Amoebiasis pathophysiology: Difference between revisions

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__NOTOC__
__NOTOC__
{{Amoebiasis}}
{{Amoebiasis}}
{{CMG}}; {{AE}} {{YD}}; {{SSK}}
{{CMG}} {{AE}} {{YD}}; {{SSK}}


==Overview==
==Overview==
''E. histolytica'' cyst is usually transmitted by the fecal-oral route (through contaminated drinking water or food) or by direct contact with infected individuals. Following transmission, ''E. histolytica'' trophozoites undergoes excystation in the small intestine, after which it migrates to the large intestine using pseudopods. The trophozoites invades the intestinal mucosa and migrates into the bloodstream. Simultaneously, they form resistant cysts in the large intestines that are then excreted in human stools. ''E. histolytica'' trophozoites secrete proteases and glycosidases to degrade the intestinal layers. Once cellular degradation occurs, upregulation of IL-8 and TNF-alpha results in the recruitment of neutrophils, macrophages, and eosinophils. The host immune system does not usually result in adequate destruction of the ''E. histolytica'' trophozoite, and the parasite continues to invade until it reaches the bloodstream, whereby it can then migrate to other organs and cause multisystem disease. On gross pathology, amebiasis may be characterized by wavy surface epithelium and formation of nodular and irregular ulcerations. On microscopic pathology, flask-shaped ulcers are characteristic, but interglandular ulcerations, hyperemia, mucosal thickening, reactive glandular hyperplasia, and neutrophilic infiltration are common findings. In late stages, amebiasis often results in tissue fibrinoid necrosis and formation of granulation tissue.
==Transmission==
==Transmission==
*''E. histolytica'' cyst is usually transmitted by the fecal-oral route through contaminated drinking water or food)
*''E. histolytica'' cyst is usually transmitted by the fecal-oral route through contaminated drinking water or food
*''E. histolytica'' cyst may also be transmitted indirectly through direct contact with infected individuals.
*''E. histolytica'' cyst may also be transmitted through direct contact with infected individuals.


