1. Gastrointestinal Hormones
Overview of the GI Tract
Digestion and Absorption
Regulation of Digestive Functions
GI Hormones and Paracrine Factors
Integration of Neural and Endocrine Signals
Signaling Mechanisms

2. Functions of the GI Tract
Ingestion: Taking in food
Digestion: Chemical and Mechanical
Absorption: moving nutrients from the lumen of
the GI tract into the cells of the body
Excretion: getting rid of undigested and
unabsorbed material
Movement: movement of ingested food
throughout the GI tract

3. Organs of the Digestive System
Accessory Digestive Organs:
Salivary glands
Liver, gall bladder
Pancreas
Digestive Tract:
Oral Cavity
Pharynx
Esophagus
Stomach
Small Intestine
Large Intestine

4. The Oral Cavity
Boundaries are:
- lips (anteriorly)
- cheeks (laterally)
- palate (superiorly)
 The oral cavity is important in:
- mastication (chewing): mechanical
digestion
- secretion of saliva for digestion
(amylase; digests starch), coating food
(mucus)
- no significant absorption of nutrients
occurs in the oral cavity

5. The Pharynx
The pharynx is the passageway from the nose
and mouth to the esophagus and respiratory
tract
Boundaries: uvula to epiglottis
During swallowing, food is directed from pharynx
to esophagus (away from respiratory tract).

6. Esophagus
The esophagus is a passageway from the
pharynx to stomach
Contains two sphincters: upper and lower
esophageal sphincters (controls flow)
Upper sphincter is skeletal (voluntary), lower
sphincter is smooth muscle (involuntary)
Peristaltic waves move food from pharynx to
stomach.

7. The Stomach
The stomach stores food, and mixes and
mechanically and chemically digests it
The stomach also secretes digestive juices
pepsin: digests protein
hydrochloric acid (acidic pH, required for
pepsin activity, and to kill ingested
bacteria)
Mucus: protects the stomach wall
Partially digested food: chyme
Little absorption occurs in the stomach
(exceptions: alcohol, aspirin…)

8. Histology of the Stomach
Cell types:
Chief cells: produce pepsinogen (inactive
precursor to pepsin)
Parietal cells: produce HCl and intrinsic factor
(absorption of vitamin B12; important in RBC
maturation)
“Endocrine” cells:
G cells: gastrin
D cells: somatostatin (paracrine)
Enterochromaffin-like cells: histamine (paracrine)

9. Small Intestine
Connects the stomach with the large intestine
It is the major site of digestion
It is also the major site of absorption
Specialized structures (villi, microvilli) increase
the surface area of the small intestine, aiding
absorption.
The small intestine has three parts (duodenum,
jejunum, and ileum)
The bile duct (from liver) and pancreatic duct
(digestive juices) empty into the duodenum.

10. Histology of the Small Intestine
Absorptive cells
Goblet cells (mucus)
Enteroendocrine cells:
secretin
cholecystokinin

11. Digestion & Absorption: Carbohydrates
Carbohydrates: small amount of digestion begins in
oral cavity (amylase). Most digestion in small
intestine:
Enzyme Digests
pancreatic amylase polysaccharides to
disaccharides
disaccharidases disaccharides into
(small intestine) monosaccharides
What’s absorbed: monosaccharides

12. Proteins: Digestion begins in stomach (pepsin),
continues in small intestine:
Enzyme Digests
trypsin, chymotrypsin, polypeptides into
carboxypeptidase small peptides
(from pancreas)
aminopeptidase
dipeptidases small peptides
into smaller
peptides
What’s absorbed: mono-, di-, and tri-peptides
Digestion & Absorption: Proteins

13. Lipids: Digestion begins in the small intestine (minor
amount in oral cavity)
Note: Lipids are not soluble in water. Thus, it is hard
for enzymes to act on them.
The first step in lipid digestion is emulsification of
lipids with bile (secreted from the liver).
Emulsification: transformation of large lipid
droplets into small lipid droplets.
This increases the surface area of lipid that can
be acted on by the digestive enzyme, pancreatic
lipase.
Digestion & Absorption : Lipids

