МОЛОДЁЖНЫЙ ПРОЕКТ ДЛЯ ТЕХ, КТО ДЕЛАЕТ ПЕРВЫЕ ШАГИ В НАУКЕ
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ARBOR VITAE: ДРЕВО ЖИЗНИ/ ARBOR VITAE: TREE OF LIFE / ARBOR VITAE: BAUM DES LEBEN Школа научного мастерства: Первый МГМУ имени И.М. Сеченова / School of Scientific Excellence: Sechenov First Moscow State Medical University / Die Schule der wissenschaftlichen Meisterschaft: die Erste Moskauer staatliche medizinische I.M. Setschenow-Universität
DOI 10.24411/2227-9490-2018-12072
Гоманова Л.И., Фокина М.А.
Современные патогенетические механизмы септического шока (обзор)
Гоманова Лилия Ильинична, студентка 3 курса Медико-профилактического факультета ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» Минздрава России (Сеченовский университет)
ORCID ID https://orcid.org/0000-0002-6713-7090
E-mail: liliya-i-gomanova@j-spacetime.com; gomanov@list.ru
Фокина Марина Анатольевна, кандидат медицинских наук, доцент, кафедра патологии фармацевтического факультета ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» Минздрава России (Сеченовский университет)
ORCID ID https://orcid.org/0000-0001-7612-6206
E-mail: marina-a-fokina@j-spacetime.com; fokina.marina.mgmu@yandex.ru
Ключевыми этапами патогенеза септического шока являются гипердинамическая, гиподинамическая фазы и стадия необратимых нарушений. Каждый из этих этапов в конечном итоге приводит к полиорганной недостаточности и развитию «шоковых органов». В современной концепции септического шока важное место отводится генетике, которая предоставляет возможности для разработки диагностических и прогностических тест-систем, определения индивидуальных рисков и, возможно, профилактических мер среди населения.
Ключевые слова: септический шок; патогенез; «теплый шок»; «холодный шок»; полиорганная недостаточность; система свёртывания крови; брадикининовая система; фибринолитическая система; система комплемента; LPS A; TNF-α; генетическая предрасположенность.
Цитирование по ГОСТ Р 7.0.11—2011:
Гоманова, Л. И., Фокина, М. А. Современные представления о патогенетических механизмах септического шока [Электронный ресурс] / Л.И. Гоманова, М.А. Фокина // Электронное научное издание Альманах Пространство и Время. — 2018. — Т. 16. — Вып. 3—4. DOI: 10.24411/2227-9490-2018-12072. Стационарный сетевой адрес: 2227-9490e-aprovr_e-ast16-3_4.2018.072.
DOI: 10.24411/2227-9490-2018-12072
Gomanova L.I., Fokina M.A. Contemporary Views of Pathogenetic Septic Shock Mechanisms
Liliya I. Gomanova, 3rd year student at Sechenov First Moscow State Medical University
ORCID ID https://orcid.org/0000-0002-6713-7090
E-mail: liliya-i-gomanova@j-spacetime.com; gomanov@list.ru
Marina A. Fokina, Ph.D. (Medicine), Associate Professor at Chair of Pathology, Department of Pharmacy, Sechenov First Moscow State Medical University
ORCID ID https://orcid.org/0000-0001-7612-6206
E-mail: marina-a-fokina@j-spacetime.com; fokina.marina.mgmu@yandex.ru
Hyper- and hypodynamic phases, as well as irreversible disturbances stage are key ones in the pathogenesis of septic shock. In the last analysis, each of these stages leads to multiple organ failure and ‘shock organs’ development. Contemporary concept of septic shock gives an important place to genetics, which provides opportunities for the development of diagnostic and prognostic test systems, the determination of individual risks and, possibly, preventive measures among the population.
This caused us to choose this review topic and ideas about the pathogenetic septic shock mechanisms presented in reviewed sources as the subject of the study. Accordingly, this also caused us to choose problem, source, narrative, and critical analysis as the main research methods.
