Enteric nervous system, GI hormones, GI motility

1. GI Physiology – I
Dr Bhawana Neupane Pant
Lecturer, Department of Physiology

2. Gastrointestinal
System: Processes
• Motility
• Digestion
• Secretion
• Absorption

4. Structure of the GI Tract
Innervation of the GI Tract
GI Peptides
Structure of the GI Tract
a) Layers of the GI tract
b) GI muscles
Innervation of the GI Tract
a) Intrinsic/Enteric nervous system
b) Extrinsic/Autonomic and central NS
Hormonal Control of GI functions
Costanzo
327-335

5. 1) Serosa
- Continuous with the mesenteries
2) Muscularis
- Longitudinal muscle
- Circular muscle
3) Submucosa
4) Mucosa
- Muscularis mucosae
- Lamina propria
- Epithelial cells
Layers of the GI tract
Structure of GI Tract

6. General Anatomy of Gut Wall
(Contains connective tissue, immune cells, capillaries, nerve endings)
(Might have role in villus movement)

7. 1) Serosa
2) Muscularis:
- Longitudinal muscle
- Circular Muscle
3) Submucosa:
4) Mucosa
Submucosal plexus (=
Meissner’s plexus
Myenteric plexus
(= Auerbach’s
plexus)
2. Innervation of the GI Tract

8. a) The Enteric/ Intrinsic
Nervous System
Primarily controls
motility (length,
intensity,
frequency,
velocity of
peristaltic waves)
Decreases tension
of sphincters
Controls secretion,
absorption,
submucosal
motility and blood
flow

9. The Enteric Nervous System
Local Reflexes = “Short Reflexes.”
Can be influenced by CNS = “Long Reflexes.”

10. Parasympathetic and Sympathetic
Innervation

11. Af f erent Ef f erent
sensory neurons f rom ent eric NS
( local af f erent s)
af f erent sympat het ic nerve f ibers
af f erent parasympat het ic nerve f ibers
2
1
entericnervoussystem
CNS
mechanorecept ors
chemorecept ors
t hermorecept ors
nocicept ors
1
2
Integration of neuronal control of GI function

12. Effector syst em
of GI innervat ion:
Interaction of ANS and ENS

13. • The enteric nervous system coordinates digestion, secretion, and motility to
optimize nutrient absorption.
• Its activity is modified by information from the CNS and from local chemical and
mechanical sensors.
Enteric Nervous System

14. What Is "Diabetic Stomach"?
“My niece takes an oral medicine for diabetes.
At least once a week, she throws up at night.
The doctor calls it "diabetic stomach." I have
never heard of this, and I have had diabetes
for 36 years. What could be the cause of her
stomach problems, and what foods may be
causing flare-ups?”
Hint:
Type II diabetic patients have autonomic
neuropathy and motor neuropathy.

15. Diabetic Stomach
• Gastroparesis is a disorder affecting people with
both type 1 and 2 diabetes in which gastric
emptying is delayed.
• Symptoms: Nausea Vomiting of undigested food
Early feeling of fullness when eating Weight loss
Abdominal bloating
• Avoid high-fat and high-fiber foods.

16. Cholinergic (Acetylcholine) - excitatory
Adrenergic (Norepinephrine) - inhibitory
Non-adrenergic, non-cholinergic neurotransmitter (NANC)
• Vasoactive Intestinal Peptide (VIP)
• Gastrin Releasing Peptide (GRP) or Bombesin
• Enkephalins (opiates)
• Neuropeptide Y
• Substance P
Neurotransmitters and Neuromodulators
in the Enteric Nervous System:
Note: There are list of putative transmitters is long; often, their physiologic significance
is uncertain; but their potential pharmacological value is high.

17. Is a disorder caused by the
absence of enteric neurons.
In the majority of affected people,
the disorder affects the short
segment of the distal colon.
In rarer cases it affects the whole
colon or even the whole GI
system.
Hirschsprung disease or congenital
megacolon

18. In children with Hirschsprung’s disease, nerves fail to form in all
or part of the large intestine (colon). Waste from digestion cannot
pass through the part of the colon lacking nerve tissue. The normal
colon swells with blocked stool.
Clinical Presentation: Failure to pass meconium,
abdominal distension, vomiting, enterocolitis
Treatment: Surgical removal of part (Pull through procedure)

19. Gastrointestinal Peptides:

20. Gastrointestinal Hormones:

21. Gastrin:
• Secreted by G cells in the antrum of stomach
• Principal physiologic actions:
– Gastric acid secretion
– Pepsin secretion
– Trophic action (growth of the mucosa of the stomach, small and large
intestine)

22. What happens in Zollinger-Ellison
Syndrome?
What happens when gastric antrum is
resected?
H+ secretion is increased
Hypertrophy of gastric mucosa
Duodenal ulcer
Steatorrhea
H+ secretion is decreased
Gastric mucosa atrophies

23. Gastrin
Stimulation
Inhibition by:
- Somatostatin (H+ stimulates, N. vagus inhibits D-cells)
- Low pH (partly at pH 3.5, completely at pH 2)
- Secretin
Stimulation by:
- N. Vagus
- Distention of the stomach
- Protein digestion products
- Calcium, alcohol, coffee
- CNS (anticipation of meal,
olfactory stimuli) AA: phenylalanine
and tryptophan
Secretin

