1st chapter of digestion

The digestive system
7/8/2019 Dr.Misbah-ul-Qamar

WHAT IS DIGESTION
Why do we eat?
Why Do We Need Energy?

Digestive system & Homeostasis

Transfer of nutrients from external to internal environment

Precise Need For Digestive System
• The basic chemical units of our food & our
body tissues are the same
• Why our food looks so different from the
tissues

This is how the digestive system renders 95% food available for body’s use

Sequence Of Nutrient Acquisition
• All inputs of nutrition are through the
gastrointestinal tract
• Excretory organs?

Functions Of Digestive System

GI functions
• Primary function
• Homeostatic function
• Digestive function
• Other functions

Digestive processes
The gastrointestinal tract perform four basic
digestive processes;
• Motility
• Secretion
• Digestion
• Absorption

Motility (movement)
• It refers to the muscular contractions…
• Process of motility
• Tonic activity of GIT
– Tone of GIT
– Functions of tone

Secretion
• Digestive juices
• Reabsorption

Digestion
• Carbs, proteins & fats

Absorption
• It occurs once the digestion is completed

General Principles Of GI
Functions
Motility (motor function),
Nervous & Hormonal Control,
Blood Circulation.

• Gastroenterology
• Proctology

Overview Of Tract Anatomy
• Continuous tube
• Length
• Parts

The muscular alimentary canal
– Mouth
– Pharynx
– Esophagus
– Stomach
– Small intestine
– Large intestine

The accessory digestive organs
Supply secretions & contribute to the breakdown
of food

Structural considerations
• Regional modifications
• Sphincters

• Upper GIT
– Consists of structures that aid in the ingestion &
digestion of food
• Lower GIT
– Consists of small & large intestine

General principles of GI motility
Characteristics Of GI Wall,
Electrical Activity Of GI Smooth
Muscle.

Characteristics of GI wall
a. Layers of smooth muscle.
b. Syncytium.

General anatomy of gut wall
The digestive tract wall has four layers from
inside (lumen) to outside
1. Mucosa
2. Submucosa
3. Muscularis externa
4. Serosa (visceral peritoneum)

Mucosa
It is the innermost, moist, epithelial membrane
that lines almost entire digestive tract
Sub-divisions?

Epithelium Of Mucosa
– Stratified squamous (in mouth, esophagus & anus)
=tough
– Simple columnar in the rest of tract
• Secretes enzymes and absorbs nutrients
• Has specialized cells also
• Brush border & its functions

Lamina propria
• Thin layer of loose connective tissue
• Resident structures

Muscularis mucosae
• It forms only a thin layer, lying in deeper layers
of mucosa.
• Function: increasing absorption

Overall functions of mucosa
• Secretion
• Protection
• Absorption

Sub-mucosa
• It is composed of moderately dense areolar
connective tissue
• Regarded as a highly vascular layer
• Also contains a part of the submucosal plexus
of nerves
• In addition contains glands & lymphatic tissue

MUSCULARIS EXTERNA
• Skeletal muscle = voluntary control
– In mouth, pharynx, upper esophagus & anus
– Control over swallowing & defecation
• Smooth muscle = involuntary control
– Inner circular fibers & outer longitudinal fibers
– Mixes, crushes & propels food along by peristalsis
• This muscle layer also contains a part of nerve
plexus

Serosa
• It is an example of serous membrane which
secretes a slippery fluid
• This membrane covers all organs & walls of
cavities forms protective covering
• Consists of connective tissue covered with
simple squamous epithelium

Lets focus on GI smooth muscle
Gastrointestinal smooth muscles
• 200-500µm in length
• 2-10µm in diameter

Gastrointestinal Smooth Muscle as a
Syncytium.
• Longitudinal muscle layer
• Circular muscle layer
• Within each bundle, the muscle fibers are electrically connected with one another through
large numbers of Gap Junctions that allow electrical signals to travel readily from one fiber to
next.
• Each muscle layer functions as a Syncytium; that is, when an action potential is elicited
anywhere within the muscle mass, it generally travels in all directions in the muscle
• Smooth muscles are arranged in bundles as parallel fibers.

What is the function of a syncytium
• It allows coordinated contraction of muscles
along their entire length
• Function of syncytial smooth muscle in
intestine housekeeping
• It produces 2 types of contractions
– Tonic contractions---- to maintain organ dimension
against an imposed load (bolus of food)
– Forceful contractions---- these produce muscle
shortening to propel the bolus along GIT

Arrangement of bundles in each layer
• How each bundle is separate & connected as
well.
• Distance travelled by each AP
• Connection b/w circular & smooth muscle
layer also exists

GI MOTILITY ACHIEVED THROUGH
ELECTRICAL ACTIVITY OF SMOOTH
MUSCLE
The motility is brought about 2 types of contractions in GIT:
Phasic (rhythmic) & Tonic

Electrical activity of gastrointestinal
smooth muscles
• Normal resting membrane potential in the
smooth muscle fibers of the gut is between -
50 to-60mV
• The smooth muscles of gastrointestinal tract is
excited by continual slow electrical activity

Electrical Activity of Gastrointestinal Smooth Muscle
Two basic types of electrical waves:
(1) Slow waves. (Between -60 and -40 mv, i.e 15 mv)
(2) Spikes.

SLOW WAVES (basic electrical rhythm)
• Slow, undulating changes in the resting membrane potential.
Rhythm of gastrointestinal contractions is determined
by the frequency of “slow waves”
• Frequency in different parts of the human GIT?
Slow waves Are NOT action potentials7/8/2019 Dr.Misbah-ul-Qamar

Slow wave potential is different from
AP
Slow wave itself is not an AP but it can give
rise to AP.
Slow wave potentials fire the APs only when
they reach threshold.
Slow waves themselves cannot cause muscle
contractions unless they generate AP (or
depolarization of contraction threshold).

