Ileus pathophysiology: Difference between revisions

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==Overview==
==Overview==
[[Ileus]] is defined as a temporary cessation of [[intestinal]] [[peristalsis]] in the absence of [[bowel obstruction|mechanical obstruction]]. The [[pathogenesis]] of [[ileus]] is based on its multifactorial [[etiology]]. [[Ileus]] is most commonly seen during the [[surgery|postoperative]] period (usually 3 days after [[surgery]]). When a [[patient]] undergoes a [[surgical procedure]], it often puts the body under significant [[stress]]. It is thought that [[ileus]] is the result of [[surgery|surgical]] [[stress]] induced [[Inflammation|inflammatory]] process, that leads to release of [[inflammatory]] and [[neuroendocrine]] mediators (such as [[nitric oxide]], [[VIP]] and [[substance P]]). Additionally, manipulation of the [[intestine]] leads to activation of [[afferent nerve|afferent]] pathways that travel to [[Brain stem]], which leads to increased [[autonomic]] output to the [[sympathetic]] [[neurons]] and increased secretion of [[adrenergic]] [[neurotransmitters]] and subsequent decreased [[intestinal]] [[motility]]. Commonly used [[analgesics]] such as [[opiates]] and [[anesthesia]] may also aggravate the development of [[ileus]]. [[Enteric nervous system|Enteric]] and [[autonomic nervous system]] disturbances can cause a severe variety of [[ilues]], named [[Intestinal pseudoobstruction|chronic intestinal pseudo-obstruction]] ([[Intestinal pseudoobstruction|CIPO]]) which may be related to some altered [[genes]]. Conditions commonly associated with [[ileus]] include [[diabetes mellitus]], [[hypothyroidism]], and [[hypoparathyroidism]]. On [[gross pathology]] findings of [[ileus]] include [[bowel]] contortion with distended [[Small intestine|small]] and [[large intestine]]. On [[Microscopic examination|microscopic]] [[histopathological]] [[analysis]], findings of [[ileus]] include [[inflammatory cells]] predominantly [[macrophage|macrophages]] and [[mast cells]].
[[Ileus]] is defined as a temporary cessation of [[intestinal]] [[peristalsis]] in the absence of [[bowel obstruction|mechanical obstruction]]. The [[pathogenesis]] of [[ileus]] is based on its multifactorial [[etiology]]. [[Ileus]] is most commonly seen during the [[surgery|postoperative]] period (usually 3 days after [[surgery]]). When a [[patient]] undergoes a [[surgical procedure]], it often puts the body under significant [[stress]]. It is thought that [[ileus]] is the result of a [[surgery|surgical]] [[stress]]-induced [[Inflammation|inflammatory]] process, that leads to the release of [[inflammatory]] and [[neuroendocrine]] mediators (such as [[nitric oxide]], [[VIP]] and [[substance P]]). Additionally, manipulation of the [[intestine]] leads to activation of [[afferent nerve|afferent]] pathways that travel to the [[brain stem]], which leads to increased [[autonomic]] output to the [[sympathetic]] [[neurons]] and increased secretion of [[adrenergic]] [[neurotransmitters]] and subsequent decreased [[intestinal]] [[motility]]. Commonly used [[analgesics]] such as [[opiates]] and [[anesthesia]] may also aggravate the development of [[ileus]]. [[Enteric nervous system|Enteric]] and [[autonomic nervous system]] disturbances can cause a severe form of [[ilues]], called [[Intestinal pseudoobstruction|chronic intestinal pseudo-obstruction]] ([[Intestinal pseudoobstruction|CIPO]]) which may be related to some altered [[genes]]. Conditions commonly associated with [[ileus]] include [[diabetes mellitus]], [[hypothyroidism]], and [[hypoparathyroidism]]. [[Gross pathology]] findings of [[ileus]] include [[bowel]] contortion with a distended [[Small intestine|small]] and [[large intestine]]. On [[Microscopic examination|microscopic]] [[histopathological]] [[analysis]], findings of [[ileus]] include [[inflammatory cells]] predominantly [[macrophage|macrophages]] and [[mast cells]].


