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| ==Pathogenesis==
| | SBP: |
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| Three factors determine the pathogenesis of the SBP:
| | Mortality of SBP remains high. 1-year mortality rate is 30-90 (1), probably due to the advanced liver disease present in the first place. |
| * '''Bacterial overgrowth in cirrhotic patients:''' secondary to decreased intestinal motility and frequent use of PPIs in this population of patients.
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| * '''Defensive intestinal barrier:''' secretory and physical barriers are defective in cirrhotic patients (1)
| | Early admission and prophylactic cephalosporins might have a role in decreasing mortality rate.(2) |
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| * '''Decreased immunity:''' both local and systemic immunity are decreased.
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| {{#ev:youtube|M502Byuiskw}}
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| ===A. Bacterial overgrowth:===
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| * Intestinal mobility decreases with cirrhosis. Increased sympathetic drive and oxidant stress are believed to be the reasons for the reduced mobility.
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| * Also, cirrhotic patients administer PPIs more frequently than other populations.
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| * The diminished intestinal mobility makes the intestinal contents more stagnant and allows the bacterial contents to overgrow and thus predisposes to SBP. (2)
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| ===B. Increased bowel permeability:===
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| Normally, the intestinal mucosa is impermeable to bacteria because of two lines of defense.(1);the secretory component and physical component. Both are affected by the development of cirrhosis.
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| # 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.
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| 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
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| to adhere to the intestinal mucosa and evade the host immune defenses.
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| 2. The physical component is the intestinal epithelium itself. Intestinal mucosa is more permeable as a result of increased oxidant stress, | |
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| NO proinflammatory cytokines & increased intercellular spaces as a result of vasodilation, edema from portal hypertension.
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| ===C. Decreased local and systemic immune responses:===
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| * 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.
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| * As a result of defective liver secretory functions, complement levels decrease (both in serum and ascitic fluid).
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| * The neutrophils seem to have declined granulocyte functions as adherence, chemotaxis, and bacterial killing.
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| Bacteria that translocates are carried through lymphatics. It can reach to 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.
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