemTxvevebSi, gansakuTrebiT didi kalibris sisxlZarRvebis media ganicdis mniSvnelovan zewolas, an elastikuri qsovilis dakargviT ganpirobebul iSemiur atrofias, rac rig SemTxvevebSi anevrizmis Camoyalibebis mizezi SeiZleba gaxdes.
ATerosklerozis paTogenezi
istoriulad, aTerogenezis warmoqmnis mraval TeoriaTa Soris upiratesoba eniWeboda or maTgans – erTis mixedviT intimaSi ujredebis proliferacia warmoadgenda sisxlidan plazmuri cilebisa da lipidebis gaJonvaze reaqcias, xolo meore Teoriis mixedviT Trombebis organizacia da maTi ganmeorebiTi warmoqmna, mTavrdeboda aTerosklerozuli folaqis warmoqmniT. hipoTezis saxiT Camoyalibebul aTerosklerozis paTogenezis Tanamedrove Teorias ewodeba dazianebaze pasuxis hipoTeza da Tanamedrove mosazrebebTan erTad moicavs adrindeli Teoriebis elementebsac. aRniSnuli Teoria Seiqmna 1973 wels, ganicada modifikacia 1986 da 1993 wlebSi da misi mixedviT aTerosklerozuli cvlilebebi warmoadgens pasuxs arteriebis endoTeliumis zogierTi formis dazianebaze. amgvari dazianeba SesaZlebelia warmoadgens endoTeliumis funqciis moSlis iseT formas, rodesac misi Camofcqvna savaldebulo ar aris, izrdeba sisxlis plazmis Semadgenlebis (lipidebis CaTvliT) ganvladoba da sisxlis monocitebsa da sabolood Trombocitebsac endoTeliumze adheziis saSualeba eZleva. mimagrebuli monocitebi mogvianebiT gadadian intimaSi da ganicdian makrofagebad transformacias. lipidebis dagrovebis Semdeg isini gardaiqmnebian qafian ujredebad da monawileobas iReben dazianebis keris Semdgom evoluciaSi. gaaqtivebuli Trombocitebidan, an monocitebidan, maT zedapirze gamoiyofili faqtorebi, ganapirobeben gluvkunTovani ujredebis migracias mediidan intimaSi. aRniSnuls axlavs gluvkunTovani ujredebis proliferacia da eqstraceluluri matriqsis Semadgenlebis sinTezi. Sesabamisad, iwyeba kolagenisa da proteoglikanebis dagroveba. endoTeliumis erTjerad an xanmokle dazianebas SesaZlebelia mohyves misi darRveuli funqciis aRdgena da dazianebis keris ukuganviTareba. ganmeorebiTi an qronikuli dazianebebi ki mTavrdeba aTeromuli folaqis CamoyalibebiT.
endoTeliumis dazianeba
samecniero literaturaSi aRwerili mravalmxrivi eqsperimentebis mimdinareobaSi, sacdel cxovelebSi endoTeliumis dazianeba xdeboda misi meqanikuri CamofcqvniT, sisxlis paTologiuri mimoqcevis zemoqmedebiT (arterio-venuri fistula), imunuri kompleqsebis daleqviT, dasxivebiTa da qimiuri nivTierebebis zemoqmedebiT. aRwerili zemoqmedebebi iwvevda gluvkunTovani ujredebis proliferacias, xolo kvebis racionSi cximebis didi raodenobiT gamoyeneba – aTeromis Camoyalibebas. aRsaniSnavia, rom endoTeliumis adreuli dazianebebi morfologiurad yalibdeboda endoTeliumis intaqtur ubnebSi. eqsperimentebSi gamovlenili disfunqciebidan yvelaze mniSvnelovania hiperqolesterinemiis adreuli gamoxatulebani – endoTeliumis ganvladobis progresuli momateba, monocitebis adheziis unaris gazrda da endoTeluri ujredebis Warbi gamravleba.
endoTelur ujredebze monocitebis adhezia ganpirobebulia gaaqtivebuli endoTeluri ujredebis zedapirze specifikuri receptoruli molekulebis warmoqmniT. sisxlZarRvTa ujredebis adheziuri molekulebis (VCAM-1) eqspresia (gamoyofa) da endoTeluri ujredis mier nawarmoebi leikocitis adheziis ganmapirobebeli molekulebi (LFA-1) warmoadgenen upiratesad dazianebadi ubnis adreul markerebs. yovelive zemoaRniSnuli sapasuxo reaqciaa, eqsperimentul hiperqolesterinemiaze. amrigad, aTerosklerozuli folaqis SemadgenlobaSi myofi endoTeluri ujredebi axdenen ujredSorisi adheziuri (ICAM-1) da sisxlZarRvTa ujredebis adheziuri molekulebis Warb eqspresias.
