Download - Chapter 3 DIGESTIVE SYSTEM PART-1
Part II – Chapter 3- 1
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• The digestive system (GIT) composed of:
1. Oral cavity
2. Alimentary tract,
3. GIT-Associated glands
• Functions of GIT are:
1. Ingestion, mastication, deglutition (swallowing),
2. Digestion
3. Absorption of food
4. Elimination of its indigestible remnants.
• Regions of the digestive system are modified and have specialized structures to be able
to perform these varied tasks.
Oral Cavity
ORAL MUCOSA: OVERVIEW • Healthy oral mucosa, composed of a wet stratified squamous epithelium non-
keratinized resting on basal lamina and fixed with underlying dense irregular
collagenous connective tissue
• Oral mucosa is subdivided into three types: lining mucosa, masticatory mucosa, and
specialized mucosa.
• Regions of the oral cavity that are exposed to considerable physical forces (gingiva,
dorsal surface of the tongue, and hard palate) are lined or covered by a masticatory
mucosa composed of parakeratinized to completely keratinized stratified squamous
epithelium.
• The remainder of the oral cavity is lined or covered by a lining mucosa, composed of
a nonkeratinized-stratified squamous epithelium
• Dorsal surface of the tongue and patches of the soft palate and pharynx their mucosa
have taste buds.
Chapter 3 DIGESTIVE SYSTEM PART-1
Part II – Chapter 3- 2
• Ducts of the three pairs of major salivary glands (parotid, submandibular, and
sublingual) open into the oral cavity, delivering saliva to moisten the mouth.
• These glands also manufacture and release the enzyme salivary amylase to break down
carbohydrates, lactoferrin and lysozymes, antibacterial agents, and secretory
immunoglobulin (IgA).
• In addition, minor salivary glands, located in the connective tissue elements of the
oral mucosa, add to the flow of saliva into the oral cavity.
• In the oral cavity, food is moistened with saliva, chewed, and isolated by the tongue,
forming spherical masses about 2cm in diameter known as a bolus, are forced by the
tongue into the pharynx to be swallowed.
• Lips bound the oral cavity anteriorly and the palato-glossal folds form the posterior
boundary of the oral cavity.
• Oral cavity components are the lips, the teeth and their associated structures, the
palate, and the tongue.
Lips • The core of the lips is composed of skeletal muscle fibers that are responsible for
lip mobility.
• The lip has three borders: outer skin, the vermilion zone, and the inner mucous
borders.
• The external aspect of the lip is covered with thin skin and is associated with sweat
glands, hair follicles, and sebaceous glands.
• This region is continuous with the vermilion zone, the pink region of the lip, which
is also covered by thin skin.
• Note that, the vermilion zone is devoid of sweat glands and hair follicles, although
occasional, nonfunctional sebaceous glands are present there.
• The interdigitation between the epithelial and connective tissue components of the
oral mucosa is highly developed, so that the capillary loops of the dermal papillae
are close to the surface of the skin, imparting a pink color to the vermilion zone.
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• The absence of functional glands in this region necessitates the occasional
moistening of the vermilion zone by the tongue.
• The mucous (internal) aspect of the lip is always wet and is lined by stratified
squamous nonkeratinized epithelium.
• The lamina propria of lip contains dense, irregular collagenous type and houses
numerous, mostly mucous, minor salivary glands.
• The cheek is similar to lip, but has more adipose tissue, and no red margin.
GINGIVA /GUM AND RAPHE OF HARD PALATE • Stratified squamous epithelium (partly keratinized) on a dense CT lamina propria, with
deeply penetrating papillae, and fastened tightly to tooth or bone.
SOFT PALATE • Fibrous and skeletal muscle core, with mucous glands;
• Pseudostratified, columnar, ciliated epithelium covers the pharyngeal side, and
stratified squamous the oral surface.
• Functions in deglutition (swallowing), speech, blowing, coughing, and sneezing.
TONGUE • Core is interlaced skeletal muscle bundles oriented in three directions, with attendant
nerves and blood vessels.
