Materiały źródłowe

• #1 The pathogenesis and management of heatstroke and heatstroke-induced lung injury

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11729746/

  In the past two decades, record-breaking heat waves have caused an increasing number of heat-related deaths, including heatstroke, globally. Heatstroke is a life-threatening systemic condition characterized by a core body temperature 40C and the subsequent development of multiple organ dysfunction syndrome. […] In recent years, extensive research has been conducted to investigate the underlying causes of heatstroke and heatstroke-induced lung injury. This review aims to consolidate and present the current understanding of the key pathogenic mechanisms involved in heatstroke and heatstroke-induced lung injury. In addition, systemic factors such as heat cytotoxicity, systemic inflammation, oxidative stress, endothelial cell dysfunction, and other factors are involved in the pathogenesis of lung injury in heatstroke.

• #2 Pathophysiological factors underlying heatstroke – PubMed

  https://pubmed.ncbi.nlm.nih.gov/16631316/

  Heatstroke is a life-threatening illness characterized by an elevated core body temperature (40 degrees C) and dysfunction of central nervous system, which results in delirium, convulsions, or coma. […] On the basis of our knowledge of the pathophysiology on heatstroke, we hypothesized that heatstroke is a form of hyperthermia associated with the acute physiological alterations, the cytotoxicity of heat, systemic inflammatory response, oxidative damage and attenuated heat-shock response leading to a syndrome of multi-organ dysfunction. […] Acute physiological alterations, such as low arterial hypotension, intracranial hypertension, cerebral hypoperfusion, cerebral ischemia, and increased intracellular metabolism rate, occurred while exposed to a high ambient temperature. […] Hyperpyrexia caused cytotoxicity, resulting the degradation and aggregation of extensive intracellular proteins, influencing the change of membrane stability and fluidity, damaging the transmembrane transport of protein and the function of surface receptor, and inducing different cytoskeletal changes.

• #3 The mechanisms behind heatstroke-induced intestinal damage | Cell Death Discovery

  https://www.nature.com/articles/s41420-024-02210-0

  With the frequent occurrence of heatwaves, heatstroke (HS) is expected to become one of the main causes of global death. […] Intestinal damage plays an initiating and promoting role in HS. […] A large number of studies have shown that intestinal damage after HS involves the body’s stress response, disruption of oxidative balance, disorder of tight junction proteins, massive cell death, and microbial imbalance. […] The current view is that the mechanism of heat injury is due to direct damage from heat and systemic inflammatory response syndrome (SIRS) caused by heat stress and endotoxin leakage. […] It is believed that the disruption of the intestinal barrier contributes to and initiates HS. […] The bodys stress response, oxidative damage, destruction of intestinal tight junction (TJ) proteins, excessive cell death, and imbalance of intestinal flora are all challenges faced by the intestine under HS.

• #4 Exertional heat stroke: pathophysiology and risk factors | BMJ Medicine

  https://bmjmedicine.bmj.com/content/1/1/e000239

  Exertional heat stroke is characterised by central nervous system dysfunction in people with hyperthermia during physical activity and can be influenced by environmental factors such as heatwaves, which extend the incidence of exertional heat stroke beyond athletics only. […] The pathophysiology of exertional heat stroke involves thermoregulatory and cardiovascular overload, resulting in severe hyperthermia and subsequent multiorgan injury due to a systemic inflammatory response syndrome and coagulopathy. […] Understanding the pathophysiology and the risk factors that lead to EHS is important for the correct diagnosis and the choice of mitigation strategies. […] EHS is characterised by central nervous system (CNS) dysfunction (eg, delirium, convulsions, or coma) with the possibility of follow-on organ or tissue damage in people with hyperthermia.

• #5 Heatstroke-Induced Inflammatory Response and Therapeutic Biomarkers

  https://www.mdpi.com/2227-9059/13/2/261

  Heatstroke primarily occurs when cardiac output is inadequate to meet the high thermoregulatory demands of the body, causing a transition from a compensable thermoregulatory phase in which heat loss exceeds heat gain to a noncompensable phase in which heat gain exceeds heat loss. […] This imbalanced thermoregulatory process ultimately results in a persistent increase in core body temperature, which sets off a malicious cycle of events that eventually results in multiorgan dysfunction or failure via directly inducing cytotoxicity, inflammatory response, and coagulation. […] The series of inflammatory response events generated during heatstroke is not fully understood yet and needs to be further studied. […] Importantly, a coordinated stress response triggered via hyperthermia during heatstroke involving endothelial cells, leukocytes, and epithelial cells plays a role in cell repair and protection against tissue damage.

• #6 How the Body Regulates Heat | Rush

  https://www.rush.edu/news/how-body-regulates-heat

  On most days, the hypothalamus reacts to increases in outdoor temperature by sending messages to the blood vessels, telling them to dilate. This sends warm blood, fluids and salts to the skin, setting off the process of evaporation. […] Problems occur when a person is in the heat for a long time or in such extremes of heat or humidity that the evaporation process fails. […] In prolonged heat exposure, the body sweats so much that it depletes itself of fluids and salts, leaving nothing to sustain the evaporation process. When this process ceases, body temperature soars and heat illnesses may result including the most serious: heatstroke.

• #7 Heat stroke pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Heat_stroke_pathophysiology

  Heat stress means perceived discomfort and physiologic strains during heat exposure. A series of physiologic events occur to adapt heat. These events include thermoregulation (with acclimatization), an acute-phase response, and production of heat shock proteins. If these sequence of actions fails to prevents body from high temperature, heat stress progresses to heat stroke. […] Heat stroke High body temperature with CNS dysfunction Tissue thermal injury Necrotic/apoptotic cell death CoagulopathiesFibrin deposition Excessive bleeding Immune modulatorsEndotoxin, cytokines Systemic inflammatory response syndrome Multi-organ failure and death […] The core body temperature is set to 37 C. Thermoregulatory center is located in hypothalamus, every 1 C in body temperature activates the peripheral and central receptors to maintain core body temperature at 37 C.

