The Gastrointestinal Physiology and

Neuro-Endocrinal System

Principle of Human Physiology by Stanfield

Berne and Levy Physiology, 7th Ed
Medical Physiology: Principles for Clinical Medicine, 4th Ed by Rhoades,
Guyton and Hall Textbook of Medical Physiology, 13th Ed
Principles of Pharmacology by Golan, David

Copyright @ Tafheem Malik

2017 Pearson Education, Inc.
 Outline

Overview of Gastrointestinal System Processes

Functional Anatomy of the Gastrointestinal System
Digestion and Absorption of Nutrients and Water
General Principles of Gastrointestinal Regulation
Gastrointestinal Secretion and Its Regulation
Gastrointestinal Motility and Its Regulation

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 Neural and Endocrine Pathways of GI Control
Enteric nervous system
Submucosal plexus
Myenteric plexus
Reflexes mediated through ENS control many GI functions
CNS contributions to neural control
Generally through communication of ANS with enteric nervous system

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 Neural and Endocrine Pathways of GI Control

GI hormones are secreted from endocrine cells in the stomach and

small intestine
Gastrin
Cholecystokinin
Secretin
Glucose-dependent insulinotropic peptide (GIP)
Glicentin
Sensory receptors in the GI tract detect the environment in the lumen to
initiate reflexes

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 Figure 20.5 Anatomy of the mouth, pharynx, esophagus, and stomach.

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 Ghrelin, a hormone secreted from the stomach, activates AGRP-NPY neurons
and stimulates food intake.

Glicentin: A 69amino acid peptide secreted by small intestinal cells. It inhibits

gastric acid secretion, stimulates insulin secretion by the pancreas,
regulates intestinal motility, and fosters the growth of intestinal mucosal
cells.

Guanylin is a 15 amino acid polypeptide that is secreted by goblet cells in the

colon.
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 Figure 20.22 Summary of neural and endocrine control of gastrointestinal function.

Lumen of digestive tract

Emotional Sight, taste,
states smell of food

LONG REFLEX PATHWAY

Chemoreceptors,
Stimulus mechanoreceptors,
osmoreceptors
SHORT REFLEX PATHWAY

Response Effector cells Enteric Autonomic Central

(change in secretory (smooth muscle or nervous nervous nervous
activity or motility) endocrine gland) system system system

Blood Hormone Endocrine cells

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 Neural and Endocrine Pathways of GI Control

Phases of gastrointestinal control

Cephalic phase: stimuli originate in head
Thoughts, taste, and smell
Requires input from CNS (long reflexes)
Gastric phase: stimuli originate in stomach
Long and short reflexes and GI hormones
Intestinal phase: stimuli originate in small intestine
Long and short reflexes and GI hormones

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 Hypothalamic-Pituitary Regulation of Energy Intake and Energy Expenditure
Hypothalamus
Satiety -MSH and CART travel to the lateral hypothalamic area to
induce satiety and to the paraventricular nucleus to stimulate
release of CRH and TRH
Paraventricular
nucleus
Anterior
Lateral pituitary
hypothalamic area CRH and TRH trigger release of ACTH
and TSH from anterior pituitary
Optic tract
Arcuate CRH TRH
nucleus
Portal vein

-MSH ACTH TSH

Leptin and Cortisol
CART
TH

Leptin from adipose

Adrenal
tissue stimulates
cortex Increased
release of -MSH and
CART from arcuate metabolism
nucleus Adipose
Thyroid gland Body
tissue
cells
TSH stimulates release
ACTH stimulates release of of thyroid hormone Cortisol and thyroid hormone
cortisol from adrenal cortex from thyroid gland increase metabolism in body
cells

Figure 20.23 Effects of satiety and orexigenic factors on food intake.

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 Hypothalamic-Pituitary Regulation of Energy Intake and Energy Expenditure

Leptin: hormone released from adipose cells when calories exceed demands
Leptin suppresses hunger and increases metabolism: satiety signal
Leptin stimulates MSH and CART (cocaine- and amphetamine-related transcript)
MSH and CART increase sympathetic activity and stimulate release of TSH and ACTH
TSH and ACTH increase metabolic rate and reduce fat storage

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 Slide 2

Hypothalamus

Paraventricular
nucleus
Lateral
hypothalamic area
Optic tract
Arcuate
nucleus

-MSH
Leptin and
CART

Leptin from adipose

tissue stimulates
release of -MSH and
CART from arcuate
nucleus Adipose
tissue

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 Figure 20.23 Effects of satiety and orexigenic factors on food intake. Slide 3

