Why Extreme Hyperthermia Is Fatal: Protein Denaturation and Cellular Collapse
Core temperature >41.5°C (106.7°F) initiates irreversible cellular damage cascades.
Molecular Mechanisms of Heat Toxicity
- Protein denaturation: Loss of tertiary/quaternary structure → enzyme inactivation, cytoskeletal collapse, loss of membrane transport.
- Membrane fluidity changes: Lipid bilayer disorder → ion channel dysfunction, Ca²⁺ influx → protease/phospholipase activation → necrosis/apoptosis.
- DNA damage: Heat shock → strand breaks, impaired repair.
- Oxidative stress: Mitochondrial uncoupling → ROS burst → lipid peroxidation.
- Inflammatory cascade: Heat shock proteins (HSP70) released → TLR4 activation → cytokine storm (IL-1, IL-6, TNF-α) → SIRS/MODS.
Organ System Failure
| System | Manifestation |
|---|---|
| CNS | Encephalopathy, seizures, cerebellar hemorrhage, cerebral edema |
| Cardiovascular | High-output failure → myocardial ischemia, arrhythmias, DIC |
| Renal | ATN (rhabdo, hypotension), cortical necrosis |
| Hepatic | Centrilobular necrosis, coagulopathy |
| GI | Mucosal ischemia → translocation, sepsis |