Shigellosis pathophysiology: Difference between revisions
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==Overview== | ==Overview== | ||
==Pathophysiology== | ==Pathophysiology== | ||
''Shigella'' infection is typically via ingestion (fecal–oral contamination); depending on age and condition of the host as few as ten bacterial cells can be enough to cause an infection. ''Shigella'' cause [[dysentery]] that results in the destruction of the epithelial cells of the intestinal mucosa in the [[cecum]] and [[rectum]]. Some strains produce [[enterotoxin]] and [[Shiga toxin]], similar to the [[verotoxin]] of [[Escherichia coli O157 H7|''E. coli'' O157:H7]].<ref>{{cite book | author = Hale TL, Keusch GT | title = Shigella. ''in:'' Baron's Medical Microbiology ''(Baron S ''et al'', eds.)| edition = 4th ed. | publisher = Univ of Texas Medical Branch | year = 1996 | url = http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed.chapter.1257 | isbn = 0-9631172-1-1 }}</ref> Both Shiga toxin and verotoxin are associated with causing [[hemolytic uremic syndrome]]. | ===Transmission=== | ||
*A small inoculum (10 to 200 organisms) is sufficient to cause shigellosis. | |||
*Most commonly, shigella is reported to be easily spread by the fecal-oral route in regions of poor sanitation. | |||
*Epidemics may be foodborne or waterborne. | |||
*Shigella can also be transmitted by flies and sexual contact. | |||
===Microscopic Pathology== | |||
The small inoculum may be attributed to the following features of the organism: | |||
*''Shigella'' contains acid resistance systems that enable the organism to survive the acidic environment in the stomach.(61) | |||
*''Shigella'' can downregulate the expresion of antibacterial proteins released by the host (human) intestinal mucosa.(118) | |||
====Phase 1:Transcytosis Using M Cells As Entry Ports=== | |||
''Shigella'' migrates to the large intestine, where it causes infection via invasion of the epithelial barrier of the large intestine. Initially, ''Shigella'' uses M cells from the basolateral side of the intestinal epithelium as entry port.(250,325) M cells are specialized cells that sample the gut lumen for pathogenic antigens and delivers these antigens to mucosal lymphoid tissue to activate an adequate immune response.(157). ''Shigella'' is transcytosed across the epithelial layer of the intestinal M cells. | |||
====Phase 2:Uptake by Macrophages==== | |||
*Following transcytosis, ''Shigella'' enters macrophages and induces cellular apoptosis. | |||
*Macrophage apoptosis results in the release of pro-inflammatory cytokines (IL-1-beta and IL-18)), which signal intestinal inflammation and consequent innate immune response. | |||
====Phase 3: Release from Apoptotic Macrophages==== | |||
*Following apoptosis and inflammation, ''Shigella'' is released from the macrophages. | |||
*Invasion of the intestinal epithelium continues from the basolateral side, and the bacteria further spreads to adjacent epithelial cells and avoids extracellular exposure by using intercellular actin polymerization processes. | |||
====Infiltration of Polymorphonuclear Neutrophils==== | |||
*As ''Shigella'' infiltrates the epithelial cells, activation of nuclear factor kappa-B (NF-KB) by ''Shigella'' generates IL-8, which in turn mediates the recruitment of polymorphonuclear neutrophils (PMN) to the site of inflammation. | |||
*PMN destroy the integrity of the intestinal epithelial barrier and allow more ''Shigella'' organisms to directly and more easily invade the intestinal epithelium. The loss of the intestinal epithelial cells results in impaired adsorption of other nutrients and fluids and leads to clinical manifestations of shigellosis (diarrhea). | |||
*''Shigella enterotoxin 1 (ShET1) and enterotoxin 2 (ShET2) are synthesized during the inflammatory process and are thought to account, at least in part, for fluid secretion that results in shigellosis-associated diarrhea. | |||
*Other Shigella toxins, such as ''Shigella dysenteriae'' serotype 1 toxin, results in cytotoxicity and development of vascular lesions at the level of the colon, the kidneys, and the central nervous system. The cytotoxic activity of the toxin is thought to cause shigella-associated complications, such as hemolytic uremic syndrome (HUS). | |||
Ultimately, more PMN are recruited and ''Shigella'' organisms are killed. | |||
===Genetics=== | |||
===Associated Conditions=== | |||
===Gross Pathology=== | |||
===Microscopic Pathology===''Shigella'' infection is typically via ingestion (fecal–oral contamination); depending on age and condition of the host as few as ten bacterial cells can be enough to cause an infection. ''Shigella'' cause [[dysentery]] that results in the destruction of the epithelial cells of the intestinal mucosa in the [[cecum]] and [[rectum]]. Some strains produce [[enterotoxin]] and [[Shiga toxin]], similar to the [[verotoxin]] of [[Escherichia coli O157 H7|''E. coli'' O157:H7]].<ref>{{cite book | author = Hale TL, Keusch GT | title = Shigella. ''in:'' Baron's Medical Microbiology ''(Baron S ''et al'', eds.)| edition = 4th ed. | publisher = Univ of Texas Medical Branch | year = 1996 | url = http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed.chapter.1257 | isbn = 0-9631172-1-1 }}</ref> Both Shiga toxin and verotoxin are associated with causing [[hemolytic uremic syndrome]]. | |||
''Shigella'' invade the host through [[epithelial cell]]s of the [[small intestine]]. Using a Type III secretion system acting as a biological syringe, the bacterium injects ''Ipa'' protein into cell, triggering bacterial invasion, and the subsequently [[lysis]] of [[Vacuole|vacuolar]] membranes. It utilizes a mechanism for its motility by which its IcsA triggers actin polymerization in the host cell in a "rocket" propulsion fashion for cell-to-cell spread. | ''Shigella'' invade the host through [[epithelial cell]]s of the [[small intestine]]. Using a Type III secretion system acting as a biological syringe, the bacterium injects ''Ipa'' protein into cell, triggering bacterial invasion, and the subsequently [[lysis]] of [[Vacuole|vacuolar]] membranes. It utilizes a mechanism for its motility by which its IcsA triggers actin polymerization in the host cell in a "rocket" propulsion fashion for cell-to-cell spread. | ||
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Overview
Pathophysiology
Transmission
- A small inoculum (10 to 200 organisms) is sufficient to cause shigellosis.
