GI Physiology I:Introduction &

Motility Mechanisms

IDP-DPT GI Section, Fall 2011Jerome W. Breslin, Ph.D.LSUHSC-NO Department of

PhysiologyMEB 7208, Tel 568-2669

jbresl@lsuhsc.edu

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

•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 www.accessmedicine.com

Single Cell Organisms

Diffusion of water and ions,

Phagocytosis/Endocytosis of larger particles, digestion &

absorption in lysosomes

Multicellular Organisms

If the shape is not hollow: Greater Ratio of Volume to Exterior Surface

Area than in a Single Cell

Shape is important!

Simple Multicellular Organisms

Organization into shapes that maximize surface area

for exchange

Cavity or Lumen for optimal

digestion and absorption

Shape is important!

Hydra(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.

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.

Anatomy ofthe GI Tract

Figure 15-1

Digestion of food and absorption of nutrients are accomplished in along tube connected to the external world at both ends; secretion andmotility of Ņthe tubeÓ are major themes in understanding the gut.

Small Intestine,3 Segments:1) Duodenum2) Jejunum3) Ileum

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 15-3

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.

Figure 15-6 General Anatomy of Gut Wall

(Contains connective tissue, immune cells, capillaries, nerve endings)

(Might have role in villus movement)

See Fig. 1-2 and Fig. 1-3 in Barrett’s book,

14

General Structure of Gut Wall: Cross Section

Folds in the small intestine increase surface area for

exchange:

Fig. 14-56 from Wilson et al, Histology Image Review Folds of Kerckring, a.k.a. valvulae conniventes

Fold of Kerckring

Villi & Crypts

Ganong, Fig. 26-27

Vander, Fig. 15-7

Microvilli on luminal surface of intestinal

epithelial cells

Area of simple

cylinderFolds of Kercking

Villi

Microvilli

Degree by which different anatomical features increase surface area in the small intestine: Increase in

Surface Area (Relative to cylinder)

Surface Area (cm2)Structure

1

600

30

3

4 cm Dia. x 260 cm L

~3,300

~10,000

~100,000

~2,000,000

GI SphinctersUnitary smooth muscle rings that act as valves

Also see Fig. 1-4 in Barrett

GI Sphincters•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

Unitary smooth muscle rings that act as valves

Digestive secretionsare mostly water,with the average amounts indicated here. Note that only100 ml are excretedin feces, so the mechanisms for waterabsorption are efficient(recall the kidneys’primary role in water and osmotic homeostasis).

Figure 15-5

Water and Solids Balance

Innervation of the GI System•Autonomic NS

•Parasympathetic Fibers•Sympathetic Fibers•Enteric Nervous System

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.”

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.

Figure 15-13

Enteric Nervous System

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, EliminationPhysical (Chewing &

Grinding) Chemical (Digestive Enzymes)Water, HCl,

Enzymes, Some Organic Waste

ProductsWater,

Electrolytes, Simple Sugars,

Amino Acids, Fatty Acids, Vitamins,

Minerals

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

GI Smooth Muscle:

Circular Muscle and

Longitudinal MuscleBerne & Levy, Fig. 31- 4ALongitudinal Muscle

Thin Muscle CoatContraction shortens intestine length & expands radiusInnervated by excitatory motor neuronsActivated by excitatory motor neuronsFew gap junctions to adjacent fibersExtracellular Ca2+ influx important in excitation-contraction coupling

Circular MuscleThick Muscle CoatContraction increases intestine length & decreases radiusInnervated by excitatory & inhibitory motor neuronsActivated by myogenic pacemakers & excitatory motor neuronsMany gap junctions to adjacent fibersIntracellular Ca2+ release important in excitation-contraction coupling

Coordinated, directional contraction of smooth muscle propels ingested food forward (Peristalsis)

See Fig. 7-3 in Barrett.

•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

Peristalsis

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

Most of the contractions of the small intestine are of the mixing and churning actions portrayed here assegmentation contractions; peristalsis and the downstream movement of materials is infrequent.

Figure 15-32

Segmental Contractions:Mixing

•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

Mixing Movements

Contraction of GI Smooth Muscle Cells

Myogenic Basis of GI phasic contraction:

Slow Waves/Basal Electrical RhythmPhase:

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

• Myogenic

• Smooth Muscle

• Interstitial Cells of Cajal

• Neurogenic

• Intrinsic (Enteric NS)

• Extrinsic (SNS and PNS)

• Endocrine

• Paracrine

Origin and Control of GI Motor Function

Origin of Phasic and

Tonic Contractions

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)

1. Slow waves only produce contraction when the threshold is achieved.2. Slow waves determine maximal rhythm of phasic contractions.

Berne & Levy, Fig. 31-6

Ganong,Fig. 26-2

3. Neurogenic and Endocrine inputs do not alter the BER, but can facilitate reaching the threshold for contraction.

BER in different segments:

•Stomach ~ 3/min

•Duodenum ~ 11-12/min

•Distal Ileum and Colon ~ 6-7/minNote - 3 slides ahead in handout

Wild-type mouse

ICC-deficient mouse

ICC-deficient mouse

ICC-deficient mouse

Interstitial Cells of Cajal (ICC) generate GI slow waves (basal

electrical rhythm)

from Horowitz et al, Annual Review of Physiology, 61:19-43, 1999)

INTERSTITIAL CELLS OF INTERSTITIAL CELLS OF CAJAL (ICC)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.

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.

PACEMAKERS FOR ELECTRICAL SLOW WAVES

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