1. GI Physiology I: Introduction & Motility Mechanisms
IDP-DPT GI Section, Fall 2011
Jerome W. Breslin, Ph.D.
LSUHSC-NO Department of Physiology
MEB 7208, Tel

2. Lecture 1 Outline Introduction to GI Physiology
Overview of the Functional Anatomy of the GI Tract.
Functions of the GI System.
Processes in the GI Tract.
Water and Solids Balance.
Enteric Nervous System
Immune Function in GI System
Splanchnic Circulation
Motility
Motility Patterns
Basic Mechanisms Underlying Motility

3. Required Reading:
Gastrointestinal Physiology, Kim E. Barrett, Chapter 1, Chapter 7 - section on peristalsis, Chapter 8 - sections on innervation, basal electrical rhythm, and motility during fasting.
Suggested Reading:
Review of Medical Physiology, William Ganong, Chapters 26 and 27.
Both are freely available for students online through the LSUHSC library website or

4. Diffusion of water and ions,
Single Cell Organisms
Diffusion of water and ions,
Phagocytosis/Endocytosis of larger particles, digestion & absorption in lysosomes

5. Multicellular Organisms
Shape is important!
If the shape is not hollow: Greater Ratio of Volume to Exterior Surface Area than in a Single Cell

6. Simple Multicellular Organisms
Shape is important!
Hydra
(Image from Wikipedia)
Cavity or Lumen for optimal digestion and absorption
Organization into shapes that maximize surface area for exchange

7. More complicated multicellular organisms:
Humans
1. Terrestrial - not living in an aqueous solution filled with nutrients.
2. Specialized tube through the body for getting nutrients to the circulatory system for delivery to tissues.

8. GI Function
Take relatively large, solids or gels, and digest them into smaller molecules that can be absorbed as nutrients, while still serving as a barrier to toxins, bacteria, parasites, etc.
Our overall objective for these lectures is to understand biological mechanisms that facilitate GI function.

9. GI: Functional Anatomy
GI system is a hollow organ, a tube through the body.
The lumen is “outside” the body’s tissues, but its environment is tightly controlled by the body.
Specialized organs for secretion of enzymes & bile.
Epithelial cells line the entire GI tract and serve as the primary barrier. Specialized epithelial cells also secrete and absorb various compounds to/from the lumen.
Epithelium, mucosa, two layers of smooth muscle, blood vessels and lymphatics, nerves.
Structure maximizes surface area for secretion and absorption (folds, villi, and crypts).
Sphincters regulate movement between segments.

11. Figure 15-3
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.

13. Figure 15-6 General Anatomy of Gut Wall
(Contains connective tissue, immune cells, capillaries, nerve endings)
(Might have role in villus movement)
The gut wall has a layered organization, with the absorptive cells lining the lumen and neural and muscular components below. Blood and lymph vasculature is abundant to transport absorbed nutrients.
See Fig. 1-2 and Fig. 1-3 in Barrett’s book,

14. General Structure of Gut Wall: Cross Section14

15. Folds in the small intestine increase surface area for exchange:
Fold of Kerckring
Fig from Wilson et al, Histology Image Review
Folds of Kerckring, a.k.a. valvulae conniventes

16. Villi & Crypts
Vander, Fig. 15-7
Ganong, Fig

17. Microvilli on luminal surface of intestinal epithelial cells

18. Area of simple cylinder 1 ~3,300
Degree by which different anatomical features increase surface area in the small intestine:
Increase in Surface Area (Relative to cylinder)
Structure
Surface Area (cm2)
Area of simple cylinder 1
~3,300
4 cm Dia. x 260 cm L
Folds of Kercking 3
~10,000
Villi 30
~100,000
Microvilli
600
~2,000,000

19. GI: Functional Anatomy
GI system is a hollow organ, a tube through the body.
The lumen is “outside” the body’s domain, but its environment is tightly controlled by the body.
Specialized organs for secretion of enzymes & bile.
Epithelial cells line the entire GI tract and serve as the primary barrier. Specialized epithelial cells also secrete and absorb various compounds to/from the lumen.
Epithelium, mucosa, two layers of smooth muscle, blood vessels and lymphatics, nerves.
Structure maximizes surface area for secretion and absorption (folds, villi, and crypts).
Sphincters regulate movement between segments.

