Human temperature regulation under heat stress in health, disease, and injury

Abstract

The human body constantly exchanges heat with the environment. Temperature regulation is a homeostatic feedback control system that ensures deep body temperature is maintained within narrow limits despite wide variations in environmental conditions and activity-related elevations in metabolic heat production. Extensive research has been performed to study the physiological regulation of deep body temperature. This review focuses on healthy and disordered human temperature regulation during heat stress. Central to this discussion is the notion that various morphological features, intrinsic factors, diseases, and injuries independently and interactively influence deep body temperature during exercise and/or exposure to hot ambient temperatures. The first sections review fundamental aspects of the human heat stress response, including the biophysical principles governing heat balance and the autonomic control of heat loss thermoeffectors. Next, we discuss the effects of different intrinsic factors (morphology, heat adaptation, biological sex, and age), diseases (neurological, cardiovascular, metabolic, and genetic), and injuries (spinal cord injury, deep burns, and heat stroke), with emphasis on the mechanisms by which these factors enhance or disturb the regulation of deep body temperature during heat stress. We conclude with key unanswered questions in this field of research.

Keywords: core temperature; environment; exercise; skin blood flow; sweating; vasodilation.

Graphical abstract

FIGURE 1.

Whole-body sweat rate and the corresponding absolute evaporative requirement for heat balance (E_req) at different combinations of metabolic heat production (M − Wk) and air temperature (T_a), indicated by A, B, and C.

FIGURE 2.

The relation between maximum evaporative heat loss (E_max), the evaporative requirement for heat balance (E_req), and the actual rate of evaporative heat loss (E_sk). The skin wettedness required for heat balance (ω_req) defines the compensability of heat stress. Under compensable heat stress (left), E_req is less than E_max, yielding a ω_req ≤1. E_sk rises until equaling E_req, at which point the rate of heat storage is zero. The area between the E_req and E_sk curves indicates heat storage. During uncompensable heat stress (right), E_req exceeds E_max, resulting in a ω_req >1. E_sk rises throughout heat stress up to the level of E_max, after which the rate of heat storage equals the E_req-E_sk (i.e., E_req-E_max) difference. Reproduced from Ref. , with permission from Autonomic Neuroscience.

FIGURE 3.

Relation between skin wettedness and sweating efficiency under ambient heat stress at rest. Reproduced from Ref. , with permission from the American Physiological Society.

FIGURE 4.

Neural pathways involved in temperature regulation during heat stress. Temperature regulation is mediated by primary somatosensory neurons located in the skin and viscera that transmit afferent information to the brain via the spinal cord. In rodents, dorsal horn neurons project to the dorsal part of the lateral parabrachial nucleus (LPBd) in the brainstem. These neurons, in turn, activate (+) neurons within the median preoptic nucleus (MnPO) of the hypothalamus. Increased activity of warm-sensitive neurons within the MnPO results in greater inhibitory input (−) to the paraventricular hypothalamus (PVH) and medial preoptic area (MPA) that provide tonic excitatory input to the dorsomedial hypothalamus (DMH). Innocuous warming has also been shown to activate ventral lateral preoptic area (vLPO) neurons resulting in greater inhibitory input to the DMH. The greater inhibitory input directed to the DMH results in less excitatory drive to the raphe pallidus area (RPa) of the brainstem that normally sends an excitatory drive to preganglionic neurons controlling cutaneous vasoconstriction (VC) and thermogenesis. The inhibition of this pathway results in a passive increase in skin blood flow (SkBF) and a decrease in heat production. In contrast, the neural pathways mediating heat loss thermoeffector responses in humans remain largely unknown. Brain imaging studies have confirmed that the preoptic area (POA) of the hypothalamus and a juxtafacial area of the brainstem are activated during heat stress and that their activity correlates with sweating. Importantly, temperature regulation during heat stress relies on the activation of specific heat loss thermoeffectors in humans, namely active cutaneous vasodilation (VD) and eccrine sweat production, rather than the withdrawal of cold-defense responses in rodents. It is therefore unclear how the neural pathways for heat-defense responses identified in rodents can be translated to humans. Image created with BioRender.com with permission.

FIGURE 5.

