Gastrointestinal perforation pathophysiology: Difference between revisions

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{{Gastrointestinal perforation}}


==Overview==
==Overview==
[[Perforation]] is full-thickness injury of the bowel wall. Perforation of the [[gastrointestinal tract]] can be due to many causes but main causes are instrumentation during [[surgery]] or [[bowel obstruction]]. Spontaneous perforation can be caused by [[inflammation]], [[connective tissue disorders]], and [[medications]]. [[Terminal ileum]] is the commonest site for spontaneous perforation and may be the [[jejunum]] and [[colon]]. In [[neonatal]] perforation, the [[terminal ileum]] and [[colon]] are the commonest sites for perforation. The pathogenesis of [[Necrotizing enterocolitis|NEC]] remains unknown but there are many factors for infection such as: Ninety percent of NEC cases occur in [[preterm]] infants due to immaturity of the [[gastrointestinal tract]]. Preterm infants have lower concentrations or more immature function of contributing [[mucosal]] defense factors than do term infants and adults. Regarding anatomy of GIT, the [[esophagus]] travels 3 regions of the body: the [[neck]], [[thorax]], and [[abdomen]]. Accordingly, it is divided into 3 parts: [[cervical]], [[thoracic]], and [[abdominal]]. <nowiki/>The gastrointestinal tract has a form of general histology with some differences that reflect the specialization in functional anatomy. The GI tract can be divided into four concentric layers in the following order: [[Mucosal|Mucosa]], [[Submucosa]], [[Muscular|muscular layer]], and [[Adventitia]] or [[serosa]]. Perforation of the [[gastrointestinal tract]] can be due to many causes but main causes are instrumentation during [[surgery]] or [[bowel obstruction]]. Spontaneous perforation can be caused by [[inflammation]], [[connective tissue disorders]], and [[medications]]. With bowel obstruction, perforation occurs [[proximal]] to the obstruction as pressure builds up within [[Bowel|the bowel]], exceeding intestinal [[perfusion pressure]], and leading to [[ischemia]] and subsequently [[necrosis]]. Acute [[colonic pseudo-obstruction]] is an acute dilatation of the [[colon]] without mechanical obstruction of the flow of intestinal contents. The mechanism of perforation in patients with acute colonic pseudo-obstruction is unknown. [[Spinal anesthesia]] and [[Pharmacological|pharmacologic]] agents are suggested to be the causes due to impairment of autonomic system.
== Anatomy of gastrointestinal tract ==
===== Esophagus =====
* The [[esophagus]] is a 25-cm-long vertical [[muscular]] tube that normally remains collapsed and that runs from the [[laryngopharynx]] in the [[neck]] through the [[thorax]] to the [[stomach]] in the [[abdomen]]. 
* The [[esophagus]] travels 3 regions of the body: the [[neck]], [[thorax]], and [[abdomen]]. Accordingly, it is divided into 3 parts: [[cervical]], [[thoracic]], and [[abdominal]].
* The cervical esophagus begins at the level of C6; it is only 5 cm long. In the neck, the esophagus is enclosed in a sheath of [[deep cervical fascia]].
===== Stomach =====
* The [[cardiac notch]] is the acute angle between the left border of the intra-abdominal [[esophagus]] and the gastric fundus.
* The body of the [[stomach]] leads to the [[pyloric antrum]], which joins the [[duodenum]] at the [[pylorus]], lying at the L1-L2 level to the right of the midline.
* The [[stomach]] has a shorter [[lesser curvature]] and a longer [[greater curvature]]. The [[lesser curvature]] is attached to the undersurface of the liver by [[lesser omentum]] and the [[greater curvature]] is attached to the transverse colon by [[greater omentum]].
===== Intestine =====
* The lower gastrointestinal tract includes most of the small intestine and all of the large intestine.
* The small bowel is anatomically divided into three portions: the duodenum, jejunum, and ileum.
* '''[[Duodenum]]''': It is about 20–25 cm long which receives [[Chyme|chymefrom]] the stomach, together with [[pancreatic]] juice containing [[Digestive enzyme|digestive enzymes]] and bile from the [[Gallbladder|gall bladder]].
* The [[duodenum]] contains [[Brunner's glands]], which produce a mucus-rich [[alkaline]] secretion containing [[bicarbonate]]. These secretions, in combination with bicarbonate from the [[pancreas]], neutralizes the stomach acids contained in the [[chyme]].