20. GI Sphincters Unitary smooth muscle rings that act as valves
Also see Fig. 1-4 in Barrett

21. Unitary smooth muscle rings that act as valves
GI Sphincters
Unitary smooth muscle rings that act as valves
Resting State
Pressure in sphincter > adjacent segments
Inhibits movement between segments
Relaxation
Pressure in sphincter = adjacent segments
Allows forward flow
Constriction
Pressure in sphincter >> adjacent segments
Prevents retrograde flow

22. Gastrointestinal System: Processes
Motility
Digestion
Secretion
Absorption
Ingestion, Swallowing, Peristalsis, Elimination
Physical (Chewing & Grinding) Chemical (Digestive Enzymes)
Water, HCl, Enzymes, Some Organic Waste Products
Water, Electrolytes, Simple Sugars, Amino Acids, Fatty Acids, Vitamins, Minerals

23. Gastrointestinal System: Processes
Motility
Digestion
Secretion
Absorption
Gastrointestinal System: Processes
Fig. 15-2

24. Water and Solids Balance
Figure 15-5
Water and Solids Balance
Digestive secretions
are mostly water,
with the average
amounts indicated
here. Note that only
100 ml are excreted
in feces, so the
mechanisms for water
absorption are efficient
(recall the kidneys’
primary role in water and
osmotic homeostasis).

25. Innervation of the GI System
Autonomic NS
Parasympathetic Fibers
Sympathetic Fibers
Enteric Nervous System

26. Enteric Nervous System
Intrinsic Control of the GI Tract: GI Reflexes
Can act independently of the CNS. Local Reflexes = “Short Reflexes.”
Cholinergic and Adrenergic Neurons.
Can be influenced by CNS. “Long Reflexes.”

27. Enteric Nervous System
Figure 15-13
Enteric Nervous System
The enteric nervous system coordinates digestion, secretion, and motility to optimize nutrient absorption. Its activity is modified by information from the CNS and from local chemical and mechanical sensors.

28. Structure of Enteric Nervous System in Gut Wall
Fig. 1-8 in Barrett.

29. Immune Function in the GI System
Gut Associated Lymphoid Tissue (GALT), including Peyer’s Patches in the lamina propria of small intestine.
Immune surveillance for potential pathogens in the small intestine.
Contains macrophages, dendritic cells, B lymphocytes, and T lymphocytes.
M Cells in the epithelium - antigen presenting cells that encounter and present antigens to B and T lymphocytes.

30. Splanchnic Circulation

31. Gastrointestinal System: Processes
Motility
Digestion
Secretion
Absorption
Ingestion, Swallowing, Peristalsis, Elimination
Physical (Chewing & Grinding) Chemical (Digestive Enzymes)
Water, HCl, Enzymes, Some Organic Waste Products
Water, Electrolytes, Simple Sugars, Amino Acids, Fatty Acids, Vitamins, Minerals

32. Motility Peristalsis = forward propulsion.
Segmental contractions: mixing.
Mouth and Esophagus: Chewing, Swallowing, Peristalsis
Stomach: Filling, Churning, Peristalsis, Emptying
Small Intestine: Segmental Contractions, Peristalsis
Large Intestine: Haustral Shuttling, Mass Movements, Defecation.
Sphincters: Regulation of Movement

34. GI Smooth Muscle: Circular Muscle and Longitudinal Muscle
Berne & Levy, Fig A
Longitudinal Muscle
Thin Muscle Coat
Contraction shortens intestine length & expands radius
Innervated by excitatory motor neurons
Activated by excitatory motor neurons
Few gap junctions to adjacent fibers
Extracellular Ca2+ influx important in excitation-contraction coupling
Circular Muscle
Thick Muscle Coat
Contraction increases intestine length & decreases radius
Innervated by excitatory & inhibitory motor neurons
Activated by myogenic pacemakers & excitatory motor neurons
Many gap junctions to adjacent fibers
Intracellular Ca2+ release important in excitation-contraction coupling

35. Coordinated, directional contraction of smooth muscle propels ingested food forward (Peristalsis)
See Fig. 7-3 in Barrett.

