**8. Gangrenous inflammation of internal organs**

Gangrenous inflammation may occur in a wide variety of internal organs, such as the vermiform appendix, gallbladder, bile duct, pancreas, lung, kidney, eyeball, etc. The lesion may be localized within the organ, but it often extends to the surrounding tissues, so as to be fatal. When the anaerobic pathogens produce gas, we call the serious condition as "emphysematous" inflammation (as a form of localized gas gangrene).

#### **8.1 Gangrenous appendicitis**

Acute appendicitis is featured by sudden onset epigastric pain radiating to pelvis and high tachycardiac fever. When perforated, generalized abdominal tenderness

#### **Figure 18.**

erythema, tenderness, or bullous lesions. Non-clostridial gas gangrene most often results from polymicrobial infection of mixed kinds of microbes, and it is mainly seen in diabetic patients [39–41]. The causative gas-producing bacteria include *Escherichia coli*, *Klebsiella pneumoniae*, *Enterobacter cloacae*, *Pseudomonas aeruginosa*, *Aeromonas hydrophila*, *Bacteroides* spp., and *Streptococcus anginosus* group (former *S. milleri* group) [42]. Groups A, B, and G streptococci also cause gas gangrene, as a form of fulminant streptococcal infection [43], as described in the Section 10.1. **Figure 5** illustrates the gas-forming fulminant group A β-hemolytic streptococcal infection, caused by a deeply ulcerated (pocket-forming) decubitus at the sacral region of a 72-year-old diabetic woman. Another diabetic male patient aged 70's with advanced rectal adenocarcinoma suddenly manifested nontraumatic and nonclostridial gas gangrene in the abdominal cavity. Massive transportal infection of

Clostridium butyricum*-induced lethal gastric gas gangrene (gross, H&E and Gram). The gastric wall demonstrates formation of gas bubbles both grossly and microscopically. The growing Gram-positive rods exhibit distinct spore formation in rugby ball-shaped bacterial bodies, morphologically consistent with* C. butyricum *(the courtesy of Dr. Mayu Fukushima, a pathologist at Hamamatsu Medical University Hospital, Hamamatsu, Japan).*

gas-forming *E. coli* resulted in the formation of foamy liver (**Figure 18**).

of organs and tissues, as described in the next section.

**8. Gangrenous inflammation of internal organs**

**8.1 Gangrenous appendicitis**

**106**

**Figure 17.**

*Pathogenic Bacteria*

microscope, and infection of *E. coli* was immunohistochemically confirmed.

Intrahepatic vascular-invasive growth of Gram-negative rods was observed under a

Emphysematous (gas-producing) inflammation may be encountered in a variety

Gangrenous inflammation may occur in a wide variety of internal organs, such as the vermiform appendix, gallbladder, bile duct, pancreas, lung, kidney, eyeball, etc. The lesion may be localized within the organ, but it often extends to the surrounding tissues, so as to be fatal. When the anaerobic pathogens produce gas, we call the serious condition as "emphysematous" inflammation (as a form of localized gas gangrene).

Acute appendicitis is featured by sudden onset epigastric pain radiating to pelvis and high tachycardiac fever. When perforated, generalized abdominal tenderness

E. coli*-induced non-clostridial gas gangrene accompanying foamy liver seen in a diabetic male patient aged 70's with advanced rectal adenocarcinoma (gross and H&E, inset: immunostain). Transportal infection of* E. coli *provoked foamy liver due to gas formation by the infected bacteria. The rods embolic in capillary vessels of the liver are immunoreactive with a monoclonal antibody against* E. coli *antigen (inset).*