Our focus was on the following issues:
(i) The role of predisposing factors in the development of septic shock as the future of preventive measures. Thus, researchers, wjose papers we reviewd, have shown that older people have more prolonged inflammatory systemic response under acute stress compared with the young people’s systemic response. Hoary age, diabetes mellitus, malignant neoplasms, lack of identification of pathogens and higher SOFA values remain independent risk factors for early death in septic shock. The sanitizing ability of non-specific defense factors upon microorganism generalization plays an important role in preventing the development of shock.
(ii) Etiological factors in the development of septic shock. Septic shock often complicates the course of purulent-inflammatory processes caused by gram-negative flora. When these bacteria are destroyed, endotoxin is released, including the septic shock trigger mechanism. Most studies of the etiology of septic shock in Russia have revealed that a particular problem in Russia today is the resistance of major pathogens to antibiotics. Their widespread use, popularity of combination antibiotic regimens and the use of new ultra-broad spectrum antibiotics have led to the emergence of microbes that have not been previously encountered in shock pathology, such as Enterococcus faecium, Stenothrophomonas maltophilia, Flavobacterium spp., Cryseobacterium spp. Today, researchers have identified the so-called 'ESCAPE' group, which includes 6 highly dangerous bacteria (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumonia, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) that are resistant to almost all existing antibiotics and that are responsible for 2/3 of all hospital infections, including septic shock.
(iii) Pathogenesis of septic shock. In accordance with modern septic shock concepts, there are two forms of shock clinically distinguished: ‘warm’ and ‘cold’. ‘Warm shock’ is observed in the early stage of septic shock, it is caused mainly by gram-positive flora, proceeds more favorably. ‘Cold shock’ is mainly caused by gram-negative flora, it is more strong form, and it is worse to treat. Some sources show that septic shock can lead from the ‘warm’ stage to ‘cold’ one with a mismatch of therapy, followed by the development of multiple organ failure, the so-called ‘irreversible’ stage.
(iv) In our review, we pay special attention to the role of gram-positive and gram-negative infections in septic shock development, considering the entire cascades sequence described by modern researchers for both cases. Since vital organs and systems undergo significant morphological and functional changes, we also consider pathological changes in ‘shock organs’ (primarily, ‘shock lung’, ‘shock kidney’, changes in liver and gastrointestinal tract).
(v) Genetic predisposition in septic shock development as a new way of studying pathogenetic pathways. As recent studies show, many inducers and mediators of cell activation during the inflammatory response are simultaneously central regulators of programmed cell death, and therefore their functioning is also important for normal morphogenesis and immunogenesis at the stage of embryonic development. Research assigns tumor necrosis factor TNF-α and its receptor leading role in triggering the inflammatory response: depending on the conditions, these factors activate opposite genetic programs such as cell activation (‘inflammatory pathway’, ‘survival’) or its death.
The relevance of studying the inflammatory reactions mechanisms involving TNF-α is not limited only to solving the problem of overcoming septic shock, since TNF-α is pleiotropic action cytokine, and dysregulation of TNF-α-dependent reactions underlies the development of many other pathological conditions of a person (in particular, chronic inflammatory, autoimmune and oncological diseases).
Our review allows us to identify the most promising trends in the study of septic shock, as well as re-conceptualize the general ideas about it. Thus, it allows to see that septic shock is a common hemodynamic disorder caused by the interaction of pathogenic microorganisms with body cells, leading to the development of circulatory hypoxia, severe metabolic disorders and multiple organ failure. At the same time, septic shock is a systemic inflammation, including mechanisms for bacterial toxin binding to mononuclear phagocytes, neutrophils and endothelial cells, which induce the cytokines release. The current identification of the correlation between the number of TNF-α-induced responses and the rate of septic shock allows for a new look at shock pathogenesis and new diagnostic patterns development. Understanding the genetic septic shock mechanisms will help identify susceptibility to it and develop new approaches to treatment.
