* This is the Veterinary Version. *
Overview of Peritonitis
Peritonitis is an inflammation of the serous membranes of the peritoneal cavity. It may be a primary disease or secondary to other pathologic conditions. Different infectious and noninfectious agents may cause peritonitis, which may result in a variety of clinical manifestations, disease progression, and outcome. Peritonitis may be acute or chronic, septic or nonseptic, local or diffuse, or adhesive or exudative. The term “tertiary peritonitis,” used in human medicine for particular cases of chronic peritonitis with a small number of bacteria or fungi, is not used in veterinary medicine.
Primary peritonitis is less common than secondary peritonitis and may be infectious or idiopathic. In infectious primary peritonitis, infectious agents spread via the bloodstream into the peritoneal cavity of animals that are often immunocompromised. Such infectious agents include feline coronavirus (FCoV), which causes feline infectious peritonitis (FIP); Nocardia spp; Mycobacterium spp; Haemophilus parasuis; and other infectious agents. Progression of primary peritonitis tends to be chronic.
Peritonitis occurs secondary to another disease as the result of exposure of the peritoneal cavity to nonspecific infectious or noninfectious agents. It is often acute and frequently results in a progressive, systemic disease. Secondary septic peritonitis is commonly associated with perforation of and leakage from GI organs (eg, traumatic reticuloperitonitis in cattle), with subsequent processes allowing transmural migration of bacteria (eg, neoplasia, intestinal ischemia), or with perforation/rupture of or leakage from other infected viscera (eg, abscesses in liver, spleen, omentum, cystitis, endometritis, pyometra). Furthermore, migration of parasites through the abdominal cavity may also result in leakage of chyme with subsequent septic peritonitis. Perforating wounds of the abdominal wall (eg, dog bites) or dehiscence of abdominal wound closure may result in laceration of viscera and inoculation of foreign material and microorganisms into the peritoneal cavity.
Microorganisms associated with septic peritonitis usually reflect the source of contamination. A mixed bacterial population is seen in GI tract perforation, whereas perforation of nongastrointestinal viscera (eg, urinary or gall bladder, uterus, prostate) or hematogeous infection of the peritoneal cavity may be more typically associated with aerobic organisms, including Escherichia coli, Streptococcus equi zooepidemicus, Staphylococcus, Proteus, Rhodococcus, Klebsiella, Salmonella, Enterobacter, Pseudomonas, or Corynebacterium.
Secondary aseptic peritonitis occurs after contamination of the abdominal cavity with chemical irritants (eg, bile, urine, drugs) or intestinal ischemia. Common conditions are urolithiasis and rupture of the urinary or gall bladder; however, these conditions are not always aseptic. The originally aseptic peritoneal inflammations may later become septic. In addition, intraperitoneal administration of drugs or fluids may result in temporary inflammatory reactions of the peritoneum. Because New World camelids show severe inflammatory reactions to infections with Dicrocoelium dentriticum, peritonitis may develop subsequent to the severe hepatitis. In large animals, peritonitis is most commonly seen in cattle, less often in horses, and rarely diagnosed in pigs, sheep, and goats. It is a serious and often fatal condition in cats (FIP). For common causes of peritonitis in various species, see Table: Common Causes of Peritonitis.
Common Causes of Peritonitis
Inflammation of the peritoneum is the result of a variety of possible pathogenetic pathways that are species-dependent (eg, peritoneal inflammatory response in cattle is characterized by extensive fibrin formation, horses tend to develop exudative peritonitis) and mainly influenced by etiology (eg, primary or secondary, septic or nonseptic). Because of the release of inflammatory mediators after contact with mechanical, chemical, or infectious agents, serosal capillary permeability is increased and results in leakage of plasma proteins, solutes, and water into the peritoneal cavity. Exudation of protein-rich fluid may result in hypoproteinemia and facilitates bacterial proliferation. The combined effect of large fluid losses into the peritoneal cavity and vasodilatory effects of absorbed toxins may produce profound hypotension and hypovolemia. The inflammation may decrease the animal's antioxidative capacity and result in oxidative stress.