and peritonism occur. Acute appendicitis is caused by the blockage of the appendiceal lumen (most commonly by fecalith impaction). The blockage results in increased luminal pressure, impaired blood flow, and invasive infection of bacterial flora. When the gangrenous process proceeds, rupture of the appendix can result [44–46]. Mixed bacterial infection is proven. Causative pathogens include *Escherichia coli*, *Bacteroides fragilis*, *B. splanchnicus*, *B. intermedius*, *Peptostreptococcus*, *Pseudomonas*, *Lactobacillus*, *Bilophila wadsworthia*, *Fusobacterium nucleatum*, *Eggerthella lent*a, and *Streptococcus anginosus* (or *milleri*) group. An average of 10.2 different microorganisms have been isolated from the infected lesion. Microscopically, the appendiceal wall reveals marked transmural collection of neutrophils and massive necrosis with the disappearance of the proper muscle layer. Colonization of cocci and rods is easily observed within the gangrenous lesion. Fibrinopurulent peritonitis is associated. Medium-sized blood vessels are thrombosed, accelerating the gangrenous change. Representative findings are displayed in **Figure 19**.

## **8.2 Gangrenous and emphysematous cholecystitis**

Gangrenous cholecystitis is defined as infection-associated transmural necrosis and perforation of the gallbladder wall, as a result of secondary ischemia due to vascular thrombosis. Mural necrosis (infarction) provokes perforation in 25% of cases. Gangrenous cholecystitis represents a form of acute acalculous cholecystitis (**Figure 20**), and the pathology and epidemiology differ from chronic cholecystitis induced by gallstones [47–49]. *Enterobacteriaceae* and anaerobic bacteria are frequently cultured from the bile. The mortality rate is high between 15 and 50%. Risk factors for the development of gangrenous cholecystitis include male sex, advanced age, delayed surgery, cardiovascular diseases, and diabetes mellitus.

Emphysematous cholecystitis is a fulminant and sinister form of acute gangrenous cholecystitis, and it is characterized by the presence of gas both in the lumen (pneumobilia) and wall of the gallbladder. Gas may be extended to the biliary tree or adjacent structures. Either clostridial or non-clostridial etiology is encountered [50]. In case of non-clostridial infection, mixed infection of rods and cocci is often proven microscopically (**Figure 21**). Emphysematous cholecystitis, a form of gas

#### **Figure 19.**

*Gangrenous appendicitis (gross, H&E and Gram). Massive necrotizing inflammation of the appendiceal wall results in perforated purulent peritonitis. A probe is inserted at the site of perforation. Gram-positive bacterial colonies are scattered in the necrotic exudation.*

Emergency laparotomy indicated an 8 mm-sized perforation in the common bile duct in association with biliary peritonitis. Gallbladder was dilated, but without gallstones. Cholecystectomy and partial resection of the common bile duct was performed. T-tube drainage and pazufloxacin administration were effective to control the infection. Surgical specimens of the common bile duct and gallbladder microscopically showed transmural necrosis with perforation/ulceration and massive infection of Gram-positive cocci. The cocci were immunoreactive for enterococcal antigens, and culture of the bile demonstrated *Enterococcus faecalis* (**Figure 22**). Neutrophilic reaction was mild in the gangrenous lesion. Scanning electron microscopy demonstrated clustered cocci at the site of perforation (**Figure 23**).

*Perforated enterococcal cholangitis (gross, H&E and immunostain). Massive infection of* Enterococcus faecalis *provokes transmural necrosis and perforation of the common bile duct (arrow). Enterococcal antigens (inset) are immunohistochemically demonstrated in the cocci overwhelmingly growing throughout the destroyed bile*

*Emphysematous cholecystitis (gas gangrene of the gallbladder) (H&E). The gallbladder wall accompanies gas bubbles released from thin long rods growing in the necrotic tissue. Co-infection of cocci (arrowheads) is noted.*

**Figure 21.**

*Pathology of Gangrene*

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

**Figure 22.**

*duct.*

**109**

*There is little cellular reaction in this highly hypoxic tissue.*

#### **Figure 20.**

*Gangrenous cholecystitis (gross, H&E and immunostain). Surgically removed gallbladder reveals marked necrotizing inflammation with bile-stained (green-colored) multiple mucosal ulceration. Bacterial colonies growing in the necrotic exudation are strongly immunoreactive for* E. coli *antigens.*

gangrene of gallbladder origin, carries a very high mortality rate. Those who suffer from diabetes mellitus or immunosuppression are especially susceptible to this serious condition.