Change in rectal temperature (ΔT_re) between groups of larger (LG; 91.5 kg) or smaller (SM; 67.6 kg) body mass during exercise eliciting absolute (top: 500 W and 600 W) or mass-specific (bottom: 6.5 W/kg and 9.0 W/kg) rates of heat production (H_prod). *Significantly greater elevation in rectal temperature in the SM group. Redrawn from Ref. , with permission from the American Physiological Society.

FIGURE 6.

Deep body temperature responses in individuals with different effective body surface areas for evaporative heat loss. The ability to produce sweat is severely limited with ectodermal dysplasia (absence of sweat glands) and quadriplegia (denervation of most sweat glands). As such, greater reductions in effective surface area are associated with lower sweat rates and higher elevations in deep body temperature. Redrawn from Ref. , with permission from the American Physiological Society.

FIGURE 7.

Time-dependent changes in rectal temperature (ΔT_re) during exercise in groups with high (HI-BF) or low (LO-BF) body fat percentages. *Significant difference between groups. Left: exercise elicited 500 W of heat production in a ∼28°C environment, with HI-BF (32.0 ± 5.6%) and LO-BF (10.8 ± 3.6% body fat) individuals pair-matched for mass. Reproduced from Ref. , with permission from the American Physiological Society. Right: exercise elicited 6.0 W/kg in a ∼40°C environment, with groups unmatched for mass but vastly different in body fat percentage (HI-BF: 30.2 ± 4.1% and LO-BF: 13.6 ± 3.8%). Reproduced from Ref. , with permission from the American Physiological Society.

FIGURE 8.

Changes in rectal temperature (ΔT_re; left) and whole body sweat loss (right) in groups of high (HI-V̇o_2max) and low (LO-V̇o_2max) aerobic capacity after 60 min of exercise at a relative intensity of ∼60% V̇o_2max and a fixed heat production of ∼540 W. Values within the bars represent the corresponding rate of heat production or relative exercise intensity. At 60% V̇o_2max, heat production was significantly higher in the HI-V̇o_2max group. At 540 W, relative intensity was significantly higher in the LO-V̇o_2max group. Redrawn from Ref. , with permission from the American Physiological Society.

FIGURE 9.

Sex differences in sweat rate relative to the required evaporation for heat balance (E_req) during exercise. Note how sex differences in sweat rate only occur at relatively high E_req (approximately ≥300 W/m²). Image created with BioRender.com with permission.

FIGURE 10.

Effects of insulin on endothelial cells. In healthy individuals, insulin binding to the IR-IGF1-R receptor activates the PI3K-Akt pathway. Phosphorylation of eNOS leads to the production of nitric oxide, which stimulates vasodilation. With insulin resistance or lack of insulin, there is increased serine phosphorylation of IR substrate and metabolic signaling with uninhibited activation of mitogenic and growth pathways. Such responses may contribute to attenuated skin blood flow responses in those with type 2 diabetes depicted at bottom. eNOS, endothelial nitric oxide synthase; IGF1-R, insulin-like growth factor-1 receptor; IR, insulin receptor; PI3K, phosphatidylinositol 3-kinase; Akt, protein kinase B.

FIGURE 11.

Graphical depiction of reduced sweating and cutaneous vasodilation in burned and subsequently grafted skin during a whole-body heat stress.

FIGURE 12.

Schematic summarizing the interactive effects of a burn injury and various modulators of the deep body temperature response to exercise. The effect of body size on the elevation in deep body temperature is shown for a 40% total body suface area (TBSA) injury during exercise at intensities eliciting a fixed absolute rate of metabolic heat production (H_prod), consistent with weight-independent activities such as cycling at a fixed work rate, and intensities eliciting a mass-specific rate of heat production, consistent with weight-bearing activities. The effect of air temperature (hot vs. temperate environments) and work intensity (moderate vs. low intensity) are shown across a range of %TBSA, from noninjured (0% TBSA injury) to 60% TBSA. Finally, the impact of 7 days of heat acclimation is shown. Adapted from Ref. , with permission from the American Physiological Society, and from Refs. –, with permission from Medicine and Science in Sports and Exercise.

FIGURE 13.

Overview of the three aspects (damage to the hypothalamus, myocardial dysfunction, epigenetic alterations) putatively associated with long-term consequences of heat stroke covered in sect. 6.3.