G I T PHYSIOLOGY NOTES

INTRODUCTION 1 Introduction 2
 All living organisms require nutritive substances and water for  Functions of the digestive system includes;
survival and growth.
1. Motility – this refers to the movement of food through the digestive
 Unlike plants which can form organic molecules using inorganic tract via the processes of (a) Ingestion: taking food into the mouth.( b)
compounds such as, CO2 , H2O and ammonia, humans and other mastication: chewing the food and mixing it with saliva.(c) deglutition:
animals most obtain their basic organic molecules from food. swallowing the food. (d) peristalsis: rhythmic wave like
contractions that move the food through the GIT.
 Food is taken in in its polymeric form, broken down by
2. Secretion – this include both endocrine and exocrine secretions. (a)
mastication and other GI processes then hydrolysed into
exocrine: H2O, Hcl, bicarbonate and many digestive enzymes are
monomers after which absorption via the intestinal mucosa into
secreted into the lumen of the GI tract. The stomach is said to secrete 2-
blood and lymph takes place. 3 litres of gastric juice daily.(b) endocrine: hormones of the stomach and
intestines.
 Digestion and absorption are the primary function of the
digestive system. 3. Digestion – this refers to the mechanical and chemical breakdown of
food substances into their smaller sub units which can be easily
 Unlike certain lower animals that have a single opening for absorbed.
ingestion and excretion( planaria), the lumen of the GIT
communicate with the environment at both ends. Through the 4. Absorption- this refers to the passage of digested end product into the
mouth and the anus. blood or lymph.

5. Storage and elimination- this refers to the temporary storage and

 The two open ends of the digestive tract permit one way
subsequent elimination of indigestible food molecules.
transport, which is ensured by a wave like muscle contraction and
by action of sphincter muscles.
 Introduction 3
 Anatomically and functionally the digestive system can be
divided into the tubular GIT and accessory organs.

 The GIT is about 9m(30ft) long and extends from the mouth
to the anus.

 Parts of the GIT include the mouth, pharynx, oesophagus,

stomach, small intestine, and large intestine.

 Accessory organs include: teeth, tongue, salivary glands,

exocrine part of the pancreas, liver, gall bladder.

Introduction 4
 Layers of the GIT;
1. mucus layer Introduction 5
2. Sub mucus layer
 Sub mucus layer;
3. Muscular layer
1. Is absent in the mouth and pharynx
4. Serous or fibrous layer.
2. Extends from the oesophagus onwards
 Mucus layer – lines the lumen of the GIT, it is the absorptive
3. A highly vascular layer of connective tissue that serve the
and major secretory layer of the GIT. It consist of the
mucosa
following parts; (a) Epithelial lining: This part is in direct
contact with the content of the GIT, and its cells vary in 4. Molecules absorbed from the columnar epithelial cells of
different parts of the GIT. The inner surface of the mouth, the mucosa enter through the blood and mucosal cells of
surface of the tongue, inner surface of the pharynx and the submucosa
oesophagus have stratified squamous epithelial cells
whereas the mucous membrane lining the rest of the GIT 5. The submucosa also contains glands and nerve plexuses
have columnar epithelial cells. (b) Lamina propria: The (meissner’s or submucosal plexus) which provide autonomic
epithelial tissue is supported by the lamina propria, which is nerve supply to the muscularis mucosae.
a thin layer of areolar connective tissue containing
numerous lymph nodules, fibroblast, macrophages,
Introduction 6
lymphocytes and eosinophils. (c) Muscularis
 Muscular layer;
mucosae: this lies just external to the lamina propria. It is
responsible for the numerous small folds in certain portions 1. Also known as muscularis externa
of the GIT; these folds increase the absorptive surface area.
2. The lips, cheeks and walls of the pharynx have skeletal
It should be noted that the muscularis mucosae is absent in
muscle fibres
the mouth and pharynx.
3. The oesophagus has both skeletal and smooth muscle fibre.
4. This layer is responsible for segmental contractions and  Serous or fibrous layer;
peristaltic movement through the GI tract
1. The outermost layer of the wall of the GI tract is called
5. The muscularis has an inner circular and outer longitudinal serous or fibrous layer.
through the GI tract but has an additional inner oblique
2. The serous layer is a binding and protective layer consisting
layer in the stomach thus making the circular layer in the
of areolar connective tissue covered with a layer of simple
stomach middle.
squamous epithelium.
6. Contraction of these layers moves the food through the GI
tract and physically pulverizes and mixes the food with 3. The fibrous layer also called fibrosa is formed by connective
digestive enzymes.
tissue and it covers the pharynx and oesophagus.
7. The myenteric or Auerbach plexus is located between the
muscle layers. Diagrammatic representation of the layers of
8. The myenteric plexus provides the main nerve supply of the the intestine.
GI tract and includes fibres and ganglia from both the
sympathetic and parasympathetic divisions of the
autonomic nervous system.