• #8 Heatstroke – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/heat-stroke/symptoms-causes/syc-20353581

  Heatstroke is a condition caused by the body overheating. This usually happens because of exposure to high temperatures or physical activity in high temperatures for too long. […] Heatstroke needs emergency care. If it’s not treated, heatstroke can quickly damage the brain, heart, kidneys and muscles. This damage gets worse the longer treatment is delayed, which increases the risk of serious complications or death. […] Heatstroke can happen as a result of: Being in a hot environment. In a type of heatstroke, called nonexertional (classic) heatstroke, being in a hot environment leads to a rise in core body temperature. This type of heatstroke typically happens after exposure to hot, humid weather, especially for a long period of time. It happens most often in older adults and in people with ongoing health conditions.

• #9 Hyperthermia – Wikipedia

  https://en.wikipedia.org/wiki/Hyperthermia

  The most common causes include heat stroke and adverse reactions to drugs. Heat stroke is an acute temperature elevation caused by exposure to excessive heat, or combination of heat and humidity, that overwhelms the heat-regulating mechanisms of the body. […] Heat stroke occurs when thermoregulation is overwhelmed by a combination of excessive metabolic production of heat (exertion), excessive environmental heat, and insufficient or impaired heat loss, resulting in an abnormally high body temperature. […] The increase in body temperature that results from a breakdown in thermoregulation affects the body biochemically. Enzymes involved in metabolic pathways within the body such as cellular respiration fail to work effectively at higher temperatures, and further increases can lead them to denature, reducing their ability to catalyse essential chemical reactions. This loss of enzymatic control affects the functioning of major organs with high energy demands such as the heart and brain.

• #10 The pathogenesis and management of heatstroke and heatstroke-induced lung injury

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11729746/

  Although lung injury is a common complication among heatstroke patients in general, the exact mechanisms of heatstroke-induced lung injury have still not been properly clarified. […] The cytotoxic effect is the first sharp edge of heat stress-induced damage to human organs. When thermoregulation is overwhelmed by environmental or endogenous heat, the core body temperature increases, exceeding 40C in patients with heatstroke. […] Studies indicate that heatstroke can have cytotoxic effects, causing damage to not only the lungs but also other organs. […] However, as research has advanced, it has become evident that heat toxicity merely acts as a triggering factor for systemic inflammation and MODS rather than being the root cause of these conditions. […] Heatstroke is a condition that worsens over time and can cause direct damage to cells due to excessive heat. Prolonged exposure to heat stress leads to cytotoxic effects, resulting in significant tissue damage, necrosis, and programmed cell death.

• #11 Heat Stroke: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/166320-overview

  Despite wide variations in ambient temperatures, humans and other mammals can maintain a constant body temperature by balancing heat gain with heat loss. When heat gain overwhelms the body’s mechanisms of heat loss, the body temperature rises, potentially leading to heat stroke. Excessive heat denatures proteins, destabilizes phospholipids and lipoproteins, and liquefies membrane lipids, leading to cardiovascular collapse, multiorgan failure, and, ultimately, death. […] The exact temperature at which cardiovascular collapse occurs varies among individuals because coexisting disease, drugs, and other factors may contribute to or delay organ dysfunction. Full recovery has been observed in patients with temperatures as high as 46C, and death has occurred in patients with much lower temperatures.

• #12 Heat stroke | Deranged Physiology

  https://derangedphysiology.com/main/required-reading/environmental-injuries-and-toxicology/Chapter-405/heat-stroke

  Heat stroke is characterised by temperature over 40.6°C, failure of thermoregulation and a decreased level of consciousness. […] Pathophysiology of heat stroke involves dehydration and the resulting failure to produce sweat leading to thermal cellular damage, shock, and a SIRS due to tissue damage, cytokine release and endotoxaemia. […] Failure of thermoregulation leads to an impairment of the cardiovascular response to heat; the cardiac output does not increase sufficiently. […] Direct cellular damage from heat occurs at extreme temperatures (49°C to 50°C) cellular necrosis occurs in less than five minutes. […] Cytokine release due to heat stress leads to a systemic inflammatory response. […] The college, in their answer to Question 23 from the first paper of 2015 also mentioned uncoupling of oxidative phosphorylation, failure of enzyme systems, increased „Membrane permeability” and increased sodium leak into cells.

• #13 Heat Stroke: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/166320-overview

  On a cellular level, heat directly influences the body by interfering with cellular processes along with denaturing proteins and cellular membranes. In turn, an array of inflammatory cytokines, interleukins and heat shock proteins (HSPs) are produced. In particular, HSP-70 allows the cell to endure the stress of its environment. Intense heat stress that is uncompensated leads to apoptosis and cell death. […] On a microvascular level, heat stroke resembles sepsis and involves inflammation, translocation of lipopolysaccharides from the gut, and activates the coagulation cascade. Certain preexisting factors, such as age, genetic makeup, and the nonacclimatized individual, may allow progression from heat stress to heat stroke, systemic inflammatory response syndrome (SIRS), multiorgan dysfunction syndrome (MODS), and ultimately death. Progression to heat stroke may occur through thermoregulatory failure, an amplified acute-phase response, and alterations in the expression of HSPs.

• #14

  https://link.springer.com/article/10.1007/s10495-024-01979-w

  Severe heat stress is characterized by cell death of direct heat damage, excessive inflammatory responses, and coagulation disorders that can lead to multiple organ dysfunction (MODS) and even death. […] Various modes of cell death, including apoptosis, pyroptosis, ferroptosis, necroptosis and PANoptosis are involved in MODS induced by heatstroke. […] Understanding the mechanism of cell death provides new targets to protect multi-organ function in HS.

• #15 Exertional heat stroke: pathophysiology and risk factors | BMJ Medicine

  https://bmjmedicine.bmj.com/content/1/1/e000239

  Systemic inflammatory response syndrome is a dysregulated defence response of the body to a noxious stressor to localise and eliminate the source of the insult. […] EHS is accompanied by a strong inflammatory response that leads to systemic inflammatory response syndrome and multi-organ damage. […] Coagulopathy is also present in the pathophysiology and manifests through disseminated intravascular coagulation, resulting in thrombosis or bleeding (or both). […] EHS pathophysiology is complex and involves an interaction of thermoregulatory and cardiovascular factors that lead to systemic inflammatory response syndrome. […] In catastrophic EHS events, systemic inflammatory response syndrome is likely initiated by endotoxaemia when the hepatic system fails to clear bacteria effectively.