Keywords: septic shock; pathogenesis; ‘warm shock’; ‘cold shock’; multiple organ failure; blood coagulation system; bradykinin system; fibrinolytic system; complement system; LPS a; TNF-α; genetic predisposition.
Cite MLA 7:
Gomanova, L. I., and M. A. Fokina. "Contemporary Views of Pathogenetic Septic Shock Mechanisms." Electronic Scientific Edition Almanac Space and Time 16.3—4 (2018). DOI: 10.24411/2227-9490-2018-12072. Web. <2227-9490e-aprovr_e-ast16-3_4.2018.072>. (In Russian).
Список литературы / References
Литература
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Daviaud F., Grimaldi D., Dechartres A., Charpentier J., Geri G., Marin N., Chiche J.D., Cariou A/, Mira J.P., Pène F. "Timing and Causes of Death in Septic Shock." Ann. Intensive Care 5.1 (2015): 16. DOI: 10.1186/s13613-015-0058-8.
Decker S.O., Sigl A., Grumaz C., Stevens P., Vainshtein Y., Zimmermann S., Weigand M.A,, Hofer S., Sohn K., Brenner T. "Immune-Response Patterns and Next Generation Sequencing Diagnostics for the Detection of Mycoses in Patients with Septic Shock-Results of a Combined Clinical and Experimental Investigation." Int. J. Mol. Sci. 18.8 (2017): E1796. DOI: 10.3390/ijms18081796. Dellinger R.P., Levy M.M., Carlet J.M., Bion J., Parker M.M., Jaeschke R., Reinhart K., Angus D.C., Brun-Buisson C., Beale R., Calandra T., Dhainaut J.F., Gerlach H., Harvey M., Marini J.J., Marshall J., Ranieri M., Ramsay G., Sevransky J., Thompson B.T., Townsend S., Vender J.S., Zimmerman J.L., Vincent J.L. "Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2008." Crit. Care Med. 36 (2008): 296—327.
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Hawkins L. Christ W.J., Rossignol D. "Inhibition of Endotoxin Response by Synthetic TLR4 Antagonists." Current Topics in Medicinal Chemistry 4 (2004): 1147—71. DOI: 10.2174/1568026043388123.
Hotchkiss R.S., Schmieg R.E. Jr, Swanson P.E., Freeman B.D., Tinsley K.W., Cobb J.P., Karl I.E., Buchman T.G. "Rapid Onset of Intestinal Epithelial and Lymphocyte Apoptotic Cell Death in Patients with Trauma and Shock." Crit. Care Med. 28.9 (2000): 3207—3217.
Hotchkiss R.S., Moldawer L.L., Opal S.M., Reinhart K., Turnbull I.R., Vincent J.L. "Sepsis and Septic Shock." Nat. Rev. Dis. Primers 30.2 (2016): 16045. DOI: 10.1038/nrdp.2016.45.
McConnell K.W., Coopersmith C.M. "Pathophysiology of Septic Shock: From Bench to Bedside." Presse Med. 45.4.Pt 2 (2016): e93—e98.
Kilbourn R.G., Griffith O.W., Gross S.S., "Pathogenetic Mechanisms of Septic Shock." N. Engl. J. Med. 4.329 (1993): 1427—1428.
Kurmyshkina O.V., Bogdanova A.A., Volkova T.O., Poltorak A.N. "Septic Shock: Innate Molecular Genetic Mechanisms of the Development of Generalized Inflammation." Russian Journal of Developmental Biology 46.4 (2015): 183—195.
Lambden S., Creagh-Brown B.C., Hunt J., Summers C., Forni L.G. "Definitions and Pathophysiology of Vasoplegic Shock." Crit. Care. 22.1 (2018): 174. DOI: 10.1186/S13054-018-2102-1.
Landesberg G., Gilon D., Meroz Y., Georgieva M., Levin P.D., Goodman S., Avidan A., Beeri R., Weissman C., Jaffe A.S., Sprung C.L. "Diastolic Dysfunction and Mortality in Severe Sepsis and Septic Shock." Eur. Heart J. 33.7 (2012): 895—903.