iseT risk-faqtorebs, rogoricaa hipertonia da Tambaqos mweveloba, SeuZlia gaxdes endoTeliumis dazianebis mizezi da gamoiwvios endoTeliumis ganvladobis momateba. sisxlis mimoqcevis zemoqmedebiT (dinebis turbulenciiT) gamowveuli endoTeliumis dazianeba, naTels hfens arteriebis gantotebasa da muclis aortaSi folaqebis ganawilebis kanonzomierebas.
makrofagebis roli da sxva anTebiT-imunuri meqanizmebis mniSvneloba
eqsperimentuli hiperqolesterinemiis dasawyisSi makrofagebi STanTqaven lipidebs da warmoqmnian qafian ujredebs, amasTan, monocitebsa da makrofagebs uCndeba receptorebi dabali simkvrivis lipoproteinebisadmi. qafiani ujredebis warmoqmnisaTvis Seucvleli dabali simkvrivis lipoproteinebis raodenoba mcirea, magram miuxedavad aRniSnulisa, maT SeuZlia gamoiyenon dabali simkvrivis lipoproteinebis modificirebuli formebi (receptorebi dabali simkvrivis lipoproteinebis identifikacias ver axdens). modifikacia gulisxmobs endoTeluri ujredebis JangviT da Trombocitebisa da leikocitebis fermentebiT gamowveul damazianebel cvlilebebs. amgvarad, qafiani ujredebi SeiZleba CaiTvalos specializebul makrofagebad. aTeromuli folaqis ganviTarebis yvela etapze isini sxvadasxva raodenobiTaa warmodgenili. savaraudod, aTerosklerozis yvelaze martiv dazianebas – cximovan laqebs, warmoadgens makrofagebidan warmoqmnili qafiani ujredebis nakrebi.
aTeromebis SemadgenlobaSi aRmoCenili T-limfocitebis (CD4+ da CD8+) roli da mniSvneloba garkveuli ar aris.
makrofagebis biologiuri aqtivobis Sedegad gamoiyofili didi raodenobiT produqtebi (dawvrilebiT aRwerili iyo anTebis ganxilvisas), SesaZloa, aTerosklerozuli dazianebebis progresiis TvalsazrisiTac asrulebdes gansazRvrul rols da iwvevdes dabali simkvrivis lipoproteinebis daJangvas. daJanguli dabali simkvrivis lipoproteinebis identifikacia xdeba receptorebis meSveobiT. dasasrul, zrdis stimulatorebsa da makrofagebis mier gamomuSavebul zrdis inhibitorebs (Trombocitebisagan warmoqmnil zrdis faqtors, fibroblastebis zrdis faqtorsa da transformaciis gamomwvev faqtor -s) SeuZliaT gamoiwvion gluvkunTovani ujredebis proliferacia da dazianebis adgilas eqstraceluluri matriqsis dagroveba.
gluvkunTovani ujredebis proliferaciis mniSvneloba
lipidebis dagrovebis garda, gluvkunTovani ujredebis proliferacia da intimaSi eqstraceluluri matriqsis daleqva is mniSvnelovani procesebia, romlebic ganapirobeben aTerosklerozuli dazianebebis progresul ganviTarebas. gluvkunTovani ujredebis proliferacia iwyeba mediidan migrirebuli an miointimis ujredebidan. aTerosklerozul kerebSi sisxlZarRvis gluvkunTovani ujredebSi aRmoCenilia mravali mitogenuri faqtori da ujredebidan warmoqmnili qemotaqsisis agentebi. zemoaRniSnuls ganapirobebs Trombocituli zrdis faqtori, romelic imyofeba Trombocitebis -granulebSi da Trombocitebis adheziis Semdeg gamoTavisufldeba dazianebis adgilas. maT gamoimuSavebs makrofagebi, endoTeluri da gluvkunTovani ujredebi. fibroblasturi zrdis faqtori, interleikin-1-isa da sxva citokinebis warmoqmna SeuZlia endoTelur ujredebs, monocitebs, makrofagebs, T-limfocitebsa da agreTve sisxlZarRvis gluvkunTovan ujredebs. Teoriulad, zrdis stimulacia SesaZlebelia gamravlebis inhibitorebis – endoTeluri da gluvkunTovani ujredebis mier gamomuSavebuli heparinis msgavsi molekulebis, an makrofagebis, an endoTeluri ujredebis mier gamomuSavebuli zrdis transformaciis faqtor -s raodenobis SemcirebiT. sisxlZarRvis gluvkunTovani ujredebi gamoimuSavebs agreTve aTeromuli folaqis ujredgareTa Semadgenlebs da axdens modifikacias. sisxlZarRvebis gluvkunTovani ujredebi didi raodenobiT qolesterinisa da qolesterinis eTerebis dagrovebis Semdeg, infiltraciis gamomwvev makrofagebTan erTad, TviT gardaiqmneba folaqis qafian ujredebad.