* '''[[Jejunum]]:''' This is the midsection of the [[small intestine]], connecting the [[duodenum]] to the [[ileum]]. It is about 2.5 m long, and contains the circular folds, and [[villi]] that increase its surface area. Products of digestion are absorbed into the [[bloodstream]] here.
* '''[[Ileum]]:''' The final section of the small intestine. It is about 3 m long, and contains [[villi]] similar to the [[jejunum]]. It absorbs mainly [[vitamin B12]] and [[Bile acid|bile acids]], as well as any other remaining nutrients.
* The [[large intestine]] is further divided into:
*# [[Cecum]] and [[appendix]]
*# [[Ascending colon]]
*# [[Right colic flexure]]
*# [[Transverse colon]]
*# [[Left colic flexure]]
*# [[Descending colon]]
*# [[Sigmoid colon]]
*# [[Rectum]]
*# [[Anus]]
[[File:Blausen 0432 GastroIntestinalSystem.png|300px|center|thumb|Gastrointestinal tract, source: By BruceBlaus. When using this image in external sources it can be cited as:Blausen.com staff (2014). "Medical gallery of Blausen Medical 2014". WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.010. ISSN 2002-4436. - Own work, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=29294591]]
== Histology of gastrointestinal tract ==
The gastrointestinal tract has a form of general histology with some differences that reflect the specialization in functional anatomy. 
The GI tract can be divided into four concentric layers in the following order:
* [[Mucosal|Mucosa]]
* [[Submucosa]]
* [[Muscular|Muscular layer]]
* [[Adventitia]] or [[serosa]]
===== Mucosa =====
* The [[Mucosal|mucosa]] is the innermost layer of the gastrointestinal tract. that is surrounding the [[lumen]].
* This layer comes in direct contact with [[chyme]]. The [[mucosa]] is made up of:
* [[Epithelium]]: innermost layer. Responsible for most digestive, absorptive and secretory processes.
* [[Lamina propria]]: a layer of connective tissue. Unusually cellular compared to most connective tissue
* [[Muscularis mucosae]]: a thin layer of smooth muscle that aids the passing of material and enhances the interaction between the epithelial layer and the contents of the lumen by agitation and peristalsis.
The mucosae are highly specialized in each organ of the gastrointestinal tract to deal with the different conditions. The most variation is seen in the epithelium.
===== Submucosa =====
The [[submucosa]] consists of a dense irregular layer of connective tissue with large [[blood vessels]], [[lymphatics]], and nerves branching into the [[mucosa]] and [[muscularis externa]]. It contains the [[submucosal plexus]], an enteric nervous plexus, situated on the inner surface of the ''[[muscularis externa]]''.
===== Muscular layer =====
* The [[Muscular|muscular layer]] consists of an inner circular layer and a [[longitudinal]] outer layer.
* The layers are not truly longitudinal or circular, rather the layers of muscle are helical with different pitches. The inner circular is helical with a steep pitch and the outer longitudinal is helical with a much shallower pitch.
* Between the two muscle layers is the myenteric plexus.
* The [[Gut tract|gut]] has intrinsic peristaltic activity due to its self-contained enteric nervous system. The rate can be modulated by the rest of the [[autonomic nervous system]].
===== Adventitia and serosa =====
* The outermost layer of the gastrointestinal tract consists of several layers of [[connective tissue]].
* Intraperitoneal parts of the GI tract are covered with [[serosa]]. These include most of the [[stomach]], first part of the [[duodenum]], all of the [[small intestine]], [[Cecum|caecum]] and [[appendix]], [[transverse colon]], [[sigmoid colon]] and [[rectum]].
* In these sections of the gut there is clear boundary between the gut and the surrounding tissue. These parts of the tract have a [[mesentery]].
* [[Retroperitoneal]] parts are covered with [[Adventitial|adventitia]]. They blend into the surrounding tissue and are fixed in position.
* These include the [[esophagus]], [[pylorus]] of the [[stomach]], distal [[duodenum]], [[ascending colon]], [[descending colon]] and [[anal canal]].
[[File:Layers of the GI Tract numbers.png|center|300px|thumb|Layers of GIT tract wall, source: By Goran tek-en - Own workThis file was derived from:2402 Layers of the Gastrointestinal Tract.jpg, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=31413107]]


