Cellular injury from cryotherapy can occur due to intracellular water crystallization, temperature-induced protein changes and membrane damage. Slow cooling crystallizes extracellular water, which decreases interstitial water in the liquid phase and draws water out of cells. This effect alters intracellular electrolyte concentrations, which modifies cellular protein structure. The cell content becomes hyperosmolar, and toxic concentrations of electrolytes may cause cell death. Vasoconstriction, endothelial injury and thromboembolism contribute to vascular insufficiency and ischemia and also causes hypo-perfusion and stasis. Endothelial injury causes thrombosis and loss of vascular integrity. Thromboembolism, from stasis and endothelial injury, may also be promoted by haemoconcentration and hyperviscosity. As the tissues thaw, edema occurs because of the melting water crystals, cellular damage, loss of endothelial integrity and thrombosis.

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