hiperlipidemiis mniSvneloba
sisxlis plazmaSi yvela lipidi cirkulaciaSi imyofeba cilasTan SekavSirebul mdgomareobaSi. plazmis lipoproteinebi warmoadgenen cximebisa da cilebis, burTulas formis kompleqss, romelTa centri Sedgeba neitraluri lipidebisagan (upiratesad trigliceridebisa da qolesterinis eTerebisagan) da garSemortymulia polaruli lipidebiTa (fosfolipidebiTa da Tavisufali qolesteriniT) da apolipoproteinebiT (apoproteinebiT). lipoproteinebis transportireba xdeba lipoprotein-gardamqmneli cilebiTa (lecitin-qolesterin aciltransferaza, lipoprotein lipaza, RviZlis lipaza da qolesterinis eTerebis gadaTavsebis cila) da lipoproteinuli receptorebiT, romlebic lipoproteinebis identifikaciis Semdeg ganapirobebs ujredebis mier maT STanTqmasa da katabolizms (dabali simkvrivis lipoproteinebi, qilomikronis narCenebi da sxva receptorebi). gasuli saukunis oTxmocian wlebSi gamoyves da daadgines aRniSnuli cilebis genebis Tanmimdevroba adamianis genomSi da, rom isini warmoadgenen zemoaRniSnuli cilebis Seqmnis kods.
hiperlipoproteinemia adreuli aTerosklerozis ganviTarebaSi zogadi movlenaa da ganpirobebulia mravali memkvidruli da SeZenili faqtorebiT, qolesterinis egzogenuri da endogenuri metabolizmis moSlilobiT. lipidebis metabolizmSi hiperlipoproteinemia SesaZlebelia iyos pirveladi genetikuri defeqtebis Sedegi an ganviTardes meoradad, iseTi paTologiebis fonze, rogoricaa nefrozuli sindromi, alkoholizmi, hipoTireoidizmi an Saqriani diabeti. aRmoCenilia lipoproteinebis anomaliis oTxi tipi – (1) dabali simkvrivis lipoproteinebis da Sesabamisad maT SemadgenlobaSi Semavali qolesterinis raodenobis momateba, (2) maRali simkvrivis “lipoproteinuli qolesterinis” dakleba, (3) qilomikronis (sisxlis plazmisa da limfis lipoproteinebis erTerTi klasi) narCenebis raodenobis momateba da (4) aranormaluri lipoprotein-a-s raodenobis momateba. erTi an ramdenime maTgani aRiniSneba im avadmyofTa 50-80%-Si, romlebic gadarCnen gadatanili miokardiumis infarqtis Semdeg. magaliTad, kargadaa Seswavlili genetikurad ganpirobebuli hiperlipoproteinemia, romelic axalgazrdebSi iwvevs mZime aTerosklerozs da warmoadgens dabali simkvrivis lipoproteinebis receptorebis defeqtebiT gamowveul ojaxur hiperqolesterinemias. aRniSnuli iwvevs RviZlis mier dabali simkvrivis lipoproteinebis Warbad STanTqmas, rasac axlavs sisxlSi dabali simkvrivis lipoproteinebis raodenobis momateba. apoproteinebis genetikuri defeqtebi SesaZlebelia hiperlipoproteinemiis ganviTarebis mizezi gaxdes da daaCqaros aTerosklerozis Camoyalibeba. magaliTad, apoprotein-E-s genetikuri variantiT ganpirobebuli, dabali simkvrivis lipoproteinebis qolesterinis donis momateba, aqveiTebs dabali simkvrivis lipoproteinebis receptorebTan mierTebis unars. aRniSnuli defeqtis mizezi calkeuli aminomJavas Secvlaa (magaliTad, arginini icvleba cisteiniT) apoprotein-E-s molekulis receptorTan SekavSirebis adgilas. aRniSnuli am kavSirebis SesaZleblobas amcirebs normasTan SedarebiT 1-2%-iT. mutaciebi aseve iwvevs sisxlis plazmaSi dabali simkvrivis lipoproteinebis SekavSirebis unaris daqveiTebasa da maTi raodenobis momatebas, romlebic ganapirobeben defeqturi apo B-100-is Seqmnas. savaraudod, apolipoproteinebis genetikuri cvalebadoba SesaZlebelia garkveul rols asrulebdes aTerosklerozisadmi ganwyobaSi.
