Bowel obstruction pathophysiology

It is thought that bowel obstruction may occur functionally as a result of abnormal anatomy or impairment of the autonomic nervous system or mechanically, which may occur acutely or chronically. An obstruction that occurs functionally or mechanically can be classified as extrinsic, intrinsic or intraluminal including tumors, strictures and foreign bodies. Excessive bowel distention can lead to ischemia, necrosis and perforation. A functional obstruction may be due to a number of genetic defects including trisomy 21 and the RET proto-oncogene mutation. Associated conditions include post-operative adhesions, complicated hernias, gastrointestinal cancers and endometriosis. Gross pathology may demonstrate adhesions, narrow lumens and volvulus. Microscopic pathology may show evidence of fibrosis, necrosis and ischemia.

• Normally, the small intestine functions to pass gastrointestinal contents for absorption. The large surface area provided by the villi, plicae circularis and valvulae conniventes (Kerckring folds) allow for this exchange to happens.^[1][2][3]
• In addition, the small bowel is free of microbes, in comparison to the large bowel that houses commensal flora that facilitate digestion and vitamin synthesis, namely vitamin K.
• Continuous transit throughout the bowel is important to prevent bowel dilatation, ischemia and necrosis.
• Obstruction of the bowel can occur functionally (due to abnormal anatomy) or mechanically, which can be acute or chronic.
• Obstructions that occur functionally or mechanically, can be classified as extrinsic, intrinsic or intraluminal obstruction:
  • Extrinsic obstructions can happen as the result of a tumor, post-operative adhesions or hernias.
  • Intrinsic obstructions can happen as a result of a tumor, stenosis or hematoma.
  • Intraluminal obstructions are sometimes referred to intramural obstructions and include, foreign bodies, intussusception and gallstones.
• However an obstruction occurs, proximal to the blockage there will be a dilated segment, whilst distal to the obstruction the segment of bowel will collapse as the contents cannot pass.
• Bowel distention occurs as air that is swallowed and gases produced by the commensal flora begins to accumulate.
• Eventually, the bowel wall becomes edematous and fluid gathers inside the lumen of the bowel. This disrupts the absorptive properties of the gut.
• Some fluid may be lost to the peritoneal cavity, moreover, the proximal obstruction can cause severe emesis which will lead to further loss of fluid that contains vital electrolytes. This process may result in metabolic alkalosis and hypovolemia.
• The obstruction also causes the normally sterile proximal bowel to become overgrown with bacteria and vomitus may contain feces.
• When a massive dilation of the bowel occurs, the vessels that perfuse the walls of the bowel become compressed and will not be able to supply the bowel loop adequately, which leads to ischemia.
• If ischemia is not reversed within a timely manner, then necrosis, volvulus and perforation may ensue.

• The association of spinal anaesthesias, drugs and nervous trauma has lead to the understanding that Ogilvie syndrome (colonic dilatation without true obstruction) may be caused by impairment of the autonomic nervous system.^[4][5][6]
• Damage to the parasympathetic fibers of S2 – S4 causes the distal colon to become atonic and become obstructed proximally.
• However, the exact mechanism is unknown, especially in patients who present with this syndrome without an obvious injury to the parasympathetic nerves.
• Acute colonic pseudo-obstruction occurs when the colon’s diameter rises quickly, which increases the tension in the colonic wall, leading to colonic ischemia and possibly, perforation with a diameter exceeding 10 – 12cm.
• A rare case of Ogilvie syndrome showed atrophic myopathy with a thinned out colonic wall, despite a perfectly intact myenteric plexus and unaffected ganglion cells, with no evidence of fibrosis or inflammation.

• The majority of paralytic (adynamic) ileus cases occur after major abdominal surgery, such as hysterectomy.
• Paralytic ileus is thought to occur with manipulation and trauma of the intestinal tract.
• Post operative dysmotility is associated with inflammation, impaired neural reflexes and the release of neural hormone peptides.
  • Inflammation:^[7]
    • Intestinal manipulation leads to intestinal ischemia, and shifting of endogenous cellular danger molecules and cytokines away from the site of trauma.
    • Leukocytic infiltration, macrophage and mast cell stimulation commences and causes muscular dysfunction, and therefore inflammation in the manipulated segment.
  • Neural reflexes:^[7]
    • Inhibitory sympathetic neural reflexes increase due to noxious spinal afferent signals, therefore, the use of epidural local anesthetics or topical capsaicin is encouraged to prevent paralytic ileus.^[8]
  • Neurohormonal peptides:^[9][10]
    • Inhibitory neurotransmitters are released and cause the gut motility to slow down.
    • Inhibitory neurotransmitters include, nitric oxide, vasoactive intestinal polypeptide, and substance P.

The development of congenital bowel obstruction is the result of multiple genetic mutations:^{[11][12][13][14]}

• Chromosome 21 trisomy can lead to imperforate anus and duodenal atresias in 50% of babies with down syndrome.
• Chromosome 7 mutation locus leads to cystic fibrosis that predisposes to a thickened meconium which may lead to an intraluminal obstruction of the terminal ileum and microcolon.
• Hirschsprung’s disease is associated with several gene mutations:
  • The RET proto-oncogene located on chromosome 10q11.21 that interacts with the EDNRB protein located on chromosome 13.
  • Mutations in the RET and 3p21, 9q31, and 19q12 genes leads to failure of migration of the enteric neural crest cells.
  • Hirschsprung syndrome is associated with PHOX2B homeobox gene mutations.
  • The following protein mutations may also lead to Hirschsprung’s disease:
    • Chromosome 5 – GDNF protein
    • Chromosome 20 – EDN3 protein
    • Chromosome 22 – SOX10 protein
    • Chromosom 1 – ECE1 protein
    • Chromosome 19 – NTN protein
    • Chromosome 2 – SIP1 protein

• Conditions associated with extrinsic bowel obstruction include:^{[15][16][17][18]}
  • Adhesions
  • Hernia
  • Volvulus
  • Endometriosis
• Conditions associated with intrinsic bowel obstruction include:^{[15][16][17][18]}
  • Large and small bowel cancers
  • Cystic fibrosis
  • Hirschsprung’s disease
  • Down syndrome
  • Strictures:
    • Anatomical
    • Inflammatory
    • Ischemic
    • Radiation
• Conditions associated with intraluminal bowel obstruction include:^{[15][16][17][18]}
  • Gastrointestinal foreign body
  • Intussusception
  • Gallstones
  • Constipation
  • Bezoar
  • Volvulus
  • Hematoma

• On gross pathology, adhesions, volvulus, narrow lumen with proximal dilatations and exudate are characteristic findings of bowel obstruction.^[18]

• On microscopic histopathological analysis, fibrosis, necrosis, and ischemia are characteristic findings of bowel obstruction.^[18]

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