• #16 Heatstroke-Induced Inflammatory Response and Therapeutic Biomarkers

  https://www.mdpi.com/2227-9059/13/2/261

  This response is regulated by the heat-shock protein family and ultimately results in altered levels of pro-inflammatory and anti-inflammatory cytokines in plasma and tissues. […] In the case of long-term hyperthermia, this inflammatory response becomes uncontrolled and results in acute physiological conditions such as hypoxia, circulatory failure, and higher metabolic demands along with direct heat-associated cytotoxicity. […] The heatstroke-associated inflammatory response is equivalent to the systemic inflammatory response syndrome (SIRS). […] Interestingly, SIRS is regulated by circulating messenger RNAs that stimulate the release of cytokines and high-mobility group box 1 protein (HMGB1), which in turn causes the overactivation of leukocytes (monocytes, and macrophages) and endothelial cells.

• #17 The pathogenesis and therapeutic strategies of heat stroke-induced liver injury | Critical Care | Full Text

  https://ccforum.biomedcentral.com/articles/10.1186/s13054-022-04273-w

  Cytokines are considered to be key mediators of SIRS in HS-induced systemic MODS and are closely related to the severity and outcome of HS. […] As one of the most ubiquitous, abundant, and evolutionarily conserved transcription and growth factors in eukaryotes, high mobility group box 1 (HMGB1) occupies an important position in the diagnosis and treatment of HS. […] The most common pathological change of HS-induced liver injury is the massive degeneration of hepatocytes including abnormal cell death, while pyroptosis exerts an important role in abnormal cell death in HS-induced liver injury. […] Excessive ROS will be produced during heat stress, which has been proven to be a key stimulator of NLRP3 inflammasome and a potential target for negative regulation of cell pyroptosis. […] The previous studies have suggested that mitophagy is closely related to the occurrence and development of various liver diseases, including viral hepatitis, liver ischemia/reperfusion (I/R) injury, and drug-induced liver injury.

• #18 Heat stroke – Wikipedia

  https://en.wikipedia.org/wiki/Heat_stroke

  Heat stroke occurs because of high external temperatures and/or physical exertion. […] The pathophysiology of heat stroke involves an intense heat overload followed by a failure of the body’s thermoregulatory mechanisms. More specifically, heat stroke leads to inflammatory and coagulation responses that can damage the vascular endothelium and result in numerous platelet complications, including decreased platelet counts, platelet clumping, and suppressed platelet release from bone marrow. […] Growing evidence also suggests the existence of a second pathway underlying heat stroke that involves heat and exercise-driven endotoxemia. […] Although its exact mechanism is not yet fully understood, this model theorizes that extreme exercise and heat disrupt the intestinal barrier by making it more permeable and allowing lipopolysaccharides (LPS) from gram-negative bacteria within the gut to move into the circulatory system. […] High blood LPS levels can then trigger a systemic inflammatory response and eventually lead to sepsis and related consequences like blood coagulation, multi-organ failure, necrosis, and central nervous system dysfunction.

• #19 Heat kills in 3 main ways. Know the signs to protect yourself : Shots – Health News : NPR

  https://www.npr.org/sections/health-shots/2023/07/23/1189506023/heres-what-happens-to-the-body-in-extreme-temperatures-and-how-heat-becomes-dead

  Of all extreme weather conditions, heat is the most deadly. […] When your body is exposed to heat, it will try to cool itself down by redirecting more blood to the skin, says Ollie Jay, a professor of heat and health at the University of Sydney, where he directs the Heat and Health Research Incubator. But that means less blood and less oxygen are going to your gut. If these conditions go on long enough, your gut can become more permeable. […] „So, nasty things like endotoxins that usually reside and stay inside the gut start leaking out of the gut, entering the circulation. And that sets off a cascade of effects that ultimately result in death,” Jay says. […] Those toxins can activate white blood cells, says Camilo Mora, a climate scientist and professor at the University of Hawaii at Manoa who has researched how heat can turn fatal. „They say, Oh my God, we’re getting attacked right now. And the white blood cells are going to attack this contamination in the blood, creating coagulation” or blood clots, Mora says. Those clots can lead to multiple organ failure.

• #20 Heatstroke-Induced Inflammatory Response and Therapeutic Biomarkers

  https://www.mdpi.com/2227-9059/13/2/261

  Overall, SIRS with other associated immune modulation during heatstroke causes DIC, leading to multiple organ failure, and even death. […] Additionally, the gut–brain barrier becomes permeable during heatstroke, allowing the migration of bacterial endotoxins and lipopolysaccharides to the circulatory system and ultimately to the brain, which causes neuroinflammation. […] In conclusion, endotoxemia and enhanced LPS levels are suggested to be involved in the induction of inflammatory response during heatstroke. […] Overall, the function of cytokines in SIRS, DIC, and the role of gut–brain axis dysbiosis in heatstroke need to be further explored.

• #21 Pathogenetic mechanisms of heatstroke and novel therapies | Critical Care | Full Text

  https://ccforum.biomedcentral.com/articles/10.1186/cc11265

  Heatstroke, a life-threatening condition defined by a rapidly increasing core temperature greater than 40C and multiple organ system dysfunction, is a leading cause of morbidity and mortality during heat waves. […] The mechanisms of multiple organ system dysfunction in heatstroke are not fully understood and include direct tissue injury and cell death resulting from heat cytotoxicity together with delayed organ dysfunction and damage secondary to activation of inflammatory and coagulation pathways. Histopathological changes include endothelial injury, disseminated intravascular thrombosis, neutrophils infiltration and apoptosis. […] Experimental evidence from rodent models of heatstroke suggest that immunomodulation of the host response may alter the clinical course of heatstroke and thereby improve outcome.

