Gastrointestinal Physiology

HERBERT IZO

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 OVERVIEW OF THE DIGESTIVE SYSTEM

• The gastrointestinal tract (GIT) consists of the

following :
• Oral cavity
• Pharynx
• Esophagus
• Stomach
• Small intestine
• Large intestine
• Anus

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 OVERVIEW OF THE DIGESTIVE SYSTEM

• The accessory organs include :

• Salivary glands
• Liver
• Gall bladder
• Pancreas

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 OVERVIEW OF THE DIGESTIVE SYSTEM

• The git provides the body with a

continual supply of water, electrolytes,
and nutrients.
• To achieve this, requires;
1. Movement of food through the tract
2. Secretion of digestive juices and
digestion of food

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 OVERVIEW OF THE DIGESTIVE SYSTEM

3. Absorption of the digestive products,

water and electrolytes
4. Circulation of blood through the GI
organs to carry away the absorbed
substances
6. Control of all these functions by the NS
and hormonal systems.
• The figure below shows the entire GIT
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 Physiologic Anatomy

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• A cross section of the GI include the following
layers from the outer surface inwards
1. The serosa _ outer layer - serous epithelium,
Connective tissue + peritoneum:
2. Longitudinal muscle
3. Circular muscle
• Between the longitudinal and circular muscle
layers lies the myenteric plexus or Auer
Bach's plexus_control mainly GI movements
• Submucosa plexus or Meissner’s plexus
lies in the submucosa_control mainly GI
secretion and local blood flow.

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4. Submucosa _ is a thick layer that consists of :
Connective tissue, blood/lymph vessels,
nerves, Sub mucosal plexus and small glands.
5. Mucosa _ is the innermost layer, it consists of;
- mucous epithelium (cells are replaced
every 5-7 days),
- lamina propria (loose connective
tissue),
- muscularis mucosa (thin muscle layer)
• Folds increase the surface area (200m2) and
epithelial cells – line the lumen and may be
absorptive or secretory.

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 Smooth Muscle Physiology
• The smooth muscle of GI is subject to
continual but slow electrical activity.
• The longitudinal muscle extend down the
tract while the circular muscle layer extend
around the gut.
• The muscle fibers are connected by gap
junctions that allow low resistant
movement of ions from cell to the next.

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 Smooth Muscle Physiology
• The electrical activity of the muscle are of two types;
1. Slow waves_ The direction, timing, and speed of
gastric peristalsis (the frequency, velocity and
direction) are determined by something called slow
waves.
- These are also called basic electric rhythms (BER)
or pace-setting potentials.

2. Spikes; true action potentials _ occur automatically

when Resting Membrane Potential (RMP) becomes
more +ve than about -40mV

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 Action Potential Mechanism for Stimulation of
Smooth Muscle Contraction
Skeletal Muscle Smooth Muscle
• ↑ [Ca2+]
• ↓ ↑ [Ca2+]
• Binds Troponin ↓
Binds Calmodulin
• ↓
↓
• Moves Tropomyosin Activates myosin kinase
• ↓ ↓
• Exposing active sites Phosphorylates myosin heads
• ↓ ↓
Myosin heads bind actin
• Myosin heads bind actin

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 Gastric Motility
• Function = Grind & mix with digestive
secretions, Move it caudally through the Tract
(law of the gut)
• Two types of movements occur in the GIT
1. Propulsive movements [PERISTALSIS] _ a
distinctive pattern of smooth muscle
contractions that propels foodstuffs distally
through the esophagus and intestines.
• It was first described by Bayliss and Starling in
1899 as a type of motility in which there is
contraction above and relaxation below a
segment being stimulated.
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 Gastric Motility
• Peristalsis is not affected to any degree
by vagotomy or sympathetectomy,
indicating its mediation by the intestine's
local, intrinsic nervous system.
• cause food to move forward along the
tract at an appropriate rate for digestion
and absorption

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 Gastric Motility
• Peristalsis is a manifestation of two major
reflexes within the enteric nervous system that
are stimulated by a bolus of foodstuff in the
lumen.
• Mechanical distension and perhaps mucosal
irritation stimulate afferent enteric neurons.
• Peristaltic waves appear when the slow
wave depolarization reaches and exceeds
threshold potential.

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2. Mixing movements _ keep the intestinal
contents thoroughly mixed at all times.
• Segmentation contractions are a common type
of mixing motility seen especially in the small
intestine
• segmental rings of contraction chop and mix
the ingesta.
• Alternating contraction and relaxation of the
longitudinal muscle in the wall of the gut also
provides effective mixing of its contents.
• Caused by sphincter when chyme reaches
sphincter
• Local constrictive contractions

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 Swallowing [Deglutition]
• Consist of three phases
1. Voluntary [buccal/oral] stage: when food is ready for
swallowing, it is pushed upward and back by the
tongue into the pharynx.
• From the pharynx, the process becomes automatic
and cannot be stopped.
2. Pharyngeal stage: bolus of food stimulates
swallowing reflex initiated in the swallowing receptor
areas located around the opening of the pharynx.

