Peritonitis pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shivani Chaparala M.B.B.S [2]

Peritonitis Main Page
Patient Information
Overview
Causes
Classification Spontaneous Bacterial Peritonitis Secondary Peritonitis
Differential Diagnosis

Primary peritonitis

• The route of infection in primary peritonitis is often presumed to be hematogenous, lymphogenous, or transmural migration through an intact gut wall from the intestinal lumen or, in women, from the vagina via the fallopian tubes. .

Postulated mechanisms

• Bacteria have been postulated to migrate from the bowel lumen into mesenteric lymph and to enter the systemic circulation via the thoracic duct(bacterial translocation).
• The role of intestinal bacterial overgrowth is uncertain because different studies have provided conflicting results. .
• Enteric bacteria could also enter the systemic circulation from the portal vein by passage through the liver or by portosystemic shunts in patients with portal hypertension.
• The hepatic reticuloendothelial system is known to be a major site for removal of bacteria from blood. It has been postulated that organisms removed from the systemic circulation by the liver contaminate hepatic lymph and pass through the permeable lymphatic walls into the ascitic fluid.
• Results of animal studies, however, have suggested that destruction of bloodborne bacteria by the reticuloendothelial system is impaired in experimental cirrhosis and in alcoholic liver disease. Infection of ascitic fluid would be facilitated by impaired reticuloendothelial clearance of bacteria from the bloodstream, which would tend to perpetuate bacteremia and increase the opportunity to cause metastatic infection at susceptible sites, such as the ascitic collection.
• In addition, alcohol abuse and cirrhosis have been reported to be associated with impaired intracellular killing by monocytes and neutrophils and with impaired opsonization and low levels of serum complement. The decrease in phagocytic activity seen in alcoholic cirrhosis is proportional to the severity of the liver disease. Impaired local defenses in the peritoneal cavity also facilitate infection of ascites.
• Opsonic activity, as reflected by low levels of complement and immunoglobulins, is reduced in the ascitic fluid of patients with the nephrotic syndrome and cirrhosis.
• Enteric bacteria may also gain access to the peritoneal cavity by directly traversing the intact intestinal wall. In an animal model, E. coli passes from the bowel into the peritoneal cavity after the introduction of hypertonic solutions into the peritoneum. A similar mechanism may explain the enteric bacterial peritonitis that frequently complicates peritoneal dialysis.
• The infrequent occurrence of bacteremia and the multiplicity of species in peritoneal fluid when anaerobic bacteria are involved suggest that transmural migration of bacteria is the probable route of infection of ascitic fluid in most of these patients. In addition, the occurrence of polymicrobial anaerobic peritonitis in two patients after infusion of vasopressin into the superior mesenteric or gastroduodenal arteries suggested that arterial vasoconstriction decreased the intestinal mucosal barrier and permitted transmural migration of enteric organisms.
• When pneumococci are present simultaneously in vaginal secretions and peritoneal fluid in prepubertal girls, an ascending infection of genital origin is likely in these patients. The alkaline vaginal secretions of prepubertal girls may be less inhibitory to bacterial growth than the acidic secretions of postpubertal women.
• Transfallopian spread is also suggested by the development of peritonitis in women with intrauterine devices.
• In women with gonococcal or chlamydial perihepatitis (Fitz-Hugh-Curtis syndrome), the route of spread is presumably from the fallopian tubes and paracolic gutters to the subphrenic space, but it may also be hematogenous.
• Although tuberculous peritonitis may result from direct entry into the peritoneal cavity of tubercle bacilli (from the lymph nodes, intestine, or genital tract in patients with active disease of these organs), it is more likely to result from hematogenous dissemination from remote foci of tuberculosis, most commonly in the lung. Tuberculous peritonitis can become clinically evident after the initial focus has healed completely.
• Infection of ascites stimulates a dramatic increase in proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1, IL-6, interferon-γ (IFN-γ), and soluble adhesion molecules in the serum, as well as, to a much greater extent, in the peritoneal exudate. These cytokines are produced by macrophages and other host cells in response to bacteria or bacterial products, such as endotoxin. In an experimental model of peritonitis, antibodies to endotoxin, but not to TNF-α, were found to prevent death and reduce bacterial numbers in the peritoneal exudate. Another potential source is direct translocation of cytokines through the intestinal barrier. Undoubtedly, many of the systemic and abdominal manifestations of peritonitis are mediated by these molecules. Furthermore, the presence of these cytokines may lead to further reduction of effective arterial blood volume, as indicated by an increase in plasma renin activity and the development of renal insufficiency. Approximately 30% of patients with primary peritonitis develop renal insufficiency, which has been found to be the most sensitive predictor of in-hospital mortality.

Secondary peritonitis

• The virulence of the bacteria that cause peritonitis is enhanced when certain microorganisms are either combined intraperitoneally with substances such as mucus, enzymes, or hemoglobin or are combined with certain other microorganisms.
• Chemical peritonitis can be produced by escape of bile or of gastric or pancreatic secretions into the peritoneal cavity. When gastric acid escapes into the peritoneal cavity, there is an outpouring of serum protein and electrolytes from the blood into the peritoneal cavity. The acidity is neutralized quickly by these buffers and by diffusion of hydrogen ions into the body fluids. Widespread necrosis may result from enzymatic digestion after intraperitoneal spillage of potent pancreatic enzymes. Escape of bile into the peritoneal cavity is generally considered to be a grave, often fatal situation. *The severity of peritonitis after escape of these intestinal secretions results in subsequent bacterial peritonitis. *Bacteria may enter the peritoneal cavity with contaminated intestinal secretions through perforations in the gastrointestinal wall or by migration through the wall of the intact gastrointestinal tract in response to irritation of the serosal surface by bile and possibly other intestinal tract secretions.
• Establishment of an anaerobic infection requires a favorable environment. These requirements are usually met by tissue devitalized as a consequence of ischemia, trauma, or neoplastic growth. When proper conditions are obtained, anaerobic organisms can achieve doubling rates equivalent to rates seen with aerobic enteric bacilli. In vivo, the rapidly expanding bacterial and inflammatory cell mass, frequently accompanied by gas production, can interrupt the blood supply to the immediately surrounding tissue and cause further tissue necrosis.
• Gram-negative anaerobic cocci and bacilli (including B. fragilis) possess endotoxins, although with much weaker biologic activity in comparison with endotoxins extracted from their aerobic counterparts. In addition, anaerobes may be resistant to host defenses.