9. Thus the Auerbach’s plexus is present between the inner

circular and outer longitudinal layer.

10. The inner circular layer of muscle in the anal canal

constitutes the internal anal sphincter, whereas the external
anal sphincter is made up of skeletal muscle.

Introduction 7
 The Enteric Nervous System
 Two major networks of nerve fibres are intrinsic to the
gastrointestinal tract: the myenteric plexus (Auerbach's
plexus), between the outer longitudinal and middle circular
muscle layers, and the submucous plexus (Meissner's
plexus), between the middle circular layer and the mucosa

 Collectively, these neurons constitute the enteric nervous

system.

 The system contains about 100 million sensory neurons,

interneurons, and motor neurons in humans—as many as
are found in the whole spinal cord—and the system is
probably best viewed as a displaced part of the CNS that is
concerned with the regulation of gastrointestinal function

 It is connected to the CNS by parasympathetic and

sympathetic fibres but can function autonomously without
these connections.

 The myenteric plexus innervates the longitudinal and

circular smooth muscle layers and is concerned primarily
with motor control, some nerve fibres of this plexus
accelerate movement by secreting excitatory
neurotransmitters
 Like Ach, serotonin and substance p, while other fibres  Other sympathetic fibres appear to end directly on
secrete inhibitory neurotransmitters such as VIP, neurotensi intestinal smooth muscle cells.
and enkephalin.
 Still other fibres innervate blood vessels, where they
 Whereas the submucous plexus innervates the glandular produce vasoconstriction. It appears that the intestinal
epithelium, intestinal endocrine cells, and submucosal blood blood vessels have a dual innervation; they have an extrinsic
vessels and is primarily involved in the control of intestinal noradrenergic innervation and an intrinsic innervation by
secretion. fibers of the enteric nervous system.

 VIP and NO are among the mediators in the intrinsic

innervation, which seems among other things to be
 Extrinsic Innervation
responsible for the hyperaemia that accompanies digestion
 The intestine receives dual extrinsic innervations from the of food.
autonomic nervous system, with parasympathetic
cholinergic activity generally increasing the activity of
intestinal smooth muscle and sympathetic noradrenergic  Saliva is the watery fluid secreted in the mouth; it is
activity generally decreasing it while causing sphincters to produced by the salivary glands.
contract.
 Salivary glands secrete about 1 – 1.5l of saliva per day.
 The preganglionic parasympathetic fibres consist of about
2/3 of the saliva comes from the submandibular gland and 1/4 from
2000 vagal efferents and other efferents in the sacral
the parotid gland.
nerves. They generally end on cholinergic nerve cells of the
myenteric and submucous plexuses.  Specific gravity of saliva is 1.002 – 1.012
 The sympathetic fibres are postganglionic, but many of  The rate of secretion varies with the activity of the body
them end on postganglionic cholinergic neurons, where the
norepinephrine they secrete inhibits acetylcholine secretion
by activating 2 presynaptic receptors.
 Thus under basal conditions the output of saliva is 0.5ml/ batholins duct into the oral cavity. Its secretion is
minute and during mastication it rises to about predominantly mucinous.
4.0ml/minute
 Other minor salivary glands; lingual mucus glands, lingual
 There are two main types of secretion from salivary glands; serous gland, buccal glands, labial glands, palatal glands.