Hypothalamus
Satiety -MSH and CART travel to the lateral hypothalamic area to
induce satiety and to the paraventricular nucleus to stimulate
release of CRH and TRH
Paraventricular
nucleus
Lateral
hypothalamic area
Optic tract
Arcuate
nucleus

-MSH
Leptin and
CART

Leptin from adipose

tissue stimulates
release of -MSH and
CART from arcuate
nucleus Adipose
tissue

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 Figure 20.23 Effects of satiety and orexigenic factors on food intake. Slide 4

Hypothalamus
Satiety -MSH and CART travel to the lateral hypothalamic area to
induce satiety and to the paraventricular nucleus to stimulate
release of CRH and TRH
Paraventricular
nucleus
Anterior
Lateral pituitary
hypothalamic area CRH and TRH trigger release of ACTH
and TSH from anterior pituitary
Optic tract
Arcuate CRH TRH
nucleus
Portal vein

-MSH ACTH TSH

Leptin and
CART

Leptin from adipose

tissue stimulates
release of -MSH and
CART from arcuate
nucleus Adipose
tissue

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 Figure 20.23 Effects of satiety and orexigenic factors on food intake. Slide 5

Hypothalamus
Satiety -MSH and CART travel to the lateral hypothalamic area to
induce satiety and to the paraventricular nucleus to stimulate
release of CRH and TRH
Paraventricular
nucleus
Anterior
Lateral pituitary
hypothalamic area CRH and TRH trigger release of ACTH
and TSH from anterior pituitary
Optic tract
Arcuate CRH TRH
nucleus
Portal vein

-MSH ACTH TSH

Leptin and Cortisol
CART

Leptin from adipose

Adrenal
tissue stimulates
cortex
release of -MSH and
CART from arcuate
nucleus Adipose
tissue

ACTH stimulates release of

cortisol from adrenal cortex

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 Figure 20.23 Effects of satiety and orexigenic factors on food intake. Slide 6

Hypothalamus
Satiety -MSH and CART travel to the lateral hypothalamic area to
induce satiety and to the paraventricular nucleus to stimulate
release of CRH and TRH
Paraventricular
nucleus
Anterior
Lateral pituitary
hypothalamic area CRH and TRH trigger release of ACTH
and TSH from anterior pituitary
Optic tract
Arcuate CRH TRH
nucleus
Portal vein

-MSH ACTH TSH

Leptin and Cortisol
CART
TH

Leptin from adipose

Adrenal
tissue stimulates
cortex
release of -MSH and
CART from arcuate
nucleus Adipose
tissue Thyroid gland

TSH stimulates release

ACTH stimulates release of of thyroid hormone
cortisol from adrenal cortex from thyroid gland

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 Figure 20.23 Effects of satiety and orexigenic factors on food intake. Slide 7

Hypothalamus
Satiety -MSH and CART travel to the lateral hypothalamic area to
induce satiety and to the paraventricular nucleus to stimulate
release of CRH and TRH
Paraventricular
nucleus
Anterior
Lateral pituitary
hypothalamic area CRH and TRH trigger release of ACTH
and TSH from anterior pituitary
Optic tract
Arcuate CRH TRH
nucleus
Portal vein

-MSH ACTH TSH

Leptin and Cortisol
CART
TH

Leptin from adipose

Adrenal
tissue stimulates
cortex Increased
release of -MSH and
CART from arcuate metabolism
nucleus Adipose
Thyroid gland Body
tissue
cells
TSH stimulates release
ACTH stimulates release of of thyroid hormone Cortisol and thyroid hormone
cortisol from adrenal cortex from thyroid gland increase metabolism in body
cells

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 Hypothalamic-Pituitary Regulation of Energy Intake and Energy
Expenditure
Neuro-Endocrinal Regulation: Orexigenic neuropeptides
Agouti-related protein (AGRP): is named after a related gene controlling hair color in
rodents. It is a powerful antagonist of the MC3R and MC4R melanocortin receptors
in the hypothalamus. Obese patients have elevated plasma levels of AGRP, and over-
expression of AGRP in animal models leads to obesity.
Neuropeptide Y (NPY): is produced in hypothalamic neurons and other neurons of the
sympathetic nervous system. It stimulates appetite via several receptors and has
other systemic functions.

