The document outlines the regulation of gastrointestinal (GI) function and motility, focusing on the patterns of motility, mechanisms controlling it, and the disturbances that can occur. It discusses the roles of myogenic activity, hormones, the enteric nervous system, and reflexes in maintaining GI motility, along with common motility disorders such as postoperative ileus and gastrointestinal stasis syndrome. Treatment approaches and key points about the intrinsic and extrinsic control of GI motility are highlighted.

1. The Regulation of Gut Function and Motility Antonia Jameson Jordan, D.V.M., Ph.D.

2. Lecture outline: Overview of GI tract function Patterns of motility Control of GI motility Motility disorders

3. GI functions: Nutrition Digestion and absorption of food Excretion Nondigested/nonabsorbed dietary food products Colonic bacteria and their metabolic products Excretory products heavy metals organic anions and cations (including drugs) Fluid and electrolyte balance Immunity

4. input output

5. GI motor activity: Functions Mixing Segmental contractions (non-propulsive) Enhance digestion and absorption Propulsion Move ingesta aborally Storage Stomach and large intestine act as reservoirs Kinds of contractions Phasic (rhythmic) Alternating contraction and relaxation Seconds Tonic Sustained Minutes to hours

6. Propulsion: Achieved by peristalsis, a wave of coordinated, progressive contractions

7. Peristalsis: http://www.wzw.tum.de/humanbiology/data/motility/35/?alt=english

8. Mixing: Achieved by segmentation Lacks the directionality of peristalsis

9. Segmenting contractions: http://www.wzw.tum.de/humanbiology/data/motility/35/?alt=english

10. Schematic of gastric emptying:

11. Gastric emptying: http://www.wzw.tum.de/humanbiology/motvid01/movie_04_1mot01.wmv

12. Control of gut motility: Myogenic GI smooth muscle has its own intrinsic rhythmicity Hormonal GI tract is the largest endocrine organ in the body Endocrine and paracrine GI hormones released from mucosa in response to: Nervous stimulation Distention Chemical stimulation Gastrin, secretin, cholecystokinin, motilin, etc. Nervous Intrinsic enteric nervous system Extrinsic Parasympathetic Sympathetic

13. Intrinsic rhythmic contractility of GI smooth muscle: Regular oscillations in membrane potential of the smooth muscle cells – slow waves Do not in themselves cause action potentials but set the timing for when action potentials can occur Enforced periods of relaxation after contraction Hormonal and neural stimuli determine whether or not action potentials occur

14. Interstitial cells of Cajal (ICC) serve as pacemakers for GI muscles: Horowitz et al. Annu. Rev. Physiol. 1999. 61: 19-43

15. Enteric nervous system: “ Second brain” Located solely within GI tissue Myenteric plexus Submucosal plexus Approximately 100 million neurons Plethora of neurotransmitters Complete reflex circuit Afferent sensory neurons Interneurons Efferent secretomotor neurons Can function independent of CNS http://www.udel.edu/biology/Wags/histopage/colorpage/cne/cnemap.GIF

16. Targets of enteric neurons: Smooth muscle cells Motility Mucosal secretory cells Gastrointestinal endocrine cells Gastrointestinal microvasculature Immunomodulatory and inflammatory cells of gut

17. Extrinsic nervous regulation: Parasympathetic Postganglionic fibers innervate smooth muscle and secretory cells Acetylcholine is main neurotransmitter, but there are others Stimulates motor and secretory activity Sympathetic Inhibits motor and secretory activity Stimulates sphincter and blood vessel contraction

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. GI reflexes: Peristalsis Enterogastric reflex Distention of small intestine suppresses secretion and motor activity in stomach Intrinsic – wholly coordinated within ENS Intestino-intestinal Gross distention of one bowel segment inhibits contractile activity elsewhere in bowel Depends on extrinsic neural connections

20. Peristaltic reflex: “ Law of the intestine” Generated within enteric nervous system Stretch afferents stimulate interneurons Proximal to site of distention, excitatory motor neurons stimulated  release of Acetylcholine and Substance P  smooth muscle contraction Distal to site of bolus, inhibitory motor neurons stimulated  release of NO, VIP, and ATP  smooth muscle relaxation.

21. Gastrointestinal motility disorders: Hypermotility  diarrhea Need to exclude other causes before assuming disordered motility is the cause Hypomotility Aganglionosis Ileus Megacolon

22. Congenital aganglionosis: Hirschsprung disease (humans) Lethal white foal syndrome Piebald lethal mutation (mice) Absence of ganglion cells in both myenteric and submucosal plexuses Defect in migration of neural crest cells Varying length of distal gut affected rectum +/- proximal colon Functional obstruction with dilatation proximal to aganglionic region

23. Postoperative ileus in horses:

24. Postoperative ileus (POI) in horses: Definition of ileus: Ineffective intestinal propulsion in the absence of a mechanical obstruction Consequence: Accumulation of gas and secretions  Overgrowth of small intestinal bacteria (SIBO) Ischemia and necrosis Dehydration Death Prevalence Between 9 and 43% of horses in post-operative period die from ileus

25. Pathophysiology of POI: Increased levels of circulation catecholamines from stress of surgery Parasympathetic hypo-activity Resection and anastamosis Physical disruption of the ENS Absence of food in gut after surgery – decreased stimulus for motility Electrolyte imbalances Inflammation

26. Prevention and treatment of POI: Allow horse to eat as soon as possible after surgery Maintain fluid and electrolyte balance Parasympathetic stimulation Bethanecol – parasympathomimetic Neostigmine – cholinesterase inhibitor Sympathetic blockade Alpha-2 adrenergic antagonists Prokinetics Metaclopromide, cisapride

27. Bugs Bunny: 3-year-old castrated male rabbit 4-day history of anorexia, lethargy, lack of feces Had dentistry one week previously Housing: indoors Diet: seeds, fruits, vegetables  being transitioned to timothy hay and commercial rabbit pellets

28. Physical exam: Quiet, alert, 10% dehydrated Abdominal discomfort on palpation Intermittent bruxism during exam

29. JAVMA, Vol 225, No. 5, September 1, 2004

30. Gastrointestinal stasis syndrome: Pathophysiology Decreased GI motility High-carbohydrate, low-fiber diet Lack of exercise Anorexia due to other causes, e.g. dental problems Lack of motility can lead to fluid loss and the inability to pass hair out of stomach  trichobezoar

31. Gastrointestinal stasis syndrome: Treatment Rehydrate Force feeding Analgesics Antimicrobials Prokinetic drugs Exercise

32. Key points: Control of GI motility Myogenic Intrinsic rhythmicity of GI smooth muscle Slow waves Interstitial cells of Cajal as pacemakers Hormonal Neural Intrinsic enteric nervous system Autonomic Parasympathetic Sympathetic Disordered motility  pathology

33. Vomiting: http://www.wzw.tum.de/humanbiology/data/motility/35/?alt=english