GASTROINTESTINAL PHYSIOLOGY

Asst. Prof. ANITA Q. SANGALANG, MD, MHPEd

Department of Physiology

The gastrointestinal (GI) system includes the GI

ORGAN EXOCRINE FUNCTIONS
tract (mouth, pharynx, esophagus, stomach, small
SECRETIONS
intestine, and large intestines) plus several
II. ACCESSORY GLANDS/ORGANS
accessory glands and organs that add secretions to
these hollow organs. Each of these organs, Salivary Salt and water  moisten food
separated from each other at key locations by Glands
sphincters, has evolved to serve specialized function. Mucus  lubricates
Amylase  polysaccharide-
Parts of the GI System and their Functions digesting
enzyme
Pancreas  secretes
enzymes and
ORGAN EXOCRINE FUNCTIONS bicarbonate
SECRETIONS  nondigestive
I. GI TRACT endocrine
Mouth,  chewing begins; functions
Pharynx  initiate swallowing Enzymes  digest
reflex carbohydrates,
Esophagus  moves food to fats, proteins,
stomach by nucleic acids
peristaltic waves Bicarbonate  neutralizes HCl
Mucus  lubricates entering small
Stomach  stores, mixes, intestines from
dissolves, and stomach
continues Liver  secretes bile
digestion of food;  nondigestive
 regulates functions
emptying of Bile salts  solubilize
dissolved food water-insoluble
into small fats
intestines Bicarbonate  neutralizes HCl
HCl  solubilizes food entering small
particles; intestines from
 kills microbes; stomach
 activates Organic waste  elimination in
pepsinogens to products & feces
pepsins trace metals
Pepsins  protein-digesting Gallbladder  stores and
enzymes concentrates
Mucus  lubricates and bile between
protects epithelial meals
surface
Small  digests and LAYERS OF THE GI TRACT
Intestine absorbs most
(SI) substances; 1. Mucosa (Innermost layer)
 mixes and propels A. Epithelium- single layer of specialized cells
contents that line the lumen
Enzymes  food digestion  enterocytes
Salt and water  maintain fluidity enteroendocrine cells
of luminal mucin-producing cells
contents  columnar epithelial cells are linked
Mucus  lubricates together by tight junctions
Large  stores and  surface area of the epithelium is
Intestine concentrates arranged into villi and crypts
(LI) / Colon undigested B. Lamina propria
matter;  loose connective tissue
 absorbs salt and  glands, capillaries, and nerve fibers
water; C. Muscularis Mucosae
 mixes and propels  thin innermost layer of intestinal
contents smooth muscle
Mucus  lubricates  gives rise to the folds and ridges of the GI
Rectum  defecation tract

UST FMS MEDICAL BOARD REVIEW 2022 1 | PHYSIOLOGY


2. Submucosa
 loose connective tissue
 Some glands are present.
 larger nerve trunks, blood vessels and lymph
vessels
 submucosal plexus (Meissner’s plexus) which
is part of the enteric nervous system (ENS)
3. Muscle Layer
 muscularis externa or muscularis propia
 Two layers:
a. Inner circular muscle layer
b. Outer longitudinal muscle layer
 between these layers is the myenteric plexus
(Auerbach’s) – which is part of the ENS
4. Serosa or Adventitia (outermost layer)
 squamous mesothelial cells
 part of the mesentery
 Mesenteric membrane secretes a thin viscous
fluid.
ROLES OF THE GI SYSTEM
1. Digestion and absorption of dietary calories
and nutrients
Nutritional Requirement:
Sedentary individual = 30 kcal/kg/day
 normally acquired via oral route of food
 assimilated by GI tract (small intestines)
 Intravenous route - other means of caloric
intake
 I.V. alimentation / total parenteral
nutrition
2. Maintenance of overall fluid & electrolyte balance
 Dietary fluid intake = 1.2 – 2 L/day
 Total fluid secreted by GIT & accessory
organs = 7– 8.5L/day
 Total fluid absorbed by small intestine
~ 8-9 L/day
 Total fluid in feces ~100 ml/day
3. Excretion of waste materials (feces)
a. nondigested / nonabsorbed food
b. colonic bacteria and metabolic products
c. excretory products -
• heavy metals i.e. iron, copper
• organic anions & cations (drugs)
d. dead and dying epithelial cells
e. water
4. Immune functions
 gut-associated lymphoid tissue (GALT)
a. protects against microbial pathogens
b. permits immunologic tolerance
Non-immunologic defenses
a. gastric acid secretion
b. intestinal mucin
c. peristalsis
d. epithelial cell permeability barrier
PHYSIOLOGIC FUNCTIONS OF THE GIT
 processes needed to perform its roles
1. Motility - is the movement that mixes and
circulates the GI contents and propels them
along the length of the tract. GI contents are
usually propelled in the orthograde direction.
UST FMS MEDICAL BOARD REVIEW 2022
GASTROINTESTINAL PHYSIOLOGY
Asst. Prof. ANITA Q. SANGALANG, MD, MHPEd
Department of Physiology
2. Secretion - refers to the processes by which
the glands associated with the GI tract
release water and substances into the tract.
3. Digestion - involves the processes by which
food and large molecules are chemically
degraded to produce smaller molecules that
can be absorbed across the wall of GI tract.
4. Absorption - refers to the processes by which
nutrient molecules are absorbed by cells that
line the GI tract and enter the bloodstream
REGULATION OF GI FUNCTION
A. Endocrine / Hormonal
B. Paracrine
C. Neurocrine
A. Endocrine Mechanism / Hormonal
 A sensing cell, an enteroendocrine cell
(EEC), responds to a stimulus (chemical or
mechanical) by secreting a hormone that
travels via the bloodstream to a target cell.
 can be stimulated by neural input or other
factors not associated with meal
B. Paracrine Mechanism
 A chemical messenger is released from a
sensing cell, EEC in the GI wall that acts on
a nearby target cell by diffusion through
the interstitial space
 Paracrine agents exert their actions on
several different cell types in the wall of the
GI tract, including:
a. smooth muscle cells
b. absorptive enterocytes
c. secretory cells in glands
d. other EEC’s
1. Histamine
 produced by the enterochromaffin-like
cells in the gastric mucosa.
 It mediates hydrochloric acid (HCl)
secretion by gastric parietal cells.
2. Serotonin (5-hydroxytryptamine [5-HT]}
 It is released from enteric neurons, mucosal
mast cells, and specialized EEC’s called
enterochromaffin cells.
 It regulates smooth muscle function and
water absorption across the intestinal wall.
3. GI Immune System
 It includes mesenteric lymph nodes, Peyer’s
patches, immunocytes (intraepithelial
lymphocytes, B & T lymphocytes, plasma
cells, mast cells, macrophages,
eosinophils).
 It secretes antibodies & inflammatory
mediators (histamine, prostaglandin,
leukotrienes, cytokines) in response to
specific food antigens and mounts an
immunologic defense against many
pathogenic microorganisms.
4. Hormones
 These include cholecystokinin, secretin,
peptide YY, proglucagon-derived peptides ½
(GLP-1/2).
2 | PHYSIOLOGY
 GASTROINTESTINAL PHYSIOLOGY
Asst. Prof. ANITA Q. SANGALANG, MD, MHPEd
Department of Physiology

