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| __NOTOC__ | | __NOTOC__ |
| {{Spontaneous bacterial peritonitis}} | | {{Spontaneous bacterial peritonitis}} |
| {{CMG}}; {{AE}} {{ADI}} {{SCh}} | | {{CMG}}; {{AE}} {{SCh}} {{AY}} |
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| ==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="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 | year= 1985 | volume= 5 | issue= 4 | pages= 634-7 | pmid=4018735 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4018735 }} </ref><ref name="pmid15138202">{{cite journal| author=Runyon BA| title=Early events in spontaneous bacterial peritonitis. | journal=Gut | year= 2004 | volume= 53 | issue= 6 | pages= 782-4 | pmid=15138202 | doi= | pmc=1774068 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15138202 }} </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>.'''[[Spontaneous bacterial peritonitis]] is thought to result from a combination of factors related to [[cirrhosis]] and [[ascites]] such as''': Altered microbial flora, Hypo-motility of the intestine, Intestinal bacterial overgrowth, Increased Intestinal mucosal [[permeability]], Bacterial translocation to [[Lymph nodes]]. Presence of [[ascites]] appears to be an important risk factor for the development of bacterial [[translocation]]. In healthy individuals, bacteria that colonize [[lymph nodes]] are killed by local immune defenses. '''However, in the setting of [[cirrhosis]], an [[acquired]] state of [[Immunodeficiency]] there is''': Malfunctioning of the [[Reticulo-endothelial system|reticulo-endothelial]] and neutrophilic system, Reduced [[Cellular]] and [[Humoral]] [[bactericidal]] function which favor the spread of [[bacteria]] to the [[blood stream]]. '''Alterations in the [[systemic]] [[immune response]]''': [[Bacteremia]] in a healthy host results in rapid coating by [[IgG]] and/or [[Complement]] components and then engulfing and killing by circulating [[neutrophils]]. '''But in [[cirrhosis]], as stated above several abnormalities have been described including''' : Decreased serum levels of [[complement]] components (C3, C4), Impaired [[chemotaxis]], Poor function and [[phagocytic]] activity of [[neutrophils]], Decreased function of [[Fc receptor|Fc]]-gamma-receptors in [[macrophages]]. '''[[Reticuloendothelial system]] [[phagocytic]] activity''': The stationary [[macrophages]], such as the [[Kupffer cell|Kupffer cells]] of the liver, assist the circulating [[neutrophils]] in the extraction and killing of particulate matter (e.g., bacteria) from the systemic circulation. In Cirrhosis, there is Hepatic [[Reticuloendothelial system]] (RES) dysfunction, [[Kupffer cells]] are decreased in number with impaired function along with the malfunctioning of the neutrophilic system. Patients with the most severe dysfunction of RES have the highest risk of [[bacteremia]] and concomitant shortened survival, due to [[sepsis]]. The presence of intrahepatic and extra hepatic porto-systemic shunts as a consequence of [[portal hypertension]], prevent circulating bacteria from encountering [[Kupffer cells]]. The final consequence of these abnormalities is the prolongation of [[bacteremia]] and eventual seeding of other sites, including AF. '''AF defense mechanisms:''' Decreased local AF opsonic activity: The arrival of bacteria to the AF does not guarantee that infection will develop. Cirrhotic AF is capable of [[humoral]] self-defense, mainly on the basis of effectiveness of the [[complement]] system, Patients with adequate activity of this vital [[bactericidal]] system usually do not develop AF bacterial infections, Patients with AF C3 < 1g/dl and a protein level < 1g/dl have an increased predisposition to [[SBP]], the [[complement]] levels may be deficient because of increased consumption of these components or because of impaired synthesis, if the [[complement]] levels are adequate to effectively kill the bacteria, infection will not develop, if [[complement]] levels are consumed and depleted, killing may be ineffective, frequent colonization of AF by bacteria decreases its antimicrobial ability and can eventually lead to the development of infection [[Bacteremia]]/ Endotoxemia leads to activation of [[cytokine]] cascade and some of these effector molecules and [[cytokines]] that help kill the bacteria have undesired side effects. [[NO]] and [[TNF]] are important mediators of the further [[vasodilation]] and [[renal failure]] that too often accompany [[SBP]]. [[Iatrogenic]] and treatment related factors like [[PPI]], and increased use of invasive procedures and catheters in patients with [[Cirrhosis]] and [[ascites]]. Other compelling factors like [[malnutrition]] and [[alcohol]] drinking also predispose to SBP.
