Mechanisms of Organ Dysfunction in Sepsis

Rachel Pool; Hernando Gomez; John A Kellum

doi:10.1016/j.ccc.2017.08.003

Mechanisms of Organ Dysfunction in Sepsis

Crit Care Clin. 2018 Jan;34(1):63-80. doi: 10.1016/j.ccc.2017.08.003. Epub 2017 Oct 18.

Authors

Rachel Pool¹, Hernando Gomez², John A Kellum³

Affiliations

¹ Department of Anesthesiology, University of Pittsburgh Medical Center, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
² Center for Critical Care Nephrology, The CRISMA (Clinical Research, Investigation, and Systems Modeling of Acute Illness) Center, Department of Critical Care Medicine, University of Pittsburgh, 3347 Forbes Avenue, Suite 220, Pittsburgh, PA 15213, USA. Electronic address: [email protected].
³ Center for Critical Care Nephrology, The CRISMA (Clinical Research, Investigation, and Systems Modeling of Acute Illness) Center, Department of Critical Care Medicine, University of Pittsburgh, 3347 Forbes Avenue, Suite 220, Pittsburgh, PA 15213, USA.

Abstract

Sepsis-associated organ dysfunction involves multiple responses to inflammation, including endothelial and microvascular dysfunction, immune and autonomic dysregulation, and cellular metabolic reprogramming. The effect of targeting these mechanistic pathways on short- and long-term outcomes depends highly on the timing of therapeutic intervention. Furthermore, there is a need to understand the adaptive or maladaptive character of these mechanisms, to discover phase-specific biomarkers to guide therapy, and to conceptualize these mechanisms in terms of resistance and tolerance.

Keywords: Inflammation; Metabolism; Microcirculation; Mitochondria; Organ dysfunction; Sepsis.

Publication types

Review

MeSH terms

Humans
Multiple Organ Failure / immunology*
Multiple Organ Failure / physiopathology*
Sepsis / immunology*
Sepsis / physiopathology*

Grants and funding

K08 GM117310/GM/NIGMS NIH HHS/United States