Gastrointestinal perforation pathophysiology: Difference between revisions

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Revision as of 22:58, 24 December 2017

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

Overview

Anatomy

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. 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). 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 of gastrointestinal perforation

Perforation is full-thickness injury of the bowel wall.
Full-thickness injury and subsequent perforation of the gastrointestinal tract can be due to many causes but main causes are instrumentation during surgery or bowel obstruction. [1-4]
Spontaneous perforation can be related to inflammatory changes or tissues weakened by medications or connective tissue disorders.
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

Acute colonic pseudo-obstruction (Ogilvie's syndrome)

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. [1,11]
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. [12] 13,14].

Spontaneous perforation in neonates

Terminal ileum is the commonest site for spontaneous perforation and may be the jejunum and colon. [1-5]
Focal hemorrhagic necrosis with well-defined margins is observed in contrast to the ischemic and coagulative necrosis seen in necrotizing enterocolitis [4,26].
The bowel appears normal proximal and distal to the perforation. [2,26-29]
The mechanism is not clear yet but may be due to absence of the muscularis propria at the perforation site. [30]

Necrotizing enterocolitis (NEC)

The terminal ileum and colon are the commonest sites for perforation. [5]

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. [7,8][39,40]. Preterm infants have lower concentrations or more immature function of contributing mucosal defense factors than do term infants and adults [4]. 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. [22,74-77].
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.

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 flora normally occurs. [8,21-24].
Ischemic insult to the GI tract has been proposed as a major contributor to NEC. [30,49,50]. Inflammatory mediators induced by ischemia, infectious agents, or mucosal irritants may cause mucosal injury. [22,73]. 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].
Hyperosmolar medications may result in NEC. Oral medications such as theophylline, multivitamins, or phenobarbital contain hypertonic additives that might irritate the intestinal mucosa. [70].

@@ Line 1: / Line 1: @@
 __NOTOC__
 {{CMG}}; {{AE}} {{MAD}}
 {{Gastrointestinal perforation}}
@@ Line 13: / Line 14: @@
 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
+== Pathophysiology of gastrointestinal perforation ==
+* Perforation is full-thickness injury of the bowel wall.
+* Full-thickness injury and subsequent perforation of the gastrointestinal tract can be due to many causes but main causes are instrumentation during surgery or bowel obstruction.  [1-4]
+* Spontaneous perforation can be related to inflammatory changes or tissues weakened by medications or connective tissue disorders.
+* 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
+==== Acute colonic pseudo-obstruction (Ogilvie's syndrome) ====
+* Acute colonic pseudo-obstruction is an acute dilatation of the colon without mechanical obstruction of the flow of intestinal contents.
-Perforation requires full-thickness injury of the bowel wall.
+* The mechanism of perforation in patients with acute colonic pseudo-obstruction is unknown.
-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]
+* Spinal anesthesia and pharmacologic agents are suggested to be the causes due to impairment of autonomic system. [1,11]
-Spontaneous perforation can be related to inflammatory changes or tissues weakened by medications or connective tissue disorders.
+* Interruption of the parasympathetic fibers from S2 to S4 leaves an atonic distal colon and a functional proximal obstruction.
-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 risk of colonic perforation are the absolute diameter of the colon (10 to 12 cm) and the duration of cecal dilation. [12] 13,14].
-As free gas accumulates in the peritoneal cavity, it can compress intra-abdominal veins or lead to respiratory insufficiency by compromising diaphragmatic function [7].
-acute colonic pseudo-obstruction
+==== Spontaneous perforation in neonates ====
-The precise mechanism by which colonic dilation occurs in patients with acute colonic pseudo-obstruction is unknown.
+* Terminal ileum is the commonest site for spontaneous perforation and may be the jejunum and colon. [1-5]
-The association with trauma, spinal anesthesia, and pharmacologic agents suggests an impairment of the autonomic nervous system.
+* Focal hemorrhagic necrosis with well-defined margins is observed in contrast to the ischemic and coagulative necrosis seen in necrotizing enterocolitis [4,26].
-Interruption of the parasympathetic fibers from S2 to S4 leaves an atonic distal colon and a functional proximal obstruction [1,11].
+* The bowel appears normal proximal and distal to the perforation. [2,26-29]
-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 mechanism is not clear yet but may be due to absence of the muscularis propria at the perforation site. [30]
-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
+==== Necrotizing enterocolitis (NEC) ====
+* The terminal ileum and colon are the commonest sites for perforation. [5]
-terminal ileum, but has also been reported in the jejunum and colon [1-5].
+* The pathogenesis of NEC remains unknown but there are many factors for infection such as:
-Focal hemorrhagic necrosis with well-defined margins is observed in contrast to the ischemic and coagulative necrosis seen in necrotizing enterocolitis [4,26].
+* Ninety percent of NEC cases occur in preterm infants due to immaturity of the gastrointestinal tract. [7,8][39,40]. Preterm infants have lower concentrations or more immature function of contributing mucosal defense factors than do term infants and adults [4]. 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. [22,74-77].
-the bowel proximal and distal to the perforation appears normal.
+* 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.
-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.
-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].
-Necrotizing enterocolitis
+* 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 flora normally occurs. [8,21-24].
-The pathology of NEC is primarily due to changes from intestinal infarction [5].
+* Ischemic insult to the GI tract has been proposed as a major contributor to NEC. [30,49,50]. Inflammatory mediators induced by ischemia, infectious agents, or mucosal irritants may cause mucosal injury. [22,73]. 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].
-The specific findings vary and depend upon the progression of the disease and the presence of underlying pathogenic factors.
+* Hyperosmolar medications may result in NEC. Oral medications such as theophylline, multivitamins, or phenobarbital contain hypertonic additives that might irritate the intestinal mucosa.  [70].
-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.