Irritable bowel syndrome pathophysiology: Difference between revisions

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**[[Immunity (medical)|Immune]] activation due to GI [[infection]] also increases [[Enteroendocrine cells|enteroendocrine]] cells, calprotectin-positive [[Macrophage|macrophages]], [[Intraepithelial lymphocyte|intraepithelial]] [[Lymphocyte|lymphocytes]], and l[[Lamina propria|amina propria]] [[T cell|T cells]] which contribute directly to [[abdominal pain]] perception. <ref name="pmid20101257">{{cite journal |vauthors=Ohman L, Simrén M |title=Pathogenesis of IBS: role of inflammation, immunity and neuroimmune interactions |journal=Nat Rev Gastroenterol Hepatol |volume=7 |issue=3 |pages=163–73 |year=2010 |pmid=20101257 |doi=10.1038/nrgastro.2010.4 |url=}}</ref><ref name="pmid22730468">{{cite journal |vauthors=Simrén M, Barbara G, Flint HJ, Spiegel BM, Spiller RC, Vanner S, Verdu EF, Whorwell PJ, Zoetendal EG |title=Intestinal microbiota in functional bowel disorders: a Rome foundation report |journal=Gut |volume=62 |issue=1 |pages=159–76 |year=2013 |pmid=22730468 |pmc=3551212 |doi=10.1136/gutjnl-2012-302167 |url=}}</ref><ref name="pmid23580243">{{cite journal |vauthors=Ohman L, Simrén M |title=Intestinal microbiota and its role in irritable bowel syndrome (IBS) |journal=Curr Gastroenterol Rep |volume=15 |issue=5 |pages=323 |year=2013 |pmid=23580243 |doi=10.1007/s11894-013-0323-7 |url=}}</ref><ref name="pmid17148502">{{cite journal |vauthors=Posserud I, Stotzer PO, Björnsson ES, Abrahamsson H, Simrén M |title=Small intestinal bacterial overgrowth in patients with irritable bowel syndrome |journal=Gut |volume=56 |issue=6 |pages=802–8 |year=2007 |pmid=17148502 |pmc=1954873 |doi=10.1136/gut.2006.108712 |url=}}</ref><ref name="pmid22180058">{{cite journal |vauthors=Jeffery IB, O'Toole PW, Öhman L, Claesson MJ, Deane J, Quigley EM, Simrén M |title=An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota |journal=Gut |volume=61 |issue=7 |pages=997–1006 |year=2012 |pmid=22180058 |doi=10.1136/gutjnl-2011-301501 |url=}}</ref><ref name="pmid19457422">{{cite journal |vauthors=Spiller R, Garsed K |title=Postinfectious irritable bowel syndrome |journal=Gastroenterology |volume=136 |issue=6 |pages=1979–88 |year=2009 |pmid=19457422 |doi=10.1053/j.gastro.2009.02.074 |url=}}</ref><ref name="pmid25611066">{{cite journal |vauthors=Joo YE |title=Alteration of fecal microbiota in patients with postinfectious irritable bowel syndrome |journal=J Neurogastroenterol Motil |volume=21 |issue=1 |pages=135–7 |year=2015 |pmid=25611066 |pmc=4288086 |doi=10.5056/jnm14133 |url=}}</ref><ref name="pmid10026328">{{cite journal |vauthors=Gwee KA, Leong YL, Graham C, McKendrick MW, Collins SM, Walters SJ, Underwood JE, Read NW |title=The role of psychological and biological factors in postinfective gut dysfunction |journal=Gut |volume=44 |issue=3 |pages=400–6 |year=1999 |pmid=10026328 |pmc=1727402 |doi= |url=}}</ref><ref name="pmid24646319">{{cite journal |vauthors=Nielsen HL, Engberg J, Ejlertsen T, Nielsen H |title=Psychometric scores and persistence of irritable bowel after Campylobacter concisus infection |journal=Scand. J. Gastroenterol. |volume=49 |issue=5 |pages=545–51 |year=2014 |pmid=24646319 |doi=10.3109/00365521.2014.886718 |url=}}</ref>
**[[Immunity (medical)|Immune]] activation due to GI [[infection]] also increases [[Enteroendocrine cells|enteroendocrine]] cells, calprotectin-positive [[Macrophage|macrophages]], [[Intraepithelial lymphocyte|intraepithelial]] [[Lymphocyte|lymphocytes]], and l[[Lamina propria|amina propria]] [[T cell|T cells]] which contribute directly to [[abdominal pain]] perception. <ref name="pmid20101257">{{cite journal |vauthors=Ohman L, Simrén M |title=Pathogenesis of IBS: role of inflammation, immunity and neuroimmune interactions |journal=Nat Rev Gastroenterol Hepatol |volume=7 |issue=3 |pages=163–73 |year=2010 |pmid=20101257 |doi=10.1038/nrgastro.2010.4 |url=}}</ref><ref name="pmid22730468">{{cite journal |vauthors=Simrén M, Barbara G, Flint HJ, Spiegel BM, Spiller RC, Vanner S, Verdu EF, Whorwell PJ, Zoetendal EG |title=Intestinal microbiota in functional bowel disorders: a Rome foundation report |journal=Gut |volume=62 |issue=1 |pages=159–76 |year=2013 |pmid=22730468 |pmc=3551212 |doi=10.1136/gutjnl-2012-302167 |url=}}</ref><ref name="pmid23580243">{{cite journal |vauthors=Ohman L, Simrén M |title=Intestinal microbiota and its role in irritable bowel syndrome (IBS) |journal=Curr Gastroenterol Rep |volume=15 |issue=5 |pages=323 |year=2013 |pmid=23580243 |doi=10.1007/s11894-013-0323-7 |url=}}</ref><ref name="pmid17148502">{{cite journal |vauthors=Posserud I, Stotzer PO, Björnsson ES, Abrahamsson H, Simrén M |title=Small intestinal bacterial overgrowth in patients with irritable bowel syndrome |journal=Gut |volume=56 |issue=6 |pages=802–8 |year=2007 |pmid=17148502 |pmc=1954873 |doi=10.1136/gut.2006.108712 |url=}}</ref><ref name="pmid22180058">{{cite journal |vauthors=Jeffery IB, O'Toole PW, Öhman L, Claesson MJ, Deane J, Quigley EM, Simrén M |title=An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota |journal=Gut |volume=61 |issue=7 |pages=997–1006 |year=2012 |pmid=22180058 |doi=10.1136/gutjnl-2011-301501 |url=}}</ref><ref name="pmid19457422">{{cite journal |vauthors=Spiller R, Garsed K |title=Postinfectious irritable bowel syndrome |journal=Gastroenterology |volume=136 |issue=6 |pages=1979–88 |year=2009 |pmid=19457422 |doi=10.1053/j.gastro.2009.02.074 |url=}}</ref><ref name="pmid25611066">{{cite journal |vauthors=Joo YE |title=Alteration of fecal microbiota in patients with postinfectious irritable bowel syndrome |journal=J Neurogastroenterol Motil |volume=21 |issue=1 |pages=135–7 |year=2015 |pmid=25611066 |pmc=4288086 |doi=10.5056/jnm14133 |url=}}</ref><ref name="pmid10026328">{{cite journal |vauthors=Gwee KA, Leong YL, Graham C, McKendrick MW, Collins SM, Walters SJ, Underwood JE, Read NW |title=The role of psychological and biological factors in postinfective gut dysfunction |journal=Gut |volume=44 |issue=3 |pages=400–6 |year=1999 |pmid=10026328 |pmc=1727402 |doi= |url=}}</ref><ref name="pmid24646319">{{cite journal |vauthors=Nielsen HL, Engberg J, Ejlertsen T, Nielsen H |title=Psychometric scores and persistence of irritable bowel after Campylobacter concisus infection |journal=Scand. J. Gastroenterol. |volume=49 |issue=5 |pages=545–51 |year=2014 |pmid=24646319 |doi=10.3109/00365521.2014.886718 |url=}}</ref>
==='''Intrinsic gastrointestinal factors'''===
==='''Intrinsic gastrointestinal factors'''===
**'''Motor abnormalities:'''
*'''Motor abnormalities:'''
***IBS is referred to as ‘[[spastic colon]]’ due to changes in [[Colon (anatomy)|colonic]] [[Motor coordination|motor]] function.
**IBS is referred to as ‘[[spastic colon]]’ due to changes in [[Colon (anatomy)|colonic]] [[Motor coordination|motor]] function.
***Manometry recordings from the [[Transverse colon|transverse]], [[Descending colon|descending]] and [[sigmoid colon]] have shown that IBS leads to changed patterns of [[Colon (anatomy)|colonic]] and [[Small intestine|small intestinal]] [[Motor coordination|motor]] function, such as increased frequency and irregularity of [[Lumen|luminal]] contractions.
**Manometry recordings from the [[Transverse colon|transverse]], [[Descending colon|descending]] and [[sigmoid colon]] have shown that IBS leads to changed patterns of [[Colon (anatomy)|colonic]] and [[Small intestine|small intestinal]] [[Motor coordination|motor]] function, such as increased frequency and irregularity of [[Lumen|luminal]] contractions.
***[[Muscle|Motor]] changes lead to symptoms of [[diarrhea]] and [[constipation]].