Cause of Rhythmicity in Smooth
Muscle
1. Waxing and waning of pumping of Na+
outward through membrane of fiber.
– It is a self regenerative process that spreads
progressively over the whole membrane.
2. Certain ion channels (e.g., Ca2+-Na+ channels)
which open periodically

Significance of slow waves in RMP
• This kind of potential leads to spontaneous
generation of action potentials in GI muscle &
makes it self excitatory.
• In other words; It causes pacemaker activity
and hence the rhythmical contractions in GI
smooth muscle.

Electrical Pacemakers For Smooth Muscle Cells (BER)
These specialized cells form a network with each other. They are interposed between
smooth muscle layers. They are connected with smooth muscle cells by gap junctions. So
that, electrical activity generated by these cells spread to adjacent smooth muscle cells.

The interstitial cells of Cajal
Shape: stellate shaped mesenchymal cells with smooth
muscle like features
Undergo cyclic changes in membrane potential due to unique
ion channels that periodically open and produce inward
(pacemaker) currents that generate slow waves.
.

Location of Cajal cells
– In stomach & small intestine, these cells are located in
outer circular muscle layer near myenteric plexus
– In colon, they are at sub-mucosal border of circular
muscle layer
• Rate of BER in different parts of gut?
– 4/min in stomach
– 12/min in duodenum
– 8/min in distal ileum
– In colon, BER rate rises from about 2/min at cecum to
about 6/min at sigmoid.

• Descending pattern of BER
– In stomach & small intestine, there is a
descending gradient in pacemaker frequency
– (pacemaker with highest frequency dominates)
• Significance of BER
– it coordinates peristaltic & other motor activity
– After vagotomy or transection of stomach wall,
peristalsis in stomach becomes irregular & chaotic

Slow waves usually Do Not cause muscle contraction.
Instead, they excite appearance of intermittent spike
potentials
The spike potentials excite the muscle contraction

Spike Potentials
• True action potential
• Occur when resting membrane potential/ peaks of slow
waves becomes more positive than – 40mV

Spike Potentials
• Frequency: 1-10 spikes/ sec (higher the slow wave
potential rises, greater the frequency of spike potentials)
• Duration : it is 10-40 times as long as AP in nerve. 10-20
msec (comparatively longer because of slowness of opening
& closing of Ca-Na channels)
• Depolarization: is caused by slow calcium-sodium
channel they allow especially large number of calcium ions
to enter along with smaller numbers of sodium ions
• Repolarization: is caused by opening of voltage gated
potassium channels

Spike Potentials
• Movement of large number of calcium into cell during
action potential causes muscle contraction.
Muscle fibers are connected with one another by gap
junctions allowing flow of ions from fiber to fiber
(Functional syncytium)

Inter-digestive motility pattern

During fasting
• Between periods of digestion, the pattern of
electrical & motor activity in GI smooth
muscle become modified
• Cycles of motor activity (called MMC) migrate
aborally.

Migrating motor complex
Serves as Inter-digestive House Keeper
• When most of the meal has been absorbed,
segmentation contraction cease and are
replaced by migrating motor complexes
between meals
• Consist of organized but weak repetitive
peristaltic wave that move a short distance
down the intestine before dying out

MMC
• Begin in the stomach – to small intestine
(distal ileum)
• Migrate down @ 5cm/min, at interval of 90
min
• Phases of MMC
– Phase I: Basal phase quiescent period
– Phase II: Pre-burst phase period of irregular
electrical & mechanical activity
– Phase III: Burst phase burst of regular activity

Migrating motor complex
Function:
Sweep the remnants of
preceding meal,
secretions, mucosal debris
and bacteria forward
toward the colon
Prepares the gut for next
meal

Migrating myoelectric cycle
• Stimulated by hormone “motilin” circulating
levels of this hormone increase at intervals of
approx. 100-120 mins (coordinated with
contractile phases of MMC)
• Inhibited by ingestion of meal (suppression of
motilin release)
• Gastric secretion, bile flow, pancreatic
secretion & mucus discharge increase during
each MMC.

Changes in voltage of the RMP
• These changes occur in addition to slow waves
& spike potentials.
• Baseline voltage level of smooth muscle RMP
can also change
• Under normal conditions, RMP averages about
-56mV
• Multiple factors can change this level

Changes in voltage of the RMP (cont’d)
• When RMP becomes less negative it is
called depolarization of membrane muscle
becomes more excitable
• When RMP becomes more negative it is
called hyperpolarization of membrane
muscle becomes less excitable

Excitatory and Inhibitory
Factors
1) Depolarization:
-stretch
-acetylcholine
-parasympathetic stimulation
-specific GIT hormones
2) Hyperpolarization:
-epinephrine and norepinephrine
-sympathetic stimulation which mainly causes norepinephrine
secretion

Tonic contraction
(sustained contraction)
• Tonic contraction is continuous contraction often lasting
for minutes to hours
• These contractions are not associated with basic
electrical rhythm of slow waves
• Intensity can be increased or decreased but it is always
present
• Some smooth muscles of GIT exhibit tonic contraction as
well as, or instead of, rhythmical contractions

Causes of tonic contractions
1. Repetitive spike potentials
greater frequency greater degree of
contraction
2. Hormones/ certain other chemical factors
these bring about continuous partial
depolarization without causing action potential
3. Continuous entry of calcium into cell interior
brought about in ways not associated with
changes in membrane potential

Areas Of GIT Where Tonic Contractions
Appear
In rings or bands of muscles i.e., sphincters that
separate different sections of digestive system
e.g.,
– Upper & lower esophageal sphincters
– Pyloric sphincter
– The sphincter of Oddi

General Principles Regarding
Nervous & Hormonal Control Of GI
Functions

Control of Gastrointestinal functions
Three modalities for gastrointestinal regulation
1. Intrinsic neural control: Enteric nervous system
2. Extrinsic neural control: Autonomic nervous
system
3. Hormonal control of gastrointestinal motility

Nervous control

Extrinsic nervous control
It is exerted through autonomic nervous system
by its both divisions:
– Parasympathetic nervous system
– Sympathetic nervous system
• Connect to intrinsic system of control.

