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TOPIC :Properties of gastrointestinal
tract ,tight junction complex .

I M Pharma
Department of

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Properties of Gastrointestinal

The intestinal wall is composed of following

✓Longitudinal muscle layer
✓Circular muscle layer

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1.Neural control of Gastrointestinal

The gastrointestinal tract has its own nervous
system, called the Enteric nervous system. It
is composed of two plexuses

✓The mysenteric plexus or Auerbach’s plexus
is an outer plexus located between the
muscle layers.

✓The submucosal plexus is an inner plexus that
lies in the submucosa

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Autonomic control of Gastrointestinal

The parasympathetic nervous system increases
the activity of the enteric nervous system. The
parasympathetic supply to the gut is made up of
cranial and sacral divisions.

✓The cranial parasympathetic innervate, by way of
the vagus nerve, the esophagus, stomach,
pancreas, and first half of the large intestine.

✓The sacral parasympathetic innervate, by way of
the pelvic nerves, the distal half of the large

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• The sympathetic nervous system usually
inhibits the activity in the gastrointestinal
tract, causing many effects opposite to those
of the parasympathetic nervous system.

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Three types of reflexes are essential for
gastrointestinal control

✓Reflexes that occur entirely within the enteric
nervous system

✓Reflexes from the gut to the sympathetic
ganglia and back to the gut

✓Reflexes from the gut to the spinal cord or
brain stem and then back to the gut

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Four major hormones are
✓ Secretin was the first gastrointestinal

hormone discovered and is secreted by the “S”
cells in the mucosa of the duodenum in response
to acidic gastric juice emptying into the
duodenum from the pylorus of the stomach.

✓Secretin has a mild effect on motility of the
gastrointestinal tract and acts to promote
pancreatic secretion of bicarbonate which in turn
helps to neutralize the acid in the small intestine.

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The primary actions of gastrin are
✓ stimulation of gastric acid secretion and
✓ stimulation of growth of the gastric mucosa.
✓ This hormone strongly contracts the gallbladder, expelling

bile into the small intestine where the bile in turn plays
important roles in emulsifying fatty substances, allowing
them to be digested and absorbed.

✓ Cholecystokinin also inhibits stomach contraction

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Gastric inhibitory peptide
✓Gastric inhibitory peptide is secreted by the

mucosa of the upper small intestine, mainly in
response to fatty acids and amino acids but to a
lesser extent in response to carbohydrate.

✓ It has a mild effect in decreasing motor activity of
the stomach and therefore slows emptying of
gastric contents into the duodenum when the
upper small intestine is already overloaded with
food products.

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Functional movements in the Gastrointestinal tract
✓Propulsive movements
✓Mixing movements
4.Gastrointestinal blood flow
✓The blood vessels of the gastrointestinal tract are a

part of the Splanchnic circulation
✓Parasympathetic stimulation increases the blood flow
✓Sympathetic stimulation decreases blood flow.

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• Mastication (chewing) is the process for which teeth
are especially designed. The anterior teeth (incisors)
providing a strong cutting action and the posterior
teeth (molars), a grinding action.

• Most of the muscles of chewing are innervated by the
motor branch of the fifth cranial nerve (trigeminal
nerve), and the chewing process is controlled by nuclei
in the brain stem. Stimulation of specific reticular areas
in the brain stem taste centers will cause rhythmical
chewing movements. Also, stimulation of areas in the
hypothalamus, amygdala, and even the cerebral cortex
near the sensory areas for taste and smell can often
cause chewing.

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• The rate of digestion is absolutely dependent
on the total surface area exposed to the
digestive secretions.

• In addition, grinding the food to a very fine
particulate consistency prevents damage to
the gastrointestinal tract and increases the
ease with which food is emptied from the
stomach into the small intestine, then into all
succeeding segments of the gut.

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• Swallowing, known scientifically as
deglutition, is the process in the human or
animal body that makes food to pass from the
mouth, to the pharynx, and into the
esophagus, while shutting the epiglottis. If this
fails and the object goes through the trachea,
then choking or pulmonary aspiration can
occur. In the human body it is controlled by
the swallowing reflex.

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Eating and swallowing are complex
neuromuscular activities consisting essentially of
three phases, an oral, pharyngeal and esophageal
phase. Each phase is controlled by a different
neurological mechanism.

Oral phase This is voluntary stage and includes
✓Trough formation
✓Movement of the bolus posteriorly

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• Pharyngeal phase : This stage is involuntary
and constitutes the passage of food from the
pharynx to the esophagus. When the
pharyngeal phase begins, other activities such
as chewing, breathing, coughing and vomiting
are concomitantly inhibited

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Nervous regulation of Swallowing

• The most sensitive tactile areas of the posterior
mouth and pharynx for initiating the pharyngeal
stage of swallowing are the tonsillar pillars.

• Impulses are transmitted from these areas
through the sensory portions of the trigeminal
and glossopharyngeal nerves into the medulla
oblongata, either into or closely associated with
the tractus solitarius, which receives essentially
all sensory impulses from the mouth.

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• The successive stages of the swallowing process
are then automatically initiated in orderly
sequence by neuronal areas of the medulla and
lower portion of the pons. This area is known as
Swallowing center.

• The motor impulses from the swallowing center
to the pharynx and upper esophagus that cause
swallowing are transmitted successively by the
5th, 9th, 10th, and 12th cranial nerves

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Esophageal stage

Esophageal stage of swallowing: The esophagus
normally exhibits two types of peristaltic

1. Primary peristalsis
2. Secondary peristalsis
• Primary peristalsis is simply continuation of

the peristaltic wave that begins in the pharynx
and spreads into the esophagus

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• If the primary peristaltic wave fails to move into the
stomach all the food that has entered the esophagus,
secondary peristaltic waves result from distention of
the esophagus itself by the retained food; these waves
continue until all the food has emptied into the

• The secondary peristaltic waves are initiated partly by
intrinsic neural circuits in the mysenteric nervous
system and partly by reflexes that begin in the pharynx
and are then transmitted upward through vagal
afferent fibers to the medulla and back again to the
esophagus through glossopharyngeal and vagal
efferent nerve fibers.

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Function of sphincter lower esophageal
sphincter (gastroesophageal sphincter)

• At the lower end of esophagus, extending
from about 2-5 cm above its juncture with the
stomach, the esophageal circular muscle
functions as lower esophageal sphincter or
gastroesophageal sphincter.

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• The stomach is a small, ‘J’-shaped pouch with

walls made of thick, elastic muscles, which stores
and helps break down food.

• Storage of large quantities of food until the food
can be processed in the duodenum

• Mixing of this food with gastric secretions until it
forms a semi fluid mixture called chyme

• Slow emptying of the food from the stomach into
the small intestine at a rate suitable for proper
digestion and absorption

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Receptive relaxation of the stomach
• As the food bolus travels through the lower

esophagus, the stomach reflexly begins to

• This phenomenon allows the stomach to
accept large amounts of food with minimal
increase in gastric pressure; it also minimizes
esophageal reflux.

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Mixing and propulsion of food in the stomach
• As long as food is in the stomach, weak

peristaltic constrictor waves, called mixing
waves, begin in the mid- to upper portions of
the stomach wall and move toward the
antrum about once every 15 to 20 seconds.
These waves are initiated by the gut wall basic
electrical rhythm.

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• Chyme
• After food in the stomach has become thoroughly

mixed with the stomach secretions, the resulting
mixture that passes down the gut is called chyme.
The degree of fluidity of the chyme leaving the
stomach depends on the relative amounts of
food, water, and stomach secretions and on the
degree of digestion that has occurred.The
appearance of chyme is that of a murky semifluid
or paste.

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Phases of digestion
1. Cephalic phase: in cephalic phase the sight

and even thought of food can stimulate
gastric secretions

2. Gastric phase: In gastric phase, after eating
has begun, the presence of food and
distension it causes also stimulate gastric

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3- Intestinal Phase: In intestinal phase, the
entry of gastric contents stimulate release of

multiple factors, which then inhibit gastric

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8.Movements of the Small intestine

• Most Digestion & Absorption occurs in the
small intestine

• No more digestion as food moves into large
intestine, where a little absorption of salt &
water does take place.

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• The three segments of small intestine (which
is more than 6 meters long) are the:
– Duodenum, only few cms.
– Jejunum, more than 2 meters
– Ileum, more than 3 meters

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MECHANISM: When small intestine filled with
chyme, it is distended, mysenteric plexus

• Due to stimulation of mysenteric plexus, a
series of constrictions occur throughout the
length of small intestine. (Area of constriction
is about 1cm),forming segmentation

• Segmentation consists of ring like contractions
along the length of small intestine.

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• Within seconds, contracted area relaxes &
previously relaxed area contracts.

• This mixes the chyme.
• Rate of segmentation contractions in

duodenum is around 7-12 / minute
• In terminal ileum it is 9 / minute
• Contents take 3-5 hours to move through the


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9.Movement of villi
• Villi present in jejunal mucosa.
• Increases surface area for absorption about 10 folds.
Peristalsis or Propulsive Movements
• Also called MMC (migrating motility complex)
• When most food is absorbed, segmentations cease
• migratory motility complex (propulsive movements)

propels unabsorbed residue from small intestine to
large intestine.

• meal motility consists of weak, repetitive,
peristaltic waves, that move a short distance .

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10.Peristaltic waves

• The function of the peristaltic waves in the
small intestine is not only to cause progression
of chyme toward the ileocecal valve but also
to spread out the chyme along the intestinal
mucosa. As the chyme enters the intestines
from the stomach and elicits peristalsis, this
immediately spreads the chyme along the
intestine; and this process intensifies as
additional chyme enters the duodenum

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Movements Caused by the Villi

• The muscularis mucosae can cause short folds to
appear in the intestinal mucosa. In addition
individual fibers from this muscle extend into the
intestinal villi and cause them to contract.The
mucosal folds increase the surface area exposed
to the chyme, thereby increasing absorption.
Also, contractions of the villi—shortening,
elongating, and shortening again results into the
increase in the flow of lymph freely from the villi
into the lymphatic system.

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Function of the Ileocecal Valve

• A principal function of the ileocecal valve is to
prevent backflow of fecal contents from the
colon into the small intestine.

• The ileocecal valve itself protrudes into the
lumen of the cecum and therefore is forcefully
closed when excess pressure builds up in the
cecum and tries to push cecal contents
backward against the valve lips.

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• The wall of the ileum for several centimeters
immediately upstream from the ileocecal
valve has a thickened circular muscle called
the ileocecal sphincter.This sphincter normally
remains mildly constricted and slows
emptying of ileal contents into the cecum.

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• Resistance to emptying at the ileocecal valve
prolongs the stay of chyme in the ileum and
thereby facilitates absorption. Normally, only
1500 to 2000 milliliters of chyme empty into
the cecum each day.

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11.Movements of the

• The principal functions of the colon are
(1)absorption of water and electrolytes from
the chyme to form solid feces
(2)storage of fecal matter until it is

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• Mixing Movements—“Haustrations”
• Large circular constrictions occur in the large intestine.

At each of these constrictions, about 2.5 centimeters of
the circular muscle contracts, sometimes constricting
the lumen of the colon almost to occlusion.

• At the same time, the longitudinal muscle of the
colon, which is aggregated into three longitudinal
strips called the teniae coli, contracts. These combined
contractions of the circular and longitudinal strips of
muscle cause the unstimulated portion of the large
intestine to bulge outward into baglike sacs called

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• Each haustration usually reaches peak
intensity in about 30 seconds and then
disappears during the next 60 seconds.

• They also at times move slowly toward the
anus during contraction, especially in the
cecum and ascending colon, and thereby
provide a minor amount of forward
propulsion of the colonic contents.

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13.Propulsive Movements—“Mass

• Propulsive Movements—“MassMovements.”
• Much of the propulsion in the cecum and

ascending colon results from the slow but
persistent haustral contractions, requiring as
many as 8 to 15 hours to move the chyme
from the ileocecal valve through the colon,
while the chyme itself becomes fecal in
quality, a semisolid slush instead of semifluid.

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• Initiation of Mass Movements by Gastrocolic
and Duodenocolic Reflexes.

• Appearance of mass movements after meals is
facilitated by gastrocolic and duodenocolic
reflexes. These reflexes result from distention
of the stomach and duodenum.

• The reflexes almost certainly are transmitted
by way of the autonomic nervous system.

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• Most of the time, the rectum is empty of
feces. This results partly from the fact that a
weak functional sphincter exists about 20
centimeters from the anus at the juncture
between the sigmoid colon and the rectum.

• There is also a sharp angulation which
contributes additional resistance to filling of
the rectum.

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Defecation Reflexes

• Ordinarily, defecation is initiated by defecation

• One of these reflexes is an intrinsic reflex
mediated by the local enteric nervous system in
the rectal wall. When faeces enter the rectum,
distention of the rectal wall initiates afferent
signals that spread through the mysenteric plexus
to initiate peristaltic waves in the descending
colon, sigmoid, and rectum, forcing faeces toward
the anus.

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• As the peristaltic wave approaches the anus,
the internal anal sphincter is relaxed by
inhibitory signals from the mysenteric plexus;
if the external anal sphincter is also
consciously, voluntarily relaxed at the same
time, defecation occurs.

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•”A tight junction,which separates the cells
into apical and basal compartments and is
at one end of the spectrum.”

•“When two adjacent epithelial cells form a
TJ, there is no extracellular space between
them and the movement of substances
through the extracellular space between the
cells is blocked.”

•“The epithelia forms a protective barrier and
has a selective permeability.”

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•Blood Brain

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Intestinal Barrier
• The intestinal lining, the largest mucosal surface has

three functions.
1. ”Serves as the vehicle or mechanism by which we obtain

nutrients from the food we eat.”

2. “Blocks the entrance into the bloodstream of potentially harmful

particles, chemicals, bacteria, and other
organism that can pose a threat to the health.”

3. “Contains chemicals called immunoglobulins that bind to

bacteria and foreign proteins to prevent them
from attaching to the gut’s lining.”

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• There are two pathways the body uses to
absorb nutrients from the gut.

1. Transcellular pathway -nutrients move through the epithelial

2. Paracellular pathway – nutrients pass between the epithelial

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• the parameters of a leaky gut:

• A “leaky gut” is caused by problems of the
competency of these tight junctions, which is a
intricate systems and highly regulated.

• This tight junction measures 10 to 15 angstrom.

• The problem with a “leaky gut” is the gut permeability is
decreased, and the body is ineffective at allowing
nutrients to pass.

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• Ganong’s review of Medical Physiology,
23rd edition
•Biopharmaceutics and pharmacokinetics –
by D.M.Brahmankar,Sunil B.Jaiswal

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