The peritoneum is the thin serous membrane that lines the peritoneal cavity. It is the largest serous surface layer in the human body and its surface area is similar to the skin. The structure is made up of a single, flat, layer of mesothelial cells, rich in microvilli. Beneath the mesothelium are a basement membrane and a loose collagen network containing vascularized connective tissue with scattered fibroblasts and macrophages. Normally there is between 5 and 20 mL of free peritoneal fluid, this can vary in women, peaking after ovulation. Normal peritoneal fluid has a specific gravity less than 1.016, protein concentration less than 3g/dL, pH between 7.5 and 8, and a white blood cell count less than 3000/μL. The peritoneum is divided anatomically into parietal and visceral components. The parietal peritoneum underlies the anterior, later, and posterior abdominal walls as well as the undersurface of the diaphragm and pelvic basin. The visceral peritoneum is reflected over the viscera within the abdominal cavity.

Once thought to be a passive barrier, the peritoneum is now understood to have numerous functions. The mesothelial cells secrete phosphatidylcholine, which provides a near frictionless environment within the peritoneum and allows intraperitoneal organs to glide over one another during peristalsis and movement. With its large surface area and semi permeable nature, it participates in fluid exchange with the extracellular fluid space at rates of over 500 mL/h. The circulation of peritoneal fluid is directed toward lymphatics on the undersurface of the diaphragm where particulate matter, up to 20 μm in size, is cleared via stomas in the diaphragmatic mesothelium and emptied into the right thoracic duct.

The peritoneum has a vigorous response to injury and inflammation. Normally sterile, the peritoneum participates in recognizing and eliminating bacteria. Mesothelial cells secrete opsonins that promote bacterial destruction, express CD40 and are aid in antigen presentation, and express intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) which aid in attachment and activation of lymphocytes, granulocytes, and monocytes in response to infectious pathogens. The mesothelial cells secrete tPA under normal conditions which participates in intraperitoneal adhesiolysis. The peritoneum has significant wound healing functions as well, secreting multiple inflammatory mediators including vascular endothelial growth factor (VEGF), PAI, and nitrogen monoxide, TGF beta, and TNF alpha in response to trauma. In response to injury, the peritoneum produces a large proinflammatory response with fibrin deposition and activation of coagulation pathways as well. Imbalance between fibrin deposition and fibrinolysis following peritoneal traumatization can lead to the organization of fibrin deposits between adjacent structures and development of intraperitoneal adhesions which will be discussed further in later sections. Unlike with cutaneous wound healing, following injury to the mesothelium there is uniform recreation of the mesothelial monolayer within 5-10 days.

PRIMARY PERITONITIS

Primary (spontaneous) peritonitis occurring in the absence of gastrointestinal perforation is caused mainly by hematogenous spread but occasionally by transluminal or direct bacterial invasion of the peritoneal cavity. Impairment of the hepatic reticuloendothelial system and compromised peripheral destruction of bacteria by neutrophils promotes bacteremia, which readily infects ascitic fluid that has reduced bacterium-killing capacity. Primary peritonitis is most closely associated with cirrhosis and advanced liver disease with a low ascitic fluid protein concentration. It is also seen in patients with the nephrotic syndrome or systemic lupus erythematosus, or after splenectomy during childhood. Recurrence is common in cirrhosis and often proves fatal.

Clinical Findings

The clinical presentation simulates secondary bacterial peritonitis, with abrupt onset of fever, abdominal pain, distention, and rebound tenderness. However, one-fourth of patients have minimal or no peritoneal symptoms. Most have clinical and biochemical manifestations of advanced cirrhosis or nephrosis. Leukocytosis, hypoalbuminemia, and a prolonged prothrombin time are characteristic findings. The diagnosis hinges upon examination of the ascitic fluid, which reveals a white blood cell count greater than 500/μL and more than 25% polymorphonuclear leukocytes. A blood-ascitic fluid albumin gradient greater than 1.1 g/dL, a raised serum lactic acid level, or a reduced ascitic fluid pH (< 7.31) supports the diagnosis. Bacteria are seen on Gram-stained smears in only 25% of cases. Culture of ascitic fluid inoculated immediately into blood culture media at the bedside usually reveals a single enteric organism, most commonly Escherichia coli, Klebsiella, or streptococci, but Listeria monocytogenes has been reported in immunocompromised hosts.