Anatomy
== Pathophysiology of gastrointestinal perforation ==
* [[Perforation]] is full-thickness injury of the bowel wall.
* Perforation of the [[gastrointestinal tract]] can be due to many causes but main causes are instrumentation during [[surgery]] or [[bowel obstruction]].<ref name="pmid16045583">{{cite journal| author=Bona D, Incarbone R, Chella B, Vecchi M, Bonavina L| title=Heartburn and multiple-site foregut perforations as primary manifestation of Crohn's disease. | journal=Dis Esophagus | year= 2005 | volume= 18 | issue= 3 | pages= 199-201 | pmid=16045583 | doi=10.1111/j.1442-2050.2005.00468.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16045583  }}</ref>
* Spontaneous perforation can be caused by [[inflammation]], [[connective tissue disorders]], and [[medications]].
* With bowel obstruction, perforation occurs [[proximal]] to the obstruction as pressure builds up within [[Bowel|the bowel]], exceeding intestinal [[perfusion pressure]], and leading to [[ischemia]] and subsequently [[necrosis]].<ref name="pmid18045463">{{cite journal| author=Browning LE, Taylor JD, Clark SK, Karanjia ND| title=Jejunal perforation in gallstone ileus - a case series. | journal=J Med Case Rep | year= 2007 | volume= 1 | issue=  | pages= 157 | pmid=18045463 | doi=10.1186/1752-1947-1-157 | pmc=2222670 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18045463  }}</ref> 


The esophagus begins in the neck and descends adjacent to the aorta through the esophageal hiatus to the gastroesophageal junction (figure 1). Perforations of the esophagus due to foreign body ingestion usually occur at the narrow areas of the esophagus such as the cricopharyngeus muscle, aortic arch, left main stem bronchus, and lower esophageal sphincter.
==== Acute colonic pseudo-obstruction (Ogilvie's syndrome) ====
The stomach is located in the left upper quadrant of the abdomen but can occupy other areas of the abdomen, depending upon its degree of distention, phase of diaphragmatic excursion, and the position of the individual. Anteriorly, the stomach is adjacent to the left lobe of the liver, diaphragm, colon, and anterior abdominal wall. Posteriorly, the stomach is in close proximity to the pancreas, spleen, left kidney and adrenal gland, splenic artery, left diaphragm, transverse mesocolon, and colon (figure 2 and figure 3).
* Acute [[colonic pseudo-obstruction]] is an acute dilatation of the [[colon]] without mechanical obstruction of the flow of intestinal contents.
When the normal anatomy of the esophagus or stomach has been disturbed, such as after Roux-en-Y gastric bypass, great care should be taken with nasogastric intubation [9].
The small bowel is anatomically divided into three portions: the duodenum, jejunum, and ileum. The duodenum is retroperitoneal in its second and third portion and forms a loop around the pancreas. The jejunum is in continuity with the fourth portion of the duodenum beginning at the ligament of Treitz; there are no true lines of demarcation that separate the jejunum from ileum. The ileocecal valve marks the beginning of the colon in the right lower quadrant. The appendix hangs freely from the cecum, which is the first portion of the colon (figure 3). Foreign bodies that perforate the small intestines most commonly occur at sites of gastrointestinal immobility (eg, duodenum).
The ascending and descending colon are retroperitoneal, while the transverse colon, which extends from the hepatic flexure to the splenic flexure, is intraperitoneal. The sigmoid colon continues from the descending colon, ending where the teniae converge to form the rectum. The anterior upper two-thirds of the rectum are located intraperitoneally and the remainder is extraperitoneal. The rectum lies anterior to the three inferior sacral vertebrae, the coccyx, and sacral vessels and is posterior to the bladder in men and the vagina in women. Foreign bodies that perforate the colon tend to occur at transition zones from an intraperitoneal location to fixed, retroperitoneal locations such as the cecum.