• the impulse is carried into the brain stem (swallowing

/deglutition center) which initiate a series of automatic
pharyngeal muscle contractions.

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 Swallowing [Deglutition]
• returning impulses cause the soft palate/uvula to
move upward to close off the nasopharynx.
• the palatopharyngeal folds on either side of the
pharynx.
• This way they form a slit through which the food
must pass into the posterior pharynx.
• larynx is pulled forward and upward under the
tongue; the epiglottis covers the glottis.
• This prevent passage of food into the trachea.

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 Swallowing [Deglutition]
• The upward movement of the pharynx also pulls up and
enlarge the opening of the esophagus.
• At the same time the upper esophageal sphincter relaxes,
thus allowing the bolus to pass through the
laryngopharynx [upper esophageal /pharyngoesophageal
sphincter] into the esophagus.
• The sphincter remain closed in between swallow.
• At the time the pharynx is raised, the esophageal
sphincter is relaxed, the entire muscular wall of the
pharynx contracts.
• Esophagus opened and fast peristaltic wave forces food
into upper esophagus (1-2 seconds)

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 Swallowing [Deglutition]
3. Esophageal stage: exhibit two types of
peristalsis
– Primary: continuation of peristalsis that begins in the
pharynx and spread to the esophagus to stomach
(8-10 seconds).
– Secondary: if primary fails to move food to stomach,
secondary peristalsis initiated by
 the enteric nervous system in esophagus as a result
of distension of the esophagus by retained food
 vagal afferent from the esophagus to the medulla
and back to the esophagus through the vagal
efferent -- stimulate peristalsis

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 Swallowing [Deglutition]
• At the lower end of the esophagus, the
esophageal circular muscle functions as lower
esophageal sphincter [physiological sphincter]
and tonically remain constricted.
• When peristaltic waves reaches the LES, it
relaxes to allow the bolus into the stomach.
• The tonic constriction of the LES prevent reflux
of stomach content into the esophagus except
under certain abnormal conditions.

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 Swallowing Abnormalities
• Gastroesophageal Reflux Disease (GERD)
• This medical condition is due to a defect in the
gastroesophageal barrier (the LES) and in anti-
reflux mechanisms.
• As a result, there is increased contact to
caustic materials such as acid, pepsin, bile,
and pancreatic enzymes.
• There are also decreased clearing
mechanisms.
• The result is that mucosal resistance is
overwhelmed.
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 Swallowing Abnormalities
• Transient LES relaxation (TLESR)
• occurs independent of swallowing and is
associated with reflux in normal individuals and
in those with esophagitis.
• TLESR is thought to be neurally controlled.
• Barrett’s esophagus
• Inflammation or esophagitis continues until the
columnar epithelium found in the stomach
replaces the epithelium of the distal
esophagus.
• It is a predisposing condition to esophageal
adenocarcinoma.
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 Swallowing Abnormalities
• Achalasia
• This medical condition involves increased LES
pressure and the absence of peristalsis.
• It results in no or incomplete LES relaxation.
• it is believed to be due to the absence of the intrinsic
plexus
• Treatment:- Life style modifications include:
• elevating the head of the bed to put the stomach at a
different level than the esophagus and losing excess
weight.
• Additionally, dietary changes can be made.
• Tobacco, alcohol, bedtime snacks, fatty foods,
chocolate, and peppermint should be avoided.

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 Stomach: Mixing & Storage of Food

• The stomach is divided into three

anatomical regions and two functional
regions.
• The anatomical regions are the fundus,
the body, and the antrum.
• The stomach is functionally divided into
two motor regions (a reservoir and a
pump).

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 Stomach: Mixing & Storage of Food

• The proximal stomach serves as a storage unit

for ingested material.
• The reservoir function of the proximal stomach
allows it to hold the meal prior to its processing
by the distal stomach.
• The proximal stomach also maintains a steady
pressure on the gastric contents so that the
“pump” in the antrum is primed.
• Gastric emptying can occur whether the subject
is supine or standing.

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 Stomach: Mixing & Storage of Food
• The stomach also functions in mixing ingested food with
gastric juices.
• This dissolves and dilutes food.
• The distal stomach acts as a preparatory chamber in
which ingested materials are reduced in size so that they
can pass through the pylorus.
• Finally, the stomach responds to feedback from the
duodenum to control the delivery rate of calories and
hydrogen ions to the duodenum.
• In this way, the distal stomach acts as an emptying
regulator.

