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{{Ileus}}
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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 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==
Ileus is defined as temporary cessation of intestinal peristalsis in the absence of mechanical obstruction. The pathogenesis of ileus is multifactorial. Intestinal peristalsis is primarily regulated by enteric nervous system, autonomic nervous system and interactions with central nervous system. However, certain medications and metabolism products may also alter the normal intestinal equilibrium leading to temporary dysfunction in intestinal movements. With increasing time, intestinal aperistalsis results in accumulation of air and fluid in the bowel lumen.
 
===Normal physiology===
===Physiology===
*The gastrointestinal tract is are 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 (ENS) is also known as intrinsic neural network consists of neurons are located in the walls of GI 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]].  
**ENS includes myenteric plexus (Auerbach's) and submucosal (Meissner's) plexuses.  
**[[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 myenteric plexus is located in the 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 submucosal plexus is located in the 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 (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 ANS consists of sympathetic and parasympathetic nervous system which control GI 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 to visceral smooth muscle activity and increases peristalsis and GI 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 visceral smooth muscle activity and increases peristalsis and GI motility.
**The [[parasympathetic nervous system]] is stimulatory to [[Viscus|visceral]] [[smooth muscle]] activity and increases [[peristalsis]] and [[Gastrointestinal tract]] motility.
**The GI tract visceral sensory afferents located in the parasympathetic ANS while the visceral motor efferents are located in both sympathetic and parasympathetic ANS.  
**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 synapse with enteric nervous system and relay information to 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)]]


===Pathophysiology===
===Pathogenesis===
*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>
*[[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>  
**The risk of postoperative ileus depends upon the type of surgery; with the highest risk associated with colorectal surgery. In fact, post-operative ileus is so common that it is sometimes regarded as a normal sequelae of surgery. Post-operative ileus lasting longer than 3 days is termed as paralytic ileus.  
*[[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 site of the surgery is the most commonly affected part of the GI tract. However, recent research has shown that inflammation of the intestinal muscle may extend from site of surgery to other parts of the 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 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>
**Abdominal incision leads to activation of inhibitory spinal reflexes which results in decreased movements of intestine, as a regulatory mechanism.
**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 painful stimuli  stimulates the spinal afferents that synapse in the spinal cord. In the spinal cord, the pre-vertebral adrenergic neurons are activated which leads to inhibition of intestinal motility via efferent nerves.
**The highest [[Risk factor|risk]] for [[ileus|postoperative ileus]] has been observed with [[Colon (anatomy)|colorectal]] [[surgery|surgeries]].
***Additionally, manipulation of intestine leads to activation of afferent pathways that travel to the brainstem. In turn, the brainstem sends increased autonomic output to the sympathetic neurons located in the inter-medio-lateral column of the thoracic cord. An increased activity of sympathetic neurons results in increased secretion of adrenergic output and decreased intestinal motility.
**In fact, [[ileus|postoperative ileus]] (due to any [[surgery]]) is so common that it is sometimes regarded as a normal [[sequelae]] of [[surgery]].  
**When a patient is undergoing a surgical procedure, it often puts the body under significant stress. This stress may lead to release of inflammatory and neuroendocrine mediators (such as nitric oxide, VIP and substance P) that may result in the development of ileus.
**[[ileus|Postoperative ileus]] that lasts longer than 3 days is termed as [[ileus|paralytic ileus]] or [[ileus|adynamic ileus]].
**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 in initiating the inflammatory process and release of chemical mediators.
**When a [[patient]] undergoes a [[surgery|surgical procedure]], it often puts the body under significant [[Stress (medicine)|stress]].  
**Recent research has shown that inhibition of inflammatory mediators (such as nitric oxide & VIP) may lead to improved gastrointestinal peristalsis and function.  
***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>
*Another chronic and a more severe form of ileus is known as chronic intestinal pseudo-obstruction (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>
***[[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.
**CIPO is a more severe form of ileus resulting from disturbances in autonomic nervous system and smooth muscle cell 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 cause of CIPO can be idiopathic, sporadic, or secondary to metabolic, connective tissue, endocrinological, neurological, and paraneoplastic disorders.
***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>
**CIPO is often due to dysfunction in the innervation of smooth muscle by the interstitial cells of Cajal resulting in partial or complete ineffective intestinal propulsion. However, any condition affecting the autonomic nervous system (both intrinsic or extrinsic), smooth muscle cells and neuromuscular junction may lead to development of CIPO.
***Moreover, [[intestine|intestinal]] distention seen in [[ileus]] is contributed to [[Serosa|serosal]] [[injury]] and may aggravate [[intestine|intestinal]] [[ischemia]].  
**The lack of intestinal propulsive movements may lead to increased intra-bowel pressure. The enhanced intra-bowel pressure may lead to malabsorption and bacterial translocation. Over time, it can progress to present with malnutrition and blood stream infection (sepsis).
***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]].
 