Pathophysiology
* The mechanism of perforation in patients with acute colonic pseudo-obstruction is unknown.
* [[Spinal anesthesia]] and [[Pharmacological|pharmacologic]] agents are suggested to be the causes due to impairment of autonomic system.<ref name="pmid19496201">{{cite journal| author=Akbulut S, Cakabay B, Ozmen CA, Sezgin A, Sevinc MM| title=An unusual cause of ileal perforation: report of a case and literature review. | journal=World J Gastroenterol | year= 2009 | volume= 15 | issue= 21 | pages= 2672-4 | pmid=19496201 | doi= | pmc=2691502 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19496201  }}</ref>
* Interruption of the parasympathetic fibers from [[S2]] to [[S4]] leaves an atonic distal colon and a functional proximal obstruction. 
* The risk of [[Colonic Perforation|colonic perforation]] are the absolute diameter of the [[colon]] (10 to 12 cm) and the duration of [[Cecum|cecal]] dilation.<ref name="pmid3180976">{{cite journal| author=Sloyer AF, Panella VS, Demas BE, Shike M, Lightdale CJ, Winawer SJ et al.| title=Ogilvie's syndrome. Successful management without colonoscopy. | journal=Dig Dis Sci | year= 1988 | volume= 33 | issue= 11 | pages= 1391-6 | pmid=3180976 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3180976  }}</ref>


Perforation requires full-thickness injury of the bowel wall.  
==== Spontaneous perforation in neonates ====
Full-thickness injury and subsequent perforation of the gastrointestinal tract can be due to a variety of etiologies, commonly instrumentation or surgery, and bowel obstruction.  [1-4]  
* [[Terminal ileum]] is the commonest site for spontaneous perforation and may be the [[jejunum]] and [[colon]].<ref name="pmid17828407">{{cite journal| author=Drewett MS, Burge DM| title=Recurrent neonatal gastro-intestinal problems after spontaneous intestinal perforation. | journal=Pediatr Surg Int | year= 2007 | volume= 23 | issue= 11 | pages= 1081-4 | pmid=17828407 | doi=10.1007/s00383-007-1999-2 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17828407 }}</ref>
Spontaneous perforation can be related to inflammatory changes or tissues weakened by medications or connective tissue disorders.  
* Focal hemorrhagic [[necrosis]] with well-defined margins is observed in contrast to the [[Ischemia|ischemic]] and [[coagulative necrosis]] seen in [[necrotizing enterocolitis]].<ref name="pmid18060416">{{cite journal| author=Holland AJ| title=Comment on Kubota et al.: focal intestinal perforation in extremely-low-birth-weight neonates: etiological consideration from histological findings. | journal=Pediatr Surg Int | year= 2008 | volume= 24 | issue= 3 | pages= 387 | pmid=18060416 | doi=10.1007/s00383-007-2076-6 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18060416  }}</ref>
With bowel obstruction, perforation occurs proximal to the obstruction as pressure builds up within the bowel, exceeding intestinal perfusion pressure, and leading to ischemia and subsequently necrosis. 5,6 .
* The [[bowel]] appears normal proximal and distal to the perforation.
As free gas accumulates in the peritoneal cavity, it can compress intra-abdominal veins or lead to respiratory insufficiency by compromising diaphragmatic function [7].  
* The mechanism is not clear yet but may be due to absence of the [[Muscularis externa|muscularis propria]] at the perforation site.<ref name="pmid18030227">{{cite journal| author=Gordon PV, Herman AC, Marcinkiewicz M, Gaston BM, Laubach VE, Aschner JL| title=A neonatal mouse model of intestinal perforation: investigating the harmful synergism between glucocorticoids and indomethacin. | journal=J Pediatr Gastroenterol Nutr | year= 2007 | volume= 45 | issue= 5 | pages= 509-19 | pmid=18030227 | doi=10.1097/MPG.0b013e3181558591 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18030227  }}</ref>


acute colonic pseudo-obstruction
==== Necrotizing enterocolitis (NEC) ====
The precise mechanism by which colonic dilation occurs in patients with acute colonic pseudo-obstruction is unknown.  
* The [[terminal ileum]] and [[colon]] are the commonest sites for perforation.<ref name="pmid11061777">{{cite journal| author=Lee SK, McMillan DD, Ohlsson A, Pendray M, Synnes A, Whyte R et al.| title=Variations in practice and outcomes in the Canadian NICU network: 1996-1997. | journal=Pediatrics | year= 2000 | volume= 106 | issue= 5 | pages= 1070-9 | pmid=11061777 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11061777  }}</ref>
The association with trauma, spinal anesthesia, and pharmacologic agents suggests an impairment of the autonomic nervous system.
Interruption of the parasympathetic fibers from S2 to S4 leaves an atonic distal colon and a functional proximal obstruction [1,11].
In patients with acute colonic pseudo-obstruction, increasing colonic diameter accelerates the rise in tension on the colonic wall, increasing the risk of colonic ischemia and perforation.  
The risk of colonic perforation increases when cecal diameter exceeds 10 to 12 cm and when the distention has been present for greater than six days [12]. The duration of dilation is probably more important than the absolute diameter of the colon [13,14].
atrophic visceral myopathy with an extremely thin colonic wall, atrophic circular, and longitudinal muscularis propria without inflammation or fibrosis, and unaffected ganglion cells and myenteric plexus [15]. [15,16].


Spontaneous perforation in neonates
* The pathogenesis of [[Necrotizing enterocolitis|NEC]] remains unknown but there are many factors for infection such as:
* Ninety percent of NEC cases occur in [[preterm]] infants due to immaturity of the [[gastrointestinal tract]].<ref name="pmid1250656">{{cite journal| author=Book LS, Herbst JJ, Jung AL| title=Carbohydrate malabsorption in necrotizing enterocolitis. | journal=Pediatrics | year= 1976 | volume= 57 | issue= 2 | pages= 201-4 | pmid=1250656 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1250656  }}</ref>
* Preterm infants have lower concentrations or more immature function of contributing [[mucosal]] defense factors than do term infants and adults.
* Preterm infants have high levels of [[cytokines]] such as [[Tumour necrosis factor|tumor necrosis factor]], [[IL-1]], [[IL-6]], [[IL-8]], [[IL-10]], [[IL-12]], and IL-18 that increase vascular permeability and attract [[inflammatory cells]].
* Human milk is more protective against NEC in preterm infants than formulas. The mucus coat of the [[intestine]] is less affected by human milk than formulas. [[Growth factors]] within human milk repair disturbed layers in intestine.


terminal ileum, but has also been reported in the jejunum and colon [1-5].
* Bacterial colonization is believed to play a pivotal role in the development of NEC. Rapid colonization of the intestinal tract by commensal bacteria from the maternal [[Rectovaginal fascia|rectovaginal]] [[flora]] normally occurs.
Focal hemorrhagic necrosis with well-defined margins is observed in contrast to the ischemic and coagulative necrosis seen in necrotizing enterocolitis [4,26].  
* [[Ischemia|Ischemic]] insult to the GI tract has been proposed as a major contributor to NEC.
the bowel proximal and distal to the perforation appears normal.
* Inflammatory mediators induced by [[ischemia]], [[infectious agents]], or mucosal irritants may cause mucosal injury.  
Although thinning or absence of the muscularis propria at the perforation site has been reported in several cases [2,26-29], it is unclear whether these changes are involved in the pathogenesis of SIP.
* Circulatory events that have been attrubuted in the development of NEC include [[perinatal asphyxia]], recurrent [[apnea]], [[hypoxia]] from severe [[Acute respiratory distress syndrome|respiratory distress syndrome]], [[hypotension]], [[congenital heart disease]], [[patent ductus arteriosus]], [[heart failure]], [[Umbilical arterial catheter|umbilical arterial catheterization]], [[anemia]], [[polycythemia]], and [[red blood cell]] and [[Exchange transfusion|exchange transfusions]].  
A role for nitric oxide synthase (NOS) has been suggested based upon a single study of a NOS knock-out mouse model that demonstrated ileal perforation with exposure to indomethacin and/or dexamethasone [30].
* Hyperosmolar medications may result in NEC. Oral medications such as [[theophylline]], [[multivitamins]], or phenobarbital contain hypertonic additives that might irritate the [[intestinal mucosa]].<ref name="pmid12496235">{{cite journal| author=Farrugia MK, Morgan AS, McHugh K, Kiely EM| title=Neonatal gastrointestinal perforation. | journal=Arch Dis Child Fetal Neonatal Ed | year= 2003 | volume= 88 | issue= 1 | pages= F75 | pmid=12496235 | doi= | pmc=1756016 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12496235  }}</ref>


Necrotizing enterocolitis
==References==
The pathology of NEC is primarily due to changes from intestinal infarction [5].
{{Reflist|2}}
The specific findings vary and depend upon the progression of the disease and the presence of underlying pathogenic factors.
The terminal ileum and colon are involved in the majority of cases
PATHOGENESIS
The pathogenesis of NEC remains unknown, but it is probably a heterogeneous disease resulting from multiple factors that result in mucosal injury in a susceptible host.
Prematurity
Approximately 90 percent of NEC cases occur in preterm infants who have been fed enterally. The following factors due to immaturity of the gastrointestinal (GI) tract and immune system are thought to predispose the preterm infant to NEC (figure 2) [7,8].
●Immature mucosal barrier with increased permeability and bacterial penetration into the intestinal wall (translocation) compared with term infants.
Mucosal defense in the gut is mediated by several interrelated components, some of which provide a physical barrier and others a biochemical and immunologic barrier [39,40]. Factors that contribute to innate resistance include luminal pH, enzymes, mucins, epithelial barriers, and gut motility, as well as nonspecific antimicrobial factors, such as lactoferrin and lysozyme.
Preterm infants have lower concentrations or more immature function of contributing mucosal defense factors than do term infants and adults [4].
Human milk
Human milk, compared with formula, is more protective against NEC in preterm infants.
Human milk feeding is associated with a lower intestinal pH to facilitate the growth of nonpathogenic bacteria, which counteract pathogenic bacteria. The mucus coat of the intestine is less affected by human milk, and growth factors within human milk (such as epidermal growth factors [EGFs]) repair disruptions in this layer.
Microbial colonization
Bacterial colonization is believed to play a pivotal role in the development of NEC because NEC does not occur in utero when the gut is sterile. After delivery, rapid colonization of the intestinal tract by commensal bacteria from the maternal rectovaginal flora normally occurs. These bacteria play a symbiotic role with the intestine through toll-like receptors by regulating the expression of genes involved in intestinal physiology, postnatal maturation, and function (eg, barrier, digestion, angiogenesis, and production of IgA), and protection against more pathologic organisms [8,21-24].
Increasingly, there is good evidence that this process of commensal bacterial colonization is disrupted in infants who develop NEC [24-27]. Several studies have shown an association between NEC and intestinal noncommensal bacterial overgrowth, which may cause mucosal injury by affecting intestinal maturation, increasing inflammation and apoptosis, and releasing endotoxins. This pathological process occurs in the absence of a primary infection [8].
Inflammatory mediators induced by ischemia, infectious agents, or mucosal irritants may further aggravate mucosal injury [22,73]. These soluble inflammatory cytokines, including tumor necrosis factor (TNF), interleukins (IL-1, IL-6, IL-8, IL-10, IL-12, and IL-18), and platelet activating factor (PAF), increase vascular permeability and attract inflammatory cells. Levels of these cytokines are increased in preterm infants with NEC and correlate with the severity of the disease [22,74-77].
Chorioamnionitis is an antenatal proinflammatory process involving the placenta and fetal membrane, which may play a contributing role in the pathogenesis of NEC. However, data are inconclusive whether it is a significant clinical risk factor, as illustrated by a systematic review of the literature [81]. The following findings were noted:
Circulatory instability
Ischemic insult to the GI tract has been proposed as a major contributor to NEC, although most infants with NEC have not had an obvious perinatal hypoxic-ischemic event [30,49,50]. Circulatory events that have been implicated in the development of NEC include perinatal asphyxia [51], recurrent apnea, hypoxia from severe respiratory distress syndrome, hypotension, congenital heart disease [52,53], patent ductus arteriosus, heart failure, umbilical arterial catheterization, anemia, polycythemia [54,55], and red blood cell [56-58] and exchange transfusions [59]. A diminished blood supply to the gut may contribute to the pathogenesis of NEC in infants exposed to cocaine [60].
Drugs
The administration of hyperosmolar medications and/or formulas can cause mucosal injury and may result in NEC [70]. Oral medications such as theophylline, multivitamins, or phenobarbital contain hypertonic additives that might irritate the intestinal mucosa. Instillation of hyperosmolar contrast agents into the bowel for diagnostic radiographic studies also can cause mucosal injury because of fluid shifts, bowel distention, and ischemia. Isotonic contrast agents should be used to avoid this complication. Hyperosmolar formulas, such as those concentrated above recommended strengths or containing multiple additives, should be avoided in the first few weeks after birth.

Latest revision as of 20:31, 1 March 2018


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

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Overview

Perforation is full-thickness injury of the bowel wall. Perforation of the gastrointestinal tract can be due to many causes but main causes are instrumentation during surgery or bowel obstruction. Spontaneous perforation can be caused by inflammation, connective tissue disorders, and medications. Terminal ileum is the commonest site for spontaneous perforation and may be the jejunum and colon. In neonatal perforation, the terminal ileum and colon are the commonest sites for perforation. The pathogenesis of NEC remains unknown but there are many factors for infection such as: Ninety percent of NEC cases occur in preterm infants due to immaturity of the gastrointestinal tract. Preterm infants have lower concentrations or more immature function of contributing mucosal defense factors than do term infants and adults. Regarding anatomy of GIT, the esophagus travels 3 regions of the body: the neck, thorax, and abdomen. Accordingly, it is divided into 3 parts: cervical, thoracic, and abdominal. The gastrointestinal tract has a form of general histology with some differences that reflect the specialization in functional anatomy. The GI tract can be divided into four concentric layers in the following order: Mucosa, Submucosa, muscular layer, and Adventitia or serosa. Perforation of the gastrointestinal tract can be due to many causes but main causes are instrumentation during surgery or bowel obstruction. Spontaneous perforation can be caused by inflammation, connective tissue disorders, and medications. With bowel obstruction, perforation occurs proximal to the obstruction as pressure builds up within the bowel, exceeding intestinal perfusion pressure, and leading to ischemia and subsequently necrosis. Acute colonic pseudo-obstruction is an acute dilatation of the colon without mechanical obstruction of the flow of intestinal contents. The mechanism of perforation in patients with acute colonic pseudo-obstruction is unknown. Spinal anesthesia and pharmacologic agents are suggested to be the causes due to impairment of autonomic system.

Anatomy of gastrointestinal tract

Esophagus
Stomach
Intestine
Gastrointestinal tract, source: By BruceBlaus. When using this image in external sources it can be cited as:Blausen.com staff (2014). "Medical gallery of Blausen Medical 2014". WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.010. ISSN 2002-4436. - Own work, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=29294591


Histology of gastrointestinal tract

The gastrointestinal tract has a form of general histology with some differences that reflect the specialization in functional anatomy. 

The GI tract can be divided into four concentric layers in the following order:

Mucosa
  • The mucosa is the innermost layer of the gastrointestinal tract. that is surrounding the lumen.
  • This layer comes in direct contact with chyme. The mucosa is made up of:
  • Epithelium: innermost layer. Responsible for most digestive, absorptive and secretory processes.
  • Lamina propria: a layer of connective tissue. Unusually cellular compared to most connective tissue
  • Muscularis mucosae: a thin layer of smooth muscle that aids the passing of material and enhances the interaction between the epithelial layer and the contents of the lumen by agitation and peristalsis.

The mucosae are highly specialized in each organ of the gastrointestinal tract to deal with the different conditions. The most variation is seen in the epithelium.

Submucosa

The submucosa consists of a dense irregular layer of connective tissue with large blood vessels, lymphatics, and nerves branching into the mucosa and muscularis externa. It contains the submucosal plexus, an enteric nervous plexus, situated on the inner surface of the muscularis externa.

