Gastrointestinal Physiology

1. Gastrointestinal Physiology Xia Qiang, PhD Department of Physiology Zhejiang University School of Medicine Email: xiaqiang@zju.edu.cn

3. Introduction • Basic processes of digestion and absorption • Propulsion and mixing of food in the alimentary tract • Secretory functions of the alimentary tract • Digestion and absorption in the gastrointestinal tract

5. The four processes carried out by the GI tract: digestion, secretion, absorption, and motility.

6. Many functions in the gut are found in specific locations along its length. Most of the absorption of nutrients occurs in the small intestine, so most of digestion is accomplished there or upstream.

7. Functions of the digestive system • Movement: propels food through the digestive system • Secretion: release of digestive juices in response to a specific stimulus • Digestion: breakdown of food into molecular components small enough to cross the plasma membrane • Absorption: passage of the molecules into the body's interior and their passage throughout the body • Elimination: removal of undigested food and wastes

8. Anatomy: Components of the digestive system

9. Structure of the alimentary canal

11. General properties of gastrointestinal smooth muscle • Low excitability • High distensibility • Tonic contraction • Autorhythmicity • High sensitivity to temperature, stretch and chemical stimulation

12. Electrophysiological properties of gastrointestinal smooth muscle • Resting membrane potential • -40~-80 mV • Ionic basis • Em (selective membrane permeability to K+, Na+, Cl- and Ca2+) • Electrogenic Na+-K+ pump

14. Slow wave (basic electrical rhythm) • The spontaneous rhythmic, subthreshold depolarizations of the cell membrane (slow wave) of the gastrointestinal tract that characterizes the underlying electrical activity of the bowel • Initiated in the interstitial cells of Cajal (ICC) (pacemaker cell)

15. Santiago Ramon Y Cajal • He and Camillo Golgi received the Nobel Prize in 1906 for introduction of the silver-chromate stain

16. Calcium imaging in ICC-MY from the guinea-pig antrum. A colocalization procedure was used to identify the Rhod-2 signal from ACK2-Alexa 488 labelled ICC-MY. Panel A shows a stack of 30 sequential optical sections made in the Z optical axis of the ACK2-Alexa 488 signal and the Rhod-2 signal; panels B and C show each signal independently. Panel D shows the stack after the colocalization algorithm was used on each confocal slice, showing that most ICC-MY were well labelled with Rhod-2. It was evident from this experiment that some, but not all, ICC-MY were well-labelled with Rhod-2 (see text for more details). The scale bar in panel D is 40 um and it applies to all images

17. Intracellularly recorded electrical activity from a guinea-pig antral ICC-MY identified with ACK2-Alexa 488. Panel A shows a network of ICC-MY labelled with ACK2-Alexa 488 visualized using fluorescence microscopy, and a single ICC-MY impaled with a LY-filled microelectrode. Panel B shows changes in membrane potential recorded intracellularly from an ICC-MY. One slow wave, marked with the horizontal line in Panel B, is shown in Panel C at an expanded time scale. The scale bar is 15 um.

18. Cyclic changes in intracellular calcium in ICC-MY in the murine jejunum. Panel A shows a single confocal image with ACK2-Alexa 488 immunore-activity (green) and Rhod-2 labelling (red) taken from a time series. ICC-MY were distinctly labelled with Rhod-2 as shown in panel B. The average fluorescence intensity delineated by the white circled region was measured from images recorded every second, shown in panel C

19. Slow wave (basic electrical rhythm) • Intensity: 10~15 mV • Frequency: 3~12 cpm • Ionic mechanism • spontaneous rhythmic changes in Na+-K+ pump activity

21. Normal BER frequencies in the gastrointestinal system

22. Spike potential (Action potential) • Duration: 10~20 ms • Ionic mechanism: • Depolarization: Ca2+ influx • Repolarization: K+ efflux

24. Neural control of gastrointestinal function • Enteric nervous system (intrinsic) • Autonomic nervous system (extrinsic)

27. Enteric (Intrinsic) nervous system • Myenteric plexus (Auerbach’s plexus) • Submucosal plexus (Meissner’s plexus) • Neurotransmitters secreted by enteric neurons • Ach, NE, ATP, serotonin, dopamine, cholecystokinin, substance P, vasoactive intestinal polypeptide, somatostatin, leu-enkephalin, met-enkephalin, bombesin, etc.

30. Autonomic nervous system • Parasympathetic nerve • Mainly ACh • Stimulatory (+) • Sympathetic nerve • NE • Inhibitory (-)

31. Afferent sensory nerve fiber from the gut • Sensory fibers with their cell bodies in the ENS terminate in the ENS • Sensory fibers with their cell bodies in the ENS send axons upward through the ANS to terminate in the prevertebral sympathetic ganglia • Sensory fibers with their cell bodies in the dorsal root ganglia or in the cranial nerve ganglia send axons to multiple area of the spinal cord or brain stem

33. Gastrointestinal reflexes • Three types • Reflexes that are integrated entirely within the enteric nervous system • Reflexes from the gut to the prevertebral sympathetic ganglia and then back to the gastrointestinal tract • Reflexes from the gut to the spinal cord or brain stem and then back to the gastrointestinal tract

34. Gastrointestinal hormones • The hormones synthesized by a large number of endocrine cells within the gastrointestinal tract • Physiological functions • Control of the digestive function • Control of the release of other hormones • Trophic action

35. Gastrointestinal hormones • Four main types • Gastrin • Secretin • Cholecystokinin (CCK) • Gastric inhibitory peptide (GIP)

38. Splanchnic circulation

39. Microvasculature of the intestinal villus

40. Digestion in the stomach

41. The swallowing reflex is coordinated by the medulla oblongata, which stimulates the appropriate sequence of contraction and relaxation in the participating skeletal muscle, sphincters, and smooth muscle groups.

42. The coordinated sequence of contraction and relaxation in the upper esophageal sphincter, the esophagus, and the lower esophageal sphincter is necessary to deliver swallowed food to the stomach.

43. Specialized cells in the stomach synthesize and secrete mucous fluid, enzyme precursors, hydrochloric acid, and hormones. The abundant smooth muscle in the stomach is responsible for gastric motility.

46. Gastric juice • Properties • pH 0.9~1.5 • 1.5~2.5 L/day • Major components • Hydrochloric acid • Pepsinogen • Mucus • Intrinsic factor

47. Hydrochloric acid • Secreted by the parietal cells • Output • Basal: 0~5 mmol/h • Maximal: 20~25 mmol/h

49. Mechanism of HCl secretion • Active transport • Huge H+ gradient (3 million)

50. Acid production by the parietal cells in the stomach depends on the generation of carbonic acid; subsequent movement of hydrogen ions into the gastric lumen results from primary active transport.