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Homeostasis
THE DIGESTIVE SYSTEM
The digestive systemcontributes tohomeostasis, in part, by
transferring nutrients,H2O, and electrolytesfrom the externalenvironment to theinternal environment.
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Mouth
Anus
Mouth
Anus
Geometrical shape = torus
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Mouth
Pharynx
Large Intestine:
CecumAscending colonTransverse colonDescending colonSigmoid colonRectum
Anus
Stomach
Small Intestine DuodenumJejunumIleum
Esophagus
Salivary glands
Liver
Gallbladder
Pancreas
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FUNCTIONS OF THE GI TRACT:
Protection
Non-immunological defenses Immunological defenses
Nutrition
Transfer nutrients, H2O, and electrolytes from external tointernal environment
Motility Secretion
Digestion
Absorption
Excretion Bile entering the gi tract contains organic anions and cations,
including drugs and drug metabolites that are either poorly
absorbed or not absorbed at all from the gi tract.
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Control of GI Functions Motility Secretion Digestion Absorption Excretion
Non-immunological Defenses
Immunological Defenses
Types of reflexarcs controlling GI
Functions1) Nervous
2) Endocrine
3) Paracrine
4) Immune
Reflex Arc
AfferentInput
Processingand
Integration
EfferentSecreto-Motor
OutputResponse
Presenceo f
St imulusDetected
The functions of the gi tract are controlled by a dynamic interplaybetween different cell types that interact directly, or through a large
number of signaling molecules to form reflex arcs.
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1. Mixing contractions
Mechanical disruption of ingested food
Mix luminal contents with digestivesecretions
Facilitate absorption of digestion products
2. Propulsive contractions
Propel luminal contents, usually in acaudal direction
3. Tonic contractions Maintain constant tone and intraluminal
pressure
Contraction of sphincters restrictsmovement of luminal contents
Gastrointestinal Motility
Contractions of muscles in the wall of the gastrointestinal tract mixcontents of the lumen with digestive secretions and propel contents along
the length of the gi tract.
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Surface epithelium
Mucus Exocrine glands (i.e., glands with ducts that empty into the lumen)
Salivary glands: saliva containing digestive enzymes and mucus
Gastric glands: HCl, digestive enzymes, and mucus
Intestinal glands: H2O, electrolytes, and mucus
Pancreas: pancreatic juice containing digestive enzymes,electrolytes, and mucus
Liver and gallbladder: bile containing bile salts
Gastrointestinal Secretion
1) During digestion of dietary components, a variety of substances aresecreted into the gastrointestinal lumen.
Enteroendocrine cells(i.e., secrete hormones and paracrinesubstances)
Gastric G cells: release gastrin
Gastric D cells: release somatostatin (SS)
Intestinal S cells: release secretin
Intestinal I cells: release cholecystokinin (CCK)
2) The presence of food within the gastrointestinal tract also induces thesecretion of hormones and paracrine substances.
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For example:
Proteins are broken down to single amino acids
Carbohydrates are broken down to simple one-sugar molecules
(i.e.,monosaccharides: glucose, galactose, and fructose)
Triglyceridesare broken down into free fatty acids andmonoacylglycerides
Gastrointestinal Digestion
The proteins, carbohydrates and fats contained in the diet consist oflarge macromolecules that cannot be absorbed across thegastrointestinal epithelium.
Digestive enzymes break these macromolecules down (hydrolysis) intoabsorbable subunits.
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Most of the absorption of nutrients, vitamins,
H2O, and electrolytes occurs from the smallintestine.
Gastrointestinal Absorption
The gastrointestinal epithelium separates outside(lumen) from insidethe body.
1) Absorption of digestion products (along with H2O,vitamins, and electrolytes) enter the body bybeing absorbed across the epithelial cell layer.
2) Absorbed nutrients leave the gastrointestinal tract in blood or lymph.
Hepatic Portal Vein
Monosaccharides, amino acids, water-soluble vitamins, etc.exit via hepatic portal vein en routeto the liver.
