1. The stomach can be divided into three anatomic (A) and two functional regions (B) Gastric reservoir Tonic contractions Gastric reservoir Tonic contractions Gastric pump Phasic contractions Gastric pump Phasic contractions B B Fundus Corpus Antrum Pylorus A A Ehrlein Figure 1

2. The relaxation of the gastric reservoir is mainly regulated by reflexes. Three kinds of relaxation can be differentiated: the receptive, adaptive and feedback-relaxation Ehrlein Figure 2 Inhibitory vagal fibre (NANC-inhibition) Nutrients CCK Relaxation of gastric reservoir ACH Vagus centre 1. Receptive relaxation Mechanical stimuli in the pharynx 3. Feedback relaxation 2. Adap tive relax ation Nutrients Tension receptors Distension NO + VIP et al.

3. The transport of digesta from the gastric reservoir into the antral pump is caused by two mechanisms: tonic contractions and peristaltic waves in the region of the gastric corpus Ehrlein Figure 3 Tonic contraction Peristaltic wave (Pump of the reservoir) Proximal antrum Backflow from antrum and flow from reservoir Pylorus Accumulation of chyme

4. The function of the gastric pump can be differentiated into three phases: A: phase of propulsion, B: phase of emptying, C: phase of retropulsion and grinding A Phase of propulsion Contraction of proximal antrum (PA) B Phase of emptying Contraction of middle antrum (MA) Propulsion of chyme into relaxing terminal antrum + duodenal contraction Transpyloric and retrograde flow + duodenal relaxation C Phase of retropulsion Contraction of terminal antrum (TA) Jet-like back-flow with grinding + duodenal contraction Phases A B CA B C 10 sec Proximal antrum Middle antrum Terminal antrum Pylorus Duodenum Pylorus PA MA TA closed open Ehrlein Figure 4

5. Liquids and small particles leave the stomach more rapidly than large particles. This discrimination is called „sieving function“ Retropulsion of large particles and clearing of the terminal antrum Ehrlein Figure 5

6. Grinding of solid particles is caused by a forceful jet-like retropulsion through the small orifice of the terminal antral contraction Onset of terminal antral contraction Pylorus closing Late phase of terminal antral contraction Pylorus closed Ehrlein Figure 6

7. Antro-duodenal co-ordination: Contractions of the proximal duodenum cease during the phases of gastric emptying.. Ehrlein Antral waves Middle antrum Terminal antrum Pylorus Proximal duodenum Lacking duodenal contractions 05101520253035 sec 1 Phases of gastric emptying 3.5 9.9 3.5 9.96.6 open closed 2 1 1 1 3 3 3 2 2 4 Figure 7 Because of different frequencies between antral and duodenal contractions, the duodenum can contract three to four times during an antral wave sec

8. Several factors of gastric and duodenal motility co-operate and modulate gastric emptying: Ehrlein A. Rapid emptying is caused by tonic contractions of the reservoir (1a), deep peristaltic waves along the gastric body (1b), deep constrictions of the antral waves (2), a wide opening of the pylorus (3), a duodenal receptive relaxation (4) and peristaltic duodenal contractions (5). B. Delayed emptying due to feedback inhibition is caused by a prolonged relaxation of the reservoir (6a), shallow peristaltic waves along the gastric body ( 6b), shallow antral waves (7), a small pyloric opening (8), a lacking duodenal relaxation (9) and segmenting duodenal contractions (10). Figure 8 5 10 A. Rapid emptying Pylorus 1a 1b 2 3 4 7 8 9 B. Delayed emptying 6a 6b

9. Balance between gastric reservoir and antral pump Figure 9 Ehrlein Gastro-gastric reflexes Excitatory reflex Inhibitory reflex Enhanced and prolonged relaxation of reservoir Distension Antral pump switched on and intensified Disten- sion

10. Pyloric activity is modulated by antral inhibitory and duodenal excitatory reflexes Figure 10 Ehrlein Descending inhibitory reflex causing pyloric relaxation Contraction of middle antrum Ascending excitatory reflex causing pyloric contractions and increasing pyloric tone Duodenal stimuli

11. An additional function of the pyloric sphincter is to prevent duodeno-gastric reflux Figure 11 Pyloric closure Inhibition Stimulation 0.5 ml oleic acid + bile into duodenum Antrum Pylorus Duod. bulb Duodenum closed open Ehrlein Duodenal stimuli like oleic acid inhibit antral contractions, evoke duodenal contractions, increase pyloric tone and elicit frequent pyloric contractions

12. Solids and liquids of the gastric chyme are emptied with different velocities. Ehrlein Lag phase Time (min) Viscous content Liquid content Solids 100 80 60 40 20 0 0 4060 80 100120 Gastric volume (%) Figure 12 Emptying of liquids is exponential, emptying of large solid particles only begins after sufficient grinding (lag phase). Afterwards the viscous chyme is mainly emptied in a linear fashion

13. Nutrients in the gut activate a feedback control and modulate gastric and duodenal motility Ehrlein Figure 13 Gastrointestinal motor patterns after a non-caloric and a nutrient meal Antrum Pylorus closed open Duodenal bulb Middle Duodenum Reduced force of antral contractions Reduced pyloric opening Reduced peristaltic waves Enhanced segmenting activity Non-caloric mealNutrient meal Feedback control causes

14. The feedback regulation of gastric emptying is performed by entero-gastric reflexes and release of intestinal hormones Ehrlein Figure 14 Ehrlein Figure 14 It causes enhanced relaxation of the gastric reservoir, inhibition of the antral pump, and reduced opening of the pyloric sphincter. Vagal center Inhibitory vagal fibers NO, VIP et al. Sensoric afferent fibers CCK ACH Enhanced relaxation and storage Stimulating cholinergic vagal fibers Nutrients Long chain fatty acids Amino acids Dipeptids Glucose Osmolality Hydrochloric acid Reduced opening of pyloric sphincter Reduced contraction Backflow + + _ ACH

15. Contractile patterns of the small intestine Ehrlein Peristaltic Stationary Clusters waves contractions of contractions Figure 15 The most frequent patterns are peristaltic waves (dashed lines), stationary contractions (arrows), and clusters of contractions, which occur either stationary at an intestinal segment or slowly migrate aborally

16. Phase III of the interdigestive motility designated as ”migrating motor complex” (MMC) oral aboral Aboral migration of phase III Velocity of the peristaltic waves 1 minute Jejunal phase III (MMC) Ehrlein Figure 16 Rectangles: strain gauge transducers, Data of dog.

17. Pathological contractile patterns of the proximal intestine Antiperistaltic waves 1 minute Jejunum oral aboral Aboral giant contractions 1 minute 0,2 Newton Duodenum oral aboral Ehrlein Figure 17 Alternating peristaltic (blue arrows) and antiperistaltic waves (red arrows). Giant contractions sometimes originate as a cluster.

18. Ehrlein Figure 18 Different kinds of contractile patterns are caused by different kinds of excitation 1, 2, 3 successive pacesetter potentials (PP) Stationary segmenting contractions are produced by brief excitation of a short intestinal segment Single peristaltic waves are produced by short excitations of a long intestinal segment Time course

19. Clustered contractions are produced by a long lasting excitation of a short intestinal segment. The cluster is stationary when the excitation remains at the same segment. When the excitation slowly moves aborally the cluster of contractions migrates along the intestine. Ehrlein Figure 19 Origin of clustered contractions 1, 2, 3 successive pacesetter potentials (PP)

20. Luminal stimuli elicit vago-vagal reflexes which activate integrating and program circuits of the enteric nervous system. These activate specific motorneurones responsible for specific contractile patterns. Ehrlein Figure 20 Central and peripheral control of contractile patterns Intestinal wall Vagal centre Intestinal lumenl Peptide (CCK)Receptors Glucose - Osmolality Long chain fatty acids Amino acids Sensory neurons Vago-vagal reflexes Interneurons Integrating circuits Program circuits Enteric nervous system Motorneurons Contractile patterns

21. Postprandial contractile patterns of the small intestine 0,2 Newton oral aboral Ehrlein Figure 21 They are composed of stationary segmenting contractions (green arrows), stationary and migrating clusters of contractions (red horizontal lines) and single short peristaltic waves (dotted lines).

22. The phase III of the migrating motor complex originates simultaneously at the stomach and duodenum and migrates within 90 to 120 minutes along the small intestine (dog) Interdigestive Cycles Phases Sporadic peristaltic waves Segmenting contractions and single peristaltic waves Motor quiescence of stomach and duodenum Contraction of reservoir Pylorus Aboral migration Accumulation of residues of chyme Phase IIPhase I Stomach Duodenum Jejunum Ileum Phase III III I II III Phase III Phase II Phase I Forceful peristaltic waves Motor quiescence Ehrlein Figure 22 The interdigestive motility consists of three phases