Treatment

Antibiotic prophylaxis is of no proven value. Systemic antibiotics with third-generation cephalosporins (eg, cefotaxime) or a β-lactam-clavulanic acid combination along with supportive treatment are begun once the diagnosis has been established.

TUBERCULOUS PERITONITIS

Pathophysiology

Tuberculosis peritonitis is encountered in 0.5% of new cases of tuberculosis. It presents as a primary infection without active pulmonary, intestinal, renal, or uterine tube involvement. Its cause is reactivation of a dormant peritoneal focus derived from hematogenous dissemination from a distant nidus or breakdown of mesenteric lymph nodes. Some cases occur as a systemic manifestation of extra-abdominal infection. Multiple small, hard, raised, whitish tubercles studding the peritoneum, omentum, and mesentery are the distinctive finding. A cecal tuberculoma, matted lymph nodes, or omental involvement may form a palpable mass.

The disease affects young persons, particularly women, and is more prevalent in countries where tuberculosis is still endemic. AIDS patients are especially susceptible to development of extrapulmonary tuberculosis such as this.

Clinical Findings

Chronic symptoms (lasting more than a week) include abdominal pain and distention, fever, night sweats, weight loss, and altered bowel habits. Ascites is present in about half of cases, especially if the disease is of long standing, and may be the primary manifestation. A mass may be felt in a third of cases. The differential diagnosis includes Crohn disease, carcinoma, hepatic cirrhosis, and intestinal lymphoma. One-fourth of patients have acute symptoms suggestive of acute bowel obstruction or peritonitis that mimics appendicitis, cholecystitis, or a perforated ulcer.

Detection of an extra-abdominal site of tuberculosis, evident in half of cases, is the single most useful diagnostic clue. Pleural effusion is present in up to 50% of patients. Paracentesis, laparoscopy, or peritoneal biopsy is applicable only in patients with ascites. The peritoneal fluid is characterized by a protein concentration above 3 g/dL with less than 1.1 g/dL serum-ascitic fluid albumin difference and lymphocyte predominance among white blood cells. Definitive diagnosis is possible in 80% of cases by culture (often taking several weeks) and direct smear. A purified protein derivative (PPD) skin test is useful only when positive (about 80% of cases). Hematologic and biochemical studies are seldom helpful, and leukocytosis is uncommon. The sedimentation rate is elevated in many cases. The presence of high-density ascites or soft tissue masses on ultrasonography or computed tomography (CT) scan supports the diagnosis. Young patients from endemic areas who present with classic symptoms or who have suggestive imaging findings should undergo diagnostic laparoscopy, which may obviate laparotomy.

Treatment

In chronic cases, nonoperative therapy is preferable if the diagnosis can be established. Most patients presenting with acute symptoms are diagnosed only by laparotomy. In the absence of intestinal obstruction or perforation, only a biopsy of a peritoneal or omental nodule should be taken. Obstruction due to constriction by a tuberculous lesion usually develops in the distal ileum and cecum, although multiple skip areas along the small bowel may exist. Localized short segments of diseased bowel are best treated by resection with primary anastomosis. Multiple strictured areas may be managed either by side-to-side bypass or a stricturoplasty of partially narrowed segments.

Combination antituberculosis chemotherapy should be started once the diagnosis is confirmed or considered likely. A favorable response is the rule, but isoniazid and rifampin must be continued for 18 months postoperatively.

GRANULOMATOUS PERITONITIS

Pathophysiology

Talc (magnesium silicate), cornstarch glove lubricants, gauze fluffs, and cellulose fibers from disposable surgical fabrics may elicit a vigorous granulomatous (a delayed hypersensitivity) response in some patients 2-6 weeks after laparotomy. The condition is uncommon now that surgeons wipe clean their gloves before handling abdominal viscera. Less rarely, granulomatous peritonitis may develop as a hypersensitivity reaction to other foreign material (eg, intestinal ascariasis or food particles from a perforated ulcer).

