2. INTRODUCTION
The various functions of the gastrointestinal
tract, including secretion, digestion, and
absorption and motility must be regulated in
an integrated way to ensure efficient
assimilation of nutrients after a meal.
3. Contd.
There are three main modalities for
gastrointestinal regulation that operate in a
complementary fashion to ensure that
function.
4. Contd.
First, endocrine regulation is mediated by the
release of hormones by triggers associated
with the meal.
Second, some similar mediators alter the
function of cells in the local area where they
are released, in a paracrine fashion.
5. Contd.
Finally, the intestinal system is endowed with
extensive neural connections.
• These include connections to the central
nervous system (extrinsic innervation), but
also the activity of a largely autonomous
enteric nervous system.
6. Contd.
The enteric nervous system integrates central
input to the gut, but can also regulate gut
function independently in response to
changes in the luminal environment.
7. ENTEROENDOCRINE CELLS
More than 15 types of hormone-secreting
enteroendocrine cells have been identified in
the mucosa of the stomach, small intestine,
and colon.
8. Contd.
Many of these secrete only one hormone and
are identified by letters (G cells, S cells, etc).
Others manufacture serotonin or histamine
and are called enterochromaffin or
enterochromaffin-like (ECL) cells, respectively.
9. Contd.
On the basis of structural similarity and, to a
degree, similarity of function, the key
hormones fall into one of two families:
(1) The gastrin family, the primary members of
which are gastrin and CCK; and
10. Contd.
(2)The secretin family, the primary members of
which are secretin, glucagon, glicentin (GLI),
vasoactive intestinal peptide (VIP), and gastric
inhibitory polypeptide (GIP).
There are also other hormones that do not fall
readily into these families.
11. Contd.
Several of these hormones have extreme
importance for controlling gastrointestinal
secretion.
Most of these same hormones also affect
motility in some parts of the gastrointestinal
tract.
12. Contd.
Although the motility effects are usually less
important than the secretory effects of the
hormones.
Some of the more important of them are the
following:
13. GASTRIN
• Gastrin is produced by cells called G cells in
the antral portion of the gastric mucosa.
• Stimuli:
(1) Ingestion of a meal and distention of the
stomach.
14. Contd.
(2) The products of proteins in the stomach.
(3) and gastrin releasing peptide, which is
released by the nerves of the gastric mucosa
during vagal stimulation.
15. Contd.
• Its principal physiologic actions are:
stimulation of gastric acid and pepsin
secretion and
stimulation of the growth of the mucosa of
the stomach and small and large intestines
(trophic action).
16.
17.
18. CHOLECYSTOKININ
• Cholecystokinin is secreted by “I” cells in the
mucosa of the duodenum and jejunum.
• Stimuli:
In response to digestive products of fat in the
intestinal contents.
19. Contd.
Contact of the intestinal mucosa with the
products of protein digestion, particularly
peptides and amino acids.
20. Contd.
• Its principal physiologic actions are:
Stimulation of pancreatic enzyme secretion
Contraction of the gallbladder (the action for
which it was named), and relaxation of the
sphincter of Oddi,
Which allows both bile and pancreatic juice to
flow into the intestinal lumen.
21. Contd.
In addition to its primary actions, CCK
augments the action of secretin in producing
secretion of an alkaline pancreatic juice. It also
inhibits gastric emptying, exerts a trophic
effect on the pancreas, increases the synthesis
of enterokinase, and may enhance the motility
of the small intestine and colon.
22. Contd.
There is some evidence that, along with
secretin, it augments the contraction of the
pyloric sphincter, thus preventing the reflux of
duodenal contents into the stomach.
Gastrin and CCK stimulate glucagon secretion,
and since the secretion ofboth gastrointestinal
hormones is increased by a protein meal,
either or both may be the “gut factor” that
stimulates glucagon secretion
23. SECRETIN
• Secretin occupies a unique position in the
history of physiology. In 1902, Bayliss and
Starling first demonstrated that the excitatory
effect of duodenal stimulation on pancreatic
secretion was due to a bloodborne factor.