The way extrinsic control is exerted!
Influence the activity in gastrointestinal tract by:
1. Acting directly on the smooth muscle and
gland
2. Altering the secretion of gastrointestinal
hormone
3. Modifying the activity of intrinsic control
(enteric nervous system)

Parasympathetics to GIT

Parasympathetic nervous system
• Parasympathetic supply to gut is divided into
– Cranial division
– Sacral division
• Cranial parasympathetic nerve fibers are almost entirely in the
vagus nerve
(except for few parasympathetic fibers to mouth & pharyngeal
regions)
• Provide extrinsic innervation to the esophagus, stomach,
pancreas and intestines(down to first half of large intestine)

(cont’d)
• The sacral division of parasympathetic supply to
gut arises from S2,3,4 segments of spinal cord
• The parasympathetic nerve fibers pass through
pelvic nerves
• Innervate distal half of large intestine, all the way
to anus
• Sigmoid colon and rectum are better supplied
with parasympathetic fibers than other parts
(these fibers execute defecation reflex)

Summary of GI parasympathetics
a) Vagus nerve:
Esophagus upto proximal 2/3rd of transverse colon
b) Pelvic parasympathetic nerve: (S-2,3,4):
Distal 1/3 of transverse colon upto anus.

(cont’d)
• Fibers travelling in vagus & pelvic nerves are
preganglionic fibers
• Postganglionic neurons of GI parasympathetic
system are located in myenteric & submucosal
plexuses

Mode of action of para-sympathetics
Stimulation of parasympathetic nerves to gut
results in increased activity of the enteric
nervous system
– This results in increased motility and relaxation of
sphincters- increased motor activity
– The secretions from glands in gastrointestinal tract
is also increased- increased secretory activity

Summary of the effects exerted by
parasympathetic system

Sympathetics to GIT
(Thoracolumbar discharge)

Sympathetic nerve supply to gut
Originate from T5 to L2 segments of spinal cord
Fibers leave spinal cord (splanchnic nerves)
Enter sympathetic chains lateral to spinal cord
To ganglia such as celiac and mesenteric ganglia
Post ganglionic fibers from here supply all the gut

Sympathetic nerve supply to gut
(cont’d)
• Neurotransmitter : Norepinephrine
• Stimulation of sympathetic nervous system inhibits the
activity of gastrointestinal tract
• Strong stimulation of sympathetics can inhibit motor movements of gut so
greatly that it can literally block movement of food
• Sympathetics innervate essentially all the GIT unlike parasympathetics
which are more extensive near oral cavity & anus

How sympathetic system exerts effects
on GIT
1. By direct effect of secreted norepinephrine
– this effect is slight
– it inhibits intestinal tract smooth muscles
– Exception is mucosal muscle which is excited
2. By an inhibitory effect of norepinephrine on
the neurons of entire enteric nervous system
– This effect has major role in its action on GIT

Intrinsic control

IT’S YOUR 2ND BRAIN!
That isn’t a butterfly in your stomach

intrinsic enteric nervous system
• Also called gut brain/ little brain/ second brain
• It is a highly developed control system
number of neurons: 100 million (nearly equal
to number in entire spinal cord)

Why it is called “brain of the gut”
• It can integrate sensory information & effect a
complex motor response independent of the
CNS.
• ENS releases a variety of neurotransmitters
just like CNS.

Enteric nervous system
• Begins in esophagus & extends to anus.
• The neurons can be excitatory or inhibitory
• Its activity can be modified by extrinsic nerves
• Sensory nerve endings which originate in GI
epithelium or gut wall also send afferent fibers to
enteric system these fibers are responsible for
local effects & also some reflexes

Plexuses of Enteric nervous system
Ganglionic & aganglionic plexuses
Ganglionated ones are mainly two
1. Inner plexus: Meissner’s/ Submucosal plexus for
secretion & local blood flow control
2. Outer plexus: Myenteric/ Aurbach plexuslie in
intermuscular plane b/w 2 layers of muscularis
propria for movement control mainly
*Aganglionic plexuses lie in other planes in gut wall

Both plexuses are connected to
autonomic system (extrinsic
control) & to each other
Both usually contain many
interstitial cells of Cajal also.

Ganglion of ENS
A ganglion is a compact body covered with a
collagen sheath.
It contains nerve cell bodies & processes
embedded in dense stroma of neurites &
Schwann cells.
Inter-ganglionic fascicles of nerve processes
connect adjacent ganglia.
Ganglion cells are variable in form (various
forms probably having different functions)

Sub-mucosal plexus
• Located in the sub-mucosal layer.
• Concerned mainly with controlling function within
the inner wall of each minute segment of intestine
• Many sensory signals originate from the GI
epithelium which are integrated in sub-mucosal
plexus to control local effects
Regional modifications
The intestine has a bi-layered sub-mucosal plexus
Esophagus lacks ganglia in sub-mucosal plexus

Submucosal plexus (cont’d)
Control local intestinal functions like:
1. Secretion
2. Blood Flow
3. Absorption
4. Local contraction of muscles in deeper parts
of mucosa

Myenteric / Auerbach’s plexus
Extends along the entire length of gastrointestinal tract
• It consists of a linear chain of many interconnecting neurons
• Neurons are present between circular and longitudinal layers
of smooth muscles
• Controls the muscle activity along the length of gut
• In organs where myenteric plexus is dense, it can be
subdivided into primary, 2ndary & tertiary plexuses (all in
same intermuscular plane)

