GI #11
Tuesday 2/18 1:00pm
Dr. Gwirtz
Kevin Stancoven
Page 1 of 7
Checked – only corrections are on last page and they are in bold in italics.
Neurohumoral Control of the GI Tract
All course slides are on the web. There are some physiology practice questions, with answers on the
website. Histology lectures will be on first exams. There will only be written histology questions on exam
1, there will be slides on the practical exam and last exam.
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Objectives
o Describe the characteristics & functions of the layers of the wall of the GI tract
o Describe the hormonal/paracrine control of GI functions
o Explain the neural control of GI functions
 Sympathetic
 Parasympathetic
 Enteric – intrinsic nervous system of GI system
o Describe local & central reflex control of GI functions
o Describe the mechanical & electrophysiological properties of GI smooth muscle cells
o Describe the function of the enteric nervous system
Major structure of GI tract & their functions
o Each part specialized for a specific function
o Mouth – receives food, chewing food, mixing with saliva
o Salivary secretions – amylase begins starch digestion
o Esophagus – passage of food
o Stomach – storage, mixing, grinding organ, secretes acid & pepsin
 Pepsin begins digestion of proteins
 Grinds food to particles less than 2 mm in diameter
o Small intestines (duodenum, jejunum, ileum) – digestion, absorption
o Proximal colon – absorption of water & electrolytes
o Descending colon – storage of fecal material
o Complex glands – secretion of enzymes
 Salivary glands, pancreas (bicarb), liver (bile)
 Bicarb neutralizes gastric acid
 Bile necessary for lipid digestion/absorption
o Epithelial cell lining – secretions, absorption
Time a meal spends in the GI tract
o Mouth to lower esophageal sphincter (LES) – 9 seconds
o Digestion in the stomach – 3-5 hours
 Depends of composition of meal
 High fat diet – spends more time in stomach because inhibitory signals from
small intestines will decrease motility – stop movement into intestines
o Time to move through the pyloric sphincter – 1-5 minutes
 Depends on pressure gradient across sphincter & consistency of chyme
o Time spent in small intestines – 4-5 hours
o Time in proximal colon – 6-7 hours
Meal spends most of
o Time in transverse colon – 9-10 hours
time in colon
o Time in distal colon – 12-24 hours
Layers of the gut wall
o Serosa (outer layer)
o Longitudinal smooth muscle
o Circular smooth muscle
 Longitudinal & circular muscle layers control gut motility
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Myenteric plexus
 Between longitudinal & circular muscle layers
o Submucosal plexus
 Between circular muscle layer & submucosa
o Submucosa
o Muscularis mucosa
o Mucosa: epithelium, lamina propria, glands, lymphatics, blood vessels, villus
 Nutrients absorbed into epithelial cells
 Amino acids & carbohydrates absorbed into blood capillaries
 Lipids absorbed into lymph vessels
Hormonal/paracrine control of GI function
o Endocrine cells release hormones
 Located in mucosa or submucosa of stomach, intestines, & pancreas
 Hormones: Substances released into bloodstream & effect various target organs
o Paracrine substances
 Released from cells located in stomach & GI immune system
 Paracrine: substance released by cell & has local effect (effect is on cells very
close to cell that released substance)
 Mast cells release histamine, which causes parietal cells to secrete acid
 Somatostatin released in response to acid & inhibits gastrin secretion from G
cells
o Hormones & paracrines
 Act on secretory cells, liver, smooth muscle cells, & sphincters
 Alter secretory & motor functions of GI tract
Hormones:
o Acetylcholine
 Neurotransmitter for parasympathetic nerves
o Gastrin
 Secreted from G cells in antrum of stomach
 Major gut hormone
o Secretin
 Secreted from duodenum
 Major gut hormone
o Cholecystokinin (CCK)
 Secreted from duodenum
 Major gut hormone
o Gastric inhibitory peptide (Glucose-dependent insulinotropic peptide)
 GIP
 Inhibits motility
 Stimulates pancreas to release insulin
o Vasoactive inhibitory peptide (VIP)
 Relaxes sphincters
o Motilin
o Bombesin (Gastrin releasing peptide, GRP)
o Somatostatin
o Histamine
o Nitric oxide
 Relaxes sphincters
o Norepinephrine, epinephrine
o Opioids, enkephalins
Information to know about the above hormones
o Site of release
o Stimulus for release
o Target organs
o Responses of target organs
o Refer to table in syllabus for the summary of this information
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GI functions controlled by autonomic & intrinsic nerves (enteric nerves)
o Smooth muscle tone
 Degree of muscle activity, contraction, relaxation
o Secretion
o Absorption
 Affected by muscle tone & secretion of enzymes
o Blood flow
Autonomic innervation of GI tract
o Parasympathetic innervation
 Vagus nerve
 Innervates all of GI tract except distal colon, rectum, & internal anal
sphincter
 Sacral/pelvic parasympathetic
 Innervates distal colon, rectum, & internal anal sphincter
 Stimulation increases the activity of the entire enteric nervous system
 Parasympathetic nerves synapse with enteric nervous system at
myenteric & submucosal plexuses
 Which effect smooth muscle, secretory cells, & endocrine cells that
release GI hormones
o Sympathetic innervation
 Fibers originate in spinal cord between T-5 & L-2
 Inhibits the activity of the GI tract
 Also synapses with enteric nervous system
Parasympathetic innervation
o Parasympathetic fibers (vagus & pelvic nerves) connect sensory receptors to the CNS
 Basically, parasympathetic stimulation of the gut increases everything
 Stimulates motility & secretion
 Relaxes smooth muscle at sphincters
o Receptors provide information such as:
 pH & osmolality of the lumen of stomach & duodenum
 Movement of material past mucosal mechanoreceptors
 Level of contractile tension or stretch within the wall
 Glucose concentration in the lumen
o This information is processed in the medulla & efferent signals are sent to gut
o These vagovagal reflexes are important for normal gut function
o Vagal efferent signals may be excitatory or inhibitory (depending on neurotransmitter
released)
 Anticipatory response to a meal
 Sight or smell of food
 In cephalic phase of digestion
 Presence of ingested food causes salivation, increases gastric & small intestinal
secretions
 Mediates receptive relaxation of LES, gastric tone, as well during cephalic phase
Sympathetic innervation
o Sympathetic stimulation of the gut usually inhibits digestive processes – mediated by NE
 Decreases gut motility & secretions
o Innervates enteric neurons, intramural blood vessels, intestinal crypts, & smooth muscles
of the sphincters
 Decreases motility & secretion
 Decreases blood flow to the intestines
 Vasoconstriction by activating alpha-receptors on blood vessels
 Contracts sphincter smooth muscles
Enteric nervous system (ENS)
o Cell bodies of neurons of the ENS are located in ganglia positioned inside the walls of the
gut
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AKA: The little brain in the gut
ENS contains about the same number of neurons as the CNS
 Both have about 108 neurons
 Myenteric nerve plexus is located between longitudinal & circular smooth
muscle layers
 Submucosal nerve plexus is located between circular smooth muscle layer &
submucosa
o Contains 3 kinds of neurons
 Sensory neurons
 Interneurons
 Motor neurons
Sensory neurons
o Mechanoreceptors
 Stretch: senses movement of chyme along mucosal surface
 Chyme is liquefied food
o Chemoreceptors
 Concentration of glucose, fats, osmolality, pH of chyme
 Secretions from stomach, small intestines, & pancreas help get the chyme to be
isoosmotic (same osmolality as the plasma)
 2 liters of gastric secretions dilute the food that you eat
 Digestion & absorption are more efficient when the chyme is
isoosmotic
o Thermoreceptors
 Deep body temperature
 Help in body temperature regulation
Neurotransmitters secreted by the ENS
o Don’t memorize
 Ach
 NE
 ATP
 Serotonin
 Dopamine
 CCK
 Substance P
 VIP
 Somatostatin
 Leu-Enkephalin
 Met-Enkephalin
 Bombesin
o Because the ENS uses a variety of neurotransmitters, it can inhibit & stimulate at the
same time to control gut motility
Myenteric Plexus – Auerbach’s Plexus
o Located between longitudinal & circular muscle layers
o Made up of neurons, ganglia, & interganglionic fiber trances
o Organized such that mechanical forces & deformation occur during muscle contraction or
stretching of the wall (as the lumen fills) will stimulate nerve endings
o Location of most of the motor neurons to the circular & longitudinal muscle layers
o Concerned with the control of motility
Submucous Plexus – Meissner’s Plexus
o Most prominent in small & large intestines
o Located in submucosal space between the mucosa & circular muscle coat
o Contains motor neurons that innervate the intestinal crypts & villi
o Can send fibers to the myenteric plexus
 Two plexuses are separated, but interconnected so that they function as a unified
nervous system
o Concerned with sensory information & secretory responses
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Unique properties of GI smooth muscles
o Outer layer – longitudinal muscles
 When contracted, shortens the length of the tube
o Inner layer – circular muscles
 When contracted, the diameter of the lumen will decrease
o Motility pattern: relaxation of circular muscle layer & contraction of longitudinal muscle
layer
 When you widen lumen of GI tract – receptive relaxation
 Peristaltic reflex – longitudinal muscle will relax & circular muscle will contract
 Receptive relaxation – longitudinal muscle will contract & circular muscle will
relax
Smooth muscle will contract in response to:
o Nerve stimulation
 Parasympathetic stimulation causes muscle to contract
o Hormonal stimulation
 Gastrin causes muscle to depolarize
 Muscle reaches threshold for action potential & will contract
o Pharmacological stimulation
 Decongestants are alpha-agonists
 Cause smooth muscle to contract
o Presence or lack of metabolites
o Cold
o Pressure, stretch, or touch
o Smooth muscle also has spontaneous activity as well (myogenic)
Contraction/Relaxation of smooth muscle
o Resting membrane potential fluctuates from -40 mV to -80 mV
 Fluctuates due to electrogenic Na-K pump in the membrane of interstitial cells
of Cajal
 Pacemaker cells located in stomach & various locations in small
intestines
 Resting membrane potentials fluctuate at different rates
 After duodenum, rate decreases as you move down the GI tract
 Called slow waves or basic electrical rhythm
 Frequency of slow waves varies throughout GI tract
 Do not cause muscle contractions
 Entry of Ca2+ into muscle cell causes contraction
 Does control the appearance of intermittent action potentials, which do cause
muscle contractions
Electrical slow waves
o Rate of occurrence
 Amplitude & frequency (to lesser extent) are modified by intrinsic & extrinsic
nerves, hormones, & paracrines
 Stomach – 3 waves per minute
 Duodenum – 12 per minute
 Terminal ileum – 8 per minute
 Proximal colon – 4 per minute
 Distal colon & rectum – 6 per minute
o Motility in GI tract determined by rate of waves
 Moves from area of faster rates (duodenum) to area of slower rates (colon)
 The law of the gut
o How does suppository get into the colon from the rectum?
 Rate of contraction in rectum is faster than proximal colon, so it pulls the
suppository into the colon
 Same mechanism also keeps feces out of rectum
o Contraction of small intestinal smooth muscle occurs when depolarization caused by
slow wave exceeds threshold for action potential and Ca2+ enters the cell (graph)
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Voltage-gated Ca2+ channels open at dashed line
 At the threshold for contraction
 Can weak muscle contraction
 Electrical threshold must be reached for action potential to be generated
 Spike potentials on top of slow wave
 Opening of a lot of Ca2+ channels – greater force of contraction
 The more action (spike) potentials – the greater the force of muscle
contraction
 Must have calcium entering smooth muscle cell for contraction
 Hormones or chemicals can bind receptors that open Ca 2+ channels or
cause release of Ca2+ from sarcoplasmic reticulum
 Don’t always need an action potential to cause muscle contraction
Action (Spike) potentials
o Occur when resting membrane potential reaches threshold – become more positive (less
negative) than -40 mV (resting potential is normally -50 to -60 mV)
o The higher the slow wave potential rises above -40 mV, the greater the frequency of
spike potentials
o Causes the entry of Ca2+ ions into smooth muscle cells, resulting in depolarization &
muscle contraction
 Gastrin will depolarize the muscle cell
o Inhibitory chemicals hyperpolarize
 Hyperpolarize: relaxes muscle cells
 Gastrin inhibitory peptide (GIP)
Relationship between slow waves, action potentials, & smooth muscle cells
o Slow waves are always present in smooth muscle
o In the “resting” state, only the slow waves occur
 Change amplitude of slow waves by stimulation by nerves or expose to
hormones
o As the muscle becomes active, action potentials begin to appear on the positive peaks of
the slow waves & muscle contraction follows
o The rate of slow waves determines the frequency of contractions
 Contractions occur at 3 per minute in stomach
 3 slow waves per minute in the stomach
o The number of action potentials on each slow wave peak determines the strength of
muscle contraction
 Slow waves don’t determine force of contraction
 Force of contraction determined by amount of Ca2+ that enters the cell
Stimuli to change resting membrane potential
o Depolarize:
 Stretch – chyme into GI tract
 Parasympathetic stimulation
 ACh
 Myenteric plexus stimulation
 ACh
 Hormones: gastrin
o Hyperpolarize:
 Sympathetic stimulation
 NE
 Hormones: Epi, VIP, GIP, secretin, NO
 Relax smooth muscle
Cell connections
o Not all smooth muscle cells are innervated by nervous systems
o GI smooth muscle cells are coupled to neighboring cells for rapid transmission of signals
between cells
 Ephatic conduction
 Functional syncytium
Defense bodies
 Force/mechanical transmissions
o Gap junctions
 Electrical & metabolite transmissions
o Junctions allow stimulation to occur in cells that are not innervated
Types of contractions
o Rhythmic contractions
 Responsible for phasic functions such as mixing & peristalsis
o Phasic contractions
 Smooth muscle makes rapid contractions followed by complete relaxation
 Typical of smooth muscle stimulated by neural activity
o Tonic contractions – at sphincters
 Smooth muscle can maintain low level of active tension for long periods of time
without cyclic contractions & relaxation
 Nerves continuously releasing neurotransmitter to keep muscle contracted
 Contractions are a continuous contraction that lasts minutes to hours. They are
caused by a series of action potentials or continual entry of Ca2+
 Typical smooth muscle activated by hormonal, pharmacological, or metabolic
factors
 Periodically relaxed with nerve or hormone signals
 Allow movement of GI contents
 Sphincter contraction doesn’t allow backflow of GI contents
Brain-Gut interaction
o Neural control of digestive processes involves both the CNS (autonomic) & enteric
nervous system
 Relation between emotional state & GI malaise is well known
o Emotional stress can cause diarrhea, constipation, GI pain, & peptic ulcers – thus
demonstrating a brain-gut connection
 Chronic stress - continually parasympathetic – high levels of acid secretion,
decreased mucous & bicarb formation = peptic ulcers
Local & central GI reflexes
o Short arc reflex – only involves myenteric plexus
 Local reflex – secretions & hormone release
 examples include segmentation, mixing contractions
o Long arc reflex – involve CNS
 Chewing, swallowing, peristalsis, defecation
Local GI reflex pathways
o Local mechanical or chemical stimulation in intestinal mucosa causes contraction above
and relaxation below the point of stimulation
o Local enteric circuitry for reflex
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