==Pathogenesis==
==Pathogenesis==
*Following transmission, ''E. histolytica'' trophozoites inhabit in the large intestine of the human host.
*Following transmission, ''E. histolytica'' trophozoites undergoes excystation in the small intestine, after which it migrates to the large intestine using pseudopods.
*In the large intestine, the trophozoites invades the intestinal mucosa into the bloodstream. Simultaneously, they form resistant cysts in the large intestines that are then excreted in human stools.
*In the large intestine, the trophozoites invades the intestinal mucosa into the bloodstream. Simultaneously, they form resistant cysts in the large intestines that are then excreted in human stools.
*Once in the bloodstream, the trophozoite migrates into the portal circulation and develops amebic liver abscess.<ref name="pmid10756002">{{cite journal| author=Espinosa-Cantellano M, Martínez-Palomo A| title=Pathogenesis of intestinal amebiasis: from molecules to disease. | journal=Clin Microbiol Rev | year= 2000 | volume= 13 | issue= 2 | pages= 318-31 | pmid=10756002 | doi= | pmc=PMC100155 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10756002  }} </ref>
*Once in the bloodstream, the trophozoite migrates into the portal circulation and develops amebic liver abscess.<ref name="pmid10756002">{{cite journal| author=Espinosa-Cantellano M, Martínez-Palomo A| title=Pathogenesis of intestinal amebiasis: from molecules to disease. | journal=Clin Microbiol Rev | year= 2000 | volume= 13 | issue= 2 | pages= 318-31 | pmid=10756002 | doi= | pmc=PMC100155 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10756002  }} </ref>
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*''E. histolytica'' trophozoites secrete proteases, which induce the release of mucin from goblet cells, resulting in glandular hyperplasia.<ref name="pmid10756002">{{cite journal| author=Espinosa-Cantellano M, Martínez-Palomo A| title=Pathogenesis of intestinal amebiasis: from molecules to disease. | journal=Clin Microbiol Rev | year= 2000 | volume= 13 | issue= 2 | pages= 318-31 | pmid=10756002 | doi= | pmc=PMC100155 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10756002  }} </ref>
*''E. histolytica'' trophozoites secrete proteases, which induce the release of mucin from goblet cells, resulting in glandular hyperplasia.<ref name="pmid10756002">{{cite journal| author=Espinosa-Cantellano M, Martínez-Palomo A| title=Pathogenesis of intestinal amebiasis: from molecules to disease. | journal=Clin Microbiol Rev | year= 2000 | volume= 13 | issue= 2 | pages= 318-31 | pmid=10756002 | doi= | pmc=PMC100155 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10756002  }} </ref>
*''E. histolytica'' is also thought to contain glycosidases that cleave glycsolyated mucin molecules, resulting in mucin degradation.<ref name="pmid2456386">{{cite journal| author=Müller FW, Franz A, Werries E| title=Secretory hydrolases of Entamoeba histolytica. | journal=J Protozool | year= 1988 | volume= 35 | issue= 2 | pages= 291-5 | pmid=2456386 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2456386  }} </ref><ref name="pmid9561780">{{cite journal| author=Spice WM, Ackers JP| title=The effects of Entamoeba histolytica lysates on human colonic mucins. | journal=J Eukaryot Microbiol | year= 1998 | volume= 45 | issue= 2 | pages= 24S-27S | pmid=9561780 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9561780  }} </ref>
*''E. histolytica'' is also thought to contain glycosidases that cleave glycsolyated mucin molecules, resulting in mucin degradation.<ref name="pmid2456386">{{cite journal| author=Müller FW, Franz A, Werries E| title=Secretory hydrolases of Entamoeba histolytica. | journal=J Protozool | year= 1988 | volume= 35 | issue= 2 | pages= 291-5 | pmid=2456386 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2456386  }} </ref><ref name="pmid9561780">{{cite journal| author=Spice WM, Ackers JP| title=The effects of Entamoeba histolytica lysates on human colonic mucins. | journal=J Eukaryot Microbiol | year= 1998 | volume= 45 | issue= 2 | pages= 24S-27S | pmid=9561780 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9561780  }} </ref>
*Once the mucin layer is degraded, ''E. histolytica'' then adheres to plasma membrane of enterocytes and uses lectins, amebapores, and proteases to cause damage by a characteristic "hit and run" phenomenon.<ref name="pmid10756002">{{cite journal| author=Espinosa-Cantellano M, Martínez-Palomo A| title=Pathogenesis of intestinal amebiasis: from molecules to disease. | journal=Clin Microbiol Rev | year= 2000 | volume= 13 | issue= 2 | pages= 318-31 | pmid=10756002 | doi= | pmc=PMC100155 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10756002  }} </ref>
*Once the mucin layer is degraded, ''E. histolytica'' then adheres to the enterocyte plasma membrane and uses lectins, amebapores, and proteases to cause damage by a characteristic "hit and run" phenomenon.<ref name="pmid10756002">{{cite journal| author=Espinosa-Cantellano M, Martínez-Palomo A| title=Pathogenesis of intestinal amebiasis: from molecules to disease. | journal=Clin Microbiol Rev | year= 2000 | volume= 13 | issue= 2 | pages= 318-31 | pmid=10756002 | doi= | pmc=PMC100155 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10756002  }} </ref>
:*Lectin: responsible for adhesion of the parasite on Gal-GalNAc residues on enterocytes
:*Lectin: responsible for adhesion of the parasite on Gal-GalNAc residues of the enterocyte
:*Amebapore: Protein that forms channels that induce cytolysis in a process similar to perforin-mediated cytolysis of cytotoxic T-cells
:*Amebapore: Protein that forms channels that induce cytolysis in a process similar to perforin-mediated cytolysis of cytotoxic T-cells
:*Protrease: Enzymes that metabolize cellular proteins
:*Protrease: Enzymes that metabolize cellular proteins
*As the trophozites creates interglandular lesions and degrades the extracellular matrix, it is propelled forward by locomotion.<ref name="pmid10756002">{{cite journal| author=Espinosa-Cantellano M, Martínez-Palomo A| title=Pathogenesis of intestinal amebiasis: from molecules to disease. | journal=Clin Microbiol Rev | year= 2000 | volume= 13 | issue= 2 | pages= 318-31 | pmid=10756002 | doi= | pmc=PMC100155 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10756002  }} </ref><ref name="pmid2897372">{{cite journal| author=Talamás-Rohana P, Meza I| title=Interaction between pathogenic amebas and fibronectin: substrate degradation and changes in cytoskeleton organization. | journal=J Cell Biol | year= 1988 | volume= 106 | issue= 5 | pages= 1787-94 | pmid=2897372 | doi= | pmc=PMC2115038 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2897372  }} </ref><ref name="pmid7957761">{{cite journal| author=Espinosa-Cantellano M, Martínez-Palomo A| title=Entamoeba histolytica: mechanism of surface receptor capping. | journal=Exp Parasitol | year= 1994 | volume= 79 | issue= 3 | pages= 424-35 | pmid=7957761 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7957761  }} </ref>
