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 568-2669
jbresl@lsuhsc.edu
Lecture 1 Outline
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Introduction to GI Physiology
Overview of the Functional Anatomy of the GI Tract.
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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
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Motility Patterns
Basic Mechanisms Underlying Motility
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Required Reading:
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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:
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Review of Medical Physiology, William Ganong,
Chapters 26 and 27.
Both are freely available for students online
through the LSUHSC library website or
www.accessmedicine.com
Single Cell Organisms
Diffusion of water and ions,
Phagocytosis/Endocytosis of larger
particles, digestion & absorption in
Multicellular Organisms
Shape is important!
If the shape is not hollow: Greater Ratio of Volume
to Exterior Surface Area than in a Single Cell
Simple Multicellular Organisms
Shape is
important!
Hydra
Cavity or Lumen
for optimal
digestion and
absorption
Organization into shapes that
maximize surface area for
(Image from Wikipedia)
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.
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.
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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.
Figure 15-1
Anatomy of
the GI Tract
Small Intestine,
3 Segments:
1) Duodenum
2) Jejunum
3) Ileum
Digestion of food and absorption of nutrients are accomplished in a
long tube connected to the external world at both ends; secretion and
motility of Ņthe tubeÓare major themes in understanding the gut.
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.
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,
General Structure of Gut Wall: Cross Section
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Folds in the small intestine
increase surface area for
exchange:
Fold of Kerckring
Fig. 14-56 from Wilson et al, Histology Image Review
Folds of Kerckring, a.k.a. valvulae
conniventes
Villi & Crypts
Vander, Fig. 15-7
Ganong, Fig. 26-27
Microvilli on luminal surface of
intestinal epithelial cells
Degree by which different anatomical features
increase surface area in the small intestine:
Increase in Surface
Area (Relative to
cylinder)
Surface Area (cm2)
1
~3,300
Folds of
Kercking
3
~10,000
Villi
30
~100,000
Microvilli
600
~2,000,000
Structure
Area of simple
cylinder
4 cm Dia. x 260 cm L
GI Sphincters
Unitary smooth muscle rings that act as valves
Also see Fig. 1-4 in Barrett
GI Sphincters
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Resting State
Unitary smooth muscle rings that act as valves
• Pressure in sphincter > adjacent
segments
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Inhibits movement between segments
Relaxation
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Pressure in sphincter = adjacent
segments
Allows forward flow
Constriction
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Pressure in sphincter >> adjacent
segments
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).
Innervation of the GI
System
Autonomic
NS
Parasympathetic
Fibers
Sympathetic Fibers
Enteric Nervous
System
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Enteric Nervous
•Intrinsic Control
of the GI
System
Tract: GI Reflexes
•Can act independently of the
CNS. Local Reflexes = “Short
Reflexes.”
•Cholinergic and Adrenergic
Neurons.
•Can be influenced by CNS.
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.
Structure of
Enteric Nervous
System in Gut
Wall
Fig. 1-8 in Barrett.
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.
Splanchnic Circulation
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
Motility
• Peristalsis = forward
propulsion.
• Segmental contractions:
• Mouth
and
Esophagus:
Chewing,
Swallowing,
mixing.
Peristalsis
• Stomach: Filling, Churning, Peristalsis, Emptying
• Small Intestine: Segmental Contractions, Peristalsis
• Large Intestine: Haustral Shuttling, Mass
Movements, Defecation.
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Sphincters: Regulation of Movement
GI Smooth Muscle:
Circular Muscle and
Longitudinal Muscle
Berne & Levy, Fig. 31- 4A
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
Coordinated, directional contraction of smooth
muscle propels ingested food forward
(Peristalsis)
See Fig. 7-3 in Barrett.
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
See Fig. 7-6 and accompanying text in Barrett.
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.
•Mix chyme
with
digestive
enzymes
and
Mixing Movements
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
Contraction of GI Smooth Muscle
Cells
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
Inactivation of voltage-dependent Ca2+ channels
Activation of Ca2+-gated K+ channels
QuickTime™ and a
decompressor
are needed to see this picture.
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
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Origin and Control of
GI Motor Function
Myogenic
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Smooth Muscle
Interstitial Cells of Cajal
Origin of Phasic
and Tonic
Contractions
Neurogenic
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Intrinsic (Enteric NS)
Extrinsic (SNS and PNS)
Endocrine
Paracrine
Modulate
Contractions
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.
Slow Waves/Basal Electrical Rhythm (BER)
Berne & Levy, Fig. 316
1. Slow waves only produce contraction when the
threshold is achieved.
2. Slow waves determine maximal rhythm of phasic
contractions.
Ganong,
Fig. 26-2
3. Neurogenic and Endocrine inputs do not alter the
BER, but can facilitate reaching the threshold for
BER in different segments:
• Stomach ~ 3/min
• Duodenum ~ 11-12/min
• Distal Ileum Note
and- Colon
~ 6-7/min
3 slides ahead
in handout
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)
INTERSTITIAL CELLS OF
CAJAL (ICC)
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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.
GI Motility: Neural
and Endocrine Inputs
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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,
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For example, ACh will enhance depolarization,
formation of spike potentials, and SM
contraction.
PACEMAKERS FOR
ELECTRICAL SLOW WAVES
Fasting Motor Pattern:
“Migrating Myoelectric Complex” (MMC)
From Stomach to the Ileum