• Covered by stratified squamous epithelium, modified over the anterior dorsum by
being thrown up with the dense lamina propria into projections called papillae of
various kinds, with special distributions:
§ Filiform - most numerous, spiky, with a partly keratinized tip which is shed.
§ Fungiform - less numerous, larger, with some taste buds in their smooth tops.
§ Circumvallate - least numerous, largest, lie along the terminal sulcus, each
surrounded by a trench, and with taste buds in its wall.
§ (Foliate - small ridges on the sides of the tongue, prominent in rabbit, vestigial
in man; also with taste buds in the walls.)
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• Lingual glands
a. Posterior mucous
b. Posterior serous of von Ebner, opening into the trenches;
c. Anterior mixed sero-mucous.
• Lingual tonsils are stratified squamous epithelium-covered aggregations of lymphoid
nodules, with shallow crypts flushed out by mucous secretions of the posterior lingual
glands.
GASTROINTESTINAL TRACT General plan
1. Mucosa (innermost)
a. Of epithelium, lamina propria and smooth muscle muscularis mucosae.
b.The epithelium in most places takes a glandular form, with simple tubular glands
and a secreting surface epithelium.
c. Some parts have discrete compound glands lying in the mucosa.
d. Single lymphoid nodules can occur anywhere.
2. GI submucosa
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a. Of fairly dense CT, with blood and lymphatic vessels, and having a plexus of
unmyelinated autonomic nerve fibers - Meissner's submucosal plexus.
b.Glands are present in a few places.
3. GI muscularis externa
a. Two or more helical layers of smooth muscle: the inner, tight 'circular'; the outer,
loosely coiled 'longitudinal'.
b.Served by a nerve fiber plexus - Auerbach's myenteric plexus, whose
parasympathetic ganglion cells lie between the muscle layers.
c. Circular coat is more developed at sphincters and valves.
4. GI serosa or adventitia/fibrosa (outermost)
a. Of loose CT, with collagen and elastic fibers, nerves and vessels.
b. The serosa has a smooth mesothelial covering, and that part of the tract is suspended
on a mesothelium-covered tissue fold - omentum or mesentery.
c. Mesothelial cells bear microvilli, are well attached, and secrete lubricants to allow
viscera to move freely.
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ESOPHAGUS • The esophagus is a muscular tube, approximately 25 cm in length.
• Along its entire length, its mucosa presents numerous longitudinal folds with
intervening grooves that cause the lumen to appear to be obstructed; however, when
the esophagus is distended the folds disappear and the lumen becomes patent
• The lumen of the esophagus, lined by a 0.5-mm-thick, stratified squamous
nonkeratinized epithelium, is usually collapsed and opens only during the process
of swallowing.
• The epithelium presents a well-developed rete apparatus as it interdigitates with the
underlying connective tissue.
• The epithelium is regenerated at a much slower rate than the remainder of the
gastrointestinal tract; the newly formed cell in the basal layer of the epithelium
reaches the free surface in about 3 weeks after formation.
• Interspersed within the keratinocytes of the epithelium are antigen-presenting cells,
known as Langerhans cells, which phagocytose and degrade antigens into small
polypeptides known as epitopes.
• These cells also synthesize major histocompatibility complex (MHC) II molecules
• Langerhans cells then migrate to lymph nodes, where they present the MHC II-
complex to lymphocytes
• Mucosa has stratified squamous epithelium ending sharply, at the gastric junction,
creating a white-red distinction between proximal and distal sides of the Z-line in
endoscopy.
• Abnormalities of the esophageal epithelium and the position of the epithelial
junction are quite common - Barrett's esophagus, where the stratified squamous
epithelium is replaced metaplastically by simple columnar epithelium with some or
all of the small-intestinal cell types.
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• Muscularis mucosae is a unusual in that it consists only of a single layer of
longitudinally oriented smooth muscle fibers that become thicker in the stomach.
• The lamina propria is unremarkable. It houses esophageal cardiac glands, which
are located in two regions of the esophagus, one cluster near the pharynx and the
other near its juncture with the stomach.
• It also houses occasional lymphoid nodules, members of the MALT (mucosa
associated lymphatic tissue) system.