| | [[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== |
| ==Pathophysiology==
| | Three factors play a role in the pathogenesis of SBP: |
| {| align=center
| | * '''[[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. |
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| {{familytree/start}}
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| {{familytree | boxstyle=background: #FFF0F5; color: #000000;| | | A01 | | A01=Patients with '''decompensated [[cirrhosis]] leading to '''[[portal Hypertension]]<ref name="pmid1505916">{{cite journal| author=Llach J, Rimola A, Navasa M, Ginès P, Salmerón JM, Ginès A et al.| title=Incidence and predictive factors of first episode of spontaneous bacterial peritonitis in cirrhosis with ascites: relevance of ascitic fluid protein concentration. | journal=Hepatology | year= 1992 | volume= 16 | issue= 3 | pages= 724-7 | pmid=1505916 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1505916 }} </ref><ref name="pmid11211904">{{cite journal| author=Cirera I, Bauer TM, Navasa M, Vila J, Grande L, Taurá P et al.| title=Bacterial translocation of enteric organisms in patients with cirrhosis. | journal=J Hepatol | year= 2001 | volume= 34 | issue= 1 | pages= 32-7 | pmid=11211904 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11211904 }} </ref>'''}}
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| {{familytree | | | |!| |}}
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| {{familytree | boxstyle=background: #FFF0F5; color: #000000;| | | B01 | | B01='''Intestinal hypo-motility''' and '''local pro-[[inflammatory]] phenomenon'''<ref name="pmid9794900">{{cite journal| author=Chang CS, Chen GH, Lien HC, Yeh HZ| title=Small intestine dysmotility and bacterial overgrowth in cirrhotic patients with spontaneous bacterial peritonitis. | journal=Hepatology | year= 1998 | volume= 28 | issue= 5 | pages= 1187-90 | pmid=9794900 | doi=10.1002/hep.510280504 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9794900 }} </ref>}}
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| {{familytree | | | |!| |}}
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| {{familytree | boxstyle=background: #FFF0F5; color: #000000;| | | C01 | | C01='''Bacterial overgrowth:'''<br>
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| Increased intestinal permeability''' and '''decreased local and systemic [[immune system]] in [[cirrhosis]] and its relation to bacterial infections and prognosis. <ref name="pmid9794900">{{cite journal| author=Chang CS, Chen GH, Lien HC, Yeh HZ| title=Small intestine dysmotility and bacterial overgrowth in cirrhotic patients with spontaneous bacterial peritonitis. | journal=Hepatology | year= 1998 | volume= 28 | issue= 5 | pages= 1187-90 | pmid=9794900 | doi=10.1002/hep.510280504 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9794900 }} </ref><ref name="pmid11693333">{{cite journal| author=Bauer TM, Steinbrückner B, Brinkmann FE, Ditzen AK, Schwacha H, Aponte JJ et al.| title=Small intestinal bacterial overgrowth in patients with cirrhosis: prevalence and relation with spontaneous bacterial peritonitis. | journal=Am J Gastroenterol | year= 2001 | volume= 96 | issue= 10 | pages= 2962-7 | pmid=11693333 | doi=10.1111/j.1572-0241.2001.04668.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11693333</ref><ref name="pmid6693068">{{cite journal| author=Rimola A, Soto R, Bory F, Arroyo V, Piera C, Rodes J| title=Reticuloendothelial system phagocytic activity in cirrhosis and its relation to bacterial infections and prognosis. | journal=Hepatology | year= 1984 | volume= 4 | issue= 1 | pages= 53-8 | pmid=6693068 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6693068 }} </ref>}}
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| {{familytree | | | |!| |}}
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| {{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>
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| :Escape of enteric bacteria to systemic circulation through:<ref name="pmid15723320">{{cite journal| author=Wiest R, Garcia-Tsao G| title=Bacterial translocation (BT) in cirrhosis. | journal=Hepatology | year= 2005 | volume= 41 | issue= 3 | pages= 422-33 | pmid=15723320 | doi=10.1002/hep.20632 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15723320 }} </ref>
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| :❑ Bacterial translocation<ref name="pmid11211904">{{cite journal| author=Cirera I, Bauer TM, Navasa M, Vila J, Grande L, Taurá P et al.| title=Bacterial translocation of enteric organisms in patients with cirrhosis. | journal=J Hepatol | year= 2001 | volume= 34 | issue= 1 | pages= 32-7 | pmid=11211904 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11211904 }} </ref>