PARASYMPATHETIC NS SYMPATHETIC NS
Cranial divisions – vagus
GASTROINTESTINAL PEPTIDE HORMONES Sacral divisions (S2, S3, S4) T5-L2 (SC)
HORMONE SOURCE TARGET ACTION
– pelvic nerve
I cells in Pancreas  Enzyme secretion
Cholecystokini duodenum & Gallbladder  Contraction Innervation to:
n
jejunum; 1. esophagus 1. Distal half of large
neurons in 2. stomach, intestine
ileum & colon 3. pancreas 2. anus
Gastric- K cells in Pancreas Exocrine: 4. small intestine
Inhibitory duodenum ↓ fluid
peptide and absorption
5. proximal half of large
jejunum Endocrine: intestine
 insulin Directly innervates GIT No direct innervation
release Preganglionic fibers Preganglionic (SC) →
G cells, Parietal cells  H+ secretion (vagus nerve) → Postganglionic (Prevertebral
Gastrin antrum of in body of Postganglionic fibers (ENS) ganglia) → Effector cells
stomach stomach
→ effector cells a. Celiac ganglia
Gastrin- Vagal nerve G cells in  Gastrin release
Releasing endings antrum of b. Superior mesenteric
peptide stomach ganglia
 cells of Liver  Glycogenolysis b. Inferior mesenteric
Glucagon pancreatic  Gluconeogenesis ganglia
islets of Neurotransmitter: Neurotransmitter:
Langerhans
Acetylcholine Norepinephrine
Guanylin Ileum & colon Small & large  Fluid absorption
intestine Actions: Actions:
Endocrine Esophageal  Smooth- Stimulatory Inhibitory
Motilin cells sphincter muscle - stimulates the following - inhibits the
in upper GI Stomach contraction functions of the GIT following functions of
tract Duodenum 1. secretory the GIT
Endocrine Intestinal Vasoactive
Neurotensin cells, smooth stimulation of
2. motor 1. secretory
wide-spread muscle histamine release 2. motor activity (except
in GI tract submucosal muscles)
Endocrine Stomach  Vagally mediated 3. Local blood flow
Peptide YY cells in ileum acid secretion (vasoconstriction)
& colon Pancreas  Enzyme &
fluid
secretion 3. Intrinsic Nervous System
S cells in Pancreas  HCO3- & fluid  Enteric Nervous System (“little brain of the
Secretin small secretion by gut”)
intestine pancreatic ducts
Stomach  Gastric-acid
 primary neural control of GI function
secretion  100 M neurons
D cells of Stomach /  Gastrin release  lies entirely in the wall of the gut
Somatostatin  Fluid absorption /
stomach & Intestine  can be modified by input from the brain
duodenum,  secretion
 cells of  nervous connections with
 Smooth-muscle
pancreatic contraction parasympathetic and sympathetic
islets Pancreas  Endocrine/exocrine nerve fibers
Liver
secretions  receives afferent fibers from sensory nerve
 Bile flow
Substance P Enteric Enteric Neurotransmitter
endings located in the epithelium or gut wall
neurons neurons
Vasoactive ENS neurons Small  Smooth- a. Myenteric (Auerbach’s) Plexuses
Intestinal intestine muscle  outer layer
Peptide relaxation
 Secretion by small
 located between the muscle layers of
Intestine proximal esophagus to rectum
 Secretion by  Actions: motor effects
Pancreas pancreas
• increase tonic contraction
• increase intensity of rhythmic
contraction
C. Neurocrine Mechanism • increase velocity of excitatory waves
 involves the release of neurotransmitters from a
nerve terminal located in the GI tract. The b. Submucosal (Meissner’s) Plexuses
neurotransmitter then influences the motor & / or  inner layer
secretory activities of the GI tract  submucosa of intestines only
 Action: regulate the secretory activities of
Innervation of the GI Tract glandular, endocrine, epithelial cells

1. Extrinsic Nervous System – nerves that innervate the

gut with cell bodies located outside the gut wall.
2.
a. Parasympathetic NS
b. Sympathetic NS