*As the trophozites creates interglandular lesions and degrades the extracellular matrix, it is propelled forward by locomotion.<ref name="pmid10756002">{{cite journal| author=Espinosa-Cantellano M, Martínez-Palomo A| title=Pathogenesis of intestinal amebiasis: from molecules to disease. | journal=Clin Microbiol Rev | year= 2000 | volume= 13 | issue= 2 | pages= 318-31 | pmid=10756002 | doi= | pmc=PMC100155 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10756002  }} </ref><ref name="pmid2897372">{{cite journal| author=Talamás-Rohana P, Meza I| title=Interaction between pathogenic amebas and fibronectin: substrate degradation and changes in cytoskeleton organization. | journal=J Cell Biol | year= 1988 | volume= 106 | issue= 5 | pages= 1787-94 | pmid=2897372 | doi= | pmc=PMC2115038 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2897372  }} </ref><ref name="pmid7957761">{{cite journal| author=Espinosa-Cantellano M, Martínez-Palomo A| title=Entamoeba histolytica: mechanism of surface receptor capping. | journal=Exp Parasitol | year= 1994 | volume= 79 | issue= 3 | pages= 424-35 | pmid=7957761 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7957761  }} </ref>
===Activation of Host Immune System===
*As the trophozoites invade, IL-8 and TNF-alpha secretion is upregulated, and the host immune cells are activated.<ref name="pmid7657801">{{cite journal| author=Eckmann L, Reed SL, Smith JR, Kagnoff MF| title=Entamoeba histolytica trophozoites induce an inflammatory cytokine response by cultured human cells through the paracrine action of cytolytically released interleukin-1 alpha. | journal=J Clin Invest | year= 1995 | volume= 96 | issue= 3 | pages= 1269-79 | pmid=7657801 | doi=10.1172/JCI118161 | pmc=PMC185748 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7657801  }} </ref><ref name="pmid9136832">{{cite journal| author=Yu Y, Chadee K| title=Entamoeba histolytica stimulates interleukin 8 from human colonic epithelial cells without parasite-enterocyte contact. | journal=Gastroenterology | year= 1997 | volume= 112 | issue= 5 | pages= 1536-47 | pmid=9136832 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9136832  }} </ref>
*As the trophozoites invade, IL-8 and TNF-alpha secretion is upregulated, and the host immune cells are activated.<ref name="pmid7657801">{{cite journal| author=Eckmann L, Reed SL, Smith JR, Kagnoff MF| title=Entamoeba histolytica trophozoites induce an inflammatory cytokine response by cultured human cells through the paracrine action of cytolytically released interleukin-1 alpha. | journal=J Clin Invest | year= 1995 | volume= 96 | issue= 3 | pages= 1269-79 | pmid=7657801 | doi=10.1172/JCI118161 | pmc=PMC185748 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7657801  }} </ref><ref name="pmid9136832">{{cite journal| author=Yu Y, Chadee K| title=Entamoeba histolytica stimulates interleukin 8 from human colonic epithelial cells without parasite-enterocyte contact. | journal=Gastroenterology | year= 1997 | volume= 112 | issue= 5 | pages= 1536-47 | pmid=9136832 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9136832  }} </ref>
*Neutrophils migrate to the site of invasion and contribute to the inflammatory damage induced by ''E. histolytica'', but are generally incapable of destroying the organism. The mechanism may which ''E. histolytica'' evades neutrophils is unknown.<ref name="pmid7657801">{{cite journal| author=Eckmann L, Reed SL, Smith JR, Kagnoff MF| title=Entamoeba histolytica trophozoites induce an inflammatory cytokine response by cultured human cells through the paracrine action of cytolytically released interleukin-1 alpha. | journal=J Clin Invest | year= 1995 | volume= 96 | issue= 3 | pages= 1269-79 | pmid=7657801 | doi=10.1172/JCI118161 | pmc=PMC185748 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7657801  }} </ref><ref name="pmid9136832">{{cite journal| author=Yu Y, Chadee K| title=Entamoeba histolytica stimulates interleukin 8 from human colonic epithelial cells without parasite-enterocyte contact. | journal=Gastroenterology | year= 1997 | volume= 112 | issue= 5 | pages= 1536-47 | pmid=9136832 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9136832  }} </ref><ref name="pmid10756002">{{cite journal| author=Espinosa-Cantellano M, Martínez-Palomo A| title=Pathogenesis of intestinal amebiasis: from molecules to disease. | journal=Clin Microbiol Rev | year= 2000 | volume= 13 | issue= 2 | pages= 318-31 | pmid=10756002 | doi= | pmc=PMC100155 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10756002  }} </ref>
*Neutrophils migrate to the site of invasion and contribute to the inflammatory damage induced by ''E. histolytica'', but are generally incapable of destroying the organism. The mechanism may which ''E. histolytica'' evades neutrophils is unknown.<ref name="pmid7657801">{{cite journal| author=Eckmann L, Reed SL, Smith JR, Kagnoff MF| title=Entamoeba histolytica trophozoites induce an inflammatory cytokine response by cultured human cells through the paracrine action of cytolytically released interleukin-1 alpha. | journal=J Clin Invest | year= 1995 | volume= 96 | issue= 3 | pages= 1269-79 | pmid=7657801 | doi=10.1172/JCI118161 | pmc=PMC185748 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7657801  }} </ref><ref name="pmid9136832">{{cite journal| author=Yu Y, Chadee K| title=Entamoeba histolytica stimulates interleukin 8 from human colonic epithelial cells without parasite-enterocyte contact. | journal=Gastroenterology | year= 1997 | volume= 112 | issue= 5 | pages= 1536-47 | pmid=9136832 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9136832  }} </ref><ref name="pmid10756002">{{cite journal| author=Espinosa-Cantellano M, Martínez-Palomo A| title=Pathogenesis of intestinal amebiasis: from molecules to disease. | journal=Clin Microbiol Rev | year= 2000 | volume= 13 | issue= 2 | pages= 318-31 | pmid=10756002 | doi= | pmc=PMC100155 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10756002  }} </ref>
*Once neutrophils are recruited, macrophages and eosinophils are also activated.<ref name="pmid10756002">{{cite journal| author=Espinosa-Cantellano M, Martínez-Palomo A| title=Pathogenesis of intestinal amebiasis: from molecules to disease. | journal=Clin Microbiol Rev | year= 2000 | volume= 13 | issue= 2 | pages= 318-31 | pmid=10756002 | doi= | pmc=PMC100155 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10756002  }} </ref>
*Once neutrophils are recruited, macrophages and eosinophils are also activated.<ref name="pmid10756002">{{cite journal| author=Espinosa-Cantellano M, Martínez-Palomo A| title=Pathogenesis of intestinal amebiasis: from molecules to disease. | journal=Clin Microbiol Rev | year= 2000 | volume= 13 | issue= 2 | pages= 318-31 | pmid=10756002 | doi= | pmc=PMC100155 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10756002  }} </ref>
*The tropohozites can then invade into the bloodsteam, whereby they can ingest red blood cells (erythrophagocytosis) and migrate into distant organs (e.g. liver, brain, lungs).
==Pathology==
==Pathology==
===Gross Pathology===
===Gross Pathology===
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:*Nodular: small (sub-centrimetric), rounded, elevated lesions with necrotic center and edematous rim
:*Nodular: small (sub-centrimetric), rounded, elevated lesions with necrotic center and edematous rim
:*Irregular: large (1-5 cm), shallow with broad elevated margins
:*Irregular: large (1-5 cm), shallow with broad elevated margins
<br>
Note: the mucosal folds may occasionally hide small colonic ulcers (false-negative results)
Note: the mucosal folds may occasionally hide small colonic ulcers (false-negative results)