• The esophageal cardiac glands produce mucus that coats the lining of the esophagus,
lubricating it to protect the epithelium as the bolus is passed into the stomach.
• Because these glands resemble glands from the cardiac region of the stomach, some
investigators suggest that they are ectopic patches of gastric tissue.
Submucosa
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• The submucosa of the esophagus houses mucous glands known as the esophageal
glands proper.
• The submucosa of the esophagus is composed of a dense, fibroelastic connective
tissue, which houses the esophageal glands proper.
• The esophagus and the duodenum are the only two regions of the alimentary canal
with glands in the submucosa.
• Electron micrographs of these tubuloacinar glands indicate that their secretory units
are composed of two types of cells, mucous cells and serous cells.
• Mucous cells have basally located, flattened nuclei and apical accumulations of
mucus-filled secretory granules.
• The second cell type is serous cell, with round, centrally placed nuclei. The secretory
granules of these cells contain the proenzyme pepsinogen and the antibacterial agent
lysozyme.
• The ducts of these glands deliver their secretions into the lumen of the esophagus.
Muscularis Externa and Adventitia
• The muscularis externa of the esophagus is composed of both skeletal and smooth
muscle cells.
• The muscularis externa of the esophagus is arranged in two layers, inner circular
and outer longitudinal.
• However, these muscle layers are unusual in that they are composed of both skeletal
and smooth muscle fibers.
• The muscularis externa of the upper third of the esophagus has mostly skeletal
muscle; the middle third has both skeletal and smooth muscle; and the lowest third
has only smooth muscle fibers.
• Auerbach's plexus occupies its usual position between the inner circular and outer
longitudinal smooth muscle layers of the muscularis externa.
• The esophagus is covered by an adventitia until it pierces the diaphragm, after which
it is covered by a serosa.
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STOMACH General structure
• Anatomical regions - cardia, fundus, corpus, pyloric antrum and pyloric canal: the
regions are histologically distinct.
• Outer covering is a serosa, from which hang omenta.
• Muscular coat of three smooth muscle layers - outer, longitudinal; middle, circular;
inner, oblique. The middle layer is more developed to form a sphincter at the pylorus.
The muscle churns the contents (chyme), and passes them periodically in regulated
amounts to the duodenum.
• Submucosa - no glands; CT carries vessels and the nerve plexus.
• Muscularis mucosae - two layers, with the inner circular one sending a few muscle
fibers up towards the lumen.
• Mucosa is deep and glandular, with only a little lamina propria tissue; produces acid
and enzymes for digestion, and undertakes some absorption, e.g., of water and
alcohol.
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Stomach mucosa
a. Empty stomach's lining is folded in ridges - rugae.
b. Surface is pitted by recesses - gastric pits/foveolae gastricae.
c. Long tubular glands extend from the muscularis mucosae up to empty into the pits. A
gland has a base, neck and isthmus.
d. The surface of the stomach and the pits are lined by simple, columnar, special mucous
epithelial cells.
e. Gastric glands throughout the body and fundus of the stomach are simple, branched
tubules with these cells:
i. Mucous surface cells are most superficial cells in the glands:
§ They form a simple columnar epithelium that covers the gastric mucosa and
extends a short distance
ii. Mucous neck cells: concentrated near the neck of the gland.
iii. Parietal/Oxyntic cells: occur peripherally and singly; large and eosinophil; packed
with mitochondria and smooth ER; have long secretory canaliculi, lined by
microvilli, and opening to the gland's lumen.
Parietal cell, right half when be active, left resting, IC=intracellular canaliculi, TV=
tubulovesicles, MV= microvilli
iv. Chief/zymogenic/peptic serous cells: in the majority; basophilic, with 'zymogen'
granules and rich granular ER. They secrete pepsinogen.
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v. Endocrine/enteroendocrine/argentaffin/enterochromaffin/ Kultschitsky cells:
§ few in number, seen with EM, silver
methods, or cytochemistry, but may
be recognized from their empty look
with H & E, and their rarity.
f. In the narrow cardiac region lie cardiac glands - compound tubular, with mucous and a few parietal cells.
g. In the pylorus, pits are much deeper, and glandular tubules are wider and more branching. The main kind of glandular cell present is pale and resembles fundic mucous neck cells.
Fundic glands Pyloric glands
Gastric secretions and cell types responsible
a. Surface mucous cells - mucus, to prevent auto-digestion of the mucosa, and
bicarbonate ions held in the mucus.
b. Chief/zymogenic cells - enzymes, e.g., pepsin, rennin, gastric lipase.
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c. Oxyntic/parietal cells - Cl-/HCO3- is exchanged basolaterally to balance the apical
Na+/H+ proton pump used to form the hydrochloric acid of the digestive juice. (The
stimulated active parietal cell has greatly extended canaliculi.)
d. Mucous neck cells - mucus and enzymes, e.g., dipeptidases.
e. Endocrine cells - hormones and amines; e.g., a hormone - gastrin - produced by the
pyloric antral G cells controls the release and formation of acid from parietal cells, and
of digestive enzymes from chief cells.
f. Parietal cells - intrinsic factor - to assist in the absorption of vitamin B12: this role is
upset when the parietal cells' proton pump is an autoimmune target in pernicious
anemia, leading to the cells' destruction.
Gastric protective mechanisms a. Digestive secretions (survived by typhoid and other bacilli, and eggs of parasites,
which do their damage in the gut and by Helicobacter pylori). H. pylori, resident in
many stomachs, may cause intestinal metaplasia - a pre-malignant state - or
peptic/gastric ulcers, in some people.
b. Mucous and bicarbonate outer coating of the epithelium.
c. A film of surfactant-like lipid secreted by the epithelium.
d. Regenerative power of the epithelium, by cell proliferation and migration (normally
renewed every few days).
e. Lymphoid nodules and lymphocytes, and other leucocytes, in the mucosa and
submucosa.
f. Tight junctions between the epithelial cells.
g. Vomiting.
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SMALL INTESTINE General structure
1. Three regions - duodenum, jejunum and ileum, anatomically and histologically distinguishable.
2. Serous coat over all except part of the duodenum and the terminal ileum, which are fixed to the abdominal wall.
3. Suspended on a mesentery carrying blood and lymphatic vessels, lymph nodes and nerves.
4. Muscularis externa has two complete layers. 5. Submucosa - occupied by Brunner's mucous, compound tubular glands in the
duodenum; elsewhere is CT as for the rest of the tract. N.B (Somatostatin, produced by enteroendocrine cells of the pylorus and duodenum, inhibits the release of gastrin and thus indirectly inhibits HCI secretion . Urogastrone (also known as human epidermal growth factor), produced b y Brunner glands of the duodenum, and gastric inhibitory peptide along with prostaglandins, produced by enteroendocrine cells in the small intestine, directly inhibit HCI secretion.)
6. Muscularis mucosae - inner, circular, and outer, longitudinal smooth muscle. Mucosa has:
i. Villi - finger- or leaf-like projections.
ii. Crypts of Lieberkuhn - simple tubular glands.
iii. Lamina propria forming the core of each villus
and lying between the gland tubules.
iv. Covering of simple columnar epithelium.
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Cytology of small-intestinal mucosa
Enterocytes are columnar absorptive epithelial cells on the villi; with a brush border (many microvilli); are held apically by junctional complexes; the many vesicles at the base of the microvilli communicate with agranular ER. They have a glycocalyx, which overlies the microvilli and binds various enzymes, including disaccharidases and dipeptidases. They have well-developed tight junctions and zonula adherens.
a. Goblet cells, with the nucleus, GER and Golgi apparatus basally, stored mucigen droplets apically.
Paneth cells, with eosinophil granules holding defensin and enzymes and tumor necrosis factor alpha and display extensive RER (basally), a large supranuclear Golgi complex, and many mitochondria. These agents have the capability of killing bacteria as well as certain protozoa.
