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Sepsis: Evidence-based pathogenesis and treatment
Sepsis can develop during the body’s response to a critical illness leading to multiple organ failure, irreversible shock, and death. Sepsis has been vexing health care providers for centuries due to its insidious onset, generalized metabolic dysfunction, and lack of specific therapy. A common facto...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Baishideng Publishing Group Inc
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291008/ https://www.ncbi.nlm.nih.gov/pubmed/34316443 http://dx.doi.org/10.5492/wjccm.v10.i4.66 |
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author | Pravda, Jay |
author_facet | Pravda, Jay |
author_sort | Pravda, Jay |
collection | PubMed |
description | Sepsis can develop during the body’s response to a critical illness leading to multiple organ failure, irreversible shock, and death. Sepsis has been vexing health care providers for centuries due to its insidious onset, generalized metabolic dysfunction, and lack of specific therapy. A common factor underlying sepsis is the characteristic hypermetabolic response as the body ramps up every physiological system in its fight against the underlying critical illness. A hypermetabolic response requires supraphysiological amounts of energy, which is mostly supplied via oxidative phosphorylation generated ATP. A by-product of oxidative phosphorylation is hydrogen peroxide (H(2)O(2)), a toxic, membrane-permeable oxidizing agent that is produced in far greater amounts during a hypermetabolic state. Continued production of mitochondrial H(2)O(2) can overwhelm cellular reductive (antioxidant) capacity leading to a build-up within cells and eventual diffusion into the bloodstream. H(2)O(2) is a metabolic poison that can inhibit enzyme systems leading to organ failure, microangiopathic dysfunction, and irreversible septic shock. The toxic effects of H(2)O(2) mirror the clinical and laboratory abnormalities observed in sepsis, and toxic levels of blood H(2)O(2) have been reported in patients with septic shock. This review provides evidence to support a causal role for H(2)O(2) in the pathogenesis of sepsis, and an evidence-based therapeutic intervention to reduce H(2)O(2) levels in the body and restore redox homeostasis, which is necessary for normal organ function and vascular responsiveness. |
format | Online Article Text |
id | pubmed-8291008 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Baishideng Publishing Group Inc |
record_format | MEDLINE/PubMed |
spelling | pubmed-82910082021-07-26 Sepsis: Evidence-based pathogenesis and treatment Pravda, Jay World J Crit Care Med Review Sepsis can develop during the body’s response to a critical illness leading to multiple organ failure, irreversible shock, and death. Sepsis has been vexing health care providers for centuries due to its insidious onset, generalized metabolic dysfunction, and lack of specific therapy. A common factor underlying sepsis is the characteristic hypermetabolic response as the body ramps up every physiological system in its fight against the underlying critical illness. A hypermetabolic response requires supraphysiological amounts of energy, which is mostly supplied via oxidative phosphorylation generated ATP. A by-product of oxidative phosphorylation is hydrogen peroxide (H(2)O(2)), a toxic, membrane-permeable oxidizing agent that is produced in far greater amounts during a hypermetabolic state. Continued production of mitochondrial H(2)O(2) can overwhelm cellular reductive (antioxidant) capacity leading to a build-up within cells and eventual diffusion into the bloodstream. H(2)O(2) is a metabolic poison that can inhibit enzyme systems leading to organ failure, microangiopathic dysfunction, and irreversible septic shock. The toxic effects of H(2)O(2) mirror the clinical and laboratory abnormalities observed in sepsis, and toxic levels of blood H(2)O(2) have been reported in patients with septic shock. This review provides evidence to support a causal role for H(2)O(2) in the pathogenesis of sepsis, and an evidence-based therapeutic intervention to reduce H(2)O(2) levels in the body and restore redox homeostasis, which is necessary for normal organ function and vascular responsiveness. Baishideng Publishing Group Inc 2021-07-09 /pmc/articles/PMC8291008/ /pubmed/34316443 http://dx.doi.org/10.5492/wjccm.v10.i4.66 Text en ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved. https://creativecommons.org/licenses/by-nc/4.0/This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. |
spellingShingle | Review Pravda, Jay Sepsis: Evidence-based pathogenesis and treatment |
title | Sepsis: Evidence-based pathogenesis and treatment |
title_full | Sepsis: Evidence-based pathogenesis and treatment |
title_fullStr | Sepsis: Evidence-based pathogenesis and treatment |
title_full_unstemmed | Sepsis: Evidence-based pathogenesis and treatment |
title_short | Sepsis: Evidence-based pathogenesis and treatment |
title_sort | sepsis: evidence-based pathogenesis and treatment |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291008/ https://www.ncbi.nlm.nih.gov/pubmed/34316443 http://dx.doi.org/10.5492/wjccm.v10.i4.66 |
work_keys_str_mv | AT pravdajay sepsisevidencebasedpathogenesisandtreatment |