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| ::• Luminal bacteria within colonize mesenteric [[lymph nodes]].<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>
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| ::• Organisms from the mesenteric [[lymph nodes]] → Systemic circulation through thoracic duct lymph → percolates through the liver and weep across Glisson's capsule → Ascitic fluid.
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| ::• Transient [[bacteremia]] → Prolonged bacteremia ( due to ↓ Reticulo endothelial system activity ) → Ascites Colonization ( due to ↓ ascitic fluid bactericidal activity ) → Spontaneous bacterial [[peritonitis]] )
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| :❑ Portal Vein
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| ::• Porto-systemic shunt
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| ::• ↓RES function in the liver
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| :❑ Lymphatic rupture
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| ::• Contaminated lymph carried by lymphatics
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| ::• Ruptured Lymphatics due to high flow and high pressure associated with [[portal hypertension]] ( '''BACTERASCITES''' )<ref name="pmid8677940">{{cite journal| author=Ho H, Zuckerman MJ, Ho TK, Guerra LG, Verghese A, Casner PR| title=Prevalence of associated infections in community-acquired spontaneous bacterial peritonitis. | journal=Am J Gastroenterol | year= 1996 | volume= 91 | issue= 4 | pages= 735-42 | pmid=8677940 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8677940 }} </ref>
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| :❑ Other source of organisms
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| ::• IV catheters, skin, urinary, and respiratory tract</div>}}
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| {{familytree | | | |!| |}}
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| {{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>
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| :❑ Endotoxemia → release of pro-inflammatory [[cytokines]] produced by [[macrophages]] and other host cells in response to bacteria in the serum and peritoneal exudate
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| ::• [[Tumor necrosis factor-α]] (TNF-α)
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| ::• [[Interleukin]] (IL)-1,6
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| ::• [[Interferon-γ]] (IFN-γ)
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| ::• [[Soluble adhesion molecules]]
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| :❑ Systemic and Abdominal manifestations of [[peritonitis]] mediated by '''[[cytokines]]'''<ref name="pmid11713936">{{cite journal| author=Such J, Hillebrand DJ, Guarner C, Berk L, Zapater P, Westengard J et al.| title=Tumor necrosis factor-alpha, interleukin-6, and nitric oxide in sterile ascitic fluid and serum from patients with cirrhosis who subsequently develop ascitic fluid infection. | journal=Dig Dis Sci | year= 2001 | volume= 46 | issue= 11 | pages= 2360-6 | pmid=11713936 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11713936 }} </ref><ref name="pmid15138202">{{cite journal| author=Runyon BA| title=Early events in spontaneous bacterial peritonitis. | journal=Gut | year= 2004 | volume= 53 | issue= 6 | pages= 782-4 | pmid=15138202 | doi= | pmc=1774068 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15138202 }} </ref>
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| ::• 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.<ref name="pmid3894229">{{cite journal| author=Dunn DL, Barke RA, Knight NB, Humphrey EW, Simmons RL| title=Role of resident macrophages, peripheral neutrophils, and translymphatic absorption in bacterial clearance from the peritoneal cavity. | journal=Infect Immun | year= 1985 | volume= 49 | issue= 2 | pages= 257-64 | pmid=3894229 | doi= | pmc=262007 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3894229 }} </ref><ref name="pmid11713936">{{cite journal| author=Such J, Hillebrand DJ, Guarner C, Berk L, Zapater P, Westengard J et al.