• #22 The pathogenesis and management of heatstroke and heatstroke-induced lung injury

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11729746/

  The lungs, which are the most susceptible organ, experience acute lung injury due to the impact of this inflammatory cascade caused by heatstroke. […] Damage to VEC morphology, characterized by an imbalance between intercellular adhesion junctions and cytoskeletal tension, leads to endothelial cell contraction and widening of intercellular gaps, resulting in increased vascular hyperpermeability; consequently, tissue oedema and the aggravation of inflammatory reactions seriously impair organ function. […] PMVEC apoptosis, necroptosis, and pyroptosis, along with the activation and dysfunction of endothelial cells, contribute significantly to the development of heatstroke-induced lung injury. […] The above studies demonstrated that PMVEC damage caused by the local inflammatory response and oxidative stress is one of the key causes of heatstroke-induced lung injury.

• #23 Pathophysiological factors underlying heatstroke – PubMed

  https://pubmed.ncbi.nlm.nih.gov/16631316/

  Heatstroke resembles sepsis in many aspects, and endotoxemia and cytokines may be implicated in its pathogenesis. […] The excessive accumulation of cytotoxic free radicals and oxidative damage may occur in the brain tissues during the genesis and development of heatstroke. […] The circulatory shock and cerebral ischemia resultant from heatstroke correlated closely with the free radicals (especially free radicals of peroxide and superoxide), the peroxidation of lipids, and low activity of antioxidase in the brain. […] Host factors or physiologically limiting factors, for instance, aging, existing illness, dehydration, deep insomnia, lack of acclimation to heat, inadequate physical fitness, and certain genetic polymorphisms were associated with a low level of Hsps expression and might favor the progression from heat stress to heatstroke. […] Some measures, such as molecular chaperonines, anti-inflammatory agents, antioxidant agents, and modulators of Hsps would be good for the patients with heatstroke.

• #24 The mechanisms behind heatstroke-induced intestinal damage | Cell Death Discovery

  https://www.nature.com/articles/s41420-024-02210-0

  The mechanism of intestinal damage is complex and interrelated. […] The activated UPR can limit protein synthesis and increase HSP70, which inhibits the NF-B pathway and reduces inflammation. […] Excess ROS can impair intestinal barrier function by reducing epithelial cell viability and damaging intestinal TJs. […] The physical barrier formed by TJ is crucial to intestinal health, which is composed of claudins, occludins, and the intracellular plaque proteins zonula occludens (ZO-1, ZO-2, and ZO-3). […] Studies have shown that upon heat stress, multiple kinases and phosphatases will phosphorylate the TJ proteins, resulting in reduced interaction of occludins and claudins with zona-occludins, thereby affecting intestinal permeability. […] The activation of MLCK is related to various factors, for example, inflammatory pathways.

• #25 The pathogenesis and therapeutic strategies of heat stroke-induced liver injury | springermedizin.de

  https://www.springermedizin.de/the-pathogenesis-and-therapeutic-strategies-of-heat-stroke-induc/23840082

  The most common pathological change of HS-induced liver injury is the massive degeneration of hepatocytes including abnormal cell death, while pyroptosis exerts an important role in abnormal cell death in HS-induced liver injury. […] HS-induced liver injury is accompanied by the activated inflammasome, which can effectively induce the activation of IL-1 and hepatocyte pyroptosis, thus leading to severe liver injury. […] The previous studies have suggested that mitophagy is closely related to the occurrence and development of various liver diseases, including viral hepatitis, liver ischemia/reperfusion (I/R) injury, and drug-induced liver injury. […] In HS-induced liver injury, the important role of mitophagy has also been confirmed. […] The dysregulation of Kupffer cells is the main explanation for the elevated endotoxin concentration.

• #26 Heat stroke | MedLink Neurology

  https://www.medlink.com/articles/heat-stroke

  Long-term consequences of heat stroke are due to a systemic inflammatory response syndrome that may lead to multi-organ dysfunction and death. […] The central nervous system is particularly vulnerable to heat stroke. […] Heat stroke is associated with cerebral ischemia as well as increased levels of interleukin-1beta, dopamine, and glutamate in the brain. […] The cause of death in heat stroke is probably not CNS damage but systemic hemodynamic deterioration.

• #27 Heat stroke with neurological involvement | Neurology perspectives

  https://www.elsevier.es/en-revista-neurology-perspectives-17-avance-resumen-heat-stroke-with-neurological-involvement-S266704962200059X

  Heat stroke is a medical emergency characterised by a systemic inflammatory response secondary to an increase in body temperature above 40C, with severe multiple organ involvement, including the central nervous system (CNS), which is particularly vulnerable to hyperthermia. […] The pathophysiological mechanism of CNS damage and the related imaging findings is not well established, but is believed to be multifactorial, involving lesions secondary to direct thermal injury, as in the case of destruction of cerebellar Purkinje cells, as well as alterations in brain perfusion, with vasodilation, potentially leading to brain oedema, and subsequent vasoconstriction secondary to hypovolaemia, causing ischaemic damage and microvascular alterations similar to those occurring in disseminated intravascular coagulation, in association with brain haemorrhages.

• #28 The pathogenesis and therapeutic strategies of heat stroke-induced liver injury | springermedizin.de

  https://www.springermedizin.de/the-pathogenesis-and-therapeutic-strategies-of-heat-stroke-induc/23840082

  Therefore, the liver not only plays a victim role in the course of HS, but also is a key factor in the pathogenesis of HS. […] In addition to direct heat injury, HS can cause liver injury through various mechanisms, including inhibiting the expression of HSP70 of hepatocytes, promoting the production of ROS, promoting the inflammatory response and pyropsis, etc. […] Excessive inflammation is an important cause of MODS in HS, while the translocation of endotoxin in the intestinal cavity caused by intestinal injury into the circulation is the key factor to trigger SIRS and MODS including liver injury in HS. […] The activation of coagulation and fibrin deposition secondary to inflammation can be regarded as an important part of the host’s defense against high fever, but the intensification of systemic inflammatory reaction may lead to systemic blood coagulation activation and microvascular failure, thus exacerbating organ dysfunction.

• #29 The pathogenesis and therapeutic strategies of heat stroke-induced liver injury | Critical Care | Full Text

  https://ccforum.biomedcentral.com/articles/10.1186/s13054-022-04273-w

  The dysregulation of Kupffer cells is the main explanation for the elevated endotoxin concentration. […] The increased expression of HSP level is related to the better prognosis of HS patients. […] In brief, the mechanism of HS-induced liver injury is not only related to systemic factors such as systemic inflammatory reaction and coagulation dysfunction but also closely related to pathological mechanisms such as abnormal death of liver cells and abnormal function of KCs.