Rupture or perforation of the forestomach, stomach, or intestine with spillage of large volumes of gastric or intestinal contents and rupture or perforation of the contaminated uterus leads to an acute septic peritonitis. Toxins produced by bacteria and tissue breakdown are readily absorbed through the peritoneum and have severe systemic effects leading to hypotension, shock, systemic inflammatory response syndrome (SIRS), and disseminated intravascular coagulation (DIC). Endotoxins and acid-base and electrolyte disturbances directly affect cardiac function, leading to reduced cardiac output and circulatory failure. Paralytic ileus is considered to be a frequent result of acute peritonitis, causing functional obstruction and an increased mortality rate. Large volumes of inflammatory exudates may be secreted into the peritoneal cavity during peritonitis and may lead to impaired respiration by impinging on the diaphragm. Spillage of small amounts of gastric or intestinal content (eg, after transcutaneous rumenocentesis, bar suture techniques for left displaced abomasum surgery) normally result in local peritonitis.
Chronic peritonitis is often characterized by extensive secretion of fibrinogen and subsequent formation of fibrinous/fibrous adhesions. Such adhesions help localize the inflammatory process (eg, traumatic reticuloperitonitis in cattle, type 3 abomasal ulcers in cattle) but may cause mechanical or functional obstruction of the GI tract. Chronic peritonitis in horses often results in recurrent colic episodes.
Clinical signs vary depending on the type and etiology of peritonitis. Affected animals may develop toxemia and septicemia, shock, hemorrhage, abdominal pain, paralytic ileus, fluid accumulation, and adhesions in varying degrees. However, there are reports of apparently clinically healthy animals having chronic bacterial peritonitis.
Shock, hypotension, acid-base disturbances, and circulatory collapse after acute septic peritonitis associated with rupture of intestines or uterus often lead to sudden death. These animals normally show only limited clinical signs of peritonitis. In less severe cases, abdominal pain and fever are common. Hypothermia can also be seen as a result of dehydration, hypovolemia, and sepsis. Abdominal pain may be permanent and severe, characterized by guarding the abdomen, stiff gait, or recumbency. In all species, pain responses are most evident in the early stages. Abdominal distention, which may be inapparent, usually is due to accumulation of peritoneal exudates, paralytic ileus, or peritoneal adhesions. Fecal output is often decreased, although frequency of defecation may be increased in the early stages of peritonitis. Animals with secondary peritonitis may also show clinical signs associated with the primary disease.
Rectal palpation is a useful diagnostic technique to evaluate the peritoneum and accessible abdominal organs in large animals; however, local peritonitic processes in the cranial abdomen (eg, traumatic reticuloperitonitis in cattle) do not result in clinical signs that can be diagnosed by rectal examination. Abdominal radiography may be used in small animals. In horses and cattle, radiography can be also used as a diagnostic tool, but high-power x-ray machines are required; therefore, this technique is limited to stationary units in veterinary clinics. Generally, ultrasonography is the most valuable diagnostic tool to examine the abdominal cavity and assess the extent, localization, and character of peritonitis. Additionally, ultrasonography allows a guided abdominocentesis, which can be used (in both large and small animals) to obtain fluid for cytologic and biochemical examination and bacteriologic culture. Diagnostic peritoneal lavage can be used if peritoneal fluid cannot be obtained by abdominocentesis. Diagnostic laparoscopy or laparotomy can be considered to verify the diagnosis. Diagnostic laparotomy is frequently used in cattle because it is inexpensive, can be performed in standing position, and is associated with few or minor complications; it also makes additional diagnostic procedures unnecessary and can often be combined with therapeutic measures.