| title=Tumor necrosis factor-alpha, interleukin-6, and nitric oxide in sterile ascitic fluid and serum from patients with cirrhosis who subsequently develop ascitic fluid infection. | journal=Dig Dis Sci | year= 2001 | volume= 46 | issue= 11 | pages= 2360-6 | pmid=11713936 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11713936 }} </ref><ref name="NavasaFollo1998">{{cite journal|last1=Navasa|first1=Miguel|last2=Follo|first2=Antonio|last3=Filella|first3=Xavier|last4=Jiménez|first4=Wladimiro|last5=Francitorra|first5=Anna|last6=Planas|first6=Ramón|last7=Rimola|first7=Antoni|last8=Arroyo|first8=Vicente|last9=Rodés|first9=Joan|title=Tumor necrosis factor and interleukin-6 in spontaneous bacterial peritonitis in cirrhosis: Relationship with the development of renal impairment and mortality|journal=Hepatology|volume=27|issue=5|year=1998|pages=1227–1232|issn=02709139|doi=10.1002/hep.510270507}}</ref>
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| ::• 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.<ref name="pmid3894229">{{cite journal| author=Dunn DL, Barke RA, Knight NB, Humphrey EW, Simmons RL| title=Role of resident macrophages, peripheral neutrophils, and translymphatic absorption in bacterial clearance from the peritoneal cavity. | journal=Infect Immun | year= 1985 | volume= 49 | issue= 2 | pages= 257-64 | pmid=3894229 | doi= | pmc=262007 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3894229 }} </ref></div>}}
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| {{familytree | | | |!| |}}
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| {{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>
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| :❑ Local response
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| Outpouring of fluid into the peritoneal cavity at sites of irritation with:
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| ::• High protein content (>3 g/dL)
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| ::• Many cells, primarily [[polymorphonuclear leukocytes]], that [[phagocytose]] and kill organisms
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| ::• Formation of Fibrinous [[exudate]] on the inflamed peritoneal surfaces → Adhesion formation between adjacent bowel, [[mesentery]], and [[omentum]]
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| ::• Localization of the inflammatory process is aided further by inhibition of motility in the involved intestinal loops
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| ::• 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
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| ::• If peritoneal defenses aided by the appropriate supportive measures control the [[inflammatory]] process, the disease may resolve spontaneously ('''Sterile ascites''')<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 | year= 1985 | volume= 5 | issue= 4 | pages= 634-7 | pmid=4018735 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4018735 }} </ref><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 | year= 1985 | volume= 5 | issue= 4 | pages= 634-7 | pmid=4018735 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4018735 }} </ref><ref name="pmid8677940">{{cite journal| author=Ho H, Zuckerman MJ, Ho TK, Guerra LG, Verghese A, Casner PR| title=Prevalence of associated infections in community-acquired spontaneous bacterial peritonitis. | journal=Am J Gastroenterol | year= 1996 | volume= 91 | issue= 4 | pages= 735-42 | pmid=8677940 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8677940 }} </ref> → Consumption of humoral bactericidal factors due to frequent colonization → Increased susceptibility to '''SBP'''<ref name="pmid3257456">{{cite journal| author=Titó L, Rimola A, Ginès P, Llach J, Arroyo V, Rodés J| title=Recurrence of spontaneous bacterial peritonitis in cirrhosis: frequency and predictive factors. | journal=Hepatology | year= 1988 | volume= 8 | issue= 1 | pages= 27-31 | pmid=3257456 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3257456 }} </ref>
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| ::• 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.<ref name="pmid3371881">{{cite journal| author=Runyon BA| title=Patients with deficient ascitic fluid opsonic activity are predisposed to spontaneous bacterial peritonitis. | journal=Hepatology | year= 1988 | volume= 8 | issue= 3 | pages= 632-5 | pmid=3371881 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3371881 }} </ref><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>
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| ::• Second possible outcome is a confined '''[[abscess]]'''
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| ::• 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.