• #30 The pathogenesis and management of heatstroke and heatstroke-induced lung injury

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11729746/

  The lung often acts as a vulnerable, affected, and injured organ in heatstroke due to its unique structure, and impaired lung function further promotes anoxic damage to other vital tissues and organs. […] Heat stress usually induces lung injury through direct thermal cytotoxic effects and secondary uncontrolled systemic inflammation. In the early stages of heatstroke, the direct thermal cytotoxic effect of high temperature on lung tissue can directly lead to cell death, promoting the production of reactive oxygen species (ROS) and accelerating cell apoptosis. […] With the progress of research on heatstroke, secondary uncontrolled systemic inflammation is considered the main cause of lung injury in heatstroke patients. […] A large number of cytokines act on pulmonary microvascular endothelial cells (PMVECs), causing structural destruction of endothelial cells, exposing tissue factors, activating the exogenous coagulation system, and inhibiting the fibrinolytic system, leading to an imbalance between coagulation and fibrinolysis, fibrinogen deposition, microthrombosis formation, and an imbalance in the pulmonary ventilation blood flow ratio, ultimately leading to ventilation dysfunction, manifested as persistent hypoxemia.

• #31 Heat kills in 3 main ways. Know the signs to protect yourself : Shots – Health News : NPR

  https://www.npr.org/sections/health-shots/2023/07/23/1189506023/heres-what-happens-to-the-body-in-extreme-temperatures-and-how-heat-becomes-dead

  „And at that point, it’s pretty irreversible,” Jay adds. […] The second way people die in high heat also has to do with your body pumping more blood to the skin. Your heart has to pump faster which can make you feel lightheaded to keep your blood pressure up. […] Those spikes in the heart rate can be triggers for a heart attack, he says, especially for the elderly and those with underlying heart conditions. […] The third deadly danger has to do with the fluids your body is losing in extreme heat. […] „People with kidney disorders can be at greater risk of a negative health outcome during extreme heat exposure,” Jay says. […] Rhabdomyolysis causes muscle tissue to break down, releasing proteins into the blood that can clog kidneys. This usually occurs in the acute phase of heatstroke.

• #32 Metabolomic profiling identifies a novel mechanism for heat stroke‑related acute kidney injury

  https://www.spandidos-publications.com/10.3892/mmr.2021.11880

  Heat stroke can induce a systemic inflammatory response, which may lead to multiorgan dysfunction including acute kidney injury (AKI) and electrolyte disturbances. […] To investigate the pathogenesis of heat stroke (HS) related AKI, a mouse model of HS was induced by increasing the animal’s core temperature to 41C. […] The HS mouse model was built successfully, with significantly increased creatinine levels detected in the serum of HS mice compared with controls, whereas microPET/CT revealed active metabolism in the whole body of HS mice. […] HE and TUNEL staining revealed that the kidneys of HS mice exhibited signs of hemorrhage and apoptosis. […] IHC and western blotting demonstrated significant upregulation of Aifm2, HMGB1 and RAGE in response to HS. […] HS associated AKI is the renal manifestation of systemic inflammatory response syndrome, and may be triggered by the HMGB1/RAGE pathway.

• #33 Metabolomic profiling identifies a novel mechanism for heat stroke‑related acute kidney injury

  https://www.spandidos-publications.com/10.3892/mmr.2021.11880

  The findings suggested that a correlation between the HMGB1/RAGE pathway and biosynthesis of unsaturated fatty acids may contribute to the progression of HS related AKI. […] Several mechanisms involved in HS are currently accepted. Systemic inflammation and MODS are reported to play key roles in the pathophysiology of HS. […] HS causes dysfunction of the intestinal barrier, leading to intercellular penetration of harmful substances such as bacteria and endotoxins within the gut lumen. […] In the present study, a mouse model of HS was constructed to examine whether the high-mobility group box 1 (HMGB1)/receptor for advanced glycosylation end products (RAGE) pathway is activated in mouse kidneys. […] The results revealed that the biosynthesis of unsaturated fatty acids, synthesis and degradation of ketone bodies, Chagas disease, D-arginine and D-ornithine metabolism and amyotrophic lateral sclerosis (ALS) pathways were the only five signaling pathways significantly enriched with differential metabolites. […] In summary, the present study suggested that HS associated AKI is the most common result of HS induced SIRS, and may be associated with the HMGB1/RAGE pathway.

• #34 The mechanisms behind heatstroke-induced intestinal damage | Cell Death Discovery

  https://www.nature.com/articles/s41420-024-02210-0

  The intestinal microbiota is imbalanced, causing the overgrowth of harmful bacteria, especially gram-negative bacteria, while the number of Lactobacillus and Bifidobacterium is significantly reduced. […] Intestinal injury caused by HS depends on the participation of various signal pathways and disease models. […] Although the mechanisms of intestinal damage caused by HS are diverse and complicated, the common effect is damage to the intestinal barrier.

• #35

  https://www.nursingcenter.com/journalarticle?Article_ID=593951&Journal_ID=230572&Issue_ID=593907

  Heat stroke (HS) is a serious and potentially life-threatening condition defined as a core body temperature 40.6[degrees]C. […] Current understanding of HS indicates that it is due to thermoregulatory failure in addition to an exaggerated acute-phase response and altered genetic expression of heat-shock proteins. […] Genetic polymorphisms likely determine susceptibility to heat. The genes involved regulate the activity of cytokines, coagulation proteins, and the very proteins involved in heat adaptation. The progression from heat stress to HS is due to a combination of events including: thermoregulatory failure, an exaggerated acute-phase response to heat, and alteration in the production of heat-shock proteins. […] The acute-phase response to heat involves endothelial cells, leukocyte response, and epithelial cells. These cells protect the body against tissue injury and will promote prompt repair in the event of injury. The pathophysiologic sequence of events in HS is similar to that found in severe sepsis.

