Shigellosis pathophysiology: Difference between revisions
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===Genetics=== | ===Genetics=== | ||
===Gross Pathology=== | ===Gross Pathology=== | ||
The following video demonstrates the gross pathological features of shigellosis: | |||
{{#ev:youtube|1D1m4rybDrc}} | {{#ev:youtube|1D1m4rybDrc}} | ||
Revision as of 22:51, 5 April 2015
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Shigellosis Microchapters |
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Diagnosis |
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Treatment |
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Shigellosis pathophysiology On the Web |
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American Roentgen Ray Society Images of Shigellosis pathophysiology |
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Risk calculators and risk factors for Shigellosis pathophysiology |
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 (rocket propulsion).
Phase 4: 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
Gross Pathology
The following video demonstrates the gross pathological features of shigellosis: {{#ev:youtube|1D1m4rybDrc}}