- Email: [email protected]
Peritonitis and fatal septicemia in an elderly woman
I
tection of spontaneous bacterial peritonitis. J Clin Microbio128:2811-2812, 1990. RtmyonBA, Antillon MR: Ascitic fluid pH and lactate:Insensitive and nonspecific tests in detecting ascitie fluid infection. Hepatology13:929-935, 1991.
Stassen WN, McCullough AJ, Bacon BR, et al.: Immediate diagnostic criteria for bacterial infection of aseitic fluid: Evaluation of ascitie fluid polymorphonuelear leucocyte count, pH, and lactate concentration, alone and in combination. Gastroenterol-
ogy 90:1247-1254, 1986. Ukah FO, Merhav H, Kramer D, et al.: Early outcome of liver transplantation in patients with a history of spontaneous bacterial peritonitis. Transplant Proc 25:1113--1115, 1993.
Peritonitis and Fatal Septicemia in an Elderly Woman Karen Demers Patrick Young Vanderbilt University Medical Center Nashville, Tennessee
The patient, a 76-year-old white female with a history of hypertension, presented to another hospital on September 15, 1994, with diffuse, nonradiating abdominal pain. The pain was worse on her right side. She had not eaten in 3 days or had a bowel movement in 4 or 5 days. She had suffered an episode of vomiting with "coffee grounds." However, the patient did not associate the vomiting with the pain. She was transferred to Vanderbilt University Medical Center.
Initial Findings The patient was found to be in tachycardia with atrial fibrillation, and was given digoxin. She had free air in her abdomen and was taken emergently to the operating room for a laparotomy. Gross spillage of intestinal contents was identified, but a perforation could not be located in any segment of the bowel. Adhesion of the omentum in the fight upper quadrant and erythematous inflammation suggested peritonitis in the area of the right pericolic gutter. The sigmoid colon was specifically explored and found to contain debris and an odor suggesting the presence of anaerobic organisms, but no gross perforation. Hospital C o u r s e After laparotomy, the patient was delivered to the surgical intensive-care unit on a ventilator. Her clinical picture ii
56
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i
indicated sepsis with metabolic acidosis. Though her blood pressure was stable, she had a marginal urinary output and difficult respiration. Over the next few days she required increasing ventilatory support and developed a fever. Vasopressor agents were given when her cardiac index fell off. She continued to deteriorate and was assigned a "do not resuscitate" status. On the eighth hospital day, it was deterrnined that bilateral below-the-knee amputations would be necessary due to
T h i s case nicely illustrates the continued value of the autopsy.
ischemic damage secondary to shockstate perfusion. The family declined, however, and requested that the patient's level of care not be increased from its established level. Vasopressors were discontinued. The patient died on hospital day 10. Postmortem Examination Autopsy was performed on September 24, approximately 3 hours after the patient's death. It was limited to "the abdomen and its contents" at the request of the patient's family. No rigor mortis was present. Blanchi
i i
© 1995 Elsevter Science Inc.
ing purple liver mortis was visible on the back. The face, neck, and upper chest were massively edematous; the eyelids were swollen shut and the lips were protuberant. Ecchymoses were scattered over the forearms. A laparotomy was observed, and was maintained open with packed gauze. There was 1-2+ pitting edema present along the pre-tibial area. The feet were cyanotic. There was an area of bright red erythema in the peritoneum overlying the right kidney. The right and left kidneys weighed 215 and 190 grams, respectively. Both showed surface modularity. The cut surface of the kidney revealed an indistinct corticomedullary junction. Vascular congestion was noted. Microscopic findings included occasional obsolescent glomeruli and scant chronic inflammation and fibrosis. The liver weighed 2,300 g and displayed a nutmeg pattern, indicating passive congestion. At microscopy, nodular lymphocytic infiltrates were noted within portal triads. There was scant fibrosis. Though there was no cirrhosis, moderate steatosis and numerous lipogranulomas were observed. The gallbladder was smooth and green with moderate cholesterolosis. The spleen weighed 300 g, was markedly soft and friable, and displayed a patchy, yellow subcapsular exudate. At microscopy, the red pulp was congested and fragmented. Mixed Gramnegative and Gram-positive organisms were detected within areas of necrosis. Numerous Gamna-Gandy
ii
Antlmicmhies and Infecttous Diseases Newsletter 14(8) 1995
i
bodies and lipogranulomas were observed. The pancreas contained mild interstitial fibrosis without active inflammation. The stomach, duodenum, and small and large intestines had glistening serosal surfaces and pale pink mucosa. The appendix had been surgically removed. No gross blood was found in the stomach, and no perforations or focal serosal inflammation were evident. The cecum and first 15 cm of colon were markedly dilated with mucosal edema. The remainder of the colon was impacted with hardened stool throughout. At microscopy, a section of the sigmoid colon demonstrated a serosal reaction consisting of fibrin deposition and foreign body giant cells, with debris consistent with stool. Multiple diverticula of various sizes were present. None showed signs of perforation or overt inflammation or necrosis. A hematoma (2 x 1 x 1 cm) was present at the junction of the sigmoid mesentery and the colon; it showed acute inflammation and contained Gram-positive organisms. The diverticula showed scant chronic inflammation with no evidence of perforation or necrosis. Postmortem blood cultures were positive for Pseudomonas aeruginosa and Enterococcus. Discussion The major findings of the autopsy, which was limited to the abdomen, were peritonitis and bacteremia. The patient, who showed laparoscopic evidence of peritoneal inflammation (but not of perforation) and developed ultimately fatal sepsis and acidosis, most likely suffered perforation of a diverticulum. Though no perforation of the gastrointestinal ((3I) tract was directly identified, the serosal giant cell reaction provided strong microscopic evidence of colonic perforation. The suspected perforation led to spillage of GI contents, including microorganisms and air, into the peritoneum. The spleen was found infected with both Gram-positive and Gram-negative organisms, probably secondary to the sepsis.