===Microscopic Pathology===
===Microscopic Pathology===
*On microscopic pathology, amebiasis is characterized by a flask ulcer (deep, microhemorrhagic ulceration involving the submucosa), which is a characteristic of advanced disease.<ref name="pmid10756002">{{cite journal| author=Espinosa-Cantellano M, Martínez-Palomo A| title=Pathogenesis of intestinal amebiasis: from molecules to disease. | journal=Clin Microbiol Rev | year= 2000 | volume= 13 | issue= 2 | pages= 318-31 | pmid=10756002 | doi= | pmc=PMC100155 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10756002  }} </ref>
*On microscopic pathology, amebiasis is characterized by formation of multiple flask-shaped ulcers (deep, microhemorrhagic ulceration involving the submucosa), which are findings associated with advanced disease.<ref name="pmid10756002">{{cite journal| author=Espinosa-Cantellano M, Martínez-Palomo A| title=Pathogenesis of intestinal amebiasis: from molecules to disease. | journal=Clin Microbiol Rev | year= 2000 | volume= 13 | issue= 2 | pages= 318-31 | pmid=10756002 | doi= | pmc=PMC100155 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10756002  }} </ref>
*Additional findings may be present in patients with amebiasis:<ref name="pmid10756002">{{cite journal| author=Espinosa-Cantellano M, Martínez-Palomo A| title=Pathogenesis of intestinal amebiasis: from molecules to disease. | journal=Clin Microbiol Rev | year= 2000 | volume= 13 | issue= 2 | pages= 318-31 | pmid=10756002 | doi= | pmc=PMC100155 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10756002  }} </ref>
*Additional findings may be present in patients with amebiasis:<ref name="pmid10756002">{{cite journal| author=Espinosa-Cantellano M, Martínez-Palomo A| title=Pathogenesis of intestinal amebiasis: from molecules to disease. | journal=Clin Microbiol Rev | year= 2000 | volume= 13 | issue= 2 | pages= 318-31 | pmid=10756002 | doi= | pmc=PMC100155 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10756002  }} </ref>
:*Interglandular ulceration
:*Interglandular ulceration
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Image: Amebiasis18.jpeg|'''Amebiasis in intestine.''' <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Adapted from Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Amebiasis18.jpeg|'''Amebiasis in intestine.''' <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Adapted from Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>


