{"id":7500,"date":"2020-09-10T10:09:59","date_gmt":"2020-09-10T07:09:59","guid":{"rendered":"http:\/\/blog.ulubat.org\/?p=7500"},"modified":"2020-09-09T21:54:42","modified_gmt":"2020-09-09T18:54:42","slug":"covid-19-patogenezi-ve-sitokin-firtinasi","status":"publish","type":"post","link":"https:\/\/blog.ulubat.org\/index.php\/genel\/covid-19-patogenezi-ve-sitokin-firtinasi\/","title":{"rendered":"COV\u0130D-19 Patogenezi ve Sitokin F\u0131rt\u0131nas\u0131"},"content":{"rendered":"\n

Merhaba de\u011ferli okurlar, bu ayki yaz\u0131mda COVID-19’un patogenezinden,<\/em><\/strong> a\u011f\u0131r hastalardaki \u00f6l\u00fcmc\u00fcl Sitokin F\u0131rt\u0131nas\u0131ndan <\/em><\/strong>ve tedavi se\u00e7eneklerinden bahsedece\u011fim. <\/p>\n\n\n\n

Bilindi\u011fi \u00fczere COV\u0130D-19 bir RNA vir\u00fcs\u00fcd\u00fcr ve yap\u0131s\u0131nda 4 ana protein i\u00e7erir. Bu proteinler; Spike(S) ,Envelop(E) ,N\u00fckleokapsid(N) ve Membran(M) <\/em>proteinleridir. <\/p>\n\n\n\n

COV\u0130D-19 ile enfekte insanlar\u0131n \u00e7o\u011funda semptom ve bulgular grip gibi bir klinik tabloyla seyredilirken, pn\u00f6moni, Akut Respiratuvar Distress Sendromu (ARDS) ve sitokin f\u0131rt\u0131nas\u0131na kadar \u00e7ok de\u011fi\u015fik klinik tablolara da neden olabilir <\/p>\n\n\n\n

Patogenez<\/h2>\n\n\n\n

H\u00fccre i\u00e7ine giri\u015f;<\/strong><\/p>\n\n\n\n

Vir\u00fcs h\u00fccre i\u00e7ine girerken farkl\u0131 mekanizmalara ba\u015fvurur.\nBunlardan en \u00f6nemlisi, S proteinini ACE2 (Angiotensin-Converting Enzyme-2)\nresept\u00f6rlerine ba\u011flayarak ger\u00e7ekle\u015ftirdi\u011fi \u201cMembran F\u00fczyonu\u201d y\u00f6ntemidir.\nMembran F\u00fczyonu s\u0131ras\u0131nda ACE2’nin giri\u015f s\u0131ras\u0131nda par\u00e7alanmas\u0131 sonucu RAAS\n(Renin-Angiotensin Aldosteron System) etkilenerek Anjiyotensin2 art\u0131\u015f\u0131na sebep\nolur. ACE2 endotel h\u00fccrelerinde de bulundu\u011fu i\u00e7in endotelyitis meydana gelir ve\napoptoz, RAAS dengelerinde bozulma sonucu iskemi, \u00f6dem ve hiperkoag\u00fclabilite\nmeydana gelir.<\/p>\n\n\n\n

 Bu y\u00f6ntem haricinde\nKlatrin proteini ba\u011f\u0131ml\u0131 veya ba\u011f\u0131ms\u0131z olarak endositozla da h\u00fcrce i\u00e7ine\ngirebilir.<\/p>\n\n\n\n

