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Disturbances of the hypothalamic-pituitary-adrenal axis and plasma electrolytes during experimental sepsis

Michael A Flierl1, Daniel Rittirsch24, Sebastian Weckbach1, Markus Huber-Lang3, Kyros Ipaktchi1, Peter A Ward4 and Philip F Stahel15*

Author Affiliations

1 Department of Orthopaedics, School of Medicine, University of Colorado, Denver Health Medical Center, Denver, CO, 80204, USA

2 Department of Trauma Surgery, University Hospital Zurich, Zurich, Switzerland

3 Department of Trauma, Hand-, Plastic-, and Reconstructive Surgery, University Hospital Ulm, Ulm, 89075, Germany

4 Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA

5 Department of Neurosurgery, University of Colorado, School of Medicine, Denver Health Medical Center, Denver, CO, 80204, USA

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Annals of Intensive Care 2011, 1:53  doi:10.1186/2110-5820-1-53

Published: 30 December 2011



Sepsis continues to be a poorly understood syndrome with a high mortality rate. While we are beginning to decipher the intricate interplay of the inflammatory response during sepsis, the precise regulation of the hypothalamic-pituitary-adrenal (HPA) axis and its impact on electrolyte homeostasis during sepsis remains incompletely understood.


Sepsis was induced in adult male Sprague-Dawley rats by cecal ligation and puncture (CLP). Plasma samples were obtained as a function of time (6-48 hrs) after CLP and compared with healthy animals (neg ctrl). Samples were analyzed for adrenocorticotropin (ACTH), corticosterone, and aldosterone levels, as well as concentrations of sodium (Na+), potassium (K+), chloride (Cl-), and magnesium (Mg2+).


ACTH levels were found to be significantly reduced 6-24 hrs after CLP in comparison to baseline levels and displayed gradual recovery during the later course (24-48 hrs) of sepsis. Plasma corticosterone concentrations exhibited a bell-shaped response, peaking between 6 and 12 hrs followed by rapid decline and concentrations below negative control levels 48 hrs after injury. Aldosterone levels in septic animals were continuously elevated between 6 and 48 hrs. Whereas plasma Na+ levels were found to be persistently elevated following CLP, levels of K+, Cl- and Mg2+ were significantly reduced as a function of time and gradually recovered during the later course of sepsis.


CLP-induced sepsis resulted in dynamic changes of ACTH, corticosterone, and aldosterone levels. In addition, electrolyte levels showed significant disturbances after CLP. These electrolyte perturbations might be evoked by a downstream effect or a dysfunctional HPA-axis response during sepsis and contribute to severe complications during sepsis.