Pathophysiologic Mechanisms of Heatstroke

The pathophysiologic effects of heat stroke are simply due to the direct effects of extreme, abnormal hyperthermia on cells within the tissues. The critical temperature associated with consistent occurrence of enzyme alterations and cell membrane instability that lead to multiple tissue and organ deterioration appears to be 109oF (43oC). Some lists that these cellular events occur as a low as 106oF (41oC). Nevertheless, high temperatures cause generalized cellular necrosis through denaturization of proteins, inactivation of enzyme systems, destruction of cell membrane lipids, and alter mitochondrial function. Global ischemia coupled with temperature-induced massive destruction of cells can lead to multiple tissue necrosis or multiple organ dysfunction syndrome (MODS). Multiple organ dysfunction syndrome can occur involving the respiratory, cardiovascular, gastrointestinal, renal, central nervous system, and coagulation system.

Specifically, the nervous system is commonly affected. Neuronal injury and cell death, the development of cerebral edema, and the occurrence of localized areas of necrosis due to intracranial hemorrhage can lead to seizures, coma and even sometimes death. Excessive hyperthermia in the hypothalamus causes damage to the thermoregulatory center, leading to abnormally controlled temperature regulation. This abnormal thermoregulation center predisposes the animal to subsequent hyperthermic episodes.

The cardiovascular system is also affected which includes increased cardiac output and hypoxia due to the increased demand from the tissues. There is also a decreased systemic vascular resistance and hypovolemia secondary to dehydration which puts additional work on the heart for perfusion. These events ultimately lead to myocardial ischemia, which subsequently leads to tachyarrhythmias and cardiogenic shock.

The gastrointestinal tract is very susceptible to decreased perfusion and secondary ischemia. This ischemic environment leads to loss of the structural integrity of the gastrointestinal tract and bacterial translocation due to plethora of bacteria in the colon. Gram-negative bacteremia, endotoxemia, and sepsis are potential sequela that can ensue along a continuum of the sepsis syndrome. Gram-negative sepsis could progress to septic shock, which leads to further decrease in cardiac output and global ischemia.

One of the most serious and profound consequences of hyperthermia occurs in the renal tissues. Direct thermal injury to the kidneys coupled with decreased perfusion, dehydration, and global ischemia commonly causes acute renal failure. Acute renal disease is exacerbated by the handling of myoglobin due to massive rhabdomyolysis from muscle necrosis. This pigment is toxic to the renal tubules and is clinically seen as dark, "machine-oil"or "coke"-colored urine.

Hematologic and coagulation abnormalities are other potential sequela that can develop initially or even several days after the hyperthermic event. Severe dehydration causes hemoconcentration, which can result in the hematocrit reaching levels as high as 70%. This high of a level in circulating red blood cells creates sludging of the blood and increased viscosity. Sludging of blood decreases oxygen delivery (DO2) and oxygen uptake (VO2) by peripheral tissues, which further worsens tissue necrosis.

The capillary and venous endothelium is very susceptible to direct thermal effects. Damaged endothelium activates the clotting cascades, compliment, and produces a systemic inflammatory response, which includes the increased adherence of leukocytes and platelets to the endothelium. If there is severe enough global ischemia and disruption of the endothelium, then platelets and coagulation factors can be consumed, especially in the gastrointestinal tract secondary to bleeding. Coagulation factors are susceptible to hyperthermia, which leads to their destruction. Furthermore, severe hyperthermia damages the liver, which can cause decreased synthesis of coagulation factors. Thus, increased platelet and white blood cell adherence, abnormal platelet consumption, sludging of the blood, and coagulation factor disruption leads to a syndrome called disseminated intravascular coagulation (DIC). Megakaryocytes apparently are very susceptible to high temperatures, which results in decreased release of platelets from the bone marrow. This thrombocytopenic event may be delayed several days and should not be confused with the low platelets counts seen earlier in the disease process.

Heat stroke also has a major impact on the acid-base status in the animal. Usually there is a mixed acid-base disorder characterized by respiratory alkalosis and metabolic acidosis. The respiratory alkalosis caused by excessive panting of the animal results in hyperventilation or "blowing off" of the CO2. The metabolic acidosis is produced by increased tissue demands, hypoxemia, and anaerobic metabolism resulting in lactic acid build up. Acid-base abnormalities have significant influence on cardiac output and normal metabolic processes in the body.