Cholera pathophysiology: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
m (Bot: Removing from Primary care)
 
(34 intermediate revisions by 5 users not shown)
Line 2: Line 2:
[[Image:Cholera Toxin.png|200px|thumb|right|Cholera Toxin. The delivery region (blue) binds membrane carbohydrates to get into cells. The toxic part (red) is activated inside the cell (PDB code: 1xtc)]]
[[Image:Cholera Toxin.png|200px|thumb|right|Cholera Toxin. The delivery region (blue) binds membrane carbohydrates to get into cells. The toxic part (red) is activated inside the cell (PDB code: 1xtc)]]
{{Cholera}}
{{Cholera}}
{{CMG}}; '''Associate Editors-In-Chief:''' [[Priyamvada Singh|Priyamvada Singh, MBBS]] [mailto:psingh13579@gmail.com]
{{CMG}}; '''Associate Editors-In-Chief:''' [[Priyamvada Singh|Priyamvada Singh, MBBS]], {{AA}}


==Overview==
==Overview==
Most of the ''V. cholerae'' bacteria do not survive the very acidic conditions of the [[stomach|human stomach]]<ref name=Hartwell>Hartwell LH, Hood L, Goldberg ML, Reynolds AE, Silver LM, and Veres RC (2004). ''Genetics: From Genes to Genomes.'' Mc-Graw Hill, Boston: p. 551-552, 572-574 (using the turning off and turning on of [[gene expression]] to make toxin proteins in cholera bacteria as a "comprehensive example" of what is known about the mechanisms by which bacteria change the mix of proteins they manufacture to respond to the changing opportunities for surviving and thriving in different chemical environments).</ref>. The few bacteria that manage to survive the stomach's acidity conserve their [[nutrient|energy and stored nutrients]] during passage through the stomach by shutting down much protein production and restart production in the favorable small intestine's environment. The toxins that interact with host cell mechanisms pump [[chloride]] ions into the small intestine, creating an ionic pressure which prevents sodium ions from entering the cell. The [[chloride]] and [[sodium]] ions create a salt water environment in the small intestines which through osmosis can pull up to six liters of water per day through the intestinal cells creating the massive amounts of diarrhea. The host can become rapidly [[dehydrated]] if an appropriate mixture of dilute salt water and sugar is not taken to replace the blood's water and salts lost in the [[diarrhea]].
Cholera is mainly caused by two pathogenic serotypes of ''V. cholerae'': O1 and O139. ''V. cholerae'' is usually transmitted via the [[fecal-oral route]] to the human host. Following [[ingestion]], the ''V. cholerae'' must overcome the host defense mechanisms such as gastric acidity, intestinal inhibitory factors, and changes in temperature and [[osmolarity]]. After gaining access to [[small intestine]], ''V. cholerae'' uses [[flagella]] to propogate through the mucus layer covering the [[small intestine]] and colonizes the small intestinal cells, using toxin-coregulated pilus (TCP) to form a [[biofilm]]. [[Diarrheal]] illness in the human host is mainly caused by production of [[enterotoxin]].<ref name=Hartwell>Hartwell LH, Hood L, Goldberg ML, Reynolds AE, Silver LM, and Veres RC (2004). ''Genetics: From Genes to Genomes.'' Mc-Graw Hill, Boston: p. 551-552, 572-574 (using the turning off and turning on of [[gene expression]] to make toxin proteins in cholera bacteria as a "comprehensive example" of what is known about the mechanisms by which bacteria change the mix of proteins they manufacture to respond to the changing opportunities for surviving and thriving in different chemical environments).</ref> <ref name="pmid198781">{{cite journal| author=Cassel D, Selinger Z| title=Mechanism of adenylate cyclase activation by cholera toxin: inhibition of GTP hydrolysis at the regulatory site. | journal=Proc Natl Acad Sci U S A | year= 1977 | volume= 74 | issue= 8 | pages= 3307-11 | pmid=198781 | doi= | pmc=431542 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=198781  }} </ref><ref name="pmid9841673">{{cite journal| author=Faruque SM, Albert MJ, Mekalanos JJ| title=Epidemiology, genetics, and ecology of toxigenic Vibrio cholerae. | journal=Microbiol Mol Biol Rev | year= 1998 | volume= 62 | issue= 4 | pages= 1301-14 | pmid=9841673 | doi= | pmc=98947 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9841673  }} </ref><ref name="pmid8389476">{{cite journal| author=Trucksis M, Galen JE, Michalski J, Fasano A, Kaper JB| title=Accessory cholera enterotoxin (Ace), the third toxin of a Vibrio cholerae virulence cassette. | journal=Proc Natl Acad Sci U S A | year= 1993 | volume= 90 | issue= 11 | pages= 5267-71 | pmid=8389476 | doi= | pmc=46697 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8389476  }} </ref><ref name="pmid4329549">{{cite journal| author=Hendrix TR| title=The pathophysiology of cholera. | journal=Bull N Y Acad Med | year= 1971 | volume= 47 | issue= 10 | pages= 1169-80 | pmid=4329549 | doi= | pmc=1749961 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4329549  }} </ref><ref name="pmid14407057">{{cite journal| author=JENKIN CR, ROWLEY D| title=Possible factors in the pathogenesis of cholera. | journal=Br J Exp Pathol | year= 1959 | volume= 40 | issue=  | pages= 474-81 | pmid=14407057 | doi= | pmc=2082309 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14407057  }} </ref><ref name=DiRita_1991>{{cite journal |author=DiRita V, Parsot C, Jander G, Mekalanos J |title=Regulatory cascade controls virulence in Vibrio cholerae |journal=Proc Natl Acad Sci U S A |volume=88 |issue=12 |pages=5403-7 |year=1991 | url=http://www.pnas.org/cgi/reprint/88/12/5403 |id=PMID 2052618}}</ref><ref name="pmid2883655">{{cite journal| author=Taylor RK, Miller VL, Furlong DB, Mekalanos JJ| title=Use of phoA gene fusions to identify a pilus colonization factor coordinately regulated with cholera toxin. | journal=Proc Natl Acad Sci U S A | year= 1987 | volume= 84 | issue= 9 | pages= 2833-7 | pmid=2883655 | doi= | pmc=304754 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2883655  }} </ref><ref name="pmid208069">{{cite journal| author=Cassel D, Pfeuffer T| title=Mechanism of cholera toxin action: covalent modification of the guanyl nucleotide-binding protein of the adenylate cyclase system. | journal=Proc Natl Acad Sci U S A | year= 1978 | volume= 75 | issue= 6 | pages= 2669-73 | pmid=208069 | doi= | pmc=392624 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=208069  }} </ref><ref name="pmid8658163">{{cite journal| author=Waldor MK, Mekalanos JJ| title=Lysogenic conversion by a filamentous phage encoding cholera toxin. | journal=Science | year= 1996 | volume= 272 | issue= 5270 | pages= 1910-4 | pmid=8658163 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8658163  }} </ref>