Muscular layer
  • The muscular layer consists of an inner circular layer and a longitudinal outer layer.
  • The layers are not truly longitudinal or circular, rather the layers of muscle are helical with different pitches. The inner circular is helical with a steep pitch and the outer longitudinal is helical with a much shallower pitch.
  • Between the two muscle layers is the myenteric plexus.
  • The gut has intrinsic peristaltic activity due to its self-contained enteric nervous system. The rate can be modulated by the rest of the autonomic nervous system.
Adventitia and serosa
Layers of GIT tract wall, source: By Goran tek-en - Own workThis file was derived from:2402 Layers of the Gastrointestinal Tract.jpg, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=31413107

Pathophysiology of gastrointestinal perforation 

Acute colonic pseudo-obstruction (Ogilvie's syndrome)

  • The mechanism of perforation in patients with acute colonic pseudo-obstruction is unknown.
  • Spinal anesthesia and pharmacologic agents are suggested to be the causes due to impairment of autonomic system.[3]
  • Interruption of the parasympathetic fibers from S2 to S4 leaves an atonic distal colon and a functional proximal obstruction.
  • The risk of colonic perforation are the absolute diameter of the colon (10 to 12 cm) and the duration of cecal dilation.[4]

Spontaneous perforation in neonates

Necrotizing enterocolitis (NEC)

  • The pathogenesis of NEC remains unknown but there are many factors for infection such as:
  • Ninety percent of NEC cases occur in preterm infants due to immaturity of the gastrointestinal tract.[9]
  • Preterm infants have lower concentrations or more immature function of contributing mucosal defense factors than do term infants and adults.
  • Preterm infants have high levels of cytokines such as tumor necrosis factor, IL-1, IL-6, IL-8, IL-10, IL-12, and IL-18 that increase vascular permeability and attract inflammatory cells.
  • Human milk is more protective against NEC in preterm infants than formulas. The mucus coat of the intestine is less affected by human milk than formulas. Growth factors within human milk repair disturbed layers in intestine.

References

  1. ↑ Bona D, Incarbone R, Chella B, Vecchi M, Bonavina L (2005). "Heartburn and multiple-site foregut perforations as primary manifestation of Crohn's disease". Dis Esophagus. 18 (3): 199–201. doi:10.1111/j.1442-2050.2005.00468.x. PMID 16045583.
  2. ↑ Browning LE, Taylor JD, Clark SK, Karanjia ND (2007). "Jejunal perforation in gallstone ileus - a case series". J Med Case Rep. 1: 157. doi:10.1186/1752-1947-1-157. PMC 2222670. PMID 18045463.
  3. ↑ Akbulut S, Cakabay B, Ozmen CA, Sezgin A, Sevinc MM (2009). "An unusual cause of ileal perforation: report of a case and literature review". World J Gastroenterol. 15 (21): 2672–4. PMC 2691502. PMID 19496201.
  4. ↑ Sloyer AF, Panella VS, Demas BE, Shike M, Lightdale CJ, Winawer SJ; et al. (1988). "Ogilvie's syndrome. Successful management without colonoscopy". Dig Dis Sci. 33 (11): 1391–6. PMID 3180976.
  5. ↑ Drewett MS, Burge DM (2007). "Recurrent neonatal gastro-intestinal problems after spontaneous intestinal perforation". Pediatr Surg Int. 23 (11): 1081–4. doi:10.1007/s00383-007-1999-2. PMID 17828407.
  6. ↑ Holland AJ (2008). "Comment on Kubota et al.: focal intestinal perforation in extremely-low-birth-weight neonates: etiological consideration from histological findings". Pediatr Surg Int. 24 (3): 387. doi:10.1007/s00383-007-2076-6. PMID 18060416.
  7. ↑ Gordon PV, Herman AC, Marcinkiewicz M, Gaston BM, Laubach VE, Aschner JL (2007). "A neonatal mouse model of intestinal perforation: investigating the harmful synergism between glucocorticoids and indomethacin". J Pediatr Gastroenterol Nutr. 45 (5): 509–19. doi:10.1097/MPG.0b013e3181558591. PMID 18030227.
  8. ↑ Lee SK, McMillan DD, Ohlsson A, Pendray M, Synnes A, Whyte R; et al. (2000). "Variations in practice and outcomes in the Canadian NICU network: 1996-1997". Pediatrics. 106 (5): 1070–9. PMID 11061777.
  9. ↑ Book LS, Herbst JJ, Jung AL (1976). "Carbohydrate malabsorption in necrotizing enterocolitis". Pediatrics. 57 (2): 201–4. PMID 1250656.
  10. ↑ Farrugia MK, Morgan AS, McHugh K, Kiely EM (2003). "Neonatal gastrointestinal perforation". Arch Dis Child Fetal Neonatal Ed. 88 (1): F75. PMC 1756016. PMID 12496235.
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