dazianebebis meqanizmSi lipidebis mniSvneloba debulebebis saxiT SeiZleba Camoyalibdes Semdegnairad:
· sisxlis plazmaSi dabali simkvrivis lipoproteinebis raodenobis momatebam an hiperlipidemiam SeiZleba gaaZlieros arteriis kedlis lipidebiT infiltraciis xarisxi.
· makrofagebs receptorebis meSveobiT, SeuZlia STanTqon dabali simkvrivis lipoproteinebi. dabali simkvrivis daJangul lipoproteinebs SeuZlia daaCqaron aTerogenezi Semdegi meqanizmebiT: (1) monocitebis qemotaqsisi; (2) monocitTa adheziis gaZliereba; (3) dazianebis adgilas makrofagebis moZraobis unaris SezRudva, ris gamoc isini ver axorcieleben Tavis funqcias da grovdebian dazianebis ubanSi; (4) zrdis faqtorebisa da citokinebis raodenobis momateba; (5) sisxlZarRvis endoTelur da gluvkunTovan ujredebze cititoqsikuri zemoqmedeba da (6) imunuri zemoqmedeba (imunogenuria). aRniSnulidan gamomdinare, aTerosklerozis ganviTarebaSi dabali simkvrivis lipoproteinebis daJangviT gamowveuli modifikaciis prevenciisaTvis SesaZlebelia gamoyenebul iyos antioqsidantebiT (magaliTad, vitamini E) mkurnaloba.
· hiperlipidemiis ganviTarebas SeuZlia uSualod gamoiwvios endoTeluri ujredis funqciis darRveva. aRniSnuli mimdinareobs ujredebis Camofcqvnis gareSe, da gamoixateba maTi fokaluri nekroziT, ganvladobis momatebiT, gamravlebis an monocitis adheziis unaris gazrdiT.
Trombozis mniSvneloba
Trombozi Zveli aTerosklerozis garTulebaa. Trombebis organizacias SeuZlia xeli Seuwyos folaqis Camoyalibebas. mZime dazianebis an endoTeliumis gaSiSvlebis gareSe arteriis kedels Trombocitebi ar miemagreba. normalur endoTelur ujredebSi, natifi bioqimiuri procesebis mimdinareobis darRvevam, SeiZleba gamoiwvios Trombis warmoqmna.
dabali simkvrivis lipoproteinebis Secvlili saxeobaa lipoprotein-a. aRniSnuli didi zomis glikoproteinuli molekulaa da gaaCnia plazminogenisadmi (fibrinolizis ZiriTadi cila) struqturuli Tvisobis maRali maCvenebeli. monawileobs ra, rogorc dabali simkvrivis lipoproteinebis, ise plazminogenis metabolizmSi, sisxlZarRvebis gluvkunTovani ujredebis proliferaciis fonze, lipoproteini-a sxvadasxva meqanizmiT, SesaZlebelia gaxdes aTerogenezis gamomwvevi. epidemiologiuri gamokvlevebiT dadgenilia, rom qolesterinisa da dabali simkvrivis lipoproteinebis saerTo donis miuxedavad, sisxlSi lipoprotein-a-s momatebul raodenobasa da gvirgvinovani arteriebisa da Tavis tvinis sisxlZarRvebis paTologias Soris mniSvnelovani korelacia aRiniSneba.