<ref name="pmid8789897">{{cite journal |vauthors=Schmidt T, Hackelsberger N, Widmer R, Meisel C, Pfeiffer A, Kaess H |title=Ambulatory 24-hour jejunal motility in diarrhea-predominant irritable bowel syndrome |journal=Scand. J. Gastroenterol. |volume=31 |issue=6 |pages=581–9 |year=1996 |pmid=8789897 |doi= |url=}}</ref><ref name="pmid2865504">{{cite journal |vauthors=Kumar D, Wingate DL |title=The irritable bowel syndrome: a paroxysmal motor disorder |journal=Lancet |volume=2 |issue=8462 |pages=973–7 |year=1985 |pmid=2865504 |doi= |url=}}</ref><ref name="pmid11215731">{{cite journal |vauthors=Simrén M, Castedal M, Svedlund J, Abrahamsson H, Björnsson E |title=Abnormal propagation pattern of duodenal pressure waves in the irritable bowel syndrome (IBS) [correction of (IBD)] |journal=Dig. Dis. Sci. |volume=45 |issue=11 |pages=2151–61 |year=2000 |pmid=11215731 |doi= |url=}}</ref>
**[[Muscle|Motor]] changes lead to symptoms of [[diarrhea]] and [[constipation]].<ref name="pmid8789897">{{cite journal |vauthors=Schmidt T, Hackelsberger N, Widmer R, Meisel C, Pfeiffer A, Kaess H |title=Ambulatory 24-hour jejunal motility in diarrhea-predominant irritable bowel syndrome |journal=Scand. J. Gastroenterol. |volume=31 |issue=6 |pages=581–9 |year=1996 |pmid=8789897 |doi= |url=}}</ref><ref name="pmid2865504">{{cite journal |vauthors=Kumar D, Wingate DL |title=The irritable bowel syndrome: a paroxysmal motor disorder |journal=Lancet |volume=2 |issue=8462 |pages=973–7 |year=1985 |pmid=2865504 |doi= |url=}}</ref><ref name="pmid11215731">{{cite journal |vauthors=Simrén M, Castedal M, Svedlund J, Abrahamsson H, Björnsson E |title=Abnormal propagation pattern of duodenal pressure waves in the irritable bowel syndrome (IBS) [correction of (IBD)] |journal=Dig. Dis. Sci. |volume=45 |issue=11 |pages=2151–61 |year=2000 |pmid=11215731 |doi= |url=}}</ref>
***[[Diarrhea]]-prone IBS patients have increased responses to [[ingestion]], [[Corticotropin-releasing hormone|CRH]] ([[Corticotropin-releasing hormone|corticotropin releasing hormone]]), [[Cholecystokinin|CCK]] ([[cholecystokinin]]), which increase the peak amplitude of high-amplitude propagating [[Contraction|contractions]] (HAPCs)  and lead to [[Abdominal pain|abdominal discomfort]] with accelerated transit through the [[Colon (anatomy)|colon]]. <ref name="pmid11374689">{{cite journal |vauthors=Chey WY, Jin HO, Lee MH, Sun SW, Lee KY |title=Colonic motility abnormality in patients with irritable bowel syndrome exhibiting abdominal pain and diarrhea |journal=Am. J. Gastroenterol. |volume=96 |issue=5 |pages=1499–506 |year=2001 |pmid=11374689 |doi=10.1111/j.1572-0241.2001.03804.x |url=}}</ref><ref name="pmid7379673">{{cite journal |vauthors=Whitehead WE, Engel BT, Schuster MM |title=Irritable bowel syndrome: physiological and psychological differences between diarrhea-predominant and constipation-predominant patients |journal=Dig. Dis. Sci. |volume=25 |issue=6 |pages=404–13 |year=1980 |pmid=7379673 |doi= |url=}}</ref><ref name="pmid9691924">{{cite journal |vauthors=Fukudo S, Nomura T, Hongo M |title=Impact of corticotropin-releasing hormone on gastrointestinal motility and adrenocorticotropic hormone in normal controls and patients with irritable bowel syndrome |journal=Gut |volume=42 |issue=6 |pages=845–9 |year=1998 |pmid=9691924 |pmc=1727153 |doi= |url=}}</ref><ref name="pmid18456567">{{cite journal |vauthors=Camilleri M, McKinzie S, Busciglio I, Low PA, Sweetser S, Burton D, Baxter K, Ryks M, Zinsmeister AR |title=Prospective study of motor, sensory, psychologic, and autonomic functions in patients with irritable bowel syndrome |journal=Clin. Gastroenterol. Hepatol. |volume=6 |issue=7 |pages=772–81 |year=2008 |pmid=18456567 |pmc=2495078 |doi=10.1016/j.cgh.2008.02.060 |url=}}</ref><ref name="pmid3569764">{{cite journal |vauthors=Kellow JE, Phillips SF |title=Altered small bowel motility in irritable bowel syndrome is correlated with symptoms |journal=Gastroenterology |volume=92 |issue=6 |pages=1885–93 |year=1987 |pmid=3569764 |doi= |url=}}</ref>
**[[Diarrhea]]-prone IBS patients have increased responses to [[ingestion]], [[Corticotropin-releasing hormone|CRH]] ([[Corticotropin-releasing