58 Gangrene
Gangrene is the term used by the clinician to describe local death of tissue (necrosis) occurring in the living body. Gangrene implies a fairly rapid process (developing in days) extending over a large visible area (a few to many centimeters) with an obvious inability of the tissues to repair or replace the gangrenous part.
Although gangrene can occur in internal organs (e.g., large intestine), it generally refers to a process occurring on the surface of the body. It may involve only the skin, or it may extend into deeper tissues such as muscle or nerves.Gangrene may be either dry or moist. Dry gangrene describes necrosis of the tissues of the extremities resulting from vascular occlusion, such as occurs in severe arteriosclerosis of the legs. Wet or moist gangrene occurs when bacteria invades dead tissue, producing putrefaction. When the gas-forming group of bacteria is involved, gas gangrene occurs. A gangrene may be dry at first, and be converted to the moist type by invading bacteria.
Clinical Manifestations
In dry gangrene, the arterial supply is gradually cut off and a drying or mummification of the tissues results. There is frequently an absence of inflammation, but pain of varying degree may precede the color changes. The soft tissue slowly and progressively shrinks and the color gradually deepens until the whole area is coal black. Constitutional symptoms may occur but are less severe than in moist gangrene.
Moist gangrene may be preceded by inflammation or trauma. The part is initially swollen and painful. The color is at first red then blue and finally turns to a green black. There is boggy swelling and putrid odor. If the moist gangrene is extensive, constitutional symptoms, such as fever, may be present.
A vivid description of hospital gangrene illustrates well the clinical aspect of moist gangrene:
A wound attacked by gangrene in its most concentrated and active form presents a horrible aspect after the first forty-eight hours.
The whole surface has become of a dark- red color, of a ragged appearance, with blood partly coagulated, and apparently half putrid, adhering at every point. The edges are everted, the cuticle separating from half to three-fourths of an inch around, with a concentric circle of inflammation extending an inch or two beyond it; the limb is usually swollen for some distance, of a white, shining color, not peculiarly sensible except in spots, the whole of it being oedematous and pasty. The pain is burning and unbearable in the part itself, while the extension of the disease, generally in a circular direction, may be marked from hour to hour; so that in from another twenty-four to forty-eight hours nearly the whole of a calf of a leg, or the muscle of a buttock, or even the wall of the abdomen may disappear, leaving a deep great hollow or hiatus of the most destructive character, exhaling a peculiar stench which can never be mistaken, and spreading with a rapidity quite awful to contemplate. The great nerves and arteries appear to resist its influence longer than the muscular structures, but these at last yield; the largest nerves are destroyed, and the arteries give way, frequently closing the scene, after repeated hemorrhages, by one which proves the last solace of the unfortunate sufferer.... The joints offer little resistance; the capsular and synovial membranes are soon invaded, and the ends of the bones laid bare. The extension of this disease is in the first instance through the cellular structures. The skin is undermined and falls in, or a painful red and soon black patch is perceived at some distance from the original mischief, preparatory to the whole becoming one mass of putridity, while the sufferings of the patient are extreme. (Buck 1902)Etiology
Gangrene can have many causes; Table VIII.58.1 indicates the major ones. Some are now quite rare but at one time were common. Using this table as a guide, we shall discuss the various causes, highlighting those that have been of major consequence throughout recorded history.
Vascular Causes
Historically, ergotism resulted from ingesting rye bread contaminated by the fungus Claviceps purpurea. It led to a permanent decrease in the caliber of arterioles and, eventually, to dry gangrene of the fingers and toes and, less commonly, of the ears and nose. Ergotism was responsible for many epidemics of gangrene during the Middle Ages in Europe. Along with erysipelas it was known as St. Anthony’s fire. Although rare, ergotism may still occur today, as ergot preparations are often used in the treatment of migraine headaches.