==Pathophysiology==
==Pathophysiology==


===Physiology===
===Physiology===
*The [[gastrointestinal tract]] is regulated by the [[enteric nervous system]], [[autonomic nervous system]] and interactions with [[central nervous system]].
*The [[gastrointestinal tract]] is regulated by the [[enteric nervous system]], [[autonomic nervous system]] and interacts with [[central nervous system]].
*The [[enteric nervous system]] ([[enteric nervous system|ENS]]) is also known as intrinsic [[Nervous system|neural network]] and consists of [[Neuron|neurons]] located in the walls of [[Gastrointestinal tract]].  
*The [[enteric nervous system]] ([[enteric nervous system|ENS]]) is also known as an intrinsic [[Nervous system|neural network]] and consists of [[Neuron|neurons]] located in the walls of [[Gastrointestinal tract]].  
**[[Enteric nervous system]] ([[enteric nervous system|ENS]]) includes [[Auerbach's plexus|myenteric plexus]] ([[Auerbach's plexus]]) and [[Meissner's plexus|submucosal plexuses]] ([[Meissner's plexus]]).  
**[[Enteric nervous system]] ([[enteric nervous system|ENS]]) includes the [[Auerbach's plexus|myenteric plexus]] ([[Auerbach's plexus]]) and [[Meissner's plexus|submucosal plexuses]] ([[Meissner's plexus]]).  
**The [[Auerbach's plexus|myenteric plexus]] is located in the [[Muscle|muscular layer]] and is also known as [[Auerbach's plexus]].  
**The [[Auerbach's plexus|myenteric plexus]] is located in the [[Muscle|muscular layer]] and is also known as the [[Auerbach's plexus]].  
**The [[Meissner's plexus|submucosal plexuses]] is located in the [[Submucosa|submucosal layer]] and is also known as [[Meissner's plexus]].
**The [[Meissner's plexus|submucosal plexuses]] is located in the [[Submucosa|submucosal layer]] and is also known as the [[Meissner's plexus]].
*The [[autonomic nervous system]] ([[autonomic nervous system|ANS]]) is also known as extrinsic [[nervous system]].  
*The [[autonomic nervous system]] ([[autonomic nervous system|ANS]]) is also known as the extrinsic [[nervous system]].  
**The [[autonomic nervous system]] ([[autonomic nervous system|ANS]]) consists of [[Sympathetic nervous system|sympathetic]] and [[parasympathetic nervous system]] which control [[Gastrointestinal tract]] function.  
**The [[autonomic nervous system]] ([[autonomic nervous system|ANS]]) consists of the [[Sympathetic nervous system|sympathetic]] and [[parasympathetic nervous system]], which control [[Gastrointestinal tract]] function.  
**The [[sympathetic nervous system]] is [[Inhibitory postsynaptic potential|inhibitory]] to [[Viscus|visceral]] [[smooth muscle]] activity and decreases [[peristalsis]] and [[Gastrointestinal tract]] motility.
**The [[sympathetic nervous system]] is [[Inhibitory postsynaptic potential|inhibitory]] to [[Viscus|visceral]] [[smooth muscle]] activity and decreases [[peristalsis]] and [[Gastrointestinal tract]] motility.
**The [[parasympathetic nervous system]] is stimulatory to [[Viscus|visceral]] [[smooth muscle]] activity and increases [[peristalsis]] and [[Gastrointestinal tract]] motility.
**The [[parasympathetic nervous system]] is stimulatory to [[Viscus|visceral]] [[smooth muscle]] activity and increases [[peristalsis]] and [[Gastrointestinal tract]] motility.
**The [[Afferent nerve|afferent]] [[Viscus|visceral]] [[sensory system]] of [[Gastrointestinal tract|GI tract]] is part of the [[parasympathetic nervous system]], while the [[Efferent nerve|efferent]] [[Viscus|visceral]] motor system are located in both [[Sympathetic nervous system|sympathetic]] and [[Parasympathetic nervous system|parasympathetic]] [[autonomic nervous system]].  
**The [[Afferent nerve|afferent]] [[Viscus|visceral]] [[sensory system]] of the [[Gastrointestinal tract|GI tract]] is part of the [[parasympathetic nervous system]], while the [[Efferent nerve|efferent]] [[Viscus|visceral]] motor system is located in both [[Sympathetic nervous system|sympathetic]] and [[Parasympathetic nervous system|parasympathetic]] [[autonomic nervous system]].  
**In addition, the extrinsic [[nervous system]] [[Chemical synapse|synapse]] with [[enteric nervous system]] and relay information to the [[central nervous system]].
**In addition, the extrinsic [[nervous system]] [[Chemical synapse|synapse]] with the [[enteric nervous system]] and relay information to the [[central nervous system]].


[[File:Neural control gut.png|center|300px|frame|Neural control of gut.(By Boumphreyfr (Own work) [CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0) or GFDL (http://www.gnu.org/copyleft/fdl.html)], via Wikimedia Commons)]]
[[File:Neural control gut.png|center|300px|frame|Neural control of gut.(By Boumphreyfr (Own work) [CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0) or GFDL (http://www.gnu.org/copyleft/fdl.html)], via Wikimedia Commons)]]


===Pathogenesis===
===Pathogenesis===
*[[Ileus]] is defined as temporary cessation of [[intestinal]] [[peristalsis]] in the absence of [[bowel obstruction|mechanical obstruction]]. The [[pathogenesis]] of [[ileus]] is based on its multifactorial [[etiology]].<ref name="pmid9833803">{{cite journal |vauthors=Kalff JC, Schraut WH, Simmons RL, Bauer AJ |title=Surgical manipulation of the gut elicits an intestinal muscularis inflammatory response resulting in postsurgical ileus |journal=Ann. Surg. |volume=228 |issue=5 |pages=652–63 |year=1998 |pmid=9833803 |pmc=1191570 |doi= |url=}}</ref><ref name="pmid7540700">{{cite journal |vauthors=Espat NJ, Cheng G, Kelley MC, Vogel SB, Sninsky CA, Hocking MP |title=Vasoactive intestinal peptide and substance P receptor antagonists improve postoperative ileus |journal=J. Surg. Res. |volume=58 |issue=6 |pages=719–23 |year=1995 |pmid=7540700 |doi=10.1006/jsre.1995.1113 |url=}}</ref><ref name="pmid10648460">{{cite journal |vauthors=Kalff JC, Schraut WH, Billiar TR, Simmons RL, Bauer AJ |title=Role of inducible nitric oxide synthase in postoperative intestinal smooth muscle dysfunction in rodents |journal=Gastroenterology |volume=118 |issue=2 |pages=316–27 |year=2000 |pmid=10648460 |doi= |url=}}</ref>  
*[[Ileus]] is defined as the temporary cessation of [[intestinal]] [[peristalsis]] in the absence of [[bowel obstruction|mechanical obstruction]]. The [[pathogenesis]] of [[ileus]] is based on its multifactorial [[etiology]].<ref name="pmid9833803">{{cite journal |vauthors=Kalff JC, Schraut WH, Simmons RL, Bauer AJ |title=Surgical manipulation of the gut elicits an intestinal muscularis inflammatory response resulting in postsurgical ileus |journal=Ann. Surg. |volume=228 |issue=5 |pages=652–63 |year=1998 |pmid=9833803 |pmc=1191570 |doi= |url=}}</ref><ref name="pmid7540700">{{cite journal |vauthors=Espat NJ, Cheng G, Kelley MC, Vogel SB, Sninsky CA, Hocking MP |title=Vasoactive intestinal peptide and substance P receptor antagonists improve postoperative ileus |journal=J. Surg. Res. |volume=58 |issue=6 |pages=719–23 |year=1995 |pmid=7540700 |doi=10.1006/jsre.1995.1113 |url=}}</ref><ref name="pmid10648460">{{cite journal |vauthors=Kalff JC, Schraut WH, Billiar TR, Simmons RL, Bauer AJ |title=Role of inducible nitric oxide synthase in postoperative intestinal smooth muscle dysfunction in rodents |journal=Gastroenterology |volume=118 |issue=2 |pages=316–27 |year=2000 |pmid=10648460 |doi= |url=}}</ref>  
*[[Intestinal]] [[peristalsis]] is primarily regulated by [[enteric nervous system]], [[autonomic nervous system]] and their interactions with [[central nervous system]] ([[central nervous system|CNS]]). However, certain [[medications]] and [[metabolic]] products may also alter the normal [[intestine|intestinal]] [[Chemical equilibrium|equilibrium]] leading to temporary dysfunction in [[intestine|intestinal]] movements. Prolonged [[intestinal]] [[peristalsis|aperistalsis]] results in accumulation of air and fluid in the [[intestine|intestinal]] [[lumen]].
*[[Intestinal]] [[peristalsis]] is primarily regulated by the [[enteric nervous system]], [[autonomic nervous system]] and their interactions with the [[central nervous system]] ([[central nervous system|CNS]]). However, certain [[medications]] and [[metabolic]] products may also alter the normal [[intestine|intestinal]] [[Chemical equilibrium|equilibrium]] leading to temporary dysfunction in [[intestine|intestinal]] movements. Prolonged [[intestinal]] [[peristalsis|aperistalsis]] results in the accumulation of air and fluid in the [[intestine|intestinal]] [[lumen]].
*The most common cause of [[ileus]] is [[abdominal surgery]].<ref name="pmid9833803">{{cite journal |vauthors=Kalff JC, Schraut WH, Simmons RL, Bauer AJ |title=Surgical manipulation of the gut elicits an intestinal muscularis inflammatory response resulting in postsurgical ileus |journal=Ann. Surg. |volume=228 |issue=5 |pages=652–63 |year=1998 |pmid=9833803 |pmc=1191570 |doi= |url=}}</ref><ref name="pmid7540700">{{cite journal |vauthors=Espat NJ, Cheng G, Kelley MC, Vogel SB, Sninsky CA, Hocking MP |title=Vasoactive intestinal peptide and substance P receptor antagonists improve postoperative ileus |journal=J. Surg. Res. |volume=58 |issue=6 |pages=719–23 |year=1995 |pmid=7540700 |doi=10.1006/jsre.1995.1113 |url=}}</ref><ref name="pmid10648460">{{cite journal |vauthors=Kalff JC, Schraut WH, Billiar TR, Simmons RL, Bauer AJ |title=Role of inducible nitric oxide synthase in postoperative intestinal smooth muscle dysfunction in rodents |journal=Gastroenterology |volume=118 |issue=2 |pages=316–27 |year=2000 |pmid=10648460 |doi= |url=}}</ref>
*The most common cause of [[ileus]] is [[abdominal surgery]].<ref name="pmid9833803">{{cite journal |vauthors=Kalff JC, Schraut WH, Simmons RL, Bauer AJ |title=Surgical manipulation of the gut elicits an intestinal muscularis inflammatory response resulting in postsurgical ileus |journal=Ann. Surg. |volume=228 |issue=5 |pages=652–63 |year=1998 |pmid=9833803 |pmc=1191570 |doi= |url=}}</ref><ref name="pmid7540700">{{cite journal |vauthors=Espat NJ, Cheng G, Kelley MC, Vogel SB, Sninsky CA, Hocking MP |title=Vasoactive intestinal peptide and substance P receptor antagonists improve postoperative ileus |journal=J. Surg. Res. |volume=58 |issue=6 |pages=719–23 |year=1995 |pmid=7540700 |doi=10.1006/jsre.1995.1113 |url=}}</ref><ref name="pmid10648460">{{cite journal |vauthors=Kalff JC, Schraut WH, Billiar TR, Simmons RL, Bauer AJ |title=Role of inducible nitric oxide synthase in postoperative intestinal smooth muscle dysfunction in rodents |journal=Gastroenterology |volume=118 |issue=2 |pages=316–27 |year=2000 |pmid=10648460 |doi= |url=}}</ref>
**The risk of [[ileus|postoperative ileus]] depends upon the type of [[surgery]]; [[Laparoscopic surgery|laparoscopic]] procedures have lower risk, compared to [[laparotomy]] which have the highest [[Risk factor|risk]].
**The risk of [[ileus|postoperative ileus]] depends upon the type of [[surgery]]; [[Laparoscopic surgery|laparoscopic]] procedures have lower risk, compared to [[laparotomy]] which have the highest [[Risk factor|risk]].
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**[[ileus|Postoperative ileus]] that lasts longer than 3 days is termed as [[ileus|paralytic ileus]] or [[ileus|adynamic ileus]].
**[[ileus|Postoperative ileus]] that lasts longer than 3 days is termed as [[ileus|paralytic ileus]] or [[ileus|adynamic ileus]].
**When a [[patient]] undergoes a [[surgery|surgical procedure]], it often puts the body under significant [[Stress (medicine)|stress]].  
**When a [[patient]] undergoes a [[surgery|surgical procedure]], it often puts the body under significant [[Stress (medicine)|stress]].  
***This [[Surgery|surgical]] [[Stress (medicine)|stress]] may lead to release of [[inflammatory]] and [[neuroendocrine]] mediators (such as [[nitric oxide]], [[VIP]] and [[substance P]]) that may result in inhibition of [[intestine|intestinal]] motility and development of [[ileus]].<ref name="pmid19580945">{{cite journal |vauthors=Doherty TJ |title=Postoperative ileus: pathogenesis and treatment |journal=Vet. Clin. North Am. Equine Pract. |volume=25 |issue=2 |pages=351–62 |year=2009 |pmid=19580945 |doi=10.1016/j.cveq.2009.04.011 |url=}}</ref>
***This [[Surgery|surgical]] [[Stress (medicine)|stress]] may lead to the release of [[inflammatory]] and [[neuroendocrine]] mediators (such as [[nitric oxide]], [[VIP]] and [[substance P]]) that may result in the inhibition of [[intestine|intestinal]] motility and development of [[ileus]].