E
DIFFUSE ENDOCRINE SYSTEM
INTRODUCTION TO GASTROINTESTINAT TRACT
MAIOR ACTIVITIES
motility movement of ingesta along the tract is regulated to allow
optimal period needed for both digestion and absorption.
:
secretions: mucosa
)
water, electrolytes, enzymes, mucus.
gall bladder ) bile.
pancreas ) bicarbonate, enzymes.
digestion: availability of digestive enzymes depends on
regulation of secretion.
absorption: motility and secretion are regulated to gain
optimal digestion and absorption.
REGULATION OF MAJOR ACTIVITIES
NEURAL
EXTERNAL INNERVATION : slmpathetic, parasympathetic.
INTRINSIC INNERVATION: network of enteric nervous system.
HORMONAT
END OC RINE, PARACRIN
inhibitory peptide
"PHASES OF DIGESTION"
CEPHALIC PHASE
GASTRIC PHASE
INTESTINAL PHASE
E
:
gastrin, secretin, cholecystokinin, gastric
REGUIATION OF GASTROINTESTINAL
TRACT E
FUNCTIONS THAT INVOLVE THE CRANIAL AND CAUDAT ENDS OF
THE TRACT ARE CONTROLLED PRINCIPALLY BY THE NERVOUS
sYsTEM (mastication, swallowing, secretion of saliva,
defecation).
FUNCTIONS BASED IN THE SEGMENTS'IN.BETWEEN' ARE
COORDINATED BY AN INTERPLAY OF NEURAL AND HORMONAL
INFLUENCES ON MUsCUIAR AND SECRETORY CELTS (propulsion
ingesta, chemical breakdown of food particles
ab sorptio n of nutrients).
of
, extraction and
Neural influences
ti)
(ii)
are exerted by:
the enteric fintrinsic) nervous system.... neurons located
in intramural myenteric and submucosal plexuses;
extrinsic nerves that link the CNS with GI tract through
parasympathetic and sympathetic pathways.
HormOnal influences are exerted by a large number of
which four hormones will be discussed: gastrin,
secretin, cholecystokinin, and gastric inhibitory peptide. The cells
GI peptides, of
that secrete these hormones are dispersed amongst the epithelial
cells lining the stomach and intestine. It is thought that microvilli on
the apical surfaces of the hormone-secreting cells have receptors for
sampling the luminal contents.
The neural and hormonal systems interact to control
motility, secretion and absorption.
(il neural activity can induce release of hormones;
[ii) hormones can modulate neural activity;
(iii) the activity of effector cells can be influenced
simultaneously by neural and hormonal activities.
NEURAL REGULATION
EXTRINSIC NERVOUS SYSTEM
Sympatfietic
Parasympathetic
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To illustrate the extensive two-way connections that exist between the GI tract and the cNS
parasympathetic and sympathetic systems, The enteric neurons receive signals from mechanoiecepiori, chemorecepiori and osmoreceptors within the GI tract and, to a considerable extent, the
intri-mural system exercises intrinsic control of motility and secretion..... but the afferent and
efferentfibresofthe ANsrendertheintrinsicneuronssubjecttopconstant"oversight"bytheCNS.
Coordinated signals between gut regions are carried by nerve circuits I entero-enteric reflexes
regulating one iegion in relation to others) and by hormones fsuch as cholecystokinin, gastrin
secretin and Sastric inhibitory peptidei.
in one part
Local reflexes contained entirely within the enteric NS can produce a response
all
of
absence
the
of the digestive tract following i stimulus in an other par! even in
extrinsic innervation
DIFFUSE ENDOCRINE SYSTEM
HORMONAT REGULATION OF GIT
Fundamental physiological principle: BASAL SECRETION
In GIT, interdigestive secretion occur in the absence of all gastrointestinal stimulation. Neural and hormonal responses to ingestion
of food or drink are superimposed on that low level of activity.
A huge number of physiological processes have to be evoked and
coordinated very precisely during the course of a meal to facilitate
the digestion, absorption and utilization of the nutrients and the
excretion of the unabsorbed residue.
The GIT has been described as the largest endocrine organ in the
body: more than 30 peptides have been identified as being
expressed within the tract. Here, we shall deal with four hormones
(gastrin, secretin, cholecystokinin, and gastric inhibitory peptide)
and two paracrine agents [histamine and somatostatin)
The enteric hormone system is diffuse: single hormone-secreting
cells are scat[ered among other types of epithelial cells in the mucosa
of the stomach and small intestine.
The apical border of the endocrine cell is in contact with the
contents of the lumen, which enables it to continually monitor the
local environment, detect changes and respond appropriately.
The endocrine cells secrete their hormones in response to fairly
specific stimuli and they stop secreting their hormones when those
stimuli are no longer present.
Gut hormones --and other peptide
or autocrine agents.
regulators-can act as paracrine
Somatostatin and histamine have very important functions as
paracrine agents involved in the secretion of gastric acid.
DIFFUSE ENDOCRINE SYSTEM
HORMONAL REGULATION OF GIT
The gastrointestinal hormones are listed in E
The enteric endocrine cells (enteroendocrine cells) occur as
single cells amongst the epithelial cells lining the lumen of the
stomach and intestines. Some (open type)have a narrow apical
pole with a tuft of microvilli extending into the lumen, where it
is thought that they sample the changing composition of the
local environment. Others {closed Wpe) do not contact the
lumen but have broad contact with the basement membrane
through which they release the content of their secretory
granules (their hormon.)
@.