hormone|corticotropin releasing hormone]]), [[Cholecystokinin|CCK]] ([[cholecystokinin]]), which increase the peak amplitude of high-amplitude propagating [[Contraction|contractions]] (HAPCs)  and lead to [[Abdominal pain|abdominal discomfort]] with accelerated transit through the [[Colon (anatomy)|colon]]. <ref name="pmid11374689">{{cite journal |vauthors=Chey WY, Jin HO, Lee MH, Sun SW, Lee KY |title=Colonic motility abnormality in patients with irritable bowel syndrome exhibiting abdominal pain and diarrhea |journal=Am. J. Gastroenterol. |volume=96 |issue=5 |pages=1499–506 |year=2001 |pmid=11374689 |doi=10.1111/j.1572-0241.2001.03804.x |url=}}</ref><ref name="pmid7379673">{{cite journal |vauthors=Whitehead WE, Engel BT, Schuster MM |title=Irritable bowel syndrome: physiological and psychological differences between diarrhea-predominant and constipation-predominant patients |journal=Dig. Dis. Sci. |volume=25 |issue=6 |pages=404–13 |year=1980 |pmid=7379673 |doi= |url=}}</ref><ref name="pmid9691924">{{cite journal |vauthors=Fukudo S, Nomura T, Hongo M |title=Impact of corticotropin-releasing hormone on gastrointestinal motility and adrenocorticotropic hormone in normal controls and patients with irritable bowel syndrome |journal=Gut |volume=42 |issue=6 |pages=845–9 |year=1998 |pmid=9691924 |pmc=1727153 |doi= |url=}}</ref><ref name="pmid18456567">{{cite journal |vauthors=Camilleri M, McKinzie S, Busciglio I, Low PA, Sweetser S, Burton D, Baxter K, Ryks M, Zinsmeister AR |title=Prospective study of motor, sensory, psychologic, and autonomic functions in patients with irritable bowel syndrome |journal=Clin. Gastroenterol. Hepatol. |volume=6 |issue=7 |pages=772–81 |year=2008 |pmid=18456567 |pmc=2495078 |doi=10.1016/j.cgh.2008.02.060 |url=}}</ref><ref name="pmid3569764">{{cite journal |vauthors=Kellow JE, Phillips SF |title=Altered small bowel motility in irritable bowel syndrome is correlated with symptoms |journal=Gastroenterology |volume=92 |issue=6 |pages=1885–93 |year=1987 |pmid=3569764 |doi= |url=}}</ref>
***[[Constipation]]-prone [[Irritable bowel syndrome|IBS]] patients show fewer high-amplitude propagating [[Contraction|contractions]] (HAPCs) as compared to [[diarrhea]] prone [[Irritable bowel syndrome|IBS]] patients, delayed transit through the [[Colon (anatomy)|colon]] and decreased [[motility]].  
**[[Constipation]]-prone [[Irritable bowel syndrome|IBS]] patients show fewer high-amplitude propagating [[Contraction|contractions]] (HAPCs) as compared to [[diarrhea]] prone [[Irritable bowel syndrome|IBS]] patients, delayed transit through the [[Colon (anatomy)|colon]] and decreased [[motility]].  
***Changes in the [[Muscle|motor]] function of the [[Colon (anatomy)|colon]] are responsible for producing the [[Gastrointestinal tract|gastrointestinal]] symptoms of [[Irritable bowel syndrome|IBS]] such as altered [[Intestine|bowel]] habits and [[abdominal pain]].<ref name="pmid18456567" />
***Changes in the [[Muscle|motor]] function of the [[Colon (anatomy)|colon]] are responsible for producing the [[Gastrointestinal tract|gastrointestinal]] symptoms of [[Irritable bowel syndrome|IBS]] such as altered [[Intestine|bowel]] habits and [[abdominal pain]].<ref name="pmid18456567" />
**'''Visceral hypersensitivity:'''
**'''Visceral hypersensitivity:'''
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{{familytree/end}}
{{familytree/end}}
<br><br><br>
<br><br><br>
**'''[[Immune]] activation and [[mucosal]] [[inflammation]]'''{{Family tree/start}}
*'''[[Immune]] activation and [[mucosal]] [[inflammation]]'''{{Family tree/start}}
{{Family tree | A01 |-|-| A02 |-|-|-| A03 | |A01= '''[[Mast cells]]'''| A02= '''[[IMMUNE]] ACTIVATION AND [[MUCOSAL]] [[INFLAMMATION]]'''| A03='''[[Lymphocytes]]'''}}
{{Family tree | A01 |-|-| A02 |-|-|-| A03 | |A01= '''[[Mast cells]]'''| A02= '''[[IMMUNE]] ACTIVATION AND [[MUCOSAL]] [[INFLAMMATION]]'''| A03='''[[Lymphocytes]]'''}}



