Spontaneous bacterial peritonitis pathophysiology: Difference between revisions

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{{Spontaneous bacterial peritonitis}}
{{Spontaneous bacterial peritonitis}}
{{CMG}}; {{AE}} {{ADI}}
{{CMG}}; {{AE}} {{SCh}} {{AY}}  
 
==Overview==
==Overview==
SBP is a result of culmination of the inability of the gut to contain bacteria and failure of the immune system to eradicate the organisms once they have escaped.<ref name="pmid15920324">{{cite journal| author=Sheer TA, Runyon BA| title=Spontaneous bacterial peritonitis. | journal=Dig Dis | year= 2005 | volume= 23 | issue= 1 | pages= 39-46 | pmid=15920324 | doi=10.1159/000084724 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15920324  }} </ref>
[[Bacterial overgrowth|Intestinal bacterial overgrowth]] in [[Cirrhosis|cirrhotic]] patients, defective intestinal barrier and defective [[Immune response|host immune response]] are the 3 determinant factors for [[Bacterial|bacterial translocation]] explaining SBP.
==Pathogenesis==
Three factors play a role in the pathogenesis of SBP:
* '''[[Bacterial overgrowth]] in [[Cirrhosis|cirrhotic patients]]:''' secondary to [[Motility|decreased intestinal motility]] and frequent use of [[Proton pump inhibitor|PPIs]] in this population of patients.