==Pathophysiology==  
==Pathophysiology==  
Cholera is mainly caused by two pathogenic serotypes of ''V. cholerae'' O1 and O139. The pathogenesis underlying acute diarrheal illness is described as follows:<ref name=Hartwell>Hartwell LH, Hood L, Goldberg ML, Reynolds AE, Silver LM, and Veres RC (2004). ''Genetics: From Genes to Genomes.'' Mc-Graw Hill, Boston: p. 551-552, 572-574 (using the turning off and turning on of [[gene expression]] to make toxin proteins in cholera bacteria as a "comprehensive example" of what is known about the mechanisms by which bacteria change the mix of proteins they manufacture to respond to the changing opportunities for surviving and thriving in different chemical environments).</ref> <ref name="pmid198781">{{cite journal| author=Cassel D, Selinger Z| title=Mechanism of adenylate cyclase activation by cholera toxin: inhibition of GTP hydrolysis at the regulatory site. | journal=Proc Natl Acad Sci U S A | year= 1977 | volume= 74 | issue= 8 | pages= 3307-11 | pmid=198781 | doi= | pmc=431542 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=198781  }} </ref><ref name="pmid9841673">{{cite journal| author=Faruque SM, Albert MJ, Mekalanos JJ| title=Epidemiology, genetics, and ecology of toxigenic Vibrio cholerae. | journal=Microbiol Mol Biol Rev | year= 1998 | volume= 62 | issue= 4 | pages= 1301-14 | pmid=9841673 | doi= | pmc=98947 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9841673  }} </ref><ref name="pmid8389476">{{cite journal| author=Trucksis M, Galen JE, Michalski J, Fasano A, Kaper JB| title=Accessory cholera enterotoxin (Ace), the third toxin of a Vibrio cholerae virulence cassette. | journal=Proc Natl Acad Sci U S A | year= 1993 | volume= 90 | issue= 11 | pages= 5267-71 | pmid=8389476 | doi= | pmc=46697 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8389476  }} </ref><ref name="pmid4329549">{{cite journal| author=Hendrix TR| title=The pathophysiology of cholera. | journal=Bull N Y Acad Med | year= 1971 | volume= 47 | issue= 10 | pages= 1169-80 | pmid=4329549 | doi= | pmc=1749961 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4329549  }} </ref><ref name="pmid14407057">{{cite journal| author=JENKIN CR, ROWLEY D| title=Possible factors in the pathogenesis of cholera. | journal=Br J Exp Pathol | year= 1959 | volume= 40 | issue=  | pages= 474-81 | pmid=14407057 | doi= | pmc=2082309 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14407057  }} </ref><ref name=DiRita_1991>{{cite journal |author=DiRita V, Parsot C, Jander G, Mekalanos J |title=Regulatory cascade controls virulence in Vibrio cholerae |journal=Proc Natl Acad Sci U S A |volume=88 |issue=12 |pages=5403-7 |year=1991 | url=http://www.pnas.org/cgi/reprint/88/12/5403 |id=PMID 2052618}}</ref><ref name="pmid2883655">{{cite journal| author=Taylor RK, Miller VL, Furlong DB, Mekalanos JJ| title=Use of phoA gene fusions to identify a pilus colonization factor coordinately regulated with cholera toxin. | journal=Proc Natl Acad Sci U S A | year= 1987 | volume= 84 | issue= 9 | pages= 2833-7 | pmid=2883655 | doi= | pmc=304754 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2883655  }} </ref><ref name="pmid208069">{{cite journal| author=Cassel D, Pfeuffer T| title=Mechanism of cholera toxin action: covalent modification of the guanyl nucleotide-binding protein of the adenylate cyclase system. | journal=Proc Natl Acad Sci U S A | year= 1978 | volume= 75 | issue= 6 | pages= 2669-73 | pmid=208069 | doi= | pmc=392624 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=208069  }} </ref><ref name="pmid8658163">{{cite journal| author=Waldor MK, Mekalanos JJ| title=Lysogenic conversion by a filamentous phage encoding cholera toxin. | journal=Science | year= 1996 | volume= 272 | issue= 5270 | pages= 1910-4 | pmid=8658163 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8658163  }} </ref>  