Clinical signs of peritonitis in cattle are often nonspecific and characterized by reduced feed intake, drop in milk production, and decreased rumination activity. In chronic cases, ruminal contractions may be present but reduced in intensity. Abdominal percussion may reveal ruminal tympany or pneumoperitoneum. Moderate fever is typical during the first 24–36 hr in cattle with acute, local peritonitis. High fever suggests acute, diffuse peritonitis. Cattle with peritonitis often have a shuffling, cautious gait with a rigid arched back, and grunt when walking or passing urine or feces. Deep palpation of the abdominal wall and pain provocation tests result in pain response. Chronic peritonitis is associated with development of fibrous adhesions. Depending on localization, rectal palpation may reveal adhesions between intestinal loops and peritoneum. Cattle may suffer from chronic indigestion (Hoflund syndrome, abomasal impaction) or toxemia, with periods of acute, severe illness caused by partial intestinal obstruction. The majority of cattle develop a localized peritonitis by extensive fibrin formation; however, in a few cases the abdominal cavity contains large volumes of turbid, infected peritoneal fluid.
Generally, the clinical signs in small ruminants, New World camelids, and pigs are similar to those in other animals. However, peritonitis is rarely diagnosed clinically in pigs, sheep, or goats, although it is not an uncommon finding on routine meat inspection after slaughter of pigs. It is more common in llamas and alpacas.
Clinical signs include colic, distended intestines on rectal examination, gastric reflux, and occasionally diarrhea. Rectal palpation may reveal tacky, dry mucosa and in some cases fibrinous or fibrous adhesions between intestinal loops and other abdominal organs. Intestinal peristaltic sounds are reduced. Tachycardia, weak pulses, poor peripheral perfusion, and fever are common. Weight loss and intermittent abdominal pain (colic) may be seen in horses with chronic peritonitis.
In small animals, anorexia and depression are nonspecific signs of peritonitis, often accompanied by vomiting and decreased defecation. The abdomen may be distended. Abdominal palpation may be painful, and abdominal masses may be detected. Icterus may be present in generalized biliary peritonitis in small animals. Abdominal radiographs may reveal GI obstruction, bowel dilatation, free abdominal air, ascites, or radiodense foreign material. Loss of serosal details in radiographs indicates abdominal fluid.
Laboratory analyses are helpful to confirm the clinical diagnosis and determine the severity of peritonitis, and should include a CBC and several biochemical parameters in blood and peritoneal fluid.
Acute, diffuse peritonitis with toxemia is usually accompanied by leukopenia, neutropenia, and a marked increase in immature neutrophils (degenerative left shift). In less severe acute peritonitis, leukocytosis may occur as a result of increased neutrophil production. Acute, localized peritonitis may reveal a normal WBC count with a regenerative left shift. The total WBC count in chronic peritonitis may be normal, with an occasional increase in lymphocytes and monocytes. Anemia may occur due to hemorrhage into the peritoneal cavity but is also commonly associated with chronic inflammatory processes. A number of abnormalities of serum biochemical parameters (eg, total protein, albumin, fibrinogen, bilirubin, LDH, alkaline phosphatase, CK) may accompany peritonitis. Hypoalbuminemia, hyperglobulinemia, and hyperbilirubinemia are frequently present. Generally, the changes in hematologic and biochemical parameters indicate inflammatory processes and tissue damage, but they are not pathognomonic for peritonitis.
The peritoneal fluid is a plasma dialysate with specific physical and chemical properties that depend on membrane permeability, concentrations and electrical charges of ions, and osmotic pressure. The fluid contains cells deriving from the mesothelium and the blood or lymphatic vessels. Under physiologic conditions, peritoneal fluid is a transudate, whereas peritonitis results in a fluid that is typically characterized as an exudate. Analysis of peritoneal fluid is a useful diagnostic method in gastroenterology, because the fluid generally reflects abdominal conditions. The volume of peritoneal fluid is frequently increased in peritonitis. In cases of septic peritonitis, samples of peritoneal fluid should be examined microbiologically to characterize infectious pathogens.