Raynaud’s Syndrome. This syndrome is characterized by marked episodic vascular spasms of the extremities. During a typical attack, one or more digits initially turn white. After a few minutes, the color changes to a bluish red. Slowly, the normal color returns. These episodes are often triggered by cold or emotional stress. In severe cases, gangrene may ensue, which is characteristically symmetrical and con-
Table VIII.58.1. Causes of gangrene
Vascular disease
Vascular spasm
Ergotism (St. Anthony’s fire)
Raynaud’s syndrome
Embolism
Arteriosclerosis
Organisms
Fat and gases
Dysproteinemias
Abnormalities of coagulation
Primary vascular disease (peripheral vascular disease) Arteriosclerosis
Thromboangiitis obliterans (Buerger’s disease) Diabetes
Vasculitis of the so-called collagen diseases
Rheumatoid arthritis
Systemic lupus erythematosus
Hypersensitivity to certain drugs
Physical agents
Bums
Cold
Trauma
Pressure
Ionizing radiation
Electrical bums
Chemical agents
Caustics
Venoms
Certain drugs
Coumadin
Heparin
Chemotherapeutic agents
Microbiological agents
Bacterial infections
Anthrax
Streptococci (necrotizing fasciitis, Fournier’s gangrene)
Mixed (postoperative synergistic gangrene)
Leprosy
Pseudomonas aeruginosa
Mycobacterial organisms (tuberculosis, Bumli ulcer) Viral infections
Herpes (simplex and zoster)
Smallpox
Chickenpox
Treponemal infections
Syphilis
Yaws
Bejel
Rickettsial infections
Rocky Mountain spotted fever
Typhus
Protozoal infections
Amebiasis cutis
Schistosomiasis cutis
Table VIΠ.58.1 (cont.)
Fungal infections
Histoplasmosis
Mucormycosis (phycomycosis)
ActinomycosisZnocardiosis
Cryptococcosis
Blastomycosis (North and South American)
fined to the fingers and toes.
It was once known as relapsing gangrene. Raynaud’s syndrome may occur alone {Raynaud’s disease) or in association with another condition usually of the collagen group of diseases {scleroderma, systemic lupus erythematosus, rheumatoid arthritis). It has also been seen as an occupational hazard in people who manipulate vibratory instruments such as jackhammers or chainsaws. Embolism. Embolism is the sudden occlusion of an artery by blood-borne particles. These may be atheromatous material dislodged from a vascular plaque upstream; vegetations from an infected heart valve; or other unusual particles such as fat (after extensive bony fractures), gas (decompression sickness), abnormal blood proteins (dysproteinemias), or blood clots. The acute vascular compromise can lead to gangrene of the extremities, usually of the dry type.Arteriosclerosis. Arteriosclerosis may be an underlying cause of embolism, and can also lead to gradual local vascular occlusion {thrombosis) of large and medium-sized arteries. It is common in the elderly and therefore has been called senile gangrene. A dry gangrene, it occurs mainly in the foot and was therefore previously called Pott’s disease of the toe. It is generally preceded by severe pain and discomfort in the lower leg and foot. A special form of arteriosclerosis is thromboangiitis obliterans or Buerger’s disease. It commonly occurs in young and middle-aged men who are heavy smokers. Finally, diabetes can predispose to arteriosclerosis of smaller vessels with eventual gangrene of the feet and toes. Diabetic gangrene is usually of the moist type. There are multiple other factors that may predispose to arteriosclerosis. They include hereditary factors and general life-style habits such as overeating of animal fats, lack of exercise, and smoking. With recent changes in these habits and better control of diabetes, arteriosclerosis and its resultant gangrene are now becoming less common. Surgical techniques are also available for replacing or recanalizing occluded arteries of the legs, so that blood supply to the feet can be restored.
Physical Agents
Various types of injuries such as frostbite, compound bony fractures of the legs, contusions, gunshot wounds, and burns, if serious enough, may be the initial factor that triggers production of gangrene. However, this complication was more prevalent before effective medical care became widely available.
Chemical Agents
Tissue can also be destroyed by chemicals either of exogenous or endogenous origin. Caustics such as carbolic acid (previously used as an antiseptic solution) have been known to cause gangrene. Venoms of certain snakes (i.e., water moccasin), spiders (i.e., brown recluse spider), and jellyfish (i.e., Portuguese man-of-war) can cause local necrosis at the site of the sting or bite. Many chemotherapeutic agents (such as those used to treat malignancies) may also lead to local tissue destruction when they inadvertently seep into the surrounding area during intravenous administration. Some systemically administered drugs may rarely cause gangrene (i.e., some anticoagulants such as coumadin).
Microbiological Agents
Many organisms produce a toxin that will directly cause cell death. Other toxins have vascular effects such as spasm or vasculitis. Some organisms produce enzymes that can break down tissue locally. Other organisms - in particular, viruses - can directly destroy cells by invasion. Only a few of the most important infections will be discussed here. Many can be found elsewhere in this work.