UST FMS MEDICAL BOARD REVIEW 2022 3 | PHYSIOLOGY


GASTROINTESTINAL MOTILITY
The primary functions of the motor activity of the GI
tract are:
1. GI motility produces peristalsis or
propulsive contractions - moving
rings of contractions that propel luminal
contents along the GI tract in a caudal
direction.
 result in the elimination of nondigested,
nonabsorbed material.
 occurs in the pharynx, esophagus, gastric
antrum and the small and large intestines.
2. It produces segmental contractions, which
produce narrow areas of contracted segments
between relaxed segments.
 result in the increased mixing or churning
of luminal contents that enhances the
digestion and absorption of dietary nutrients.
3. It allows the stomach and large intestines
to act as reservoirs for holding the
luminal contents.
 made possible by sphincters that separate the
organs of the GI tract.
ELECTROPHYSIOLOGY OF THE GI SMOOTH
MUSCLE
 The electrical and mechanical properties
of GI smooth muscle needed to perform
its functions include:
1. Rhythmic contraction - alternating
contraction and relaxation of individual
muscle cells.
 allows the movement of the GI tract from
orad to caudad
2. Tonic contraction - sustained contraction of
each individual muscle cells.
 allows some of the GI organs to function as
reservoirs.
Electrical Activity of the GI Smooth Muscle
 Resting Membrane Potential / Slow Waves / Basic
Electrical Rhythm
 The RMP of the GI smooth muscle cells ranges
from approximately - 40 to - 80 mV.
 The Na+K+-ATPase contributes significantly to the
RMP of the GI smooth muscle.
 In GI smooth muscle, the RMP characteristically
varies or oscillates. These oscillations are called
slow waves or basic electrical rhythm (BER).
 The frequency of slow waves varies from the
stomach to the large intestine.
 generated by the interstitial cells of Cajal (ICCs),
located between the circular and longitudinal
layers of the muscularis externa & other places
in the wall of the GI tract. ICCs are the
“pacemaker” cells of the GI smooth muscle
 modulated by hormones, paracrine substances,
and neurocrine mediators
Action Potentials
UST FMS MEDICAL BOARD REVIEW 2022
GASTROINTESTINAL PHYSIOLOGY
Asst. Prof. ANITA Q. SANGALANG, MD, MHPEd
Department of Physiology
 Action potentials (AP’s) in GI smooth muscles are
more prolonged (10 - 20 msec) than those of
skeletal muscle.
 have little or no overshoot
 The rising phase of the AP is caused by ion flow
through channels that conduct both Ca2+ and
Na+ and are relatively slow to open.
 Ca2+ that enters the cell during the AP helps to
initiate contraction by activating the openings of
K + channels.
 When the membrane potential of GI smooth
muscle reaches the electrical threshold, a train of
action potential is fired. These AP’s enhance the
contractile force of the smooth muscles cells.
Stronger contractions are produced by AP’s that
are intermittently triggered near the peaks of the
slow waves. The greater the number of AP’s that
occur, the more intense is the muscle
contraction.
• Between trains of AP’s, the tension
developed by the GI smooth
muscle fails but not to zero. This baseline
tension is called tone.
Relationship between Action Potential and
Smooth Muscle Tension
 These activities are regulated, in large part, by
both neural and hormonal stimuli. Modulation
of GI smooth muscle contraction is largely a
function of [Ca 2+].
Agonists regulate [Ca2+] by
1. activating G-protein-linked receptors which
results in the formation of IP3 and release
of Ca2+ from intracellular stores
2. opening and closing plasma-membrane Ca
2+
channels
 Acetylcholine (Ach) and substance P
• predominant neurotransmitter of excitatory
motor neurons.
 Vasoactive intestinal peptide (VIP) and nitric
oxide (NO)
• inhibitory.
• hyperpolarize the smooth muscle cells and
may diminish or abolish action potential
spikes.
 Different neural or hormonal inputs increase or
decrease the frequency with which membrane-
voltage Vm exceeds threshold and produces an
AP and thus increases muscle contractility.
 Smooth muscle activity is also regulated by
luminal food and digestive products. They
activate mucosal chemical and mechanical
receptors, thus inducing hormone release or
stimulating the ENS and controlling smooth
muscle functions.
4 | PHYSIOLOGY
 GASTROINTESTINAL PHYSIOLOGY
Asst. Prof. ANITA Q. SANGALANG, MD, MHPEd
Department of Physiology

• specialized smooth muscle that is both

Differences Between a Slow Wave anatomically and pharmacologically distinct from
and a Spike Potential adjacent muscle in the distal end of the
esophagus and proximal portion of the stomach
SLOW WAVE SPIKE POTENTIAL • Primary Functions of the LES:
Not an action potential a. permit coordinated movement of ingested
slow undulating changes in True action potential food into the stomach from the esophagus
the RMP after swallowing or deglutition
Basic electrical rhythm
b. prevent reflux of gastric contents into the
excited by slow wave
esophagus
caused by interstitial cells potential when it reaches
of Cajal (intestinal the RMP threshold (more 4. Pyloric Sphincter
pacemaker) positive than -40mv) • a ring of smooth muscle and connective tissue
NV: -50 to -60 mv between the antrum and the duodenum
does not elicit contractions causes muscle
• The pressure of the pyloric sphincter regulates,
contractions
in part, gastric emptying and prevents duodenal
Intensity: 5-15 mv
Frequency: gastric reflux.
Stomach: 3/min • quite short and is a relatively poor barrier (i.e.
Duodenum: 10-13/min it can resist only a small pressure gradient).
Ileum: 8-9/min • The stomach, duodenum, biliary tract, and
Colon: 6-8/min pancreas – which are closely related
Depolarization by: embryologically -- function as a unit.
stretch • Coordinated contraction and relaxation of the
acetylcholine antrum, pylorus, and duodenum (referred to as
parasympathetic NS
“antroduodenal cluster unit”) are probably more
Hyperpolarization by: important than simply the pressure produced by
Norepinephrine the pyloric smooth muscle per se.
Sympathetic NS 5. Sphincter of Oddi
• regulates the movement of the contents of
GI SPHINCTERS the common bile duct into the duodenum
 specialized circular muscles that separate 6. Ileocecal Sphincter
segments of the GI tract through which food • separates the ileum and the cecum
products pass • distention of the ileum results in relaxation of the
 function as barriers to flow by maintaining a sphincter, whereas, distention of the
positive resting pressure that serves to separate proximal (ascending) colon causes
the two adjacent organs, in which lower contraction of the ileocecal sphincter.
pressures prevail. Thus, they regulate both Consequently, ileal flow into the colon is
antegrade (forward) and retrograde (reverse) regulated by luminal contents and pressure,
movement. both proximal and distal to the ileocecal
 As a general rule, stimuli proximal to a sphincter sphincter.
cause sphincteric relaxation, whereas, stimuli
distal to a sphincter induce sphincteric 7. Internal Anal Sphincter
contraction. • both circular and longitudinal smooth muscle.
 effectively serve as one-way valves • under involuntary control.
 The location of a sphincter determines its • The high resting pressure of the overall anal
function. sphincter predominantly reflects the resting
 Changes in sphincter pressure are coordinated tone of the internal anal sphincter. It
with the smooth muscle contractions in the contributes 70-80 of anal tone at rest.
organs on either side. • Distention of the rectum initiates the
This coordination depends on both the rectosphincteric reflex by relaxing the internal
Intrinsic properties of sphincteric smooth anal sphincter.
muscle and neurohumoral stimuli. 8. External Anal Sphincter
 All GI sphincters are under the control of the • encircles the rectum
enteric nervous system, vagus nerve, and • contains only striated muscles
sympathetic nerves. • controlled by both voluntary and involuntary
mechanisms
1. Upper Esophageal Sphincter (UES) • produces 20-30% of anal tone at rest
• separates the pharynx from the upper part of
the esophagus MASTICATION (CHEWING)
• striated muscle  a voluntary and but more frequently, a reflex
• has the highest resting pressure of all the GI behavior
sphincters  controlled by the somatic nerves to the skeletal
muscles of the mouth and jaw
2. Lower Esophageal Sphincter (LES)
• separates the esophagus from the stomach