Diverticular Disease Diverticulosis is a normally benign condition in which small sections of bowel---consisting of mucosa, attenuated longitudinal muscle, serosa and fat--herniate between the tenia coli. Generally, this occurs in the sigmoid colon at areas of pre-existing weakness. Diverticular diseases may be considered disorders of Western civilization: although the pathogenesis of diverticulosis has not been absolutely defined, it is believed to result from a diet of mostly low-fiber foods. A low-fiber diet leads to reduced water retention and thus lower stool bulk in the sigmoid colon, The reduced bulk necessi-
Diverficulosis is considered a disorder of Western civilization caused by a diet of low-fiber foods.
tates a greater pressure for the generation of effective peristalsis as well as increased intraluminal pressures (based on LaPlace's Law: pressure = wall tension/luminal radius). In turn, increased intraluminal pressures leads to collagen degeneration and thereby wall weakening. This hypothetical scenario is supported by the observation that patients with congenital connective tissue defects, such as Marfan's syndrome, have an increased incidence of diverticulosis. In general, diverticulosis manifests no symptoms and is discovered only incidentally at x-ray, endoscopy or other such diagnostic studies. When symptoms are present, they typically include crampy pain in the left lower quadrant (LLQ), constipation (perhaps alternating with diarrhea), and abdominal distention relieved by release of flatus. Although diverticulosis has sometimes been noted to follow irritable bowel
syndrome, the literature is highly skeptical of a connection between the two conditions. Treatments for diverticulosis include a high-fiber diet and measures to soften the stool so as to promote one or two bowel movements per day. Diverticulitis entails the inflammation, and often the perforation, of a preexisting diverticulum. It is one of the most common causes of GI perforation in the elderly, especially microperforation followed by an exuberant serosal inflammatory reaction like that seen in the current patient. The inflammation is almost always symptomatic. Symptoms generally include LLQ pain, nausea and vomiting, constipation, and fever. Laboratory studies characteristically reveal leukocytosis with a left shift. The inflammation is, in a sense, an attempt by the body to stanch the spread of infection. If this attempt is unsuccessful, peritonitis can ensue. Sometimes, as in the current case, diverticular perforation is strongly suspected but not directly observed. In a study of 248 patients with "perforating" diverticulitis who underwent exploratory surgery, 218 had peritonitis though perforation could be directly demonstrated in only 95. Suggested explanations for the occult perforation included its view obscured by epiploic fat, and dissection of the perforation along the bowel wall leading to rupture at a site away from the bowel. Thus, it is not unusual that a perforation was not found in our patient despite the presence of gross fecal material in the peritoneum. On the other hand, several aspects of the current case are unusual. Free diverticular perforations are a rare though serious complication of diverticulitis. While such perforations require immediate surgery, they seldom lead to sepsis and death when aggressively managed. In addition, the pain they cause typically appears in the LLQ, in the area of the sigmoid colon; our patient's pain was on the right side. It is possible for a redundant loop of sigmoid colon to swing to the right, thereby causing pain in the right lower quadrant (RLQ). Therefore, our patient was unusual in her acquisition of the complication, in her clinical
ii
Antimlcrobics and Infectious Diseases Newsletter 14(8) 1995
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57
