Gastrointestinal System Lectures

PHPY 303.3
Instructor: Dr. Francisco Cayabyab
Department of Surgery

Office: Rm. GD30.5 D-Wing,

Health Science Building

Tel: 966-8191

Email: frank.cayabyab@usask.ca

Website: http://medicine.usask.ca/profiles/surgery/neurosurgery/f.-
cayabyab.php

Google scholar:
https://scholar.google.ca/citations?user=Ecr01LUAAAAJ
PHPY 303 GI Lecture #1 Second MIDTERM-March 28th!!!

Functional Anatomy,
Communication Pathways,
and Neurohumoral Regulation
of the GI Tract
Old Boron Chapters New Chapters
4 3 (Signal Transduction)
40 41 (Organization of GI System)
41 42 (Gastric Function)
42 43 (Pancreatic and Salivary Glands)
43 44 (Small and Large Intestine Fluid Secretion/Absorption)
44 45 (Digestion and Absorption of Carbs and Proteins)
45 46 (Liver, Bile and Fat Digestion)
Use textbook only for clarification.
Will not be tested on material not covered in class!
 Objectives
Describe structure/design features of GI
tract and communication pathways
regulating GI functions (Overview)
Identify important neurocrine, endocrine,
immune and paracrine factors for normal
GI function
 Structures of DigestiveStomach,
Tractsm. intestine
liver>
<stomach
gall bladder>

<duodenum
Oral Cavity
<jejenum

<ileum
Colon
Caecum> <appendix

Abdomen <rectum
Thoracic <transverse
<ascending
<esophagus descending>

rectum>
 Structures and
functions of the
digestive system

GI organs

Accessory organs
 Overview: Impact of GI Health on All Other Organ Systems

Gut microflora
and probiotics
can impact
stress and
behaviour
Water keeps
blood volume
Electrolytes,
nutrients for
optimal
muscle and
nerve activity
Overall Function of the Digestive System
To provide continuous supply of water, electrolytes,
and nutrients requires:
Digestion-breakdown of food
Absorption of breakdown products by specialized
absorptive epithelial cells
Secretion of digestive enzymes and fluids by secretory
(exocrine) cells
Motility transit of food- involving primarily smooth
muscle
Excretion of undigested foodstuff
Immune barrier function keep bacteria outside body
-Circulation of blood to carry away nutrients and hormones
-Nervous, hormonal, and paracrine regulation of
gastrointestinal functions
 Host Defense: Mucosal Immune
System and Commensal Bacteria
Commensal bacteria
Contribute to digestion of food (e.g., dietary
fiber by fermentation)
Provide essential nutrients (e.g.,
secondary and deconjugated bile acids)
Prevent pathogenic microorganisms from
colonizing intestine (e.g., c. difficile, v.
cholerae (lumen), salmonella and listeria
(invasive))

Human Intestinal microbiota

1013 1014 microorganisms
72 bacterial phylotypes

1ml in large intestine

- 1000 species
- 1 trillion organisms
Powerful Poo!- Capsules
Containing Frozen Faeces
Could Cure Clostridium
difficile Infection

Fecal transplant pills

Nasogastric tube
Cultured intestinal bacteria from
Enema
healthy individuals
 Commensal bacteria Probiotics
beneficial friendly bacteria reside in
lumen of gut
Host intestine
Must remain hypo-responsive to
commensal bacteria
Must be able to defend against
invasive pathogenic bacteria
Balance between inflammatory
response against invasive
pathogens and suppressive
mechanisms against commensal
bacteria
Probiotics increase growth of
commensal bacteria (friend),
reduces pathogenic bacteria (foe)
(Will be on exam!!)
 Elements of Cell-Cell
Communication in the GI Tract
Chemoreceptors - stimulated by elevated levels
of H+, protein, fat and carbohydrate
Osmoreceptors - stimulated by elevated
osmolality
Mechanoreceptors stimulated by distension

The GI tract is further regulated by:

Neural reflexes (ANS)
Extensive enteric nervous system found in the wall of
the digestive tract
Hormones, paracrine factors
Overview of Neural Control of GI System
Higher centers can
regulate ENS
Vagovagal reflex -Afferent
signals integrate in CNS
autonomic centers and
relay back to GI organs
via PSNS efferents
X Vagovagal reflex is an
example of how gut
medulla function can be controlled
by longer neural reflexes
X=ENS can function
independently of extrinsic
inputs
Extrinsic Branches of the Autonomic Nervous System
Parasympathetic Sympathetic

(Excitatory) (Inhibitory)

A: Preganglionic parasympathetic innervation by the vagus (cranial nerve 10)

and pelvic nerves of the sacral spinal cord. Dashed line - input for striated
muscle
B: Postganglionic sympathetic innervation from the coeliac ganglion (CG),
superior mesenteric ganglion (SMG) and inferior mesenteric ganglion (IMG)
Autonomic Nervous System and
Enteric Nervous System
Inputs from the
autonomic nervous
system can regulate the
enteric nervous system
Parasympathetic inputs
originate from the vagus
nerve and the pelvic
nerve
Sympathetic inputs are
from three main ganglia:
Coeliac
Superior mesenteric
Inferior mesenteric
 Plexuses of the ENS and Relationship to
Functional Layers of the Small Intestine
Organization
Ganglia of the wall of
No Ganglia the intestine
Ganglia into
functional
layers is
similar in:
Duodenum
Jejunum
Ileum
Networks of Interstitial cells of Cajal (ICC) = pacemaker cells