UST FMS MEDICAL BOARD REVIEW 2022 5 | PHYSIOLOGY


Functions of Chewing
1. lubricates food by mixing it with salivary mucus
2. initiates digestion of starch through salivary
amylase
3. mechanically chops food into smaller pieces
so that it can be easily swallowed and
propelled more easily and more readily
mixed with the digestive secretions of the
stomach and duodenum.
 Although chewing prolongs the subjective
pleasure of taste, it does not appreciably alter
the rate at which food is digested and
absorbed. On the other hand, attempting to
swallow a large particle of food can lead to
choking if the particle lodges over the trachea,
blocking the entry of air into the lungs.
The Chewing Reflex
Bolus of food → initiates reflex inhibition of muscle
of mastication → allows the lower jaw to drop →
stretch reflex of the jaw muscles that lead to
rebound contraction → raises the jaw to cause
closure of the teeth → bolus of food
DEGLUTITION (SWALLOWING)
 A rigidly ordered sequence of events that propel
food from the mouth to the stomach
 Initially voluntary, later, a reflex
 Swallowing center: medulla, lower pons (CN V, IX,
X, XII)
Phases of Swallowing
1. Oral Phase (Voluntary)
 food broken down, moistened to form a bolus
that is moved toward the oropharynx
 accomplished by pressing food against the hard
palate with the tongue
2. Pharyngeal Phase
 touch receptors in pharynx stimulated by food
to initiate swallowing reflex
 occurs in <1 second
 respiration is inhibited
3. Esophageal phase
 respiration resumes
a. Primary peristalsis
b. Secondary peristalsis – frequently
repetitive
Note: Swallowing induces relaxation (receptive
relaxation) of LES and proximal stomach
ESOPHAGEAL MOTILITY
Esophagus
 18 - 26 cm hollow muscular tube
 lined with a stratified squamous epithelium
 no serosa
Parts:
 Upper 1/3 – striated muscles
 Middle 1/3 – striated & smooth muscle
 Lower 1/3 – smooth muscle
UST FMS MEDICAL BOARD REVIEW 2022
GASTROINTESTINAL PHYSIOLOGY
Asst. Prof. ANITA Q. SANGALANG, MD, MHPEd
Department of Physiology
Types of Peristalsis in Esophagus
1. Primary peristalsis - continuation of peristaltic
waves from the pharynx
2. Secondary peristalsis - results from distention of
the esophagus
Motor Functions of the Esophagus
 conduit that moves food from the pharynx to the
stomach
 Innervation: vagus nerve
1. somatic fibers - striated muscles
2. visceral fibers (preganglionic
parasympathetic) – smooth m.
 Sphincters:
1. UES – prevents the entry of air
2. LES – prevents the entry of gastric contents
GASTRIC MOTILITY
Functions of Gastric Motility
1. The receipt of ingested material represents the
reservoir function of the stomach and occurs
as smooth muscle relaxes.
- occurs primarily in the proximal portion of
the stomach.
2. Ingested material is churned and altered to
a form that rapidly empties from the
stomach through the pylorus and facilitates
normal jejunal digestion and absorption.
3. The antrum, pylorus, and proximal part of
the duodenum function as a single unit for
emptying into the duodenum the modified
gastric contents (“chyme”), consisting of
both partially digested food material and
gastric secretions.
Electrophysiology of the Stomach
 electrical rhythm of the stomach lasts 10x longer
and does not overshoot.
 produces gastric smooth muscle contraction
when the depolarization exceeds the threshold
for contraction.
 the greater the extent of depolarization and the
longer the muscle cell remains depolarized
above the threshold, the greater is the force of
contraction.
Regulation of Gastric Contractions
1. Endocrine
 stimulate gastric contractility
Substance P
Gastrin
 inhibits gastric contractility
Norepinephrine
2. Neurocrine
a. Extrinsic Neurons
Parasympathetic NS - vagus
 excitatory to gastric smooth muscle
motility and gastric secretions
Sympathetic NS - celiac plexus;
 inhibitory
b. Intrinsic Neurons
6 | PHYSIOLOGY