Arteriosklerozi
arteriosklerozis dros kalcinoziTa da skleroziT dazianebas eqvemdebareba saSualo da mcire sididis arteriebis Sua Sre. aRniSnuli paTologiis gamomwvevi mizezebi ucnobia. gakirva ar ukavSirdeba sisxlZarRvebis anTebas. arteriaTa Sida da gareTa SreebSi, rogorc wesi, cvlilebebi ar aRiniSneba. daleqili kalciumi sisxlZarRvebs ar aviwroebs. gakirvis ubnebSi SeiZleba gaZvalebis (osifikaciis) kerebis aRmoCena. aTerosklerozTan SeuRlebuli arteriosklerozi, erTi sisxlZarRvis farglebSic ki, gansxvavebuli genezisis paTologiuri procesebia. Sua Sris kalcinozi da sklerozi aRiniSneba kidurebisa da sasqeso organoebis arteriebSi. arteriosklerozi ormocdaaTi wlis asaks gadaSorebul pirTa paTologiaa.
hipertenzia da arteriolosklerozi
hipertenzia
termini “hipertenzia”, farTo gagebiT, gulisxmobs sisxlZarRvebSi, Rru organoebSi an sxeulis RruebSi, hidrostatiuri wnevis momatebas. winamdebare TavSi saubari iqneba, mxolod sisxlZarRvovan paTologiaze. arteriuli hipertenziis mTvari klinikuri niSania – sisxlis arteriuli wnevis mdgradi momateba. am paTologiis ZiriTad samiznes warmoadgenen sxvadasxva kalibris arteriebi.
Zogadi monacemebi
arteriuli hipertenzia, Tanamedrove medicinis mniSvnelovani problemaa – igi Zlier gavrcelebulia da misi mogvianebiTi Sedegebi iwvevs mravali organosa da sistemis dazianebas. aTerosklerozTan erTad, hipertenzia iTvleba gulis iSemiuri daavadebis, cerebrovaskuluri avadmyofobebis, aortis ganSrevebadi anevrizmebisa da Tirkmelebis ukmarisobis mniSvnelovan risk-faqtorad. hipertenziis, rogorc avadmyofuri movlenis “zRvari” ar arsebobs, magram diastoluri wnevis mdgradad momateba, vercxliswylis svetis 90 mm niSnulamde da metad, da sistoluri wnevis – 140 mm niSnulamde da metad, ganixileba, rogorc arteriuli hipertenziis niSnebi.
skrininguli (masobrivi) gamokvlevebiT dadgenilia, rom planetis mosaxleobis 25% avadmyofobs hipertenziiT. asakis matebasTan erTad, progresulad izrdeba hipertenziiT avadoba. ufrosi asakis jgufebSi gaCenili avadmyofoba ufro msubuqi formiT gamovlindeba, vidre axalgazrdebSi. afrikuli warmoSobis pirebi orjer ufro xSirad avaddebian hipertenziiT, vidre evropelebi.
arteriuli hipertenziis yvela SemTxvevis 90-95% pirveladi idiopaTiuri, anu esenciuri hipertenziaa (hipertonuli avadmyofoba, hipertonia). terminebi “idiopaTiuri” (daudgeneli warmoSobis) da “esenciuri” (“sufTa saxis avadmyofoba”) dReisaTvis veRar inarCunebs Tavdapirvel azrobriv datvirTvas, magram ramdenadme asaxavs movlenaTa ganviTarebas. postsabWoTa sivrceSi, isev popularulia termini “hipertonuli avadmyofoba”, romelic avadmyofobaTa saerTaSoriso klasifikaciis nozologiuri formebis CamonaTvalSi Seesabameba – “esenciur hipertonias”.
arteriuli hipertenziis yvela SemTxvevis darCenili 5-10% – meoradi hipertenziaa. mis warmoSobas ganapirobebs Tirkmelebis dazianebebi, Tirkmelebis arteriebis stenozi (magaliTad, aTerosklerozuli folaqebiT) an sxva mizezebi.
esenciuri da meoradi hipertenziebis klinikuri mimdinareoba SeiZleba iyos keTilTvisebiani an avTvisebiani.