Myenteric plexus
Can have excitatory and inhibitory effects by use of multiple
neurotransmitters.
• Excitatory neurotransmitters: Acetylcholine and Substance P
• Inhibitory neurotransmitters: NO and VIP
– (inhibitory signals are useful for inhibiting some of
intestinal sphincter muscles control movement of
food along successive segments)
• Pyloric sphincter (controls emptying of stomach)
• Sphincter of ileocecal valve (controls emptying
from small intestine into cecum)

Overall Effects of stimulation of Myenteric plexus
1. Increased tone of gut wall
2. Increased intensity of rhythmical contraction
3. Increased rate of rhythmical contractions
4. Increased velocity of conduction of excitatory
waves along the gut wall

Chagas disease
• Submucosal & myenteric plexus neuropathy can impair
motility.
• For example: A protozoan infestation of these plexus
neurons can lead to chagas disease which causes
distention & structural enlargements of esophagus &
colon.
• Regions with neuropathy can constrict but not relax
muscular layers the asymptomatic sections continue
to deliver food food is retained just proximal to
constricted area retention stretches these areas &,
over time, enlarges and contorts them.

Megacolon (Hirschsprung disease)
• Congenital abnormality of colonic motility
• Lack or deficiency of ganglion cells in myenteric plexus
and submucosal plexus in a segment of sigmoid colon-
aganglionic megacolon
• Cause of aganglionic area
– Failure of normal cranial to caudal migration of neural
crest cells during development
– Mutation in the gene of a receptor (endothelin B receptor)
which is required for normal migration of crest cells
• Characterized by anorexia, abdominal distention and
lassitude. Children with this disease defecate
infrequently; once every week

Megacolon
• Is diagnosed In infancy
• Defecation reflex and normal peristalsis fails to
occur in affected segment-rare bowel movement
occurring once every several days
• Allows tremendous quantities of fecal matter to
accumulate in colon-distended colon
• Symptoms can be completely relieved completely
if aganglionic segment is surgically removed and
the portion of colon above it anastomosed to the
rectum

Gut feeling????

GI sensory nervous system
• Many afferent sensory nerve fibers innervate
the gut
• Cell bodies of these afferent fibers are located
in
– Enteric nervous system or
– Dorsal root ganglia of spinal cord

GI sensory nervous system (cont’d)
• Sensory nerve endings originate in the GI
epithelium or gut wall
• Afferent signals are sent to both plexuses of
enteric system
• In addition to enteric system, afferents are sent
to
– Prevertebral ganglia of sympathetic system
– Spinal cord
– To brain stem (In vagus nerves) 80% of fibers in
vagus are afferent

Apprising enteric nervous system
• Enteric nervous system receive sensory inputs
from the receptors present in the epithelium
• Three main types of sensory receptors are
present in wall of digestive tract
1. Chemoreceptors
2. Mechanoreceptors
3. Osmoreceptors
4. Other sensory receptors are mesenteric
receptors, thermoreceptors & pain receptors
(nociceptors)

Sensations exerting through ENS
Stimulation of these receptors alter the activity
of gastrointestinal effector cells by:
• Eliciting neural reflexes
• Secretion of hormones

For example:
• Mechanoreceptors
• Chemoreceptors
These receptors respond to:
– stretch
– Osmolarity
– pH
– presence of substrate &
– end products of digestion
They initiate reflexes that:
– Activate or inhibit digestive glands
– Mix lumen contents & move them along

Input & response produced by GI
afferents
• Sensory fibers of these nerves can be
stimulated by
– Irritation of gut mucosa
– Excessive distension of gut
– Presence of specific chemical substances in gut
• Signals through these fibers can cause
excitation or inhibition of intestinal movement
or secretion

Most prompt function of GI sensory
system….. Reflex control
• They can elicit local reflexes within gut wall
itself
• They can cause reflexes that are relayed to gut
from either pre-vertebral ganglia or basal
regions of brain

REFLEX CONTROL

Reflex control of GIT
• There are 3 types of reflexes which are
essential to gastrointestinal control
• These reflexes are supported by
– Anatomical arrangement of enteric nervous
system
– Connection of enteric nervous system with
sympathetic & parasympathetic systems

Types of GI reflexes
• Solely gut wall reflexes (local reflexes)
• Reflex from gut to ganglia to gut(short
reflexes)
• Reflex from gut to CNS to gut(long reflexes)

Gut wall reflexes
1) Reflexes that occur entirely within enteric
nervous system of GIT.
-Reflexes that control GI secretions,
-Peristalsis and mixing
-Also control local inhibitory effects

From gut to ganglia to gut
2) Reflexes from GIT to prevertebral sympathetic
ganglia and then back to GIT.
-these reflexes transmit signals long distance to other
areas of GIT
Examples
Gastro-colic reflex (signals from stomach to cause
evacuation of colon)
Entero-gastric reflex (signals from colon & small intestine
to inhibit stomach motility & secretion)
Colono-ileal reflex(from colon to inhibit emptying of ileal
contents into colon)

From gut to CNS to gut
3) Reflexes from GIT to spinal cord or brain stem and then back
to GIT.
-examples
1) Reflexes from stomach & duodenum to brainstem & back to
stomach (by way of vagus nerves)vagovagal reflex
2) Pain reflex cause general inhibition of entire GIT
3) Defecation reflex, it travels from colon & rectum to spinal cord
Signals from spinal cord produce powerful colonic, rectal &
abdominal contractions required for defecation

Enteric circuits could be independent
also
• PSNS and SNS nerves usually synapse with components of
ENS.
• ENS nerves are organized into myenteric & submucosal
plexuses.
• Many GI actions are regulated solely by neural circuits in
which a mechanoreceptor or chemoreceptor is stimulated
in mucosa and transmit the signal back to neurons in
submucosal plexus which stimulate other neurons in
submucosal & myenteric plexus regulation of endocrine
or secretory cells.
• Neurons of ENS are supported by enteric glial cells which
structurally & functionally resemble astrocytes in brain.