• #36

  https://www.nursingcenter.com/journalarticle?Article_ID=593951&Journal_ID=230572&Issue_ID=593907

  The third event in the progression of heat stress to HS involves the production of heat-shock proteins. The production of special heat resistant proteins or stress proteins is controlled at the level of gene transcription in the DNA of the chromosomes. […] When the synthesis of heat-shock proteins is blocked or altered, as in a genetic polymorphism, at the gene transcription level or by antibodies, the cells are rendered extremely sensitive to heat stress. […] Exposure to excessive heat may cause illness, as heat directly induces tissue injury, the severity of which is dependent upon the critical thermal maximum (ie, the level and duration of core heating).

• #37 The Gastrointestinal Exertional Heat Stroke Paradigm: Pathophysiology, Assessment, Severity, Aetiology and Nutritional Countermeasures

  https://www.mdpi.com/2072-6643/12/2/537

  Exertional heat stroke (EHS) is a life-threatening medical condition involving thermoregulatory failure and is the most severe condition along a continuum of heat-related illnesses. […] Current EHS policy guidance principally advocates a thermoregulatory management approach, despite growing recognition that gastrointestinal (GI) microbial translocation contributes to disease pathophysiology. […] The aetiology of GI barrier integrity loss following exertional-heat stress is poorly understood, though may directly relate to localised hyperthermia, splanchnic hypoperfusion-mediated ischemic injury, and neuroendocrine-immune alterations. […] A gastrointestinal paradigm of EHS pathophysiology (also known as “endotoxemia” or “heat sepsis”) has gained momentum as a secondary pathway through which to focus EHS management.

• #38 The Gastrointestinal Exertional Heat Stroke Paradigm: Pathophysiology, Assessment, Severity, Aetiology and Nutritional Countermeasures

  https://www.mdpi.com/2072-6643/12/2/537

  The GI EHS paradigm was first introduced as a novel pathophysiological concept in the early 1990s, before integration into conventional EHS medical classifications in 2002. […] The broad scientific basis of the GI EHS paradigm centers the notion that sustained exertional-heat strain initiates damage to the GI barrier, which consequently permits GI MT into the circulating blood. […] Failure of GI microbial detoxification mechanisms permits binding of unique GI pathogen associated-molecular patterns (PAMP) to toll-like receptors (TLR) located on cell surface membranes. […] The GI EHS paradigm is considered to be the primary cause of EHS in cases where Tcore remains below the threshold (~42–44 °C) of heat cytotoxicity. […] The specific aetiology of exertional-heat stress induced GI barrier integrity loss is poorly defined, but likely relates to the direct effects of localised hyperthermia, ischemia-reperfusion injury and neuroendocrine-immune alterations.

• #39

  https://www.vin.com/apputil/content/defaultadv1.aspx?pId=22915&catId=124655&id=8896657&ind=419&objTypeID=17

  Heatstroke is caused by the inability to dissipate accumulated heat. In dogs it is characterized by core temperatures above 105.8F (41C) with CNS dysfunction. It results from exposure to a hot and humid environment or from strenuous physical exercise. Activation of inflammatory and haemostatic pathways initiates a systemic inflammatory response syndrome (SIRS) which often progresses to multi-organ dysfunction syndrome (MODS). Serious complications of heatstroke include rhabdomyolysis, acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), and disseminated intravascular coagulation (DIC). […] High body temperatures initiate a myriad of inflammatory, coagulation, and tissue damage processes, varying in severity and progression between dogs. Thermal endothelial cell injury leads to diffuse vascular damage and initiation of coagulation and subsequent microvascular thrombosis. In addition, multiorgan cellular necrosis further stimulates the coagulation system and results in DIC, an important factor in the morbidity and mortality of heatstroke patients. The injured endothelium releases thromboplastin and factor XII, which activates coagulation and the complement cascade, inducing SIRS and widespread DIC.

• #40 Acute Management of Heat Stroke: Facts and Figures | IntechOpen

  https://www.intechopen.com/chapters/88937

  Heat stroke is a life-threatening medical emergency causing multiple organ dysfunction that if not treated, can be fatal. […] Pathophysiology is exposure to higher temperatures with impaired thermoregulation. […] The increase in body temperature causes intestinal mucosal injury, and the release of endotoxins and proinflammatory mediators interleukins 1 and 6 from muscles to the systemic circulation, these chemicals leucocytes and endothelial cells, and the release of various cytokines and HMGB (high mobility group box 1 protein), all in combination stimulate SIRS (systemic inflammatory response syndrome). […] The heat stroke thus generates inflammatory and coagulopathy responses; the direct effect of heat also causes endothelial injury and generates microthromboses, leading to a disseminated intravascular coagulation (DIC) response. […] Heat stroke generates a systemic inflammatory and coagulopathy response in combination with heat injury causes organ dysfunctions.

• #41 Heatstroke in Dogs | Today’s Veterinary Practice

  https://todaysveterinarypractice.com/emergency-medicine-critical-care/todays-technician-heatstroke-in-dogs/

  A minimum nonpyrogenic body temperature elevation of 1.8°F (1°C) can activate heat receptors found in the periphery, triggering the thermoregulatory center, which in turn induces constriction of renal and splanchnic vessels, tachycardia, and cutaneous vasodilation. These processes result in increased blood flow to the skin, where it can be cooled. […] The acute-phase response is a coordinated cellular response that occurs in inflammatory events, such as infection, surgery, trauma, burns, immune-mediated diseases, and nonpyrogenic hyperthermia. During nonpyrogenic hyperthermia, this response is stimulated in an attempt to protect tissues from excessive heat and promote repair. […] The acute-phase response also initiates production of heat shock proteins (HSPs). […] When cells are exposed to an increased temperature, HSPs protect against protein denaturation. They prevent disaggregation of denatured proteins, refold denatured proteins, protect against endotoxin leakage across the intestines, and reduce cerebral ischemia.