Various streptococci, including Streptococcus pyogenes (group A beta hemolytic strep.), have been found to be the cause of certain varieties of gangrene. Of historical importance is hospital gangrene, also known as necrotizing fasciitis and pourriture des hδpitaux. This form of gangrene was the scourge of hospitals in the preantiseptic era. Today it is almost never seen. Trauma is usually the initiating factor, whereas predisposing factors are diabetes, alcoholism, and a generally debilitated state. Within 48 to 96 hours, gangrene would set into a wound and characteristically was rapidly progressive and deeply destructive.
The patient would become febrile and eventually succumb. Although some authorities feel that this type of gangrene was due solely to S. pyogenes, there is now more evidence to suggest that other organisms (alone or in combination) may give a simi-Iar clinical picture. Another streptococcal gangrene, CaWedFourniersgangrene, is an acute gangrene localized to the scrotum. Finally, anaerobic streptococci in combination with other bacteria such as Staphylococcus aureus are the cause of postoperative synergistic gangrene. After a few days or weeks, gangrene develops around an abdominal or thoracic surgical wound site. The process is rapidly progressive and may, if left untreated, lead to the death of the patient.
History and Geography
Ergotism has long been an important cause of certain epidemics of gangrene in humankind. Gangrene of the limbs has been recognized since ancient times, and a description of gangrene following trauma appears in Hippocrates. It is probable that gangrene in ancient Greece and Rome was due mainly to infections initiated by trauma of either accidental or military origin.
In temperate and Arctic zones of the world, cold injuries causing frostbite that led to gangrene have always occurred. Explorers of cold regions were often affected, and gangrene produced by cold injury has also been a tremendous problem in troops engaged in wartime activities. Gangrene, for example, was quite prevalent among soldiers during Napoleon Bonaparte’s invasion of Russia. Yet frostbite was only one of the causes of gangrene associated with military activity. Trauma from penetrating wounds, contusion of soft tissues, and compound bony fractures were often the initial insult. The introduction of gunpowder in Europe in the sixteenth century produced a tremendous loss of life and limbs from gangrene that developed in these traumatic wounds. Poor hygienic conditions and overcrowding in hospitals led to epidemic wound infections. Because hospital gangrene was rapidly progressive and lethal, many lives were lost, particularly during the Napoleonic Wars, the Crimean War, and the American Civil War. In many cases, there were almost as many soldiers killed from wounds and gangrene as were killed in action.
By the time of World War I, hospital gangrene was much less prevalent. The art of amputation and setting of fractures was advanced by the important contributions of such surgeons as Ambroise Pare in the sixteenth century, Pierre-Joseph Desault in the eighteenth, and John Bell at the turn of the nineteenth, among others. Their work significantly contributed to decreased mortality from gangrene. The concept of antisepsis and asepsis was introduced in the late nineteenth century with the work of Louis Pasteur. This concept, when applied to management of wounds, is known as Listerism, in honor of Lord Joseph Lister, who was the first to recognize the value and clinical application of Pasteur’s discovery. Finally, the introduction of penicillin in the early 1940s totally eradicated hospital gangrene.
Arteriosclerosis is probably as old as humankind. Leonardo da Vinci, in the fifteenth century, illustrated the arteries of a subject with senile arteriosclerosis in one of his anatomic sketches. Along with prolonged life expectancy has come a greater susceptibility to degenerative diseases such as arteriosclerosis and other vascular disorders. In the early nineteenth century, it gradually became clear that organic occlusion of the arteries could cause dry gangrene. Maurice Raynaud, in his now famous 1862 thesis, On Local Asphyxia and Symmetrical Gangrene of the Extremities, attempted to prove that there was a disease of the arterial system that might produce gangrene, but in which arterial obliteration was not present. Only recently have the roles of life-style, diabetes, and hypertension been recognized as contributing factors in the production of arteriosclerosis. Fortunately, widespread public education is now contributing to the decline of severe peripheral vascular disease and its associated gangrene.
In advanced countries of the world today, gangrene is much less common. Infectious gangrenes are easily treated or avoided by the appropriate antiinfective agents. However, there are now a growing number of individuals who are immunosuppressed from chemotherapeutic agents and corticosteroids, which are used to prevent rejection in transplant patients, and to treat various cancers and autoimmune diseases such as rheumatoid arthritis. In such an immunocompromised state, these patients are at increased risk of developing unusual infectious gangrenes whose etiologic agents may not be easily recognized or be readily treatable.
Diane Quintal and Robert Jackson
Bibliography
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