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Review
. 2018 Oct 25;7(11):149.
doi: 10.3390/antiox7110149.

Heat Sepsis Precedes Heat Toxicity in the Pathophysiology of Heat Stroke-A New Paradigm on an Ancient Disease

Chin Leong Lim  1
Affiliations
Review

Heat Sepsis Precedes Heat Toxicity in the Pathophysiology of Heat Stroke-A New Paradigm on an Ancient Disease

Chin Leong Lim. Antioxidants (Basel). .

Abstract

Heat stroke (HS) is an ancient illness dating back more than 2000 years and continues to be a health threat and to cause fatality during physical exertion, especially in military personnel, fire-fighters, athletes, and outdoor laborers. The current paradigm in the pathophysiology and prevention of HS focuses predominantly on heat as the primary trigger and driver of HS, which has not changed significantly for centuries. However, pathological and clinical reports from HS victims and research evidence from animal and human studies support the notion that heat alone does not fully explain the pathophysiology of HS and that HS may also be triggered and driven by heat- and exercise-induced endotoxemia. Exposure to heat and exercise stresses independently promote the translocation of lipopolysaccharides (LPS) from gram-negative bacteria in the gut to blood in the circulatory system. Blood concentration of LPS can increase to a threshold that triggers the systemic inflammatory response, leading to the downstream ramifications of cellular and organ damage with sepsis as the end point i.e., heat sepsis. The dual pathway model (DPM) of HS proposed that HS is triggered by two independent pathways sequentially along the core temperature continuum of >40 °C. HS is triggered by heat sepsis at Tc < 42 °C and by the heat toxicity at Tc > 42 °C, where the direct effects of heat alone can cause cellular and organ damage. Therefore, heat sepsis precedes heat toxicity in the pathophysiology of HS.

Keywords: endotoxemia; guts barrier; heat stroke; lipopolysaccharides; sepsis; systemic inflammation.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The heat sepsis pathway in the dual pathway model (DPM) of heat stroke (HS). (A) Exercise and heat stresses cause the permeability of the gut epithelium to increase, which leads to the leakage of gram-negative bacteria and lipopolysaccharides (LPS) from the gut into the circulatory system (B). In a healthy state, when immune functions are not compromised, LPS in the circulation is removed from the body by monocytes, high density lipoproteins, and LPS-specific antibodies. Under these circumstance, the physical task is completed without heat-related health consequences i.e., heat tolerance (C). However, when undertaking the same physical task in a state of immune suppression (D) can compromise LPS clearance, which leads to the accumulation of LPS in the blood i.e., endotoxemia (E). The concentration of LPS in the blood reaches a threshold that triggers the systemic inflammatory response (SIR), which can lead eventually to sepsis. The resulting clinical presentation include massive blood coagulation, necrosis, cellular damage, multi-organ failure, and central nervous system disturbances (F), which are seen in HS victims i.e., a state of heat intolerance (G). In this pathway, the state of the immune system can function as a switch between heat tolerance and intolerance i.e., transient heat tolerance. Examples of circumstances that can cause immune suppression are also suggested in the diagram (H).
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