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 Gastric Emptying

• Swallowing causes the proximal stomach

to relax to receive a bolus of food.
• This swallowing-induced relaxation is
referred to as receptive relaxation.
• Food in the stomach initiates weak
peristaltic waves [constrictor waves or
mixing waves] which begins in the mid
portion of the stomach wall and continue
towards the antrum.
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 Gastric Emptying

• The waves are initiated by the basic

electrical rhythms [BER] and consist of
slow waves.
• Gastric slow waves originate in a group of
longitudinal muscle cells found in the
greater curvature of the stomach.
• Slow waves are generated in this region
and spread circumferentially.

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 Gastric Emptying

• The slow waves move continuously

through the distal stomach in both the fed
and the fasting states at a rate of about 3
waves per minute.
• Peristaltic waves appear when the slow
wave depolarization reaches and
exceeds threshold potential.
• This threshold is reached more so when
certain conditions occur.
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 Gastric Emptying

• These include: gastric distension, irritations,

breakdown products, vagal stimulation, and the
presence of hormones such as gastrin.
• An increase in the depolarization causes an
increase in contraction strength, making it
possible for food to move through.
• As waves of peristalsis approach the pylorus,
they increase in speed and in strength.
• The pylorus only allows 2-7 ml of liquid to enter
the duodenum before the pylorus contracts.

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 Gastric Emptying

• This liquid consists of gastric secretions,

digested and solubilized portions of the meal
and very small particles of food (<0.25 mm in
diameter).
• The closed pylorus drives solid particles of food
backwards and the particles are sheared as they
are jetted back into the proximal stomach.
• The force of the jet-like retropulsion of food is
due to increased in pressure in the terminal
antrum as the food approaches the closed
pylorus
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 Gastric Emptying

• The pylorus functions to limit the size of

particles emptied into the duodenum after
a meal and acts to prevent reflux of the
duodenal contents into the stomach.
• The rate of gastric emptying depends on
the rate at which chyme is broken down
into small particles.
• The process continues until all digestible
food is discharged into the duodenum.
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 Control of Gastric Emptying
• There are several signals that determine the rate
of gastric emptying.
• The volume of the bolus helps determine the
rate at which the contents are empted into the
duodenum.
• The osmolality of fluids also affects gastric
emptying.
• Hypotonic and hypertonic fluids empty more
slowly than isotonic fluids.

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 Control of Gastric Emptying
• pH has an effect on the emptying of gastric
contents.
• Gastric emptying is slower when the pH is low
(H+ concentration is high).
• caloric content has an effect on gastric
emptying.
• The duodenum controls the rate of gastric
delivery by monitoring calories.
• Gastric emptying is inhibited or takes longer for
a larger load of calories than for smaller ones.

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 Control of Gastric Emptying
• Additionally, the rate of gastric emptying is
increased by laying on the hunger, mild
exercise, and laying on the right side.
• Emotional stress, strenuous exercise and
deep pain decrease the rate of gastric
emptying.
• During fasting, there is a cyclic pattern of
activity called the migrating motor
complex (MMC).
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 Control of Gastric Emptying
• It is divided into three phases.
• Phase I is a quiescent period where no
contractions occur. It lasts for 45 minutes
to an hour.
• Phase II is a period during which there are
intermittent contractions. It lasts for 30-45
minutes.
• Phase III lasts for about 5-10 minutes.
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 Control of Gastric Emptying
• During this period of time, there are intense
contractions [hunger pangs].
• The MMC continues to cycle until a meal is
taken.
• The intense contractions are responsible for
emptying large objects that do not pass to the
pylorus during the digestive phase.
• The strength of the MMCs is increased by the
hormone motilin that is in the small intestine.
• Motilin levels reach a peak level during phase
three.

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 Pathophysiology of Gastric Motility

• Delay of gastric emptying may be caused by

failure of the driving force for emptying or by
increased resistance to flow at the pylorus.
• Gastroparesis is often associated with diabetic
neuropathy and eating disorders.
• Dumping syndrome is a condition that is mainly
caused by incompetence of the antropyloric
sphincter which allows hyperosmolar, high
calorie materials to be emptied too quickly into
the small bowel.

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 Pathophysiology of Gastric Motility

• The result is that the materials pass to the

jejunum without becoming isotonic first.
• This results in sweating, pallor, and
massive cramps.
• A dumping syndrome can occur post-
surgically, most frequently after the
removal of the antrum (antrectomy).