Neurons of ENS produce
acetylcholine and substance P
which are stimulatory to gastric
contractions.
Gastric Filling and Accomodation
 Gastric accommodation is the active dilatation
of the fundus
 Receptive relaxation of the fundus and body
occurs after the relaxation of LES
 The stomach can receive volume as large as 1.5
liters without an increase in intragastric pressure
 Relaxation in the fundus is primarily regulated by
a vagovagal reflex.
 Vagotomy abolishes a major portion of gastric
accommodation, so increases in intragastric
volume produce greater increases in intragastric
pressure.
Mixing and Emptying of Gastric Contents
 When food enters the stomach, they settle in the
fundus and body.
 The muscle layers in the fundus and body are
thin; As a result, the contents of the fundus and
the body settle into layers based on the density
of the contents.
 Gastric contractions begin in the middle of the
body of the stomach and travel toward the
pylorus. They increase in force and velocity as
they approach the gastroduodenal junction, and
emptied into the duodenal bulb.
1. Liquids flow around the mass of food
contained in the body of the stomach and
are emptied more rapidly into the
duodenum.
a. Water and isotonic saline are the
substances most rapidly emptied.
b. Acidic and caloric fluids are emptied
more slowly.
2. Fats tend to form an oily layer on top of the
other gastric contents. They are emptied
later than are the other gastric contents.
3. Solids do not leave the stomach as such.
They must first be reduced in size (< 2mm).
4. Large (> 2 mm) or indigestible particles
cannot pass through the pyloric ring. They
are retained in the stomach for even longer
periods.
Mechanical Actions of Stomach and its Content
A. Propulsion - movement of solid particles toward
the antrum that is accomplished by the
interaction of propulsive gastric contractions and
occlusion of the pylorus.
B. Grinding – churning of a bolus of material is
trapped near the antrum to help reduce the size
of the particles
UST FMS MEDICAL BOARD REVIEW 2022
GASTROINTESTINAL PHYSIOLOGY
Asst. Prof. ANITA Q. SANGALANG, MD, MHPEd
Department of Physiology
C. Retropulsion - particles larger than 2 mm are
propelled back into the body of the stomach for
pulverization and shearing.
 Propulsion, grinding, and retroplusion are
repeated multiple times until the gastric
contents are emptied.
 Particles larger than 2 mm are initially retained
into the stomach but are eventually emptied
into the duodenum by migrating myoelectric
complexes during the interdigestive period that
begins two hours or more after eating.
Functions of the Gastroduodenal Junction
1. allows the carefully regulated emptying of
gastric contents at a rate consistent with the
ability of the duodenum to process the chyme.
2. prevents regurgitation of the duodenal contents
back into the stomach.
Regulation of Gastric Emptying
1. Extrinsic Neurons
a. Parasympathetic NS - both excitatory &
inhibitory to the pyloric sphincter
b. Sympathetic NS - stimulates constriction of
the pyloric sphincter
2. Intrinsic Neurons - ENS
a. Ach - stimulates constriction of the pyloric
sphincter
b. VIP - inhibit constriction of the pyloric
sphincter
c. NO - inhibit constriction of the pyloric
sphincter
3. Hormones – stimulate constriction of the pyloric
sphincter
a. cholecystokinin (CCK)
b. gastrin
c. gastric inhibitory peptide (GIP)
d. secretin
Gastric Emptying is slowed by
1. Duodenal pH < 3.5 - acid in the duodenum
releases secretin  inhibits antral
contraction + stimulates contraction of the
pyloric sphincter
2. Fatty acids or monoglycerides in the duodenum
 release of CCK and GIP from the duodenum
and jejunum  decrease gastric emptying
3. Hypertonic solutions in the duodenum
7 | PHYSIOLOGY

 hyperosmotic solutions in the duodenum
and jejunum  release an unidentified
hormone  slows rate of gastric emptying
4. Amino acids and peptides in the duodenum -
release:
a. gastrin - increases the strength of antral
contractions + constriction of pyloric
sphincter
b. CCK - constrict pyloric sphincter
c. GIP - constrict pyloric sphincter
Control of Gastric Emptying
SMALL INTESTINAL MOTILITY
Functions of Small Intestinal (SI) Motility
1. serves to mix chyme with digestive secretions.
2. brings chyme into contact with the absorptive
surface of the microvilli,
3. propels chyme toward the colon.
Basic Electrical Rhythm of the Duodenal Bulb
 10-13 slow waves /minute
 The basic electrical rhythm (BER) of the
duodenal bulb is influenced by the BER of
both the stomach and the postbulbar
duodenum.
 The duodenal bulb contracts irregularly. The
contractions of the antrum and duodenum
are coordinated: when the antrum
contracts, the duodenal bulb relaxes.
Electrophysiology of the SI Muscle
 The BER of the smooth muscles of the small
intestines occurs regularly.
 It is highest in the duodenum and declines
along the length of the small intestines.
 Duodenum - 10-13 slow waves/minute
 Terminal ileum –8-9 slow waves/minute
 Regulation: The BER of the small intestinal
smooth muscle is entirely intrinsic but the
autonomic nervous system modulates
contractile activity.
Types of Movement of the Small Intestine
1. Segmentation
 most frequent type
 characterized by closely spaced contraction of
the circular muscle layer.
 divides the small intestines into small
neighboring segments.
UST FMS MEDICAL BOARD REVIEW 2022
GASTROINTESTINAL PHYSIOLOGY
Asst. Prof. ANITA Q. SANGALANG, MD, MHPEd
Department of Physiology
 effectively mixes chyme with digestive
secretions.
 regulated by neural pathways (ENS) and
hormonal mediators (CCK)
Segmentation
2. Peristalsis
 progressive contraction of successive
sections of circular smooth muscle.
 moves along the GI tract in an orthograde
direction.
 occurs in the small intestines but usually
involves only a short length of small
intestines.
 regulated by neural and hormonal controls:
(a) released orad to a site of intestinal
distention - stimulatory
Acetylcholine
Substance P
(b) released caudad to a site of
intestinal distention; inhibitory:
VIP
Nitric oxide
MIGRATING MYOELECTRIC COMPLEX
 In the fasting state, the small intestine is
relatively quiescent but exhibits synchronized,
rhythmic changes in both electrical and motor
activity.
 consists of bursts of intense electrical and
contractile activity of the stomach and small
intestine in the fasting state
 more propulsive than in the fed state
 repeats every 75-90 minutes unless a meal is
ingested, in which case the migarting
myoelectric comples (MMC) is suspended
 housekeeper of the small intestines
Phases of MMC
1. Prolonged quiescent period
2. Period of increasing action potential frequency
and contractility
3. Period of peak electrical and mechanical activity
 lasts about 10 minutes
 large contractions that propagate along the
length of the intestines are stimulated by
motilin and sweep any remaining gastric
and intestinal contents out into the colon
 pylorus and ileocecal valve open fully during
this phase, so even large undigested items
can eventually pass.
4. Period of declining activity that merges into the
next quiescent period
Motilin - a 22-amino-acid peptide synthesized in
duodenal mucosa and released just before the
initiation of phase 3 of the MMC cycle
8 | PHYSIOLOGY