Orexigenic factors oppose satiety factors

NPY
AgRP
Promote eating
Decrease metabolism
Increase parasympathetic activity
Decrease sympathetic activity
Inhibit secretion of TSH and ACTH

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 Neuro-endocrinal regulation: Satiety neuropeptides
Cocaine and amphetamine regulated transcript (CART): is a neuropeptide precursor
protein that is abundant in the hypothalamus. It is upregulated after cocaine or
amphetamine administration. CART-derived peptides reduce food intake when injected
into the third cerebral ventricle, and probably have several other functions within the
central nervous system.
Pro-opiomelanocortin (POMC): is the precursor protein for melanocyte stimulating
hormone (MSH), adrenocorticotropic hormone (ACTH), -endorphin and others. It is also
involved in the regulation of sexual behavior in both males and females. The expression
of POMC is regulated by insulin and leptin as well as gonadal steroids. The release
of a POMC product, -endorphin, is regulated by NPY.
-melanocyte stimulating hormone (-MSH): is the effective peptide that binds to
receptors on neurons and other tissues. It inhibits food intake and fat deposition.

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 Regulation of Food Intake

Short-term regulation: hunger versus satiety

Satiety factors
Insulin
CCK
Neural input from mechanoreceptors and chemoreceptors
Orexigenic factors
Ghrelin, secreted by gastric fundal cells during the fasting state
endogenous growth hormone-releasing peptide
acts synergistically with GHRH to promote GH release
acting on a receptor that is distinct from the GHRH receptor
(501-502- Golan, David E. Principles of Pharmacology)

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Note that insulin
stimulates satiety and
inhibits hunger
(appetite), similar to
glucose and leptin.
 Inhibits food intake and ghrelin secretion
Stimulates insulin secretion

-R

Those of particular interest here are highlighted in blue.

In this table ghrelin is the only hormone which stimulates feeding.

Several others are now recognized, but are not completely
understood yet. Some will be mentioned later.
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 Guanylin
Uroguanylin (or guanylin) is (also
added to the table) secreted into the
lumen by goblet cells and
enterocytes and, acting in paracrine
and autocrine fashion, inhibits Na+
absorption and stimulates both Cl
and HCO3 secretion via the cystic
fibrosis transporter regulator (CFTR),
resulting in decreased osmotic
gradient for water absorption or
increased osmotic secretion. This
can merely maintain lumen fluidity or
produce diarrhea if too active. The
hormone also acts on the kidneys to
help maintain osmotic homeostasis.
It is the most significant hormone
secreted by colonic cells.

UroG; uroguanylin, equivalent to guanylin

GC-C; guanylyl cyclase-C receptor

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 Gastrointestinal Secretion and Its Regulation

Saliva secretion
Acid and pepsinogen secretion in the stomach
Secretion of pancreatic juice and bile
Rates of fluid movement in the digestive tract

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 Mouth GI tract

One function of bitter receptors in the gut is to

detect toxic compounds and stimulate vomiting.

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 Saliva Secretion

Taste and texture of food stimulate

mechanoreceptors and chemoreceptors in the
mouth
Relayed to the salivary center of the medulla,
which regulates the autonomic nervous system
Sight and smell input from cerebral cortex also
affects the salivary center
Salivation stimulated
Parasympathetic activation: watery saliva
Sympathetic activation: protein-rich, viscous saliva

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 Figure 20.24 Mechanism of gastric acid secretion. Physiochemical reaction

Lumen of
gastric gland H+ Cl
K+ H+ Cl Cl
H+

ADP
K+ ATP
K+ + Pi
K+ H+
CA Cl
CO2 + H2O H2CO3 Cl
Cl
HCO3

Parietal cells
Interstitial uid HCO3 Cl
Capillary

Blood HCO3 Cl

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 Acid and Pepsinogen Secretion in the Stomach

Parietal cells produce hydrochloric acid

Carbonic anhydrase catalyzes production of
bicarbonate and H+
H+ is actively secreted into lumen of the stomach
Bicarbonate is transported into interstitial fluid for Cl
Cl diffuses into lumen of the stomach through channels
Net result of acid production
H+ and Cl are secreted into lumen of the stomach
Bicarbonate enters the interstitial fluid and then blood

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 What is the role of carbonic anhydrase in stomach
acid secretion? Which other ions are secreted
along with hydrogen ions?

