Gut motility lecture


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I give this lecture in the Function and Dysfunction course for first-year veterinary students. The fluoroscopic videos of a vomiting dog was very well received.

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  • Your schedule says the title of this lecture is the regulation of gut function and motility, But I will be focusing on the gi motility this is in itself a huge topic so I will be thinking of it from the perspective of clinical relevance THIS IS NOT THE MOST Palatable subject in veterinary medicine, but it may be one of the most relevant. Motility disorders can result diarrhea, constipation, vomiting, heartburn.
  • Gut motility lecture

    1. 1. The Regulation of Gut Function and Motility Antonia Jameson Jordan, D.V.M., Ph.D.
    2. 2. Lecture outline: <ul><li>Overview of GI tract function </li></ul><ul><li>Patterns of motility </li></ul><ul><li>Control of GI motility </li></ul><ul><li>Motility disorders </li></ul>
    3. 3. GI functions: <ul><li>Nutrition </li></ul><ul><ul><li>Digestion and absorption of food </li></ul></ul><ul><ul><li>Excretion </li></ul></ul><ul><ul><ul><li>Nondigested/nonabsorbed dietary food products </li></ul></ul></ul><ul><ul><ul><li>Colonic bacteria and their metabolic products </li></ul></ul></ul><ul><ul><ul><li>Excretory products </li></ul></ul></ul><ul><ul><ul><ul><li>heavy metals </li></ul></ul></ul></ul><ul><ul><ul><ul><li>organic anions and cations (including drugs) </li></ul></ul></ul></ul><ul><li>Fluid and electrolyte balance </li></ul><ul><li>Immunity </li></ul>
    4. 4. input output
    5. 5. GI motor activity: <ul><li>Functions </li></ul><ul><ul><li>Mixing </li></ul></ul><ul><ul><ul><li>Segmental contractions (non-propulsive) </li></ul></ul></ul><ul><ul><ul><ul><li>Enhance digestion and absorption </li></ul></ul></ul></ul><ul><ul><li>Propulsion </li></ul></ul><ul><ul><ul><li>Move ingesta aborally </li></ul></ul></ul><ul><ul><li>Storage </li></ul></ul><ul><ul><ul><li>Stomach and large intestine act as reservoirs </li></ul></ul></ul><ul><li>Kinds of contractions </li></ul><ul><ul><li>Phasic (rhythmic) </li></ul></ul><ul><ul><ul><li>Alternating contraction and relaxation </li></ul></ul></ul><ul><ul><ul><ul><li>Seconds </li></ul></ul></ul></ul><ul><ul><li>Tonic </li></ul></ul><ul><ul><ul><li>Sustained </li></ul></ul></ul><ul><ul><ul><ul><li>Minutes to hours </li></ul></ul></ul></ul>
    6. 6. Propulsion: <ul><li>Achieved by peristalsis, a wave of coordinated, progressive contractions </li></ul>
    7. 7. Peristalsis:
    8. 8. Mixing: <ul><li>Achieved by segmentation </li></ul><ul><li>Lacks the directionality of peristalsis </li></ul>
    9. 9. Segmenting contractions:
    10. 10. Schematic of gastric emptying:
    11. 11. Gastric emptying:
    12. 12. Control of gut motility: <ul><li>Myogenic </li></ul><ul><ul><li>GI smooth muscle has its own intrinsic rhythmicity </li></ul></ul><ul><li>Hormonal </li></ul><ul><ul><li>GI tract is the largest endocrine organ in the body </li></ul></ul><ul><ul><li>Endocrine and paracrine </li></ul></ul><ul><ul><li>GI hormones released from mucosa in response to: </li></ul></ul><ul><ul><ul><li>Nervous stimulation </li></ul></ul></ul><ul><ul><ul><li>Distention </li></ul></ul></ul><ul><ul><ul><li>Chemical stimulation </li></ul></ul></ul><ul><ul><li>Gastrin, secretin, cholecystokinin, motilin, etc. </li></ul></ul><ul><li>Nervous </li></ul><ul><ul><li>Intrinsic enteric nervous system </li></ul></ul><ul><ul><li>Extrinsic </li></ul></ul><ul><ul><ul><li>Parasympathetic </li></ul></ul></ul><ul><ul><ul><li>Sympathetic </li></ul></ul></ul>