==Pathophysiology==
* '''Defective intestinal barrier:''' secretory and physical barriers (which normally prevent bacteria from moving from the [[Lumen|intestinal lumen]]) are defective in [[Cirrhosis|cirrhotic patients]] <ref name="pmid16680233">{{cite journal |vauthors=Căruntu FA, Benea L |title=Spontaneous bacterial peritonitis: pathogenesis, diagnosis, treatment |journal=J Gastrointestin Liver Dis |volume=15 |issue=1 |pages=51–6 |year=2006 |pmid=16680233 |doi= |url=}}</ref>
===<font color="#0000FF">Pathogenesis of spontaneous bacterial peritonitis</font>===
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{| align=center
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{{familytree/start}}
{{familytree | boxstyle=background: #FFF0F5; color: #000000;| | | A01 | | A01=Patients with '''Decompensated Cirrhosis leading to '''Portal Hypertension'''}}
{{familytree | | | |!| |}}
{{familytree | boxstyle=background: #FFF0F5; color: #000000;| | | B01 | | B01='''Hypo-motility''' and '''local pro-inflammatory phenomenon'''}}
{{familytree | | | |!| |}}
{{familytree | boxstyle=background: #FFF0F5; color: #000000;| | | C01 | | C01='''Bacterial overgrowth''''''Increased intestinal permeability''' and '''Decreased local and systemic immune system'''}}
{{familytree | | | |!| |}}
{{Familytree|boxstyle=background: #FFF0F5; color: #000000;width: 400px; text-align: left; font-size: 90%; padding: 0px;| | | D01 | |D01=<div style="padding: 15px;"><BIG>'''Routes of entry of pathogens into the ascitic fluid'''</BIG>
:Escape of enteric bacteria to systemic circulation through:
:❑ Bacterial translocation
::• Luminal bacteria within colonize mesenteric lymph nodes
::• Organisms from the mesenteric lymph nodes → Systemic circulation through thoracic duct lymph → percolates through the liver and weep across Glisson's capsule → Ascitic fluid ( '''BACTERASCITES''' )
::• Transient bacteremia → Prolonged bacteremia ( due to ↓ Reticulo endothelial system activity ) → Ascites Colonization ( due to ↓ ascitic fluid bactericidal activity ) → Spontaneous bacterial peritonitis )
:❑ Portal Vein
::• Porto-systemic shunt
::• ↓RES function in the liver
:❑ Lymphatic rupture
::• Contaminated lymph carried by lymphatics
::• Ruptured Lymphatics due to high flow and high pressure associated with portal hypertension
:❑ Other source of organisms
::• IV catheters, skin, urinary, and respiratory tract</div>}}
{{familytree | | | |!| |}}
{{Familytree|boxstyle=background: #FFF0F5; color: #000000;width: 400px; text-align: left; font-size: 90%; padding: 0px;| | | E01 | |E01=<div style="padding: 15px;"><BIG>'''Endotoxemia''' and '''Cytokine response'''</BIG>
:❑ Endotoxemia → release of pro-inflammatory cytokines produced by macrophages and other host cells in response to bacteria in the serum and peritoneal exudate
::• Tumor necrosis factor-α (TNF-α)
::• Interleukin (IL)-1,6
::• Interferon-γ (IFN-γ)
::• Soluble adhesion molecules
:❑ Systemic and Abdominal manifestations of peritonitis mediated by '''cytokines'''
::• The effector molecules ('''Nitric oxide''') and cytokines,'''Tumour necrosis factor''' (TNF) that help kill the bacteria have undesired side effects as they cause ''vasodilation'' and '''renal failure''' that accompany SBP.
::• Studies have shown that the presence of whole bacteria or DNA, in serum and ascitic fluid leads to stimulation of immune defences, effector molecules, and cytokines which in turn impact on hemodynamics, renal function and survival</div>}}
{{familytree | | | |!| |}}
{{Familytree|boxstyle=background: #FFF0F5; color: #000000;width: 400px; text-align: left; font-size: 90%; padding: 0px;| | | F01 | |F01=<div style="padding: 15px;"><BIG>'''Host response'''</BIG>
:❑ Local response
Outpouring of fluid into the peritoneal cavity at sites of irritation with:
::• High protein content (>3 g/dL)
::• Many cells, primarily polymorphonuclear leukocytes, that phagocytose and kill organisms
::• Formation of Fibrinous exudate on the inflamed peritoneal surfaces → Adhesion formation between adjacent bowel, mesentery, and momentum
::• Localization of the inflammatory process is aided further by inhibition of motility in the involved intestinal loops
::• The extent and rate of intraperitoneal spread of contamination depend on the volume and nature of the exudate and on the effectiveness of the localizing processes
::• If peritoneal defenses aided by the appropriate supportive measures control the inflammatory process, the disease may resolve spontaneously ('''Sterile ascites''') → Consumption of humoral bactericidal factors due to frequent colonization → Increased susceptibility to '''SBP'''
::• If the ascitic fluid bactericidal activity is poor-moderate → '''Culture negative neutrocytic ascites''' (CNNA) or '''SBP''' → delay / inappropriate treatment → ''death'' due to sepsis and multi organ failure.
::• Second possible outcome is a confined '''abscess'''
::• A third possible outcome results when the peritoneal and systemic defense mechanisms are unable to localize the inflammation, which progresses to '''spreading diffuse peritonitis''' due to increased virulence of bacteria, greater extent and duration of contamination, and impaired host defenses.
:❑ Systemic response
Gastrointestinal
::• Paralysis of the bowel due to local inflammation
::• Progressive accumulation of fluid and electrolytes in the lumen of the adynamic bowel → distention of the bowel → inhibition of the capillary inflow and secretions
Cardiovascular
::• Shift of fluid into the peritoneal cavity and bowel lumen → ↓ Effective circulating blood volume → ↑ Hematocrit
::•
::•
::•
::•
::•
::•
::•
::• </div>}}
{{family tree/end}}
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* '''[[Immunity suppression|Decreased immunity]]:''' both local and systemic immunity are decreased in [[Cirrhosis|cirrhotic patients]].
===A. Bacterial overgrowth:===
* [[Motility|Intestinal motility]] decreases with [[cirrhosis]]. Increased [[Sympathetic control|sympathetic drive]] and [[Oxidant|oxidant stress]] are believed to be the reasons for the reduced mobility.
* Also, [[Cirrhosis|cirrhotic patients]] administer [[Proton pump inhibitor|PPIs]] more frequently than other patient populations.
* The diminished [[Motility|intestinal motility]] makes the intestinal contents more stagnant and allows the [[Bacteria|bacterial contents]] to overgrow and thus predisposes to SBP.<ref name="pmid9794900">{{cite journal |vauthors=Chang CS, Chen GH, Lien HC, Yeh HZ |title=Small intestine dysmotility and bacterial overgrowth in cirrhotic patients with spontaneous bacterial peritonitis |journal=Hepatology |volume=28 |issue=5 |pages=1187–90 |year=1998 |pmid=9794900 |doi=10.1002/hep.510280504 |url=}}</ref>