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 Acid and Pepsinogen Secretion in the Stomach

Acid secretion
Parasympathetic nervous system
Gastrin
Histamine (paracrine)
Pepsinogen secretion regulated in sync with acid
secretion
Parasympathetic nervous system
Gastrin
Histamine

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 Figure 20.25a Regulation of gastric secretion. Slide 1

Sight, smell, taste of food;

chewing and swallowing

Parasympathetic activity

G cells

Gastrin secretion

Plasma gastrin

Parietal and chief cells

Acid and pepsinogen secretion

Cephalic-phase control of gastric secretion

Initial stimulus
Physiological response
Result
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 Acid and Pepsinogen Secretion in the Stomach

Cephalic-phase regulation of secretion

Stimuli increase acid and pepsinogen secretion
Sight of food
Taste
Smell
Chewing
Swallowing
All activate the parasympathetic nervous system
Parasympathetic nervous system stimulates gastrin
secretion

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 Figure 20.25a Regulation of gastric secretion. Slide 2

Sight, smell, taste of food;

chewing and swallowing

Cephalic-phase control of gastric secretion

Initial stimulus
Physiological response
Result
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 Figure 20.25a Regulation of gastric secretion. Slide 3

Sight, smell, taste of food;

chewing and swallowing

Parasympathetic activity

G cells

Gastrin secretion

Plasma gastrin

Cephalic-phase control of gastric secretion

Initial stimulus
Physiological response
Result
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 Figure 20.25a Regulation of gastric secretion. Slide 4

Sight, smell, taste of food;

chewing and swallowing

Parasympathetic activity

G cells

Gastrin secretion

Plasma gastrin

Parietal and chief cells

Acid and pepsinogen secretion

Cephalic-phase control of gastric secretion

Initial stimulus
Physiological response
Result
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 The parietal cell is under neural and
hormonal control.

Medical Physiology. Principles for Clinical Medicine

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 Acid and Pepsinogen Secretion in the Stomach
Gastric-phase regulation of secretion
Stimuli of gastric secretion
Proteins, peptides, and amino acids
Distension of stomach
Short and long reflex pathways trigger gastrin, acid, and
pepsinogen release

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 Figure 20.25b Regulation of gastric secretion.

Proteins and protein digestion products

in stomach; distension of stomach

Chemoreceptors and mechanoreceptors

Detect and respond

Short and long reexes

G cells

Gastrin secretion

Plasma gastrin

Parietal and chief cells

Acid and pepsinogen secretion

Gastric-phase control of gastric secretion

Initial stimulus
Physiological response
Result
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 Acid and Pepsinogen Secretion in the Stomach

Inhibition of secretion
Gastric phase
Exit of food removes stimuli for secretion
Increased acidity inhibits gastrin release
Intestinal phase
Effects of food entry into the duodenum
Increased osmolarity
Increased fat and acid
Increased distension
Long and short reflex pathways inhibit acid and
pepsinogen secretion

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 Secretion of Pancreatic Juice and Bile

Acinar cells
Small volume of primary secretion contains water,
electrolytes, and digestive enzymes
Duct cells
Large volume
Bicarbonate-rich secretion

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 Cholecystokinin (CCK)
hormones secreted by the duodenum in response to the partially
digested output from the stomach, which is called chyme.
Fatty meals are particularly effective.
Delays gastric emptying, stimulates pancreatic enzyme
production,
causes the gall bladder to contract,
promotes insulin release by the pancreas
produces a sensation of fullness or satiation.
Signals to the brain via the vagus nerve (neurocrine), and by
direct CNS stimulation (endocrine).
Other insulin stimulating hormones Glucose-dependent insulinotropic
peptide (GIP), glucagon-like peptide 1 (GLP-1) and glucagon-like
peptide 2 (GLP-2) and (incretins) in the same group are
oxyntomodulin.

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 Secretion of Pancreatic Juice and Bile

CCK and secretin: primary stimulants

Enzyme and bicarbonate secretion regulated independently
Composition of pancreatic juice varies based on lumenal contents
CCK stimulates acinar cells to secrete enzymes
Small stimulant for bicarbonate release
CCK potentiates secretin effects on bicarbonate release
Secretin stimulates duct cells to secrete bicarbonate
Small stimulant for enzyme release
Secretin potentiates CCK effects on enzyme release
Stimuli for CCK release
Fat and amino acids in duodenum
Stimuli for secretin release
Acidity in duodenum

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 Figure 20.26 Stimulation of the secretion of bicarbonate-rich fluid by acidity in the duodenum. Slide 1
Acid in duodenum