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| :❑ Systemic response
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| [[Gastrointestinal]]
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| ::• [[Paralysis]] of the bowel due to local [[inflammation]]
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| ::• Progressive accumulation of fluid and electrolytes in the lumen of the adynamic bowel → distention of the bowel → inhibition of the capillary inflow and secretions
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| ::• GI bleeding because of excessive [[inflammation]] and tissue damage → ↑ [[vasodilatation]] and ↓organ perfusion
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| [[Cardiovascular]]
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| ::• Shift of fluid into the peritoneal cavity and bowel lumen → ↓ Effective circulating blood volume → ↑ [[Hematocrit]] and
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| ::• ↑Fluid and electrolyte loss by coexistent [[fever]], [[vomiting]], [[diarrhea]] → decreased venous return to the right side of the heart → decrease in [[cardiac output]] → [[hypotension]] → activation of the [[sympathetic nervous system]] and manifestations such as [[sweating]], [[tachycardia]], and [[cutaneous]] [[vasoconstriction]] (i.e., cold, moist skin and mottled, [[cyanotic]] extremities).
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| ::• If the blood volume replaced is sufficient enough as so to increase the [[cardiac output]] 2-3 times normal ( to satisfy the increased metabolic needs of the body in the presence of infection) a halt in the progression of the disease is seen.
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| ::• Failure to sustain increased [[cardiac output]] results in progressive [[lactic acidosis]], [[oliguria]], [[hypotension]], and ultimately death if the [[infection]] cannot be controlled.
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| [[Respiratory]]
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| ::• [[Intra-peritoneal]] [[inflammation]] → high and fixed [[diaphragm]] → pain on respiration → basilar [[atelectasis]] with intrapulmonary shunting of blood
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| ::• Decompensation of [[respiratory]] function due to delay in the intervention → [[hypoxemia]] + [[hypo-capnia]] ([[respiratory alkalosis]]) followed by [[hypercapnia]] ([[respiratory acidosis]])
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| ::• [[Pulmonary edema]] results because of increased pulmonary capillary leakage as a consequence of [[hypo-albuminemia]] or direct effects of bacterial toxins ([[adult respiratory distress syndrome]]) → progressive [[hypoxemia]] with decreasing pulmonary compliance which needs a [[ventilator]] assistance with increasingly higher concentrations of inspired [[oxygen]] and [[positive end-expiratory pressure]].
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| [[Renal]]
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| ::• SBP → Splanchnic arterial [[vasodilation]] and systemic [[vascular resistance]] → ↓ Effective [[arterial]] blood volume → stimulation of systemic [[vasoconstrictors]] ([[RAAS]], [[Sympathetic Nervous System]], [[Arginine vasopressin]]) → renal [[vasoconstriction]]
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| ::• Advanced [[cirrhosis]] → ↓ production of local [[vasodilators]] and ↑ production of local [[vasoconstrictors]]<ref name="pmid11713936">{{cite journal| author=Such J, Hillebrand DJ, Guarner C, Berk L, Zapater P, Westengard J et al.| title=Tumor necrosis factor-alpha, interleukin-6, and nitric oxide in sterile ascitic fluid and serum from patients with cirrhosis who subsequently develop ascitic fluid infection. | journal=Dig Dis Sci | year= 2001 | volume= 46 | issue= 11 | pages= 2360-6 | pmid=11713936 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11713936 }} </ref> → Hepatorenal syndrome and death.<ref name="pmid15138202">{{cite journal| author=Runyon BA| title=Early events in spontaneous bacterial peritonitis. | journal=Gut | year= 2004 | volume= 53 | issue= 6 | pages= 782-4 | pmid=15138202 | doi= | pmc=1774068 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15138202 }} </ref>
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| ::• ↓ Organ perfusion → [[Ischemic]] and Toxic [[Acute Tubular Necrosis]] → [[Acute Renal Failure]] → Death in (30-40%) of patients.