presentation, and in her course. Though rare, free perforation is among the most serious complications of diverticulitis. Presenting symptoms, beyond those of diverticulitis, include abdominal wall rigidity, loss of peristaltic sounds over the affected bowel region, and, often, pain at digital rectal examination. A plain film of the abdomen may or may not reveal the presence of free air in the abdomen, as experienced by our patient. Computed tomography (CT) is the diagnostic method of choice in such cases, as it also can assist in the search for other possibilities among the differential diagnoses. When CT is unavailable, a plain f'dm should be obtained with water-soluble contrast (barium causes a sterile peritonitis if it leaks from the bowel). Care should be taken in systematically evaluating this condition, as the correct preoperative diagnosis is made in only 50% of cases. A more common complication of diverticulitis is "contained" perforation. This process starts in the manner of a free perforation, except that the structures surrounding the colon---the omentum and pericolic fat---effectively contain the spread of intestinal contents. The result is usually an abscess that may then either resolve, organize or become chronic. When it organizes (often the case), the result is a fibrous stricture around the colon wall, which at radiography can resemble the "applecore" lesion associated with adenocarcinoma of the colon. On physical exam, patients often have a palpable, rigid colon secondary to fibrosis. Otherwise, the symptoms and signs are the same as for uncomplicated diverticulitis. Fistulae may also result from diverticulitis. Generally a late-stage complication, they often go unrecognized. A fistula can communicate with nearby organ surfaces, including those of the bladder, vagina, uterus, and skin. The colon-to-bladder type represents over 50% of such fistulae and often presents as recurrent urinarytract infection. Forty percent of these cases also present with pneumaturia. They may be surgically resected in certain cases, but are generally
dersurface of the diaphragm that open into the peritoneum by way of stomata. As the diaphragm stretches, fluid flows into these lymph channels from the peritoneum; and as it contracts, the fluid empties into efferent ducts. One-way valves prevent backflow. By this mechanism, bacteria and other particles less than 10 micrometers in diameter can be rapidly cleared. In canine experiments, bacteria were detected in the thoracic duct within 6 min after their injection into the peritoneum, and in the blood within 12 min. Moreover, in 1944 it was demonstrated that placing humans with peritonitis in the semiupright position delayed absorption of bacteria into the blood, and that placing them head down accelerated the process. Some bacteria passed in this way from the peritoneum into the circulation would on autopsy show up in the anterior mediastinal lymph nodes, despite sterility of the remainder of the thoracic cavity. Whether this was true in our patient could not be determined due to the limited extent of the autopsy. Nonetheless, as Pseudomonas and Enterococci were cultured from her blood, it can be assumed that the peritonitis led to the septicemia. Another assumption must be made in our patient due to the absence of direct evidence of perforation: that the observed peritonitis was secondary rather than primary. Supporting this assumption, whereas primary peritonitis most often involves only a single species, secondary peritonitis usually involves a combination of bacteria. Also, primary peritonitis in adults is usually accompanied by liver cirrhosis, for which our patient was negative. Primary peritonitis is also occasionally found in patients with FiE-Hugh-Curtis syndrome (a gonnococcal perihepadtis found exclusively in women) or systemic lupus erythematosus. However, there was no suggestion that our patient had either of these diseases. The observed peritonitis was more likely secondary to intraabdominal spillage. Secondary peritonitis usually involves a mixture of flora in which Gram-negative bacilli and anaerobes
managed medically. Colovaginal fistulae represent approximately 20% of cases, and are usually managed medically. Colouterine fistulae are much more rare, with only 17 cases reported in the world literature. Colocutaneous fistulae, which characteristically present as a suppurant lesion on the thighs or buttocks but rarely occur spontaneously, are generally a complication of surgery.
Peritonitis The peritoneal cavity is the largest extravascular space in the body. Usually, however, the viscera make contact
Diverticulosis becomes a potentially fatal disease when the diverticuli become infected and inflamed, which may then lead to perforation.