\u0130mmun Yan\u0131t;<\/strong><\/p>\n\n\n\n

COVID-19\u2019da Sitotoksik T h\u00fccreleri ve makrofajlar da patogenezde ba\u015frold\u00fcr. Viral \u00e7o\u011falman\u0131n\/yay\u0131lman\u0131n s\u0131n\u0131rland\u0131r\u0131lmas\u0131 ve enfekte h\u00fccrelerin temizlenmesi, pro-inflamatuar sitokinlerin ve CD4+\/CD8+ T h\u00fccre aktivasyonu i\u00e7in do\u011fal ve kazan\u0131lm\u0131\u015f ba\u011f\u0131\u015f\u0131kl\u0131k birlikte yan\u0131t vermelidir; fakat hastal\u0131k \u015fiddeti ve proinflamatuar sitokin seviyeleri ve ba\u011f\u0131\u015f\u0131kl\u0131k h\u00fccreleri aras\u0131nda anlaml\u0131 bir ili\u015fki bulunmu\u015f ve ba\u011f\u0131\u015f\u0131kl\u0131k d\u00fczensizli\u011fi ile y\u00fcksek seviyedeki proinflamatuar sitokinlerin doku hasar\u0131na neden olabilece\u011fi d\u00fc\u015f\u00fcn\u00fclm\u00fc\u015ft\u00fcr. \u00c7ok yeni bir vir\u00fcs oldu\u011fu i\u00e7in de patofizyolojik mekanizma b\u00fcy\u00fck \u00f6l\u00e7\u00fcde bilinmiyor. <\/p>\n\n\n\n

Sonu\u00e7 olarak, hem vir\u00fcs partik\u00fcl\u00fc hem de a\u015f\u0131r\u0131 ba\u011f\u0131\u015f\u0131kl\u0131\u011f\u0131n patogenezde \u00f6nemli rol oynad\u0131\u011f\u0131 g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. <\/p>\n\n\n\n

Antikor Yan\u0131t\u0131;<\/strong><\/p>\n\n\n\n

COVID-19 seyrinde IgM ve IgG tipi antikorlar olu\u015fmaktad\u0131r.\nEn erken 4. G\u00fcnde tespit edilen ve hastalar\u0131n %94.2\u2019sinde  15. g\u00fcn sonras\u0131nda IgG tipi antikor\nsaptanm\u0131\u015ft\u0131r.<\/p>\n\n\n\n

Sitokin F\u0131rt\u0131nas\u0131 <\/h2>\n\n\n\n

COVID-19 hastal\u0131\u011f\u0131nda mortaliteyi artt\u0131ran en b\u00fcy\u00fck\netmenlerden biri, sitokin f\u0131rt\u0131nas\u0131 dedi\u011fimiz a\u015f\u0131r\u0131 ba\u011f\u0131\u015f\u0131kl\u0131k yan\u0131t\u0131d\u0131r. Bu\nvir\u00fcs\u00fcn neden oldu\u011fu doku hasar\u0131 sonucu makrofaj ve gran\u00fclositlerin a\u015f\u0131r\u0131\naktivasyonu ve a\u015f\u0131r\u0131 miktarda proinflamatuar \u00fcretimi ile \u201cSitokin F\u0131rt\u0131nas\u0131\u201d\nmeydana gelir. A\u011f\u0131r hastalarda sitokin f\u0131rt\u0131nas\u0131n\u0131n ARDS\u2019ye ilerledi\u011fi de\nbulunmu\u015ftur.<\/p>\n\n\n\n

Bu hastalarda  serum\nCRP, LDH, Ferritin, Kreatinin, CK, IL-6 ve D-Dimerin artt\u0131\u011f\u0131 g\u00f6r\u00fclm\u00fc\u015ft\u00fcr.\nBa\u015flang\u0131\u00e7ta; IL-1\u03b2 , IL-1RA , IL-7, IL-8, IL-10, IFN\u0263, MCP-1 , MIP-1A VE 1B,\nG-CSF, TNF\u03b1 gibi sitokinlerin artt\u0131\u011f\u0131 g\u00f6r\u00fclm\u00fc\u015ft\u00fcr.<\/p>\n\n\n\n

Yo\u011fun bak\u0131m hastalar\u0131nda IL-2, IL-6, IL-8, IL-10, IL-17, MCP-1, MIP-1A, TNF\u03b1 seviyeleri y\u00fcksek bulunmu\u015ftur. Ayr\u0131ca a\u011f\u0131r vakalarda IL-2, IL-6 ,IL-8 ,IL -10 ve TNF\u03b1 daha y\u00fcksektir. Sitokin f\u0131rt\u0131nas\u0131na katk\u0131da bulunan en \u00f6nemli sitokinlerden biri IL-6 <\/em><\/strong>oldu\u011fu i\u00e7in ayr\u0131 bir ba\u015fl\u0131kta bahsedece\u011fim.<\/p>\n\n\n\n