 After a meal motilin levels fall and the MMC
cannot be resumed until they rise again.
. Phases of Migrating Myoelectric Complex
Reflex Control SI Motility
 Law of the intestine - when a bolus of
material is placed in the small intestines, the
intestines typically contract behind the bolus
and relax ahead of it. This action propels the
bolus in an orthograde direction.
 Intestinointestinal reflex – overdistention of
one segment of the intestine relaxes the
smooth muscle in the rest of the intestine
 Gastroileal reflex, increased motor and
secretory activities in the stomach increase the
motility of the terminal part of the ileum and
accelerate the movement of material through
the ileocecal sphincter.
Emptying of the Ileum
 The ileocecal sphincter valve separates the
terminal end of the ileum from the cecum.
Normally this valve is closed.
 Distention of the distal ileum promotes
peristalsis in the ileum and thus the opening of
the ileocecal sphincter.
 Ileal emptying occurs at a rate that allows the
colon to absorb most of the salts water in the
chyme.
LARGE INTESTINAL MOTILITY
Parts of the Large Intestine
1. ascending colon
2. transverse colon
3. descending colon
4. sigmoid colon
5. rectum
6. anus
 The longitudinal muscle layer of the muscularis
externa is concentrated into three bands called
taenia coli.
 The longitudinal muscle layer between the taenia
coli is thin.
 In contrast, the longitudinal muscle of the rectum
and anal canal is substantial and continuous.
Functions of the Large Intestine
1. reabsorbs remaining fluid and electrolytes
that were used during movement of the meal
along the GIT. It converts the liquid content of
Ileocecal materials to solid and semi-solid
UST FMS MEDICAL BOARD REVIEW 2022
GASTROINTESTINAL PHYSIOLOGY
Asst. Prof. ANITA Q. SANGALANG, MD, MHPEd
Department of Physiology
stool containing only about 50-100 ml of
water per day
2. digests and absorbs the components of the
meal that cannot be digested and absorbed
more proximally
3. avidly absorbs the short chain-fatty acids
formed by the catabolism (or fermentation) of
dietary carbohydrates that are not absorbed
in the small intestines
4. communicates with other GI segments to
optimally integrate function (ie.gastrocolic
reflex)
5. serves as a reservoir. It stores the waste
products of the meal
6. eliminates its contents in a regulated and
controlled fashion, largely under voluntary control
Functional Parts of the Large Intestine
1. Proximal part
 cecum, ascending colon, transverse colon
 where most of the fluid and electrolyte
absorption occurs
 where bacterial fermentation takes place
2. Distal part
 descending colon and rectosigmoid
 provides final dessication
 serves as storage organ for colonic material
before defecation
Electrophysiology of the Colon
1. Circular Muscle
Types of interstitial cells of colon
a. Those near inner border of the circular
muscle layer - produce 6-8 slow waves /
minute, high amplitude
b. Those near the outer border of the
circular muscle layer
 produce myenteric potential oscillations
 higher frequency, low amplitude
 The circular muscle layer of the colon does
not usually fire action potentials.
 Acetylcholine enhances contractions by
increasing the duration of some of the slow
waves.
2. Longitudinal Muscle - fires AP at the peaks of the
myenteric potential oscillations.
Regulation of Large Intestinal Motility
1. Extrinsic Neurons - modulates the control of
colonic motility by the ENS (except defecation
reflex)
a. Parasympathetic NS:
Vagus nerve - causes segmental
contractions of proximal colon
Pelvic nerve - causes expulsive movements
of the distal colon and sustained
contractions of some segments.
b. Sympathetic NS – inhibits colonic moveme
9 | PHYSIOLOGY

2. Intrinsic Neurons
ENS - directly controls the contractile behavior
of the colon
Acetylcholine stimulatory
Substance P
VIP
Nitric oxide inhibitory
Types of Movements of the Large Intestine
1. Short-duration contraction
 It originates in the circular muscle.
 stationary pressure waves that persist for 8
seconds
2. Long-duration contraction
 It is produced by the taeniae coli.
 It lasts for 20-60 seconds.
 It may propagate over short distances.
 The propagation may move orally as
well as aborally, particularly in the more
proximal segments of the colon.
 The BER that governs the rate and
origination sites of smooth muscle
contraction in the small intestine does
not traverse the ileocecal valve to
continue in the colon.
 The two predominant motility patterns
of the large intestine are directed not
to propulsion of the colonic contents but
rather to mixing of the contents and retarding
their movement, thereby providing them
with ample time in contact with the
epithelium. Both these patterns originate
largely in response to local conditions, such
as distention.
2. “High-amplitude propagating contraction”
 It is a motility pattern that is of high
intensity
 It produces mass movement of
feces exclusively in an aboral
direction, along the length of the
large intestine from the cecum to
the rectum.
 It is designed to clear the colon of its
contents. However, although such motility
pattern can clearly be associated with
defecation, it does not necessarily result
in defecation.
 It occurs approximately 10x/day in
healthy individuals.
 There is considerable variability among
individuals with respect to the rate at
which colonic contents are transported
from the cecum to the rectum. Although
small intestinal transit times are relatively
constant in healthy adults, the contents
may be retained in the large intestines
anywhere from hours to days without
significant dysfunction.
UST FMS MEDICAL BOARD REVIEW 2022
GASTROINTESTINAL PHYSIOLOGY
Asst. Prof. ANITA Q. SANGALANG, MD, MHPEd
Department of Physiology
Reflex Control of Large Intestinal
Motility
 Colonocolonic reflex - distention of one
part of the colon causes a relaxation in other
parts of the colon . Partly mediated by the
sympathetic fibers.
 Gastrocolic reflex - after a meal enters
the stomach, there is an increase in the
motility of proximal and distal colon and the
frequency of mass movements. This reflex
depends on the autonomic innervation to
the colon, hormones such as CCK and
gastrin may also be involved.
 Orthocolic reflex is activated on rising
from bed and promotes a morning urge to
defecate.
RECTUM AND ANAL CANAL
DEFECATION REFLEX
 expulsion of indigestible residues from the GI
tract.
 both a reflex and a voluntary action.
 Stimulus: rectal filling
 Reflex center: sacral spinal cord
 Innervation:
 Parasympathetic (pelvic nerve) - relaxation of the
internal anal sphincter
 Skeletal motor nerve – voluntary action; relaxation
of the external anal sphincter
 Note: The role of the sympathetic nervous system
is not significant in normal defecation.
 The rectum is usually empty.
 The anal canal is kept tightly closed by the anal
sphincters. Just before defecation a mass
movement in the sigmoid causes the rectum to fill.
 Distention of the rectum with feces initiates the
rectosphincteric reflex by relaxing the internal anal
sphincter via the release of VIP and the generation
of nitric oxide.
 Relaxation of the internal anal sphincter permits
the anal sampling mechanism which can
distinguish whether the rectal contents re solid,
liquid, or gaseous in nature.
 After toilet training, sensory nerve endings in the
anal mucosa then generate reflexes that initiate
appropriate activity of the external anal sphincter
to either retain the rectal contents or permit
voluntary expulsion (e.g. flatus).
 If defecation is not desired, continence is
maintained by an involuntary reflex – via the
spinal cord - that contracts the external anal
sphincter.
 If defecation is desired, a series of both voluntary
and involuntary events occurs that include the
voluntary relaxation of the external anal
sphincter.
 Evacuation is preceded by deep breath which
moves the diaphragm downward. The glottis then
closes, and contractions of the respiratory muscles
on full lungs elevate both intrathoracic and
intrabdominal pressures.
 Contractions of abdominal wall muscles further
increase intraabdominal pressure. The increase in
10 | PHYSIOLOGY
 GASTROINTESTINAL PHYSIOLOGY
Asst. Prof. ANITA Q. SANGALANG, MD, MHPEd
Department of Physiology