with the peritoneum along their serosal borders, so that the space normally contains only 50 ml of fluid or less. This fluid's minimal bacteriocidal activity appears to be complement-based. In adults, the peritoneal surface area is nearly two square meters. Peritonitis can produce an inflammatory infiltrate that creates a hyperosmolar environment, which in turn promotes a net inflow of 300-500 ml of water per hour. The ensuing hypovolemia can be lethal; acute generalized peritonitis can have a hemodynamic effect like that of a burn covering more than 50% of body surface area. To prevent this, aggressive fluid resuscitation must be instituted. Particulate matter is absorbed at the peritoneum via the diaphragmatic lymphatics, specialized vessels on the un-
i
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Antimicrobics and Infectious Diseases Newsletter 14(8) 1995
predominate, especially if the source is colonic. The colonic contents typically contain 101° to 1011 bacteria per gram. Hundreds of different species may be present in each gram. The body usually clears all but very few through a combination of host defenses, especially the diaphragmatic lymphatics, mast-cell degranulation and complement activation. Several teams of researchers have investigated peritoneal clearance by injecting various cocktails of bacteria into rat peritoneum. They have found that, in peritonitis secondary to intra-abdominal spillage from the colon or distal ileum, specific species tend to survive. Indeed, Pseudomonas and Enterococci are noted to survive particularly well, and are found in an average of 8% and 17% of cases, respectively. Furthermore, it has been observed that when pure cultures of Escherichia coli and Enterococcus species are injected into peritoneal cavities of rats, only E. coli results in the death of the rat. Other species, including Enterococci, appear innocuous. For this reason, the role Enterococcal infections in the pathogenesis of peritonitis remains conlxoversial. These findings are also consistent with the possible synergistic effect of Enterococci in peritonitis suggested by some researchers. They hypothesize that, whereas Enterococci are not pathogenic per se, they may play some role in protecting other microbial species against host defenses, in creating a hospitable environment for other microbes, or in provision of growth factors to other microbial species. Before surgery was used to treat intra-abdominal infections, about 90% of patients died from sepsis. When surgery grew in use, the mortality rate dropped below 50%. Though it fell still further
i
with the discovery and use of penicillin, it remains at about 25% today. Clearly, the combination of Enterococci and P. aeruginosa in the blood is potentially lethal. Septicemia from P. aeruginosa alone is noted to be especially deadly. On the other hand, the clinical severity of Enterococcal septicemia depends on whether other species are also present in the blood. If none other is present, the infection is fatal in about 20% of cases. Polymicrobial Enterococcal septicemias present a 58% mortality risk.
Conclusions Autopsy definitively demonstrated peritonitis, diverticula, and sepsis, and provided evidence suggesting colonic perforation. These findings, the patient's clinical course and the literature together suggest that she experienced diverticular rupture leading to peritonitis and septicemia. The presumed cause of death was septic shock. Our conclusions concerning the sequence of ultimately fatal events hinge on the assumption that a GI rupture occurred. Though there is little, if any, gross direct evidence for the assumption, there is at least indirect evidence of colonic perforation in the serosal giant-cell reaction. Also, no evidence suggests that the peritonitis was secondary to some other potential cause, such as pancreatitis, pelvic inflammatory disease or appendix rupture (our patient's appendix had been previously removed). Assuming, then, that the serosal reaction implicates a GI rupture as the cause of peritonitis, what is the most likely reason for the rupture? Possibilities include colon cancer, bowel ischemia, and inflammatory bowel disease. How-
ever, the most likely cause was diverticulitis.
Bibliography Ahrenholz DH, Simmons RL: Peritonitis and other int~a--abdominal infections. In: Howard RJ, Simmons RL (eds): Surgical Infectious Diseases. 2nd edition. Appleton, Lange: Norwalk, Conn., 1987, pp. 605646. Almy TP, Howell DA: Diverticular disease of the colon. N Engl J Med 302:324--331, 1980. Ambrosetti P, Robert J, Witzig IA, et al.: Incidence, outcome and proposed management of isolated abscesses complicating acute left-sided colonic diverticulitis. Dis Colon Rectum 35:1072-1076, 1992. Hau T: Bacteria, toxins, and the peritoneum. World J Surg 14:167-175, 1990. Huettner PC, Fmkler NJ, Welch WR: Colouterine fistula complicating diverticulitis; charcoal challenge test aids in diagnosis. Obstet Gyneco180:550-552, 1992. Jones DI: ABC of eolorectal disease. Diverticular disease. Br Med .T304:1435-1437, 1992. Khan AL, Ah---SeeAK, Crofts TI, et al.: Surgical management of the septic complications of diverticular disease. Ann R Coil Surg Engl 77:16--20, 1995. Killingback M: Management of perforative diverticulitis. Surg Clin N Am 63:97115, 1983. Lewis CM, Zervos MJ: Clinical manifestations of enterococeal infection. Eur I Clin Mierobiol Infect Dis 9:111-117, 1990. Rege RV, Nahrwold DL: Diverticular disease. Curr Probl Surg 26:133--189, 1989. Sarin S, Boulos PB: Long-term outcome of patients presenting with acute complications of diverticular disease. Ann R Coil Surg Eng176:117-120, 1994. Spiro HM: Clinical Gastroenterology. 4th Edition. New York, McGraw-Hill, 1993. pp 585-598.
