FIGURE 2.

Working hypothesis of proposed glial pathogenic mechanism of postoperative ileus—Enteric glia are very sensitive to mechanical stimulation and mechanical forces generated during peristalsis. Touch, stretch, shear stress, pressure, compression, membrane perturbations and centrifugal forces all operate during peristalsis. Mechanosensation is a normal function of enteric glia in the modulation of motility through interactions with the ENS. Abnormal mechanical forces encountered during GI surgery such as gut manipulation, surgical insult, fluid edema or high pressure pneumoperitoneum encountered in minimal invasive laparoscopic surgery, may activate enteric glia (and immune cells) in the muscularis externa contributing to the induction of a reactive enteric glial cell phenotype. Reactive glia in coordination with immune cells release pro-inflammatory mediators that disrupt the ENS to cause GI dysmotility associated with POI and POGD. Signs and symptoms include nausea, vomiting, Pain distention, bloating and constipation. Pain pathways also activate the sympathetic nervous system which has inhibitory effects on GI motility. Additionally, opioids, commonly used during the perioperative period to treat pain, activate peripheral µ opioid receptors in the ENS and further depress peristalsis.