Cancer

　　

In typical cryosurgical protocols, after freezing was completed the cooling system keeps the tissue frozen for a desired period of time, followed by heating and thawing. The cells near the cryosurgical probe surface will be cooled with a higher cooling rate and to lower temperatures than those farther away from the probe. The cells at different locations in the frozen lesion will be at different temperature for various periods of times, as a function of their distance from the probe surface, the cooling material employed, the shape of the cryosurgical probes, the number of the cryosurgical probes used, the type of tissue frozen.

Cell damage during cooling and freezing occurs at several length scales: nanoscale (Armstrong) - molecular, mesoscale (micron) - cellular and macroscale (millimeter) - whole tissue. The damage during cryosurgery is of two types, acute - immediately during cryosurgery and long term.

The effect of cooling

Most types of mammalian cells and tissues can withstand low, non-freezing temperatures for short periods of time. The phenomena related to cooling occur primarily at the nanoscale, with typical consequences at the mesoscale.

Cells are entities with a highly specific intracellular chemical content, separated from the non-specific extracellular solution by the cell membrane. The cell membrane acts as a selective barrier between the intracellular and the extracellular milieu. The membrane selectively controls the transport of chemical species into and out of the cell. Therefore the membrane must be mostly impermeable except at particular sites where it can control the mass transfer. The by-layer lipid structure of the cell membrane makes it impermeable. The mass transfer through the cell membrane is controlled through membrane proteins that span the membrane.

Mammalian cells have become optimized to function at the temperature in which the organism lives.
One aspect of cooling the cell to temperatures lower than their normal physiological temperature is the lipid phase transition process.

Normally the membrane proteins control the intracellular composition by selectively introducing and removing ionic species from the cell interior. However life processes are temperature dependent chemical reactions. Lowering the temperature also reduces the efficiency of the membrane proteins and their ability to control the intracellular content. Therefore, during cooling, the intracellular composition and in particular the intracellular ionic content begins to change as undesirable ions diffuse into the cells and are not removed.

Additional mechanisms of damage relate to the cytoskeleton. The cytoskeleton structure depends on chemical bonds between membrane proteins and the cell scaffold. Lowering the temperature weakens these bonds and makes them particularly vulnerable to mechanical damage.