Cholera is mainly caused by two pathogenic serotypes of ''V. cholerae'': O1 and O139. The pathogenesis underlying acute [[diarrheal]] illness is as follows:<ref name=Hartwell>Hartwell LH, Hood L, Goldberg ML, Reynolds AE, Silver LM, and Veres RC (2004). ''Genetics: From Genes to Genomes.'' Mc-Graw Hill, Boston: p. 551-552, 572-574 (using the turning off and turning on of [[gene expression]] to make toxin proteins in cholera bacteria as a "comprehensive example" of what is known about the mechanisms by which bacteria change the mix of proteins they manufacture to respond to the changing opportunities for surviving and thriving in different chemical environments).</ref><ref name="pmid198781">{{cite journal| author=Cassel D, Selinger Z| title=Mechanism of adenylate cyclase activation by cholera toxin: inhibition of GTP hydrolysis at the regulatory site. | journal=Proc Natl Acad Sci U S A | year= 1977 | volume= 74 | issue= 8 | pages= 3307-11 | pmid=198781 | doi= | pmc=431542 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=198781  }} </ref><ref name="pmid9841673">{{cite journal| author=Faruque SM, Albert MJ, Mekalanos JJ| title=Epidemiology, genetics, and ecology of toxigenic Vibrio cholerae. | journal=Microbiol Mol Biol Rev | year= 1998 | volume= 62 | issue= 4 | pages= 1301-14 | pmid=9841673 | doi= | pmc=98947 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9841673  }} </ref><ref name="pmid8389476">{{cite journal| author=Trucksis M, Galen JE, Michalski J, Fasano A, Kaper JB| title=Accessory cholera enterotoxin (Ace), the third toxin of a Vibrio cholerae virulence cassette. | journal=Proc Natl Acad Sci U S A | year= 1993 | volume= 90 | issue= 11 | pages= 5267-71 | pmid=8389476 | doi= | pmc=46697 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8389476  }} </ref><ref name="pmid4329549">{{cite journal| author=Hendrix TR| title=The pathophysiology of cholera. | journal=Bull N Y Acad Med | year= 1971 | volume= 47 | issue= 10 | pages= 1169-80 | pmid=4329549 | doi= | pmc=1749961 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4329549  }} </ref><ref name="pmid14407057">{{cite journal| author=JENKIN CR, ROWLEY D| title=Possible factors in the pathogenesis of cholera. | journal=Br J Exp Pathol | year= 1959 | volume= 40 | issue=  | pages= 474-81 | pmid=14407057 | doi= | pmc=2082309 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14407057  }} </ref><ref name=DiRita_1991>{{cite journal |author=DiRita V, Parsot C, Jander G, Mekalanos J |title=Regulatory cascade controls virulence in Vibrio cholerae |journal=Proc Natl Acad Sci U S A |volume=88 |issue=12 |pages=5403-7 |year=1991 | url=http://www.pnas.org/cgi/reprint/88/12/5403 |id=PMID 2052618}}</ref><ref name="pmid2883655">{{cite journal| author=Taylor RK, Miller VL, Furlong DB, Mekalanos JJ| title=Use of phoA gene fusions to identify a pilus colonization factor coordinately regulated with cholera toxin. | journal=Proc Natl Acad Sci U S A | year= 1987 | volume= 84 | issue= 9 | pages= 2833-7 | pmid=2883655 | doi= | pmc=304754 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2883655  }} </ref><ref name="pmid208069">{{cite journal| author=Cassel D, Pfeuffer T| title=Mechanism of cholera toxin action: covalent modification of the guanyl nucleotide-binding protein of the adenylate cyclase system. | journal=Proc Natl Acad Sci U S A | year= 1978 | volume= 75 | issue= 6 | pages= 2669-73 | pmid=208069 | doi= | pmc=392624 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=208069  }} </ref><ref name="pmid8658163">{{cite journal| author=Waldor MK, Mekalanos JJ| title=Lysogenic conversion by a filamentous phage encoding cholera toxin. | journal=Science | year= 1996 | volume= 272 | issue= 5270 | pages= 1910-4 | pmid=8658163 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8658163  }} </ref>  
===Transmission===  
===Transmission===  
*''V. cholerae''is usually transmitted via the [[oro-fecal]] route to the human host.
*''V. cholerae'' is usually transmitted via the [[fecal-oral route]] to the human host.
*Following [[ingestion]], the ''V. cholerae'' must overcomes the host defense mechanisms such as gastric acidity intestinal inhibitory factors, change in temperature and [[osmolarity]].
*Following [[ingestion]], the ''V. cholerae'' must overcome host defense mechanisms such as gastric acidity, intestinal inhibitory factors, and changes in temperature and [[osmolarity]].
*Infective dose varies from 102-106.
*Infective dose varies from 102-106.
*[[Incubation period]] varies from few hours to few days.
*The [[incubation period]] varies from a few hours to a few days.