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 MOVEMENT IN SMALL INTESTINE

• Two types
• Mixing contractions [segmentation
contractions]
• Propulsive contractions _ occurs in any part of
the SI and they move anal ward at a rate of
0.5-2.0cm/sec.
• They are usually weak and die out after 3-5 cm
• peristaltic rush-- fast propulsion to cecum
example: infectious diarrhea

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 MOVEMENT IN SMALL INTESTINE

• On reaching the ileaocecal valve, the chyme is

sometimes blocked for several hours until the
person eats another meal _ gastroenteric
[gastroileal] reflex
• This intensify the peristalsis in the ileum and
forces the remaining chyme through the
ileocecal valve into the cecum.
• It should be emphasize that the difference
between the segmental and peristaltic
movements is not as great as might be
implied.
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 MOVEMENTS OF THE COLON

• The principle functions of the colon are

• Absorption of water and electrolytes and
• Storage of fecal matter until it can be
expelled.
• Types of peristalsis in small intestine is
rare in colon.

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 MOVEMENTS OF THE COLON
• The movements in the colon are very sluggish.
• Mixing movements- haustration
– The combined contraction of circular and longitudinal
muscles cause the unstimulated portion of the large
intestine to bulge outward into bag like sac called
haustrations
– Fecal material dug into and rolled over exposing all
material to surface of large intestine
– This lead to absorption of fluid and dissolved
substances which may account for abt 80-200 ml of
chyme lost in feces

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 MOVEMENTS OF THE COLON
• Propulsive- "mass" movement
– modified type of peristalsis which force mass feces
into the rectum
– Occur only a few times a day (most regularly within 1
hr after breakfast)
– When this occur the desire to defecate is felt
– The appearance of mass movement after meals is
facilitated by Gastro-colic and duodeno-colic reflexes
– The reflexes result from distension of the stomach
and duodenum.
– Extrinsic nerves control most mass movement

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 Defecation

• mass peristalsis pushes feces into rectum

• stretch receptors are excited, initiating the
defecation reflex
• receptors send impulses to the sacral
spinal cord
• motor fibers from the sacral cord
(parasympathetics) to descending colon,
sigmoid, rectum, anus
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 Defecation

• longitudinal muscles in rectum shorten,

increasing pressure
• internal anal sphincter opens
• feces are propelled into the anal canal
• external anal sphincter under voluntary
control.
• If it remains constricted, defecation is
postponed
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 Disorders of Large Intestine
• Constipation _ slow movt of feces through the LI.
• Associated with dry hard feces
• Causes include irregular bowel movt habits, use
of laxative (atonic colon)
• Megacolon [Hirschsprung’s disease]
_accumulation large amount of feces due to
prolong constipation
• Diarrhea _ rapid movt of fecal matter through the
large intestine.
• Causes include enteritis, psychogenic,
ulcerative colitis

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 SECRETION OF SALIVA

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 SECRETION OF SALIVA
• Saliva - mixture from salivary glands -
1500 ml every 24 hours
• Saliva contains salivary amylase, an α-
amylase: begins starch digestion.
• Saliva also contains lysozyme, kallekrein,
RNAase,DNAase, and IgA.
• In individuals deficient in saliva
[xerostomia], dental caries and buccal
infections result.
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 SECRETION OF SALIVA
• Secretion is highly active.
• Fluid secreted by acinar cells resembles
plasma in electrolytes, duct cells make
modifications.
• ANS, particularly parasympathetic, exert
major controls.
• Salivary mucus lubricates food.

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 Structure of salivary glands

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 Structure of salivary glands
• Serous cells secrete water, electrolytes,
amylase.
• Mucous cells secrete mucus.
• Acini [secretory endpieces], intercalated
ducts, striated ducts, and excretory ducts.
• Salivary glands may produce 1 ml/min per g
gland [prodigious].
• Oxygen consumption of active gland is very
high.
• Blood flow to active gland is 10X that to active
skeletal muscle.

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 Two-stage model of salivary secretion

1. Endpieces [with intercalated ducts?] produce

isotonic primary secretion that resembles
plasma in ionic composition.
• Concentration of amylase and rate of secretion
of water and electrolytes depends on nature of
stimuli to gland.
• Secretion of amylase: zymogen granules
released by exocytosis
2. Striated, extralobular, and excetory ducts
modify saliva by extracting Na+ and Cl -as
well as secreting K+ and HCO3-.

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• Composition of saliva:
• always hypotonic to plasma with
elevated K+ and HCO3- relative to
plasma.
• The higher the flow rate, the closer to
isotonic is saliva.
• At rest saliva is alkaline, pH is near 8
during active secretion, partly due to
elevated HCO3-.