Lymphatics
Lipid digestion products and fat-soluble vitamins are packagedwithin chylomicrons(a type of lipoproteins) and cannot entercapillaries, but exit via the lymph vessels.
epithelium
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The digest ive tract wal l consists of four layers:
2) Submucosa Layer of connective
tissue, containinglarger blood andlymph vessels.
4) Serosa Outer connective
tissue covering
3) Muscularis Externa Smooth muscle coat
(longitudinal and
circular musclelayers)
1) Mucosa Lines the luminal
surface (divided intothree layers).
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3) Lamina Propria
Middle layer of
connective tissue
The Mucosa:
Consists of three layers
1) Mucous membrane Inner surface
epithelial cell layer,separating outsidefrom inside thebody..
2) Muscularis Mucosae
Thin layer ofsmooth muscle
adjacent to thesubmucosa.
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The Submucosa: Area under the
mucosa betweenthe muscularismucosae and thecircular smoothmuscle layer
Contains: Connective tissue
Large blood vessels
Large lymph vessels
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2) Longitudinal musclelayer
Outermost layer
whose contractionshortens andstiffens the wall.
The Muscular is Externa:
Consists of two relatively thick layers of smooth muscle
1) Circular muscle layer Innermost layer
whose contractionnarrows the lumen.
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The Serosa:
Connective tissue covering.
Continuous with the
mesentery suspendingthe digestive organsfrom the inner wall ofthe abdominal cavity.
Mesentery
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Two connected networks of
neuronal ganglia and nervefibers.
Submucosal plexus
Myenteric plexus
The Intr in sic Nerve Plexuses:
EntericNervousSystem
(ENS)
MotilitySecretion
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The ENS is extremely large (~100 million neurons) and its ultrastructuralorganization and neuronal diversity are more like brain than peripheralnerve.
The Enteric Nervous System (ENS), the brain of the gut
Acts as a microcomputerwith itsown independent software.
Organized for programmedreflexive operations using neuralelements contained within thewall of the gi tract itself.
1. Intrinsic primary afferentneurons(IPANs) respond tochanges in luminal contentsand distention of the gutwall and convey informationto ENS interneurons.
Reflex Arc
AfferentInput
Processingand
Integration
EfferentSecreto-Motor
OutputResponse
Presence o fSt imulusdetected
2. ENS interneurons integrate information and formulate programmedcommands
3. ENS efferent motor and secretomotor neurons, etc. act to changebehavior of target cells.
The ENS is a center of integrative neuronal activity that is able to controlthe behavior of the gut by neural reflexes, even in the absence of CNS.
ENSefferentneurons
ENSinterneurons
IPANs
ENS
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CNS Also organized for programmed reflexive operations that can modulate
the ENS programs.
1. Extrinsic primary afferentneurons(EPANs)respondto changes in luminalcontents and distention ofthe gut wall and conveyinformation to the CNS.
CNS interneurons andcentersintegrate informationabout events in the gi tractwith other sensory informationand formulate efferentcommands.
CNS efferent neuronsconvey commands to the gi tract
Somatic motor neuronsto areas containing skeletal muscle, and
Autonomic neurons(sympathetic and parasympathetic) to areasthat contain the ENS
Reflex ArcAfferent
Input
Processingand
Integration
EfferentSecreto-Motor
OutputResponse
Presence o fSt imulusdetected
CNSefferentneurons
Spinal cordMedulla
Higher centers
EPANs
CNS
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An understanding of neural reflexive pathways withinthe ENS and those that involve the CNS is essential to
understanding the behavior of the gi tract.