Their research led to the identification of the
first hormone, secretin.
24. Contd.
• They also suggested that many chemical
agents might be secreted by cells in the body
and pass in the circulation to affect organs
some distance away. Starling introduced the
term hormone to categorize such “chemical
messengers.”
• Modern endocrinology is the proof of the
correctness of this hypothesis.
25. Contd.
Secretin is secreted by S cells that are located
deep in the glands of the mucosa of the upper
portion of the small intestine.
Stimuli:
in response to acidic gastric juice emptying
into the duodenum.
by the products of protein digestion.
26. Contd.
Its principal physiologic actions are:
Secretin increases the secretion of
bicarbonate by the duct cells of the pancreas
and biliary tract.
It thus causes the secretion of a watery,
alkaline pancreatic juice.
27. Contd.
It also augments the action of CCK in
producing pancreatic secretion of digestive
enzymes.
It decreases gastric acid secretion and may
cause contraction of the pyloric sphincter.
28. GIP (Gastric inhibitory peptide)
• It is produced by K cells in the mucosa of the
duodenum and jejunum.
• Stimuli:
Its secretion is stimulated by glucose and fat
in the duodenum.
To a lesser extent amino acids increases its
secretion.
29. Contd.
• Its principal physiologic actions are:
In large doses it inhibits gastric secretion and
motility.
However, it now appears that it does not have
significant gastric inhibiting activity when
administered in physiological dose.
30. Contd.
In the meantime, it was found that GIP
stimulates insulin secretion.
The glucagon derivative GLP-1 also stimulates
insulin secretion and is said to be more potent
in this regard than GIP.
Therefore, it may also be a physiologic B cell-
stimulating hormone of the gastrointestinal
tract.
31. MOTILIN
• It is secreted by enterochromaffin cells and
Mo cells in the stomach, small intestine, and
colon.
• It acts on G protein-coupled receptors on
enteric neurons in the duodenum and colon
and produces contraction of smooth muscle in
the stomach and intestines.
32. Contd.
• it is a major regulator of the migrating motor
complexes (MMCs) that control
gastrointestinal motility between meals.
Conversely, when a meal is ingested, secretion
of motilin is suppressed until digestion and
absorption are complete.
33. VIP
• It is found in nerves in the gastrointestinal
tract and thus is not itself a hormone, despite
its similarities to secretin.
• In the intestine, it markedly stimulates
intestinal secretion of electrolytes and hence
of water
34. Contd.
• VIP-secreting tumors (VIPomas) have been
described in patients with severe diarrhea.
• Its other actions include relaxation of
intestinal smooth muscle, including
sphincters; dilation of peripheral blood
vessels; and inhibition of gastric acid
secretion.
35. SOMATOSTATIN
• Somatostatin, the growth-hormone-inhibiting
hormone originally isolated from the
hypothalamus, is secreted as a paracrine
fashion by D cells in the pancreatic islets and
by similar D cells in the gastrointestinal
mucosa.
36. Contd.
• It exists in tissues in two forms, somatostatin
14 and somatostatin 28, and both are
secreted.
• Somatostatin inhibits the secretion of gastrin,
VIP, GIP, secretin, and motilin.
37. Contd.
• Its secretion is stimulated by acid in the
lumen, and it probably acts in a paracrine
fashion to mediate the inhibition of gastrin
secretion produced by acid.
38. Contd.
• It also inhibits pancreatic exocrine secretion;
gastric acid secretion and motility; gallbladder
contraction; and the absorption of glucose,
amino acids, and triglycerides.
39. PEPTIDE YY
• It also inhibits gastric acid secretion and
motility and is a good candidate to be the
gastric inhibitory peptide.
• Its release from the jejunum is stimulated by
fat.
40. Contd.
• The integrated action of gastrin, CCK, secretin,
and GIP in facilitating digestion and utilization
of absorbed nutrients is summarized in figure
below:
