Physiology

Human cold stress should induce adaptive behavioral reactions such as an attempt to find heat or shelter. In addition, complex endocrinologic and cardiovascular physiologic responses are engaged. Peripheral cooling of the blood activates the preoptic anterior hypothalamus. This central thermostat orchestrates temperature regulation. This dynamic process encompasses catecholamine release, thyroid stimulation, shivering thermogenesis, and peripheral vasoconstriction.

Cutaneous circulation is one of the keys to maintenance of thermoneutrality. Baseline cutaneous circulation greatly exceeds the nutritional requirements. This reflects the skin’s “radiator” function to maintain thermostability. Cutaneous blood flow in the euthermic 70-kg human averages 200 to 250 mL/min. Heat stress causes vasodilation that can increase this amount to 7000 mL/min. In contrast, extreme cold-induced vasoconstriction reduces flow tenfold to less than 50 mL/min.

During cold stress, peripheral vasoconstriction limits radiant heat loss. Acral skin structures (fingers, toes, ears, nose) contain a plethora of arteriovenous anastomoses. These arteriovenous anastomoses shut down in the cold, causing drastic reductions in blood flow. This “life-versus-limb” mechanism reflects the homeostatic attempt to prevent systemic hypothermia.

In contrast to heat exposure, humans do not appear to display significant physiologic adaptation to the cold. Exposure of extremities to temperatures down to 15° C results in maximal peripheral vasoconstriction with minimal blood flow. Continued exposure to progressively colder temperatures down to 10° C produces the “hunting response,” which is cold-induced vasodilation.²² These periods of vasodilation, recurring in 5- to 10-minute cycles, interrupt vasoconstriction and serve to protect the extremity. Eskimos as well as Lapps and others of Nordic extraction are capable of stronger cold-induced vasodilation than that in individuals from tropical regions. Measurement of the speed of cold-induced vasodilation may help predict an individual’s risk for cold injury.²³ There is evidence of adaptation rather than pure genetic control.²⁴

Pathophysiology

The pathologic phases that occur with local cold injury often overlap and vary with the extent and rapidity of the cold response (Box 139-1). Frostbite occurs when the tissue supercools well below 0° C. The required temperature is at least −4° C and may be as low as −10° C.

There are two putative mechanisms of tissue injury: architectural cellular damage from ice crystal formation and microvascular thrombosis and stasis.²⁵ In the prefreeze phase, tissue temperatures drop below 10° C and cutaneous sensation is lost. Before ice crystal formation, microvascular vasoconstriction occurs along with endothelial leakage of plasma into the interstitium. Radiation and conduction of heat from deeper tissues prevent crystallization until the skin temperature drops well below 0° C.²⁶ In the freeze-thaw phase, the timing, location, and rate of ice crystal formation depend on the exposure circumstances. In addition to ambient temperatures, wind and moisture increase the freezing rate.

During usual exposure conditions, ice crystal formation initially occurs extracellularly. This results in diapedesis of water exiting the cell to maintain osmotic equilibrium. Cellular dehydration increases the intracellular osmolarity and electrolyte concentrations. When approximately one third of the cellular volume is lost, cellular collapse and death result. These may occur with or without direct architectural damage from the crystals. Extracellular crystallization also increases the tissue pressure on cell membranes and surrounding vascular structures. Sludging, stasis, and cessation of flow occur at the capillary level.

The third phase, progressive microvascular collapse, first affects venules and then arterioles. Red blood cells sludge and form microthrombi during the first few hours after the tissues are thawed. Factors adversely affecting flow include hypoxic vasospasm, hyperviscosity, and direct endothelial cell damage. Anaerobic metabolism subsequently extends the surrounding injury. Tissues are deprived of nutrients and oxygen. Ultimately, plasma leakage and arteriovenous shunting result in thrombosis, increased tissue pressure, ischemia, and necrosis.

Some direct skin injury is reversible. For example, frozen skin grafted to a normal site can survive. The histopathology of frostbite suggests that some changes in the epidermis are primary and some reflect damage to the endothelial cells. During initiation of rewarming, these tissues are revitalized.

An additional insult, progressive dermal ischemia, is partially mediated by thromboxane.²⁷ Fluid analysis of clear vesicles identifies prostaglandins. When subdermal vascular plexuses are injured, hemorrhagic blisters develop that also contain these prostanoids. The arachidonic acid breakdown products released from underlying damaged tissue into the blister fluid include both prostaglandins and thromboxane. These mediators produce platelet aggregation, vasoconstriction, and leukocyte immobilization.²⁸

The ultimate determinant of progressive tissue damage appears to be injury to the microvasculature. Endothelial cells are the tissue most susceptible to freezing injury. After thawing, the vasculature is patent only temporarily. Platelet and erythrocyte aggregates promptly clog and distort the vasculature. Intense vasoconstriction coupled with arteriovenous shunting occurs at the interface between normal and damaged tissue. The injured viable vasculature remains distorted. Local arteritis, medial degeneration, and intimal proliferative thickening are seen. Nerve and muscle tissues are also more susceptible than connective tissue to cold injury. For example, nonviable hands and feet can be moved after thawing if the tendons are intact.

Edema progresses for 48 to 72 hours after tissue is thawed. Leukocyte infiltration, thrombosis, and early necrosis become apparent as this edema resolves. The dry gangrene carapace of frostbite is superficial in comparison to arteriosclerosis-induced, full-thickness gangrene. Although the historical surgical aphorism was “frostbite in January, amputate in July,” advances in imaging modalities can accelerate the identification of the demarcation between viable and nonviable tissue.²¹

Predisposing Factors

The extent of peripheral cold injury is determined by the type and duration of cold contact with the skin (Box 139-2).²⁹ Predisposing risks include physiologic, mechanical, psychological, environmental, and cardiovascular factors.