IL-6 etkisi;<\/strong><\/p>\n\n\n\n

Cis sinyal yola\u011f\u0131 \u00fczerinden B, T h\u00fccreleri, do\u011fal ba\u011f\u0131\u015f\u0131kl\u0131k\nh\u00fccreleri \u00fczerinde pleitropik* etki yapar ve klinik olarak ate\u015f ,\u00f6ks\u00fcr\u00fck ,\nyorgunluk , kas ve eklem a\u011fr\u0131lar\u0131na sebep olur.<\/p>\n\n\n\n

Trans yola\u011f\u0131nda da y\u00fcksek yo\u011funlukta IL-6 bulunur ve\nendotelyal h\u00fccreleri aktive eder. Bunun sonucunda VEGF, IL-1b, IL-2 vb. bir\u00e7ok\nsitokin sal\u0131n\u0131r ve endotel h\u00fccrelerinde E-kadherin ekspresyonu azalmas\u0131 ile\nsitokin f\u0131rt\u0131nas\u0131 ger\u00e7ekle\u015fir. Ayr\u0131ca VEGF ve azalm\u0131\u015f E-kadherin ekspresyonu\nHipotansiyon ve ARDS\u2019ye neden olur.<\/p>\n\n\n\n

*=tek bir genin bir\u00e7ok fenotipik \u00f6zellik \u00fczerindeki genetik etkisi. (Kaynak: Wikipedia.) <\/p>\n\n\n\n

N\u00f6trofil-Lenfosit Oran\u0131(NLR) ;<\/strong><\/p>\n\n\n\n

\u015eiddetli hastalarda g\u00f6r\u00fclen ba\u015fka bir patoloji ise n\u00f6trofil-lenfosit oran\u0131n\u0131n artmas\u0131d\u0131r. Artm\u0131\u015f NLR\u2019nin k\u00f6t\u00fc prognozla ili\u015fkisi bulunmu\u015ftur. Bu hastalarda lenfopeni yayg\u0131n g\u00f6r\u00fclm\u00fc\u015f. T h\u00fccreleri, B h\u00fccreleri, NK h\u00fccreleri yan\u0131 s\u0131ra monosit, eozinofil ve bazofillerde de azalma g\u00f6zleniyor <\/p>\n\n\n\n

Sitokin F\u0131rt\u0131nas\u0131 Tedavi Yakla\u015f\u0131mlar\u0131 <\/h2>\n\n\n\n

Sitokin F\u0131rt\u0131nas\u0131 geli\u015fen hastada, erken tan\u0131 ve tedavi mortalite ve morbiditede azalamas\u0131nda \u00f6nemlidir. Lanipavir\/Ritanavir gibi antivirallerin bu hastalarda standart tedavilere k\u0131yasla pek fark\u0131 olmad\u0131\u011f\u0131 g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. COV\u0130D-19\u2019da antiviraller ve immunmod\u00fclat\u00f6r ila\u00e7lar birlikte verilmelidir ki etkili olunabilinsin. <\/p>\n\n\n\n

Gerideki ba\u015fl\u0131klarda bahsetti\u011fim IL-6 fazlal\u0131\u011f\u0131 \u00f6l\u00fcmc\u00fcl oldu\u011fu i\u00e7in IL-6\u2019y\u0131 inhibe eden spesifik monoklonal olan Tocilizumab kullan\u0131m\u0131 ile Sitokin F\u0131rt\u0131nas\u0131n\u0131n kontrol alt\u0131na al\u0131nabilece\u011fi g\u00f6zlendi. \u00c7in’de yap\u0131lan bir \u00e7al\u0131\u015fmada, 21 hastada tek doz Tocilizumab kullan\u0131m\u0131 sonras\u0131 5 g\u00fcn i\u00e7inde ate\u015f kontrol alt\u0131na al\u0131nd\u0131. Ayr\u0131ca CRP d\u00fc\u015ft\u00fc, Oksijen ihtiyac\u0131, lenfosit say\u0131lar\u0131 ve radyolojik bulgular iyile\u015fti. Bu arada Tocilizumab\u2019\u0131n f\u0131rsat\u00e7\u0131 enfeksiyonlar\u0131n riskini artt\u0131rd\u0131\u011f\u0131 da unutulmamal\u0131d\u0131r.<\/p>\n\n\n\n