- Most commonly, shigella is reported to be easily spread by the fecal-oral route in regions of poor sanitation.
- Epidemics may be foodborne or waterborne.
- Shigella can also be transmitted by flies and sexual contact.
=Microscopic Pathology
The small inoculum may be attributed to the following features of the organism:
- Shigella contains acid resistance systems that enable the organism to survive the acidic environment in the stomach.(61)
- Shigella can downregulate the expresion of antibacterial proteins released by the host (human) intestinal mucosa.(118)
=Phase 1:Transcytosis Using M Cells As Entry Ports
Shigella migrates to the large intestine, where it causes infection via invasion of the epithelial barrier of the large intestine. Initially, Shigella uses M cells from the basolateral side of the intestinal epithelium as entry port.(250,325) M cells are specialized cells that sample the gut lumen for pathogenic antigens and delivers these antigens to mucosal lymphoid tissue to activate an adequate immune response.(157). Shigella is transcytosed across the epithelial layer of the intestinal M cells.
Phase 2:Uptake by Macrophages
- Following transcytosis, Shigella enters macrophages and induces cellular apoptosis.
- Macrophage apoptosis results in the release of pro-inflammatory cytokines (IL-1-beta and IL-18)), which signal intestinal inflammation and consequent innate immune response.
Phase 3: Release from Apoptotic Macrophages
- Following apoptosis and inflammation, Shigella is released from the macrophages.
- Invasion of the intestinal epithelium continues from the basolateral side, and the bacteria further spreads to adjacent epithelial cells and avoids extracellular exposure by using intercellular actin polymerization processes.
Infiltration of Polymorphonuclear Neutrophils
- As Shigella infiltrates the epithelial cells, activation of nuclear factor kappa-B (NF-KB) by Shigella generates IL-8, which in turn mediates the recruitment of polymorphonuclear neutrophils (PMN) to the site of inflammation.
- PMN destroy the integrity of the intestinal epithelial barrier and allow more Shigella organisms to directly and more easily invade the intestinal epithelium. The loss of the intestinal epithelial cells results in impaired adsorption of other nutrients and fluids and leads to clinical manifestations of shigellosis (diarrhea).
- Shigella enterotoxin 1 (ShET1) and enterotoxin 2 (ShET2) are synthesized during the inflammatory process and are thought to account, at least in part, for fluid secretion that results in shigellosis-associated diarrhea.
- Other Shigella toxins, such as Shigella dysenteriae serotype 1 toxin, results in cytotoxicity and development of vascular lesions at the level of the colon, the kidneys, and the central nervous system. The cytotoxic activity of the toxin is thought to cause shigella-associated complications, such as hemolytic uremic syndrome (HUS).
Ultimately, more PMN are recruited and Shigella organisms are killed.
Genetics
Associated Conditions
Gross Pathology
===Microscopic Pathology===Shigella infection is typically via ingestion (fecal–oral contamination); depending on age and condition of the host as few as ten bacterial cells can be enough to cause an infection. Shigella cause dysentery that results in the destruction of the epithelial cells of the intestinal mucosa in the cecum and rectum. Some strains produce enterotoxin and Shiga toxin, similar to the verotoxin of E. coli O157:H7.[1] Both Shiga toxin and verotoxin are associated with causing hemolytic uremic syndrome.
Shigella invade the host through epithelial cells of the small intestine. Using a Type III secretion system acting as a biological syringe, the bacterium injects Ipa protein into cell, triggering bacterial invasion, and the subsequently lysis of vacuolar membranes. It utilizes a mechanism for its motility by which its IcsA triggers actin polymerization in the host cell in a "rocket" propulsion fashion for cell-to-cell spread.
The most common symptoms are diarrhea, fever, nausea, vomiting, stomach cramps, and straining to have a bowel movement. The stool may contain blood, mucus, or pus (e.g. dysentery). In rare cases, young children may have seizures. Symptoms can take as long as a week to show up, but most often begin two to four days after ingestion. Symptoms usually last for several days, but can last for weeks. Shigella is implicated as one of the pathogenic causes of reactive arthritis worldwide.[2]
Severe dysentery can be treated with ampicillin, TMP-SMX, or fluoroquinolones such as ciprofloxacin.
Histopathology of Shigellosis (Bacillary Dysentery)
{{#ev:youtube|1D1m4rybDrc}}
References
- ↑ Hale TL, Keusch GT (1996). Shigella. in: Baron's Medical Microbiology (Baron S et al, eds.) (4th ed. ed.). Univ of Texas Medical Branch. ISBN 0-9631172-1-1.
- ↑ Hill Gaston JS, Lillicrap MS (2003). "Arthritis associated with enteric infection". Best practice & research. Clinical rheumatology. 17 (2): 219–39. PMID 12787523.