Clinical Findings

Besides abdominal pain, which is often out of proportion to the low-grade fever, there may be nausea and vomiting, ileus, and other systemic complaints. Abdominal tenderness is usually diffuse but mild. Free abdominal fluid, if detectable, should be tapped and inspected for the diagnostic Maltese cross pattern of starch particles.

Treatment

Reoperation achieves little and should be avoided if the diagnosis can be made. Most patients undergo reexploration because they present an erroneous impression of postoperative bowel obstruction or peritoneal sepsis. The diffuse hard, white granulomatous masses studding the peritoneum and omentum are easily mistaken for cancer or tuberculosis unless a biopsy specimen is taken to demonstrate foreign body granulomas.

If granulomatous peritonitis is suspected, the response to treatment with corticosteroids or other anti-inflammatory agents is often so dramatic as to be diagnostic in itself. After clinical improvement, intravenous methylprednisolone can be replaced by oral prednisone for 2-3 weeks. The disease is self-limited and does not predispose to late intestinal obstruction.

ACUTE BACTERIAL SECONDARY PERITONITIS

Pathophysiology

Peritonitis is an inflammatory or suppurative response of the peritoneal lining to direct irritation. Peritonitis can occur after perforating, inflammatory, infectious, or ischemic injuries of the gastrointestinal or genitourinary system. Common examples are listed in Table 22–1. Secondary peritonitis results from bacterial contamination originating from within viscera or from external sources (eg, penetrating injury). It most often follows disruption of a hollow viscus. Extravasated bile and urine, although only mildly irritating when sterile, are markedly toxic if infected and provoke a vigorous peritoneal reaction. Gastric juice from a perforated duodenal ulcer remains mostly sterile for several hours, during which time it produces a chemical peritonitis with large fluid losses; but if left untreated, it evolves within 6-12 hours into bacterial peritonitis. Intraperitoneal fluid dilutes opsonic proteins and impairs phagocytosis. Furthermore, when hemoglobin is present in the peritoneal cavity, E coli growing within the cavity can elaborate leukotoxins that reduce bactericidal activity. Limited, localized infection can be eradicated by host defenses, but continued contamination invariably leads to generalized peritonitis and eventually to septicemia with multiple organ failure.

Factors that influence the severity of peritonitis include the type of bacterial or fungal contamination, the nature and duration of the injury, and the host’s nutritional and immune status. The grade of peritonitis varies with the cause. Clean (eg, proximal gut perforations) or well-localized (eg, ruptured appendix) contaminations progress to fulminant peritonitis relatively slowly (eg, 12-24 hours). In contrast, bacteria associated with distal gut or infected biliary tract perforations quickly overwhelm host peritoneal defenses. This degree of toxicity is also characteristic of postoperative peritonitis due to anastomotic leakage or contamination. Conditions that ordinarily cause mild peritonitis may produce life-threatening sepsis in an immunocompromised host.

Causative Organisms

Systemic sepsis due to peritonitis occurs in varying degrees depending on the virulence of the pathogens, the bacterial load, and the duration of bacterial proliferation and synergistic interaction. Except for spontaneous bacterial peritonitis, peritonitis is almost invariably polymicrobial; cultures usually contain more than one aerobic and more than two anaerobic species. The microbial picture reflects the bacterial flora of the involved organ. As long as gastric acid secretion and gastric emptying are normal, perforations of the proximal bowel (stomach or duodenum) are generally sterile or associated with relatively small numbers of gram-positive organisms. Perforations or ischemic injuries of the distal small bowel (eg, strangulated hernia) lead to infection with aerobic bacteria in about 30% of cases and anaerobic organisms in about 10% of cases. Fecal spillage, with a bacterial load of 10¹² or more organisms per gram, is extremely toxic.

Aerobic bacteria account for the majority of bacterial contamination and include both Gram-negative and Gram-positive species. The most frequent Gram-negative organisms encountered include E coli, Klebsiella, Enterobacter, Proteus mirabilis, and infrequently Pseudomonas aeruginosa. Among the more common Gram-positive organisms seen are Enterococcus, Streptococcus, and less commonly Staphylococcus aureus, and Coagulase-negative Staphylococcus. Bacteroides, clostridia, and other anaerobes make up the common anaerobic pathogens encountered. Fungi are rarely encountered though may be present in immunocompromised patients, when present, Candida are the predominant species.