### **8.3 Gangrenous cholangitis**

Gangrenous cholangitis is a severe form of acute cholangitis without biliary stones [47, 51, 52]. Varied pathogens such as *Enterococcus*, *Escherichia coli*, and *Pseudomonas aeruginosa* cause ascending biliary tract infection [53].

A 70-year-old man complained of epigastralgia, vomiting, and difficulty in walking. Abdominal computed tomography scan suggested panperitonitis.

#### **Figure 21.**

*Emphysematous cholecystitis (gas gangrene of the gallbladder) (H&E). The gallbladder wall accompanies gas bubbles released from thin long rods growing in the necrotic tissue. Co-infection of cocci (arrowheads) is noted. There is little cellular reaction in this highly hypoxic tissue.*

Emergency laparotomy indicated an 8 mm-sized perforation in the common bile duct in association with biliary peritonitis. Gallbladder was dilated, but without gallstones. Cholecystectomy and partial resection of the common bile duct was performed. T-tube drainage and pazufloxacin administration were effective to control the infection. Surgical specimens of the common bile duct and gallbladder microscopically showed transmural necrosis with perforation/ulceration and massive infection of Gram-positive cocci. The cocci were immunoreactive for enterococcal antigens, and culture of the bile demonstrated *Enterococcus faecalis* (**Figure 22**). Neutrophilic reaction was mild in the gangrenous lesion. Scanning electron microscopy demonstrated clustered cocci at the site of perforation (**Figure 23**).

#### **Figure 22.**

gangrene of gallbladder origin, carries a very high mortality rate. Those who suffer from diabetes mellitus or immunosuppression are especially susceptible to this

*Gangrenous cholecystitis (gross, H&E and immunostain). Surgically removed gallbladder reveals marked necrotizing inflammation with bile-stained (green-colored) multiple mucosal ulceration. Bacterial colonies*

*Gangrenous appendicitis (gross, H&E and Gram). Massive necrotizing inflammation of the appendiceal wall results in perforated purulent peritonitis. A probe is inserted at the site of perforation. Gram-positive bacterial*

Gangrenous cholangitis is a severe form of acute cholangitis without biliary stones [47, 51, 52]. Varied pathogens such as *Enterococcus*, *Escherichia coli*, and

A 70-year-old man complained of epigastralgia, vomiting, and difficulty in walking. Abdominal computed tomography scan suggested panperitonitis.

*Pseudomonas aeruginosa* cause ascending biliary tract infection [53].

*growing in the necrotic exudation are strongly immunoreactive for* E. coli *antigens.*

serious condition.

**Figure 20.**

**108**

**Figure 19.**

*Pathogenic Bacteria*

*colonies are scattered in the necrotic exudation.*

**8.3 Gangrenous cholangitis**

*Perforated enterococcal cholangitis (gross, H&E and immunostain). Massive infection of* Enterococcus faecalis *provokes transmural necrosis and perforation of the common bile duct (arrow). Enterococcal antigens (inset) are immunohistochemically demonstrated in the cocci overwhelmingly growing throughout the destroyed bile duct.*

Luminal obstruction of the bile duct by pancreatobiliary malignancy is often associated with bactibilia and provokes secondary (ascending) bacterial infection. Enterococci often colonize the cancer tissue, and obstructive cholangitis and liver abscess may follow [54]. They are responsible for postoperative septic complications. The surgical specimen of cholangiocellular carcinoma in a female patient aged 80's showed necrotizing inflammation of the intrahepatic bile duct, as illustrated in **Figure 25**. Gram-positive cocci infected the necrotic cancer tissue. Culture of the