After-hyperpolarization mechanosensory

types of neurotransmitters secreted by enteric
neurons
From excitatory motor neurons
1. Acetylcholine
2. Substance P
From inhibitory motor neurons
1. ATP
2. Nitric oxide
3. VIP
From secreto-motor neurons
1. ACH
2. VIP
3. Histamine
Others
1. Norepinephrine
2. Serotonin
3. Dopamine
4. Cholecystokinin
5. Somatostatin
6. Leu-enkephalin, met-
enkephalin
7. Bombesin

Functions of neurotransmitters
secreted by enteric neurons
Through the extensive variety of
neurotransmitters and regulatory molecules ,
enteric system exerts multiple functions, e.g.,
• Acetylcholine most often excites GI activity
• Norepinephrine almost always inhibit GI
activity
• Epinephrine (secreted from adrenal medullae)
also inhibits GIT

• Specific functions of many of transmitters are not
well known
• Substance P contracts wall muscle & increases
salivary secretions.
• Enkephalins constrict circular muscle around
sphincters & decrease intestinal secretions.
• GRP (gastric-releasing peptide) acts on glands
only increases gastrin secretion.
• Neuropeptide Y relaxes wall muscle & decreases
intestinal secretions.

May act in hormonal fashion

Variety of actions achieved through
neurotransmitters
• In submucosal plexus, secretory neurons
primarily use VIP and ACh as
neurotransmitters, whereas sensory nerves
use substance P.
• In myenteric plexus, motor neurons use ACh
and nitric oxide, sensory neurons use
substance P, and the interneurons use ACh
and serotonin.

Pharmacological importance of certain
enteric neurotransmitters
• Certain enteric neurotransmitters are also
used elsewhere in the body.
• For example: A person on serotonin reuptake
inhibitors.
• These drugs alter serotonin levels regulating
GIT also.
• Patient may experience decreased GI motility
as a side effect

Neuro-muscular junction in GIT
It is the site where NTs are released from axons
of motor neurons to act on:
– Smooth muscle fibers
– Interstitial cells of Cajal
– Glands
– BVs

Structural significance
• These are simpler structures than motor end
plates of skeletal muscles.
• NTs are released from multiple varicosities of
motor axons which spread out along the axon.
• This is an adaptation for simultaneous
application of NT to a large number of muscle
fibers from a small number of motor axons.

Synaptic transmission in ENS is
modulated through pre & post-
synaptic actions

Synaptic transmission
• Slow EPSPs cause long lasting responses of
gut effectors during physiological stimuli
• Fast EPSPs cause rapid transfer of
information b/w elements of enteric
microcircuits
• Slow IPSPs e.g., shunting of blood by
sympathetic stimulation during exercise

Synaptic transmission (cont’d)
• Presynaptic inhibition: a mechanism for
selective shutdown of a microcircuit
• Presynaptic facilitation: selective
enhancement

Non-neural control
Endocrine regulation
Source
Route of travel
Effector areas
Examples
Paracrine regulation

Hormonal control
The gut hormones constitute a group of hormones secreted by
enteroendocrine cells in the stomach, pancreas & small intestine
that control various functions of digestive organs
Enteroendocrine cells do not form endocrine glands but are
spread throughout the digestive tract.
They exert their autocrine & paracrine actions also that integrate
all of GI function

hormones are released into portal circulation
They exert physiological actions on target cells
with specific receptors for the hormone
Effects of the hormones persist even after all
nervous connections have been severed

Gastrointestinal regulatory substances

GI hormones belong to
Gastrin family
• Gastrin
• CCK
Secretin family
• Secretin
• Glucagon
• VIP (Vasoactive intestinal peptide)
• GIP (Gastric inhibitory peptide)
Others
• Motilin family
• Peptide YY
• Substance P

Few more GI hormones
Secreted by enteroendocrine cells in the mucosa
of GIT
1. Somatostatin family
2. Ghrelin

Gastrin
• Chemical Nature: Polypeptide hormone
secreted in two forms: G-34 and G-17
• Source: Produced by G cells in the antral
portion of the gastric mucosa
• Also secreted in duodenum & jejunum

Gastrin (cont’d)
Stimulant phases for secretion
– secreted from stomach during gastric phase of gastric
secretion
– from small intestine during intestinal phase
Stimulatory factors are
– Luminal: Presence of food in stomach peptide, amino
acids
– Stimulation of local nervous plexus in stomach & intestine
– Vasovagal reflex during gastric phase of gastric secretion
– Blood: Ca, Epinephrine
–

Gastrin (cont’d)
• Inhibitory factors for gastrin:
– Luminal: acid, somatostatin
– Blood: secretin, GIP, VIP, glucagon, calcitonin

Feedback inhibition of gastrin
Release is inhibited by highly acidic pH (<2.0).
Acid in antrum inhibit gastrin secretion by 2
ways
• Direct action on G cell
• Stimulate release of somatostatin by D cell
In condition which parietal cells are damaged
(pernicious anemia) gastrin level is elevated.