Intraoperative cultures were obtained frequently in the past if purulence was encountered in the surgical field. Given the polymicrobial nature of peritonitis following intestinal tract perforations these cultures may provide little information that impact postoperative management.

Clinical Findings

By estimating the severity of peritonitis from clinical and laboratory findings, the need for specific organ-supportive care and surgery can be determined.

See Chapter 21 for details of radiologic and other investigations.

Symptoms & Signs

The clinical manifestations of peritonitis reflect the severity and duration of infection and the age and general health of the patient. Physical findings can be divided into: (1) abdominal signs arising from the initial injury and (2) manifestations of systemic infection. Acute peritonitis frequently presents as an acute abdomen. Local findings include abdominal pain, tenderness, guarding or rigidity, distention, free peritoneal air, and diminished bowel sounds—signs that reflect parietal peritoneal irritation and resulting ileus. Systemic findings include fever, chills or rigors, tachycardia, sweating, tachypnea, restlessness, dehydration, oliguria, disorientation, and, ultimately, refractory shock. Shock is due to the combined effects of hypovolemia and septicemia with multiple organ dysfunction. Recurrent unexplained shock is highly predictive of serious intraperitoneal sepsis.

The findings in abdominal sepsis are modified by the patient’s age and general health. Physical signs of peritonitis are subtle or difficult to interpret in both very young and very old patients as well as in those who are chronically debilitated, immunosuppressed, or receiving corticosteroids and in postoperative patients. Paracentesis or diagnostic peritoneal lavage may be occasionally useful in equivocal cases and in senile or confused patients. A white blood cell count of greater than 200 cells/μL is indicative of peritonitis, with virtually no false-positive and minimal false-negative errors. Delayed recognition is a major cause of the high mortality rate of peritonitis.

Familial Mediterranean fever (periodic peritonitis, familial paroxysmal polyserositis) is a rare genetic condition that affects individuals of Mediterranean genetic background. Its exact cause is unknown. Patients present with recurrent bouts of abdominal pain and tenderness along with pleuritic or joint pain. Fever and leukocytosis are common. Colchicine prevents but does not treat acute attacks. Provocative testing by infusion of metaraminol (10 mg) induces abdominal pain within 2 days.

Laparoscopy has superseded laparotomy in suspect individuals. Free fluid and inflamed peritoneal surfaces are found, but smears and cultures are negative. The appendix should be removed to simplify diagnosis in subsequent episodes. Secondary amyloidosis with renal failure is a late complication that is preventable by a long-term colchicine therapy.

Treatment

A. Preoperative Care

The presentation of patients with pertitoneal inflammation following bacterial contamination can range from mild to life threatening. It is necessary to approach each patient with the same goals of diagnosis and prompt treatment in mind. Initial management consists of assessing the patient’s resuscitative needs and determining underlying pathology. Once resuscitation is begun, antibiotics administration and other supportive care measures should be pursued followed by imaging and treatment considerations.

Antibiotic administration should be initiated once the diagnosis is made. Antibiotics should be directed against the most likely source and cover the aerobic and anaerobic organisms commonly encountered in gut perforation. Intravenous antibiotics are first line to ensure therapeutic serum levels in the early course of treatment given like ileus and unreliable oral absorption.

While antibiotics are a mainstay in the preoperative treatment of secondary peritonitis, their role in the postoperative period is less clear. Extended postoperative antibiotic courses may offer little benefit when compared with discontinuing antibiotics in the first 24 hours postoperatively in the prevention of intraperitoneal abscess or surgical site infection but can place patients at higher risk for antibiotic related complications and add to resistance in the community.

If the decision is made to continue antibiotics in the postoperative course historically they have been continued until the patient has been afebrile with a normal white blood cell count and a white blood cell count differential with less than 3% band forms. Provided the patient is tolerating a diet there is no added benefit to using intravenous antibiotics over comparable oral agents.