SemTxvevaTa umravlesobaSi, mcired momatebuli arteriuli wneviT mimdinare hipertenzia (keTilTvisebiani mimdinareoba), SenarCundeba mravali wlis ganmavlobaSi. miuxedavad imisa, rom keTilTvisebiani mimdinareoba damaxasiaTebelia pirveladi, esenciuri hipertenziisTvis, igi SeiZleba aRiniSnos meoradi hipertenziis drosac. hipertenziiT daavadebulTa daaxloebiT 5%-s aReniSneba arteriuli wnevis swrafi gazrda (avTvisebiani mimdinareoba), rasac 1-2 wlis ganmavlobaSi SeuZlia gamoiwvios sikvdili. hipertenziis avTvisebiani formis klinikuri suraTi moicavs mZime hipertenzias (diastoluri wneva, TiTqmis yovelTvis, v.wy. svetis 120 mm-sa da metis farglebSia), Tirkmelebis ukmarisobas, Tvalis badura garsSi sisxCaqcevebisa da TeTri ubnebis gaCenas, mxedvelobis nervis diskos SeSupebas.
hipertenziis paTogenezi da morfologia
arteriuli wneva sakmaod rTuli movlenaa da mis warmoqmnas ganapirobebs mravali genetikuri da garemo faqtorebis urTierTqmedeba. aRniSnulis gamo, hipertenziis paTogenezi dRemde, bolomde garkveuli ar aris.
sisxlis normaluri wnevis regulacia
arteriuli wneva warmoiqmneba ori ZiriTadi da aramudmivi hemodinamikuri maCveneblis – gulis mier gamotyorcnili sisxlis moculobisa (gulis wuTmoculoba) da sisxlZarRvebis zogadi periferiuli winaaRmdegobis, urTierTqmedebiT. gulis wuTmoculoba – gulis parkuWebis mier 1 wuTis ganmavlobaSi gamotyorcnili sisxlis moculobaa da igi normaSi 4-6 l/wT-s tolia. meore maCvenebeli asaxavs sisxlis mimoqcevis didi wris sisxlZarRvebiT (ZiriTadad, arteriolebiTa da kapilarebiT) sisxlis mimoqcevisadmi ganviTarebul winaaRmdegobas. misi gamoTvla xdeba aortisa da Rru venebis saSualo wnevebis SefardebiT, 1 wamis ganmavlobaSi gadinebul sisxlis saSualo moculobasTan. periferiuli winaaRmdegobis sidide damokidebulia arteriolebis sanaTuris sidideze, romelsac gansazRvravs sisxlZarRvis kedlis sisqe da agreTve, vazokonstriqciisa da dilataciis xarisxis ganmapirobebeli, nervul-humoruli meqanizmebi. vazokonstriqciis agentebia – angiotenzin II, kateqolaminebi, Tromboqsani, leikotrienebi da endoTelini. vazodilatatorebis jgufSi Sedis – kininebi, prostaglandinebi da azotis Jangeuli. CamoTvlili mediatorebi moqmedeben gluvkunTovani ujredebis zedapirze arsebul, specifikur receptorebTan mimagrebiT. adgilobriv vazodilatatorebs agreTve, warmoadgenen hipoqsia da metabolizmis zogierTi produqti – rZemJava, wyalbadis ionebi, adenozini (purinuli fuZis adeninisa da monosaqarid ribozas naerTi). sisxlis dinebis moculobis gazrdisas, iwyeba vazokonstriqcia, rac qsovilebs icavs hiperperfuziis (sisxliT gadavsebis) ganviTarebisagan. savaraudod, aRniSnul process adgilobrivad warmarTavs adenozini. vazokonstriqciis ganviTarebas axlavs gulis muSaobismieri datvirTvis gazrda, gulis wuTmoculobis Semcireba da hiperperfuziis koreqcia. dReisaTvis, arteriuli hipertenzia ganixileba, rogorc mraval faqtorze damokidebuli avadmyofoba da am faqtorebma SeiZleba gamoiwvios mimoqcevaSi myofi sisxlis moculobisa da arteriolaTa saerTo winaaRmdegobis urTierTkavSiris Secvla.
sisxlis wnevis regulaciaSi mniSvnelovani adgili ukavia Tirkmelebs, romlebic sxvadasxva sistemebisa da meqanizmebis meSveobiT, axorcieleben sisxlis wnevis regulacias. pirveli sistema, anu iuqstaglomeruluri kompleqsis zonaSi ganTavsebuli renin-angiotenzuri sistema, warmoqmnis angiotenzin II-s, romelic periferiuli winaaRmdegobisa da mimoqcevaSi myofi sisxlis moculobis regulaciiT, cvlis arteriuli wnevis dones. sxva meqanizmebis moqmedebaSi moyvanas ganapirobebs aldosteronis sekreciis stimulacia – izrdeba Tirkmelebis milakebis distaluri nawilis mier natriumisa da wylis reabsorbcia.