Reflex Arc
AfferentInput
Processing
andIntegration
EfferentSecreto-Motor
OutputResponse
Presence ofStimulusdetected
ENSefferentneurons
ENSinterneurons
IPANs
Reflex Arc
AfferentInput
Processingand
Integration
EfferentSecreto-MotorOutput
Response
Presence o fSt imulusdetected
CNSefferent
neurons
Spinal cordMedulla
Higher centers
EPANs
ENS
CNS
C t l
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InterneuronsIntegrativeCircuitry
MotorPrograms
~
SympatheticNeurons
ParasympatheticNeurons
ExtrinicPrimaryAfferent
Neurons(sensory)
Autonomic
Nervous System
InterneuronsIntegrative
Circuitry
MotorPrograms
~IntrinsicPrimaryAfferentNeurons(sensoryIPANs)
SecretomotorMotor
Vasomotor
Excitatory
Inhibitory
Neurons
Enteric Nervous System
CentralNervousSystem
IPANReceptor
EPANReceptor EFFECTORS
Smooth muscle
Epithelial cells
Vasculature
Entero-endocrinecells
Immune cells
InterstitialCells of
Cajal
Entero-endocrinecells
Chemical
signal
Short-LoopNeuronal Reflex
PathwayUtilizes only neuralelements within the
ENS
THE BRAIN-GUT AXISShort-Loop (ENS)
andLong-Loop(CNS)
NeuralReflexive Pathways
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ENS or entericneurons:
1. ENS intrinsic primary afferent neurons (IPANs) Convey information about lumenal contents to ENS interneurons
2. ENS Interneurons(ascending and descending) Process and integrate sensory information Control behavior of efferent neurons
3. ENS efferent neurons
a. muscle motor neurons Excitatory and inhibitory innervation of smooth muscle
b. ENS secretomotor neurons Innervate the mucosa Control secretion
c. ENS vasomotor neurons
Control blood flow
d. ENS intestinofugal neurons Neuronal cell bodies within the ENS, but send axonal
projections to sympathetic prevertebral ganglia.
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Called IPANs, rather than sensory afferent neurons, because they do notconvey sensationfrom the intestine to the CNS.
Rather, IPANsare ENS afferent neurons that convey information aboutlumenal contents to ENS interneurons to initiate short-loop neuralreflexes.
No IPAN nerve endings reach the lumen of the gut.
How do IPANs detect the presence and composition of lumenalcontents?
1. Presence of contents within the lumen
IPANs within the wall of the gut respond directly to beingstretched when the wall is distended due to contents withinthe lumen.
2. Composition of the lumenal contents IPANs may respond indirectlyto intralumenal stimuli
IPAN nerve endings possess receptors for chemicalmessengers (hormones, paracrine substances) releasedfrom entero-endocrine cells in the mucosal epithelium
into the lamina propria.
Intrinsic Primary Afferent Neurons (IPANs)
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Entero-endocrine cellsin the mucosal epithelium
1. When stimulated, release chemical messengers (hormones,
paracrine substances)into the lamina propria
a) These messengers bind to receptors on IPAN (and EPAN (seelater)) nerve endings.
2. Tasteand feelthe presence of luminal contents
a) Tastethe chemical constituents of the luminal contents.
Receptors (taste buds like on the tongue) on the apicalmembrane sensitive to:
Changes in pH
Protein digestion products
Fat digestion products
D-glucose
Chemical irritants
Changes in solute concentration
b) Feelthe mechanical distortion of the mucosa by shear force,pressure, volume, etc. caused by the presence of luminalcontents.
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Intraluminal
chemical ormechanicalstimulus
Intrinsic Primary AfferentNeuron (IPAN)
ENS neuronal network
Altered motility
Altered secretion
Short loop neural reflexAll neural elements involved in thereflex are contained within the wallof the GI tract.
Entero-
endocrinecell
Distentionand stretch ofthe gut wall
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The ENS and Entero-Endocrine Cells
Specific intraluminal stimuli lumen first activate entero-
endocrine cel lsare strategically positioned in the mucosa totaste and feel luminal contents and release mediators thatactivate IPANs.
Entero-endocrine cells in the stomach
G-cells secrete gastrin
D-cells secrete somatostatin
etc.
Entero-endocrine cells in the small intestine
S-cells secrete secretin
I-cells secrete cholecystokinin
Enterochromaffin cells (EC) secrete serotonin (5HT)
etc.
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Enterochromaffin cell (EC)
Synthesize and store serotonin (5-hydroxytryptamine or 5HT) Taste luminal contents
Nutients
Hyperosmolality
Change in pH
Luminal irritants
Invading enteropathogenic microorganisms
Feel luminal contents
Mechanical forces on the exerted on the mucosal surface
In response to the detection of luminal stimuli, EC release 5HT into thelamina propria.
