Metabolic theory of septic shock

Abstract

Septic shock is a life threatening condition that can develop subsequent to infection. Mortality can reach as high as 80% with over 150000 deaths yearly in the United States alone. Septic shock causes progressive failure of vital homeostatic mechanisms culminating in immunosuppression, coagulopathy and microvascular dysfunction which can lead to refractory hypotension, organ failure and death. The hypermetabolic response that accompanies a systemic inflammatory reaction places high demands upon stored nutritional resources. A crucial element that can become depleted early during the progression to septic shock is glutathione. Glutathione is chiefly responsible for supplying reducing equivalents to neutralize hydrogen peroxide, a toxic oxidizing agent that is produced during normal metabolism. Without glutathione, hydrogen peroxide can rise to toxic levels in tissues and blood where it can cause severe oxidative injury to organs and to the microvasculature. Continued exposure can result in microvascular dysfunction, capillary leakage and septic shock. It is the aim of this paper to present evidence that elevated systemic levels of hydrogen peroxide are present in septic shock victims and that it significantly contributes to the development and progression of this frequently lethal condition.

Corrected QT interval anomalies are associated with worse prognosis among patients suffering from sepsis

“…QTc duration is influenced by several metabolic and metabolism‐dependent conduction derangements . Many such derangements, like hyperglycaemia, hypokalaemia and liver function anomalies, impact the length of the QTc interval, reflecting their complex effects on the period of electrical repolarisation of the cardiac conduction system.…”

Analysis of Spatiotemporal Urine Protein Dynamics to Identify New Biomarkers for Sepsis-Induced Acute Kidney Injury

“…GO analysis revealed that the protein metabolic process was the first altered in the early stage of sepsisinduced AKI. The increase in total cellular metabolism was to provide the energy needed to sustain immune system activation (Pravda, 2014). Mitochondria-centered structural and metabolic alterations occur prior to the onset of AKI, supporting a causative, pathogenic role of mitochondrial damage in kidney injury (Parikh et al, 2015).…”

Myricitrin attenuates memory impairment in a rat model of sepsis-associated encephalopathy via the NLRP3/Bax/Bcl pathway

“…Neuroinflammation occurs during sepsis, resulting in an increased demand for energy and metabolism by neuronal cells [15]. This leads to mitochondrial dysfunction and increased oxidative stress in neuronal cells [8].…”