<ref name="pmid19580945">{{cite journal |vauthors=Doherty TJ |title=Postoperative ileus: pathogenesis and treatment |journal=Vet. Clin. North Am. Equine Pract. |volume=25 |issue=2 |pages=351–62 |year=2009 |pmid=19580945 |doi=10.1016/j.cveq.2009.04.011 |url=}}</ref>
***[[Stress (medicine)|Stress]] inducing conditions may lead to increased recruitment of [[dendritic cells]], [[natural killer cells]], [[monocytes]], [[T cells]], [[macrophages]], and [[mast cells]]. The [[macrophages]] and [[mast cells]] are considered the key [[Cells (biology)|cells]] leading to the initiation and maintenance of the [[inflammatory]] process and release of chemical mediators.
***[[Stress (medicine)|Stress]] inducing conditions may lead to increased recruitment of [[dendritic cells]], [[natural killer cells]], [[monocytes]], [[T cells]], [[macrophages]], and [[mast cells]]. The [[macrophages]] and [[mast cells]] are considered the key [[Cells (biology)|cells]] leading to the initiation and maintenance of the [[inflammatory]] process and release of chemical mediators.
***Recent research has shown that inhibition of [[inflammatory]] mediators (such as [[nitric oxide]] & [[Vasoactive intestinal peptide|VIP]]) may lead to improved [[gastrointestinal]] [[peristalsis]] and function.  
***Recent research has shown that inhibition of [[inflammatory]] mediators (such as [[nitric oxide]] & [[Vasoactive intestinal peptide|VIP]]) may lead to improved [[gastrointestinal]] [[peristalsis]] and function.  
***The site of the [[surgery]] is the most common affected part of the [[Gastrointestinal tract|GI tract]]. However, recent research has shown that [[inflammation]] of the [[intestine|intestinal]] [[muscle]] may extend from site of [[surgery]] to other parts of the [[Gastrointestinal tract|intestinal tract]].<ref name="pmid11740765">{{cite journal |vauthors=Bederman SS, Betsy M, Winiarsky R, Seldes RM, Sharrock NE, Sculco TP |title=Postoperative ileus in the lower extremity arthroplasty patient |journal=J Arthroplasty |volume=16 |issue=8 |pages=1066–70 |year=2001 |pmid=11740765 |doi=10.1054/arth.2001.27675 |url=}}</ref>
***The site of the [[surgery]] is the most common affected part of the [[Gastrointestinal tract|GI tract]]. However, recent research has shown that [[inflammation]] of the [[intestine|intestinal]] [[muscle]] may extend from the site of [[surgery]] to other parts of the [[Gastrointestinal tract|intestinal tract]].<ref name="pmid11740765">{{cite journal |vauthors=Bederman SS, Betsy M, Winiarsky R, Seldes RM, Sharrock NE, Sculco TP |title=Postoperative ileus in the lower extremity arthroplasty patient |journal=J Arthroplasty |volume=16 |issue=8 |pages=1066–70 |year=2001 |pmid=11740765 |doi=10.1054/arth.2001.27675 |url=}}</ref>
***Moreover, [[intestine|intestinal]] distention seen in [[ileus]] is contributed to [[Serosa|serosal]] [[injury]] and may aggravate [[intestine|intestinal]] [[ischemia]].  
***Moreover, [[intestine|intestinal]] distention seen in [[ileus]] is contributed to [[Serosa|serosal]] [[injury]] and may aggravate [[intestine|intestinal]] [[ischemia]].  
***Prolonged [[ileus]] leads to increased contact between various segments of [[intestine]] which predispose to [[fibrosis|fibrous]] adhesion formation, thereby further contributing to the severity of [[ileus]]. <ref>Lundin C, Sullins KE, White NA and al. Induction of peritoneal adhesions with small intestinal ischaemia and distention in the foal. ''Equine Vet J'' 21: 451, 1989</ref><ref>Vachon AM, Fisher AT. Small intestinal herniation through the epiploic foramen: 53 cases (1987-1993). ''Equine Vet J'' 27: 373, 1995</ref>
***Prolonged [[ileus]] leads to increased contact between various segments of [[intestine]] which predispose to [[fibrosis|fibrous]] adhesion formation, thereby further contributing to the severity of [[ileus]]. <ref>Lundin C, Sullins KE, White NA and al. Induction of peritoneal adhesions with small intestinal ischaemia and distention in the foal. ''Equine Vet J'' 21: 451, 1989</ref><ref>Vachon AM, Fisher AT. Small intestinal herniation through the epiploic foramen: 53 cases (1987-1993). ''Equine Vet J'' 27: 373, 1995</ref>
***[[Abdomen|Abdominal]] conditions such as [[gastroenteritis]] and [[peritonitis]] may also affect the [[intestinal]] [[motility]] leading to [[ileus]].
***[[Abdomen|Abdominal]] conditions such as [[gastroenteritis]] and [[peritonitis]] may also affect the [[intestinal]] [[motility]] leading to [[ileus]].
**Abdominal [[incision]] leads to activation of [[inhibitory]] [[spinal cord|spinal]] [[reflex]] which results in decreased movements of [[intestine]], as a regulatory mechanism.<ref name="pmid8967419">{{cite journal |vauthors=Barquist E, Bonaz B, Martinez V, Rivier J, Zinner MJ, Taché Y |title=Neuronal pathways involved in abdominal surgery-induced gastric ileus in rats |journal=Am. J. Physiol. |volume=270 |issue=4 Pt 2 |pages=R888–94 |year=1996 |pmid=8967419 |doi=10.1152/ajpregu.1996.270.4.R888 |url=}}</ref>
**Abdominal [[incision]] leads to the activation of [[inhibitory]] [[spinal cord|spinal]] [[reflex]] which results in decreased movements of the [[intestine]], as a regulatory mechanism.<ref name="pmid8967419">{{cite journal |vauthors=Barquist E, Bonaz B, Martinez V, Rivier J, Zinner MJ, Taché Y |title=Neuronal pathways involved in abdominal surgery-induced gastric ileus in rats |journal=Am. J. Physiol. |volume=270 |issue=4 Pt 2 |pages=R888–94 |year=1996 |pmid=8967419 |doi=10.1152/ajpregu.1996.270.4.R888 |url=}}</ref>
***The [[pain|painful]] stimuli stimulates the [[spinal cord|spinal]] [[Afferent nerve|afferents]] that [[synapse]] in the [[spinal cord]]. The [[Prevertebral ganglia|prevertebral adrenergic neurons]] in the [[spinal cord]] activate and inhibit [[intestine|intestinal]] [[motility]] via [[Efferent nerve|efferent nerves]] ([[Sympathetic nervous system|sympathetic ANS]]).
***The [[pain|painful]] stimulates the [[spinal cord|spinal]] [[Afferent nerve|afferents]] that [[synapse]] in the [[spinal cord]]. The [[Prevertebral ganglia|prevertebral adrenergic neurons]] in the [[spinal cord]] activate and inhibit [[intestine|intestinal]] [[motility]] via [[Efferent nerve|efferent nerves]] ([[Sympathetic nervous system|sympathetic ANS]]).
***Additionally, manipulation of [[intestine]] leads to activation of [[Afferent nerve|afferent]] pathways that travel to [[brain stem]]. In turn, [[brain stem]] increases [[autonomic]] output to the [[sympathetic]] [[neurons]] located in the inter-medio-lateral column of the [[spinal cord|thoracic cord]]. The increased activity of [[sympathetic]] [[neurons]] results in increased [[secretion]] of [[adrenergic]] output and subsequent decreased [[intestinal]] [[motility]].
***Additionally, manipulation of the [[intestine]] leads to the activation of [[Afferent nerve|afferent]] pathways that travel to the [[brain stem]]. In turn, the [[brain stem]] increases [[autonomic]] output to the [[sympathetic]] [[neurons]] located in the inter-medio-lateral column of the [[spinal cord|thoracic cord]]. The increased activity of [[sympathetic]] [[neurons]] results in increased [[secretion]] of [[adrenergic]] output and subsequent decreased [[intestinal]] [[motility]].
*There is a [[chronic]] and severe form of [[ileus]], known as [[Intestinal pseudoobstruction|chronic intestinal pseudo-obstruction]] ([[Intestinal pseudoobstruction|CIPO]]).<ref name="Di NardoDi Lorenzo2017">{{cite journal|last1=Di Nardo|first1=G.|last2=Di Lorenzo|first2=C.|last3=Lauro|first3=A.|last4=Stanghellini|first4=V.|last5=Thapar|first5=N.|last6=Karunaratne|first6=T. B.|last7=Volta|first7=U.|last8=De Giorgio|first8=R.|title=Chronic intestinal pseudo-obstruction in children and adults: diagnosis and therapeutic options|journal=Neurogastroenterology & Motility|volume=29|issue=1|year=2017|pages=e12945|issn=13501925|doi=10.1111/nmo.12945}}</ref><ref name="pmid23831693">{{cite journal |vauthors=Iida H, Ohkubo H, Inamori M, Nakajima A, Sato H |title=Epidemiology and clinical experience of chronic intestinal pseudo-obstruction in Japan: a nationwide epidemiologic survey |journal=J Epidemiol |volume=23 |issue=4 |pages=288–94 |year=2013 |pmid=23831693 |pmc=3709546 |doi= |url=}}</ref><ref name="pmid23108319">{{cite journal |vauthors=Yeung AK, Di Lorenzo C |title=Primary gastrointestinal motility disorders in childhood |journal=Minerva Pediatr. |volume=64 |issue=6 |pages=567–84 |year=2012 |pmid=23108319 |doi= |url=}}</ref>
*There is a [[chronic]] and severe form of [[ileus]], known as [[Intestinal pseudoobstruction|chronic intestinal pseudo-obstruction]] ([[Intestinal pseudoobstruction|CIPO]]).<ref name="Di NardoDi Lorenzo2017">{{cite journal|last1=Di Nardo|first1=G.|last2=Di Lorenzo|first2=C.|last3=Lauro|first3=A.|last4=Stanghellini|first4=V.|last5=Thapar|first5=N.|last6=Karunaratne|first6=T. B.|last7=Volta|first7=U.|last8=De Giorgio|first8=R.|title=Chronic intestinal pseudo-obstruction in children and adults: diagnosis and therapeutic options|journal=Neurogastroenterology & Motility|volume=29|issue=1|year=2017|pages=e12945|issn=13501925|doi=10.1111/nmo.12945}}</ref><ref name="pmid23831693">{{cite journal |vauthors=Iida H, Ohkubo H, Inamori M, Nakajima A, Sato H |title=Epidemiology and clinical experience of chronic intestinal pseudo-obstruction in Japan: a nationwide epidemiologic survey |journal=J Epidemiol |volume=23 |issue=4 |pages=288–94 |year=2013 |pmid=23831693 |pmc=3709546 |doi= |url=}}</ref><ref name="pmid23108319">{{cite journal |vauthors=Yeung AK, Di Lorenzo C |title=Primary gastrointestinal motility disorders in childhood |journal=Minerva Pediatr. |volume=64 |issue=6 |pages=567–84 |year=2012 |pmid=23108319 |doi= |url=}}</ref>
**[[Intestinal pseudoobstruction|CIPO]] is a severe form of [[ileus]] resulting from disturbances in [[enteric nervous system]], [[autonomic nervous system]] and [[Smooth muscle|smooth muscle cell]] function.   
**[[Intestinal pseudoobstruction|CIPO]] is a severe form of [[ileus]] resulting from disturbances in the [[enteric nervous system]], [[autonomic nervous system]] and [[Smooth muscle|smooth muscle cell]] function.   
**The cause of [[Intestinal pseudoobstruction|CIPO]] can be [[idiopathic]], sporadic, or secondary to [[matabolism|metabolic]], [[connective tissue]], [[Endocrinology|endocrinologic]], [[Neurology|neurologic]], and [[Paraneoplastic syndrome|paraneoplastic disorders]].<ref name="pmid15880314">{{cite journal |vauthors=Stanghellini V, Cogliandro RF, De Giorgio R, Barbara G, Morselli-Labate AM, Cogliandro L, Corinaldesi R |title=Natural history of chronic idiopathic intestinal pseudo-obstruction in adults: a single center study |journal=Clin. Gastroenterol. Hepatol. |volume=3 |issue=5 |pages=449–58 |year=2005 |pmid=15880314 |doi= |url=}}</ref>
**The cause of [[Intestinal pseudoobstruction|CIPO]] can be [[idiopathic]], sporadic, or secondary to [[matabolism|metabolic]], [[connective tissue]], [[Endocrinology|endocrinologic]], [[Neurology|neurologic]], and [[Paraneoplastic syndrome|paraneoplastic disorders]].<ref name="pmid15880314">{{cite journal |vauthors=Stanghellini V, Cogliandro RF, De Giorgio R, Barbara G, Morselli-Labate AM, Cogliandro L, Corinaldesi R |title=Natural history of chronic idiopathic intestinal pseudo-obstruction in adults: a single center study |journal=Clin. Gastroenterol. Hepatol. |volume=3 |issue=5 |pages=449–58 |year=2005 |pmid=15880314 |doi= |url=}}</ref>
**[[Intestinal pseudoobstruction|CIPO]] is often due to dysfunction in [[Nerve|innervation]] of [[smooth muscle]] by the [[interstitial cells of Cajal]] resulting in partial or complete ineffective [[intestine|intestinal]] propulsion. However, any condition affecting the [[enteric nervous system]], [[autonomic nervous system]], [[smooth muscle cells]] and [[neuromuscular junction]] may lead to development of [[Intestinal pseudoobstruction|CIPO]].
**[[Intestinal pseudoobstruction|CIPO]] is often due to dysfunction in [[Nerve|innervation]] of [[smooth muscle]] by the [[interstitial cells of Cajal]] resulting in partial or completely ineffective [[intestine|intestinal]] propulsion. However, any condition affecting the [[enteric nervous system]], [[autonomic nervous system]], [[smooth muscle cells]] and [[neuromuscular junction]] may lead to development of [[Intestinal pseudoobstruction|CIPO]].
**The lack of propulsive [[intestine|intestinal]] movements may lead to increased intra-[[lumen|luminal]] [[pressure]].  
**The lack of propulsive [[intestine|intestinal]] movements may lead to increased intra-[[lumen|luminal]] [[pressure]].  
**The enhanced intra-[[lumen|luminal]] [[pressure]] leads to [[malabsorption]] and [[Small intestinal bacterial overgrowth syndrome|bacterial overgrowth]]. Over time, it can progress to present with [[malnutrition]] and [[sepsis]].
**The enhanced intra-[[lumen|luminal]] [[pressure]] leads to [[malabsorption]] and [[Small intestinal bacterial overgrowth syndrome|bacterial overgrowth]]. Over time, it can progress to present with [[malnutrition]] and [[sepsis]].
*The other common cause of [[ileus]] are the [[drugs]] that affect [[intestinal]] [[motility]] and [[Electrolyte disturbance|alteration in electrolyte levels]].
*The other common cause of [[ileus]] are the [[drugs]] that affect [[intestinal]] [[motility]] and [[Electrolyte disturbance|alteration in electrolyte levels]].
**Drugs affecting [[intestinal]] [[motility]] primarily includes antimotility agents and [[Anesthesia|anesthetics]].
**Drugs affecting [[intestinal]] [[motility]] primarily include antimotility agents and [[Anesthesia|anesthetics]].
***[[Anesthesia|Anesthetic drugs]]: [[Anesthesia|Anesthetic agents]] have a direct [[inhibitory]] effect on the [[intestine|intestinal]] [[motility]]. Long acting [[Anesthesia|anesthetic agents]] such as [[bupivacaine]] are more frequently associated with [[ileus|postopertaive ileus]] as compared to short acting agents such as [[propofol]].
***[[Anesthesia|Anesthetic drugs]]: [[Anesthesia|Anesthetic agents]] have a direct [[inhibitory]] effect on the [[intestine|intestinal]] [[motility]]. Long-acting [[Anesthesia|anesthetic agents]] such as [[bupivacaine]] are more frequently associated with [[ileus|postopertaive ileus]] as compared to short-acting agents such as [[propofol]].
***[[Opiates]]: The use of [[opiates]] for [[pain]] alleviation is not without [[side effects]]. In fact [[opioid]] use has been associated with significant increase in the occurrence of [[ilues|postoperative ileus]]. [[Opioid]] [[medications]] that activate the µ (mu) [[Receptor (biochemistry)|receptors]] have been associated with decreased release of [[acetylcholine]] from [[cholinergic]] [[neurons]], resulting in delayed [[intestinal]] [[motility]]. The most common [[opioid]] [[pain]] [[medication]], [[morphine]] initially activates the [[migrating myoelectric complex]] and later on results in [[atony]] resulting in [[inhibition]] of propulsion and delay in [[intestinal]] transit.
***[[Opiates]]: The use of [[opiates]] for [[pain]] alleviation is not without [[side effects]]. In fact, [[opioid]] use has been associated with significant increase in the occurrence of [[ilues|postoperative ileus]]. [[Opioid]] [[medications]] that activate the µ (mu) [[Receptor (biochemistry)|receptors]] have been associated with decreased release of [[acetylcholine]] from [[cholinergic]] [[neurons]], resulting in delayed [[intestinal]] [[motility]]. The most common [[opioid]] [[pain]] [[medication]], [[morphine]], initially activates the [[migrating myoelectric complex]] and later results in [[atony]], resulting in [[inhibition]] of propulsion and delay in [[intestinal]] transit.
**[[Electrolyte abnormalities]] such as [[hypokalemia]], [[hyponatremia]], [[hypocalcemia]], [[hypomagnesemia]], and [[metabolic acidosis]] may also lead to the development of [[intestine|intestinal]] [[ileus]].
**[[Electrolyte abnormalities]] such as [[hypokalemia]], [[hyponatremia]], [[hypocalcemia]], [[hypomagnesemia]], and [[metabolic acidosis]] may also lead to the development of [[intestine|intestinal]] [[ileus]].


