Gangrene

Gangrene
Synonyms	Gangrenous necrosis
Dry gangrene affecting the toes as a result of peripheral artery disease
Specialty	Infectious disease, general surgery
Risk factors	Diabetes, atherosclerosis, peripheral arterial disease, Raynaud syndrome[1]

Gangrene is a type of necrosis caused by a critically insufficient blood supply.^[2][1] This potentially life-threatening condition may occur after an injury or infection, or in people suffering from any chronic health problem affecting blood circulation.^[1] The primary cause of gangrene is reduced blood supply to the affected tissues, which results in cell death.^[3] Diabetes and long-term smoking increase the risk of gangrene.^[1][3]

Gangrene is not a communicable disease; it does not spread from person to person, though the infection associated to some forms can. The types of gangrene differ in symptoms, and include dry gangrene, wet gangrene, gas gangrene, internal gangrene, and necrotizing fasciitis.^[2][1] Surgical removal of gangrenous tissue and antibiotics are the mainstays of treatment for gangrene.^[4] After the gangrene is treated, the underlying cause is addressed. This includes lifestyle modification such as smoking cessation, better control of diabetes, revascularization or, rarely, medical therapy to stop vascular spasm or the production of cold-induced vascular obstruction by cold-precipitated cryoglobulins.

Causes

Gangrene is caused by a critically insufficient blood supply (e.g., peripheral vascular disease) or infection.^[3][5][6] It is associated with diabetes^[7] and long-term tobacco smoking.^[1][3] This condition most commonly occurs in the lower extremities (legs and feet).

Types

An illustration showing four different stages of gangrene, including one (Fig. 4 top right) caused by an obstacle to the return of the venous blood due to heart disease.

Dry

Dry gangrene is a form of coagulative necrosis that develops in ischemic tissue, where the blood supply is inadequate to keep tissue viable. Dry gangrene is often due to peripheral artery disease, but can be due to acute limb ischemia. The limited oxygen in the ischemic limb limits putrefaction and bacteria fail to survive. The affected part is dry, shrunken and dark reddish-black. The line of separation usually brings about complete separation, with eventual falling off of the gangrenous tissue if it is not removed surgically, a process called autoamputation.

Dry gangrene is the end result of chronic ischemia without infection. If ischemia is detected early, when ischemic wounds rather than gangrene are present, the process can be treated by revascularization (via vascular bypass or angioplasty). However, once gangrene has developed, the affected tissues are not salvageable.

Diabetes mellitus is a risk-factor for peripheral vascular disease and thus for dry gangrene, but also a risk factor for wet gangrene, particularly in patients with poorly controlled blood-sugars, as elevated serum glucose creates a favorable environment for bacterial infection.^[8]

Wet

Wet gangrene of the foot

Wet, or infected, gangrene is characterized by thriving bacteria and has a poor prognosis (compared to dry gangrene) due to sepsis resulting from the free communication between infected fluid and circulatory fluid. In wet gangrene, the tissue is infected by saprogenic microorganisms (Clostridium perfringens or Bacillus fusiformis, for example), which cause tissue to swell and emit a fetid smell. Wet gangrene usually develops rapidly due to blockage of venous (mainly) or arterial blood flow. The affected part is saturated with stagnant blood, which promotes the rapid growth of bacteria. The toxic products formed by bacteria are absorbed, causing systemic manifestation of sepsis and finally death. The affected part is edematous, soft, putrid, rotten, and dark.

Because of the high mortality associated with infected gangrene, an emergency salvage amputation, such as a guillotine amputation, is often needed to limit systemic effects of the infection.^[9] Such an amputation can be converted to a formal amputation, such as a below or above knee amputation.^[9]

Gas

Gas gangrene is a bacterial infection that produces gas within tissues. It can be caused by Clostridium, most commonly alpha toxin-producing C. perfringens, or various nonclostridial species.^[6][10] Infection spreads rapidly as the gases produced by bacteria expand and infiltrate healthy tissue in the vicinity. Because of its ability to quickly spread to surrounding tissues, gas gangrene should be treated as a medical emergency.

Gas gangrene is caused by bacterial exotoxin-producing clostridial species, which are mostly found in soil, and other anaerobes such as Bacteroides and anaerobic streptococci. These environmental bacteria may enter the muscle through a wound and subsequently proliferate in necrotic tissue and secrete powerful toxins, which destroy nearby tissue, generating gas at the same time. A gas composition of 5.9% hydrogen, 3.4% carbon dioxide, 74.5% nitrogen, and 16.1% oxygen was reported in one clinical case.^[11]

Gas gangrene can cause necrosis, gas production, and sepsis. Progression to toxemia and shock is often very rapid.