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1. Parasympathetic nervous system is major
physiologic controller of salivary glands.
• Cutting parasympathetics causes atrophy.
• Stimulation of parasympathetic nerves causes
increased secretion of saliva and increased
blood flow.
• Acinar cells and ducts have cholinergic nerve
endings.
2. Sympathetic nerves; Stimulation of
sympathetic nerves transiently stimulates
salivary secretion.
• Sympathetic stimulation decreases gland blood
flow.
• Cutting sympathetic nerves causes no defect in
function.
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 GASTRIC SECRETIONS

• Functions of the stomach.

• Serves as a reservoir, allowing the ingestion of
large meals, which are emptied at a controlled
rate into the duodenum.
• Secretes HCl, pepsinogens, intrinsic factor,
HCO3-, and mucus. HCl kills most micro-
organisms that are ingested and activates
pepsinogens to pepsins.
• Pepsins begins the digestion of proteins.

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 GASTRIC SECRETIONS

• Intrinsic factor (IF) is necessary for normal

absorption of vitamin B12.
• Mucus and HCO3- help protect the gastric
mucosa from its own secretions.
• The production of IF is the only gastric
function necessary for life!

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 Structure of the gastric mucosa

• Covered with columnar epithelial cells that

secrete mucus and an alkaline fluid.
• Numerous pits that are the openings of gastric
glands.
• Three glandular areas: cardiac [just below LES],
oxyntic [acid secreting],fundus and body down
to notch], and pyloric [below notch].
• Cardiac glands are tortuous and contain mostly
mucus secreting cells.

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 Structure of the gastric mucosa

• Oxyntic glands contain parietal cells, chief cells,

and mucus secreting cells.
• Pyloric glands contain few chief and parietal
cells, mostly mucus secreting cells and G
[gastrin secreting cells].
• When surface epithelial cells are exfoliated,
mucous neck cells migrate out of glands and
differentiate into surface cells.
• Capacity to repair damage in this way is
impressive.

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 Gastric Juice

1. Mixture of secretions of surface and gland cells.

• Contains salts, water, HCl, pepsinogens, intrinsic factor,
mucus, and HCO3-.
• Rate of secretion of all of these increases after a meal.
2. Ionic composition of gastric juice.
• Depends on rate of secretion.
• The higher the rate of secretion, the greater the
[HCl].
• At lower rates there is proportionately more Na+ and
less H+.

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 Gastric Juice

HCl secretion
1. Rate of HCl secretion.
• Varies among individuals: basal rate from
1 to 5 mmoles/hr.
• With maximal stimulation by pentagastrin:
6 to 40 mmoles/hr.
• May depend on number of parietal cells
present.
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 Gastric Juice

• Gastric ulcer patients secrete less and duodenal

ulcer patients secrete more HCl than normal on
average.
2. Cellular mechanisms of HCl secretion.
• Both H+ and Cl- are transported against net
electrochemical difference from blood to lumen.
• H+,K+-ATPase in the membrane of the
secretory canaliculus actively takes up K+ and
extrudes H+ into the lumen using the energy of
ATP to do this.
• Extrusion of H+ makes cellular [HCO3-] rise.

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 Gastric Juice

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 Gastric Juice
• Pepsins.
• Group of proteases secreted by chief cells.
Secreted as pepsinogens with acid-labile
linkages.
• HCl converts them to active pepsins.
• pH optima below 3.
• Irreversibly inactivated at neutral pH.
• Digest 10 to 20% of protein in a meal to
peptides, but not necessary for protein digestion
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 Gastric Juice
• Intrinsic factor [IF]
• is glycoprotein of MW 45,000 secreted by
parietal cells; its rate of secretion parallels acid
secretion.
• IF binds all physiological forms of vitamin B12.
• IF-B12 complex resists digestion.
• Receptors in ileum bind complex of IF and B12
and take up B12.
• In absence of IF, B12 is malabsorbed leading to
pernicious anemia.
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 Gastric Juice
• Secretion of mucus and HCO3-
• by the epithelium of the stomach forms the
gastric mucosal barrier that protects the
mucosal surface from HCl and pepsins.
• This protection requires both mucus and HCO3-
.
• Mucus provides a slowly mixing layer that
entraps HCO3- to neutralize H+ as it diffuses
through the mucous and allows the pH of the
epithelial cell surface to be near neutral when
the pH of gastric juice is about 2.

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 Control of gastric acid secretion

• ACh, histamine, and gastrin each bind to

specific receptors on the plasma membrane of
the parietal cell and stimulate HCl secretion.
• Each of these agonists potentiates the effects of
the others and blockers of one agonist usually
partially block the others.
• ACh is neurocrine regulator.
• Gastrin is endocrine.
• Histamine is paracrine.