The parameters of the classic transudate-exudate categorization system are shown in ( Characteristics of Transudates and Exudates in Cattle, Horses, Dogs, and Cats). A peritoneal fluid showing properties of both a transudate and an exudate is commonly called a modified transudate. Use of a scoring system allows further classification as mild, moderate, or severe peritonitis. In practice, however, analysis of peritoneal fluid may be inconsistent, leading to inconclusive results. Therefore, the diagnostic value of this traditional concept is limited. To improve the sensitivity of the distinction between an exudate and transudate of pleural and peritoneal effusions in human medicine, Light’s criteria (fluid to serum protein ratio >0.5, fluid to serum LDH ratio >0.6, or fluid LDH activity >200 U/L), cutoff values for ratios between peritoneal fluid and plasma or serum of various parameters (eg, lactate, glucose, enzymes), and the serum-ascites albumin gradient (SAAG) have been established. These concepts have been applied to some animal species (ie, horses, cattle, small animals).
Characteristics of Transudates and Exudates in Cattle, Horses, Dogs, and Cats
Under physiologic conditions, the ratio between lymphocytes and neutrophils is close to 1:1. Acute peritonitis usually results in an increased number of leukocytes, and the percentage of neutrophils can be 60%–90%. However, in cases of peracute septic inflammation, the number of leukocytes may decrease due to necrosis and cell damage. Histologically, a high rate of degenerative leukocytes (cytolysis, karyorrhexis, or karyolysis) can be found. In chronic peritoneal inflammation, the proportion of neutrophils decreases and the proportion of monocytes increases. The presence of intra- or extracellular bacteria confirms septic peritonitis. Gram-staining enables differentiation between gram-positive and gram-negative bacteria and facilitates early antibiotic treatment.
The physiologic total protein concentration in peritoneal fluid is 20–25 g/L. The normal protein ratio between peritoneal fluid and serum is lower than 1:2. The SAAG is calculated by subtracting the peritoneal fluid albumin concentration from the serum concentration. The cutoff value of 11 g/L for people seems suitable for monogastric animals. However, the reference values for protein ratio and SAAG are not applicable to dairy cattle, mainly because of their higher serum protein and albumin concentrations than those of monogastric animals and people. In addition, in cattle, the protein ratio and SAAG did not show higher diagnostic values than the total protein concentration in peritoneal fluid alone.
In healthy animals, glucose concentration is the same in both serum and peritoneal fluid. Bacterial infection of the peritoneal cavity results in a major decrease of peritoneal glucose concentration. A peritoneal fluid:serum ratio of glucose concentrations <0.5 is highly sensitive and specific for septic peritonitis. Because in animals with septic peritonitis the glucose concentration in peritoneal fluid frequently falls below the detection limit, it is often not even necessary to measure the glucose concentration in serum.
Intestinal ischemia results in an increase of l-lactate concentration in plasma and peritoneal fluid. Although an association exists between l-lactate concentration in peritoneal fluid and plasma, l-lactate in peritoneal fluid is considered to be more closely correlated to the severity of intestinal ischemia. Physiologically, l-lactate concentration in peritoneal fluid is lower than that in plasma (in healthy horses, the ratio is ~1:2). This ratio is reversed in colicky horses with intestinal ischemia, cows with abomasal volvulus, and dogs with gastric dilatation volvulus. Similar to that in horses, an increased l-lactate concentration in peritoneal fluid has been found in cattle with abomasal volvulus and dogs with gastric dilatation volvulus. In addition, lactate is also a bacterial metabolite (predominately d-lactate); therefore, increased lactate concentration in peritoneal fluid may also indicate septic peritonitis. The accuracy of peritoneal lactate concentration in differentiating septic and nonseptic peritonitis varies between species (eg, 90%–95% in dogs but 65%–70% in cats).
Inflammation can be monitored using acute phase proteins such as C-reactive protein or haptoglobin (in cattle) as markers. Acute phase protein concentrations are increased in peripheral blood and in peritoneal fluid in animals with peritonitis; however, these parameters are general indicators for inflammation and not specific for peritonitis.
