Mechanism of Action

The mechanism of action in cryotherapy and cryosurgery involves 3 phases

  1. Heat Transfer

    The mechanism by which cryotherapy destroys the targeted cells is the extremely rapid transfer of heat from the tissue to a cryogen. When the cryogen evaporates, it takes heat from its surroundings causing a freezing effect. 1,2

    When using Hydrozid, the cryogen, HFC134a (norflurane), is applied directly on the skin, and evaporation occurs during which a significant amount of thermal energy, in the skin is rapidly transferred to the cryogen. This evaporation is almost immediate almost and simultaneously greatly lowers the temperature of the skin.

    1. Sharma VK, Khandpur S. Guidelines for cryotherapy. IJDVL Indian Journal of Dermatology, Venereology and Leprology 2009; 75: 90-100

    2. Graham GF, Tuchay SM. Chapter 32 Therapeutic Principles and Techniques in a W. Abramovits et al. (eds.), Dermatological Cryosurgery and Cryotherapy. Springer-Verlag London 2016.

  2. Cell Death

    Cell death or necrosis occurs during the thaw, right after the cell is frozen 3. When the cells are frozen, their liquid content (cytoplasm) freezes and expands. Subsequently, their membrane also freezes and loses its elasticity. Hence, the expansion of the cytoplasm is able to rupture of the cell membrane releasing its content and the cell organelles to stop functioning which results in cell death or necrosis. Because of the hyperosmotic intracellular conditions, ice crystals do not form until -5°C to -10°C. The transformation of water to ice concentrates the extracellular solutes and results in an osmotic gradient across the cell membrane, causing further damage 1.

    Slow freezing produces extracellular ice formation whereas rapid freezing produces intracellular ice formation and thus maximizing cell damage due to rupture of cells during thawing 2. Simultaneous with rapid freezing, repeated freeze-thaw cycles are more effective than a single long freezing period 2.

    In each freeze-thaw cycle more cell damage is initiated, and the constantly changing osmotic potential of the cells results in fluid movement of the cells3. Epithelial cells as such as keratocytes and melanocytes are more susceptible to freezing than the collagen fibres and fibroblasts in the underlying dermis. Keratinocytes require a fast freeze to lethal temperatures at -20 to -30 °C 2.

    Melanocytes are more delicate and only require a temperature at -4 to -7ºC for cell destruction 2. This fact is the reason for the resulting hypopigmentation following cryotherapy on darker-skinned individuals 1. Malignant lesions usually require a temperature of -50° C, while benign lesions only require a temperature of -20°C to -30°C 2,4.

    Hydrozid demonstrably delivers temperatures of about -50º Celsius to the area of treatment 5. This is optimal to perform cryotherapy and cryosurgery as it ensures cell death through the rapid formation of through the formation of the intra- and extracellular ice crystals and, at the same time, avoid the risk of scarring associated with the lower freeze temperatures

    1. Sharma VK, Khandpur S. Guidelines for cryotherapy. IJDVL Indian Journal of Dermatology, Venereology and Leprology 2009; 75: 90-100

    2. Graham GF, Tuchay SM. Chapter 32 Therapeutic Principles and Techniques in a W. Abramovits et al. (eds.), Dermatological Cryosurgery and Cryotherapy. Springer-Verlag London 2016.

    3. Kaouk JH, Aron M, Rewcastle JC, Gill IS.Cryotherapy: clinical endpoints and their experimental foundations. Urology. 2006 Jul;68(1 Suppl):38-44

    4. Mayeaux Jr EJ. The Essential Guide to Primary Care Procedures. 2nd Edition. June 2015

    5. Danish Technical Institute (DTI). Hydrozid Evaporation Temperature Measurement when applied to a Surface. January 2018

  3. Inflammation

    The last response to cryotherapy is inflammation, which is usually observed as erythema or redness of the skin or mucous membranes and swelling (oedema) 1. Inflammation is the response to cell death and helps in local cell destruction.

    1. Graham GF, Tuchay SM. Chapter 32 Therapeutic Principles and Techniques in a W. Abramovits et al. (eds.), Dermatological Cryosurgery and Cryotherapy. Springer-Verlag London 2016.