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 In vivo control of gastric acid secretion

1. Cephalic phase:
• elicited before food reaches stomach.
• Elicited by sight, smell, taste of food.
• Acid secretion can reach 40% of maximal rate.
• Mediated entirely by vagal impulses: bilateral
truncal vagotomy abolishes it.
• Cholinergic neurons in vagus and plexuses play
a major role by mechanisms discussed above
[ACh promotes release of gastrin and histamine
and has direct effect as well].
• In absence of buffering by food, pH falls rapidly.
• This limits amount of HCl in cephalic phase.
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 In vivo control of gastric acid secretion

2. The gastric phase:

• elicited by the presence of food in the
stomach.
• Stimuli are distension and presence of amino
acids and peptides.
• These two types of stimuli potentiate each
other.
• Distension of body and fundus causes reflex
[local and central] release of ACh near parietal
cells and release of gastrin by a vagal reflex.
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 In vivo control of gastric acid secretion

• Distension of antrum causes gastrin release by a vagal

reflex.
• Amino acids [especially tryptophan and phenylalanine]
and peptides directly stimulate G-cells to release
gastrin.
• Ingestion of Ca2+, caffeine, and alcohol can stimulate
acid secretion, but decaffeinated coffee is as potent as
regular coffee and diluted alcohol [less than 16 vol%]
is not effective.
• All the gastric phase stimuli are blocked by a low
pH [2 or less] of gastric contents.
• In patients with duodenal ulcers, this inhibitory
mechanism may be less effective.
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 In vivo control of gastric acid secretion

3. The intestinal phase of gastric secretion:

• brought about by the presence of chyme in the
duodenum.
• Early in gastric emptying, when pH of gastric
• chyme is pH 3 and above, intestinal influences
are primarily stimulatory to gastric acid
secretion.
• Later, when the buffer capacity of the
gastric contents is exhausted, gastric pH
falls to 2 and below, and then mechanisms that
originate in the duodenum and upper jejunum
that inhibit HCl secretion prevail.
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 In vivo control of gastric acid secretion

• Stimulatory mechanisms:
• The presence of amino acids and peptides in the
duodenum and proximal jejunum elicits the release of
gastrin from G cells present there.
• Entero-oxyntin, a hormone released from the
duodenum in response to distension enhances the
response of parietal cells to gastrin.
• Inhibitory mechanisms:
• The presence of acid, fats, and fat digestion
products in the duodenum and proximal jejunum
evoke mechanisms that inhibit gastric acid secretion.
• Acid in the duodenum causes release of secretin.
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 In vivo control of gastric acid secretion

• Secretin inhibits gastrin release and also

directly inhibits acid secretion by the
parietal cells.
• Acid in the duodenum stimulates the
release of a hormone called
bulbogastrone that inhibits parietal cell
HCl secretion.
• Acid in the duodenum also evokes local
and central neural reflexes that inhibit
HCl secretion.
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 In vivo control of gastric acid secretion

• Long chain fatty acids and 2-

monoglycerides in the duodenum and
proximal jejunum elicit release of CCK and
GIP (gastric inhibitory peptide).
• GIP suppresses acid secretion both by
inhibiting gastrin release and by direct effects
on the parietal cell.
• CCK also inhibits acid secretion by parietal
cells.
• Hyperosmotic solutions in the duodenum
cause release of an unidentified hormone that
inhibits acid secretion.
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 Pathogenesis of gastric and duodenal
ulcers
• Among the mechanisms that are
believed to contribute to ulcer formation
are
1) diminished effectiveness of the gastric
mucosal barrier,
2) hypersecretion of acid, and
3) infection by Helicobacter pylori.

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 PANCREATIC SECRETIONS

• Pancreas has exocrine and endocrine parts.

• Exocrine secretion drains into duodenum and
contains HCO3- and enzymes for digesting all
major foodstuffs.
• Exocrine secretion controlled by neural and
hormonal influences.
• Pancreatic juice considered to consist of an
enzyme component [secreted by acini] and
an aqueous component [secreted by duct
epithelium].

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 PANCREATIC SECRETIONS

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 PANCREATIC SECRETIONS

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 PANCREATIC SECRETIONS
• Structure resembles salivary glands.
• Acinar cells drained by tiny intercalated
ducts, which drain into intralobular
ducts, which drain into extralobular
ducts, which converge into larger ducts.
• One main duct drains the pancreas and
joins common bile duct.