Fibrinogen concentration in peritoneal fluid may be increased in animals with peritonitis. However, fibrinogen concentration has limited diagnostic value, because there is only a weak association between peritoneal and blood fibrinogen concentration. An increased concentration of the fibrin degradation product d-dimer indicates intestinal ischemia and inflammation with high sensitivity and specificity. Normal values for human plasma are <0.3 mg/L. Reference values for small animals and horses seem to be similar to those in people. The peritoneal fluid d-dimer concentration in healthy cows is <0.6 mg/L; increased values indicate peritonitis with high sensitivity and specificity.
Inflammation, intestinal ischemia, and reperfusion affect the activities of several enzymes (alkaline phosphatase [ALP], AST, CK, LDH) in peritoneal fluid and peripheral blood. CK activity is primarily increased in serum and peritoneal fluid in cases of intestinal ischemia. The origin of CK is thought to be the muscular layer of the strangulated, ischemic intestines. However, other tissues (eg, striated muscle after colic episodes in horses) may be sources of higher CK activities; therefore, the sensitivity and specificity of CK are low.
LDH activity is a measure of inflammatory response and has been used to differentiate exudate from transudate (peritoneal fluid:serum LDH ratio >0.6; LDH activity of peritoneal fluid >200 U/L). The reference values for monogastric animals, but not those for cattle, are similar to those for people. For cattle, a cut-off value of 960 U/L has been identified.
An increase of ALP during intestinal ischemia and reperfusion has been found in peritoneal fluid of horses with colic and cows with displaced abomasum. However, the origin of the ALP was not exclusively the damaged stomach or intestine. Other sources of the increased ALP activity in these cases include hepatocytes and granulocytes. Normally, serum ALP activity does not show major changes during intestinal ischemia.
Increased concentrations of protein and globulin in serum and peritoneal fluid are often seen in cats with FIP. However, neither parameter is accurate enough for diagnosis, especially if measured in serum. Calculation of the albumin:globulin ratio may improve the diagnostic value. The traditional Rivalta’s test simply differentiates transudates from exudates. Although it produces false-positive results in cats with septic bacterial peritonitis, it still seems useful for FIP diagnosis. The widely used parameter α-1-acid glycoprotein indicates inflammation but is not specific for FIP. Serum anti-feline coronavirus (FCoV) antibody titers must be interpreted critically, because many healthy cats are anti-FCoV-antibody positive. The diagnostic value of anti-FCoV antibody titers in peritoneal fluid is still under discussion. A number of advanced diagnostic methods (eg, immunofluorescent staining of FCoV antigen in peritoneal macrophages, ELISA to detect antigen-antibody complexes in serum, reverse transcriptase-PCR) have been introduced as diagnostic measures to improve accuracy of FIP diagnosis. Generally, the laboratory tests performed on peritoneal fluid are superior to those that use serum. Further immunohistochemistry for intracellular FCoV antigen in macrophages derived from ocular or dermal lesions of FIP cats may aid the diagnosis. (Also see Feline Infectious Peritonitis.)
Although the mesothelium of the peritoneum is able to regenerate rapidly, peritonitis must be considered a severe, life-threatening disease with a guarded prognosis. Prognosis strongly depends on the character and severity of the disease and, therefore, must be determined individually. General survival rates of 50%–70% have been reported, with much lower rates for return of productivity in farm animals. In horses, the prognosis for further use in equestrian sport is guarded. Furthermore, horses that survive peritonitis frequently suffer from recurrent colic episodes. Despite new developments in therapy, the prognosis for cats with FIP remains poor. It is still a lethal disease with no effective long-term treatment.