5HT binds to receptors on IPANs in the lamina propria to initiate ashort-loop neural reflex within the ENS that result in changes insecretion and motility.
An example of an entero-endocrine cell:
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Chemical or Mechanical Stimulation
Circular Muscle
Serosa
Submucous plexus
Myenteric plexus
Mucosa
Lumen
Lamina propria IPANs
SecretomotorNeurons
Interneurons
ECcellHT
ACh
Cl-
Intraluminal stimuli may initiate short-loop reflexes that altersecretion by epithelial cells.
Longitudinal Muscle
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Circular Muscle
Longitudinal Muscle
Submucous plexus
Myenteric plexus
Mucosa
Lumen
Lamina propria
IPANs
Excitatory motor neuron
Inhibitory motor neuron
ECcell
Interneurons
HT
Chemical or Mechanical Stimulation
Intraluminal stimuli may initiate short-loop reflexes that altercontractions in the muscularis externa.
Serosa
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Entero-Endocrine Cells
Example: enterochromaffin cells (EC) Removal of 5HT from the lamina propria
5HT is a base At physiological pH, 5HT is positively charged and cannot
freely enter cells to be metabolized by intracellular enzymes(e.g.,monoamine oxidase or MAO)
Inactivation of 5HT occurs mainly by transporter-mediateduptake into enterocytes.
The serotonin reuptake transporter(SERT or HTT) is theprimary molecule responsible for inactivating 5HT in the gut.
NOTE:
Transcription of SERT is decreased in patients with inflammatory
bowel disease (IBD) or irritable bowel syndrome (IBS). This contributes to
Increased water in stools
Increased colonic motility
Alternating patterns of diarrhea and constipation
InterneuronsCentral
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InterneuronsIntegrativeCircuitry
MotorPrograms
~
SympatheticNeurons
ParasympatheticNeurons
ExtrinicPrimaryAfferentNeurons(sensory)
AutonomicNervous System
InterneuronsIntegrative
Circuitry
Motor
Programs
~IntrinsicPrimaryAfferentNeurons(sensoryIPANs)
SecretomotorMotor
Vasomotor
Excitatory
Inhibitory
Neurons
Enteric Nervous System
CentralNervousSystem
IPANReceptor
EPANReceptor EFFECTORS
Smooth muscle
Epithelial cells
Vasculature
Entero-endocrinecells
Immune cells
InterstitialCells of
Cajal
Entero-endocrinecells
Chemical
signal
Short-LoopNeuronal Reflex
PathwayUtilizes only neuralelements within the
ENS
BRAIN OF THE GUT
InterneuronsCentral
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Long-LoopNeuronal Reflex
PathwayUtilizes neural elementswithin both the CNS and
the ENS
Entero-endocrinecells
Chemical
signal
InterneuronsIntegrativeCircuitry
MotorPrograms
~
SympatheticNeurons
ParasympatheticNeurons
ExtrinicPrimaryAfferentNeurons(sensory)
AutonomicNervous System
InterneuronsIntegrative
Circuitry
Motor
Programs
~IntrinsicPrimaryAfferentNeurons(sensoryIPANs)
SecretomotorMotor
Vasomotor
Excitatory
Inhibitory
Neurons
Enteric Nervous System
CentralNervousSystem
IPANReceptor
EPANReceptor EFFECTORS
Smooth muscle
Epithelial cells
Vasculature
Entero-endocrinecells
Immune cells
InterstitialCells of
Cajal
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Circular Muscle
Longitudinal Muscle
Submucous plexus
Myenteric plexus
Mucosa
Lumen
Lamina propria
Extrinsic primary afferent neuron
CNS
HT
Chemical or Mechanical Stimulation
Pain and Nausea
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1. CNS sensory extrinsic
primary afferentneurons (EPANs)carryinformation from the GItract to the CNS.