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tection of spontaneous bacterial peritonitis. J Clin Microbio128:2811-2812, 1990. RtmyonBA, Antillon MR: Ascitic fluid pH and lactate:Insensitive and nonspecific tests in detecting ascitie fluid infection. Hepatology13:929-935, 1991.
Stassen WN, McCullough AJ, Bacon BR, et al.: Immediate diagnostic criteria for bacterial infection of aseitic fluid: Evaluation of ascitie fluid polymorphonuelear leucocyte count, pH, and lactate concentration, alone and in combination. Gastroenterol-
ogy 90:1247-1254, 1986. Ukah FO, Merhav H, Kramer D, et al.: Early outcome of liver transplantation in patients with a history of spontaneous bacterial peritonitis. Transplant Proc 25:1113--1115, 1993.
Peritonitis and Fatal Septicemia in an Elderly Woman Karen Demers Patrick Young Vanderbilt University Medical Center Nashville, Tennessee
The patient, a 76-year-old white female with a history of hypertension, presented to another hospital on September 15, 1994, with diffuse, nonradiating abdominal pain. The pain was worse on her right side. She had not eaten in 3 days or had a bowel movement in 4 or 5 days. She had suffered an episode of vomiting with "coffee grounds." However, the patient did not associate the vomiting with the pain. She was transferred to Vanderbilt University Medical Center.
Initial Findings The patient was found to be in tachycardia with atrial fibrillation, and was given digoxin. She had free air in her abdomen and was taken emergently to the operating room for a laparotomy. Gross spillage of intestinal contents was identified, but a perforation could not be located in any segment of the bowel. Adhesion of the omentum in the fight upper quadrant and erythematous inflammation suggested peritonitis in the area of the right pericolic gutter. The sigmoid colon was specifically explored and found to contain debris and an odor suggesting the presence of anaerobic organisms, but no gross perforation. Hospital C o u r s e After laparotomy, the patient was delivered to the surgical intensive-care unit on a ventilator. Her clinical picture ii
56
0t69-417X/95/$0.00 ÷ 9.50
i
indicated sepsis with metabolic acidosis. Though her blood pressure was stable, she had a marginal urinary output and difficult respiration. Over the next few days she required increasing ventilatory support and developed a fever. Vasopressor agents were given when her cardiac index fell off. She continued to deteriorate and was assigned a "do not resuscitate" status. On the eighth hospital day, it was deterrnined that bilateral below-the-knee amputations would be necessary due to
T h i s case nicely illustrates the continued value of the autopsy.
ischemic damage secondary to shockstate perfusion. The family declined, however, and requested that the patient's level of care not be increased from its established level. Vasopressors were discontinued. The patient died on hospital day 10. Postmortem Examination Autopsy was performed on September 24, approximately 3 hours after the patient's death. It was limited to "the abdomen and its contents" at the request of the patient's family. No rigor mortis was present. Blanchi
i i
© 1995 Elsevter Science Inc.
ing purple liver mortis was visible on the back. The face, neck, and upper chest were massively edematous; the eyelids were swollen shut and the lips were protuberant. Ecchymoses were scattered over the forearms. A laparotomy was observed, and was maintained open with packed gauze. There was 1-2+ pitting edema present along the pre-tibial area. The feet were cyanotic. There was an area of bright red erythema in the peritoneum overlying the right kidney. The right and left kidneys weighed 215 and 190 grams, respectively. Both showed surface modularity. The cut surface of the kidney revealed an indistinct corticomedullary junction. Vascular congestion was noted. Microscopic findings included occasional obsolescent glomeruli and scant chronic inflammation and fibrosis. The liver weighed 2,300 g and displayed a nutmeg pattern, indicating passive congestion. At microscopy, nodular lymphocytic infiltrates were noted within portal triads. There was scant fibrosis. Though there was no cirrhosis, moderate steatosis and numerous lipogranulomas were observed. The gallbladder was smooth and green with moderate cholesterolosis. The spleen weighed 300 g, was markedly soft and friable, and displayed a patchy, yellow subcapsular exudate. At microscopy, the red pulp was congested and fragmented. Mixed Gramnegative and Gram-positive organisms were detected within areas of necrosis. Numerous Gamna-Gandy
ii
Antlmicmhies and Infecttous Diseases Newsletter 14(8) 1995
i
bodies and lipogranulomas were observed. The pancreas contained mild interstitial fibrosis without active inflammation. The stomach, duodenum, and small and large intestines had glistening serosal surfaces and pale pink mucosa. The appendix had been surgically removed. No gross blood was found in the stomach, and no perforations or focal serosal inflammation were evident. The cecum and first 15 cm of colon were markedly dilated with mucosal edema. The remainder of the colon was impacted with hardened stool throughout. At microscopy, a section of the sigmoid colon demonstrated a serosal reaction consisting of fibrin deposition and foreign body giant cells, with debris consistent with stool. Multiple diverticula of various sizes were present. None showed signs of perforation or overt inflammation or necrosis. A hematoma (2 x 1 x 1 cm) was present at the junction of the sigmoid mesentery and the colon; it showed acute inflammation and contained Gram-positive organisms. The diverticula showed scant chronic inflammation with no evidence of perforation or necrosis. Postmortem blood cultures were positive for Pseudomonas aeruginosa and Enterococcus. Discussion The major findings of the autopsy, which was limited to the abdomen, were peritonitis and bacteremia. The patient, who showed laparoscopic evidence of peritoneal inflammation (but not of perforation) and developed ultimately fatal sepsis and acidosis, most likely suffered perforation of a diverticulum. Though no perforation of the gastrointestinal ((3I) tract was directly identified, the serosal giant cell reaction provided strong microscopic evidence of colonic perforation. The suspected perforation led to spillage of GI contents, including microorganisms and air, into the peritoneum. The spleen was found infected with both Gram-positive and Gram-negative organisms, probably secondary to the sepsis.
