Spontaneous bacterial 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] Ahmed Younes M.B.B.CH [3]

Intestinal bacterial overgrowth in cirrhotic patients, defective intestinal barrier and defective host immune response are the 3 determinant factors for bacterial translocation explaining SBP.

Three factors play a role in the pathogenesis of SBP:

• Bacterial overgrowth in cirrhotic patients: secondary to decreased intestinal motility and frequent use of PPIs in this population of patients.

• Defective intestinal barrier: secretory and physical barriers (which normally prevent bacteria from moving from the intestinal lumen) are defective in cirrhotic patients ^[1]

• Decreased immunity: both local and systemic immunity are decreased in cirrhotic patients.

• Intestinal motility decreases with cirrhosis. Increased sympathetic drive and oxidant stress are believed to be the reasons for the reduced mobility.
• Also, cirrhotic patients administer PPIs more frequently than other patient populations.
• The diminished intestinal motility makes the intestinal contents more stagnant and allows the bacterial contents to overgrow and thus predisposes to SBP.^[2]

Normally, the intestinal mucosa is impermeable to bacteria because of two lines of defense^[2];the secretory component and physical component. Both are affected by the development of cirrhosis.

• The secretory defense mechanism is composed of mucins, immunoglobulins and bile salts. Bile salts are protective through preventing adherence and internalization of bacteria. Bile acids are decreased in cirrhosis partly due to reduced secretion from diseased liver and partly from increased conjugation by the flourishing intestinal flora. This gives bacteria easier access through the mucosa especially that E.coli (which is the most common strain isolated from SBP patients) has high ability to adhere to the intestinal mucosa and evade the host immune defenses.
• The physical component is the intestinal epithelium itself. Intestinal mucosa is more permeable as a result of increased oxidant stress,NO proinflammatory cytokines & increased intercellular spaces as a result of vasodilation, edema from portal hypertension.

• Kupffer cells (local macrophages of the liver) normally contribute in eradicating infection with neutrophils. But as a result of the extrahepatic portosystemic shunts, bacteria in the circulation do not come in contact with these cells.
• As a result of defective liver synthetic functions, complement levels decrease (both in serum and ascitic fluid).
• The neutrophils seem to have declined granulocyte functions as adherence, chemotaxis, and bacterial killing.

Bacteria that translocate are carried through lymphatics. It can reach the ascitic fluid either through the circulation then through the liver. It can have access to the peritoneal cavity. Another way is through rupture of the lymphatic vessel carrying the contaminated lymph under pressure from portal hypertension and the increased lymph content.