2. CNS efferent autonomicnervesfrom the CNSinnervate the ENS.
Sympathetic nerves
Parasympatheticnerves
Nerves Extr in sic to the Gut Wall:Connect ions to the CNS
Autonomic nervous systeminput from the CNS modifiesthe ongoing activity of the
ENS.
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Altered motility
Altered secretion
Long loop neural reflex
ENS neuronal network
Autonomic Nervous Output
ParasympatheticNervous System
SympatheticNervous System
CNS neural elements in the brainand spinal cord are involved inlong-loop neural reflexes and alterparasympathetic and sympatheticneural input to the ENS.
CNS neuronal network(brain and spinal cord)
Intraluminal
chemical ormechanicalstimulus
CNS Extrinsic PrimaryAfferent Neuron (EPAN)
Entero-
endocrinecell
Distentionand stretch ofthe gut wall
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EPANs that convey information from the gastrointestinaltract to the CNS consist of the following three types:
1) Vagal afferent neurons
EPANs within the vagus nerves (X) that convey information tothe medulla
Neuronal cell bodies within vagal ganglia outside of themedulla.
2) Spinal visceral afferent neurons EPANs within the splanchnic nerves (i.e., spinal nerves levels
that convey information from the viscera to the spinal cordsegments T1 to L2 .
Neuronal cell bodies within dorsal root ganglia outside ofthe spinal cord at these levels
3) Pelvic afferent neurons EPANs within the pelvic nerves (i.e., spinal nerves at spinal cord
levels S2 to S4) that convey information to spinal cord levels
Neuronal cell bodies contained in dorsal root gangliaoutside of the spinal cord at these levels
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Circular muscle
Longitudinal muscle
Submucous plexus
Myenteric plexus
Medulla
Vagalganglion
Vagal Primary AfferentNeurons (EPANs)
Parasympatheticpreganglionic
neuron
Vagus Nerve
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Circular muscle
Longitudinal muscle
Submucous plexus
Myenteric plexus
Spinal cord(S2-S4)
Dorsal rootganglion
Parasympatheticpreganglionic
neuron
Pelvic Nerve
Pelvic Primary AfferentNeurons (EPANs)
S i l d
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Circular muscle
Longitudinal muscle
Submucous plexus
Myenteric plexus
Spinal cord(T1-L2) Dorsal root ganglion
Sympathetic prevertebral ganglion
Sympatheticparavertebral ganglion
Sympatheticpost-ganglionic neuron
Sympatheticpre-ganglionic neuron
ENSintestinofugalneuron
Splanchnic Nerves
Spinal Visceral Afferent Neurons (EPANs)
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CNS Efferent Secreto-Motor Output to the GI Tract:
1. Somatic efferents (motor neurons) to striated muscle
Cranial nerves from the brainstem (medulla and pons)
Spinal nerves from sacral spinal cord (pudendal nerves)
2. Visceral efferents (autonomic nervous system (ANS))
Cranio-Sacral Division: Parasympathetic preganglionicneurons
Cranial nerves
Spinal nerves from segments S2- S4 forming the pelvic nerves
Thoraco-Lumbar Division: Sympathetic preganglionic neuronsfrom spinal cord segments T1 to L2
Splanchnic nerves
CNS Eff t S t M t O t t t th GI T t
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Somatic motor neurons innervating striated muscle within the
gastrointestinal tract are found in:1. Cranial nerves (VII, IX, X, and XII), originating from the
brainstem, innervating striated muscle of the jaws, tongue, oralcavity, pharynx, and upper esophagus.
2. Pudendal nerves, originating from the sacral spinal cord,
innervating the striated muscle of the external anal sphincter.
CNS Efferent Secreto-Motor Output to the GI Tract:1. Somatic efferents (motor neurons) to striated muscle
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AutonomicNervous System
CNS Efferent Secreto-Motor Output to the GI Tract:2. Visceral efferents (autonomic nervous system (ANS))
CNS Eff t S t M t O t t t th GI T t
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CNS Efferent Secreto-Motor Output to the GI Tract:2. Visceral efferents (autonomic nervous system (ANS))
a. Cranio-Sacral Division: Parasympathetic preganglionicneurons
1) Cranial nerves from the brainstem
Axons from parasympathetic preganglionic neurons within thebrainstem exit and synapse on postganglionicparasympathetic neurons within parasympathetic gangliaclose to, or within, the target organ (long preganglionic fiber;
short postganglionic fiber). For example, parasympathetic postganglionic neurons
that innervate the salivary glands are located within thesubmandibular and otic ganglia close to the salivaryglands.
