HORMONAL AND NEURAL CONTROL OF DIGESTIVE

3 Cell Interactions

PARACRINE ENDOCRINE NEUROCRINE

Immediate/adjacent Hormones - bloodstream 1 cell sends signals down long path

neighbours to another cell
Target cells have specific
Direct
receptors
Far away

Enteric Nervous System

PLEXUS LOCATION FUNCTION

MYENTERIC Between 2 muscle layers Primary control over gut motility

 Circular muscle
layer
 Longitudinal muscle
layer

SUBMUCOUS Submucosa Sensing environment within

AL lumen
Regulating GI blood flow
Controlling epithelial cell
function
SENSORY INTERNEURON MOTOR

Receive info from mucosa and Ascending and descending Control GI motility and
muscle between sensory and motor secretion
Relay along myenteric plexus along
length of GIT

Neurotransmitters

ANS and the Gut

SYMPATHETIC PARASYMPATHETIC

GANGLIA LOCATION More distant site from target Close or within target organs or tissues
 organs

DIGESTIVE Inhibit Stimulate

ACTIVITY
 Vasoconstriction
 Reduced secretion
 Muscle relaxation

MOTOR Adrenergic In gut wall

POSTGANGLIONIC
Cell bodies in prevertebral
ganglia - not in gut

SENSORY Splanchnic nerves Vagal nerve: oesophagus -->

AFFERENT transverse colon
Endings in gut walls
Pelvic nerve (not part of sensory):
Cell bodies in dorsal root ganglia
descending colon --> anus
- outside gut
Cell bodies in nodose ganglia - outside
gut

Peristalsis: contraction of circular muscle proximal to bolus, relaxation of distal muscle

 Irritation --> rapid and powerful peristalsis - e.g. infectious diarrhoea

Defaecation
 ANS and intrinsic control of myenteric plexus
 Augmented by PNS activity - e.g. major trauma, SCI
  Defaecation requirements
o Relaxation of external anal sphincter

o Descent of pelvic floor

o Puborectalis (sling) relaxing

o Anorectal angle: at rest 90 degrees, 140 degrees for easy defaecation (straighter e.g. from squat)

 Faeces entering --> increased pressure on rectum/distension --> rectum stretch --> relax internal anal sphincter
 Rectum stretch stimulates myenteric plexus --> peristaltic contractions in descending colon downwards --> myenteric
plexus relaxes internal sphincter --> if external sphincter voluntarily relaxes, defaecation

Enteroendocrine Cells: hormone secreting cells in mucosa of stomach, small intestine and colon
 May produce:
o a single hormone - e.g. G cell, S cell

o 5-hydroxytryptophan (serotonin) and other hormones - e.g. enterochromaffin cell

o Amine or polypeptide - e.g. neuroendocrine cell

OPEN TYPE CLOSED TYPE

Apical membrane in contact with GI lumen No contact with luminal surface

(receptor)
e.g. enterochromaffin cell which secretes
Secretion occurs in basolateral membrane
histamine

Endocrine Regulation
 HORMONE PRODUCED BY ACTIONS CONTROL
GASTRIN FAMILY
GASTRIN G cell in mucosal  Stimulation of gastric acid and FEEDBACK LOOPS: Prevent
gland of gastric pepsin secretion overproduction of acid  peptic ulcers
antrum  Stimulation of gastric motility  As gastrin plasma levels fall, so
 Release of histamine from does acid levels
Can also be found enterochromaffin cell Acid in antrum inhibits gastrin by:
in foetal  Stimulate insulin secretion after  Direct action on G cell
pancreatic islet, protein meal (not carbs)  Stimulates release of
hypothalamus, somatostatin by D cell (ultimate
medulla inhibitor) – paracrine – inhibits G
oblongata, vagus cell gastrin secretion
nerve
When acid enters duodenum
 Secretin  inhibits gastrin
stimulated acid secretion
CCK I cell in crypts of Stimuli for secretion: food (lipids mostly, Through CCK receptors: 2 types
intestine – most in AA too) CCK-A Periphery, brain
duodenum and  Enzyme rich secretions by pancreas CCK-B Brain (gastrin receptor
proximal jejunum  Contraction of gallbladder and virtually identical to CCK-B
relaxation of sphincter of Oddi receptor)
(bottom of bile duct) – stimulating
liver ductal for bile 1. CCK binds to receptor
 Inhibition of gastric emptying 2. Activates phospholipase C
 Increases motility of small intestine 3. Production of IP3, DAG
and colon 4. Increases intracellular Ca2+
 Augments contraction of pyloric 5. Activates protein kinase
sphincter 6. Releases granules of pancreatic
 Increases glucagon secretion enzyme
 Induces satiety – hypothalamus
Also stimulates vagus nerve to pancreas
 release pancreatic enzymes