Lessnau K.-D., Lazo K.G.G., Ishikawa O., Peralta R., Jiang C., Pinsky M.R., Kanaparthi L.K. "Distributive Shock Workup." Medscape. N.p., 5 Jan. 2018. Web. <https://emedicine.medscape.com/article/168689-workup>.
Pinheiro da Silva F., Machado M.C.C. "Septic Shock and the Aging Process: A Molecular Comparison." Front Immunol. 25.8 (2017): 1389. DOI: 10.3389/fimmu.2017.01389.
Ryoo S.M., Kang G.H., Shin T.G., Hwang S.Y., Kim K., Jo Y.H., Park Y.S., Choi S.H., Yoon Y.H., Kwon W.Y., Suh G.J., Lim T.H., Han K.S., Choi H.S., Chung S.P., Kim W.Y. "Korean Shock Society (KoSS) Investigators, Clinical Outcome Comparison of Patients with Septic Shock Defined by the New Sepsis-3 Criteria and by Previous Criteria." J. Thorac. Dis. 10.2 (2018): 845—853.
Singer M., Deutschman C.S., Seymour C.W., Shankar-Hari M., Annane D., Bauer M., Bellomo R., Bernard G.R., Chiche J.D., Coopersmith C.M., Hotchkiss R.S., Levy M.M., Marshall J.C., Martin G.S., Opal S.M., Rubenfeld G.D., van der Poll T., Vincent J.L., Angus D.C. "The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)." JAMA 315.8 (2016):801—810. DOI: 10.1001/jama.2016.0287.
References:
Bleiblo F., Michael P., Brabant D., Ramana C.V., Tai T., Saleh M., Parrillo J.E., Kumar A., Kumar A. "The Role of Immunostimulatory Nucleic Acids in Septic Shock." Int. J. Clin. Exp. Med. 5.1 (2012):1—23.
Bondarenko V.M., Ryabichenko E.V., Vetkova L.G. "Molecular Aspects of the Damaging Effect of Bacterial Lipopolysaccharides." Microbiological Journal 3 (2004): 98—105. (In Russian).
Daviaud F., Grimaldi D., Dechartres A., Charpentier J., Geri G., Marin N., Chiche J.D., Cariou A/, Mira J.P., Pène F. "Timing and Causes of Death in Septic Shock." Ann. Intensive Care 5.1 (2015): 16. DOI: 10.1186/s13613-015-0058-8.
Decker S.O., Sigl A., Grumaz C., Stevens P., Vainshtein Y., Zimmermann S., Weigand M.A,, Hofer S., Sohn K., Brenner T. "Immune-Response Patterns and Next Generation Sequencing Diagnostics for the Detection of Mycoses in Patients with Septic Shock-Results of a Combined Clinical and Experimental Investigation." Int. J. Mol. Sci. 18.8 (2017): E1796. DOI: 10.3390/ijms18081796.
Dellinger R.P., Levy M.M., Carlet J.M., Bion J., Parker M.M., Jaeschke R., Reinhart K., Angus D.C., Brun-Buisson C., Beale R., Calandra T., Dhainaut J.F., Gerlach H., Harvey M., Marini J.J., Marshall J., Ranieri M., Ramsay G., Sevransky J., Thompson B.T., Townsend S., Vender J.S., Zimmerman J.L., Vincent J.L. "Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2008." Crit. Care Med. 36 (2008): 296—327.
Gurevitch J., Frolkis I., Yuhas Y., Paz Y., Matsa M., Mohr R., Yakirevich V. "Tumor Necrosis Factor-alpha Is Released from the Isolated Heart Undergoing Ischemia and Reperfusion." J Am Coll Cardiol. 28.1 (1996): 247—252.
Hawkins L. Christ W.J., Rossignol D. "Inhibition of Endotoxin Response by Synthetic TLR4 Antagonists." Current Topics in Medicinal Chemistry 4 (2004): 1147—71. DOI: 10.2174/1568026043388123.