Chemoreceptors

Detect and respond

Short and long reexes

Endocrine cells

Secretin secretion Negative

feedback

Plasma secretin

Pancreatic duct cells

Secretion of
bicarbonate-rich uid

Duodenum

Neutralization of acid

Acid in duodenum

Initial stimulus
Physiological response
Result

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 Figure 20.26 Stimulation of the secretion of bicarbonate-rich fluid by acidity in the duodenum. Slide 2
Acid in duodenum

Initial stimulus
Physiological response
Result

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 Figure 20.26 Stimulation of the secretion of bicarbonate-rich fluid by acidity in the duodenum. Slide 3
Acid in duodenum

Chemoreceptors

Detect and respond

Short and long reexes

Initial stimulus
Physiological response
Result

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 Figure 20.26 Stimulation of the secretion of bicarbonate-rich fluid by acidity in the duodenum. Slide 4
Acid in duodenum

Chemoreceptors

Detect and respond

Short and long reexes

Endocrine cells

Secretin secretion

Plasma secretin

Initial stimulus
Physiological response
Result

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 Figure 20.26 Stimulation of the secretion of bicarbonate-rich fluid by acidity in the duodenum. Slide 5
Acid in duodenum

Chemoreceptors

Detect and respond

Short and long reexes

Endocrine cells

Secretin secretion

Plasma secretin

Pancreatic duct cells

Secretion of
bicarbonate-rich uid

Initial stimulus
Physiological response
Result

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 Figure 20.26 Stimulation of the secretion of bicarbonate-rich fluid by acidity in the duodenum. Slide 6
Acid in duodenum

Chemoreceptors

Detect and respond

Short and long reexes

Endocrine cells

Secretin secretion Negative

feedback

Plasma secretin

Pancreatic duct cells

Secretion of
bicarbonate-rich uid

Duodenum

Neutralization of acid

Acid in duodenum

Initial stimulus
Physiological response
Result

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 Secretion of Pancreatic Juice and Bile

Regulation of bile secretion into duodenum

Secretin
Stimulates bile secretion from liver
CCK
Stimulates gallbladder contraction
Stimulates relaxation of sphincter of Oddi

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 Figure 20.27 The mechanisms by which secretin and CCK regulate the entry of bile into the duodenum. Slide 1

Duodenum

Acid Protein digestion

products and fat

Plasma secretin Plasma CCK

Liver Gallbladder Sphincter of Oddi

Bile secretion Contraction Relaxation

Duodenum

Bile

Neutralization of acid Emulsication of fats

Initial stimulus
Physiological response
Result
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 Incretins (Anorexigenic Neuropeptide)

Glucose absorption from the gut or hepatic release stimulates insulin secretion from the
pancreas, but intestinal glucose also stimulates incretin secretion.
Incretins are Glucose-dependent insulinotropic peptide (GIP), and Glucogon-like peptides
1 (GLP-1). GIP secreted from K cells, and GLP-1 hormone is secreted by L-cells. Both
are most potent hormones which act synergistic with glucose to stimulate insulin secretion
from the pancreas.
 Incretins (Anorexigenic Neuropeptide)

The incretins are a family of peptides derived post-transcriptionally from the preproglucagon polypeptide.

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 Incretins (Anorexigenic Neuropeptide)

Glucagon like peptide-1 (GLP-1): Secreted from L-cells of the ileum and colon (as well as
neurons of the solitary tract) this hormone/neurotransmitter has a half-life of only 1-2
minutes, but has receptors in the brain, gut and pancreas. It stimulates insulin secretion
by -cells of the pancreas and suppresses appetite in the brain. GLP-1 analogs are now
used in treatment of obesity in type 2 diabetes.

Oxyntomodulin (OXM): Also secreted from L-cells of the ileum and colon this hormone
appears to exert its effect through receptors for GLP-1 as well as OXM specific receptors.

Glucose-dependent insulinotropic peptide (GIP): Secreted from K-cells of the small

intestine this hormone inhibits gastric motility and stimulates insulin secretion, thus having
an inhibitory effect on appetite.

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 Synergism between oral glucose and the incretin hormones:
Intravenous glucose does not stimulate insulin as much as it does oral glucose
intake (even at the same blood levels).
synergism is via a simultaneous inhibition of glucagon by GLP-1.