Positive feedback loop:

 1. CCK
2. Enzyme release
3. More digestive products
4. More CCK
5. Stops when digestive products
move to next part of small
intestine (after duodenum)
SECRETIN FAMILY
SECRETIN S cells in crypts of Stimuli for secretion: low pH (below 4) in Cannot be released if duodenal pH rises
intestine – most in duodenum above 4.5pH
duodenum Acts with CCK and Ach to stimulate bicarb Inhibited by somatostatin
secretion = buffer for acid
Acts via cAMP
 Fluid and bicarb-rich secretion by
pancreas’ duct cells
 Bicarb-rich secretion in bile/biliary
tract
Above 2 dotpoints = watery, alkaline
pancreatic juice
 Inhibition of gastric emptying
 Reduces gastric acid secretion
 Pyloric sphincter contraction
 Stimulates growth of exocrine
pancreas
GLUCAGON Alpha cell of  Increase glycogenolysis
pancreatic islet  Increase gluconeogenesis
VIP (vasoactive ENS (myenteric, Stimulated by oesophageal and gastric
intestinal submucosal distension, vagal stimulation, fatty acid
peptide) plexus), brain, and ethanol in duodenum – not affected
autonomic nerves by AA and glucose
 Increase electrolyte and water
secretion from small intestine
 Intestinal circular smooth muscle
relaxation
 Longitudinal smooth muscle
 contraction
 Increase pancreatic secretion
 Inhibit gastric acid secretion and
motility
GIP (gastrin K cell in duodenal Stimulated by glucose and fat in
inhibitory and jejunal duodenum, acid in stomach
peptide) mucosa  Insulin release
 Mild effect in decreasing gastric
motility
 Directly inhibiting parietal cells -
inhibit gastric acid secretion
 Indirectly inhibiting release of
gastrin via somatostatin – inhibit
gastric acid secretion
OTHERS
MOTILIN Enterochromaffin  GI tract smooth muscle contraction 1. Acts on G-protein coupled
cell, M cell in  Major regulator of MMC (migrating receptor on enteric neurons in
duodenum and motor complex) – stomach and stomach and duodenum
jejunum small intestine every 90 mins 2. GI smooth muscle contraction
through fasted person
Circulating level increased at 90-100
mins in interdigestive state
SOMATOSTATIN Found in In response to acid in stomach Secreted in larger amount into gastric
hypothalamus  Powerful inhibitor: inhibit secretion lumen > circulation
of gastrin, VIP, GIP, secretin,
D cell in stomach, motilin, insulin, glucagon
duodenum,  Increase fluid absorption and
pancreatic iselt decrease secretion from intestine
 Decrease endocrine and exocrine
pancreatic secretion
 Decrease bile flow and gallbladder
secretion
 Decrease gastric acid secretion and
motility
 Decrease absorption of glucose and
 AA

Stomach

STOMACH DESCRIPTION

STRUCTURE 0.8-1.5L
Body: upper 2/3
Antrum: lower 1/3

Food processed in stomach ultimately forced through pylorus into

duodenum

FUNCTIONS  Accommodation: storage of food

 Mixing with gastric secretions to from chyme (semifluid
mixture): in antrum
 Emptying of chyme at suitable rate for digestion: into small
intestine slowly = controlled transit to absorb nutrients

MIXING/  Peristaltic constrictor waves to move food towards antrum

PROPULSION = blender
 Antrum: mixes food and exposed more food to digestive
juices secreted by stomach walls
 Migrating myoelectric complex (MMC): set of very intense
antral activity - moves chyme to duodenum to clear
 particles from the stomach
 10-20 minutes of intense antral contractions every 1-
2 hours during fasting
 Pylorus
 Chyme passed into duodenum
 Most of it pushed back upstream by strong
contractions to increase mixing
o Partially closed - churning in antrum, chyme
hitting against back then becomes less than
3mm = easily passed into pylorus