Where there is ENS, the postganglionic
parasympathetic neurons are located within the ENS(except for the distal colon).
2) Pelvic nerves from the sacral spinal cord
Synapse on postganglionic parasympathetic neuronspostganglionic neurons within the ENS in the distal colon.
CNS Eff t S t M t O t t t th GI T t
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CNS Efferent Secreto-Motor Output to the GI Tract:2. Visceral efferents (autonomic nervous system (ANS))
b) Thoraco-Lumbar Division: Sympathetic preganglionic neuronsfrom spinal cord segments T1 to L2
1) Axons from sympathetic preganglionic neurons exit the spinalcord and enter the sympathetic paravertebral ganglia at thesame level.
2) The synapse with the sympathetic postganglionic neuron mayoccur at different locations
(a) Within the sympathetic paravertebral ganglion (at the samelevel or at another level)
In this case, the sympathetic postganglionic fiber exits theparavertebral ganglion chain to innervate the distant target(short preganglionic fiber; long postganglionic fiber).
(b) Within a sympathetic prevertebral ganglion, close to thewall of the gi tract, after passing through the paravertebralganglion (long preganglionic fiber; short postganglionicfiber).
In this case, the sympathetic postganglionic fiber exits theprevertebral ganglion to innervate the target (the ENS).
Splanchnicnerves
Parotid
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SpinalNerves(pelvic nerve)
Sympathetic
Liver
Gall
bladder
Pancreas
Small
intestine
Colon
Rectum
Cranialnerves
Salivary
glands
Parasympathetic
Parotidgland
Stomach
Spleen
The thoraco-lumbar
efferent autonomicneuronscomprisethe sympatheticdivisionof theautonomic nervoussystem.
Splanchnicnerves
AutonomicNervous System:
The cranio-sacralefferent autonomicneuronscomprisethe parasympatheticdivisionof theautonomic nervoussystem.
Parasympathetic preganglionic fiber
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Salivary Glands
Salivary glands
Preganglionic parasympathetic neurons
Neuronal cell bodies in superiorand inferior salivary nucleiof the medulla
Preganglionic nerve fibers in cranial nerves (VII, and IX) project tosubmandibular and otic ganglia near salivary glands.
Postganglionic parasympathetic neurons
Neuronal cell bodies in submandibular and otic ganglia
Postganglionic nerve fibers project to and innervate the salivary
glands
Submandibularand
Otic Ganglia
Parasympathetic postganglionicfiber
y p p g g
ParasympatheticNervous System:
Salivary Glands
Parasympathetic Nervous System:
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Esophagus through Transverse Colon, Liver,Gallbladder, and Pancreas
Preganglionic parasympathetic neurons
Preganglionic neuronal cell bodies in dorsal motornucleusand nucleus ambiguusof the medulla
Preganglionic nerve fibers in cranial nerve X (vagusnerves) project to postganglionic neurons within theganglia within target organs
Postganglionic parasympathetic
neuronsParasympathetic postganglionic
neuronal cell bodies in gangliawithin target organs (e.g.,intrapancreatic ganglia, ENS,etc.)
Parasympathetic postganglionicnerve fibers project to targettissues (e.g., pancreatic acinarcells, ENS interneurons, etc.)
Alter secretion, motility,
absorption, etc.