Revision as of 02:17, 31 October 2017

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

Overview

IBS is caused by the complex interaction of various factors such as intrinsic gastrointestinal factors, CNS dysregulation and psychosocial factors, genetic and environmental factors. Intrinsic gastrointestinal factors include motor abnormalities, visceral hypersensitivity, immune activation and mucosal inflammation, altered gut microbiota and abnormal serotonin pathways. Visceral hypersensitivity is a decreased threshold for the perception of visceral stimuli that affects spinal excitability brain stem and cortical modulation, activation of specific gastrointestinal mediators and recruitment of peripheral silent nociceptors. Immune activation and mucosal inflammation involves an interaction of lymphocytes, mast cells and proinflammatory cytokines. Environmental factors encompass dietary changes and infections. Psychosocial factors such as stress, anxiety and depression directly shape adult connectivity in the executive control network consisting of structures such as the insula, anterior cingulate cortex and the thalamus. Semipermanent/permanent changes in complex neural circuits lead to central pain amplification and contribute to abdominal pain in IBS patients. The dorsolateral prefrontal cortex activity (responsible for vigilance and alertness of the human brain) and the mid-cingulate cortex (engaged in attention pathways and responses) is reduced in IBS patients, which may lead to alterations in the subjective sensations of pain. Genetic factors also play a role in IBS. It has high twin concordance and familial aggregation. It is associated with Single nucleotide polymorphisms (SNPs) in genes involved in immune activation, neuropeptide hormone function, oxidative stress, nociception, permeability of the GI tract, host-microbiota interaction, inflammation, and TNF activity.

Pathophysiology

Pathogenesis

IBS is an interplay between four main factors:


 
 
 
 
 
CNS dysregulation and psychosocial factors
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Intrinsic gastrointestinal factors:
Motor abnormalities
Visceral hypersensitivity
Immune activation and mucosal inflammation
• Altered gut microbiota
• Abnormal serotonin pathways
 
 
IRRITABLE BOWEL SYNDROME
 
 
 
Genetic factors:
Twin concordance
• Familial aggregation
Single Nucleotide Polymorphisms(SNPs)
TNF polymorphism
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Environmental factors
 
 
 

Environmental factors

Intrinsic gastrointestinal factors


 
 
 
 
 
 
 
 
 
 
 
 
Spinal hyperexcitability
 
Activation of
N-methyl D aspartate (NMDA) receptor
nitric oxide
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Central (brainstem and cortical) modulation
 
Increased activation of:
• Anterior cingulate cortex
Thalamus
insula
 
 
 
 
 
 
 
 
 
 
 
Visceral hypersensitivity
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Activation of specific gastrointestinal mediators
 
Kinins and serotonin activation lead to afferent nerve fiber sensitization
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Recruitment of peripheral silent nociceptors
 
Increased end organ sensitivity due to hormonal or immune activation