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 Effects of Oxyntomodulin in humans
Incretins (Anorexigenic Neuropeptide)

https://doi.org/10.1016/j.molmet.2013.12.0012014

Oxyntomodulin, secreted from L-cells of the ileum and colon has dramatic effects on food
intake, metabolism and secretions from the pancreas and other tissues. It acts synergistically
with GLP-1 and together they are an interesting prospect for diabetes control as well as
weight loss.

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 Hypocretins/Hypothalamic Orexin
(orexigenic Neuropeptide)
Orexins A & B: This important pair of neurotransmitters (also known as
hypocretins 1 & 2) are derived from a common precursor together with their G-
protein linked receptors OX1-R and OX2-R. They have a major role in
arousal from sleep and food seeking behavior. Damage to the orexin signaling
system leads to narcolepsy.
Their role in human appetite is still investigational, even though they were first
recognized as antagonistic to the incretins.

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 Motilin

Chemistry - linear 22 AA peptide - unrelated to other hormones

Stimuli/release -
- Released from M-cells of duodenum and proximal jejunum during fasting
at 100 min intervals
- Release is under neural control

Physiological effects -
- Stimulates upper G.I. motility
- Accounts for the migrating motility complex, housekeeping
contractions
- Series of intense antral contraction and pyloric sphincter relaxation

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 Paracrines Orexigenic

Somatostatin (GHRH)
- Found in gastric/duodenal mucosa and pancreas
- Release - stimulated by acid, inhibited by Ach
- Inhibits release of all gut hormones
- Directly inhibits parietal cell acid secretion
- Mediates acid induced inhibition of gastrin release

Histamine
- Gastrin and Ach cause release from cells in stomach
- Stimulates acid secretion
- Histamine H2 receptor blockers Acid secretion
- Cimetidine (Tagamet), Ranitidine (Zantac)
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 Neurocrines

Peptide Location Action

VIP Gut mucosa and SM Relaxation of gut SM
GRP (Bombesin Gastric mucosa Gastrin Release
Anorexigenic)
Gut mucosa and SM SM tone
Enkephalins
(orexigenic)

VIP, vasoactive intestinal peptide

GRP, gastrin-releasing peptide

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 Outline

20.1 Overview of Gastrointestinal System

Processes
20.2 Functional Anatomy of the Gastrointestinal
System
20.3 Digestion and Absorption of Nutrients and
Water
20.4 General Principles of Gastrointestinal
Regulation
20.5 Gastrointestinal Secretion and Its Regulation
20.6 Gastrointestinal Motility and Its Regulation

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 Activation of Visceral Smooth Muscle
Visceral smooth muscle activity is primarily controlled by the enteric nervous
system (ENS) which consists of two neural plexuses embeded within the
musculature of the GI tract.

Myenteric plexus (Auerbach's):

a linear plexus extending all the way down the intestinal wall between the
longitudinal and circular muscle layers, it controls motor activity along the
length of the gut
Principle functions:
increasing muscle tone of the gut
increasing intensity of rhythmical contraction
increasing the rate of contraction
Submucosal plexus (Meissner's):
a more disorganized plexus, it lies in the submucosa
controls mainly GI secretion and local blood flow
controls function of each minute segment

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 20.7 Gastrointestinal Motility and Its Regulation

GI motility
Movements of the wall of the GI tract
Due primarily to contractions of the muscularis externa
(outer muscle layers)
Function: mix and propel GI tract contents.

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 Electrical Activity in GI Smooth Muscle

Spontaneous slow waves of depolarization = slow

waves
Frequency of waves = Basic Electric Rhythm
BER varies in different areas of the GI tract
Height of BER is affected by neural and hormonal
input
Parasympathetic excitation
Sympathetic inhibition

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 Relationship Between Electrical and Mechanical Activity in Smooth Muscle :
Gastric motility

Stomach

Larger depolarizations stronger contractions

Action potentials even stronger contractions

Functions of gastric smooth muscle -
- Relaxes to accommodate food - orad area
(receptive relaxation)
- Mixes food with gastric juice - caudad area
(retropulsion)
- Propels chyme into duodenum - caudad area
(antral pump)

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 Intestines
Action potentials required
for force
Strength of contraction

may also mediate

varies with frequency of
enteric innervation
action potentials

Rhythmic fluctuation of the

membrane potential between -
65 and -45 mV initiated by
interstitial cells of Cajal (ICC),
which are stellate mesencyhmal
pacemaker-like cells located in
the GI tract, contribute to slow
wave generation.
Not well depicted Slow waves are cyclic
here
depolarization of the smooth
muscle cells, most of which do
not reach threshold for action
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potential generation.
 Note that a single interstitial cell of Cajal may innervate
both the longitudinal and the circular muscle layers.
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 Peristalsis and Segmentation