1. A serous secretion containing an alpha amylase (previously

known as ptyalin); this is the enzymes for the digestion of
starches. Composition of saliva
2. A mucous secretion, containing mucin, which is important  Saliva contains 99.5% water and 0.5% solutes.
for lubrication purposes.
 The solutes can be classified as organic, inorganic, and
3. There is also lingual lipase, secreted by the Ebners gland. gases.

 Gases include oxygen, carbon dioxide, and nitrogen.

 Human saliva is secreted by three main salivary glands  The organic substances are made up of enzymes; amylase,
maltase, lingual lipase, lysozyme, phosphatase, carbonic
 Parotid glands; are the largest of the salivary glands, it
anhydrase etc. And other organic substances like mucin and
empties into the oral cavity via the stensons duct. Its
albumin, blood group antigens, amino acids, creatinine,
secretion is mainly serous
xanthine etc.
 Submaxillary gland, saliva from these glands empty into the
 Inorganic substances like sodium, calcium, potassium,
oral cavity via the Whartons duct, its secretions are
bicarbonate, bromide, chloride, fluoride, phosphate etc.
seromucinous.

 Sublingual glands; is the smallest of the major types of

glands. They empty into the duct of ravinus and via the
Submucous gland
Ionic Composition of Saliva
 The ionic composition of saliva varies considerably from
species to species and from gland to gland.

 In general, however, saliva secreted in the acini is probably

isotonic, with concentrations of Na+, K+, Cl–, and HCO3– that
are close to those in plasma.

 The excretory ducts and probably the intercalated ducts

that drain into them modify the composition of the saliva by
extracting Na+ and Cl– and adding K+ and HCO3–.

 The ducts are relatively impermeable to water. Therefore, at

low salivary flows, the saliva that reaches the mouth is
hypotonic, slightly acidic, and rich in K+ but relatively
depleted of Na+ and Cl–.

 When salivary flow is rapid, there is less time for ionic

composition to change in the ducts. Consequently, although
still hypotonic in humans, saliva is closer to isotonic, with
higher concentrations of Na+ and Cl–.

 Aldosterone increases the K+ concentration and

reduces the Na+ concentration of saliva in an action
analogous to its action on the kidneys.
 Functions of saliva  It aids swallowing, the mucin content act as a lubricant.

 Lingual lipase secreted by the Ebners gland is active in the

 Alpha amylase aids in the digestion of cooked starch.
stomach and digest up to 30% of triglycerides in the
 It aids in speech by keeping the mouth moist, so that the stomach.
lips and tongue can move easily to produce speech.
 Regulation of water balance
 It is important for the appreciation of taste, as it enables
 Regulation of body temperature, in lower animals.
molecules to dissolve on the surface of the tongue thereby
bringing the molecule in contact with the taste buds leading
Control of Salivary Secretion
to the stimulation of taste buds.
 Salivary secretion is under neural control. Stimulation of the
 It is important for dental and oral hygiene, by washing away
parasympathetic nerve supply causes profuse secretion of
oral pathogenic bacteria and food particles that provide
watery saliva with a relatively low content of organic
metabolic support for the oral pathogens. Thus decreasing
material.
the risk for dental caries and halitosis. Dental caries are also
inhibited by salivary bicarbonate which neutralizes residual  Associated with this secretion is a pronounced vasodilation
acids. in the gland, which appears to be due to the local release of
VIP. This polypeptide is a co-transmitter with acetylcholine
 It is bactericidal, the thiocyanate ions and proteolytic
in some of the postganglionic parasympathetic neurons.
enzymes in saliva (lysozymes) help to kill oral bacteria.
 Atropine and other cholinergic blocking agents reduce
 It prevents calcium from dissolving out of the teeth, at its
salivary secretion.
normal pH of 7.0. Saliva is saturated with calcium ions and
thus prevents calcium loss from the teeth.  Stimulation of the sympathetic nerve supply causes
vasoconstriction and, in humans, secretion of small amounts
 It provides optimal pH for the digestive function of salivary
of saliva rich in organic constituents from the
amylase.
submandibular glands.
 Food in the mouth causes reflex secretion of saliva, and so 1. It serves as a short-term storage reservoir, allowing a rather
does stimulation of the vagal afferent fibers at the gastric large meal to be consumed quickly and dealt with over an
end of the oesophagus. Salivary secretion is easily extended period of time.
conditioned, as shown in Pavlov's original experiments
2. It is in the stomach that substantial enzymatic digestion is
Applied physiology initiated, particularly of proteins.

