Gangrene

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Gangrene is the "death and putrefaction of tissue usually due to a loss of blood supply."[1] While it is often assumed to be a result of direct infection, especially with Clostridium perfringens, it certainly is not limited to a toxin-producing bacterium such as Cl. perfringens. It can be secondary to completely or partially blocked blood vessels, or blood vessels that are so damaged that they cannot function properly, or even to blood vessel spasm caused by chemicals in the body (e.g., thromboxane).

A distinction is sometimes made between "wet gangrene" is caused by bacteria that destroy body tissue, and dry gangrene caused by noninfectious interference with blood supply. Blurring into "gangrene" are conditions such as necrotizing fascitis, popularly called "flesh-eating bacteria", where the bacteria, such as Streptococcus pyogenes in necrotizing cellulitis and Fournier gangrene, are directly destroying tissue and blood vessels.

Differential diagnosis

While it may initially present as cellulitis, factors to increase the index of suspicion include pain disproportionate to visible damage, and general systemic disorders such as hypotension.

Treatment

The core of conventional medical treatment is to remove, surgically or by other means, clearly dead tissue whose breakdown products will aggravate the systemic condition. Beyond that, a wide variety of methods are used to improve blood supply, or at least the functions impaired by inadequate blood supply.[2] Steps are taken to address the causes. For example, anticoagulants are used to prevent blood from clotting, and surgery restores blood supply to the affected part of the body. If infection is present, antibiotics will be considered necessary, and sometimes, hyperbaric oxygen treatment is used.Gangrene bbc.co.uk Health</ref>

Improving circulatory function

If the blood supply is caused by a blockage in a blood vessel, thrombolytic drugs may be used to dissolve it, perhaps in combination with endovascular interventions ranging from angioplasty to stenting to atherectomy to endovascular removal of the obstruction. It may be necessary to graft a bypassing blood vessel, using natural or synthetic materials, around the area of blockage.

Supporting cirulation

During treatment, hyperbaric oxygen therapy may be able to increase the oxygenation of the dying tissue. If a compartment syndrome, as in Fournier's, is blocking blood flow, surgical opening of the body compartment can release the pressure occluding the blood flow, and return normal circulation.

Treating the cause of destruction

When the tissue death is due to an infectious process, appropriate drugs are used. Surgical debridement of dead tissue remains a mainstay of treatment.

Antitoxins

In some cases, the actual cellular damage is being caused by an exotoxin, and neutralization of that toxin or related chemical messengers (e.g., tumor necrosis factor-alpha is appropriate.

Antibiotics

In other cases, when an infection is the cause, antibiotics are appropriate, but almost always in combination with surgery. Given that gangrene is a medical emergency, empirical antibiotic therapy is often appropriate to start in the emergency room and as a preparation for surgery. Tissue samples taken during surgery can guide antibiotic choice.

The assumption in empirical treatment is that Clostridia are the causative agents. Since that is not a given, the initial therapy should cover Gram-positive, pathogenic anaerobes, and Gram-negative forms, and should be intravenous.

Empirical antibiotics[2]
Agent Coverage Comments
Penicillin G Gram-positive, penicillin sensitive Use alternatives, such as ceftriaxone or vancomycin, if community experience shows strong penicillin resistance
Ceftriaxone Broad-spectrum; greatest activity against Gram-negative forms, but with lower efficacy against gram-positive organisms although higher efficacy against resistant Gram-positive organisms Alternative to vancomycin in sensitive patients
Gentamicin Principally gram-negative Not first-line drug
Clindamycin Gram-positive and some Gram-negative activity Especially appropriate if Staphylococcus or Streptococcus are suspected, but not Enterococcus
Linezolid Enterococcus, Staphylococcus, and bactericidal against most Streptococcus Alternative to vancomycin in sensitive patients
Metronidazole Anaerobes

Homeopathic treatment

Some homeopathic treatments have been used. [3] homeopathic remedies are prescribed in the belief that they will strengthen a person's own defenses and to initiate healing. Some homeopathic remedies for gangrene include Arsenicum Album, Secale (from rye/ergot), and Carbo vegetabilis (from charcoal), amongst many others[4]. Ergot preparations are strong vasoconstrictors that can cause chemically-induced gangrene, hence their use as a homeopathic similar.

Specific syndromes

Clostridia

Clostridium perfringens are most often associated with gas gangrene, but this condition also can be due to related species, including Cl. septicum and Cl. novyi. cause most of the cases.[2] They are likely to be in the wound, but also can transfer toxins from a distant site.

The mechanism of destruction appears to involve collagenases, which require a C-terminal collagen-binding domain (CBD) of these enzymes as the minimal segment required to bind to collagen fibril. Collagen binding efficiency of CBD is more pronounced in the presence of [calcium|Ca++ ion]]. [5]

References

  1. Anonymous (2023), Gangrene (English). Medical Subject Headings. U.S. National Library of Medicine.
  2. 2.0 2.1 2.2 Anil Shukla, Carlo L Rosen, Jason K Wong (December 4, 2007), "Gas Gangrene", eMedicine
  3. "Gangrene (for laymen)", BBC healty
  4. , Gangrene, Homeopathy for everyone
  5. Philominathan ST, Koide T, Hamada K, Yasui H, Seifert S, Matsushita O, Sakon J. (2009 Feb 10 (epub)), "Unidirectional binding of clostridial collagenase to triple helical substrates", J Biol Chem