Definition Heatstroke is hyperthermia accompanied by a systemic inflammatory response causing multiple organ dysfunction and often death. It’s a condition caused by your body overheating, usually as a result of prolonged exposure to or physical exertion in high temperatures. This most serious form of heat injury, heatstroke can occur if your body temperature rises to 104 F (40 C) or higher. It's one of three heat-related syndromes, with heat cramps being the mildest and heatstroke being the most severe. Heatstroke occurs when compensatory mechanisms for dissipating heat fail and core temperature increase substantially. Inflammatory cytokines are activated, and multiple organ dysfunctions may develop. Endotoxin from GI flora may also play a role. Organ dysfunction may occur in the CNS, skeletal muscle (rhabdomyolysis), liver, kidneys, lungs (acute respiratory distress syndrome), and heart. The coagulation cascade is activated, sometimes causing disseminated intravascular coagulation. Hyperkalemia and hypoglycemia may occur.