24. Cholecystokinin
- secreted by I cells in the mucosa of the duodenum, the jejunum
• Primary functions:
- Stimulation of pancreatic enzyme secretion
- The contraction of the gall bladder and relaxation of sphincter of
Oddi
- Growth of the exocrine pancreas and gallbladder
• Secondary functions:
- Augments the action of secretin in producing secretion of an
alkaline pancreatic juice
- Increases the synthesis of enterokinase
- May enhance the motility of the small intestine and colon

25. CCK Functions

26. CCK
Stimulation
Stimulation by:
- Digestion products of fat and protein (most potent long fatty acid chains)
- Meals stimulate CCK secretions of gut and CNS simultaneously

27. Secretin
Secreted by S cells in upper small-intestinal
mucosa.
Stimulates water and alkali secretions from
pancreas and biliary tract
Inhibits gastrin release, suppresses gastric
acids
It also augments the action of CCK in
producing pancreatic secretion of digestive
enzyme
The secretion of secretin is increased by the
products of protein digestion and by acid
bathing the mucosa of the upper small
intestine.

28. Secretin Stimulation
- contact with acidic chyme
-also stimulated by fatty acids

29. IV: GIP
old name: Gastric Inhibitory Peptide
new name: Glucose-dependent Insulinotropic Peptide
- Secreted by K-cells in duodenum and jejunum

30. GIP Functions
Major function:
-Release of insulin
Action as enterogastrone controversial:
- Inhibits gastrin release and acid secretion
- Inhibits gastric and intestinal motility
??

31. GIP Stimulation
Stimulated by
- Glucose in upper small intestine
- Long-chain fatty acids
- Certain AA
(different than those for gastrin and CCK)
Inhibited by
- High levels of insulin or glucagon
(unclear if physiologic?)

32. C. Candidate Hormones
• produced by pancreatic islet cells and
endocrine cells
• released most potently by protein
digestion products
• also released by vagal stimulation and
Ach
I: Motilin
II: Pancreatic Polypeptide
III: Enteroglucagon

33. II: Enteroglucagon
• secreted by intestinal mucosal cells of colon and terminal ilium
• stimulated by intraluminal glucose and fat
• same effects as glucagon but less potent (glycogenolysis and gluconeogenesis,
lipolysis)
• might inhibit gastrin release and gastric acid secretion (not established)
III: Pancreatic Polypeptide
• Secreted by the pancreas
• Stimulated by ingestion of carbohydrates, proteins, or lipids
• Inhibits pancreatic secretion of HCO3
- and enzymes
• Physiologic role uncertain
I: Motilin
• primarily in duodenum by M cells
• physiologic stimuli not known
• initiates the MMC migrating motor complex (see motility lecture)
Candidate Hormones

34. D. Paracrines
• Secreted into the interstitial fluid
and
diffuse to adjacent cells
• The site of secretion must be
only a short distance from the
site of action.
1. Somatostatin
2. Histamine

35. Somatostatin
• Secreted by D-cells in gastric mucosa
• Delta cells in the pyloric antrum, the duodenum and the pancreatic
islets
• Both paracrine and endocrine
• Suppresses gastric secretions
• Inhibits motility and tone of stomach and small intestines and gall
bladder
• Inhibits formation of liver bile
• Inhibits the release of ALL known GI hormones
• Inhibits saliva, gastric, pancreatic, small intestinal and liver
secretions
• Inhibits splanchnic blood flow
• Inhibits intestinal absorption
• In brain it inhibits GH release
• In pancreas, inhibitor of insulin and glucagon
Octreotide : analogue of somatostatin

36. Action Gastrin CCK Secretin GIP
Acid secretion
Pancreatic HCO3
- secretion
Pancreatic enzyme secretion
Bile HCO3
-
Gallbladder contraction
Gastric emptying
Gastric Mucosal growth
Pancreatic growth
Insulin Secretion
S = stimulates; I = inhibits
Actions of GI hormones
I
S
S
S
S
S
S
S S
I
S
S
I

37. GI Motility

38. Skeletal muscle:
• Upper esophagus
• External anal sphincter
Smooth muscle: (of the
visceral or unitary type):
• Rest of GI tract
GI Muscles

39. In comparison to skeletal muscle:
Energy: Low (up to 300x less)
Force: High
Shortening: High
Time: Long (tonic)
Speed: Slow

41. Basic Electrical Activity
SLOW WAVES:
- Due to rhythmic changes in membrane potential initiated by Interstitial cells of Cajal
(pacemaker cells)
- Not responsible for contractions but determine the frequency of contractions
SPIKE POTENTIALS:
- Develop on top of slow waves when they reach threshold potential (~ -40mV)
- The higher amplitude  the more spike potentials  the stronger gut motility
Membrane
potential

42. • Frequency of electric activity determines the frequency of
contractions
• Basic Electrical Rhythm in different parts
• Stomach ~ 3/min
• Duodenum ~ 11-12/min
• Distal Ileum ~ 6-7/min

43. Objectives of Today’s
Class:
• Structure of GI Wall
• Enteric Nervous System
and Its Interaction with
ANS and CNS
• Understanding GI
Hormones
• Electric Basis of Motility in
GI – Slow Waves

44. Motility
Mouth and Esophagus: Chewing, Swallowing,
Peristalsis
Stomach: Filling, Churning, Peristalsis, Emptying
Small Intestine: Segmental Contractions, Peristalsis
Large Intestine: Haustral Shuttling, Mass
Movements, Defecation.
Sphincters: Regulation of Movement

46. Tonic Contractions
“Latch Mechanism” and
slow myosin ATPase allow
SM to maintain contraction
with little energy and
excitatory signal from
nerves or hormones

47. Phasic Contractions
Peristalsis Segmentation