14. Emulsification of Lipids by Bile
 Bile acts on lipids in a way similar to
detergent acting on greasy water:
bile
large lipid droplet
lipase

15. Absorption of Lipids
 Bile also helps absorption of products of lipid
digestion, forming micelles (free fatty acids,
glycerol, cholesterol).
 Absorption of lipids is required for absorption of
fat-soluble vitamins (vitamins A, D, E, K)

16. Digestion and Absorption: Nucleic Acids
 Food also contains RNA and DNA (also from
shed cells of the GI tract).
 The pancreas releases nucleases into the small
intestine.
 Nucleases digest RNA and DNA into
components.
Digestion and absorption of dietary nucleic acids
probably not important for DNA/RNA synthesis.

17. Absorption in the Small Intestine: Water
 About 9 liters of water enters the digestive tract
each day.
 About 8 liters of this is absorbed by the small
intestine (by osmosis, following movement of
ions).

18. Large Intestine
Last portion of the digestive tract.
No digestion occurs in the large intestine.
In the large intestine, there is absorption of
water (about 1 liter/day) and salts from feces
(undigested, unabsorbed food).
Bacteria produce vitamin K, B vitamins.
Secretion of mucus (lubrication of feces)
Contractions move feces along large intestine
and rectum, to be expelled out of the anal
canal.

19. Accessory Digestive Organs
 Pancreas: exocrine portion produces digestive
enzymes, bicarbonate
 Liver: Produces bile, stores glycogen,
interconverts nutrients (gluconeogenesis),
detoxifies toxic substances (alcohol, drugs,
ammonia…), makes blood proteins (albumin,
fibrinogen, clotting factors)
Gallbladder: concentrates and stores bile

20. Regulation of Digestion
Allow communication between different parts of
the digestive tract
Ensure the presence of sufficient secretions
when food present
Help avoid overabundance of secretions in
absence of food
Two types of mechanisms: neural and endocrine

21. Neural Control of Digestion
Neural control of digestion is controlled largely by the
parasympathetic nervous system, and local (enteric) reflexes.
Activation of the parasympathetic system results in secretion
of digestive juices, increased motility of the stomach, and
slowing down movement of food from the stomach to small
intestine.
Stimuli: Thought, sight, taste of smell of food; distension of GI
tract; chemoreceptors detecting nutrients, pH.
Example: Thought, chewing, or taste of food activates
parasympathetic system, resulting in increased release of
mucus, HCl, and pepsin in the stomach.
The goal of this is to prepare the stomach for oncoming food.

22. Intestinal Phase of Gastric Secretion
(~ 10% of total)
(due to some G cells extending from
antrum into the duodenum)
Important aspect of intestinal phase is feedback
regulation and inhibition
Involves interactions between duodenal contents
and duodenal hormones, including their actions
on pancreas, liver, gall bladder, and stomach

23. G
gastrin
circulation
HCl
vagus
nerve
FOOD
Distension
Peptides
2. Gastric Phase of
Gastric Secretion
(approx 60% of total)
(initiated by gastric events)
G
gastrin
circulation
HCl
vagus
nerve
1. Cephalic Phase of
Gastric Secretion (approx.
30% of total)
(initiated by brain)
B. Functional Phases of Gastric Secretion

24. C. G.I. HORMONESC. G.I. HORMONES
Structure ofStructure of SecretinSecretin (27 AA)(27 AA)
(comparison with other GI hormones)(comparison with other GI hormones)
Gastrin (17 AA)Gastrin (17 AA)
Cholecystokinin (CCK (33 AA))Cholecystokinin (CCK (33 AA))
++ HH++
++ psnognpsnogn
++ motil.motil.
++ LESLES
++ growthgrowth
++ panc enzpanc enz
++ G.B.G.B.
++ growthgrowth
- OddiOddi
- gastr emptyinggastr emptying
- synrg w/ Secretinsynrg w/ Secretin
++ HCO3 outputHCO3 output
++ psnognpsnogn
++ synrg w/ CCKsynrg w/ CCK
- gastr emptyinggastr emptying
-- HH++

25. Endocrine Control of Digestion
Gastrin:
- produced from the stomach (G cells)
- release increased by stomach
distension, peptides, amino acids, alcohol,
caffeine, parasympathetic innervation
- release inhibited by highly acidic pH
(< 2.0)
- functions: increases gastric (stomach)
secretions (primarily HCl); increases
histamine release; increases gastric motility;
opens pyloric sphincter (between stomach
and small intestine), relaxes ileocecal
sphincter, stimulates growth of gastric
mucosa.