Waves of contraction in muscularis mucosae in

response to basic electrical rhythm
1. Propulsive- Peristalsis Movement
Propels contents forward
2. Segmentation
Mixes contents

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 Peristalsis and Segmentation

Peristalsis
Proximal segment
Circular muscle contracts;
longitudinal muscle relaxes
Diameter decreases
Distal segment
Circular muscle relaxes;
longitudinal muscle contracts
Diameter increases
Contents propelled forward
from area of small diameter to
area of large diameter Figure 20.30a Comparison of peristalsis and
segmentation.

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 Propulsive Movements - Peristalsis

Stimuli that initiate peristalsis -

- Distention - orad contraction with downstream
receptive relaxation = Law of the Gut
- Irritation of gut epithelium
- Parasympathetic nervous system

Function -
- Myenteric plexus required
- Atropine (blocks Ach receptors) - peristalsis
- Congenital absence of plexus - no peristalsis

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 Peristalsis and Segmentation

Segmentation
A type of motility of the small intestine
Requires circular muscle layer
Alternating contractions between intestinal segments
Mixes chyme

Figure 20.30b Comparison of peristalsis and segmentation.

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 Neural Regulation
Enteric Nervous System
located in wall of GI tract
begins in esophagus and ends at anus
controls peristaltic activity/GI motility
(myenteric plexus)
affected by parasympathetic and sympathetic nervous
systems
Acetylcholine increase GI motility
Norepinephrine and epinephrine inhibit GI activity
also influences GI secretions
(submucosal plexus)

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PACAP = pituitary adenylate
Distension
cyclase activating polypeptide

Local serotonin (5-HT) release is the initiator of the peristaltic waves, but other
neurotransmitters actually control the smooth muscles of the GI tract via
interneurons. Acetylcholine and substance P stimulate contraction while nitric
oxide (NO) and vasoactive intestinal peptide (VIP) cause relaxation.


But sensory signals from the viscera to the CNS can

provide inhibitory signals to peristalsis (and blood flow)
to decrease GI activity.
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 Serotonin (5-hydroxytryptamine; 5HT)

EC cell

Most
GI cells

Note the myriad of receptor subtypes which respond to 5HT.

5HT3 and 5HT4 are the most important for GI motility, while 5HT2B helps
regulate Interstitial Cells of Cajal, thus influencing contraction.
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 Chewing / Mastication

Control is both voluntary and involuntary

Chewing reflex: cyclical reflex
Normally, jaw muscles are active; hold mouth closed
Food enters mouth; inhibits jaw muscles
Jaw dropping relieves pressure of food; contracts
Pressure from food restored; inhibited

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 Mastication (chewing): Nervous control of chewing

The mouth and pharynx are predominantly under voluntary control, although
chewing and swallowing do have involuntary components.

Mastication (chewing) includes mixing of fluid, amylase and lingual lipase with
food to begin digestion. When a person is chewing food, the concentration of
ions in saliva changes with an increase in Na+, Cl-, and HCO3-
Innervation:

- 5th cranial nerve innervates muscles of mastication

- Controlled by nuclei in brain stem

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 Swallowing

Chewed food + saliva = bolus

Tongue moves bolus to pharynx
Initiates swallowing reflex
Integration center = swallowing center of medulla
oblongata
1. Buccal phase: voluntary phase
2. Pharyngeal phase: involuntary phase controlled by
the swallowing center in medulla and lower pons;
involves relaxation and closure of upper esophageal
sphincter (UES)
3. Esophageal phase: involuntary phase controlled by
swallowing center and enteric nervous system;
involves relaxation, followed by closure of lower
esophageal sphincter (LES)

