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Gas gangrene (also known as clostridial myonecrosis and myonecrosis) is a
bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were am ...
l
infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable di ...
that produces tissue gas in
gangrene Gangrene is a type of tissue death caused by a lack of blood supply. Symptoms may include a change in skin color to red or black, numbness, swelling, pain, skin breakdown, and coolness. The feet and hands are most commonly affected. If the gan ...
. This deadly form of gangrene usually is caused by '' Clostridium perfringens'' bacteria. About 1,000 cases of gas gangrene are reported yearly in the United States. Myonecrosis is a condition of
necrotic Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated dige ...
damage, specific to
muscle tissue Muscle tissue (or muscular tissue) is soft tissue that makes up the different types of muscles in most animals, and give the ability of muscles to contract. Muscle tissue is formed during embryonic development, in a process known as myogenesis. ...
. It is often seen in infections with ''C. perfringens'' or any of myriad soil-borne
anaerobic bacteria An anaerobic organism or anaerobe is any organism that does not require molecular oxygen for growth. It may react negatively or even die if free oxygen is present. In contrast, an aerobic organism (aerobe) is an organism that requires an oxygenat ...
. Bacteria cause myonecrosis by specific
exotoxin An exotoxin is a toxin secreted by bacteria. An exotoxin can cause damage to the host by destroying cells or disrupting normal cellular metabolism. They are highly potent and can cause major damage to the host. Exotoxins may be secreted, or, sim ...
s. These
microorganism A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is sometimes hyphenated (''micro-organism''), especially in old ...
s are opportunistic and, in general, enter the body through significant skin breakage. Gangrenous infection by soil-borne bacteria was common in the combat injuries of soldiers well into the 20th century, because of non-sterile
field surgery Battlefield medicine, also called field surgery and later combat casualty care, is the treatment of wounded combatants and non-combatants in or near an area of combat. Civilian medicine has been greatly advanced by procedures that were first ...
and the basic nature of care for severe projectile wounds. Other causes of myonecrosis include
envenomation Envenomation is the process by which venom is injected by the bite or sting of a venomous animal. Many kinds of animals, including mammals (e.g., the northern short-tailed shrew, ''Blarina brevicauda''), reptiles (e.g., the king cobra), spiders ...
by snakes of the genus '' Bothrops'' (family
Viperidae The Viperidae (vipers) are a family of snakes found in most parts of the world, except for Antarctica, Australia, Hawaii, Madagascar, and various other isolated islands. They are venomous and have long (relative to non-vipers), hinged fangs th ...
), ischemic necrosis, caused by vascular blockage (e.g., diabetes type II),
tumour A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
s that block or hoard blood supply, and
disseminated intravascular coagulation Disseminated intravascular coagulation (DIC) is a condition in which blood clots form throughout the body, blocking small blood vessels. Symptoms may include chest pain, shortness of breath, leg pain, problems speaking, or problems moving parts ...
or other thromboses.


Presentation

Gas gangrene can cause myonecrosis (muscle tissue death), gas production, and
sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
. Progression to toxemia and
shock Shock may refer to: Common uses Collective noun *Shock, a historic commercial term for a group of 60, see English numerals#Special names * Stook, or shock of grain, stacked sheaves Healthcare * Shock (circulatory), circulatory medical emerge ...
is often very rapid. It can easily be noticed by the large, blackened sores that form, as well as a degree of loud and distinctive crepitus caused by gas escaping the necrotic tissue.


Symptoms

A multitude of symptoms is associated with Gas gangrene. Distinctively, black lesions on the skin appear in a bubble form which allows visualization of gas-producing bacteria. Symptoms include: * Skin discoloration * "Foul, sweet" smelling discharge from lesions formed on skin * Distinctive black, bubble lesions on skin * Necrosis * Fever * Pain following site of surgery or trauma * Lightheadedness * Rapid heart rate * Numbness on affected site * Blisters * Air in subcutaneous tissues * Swelling * Jaundice


Etiology

''Clostridium'' species produce more toxins and exhibit higher degrees of
virulence Virulence is a pathogen's or microorganism's ability to cause damage to a host. In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its ability to ...
than any other bacterial taxon. ''Clostridium'' infections are usually opportunistic, and occur in individuals with serious preexisting medical conditions. However, ''Clostridium'' infections are also known to occur in healthy individuals. Four species of ''Clostridium'' (''Clostridium botulinum'', ''Clostridium perfringens'', ''Clostridium tetani'', and ''Clostridium sordelli'') are responsible for most human infections. Since ''Clostridium'' is an obligate anaerobe taxon, the bacterium infects hypoxic tissues, which had become anaerobic due to restricted blood flow, degradation of blood vessels, or
atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheromatous plaque. At onset there are usually no s ...
. Immunocompromised individuals exhibit higher susceptibility for infection and higher mortality rates.


Virulence factors

Members of the ''Clostridium'' species exhibit a plethora of virulence factors. Common virulence factors associated with gas gangrene include alpha toxin and theta toxin. ''Clostridium perfingens'' causes 80–90% of infections and produces both these toxins. ; Alpha toxin (α-toxin) ''Clostridium perfingens'' alpha toxin is widely associated with gas gangrene as it is its main virulence factor whilst invading its host. Alpha toxin is associated with hemolysis, thus restricting blood flow towards the area of infection. As the surrounding circulatory system collapses, neutrophils and monocytes, eosinophils and basophils cannot reach target areas of infection. The hemolytic activity of alpha toxin produces an anaerobic environment essential for the proliferation of the bacteria. Alpha toxin also exhibits the ability to infiltrate surrounding cellular tissue and cause a cascade of aberrant biochemical activity. ; Theta toxin (Θ-toxin) Theta toxin is also employed by ''Clostridium perfingens'' as a virulence factor. Theta toxin also promotes vascular degradation as its counterpart alpha toxin. A platelet-activation factor is employed which triggers an acute inflammatory response in nearby tissues. This inflammatory response leads to constriction of surrounding arteries and promotes an anaerobic environment for ''Clostridium perfingens'' growth and pathophysiology. ; Beta toxin (β-toxin) Beta toxin is an integral virulence factor in promoting enterocolitics and enterotoxemia. This toxin uses pores in the cellular biolipid membrane to import a pathogenic factor into organisms.


Pathophysiology

Gas gangrene is caused by
exotoxin An exotoxin is a toxin secreted by bacteria. An exotoxin can cause damage to the host by destroying cells or disrupting normal cellular metabolism. They are highly potent and can cause major damage to the host. Exotoxins may be secreted, or, sim ...
-producing ''
Clostridium ''Clostridium'' is a genus of anaerobic, Gram-positive bacteria. Species of ''Clostridium'' inhabit soils and the intestinal tract of animals, including humans. This genus includes several significant human pathogens, including the causative a ...
'' species (most often '' C. perfringens'', and '' C. novyi'', but less commonly '' C. septicum'' or '' C. ramnosum''), which are mostly found in soil, but also found as normal
gut flora Gut microbiota, gut microbiome, or gut flora, are the microorganisms, including bacteria, archaea, fungi, and viruses that live in the digestive tracts of animals. The gastrointestinal metagenome is the aggregate of all the genomes of the gut m ...
, and other
anaerobe An anaerobic organism or anaerobe is any organism that does not require molecular oxygen for growth. It may react negatively or even die if free oxygen is present. In contrast, an aerobic organism (aerobe) is an organism that requires an oxygenate ...
s (e.g., ''
Bacteroides ''Bacteroides'' is a genus of Gram-negative, obligate anaerobic bacteria. ''Bacteroides'' species are non endospore-forming bacilli, and may be either motile or nonmotile, depending on the species. The DNA base composition is 40–48% GC. Unus ...
'' and anaerobic
streptococci ''Streptococcus'' is a genus of gram-positive ' (plural ) or spherical bacteria that belongs to the family Streptococcaceae, within the order Lactobacillales (lactic acid bacteria), in the phylum Bacillota. Cell division in streptococci occu ...
). Bacterium of the Clostridial species produce two toxins: alpha and theta toxins, which cause necrotizing damage to tissues. Other organisms may occasionally cause gas gangrene (for example, '' Klebsiella pneumoniae'' in the context of
diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...
). A gas composition of 5.9% hydrogen, 3.4% carbon dioxide, 74.5% nitrogen, and 16.1% oxygen was reported in one clinical case. Myonecrosis differs slightly from other types of necrosis. While the underlying causes are almost identical, the type of affected tissue (in particular, muscle tissue) is significantly more important for the patient's general health. Superficial necrosis is unsightly and can lead to unattractive scarring, but otherwise does not affect the patient's likelihood of survival or physical capability to the same extent. However, massive myonecrosis will likely result in the loss of movement of the entire region. If the necrotic damage is allowed to continue throughout an affected limb, then often that entire limb is lost permanently. It is often difficult to identify the extent of muscle damage, as ''C. perfringens'' may be at work in deeper fascial layers below the skin. Unlike other anaerobic infections, discharge in these infections is often not purulent (filled with pus). Instead, the discharge is often described as "sweetly putrid" or "dishwater pus" because it is much thinner than normal pus. This is due to the
lysis Lysis ( ) is the breaking down of the membrane of a cell, often by viral, enzymic, or osmotic (that is, "lytic" ) mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a ''lysate''. In molecular b ...
of
neutrophil Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying ...
s, a type of white blood cell, caused by the lecithinases and other toxins released by ''Clostridium'' species. Soil-borne anaerobes are particularly well-adapted to surviving harsh conditions. Often, a scarcity of nutrition and competition for resources from numerous other species occurs. Changes in pH and temperature are often significant, also. Bacteria often possess the ability to create exotoxins to assist them in competing with other microbes in their natural environments. When such bacteria are able to enter a living host, they encounter a vast supply of nutrients, warm conditions, and an abundance of water. This enables the microbes to rapidly proliferate, far in excess of the immune system's capability to defend, as prokaryotic bacteria possess a far greater capacity for multiplication than the host's immune system. The combination of bacterial load and ability to multiply is the basis for the microbes' ability to cause massive infection. Alongside such rapid proliferation is a corresponding mass-production of exotoxin that causes severe damage to local tissue in the host. One such exotoxin is alpha toxin, which is produced by ''C. perfringens'' and is the key
virulence factor Virulence factors (preferably known as pathogenicity factors or effectors in plant science) are cellular structures, molecules and regulatory systems that enable microbial pathogens (bacteria, viruses, fungi, and protozoa) to achieve the following ...
in its pathogenesis. Massive infection, gross injury, and depletion of the host's immune capability result in system-wide
sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
. This is partly due to the burden on the immune system, its corresponding release of inflammatory
cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in au ...
s, and the distribution of bacterial toxins. Massive infection is likely to result in death from a combination of system-wide
septic shock Septic shock is a potentially fatal medical condition that occurs when sepsis, which is organ injury or damage in response to infection, leads to dangerously low blood pressure and abnormalities in cellular metabolism. The Third International C ...
and the unintentionally damaging effects of the immune response. In animals, disability and distress caused by all of these factors markedly increase the chance of predation.