• #42 Protective effect and mechanism of mesenchymal stem cells on heat stroke induced intestinal injury

  https://www.spandidos-publications.com/10.3892/etm.2020.9051

  Heat stroke (HS) is considered to be a severe systemic inflammatory reaction disease that is caused by high fever. The mortality of HS is high worldwide due to the lack of effective treatments. Presently, mesenchymal stem cells (MSCs) have been demonstrated to serve roles in inflammation and immune regulation. Therefore, the current study aimed to investigate the protective effect and mechanism of MSCs against the HS-induced inflammatory response and organ dysfunction. […] The results indicated that MSC infusion had therapeutic effects on HS of rats by regulating the circulatory and intestinal inflammatory response. Moreover, MSCs may be able to protect organ function and promote tissue repair in HS. […] It has been hypothesized that the early onset of HS is due to intestinal ischemia, which results in intestinal mucosal barrier function damage and leads to the induction of the intestinal flora and the systemic inflammatory response.

• #43 Heat stroke | MedLink Neurology

  https://www.medlink.com/articles/heat-stroke

  Heatstroke is a heat-related illness marked by a sudden rise in core body temperature above 40C along with central nervous system dysfunction. […] Pathological studies reveal organ damage, inflammation, and thrombosis. […] Understanding individual susceptibility, genetic factors, and biomarkers are crucial for precision-based public health interventions. […] Cause of heat stroke is loss of thermoregulation with hyperpyrexia. […] Heat stroke is a total breakdown of thermoregulation, and two classical forms are nonexertional heat stroke and exertional heat stroke, which typically follows strenuous sports. […] The pathophysiology involves the strain on thermoregulation and cardiovascular systems, leading to severe hyperthermia and multiorgan injury due to systemic inflammation and coagulopathy.

• #44 (PDF) Heatstroke: Pathogenesis, diagnosis and Treatment

  https://www.academia.edu/14356639/Heatstroke_Pathogenesis_diagnosis_and_Treatment

  Heatstroke is a severe condition characterized by hyperthermia, neurological abnormalities, and dry skin, typically following heat exposure or strenuous activity. […] Effective cooling methods, such as evaporative cooling, are essential, as no pharmacological treatment has proven beneficial. […] Studies indicate an urgent need to explore underlying mechanisms and alternative treatments for improved patient outcomes. […] Classic heat stroke may demonstrate a rapidly worsening organ dysfunction course leading to death even though cooling procedures and intensive care management are promptly started. […] The lack of efficient regulatory control under such severe stress conditions makes the cardiovascular system of anaemic animals more vulnerable to heat stress. […] The results of the present study showed deleterious effects of heat stress in both the groups.

• #45 Heatstroke – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/heat-stroke/symptoms-causes/syc-20353581

  Doing strenuous activity. Exertional heatstroke is caused by an increase in core body temperature brought on by intense physical activity in hot weather. […] In either type of heatstroke, your condition can be brought on by: Wearing heavy clothing that prevents sweat from evaporating easily and cooling the body. […] Heatstroke can result in a number of complications, depending on how long the body temperature is high. Serious complications include: Vital organ damage. Without a quick response to lower the body temperature, heatstroke can cause the brain or other vital organs to swell, possibly resulting in permanent damage. […] Death. Without prompt and adequate treatment, heatstroke can be fatal. […] Heatstroke is predictable and preventable. Take these steps to prevent heatstroke during hot weather: Wear loose-fitting, lightweight clothing. Excess clothing or clothing that fits tightly doesn’t allow your body to cool properly.

• #46 Exertional heat stroke: pathophysiology and risk factors | BMJ Medicine

  https://bmjmedicine.bmj.com/content/1/1/e000239

  A person’s ability to thermoregulate is closely linked to the ability of the cardiovascular system to cope with central and peripheral blood flow demands to support metabolic and thermoregulatory requirements. […] During vigorous exercise, heat is produced by skeletal muscle contractions at rates that are 15-18 times greater than the basal metabolic rate. […] Effective thermoregulatory pathways must be active to provide means for heat loss to prevent EHS during severe or prolonged physical activity. […] A thermoregulatory failure underlying EHS would signify a suppressed ability to dissipate heat coupled with high rates of heat storage, which would result in a marked elevation in core temperature. […] The leaky gut hypothesis has been linked to EHS pathophysiology because of observations that in patients with extreme EHS, high levels of lipopolysaccharide (a cell wall component of Gram negative bacteria) are observed.

• #47 Heat-related Illnesses | Heat | CDC

  https://www.cdc.gov/niosh/heat-stress/about/illnesses.html

  Heat stroke is the most serious heat-related illness. It occurs when the body can no longer control its temperature: the body’s temperature rises rapidly, the sweating mechanism fails, and the body is unable to cool down. When heat stroke occurs, the body temperature can rise to 106F or higher within 10 to 15 minutes. Heat stroke can cause permanent disability or death if the person does not receive emergency treatment. […] Rhabdomyolysis (rhabdo) is a medical condition associated with heat stress and prolonged physical exertion. Rhabdo causes the rapid breakdown, rupture, and death of muscle. When muscle tissue dies, electrolytes and large proteins are released into the bloodstream. This can cause irregular heart rhythms, seizures, and damage to the kidneys.

• #48 Heatstroke (Proceedings)

  https://www.dvm360.com/view/heatstroke-proceedings

  Heatstroke can be defined as severe hyperthermia resulting in thermal injury to tissues. […] Heat stroke occurs when these compensatory mechanisms fail or are overwhelmed and must be differentiated from pyrexia. […] The damaging effects of heatstroke are due to direct cellular injury and destruction of enzymes. […] Peripheral vasodilation and decreased peripheral vascular resistance leads to hypovolemia. Hemoconcentration due to dehydration can predispose to red blood cell sludging and subsequent thrombosis. […] Neuronal degeneration and necrosis results in cerebral edema. […] Thermal injury injury causes hepatocellular destruction, cholestasis, and dysfunction of the hepatic reticuloendothelial system. […] Direct thermal injury along with hypoxia due to decreased circulating volume and increased metabolic demand for oxygen predisposes the kidneys to acute tubular nephrosis. […] Prognosis for the heatstroke patient is guarded. If hyperthermia is corrected immediately, systemic thermal injury may be minimal and chances of recovery can be fair.