26. Endocrine Control of Digestion
Histamine:
Produced by enterochromaffin-like cells (ECL
cells) of the stomach.
Release is stimulated by gastrin.
Action: increase HCl secretion from parietal
cells (major factor in HCl secretion).

27. H/K
P
H/K
P
histamine-
secreting cell
Acetylcholine
neural input
neurocrineneurocrine
Gastrin
hormonal input
endocrineendocrine
PARIETAL cell
paracrineparacrine
release of
histamine
histamine
receptor
ACh
receptor
gastrin
receptor
transduction-
activation events
HCl
secretion
Combined neurocrine, endocrine and paracrine
events in the activation of gastric HCl secretion
ECL cell
G cellG cell
circulationcirculation
ECL cell =
enterochromaffin-like cell
G cell =G cell =
gastrin-secreting cellgastrin-secreting cell
HOW IT WORKS AT THE RECEPTOR LEVEL
neural input
neural input
chemical inputchemical input

28. H/K
P
H/K
P
histamine-
secreting cell
Acetylcholine
neural input
neurocrineneurocrine
Gastrin
hormonal input
endocrineendocrine
PARIETAL cell
paracrineparacrine
release of
histamine
histamine
receptor
ACh
receptor
gastrin
receptor
transduction-
activation events
HCl
secretion
Combined neurocrine, endocrine and paracrine
events in the activation of gastric HCl secretion
ECL cell
G cellG cell
circulationcirculation
ECL cell =
enterochromaffin-like cell
G cell =G cell =
gastrin-secreting cellgastrin-secreting cell
HOW IT WORKS AT THE RECEPTOR LEVEL
H-2 receptor blockers
H/K ATPase pump inhibitors
Tagamet
Zantac
Pepcid
Prilosec
Nexium
Aciphex
neural input
neural input
chemical inputchemical input

29. Turning the G-cell On
and Off
ACh ACh
ACh GRP
(Somatostatin)
cell
(Gastrin)
cellSS
GRP
neuron
digested
protein
H+
vagus
nerve
Circulating
Gastrin
GD
+-
++
cholinergic
neuron
gastric
mucosa
Gastric LumenGastric Lumen

30. Turning the G-cell On
and Off
ACh ACh
ACh GRP
(Somatostatin)
cell
(Gastrin)
cellSS
GRP
neuron
digested
proteinH+
vagus
nerve
Circulating
Gastrin
GD
+
++
cholinergic
neuron
gastric
mucosa
Gastric Lumen
SS = somatostatin
-

31. Endocrine Control of Digestion
Somatostatin
Produced by D cells of the stomach
Secretion is stimulated by activation of the
sympathetic nervous system and by acidic pH, and is
inhibited by activation of the parasympathetic nervous
system, continuously released, overridden by gastrin
and nerves.
Actions: inhibit gastrin and histamine secretion
(decreased acid release and gastric motility); also
directly inhibits acid release from parietal cells.

32. Secretin:
- Produced by duodenum (enteroendocrine cells
of the small intestine); crypts of Lieberkühn
- stimulated by arrival of acidic chyme in
duodenum.
- functions: stimulates bicarbonate secretion
from pancreas; inhibits gastric secretion
(decreases HCl production by inhibiting gastrin
release); decreases gastric motility (slowing
rate of gastric digestion and delivery to the
small intestine), increases hepatic bile
production, increases CCK, promotes growth
and maintenance of the pancreas.
Endocrine Control of Digestion

33.  Cholecystokinin (CCK):
- produced by enteroendocrine cells of the
duodenum
- release stimulated by fatty acids in
duodenum (also amino acids, acidic chyme)
- functions: causes gallbladder contraction
(bile to small intestine); stimulates release of
pancreatic enzymes; decreases gastric
motility and secretion (increases somatostatin
release).
Endocrine Control of Digestion