Diagnosis

Various diagnostic methods can be employed in the diagnosis of Gas gangrene. Due to low incidence of myonecrosis it is an easy-to-overlook diagnosis. As bacterial infections mostly exhibit the same symptoms, early diagnosis of gas gangrene rarely occurs. The ambiguous symptoms only contribute to a poorer prognosis. Diagnostic methods include: * Biopsy of affected tissue * Cultures of fluids from inflicted area * Magnetic resonance imaging to visualize necrotized subcutaneous tissues * X-rays for air pockets in affected tissues * Microscopy identification of strain of bacteria sampled from fluids of inflicted area * Gram stain


Treatment

Treatment is usually
debridement Debridement is the medical removal of dead, damaged, or infected tissue to improve the healing potential of the remaining healthy tissue. Removal may be surgical, mechanical, chemical, autolytic (self-digestion), and by maggot therapy. I ...
and excision, with
amputation Amputation is the removal of a limb by trauma, medical illness, or surgery. As a surgical measure, it is used to control pain or a disease process in the affected limb, such as malignancy or gangrene. In some cases, it is carried out on indi ...
necessary in many cases. Water-soluble
antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention ...
s (such as penicillin) alone are not effective because they do not penetrate ischaemic
muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of mus ...
s sufficiently to be effective. Penicillin is effective against ''C. perfringens''. When gas gangrene occurs in such regions as the abdominal cavity, the patient can be treated in a hyperbaric chamber, which contains a pressurized oxygen-rich atmosphere. The oxygen saturates the infected tissues and thereby prevents the growth of the obligately anaerobic clostridia. The growth of ''C. perfringens'' is inhibited when the
availability In reliability engineering, the term availability has the following meanings: * The degree to which a system, subsystem or equipment is in a specified operable and committable state at the start of a mission, when the mission is called for at ...
of oxygen is equivalent to a
partial pressure In a mixture of gases, each constituent gas has a partial pressure which is the notional pressure of that constituent gas as if it alone occupied the entire volume of the original mixture at the same temperature. The total pressure of an ideal g ...
of around 9–10 kPa (compare to 4–5 kPa in venous blood under normal conditions, with 11–13 kPa in arteries and 21 kPa in air at sea level), so if the treatment is started early, this condition can mostly be cured.