• #49 Pathogenetic mechanisms of heatstroke and novel therapies | Critical Care | Full Text

  https://ccforum.biomedcentral.com/articles/10.1186/cc11265

  Administration of an IL-1 receptor antagonist, corticosteroids or activated protein C before the onset of heatstroke attenuates the multiple organ system dysfunction and improves survival. […] Using this experimental model, we report that immunomodulating the host systemic inflammatory and coagulation responses failed to translate into improved survival, suggesting that further basic research on the pathogenesis of heatstroke is required.

• #50 Heat-related illnesses – Knowledge @ AMBOSS

  https://www.amboss.com/us/knowledge/heat-related-illnesses/

  Heatstroke is a life-threatening heat-related illness characterized by severe hyperthermia (with a body temperature typically 40C) and severe CNS dysfunction. […] The cornerstone of treatment is aggressive active cooling to reduce core body temperature to less than 40C. […] In hyperthermia, the hypothalamic thermoregulatory response is inadequate to maintain a normal temperature. […] High body temperature protein denaturation, phospholipid and lipoprotein damage, and membrane lipid liquefaction cell damage and loss of function (including myocardiocytes and neurons) cardiovascular collapse multi-organ failure and possibly death. […] Heatstroke is primarily caused by strenuous physical activity increasing heat generation. […] Active cooling is the highest priority for patients with heatstroke and should be considered even before initiating transport.

• #51 The pathogenesis and therapeutic strategies of heat stroke-induced liver injury | springermedizin.de

  https://www.springermedizin.de/the-pathogenesis-and-therapeutic-strategies-of-heat-stroke-induc/23840082

  However, at the same time, KCs are also the main source of inflammatory factors in the liver. […] The increased expression of HSP level is related to the better prognosis of HS patients. […] In HS-induced liver injury, PARP blockage has also emerged as a promising treatment. […] The mechanism of HS-induced liver injury is not only related to systemic factors such as systemic inflammatory reaction and coagulation dysfunction but also closely related to pathological mechanisms such as abnormal death of liver cells and abnormal function of KCs. […] Therefore, for the treatment of HS-induced liver injury, we should not only implement systematic and supportive treatment but also target the liver for precise treatment.

• #52 Protective effect and mechanism of mesenchymal stem cells on heat stroke induced intestinal injury

  https://www.spandidos-publications.com/10.3892/etm.2020.9051

  The results of the current study demonstrated that the levels of IL-1, IL-6 and TNF- in intestinal tissues of the rats in the control group increased to varying degrees at day 1 following successful modeling. […] The current study proposed the use of MSCs for the treatment of HS and reported that MSCs effectively alleviated the inflammatory response of the whole body and local tissue, and protected the intestinal mucosal barrier. The present study demonstrated the anti-inflammatory and protective effects of MSCs on organs and provided new theories and methods for the treatment of HS, which are required to improve the prognosis of patients with HS.

• #53 Development and validation of a prognostic model of survival for classic heatstroke patients: a multicenter study | Scientific Reports

  https://www.nature.com/articles/s41598-023-46529-7

  In this study, poor prognosis of CHS was found to be associated with social isolation and inability to care for oneself. […] Elevated core temperature can cause thermoregulation failure, exacerbate acute-phase responses, and alter heat shock protein expression, potentially leading to progression from heat stress to heat stroke. […] The GCS score provides a straightforward and trustworthy means to assess the severity and prognosis of patients with CNS conditions. […] PCT is a biomarker of systemic inflammation, particularly of bacterial origin, and is useful in clinical practice for diagnosing and predicting the prognosis of bacterial infections. […] Liver injury is a common complication of CHS and a significant cause of mortality. […] This is the first study, to our knowledge, to develop and externally validate a prognostic model for predicting the in-hospital survival of CHS patients based on social risk factors, clinical data and hematologic indices. […] In conclusion, we designed and externally validated a prognostic prediction model for CHS.

• #54 Development and validation of a prognostic model of survival for classic heatstroke patients: a multicenter study | Scientific Reports

  https://www.nature.com/articles/s41598-023-46529-7

  The baseline sociodemographic characteristics, clinical data and hematological parameter were analyzed as potential prognostic factors affecting in-hospital survival using LASSO regression. […] Significant or near-significant associations were found between social isolation, self-care ability, comorbidities, body temperature, heart rate, GCS, PCT, AST, and diarrhea and poor outcomes in CHS hospitalized patients. […] A predictive model was established for estimating the probability of in-hospital survival utilizing the nine independent prognostic factors identified by LASSO and multivariate Cox regression analyses. […] The model allows for the incorporation of social risk factors, clinical data and hematological indices to provide personalized, patient-specific in-hospital survival estimates and can be utilized for risk stratification and prognosis analysis of CHS patients.

• #55 Research advances in pathogenesis of heat stroke

  https://xuebao.301hospital.com.cn/en/article/doi/10.3969/j.issn.2095-5227.2020.12.014

  Heat stroke is an imbalance of heat production and heat dissipation due to exposure to a thermal environment and/or intense exercise, characterized by increasing core temperature and central nervous system abnormalities such as altered mental state, convulsions or coma, accompanied by a life-threatening clinical syndrome of multiple organ damage. […] The common pathophysiological processes of heat stroke include oxidative stress, inflammatory reaction, coagulation dysfunction, rhabdomyolysis, intestinal micro-dysbiosis and so on. […] These pathological processes damage tissues and organs in a variety of ways, resulting in multiple organ dysfunction syndrome. […] This paper reviews the pathophysiological studies on the pathogenesis of heat stroke in recent years, in order to provide new ideas for its clinical treatment and further research.

• #56 SafetyLit: Heat stroke: pathogenesis, diagnosis, and current treatment

  https://www.safetylit.org/citations/index.php?fuseaction=citations.viewdetails&citationIds[]=citjournalarticle_838712_7

  Recently, the incidence of heat-related illnesses has exhibited a steadily upward trend, closely associated with several environmental factors such as climate change and air pollution. […] Current knowledge suggests that the pathogenesis of heat stroke is complex and varied, including inflammatory response, oxidative stress, cell death, and coagulation dysfunction. […] This review consolidated recent research progress on the pathophysiology and pathogenesis of heat stroke, with a focus on the related molecular mechanisms. […] aiming to offer a comprehensive research roadmap for more in-depth researches into the mechanisms of heat stroke and the reduction in the mortality of heat stroke in the future.

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