Parasympathetic Nervous System:
X
Parasympathetic Nervous System:
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Descending Colon to Anus
Preganglionic parasympathetic neurons
Neuronal cell bodies in intermediolateral cell column ofspinal cord segments S2 to S4
Preganglionic nerve fibers contained in spinal nervesform the pelvic nerveswhich project to postganglionicneurons in the ENS of the distal colon
Postganglionicparasympathetic neurons
Postganglionic nerve fibersproject to ENS interneurons
Alter activity within the
ENSAlter secretion, motility,
and absorption
Pelvicnerve
Parasympathetic Nervous System:
Spinal
nerves
Parotid
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Sympathetic
Spinal nerves
Splancnicnerves
Liver
Gall bladder
Pancreas
Small
intestine
Colon
Rectum
Salivary
glands
Parotidgland
Stomach
Spleen
Sympathetic Nervous
System:the thoraco-lumbar divisionof the autonomic nervoussystem.
Sympathetic preganglionic fiber
Sympathetic postganglionic fiber
Prevertebralsympathetic ganglia
Paravertebralsympathetic ganglia
(chain ganglia)
(e.g.,superior mesenteric
ganglia, inferior mesentericganglia, celiac ganglia, etc.close to the wall of the gi tract)
Sympathetic preganglionic fibers leave the spinal cord through spinalnerves (T1 to L2)
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nerves (T1 to L2) These axons enter the nearest sympathetic
paravertebralganglion and have one of three fates:
1
2
23
The postganglionic neuron exits to innervatean ENS neuron.
1. Synapse on a
postganglionic neuron withinthe paravertebral ganglionat the same level
2. Travel up or down a fewsegments to synapse on apostganglionic neuron within
a paravertebral ganglion In the above cases, the
postganglionicsympathetic neuron exitsthe paravertebral chainganglia to innervate a
target tissue.3. Pass thru the paravertebral ganglion
to synapse on a postganglionicneuron within a prevertebralganglion;
Salivary glands
P li i h i
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Preganglionic sympathetic neurons
Preganglionic neuronal cell bodies in spinalcord intermediolateral cell column (T1-L2)
Preganglionic nerve fibers enter
paravertebral (i.e., beside the vertebra)sympatheticchain gangliato synapse onpostganglionic neurons
Postganglionic fibers ascendthe paravertebral sympathetic
chain ganglia to the superiorcervical gangliaand exit toinnervate the salivary glands
Alter salivary gland secretionand blood flow
Postganglionicsympathetic neurons
Postganglionic neuronalcell bodies withinparavertebral sympatheticchain ganglia
Paravertebralganglia
Superiorcervicalganglion
2
1
Esophagus through Entire Colon, Liver, Gallbladder, andPancreas
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Pancreas
Preganglionic sympathetic neurons
Neuronal cell bodies in spinal cord intermediolateral cellcolumn (T1-L2)
Preganglionic nerve fiberspass through paravertebral sympathetic chain
ganglia without synapsing and
project toprevertebral sympathetic ganglianear theGI tract where they synapse on postganglionicneuronal cell bodies.
Postganglionic sympatheticneurons
Neuronal cell bodies in outlyingprevertebral sympathetic ganglia(e.g.,superior mesenteric, inferior
mesenteric, and celiac ganglia)Postganglionic sympathetic fibers
project to ENS interneurons
Alter neuronal activity withinthe ENS
Alter secretion, motility,and absorption, etc.
Prevertebralganglia
Paravertebral
ganglia
333
Spinal cord
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ENSintestinofugalneuron
Sympatheticpost-ganglionic neuron
Sympatheticpre-ganglionic neuron
Spinal Visceral Afferent Neurons (EPANs)
Neural input to the sympathetic postganglionicneuron within the prevertebral sympatheticganglia:
a) Sympathetic preganglionic fiber from thespinal cord
b) Collateral fiber from spinal visceralafferent neuron
c) Collateral fiber from ENS intestinofugalneuron
Spinal cord(T1-L2) Dorsal root ganglion
Sympathetic prevertebralganglion
Sympathetic paravertebralganglion
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1) Short-loop (Intrinsic) reflex
All elements within the ENS.
2) Long-loop (Extrinsic) reflex
Afferent: spinal visceral, vagal, and pelvic nerves
Convergence of sensory input, processing, integration:spinal cord, brainstem, midbrain, hypothalamus
Efferent: sympathetic or parasympathetic
3) Intermediate loop (prevertebral ganglionic) reflex
Collateral sensory fibers from sensory ENS intestinofugalneurons and spinal visceral afferents to prevertebral ganglia
modify efferent sympathetic neural traffic.