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| [[Metabolic]]
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| ::• [[Infection]] → ↓body stores of [[Glycogen]] → catabolism of protein (muscle) and →extreme wasting and rapid weight loss of severely infected patients
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| ::• Infection → ↓Body heat production → exhaustion and death
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| [[Central nervous system]]
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| ::• [[Hepatic Encephalopathy]] may occur due to [[inflammation]], [[Oxidative stress]] and Intestinal [[ammonia]] production on crossing the [[blood-brain barrier]] → [[altered mentation]].
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| [[Hematological]]
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| ::• [[Sepsis]] → [[DIC]]</div>}} | |
| {{family tree/end}}
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| |}
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| <br>
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| <br>
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| ==Diagramatic representation of pathological bacterial translocation and the associated host response==
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| === Bacterial Translocation ===
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| It is defined as the translocation of either bacteria or bacterial products such as lipopolysacharides (LPS), bacterial DNA, peptidoglycans, muramyl-dipeptides from gut into mesenteric lymph nodes.<ref name="pmid154474">Berg RD, Garlington AW (1979) [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=154474 Translocation of certain indigenous bacteria from the gastrointestinal tract to the mesenteric lymph nodes and other organs in a gnotobiotic mouse model.] ''Infect Immun'' 23 (2):403-11. PMID: [https://pubmed.gov/154474 154474]</ref>
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| '''Physiological:''' It is the normal bacterial translocation in healthy individuals due to lack of pro-inflammatory responses against commensal bacteria. Physiological translocation is crucial for the development of host immunity response.
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| '''Pathological:''' It is developed due to abnormal increase in physiological translocation in both rate and degree by breaking the normal immunological barriers.
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| '''Barriers that limit pathological transmission:'''
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| # '''Interstinal lumen and it's secretory components such as inner and outer mucus layer, antimicrobial peptides''': This is the primary barrier that limit direct contact between the intestinal bacteria and the epithelial cell surface
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| # '''Epithelial barrier with the gut-associated lymphatic tissue (GALT) and autonomic nervous system''': This is a mechanical barrier with local immunological response elements (e.g., TNF and other pro-inflammatory cytokines) that rapidly detects and kill the pathogen that manage to penetrate
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| # '''Systemic immune system:''' This includes hematogenous (portal venous) and lymphatic (ductus thoracicus) route of delivery that acts as a third immune barrier to prevent or minimize the pathogen to disseminate systemically from local immune system such as lymph nodes.
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| === '''Mechanism of pathological bacterial translocation''' ===
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| Breaking these immune barriers can progress physiological BT into pathological BT.
