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Frostbite can cause severe cellular damage when exposed to extreme cold for extended periods. As ice crystals form inside the cells, they expand and Thaw. This expansion and contraction can tear the cell membranes, leading to mechanical damage. Damage often results in cell rupture due to the increased volume of ice compared to liquid water.
The integrity of the cell is compromised, leading to potential cell death as the cell's components spill out. With the membrane broken, cells cannot maintain essential functions such as barrier protection and nutrient regulation. The intracellular environment is thus disrupted, pointing towards inevitable cell death.

Frostbite doesn't just take its toll on the cells directly; it also impacts blood flow. In extremely cold environments, the body attempts to conserve heat by directing blood away from the skin surface toward the core. This response decreases blood circulation to the extremities, like fingers and toes.
The blood vessels constrict, a response intended to protect vital organs, but it sadly reduces the vital oxygen and nutrient supply to the tissues on the periphery. Without this blood supply, the affected tissues cannot maintain cellular processes efficiently. Oxygen and nutrients are vital for cell repair and survival, and without them, the cells face increased risk of damage and death.

With both cellular injury and restricted blood flow, the situation can escalate to tissue death. When the cells within tissue die, the tissue as a whole begins to degrade. The lack of fresh blood supplies further strains the efforts of the body to recover.
Once a significant number of cells in a particular area die, it leads to the death of the entire tissue. This area of dead tissue, called necrosis, can no longer function or heal. The affected parts thus lose their structured function and can develop gangrene if left unchecked.

Unfortunately, the damage from severe frostbite often becomes permanent because of the cascade of events leading to tissue death. Human tissues have very limited regenerative abilities once the damage is extensive.
When a tissue has died, it cannot regenerate or repair itself to its original state. Medical intervention can help limit further damage, but it cannot restore the dead tissues. Because of this, early medical assistance is crucial in frostbite cases. Once an area is considered necrotic, the only option may be surgical removal.