Deneysel Sepsis Modelleri
Özet
Sepsis teriminin tanımlaması yapılalı yaklaşık 2000 yıldan fazla süre geçmiş olsa da klinik tanımlaması hali hazırda yakın zamanda yapılmıştır. Küresel anlamda önemli sağlık sorunlarının başını çeken, yaygın ve yıkıcı bir sendrom olarak ifade edilmektedir. Sepsisli hastalar için yıllık bakım maaliyetinin 16,7 milyar dolar olduğu tahmin edilmektedir. Sepsis patojen mikroorganizmaların ve toksik karakterdeki metabolitlerin dolaşım sistemi içerisinde tüm vücuda yayıldığı buna doku perfüzyon bozukluğunun da eşlik ettiği sistemik inflamatuvar yanıt ve sonrasında ortaya çıkan klinik tablo olarak tanımlanabilir. Meydana gelen klinik tabloda enfeksiyona karşı gelişen düzensiz bir konakçı yanıtı organ disfonksiyonuna ve çoklu organ yetmezliğine sebep olarak canlı yaşamı için tehdit oluşturmaktadır. Sepsisin etiyolojisini incelediğimizde gram (+) ve gram (-) birçok türden bakteri çeşidiyle birlikte bazı mantar türlerinin bulunduğunu görmekteyiz. Sepsis çeşitli mikroorganizmalar tarafından oluşabilir ancak en yaygın nedeni bakteriyel etkenlerdir ve bunların yaklaşık %60-70’ ini gram negatif türlerden kaynaklıdır. Sepsisin fizyopatolojisi oldukça kompleks ve karmaşıktır. Mikroorganizmalara ait toksinler ve hücresel metabolitler dolaşım sisteminde bulunan mononükleer fagositleri, vasküler endotel hücrelerini ve diğer hücreleri uyararak kimyasal mediatörlerin salınımına neden olmaktadır. Sepsis dünya genelinde hem insanlar üzerinde en fazla araştırmanın yapıldığı hem de hayvanlarda deneysel çalışmaların en çok yapıldığı modeller içerisinde yer alır. Deney hayvanlarında sıklıkla kullanılan modellemelere baktığımızda ise temel olarak; endotoksemi sepsis modeli, canlı patojen sepsis modeli, intraperitoneal sepsis modelleri, pnömoni sepsis modeli ve implantasyon sepsis modeli olarak sıralanmaktadır. Sonuçta sepsis basit bir bakteriyemiden başlayarak septik şoka ve ilerleyen aşamada çoklu organ yetmezliğine kadar ulaşan önemli bir klinik tabloya dönüşebilmektedir. Sepsisin karmaşık patofizyolojisini detaylı açıklayabilmek ve yeni tedavi stratejileri geliştirmek için mevcut modelleri iyileştirmeye ve yeni deneysel sepsis modelleri oluşturmaya odaklanmamız gerekmektedir.
Although the term sepsis was defined over 2000 years ago, its clinical definition has only recently been established. It is described as a widespread and devastating syndrome that ranks among the most significant global health problems. The annual cost of care for patients with sepsis is estimated at $16.7 billion. Sepsis can be defined as a systemic inflammatory response and subsequent clinical picture that occurs when pathogenic microorganisms and toxic metabolites spread throughout the body via the circulatory system, accompanied by tissue perfusion impairment. The resulting clinical picture involves an irregular host response to infection, leading to organ dysfunction and multiple organ failure, which poses a threat to life. When examining the etiology of sepsis, we see that it involves many types of gram-positive and gram-negative bacteria, as well as certain types of fungi. Sepsis can be caused by various microorganisms, but the most common cause is bacterial agents, approximately 60-70% of which are gram-negative species. The pathophysiology of sepsis is quite complex and intricate. Toxins and cellular metabolites belonging to microorganisms stimulate mononuclear phagocytes, vascular endothelial cells, and other cells in the circulatory system, causing the release of chemical mediators. Sepsis is one of the most researched models in humans worldwide and one of the most studied experimental models in animals. When we look at the models frequently used in experimental animals, they are basically listed as: endotoxemia sepsis model, live pathogen sepsis model, intraperitoneal sepsis models, pneumonia sepsis model, and implantation sepsis model. Ultimately, sepsis can evolve from a simple bacteremia into a significant clinical condition, progressing to septic shock and, in advanced stages, to multiple organ failure. To thoroughly elucidate the complex pathophysiology of sepsis and develop new treatment strategies, we must focus on improving existing models and creating new experimental sepsis models.
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