Hotchkiss R.S., Schmieg R.E. Jr, Swanson P.E., Freeman B.D., Tinsley K.W., Cobb J.P., Karl I.E., Buchman T.G. "Rapid Onset of Intestinal Epithelial and Lymphocyte Apoptotic Cell Death in Patients with Trauma and Shock." Crit. Care Med. 28.9 (2000): 3207—3217.
Hotchkiss R.S., Moldawer L.L., Opal S.M., Reinhart K., Turnbull I.R., Vincent J.L. "Sepsis and Septic Shock." Nat. Rev. Dis. Primers 30.2 (2016): 16045. DOI: 10.1038/nrdp.2016.45.
Kilbourn R.G., Griffith O.W., Gross S.S., "Pathogenetic Mechanisms of Septic Shock." N. Engl. J. Med. 4.329 (1993): 1427—1428.
Kurmyshkina O.V., Bogdanova A.A., Volkova T.O., Poltorak A.N. "Septic Shock: Innate Molecular Genetic Mechanisms of the Development of Generalized Inflammation." Russian Journal of Developmental Biology 46.4 (2015): 183—195.
Lambden S., Creagh-Brown B.C., Hunt J., Summers C., Forni L.G. "Definitions and Pathophysiology of Vasoplegic Shock." Crit. Care. 22.1 (2018): 174. DOI: 10.1186/S13054-018-2102-1.
Landesberg G., Gilon D., Meroz Y., Georgieva M., Levin P.D., Goodman S., Avidan A., Beeri R., Weissman C., Jaffe A.S., Sprung C.L. "Diastolic Dysfunction and Mortality in Severe Sepsis and Septic Shock." Eur. Heart J. 33.7 (2012): 895—903.
Lessnau K.-D., Lazo K.G.G., Ishikawa O., Peralta R., Jiang C., Pinsky M.R., Kanaparthi L.K. "Distributive Shock Workup." Medscape. N.p., 5 Jan. 2018. Web. <https://emedicine.medscape.com/article/168689-workup>.
Maltseva L.A., Bazilenko D.V., "Pathogenesis of Severe Sepsis and Septic Shock: Analysis of Modern Concepts." Emergency Medicine 7 (2015): 35—40. (In Russian).
McConnell K.W., Coopersmith C.M. "Pathophysiology of Septic Shock: From Bench to Bedside." Presse Med. 45.4.Pt 2 (2016): e93—e98.
Nesterenko A.N. "Immune Distress as a Pathogenetic and Thanatogenetically Significant Syndrome in Severe Sepsis and Septic Shock: Clinical and Pathologic Rationale for Early Replacement Immunocorrection." Emergency Medicine 6 (2013). Web. <http://www.mif-ua.com/archive/article/37238>. (In Russian).
Pinheiro da Silva F., Machado M.C.C. "Septic Shock and the Aging Process: A Molecular Comparison." Front Immunol. 25.8 (2017): 1389. DOI: 10.3389/fimmu.2017.01389.
Ryoo S.M., Kang G.H., Shin T.G., Hwang S.Y., Kim K., Jo Y.H., Park Y.S., Choi S.H., Yoon Y.H., Kwon W.Y., Suh G.J., Lim T.H., Han K.S., Choi H.S., Chung S.P., Kim W.Y. "Korean Shock Society (KoSS) Investigators, Clinical Outcome Comparison of Patients with Septic Shock Defined by the New Sepsis-3 Criteria and by Previous Criteria." J. Thorac. Dis. 10.2 (2018): 845—853.
Singer M., Deutschman C.S., Seymour C.W., Shankar-Hari M., Annane D., Bauer M., Bellomo R., Bernard G.R., Chiche J.D., Coopersmith C.M., Hotchkiss R.S., Levy M.M., Marshall J.C., Martin G.S., Opal S.M., Rubenfeld G.D., van der Poll T., Vincent J.L., Angus D.C. "The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)." JAMA 315.8 (2016):801—810. DOI: 10.1001/jama.2016.0287.
