Gangrene
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Definition- Gangrene is a disease of the skin
and soft tissues, and sometimes internal
tissues and organs, that result in death of
tissues (necrosis)
Forms/Types
Dry gangrene- sometimes called
mummification is the slow onset form, most
commonly associated with chronic diseases
e.g. Diabetes
Wet gangrene- also known as moist
gangrene, is the sudden onset (acute) form
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Causes- Dry Gangrene
All forms of gangrene results from the loss of
blood supply to a tissue often at the
extremities, which deprives the tissue oxygen
and nutrients, causing the tissue to die
(necrosis)
Mortification is a type of gangrene where a
portion of tissues dies all at once, whereas
ulceration involves death at a molecular or
cellular level
Reason behind necrosis and tissue death
differ depending on the specific type of
gangrene
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In dry gangrene, the necrosis is caused by slow
progressive loss of blood supply (perfusion)
In wet gangrene, necrosis results from sudden loss
of perfusion and is worsened by the involvement of
bacteria
Diabetes and blood vessels disease e.g.
atherosclerosis are the most common cause of dry
gangrene
Dry gangrene is more likely to occur in older
people with diabetic foot- a common complication
of undiagnosed or uncontrolled DM
In DM, the circulation of blood to the feet worsens
and there is a higher likelihood of any foot
ulcer/wound to go unnoticed by the patient (due to
diabetic neuropathy-nerve damage thus loss of
sensation)
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Causes…..
“Senile gangrene” caused by “aged” blood
vessels and therefore affects older patients.
This can also occur in younger people with
arteriosclerosis (arterial narrowing) caused by
syphilis and alcohol and cigarettes addiction
Surgery-any operation involving the ligation of
an artery e.g. treatment of an aneurysm can
shut off blood supply to cause gangrene. This
form is usually dry but can also become wet
gangrene
Mechanical constriction- e.g. gangrene can be
revealed when pressure splints are removed.
Trauma or injury can also cause mechanical
constriction
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Causes….
Severe burns- scalds & cold- heat, chemical agents
(carbonic acids, caustic potash, nitric and sulphuric
acid), and cold (frostbite), can lead to dry gangrene.
If treatment involves wet or oily dressings, then wet
gangrene can develop.
Reynaud's disease-condition in which spasms of
blood vessels cause impaired circulation to the end
of fingers and toes, especially in cold weather, is
implicated in some cases of gangrene
Angiosclerosis and intermittent claudication can be
associated with gangrene
Eating large qualities of coarse rye bread, long-term
intake of ergot, (a fungus that can infect rye) is
implicated in gangrene development as ergotism
involves vasoconstriction
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Causes….Wet Gangrene
Injury- deep crushing or penetrating wounds that are
sustained in conditions that allow bacterial infection
to take hold can lead to gangrene. This is usually
seen in war zones, railways, machinery and street
accidents if lacerated and bruised tissues are
contaminated with soil or dirt.
Mechanical constriction-rarely blood flow constriction
caused by pressure from bandages, fractures,
tumours etc can lead to gangrene
Overlap btwn wet & dry gangrene (embolic
gangrene)-the sudden occlusion of an artery due to
an embolism can lead to dry gangrene, but this can
also increase the risk of infection thus leading to wet
gangrene
Any case of dry gangrene can progress to wet
gangrene if there is an opportunity for bacterial
infection
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Risk Factors
Smoking
Obesity
Excessive alcohol intake
Impaired immune system due to HIV
infection, chemotherapy, radiation therapy
Intravenous drug use
Rarely anticoagulant use- Warfarin especially
if used in combination with Heparin
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Clinical features
Incubation period 24hrs
Followed by severe sudden onset of pain which is
characteristic, followed by loss of sensation and
inability to move the part
Loss of pulse in arteries, cold extremities
Loss of colour in the affected part- initially
discoloured but eventually turning dry and dark,
going through red to black colour (frank gangrene)
in dry gangrene, or being swollen and foul smelling
in wet gangrene, in gas gangrene producing a
particular foul smelling brownish pus
Shinny appearance to the skin, shedding/peeling of
skin- a clear line forming between affected and
healthy skin,
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If the gangrene is internal, there may not be
any external signs but may present with the
following symptoms as a result of septic
shock and features of
toxaemia- ,tachycardia, restlessness, thirst,
hypotension, fever, confusion, nausea,
vomiting & diarrhoea, shortness of breath
Signs and symptoms peculiar to gas
gangrene-the infected area of skin can
quickly extend with some changes which
are visible i.e.
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Very painful and swollen
Pale at first, but becomes red or bronze before
finally turning blackish green in colour
When palpated, a crackling sensation is elicited
(crepitus) due to the movement of gas under the
skin (subcutaneous emphysema)
The gas is produced by the bacteria causing
infection and is highly toxic, causing the necrosis
to spread quickly
Blisters filled with brown-red fluid
Foul smelling brown-red or bloody fluid when the
tissue affected is drained or leaked
(seroanguinous discharge)
Certain muscles are more likely to be affected by
gas gangrene e.g. sides of the trunk, under the
arms , buttocks, thighs. 14
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Diagnosis and Investigation
Suspicion of gangrene through history and
physical examination, exposure to trauma
and infections
X-ray- reveals gas bubbles in muscle tissue
MRI and CT scan to determine the extent of
muscle involvement
Olfactory test to detect the unique, foul smell
that indicate gas gangrene
FBC
Blood culture
Swab (wet gangrene) for Gram staining
Direct laboratory examination of samples of
the affected tissue and any discharge
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Treatment
Emergency treatment is required to prevent/reduce
the risk of serious complications and death
In all cases of gangrene caused by chronic disease,
prevention is far much better than cure
Prevention is also important in avoiding the acute
risks of gangrene e.g. from injury, or extreme cold.
Particular treatment is dependent on the specific
type, location and extent of diseased tissue
Antibiotic therapy (parenteral)
Reconstructive surgery – skin grafting
Amputation of an extremity or even a limb to halt the
spread of gangrene
Oxygen therapy (high pressure O₂) creates a
bacteriocidal and bacteriostatic effect and improves
oxygen supply to the wound by encouraging the
formation of new blood vessels
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Treatment…..
Prophylaxis
Deep wounds don’t stitch them
Thoroughly wash with normal saline
Cut off all dead tissues (debridement)
Remove anaerobic condition which would be
favourable for their growth.
Gun shots or contaminated wounds should be left
open (do not suture).
Review wound for several days.
If not infected do secondary suturing on the 6th day.
Antibiotics therapy
Penicillins if wound is heavily contaminated or patient
undergoing surgery/Erythromycin if sensitive to
Penicillins.
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Rx….
Curative therapy (established gas gangrene)
Remove all dead tissues and muscles around
the limb.
Give other supportive measures;
*High O2 concentration
*Antiserum-Immunoglobulin
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Gas gangrene (Clostridial necrosis)
◦ Its a form of necrosis with infection of muscles by toxin
producing Clostridium welchii (perfringens) and other
species of clostridium
◦ It’s a Gram positive spore forming bacillus producing
powerful exotoxin.
◦ This toxins have various activities including;
phospholipase-breakdown of phospholipids,
Collagenase- breaks down collagens, protenase-
breaks down proteins, hyaluronidase-breaks down the
hyaline matrix.
◦ This property facilitates the organism to become
aggressive and have local spread along the tissue
planes, which break down tissues with production of
gases like CO₂, H₂S and NH₃ from the breakdown of
protein hence the name gas gangrene.
◦ The organism also found in soil and animal dropping
just like C. tetani
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Gas Gangrene…..
Is a virulent form of wet gangrene . It is
associated with poorly cleansed wounds
e.g. wounds sustained in wars, deep
crushing or penetrating injuries that
become infected with bacteria Clostridium .
In addition to injuries, gas gangrene can
result from surgery of the abdomen where
the GIT has been opened. Occasionally may
be found in amputation of lower limbs
where there is ischaemia and also found to
follow criminal abortion or puerperial
infection
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Causes
Is caused by an anaerobic , Gram positive,
spore forming bacillus of the genus
Clostridium. Clostridium perfringens is the
most common aetiologic agent that causes
gas gangrene
Other species; C. bifermentans, C. septicum,
C.sporogens, C.novyi, C. fallax,
C. histolyticum, and C. tertium
These organisms are true saprophytes and
are found in the soil and dust, have also been
isolated from mucous membranes of human,
including the GI tract, female genital tract,
skin (around perineum)
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Clostridium perfringens produces at least 20 toxins
including
Alpha toxin-lethal, necrotizing, haemolytic,
cardiotoxic.
Beta toxin- lethal, necrotizing
Epstein toxin- lethal
Iota toxin- lethal, necrotizing
Delta toxin- lethal, haemolytic
Phi toxin
Kappa toxin
Lambda toxin
Nu toxin
Mu toxin
Lethal as tested by injection in mice
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Causes…
Classes of gas gangrene can be classified as post-
traumatic, post-operative, or spontaneous
Post-traumatic- (60% of all cases)from automobile
collision, crush injuries, compound fractures,,
gunshot wounds, thermal or electrical burns,
frostbite, farm or industrial injuries contaminated
with soil, I.M or subcutaneous injections with Insulin,
Epinephrine, Quinine, Heroine,
Post-operative- follows cases of colon resection,
ruptured appendix, bowel perforations, biliary or
other GI surgery, laparoscopic cholecystectomy &
colonoscopy, liposuction, septic back-street
abortions
Spontaneous- without external wound or injury, seen
in colorectal adecarcinoma, haematologic malignancy,
chemotherapy (C. septicum), diabetes, colitis
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Clinical Features
Depends on the underlying condition
Sudden onset of severe pain
Feeling of heaviness in the affected extremity
Low grade fever
Local swelling and seroanguinous exudate
Skin characteristically turns to a bronze colour,
with skin blebs and haemorrhagic bullae
Crepitus following gas production- may not be
elicited due to oedema
Tenderness on palpation
Tachycardia
Late signs- hypotension, renal failure
Altered mental status
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Ddx
Bacterial sepsis
Elective abortion
Emphysematous cholecystitis
Septic shock
Toxic shock syndrome
Vibrio infections
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Investigations
Lactate dehydrogenase increased due to haemolytic
anaemia
Serum calcium levels
FHG-Leukocytosis
Gram stain of the exudate or infected tissues reveals
“box-car”- large Gram positive bacilli without
neutrophils
Blood cultures- may grow the Clostridial species
Biochemistry-UECs- show metabolic acidosis and
deranged renal function
X-ray- shows typical feathering pattern of gas in
soft tissues
CT scan in abdominal cases of gas gangrene
MRI- to detect necrotizing soft tissue infection
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Management
The combination of aggressive surgical
debridement and effective antibiotic therapy
Crystalline Penicillin 2.4MU was the drug of
choice, currently combination of Penicillin and
Clindamycin
Protein synthesis inhibitors e.g. Clindamycin,
Chloramphenicol, Rifampicin, Tetracycline are
also effective because they inhibit the synthesis
of Clostridial exotoxins and lessen the local and
systemic toxic effects of these proteins
Comdination of Clindamycin + Metronidazole
for patients allergic to Penicillins
Supportive care for end-organ failure- renal
failure
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Synergistic Gangrene
Also called progressive bacterial gangrene or
Melency’s gangrene.
It’s caused by synergistic action of 2 or more
organism commonly-aerobic haemolytic
staphylococcus and micro-aerobic non
haemolytic streptococcus
More common in diabetic patients and related
to trauma or infection.
Fournier’s gangrene
It is when synergistic gangrene affects the
scrotum or perineum
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Clinical features:
There may be no precipitating factors but
mostly follows infection or recent surgery.
Formerly called progressive post-operative
gangrene
At the site of gangrene and surrounding area
has cellulitis which is rapidly progressive.
The place is exquisitely tender (very tender)
Offensive smell or odour (H₂S, NH₃)
Patient becomes profoundly septic and sick
looking, wasted and febrile.
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Treatment
I.V broad spectrum antibiotics.
Take patient to theatre under general
anaesthesia to debride the tissues.
Inspect wound twice a day for any evidence of
spread.
Continue until there is any sign of granulation
(healing).
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Fournier’s Gangrene
Is a necrotizing fasciitis of the perineal,
perianal or genital areas impaired immunity
from immunosuppressant drugs, diseases is a
factor to susceptibility of Fournier’s gangrene
Trauma to the genitalia introduce bacteria that
initiate the infectious process.
Pathologic evaluation reveals
Necrosis of the superficial and deep fascial planes.
Fibrinoid coagualation of the nutrient
arterioles.
Polymorphonuclear cell infiltration.
Microorganisms identified within the involved
tissues
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Causes
Common causative micro-organisms are;
◦ Streptococcal species(aerobic/anaerobic)
◦ Staphylococcal species
◦ Enterobacteriaceae
◦ Anaerobic organisms
◦ Fungi
◦ Escherichia
◦ Bacteroids
◦ Staphylococcus
◦ Enterococcus
◦ Pseudomonas
◦ Klebsiella
◦ Clostridium
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The necrotizing process commonly originates from
an infection in the anorectum, urogenital tract or the
skin of the genitalia.
Anorectal causes – perianal, perirectal, ischiorectal,
abscesses, anal fissures, colonic perforations.
Urogenital causes – infections in the bulbourethral
glands, urethral injury, latrogenic injury secondary
to urethral structure, manipulation, epididymitis,
orchitis and lower urinary tract infection(long term
indwelling urethral catheters)
Dermatologic causes – ulceration due to scrotal
pressure and trauma, inadequate perineal hygiene.
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Predisposing factors
Any condition that depresses the cellular immunity
e.g.
◦ DM(present in 60% of the cases)
◦ Morbid obesity
◦ Alcoholism
◦ Cirrhosis
◦ Extreme of ages
◦ Vascular disease of the pelvis
◦ Malignancies-leukaemia
◦ Systemic lupus erythematosis
◦ Crohn’s disease
◦ HIV infection
◦ Malnutrition
◦ Iatrogenic immunosuppression e.g. from long-term
corticosteroid therapy
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Clinical features
Intense pain and tenderness in the genitalia.
Prodromal symptoms e.g. fever and lethergy
for 2-7 days
Intense genital pain and tenderness
associated with oedema of the overlying skin
and pruritis; erythema of the overlying skin.
Dusky appearance of the overlying skin
subcutaneous crepitation.
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Obvious gangrene of a portion of the
genitalia, purulent discharge from wounds.
A foul smelling discharge secondary to
infection with anaerobic bacteria.
Systemic symptoms – fever, tachycardia,
hypotension.
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DDx
Balanitis
Cellulitis
Acute epididymitis
Necrotizing fasciitis
Gas gangrene
Hernia infected
Hydrocoele
Orchitis
Testicular tortion
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Investigations
Complete blood count – leukocytosis
Arterial blood gas sampling(ABG) – elevated
BUN/creatinine ratio.
Blood and urine cultures
Culture of any fluid or abscess from wounds.
Coagulation profile – prothrombin time, activated
partial thromboplastin time(APPT)
Ultrasound to detect fluid/gas within the soft tissues.
Gas in the scrotal wall is the sonographic hallmark of
Fournier’s gangrene.
An incisional biopsy at the time of surgical
debridement
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Management
Surgery is necessary for definitive diagnosis and
excision of necrotic tissues.
Aggressive resuscitation in patients with signs of
toxicity by giving oxygen supplementation.
Establish I.V access and continuous cardiac
monitoring.
Crystalloids in dehydrated patients.
Early broad spectrum antibiotics to cover the
causative organisms e.g. Clindamycin,
Ciprofloxacin.
Gram positive + anaerobes
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Others
Ampicillin + sulbactam
Ticarcillein+Clavulanate
Piperacillin+Tazobactam in combination with
an Aminoglycoside and Metronidazole
Reconstruction after the infection clears and
healthy granulation tissues develop.
Tetanus Prophylaxis especially in cases of
trauma.
Address the co-morbid conditions e.g. DM
alcoholism.
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Prognosis
Prognosis for patients following reconstructive
surgery for Fournier’s Gangrene is usually good.
The scrotum has a remarkable ability to heal and
regenerate once the infection and necrosis have
subsided.
50% of men with penile involvement have pain on
erection due to genital scarring.
In extensive soft tissue loss, lymphatic drainage
may be impaired leading to dependent oedema
and cellulitis.
Death usually results from systemic illnesses e.g.
sepsis,(from Gram negative bacteria)
coagulopathy, acute renal failure, diabetic
ketoacidosis or multiple organ failure.
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