    13. 13. Intrinsic rhythmic contractility of GI smooth muscle: <ul><li>Regular oscillations in membrane potential of the smooth muscle cells – slow waves </li></ul><ul><li>Do not in themselves cause action potentials but set the timing for when action potentials can occur </li></ul><ul><li>Enforced periods of relaxation after contraction </li></ul><ul><li>Hormonal and neural stimuli determine whether or not action potentials occur </li></ul>
    14. 14. Interstitial cells of Cajal (ICC) serve as pacemakers for GI muscles: Horowitz et al. Annu. Rev. Physiol. 1999. 61: 19-43
    15. 15. Enteric nervous system: <ul><li>“ Second brain” </li></ul><ul><li>Located solely within GI tissue </li></ul><ul><ul><li>Myenteric plexus </li></ul></ul><ul><ul><li>Submucosal plexus </li></ul></ul><ul><li>Approximately 100 million neurons </li></ul><ul><li>Plethora of neurotransmitters </li></ul><ul><li>Complete reflex circuit </li></ul><ul><ul><li>Afferent sensory neurons </li></ul></ul><ul><ul><li>Interneurons </li></ul></ul><ul><ul><li>Efferent secretomotor neurons </li></ul></ul><ul><li>Can function independent of CNS </li></ul>
    16. 16. Targets of enteric neurons: <ul><li>Smooth muscle cells </li></ul><ul><ul><li>Motility </li></ul></ul><ul><li>Mucosal secretory cells </li></ul><ul><li>Gastrointestinal endocrine cells </li></ul><ul><li>Gastrointestinal microvasculature </li></ul><ul><li>Immunomodulatory and inflammatory cells of gut </li></ul>
    17. 17. Extrinsic nervous regulation: <ul><li>Parasympathetic </li></ul><ul><ul><li>Postganglionic fibers innervate smooth muscle and secretory cells </li></ul></ul><ul><ul><ul><li>Acetylcholine is main neurotransmitter, but there are others </li></ul></ul></ul><ul><ul><li>Stimulates motor and secretory activity </li></ul></ul><ul><li>Sympathetic </li></ul><ul><ul><li>Inhibits motor and secretory activity </li></ul></ul><ul><ul><li>Stimulates sphincter and blood vessel contraction </li></ul></ul>
    18. 18. Central Autonomic Neural Network Effector Systems (muscle, secretory epithelium, endocrine cells, vasculature) Enteric Nervous System (myenteric plexus, submucous plexus) Parasympathetic Nervous System Intermediate cells Parasympathetic ganglia Sympathetic ganglia Nodose ganglia Dorsal-root ganglia Sympathetic Nervous System Central Nervous System
    19. 19. GI reflexes: <ul><li>Peristalsis </li></ul><ul><li>Enterogastric reflex </li></ul><ul><ul><li>Distention of small intestine suppresses secretion and motor activity in stomach </li></ul></ul><ul><ul><li>Intrinsic – wholly coordinated within ENS </li></ul></ul><ul><li>Intestino-intestinal </li></ul><ul><ul><li>Gross distention of one bowel segment inhibits contractile activity elsewhere in bowel </li></ul></ul><ul><ul><li>Depends on extrinsic neural connections </li></ul></ul>
    20. 20. Peristaltic reflex: <ul><li>“ Law of the intestine” </li></ul><ul><li>Generated within enteric nervous system </li></ul><ul><li>Stretch afferents stimulate interneurons </li></ul><ul><ul><li>Proximal to site of distention, excitatory motor neurons stimulated  release of Acetylcholine and Substance P  smooth muscle contraction </li></ul></ul><ul><ul><li>Distal to site of bolus, inhibitory motor neurons stimulated  release of NO, VIP, and ATP  smooth muscle relaxation. </li></ul></ul>
    21. 21. Gastrointestinal motility disorders: <ul><li>Hypermotility  diarrhea </li></ul><ul><ul><li>Need to exclude other causes before assuming disordered motility is the cause </li></ul></ul><ul><li>Hypomotility </li></ul><ul><ul><li>Aganglionosis </li></ul></ul><ul><ul><li>Ileus </li></ul></ul><ul><ul><li>Megacolon </li></ul></ul>
    22. 22. Congenital aganglionosis: <ul><li>Hirschsprung disease (humans) </li></ul><ul><li>Lethal white foal syndrome </li></ul><ul><li>Piebald lethal mutation (mice) </li></ul><ul><li>Absence of ganglion cells in both myenteric and submucosal plexuses </li></ul><ul><ul><li>Defect in migration of neural crest cells </li></ul></ul><ul><li>Varying length of distal gut affected </li></ul><ul><ul><li>rectum +/- proximal colon </li></ul></ul><ul><li>Functional obstruction with dilatation proximal to aganglionic region </li></ul>