==Genetics==
==Genetics==
There is no detected [[genetic disorder]] related to [[ileus]], nevertheless some cases of [[Intestinal pseudoobstruction|CIPO]] are related to alteration in [[FLNA]] and [[ACTG2]] [[genes]].
There is no detected [[genetic disorder]] related to [[ileus]], nevertheless, some cases of [[Intestinal pseudoobstruction|CIPO]] are related to alteration in [[FLNA]] and [[ACTG2]] [[genes]].
   
   
==Associated Conditions==
==Associated Conditions==
Line 69: Line 69:


==Gross Pathology==
==Gross Pathology==
[[Gross pathology|gross pathologic]]<nowiki/>y, findings of [[ileus]] include:<ref name="pmid18387380">{{cite journal |vauthors=Batke M, Cappell MS |title=Adynamic ileus and acute colonic pseudo-obstruction |journal=Med. Clin. North Am. |volume=92 |issue=3 |pages=649–70, ix |year=2008 |pmid=18387380 |doi=10.1016/j.mcna.2008.01.002 |url=}}</ref>
[[Gross pathology|gross pathologic]]<nowiki/> findings of [[ileus]] include:<ref name="pmid18387380">{{cite journal |vauthors=Batke M, Cappell MS |title=Adynamic ileus and acute colonic pseudo-obstruction |journal=Med. Clin. North Am. |volume=92 |issue=3 |pages=649–70, ix |year=2008 |pmid=18387380 |doi=10.1016/j.mcna.2008.01.002 |url=}}</ref>
*[[Bowel]] contortion
*[[Bowel]] contortion
*Distended [[Small intestine|small]] and [[large intestine]]
*Distended [[Small intestine|small]] and [[large intestine]]