Diverticular Disease Diverticulosis is a normally benign condition in which small sections of bowel---consisting of mucosa, attenuated longitudinal muscle, serosa and fat--herniate between the tenia coli. Generally, this occurs in the sigmoid colon at areas of pre-existing weakness. Diverticular diseases may be considered disorders of Western civilization: although the pathogenesis of diverticulosis has not been absolutely defined, it is believed to result from a diet of mostly low-fiber foods. A low-fiber diet leads to reduced water retention and thus lower stool bulk in the sigmoid colon, The reduced bulk necessi-
Diverficulosis is considered a disorder of Western civilization caused by a diet of low-fiber foods.
tates a greater pressure for the generation of effective peristalsis as well as increased intraluminal pressures (based on LaPlace's Law: pressure = wall tension/luminal radius). In turn, increased intraluminal pressures leads to collagen degeneration and thereby wall weakening. This hypothetical scenario is supported by the observation that patients with congenital connective tissue defects, such as Marfan's syndrome, have an increased incidence of diverticulosis. In general, diverticulosis manifests no symptoms and is discovered only incidentally at x-ray, endoscopy or other such diagnostic studies. When symptoms are present, they typically include crampy pain in the left lower quadrant (LLQ), constipation (perhaps alternating with diarrhea), and abdominal distention relieved by release of flatus. Although diverticulosis has sometimes been noted to follow irritable bowel
syndrome, the literature is highly skeptical of a connection between the two conditions. Treatments for diverticulosis include a high-fiber diet and measures to soften the stool so as to promote one or two bowel movements per day. Diverticulitis entails the inflammation, and often the perforation, of a preexisting diverticulum. It is one of the most common causes of GI perforation in the elderly, especially microperforation followed by an exuberant serosal inflammatory reaction like that seen in the current patient. The inflammation is almost always symptomatic. Symptoms generally include LLQ pain, nausea and vomiting, constipation, and fever. Laboratory studies characteristically reveal leukocytosis with a left shift. The inflammation is, in a sense, an attempt by the body to stanch the spread of infection. If this attempt is unsuccessful, peritonitis can ensue. Sometimes, as in the current case, diverticular perforation is strongly suspected but not directly observed. In a study of 248 patients with "perforating" diverticulitis who underwent exploratory surgery, 218 had peritonitis though perforation could be directly demonstrated in only 95. Suggested explanations for the occult perforation included its view obscured by epiploic fat, and dissection of the perforation along the bowel wall leading to rupture at a site away from the bowel. Thus, it is not unusual that a perforation was not found in our patient despite the presence of gross fecal material in the peritoneum. On the other hand, several aspects of the current case are unusual. Free diverticular perforations are a rare though serious complication of diverticulitis. While such perforations require immediate surgery, they seldom lead to sepsis and death when aggressively managed. In addition, the pain they cause typically appears in the LLQ, in the area of the sigmoid colon; our patient's pain was on the right side. It is possible for a redundant loop of sigmoid colon to swing to the right, thereby causing pain in the right lower quadrant (RLQ). Therefore, our patient was unusual in her acquisition of the complication, in her clinical
ii
Antimlcrobics and Infectious Diseases Newsletter 14(8) 1995
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57