Enteroendocrine cells with hormone- and serotonin-containing basal granules. They secrete gastrin, cholecystokinin, gastric inhibitory peptide, and several other hormones Some of the open DNES cells possess taste receptors similar to those of the taste buds located on the tongue. It is important to note that the taste cells of the gastrointestinal tract communicate with the islets of Langerhans, signaling the beta cells to release insulin once sweet taste is detected in the lumen.
a. Undifferentiated columnar crypt stem cells: few microvilli; able to divide, migrate,
differentiate into the other kinds, function, and be extruded at the villus tip, over
approximately four days.
b. Villus core has the basal lamina for the epithelium, a central lymphatic capillary
(lacteal), blood vessels, smooth muscle fibers. The loose stroma of reticular and elastic
fibers is heavily infiltrated by WBCs, e.g., CD4+ helper-inducer lymphocytes and
eosinophils, and plasma cells.
c. Ileum has Peyer's patches of extensive lymphoid tissue, erasing villi, breaking into
the epithelium, and interrupting the muscularis mucosae to invade the submucosa.
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Elsewhere, only solitary lymphoid nodules are to be seen. The epithelium domed over
the Peyer's-patch follicles is specialized, with M cells, which transport antigen and
otherwise assist immune functions.
Functions of small-intestinal mucosa 1. Secretory
a. Goblet cells give mucus.
b. Columnar cells make disaccharidases and other digestive enzymes which, as ecto-
enzymes, remain tethered in the microvillous membrane, so constituting one
component of the glycocalyx.
c. Paneth cells form defensins, etc, for defense.
d. Endocrine cells produce hormones to coordinate the functions of the gut, liver and
pancreas.
e. Simple tubular intestinal glands/glands of Lieberkuhn also contribute to the enteric
juice. These secretions are additional to those already present from:
f. Salivary and esophageal glands.
g. Stomach mucosa.
h. Pancreas and liver, introduced into the duodenum.
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i. Brunner's duodenal glands (alkaline mucus led into the bottom of crypts).
2. Gut mucosal absorption of materials degraded by the secretions.
a. Membrane transports, active and passive, of many kinds, with appropriate pumps,
channels, and transporters. The tricky part is to get lipid in across a barrier based on
lipids - the cell membrane, and back out again.
b. Pathway, through the absorptive cell, from the lumen to the lacteal capillary lumen
for lipid:
i. hydrolysis, by mostly pancreatic lipase, of the dietary triacylglycerols;
ii. interaction of the resulting free fatty acids and monoacylglycerol with bile, to form
micelles for solubilization;
iii. in this form, the lipids can be transported through the enterocyte's apical
membrane;
iv. In the apical smooth ER (SER), the lipids are re-acylated to triacylglycerol, and
bound to a protein for intracellular transport.
v. Meanwhile, the GER is producing proteins to which some lipid is added -
apolipoproteins - which meet up with the apically reacylated lipid at the SER,
where
vi. The apoplipoprotein is used as a kind of cage, into the core/interior of which
increasing amounts of lipid are introduced, as the lipid droplet - the chylomicron -
is assembled.
vii. The Golgi complex is the accumulation centre for the chylomicrons before their
basolateral secretion by exocytosis into the baso-lateral intercellular space.
viii.The chylomicrons and similar smaller lipid bodies pass through the basal lamina to
enter the lacteal lymph capillary, giving the gut and mesenteric lymphatic vessels
their white color, and constituting chyle.
3. Devices for increasing the effective gut surface area for absorption:
a. the long length of the gut;
b. villi;
c. microvilli on absorbing cells;
d. plicae circulares/valves of Kerckring high folds of mucosa
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e. Contractions of villus muscle, muscularis mucosae, and two main muscle coats;
(microvilli can slowly elongate, but not contract and relax.)
4. Changes within small intestine during descent:
a. Goblet cells increase in number.
b. Villi become more finger-like.
c. Lymphoid tissue increases.
d. Plicae circulares diminish.
5. Protective mechanisms of the gut:
a. alkaline mucus of Brunner's glands;
b. lubricating and protective goblet-cell mucus;
c. immune responses by APCs, lymphocytes and plasma cells;
d. rapid reactions of eosinophils, macrophages, and neutrophils
e. lysozyme and other antimicrobial contributions of Paneth cells;
f. barrier of tight junctions between the enterocytes;
g. diarrhea;
h. Rapid regeneration by the epithelium.