pressure helps to force feces through the relaxed Effects:

sphincters.
 Adoption of a sitting or squatting position alters
the relative orientation of the intestines and
surrounding muscular structures by straightening
the path for the exit of feces.
 After voluntary relaxation of the external anal
sphincter, rectal contractions move the feces out
of the body,
2. Sympathetic NS
 If a delay in defecation is needed or desired,
voluntary contraction of the external anal
sphincter is usually sufficient to override the
series of reflexes initiated by rectal distention.
a. ↑ synthesis of amylase & mucins
b. contraction of myoepithelial cells
c. enhances transport activities of ductular
epithelium
d. ↑ blood flow (ACH and VIP cause
vasodilatation)
e. stimulates metabolism & growth
 superior cervical ganglion
 travels along the surfaces of blood vessel wall
to the salivary glands
 slight increase in salivary secretions

GASTROINTESTINAL SECRETION STOMACH

Glandular Regions of the Stomach

SALIVARY GLANDS
1. Cardiac glandular region
Types of Salivary Glands
 surface epithelial cells (HCO3-)
1. Parotid – serous secretions  mucus neck cells (mucus)
2. Sublingual – mainly mucous 2. Oxyntic glandular region
3. Submandibular – mixed  surface epithelial cells (HCO3-)
4. Buccal glands – mucus only  mucus neck cells (mucus)
 parietal cells (HCl, intrinsic factor)
Major Types of Salivary Secretions  chief cells (pepsinogen)
1. Serous secretion (ptyalin or α amylase) –  ECL cells (histamine)
digesting starches  D cells (somatostatin)
2. Mucus secretion (mucin) – lubricating and 3. Pyloric glandular region
surface protective purposes  surface epithelial cell (HCO3-)
 mucus neck cells (mucus)
Functions of Saliva  chief cells (pepsinogen)
1. maintaining healthy oral tissues  G cells (gastrin)
2. digestion  D cells (somatostatin)
3. neutralization of refluxed gastric contents
4. mucosal growth and protection of the GI tract
 The final salivary secretion is hypotonic, slightly
alkaline
 Salivary amylase works best at a neutral pH.
 large salivary flow rate, low osmolality, high
potassium

Composition of Saliva Functional Parts of the Stomach

1. Proteins/Enzymes (amylase/lipase) Ionic Composition of Gastric Juice

2. Glycoproteins (mucin)  the higher the rate of secretion, the higher the
3. Lysozymes [H+]
4. Electrolytes (Na, K, HCO3, Ca, Mg, Cl-, Flouride)  at high flow rates, Na decreases H increases
5. Water  at high flow rates, approaches isotonic HCl
 K+ always > than in plasma
Metabolism & Blood Flow of Salivary Glands  Cl- is major anion
 maximal rate of saliva production 1 mL/min/g of  H+ & Cl- secreted against electro-chemical
gland gradient
 increased blood flow, increased metabolism (both
are proportional to saliva formation)

Neural Control of Salivary Secretion

1. Parasympathetic NS
 primary neural control
 salivatory nuclei CN 7 & 9
 stronger, long-lasting effects
 affects both acinus and ducts
Ionic Composition of Gastric Acid Juice
UST FMS MEDICAL BOARD REVIEW 2022 11 | PHYSIOLOGY