Image: Entamoeba_histolytica01.jpeg| Entamoeba histolytica. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Entamoeba_histolytica03.jpeg| Entamoeba histolytica. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Entamoeba_histolytica04.jpeg| Entamoeba histolytica. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Entamoeba_histolytica05.jpeg| Entamoeba histolytica. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Entamoeba_histolytica06.jpeg| Entamoeba histolytica. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Entamoeba_histolytica07.jpeg| Entamoeba histolytica. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Entamoeba_histolytica08.jpeg| Entamoeba histolytica. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Entamoeba_histolytica09.jpeg| Entamoeba histolytica. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Entamoeba_histolytica11.jpeg| Entamoeba histolytica. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
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Latest revision as of 21:17, 10 March 2016

Amoebiasis Microchapters

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Yazan Daaboul, M.D.; Serge Korjian M.D.

Overview

E. histolytica cyst is usually transmitted by the fecal-oral route (through contaminated drinking water or food) or by direct contact with infected individuals. Following transmission, E. histolytica trophozoites undergoes excystation in the small intestine, after which it migrates to the large intestine using pseudopods. The trophozoites invades the intestinal mucosa and migrates into the bloodstream. Simultaneously, they form resistant cysts in the large intestines that are then excreted in human stools. E. histolytica trophozoites secrete proteases and glycosidases to degrade the intestinal layers. Once cellular degradation occurs, upregulation of IL-8 and TNF-alpha results in the recruitment of neutrophils, macrophages, and eosinophils. The host immune system does not usually result in adequate destruction of the E. histolytica trophozoite, and the parasite continues to invade until it reaches the bloodstream, whereby it can then migrate to other organs and cause multisystem disease. On gross pathology, amebiasis may be characterized by wavy surface epithelium and formation of nodular and irregular ulcerations. On microscopic pathology, flask-shaped ulcers are characteristic, but interglandular ulcerations, hyperemia, mucosal thickening, reactive glandular hyperplasia, and neutrophilic infiltration are common findings. In late stages, amebiasis often results in tissue fibrinoid necrosis and formation of granulation tissue.

Transmission

  • E. histolytica cyst is usually transmitted by the fecal-oral route through contaminated drinking water or food
  • E. histolytica cyst may also be transmitted through direct contact with infected individuals.

Pathogenesis

  • Following transmission, E. histolytica trophozoites undergoes excystation in the small intestine, after which it migrates to the large intestine using pseudopods.
  • In the large intestine, the trophozoites invades the intestinal mucosa into the bloodstream. Simultaneously, they form resistant cysts in the large intestines that are then excreted in human stools.
  • Once in the bloodstream, the trophozoite migrates into the portal circulation and develops amebic liver abscess.[1]