Gastrin (cont’d)
• Actions:
– stimulates gastric glands to secrete gastric juice with more
pepsin & HCl
– Accelerates gastric motility
– Promotes growth of gastric mucosa
– Stimulates pancreatic juice secretion
MOA: it induces the insertion of K/H ATPase pumps into the apical
membrane of parietal cells ( which in turn increases H+ release)
• Abnormally elevated in following conditions:
– ZE syndrome
– gastrinoma

Zollinger-Ellison syndrome
• Gastrin is produced at excessive levels
• Often by a gastrinoma of the duodenum or the
pancreas
How it occurs
• In autoimmune gastritis, the immune system
attacks parietal cells hypochlorhydria
elevated gastrin level in attempt to
compensate eventually, all parietal cells lost &
loss of negative feedback on gastrin.
Gastrinoma is gastrin producing tumor, mostly benign

Pentagastrin
• Synthetic gastrin, composed of terminal four
amino acids of natural gastrin plus the amino
acid alanine.
• Has all physiological properties of natural
gastrin

Cholecystokinin/ Pancreozymin
Nature: Polypeptide in nature, contain 33 amino
acids
Source: Secreted by I cells of the mucosa of
upper small intestine( duodenum and jejunum)
A small quantity secreted in ileum also.
Stimuli: Secretion is stimulated by products of
protein and fat digestion and acid

Functions of CCK
1. Pancreatic juice secretion(
pancreatic enzyme and
bicarbonate)
2. Contraction of gall bladder and
relaxation of sphincter of oddi
3. Inhibits gastric motility &
emptying
4. Trophic effect on pancreas
• Increases motility of intestine
• Augments contraction of pyloric
sphincter
• As a whole it is responsible for
stimulating the digestion of fat &
protein.
• Also induces satiety by acting
through hypothalamus.

Control of CCK secretion

secretin
Nature: 27 amino-acid polypeptide
Its structure is similar to glucagon, VIP, GIP
Stored in an inactive form (prosecretin)
t1/2 : 5 min
Source: Secreted by S cells located in the mucosa of
upper small intestine (duodenum, jejunum and ileum)
Stimuli: Secretion is increased by products of protein
digestion, bile acid, fatty food & increased acidity in
duodenal content (pH< 4.5-5).
Inhibited by somatostatin.

Functions of secretin
1. Stimulate pepsin, pancreatic bicarbonate and biliary
bicarbonate secretion.
2. Also has trophic action of exocrine pancreas
3. Inhibits gastric acid secretion
• Inhibit motility of stomach
• Causes constriction of pyloric sphincter
• Enhances action of cholecystokinin on pancreatic
secretion
1. Inhibits gastric emptying by causing contraction of
pyloric sphincter

Combined action of secretin & CCK on
pancreas

Gastric Inhibitory Peptide ( GIP)
New name: Glucose dependent insulino-tropic polypeptide
Nature: a member of secretin family, peptide hormone
Source: Secreted by K cells in the mucosa of duodenum and
jejunum GIP receptors are found on beta cells of pancreas
Stimuli: Secretion is stimulated by glucose and fats in
duodenum, acid in stomach
Functions:
1. Main action: Stimulate insulin release
2. Inhibits gastric acid secretion by directly inhibiting parietal
cells or indirectly inhibit gastrin release via somatostatin
3. Mild effect in decreasing gastric motility

Vasoactive intestinal peptide (VIP)
• 28 amino-acid polypeptide
• Released in response to esophageal & gastric
distention, vagal stimulation, fatty acid &
ethanol in duodenum
• Amino acid & glucose do not affect VIP release
• t1/2: 2 min in circulation

Actions of VIP
• It seems to induce smooth muscle relaxation
(stomach, gallbladder), stimulate secretion of
water in pancreatic juice & bile cause
inhibition of gastric acid secretion &
absorption from intestinal lumen
• Also stimulate pepsinogen secretion from
chief cells
• Also found in heart & causes coronary
vasodilation through effect on CVS

Somatostatin
It basically is growth hormone inhibitory hormone
(GH-IH)
Nature: Peptide in nature
Source: it was first found in hypothalamus. In GIT it
is secreted by D cells in stomach, duodenum &
pancreatic islets
Presented in 2 forms
Somatostatin 14: from hypothalamus
Somatostatin 28: from GIT

Somatostatin (cont’d)
Stimuli: Its secretion is stimulated by acid in the
lumen
Also the presence of chyme with glucose & proteins
in stomach & small intestine
Functions:
1. It inhibits the secretion of gastrin, secretin, VIP,
GIP, motilin, insulin, glucagon & GH.
2. Also inhibits secretion of exocrine pancreas

Action Of Somatostatin On GIT
Results In
• Increased fluid absorption & decreased
secretion from intestine
• Decreased bile flow & gall bladder contraction
• Decreased gastric acid secretion & motility
• Decreased absorption of glucose, amino acids
& triglycerides

Motilin:
Nature: Polypeptide, containing 22 amino acids
Source: Secreted by enterochromaffin cells and M cells in mucosa of
stomach, duodenum and jejunum
Stimulus: Its levels are increased in interdigestive periods.
when food is ingested, there is suppression of secretion of motilin
Function:
1. Regulator of the migrating motor complexes that control motility
of GIT between meals
• accelerates gastric emptying
• Increases mixing & propulsive movements of small intestine
• Increases peristalsis in colon

Ghrelin
• Recently discovered peptide hormone
• Synthesized by epithelial cells in fundus of stomach. Mainly
secreted by oxyntic cells in the mucosa of stomach
• Stimulant for secretion:
– secretion increases during fasting
– Decreased when stomach full
• Actions:
– promotes secretion of growth hormone
– Induces appetite & food intake by acting via feeding center in
hypothalamus
– Stimulates gastric emptying

Peptide YY
• Fat is the major stimulant
• Inhibit GI motility
• Mainly fat causes its release from jejunum

Some other hormones which are
believed to act on GIT
Secreted by mucosa of GIT:
• Enkephalin
• Dynorphin
• Neurotensin
• Serotonin
• Urogastrone
• Enterocrinin
• Villikinin
• Gaunylin
• Bombesin

Actions of GI hormones
Actions Gastrin CCK Secre
tin
GIP
Acid secretion S I
Pancreatic HCO3 secretion S S
Pancreatic enzyme secretion S
Bile HCO3 S
Gallbladder contraction S
Gastric emptying I I
Gastric mucosal growth S
Pancreatic growth S S
Insulin secretion S

Paracrine control
• Other than hormones, GIT is affected by non-
neural signaling molecules which act in
paracrine fashion.
– Histamine (monoamine)
– Prostaglandins(eicosanoid)
– Somatostatin (peptide)
• Histamine is released in stomach, whereas
both prostaglandins & somatostatin are more
widespread in their release & actions.