SBP is a result of culmination of the inability of the gut to contain bacteria and failure of the immune system to eradicate the organisms once they have escaped. Following steps may explain the underlying process in a comprehensive way:
===B. Increased bowel permeability:===
* Spontaneous bacterial peritonitis is thought to result from a combination of factors related to cirrhosis and ascites such as:
===Natural barriers===
====Routes of infection====
* Hematogenous
* Lymphogenous
* Transmural migration through an intact bowel wall from the intestinal lumen
* Bacterial translocation: Enteric bacteria from the bowel lumen → Mesenteric lymph nodes → Systemic circulation (via the thoracic duct)
* Enteric bacteria → Portal vein → liver / portosystemic shunts ( in portal hypertension) → Systemic circulation.
* Conn and Fessel 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
* Enteric bacteria may also gain access to the peritoneal cavity by traversing directly the intact intestinal wall.
*
====Hypo-motility====
* Distal propulsion of luminal contents by intestinal peristalsis is a critical factor in the inhibition of bacterial colonization and replication in the proximal gastro-intestinal tract, which leads to bacterial overgrowth.
====Intestinal mucosal permeability====
====Altered microbial flora====
====Intestinal bacterial overgrowth====
* Probably due to disturbances in the intestinal peristalsis, gastric acid and mucosal immunity in cirrhotic patients.
* Studies have shown that the incidenceof bacterial overgrowth in the small intestine was significantly higher in liver cirrhotic patients with history of SBP than in those without SBP (70% vs. 20%).
* Once bacteria reach a critical concentration in the gut lumen, they “spill over”, and escape the gut, “translocating” to mesenteric lymph nodes.Then they enter lymph, blood, and eventually ascitic fluid.<ref name="pmid7890896">{{cite journal| author=Runyon BA, Squier S, Borzio M| title=Translocation of gut bacteria in rats with cirrhosis to mesenteric lymph nodes partially explains the pathogenesis of spontaneous bacterial peritonitis. | journal=J Hepatol | year= 1994 | volume= 21 | issue= 5 | pages= 792-6 | pmid=7890896 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7890896  }} </ref>


===Intestinal permeability===
Normally, the [[intestinal mucosa]] is impermeable to [[bacteria]] because of two lines of defense<ref name="pmid9794900">{{cite journal |vauthors=Chang CS, Chen GH, Lien HC, Yeh HZ |title=Small intestine dysmotility and bacterial overgrowth in cirrhotic patients with spontaneous bacterial peritonitis |journal=Hepatology |volume=28 |issue=5 |pages=1187–90 |year=1998 |pmid=9794900 |doi=10.1002/hep.510280504 |url=}}</ref>;the secretory component and physical component. Both are affected by the development of cirrhosis.
===Hepatic Reticulo endothelial system activity===
* The '''secretory defense''' mechanism is composed of [[Mucin|mucins]], [[immunoglobulins]] and [[bile salts]]. Bile salts are protective through preventing adherence and internalization of bacteria. [[Bile acid|Bile acids]] are decreased in cirrhosis partly due to reduced secretion from [[Cirrhosis|diseased liver]] and partly from [[Conjugation|increased conjugation]] by the flourishing [[intestinal flora]]. This gives bacteria easier access through the [[Mucosal|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 system|immune defenses]].
====Porto-systemic shunting====
* The physical component is the [[intestinal epithelium]] itself. [[Intestinal mucosa]] is more permeable as a result of increased [[Oxidant|oxidant stress]],[[Cytokines|NO proinflammatory cytokines]] & increased intercellular spaces as a result of [[vasodilation]], [[edema]] from [[portal hypertension]].
====Phagocytic response====
===Serum factors===


===Bacterial translocation===
===C. Decreased local and systemic immune responses:===
===Routes of transmission===
* [[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.
===Reticulo endothelial dysfunction===
* As a result of defective liver synthetic functions, [[complement]] levels decrease (both in [[serum]] and [[Ascites|ascitic fluid]]).
===Alterations in the systemic immune response===
* The [[neutrophils]] seem to have declined [[Granulocyte|granulocyte functions]] as adherence, [[chemotaxis]], and bacterial killing.
===Ascitic fluid defense mechanisms===
===Cytokine response===