===Colonisation===  
===Colonization===  
*After gaining access to [[small intestine]], it uses [[flagella]] to propogate through the mucus layer covering small intestine and colonises the small intestinal cells using toxin-coregulated pilus (TCP) forming a [[biofilm]].
*After gaining access to [[small intestine]], ''V. cholerae'' uses [[flagella]] to propagate through the mucus layer covering [[small intestine]] and colonizes the small intestinal cells using toxin-coregulated pilus (TCP) forming a [[biofilm]].


===Enterotoxin===
===Enterotoxin===  
*The production of enterotoxin protein in the small intestinal cells is the main mechanism responsible for causing acute diarrheal illness.
*[[Diarrheal]] illness in human host is mainly caused by production of [[enterotoxin]].
*The production of [[enterotoxin]] protein in the small intestinal cells is the main mechanism responsible for causing acute [[diarrheal]] illness.
*It has 5B subunits and 2A subunits.
*It has 5B subunits and 2A subunits.
*B subunit binds the enterocytes via GM1 ganglioside receptors and cause interanlisation of A subunit in the cells via endocytosis.
**B subunits bind the [[enterocytes]] via GM1 [[ganglioside]] receptors and cause internalization of A subunits in the cells via [[endocytosis]].
*A subunit than binds and activates adenylate cyclase enzyme in the enterocytes increasing the level of cAMP.
**A subunits then bind and activate the [[adenylate cyclase]] enzyme in the enterocytes, increasing the levels of [[cAMP]].
*Increased levels of enterotoxin causes activation of the [[cystic fibrosis transmembrane conductance regulator]] (CFTR),r causing increased secretion of water, sodium and chloride from enterocytes causing watery diarrhea.
*Increased levels of [[enterotoxin]] cause activation of the [[cystic fibrosis transmembrane conductance regulator]] (CFTR), causing increased secretion of water, [[sodium]], and [[chloride]] from [[enterocytes]], which causes watery [[diarrhea]].
 