EMPTYING  Mix food with gastric juices

 Trituration: mixed and broken down food less to 3mm to go
through pylorus
 Pylorus tonically contracts to allow fluid to pass easily, but
not unprocessed food
 Regulated by duodenum
 Prevents excess food into intestine = allows
reabsorption of nutrients
 Inhibition of stomach emptying mediated by nervous
reflexes and hormones, will occur if:
o Distension of duodenum

o High acidity of chyme

 o Hypertonic and hypotonic chyme

o Breakdown of proteins, but sometimes fat

o Irritation of duodenum

Small Intestine

SMALL INTESTINE DESCRIPTION

PROCESS Stretching of intestine causes peristalsis = forward

movement and missing
Slow movement = 1cm/min = greater absorption of
nutrients = 3-5 hours

HORMONES INCREASE  Gastrin

PERSITALSIS
 CCK
 Insulin
 Motilin
 Serotonin

HORMONES INHIBIT  Secretin

PERSITALSIS
 Glucagon

PERISTALSIS Weak - slow movement of food for nutrient absorption

Clinical Conditions
Vagotomy --> historically treated incurable peptic ulcers (increased GI bleeding) but had to be careful where to cut vagal
nerve

DISEASE DEFINITION CAUSES EFFECTS TREATMENT

HIRSCHSPRUNG' Infant born with Failure of ENS in 1 part of colon Obstruction Resect affected segments
S severe constipation (usually distal) proximally -
Adjacent segments may have
large, dilated
some abnormalities with ENS -
loss bowel
GI motility still affected

IRRITABLE Have pain, Alterations in signalling pathway Pain Drugs targeting serotonergic
BOWEL constipation and/or in serotonin (90% found in gut) pathways
Constipation
SYNDROME diarrhoea but organic
 IBS diarrhoea: 5HT3
(IBS) pathology Diarrhoea
receptor antagonist
Alosetron - not approved
in AUS due to side
effects
 Partial 5HT4 receptor
agonist Tegaserod -
banned due to
significant cardiotoxic
effects

ACHALASIA/ Stricture/no relaxation Failure of inhibition = unopposed Dilated/

BIRD'S BEAK of lower oesophageal excitation = nitric issues widened
OESOPHAGUS sphincter oesophagus

GASTROPARESIS Marked delay in Nausea, Hard to treat as sometimes

 gastric emptying vomiting, early does not respond well
satiety (full
Usually in young
after few bites)
women, misdiagnosed
as an eating disorder

PARADOXICAL External anal History of chronic constipation Biofeedback: retraining

PUBORECTALIS sphincter not relaxing, since childhood - e.g. stress sphincters to work properly
SYNDROME/ straining to do during potty time again
so/clenching tight
OBSTRUCTIVE
DEFAECATION
Forcing bowel
movement down
closed external

ZOLLINGER- Rare disease due to 1. Excess gastrin production Severe peptic

ELLISON (ZE) tumour (benign or 2. Excess acid secretion ulcer disease
SYNDROME malignant) composed 3. No inhibition in unusual
of gastrin secreting 4. Ulcers sites e.g. 3rd or
cells  sustained very 4th part of
high plasma levels of duodenum
gastrin  marked and even without
sustained over- precipitating
secretion of gastric factors (H.
acid pylori, NSAIDs)

Often occurs in
pancreas – weird since
virtually no gastrin
 usually here

History of GI bleeding

GASTRITIS Inflammation due to  H. pylori: contaminated Abdominal

mucous lining and food/water or close pain
acid not balanced contact, bicarb and
Stomach
ammonia to neutralise
cancer
acid, CAG gene – produce
Ongoing acid toxin injecting cells =
exposure with inflammation, affect stem
exposed stomach cells  cancer
lining  ulcer  Medications: non-steroidal
anti-inflammatory drugs
(NSAIDs) – e.g. aspirin –
Acute gastritis can reduces secretion  acid
become chronic damage, gastritis
 Intestinal metaplasia:
acid-secreting stomach
cells  intestinal cells 
chronic gastritis 
increased risk of stomach
cancer

Malignant Intestinal pain Octreotide (somatostatin

complete analogue) to alleviate
Discomfort
obstruction abdominal pain and discomfort