LARGE INTESTINE
General features
• Crypts, but no villi or plicae circulares.
• Columnar epithelial cells are
i. Undifferentiated
ii. Goblet (numerous);
iii. Colonocytes, absorbing, with microvilli, for
water, and some products of bacterial
metabolism of the faeces; (some excretion
occurs).
iv. Endocrine cells are also present.
• Dehydrating faeces need lubrication; hence many goblet cells are present in the simple
columnar epithelium.
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Regional details of large intestine
a. Colon and caecum: outer longitudinal muscle coat is gathered into three bands -
taeniae coli - which pucker or sacculate the tube, forming haustrations.
b. Appendix: continuous muscle coats; few crypts; the
mucosa is mainly occupied by lymphoid tissue; the
muscularis mucosae may be deficient and lymphoid
tissue seen in the submucosa. The wall may be thick.
With age the lumen may be blocked off/occluded by
fibrosis.
c. Rectum: outer longitudinal muscle is one continuous sheet.
d. Anal canal
i.Morgagni's anal columns are 6-10 vertical mucosal folds.
ii.Dentate line lies at the level of the bases of the columns, where there are tiny flaps
and pockets - anal valves and sinuses.
iii.The histological epithelial anal transitional zone (ATZ) lies between unbroken
simple columnar colo-rectal epithelium and lower stratified squamous epithelium.
iv.The ATZ - the common site of anal cancers - is very variable in its extent and outline,
in its kinds of epithelia, and the number of crypts.
v.Submucosal veins display periodic dilations. Deterioration of their supporting
connective tissue permits enlargement and prolapsed
vi.Hemorrhoids.
vii.The complex anal musculature includes external skeletal-muscle and internal
smooth-muscle sphincters. (The muscles and their innervations are particularly at risk
of stretching and damage in women giving birth.)
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ENTEROENDOCRINE CELLS
• They are widely distributed throughout the stomach and intestine, and are part of the
APUD system.
Morphology
1. Enteroendocrine cells usually are wedge-shaped cells tucked in among the other
epithelial cells. Some enteroendocrine cells contact the lumen using their surface
microvilli; other cells do not. All cells rest on the basement membrane and contain
prominent granules. There are many morphologic classes of granules.
2. Enteroendocrine cells synthesize polypeptide hormones such gastrin,
cholecystokinin, and secretin. The precise physiologic role of each hormone in
digestion is not always well –delineated.
3. Some enteroendocrine cells secrete candidate hormones, polypeptide that has a
well-defined set of pharmacologic properties but a poorly understood physiologic role
in digestion. Motilin and VIP (vasoactive intestinal peptide) are examples of candidate
hormones.
Gastric enteroendocrine cells
1. G cells secrete gastrin, a polypeptide that stimulates secretion of hydrochloric acid
(HCl) by parietal cells. G cells are present throughout the lower portion of the stomach
end are particularly prominent in the pyloric antrum.
2. EC cells secrete serotonin, which influences gut motility. EC cells are scattered
throughout the gastric mucosa.
3. A cells secrete glucagon and are present only in the upper one-third of the gastric
mucosa.
4. D cells secrete somatostatin and are present in the upper and lower portions of the
stomach. D cells are sparse, if present at all, in the middle portion.
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Intestinal enteroendocrine cells
1. D cells secrete somatostatin and are present in the duodenum. A subclass of D cells
secretes VIP, which regulates water and ion secretion and gut motility.
2. EC cells, prevalent throughout the intestines, secrete serotonin, motilin, and
substance P. These hormones are thought to regulate gut motility.
3. G cells, present in the duodenum and pylorus, secrete gastrin, which regulates
parietal cell secretion of HCl.
4. I cells, present in the small intestines, secrete cholecystokinin, a peptide that
influences pancreatic secretion and gallbladder emptying.
5. K cells, present in the small intestines, secrete gastric inhibitory peptide (GIP), a
peptide that is antagonistic to gastrin.
6. L cells, present in the small intestines and colon, secrete glucagon, a polypeptide
that alters hepatic glycogenolysis.
7. S cells secrete secretin, a peptide that modifies pancreatic and biliary water and ion
secretion.