Invasion of Intestinal Mucosa

  • E. histolytica trophozoites secrete proteases, which induce the release of mucin from goblet cells, resulting in glandular hyperplasia.[1]
  • E. histolytica is also thought to contain glycosidases that cleave glycsolyated mucin molecules, resulting in mucin degradation.[2][3]
  • Once the mucin layer is degraded, E. histolytica then adheres to the enterocyte plasma membrane and uses lectins, amebapores, and proteases to cause damage by a characteristic "hit and run" phenomenon.[1]
  • Lectin: responsible for adhesion of the parasite on Gal-GalNAc residues of the enterocyte
  • Amebapore: Protein that forms channels that induce cytolysis in a process similar to perforin-mediated cytolysis of cytotoxic T-cells
  • Protrease: Enzymes that metabolize cellular proteins
  • As the trophozites creates interglandular lesions and degrades the extracellular matrix, it is propelled forward by locomotion.[1][4][5]

Activation of Host Immune System

  • As the trophozoites invade, IL-8 and TNF-alpha secretion is upregulated, and the host immune cells are activated.[6][7]
  • Neutrophils migrate to the site of invasion and contribute to the inflammatory damage induced by E. histolytica, but are generally incapable of destroying the organism. The mechanism may which E. histolytica evades neutrophils is unknown.[6][7][1]
  • Once neutrophils are recruited, macrophages and eosinophils are also activated.[1]
  • The tropohozites can then invade into the bloodsteam, whereby they can ingest red blood cells (erythrophagocytosis) and migrate into distant organs (e.g. liver, brain, lungs).

Pathology

Gross Pathology

On gross pathology, the following findings may be present in patients with amebiasis:[1]

  • Wavy surface epithelium (results from focal release of mucin and spasm of the muscular layer)
  • Nodular and/or irregular ulcers in the cecum (most common), sigmoid colon, and rectum. Early ulcers are usually in the interglandular epithelium.
  • Nodular: small (sub-centrimetric), rounded, elevated lesions with necrotic center and edematous rim
  • Irregular: large (1-5 cm), shallow with broad elevated margins

Note: the mucosal folds may occasionally hide small colonic ulcers (false-negative results)

Microscopic Pathology

  • On microscopic pathology, amebiasis is characterized by formation of multiple flask-shaped ulcers (deep, microhemorrhagic ulceration involving the submucosa), which are findings associated with advanced disease.[1]
  • Additional findings may be present in patients with amebiasis:[1]
  • Interglandular ulceration
  • Hyperemia
  • Thickened mucosa
  • Reactive glandular hyperplasia
  • Stromal edema
  • Infiltration of neutrophils, eosinophils (rare), and macrophages
  • Lymphoid aggregates
  • Detection of amebas on surface exudate
  • Tissue necrosis, usually fibrinoid (advanced lesion)
  • Formation of granulation tissue (advanced lesion)

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References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 Espinosa-Cantellano M, Martínez-Palomo A (2000). "Pathogenesis of intestinal amebiasis: from molecules to disease". Clin Microbiol Rev. 13 (2): 318–31. PMC 100155. PMID 10756002.
  2. ↑ Müller FW, Franz A, Werries E (1988). "Secretory hydrolases of Entamoeba histolytica". J Protozool. 35 (2): 291–5. PMID 2456386.
  3. ↑ Spice WM, Ackers JP (1998). "The effects of Entamoeba histolytica lysates on human colonic mucins". J Eukaryot Microbiol. 45 (2): 24S–27S. PMID 9561780.
  4. ↑ Talamás-Rohana P, Meza I (1988). "Interaction between pathogenic amebas and fibronectin: substrate degradation and changes in cytoskeleton organization". J Cell Biol. 106 (5): 1787–94. PMC 2115038. PMID 2897372.
  5. ↑ Espinosa-Cantellano M, Martínez-Palomo A (1994). "Entamoeba histolytica: mechanism of surface receptor capping". Exp Parasitol. 79 (3): 424–35. PMID 7957761.
  6. ↑ 6.0 6.1 Eckmann L, Reed SL, Smith JR, Kagnoff MF (1995). "Entamoeba histolytica trophozoites induce an inflammatory cytokine response by cultured human cells through the paracrine action of cytolytically released interleukin-1 alpha". J Clin Invest. 96 (3): 1269–79. doi:10.1172/JCI118161. PMC 185748. PMID 7657801.
  7. ↑ 7.0 7.1 Yu Y, Chadee K (1997). "Entamoeba histolytica stimulates interleukin 8 from human colonic epithelial cells without parasite-enterocyte contact". Gastroenterology. 112 (5): 1536–47. PMID 9136832.
  8. ↑ 8.00 8.01 8.02 8.03 8.04 8.05 8.06 8.07 8.08 8.09 8.10 8.11 8.12 8.13 8.14 8.15 8.16 8.17 8.18 8.19 "Public Health Image Library (PHIL)".


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