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Phys Ch 62
General Principles of GI Motility
 Intestinal wall (from outer surface inward) composed of serosa, longitudinal smooth muscle layer, circular
smooth muscle layer, submucosa, and mucosa
o Sparse bundles of smooth muscle fibers (mucosal muscle) like in deeper layers of mucosa
 Individual smooth muscle fibers in GI tract arranged in bundles of as many as 1000 parallel fibers
o Within each bundle, muscle fibers electrically connected with one another through large numbers of gap
junctions that allow low-resistance movement of ions from one muscle cell to the next
o Electrical signals that initiate muscle contraction can travel readily from one fiber to the next within
each bundle but more rapidly along length of bundle than sideways
o Each bundle of smooth muscle fibers is partly separated from the next by LCT, but muscle bundles fuse
with one another at many points, so in reality each muscle layer represents a branching latticework of
smooth muscle bundles
o Each muscle layer functions as a syncytium; when AP elicited anywhere within the muscle mass, it
generally travels in all directions in the muscle; distance it travels depends on excitability of muscle
 Sometimes it stops after only a few mm and other times, it travels many cm or the entire length
and breadth of intestinal tract
o Few connections exist between longitudinal and circular muscle layers, so excitation of one of these
layers often excites the other as well
 Smooth muscle of GI tract excited by almost continual, slow, intrinsic electrical activity along membranes of
muscle fibers; activity can be slow waves or spikes; voltage of resting membrane potential of GI smooth muscle
can be made to change to different levels to control motor activity of GI tract
o Slow waves – most GI contractions; rhythmical in frequency; waves not APs but slow, undulating
changes in resting membrane potential
 Frequency is about 3 per minute in the stomach, as much as 12 in the duodenum, and about 8-9
in the terminal ileum
 Caused by complex interactions among smooth muscle cells and specialized cells (interstitial
cells of Cajal) that act as electrical pacemakers for smooth muscle cells
 Cells of Cajal form network with each other and are interposed between smooth muscle
layers with synaptic-like contacts to smooth muscle cells
 Cells undergo cyclic changes in membrane potential due to unique ion channels that
periodically open and produce inward (pacemaker) currents that generate slow wave
activity
 Slow waves usually don’t cause muscle contraction by themselves in most parts of GI tract,
except in stomach; mainly excite appearance of intermittent spike potentials, and spike
potentials in turn actually excite muscle contraction
o Spike potentials – true APs; occur automatically when resting membrane potential of GI smooth muscle
becomes more positive
 The higher the slow wave potential rises, the greater the frequency of the spike potentials
 Spike potentials last 10-40x as long in GI muscle as APs in large nerve fibers
 In nerve fibers, APs caused almost entirely by rapid entry of Na+ through Na+ channels to interior
of fibers; in GI smooth muscle fibers, channels responsible for APs allow large numbers of Ca2+
to enter along with smaller numbers of Na+ (calcium-sodium channels)
 Calcium-sodium channels much slower to open and close than rapid sodium channels of
large nerve fibers
 Slowness of opening and closing of calcium-sodium channels accounts for long duration
of APs
 Factors that depolarize the membrane are stretching of the muscle, stimulation by acetylcholine released from
endings of PNS nerves, and stimulation by several specific GI hormones
 Important factors that hyperpolarize membrane are effect of norepinephrine or epinephrine on fiber membrane
and stimulation of SNS nerves that secrete mainly norepinephrine at their endings
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Smooth muscle contraction occurs in response to entry of Ca2+ into muscle fiber; Ca2+, acting through calmodulin
control mechanism, activate myosin filaments in fiber, causing attractive forces to develop between myosin
filaments and actin filaments, thereby causing muscle to contract
o Slow waves don’t cause Ca2+ to enter smooth muscle fiber (only Na+); slow waves themselves usually
cause no muscle contraction
o During spike potentials, generated at peaks of slow waves, significant quantities of Ca2+ enter fibers and
cause most of the contraction
 Some smooth muscle of GI tract exhibits tonic contraction as well as or instead of rhythmical contractions
o Tonic contraction is continuous, not associated with basic electrical rhythm of slow waves, often lasting
several minutes or hours
o Tonic contraction often increases or decreases in intensity but continues contracting
o Tonic contraction sometimes caused by continuous repetitive spike potentials; the greater the
frequency, the greater the degree of contraction
o At other times, tonic contraction caused by hormones or other factors that bring about continuous
partial depolarization of smooth muscle membrane without causing APs
o Tonic contraction can also be caused by continuous entry of Ca2+ into interior of cells brought about in
ways not associated with changes in membrane potential
Neural Control of GI Function – Enteric Nervous System
 Enteric nervous system – lies entirely in wall of gut, beginning in esophagus and extending to anus
o Composed mainly of 2 plexuses: outer plexus lying between longitudinal and circular muscle layers
(myenteric plexus or Auerbach’s plexus) and inner plexus (submucosal plexus or Meissner’s plexus) that
lies in submucosa
o Myenteric plexus controls mainly GI movements, and submucosal plexus controls mainly GI secretion
and local blood flow
o SNS and PNS fibers connect to both myenteric and submucosal plexuses
 Enteric nervous system can function independently of extrinsic nerves, but stimulation by PNS
and SNS greatly enhance or inhibit GI functions
 Sensory nerve endings originate in GI epithelium or gut wall and send afferent fibers to both plexuses of enteric
system, as well as to prevertebral ganglia of SNS, spinal cord, and in vagus nerves all the way to brain stem
o Sensory nerves can elicit local reflexes in gut wall itself or other reflexes that are relayed to gut from
either prevertebral ganglia or basal regions of brain
 Myenteric plexus – consists mostly of linear chain of neurons that extends entire length of GI tract
o Concerned mainly with controlling muscle activity along length of gut
o When plexus stimulated, principal effects are
 Increased tonic contraction (tone) of gut wall
 Increased intensity of rhythmical contractions
 Slightly increased rate of rhythm of contraction
 Increased velocity of conduction of excitatory waves along gut wall, causing more rapid
movement of gut peristaltic waves
o Has inhibitory fibers that secrete inhibitory transmitter (vasoactive intestinal polypeptide); signals useful
for inhibiting some of intestinal sphincter muscles that impede movement of food along successive
segments of GI tract, such as pyloric sphincter and sphincter of ileocecal valve (controls emptying from
small intestine into cecum)
 Submucosal plexus – mainly concerned with controlling function in inner wall of each minute segment of
intestine; many sensory signals originate from GI epithelium and are integrated in submucosal plexus to help
control local intestinal secretion, local absorption, and local contraction of submucosal muscle that causes
various degrees of infolding of GI mucosa
 Acetylcholine most often excites gastrointestinal activity
 Norepinephrine and epinephrine almost always inhibit GI activity (epinephrine reaches GI tract mainly by way of
blood after it is secreted by adrenal medullae into circulation)
 Except for a few PNS fibers to mouth and pharyngeal regions of alimentary tract, cranial PNS fibers almost
entirely in vagus nerves
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Provide extensive innervation to esophagus, stomach, and pancreas and somewhat less to intestines
down through first half of large intestine
Sacral parasympathetics – originate in S2-S4 and pass through pelvic nerves to distal half of large intestine all the
way to anus
o Sigmoidal, rectal, and anal regions considerably better supplied with PNS fibers than other intestinal
areas; fibers function to execute defecation reflexes
Postganglionic neurons of GI PNS system located mainly in myenteric and submucosal plexuses; stimulation of
PNS nerves cause general increase in activity of entire enteric nervous system, enhancing GI function
SNS fibers to GI tract originate from T5-L2; mot preganglionic fibers that innervate gut, after leaving cord, enter
sympathetic chains that lie lateral to spinal column, and many fibers then pass on through chains to outlying
ganglia (celiac ganglion, various mesenteric ganglia)
o Most postganglionic SNS fibers spread through postganglionic sympathetic nerves to all parts of gut
o Sympathetics innervate essentially all of GI tract (not heavy on the oral cavity and anus like PNS)
o SNS nerve endings secrete mainly norepinephrine and small amounts of epinephrine
o Stimulation of SNS inhibits activity of GI tract by
 To slight extent, direct effect of secreted norepinephrine to inhibit intestinal tract smooth
muscle (except mucosal muscle, which it excites)
 To major extent, inhibitory effect of norepinephrine on neurons of entire enteric nervous
system
o Strong stimulation of SNS can inhibit motor movements of gut so greatly that this can block movement
of food through GI tract
Some afferent sensory nerves have cell bodies in enteric nervous system itself, and some in DRG of spinal cord
o Sensory nerves can be stimulated by irritation of gut mucosa, excessive distension of gut, or presence of
specific chemical substances in gut
o Signals transmitted through fibers can cause excitation or inhibition of intestinal movements or
intestinal secretion
o Some sensory signals from gut go all the way to multiple areas of spinal cord and brain stem
 80% of nerve fibers in vagus nerves afferent rather than efferent and transmit sensory signals
from GI tract to medulla, which initiates vagal reflex signals that return to GI tract to control it
Anatomical arrangement of enteric nervous system and its connections with SNS and PNS support 3 types of GI
reflexes essential to GI control
o Reflexes that are integrated entirely within gut wall enteric nervous system – include reflexes that
control much GI secretion, peristalsis, mixing contractions, local inhibitory effects, and so forth
o Reflexes from gut to the prevertebral sympathetic ganglia and then back to GI tract – transmit signals
long distances to other areas of GI tract, such as signals from stomach to cause evacuation of colon
(gastrocolic reflex), signals from colon and small intestine to inhibit stomach motility and stomach
secretion (enterogastric reflexes), and reflexes from colon to inhibit emptying of ileal contents into
colon (colonoileal reflex)
o Reflexes from gut to spinal cord or brain stem and then back to GI tract – include
 Reflexes from stomach and duodenum to brain stem and back to stomach by way of vagus
nerves to control gastric motor and secretory activity
 Pain reflexes that cause general inhibition of entire GI tract
 Defecation reflexes that travel from colon and rectum to spinal cord and back again to produce
powerful colonic, rectal, and abdominal contractions required for defecation (defecation
reflexes)
GI hormones released into portal circulation and exert physiological actions on target cells with specific
receptors for hormone; effects of hormones persist even after all nervous connections between site of release
and site of action have been severed
o Most of same hormones that control GI secretion also affect motility in some parts of GI tract; motility
effects usually less important than secretory effects of hormones
o Gastrin – secreted by G cells of antrum of stomach in response to stimuli associated with ingestion of a
meal (distention of stomach, products of proteins, and gastrin releasing peptide released by nerves of
gastric mucosa during vagal stimulation); primary actions are stimulation of gastric acid secretion and
stimulation of growth of gastric mucosa
o CCK – secreted by I cells in mucosa of duodenum and jejunum mainly in response to digestive products
of fat, fatty acids, and monoglycerides in intestinal contents
 Strongly contracts gallbladder, expelling bile into small intestine, where bile emulsifies fatty
substances, allowing them to be digested and absorbed
 Inhibits stomach contraction moderately, slowing emptying of food from stomach to give
adequate time for digestion of fats in upper intestinal tract
 Inhibits appetite to prevent overeating during meals by stimulating sensory afferent nerve fibers
in duodenum, which send signals bny way of vagus nerve to inhibit feeding centers in brain
o Secretin – secreted by S cells in mucosa of duodenum in response to acidic gastric juice emptying into
duodenum from pylorus of stomach
 Has mild effect on motility of GI tract
 Promotes pancreatic secretion of bicarbonate, which helps neutralize acid in small intestine
o Gastric inhibitory peptide (GIP) – secreted by mucosa of upper small intestine, mainly in response to
fatty acids and amino acids, but to lesser extent in response to carbohydrate
 Has mild effect in decreasing motor activity of stomach and therefore slows emptying of gastric
contents into duodenum when upper small intestine already overloaded with food products
 At blood levels lower than those needed to inhibit gastric motility, stimulates insulin secretion
(also called glucose-dependent insulinotropic peptide)
o Motilin – secreted by stomach and upper duodenum during fasting
 Increases GI motility
 Released cyclically and stimulates waves of GI motility (interdigestive myoelectric complexes)
that move through stomach and small intestine every 90 minutes in a fasted person
 Secretion inhibited after ingestion
Functional Types of Movements in GI Tract
 Propulsive movements (peristalsis) – cause food to move forward along tract at appropriate rate to
accommodate digestion and absorption
o Contractile ring appears around gut and moves forward (like squeezing a tube of toothpaste and sliding
your fingers down it); any material in front of the contractile ring is moved forward
o Inherent property of many syncytial smooth muscle tubes; stimulation at any point in the gut can cause
contractile ring to appear in circular muscle, and this ring spreads along gut tube
o Usual stimulus for intestinal peristalsis is distension of gut
o Strong PNS signals to gut will elicit strong peristalsis
o Peristalsis occurs only weakly or not at all in any portion of the GI tract that has congenital absence of
myenteric plexus
o Peristalsis greatly depressed or blocked in entire gut when person treated with atropine to paralyze
cholinergic nerve endings of myenteric plexus (effectual peristalsis requires active myenteric plexus)
o Can occur in either direction from a stimulated point, but normally dies out rapidly in orad (toward the
mouth) direction while continuing a considerable distance toward anus
 Directionality because myenteric plexus is polarized in anal direction
o When segment of intestinal tract excited by distention and thereby initiates peristalsis, contractile ring
causing peristalsis normally begins on orad side of distended segment and moves toward distended
segment, pushing instestinal contents in anal direction for 5-10 cm before dying out
 At same time, gut sometimes relaxes several cm downstream toward anus (receptive
relaxation), thus allowing food to be propelled more easily toward anus than toward mouth
 Above pattern doesn’t occur in absence of myenteric plexus, so it is called the myenteric reflex
or peristaltic reflex
 Peristaltic reflex plus anal direction of movement of peristalsis called “law of the gut”
 Mixing movements – keep intestinal contents thoroughly mixed at all times; in some areas, peristaltic
contractions themselves cause most of the mixing (especially true when forward progression of intestinal
contents blocked by a sphincter so that peristaltic wave can then only churn intestinal contents, rather than
propelling them forward)
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At other times, local intermittent constrictive contractions occur every few cm in gut wall; constrictions
last 5-30 sec; then new constrictions occur at other points in gut, thus chopping and shearing contents
Peristaltic and constrictive movements modified in different parts of GI tract for proper propulsion and mixing
GI Blood Flow – Splanchnic Circulation
 Blood vessels of GI system are part of more extensive system called splanchnic circulation; includes blood flow
through gut itself plus blood flows through spleen, pancreas, and liver
o Design of system is such that all blood that courses through gut, spleen, and pancreas then flows
immediately into liver by way of portal vein
o In liver, blood passes through millions of minute liver sinusoids and finally leaves liver by way of hepatic
veins that empty into vena cava of general circulation
o Allows reticuloendothelial cells that line liver sinusoids to remove bacteria and other particulate matter
that might enter blood from GI tract, thus preventing direct transport of potentially harmful agents into
remainder of body
o Nonfat, water-soluble nutrients absorbed from gut (such as carbs and proteins) transported in portal
venous blood to same liver sinusoids; both reticuloendothelial cells and principal parenchymal cells of
liver (hepatic cells) absorb and store temporarily from ½-¾ of nutrients
o Much chemical intermediary processing of nutrients occurs in liver cells
o Almost all fats absorbed from intestinal tract not carried in portal blood but instead absorbed into
intestinal lymphatics and conducted to systemic circulating blood by way of thoracic duct
 On entering wall of gut, arteries branch and send smaller arteries circling in both directions around gut, with tips
of arteries meeting on side of gut wall opposite the mesenteric attachment
o From circling arteries, even smaller arteries penetrate into intestinal wall and spread along the muscle
bundles, into the intestinal villi, and into submucosal vessels beneath epithelium to serve secretory and
absorptive functions of gut
o In each intestinal villus, small arteriole and venule interconnect with system of multiple looping
capillaries; walls of arterioles are highly muscular and highly active in controlling villus blood flow
 Under normal conditions, blood flow in each area of GI tract, as well as in each layer of gut wall, directly related
to level of local activity
o During active absorption of nutrients, blood flow in villi and adjacent regions of submucosa increased by
as much as 8x
o Blood flow in muscle layers of intestinal wall increases with increased motor activity in gut
 Several vasodilator substance released from mucosa of intestinal tract during digestive process; most are
peptide hormones, including CCK, vasoactive intestinal peptide, gastrin, and secretin; hormones control specific
motor and sensory activities of gut
 Some GI glands release kallidin and bradykinin into gut as they secrete other substances as well; kinins powerful
vasodilators that cause much of increased mucosal vasodilation that occurs along with secretion
 Decreased oxygen concentration in gut wall can increase intestinal blood flow at least 50-100%; increased
mucosal and gut wall metabolic rate during gut activity lowers oxygen concentration enough to cause much of
vasodilation; decrease in oxygen also leads to increase of adenosine (vasodilator)
 Arterial flow into villus and venous flow out are in opposite directions; because of this, much of blood oxygen
diffuses out of arterioles directly into adjacent venules without ever being carried in blood to tips of villi (as
much as 80% of oxygen takes short-circuit route and is not available for local metabolic functions of villi)
o Under normal conditions, this shunt not harmful to villi, but in disease conditions in which blood flow to
gut becomes greatly curtailed, such as in circulatory shock, oxygen deficit in tips of villi can become so
great that villus tip or even whole villus suffers ischemic death and can disintegrate
o In many GI diseases, villi become seriously blunted, leading to greatly diminished intestinal absorptive
capacity
 Stimulation of PNS going to stomach and lower colon increases local blood flow at same time that it increases
glandular secretion; increased flow results secondarily from increased glandular activity and not as direct effect
of nervous stimulation
 SNS stimulation has direct effect on essentially all GI tract to cause intense vasoconstriction of arterioles with
greatly decreased blood flow
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After a few minutes of vasoconstriction, flow often returns to near normal by means of autoregulatory
escape; local metabolic vasodilator mechanisms elicited by ischemia and override SNS vasoconstriction
SNS vasoconstriction in gut allows shutoff of GI and other splanchnic blood flow for short periods of time during
heavy exercise, when skeletal muscle and heart need increased flow
o In circulatory shock, when all body’s vital tissues are in danger of cellular death for lack of blood flow,
especially brain and heart, SNS stimulation can decrease splanchnic blood flow to very little for hours
o SNS stimulation causes strong vasoconstriction of large-volume intestinal and mesenteric veins;
decreases volume of these veins, displacing large amounts of blood into other parts of circulation
o In hemorrhagic shock or other states of low blood volume, above mechanism provides as much as 200400 mL of extra blood to sustain general circulation