**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]] 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 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>
**[[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>
**[[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 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]].
**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]].
***[[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]].


==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]].
==Associated Conditions==
*[[Diabetes mellitus]]<ref name="pmid7208886">{{cite journal |vauthors=Hoeffel JC, Senot P, Champigneulle B, Drouin P |title=Gastric retention and gastric ileus in diabetes mellitus |journal=Radiologe |volume=20 |issue=11 |pages=540–2 |date=November 1980 |pmid=7208886 |doi= |url=}}</ref>
*[[Hypothyroidism]]<ref name="pmid21303532">{{cite journal |vauthors=Rodrigo C, Gamakaranage CS, Epa DS, Gnanathasan A, Rajapakse S |title=Hypothyroidism causing paralytic ileus and acute kidney injury - case report |journal=Thyroid Res |volume=4 |issue=1 |pages=7 |date=February 2011 |pmid=21303532 |pmc=3041782 |doi=10.1186/1756-6614-4-7 |url=}}</ref>
*[[Hypoparathyroidism]]<ref name="LordSillin2010">{{cite journal|last1=Lord|first1=Reginald V. N.|last2=Sillin|first2=Lelan F.|title=Motility Disorders of the Small Bowel|year=2010|pages=17–26|doi=10.1007/978-1-84996-372-5_2}}</ref>
*[[Hirschsprung disease]]<ref name="pmid10661850">{{cite journal |vauthors=Kubota A, Imura K, Yagi M, Kawahara H, Mushiake S, Nakayama M, Kamata S, Okada A |title=Functional ileus in neonates: Hirschsprung's disease-allied disorders versus meconium-related ileus |journal=Eur J Pediatr Surg |volume=9 |issue=6 |pages=392–5 |date=December 1999 |pmid=10661850 |doi=10.1055/s-2008-1072290 |url=}}</ref><ref name="pmid14837740">{{cite journal |vauthors=EHRENPREIS T |title=Meconium ileus and Hirschsprung's disease |journal=Acta Paediatr |volume=40 |issue=3 |pages=227–32 |date=May 1951 |pmid=14837740 |doi= |url=}}</ref>
*[[Orthostatic hypotension]]<ref name="pmid28883237">{{cite journal |vauthors=Izumi Y, Masuda T, Horimasu Y, Nakashima T, Miyamoto S, Iwamoto H, Fujitaka K, Hamada H, Hattori N |title=Chronic Intestinal Pseudo-obstruction and Orthostatic Hypotension Associated with Small Cell Lung Cancer that Improved with Tumor Reduction after Chemoradiotherapy |journal=Intern. Med. |volume=56 |issue=19 |pages=2627–2631 |date=October 2017 |pmid=28883237 |pmc=5658530 |doi=10.2169/internalmedicine.8574-16 |url=}}</ref>
*[[Brain tumor|CNS neoplasms]]<ref name="pmid24999843">{{cite journal |vauthors=Stengel A, Taché Y |title=Brain peptides and the modulation of postoperative gastric ileus |journal=Curr Opin Pharmacol |volume=19 |issue= |pages=31–7 |date=December 2014 |pmid=24999843 |pmc=4254047 |doi=10.1016/j.coph.2014.06.006 |url=}}</ref>
*[[Leiomyosarcoma|Leiomyosarcomas]]<ref name="pmid455259">{{cite journal |vauthors=Deck KB, Silverman H |title=Leiomyosarcomas of the small intestine |journal=Cancer |volume=44 |issue=1 |pages=323–5 |date=July 1979 |pmid=455259 |doi= |url=}}</ref>
*[[Radiation enteritis]]<ref name="pmid2916344">{{cite journal |vauthors=Moeschl P, Miholic J |title=[Ileus following radiotherapy: importance and therapeutic aspects of surgery for late radiation injuries of the intestine] |language=German |journal=Wien. Klin. Wochenschr. |volume=101 |issue=2 |pages=84–7 |date=January 1989 |pmid=2916344 |doi= |url=}}</ref>
*[[Chagas disease]]<ref name="pmid5879587">{{cite journal |vauthors=Ferreira JA, Giani CA, Buiatti JB |title=[Megacolon. Complications] |language=Spanish; Castilian |journal=Prensa Med Argent |volume=52 |issue=36 |pages=2069–71 |date=October 1965 |pmid=5879587 |doi= |url=}}</ref>