Nerve to muscle communication; and nerve to epithelial cell communication

 ICC Functions in the Gut
MyP
Generation of slow
wave activity
Coordination of active
DMP
propagation of slow
waves
Transduction of motor
neural inputs from
Interstitial Cells of Cajal (ICC) ENS to muscle
are Coupled to Smooth Muscle
Mechanosensation of
ICC
stretch of GI muscles
(gap junction
contacts for Destruction of ICCs in
electrotonic
coupling of
muscle cells
diabetes leads to
syncytium) impaired gastric
motility = gastroparesis
 ICCs require functional c-kit receptors

Nexus=
Gap
ICC Junctions

Slow waves
normal mouse c-kit = a receptor-type tyrosine kinase
binds to ligand stem cell factor

Mouse lacking ICCs

c-kit mutations lead to abnormal development

of nerve ganglia and ICC in myenteric plexus.
Regulation of Gastrointestinal Tract by
Peptides/Non-peptide Mediators

GI tract modulated by hormones (endocrines),

paracrines, neurocrines or immune/juxtacrine
factors
Mediators are peptides, derivatives of amino
acids, or non-peptides from various sources
All GI hormones are peptides, but not all
peptides in the GI tract are hormones
Cell-cell Communication in the Gut:
Four Regulatory Pathways
Endocrine mediators
released in response to neural
activity and chemical and
mechanical signals triggered
by foodstuff, act at distant site
Paracrine/immune/neurocrine
substances act in immediate
area of release
Like neurotransmitters,
paracrine mediators readily
metabolized or reabsorbed to
limit duration of activity
Blood Supply to the Digestive Organs

Splanchnic circulation is
critical for delivery of GI
hormones (gastrin, CCK,
secretin, GIP, motilin)
Blood flows from intestine
to liver first via portal vein
Criteria that define a gastrointestinal hormone

A physiologic event in one segment alters activity of

another (distant site)
Effect persists after neural connections have been
severed
A substance isolated from site of stimulation must
mimic effect of physiologic stimulus when given
intravenously
Hormone identified chemically and structure
confirmed by synthesis
 (Know for exam!!)
Sources of Five GI Hormones

Distribution of GI peptides with full status as hormones

Shaded regions indicate major release sites under
normal conditions
*Trophic factor = promotes growth of mucosa and
pancreas (seen in gastrinoma)
Pure GI Hormones and Actions
Hormone (cellular source)
Gastrin (G cells, antrum
of stomach)
CCK (I cells in
* * duodenum and jejunum,
neurons in ileum and
colon)
Secretin (S cells in small
intestine)
GIP (K cells in
duodenum and jejunum)
* Motilin (Endocrine cells
in upper GI tract, not yet
named)
*Enterogastrones inhibit gastric function
Related table 40-1,
pg.885, Ch. 40
Medical Physiology
 Endocrine Cells in Gut
C lumen

ECL

A- Open endocrine cells contact

lumen, e.g., gastrin G-cells
B- Closed endocrine cells do not
C- Open endocrine cells in human
jejunum amid enterocytes
Note secretory granules at basolateral pole,
Close to capillaries
 Paracrines

Released from enteroendocrine cells (e.g.,

enterochromaffin-like cells (ECL) secrete
histamine)
Diffuse through the extracellular space to their
target tissues
Interact with receptors close to site of release,
and biological effects limited by short distances
for diffusion (like neurocrines)
But often big effects due to scattered and
abundant distributions of paracrine cells
Two Important Paracrine Agents
Histamine, a derivative of amino acid histidine and not a
peptide, is an important regulator acting as a paracrine
Produced by enterochromaffin-like cells (ECL)
Released by gastrin
Stimulates acid secretion by stomach
Potentiates actions of Ach and gastrin on acid secretion
Antacid medications, cimetidine (Tagamet) and ranitidine
(Zantac), block H2 histamine receptors

Somatostatin, a GI peptide, functions physiologically as

a paracrine (from somatostatin D cells)
Inhibits gastrin release when antral mucosa is acidified and
directly inhibits gastric acid secretion from parietal cells
Distributed in gastric and duodenal mucosa and the pancreas
Inhibits release of all gut hormones
 Other Paracrine and Immune
Mediators in the Gut

Histamine also functions as a

juxtacrine/immune mediator
 Juxtacrine (Immune)
Communication
Mast cells in the lamina propria release
histamine which affect intestinal smooth
muscle cells and epithelial cells

Histamine (red granules)

in a mast cell within gut wall.
 Neurocrines
Released near target tissue (like paracrines)
Peptides (e.g., VIP from enteric nerves relaxes GI
smooth muscle), non-peptides (Ach), or gases (NO)
Need to diffuse across a narrow gap (a synapse)
May stimulate or inhibit release of endocrines or
paracrines
GRP (vagal-stimulated release) mediates vagal
release of gastrin
Acetylcholine, though not a peptide, stimulates
acid secretion from gastric parietal cells
 Neurocrines
GI peptides in nerves function physiologically as neurocrines
PEPTIDE LOCATION ACTION

VIP Mucosa and Secretion/

muscle of gut Relaxation of gut
smooth muscle
GRP (mammal) or Gastric mucosa Gastrin release
bombesin (frog)
Enkephalins (Leu-, Mucosa and Smooth
Meth-enkephalins) muscle muscle tone
GRP, gastrin-releasing peptide; VIP, vasoactive intestinal peptide
Substance P and neurotensin, found in brain and GI tract mucosa, stimulate
intestinal motility (excitatory) and gallbladder contraction