===Virulence factors===
===Virulence factors===
The different virulence factors involved in the pathogenesis of ''V. cholerae'' involve activation of transcriptional factors such as ToxR, TcpP and ToxT. Different toxins expressed by these transcriptional factors include:  
The different [[virulence factors]] involved in the pathogenesis of ''[[V. cholerae]]'' involve activation of [[transcription factors]] such as ToxR, TcpP, and ToxT. Different toxins expressed by these [[transcription factors]] include:  
*Zona occludens toxin (zot, causes invasion by decreasing intestinal tissue resistance)  
*Zona occludens toxin (zot, causes invasion by decreasing intestinal tissue resistance)  
*Accessory cholera toxin (ace, increases fluid secretion)  
*Accessory cholera toxin (ace, increases fluid secretion)  
*Toxin-coregulated pilus (tcpA, essential colonisation factor and receptor for the CTXf phage)  
*Toxin-coregulated pilus (tcpA, essential colonization factor and receptor for the CTXf phage)  
*NAG-specific heat-labile toxin (st)
*NAG-specific heat-labile toxin (st)
*Outer membrane porin proteins (ompU and ompT).
*Outer membrane porin proteins (ompU and ompT)


== References ==
== References ==
{{Reflist|2}}
{{Reflist|2}}


[[Category:Neurotoxins]]
[[Category:Foodborne illnesses]]
[[Category:Bacterial diseases]]
[[Category:Water-borne diseases]]
[[Category:Pandemics]]
[[Category:Biological weapons]]
[[Category:Neglected diseases]]
[[Category:Overview complete]]
[[Category:Infectious disease]]
{{WikiDoc Help Menu}}
{{WikiDoc Help Menu}}
{{WikiDoc Sources}}
{{WikiDoc Sources}}
[[Category:Gastroenterology]]
[[Category:Emergency medicine]]
[[Category:Disease]]
[[Category:Up-To-Date]]
[[Category:Infectious disease]]
[[Category:Pediatrics]]

Latest revision as of 20:55, 29 July 2020

Cholera Toxin. The delivery region (blue) binds membrane carbohydrates to get into cells. The toxic part (red) is activated inside the cell (PDB code: 1xtc)

Cholera Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Cholera from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications, and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

X Ray

CT

MRI

Other diagnostic studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Case Studies

Case #1

Cholera pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Cholera pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Cholera pathophysiology

CDC on Cholera pathophysiology

Cholera pathophysiology in the news

Blogs on Cholera pathophysiology

Directions to Hospitals Treating Cholera

Risk calculators and risk factors for Cholera pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editors-In-Chief: Priyamvada Singh, MBBS, Aysha Anwar, M.B.B.S[2]

Overview

Cholera is mainly caused by two pathogenic serotypes of V. cholerae: O1 and O139. V. cholerae is usually transmitted via the fecal-oral route to the human host. Following ingestion, the V. cholerae must overcome the host defense mechanisms such as gastric acidity, intestinal inhibitory factors, and changes in temperature and osmolarity. After gaining access to small intestine, V. cholerae uses flagella to propogate through the mucus layer covering the small intestine and colonizes the small intestinal cells, using toxin-coregulated pilus (TCP) to form a biofilm. Diarrheal illness in the human host is mainly caused by production of enterotoxin.[1] [2][3][4][5][6][7][8][9][10]

Pathophysiology

Cholera is mainly caused by two pathogenic serotypes of V. cholerae: O1 and O139. The pathogenesis underlying acute diarrheal illness is as follows:[1][2][3][4][5][6][7][8][9][10]

Transmission

  • V. cholerae is usually transmitted via the fecal-oral route to the human host.
  • Following ingestion, the V. cholerae must overcome host defense mechanisms such as gastric acidity, intestinal inhibitory factors, and changes in temperature and osmolarity.
  • Infective dose varies from 102-106.
  • The incubation period varies from a few hours to a few days.