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| {| border="1"
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| ! rowspan="5" |Bacterial Translocation
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| ! colspan="3" |[[File:Pathophysiology of bacterial tranlocation.jpg|800px]]
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| <SMALL><SMALL><SMALL>Adapted from '''Journal of hepatology:Pathological bacterial translocation in liver cirrhosis'''.<ref name=AASLD2013>{{cite web
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| | title = Pathological bacterial translocation in liver cirrhosis
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| | url = http://www.journal-of-hepatology.eu/article/S0168-8278(13)00602-8/abstract
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| }}</ref></SMALL></SMALL></SMALL>
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| |-
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| ! rowspan="2" |'''I. Immune response by'''
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| '''gut associated lymphoid tissue'''
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| !'''A'''. '''Innate immunity'''
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| |Innate immunity is the first line of defense mechanism against invading pathogen that detects common bacterial motifs such as microbial-associated molecular patterns (MAMPs) through germline-coded pattern-recognition receptors (PRR) on intestinal cells.<ref name="pmid11477402">Akira S, Takeda K, Kaisho T (2001) [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11477402 Toll-like receptors: critical proteins linking innate and acquired immunity.] ''Nat Immunol'' 2 (8):675-80. [http://dx.doi.org/10.1038/90609 DOI:10.1038/90609] PMID: [https://pubmed.gov/11477402 11477402]</ref>
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| '''Mechanism of breaking of innate immunity'''
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| # Dendritic cells below the epithelial layer allows pathogen via dendritic processes with out affecting tight junction function.
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| # Disruption of epithelial barrier by antigenic properties of the pathogen with the underlying epithelial layer and compromises its epithelial integrity.
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| # Access provided by M- cells overlying payers patches with in the villous epithelium through antigen presenting cells.<ref name="pmid19907495">Hase K, Kawano K, Nochi T, Pontes GS, Fukuda S, Ebisawa M et al. (2009) [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19907495 Uptake through glycoprotein 2 of FimH(+) bacteria by M cells initiates mucosal immune response.] ''Nature'' 462 (7270):226-30. [http://dx.doi.org/10.1038/nature08529 DOI:10.1038/nature08529] PMID: [https://pubmed.gov/19907495 19907495]</ref>
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| !B. Adaptive immunity
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| |align=center|Bacterial translocation through epithelial cells
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| ⬇
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| Release of chemokines form epithelial cells
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| ⬇
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| Recruitment of dendritic cells towards mucosa
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| ⬇
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| Dendritic cells induces adaptive immunity through mucosal B and T lymphocytes<ref name="pmid22611024">Muñoz L, José Borrero M, Ubeda M, Lario M, Díaz D, Francés R et al. (2012) [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=22611024 Interaction between intestinal dendritic cells and bacteria translocated from the gut in rats with cirrhosis.] ''Hepatology'' 56 (5):1861-9. [http://dx.doi.org/10.1002/hep.25854 DOI:10.1002/hep.25854] PMID: [https://pubmed.gov/22611024 22611024]</ref>
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| ⬇
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| '''a'''. Bacterial antigen present to Matured T- lymphocytes, followed by activation B-lymphocytes through T- helper cells
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| '''b'''. Antigen presenting cells present microbial antigen to matured B- lymphocytes, eventually B-cell releases Ig-A mucosal immunoglobulins against pathogen and it's product
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| '''Mechanism of breaking adaptive immunity:''' Due to the underlying immunocompromised states such as cirrhosis, there is a depletion of both T and B cells and hypogamaglobilinemia, results in weak development of adaptive immunity with insufficient bacterial killing that leads to lethal dissemination of commensal bacteria.<ref name="pmid22306056">Kirkland D, Benson A, Mirpuri J, Pifer R, Hou B, DeFranco AL et al. (2012) [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=22306056 B cell-intrinsic MyD88 signaling prevents the lethal dissemination of commensal bacteria during colonic damage.] ''Immunity'' 36 (2):228-38. [http://dx.doi.org/10.1016/j.immuni.2011.11.019 DOI:10.1016/j.immuni.2011.11.019] PMID: [https://pubmed.gov/22306056 22306056]</ref><ref name="pmid21932384">Doi H, Iyer TK, Carpenter E, Li H, Chang KM, Vonderheide RH et al. (2012) [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=21932384 Dysfunctional B-cell activation in cirrhosis resulting from hepatitis C infection associated with disappearance of CD27-positive B-cell population.] ''Hepatology'' 55 (3):709-19. [http://dx.doi.org/10.1002/hep.24689 DOI:10.1002/hep.24689] PMID: [https://pubmed.gov/21932384 21932384]</ref><ref name="pmid7911786">Gautreaux MD, Deitch EA, Berg RD (1994) [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=7911786 T lymphocytes in host defense against bacterial translocation from the gastrointestinal tract.] ''Infect Immun'' 62 (7):2874-84. PMID: [https://pubmed.gov/7911786 7911786]</ref><ref name="pmid6966611">Owens WE, Berg RD (1980) [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=6966611 Bacterial translocation from the gastrointestinal tract of athymic (nu/nu) mice.] ''Infect Immun'' 27 (2):461-7. PMID: [https://pubmed.gov/6966611 6966611]</ref>
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| ! colspan="2" |II. Mesenteric lymph nodes (MLN)
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| |In a healthy gut, dendritic cells transport pathological bacteria to mesenteric lymph nodes which induces local immune response and are killed without inducing systemic immunity.