Gastrointestinal paracrines
Paracrine Releasing cells Releasing
structures
Paracrine function
Histamine Enterochromaffin-
like cells, mast cells
Stomach Increase gastric acid
secretion
Prostaglandins Cells lining
gastrointestinal
tract
Mucosa Increase blood flow
& mucus and HCO3
-
secretion
Somatostatin D cells Stomach and
pancreas
Inhibits peptide
hormones & gastric
acid secretion

How could NSAIDS affect GIT
• Prostaglandins are cyclooxygenase products
derived from arachidonic acid.
• Prostaglandins have an important role in
maintaining mucosal integrity.
• Cyclooxygenase inhibitors (i.e., aspirin & other
nonsteroidal anti-inflammatory drugs) can
cause stomach irritation.

General digestive phases
• Stomach and duodenal function can be divided
into 3 discrete phases:
• Cephalic phase
• Gastric phase
• Intestinal phase
• These phases allow for preparation, timing &
regulation feedback, e.g.,
– Cephalic is primarily feedforward regulation
– Gastric & intestinal phases are feedback mechanisms

Cephalic phase
• It is triggered by the thought of food or
conditions suggestive of previous food intake
(e.g., classical conditioning to eat after hearing a
dinner bell).
• Chemoreceptors & mechanoreceptors in the oral,
nasal cavities & throat that are stimulated by
tasting, chewing, swallowing & smelling food.
• Cephalic phase is primarily neural and causes ACh
& VIP release which stimulate secretion by
salivary glands, stomach, pancreas, & intestines.

• Gastric phase
• It begins when food & oral secretions enter the
stomach.
• It coincides with distention & stomach contents (amino
acids & peptides) and elicits neural, hormonal &
paracrine GI response.
Example of combination of signaling molecules : Gastric
acid secretion.
• It includes:
– ACh neural
– Gastrin  hormonal
– Histamine paracrine

• Intestinal phase
• It begins when stomach contents enter the duodenum.
• It is linked to digested constituents of proteins & fats as
well as H+.
• It initiates primarily hormonal but also paracrine &
neural response.
• During this phase following are secreted
• CCK
• Gastrin
• Secretin
• GIP

Feeding tubes and intravenous feeding
• Feeding tubes are used to provide nutritional support in
certain conditions like:
– Patients with swallowing disorders
– Patients on mechanical ventilation
• Examples of feeding tubes are:
– NG tube (nasogastric)
– ND tube (nasoduodenal)
– PEG tube (percutaneous endoscopic gastrostomy)
• These deliver the nutrients past obstructed areas
thereby bypass majority of digestive phase initiation cues.
• This requires the feeding tube formula to be prepared in a
manner that will not require upper GI processing of food

• Nutrients infused intravenously bypass the
entire GI system so care must be taken to
include all required nutrients.
• Less kcals are necessary as 7% of energy
consumed by mouth is used to digest &
absorb nutrients.

Functional types of movements in the gastrointestinal tract
Muscular contractions mix and move forward the contents
of digestive tract
Mechanical activity of GIT can be classified as:
Fed state motility: in this state two types of movements
occur in digestive tract
1. Propulsive movement: Peristalsis (wave-like contractions)
2. Mixing movements: also called segmentation
Fasting state motility: Migrating motor complex (MMC)

Basic difference b/w propulsive &
mixing movements
Propulsion Mixing
Its basic rhythm is peristalsis Basic rhythm: segmentation
Adjacent segments of alimentary canal
alternately contract & relax
Non-adjacent segments of alimentary
canal contract & reax
Food is moved distally along the tract Food is moved forward, then backward
Primarily propulsive, some mixing may
occur
Primarily mixes food & breaks it down
mechanically, some propulsion may occur

Propulsive movements
• Is the basic movement of GIT that pushes the contents
forward through the digestive tract from esophagus to
rectum
• It occurs at an appropriate rate to accommodate
digestion & absorption of food in gut
• The propulsive movements are modified in different
parts of GIT for proper functioning
• The basic propulsive movement of GIT is peristalsis

What is peristalsis
It is the involuntary constriction & relaxation of
muscles of intestine, creating wave like
movements which push the contents forward

Peristaltic stimuli
• Distention of the gut
• Chemical irritation of gut epithelium
• Physical irritation
• Strong parasympathetic signal

Mechanism of peristalsis
• The usual stimulus for peristalsis is distension of gut
stretching of gut wall stimulation of enteric nervous
system
• Contractile ring appears in circular muscle 2-3cm
behind the point of distention around the gut and then
moves forward
• Segment of gut distal to contractile ring relaxes
• Any material in front of contractile ring moves forward

Peristalsis

Control of peristalsis
Peristalsis is mediated by integrated activity of enteric
nervous system especially Myenteric plexus .
Peristalsis does not occur in the segment of GIT that has
congenital absence of myenteric plexus.
Also modified by extrinsic nervous system.
Increased by the action of gastrin, CCK, insulin, motilin &
serotonin while decreased by secretin & glucagon
It is greatly depressed or completely blocked by
anticholinergics (eg: atropine)

Other body tubes with peristaltic
activity
• Bile ducts
• Glandular ducts
• ureters

Peristaltic reflex
• complex pattern of appearance of contractile
ring on orad side of distended segment+
receptive relaxation
Receptive relaxation
– it is the relaxation of several centimeters of gut
wall ahead of distended part (toward anus)
– It allows the food to be propelled more easily
• It is called myenteric reflex also