Colonization

Enterotoxin

Virulence factors

The different virulence factors involved in the pathogenesis of V. cholerae involve activation of transcription factors such as ToxR, TcpP, and ToxT. Different toxins expressed by these transcription factors include:

  • Zona occludens toxin (zot, causes invasion by decreasing intestinal tissue resistance)
  • Accessory cholera toxin (ace, increases fluid secretion)
  • Toxin-coregulated pilus (tcpA, essential colonization factor and receptor for the CTXf phage)
  • NAG-specific heat-labile toxin (st)
  • Outer membrane porin proteins (ompU and ompT)

References

  1. ↑ 1.0 1.1 Hartwell LH, Hood L, Goldberg ML, Reynolds AE, Silver LM, and Veres RC (2004). Genetics: From Genes to Genomes. Mc-Graw Hill, Boston: p. 551-552, 572-574 (using the turning off and turning on of gene expression to make toxin proteins in cholera bacteria as a "comprehensive example" of what is known about the mechanisms by which bacteria change the mix of proteins they manufacture to respond to the changing opportunities for surviving and thriving in different chemical environments).
  2. ↑ 2.0 2.1 Cassel D, Selinger Z (1977). "Mechanism of adenylate cyclase activation by cholera toxin: inhibition of GTP hydrolysis at the regulatory site". Proc Natl Acad Sci U S A. 74 (8): 3307–11. PMC 431542. PMID 198781.
  3. ↑ 3.0 3.1 Faruque SM, Albert MJ, Mekalanos JJ (1998). "Epidemiology, genetics, and ecology of toxigenic Vibrio cholerae". Microbiol Mol Biol Rev. 62 (4): 1301–14. PMC 98947. PMID 9841673.
  4. ↑ 4.0 4.1 Trucksis M, Galen JE, Michalski J, Fasano A, Kaper JB (1993). "Accessory cholera enterotoxin (Ace), the third toxin of a Vibrio cholerae virulence cassette". Proc Natl Acad Sci U S A. 90 (11): 5267–71. PMC 46697. PMID 8389476.
  5. ↑ 5.0 5.1 Hendrix TR (1971). "The pathophysiology of cholera". Bull N Y Acad Med. 47 (10): 1169–80. PMC 1749961. PMID 4329549.
  6. ↑ 6.0 6.1 JENKIN CR, ROWLEY D (1959). "Possible factors in the pathogenesis of cholera". Br J Exp Pathol. 40: 474–81. PMC 2082309. PMID 14407057.
  7. ↑ 7.0 7.1 DiRita V, Parsot C, Jander G, Mekalanos J (1991). "Regulatory cascade controls virulence in Vibrio cholerae". Proc Natl Acad Sci U S A. 88 (12): 5403–7. PMID 2052618.
  8. ↑ 8.0 8.1 Taylor RK, Miller VL, Furlong DB, Mekalanos JJ (1987). "Use of phoA gene fusions to identify a pilus colonization factor coordinately regulated with cholera toxin". Proc Natl Acad Sci U S A. 84 (9): 2833–7. PMC 304754. PMID 2883655.
  9. ↑ 9.0 9.1 Cassel D, Pfeuffer T (1978). "Mechanism of cholera toxin action: covalent modification of the guanyl nucleotide-binding protein of the adenylate cyclase system". Proc Natl Acad Sci U S A. 75 (6): 2669–73. PMC 392624. PMID 208069.
  10. ↑ 10.0 10.1 Waldor MK, Mekalanos JJ (1996). "Lysogenic conversion by a filamentous phage encoding cholera toxin". Science. 272 (5270): 1910–4. PMID 8658163.


Template:WikiDoc Sources

Retrieved from "https://www.wikidoc.org/index.php?title=Cholera_pathophysiology&oldid=1635996"