Revision as of 14:50, 14 January 2021

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Akshun Kalia M.B.B.S.[2]

Overview

Ileus is defined as a temporary cessation of intestinal peristalsis in the absence of mechanical obstruction. The pathogenesis of ileus is based on its multifactorial etiology. Ileus is most commonly seen during the postoperative period (usually 3 days after surgery). When a patient undergoes a surgical procedure, it often puts the body under significant stress. It is thought that ileus is the result of a surgical stress-induced inflammatory process, that leads to the release of inflammatory and neuroendocrine mediators (such as nitric oxide, VIP and substance P). Additionally, manipulation of the intestine leads to activation of afferent pathways that travel to the brain stem, which leads to increased autonomic output to the sympathetic neurons and increased secretion of adrenergic neurotransmitters and subsequent decreased intestinal motility. Commonly used analgesics such as opiates and anesthesia may also aggravate the development of ileus. Enteric and autonomic nervous system disturbances can cause a severe form of ilues, called chronic intestinal pseudo-obstruction (CIPO) which may be related to some altered genes. Conditions commonly associated with ileus include diabetes mellitus, hypothyroidism, and hypoparathyroidism. Gross pathology findings of ileus include bowel contortion with a distended small and large intestine. On microscopic histopathological analysis, findings of ileus include inflammatory cells predominantly macrophages and mast cells.

Pathophysiology

Physiology

Neural control of gut.(By Boumphreyfr (Own work) [CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0) or GFDL (http://www.gnu.org/copyleft/fdl.html)], via Wikimedia Commons)

Pathogenesis

Genetics

There is no detected genetic disorder related to ileus, nevertheless, some cases of CIPO are related to alteration in FLNA and ACTG2 genes.

Associated Conditions

Gross Pathology

gross pathologic findings of ileus include:[23]

Microscopic Features

On microscopic histopathological analysis, findings of ileus include inflammatory cells predominantly macrophage and mast cells.