Prognosis

Gas gangrene left untreated is a potentially fatal infection. Early diagnosis of the type of infection and species causing the infection will improve prognosis tremendously. Preventive measures are employed universally through medical facilities to stymie bacterial infections in patients. Reducing the susceptibility of infection will promote a better prognosis by practicing good hygiene and preventing the contraction of diseases which produce hypoxia or an immunocompromised state. Following resolution of myonecrosis, patients will often require further care following the deleterious effects caused by the infection. Skin grafts are often required following removal of necrotic tissues. Former patients will still require hyperbaric oxygen therapy to prevent a recurring infection.


Epidemiology

''Clostridium'' species are found in abundance in soil, especially soil used for animal husbandry. In medical facilities, it thrives when unhygienic circumstances prevail. In the United States, the incidence of myonecrosis is only about 1,000 cases per year. During
World War I World War I (28 July 1914 11 November 1918), often abbreviated as WWI, was List of wars and anthropogenic disasters by death toll, one of the deadliest global conflicts in history. Belligerents included much of Europe, the Russian Empire, ...
and
World War II World War II or the Second World War, often abbreviated as WWII or WW2, was a world war that lasted from 1939 to 1945. It involved the World War II by country, vast majority of the world's countries—including all of the great power ...
, Clostridial myonecrosis was found in 5% of wounds, but with improvement in wound care, antisepsis and the use of
antibiotics An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and preventio ...
, the incidence had fallen to 0.1% of war-related wound infections by the
Vietnam War The Vietnam War (also known by #Names, other names) was a conflict in Vietnam, Laos, and Cambodia from 1 November 1955 to the fall of Saigon on 30 April 1975. It was the second of the Indochina Wars and was officially fought between North Vie ...
. With the best of care—including early recognition, surgical care, antibiotic treatment, and
hyperbaric oxygen therapy Hyperbaric medicine is medical treatment in which an ambient pressure greater than sea level atmospheric pressure is a necessary component. The treatment comprises hyperbaric oxygen therapy (HBOT), the medical use of oxygen at an ambient pressure ...
—the mortality rate is 20-30% and can be as low as 5-10%. If untreated, the disease has a 100% fatality rate.


Additional images

Image:Hemipelvectomy gas gangrene.jpg,
Hemipelvectomy Hemipelvectomy, also known as a pelvic resection, is a surgical procedure that involves the removal of portion of the pelvic girdle. This procedure is most commonly performed to treat oncologic conditions of the pelvis. Hemipelvectomy can be furthe ...
for gas gangrene Image:Gas gangrene pathology slide.jpg,
Muscle biopsy In medicine, a muscle biopsy is a procedure in which a piece of muscle tissue is removed from an organism and examined microscopically. A muscle biopsy can lead to the discovery of problems with the nervous system, connective tissue, vascula ...
examined under the microscope (haematoxylin-eosin stain, zoom 100×): the large white areas between the muscle fibers are due to gas formation. Image:Clostridium perfringens gas gangrene.jpg,
Gram stain In microbiology and bacteriology, Gram stain (Gram staining or Gram's method), is a method of staining used to classify bacterial species into two large groups: gram-positive bacteria and gram-negative bacteria. The name comes from the Danish b ...
of a muscle biopsy showing
Gram-positive In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. Gram-positive bact ...
,
rod-shaped A bacillus (), also called a bacilliform bacterium or often just a rod (when the context makes the sense clear), is a rod-shaped bacterium or archaeon. Bacilli are found in many different taxonomic groups of bacteria. However, the name '' Baci ...
,
anaerobic Anaerobic means "living, active, occurring, or existing in the absence of free oxygen", as opposed to aerobic which means "living, active, or occurring only in the presence of oxygen." Anaerobic may also refer to: * Anaerobic adhesive, a bonding a ...
, spore-forming bacteria in the infected muscle tissue: The result is highly compatible with an infection with ''C. perfringens''. Image:Gas gangrene shoulder.jpg, Gas gangrene of the shoulder.


See also

* Blackleg (a similar disease in
livestock Livestock are the domesticated animals raised in an agricultural setting to provide labor and produce diversified products for consumption such as meat, eggs, milk, fur, leather, and wool. The term is sometimes used to refer solely to ani ...
) *
List of cutaneous conditions Many skin conditions affect the human integumentary system—the organ system covering the entire surface of the body and composed of skin, hair, nails, and related muscle and glands. The major function of this system is as a barrier agai ...


References

{{Bacterial cutaneous infections Gangrene Bacterium-related cutaneous conditions ja:ガス壊疽