Gastrointestinal peptides may act as endocrine, neurocrine,
paracrine, or autocrine agents 11
Local influences on activities of GI endocrine cells are depicted
i" E. In the antrum of the stomach, G-cells secrete gastrin in
response to stimuli from components of the foodstuff, Gastrin
increases the release of acid, so that D cells release
somatostatin which acts as a paracrine inhibitor of gastrin
secretion.
Regulation of secretion of gastric juice is summarized
i,
E
Many of the gastrointestinal peptides are present also in brain,
where they participate in regulating appetite and in the control
of energy metabolism.
DIFFUSE ENDOCRINE SYSTEM
GASTROINTESTINAL HORMONES
GASTRIN
Site of formation: antrum[stomach) and duodenum
Main action: stimulates secretion of acid in stomach
Secretion stimulated by: activation of vagus nerve;
stretching of stomach muscle;
contact of chyme with
G cells.
SECRETIN
Site of formation: upper small intestine
Main action: stimulates pancreas to secrete water and bicarbonate;
inhibits HCI secretion in stomach
Secretion stimulated by acid pH in duodenum
CHOLECYSTOKININ (CCK)
Site of
formation: upper small intestine
Main action: stimulates secretion of pancreatic enzymes;
contraction of gall bladder.
Secretion stimulated by products of digestion and bile acids in small
intestine.
GASTRIC INHIBITORY PEPTIDE (GIP)
Site of formation: upper small intestine
Main action: stimulates secretion of insulin by pancreatic islets
Secretion stimulated by hyperosmolality of glucose in duodenum
SOMATOSTATIN
Site of formation: stomach and upper small intestine
Main action: inhibits secretion of gastrin and secretin
Secretion stimulated by acid pH in stomach and duodenum.
DIFFUSE ENDOCRINE SYSTEM
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DIFFUSE ENDOCRINE STSTEIT{
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DIFFUSE ENDOCRINE SYSTEM
Secretion of gastric juice
E
[A] Cephalic phase
NEURAL....,,.... via vagus
mediated by acetylcholine at parietal cell
[B) Gastric phase
NEURAL and HORMONAL
Distension..... via vago-vagal reflexes
Luminal contents .....
breakdown products of proteins
alcohol
caffeine
Modulation by somatostatin from D cells
(C) Intestinal phase
HORMONAL and NEURAT
....... mainly inhibitory
Hormones in response to neural stimuli
and luminal contents:
secretin ..... in response to hydrogen ions
cholecystokinin....in response to fats, peptides
and amino acids
Distension.... reflexes within enteric nervous system
Gastric acidity [pH-2)
Necessary for conversion of pepsinogen to pepsin
Unfolds proteins to expose peptide bonds
Inhibits growth of bacteria
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DIFFUSE ENDOCRINE SYSTEM
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GI HORMONES
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DIFFUSE ENDOCRINE SYSTEM
GI HORMONES DURING INTESTINAL PHASE [PaTt 1J
"Gastric emptying" is regulated to reduce the risk of overloading the small intestine. Chyme [a very acidic, semi-liquid
mixture of gastric secretions and partially digested food) is
delivered to the duodenum in frequent small spurts. The final
breakdown of proteins, carbohydrates and fats is achieved in
the intestine by'
(i) membrane-bound enzymes associated with the brush
border of the epithelial cells;
[ii) enzymes from the exocrine pancreas.
Basic desiderata to facilitate completion of the digestive
processes within the intestine:
(i) conversion of acid gastric effluent to neutral/alkaline pH,
making it a suitable medium for activity of digestive enzymes
in intestine;
(ii) delivery of digestive enzymes from exocrine pancreas;
[iii) delivery of bile from gall bladder
The duodenal mucosa is sensitive to changes in osmolality,
pH, polypeptide content and lipid content of chyme. Changes
in these variables act as stimuli for (neural andJ hormonal
responses that regulate gastric emptying and subsequent
digestive processes.
DIFFUSE ENDOCRINE SYSTEM
GI HORMONES DURING INTESTINAL PHASE [PaTt 2J
The hormonal responses:
(A) acidity elicits release of secretin, which acts on stomach,
exocrine pancreas and liver to neutralize the acid by:
Inhibiting
release of gastrin, gastric secretion and gastric emptying.....
..... thus reducing the load of acid entering the duodenum;
Stimulating secretion of bicarbonate-rich pancreatic juice and bile....
........to neutralize the acid chyme.
(B) polypeptides and lipids elicit release of cholecystokinin,
which has many effects on GIT:
[iJ inhibiting secretion of gastric acid and gastric emptying;
(ii) stimulating release of enzymes by the pancreas and of bile from the
gall bladder ...... to digest proteins and lipids
(C) tryperosmolality due to [glucose] in intestinal lumen
induces release of gastric inhibitory polypeptide [GIP) from
endocrine cells in the duodenum. GIP stimulates B- cells in
pancreatic islets to cosecrete insulin and amylin, thus
regulating [glucose] in blood:
fiJinsulin promotes transfer
of glucose from blood to meet energy
needs of active cells or to enter energy stores in
adipose tissue;
livel muscle, or
[iiJ amylin slows the appearance of ingested glucose in bloodby
{a) ortewxc DIGESTIVE ACTtvITtES of stomach and intestine
[inhibits secretion of gastric juice, slows gastric emptying, inhibits
secretion of pancreatic enzymes, inhibits release of bile from gall
bladderJ.
[b)
rNHrnrrrNc FoRMATToN oF NEW GLUCoSE By GLUCoNEoGENESIS
(inhibits secretion of the gluconeogenic hormone, glucagon, by
cr-cells of the endocrine pancreas).