Adequate therapy depends on the diagnosis and the results of physical examination and laboratory analyses. In severe cases of septic peritonitis, the initial treatment must be directed toward saving the life of the animal and stabilizing cardiovascular and other organ functions. In severe cases, euthanasia is a consideration. Therapy should include treatment of hypovolemic/toxemic shock, aggressive anti-inflammatory therapy, and treatment of the metabolic and rheologic disturbances (eg, electrolyte and acid-base disorders, disseminated intravascular coagulation). Replacement fluids, electrolytes, plasma, or whole blood may be necessary to maintain cardiac output and improve circulation. It is of major importance to prevent circulatory failure from complications of disseminated intravascular coagulation. Antioxidative treatment using vitamins C and E or short-acting glucocorticoids might be useful. Additional prokinetic drugs might be necessary to increase and coordinate the motility of the GI tract.
Appropriate antimicrobial therapy should be started once septic peritonitis is suspected or confirmed. Peritoneal fluid samples should be obtained for culture and sensitivity testing. Parenteral broad-spectrum antimicrobial therapy must be applied initially. Aminoglycoside or fluoroquinolone antibiotics are effective against gram-negative organisms, and penicillins or cephalosporins are effective against gram-positive bacteria. The antimicrobial drug may be changed later according to the results of cytology and culture and sensitivity testing. Antimicrobial and anti-inflammatory treatment should continue through the healing period.
If possible, therapy should be initiated to eliminate the cause of peritonitis. In animals with suspected leakage of abdominal organs, surgery should be performed immediately to explore the abdomen and repair the defects, followed by peritoneal lavage with an isothermic, isotonic, balanced electrolyte solution before the abdominal cavity is closed. Although frequently performed, there is no proven clinical benefit in adding antimicrobial drugs to the lavage solution. Solutions containing antiseptics (eg, povidone-iodine) also have no proven clinical benefit and may even function as chemical irritants and exacerbate the inflammation. Heparin treatment may be considered in cases of DIC and may prevent extensive fibrin formation within the peritoneal cavity.
The application of abdominal drains and subsequent lavage is possible in small and large animals to treat severe peritonitis, removing septic and proinflammatory material from the abdominal cavity. Whereas the removal of septic peritoneal fluid is generally accepted as beneficial, the efficacy of repeated peritoneal lavage is under debate. Whereas some reports describe positive effects, others claim that intensive lavage may disturb healing of the epithelium and result in further spread of the inflammation. The composition of the lavage solution is also under debate; there are no or very few advantages to adding antibiotics or antiseptics. The decision to manage peritoneal drainage is based on the severity of the case, experience level, intensive care possibility, and equipment. Maintenance of drain patency can be difficult, especially in cattle, caused by the extensive fibrin formation in the abdominal cavity. In animals treated by peritoneal drainage or lavage, serum protein and electrolyte levels should be monitored periodically, because both are lost with drainage of exudate.
Nutritional support should be anticipated, because many animals with peritonitis will not eat. Enteral nutrition helps to maintain the health of the intestinal mucosa; however, vomiting (dogs and cats) or anorexia may force the consideration of alternatives. In ruminants and New World camelids, transfaunation using rumen fluid obtained from other animals or commercially available products has proved beneficial. In certain animals, total or partial parenteral nutrition may be necessary to provide a portion of the nutritional requirements while enteral nutrition is being initiated. Administration of antioxidants and vitamins should be considered. Vomiting is sometimes a sequela of peritonitis in small animals; antiemetic treatment is indicated in such cases.
Feline coronaviral infection may cause a primary feline infectious peritonitis (FIP). Therapy is palliative (eg, interferon therapy, glucocorticoids, supportive therapy) and directed toward slowing down the inflammation. However, no effective long-term therapy is available. Commercial vaccines for prophylaxis are available in some countries; however, there are conflicting reports on their efficacy and safety. The vaccine is not effective when administered to animals already exposed to FCoV; however, it may offer some protection when administered to seronegative animals.
In chronic adhesive peritonitis, laparoscopy or laparotomy may be considered to cut adhesions that prevent intestinal motility or to remove/drain intestinal abscesses. However, the success of such interventions might be limited.
* This is the Veterinary Version. *