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 Nervous Control of Swallowing
Swallowing Afferent Vagal Pathways
Center Efferent Vagal Pathways
Swallowing Center - medulla A Non-vagal Nuclei
- Sensory input from pharnyx A B C B Nucleus Abiguus
C Dorsal Motor Nucleus
and esophagus Myenteric Ganglia
- Coordinates activity from UES Upper Esophageal Sphincter
vagal nuclei with other centers
(e.g. inhibits respiratory Pharynx

center)
UES
Pharyngeal Phase -
Striated
- Food in pharynx afferent Muscle
sensory input via
vagus/glossopharyngeal N.
swallowing center brain Smooth
stem nuclei efferent input Muscle

to pharynx.
Longitudinal Layer
Myenteric Circular Layer
Plexus Vagus
Nerve

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 Swallowing Reflex

Bolus descends in pharynx, pressing on

epiglottis
Epiglottis covers glottis so food does not
enter trachea
Inspiration is inhibited
Upper esophageal sphincter relaxes
Bolus enters esophagus
Sphincter closes behind bolus
Bolus stretches esophagus, triggering
peristalsis
Peristalsis propels bolus to stomach
Travel time is approximately 9 seconds

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 Swallowing reflex

Bolus arrives at stomach

Triggers relaxation of lower esophageal sphincter
Bolus enters stomach
If necessary, secondary peristalsis waves occur to move
bolus into stomach
Receptive relaxation of stomach
Swallowing center also initiates relaxation of stomach
smooth muscle as it prepares for receipt of bolus

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 Figure 20.31 Events of the swallowing reflex. Slide 2

Epiglottis
moves
downward
and covers
glottis

Glottis moves Upper esophageal

upward sphincter opens
and closes

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 Figure 20.31 Events of the swallowing reflex. Slide 3

Upper esophageal
sphincter closes
Contracting muscles
Wave of peristalsis
travels along Relaxing muscles
Upper esophageal esophagus
sphincter opens

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 Figure 20.31 Events of the swallowing reflex. Slide 4

Upper esophageal Lower esophageal

sphincter closes sphincter opens
Contracting muscles
Wave of peristalsis
travels along Relaxing muscles
esophagus

Stomach

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 Figure 20.31 Events of the swallowing reflex. Slide 5

Secondary wave
of peristalsis in
esophagus

Lower esophageal
sphincter opens

Stomach

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 Gastric Motility

Functions
Mix chyme
Regulate gastric emptying
Mechanism
Peristalsis
Coordinated by enteric nervous system

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 Gastric Motility

Gastric motility patterns

Waves of peristalsis
Upper body pylorus
Strengthen as they approach the pylorus
Functions in mixing of chyme
Pyloric sphincter closed
Functions in gastric emptying
Stronger contractions open pyloric sphincter
Factors governing emptying rate
Volume of chyme in stomach
Strength of gastric peristalsis

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 Gastric Motility

Migrating motility complex

Wave of intense contractions
Travels short distances
Occurs between meals to clear stomach

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 Gastric Motility

Regulation of gastric motility

Increase force
Gastrin
Decrease force
CCK
Secretin
GIP

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 Gastric Motility

Phases of regulation
Cephalic-phase excitations
Anger, aggression
Cephalic-phase inhibitions
Pain, fear, depression
Gastric-phase excitatory stimulus
Distension of stomach
Intestinal-phase inhibitory stimuli
Distension of duodenum
Contents: osmolarity, acidity, fat

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 Gastric Motility

Vomiting
Stimuli
Illness
Emotions
Pain
Distension in GI tract
Rotation of head
Ingestion of certain substances (emetics)
Reflex mediated through vomiting center in medulla

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 Motility of the Small Intestine

Segmentation mixes chyme

Peristalsis propels chyme forward
Regulation of motility in small Intestine
Distension: increases motility
Autonomic nervous system
Parasympathetic excites
Sympathetic inhibits
Hormones: gastrin stimulates motility

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 Motility of the Small Intestine

Motility reflexes
Intestino-intestinal reflex
Injury or severe stress inhibits intestinal contractions
Ileogastric reflex
Distension of ileum inhibits gastric motility
Gastroileal reflex
Presence of chyme in stomach increases motility in ileum

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 Motility of the Colon

Haustrations
Proximal colon
Like segmentation, but slower
Mass movement
Propels bolus (material) toward rectum
Similar to peristalsis
Contraction lasts longer than relaxation

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 Motility of the Colon

Regulation of colon motility

Colonocolonic reflex
Distension of colon in one area causes relaxation of other
areas of colon
Gastrocolic reflex
Food in stomach increases colonic motility

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 Motility of the Colon

Defecation
Voluntary and involuntary control
Distension of colon activates stretch receptors
Smooth muscle of rectum contracts
Increases pressure in rectum
Peristaltic contractions of sigmoid colon propel more
fecal material into the rectum, increasing pressure
Internal anal sphincter relaxes simultaneously as
external anal sphincter contracts
Both sphincters relax
Defecation

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