meore sistemiT xdeba natriumis homeostazis SenarCuneba. renin-angiotenzuri sistemis garda, am procesis monawile sxva ori mniSvnelovani faqtoria – gorglebiT filtraciis siswrafe da, misgan damoukideblad, SardTan erTad natriumis ionebis gamodevna (natriumurezi). mimoqcevaSi myofi sisxlis moculobis SemcirebasTan erTad, mcirdeba gorglebiT filtraciis siswrafec, rac iwvevs milakebis proqsimalur nawilSi natriumis reabsorbciis gazrdas. damoukidebel faqtors miekuTvneba winagulebis kunTovani qsovilis mier, gafarToebaze pasuxad, gamomuSavebuli natriumurezuli peptidi, romelic milakebis distalur nawilSi Trgunavs natriumis reabsorbcias da xels uwyobs vazodilatacias.
mesame sistemas warmoadgens Tirkmelebis vazodepresoruli substanciebi. am jgufSi gaerTianebulia prostaglandinebi, kalikrein-kininuri sistema, Trombocitebis gamaaqtivebeli faqtori da azotis Jangi. Tirkmelebis sxvadasxva dazianebebiT ganpirobebuli, aRwerili sami sistemis gamarTuli muSaobis darRveva qmnis meoradi hipertenziis ganviTarebis winapirobas, magram amavdroulad, eWvgareSea, rom maT gansazRvruli adgili ukavia esenciuri hipertenziis paTogenezSic.
esenciuri hipertenziis ganviTarebis meqanizmi
miuxedavad imisa, rom esenciuri hipertenziis konkretuli gamomwvevi mizezi, SemTxvevaTa umravlesobaSi ucnobia, arsebobs misi meqanizmebis ganviTarebis mravali Teoria. dReisaTvis dadgenilia, rom esenciuri hipertenzia raime erTi defeqtiT gamowveuli paTologia ara aris. mis sawyis etapze mizezi SeiZleba iyos gulis wuTmoculobis an periferiuli winaaRmdegobis gazrda, amasTan hipertenziis paTogenezSi monawileobs memkvidruli da garemo faqtorebic.
orive mSobelis hipertoniiT avadoba ganapirobebs maT SvilebSi hipertenziis ganviTarebis maRal risks. tyupebisa da maTi ojaxis wevrebis gamokvleva, aseve warmoaCens genetikuri faqtorebis rols hipertenziis warmoSobaSi. savaraudod, genetikuri dazianebebi ganapirobebs TirkmelebSi natriumis reabsorbcias an mis gadatanas kalciumTan erTad sisxlZarRvTa gluv kunTebSi. amasTan dadgenilia, rom hipertoniiT daavadebulTa Soris, angiotenzinogenis genis zogadi variantis matareblebSi, aRiniSneba hipertenziis gamomwvevi plazmuri angiotenzinis maRali koncentraciis arseboba.
hipertenziis ganmapirobebeli genetikuri darRvevebis eqspresiaSi monawileobs garemo faqtorebi, ris sailustraciod gamodgeba CineTis mosaxleobis hipertenziiT avadobis dabali maCvenebeli, aSS-Si mcxovreb Cinuri warmoSobis mosaxleobasTan SedarebiT. garemo faqtorebs miekuTvneba – qronikuli stresebi, Tambaqos mweveloba, hipodinamia da sakvebTan erTad sufris marilis Warbi moxmareba. mosaxleobis sxvadasxva jgufebis gamokvlevis magaliTze, kavSiri sakvebTan erTad natriumis miRebasa da hipertenziis dones Soris – savsebiT sarwmunoa. natriumis Warbi moxmareba zrdis hipertenziis ganviTarebis albaTobasa da mimdinareobis simZimes.
sisxlZarRvebsa da gulSi ganviTarebuli cvlilebebi
rogorc zemoT iyo xsenebuli, hipertenzia xels uwyobs da aCqarebs aTerosklerozis ganviTarebas. hipertoniiT daavadebulTa msxvil da saSualo kalibris arteriebSi viTardeba aTerosklerozuli folaqebi da maTgan gamomdinare yvela garTulebani. wvrili kalibris arteriebis – arteriolebis hipertenziuli dazianebebi gamovlindeba hialinuri da hiperplastiuri arterioloskleroziT.