presentation, and in her course. Though rare, free perforation is among the most serious complications of diverticulitis. Presenting symptoms, beyond those of diverticulitis, include abdominal wall rigidity, loss of peristaltic sounds over the affected bowel region, and, often, pain at digital rectal examination. A plain film of the abdomen may or may not reveal the presence of free air in the abdomen, as experienced by our patient. Computed tomography (CT) is the diagnostic method of choice in such cases, as it also can assist in the search for other possibilities among the differential diagnoses. When CT is unavailable, a plain f'dm should be obtained with water-soluble contrast (barium causes a sterile peritonitis if it leaks from the bowel). Care should be taken in systematically evaluating this condition, as the correct preoperative diagnosis is made in only 50% of cases. A more common complication of diverticulitis is "contained" perforation. This process starts in the manner of a free perforation, except that the structures surrounding the colon---the omentum and pericolic fat---effectively contain the spread of intestinal contents. The result is usually an abscess that may then either resolve, organize or become chronic. When it organizes (often the case), the result is a fibrous stricture around the colon wall, which at radiography can resemble the "applecore" lesion associated with adenocarcinoma of the colon. On physical exam, patients often have a palpable, rigid colon secondary to fibrosis. Otherwise, the symptoms and signs are the same as for uncomplicated diverticulitis. Fistulae may also result from diverticulitis. Generally a late-stage complication, they often go unrecognized. A fistula can communicate with nearby organ surfaces, including those of the bladder, vagina, uterus, and skin. The colon-to-bladder type represents over 50% of such fistulae and often presents as recurrent urinarytract infection. Forty percent of these cases also present with pneumaturia. They may be surgically resected in certain cases, but are generally
dersurface of the diaphragm that open into the peritoneum by way of stomata. As the diaphragm stretches, fluid flows into these lymph channels from the peritoneum; and as it contracts, the fluid empties into efferent ducts. One-way valves prevent backflow. By this mechanism, bacteria and other particles less than 10 micrometers in diameter can be rapidly cleared. In canine experiments, bacteria were detected in the thoracic duct within 6 min after their injection into the peritoneum, and in the blood within 12 min. Moreover, in 1944 it was demonstrated that placing humans with peritonitis in the semiupright position delayed absorption of bacteria into the blood, and that placing them head down accelerated the process. Some bacteria passed in this way from the peritoneum into the circulation would on autopsy show up in the anterior mediastinal lymph nodes, despite sterility of the remainder of the thoracic cavity. Whether this was true in our patient could not be determined due to the limited extent of the autopsy. Nonetheless, as Pseudomonas and Enterococci were cultured from her blood, it can be assumed that the peritonitis led to the septicemia. Another assumption must be made in our patient due to the absence of direct evidence of perforation: that the observed peritonitis was secondary rather than primary. Supporting this assumption, whereas primary peritonitis most often involves only a single species, secondary peritonitis usually involves a combination of bacteria. Also, primary peritonitis in adults is usually accompanied by liver cirrhosis, for which our patient was negative. Primary peritonitis is also occasionally found in patients with FiE-Hugh-Curtis syndrome (a gonnococcal perihepadtis found exclusively in women) or systemic lupus erythematosus. However, there was no suggestion that our patient had either of these diseases. The observed peritonitis was more likely secondary to intraabdominal spillage. Secondary peritonitis usually involves a mixture of flora in which Gram-negative bacilli and anaerobes
managed medically. Colovaginal fistulae represent approximately 20% of cases, and are usually managed medically. Colouterine fistulae are much more rare, with only 17 cases reported in the world literature. Colocutaneous fistulae, which characteristically present as a suppurant lesion on the thighs or buttocks but rarely occur spontaneously, are generally a complication of surgery.
Peritonitis The peritoneal cavity is the largest extravascular space in the body. Usually, however, the viscera make contact
Diverticulosis becomes a potentially fatal disease when the diverticuli become infected and inflamed, which may then lead to perforation.