 
Bacteria that translocate are carried through [[lymphatics]]. It can reach the [[Ascitic|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.
*
** Prolonged [[bacteremia]] secondary to compromised host defenses
** Intrahepatic shunting of colonized [[blood]] and
** Defective bactericidal activity within the ascitic fluid.<ref name="pmid6500513">{{cite journal | author = Runyon BA, Hoefs JC | title = Culture-negative neutrocytic ascites: a variant of spontaneous bacterial peritonitis | journal = Hepatology | volume = 4 | issue = 6 | pages = 1209–11 | year = 1984 | pmid = 6500513 | doi = 10.1002/hep.1840040619| url = | issn = }}</ref> Contrary to earlier theories, transmucosal migration of bacteria from the gut to the ascitic fluid is no longer considered to play a major role in the etiology of SBP.<ref name="pmid3371881">{{cite journal | author = Runyon BA | title = Patients with deficient ascitic fluid opsonic activity are predisposed to spontaneous bacterial peritonitis | journal = Hepatology | volume = 8 | issue = 3 | pages = 632–5 | year = 1988 | pmid = 3371881 | doi = 10.1002/hep.1840080332| url = | issn = }}</ref><ref name="pmid15920324">{{cite journal| author=Sheer TA, Runyon BA| title=Spontaneous bacterial peritonitis. | journal=Dig Dis | year= 2005 | volume= 23 | issue= 1 | pages= 39-46 | pmid=15920324 | doi=10.1159/000084724 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15920324  }} </ref>
 
With respect to compromised [[immune system|host defenses]], patients with severe acute or chronic liver disease are often deficient in [[Complement system|complement]] and may also have malfunctioning of the [[neutrophil]]ic and [[reticuloendothelial systems]].<ref name="pmid19561863">Alaniz C, Regal RE (2009) [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19561863 Spontaneous bacterial peritonitis: a review of treatment options.] ''P T'' 34 (4):204-10. PMID: [https://pubmed.gov/19561863 19561863]</ref>
 
As for the significance of ascitic fluid proteins, it was demonstrated that cirrhotic patients with ascitic protein concentrations below 1 g/dL were 10 times more likely to develop SBP than individuals with higher concentrations.<ref name="pmid3770358">Runyon BA (1986) [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=3770358 Low-protein-concentration ascitic fluid is predisposed to spontaneous bacterial peritonitis.] ''Gastroenterology'' 91 (6):1343-6. PMID: [https://pubmed.gov/3770358 3770358]</ref> It is thought that the antibacterial, or opsonic, activity of ascitic fluid is closely correlated with the protein concentration.<ref name="pmid4018735">{{cite journal | author = Runyon BA, Morrissey RL, Hoefs JC, Wyle FA | title = Opsonic activity of human ascitic fluid: a potentially important protective mechanism against spontaneous bacterial peritonitis | journal = Hepatology | volume = 5 | issue = 4 | pages = 634–7 | year = 1985 | pmid = 4018735 | doi = 10.1002/hep.1840050419| url = | issn = }}</ref> Additional studies have confirmed the validity of the ascitic fluid protein concentration as the best predictor of the first episode of SBP.<ref name="pmid19561863"/>


==References==
==References==
{{reflist|2}}
{{reflist|2}}


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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]

Overview

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

Pathogenesis

Three factors play a role in the pathogenesis of SBP:

A. Bacterial overgrowth:

B. Increased bowel permeability:

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.

C. Decreased local and systemic immune responses:

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.

References

  1. Căruntu FA, Benea L (2006). "Spontaneous bacterial peritonitis: pathogenesis, diagnosis, treatment". J Gastrointestin Liver Dis. 15 (1): 51–6. PMID 16680233.
  2. 2.0 2.1 Chang CS, Chen GH, Lien HC, Yeh HZ (1998). "Small intestine dysmotility and bacterial overgrowth in cirrhotic patients with spontaneous bacterial peritonitis". Hepatology. 28 (5): 1187–90. doi:10.1002/hep.510280504. PMID 9794900.