**6.2 Nontraumatic gas gangrene**

*C. perfringens* commonly resides in the gut lumen of healthy individuals, so that the nontraumatic gas gangrene is encountered in the internal organs such as the gut, bile duct, and pancreas [26, 27]. Representative autopsy cases are presented below.

The pancreas is occasionally assaulted by *C. perfringens* [28–30]. An autopsy case of fulminant pancreatitis (emphysematous pancreatitis) in a 66-year-old diabetic man, presenting just a two-day clinical course, is demonstrated. Diabetes mellitus was poorly controlled. The patient suffered sudden abdominal and back pain, and acute pancreatitis was diagnosed by a markedly elevated serum amylase level. Abdominal computed tomography scan demonstrated gas retention in the pancreatic head, intrahepatic branches of the bile duct, and in the abdominal cavity. At autopsy, features of acute hemorrhagic and necrotizing pancreatitis with infiltration of neutrophils were observed (**Figure 12**). Clusters of rods were identified in necrotic, gas-forming areas, and the bacteria grew also along the pancreatic duct. Neutrophilic reaction was sparse in the hypoxic area showing bacterial growth. Not all of the bacteria were stained blue with Gram stain (some remain unstained), and the formation of spores was abortive within the living body (**Figure 13**). These microscopic features were consistent with infection of *C. perfringens*.

Another case of pancreatic gas gangrene in a diabetic male patient aged 70's showed numerous Gram-positive rods around the gas-filled space formed in the necrotic pancreas, confirming the diagnosis of *C. perfringens* infection. Gross and microscopic findings of the foamy liver are illustrated in **Figure 14**. The cut surface of the formalin-fixed liver shows numerous gas-filled spaces, giving characteristic spongy/foamy appearance.

Nontraumatic gas gangrene may be associated with colon cancer [31, 32]. An 81-year-old female patient with rectal cancer became acutely ill with abdominal pain and paralytic ileus. The patient soon died of septic shock. Autopsy clarified nontraumatic gas gangrene of the colorectum caused by clostridial infection in rectal adenocarcinoma. The growth of Gram-positive, gas-forming rods was observed in the cancer tissue, crypts of the noncancerous colorectal mucosa, and also in the liver. Gangrenous inflammation was observed in the entire layer of the colorectal wall. Acute tubular necrosis represented the shock kidney. The microscopic appearance is displayed in **Figure 15**.

Gastric gas gangrene is infrequently experienced [33]. A 65-year-old diabetic male patient underwent endoscopic mucosal resection of intramucosal gastric

#### **Figure 12.**

*Clostridial acute hemorrhagic and necrotizing pancreatitis (CT scan and H&E). Computed tomography scan demonstrates gas formation in the pancreatic head (arrowhead). At autopsy, neutrophils infiltrate the pancreatic parenchyma, giving features of severe acute pancreatitis.*

massive ischemic necrosis (gangrene) of the soft tissue involving the striated muscle. Gas production is quite characteristic, and the involved tissue thus reveals crepitation on touch (**Figure 11**). The gas is composed of 5.9% hydrogen, 3.4% carbon dioxide, 74.5% nitrogen, and 16.1% oxygen. As the bacteria grow under an anaerobic condition, the degree of ischemia in the involved tissues and organs becomes advanced. Tissue necrosis is accelerated by α-toxin production of the microbe. Putrid odor is associated. Intravascular hemolysis is a common event due to bacterial production of hemolysin (α-toxin). The prognosis is very poor. The disease is also called as clostridial histotoxic syndrome. Gram-positive rods are

*Traumatic gas gangrene of the right thigh (gross appearance). Gas-forming gangrenous process of the soft tissue results in marked swelling of the thigh. Crepitation was palpable on touch. Surgical debridement has been*

*Immunohistochemical identification of MRSA in formalin-fixed, paraffin-embedded sections (H&E, Gram and immunostain). The Gram-positive coccal colonies in the gangrenous decubital lesion express staphylococcal antigens, protein A (staphylococcal IgG Fc-binding protein) and penicillin-binding protein 2*<sup>0</sup> *(PBP2*<sup>0</sup>

*),*

microscopically localized adjacent to gas bubbles (see below).

*confirming the nature of MRSA. Streptococcal antigens are negative.*

**Figure 10.**

*Pathogenic Bacteria*

**Figure 11.**

**102**

*performed for the treatment purpose.*

#### **Figure 13.**

C. perfringens *grown in acute necrotizing pancreatitis (H&E and Gram). Gas bubbles are observed in the necrotic pancreatic tissue with sparse inflammatory infiltration. The rods growing in the bubble are unevenly Gram-positive (some bacilli are not stained blue). Spores (representing unstained dots in the bacterial body) are only focally recognizable in the living body.*

#### **Figure 14.**

*Gas gangrene involving the liver (gross and Gram). Numerous gas bubbles replace the liver parenchyma, giving foamy or spongy appearance. The hepatocytes reveal ischemic changes, and Gram-positive rods are clustered around the gas bubble. Note that the condition allowing the growth of obligate anaerobic* Clostridium perfringens *must be highly hypoxic.*

adenocarcinoma located at the gastric angle. Next day, he became acutely ill with abdominal pain and distention, and circulatory collapse soon followed. At autopsy, colonization of Gram-positive rods was noted at the base of ulcer caused by the endoscopic operation (**Figure 16**). The liver revealed multifocal foamy appearance due to gas formation by Gram-positive rods growing among the liver cell cord. The final diagnosis was gas gangrene caused by clostridial infection on the iatrogenic gastric mucosal trauma.