34. Endocrine Control of Digestion
Gastric Inhibitory Peptide (GIP):
Secretion: Enteroendocrine cells in the small
intestine mucosa Crypts of Lieberkuhn
Stimulus: Chyme rich in triglycerides, fatty acids,
and glucose enter the small intestine.
Actions:
 Stimulates release of insulin by beta cells
 Inhibits gastric secretion and motility
 Stimulates lipogenesis by adipose tissue
 Stimulates glucose use by skeletal muscle cells

35. Endocrine Control of Digestion
Vasoactive Intestinal Peptide (VIP):
Secretion: Enteroendocrine cells in the small
intestine mucosa Crypts of Lieberkuhn
Stimulus: Chyme entering the small intestine.
Actions:
 Stimulates buffer secretion
 Inhibits gastric secretion
 Dilates intestinal capillaries

36. Control of Gastric Acid Secretion
How does a parietal cell secrete hydrochloric
acid?
CO2 + H20 H2CO3 H+
+ HCO3
-
Cl-
Cl-H+
HCO3-

37. Control of Gastric Acid Secretion
ECL
parietal
cellG Cell
HCl
Gastrin
histamine
D Cell
somatostatin (-)SECRETIN
CCK

38. Integration of Neural and Endocrine
Functions: Central Effects
CNS: Thoughts, taste, smell of food; chewing –
activates parasympathetic nervous system
(neurotransmitter: acetylcholine).
ACh acts directly on parietal cells to increase
acid secretion.
Ach increases gastrin release, inhibits
somatostatin release (increased gastric
secretion and motility).
Sympathetic input (activity, stress): increased
somatostatin release (inhibiting gastrin secretion
– decreased gastric secretion and motility)

39. Integration of Neural and Endocrine
Functions
ECL
parietal
cellG Cell
HCl
Gastrin
histamine
D Cell
somatostatin (-)SECRETIN
CCK
ACh(-)
(+) (+)
Vagus N.
Digested protein
(+)

40. Integration of Neural and Endocrine
Functions: Local Reflexes
Mechanoreceptors in the walls of the GI tract detect
movement of food into an organ
Example: In the stomach distension causes
activation of the parasympathetic system,
increasing gastrin secretion and acid release, and
decreasing somatostatin secretion.
Chemoreceptors detect nutrients and pH.
Example: Presence of amino acids, alcohol, or
caffeine in the stomach increases gastrin release.
Presence of fatty acids in the duodenum causes
release of CCK.

41. Signaling Mechanisms
Histamine: Receptor coupled to Gs – increases
cyclic AMP production and acts via PKA.
Results in phosphorylation and increased
transport of proton pumps to cell membrane.
Gastrin: Receptor coupled to Go/IP3/DAG;
increased intracellular calcium, and activation of
PKC (PKC also phosphorylates proton pumps).
Somatostatin: Receptor coupled to Gi – inhibits
cyclic AMP production, decreasing PKA
signaling.

42. Signaling Mechanisms
CCK: Receptor coupled to Go (increased
calcium causes somatostatin release)
Secretin: Receptor couple to Gs (increased
cyclic AMP, causes increased secretion of
bicarbonate from the pancreas)

43. Integration of Gastric SecretionIntegration of Gastric Secretion
++
++
++++
++
++

44. Integration of Gastric SecretionIntegration of Gastric Secretion
++ ++
++
--
-- --
++
++++
++
++

45. D. Duodenal Integration & Control: 1. Response to Acidity
Regulation by Secretin
HCl + NaHCOHCl + NaHCO33 NaCl + CONaCl + CO22 + H+ H22OO
+
+
-
+
gall
bladder
liver
HCl
⇓HCl
⇓motility
NaCl
+ H2O
HCO3
HCl
NaHC
O 3
N
aH
C
O
3
Secretin
Secretin

46. Regulation by CCK (Cholecystokinin)
CCK
CCK
gall
bladder
⇑Bile
FOOD
+
-
liver
+
fats &
peptides
bile &
enzymes
fat &
protein
digestion
- HCl⇓
2. Duodenal Response to Food