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 PANCREATIC SECRETIONS
• The aqueous component of pancreatic juice.
• At low flow rates, the aqueous component is
isotonic and resembles plasma in its
concentrations of Na+ and K+, but has lower Cl-
and higher HCO3- than plasma.
• Upon stimulation by secretin, the major
physiological stimulus for secretion, HCO3- rises
even higher and Cl- falls.
• Spontaneous secretion:

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 PANCREATIC SECRETIONS
• In absence of secretin stimulation the
aqueous component is produced by
intercalated and intralobular ducts.
• This secretion has a high HCO3- relative to Cl-,
but as it flows down the duct system HCO3-
exchanges for Cl-; the final fluid has elevated
HCO3- and decreased Cl-, relative to plasma.
• Acinar cells also secrete water and ions along
with their enzymes.
• This acinar fluid resembles plasma in its ionic
composition.

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 PANCREATIC SECRETIONS
• Upon stimulation by secretin:
• the fluid secreted by the intralobular ducts
does not change, but there is dramatic
increase in the rate of a HCO3- rich
solution by the extra lobular ducts.
• The source of the HCO3- secreted by the
• extra lobular ducts is plasma, not
metabolically produced CO2.
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• Enzyme component of pancreatic juice.
• Contains enzymes for digestion of all major foodstuffs.
• Major proteases are secreted in pro-enzyme form; they
are:
• trypsinogen, chymotrypsinogen, and
procarboxypeptidase.
• Trypsin inhibitor is present [to protect pancreas].
• Pancreatic amylase is secreted in active form.
• Lipases in pancreatic juice include triacylglycerol
hydrolase (aka pancreatic lipase), cholesterol ester
hydrolase, and phospholipase A2.
• Enzymes that degrade nucleic acids are present.

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 Regulation of secretion of pancreatic
juice.
1. Cephalic phase of pancreatic secretion.
• Vagal stimulation enhances pancreatic secretion.
• Gastrin released from stomach by vagal impulses is a
major mediator of cephalic phase pancreatic secretion.
2. Gastric phase.
• Gastrin released in response to gastric distension and
presence
• of amino acids and peptides stimulates pancreas.
• Vagovagal reflexes elicited by gastric distension
stimulate pancreas to secrete low volume, high enzyme
juice.

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 Regulation of secretion of pancreatic
juice.
3. Intestinal phase.
• Acid in duodenum elicits secretin.
• Secretin stimulates extra lobular ducts to secrete large
volume of HCO3- rich aqueous component.
• Fat digestion products in duodenum cause release of
CCK.
• CCK is the major physiological stimulus for release of
enzyme component by acinar cells.
• CCK and secretin potentiate the effects of one
another.
• Secretion of aqueous component and enzyme
component also stimulated by a vagovagal reflex that
is important early in the intestinal phase.

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 Intestinal Secretion
• Gross Anatomy duodenum = shortest, 25 cm
jejunum = 2.5 meters long
ileum = 3.6 m long; joins to large intestine at
the ileocecal valve [sphincter]
• Histology of the Small Intestine
• EXTERNAL SEROSA
• MUSCULAR ( LONGITUDINAL, CIRCULAR )
• SUBMUCOSA
• SIMPLE COLUMNAR EPITHELIUM (MUCOSA)
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 Intestinal Secretion
• 1. Specializations for absorption: -circular folds of
submucosa
-villi = folds of mucosa
-microvilli = folds of the apical plasma membrane
(“brush border”)
• 2. Mucosa : simple columnar epithelium, with some
goblet cells Crevices = crypts of Lieberkuhn (intestinal
glands), secrete intestinal juice
• Cell types: mucus-secreting cells [Goblet Cells];
• Paneth cells, secreting lysozyme AND they are
phagocytic, regulating normal flora in the small intestine
• Enteroendocrine cells - secrete secretin, CCK,

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 Intestinal Secretion
• 3. The sub mucosa contain cells called :
Brunner's glands located in the few cm of
the duodenum- these cells produce mucus

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• Intestinal juice (1-2 liters/day)
• Amino peptidase - cleaves amino acids
from amino end of proteins
• Maltase_ Maltose Glucose + Glucose
• Sucrase_ Sucrose Glucose + Fructose
• Lactase Lactose Glucose + Galactose
• Enterokinase - activates trypsinogen

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• The function of the mucus secreted by the
Brunner’s gland is to protect the duodenal
wall from digestion by the highly acidic
juice.
• Large Intestine
• Ascending, Transverse, Descending,
Sigmoid Colon
– Water & electrolyte absorption
– Trash compacting
– Bacterial fermentation, byproducts
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 Liver and Gall Bladder
• THE LIVER IS THE LARGEST INTERNAL
ORGAN OF THE BODY
• A. Gross Anatomy: Just inferior to diaphragm
• 2 principal lobes= R (larger) , L, separated by
ligament.
• The small quadrate lobe inferiorly and a
posterior caudate lobe are part of the right lobe
• Gall Bladder: a sac on the inferior side of the R
lobe; cystic duct joins with hepatic duct to form
common bile duct

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 Liver and Gall Bladder
• B.Histology
• 1. hepatic lobules: hepatocytes in cords arranged around
a central vein
-classical lobule: hexagon; peripheral portal triads;
-sinusoids with macrophages (Kupffer cells) lining
2.Bile secreted by hepatocytes into small canaliculi
between hepatocytes;
• these merge into larger and larger bile ducts, and
eventually into hepatic ducts-->common hepatic duct--
>joins with cystic duct to make: Common bile duct

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 Liver and Gall Bladder
• C. Role and Composition of Bile :
• 800-1000 ml/day, by hepatocytes
• 1.consists of water, bile acids, bile salts, cholesterol,
lecithin, bile pigments, and ions
• 2.Functions
• -emulsify fats and helps in fat absorption (increases
surface area for lipases to work; makes cholesterol
soluble)
• -Bilirubin= breakdown product of Hb, esp. heme (Fe and
globin recycled)
Excreted into bile ducts
Breaks down in intestine, gives feces its color

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 Liver and Gall Bladder
• 3.control of secretion: like other areas of
GI tract
• -parasympathetic stimulation Increases
bile secretion
• -blood flow thru liver increases
• -CCK stimulates contraction of gall bladder
and duct
• Function of gall bladder = storage,
concentration of bile
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 Functions of the Liver
• vital to life.
• 1.CHO metabolism: maintains normal blood glucose
level
• -Converts glucose in blood into glycogen for storage,
thus effectively removing the glucose from the blood
• -converts stored glycogen to glucose and releases it into
the blood, thereby Increasing blood glucose levels
• -can also convert amino acids, lactic acid  glucose
• -can convert other sugars fructose/galactose  glucose
• -can convert glucose to triglycerides

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 Functions of the Liver
• 2.Lipid metabolism in the liver
• -breaks down fatty acids into acetyl CoA (B-
oxidation)
• -converts acetyl CoAs into ketones
(ketogenesis)
• -synthesizes lipoproteins, which transport fatty
acids, triglycerides, and cholesterol to and from
body cells
• -synthesizes cholesterol, which is used to make
bile salts

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 Functions of the Liver
• 3. Protein metabolism in the liver
• -deaminates amino acids so that they can be
used for ATP synthesis or changed to CHO, fats
• - converts NH3 from amino acids into the less
toxic urea, which is excreted in the urine
• -synthesis of plasma proteins (including clotting
factors)
• -transamination

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 Functions of the Liver
• 4.Processing of drugs and hormones
• -detoxificates or excretes drugs into bile, e.g.,
antibiotics and can
• -alter or excrete thyroid hormones, steroid
hormones
• 5. Excretion of bilirubin (high levels can be toxic)
• 6.Synthesis of bile salts: used in small int. For
emulsification, absorption of lipids

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 Functions of the Liver
• 7.Storage
• -glycogen
• -vits ADEK and B12
• -minerals: Cu, Fe
• 8.Phagocytosis: of old RBCs and WBCs
and some bacteria
• Read about gallstones

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 Digestion and Absorption
• Hydrolysis
• Carbohydrates, Fats, & Proteins
• Digestive Enzymes

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 Carbohydrates: Sucrose,
Lactose, & Starch

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 Fats: Triglycerides, Cholesterol
esters, Cholesterol

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 Proteins

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 Absorption

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~9-10 liters of fluids are
absorbed each day
• ~7-9 liters are absorbed in the
small intestine
• ~.3-2 liters of water & ions are
absorbed in the large intestine
• <1% is absorbed in the oral
cavity, esophagus, & stomach combined
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• Cellular Mechanism for Absorption
• Active Transport &
• Diffusion
• Carbohydrate Absorption:
• Na+ Cotransport
• Protein Absorption
• Na+ Cotransport

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 Fat Absorption

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• fat absorption: by simple diffusion.
-short-chain fatty acids pass into
epithelial cells by simple diffusion and then
directly into the blood
-long chain fatty acids are absorbed via
bile salts.
• Micelles of bile salts: the aqueous parts
are soluble in the blood; the long-chain
fatty acids dissolve in the inner nonpolar
part.

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• Thus, the micelles with their long-chain fatty
acids are absorbed into the epithelial cells.
• The bile salts are reabsorbed and then returned
to the liver for re-use via the hepatic portal
circulation = enterohepatic circulation.
-glycerol and fatty acids inside the epithelial
cells are recombined to form triglycerides, which
then combine with a protein coat =
chylomicrons.
• These are absorbed into the lacteals, not directly
into the blood.

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 Ion Absorption:

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• Large Intestine
• Water & Ion Absorption
• Na+ Co transport
• Cl- Diffusion
• Water Diffusion

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