*The other common cause of ileus are the drugs that affect intestinal motility and alteration in electrolyte levels.
==Gross Pathology==
**Drugs affecting intestinal motility primarily includes antimotility agents and other drugs such as opiates, vincristine.
[[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>
**Abdominal conditions such as gastroenteritis and peritonitis may also affect the intestinal motility leading to ileus.
*[[Bowel]] contortion
**Electrolyte abnormalities such as hypokalemia, hypercalcemia, hypermagnesemia, acidosis
*Distended [[Small intestine|small]] and [[large intestine]]


 
==Microscopic Features==
 
On [[Microscopic examination|microscopic]] [[histopathological]] [[analysis]], findings of [[ileus]] include [[inflammatory cells]] predominantly [[macrophage]] and [[mast cells]].
**Anesthetic drugs: Anesthetic agents have a direct inhibitory effect on the intestinal motility. Long acting anesthetic agents such as bupivacaine are more frequently associated with postopertaive ileus as compared to short acting agents such as propofol.
**Opiates: The use of opiates for pain alleviation is not without side effects. Infact opiod use has been asssociated with significant increase in the occurence of postoperative ileus. Opiod medications that activate the µ receptors have been associated with decreased release of acetylcholine from cholinergic neurons, resulting in delayed intestinal motility. The most common opiod 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.
 
*Inhibitory neural [[reflexes]]
*[[Inflammation]]: Ileus may increase adhesion formation, because intestinal segments have more prolonged contact, allowing fibrous adhesions to form, and intestinal distention causes serosal injury and [[ischemia]]. Intestinal distention has been shown to cause adhesions in foals. <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> In a recent survey of ACVS diplomates on drugs to prevent ileus and therefore prevent [[adhesions]]. The drug used in this survey was [[lidocaine]], [[erythromycin]], and cisapride. <ref>Van Hoogmoed and Snyder</ref> Some respondents also mentioned the importance of walking horses postoperatively to stimulate motility. Repeat celiotomy to decompress chronically distended [[small intestine]] and remove fibrinous adhesions is also a useful method of treating ileus and reducing adhesions, and it has been associated with a good outcome. <ref>Vachon AM, Fisher AT. Small intestinal herniation through the epiploic foramen: 53 cases (1987-1993). ''Equine Vet J'' 27: 373, 1995</ref><ref>Southwood LL, Baxter GM. Current concepts in management of abdominal adhesions. ''Vet Clin North Am Eq Prac'' 13:2 415 1997</ref>
*Neurohumoral [[peptides]]


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


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Latest revision as of 14:51, 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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