Gut motility lecture

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.

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