References

  1. ↑ 1.0 1.1 Kalff JC, Schraut WH, Simmons RL, Bauer AJ (1998). "Surgical manipulation of the gut elicits an intestinal muscularis inflammatory response resulting in postsurgical ileus". Ann. Surg. 228 (5): 652–63. PMC 1191570. PMID 9833803.
  2. ↑ 2.0 2.1 Espat NJ, Cheng G, Kelley MC, Vogel SB, Sninsky CA, Hocking MP (1995). "Vasoactive intestinal peptide and substance P receptor antagonists improve postoperative ileus". J. Surg. Res. 58 (6): 719–23. doi:10.1006/jsre.1995.1113. PMID 7540700.
  3. ↑ 3.0 3.1 Kalff JC, Schraut WH, Billiar TR, Simmons RL, Bauer AJ (2000). "Role of inducible nitric oxide synthase in postoperative intestinal smooth muscle dysfunction in rodents". Gastroenterology. 118 (2): 316–27. PMID 10648460.
  4. ↑ Doherty TJ (2009). "Postoperative ileus: pathogenesis and treatment". Vet. Clin. North Am. Equine Pract. 25 (2): 351–62. doi:10.1016/j.cveq.2009.04.011. PMID 19580945.
  5. ↑ Bederman SS, Betsy M, Winiarsky R, Seldes RM, Sharrock NE, Sculco TP (2001). "Postoperative ileus in the lower extremity arthroplasty patient". J Arthroplasty. 16 (8): 1066–70. doi:10.1054/arth.2001.27675. PMID 11740765.
  6. ↑ Lundin C, Sullins KE, White NA and al. Induction of peritoneal adhesions with small intestinal ischaemia and distention in the foal. Equine Vet J 21: 451, 1989
  7. ↑ Vachon AM, Fisher AT. Small intestinal herniation through the epiploic foramen: 53 cases (1987-1993). Equine Vet J 27: 373, 1995
  8. ↑ Barquist E, Bonaz B, Martinez V, Rivier J, Zinner MJ, Taché Y (1996). "Neuronal pathways involved in abdominal surgery-induced gastric ileus in rats". Am. J. Physiol. 270 (4 Pt 2): R888–94. doi:10.1152/ajpregu.1996.270.4.R888. PMID 8967419.
  9. ↑ Di Nardo, G.; Di Lorenzo, C.; Lauro, A.; Stanghellini, V.; Thapar, N.; Karunaratne, T. B.; Volta, U.; De Giorgio, R. (2017). "Chronic intestinal pseudo-obstruction in children and adults: diagnosis and therapeutic options". Neurogastroenterology & Motility. 29 (1): e12945. doi:10.1111/nmo.12945. ISSN 1350-1925.
  10. ↑ Iida H, Ohkubo H, Inamori M, Nakajima A, Sato H (2013). "Epidemiology and clinical experience of chronic intestinal pseudo-obstruction in Japan: a nationwide epidemiologic survey". J Epidemiol. 23 (4): 288–94. PMC 3709546. PMID 23831693.
  11. ↑ Yeung AK, Di Lorenzo C (2012). "Primary gastrointestinal motility disorders in childhood". Minerva Pediatr. 64 (6): 567–84. PMID 23108319.
  12. ↑ Stanghellini V, Cogliandro RF, De Giorgio R, Barbara G, Morselli-Labate AM, Cogliandro L, Corinaldesi R (2005). "Natural history of chronic idiopathic intestinal pseudo-obstruction in adults: a single center study". Clin. Gastroenterol. Hepatol. 3 (5): 449–58. PMID 15880314.
  13. ↑ Hoeffel JC, Senot P, Champigneulle B, Drouin P (November 1980). "Gastric retention and gastric ileus in diabetes mellitus". Radiologe. 20 (11): 540–2. PMID 7208886.
  14. ↑ Rodrigo C, Gamakaranage CS, Epa DS, Gnanathasan A, Rajapakse S (February 2011). "Hypothyroidism causing paralytic ileus and acute kidney injury - case report". Thyroid Res. 4 (1): 7. doi:10.1186/1756-6614-4-7. PMC 3041782. PMID 21303532.
  15. ↑ Lord, Reginald V. N.; Sillin, Lelan F. (2010). "Motility Disorders of the Small Bowel": 17–26. doi:10.1007/978-1-84996-372-5_2.
  16. ↑ Kubota A, Imura K, Yagi M, Kawahara H, Mushiake S, Nakayama M, Kamata S, Okada A (December 1999). "Functional ileus in neonates: Hirschsprung's disease-allied disorders versus meconium-related ileus". Eur J Pediatr Surg. 9 (6): 392–5. doi:10.1055/s-2008-1072290. PMID 10661850.
  17. ↑ EHRENPREIS T (May 1951). "Meconium ileus and Hirschsprung's disease". Acta Paediatr. 40 (3): 227–32. PMID 14837740.
  18. ↑ Izumi Y, Masuda T, Horimasu Y, Nakashima T, Miyamoto S, Iwamoto H, Fujitaka K, Hamada H, Hattori N (October 2017). "Chronic Intestinal Pseudo-obstruction and Orthostatic Hypotension Associated with Small Cell Lung Cancer that Improved with Tumor Reduction after Chemoradiotherapy". Intern. Med. 56 (19): 2627–2631. doi:10.2169/internalmedicine.8574-16. PMC 5658530. PMID 28883237.
  19. ↑ Stengel A, Taché Y (December 2014). "Brain peptides and the modulation of postoperative gastric ileus". Curr Opin Pharmacol. 19: 31–7. doi:10.1016/j.coph.2014.06.006. PMC 4254047. PMID 24999843.
  20. ↑ Deck KB, Silverman H (July 1979). "Leiomyosarcomas of the small intestine". Cancer. 44 (1): 323–5. PMID 455259.
  21. ↑ Moeschl P, Miholic J (January 1989). "[Ileus following radiotherapy: importance and therapeutic aspects of surgery for late radiation injuries of the intestine]". Wien. Klin. Wochenschr. (in German). 101 (2): 84–7. PMID 2916344.
  22. ↑ Ferreira JA, Giani CA, Buiatti JB (October 1965). "[Megacolon. Complications]". Prensa Med Argent (in Spanish; Castilian). 52 (36): 2069–71. PMID 5879587.
  23. ↑ Batke M, Cappell MS (2008). "Adynamic ileus and acute colonic pseudo-obstruction". Med. Clin. North Am. 92 (3): 649–70, ix. doi:10.1016/j.mcna.2008.01.002. PMID 18387380.

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