Law of gut:
• Peristaltic reflex and anal direction of movement of
peristalsis is called law of gut
• Peristalsis can occur in either direction from
stimulated point but it normally dies out rapidly in
orad direction while continuing for considerable
distance( 5-10cm) towards anus

Mixing movement:
• These are local intermittent constrictive contractions occuring
every few centimeters in the gut wall
• These movements differ in different parts of alimentary tract
• Last for 5-30seconds
• The areas for appearance of these mixing constrictions keep
shuffling among different points of gut
• These movements are modified in different parts of GIT for proper
mixing

Functions of mixing movements
• Chop and shear the contents of GIT.
• Mix the food with digestive juices
• Facilitate the absorption by exposing all parts
of gastrointestinal contents to absorptive
surfaces

In some areas
• The peristaltic contractions cause most of the
mixing
• Example
• Specially true when forward progression of
intestinal contents is blocked by a shincter
• In this case, peristaltic wave can only churn
the contents instead of moving them forward

SPLANCHNIC CIRCULATION
Gastrointestinal blood flow

Gastrointestinal Blood Flow
• GI vessels are a part of splanchnic circulation
(visceral circulation).
• Splanchnic circulation consists of:
Portal circulatory system+ arterial blood flow into the liver

Unique feature of splanchnic
circulation
• Blood from mesenteric bed (from GIT &
pancreas) & spleen forms a major amount of
blood flowing to the liver
• This flow is called portal system

Design of gastrointestinal blood flow system
Blood from GIT, spleen, pancreas, liver
(portal vein)
Liver sinusoids
( hepatic vein)
Inferior Vena Cava

Significance of GI blood flow through
liver
• It prevents direct transport of potentially harmful
agents into body’s circulation
– Sinusoids of liver are lined by reticulo-endothelial cells
– These cells remove bacteria & other particulate
matter that might enter blood from GIT
• Chemical intermediary processing of certain
nutrients also occur in liver cells
– Both reticuloendothelial & hepatic cells absorb 7 store
nutrients (non-fat & water soluble) temporarily

Arterial blood supply to GIT is
achieved through
• Celiac artery to stomach
• Superior mesenteric arteries
• Inferior mesenteric arteries

Distribution of blood flow
• Stomach 35ml/100gm/minute
• Intestine 50ml
• Pancreas 80ml

Anatomy of the GI blood supply
• Arteries supply walls of small & large
intestines by forming an arching arterial
system
• What that means arteries give off circling
branches which then dig deeper

How arching system is formed
• Upon entering the walls, arteries branch & send
smaller arteries
• Smaller arteries circle around the gut in both
directions
• Tips of arteries meet on the side of gut wall
opposite to mesenteric attachment
• Smaller arteries from circling arteries penetrate
into intestinal wall & spread
1. Along muscle bundles
2. Into intestinal villi
3. Into submucosal vessels beneath epithelium

“Countercurrent”
Blood Flow in Villi
• It refers to the
specific pattern of
blood flow in villi of
intestine which could
vary in different
conditions.

“Countercurrent”
Blood Flow in Villi
• Arterial flow into villus is in opposite direction
to its venous out flow, So 80% O2 and other
nutrients diffuse directly from arterial end to
venous end without reaching the tip
• Under normal conditions it is not harmful
• Under diseased conditions like circulatory
shock ischemic death of villi may occur

Regulation of GI blood flow
• Intrinsic regulation
– Local metabolic control
– Local reflexes
– Locally produced vasoactive substances
• Extrinsic regulation
– Sympathetic innervation decrease in blood flow
– Circulatory vasoactive substances
(catecholamines)
– Systemic hemodynamic changes

Local metabolic control
• Responds by local vasodilator factors eg:
– Decreased oxygen
– Increased cellular metabolism

Other intrinsic factors
• Local reflexes occur as a response to the
presence of luminal contents
• Locally produced vasoactive substances
– Gastrin
– Secretin
– cholecystokinin

Nervous control of GI blood flow
• Parasympathetic stimulation: increased local
blood flow
• Sympathetic stimulation: decreased blood
flow due to intense vasoconstriction of
arterioles (but not for long time)

Importance of nervous depression of
GI blood flow
Sympathetic vasoconstriction takes place in gut in
conditions like
– Heavy exercise
– Circulatory shock
1. This vasoconstriction allows shutoff of GI blood
flow for short time when other parts of body
need extra blood flow
2. In dire situations (hemorrhagic shock)
Constriction of large volume GI veins displaces
large amount of blood into other parts of
circulation

Effect of gut activity on GI blood flow
Under normal conditions
• blood flow is directly proportional to level of local
activity
After a meal
• Motor, secretory & absorptive activity increases
• blood flow increases greatly at first
• 2-4 hours later, blood flow decreases back to
resting level

Causes of increased blood flow during
activity
1. Increased metabolic rate during activity decreased O2
concentration increased blood flow upto 50-100%
2. Vasodilator substances released from mucosa during digestive
process
Examples:
1. cholecystokinin,
2. VIP (vasoactive intestinal peptide),
3. gastrin
4. secretin
3. Mucosal vasodilation due to release of kinins from GI glands into
gut wall
Examples
1. kallidin
2. bradykinin

Summary of Main Factors increasing
GIT blood flow
Increased GIT activity
Vasodilators e.g., Cholecystokinin, VIP, Gastrin, Secretin, Kallidin, Bradykinin and Adenosin
Vasodilation due to decreased O2
Parasympathetic activation

Auto-regulatory escape
• Sympathetic stimulation causes intense
vasoconstriction and greatly decreased blood flow.
• After a few minutes of decreased blood flow local
metabolic vasodilator mechanisms elicited due to
ischemia cause re-vasodilation of vessels. This is called
autoregulatory escape

1st chapter of digestion

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