Pulmonary gangrene is a rare form of acute and severe necrotizing pneumonia [55–57]. A necrotic process with cavity formation is observed in a pulmonary segment or lobe. The term pulmonary gangrene is applied when a large amount of lung tissue is sloughed off. The extent of necrosis is far extensive in pulmonary gangrene when compared with usual pulmonary abscess (**Figure 26**). The lesion is often located in the upper lobe of the lung. Thrombosis of large and small vessels plays a significant role in the ischemic pathogenesis. *Klebsiella pneumoniae* is often isolated from the gangrenous lesion. Infection of anaerobes should be the cause of foul smell. The anaerobes may secondarily infect the lung slough under the progres-

Emphysematous pyelonephritis is a severe, multifocal, necrotizing, and gasforming form of acute ascending bacterial infection of the renal parenchyma. Extracapsular extension is common. The disease is most often seen in patients with

*Enterobacteriaceae*, particularly *Escherichia coli* and *Klebsiella pneumoniae* [58–60]. *E. coli*-induced emphysematous pyelonephritis in a male patient aged 60's is demonstrated. The patient suffering from alcoholic cirrhosis manifested lumbar pain and high fever. Septic shock killed the patient. The total clinical course was

*Enterococcal intrahepatic cholangitis superimposed on cholangiocellular carcinoma in the surgically resected liver (gross and H&E). Colonization of culture-proven* Enterococcus faecalis *is demonstrated in the necrotic cancer tissue (arrowheads), provoking acute intrahepatic cholangitis. Asterisk indicates poorly differentiated*

*adenocarcinoma. High-powered H&E picture of the cocci is shown in the right panel.*

**8.5 Emphysematous pyelonephritis and renal papillary necrosis**

poorly controlled diabetes mellitus. The common causative pathogens are

bile was positive for *Enterococcus faecalis*.

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

**8.4 Pulmonary gangrene**

*Pathology of Gangrene*

sively anaerobic environment.

**Figure 25.**

**111**

#### **Figure 23.**

*Scanning electron microscopy of perforated enterococcal cholangitis. Numerous cocci, 0.7 μm in size, are clustered at the site of perforation. Bar indicates 5 μm.*

A diabetic lady aged 40's complaining of severe abdominal and back pain visited an emergency suite. Diabetes mellitus had been poorly controlled. Mild obstructive dilatation of the bile duct and gallbladder were associated. Endoscopic retrograde biliary drainage was performed, but the patient soon died of septic shock. Autopsy demonstrated severe gangrenous and acalculous cholangitis and cholecystitis. Necrotic change with active growth of Gram-negative rods was proven in the biliary tree. Immunostaining using a monoclonal antibody disclosed the *Pseudomonas aeruginosa* antigen in the invasive bacilli (**Figure 24**). Neutrophilic reaction was relatively mild. The lower (intrapancreatic) part of the common bile duct remained intact. The association of diabetes mellitus was evident: the pancreatic islets revealed pronounced deposition of amyloid substances, and the kidney showed diabetic glomerulosclerosis with nodular lesions.

#### **Figure 24.**

*Acute* Pseudomonas *cholangitis (H&E and immunostain). Diabetes mellitus accelerated severe necrotizing (gangrenous) inflammation of the extrahepatic biliary tree. Neutrophilic reactions are limited. The rods are immunoreactive for a* Pseudomonas aeruginosa *antigen visualized with a monoclonal antibody. Acalculous necrotizing cholecystitis was associated.*

### *Pathology of Gangrene DOI: http://dx.doi.org/10.5772/intechopen.93505*

Luminal obstruction of the bile duct by pancreatobiliary malignancy is often associated with bactibilia and provokes secondary (ascending) bacterial infection. Enterococci often colonize the cancer tissue, and obstructive cholangitis and liver abscess may follow [54]. They are responsible for postoperative septic complications. The surgical specimen of cholangiocellular carcinoma in a female patient aged 80's showed necrotizing inflammation of the intrahepatic bile duct, as illustrated in **Figure 25**. Gram-positive cocci infected the necrotic cancer tissue. Culture of the bile was positive for *Enterococcus faecalis*.
