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Mitochondrial Dysregulation in Sepsis: A Literature Review
Julie-Kathryn Graham1, Kathleen Stacy
1Author Affiliations: Assistant Professor (Dr Graham), School of Nursing at San Diego State University; Clinical Associate Professor (Dr Stacy), The Hahn School of Nursing at the University of San Diego, California.
Background:
Until 2016, the condition Sepsis was widely understood to be the systemic immune response syndrome in the presence or suspicion of an infectious source. Systemic immune response syndrome, an adaptive response, has been repeatedly demonstrated to lack specificity for sepsis. The current definition of sepsis describes a dysregulated host response to infection, yet the dysregulated nature of the response has yet to be defined. Successful recognition and management of sepsis are critically dependent on understanding and operationalizing the definition of sepsis.
Objective:
The authors sought to review the current literature on sepsis and its relationship to oxygen downregulation within the mitochondria along the electron transport chain.
Methods:
Articles retrieved from databases PubMed and CINAHL, pertaining to human cells, post 2001, in English, original experimental, quasi-experimental, or cohort design. Articles were selected and retrieved by the first author and synthesized by both authors.
Results:
The 10 articles included in the review were all bench science cellular studies. They demonstrated consistent, statistically significant differences when investigating mitochondrial oxygen downregulation in sepsis versus control, offering strong, statistically significant support for the hypothesis of mitochondrial dysregulation in the septic host.
Conclusions:
The evidence makes a compelling case for mitochondrial dysregulation to inform the current definition of sepsis as a dysregulated host response. As the evidence points to a linear, progressive time/exposure-dependent disruption in oxygen downregulation in sepsis at the cellular level, it lends credence to the recommendations for early intervention and its relationship with survivability. Time is not on the side of the individual with sepsis.
Insights
Mitochondrial dysfunction, specifically oxygen downregulation, is a key feature of sepsis. This cellular-level disruption supports early intervention strategies for improved sepsis survival rates.
Area of Science:
- Cellular biology
- Pathophysiology
- Biochemistry
Background:
- Sepsis definition evolved from systemic immune response syndrome to a dysregulated host response to infection.
- Previous sepsis definitions lacked specificity, hindering accurate recognition and management.
- Understanding the precise nature of dysregulation is crucial for effective sepsis care.
Purpose of the Study:
- To review literature on sepsis and mitochondrial oxygen downregulation in the electron transport chain.
- To investigate the cellular mechanisms underlying sepsis-related mitochondrial dysfunction.
- To explore the link between mitochondrial dysregulation and sepsis severity.
Main Methods:
- Systematic literature review of studies published post-2001.
- Inclusion of human cellular studies with experimental, quasi-experimental, or cohort designs.
- Data synthesis by both authors after initial retrieval by the first author.
Main Results:
- Included studies focused on bench science and cellular investigations.
- Consistent, statistically significant differences in mitochondrial oxygen downregulation were observed in sepsis versus control groups.
- Findings provide strong support for the hypothesis of mitochondrial dysregulation in sepsis.
Conclusions:
- Mitochondrial dysregulation is a critical component of sepsis, informing its definition.
- Evidence suggests a time- and exposure-dependent disruption of oxygen downregulation at the cellular level.
- Early intervention is crucial for improving sepsis survivability, highlighting the urgency of treatment.
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