*There is redundancy!!
Neural reflexes possible at three levels:
InterneuronsIntegrative
CentralNervous THE BRAIN-GUT AXIS
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IntegrativeCircuitry
MotorPrograms
~
SympatheticNeurons
ParasympatheticNeurons
ExtrinicPrimaryAfferentNeurons
(sensory)
AutonomicNervous System
InterneuronsIntegrative
Circuitry
Motor
Programs
~IntrinsicPrimaryAfferentNeurons(sensoryIPANs)
SecretomotorMotor
Vasomotor
Excitatory
Inhibitory
Neurons
Enteric Nervous System
NervousSystem
IPANReceptor
EPANReceptor EFFECTORS
Smooth muscle
Epithelial cells
Vasculature
Entero-endocrinecells
Immune cells
InterstitialCells of
Cajal
Entero-endocrinecells
Chemical
signal
Short-Loop (ENS)and
Long-Loop(CNS)Neural
Reflexive Pathways
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When stimulatedappropriately, entero-endocrine cells in themucosa release paracrinesubstances into thelamina propria andhormones into the blood.
GI paracrinesubstances andhormones influence
Secretion
Motility
Gastrointest inal Paracr ine
Substances and Hormones:
Endocrine/Paracrine Regulation
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Endocrine/Paracrine Regulationof Gastrointestinal Function
GI tract is the largest endocrine organMucosal endocrine cells -- peptide hormones
Mucosal paracrine cells -- paracrine peptides
ENS neurons -- neurocrine peptides
GI tract is the largest immune organ Immune cells -- paracrine peptides
-- histamine
-- prostaglandins
-- etc.
Endocrine/paracrine regulators of gi functionoperate in concert with neural regulation.
Endocrine/Paracrine Regulation
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Endocrine/Paracrine Regulationof Gastrointestinal Function
GI tract as a paracrine organ
GI paracrine cellsare similar to endocrine cells Paracrine substances are secreted into interstitial space in
response to appropriate stimuli.
Paracrine substances diffuse to local target cells
IPANs and EPANs
Absorptive cells
Other endocrine cells
ENS cells
Secretory cells
Paracrine cells
Immune cells
Etc.
Example:Gastric D cells release somatostatin(SS), a paracrine peptide, that inhibits acidsecretion by nearby gastric parietal cells.
Endocrine/Paracrine Regulation
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Endocrine/Paracrine Regulationof Gastrointestinal Function
GI tract as an endocrine organ
GI endocrine cells GI hormones are secreted into blood in response to an
appropriate stimulus.
GI hormones act at distant target cells
Absorptive cells
Other endocrine cells IPANs and EPANs
ENS cells
Secretory cells
Paracrine cells
Immune cells
Etc.
Example: Secretin, a hormone released into theblood by the small intestine, stimulates gastric Dcells to release SS that inhibits acid secretion bygastric parietal cells.
Endocrine/Paracrine Regulation
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gof Gastrointestinal Function
GI tract as an immune organ GI immune cells
Release paracrine substances into interstitial space inresponse to appropriate stimuli.
bacterial antigenic proteins
cytokines
histamine
peptides prostaglandins
Paracrine substances released from immune cells diffuseto local target cells
Absorptive cells
Endocrine cells IPANs and EPANs
ENS cells
Secretory cells
Paracrine cells
Other immune cells
Etc.
Control of GI Functions
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Control of GI Functions Digestion Secretion
Absorption Motility Excretion
Non-immunological Defenses Immunological Defenses
Types of reflexarcs controllingGI Functions
1) Nervous
2) Endocrine
3) Paracrine
Reflex Arc
AfferentInput
Processingand
Integration
EfferentSecreto-MotorResponse
Presenceo f
s t imu lus
The functions of the gi tract are controlled by a dynamic interplaybetween different cell types that interact directly, or through a large
number of signaling molecules to form reflex arcs.