with the peritoneum along their serosal borders, so that the space normally contains only 50 ml of fluid or less. This fluid's minimal bacteriocidal activity appears to be complement-based. In adults, the peritoneal surface area is nearly two square meters. Peritonitis can produce an inflammatory infiltrate that creates a hyperosmolar environment, which in turn promotes a net inflow of 300-500 ml of water per hour. The ensuing hypovolemia can be lethal; acute generalized peritonitis can have a hemodynamic effect like that of a burn covering more than 50% of body surface area. To prevent this, aggressive fluid resuscitation must be instituted. Particulate matter is absorbed at the peritoneum via the diaphragmatic lymphatics, specialized vessels on the un-
i
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Antimicrobics and Infectious Diseases Newsletter 14(8) 1995
predominate, especially if the source is colonic. The colonic contents typically contain 101° to 1011 bacteria per gram. Hundreds of different species may be present in each gram. The body usually clears all but very few through a combination of host defenses, especially the diaphragmatic lymphatics, mast-cell degranulation and complement activation. Several teams of researchers have investigated peritoneal clearance by injecting various cocktails of bacteria into rat peritoneum. They have found that, in peritonitis secondary to intra-abdominal spillage from the colon or distal ileum, specific species tend to survive. Indeed, Pseudomonas and Enterococci are noted to survive particularly well, and are found in an average of 8% and 17% of cases, respectively. Furthermore, it has been observed that when pure cultures of Escherichia coli and Enterococcus species are injected into peritoneal cavities of rats, only E. coli results in the death of the rat. Other species, including Enterococci, appear innocuous. For this reason, the role Enterococcal infections in the pathogenesis of peritonitis remains conlxoversial. These findings are also consistent with the possible synergistic effect of Enterococci in peritonitis suggested by some researchers. They hypothesize that, whereas Enterococci are not pathogenic per se, they may play some role in protecting other microbial species against host defenses, in creating a hospitable environment for other microbes, or in provision of growth factors to other microbial species. Before surgery was used to treat intra-abdominal infections, about 90% of patients died from sepsis. When surgery grew in use, the mortality rate dropped below 50%. Though it fell still further
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with the discovery and use of penicillin, it remains at about 25% today. Clearly, the combination of Enterococci and P. aeruginosa in the blood is potentially lethal. Septicemia from P. aeruginosa alone is noted to be especially deadly. On the other hand, the clinical severity of Enterococcal septicemia depends on whether other species are also present in the blood. If none other is present, the infection is fatal in about 20% of cases. Polymicrobial Enterococcal septicemias present a 58% mortality risk.
Conclusions Autopsy definitively demonstrated peritonitis, diverticula, and sepsis, and provided evidence suggesting colonic perforation. These findings, the patient's clinical course and the literature together suggest that she experienced diverticular rupture leading to peritonitis and septicemia. The presumed cause of death was septic shock. Our conclusions concerning the sequence of ultimately fatal events hinge on the assumption that a GI rupture occurred. Though there is little, if any, gross direct evidence for the assumption, there is at least indirect evidence of colonic perforation in the serosal giant-cell reaction. Also, no evidence suggests that the peritonitis was secondary to some other potential cause, such as pancreatitis, pelvic inflammatory disease or appendix rupture (our patient's appendix had been previously removed). Assuming, then, that the serosal reaction implicates a GI rupture as the cause of peritonitis, what is the most likely reason for the rupture? Possibilities include colon cancer, bowel ischemia, and inflammatory bowel disease. How-
ever, the most likely cause was diverticulitis.
Bibliography Ahrenholz DH, Simmons RL: Peritonitis and other int~a--abdominal infections. In: Howard RJ, Simmons RL (eds): Surgical Infectious Diseases. 2nd edition. Appleton, Lange: Norwalk, Conn., 1987, pp. 605646. Almy TP, Howell DA: Diverticular disease of the colon. N Engl J Med 302:324--331, 1980. Ambrosetti P, Robert J, Witzig IA, et al.: Incidence, outcome and proposed management of isolated abscesses complicating acute left-sided colonic diverticulitis. Dis Colon Rectum 35:1072-1076, 1992. Hau T: Bacteria, toxins, and the peritoneum. World J Surg 14:167-175, 1990. Huettner PC, Fmkler NJ, Welch WR: Colouterine fistula complicating diverticulitis; charcoal challenge test aids in diagnosis. Obstet Gyneco180:550-552, 1992. Jones DI: ABC of eolorectal disease. Diverticular disease. Br Med .T304:1435-1437, 1992. Khan AL, Ah---SeeAK, Crofts TI, et al.: Surgical management of the septic complications of diverticular disease. Ann R Coil Surg Engl 77:16--20, 1995. Killingback M: Management of perforative diverticulitis. Surg Clin N Am 63:97115, 1983. Lewis CM, Zervos MJ: Clinical manifestations of enterococeal infection. Eur I Clin Mierobiol Infect Dis 9:111-117, 1990. Rege RV, Nahrwold DL: Diverticular disease. Curr Probl Surg 26:133--189, 1989. Sarin S, Boulos PB: Long-term outcome of patients presenting with acute complications of diverticular disease. Ann R Coil Surg Eng176:117-120, 1994. Spiro HM: Clinical Gastroenterology. 4th Edition. New York, McGraw-Hill, 1993. pp 585-598.
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AntimleroblcsandInfectiousDiseasesNewsletter14(8)1995
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