Pathophysiology of frostbite (1,2)
Injury caused by the freezing of tissue can be divided into 4 overlapping pathological phases:
- pre-freeze 
- presence of tissue cooling with accompanying vasoconstriction and ischaemia
 - does not involve actual ice crystal formation
 - there is hyperesthesia and parasthaesia due to neuronal cooling and ischaemia
 
 - freeze-thaw phase 
- formation of ice crystals intracellularly (during a more rapid-onset freezing injury) or extracellularly (during a slower freeze)
 - results in protein and lipid derangement, cellular electrolyte shifts, cellular dehydration, cell membrane lysis, and cell death
 - thawing process may initiate ischemia-reperfusion injury and the inflammatory response
 
 - vascular stasis phase
- vessels may fluctuate between constriction and dilation
 - blood may leak from vessels or coagulate within them
 
 - late ischaemic phase
- caused by progressive tissue ischemia and infarction from a cascade of event e.g. - inflammation mediated by thromboxane A2, prostaglandin F2α, bradykinins, and histamine; intermittent vasoconstriction of arterioles and venules; continued reperfusion injury; showers of emboli coursing through the microvessels; and thrombus formation in larger vessels
 - cell death is caused by destruction of the microcirculation
 
 
Reference:
- Sheridan RL, Goverman JM, Walker TG. Diagnosis and treatment of frostbite. N Engl J Med. 2022 Jun 9;386(23):2213-20.
 - McIntosh SE, Freer L, Grissom CK, et al. Wilderness Medical Society clinical practice guidelines for the prevention and treatment of frostbite: 2024 update. Wilderness Environ Med. 2024 Jun;35(2):183-97.