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| In immunocompromised state, lack of local immune response by MLN is reduced, eventually permits the translocation of intestinal bacteria systemically, which eventually may lead to sepsis and death.
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|
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| '''Mechanism involving in spreading bacteria beyond MLN:'''<ref name="pmid6693068">{{cite journal| author=Rimola A, Soto R, Bory F, Arroyo V, Piera C, Rodes J| title=Reticuloendothelial system phagocytic activity in cirrhosis and its relation to bacterial infections and prognosis. | journal=Hepatology | year= 1984 | volume= 4 | issue= 1 | pages= 53-8 | pmid=6693068 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6693068 }} </ref><ref name="pmid11950821">{{cite journal| author=Trevisani F, Castelli E, Foschi FG, Parazza M, Loggi E, Bertelli M et al.| title=Impaired tuftsin activity in cirrhosis: relationship with splenic function and clinical outcome. | journal=Gut | year= 2002 | volume= 50 | issue= 5 | pages= 707-12 | pmid=11950821 | doi= | pmc=1773217 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11950821 }} </ref> | | * '''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> |
| * Deficient innate and adaptive immunity
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| * Impaired chemotactic, opsonic, phagocytic activity of macropharges
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| * Impaired RES activity
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| ! colspan="2" |III. Systemic immune response
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| |Translocation beyond MLN through hematogenous or lymphatic path is specific and depends on the microbial-specific systemic immune response.<ref name="pmid10864873">{{cite journal| author=Macpherson AJ, Gatto D, Sainsbury E, Harriman GR, Hengartner H, Zinkernagel RM| title=A primitive T cell-independent mechanism of intestinal mucosal IgA responses to commensal bacteria. | journal=Science | year= 2000 | volume= 288 | issue= 5474 | pages= 2222-6 | pmid=10864873 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10864873 }}</ref> Lymphatic and portalvenous route in parallel are disrupt in liver cirrhosis which results in dissemination of bacterial pathogen.
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| |}
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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> |
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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<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. |
| | * 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]]. |
| | * 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]]. |
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| | ===C. Decreased local and systemic immune responses:=== |
| | * [[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 [[Ascites|ascitic fluid]]). |
| | * The [[neutrophils]] seem to have declined [[Granulocyte|granulocyte functions]] as adherence, [[chemotaxis]], and bacterial killing. |
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|
| | | 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. |
| <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 | year= 1988 | volume= 8 | issue= 3 | pages= 632-5 | pmid=3371881 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3371881 }} </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>
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| 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>
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| 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 | year= 1985 | volume= 5 | issue= 4 | pages= 634-7 | pmid=4018735 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4018735 }} </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"/>
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| ==References== | | ==References== |
| {{reflist|2}} | | {{reflist|2}} |
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| {{WH}}
| | [[Category:Emergency mdicine]] |
| {{WS}}
| | [[Category:Disease]] |
| | | [[Category:Up-To-Date]] |
| [[Category:Gastroenterology]] | |
| [[Category:Emergency medicine]] | |
| [[Category:Infectious disease]] | | [[Category:Infectious disease]] |