36. Peristalsis Propulsive contraction of the circular muscle
Evoked by distention of intestinal wall
Does not occur after paralysis of ENS
Longitudinal muscle ahead of bolus contracts, circular muscle layer relaxes, and segment receives the aborally moving intestinal contents
Circular muscle behind bolus contracts, longitudinal muscle simultaneously relaxes
Provides propulsive force necessary to move the contents into the receiving segment

37. See Fig. 7-6 and accompanying text in Barrett.

38. Figure 15-32 Segmental Contractions: Mixing Most of the contractions
of the small intestine are
of the mixing and churning
actions portrayed here as
segmentation contractions;
peristalsis and the
downstream movement
of materials is infrequent.
Figure legend in text has mispelled peristalsis.

39. Mixing Movements
Mix chyme with digestive enzymes and increase contact between intraluminal contents and the epithelium for final digestion and absorption
Non-propagating Circular muscle contractions
Circular muscles on either side of contracting band remain relaxed, i.e., receiving segments on both sides of the zone of contraction, resulting in propagation of intestinal contents in both an oral and aboral direction

40. Contraction of GI Smooth Muscle Cells

41. Myogenic Basis of GI phasic contraction: Slow Waves/Basal Electrical Rhythm
Phase:
0 – Resting membrane potential
Outward K+ current
1 – Upstroke Depolarization
Activation of voltage-dependent Ca2+ channels
2 – Transient Repolarization
Inactivation of voltage-dependent Ca2+ channels
Activation of voltage gated K+ channels
3 – Plateau Phase
Balance of inward Ca2+ current and outward K+
currents
4 – Repolarization
Activation of Ca2+-gated K+ channels

43. Figure legend in text has mispelled peristalsis.
Rhythmic waves of smooth muscle contraction in the gut are the result of waves of action potentials moving along via gap junctions. Fig. 8-3 in Barrett

44. Origin and Control of GI Motor Function
Myogenic
Smooth Muscle
Interstitial Cells of Cajal
Neurogenic
Intrinsic (Enteric NS)
Extrinsic (SNS and PNS)
Endocrine
Paracrine
Origin of Phasic and Tonic Contractions
Modulate Contractions

45. Slow Waves = Basal Electrical Rhythm (BER)
Depolarizations of smooth muscle cells
Controlled by Intersitial Cells of Cajal (ICC)
BER is propogated via gap junctions to a limited number of adjacent cells.
BER is propogated in the aboral direction.

46. Slow Waves/Basal Electrical Rhythm (BER)
Berne & Levy, Fig. 31-6
1. Slow waves only produce contraction when the threshold is achieved.
2. Slow waves determine maximal rhythm of phasic contractions.

47. Ganong,
Fig. 26-2
3. Neurogenic and Endocrine inputs do not alter the BER, but can facilitate reaching the threshold for contraction.

48. BER in different segments:
Stomach ~ 3/min
Duodenum ~ 11-12/min
Distal Ileum and Colon ~ 6-7/min
Note - 3 slides ahead in handout

49. from Horowitz et al, Annual Review of Physiology, 61:19-43, 1999)
Interstitial Cells of Cajal (ICC) generate GI slow waves (basal electrical rhythm)
Wild-type mouse
ICC-deficient mouse
ICC-deficient mouse
ICC-deficient mouse
from Horowitz et al, Annual Review of Physiology, 61:19-43, 1999)

51. INTERSTITIAL CELLS OF CAJAL (ICC)
Cells mediate between efferent neurons and smooth muscle cells:
Responsible for slow waves and pacemaker activity of smooth muscle.
Also amplify neuronal input.
Central to GI motility regulation.
Loss of ICC implicated in many human motility disorders (Hirshsprung’s disease, severe constipation, IBD, etc).
Current evidence suggests that mechanism involves Ca++ release from IP3-operated stores – this triggers Ca++ uptake by mitochondria leading to generation of pacemaker currents.

52. GI Motility: Neural and Endocrine Inputs
BER is minimally affected by neural and endocrine influences. It is intrinsic to ICC and SM.
However, neurogenic and endocrine stimuli can influence membrane potential of SM,
For example, ACh will enhance depolarization, formation of spike potentials, and SM contraction.

53. PACEMAKERS FOR ELECTRICAL SLOW WAVES

54. Fasting Motor Pattern:
“Migrating Myoelectric Complex” (MMC)
From Stomach to the Ileum