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irritable-bowel-syndrome-ibs-pathogenesis-and-clinical-findings

Irritable Bowel Syndrome (IBS): Pathogenesis and clinical findings Authors: Ben Campbell Reviewers: Mehul Gupta Kiana Hampton Yan Yu* Edwin Cheng* * MD at time of publication Note: *Several signaling pathways in the gut are believed to play a role in IBS. The serotonin pathway is represented here for illustrative purposes, and it is a common target of therapy. Pathogenesis is multifactorial, not fully understood, and may arise from any one or a combination of these factors Genetic factors are believed to influence many of these pathways Environmental factors Gut infection, ischemia, injury, chronic low-level inflammation, altered microbiome Abnormal gut chemical milieu (cytokines, lymphocytes, mast cells, hormones) One common pathway: altered quantity or activity of serotonin-releasing enterochromaffin * cells and serotonin reuptake transporters in gut Serotonin is a key stimulator of gut muscle contraction and sensory signaling Altered bowel motility Bowel motility can ↑, ↓ or alternate ↑/↓ Psychosocial factors Anxiety, depression, adverse experiences, dysregulated stress response Brain can alter normal reflexes of enteric nervous system (e.g. via hypothalamic stress hormone release) ↑ Activity of sensory receptors in gut + recruitment of formerly ”silent” receptors Altered visceral bowel sensation Visceral hypersensitivity Complex mechanisms ↓ Brain’s ability to modulate pain signals from gut; ↑ vigilance to pain Irritable Bowel Syndrome Disorder of brain-gut interaction with gastrointestinal manifestations Not a predominantly inflammatory condition During times of ↑ bowel motility: No lesions in gut mucosa (Absence of ”red flags” for organic disease) ↑ Impacts of other factors that precipitate diarrhea Dietary sensitivity (e.g. to intake of fermentable oligo/di/ monosaccharides and polyols— FODMAPs—which draw water into gut lumen by osmosis) ↑ Impacts of other factors that precipitate constipation Dietary sensitivity (e.g. to inadequate intake of motility- promoting fibre) During times of ↓ bowel motility: ↑ Time for water absorption from feces and bacterial fermentation ↑ Hard stool and trapped gas in bowel ↑ Number and sensitivity of active pain receptors (nociceptors) in gut Hyperalgesia ↑ Response to painful stimulus Stretch receptors in gut stimulate pain in normally unconscious neural pathways Allodynia Pain in response to normal stimulus ↑ Peristalsis ↓ Time for water absorption from feces ↑ Water volume in gut lumen ↑ Stretch / stimulation of visceral afferent nerves in gut Absence of bloody stool and anemia Absence of nocturnal symptoms and inflammatory markers Constipation Bloating Diffuse abdominal pain All symptoms may exacerbate psychosocial factors Bowel distension Diarrhea Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published April 30, 2022 on www.thecalgaryguide.com