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. Digestion & Absorption: Proteins
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

13. Digestion & Absorption : Lipids
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.

14. Emulsification of Lipids by Bile
Bile acts on lipids in a way similar to detergent acting on greasy water:
large lipid droplet
bile
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. B. Functional Phases of Gastric Secretion
1. Cephalic Phase of Gastric Secretion (approx. 30% of total)
(initiated by brain)
2. Gastric Phase of Gastric Secretion (approx 60% of total)
(initiated by gastric events)
vagus nerve
vagus nerve
FOOD
HCl
HCl
Distension
Peptides
circulation
circulation G G
gastrin
gastrin

24. C. G.I. HORMONES Gastrin (17 AA) Cholecystokinin (CCK (33 AA))
+ psnogn
+ motil.
+ LES
+ growth
Gastrin (17 AA)
Cholecystokinin (CCK (33 AA))
+ panc enz
+ G.B.
+ growth
Oddi
gastr emptying
synrg w/ Secretin
+ HCO3 output
+ psnogn
+ synrg w/ CCK
gastr emptying
- H+
Structure of Secretin (27 AA) (comparison with other GI hormones)

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

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

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

30. Turning the G-cell On and Off
vagus
nerve
ACh
ACh
Circulating
cholinergic neuron
GRP
Gastrin
gastric mucosa
neuron
ACh
GRP + D - G
(Somatostatin)
(Gastrin)
cell SS
cell + + H+
digested
protein
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. Endocrine Control of Digestion
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.

33. Endocrine Control of Digestion
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).

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? H+
Cl-
CO2 + H H2CO H+ + HCO3-
HCO3-
Cl-

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

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
Vagus N.
ACh
(-)
(+)
D Cell
(+)
CCK
HCl
SECRETIN
somatostatin (-)
parietal
cell
G Cell
ECL
histamine
Gastrin
(+)
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 Secretion+ +

44. Integration of Gastric Secretion+ - + +

45. + + - D. Duodenal Integration & Control: 1. Response to Acidity
Regulation by Secretin
liver +
HCO3
NaHCO3 +
gall
bladder - 
HCl 
motility
Secretin
NaCl
+ H2O
HCl
NaHCO3 +
HCl
HCl + NaHCO NaCl + CO2 + H2O

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