Any conditions affecting judgment can jeopardize the physiologically tropical human. In urban settings, cold injuries are often attributed to psychiatric impairment or intoxication, primarily ethanol intoxication. Ethanol also produces peripheral vasodilation, which increases heat loss. Blunting of self-protective instincts can cause people to fail to undertake appropriate adaptive maneuvers to minimize exposure to cold.

Although air alone is a poor thermal conductor, associated cold and wind (wind chill index) markedly increase heat loss. Direct skin contact with good thermal conductors such as metal, water, and volatile liquids affects the extent and rapidity of tissue destruction. Commercial aerosol spray propellants, such as propane and butane, and carbon dioxide in fire extinguishers are potentially hazardous.³⁰ Liquid oxygen and Freon can also cause frostbite.^31,32 Overenthusiastic application of standard ice packs in the treatment of soft tissue injuries can also result in tissue loss.³³ Cryotherapy is commonly prescribed in sports medicine. In addition to improper use of cold packs, vapor coolant sprays such as chloroethane can cause frostbite.^34,35

Symptoms and Signs

“Frostnip” is a superficial cold insult manifested by transient numbness and tingling that resolves after rewarming. This does not represent true frostbite because no tissue destruction occurs.

The symptoms of frostbite usually reflect the severity of the exposure. The most common presenting symptom is numbness, found in more than 75% of patients. All patients have some initial sensory deficiency in light touch, pain, or temperature. Anesthesia is produced by intense vasoconstrictive ischemia and neurapraxia. Acral areas and distal extremities are the usual insensate sites. The distal extremities—the fingers, toes, nose, ears, and penis—are specific locations at risk. Patients often complain of clumsiness and report a “chunk of wood” sensation in the extremity. The history of complete acute anesthesia in a painful cold digit suggests a severe injury.

Classically, the initial presentation of frostbite is deceptively benign. Most patients do not arrive in the emergency department with frozen, insensate tissue. Frozen tissues often appear mottled or violaceous-white, waxy, or pale yellow. In severe cases, the examiner will not be able to roll the dermis over bone prominences. Rapid rewarming results in an initial hyperemia, even in severe cases. After thawing, partial return of sensation should be expected until blebs form.²¹

Favorable initial symptoms include normal sensation, warmth, and color. Soft, pliable subcutaneous tissue suggests a superficial injury. A residual violaceous hue after rewarming is ominous. Early formation of clear large blebs that extend to the tips of the digits is more favorable than delayed appearance of smaller hemorrhagic blebs. These dark vesicles are produced by damage to the subdermal vascular plexuses. Vesicles and large bullae usually form in 1 to 24 hours.

Lack of edema formation suggests significant tissue damage. Post-thaw edema usually develops in less than 3 hours. In severe cases, frostbitten skin forms an early black, dry eschar until mummification and apparent demarcation.

Historically, frostbite, like burns, has been classified into degrees of injury. Anesthesia and erythema are characteristic of first-degree frostbite. Superficial vesiculation surrounded by edema and erythema is considered second-degree frostbite. Third-degree frostbite produces deeper hemorrhagic vesicles. Fourth-degree injuries extend into subcuticular, osseous, and muscle tissues.

Classification by degrees is often incorrect in relation to the actual severity of the frostbite and thus therapeutically misleading. Mills suggests two simple retrospective classifications.20,21 Superficial or mild frostbite does not entail eventual tissue loss, whereas deep or severe frostbite does result in tissue loss. As a result, it is not feasible to predict, on presentation, the eventual tissue loss. Another classification attempts to establish severity on the basis of clinical features coupled with early bone scan results.^17,36 Significant pain usually accompanies reestablishment of perfusion. With partial tissue destruction, intermittent pain may be noticed during ongoing exposure. The dull continuous ache evolves into a throbbing sensation in 48 to 72 hours. This often persists until tissue demarcation several weeks to months later. Nonfreezing cold injury occurs when tissue fluids have not frozen. Chilblain (pernio) is a mild form of cold injury that often follows repetitive exposure. These “cold sores” appear less than 24 hours after exposure and usually affect facial areas, the dorsa of the hands and feet, and the pretibial areas. Young women with a history of Raynaud’s phenomenon or systemic lupus erythematosus or with antiphospholipid antibodies are especially at risk. Persistent vasospasm and vasculitis result in burning, pruritus, erythema, and mild edema. Plaques, blue nodules, and ulcerations can develop and last 1 to 2 weeks.

The other common nonfreezing cold injury is trench foot (immersion foot). This remains a significant threat during recreational activities and military expeditions in cold, wet climates. Trench foot is produced by prolonged exposure to wet cold at temperatures above freezing.⁶ It usually develops slowly during several days and results in neurovascular damage in the absence of ice crystal formation. Immersion foot commonly develops while a person is wearing sweat-dampened or neoprene socks, vapor-barrier boots, or constrictive gaiters. Patients who soak their feet for hours each night in cool water for pain relief are also at risk.

The clinical presentation varies. Most patients’ symptoms include cool, pale feet that are numb or tingle. Later the feet appear cyanotic, cold, and edematous. Often, numbness and leg cramping are present. The clinical hallmark is that after rewarming, the skin remains erythematous, dry, and very painful to touch. Rubor on dependency and pallor on elevation are caused by vasomotor paralysis. Infrared thermography in response to a cold stress may support the diagnosis and assess its severity.¹⁷

Bullae that are indistinguishable from those seen with frostbite commonly develop. Vesiculation may proceed to ulceration and liquefaction gangrene in severe cases. Protracted symptoms of pain during weightbearing, cold sensitivity, and hyperhidrosis often last for years. Prevention of trench foot often requires continual drying of socks.