Sitokin f\u0131rt\u0131nas\u0131nda IL-1\u2019de \u00f6nemlidir ve IL-1\u2019in antagonisti Anakinra\u2019n\u0131n da yararl\u0131 olabilece\u011fi d\u00fc\u015f\u00fcn\u00fcl\u00fcyor. Ayr\u0131ca JAK-STAT yola\u011f\u0131n\u0131 inhibe eden Tofacitinib ve Baristinib gibi ila\u00e7larda etkili olabilir. <\/p>\n\n\n\n

Son s\u00f6z ;<\/h3>\n\n\n\n

Sars-Cov-2 adl\u0131 vir\u00fcs \u00e7ok yeni bir vir\u00fcs oldu\u011fu i\u00e7in patogenezi,\netkileri ve tedavisi tam anlam\u0131yla bilinmiyor. Bu yaz\u0131mda da genellikle T\u00fcrk\nbilim insanlar\u0131n\u0131n yazd\u0131\u011f\u0131 makalelerden bir derleme yap\u0131p sizlere az \u00e7ok\nbilinen bilgileri aktarmaya \u00e7al\u0131\u015ft\u0131m. Tabi ki de bilgiler \u00e7ok h\u0131zl\u0131 de\u011fi\u015fti\u011fi\ni\u00e7in yaz\u0131y\u0131 yazd\u0131\u011f\u0131m zaman ve yay\u0131nlad\u0131\u011f\u0131m zaman aras\u0131ndaki s\u00fcreden dolay\u0131\nbilgilerimiz artm\u0131\u015f veya de\u011fi\u015fmi\u015f de olabilir.<\/p>\n\n\n\n

D\u00fcnyada salg\u0131n hala devam ediyor ve ne zaman sona erece\u011fi veya sona erip ermeyece\u011fi bile belirsiz. \u015euan yapmam\u0131z gereken \u015feyler maskenizi takmak, sosyal mesafemize dikkat etmek ve en \u00f6nemlisi el hijyenine \u00e7ok dikkat etmek. Yaz\u0131m\u0131 okudu\u011funuz i\u00e7in te\u015fekk\u00fcrler , geri bildirimlerinizi bekliyorum.<\/p>\n\n\n\n

Kaynak\u00e7a;<\/h5>\n\n\n\n

1-Mavi D,\n\u0130nkaya A\u00c7. COVID-19: \u0130mm\u00fcn patogenez. FLORA 2020;25(28 May\u0131s 2020).<\/p>\n\n\n\n

 2-Celikel Acar B. Cytokine Release Syndrome and Treatment\nin COVID-19. Turkish J Pediatr Dis 2020;14(suppl): 55-59.<\/p>\n\n\n\n

3-Ayhanc\u0131 T., Alt\u0131ndis M. COVID-19 Imm\u00fcnopatogenezi ve Sitokin F\u0131rt\u0131nas\u0131, J Biotechnol and Strategic Health Res. 2020;1(\u00d6zel Say\u0131):65-69<\/p>\n","protected":false},"excerpt":{"rendered":"

Merhaba de\u011ferli okurlar, bu ayki yaz\u0131mda COVID-19’un patogenezinden, a\u011f\u0131r hastalardaki \u00f6l\u00fcmc\u00fcl Sitokin F\u0131rt\u0131nas\u0131ndan ve tedavi se\u00e7eneklerinden bahsedece\u011fim. Bilindi\u011fi \u00fczere COV\u0130D-19<\/p>\n","protected":false},"author":346,"featured_media":7503,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[1,5,25,19,165],"tags":[652,653,693,926,1064,159],"acf":[],"views":2241,"_links":{"self":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/7500"}],"collection":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/users\/346"}],"replies":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/comments?post=7500"}],"version-history":[{"count":2,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/7500\/revisions"}],"predecessor-version":[{"id":7505,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/7500\/revisions\/7505"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/media\/7503"}],"wp:attachment":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/media?parent=7500"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/categories?post=7500"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/tags?post=7500"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}