23. The antral waves are associated with a wide opening of the pylorus and inhibition of duodenal contractions followed by duodenal peristaltic waves occurring at maximal frequency. Ehrlein Figure 23 Middle Antrum Pyloric diameter Duodenal bulb Duodenum Gastric phases III 1 min P A P P 0 mm 6 mm Stomach is cleaned of residues of chyme and secretions. Gastric phase III consisting of 1 - 3 forceful contractions of the gastric reservoir and lumen occluding peristaltic waves occurring at intervals of 2-3 min

24. Phase III (MMC) of the small intestine Ehrlein Intestinal phase III oral Successsive peristaltic waves Chyme Slow aboral migration of phase III aboral Time (about 20 sec) Figure 24 The peristaltic waves clean the intestinal segment from chyme which accumulates aborally. Because the successive waves start and end further aborally the phase III slowly migrates distally

25. Postprandial motility is characterised by a lower amplitude of the antral waves occurring at maximal frequency, rhythmic pyloric opening and closure and co-ordinated duodenal contractions occurring in sequence with the antral waves Ehrlein Figure 25 Ingestion of a meal suppresses the interdigestive motility and induces a fed motor pattern

26. C: A special feature of the large intestine are multiple segmenting contractions of long duration migrating aborally. They divide digesta into boli pushing them slowly aborally. The motility tracings show a rise of the baseline superimposed by phasic contractions Ehrlein Figure 26 Contractile patterns of the large intestine A A B B C C Colonic segmenting contractions migrating aborally aboral migration small aboral flow backflow low propulsion Shallow peristaltic waves of caecum and colon Shallow peristaltic waves at haustrated colon slow aboral propulsion

27. Motility of the large intestine in pig A: Haustral movements of the caecum result in clustered contractions. B: The ileum is emptied by giant contractions. They occur either isolated or in co-ordination with peristaltic waves of the caecum and colon. Additional colonic waves originate at the beginning of the colonic coil. Caecum Ehrlein J1 J2 C1 C2 C3 Co1 Co2 Co3 Ileum Colon Distal colon Caecum C1 C2 C3 1 min Ileum - Caecum - Colon 1 min Co3 Co1 Co2 C1 J2 J1 Giant contractions Colonic wave Figure 27 A A B B

28. SC1 SC2 SC3 Spiral colon Peristaltic wave Caecal motility is characterised by peristaltic and antiperistaltic waves. In the colon peristaltic waves and giant contractions are the dominant feature. In the spiral colon prolonged segmenting contractions divide digesta into boli and push them distally. Caecum Colon Co1 Co2 Co3 Co4 C2 C3 C4 Ileum SC1 SC2 SC3 C1 Co2 Spiral colon Caecum Colon C4 C3 C2 C1 Co1 Co2 1 min Co3 C1 Co1 Co2 Co4 Giant contraction Ehrlein Figure 28 Motility of caecum and colon in sheep.

29. J1 C1 C2 C3 C4 C5 1 min Colon Co1 Co2 Co3 Giant contractions 1 min Caecum Caecal motility is characterised by peristaltic and antiperistaltic waves. Migrating segmenting contractions are the dominant feature of the single haustrated colon. Co3 J1 Co2 Co1 C1 C2 C3 C4 C5 Colon Caecum Ileum Ehrlein Figure 29 Motor patterns of the large intestine in rabbits

30. A: Slow paper speed. The CMC’s occur at all parts of the colon at intervals of 20-30 min. B: High paper speed. The CMC’s consist of a rise of the baseline super- imposed of phasic contractions. The onset of the CMC‘s obviously differs along the colon (indicated by lines). A: Slow paper speed. The CMC’s occur at all parts of the colon at intervals of 20-30 min. B: High paper speed. The CMC’s consist of a rise of the baseline super- imposed of phasic contractions. The onset of the CMC‘s obviously differs along the colon (indicated by lines). Ehrlein A A B B Colonic motor complex (CMC) aboral oral Phasic contractions 15 min 5 min Figure 30 Colonic motor complexes (CMC’s) of the canine colon

31. (1) Normal segmenting contractions of the proximal jejunum (2) Start of a retrograde giant contraction in proximal jejunum; (3) Retropelled digesta reach the duodenum and (4) are forced across the widely opened pylorus into the antrum; (5) The giant contraction proceeds to the antrum, the chyme accumulates in the gastric reservoir. 1 2 3 4 5 1 2 3 4 5 Antrum Pylorus (P) Bulbus Prox. duod. Distal duod. closed open 1 min Retrograde giant contraction Vomiting Duodenum P P Stomach P Jejunum Ehrlein Figure 31 Retrograde giant contraction followed by vomiting