formation by *C. perfringens*. Surgically curable *C. butyricum*-induced intestinal gas

*Gastric gas gangrene in a 65-year-old diabetic male patient (gross and H&E). Red-swollen stomach after endoscopic mucosal resection for early gastric cancer has an artificial ulcer at the gastric angle. Rods colonize the ulcer base. Gas formation is evident in the liver tissue (inset). Arrowheads indicate bacterial colonies (the courtesy of Dr. Chunlin Ye, Emergency Department, Saishukan Hospital, Kitanagoya, Japan).*

*Rectal cancer-associated nontraumatic gas gangrene in an 81-year-old female patient (gross and H&E). The rectal cancer (arrow) and the edematous proximal colon reveal hemorrhagic necrosis. Gas formation is observed in the tissue of rectal adenocarcinoma with marked ischemic change. Large-sized rods colonize the crypts of the non-cancerous necrotic colorectal mucosa (the courtesy of Dr. Hirokazu Kurohama, Regional Pathological Diagnosis Support Center, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan).*

Gas gangrene is commonly caused by clostridial infection, but non-clostridial bacteria may also provoke gas gangrene mostly in the extremities [36–38]. Early diagnosis and therapy are required, because the disease rapidly progresses to fatal toxemia. This unique dermatologic emergency is featured by the detection of nontraumatic subcutaneous emphysema of the leg with or without association of

gangrene is described in the Section 14.3.

**7. Non-clostridial gas gangrene**

**Figure 15.**

*Pathology of Gangrene*

*DOI: http://dx.doi.org/10.5772/intechopen.93505*

**Figure 16.**

**105**

*C. septicum* may cause spontaneous, nontraumatic gas gangrene [34], and *C. sordellii* may induce gas gangrene of the uterus, as a consequence of spontaneous abortion, normal vaginal delivery, and traumatic injury [35]. As illustrated in **Figure 17**, *C. butyricum* happened to infect the stomach, resulting in fulminant death of a male patient aged 60's. *C. butyricum*, a resident of healthy human gut, uniquely produces butyric acid as a metabolite, hence named. Foamy appearance of the gastric wall was quite characteristic. The liver also appeared foamy/spongy. The formation of spores inside the rugby ball-shaped Gram-positive rod bodies is microscopically characteristic of *C. butyricum*. This is in sharp contrast to poor spore

#### **Figure 15.**

*Rectal cancer-associated nontraumatic gas gangrene in an 81-year-old female patient (gross and H&E). The rectal cancer (arrow) and the edematous proximal colon reveal hemorrhagic necrosis. Gas formation is observed in the tissue of rectal adenocarcinoma with marked ischemic change. Large-sized rods colonize the crypts of the non-cancerous necrotic colorectal mucosa (the courtesy of Dr. Hirokazu Kurohama, Regional Pathological Diagnosis Support Center, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan).*

#### **Figure 16.**

adenocarcinoma located at the gastric angle. Next day, he became acutely ill with abdominal pain and distention, and circulatory collapse soon followed. At autopsy, colonization of Gram-positive rods was noted at the base of ulcer caused by the endoscopic operation (**Figure 16**). The liver revealed multifocal foamy appearance due to gas formation by Gram-positive rods growing among the liver cell cord. The final diagnosis was gas gangrene caused by clostridial infection on the

*Gas gangrene involving the liver (gross and Gram). Numerous gas bubbles replace the liver parenchyma, giving foamy or spongy appearance. The hepatocytes reveal ischemic changes, and Gram-positive rods are clustered around the gas bubble. Note that the condition allowing the growth of obligate anaerobic* Clostridium

C. perfringens *grown in acute necrotizing pancreatitis (H&E and Gram). Gas bubbles are observed in the necrotic pancreatic tissue with sparse inflammatory infiltration. The rods growing in the bubble are unevenly Gram-positive (some bacilli are not stained blue). Spores (representing unstained dots in the bacterial body)*

*C. septicum* may cause spontaneous, nontraumatic gas gangrene [34], and *C. sordellii* may induce gas gangrene of the uterus, as a consequence of spontaneous abortion, normal vaginal delivery, and traumatic injury [35]. As illustrated in **Figure 17**, *C. butyricum* happened to infect the stomach, resulting in fulminant death of a male patient aged 60's. *C. butyricum*, a resident of healthy human gut, uniquely produces butyric acid as a metabolite, hence named. Foamy appearance of the gastric wall was quite characteristic. The liver also appeared foamy/spongy. The formation of spores inside the rugby ball-shaped Gram-positive rod bodies is microscopically characteristic of *C. butyricum*. This is in sharp contrast to poor spore

iatrogenic gastric mucosal trauma.

perfringens *must be highly hypoxic.*

**Figure 13.**

*Pathogenic Bacteria*

**Figure 14.**

**104**

*are only focally recognizable in the living body.*

*Gastric gas gangrene in a 65-year-old diabetic male patient (gross and H&E). Red-swollen stomach after endoscopic mucosal resection for early gastric cancer has an artificial ulcer at the gastric angle. Rods colonize the ulcer base. Gas formation is evident in the liver tissue (inset). Arrowheads indicate bacterial colonies (the courtesy of Dr. Chunlin Ye, Emergency Department, Saishukan Hospital, Kitanagoya, Japan).*

formation by *C. perfringens*. Surgically curable *C. butyricum*-induced intestinal gas gangrene is described in the Section 14.3.