3. Vigorous contractions of gastric smooth muscle mix and grind

 Hypo salivation
foodstuffs with gastric secretions, resulting in liquefaction of food,
 Xerostomia a prerequisite for delivery of the ingesta to the small intestine.

 Hyper salivation 4. As food is liquefied in the stomach, it is slowly released into the
small intestine for further processing.
 Chorda tympani syndrome

 Paralytic secretion of saliva

 Core gastric physiology is presented as the following
 Mumps topics:
 Sjogren’s syndrome.  Gross and microscopic anatomy of the stomach

Gastric physiology  Gastric motility - filling and emptying

 Foodstuffs entering the stomach have been, to at least  Gastric secretions

some extent, crushed and reduced in size by mastication,
 Absorption in the stomach
and impregnated with saliva. The stomach provides four
basic functions that assist in the early stages of digestion  One meal in the life of the stomach
and prepare the ingested meals for further processing in the
small intestine:
Gross and microscopic anatomy of
the stomach.
  The wall of the stomach is structurally similar to other parts
of the digestive tube, with the exception that the stomach
has an extra, oblique layer of smooth muscle inside the
circular layer, which aids in performance of complex
grinding motions.

 In the empty state, the stomach is contracted and its

mucosa and submucosa are thrown up into distinct folds
called rugae; when distended with food, the rugae are
"ironed out" and flat. The image to the right shows rugae on
the surface of a dog's stomach.

 Within the stomach there is an abrupt transition from

stratified squamous epithelium extending from the
 The stomach is an expanded section of the digestive tube oesophagus to a columnar epithelium dedicated to
between the oesophagus and small intestine. Its secretion.
characteristic J shape is shown, along with terms used to
 In most species, this transition is very close to the
describe the major regions of the stomach. Seen in the
oesophageal orifice, but in some, particular horses and
figure on the left in the slide above.
rodents, stratified squamous cells line much of the fundus
 The right side of the stomach shown above is called the and part of the body.
greater curvature and that on the left the lesser curvature.
 The image to the right is of the mucosal surface of an
 The most distal and narrow section of the stomach is equine stomach showing oesophageal epithelium (top) and
termed the pylorus - as food is liquefied in the stomach it glandular epithelium (bottom). The creatures attached to
passé \\s through the pyloric canal into the small intestine. the surface are bots, larval forms of Gasterophilus.
 In humans, the stomach has columnar epithelium 1. Mucous cells: secrete an alkaline mucus that protects the
epithelium against shear stress and acid

2. Parietal cells: secrete hydrochloric acid

3. Chief cells: secrete pepsin, a proteolytic enzyme

4. G cells: secrete the hormone gastrin

5. Enterochromaffin cells; secretes serotonin

6. Enterochromaffin like cells; secretes histamine

 There are differences in the distribution of these cell types

among regions of the stomach - for example, parietal cells
are abundant in the glands of the body, but virtually absent
in pyloric glands.

 The micrograph below shows a gastric pit invaginating into

the mucosa (fundic region of a raccoon stomach).
 If the lining of the stomach is examined with a hand lens,
one can see that it is covered with numerous small holes.  Notice that all the surface cells and the cells in the neck of
These are the openings of gastric pits which extend into the the pit are foamy in appearance - these are the mucous
mucosa as straight and branched tubules, forming gastric cells.
glands.  The other cell types are farther down in the pit and, in this
 Four major types of secretory epithelial cells cover the image, difficult to distinguish.
surface of the stomach and extend down into gastric pits 
and glands:
Diagram showing cross- section of the GI
tract

Gastric motility: filling and emptying

 Contractions of gastric smooth muscle serves two basic
functions:
 Ingested food is crushed, ground and mixed, liquefying it to effective gastric grinder; they occur about 3 times per
form what is called chyme. minute in people and 5 to 6 times per minute in dogs.
Gastric distension strongly stimulates this type of
 Chyme is forced through the pyloric canal into the small
contraction, accelerating liquefaction and hence, gastric
intestine, a process called gastric emptying.
emptying. The pylorus is functionally the part of this region
 The stomach can be divided into two regions on the basis of of the stomach - when the peristaltic contraction reaches
motility pattern: an accordian-like reservoir that applies the pylorus, its lumen is effectively obliterated - chyme is
constant pressure on the lumen and a highly contractile thus delivered to the small intestine in spurts.
grinder.
 The lower stomach, composed of the lower body and
 The upper stomach, composed of the fundus and upper antrum, develops strong peristaltic waves of contraction
body, shows low frequency, sustained contractions that are that increase in amplitude as they propagate toward the
responsible for generating a basal pressure within the pylorus.
stomach.
 These powerful contractions constitute a very effective
 Importantly, these tonic contractions also generate a gastric grinder; they occur about 3 times per minute in
pressure gradient from the stomach to small intestine and people and 5 to 6 times per minute in dogs.
are thus responsible for gastric emptying.
 Gastric distension strongly stimulates this type of
 Interestingly, swallowing of food and consequent gastric contraction, accelerating liquefaction and hence, gastric
distention inhibits contraction of this region of the stomach, emptying.
allowing it to balloon out and form a large reservoir without
 The pylorus is functionally part of this region of the
a significant increase in pressure.
stomach - when the peristaltic contraction reaches the
 The lower stomach, composed of the lower body and pylorus, its lumen is effectively obliterated - chyme is thus
antrum, develops strong peristaltic waves of contraction delivered to the small intestine in spurts.
that increase in amplitude as they propagate toward the
pylorus. These powerful contractions constitute a very
  Liquids readily pass through the pylorus in spurts, but solids
must be reduced to a diameter of less than 1-2 mm before
passing the pyloric gatekeeper.

 Larger solids are propelled by peristalsis toward the

pylorus, but then refluxed backwards when they fail to pass
through the pylorus - this continues until they are reduced
in size sufficiently to flow through the pylorus.

 At this point, you may be asking "What happens to solids

that are indigestible - for example, a rock or a penny?

 Will it remain forever in the stomach?" If the indigestible

 Gastric motility is controlled by a very complex set of neural solids are large enough, they indeed cannot pass into the
and hormonal signals. small intestine, and will either remain in the stomach for
long periods, induce a gastric obstruction or, as every cat
 Nervous control originates from the enteric nervous system owner knows, be evacuated by vomiting.
as well as parasympathetic (predominantly vagus nerve) and
sympathetic systems.  However, many of the indigestible solids that fail to pass
through the pylorus shortly after a meal do pass into the
 A large battery of hormones has been shown to influence small intestine during periods between meals.
gastric motility - for example, both gastrin and
cholecystokinin act to relax the proximal stomach and  This is due to a different pattern of motor activity called the
enhance contractions in the distal stomach. migrating motor complex, a pattern of smooth muscle
contractions that originates in the stomach, propagates
 The bottom line is that the patterns of gastric motility likely through the intestines and serves a housekeeping function
are a result from smooth muscle cells integrating a large to periodically sweep out the gastrointestinal tract
number of inhibitory and stimulatory signals.
 pepsinogen and inactivation of ingested microorganisms
such as bacteria.

 Proteases: Pepsinogen, an inactive zymogen, is secreted

into gastric juice from both mucous cells and chief cells.
GASTRIC SECRETIONS Once secreted, pepsinogen is activated by stomach acid into
the active protease pepsin, which is largely responsible for
the stomach's ability to initiate digestion of proteins. In
 Other than the function of storage, churning and grinding of young animals, chief cells also secrete chymosin (renin), a
food substances, the other functions of digestion, protease that coagulates milk protein allowing it to be
protection, haemopoesis and excretion are imbedded into retained more than briefly in the stomach.
the functions of gastric juice. The stomach is famous for its  Hormones: The principal hormone secreted from the gastric
secretion of acid, but acid is only one of four major epithelium is gastrin, a peptide that is important in control
secretory products of the gastric epithelium, all of which are of acid secretion and gastric motility.
important either to the digestive process or to control of
gastric function:

 Mucus: The most abundant epithelial cells are mucous cells, Properties and composition of gastric
which cover the entire luminal surface and extend down juice
into the glands as "mucous neck cells". These cells secrete
bicarbonate-rich mucus that coats and lubricates the gastric Gastric juice is the mixture of secretions from different
surface, and serves an important role in protecting the glands of the stomach.
epithelium from acid and other chemical insults.
PROPERTIES OF GASTRIC JUICE.
 Acid: Hydrochloric acid is secreted from parietal cells into
 Volume : 1200 to 1500 ml/day. Secretions up to 3000ml
the lumen where it establishes an extremely acidic
have been documented.
environment. This acid is important for activation of
 Reaction : gastric juice is highly acidic with pH of 0.9 to 1.2.  Bicarbonate
The acidity of gastric juice is due to the presence of
 Chloride
hydrochloric acid.
 Phosphate
 Specific gravity : 1.002 to 1.004
 Sulphate
COMPOSITION OF GASTRIC JUICES

 Gastric juice contains 99.5% of water and 0.5% solids. Mechanism of Acid Secretion
The solids are organic and inorganic substances as follows.  The hydrogen ion concentration in parietal cell secretions is
roughly 3 million fold higher than in blood, and chloride is
 Pepsin
secreted against both a concentration and electric gradient.
 Rennin
 Thus, the ability of the parietal cell to secrete acid is
 Gastric lipase dependent on active transport.

 Gelatinasse  The key player in acid secretion is a H+/K+ ATPase or "proton

pump" located in the cannalicular membrane.
 Urease
 This ATPase is magnesium-dependent, and not inhabitable
 Mucus by ouabain.
 Intrisinc factor  The current model for explaining acid secretion is as follows:
 Hydrochloric acid

 Sodium  Hydrogen ions are generated within the parietal cell from
 Calcium dissociation of water. The hydroxyl ions formed in this
process rapidly combine with carbon dioxide to form
 Potassium
 bicarbonate ion, a reaction cataylzed by carbonic  Parietal cells bear receptors for three stimulators of acid
anhydrase. secretion, reflecting a triumverate of neural, paracrine and
endocrine control:
 Bicarbonate is transported out of the basolateral membrane
in exchange for chloride. 1. Acetylcholine (muscarinic type receptor)

 The outflow of bicarbonate into blood results in a slight 2. Gastrin

elevation of blood pH known as the "alkaline tide".
3. Histamine (H2 type receptor)
 This process serves to maintain intracellular pH in the
 Histamine from Enterochromaffin-like cells may well be the
parietal cell.
primary modulator, but the magnitude of the stimulus
 Chloride and potassium ions are transported into the lumen appears to result from a complex additive or multiplicative
of the cannaliculus by conductance channels, and such is interaction of signals of each type.
necessary for secretion of acid.
 For example, the low amounts of histamine released
 Hydrogen ion is pumped out of the cell, into the lumen, in constantly from mast cells in the gastric mucosa only weakly
exchange for potassium through the action of the proton stimulate acid secretion, and similarly for low levels of
pump; potassium is thus effectively recycled. gastrin or acetylcholine. However, when low levels of each
are present, acid secretion is strongly forced
 Accumulation of osmotically-active hydrogen ion in the
cannaliculus generates an osmotic gradient across the  . Additionally, pharmacologic antagonists of each of these
membrane that results in outward diffusion of water - the molecules can block acid secretion.
resulting gastric juice is 155 mM HCl and 15 mM KCl with a
 Histamine's effect on the parietal cell is to activate
small amount of NaCl
adenylate cyclase, leading to elevation of intracellular cyclic
AMP concentrations and activation of protein kinase A
(PKA).
Control of Acid Secretion
 One effect of PKA activation is phosphorylation of  Somatostatin inhibits secretion of gastrin and histamine,
cytoskeletal proteins involved in transport of the H+/K+ and appears to have a direct inhibitory effect on the parietal
ATPase from cytoplasm to plasma membrane. cell.

 Binding of acetylcholine and gastrin both result in elevation

of intracellular calcium concentrations.
Drug therapy for suppressing gastric acid
secretion.
 Several additional mediators have been shown to result in
gastric acid secretion when infused into animals and people,  Understanding the mechanisms involved in secretion of acid
including calcium, enkephalin and bombesin. from the parietal cell led to development of several drugs
capable of inhibiting acid secretion. These drugs are widely
 Calcium and bombesin both simulate gastrin release, while
used in humans for treatment of acid reflux disorders such
opiate receptors have been identified on parietal cells.
as heartburn and gastroesophageal reflux disease.
 It is unclear whether these molecules have a significant
 The most effective inhibitors fall into two classes.
physiologic role in parietal cell function.
 H2 Receptor Antagonists
 A variety of substances are capable of reducing gastric acid
secretion when infused intravenously, including  Histamine is clearly one of the primary regulators of acid
prostaglandin E2 and several peptides hormones, including secretion, and the parietal cell receptor for histamine is of
secretin, gastric inhibitory peptide, glucagon and the H2 type.
somatostatin.
 Evidence of histamine's role in acid secretion is strongly
 PGE2, secretin and somatostatin may be physiologic supported by finding that H2 receptor antagonists are quite
regulators. effective in inhibiting acid secretion.

 Examples of H2 antagonists commonly used to suppress

gastric acid secretion include cimetidine (Tagamet HB),
 ranitidine (Zantac 75), famotidine (Pepcid AC) and nizatidine  Other inhibitors, including lansoprazole (Prevacid),
(Axid AR). esomeprazole (Nexium), rabeprazole (Aciphex) and
pantoprazole (Protonix) have similar modes of action.
 These drugs, particularly cimetidine, are among the most
widely prescribed drugs in man.

 They are also useful for management of certain gastric

diseases in dogs and horses.

 Antihistamines that engage H1 receptors (e.g. those used to

treat colds) have no effect on acid secretion. METHODS OF STUDY OF REGULATION OF
GASTRIC SECRETIONS
 Proton Pump Inhibitors

 Acid secretion is absolutely dependent on function of the

Pavlov’s pouch
H+/K+ ATPase or proton pump located in the cannilicular
membrane of the parietal cell.  Pavlov’s pouch was designed by Russian scientist Pavlov in
dogs during his studies on conditioned reflexes
 Several drugs have been developed that non-competively
bind and inactivate the ATPase, resulting in strong inhibition  A part of the stomach is incompletely separated from the
of acid secretion. main portion and made into a small bag like pouch, which is
called the Pavlov’s pouch
 Omeprazole (Prilosec) is an acid-activated prodrug that
binds covalently to two cysteines on the ATPase, resulting in  The pouch receives it’s nerve supply from the vagus nerve
its irreversible inactivation. (parasympathetic) and its sympathetic supply from nerve
fibers running through the blood vessels.
 The pouch is used to demonstrate different phases of Sham feeding
gastric secretion particularly the cephalic phase and is used
 Otherwise called false feeding, it was devised by Pavlov to
to demonstrate the role of the vagus in the cephalic phase.
demonstrate the regulation of gastric secretion.
Heidenhain’s pouch
 A hole is made on the neck of an anesthetized dog
 The heidenhain’s pouch is a modification of the pavlov’s
 Oesophagus is transversely cut. The cut ends are drawn out
pouch ,so in this case there is a complete separation of the
through the neck.
pouch from the isthmus resulting in a disconnection in the
parasympathetic supply. However sympathetic supply is  When the dog eats food, it comes out through the cut end
maintained as the blood vessels are not severed. of the oesophagus
 This pouch is useful in demonstrating the role of the  But the dog has the satisfaction of eating the food. It is
sympathetic nerve and hormones in regulating gastric acid called sham feeding.
secretion after vagotomy.
 This experimental procedure is supported by the
preparation of pavlov’s pouch with a fistula from the
stomach. The fistula opens to the exterior and it is used to
Bickel’s pouch
observe the gastric secretion . The animal is used for
 This is a completely denervated pouch. It is used to experimental purpose after a weeks time when healing is
demonstrate the roles of hormones in gastric secretions. completed.

Farrel and Ivy pouch Advantage of sham feeding.

 This is a transplanted bickel’s pouch in this case the pouch is  It is useful to demonstrate the secretion of gastric juice
transplanted into subcutaneous tissues of the abdominal during cephalic phase. In the same animal after vagotomy,
wall in the same animal. New blood vessels develop after sham feeding does not induce gastric secretion. It proves
some days. This pouch is used to study the role of hormones the role of the vagus nerve during cephalic phase.
during the gastric and intestinal stage of gastric secretion.
One meal in the life of the stomach system, resulting in release of acetylcholine in the vicinity of
G cells and parietal cells. Binding of acetylcholine to its
 The stomach functions dynamically, in parallel with meals. receptor on G cells induces secretion of the hormone
Consider the stomach's most notable activity - secretion of gastrin, which, in concert with acetylcholine and histamine,
acid. Acid is secreted in large quantities when the stomach stimulates parietal cells to secrete small amounts of acid.
is distended with food, which is useful because it facilitates Additionally, a low level of gastric motility is induced. In
the initial breakdown of proteins. However, once the meal essense, the gastric motor is turned on and begins to idle.
has been liquefied and the stomach has emptied, acid
 Gastric phase ("full steam ahead"): When a meal enters the
secretion trickles to a stop and remains shut off during the
stomach several additional factors come into play, foremost
interdigestive period. This shut-off in acid secretion is a
among them distension and mucosal irritation.
good thing - otherwise excessive acid would damage the
mucosa of the stomach and small intestine, as happens in  Distension excites stretch receptors and irritation activates
certain disease states. chemoreceptors in the mucosa. These events are sensed by
enteric neurons, which secrete additional acetylcholine,
 Gastric function is often classified into three phases in which
further stimulating both G cells and parietal cells; gastrin
secretory and motor activities are tightly coupled. Try
from the G cells feeds back to the parietal cells, stimulating
identifying these phases in yourself or your loved ones
it even further. Additionally, activation of the enteric
around meal time:
nervous system and release of gastrin cause vigorous
 smooth muscle contractions. The net result is that secretory
and motor functions of the stomach are fully turned on -
 Cephalic phase ("wake up call"): Seeing, smelling and lots of acid and pepsinogen are secreted, pepsinogen is
anticipating food in perceived in the brain and the brain converted into pepsin and vigorous grinding and mixing
informs the stomach that it should prepare for receipt of a contractions take place. However, there is a mechanism in
meal. place in the stomach to prevent excessive acid secretion - if
 This communication is composed of parasympathetic stimuli luminal pH drops low enough (less than about 2), motility
transmitted through the vagus nerve to the enteric nervous and secretion are temporarily suspended.
 Intestinal phase ("step on the brakes"): As food is liquefied
in the stomach, it is emptied into the small intestine. Its
seems to be important for the small intestine to be able to
slow down gastric emptying, probably to allow it time to
neutralize the acid and efficiently absorb incoming
nutrients. Biznekx says eat well and enjoy U ain’t well

 Hence, this phase of gastric function is dominated by the

small intestine sending inhibitory signals to the stomach to
slow secretion and motility. Two types of signals are used:
nervous and endocrine. Distension of the small intestine, as
well as chemical and osmotic irritation of the mucosa is
transduced into gastric-inhibitory impulses in the enteric
nervous system - this nervous pathway is called the
enterogastric reflex. Secondly, enteric hormones such as
cholecystokinin and secretin are released from cells in the
small intestine and contribute to suppression of gastric
activity.

 Collectively, enteric hormones and the enterogastric reflex

put a strong brake on gastric secretion and motility. As the
ingesta in the small intestine is processed, these stimuli
diminish, the damper on the stomach is released, and its
secretory and motor activities resume