    23. 23. Postoperative ileus in horses:
    24. 24. Postoperative ileus (POI) in horses: <ul><li>Definition of ileus: </li></ul><ul><ul><li>Ineffective intestinal propulsion in the absence of a mechanical obstruction </li></ul></ul><ul><li>Consequence: </li></ul><ul><ul><li>Accumulation of gas and secretions  </li></ul></ul><ul><ul><ul><li>Overgrowth of small intestinal bacteria (SIBO) </li></ul></ul></ul><ul><ul><ul><li>Ischemia and necrosis </li></ul></ul></ul><ul><ul><ul><li>Dehydration </li></ul></ul></ul><ul><ul><ul><li>Death </li></ul></ul></ul><ul><li>Prevalence </li></ul><ul><ul><li>Between 9 and 43% of horses in post-operative period die from ileus </li></ul></ul>
    25. 25. Pathophysiology of POI: <ul><ul><li>Increased levels of circulation catecholamines from stress of surgery </li></ul></ul><ul><ul><li>Parasympathetic hypo-activity </li></ul></ul><ul><ul><li>Resection and anastamosis </li></ul></ul><ul><ul><ul><li>Physical disruption of the ENS </li></ul></ul></ul><ul><ul><li>Absence of food in gut after surgery – decreased stimulus for motility </li></ul></ul><ul><ul><li>Electrolyte imbalances </li></ul></ul><ul><ul><li>Inflammation </li></ul></ul>
    26. 26. Prevention and treatment of POI: <ul><li>Allow horse to eat as soon as possible after surgery </li></ul><ul><li>Maintain fluid and electrolyte balance </li></ul><ul><li>Parasympathetic stimulation </li></ul><ul><ul><li>Bethanecol – parasympathomimetic </li></ul></ul><ul><ul><li>Neostigmine – cholinesterase inhibitor </li></ul></ul><ul><li>Sympathetic blockade </li></ul><ul><ul><li>Alpha-2 adrenergic antagonists </li></ul></ul><ul><li>Prokinetics </li></ul><ul><ul><li>Metaclopromide, cisapride </li></ul></ul>
    27. 27. Bugs Bunny: <ul><li>3-year-old castrated male rabbit </li></ul><ul><li>4-day history of anorexia, lethargy, lack of feces </li></ul><ul><li>Had dentistry one week previously </li></ul><ul><li>Housing: indoors </li></ul><ul><li>Diet: seeds, fruits, vegetables  being transitioned to timothy hay and commercial rabbit pellets </li></ul>
    28. 28. Physical exam: <ul><li>Quiet, alert, 10% dehydrated </li></ul><ul><li>Abdominal discomfort on palpation </li></ul><ul><li>Intermittent bruxism during exam </li></ul>
    29. 29. JAVMA, Vol 225, No. 5, September 1, 2004
    30. 30. Gastrointestinal stasis syndrome: <ul><li>Pathophysiology </li></ul><ul><ul><li>Decreased GI motility </li></ul></ul><ul><ul><ul><li>High-carbohydrate, low-fiber diet </li></ul></ul></ul><ul><ul><ul><li>Lack of exercise </li></ul></ul></ul><ul><ul><ul><li>Anorexia due to other causes, e.g. dental problems </li></ul></ul></ul><ul><ul><li>Lack of motility can lead to fluid loss and the inability to pass hair out of stomach  trichobezoar </li></ul></ul>
    31. 31. Gastrointestinal stasis syndrome: <ul><li>Treatment </li></ul><ul><ul><li>Rehydrate </li></ul></ul><ul><ul><li>Force feeding </li></ul></ul><ul><ul><li>Analgesics </li></ul></ul><ul><ul><li>Antimicrobials </li></ul></ul><ul><ul><li>Prokinetic drugs </li></ul></ul><ul><ul><li>Exercise </li></ul></ul>
    32. 32. Key points: <ul><li>Control of GI motility </li></ul><ul><ul><li>Myogenic </li></ul></ul><ul><ul><ul><li>Intrinsic rhythmicity of GI smooth muscle </li></ul></ul></ul><ul><ul><ul><ul><li>Slow waves </li></ul></ul></ul></ul><ul><ul><ul><li>Interstitial cells of Cajal as pacemakers </li></ul></ul></ul><ul><ul><li>Hormonal </li></ul></ul><ul><ul><li>Neural </li></ul></ul><ul><ul><ul><li>Intrinsic enteric nervous system </li></ul></ul></ul><ul><ul><ul><li>Autonomic </li></ul></ul></ul><ul><ul><ul><ul><li>Parasympathetic </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Sympathetic </li></ul></ul></ul></ul><ul><li>Disordered motility  pathology </li></ul>
    33. 33. Vomiting: