|
|
| (51 intermediate revisions by 6 users not shown) |
| Line 1: |
Line 1: |
| __NOTOC__ | | __NOTOC__ |
| {{Spontaneous bacterial peritonitis}} | | {{Spontaneous bacterial peritonitis}} |
| {{CMG}}; {{AE}} {{ADI}} {{SCh}} | | {{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="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>
| | [[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<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>==
| | Three factors play a role in the pathogenesis of SBP: |
| ===<font color="#0000FF">Pathogenesis of spontaneous bacterial peritonitis<ref name="pmid8775093">{{cite journal| author=Guarner C, Runyon BA| title=Spontaneous bacterial peritonitis: pathogenesis, diagnosis, and management. | journal=Gastroenterologist | year= 1995 | volume= 3 | issue= 4 | pages= 311-28 | pmid=8775093 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8775093 }} </ref></font>===
| | * '''[[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. |
| <br>
| |
| <br>
| |
| <br>
| |
| {| align=center
| |
| |-
| |
| |
| |
| {{familytree/start}}
| |
| {{familytree | boxstyle=background: #FFF0F5; color: #000000;| | | A01 | | A01=Patients with '''Decompensated Cirrhosis<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> leading to '''Portal Hypertension<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>'''}}
| |
| {{familytree | | | |!| |}}
| |
| {{familytree | boxstyle=background: #FFF0F5; color: #000000;| | | B01 | | B01='''Hypo-motility<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>''' and '''local pro-inflammatory phenomenon'''}}
| |
| {{familytree | | | |!| |}}
| |
| {{familytree | boxstyle=background: #FFF0F5; color: #000000;| | | C01 | | C01='''Bacterial overgrowth'''<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> intestine dysmotility and bacterial overgrowth in cirrhotic patients with spontaneous bacterial peritonitis.<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>''' '''Increased intestinal permeability''' and '''Decreased local and systemic immune system in cirrhosis and its relation to bacterial infections and prognosis. <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>}}
| |
| {{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:<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>
| |
| :❑ 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>
| |
| ::• 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
| |
| ::• 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 ( '''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>
| |
| :❑ 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'''<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>
| |
| ::• The effector molecules ('''Nitric oxide''') and cytokines,'''Tumour necrosis factor''' (TNF) that help kill the bacteria<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> have undesired side effects as they cause ''vasodilation'' and '''renal failure''' that accompany SBP.<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>
| |
| ::• Studies have shown that the presence of whole bacteria or DNA, in serum and ascitic fluid leads to stimulation of immune defences<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>, 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''')<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>
| |
| ::• 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
| |
| ::• GI bleeding because of excessive inflammation and tissue damage → ↑ vasodilatation and ↓organ perfusion
| |
| Cardiovascular
| |
| ::• Shift of fluid into the peritoneal cavity and bowel lumen → ↓ Effective circulating blood volume → ↑ Hematocrit and
| |
| ::• ↑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).
| |
| ::• 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.
| |
| ::• Failure to sustain increased cardiac output results in progressive lactic acidosis, oliguria, hypotension, and ultimately death if the infection cannot be controlled.
| |
| Respiratory
| |
| ::• Intraperitoneal inflammation → high and fixed diaphragm → pain on respiration → basilar atelectasis with intrapulmonary shunting of blood
| |
| ::• Decompensation of respiratory function due to delay in the intervention → hypoxemia + hypocapnia (respiratory alkalosis) followed by hypercapnia (respiratory acidosis)
| |
| ::• Pulmonary edema results because of increased pulmonary capillary leakage as a consequence of hypoalbuminemia 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.
| |
| Renal
| |
| ::• SBP → Splanchnic arterial vasodilation and csystemic vascular resistance → ↓ Effective arterial blood volume → stimulation o systemic vasoconstrictors (RAAS, Sympathetic Nervous System, Arginine vasopressin) → renal vasoconstriction
| |
| ::• Advanced cirrhosis → ↓ production of local vasodilators and ↑ production o 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>
| |
| ::• ↓ Organ perfusion → Ischemic and Toxic Acute Tubular Necrosis → Acute Renal Failure → Death in (30-40%) of patients.
| |
| Metabolic
| |
| ::• Infection → ↓body stores of Glycogen → catabolism of protein (muscle) and →extreme wasting and rapid weight loss of severely infected patients
| |
| ::• Infection → ↓Body heat production → exhaustion and death
| |
| Central nervous system
| |
| ::• Hepatic Encephalopathy may occur due to inflammation, Oxidative stress and Intestinal ammonia production on crossing the blood brain barrier → altered mentation.
| |
| Hematological
| |
| ::• Sepsis → DIC</div>}}
| |
| {{family tree/end}}
| |
| |}
| |
| <br>
| |
| <br>
| |
| | |
| | |
| Following steps may explain the underlying process in a comprehensive way:
| |
| * Spontaneous bacterial peritonitis is thought to result from a combination of factors related to cirrhosis and ascites such as:
| |
|
| |
|
| ===Natural barriers===
| | * '''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> |
| ====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=== | | * '''[[Immunity suppression|Decreased immunity]]:''' both local and systemic immunity are decreased in [[Cirrhosis|cirrhotic patients]]. |
| ===Hepatic Reticulo endothelial system activity===
| | ===A. Bacterial overgrowth:=== |
| ====Porto-systemic shunting====
| | * [[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. |
| ====Phagocytic response==== | | * Also, [[Cirrhosis|cirrhotic patients]] administer [[Proton pump inhibitor|PPIs]] more frequently than other patient populations. |
| ===Serum factors===
| | * 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> |
|
| |
|
| ===Bacterial translocation=== | | ===B. Increased bowel permeability:=== |
| ===Routes of transmission===
| |
| ===Reticulo endothelial dysfunction===
| |
| ===Alterations in the systemic immune response===
| |
| ===Ascitic fluid defense mechanisms<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>===
| |
| ===Cytokine response===
| |
|
| |
|
| | 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]]. |
|
| |
|
| *
| | ===C. Decreased local and systemic immune responses:=== |
| ** Prolonged [[bacteremia]] secondary to compromised host defenses | | * [[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. |
| ** Intrahepatic shunting of colonized [[blood]] and
| | * As a result of defective liver synthetic functions, [[complement]] levels decrease (both in [[serum]] and [[Ascites|ascitic fluid]]). |
| ** 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>
| | * The [[neutrophils]] seem to have declined [[Granulocyte|granulocyte functions]] as adherence, [[chemotaxis]], and bacterial killing. |
|
| |
|
| 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>
| | 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. |
| | |
| 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"/>
| |
|
| |
|
| ==References== | | ==References== |
| {{reflist|2}} | | {{reflist|2}} |
|
| |
|
| {{WH}}
| | [[Category:Emergency mdicine]] |
| {{WS}}
| | [[Category:Disease]] |
| | | [[Category:Up-To-Date]] |
| [[Category:Gastroenterology]] | |
| [[Category:Emergency medicine]] | |
| [[Category:Infectious disease]] | | [[Category:Infectious disease]] |