Other

• Necrotizing fasciitis is an infection that spreads deep into the body along tissue planes.
• Noma is a gangrene of the face.
• Fournier gangrene is a type of necrotizing fasciitis that usually affects the genitals and groin.^[12]
• Venous limb gangrene may be caused by heparin-induced thrombocytopenia and thrombosis (HITT).^[13]
• Severe mesenteric ischemia may result in gangrene of the small intestine.
• Severe ischemic colitis may result in gangrene of the large intestine.

Treatment

Surgical removal of all dead tissue is the mainstay of treatment for gangrene. Often, gangrene is associated with underlying infection, and thus the gangrenous tissue must be debrided to hinder the spread of the associated infection. The extent of surgical debridement needed depends on the extent of the gangrene, and may be limited to the removal of a finger, toe, or ear, but in severe cases may involve a limb amputation

Dead tissue alone does not require debridement, and in some cases, such as dry gangrene, the affected falls off (auto-amputates), making surgical removal not necessary.

As there is often infection associated with gangrene, antibiotics are often a critical component of the treatment of gangrene. The life-threatening nature of gangrene requires treatment with intravenous antibiotics in an inpatient setting.

After the gangrene is treated with debridement and antibiotics, the underlying cause of gangrene can be treated. In the case of gangrene due to critical limb ischemia, revascularization can be performed to treat the underlying peripheral artery disease.

Most amputations are performed for ischemic disease of the lower extremity. Of dysvascular amputations, 15–28% of patients undergo contralateral limb amputations within 3 years. Of elderly persons who undergo amputations, 50% survive the first 3 years.^[14]

In the United States, 30,000–40,000 amputations are performed annually. An estimated 1.6 million individuals are living with the loss of a limb in 2005; these estimates are expected to more than double to 3.6 million such individuals by 2050.^[15] Antibiotics alone are not effective because they may not penetrate infected tissues sufficiently.^[16] Hyperbaric oxygen therapy (HBOT) treatment is used to treat gas gangrene. HBOT increases pressure and oxygen content to allow blood to carry more oxygen to inhibit anaerobic organism growth and reproduction.^[17] A regenerative medicine therapy was developed by Dr. Peter DeMarco to treat diabetic gangrene to avoid amputations. Growth factors, hormones, and skin grafts have also been used to accelerate healing for gangrene and other chronic wounds.

Angioplasty should be considered if severe blockage in lower leg vessels (tibial and peroneal artery) leads to gangrene.^[18]

History

Confederate Army Private Milton E. Wallen lies in bed with a gangrenous amputated arm

As early as 1028, fly maggots were commonly used to treat chronic wounds or ulcers to prevent or arrest necrotic spread,^[19] as some species of maggots consume only dead flesh, leaving nearby living tissue unaffected. This practice largely died out after the introduction of antibiotics, acetonitrile and enzyme to the range of treatments for wounds. In recent times, however, maggot therapy has regained some credibility and is sometimes employed with great efficacy in cases of chronic tissue necrosis.

The French Baroque composer Jean-Baptiste Lully contracted gangrene in January 1687 when, while conducting a performance of his Te Deum, he stabbed his own toe with his pointed staff (which was used as a baton). The disease spread to his leg, but the composer refused to have his toe amputated, which eventually led to his death in March of that year.^[20]

Former king of France Louis XIV died of gangrene in his leg on 1 September 1715, just before his 77th birthday, after reigning for 72 years.^[21]

John M. Trombold wrote: "Middleton Goldsmith, a surgeon in the Union Army during the American Civil War, meticulously studied hospital gangrene and developed a revolutionary treatment regimen. The cumulative Civil War hospital gangrene mortality was 45 percent. Goldsmith's method, which he applied to over 330 cases, yielded a mortality under 3 percent."^[22]Goldsmith advocated the use of debridement and topical and injected bromide solutions on infected wounds to reduce the incidence and virulence of “poisoned miasma.” Copies of his book^[23] were issued to Union surgeons to encourage the use of his methods.^[24]

Etymology

The etymology of gangrene derives from the Latin word gangraena and from the Greek gangraina (γάγγραινα), which means "putrefaction of tissues".^[25] It has no etymological connection with the word green, despite the affected areas turning black, green, or yellowish brown. It is coincidence that, in Lowland Scots, the words "gang green" (go green) can be said to be an eggcorn for gangrene, as it describes the symptoms of the affliction.

See also

• Allan Pinkerton, one of the co-founders of the Pinkerton Detective Agency, who succumbed to gangrene of the tongue after slipping on the sidewalk.

References

External links

• Media related to Gangrene at Wikimedia Commons