GASTRIC ACID SECRETION
 Basal rate of secretion: 1-5 mEq/hr
 Maximal rate of secretion: 6-40 mEq/hr
 Parietal cell release acid at pH 1- 2
 The parietal cells release acid against a
concentration gradient (pH7 in the parietal
cytosol, pH1 in the lumen of the gastric gland).
 Cl- enters the gastric lumen against both
chemical and electrical potential differences.
 H+ and Cl- are actively transported (energy-
requiring) by separate pumps in parietal cells
against gradient.
 H+K+-ATPase - primary H+ pump; - exchanges
H+ for K+
 Cl-,HCO3- countertransporter - mediates HCO3-
efflux out of the parietal cell across its basolateral
membrane.
Control of Gastric Acid Secretion
Agonists of Gastric Acid Secretion
1. Acetylcholine
 a neurocrine agonist
 released by cholinergic nerve terminals
 Mechanism:
binds to M3 muscarinic receptors and
opens Ca++ channels in the apical
membrane hence activating the
phospholipase C pathway. This leads to
elevation of intracellular Ca++
concentration which enhances HCl
secretion by:
(a) activation of basolateral K+ channels
 causing more H+ and K+ATPase
molecules and Cl- channels to be
inserted into the apical plasma
membrane
(b) inhibits release of somatostatin by
D cells
2. Gastrin
 an endocrine agonist
 produced by G cells in the mucosa of the
antrum
 Mechanism:
 binds to CCK-B receptors to elevate
intracellular concentration of Ca++
 activating basolateral K+ channels to
hyperpolarize cell  causing more
H+K+ATPase & Cl- channels to be
inserted into the apical membrane.
3. Histamine
 paracrine agonist
 produced by ECL cells when stimulated by
gastrin
UST FMS MEDICAL BOARD REVIEW 2022
GASTROINTESTINAL PHYSIOLOGY
Asst. Prof. ANITA Q. SANGALANG, MD, MHPEd
Department of Physiology
 strongest agonist of HCl secretion
 Mechanism:
 binds to H2 receptors on parietal cells
plasma membranes hence:
 activating adenyl cyclase and elevating
the cytosolic concentration of cAMP:
 activating basolateral K+ channels 
hyperpolarizes cell, activating apical Cl-
channels  causing more H+,K+ATPase
molecules and Cl- channels to be
inserted in the apical plasma membrane
Endogenous Antagonists of Acid Secretion
1. Somatostatin
 released by D cells near the bases of the
gastric glands. D cells are found both in the
corpus and the antrum
 most important antagonist of HCl secretion
2. Prostaglandin E & I
Mechanism: It inhibits parietal cell HCl
secretion
Misoprostol – prostaglandin analogue
3. Epidermal Growth Factor
Mechanism: It stimulates Gαi - inhibit adenylyl
cyclase hence suppressing HCl secretion by
parietal cells.
Phases of Gastric Acid Secretion
1. Basal / Interdigestive Phase
 rate of acid secretion between meals is low
 follows a circadian rhythm: acid secretion is
lowest in the morning before awakening and
highest in the evening.
 Acid secretion is a direct function of thr
number of parietal cells.
 The number of parietal cells is influenced,
at least in part; by body weight.
 Men have higher rates of basal acid secretion
than women.
 Considerable variability in basal acid secretion
is also seen among normal individuals.
 Resting intragastric pH = 3 - 7 Basal
(unstimulated) rate of secretion: 1 – 5
mEq/hour
 Maximal rate of secretion : 6 – 40 mEq/hr
2. Cephalic phase
 elicited by the sight, smell, and taste of
food
 accounts for 30% of acid secreted
a. Vagus nerve
 mediates the cephalic phase. It
stimulates the enteric NS.
 Acetylcholine - directly stimulates
parietal cell to secrete HCl
 directly stimulates release of
gastrin from G cells and histamine
from ECL cells.
b. Others:
 low glucose level
 neuropeptides in the brain
 The cephalic phase is self-regulated: low pH in
the gastric lumen inhibits HCl secretion by
parietal cells
12 | PHYSIOLOGY

3. Gastric Phase
 elicited by the presence of food in the stomach.
 accounts for 50-60% of acid secreted
Stimuli:
a. Gastric distention
 stimulates cholinergic mechanoreceptors in
the gastric wall released onto the parietal
cells which directly stimulates them to
secrete HCl, and onto antral G cells, which
are stimulated to release gastrin.
b. Amino acid (tryptophan,phenylanlanine),
peptides
 stimulates gastrin release from antral
G cells
c. Others : Ca++, caffeine, alcohol - effects are
enhanced by gastric distension
 Once the buffering capacity of the gastric
contents is saturated, gastric pH falls rapidly
and inhibits further acid release. In this way,
the acidity of gastric contents regulates
itself
Gastric Phase of Gastric Acid Secretion
4. Intestinal Phase
Intestinal Phase of Gastric Acid Secretion
a. Stimulation
 when gastric lumen pH 3
 duodenal distension  vagovagal
reflexes  stimulate parietal and
antral G cells
 Amino acids and peptides - stimulate
duodenal & jejunal G cells  release
gastrin
 release of entero-oxyntin which
stimulates HCl secretion
UST FMS MEDICAL BOARD REVIEW 2022
GASTROINTESTINAL PHYSIOLOGY
Asst. Prof. ANITA Q. SANGALANG, MD, MHPEd
Department of Physiology
b. Inhibition
 acid (pH<3) in the antrum of the
stomach
 acid in duodenum – inhibits parietal cell
release of HCl
 fat digestion products - release
hormones that inhibit acid secretion by
parietal cells
 Hyperosmotic solutions in the duodenum -
release enterogastrones that inhibit
gastric acid secretion
PEPSINOGEN
 major digestive constituent of gastric secretion
 stored in cytoplasm inside zymogen granules in
chief cells and released by exocytosis
 secreted as an inactive proenzyme converted to
pepsin by:
1. cleavage of linkages by HCl
2. Pepsin - acts proteolytically (pH<3) on
pepsinogens to form more pepsins
 initiates protein digestion by splitting certain
amino acid linkages in proteins to create short
amino acid chains.
 may digest 20% of the protein in a typical meal
 inactivated by neutral pH of duodenum
Agonists of Pepsinogen Secretion
 Most agents that stimulate gastric acid secretion
also release pepsinogen from chief cells
1. Acetylcholine
2. Gastrin
3. HCl
4. Secretin
5. CCK
INTRINSIC FACTOR
 a glycoprotein secreted by the parietal cells in
response to the same stimuli that elicit HCl
secretion
 needed for absorption of vitamin B12 in the
terminal ileum
 Intrinsic factor secretion is the only gastric
function that is essential to life.
Pernicious anemia – a condition wherein the
erythrocyte production is defective caused by
autoimmune attack against parietal cell
MUCUS
secretion that contains the glycoprotein mucin.
 a tetramer linked together by disulfide bonds, It is
80% carbohydrates.
 subject to proteolysis by pepsins.
 secreted by mucus neck cells located in the necks
of gastric glands and surface epithelial cells of the
stomach.
 secretion is stimulated by acetylcholine.
 protects gastric mucosa:
 lubricating property
 inhibits pepsin
 alkalinity protects against self-digestion
13 | PHYSIOLOGY

BICARBONATE
 The gastric epithelial cells secrete a
watery fluid that contains HCO3- that is
higher in amount than plasma making the
mucus layer alkaline
 Stimulus : acetylcholine
Gastric Mucosal Barrier
 the protective mucus gel layer that forms on the
luminal surface of the stomach
 0.2mm thick
 separates the HCO3- -rich secretions of the
epithelium from the acidic contents of the gastric
lumen.
 allows the pH of the epithelium to be maintained
at nearly neutral pH despite a luminal pH 2.
 slows the diffusion of HCl & pepsin to the
epithelial cells.
Aspirin, NSAIDs - inhibit secretion of both mucus &
HC03-can cause gastritis and gastric ulcer
Adrenergic agonists - diminish HCO3- secretion; can
cause stress ulcers
PANCREAS
 The pancreas weighs < 100 grams , secretes 1
kg/day of pancreatic juice.
1. Endocrine pancreas – Islet of Langerhans. It
secretes
a. insulin
b. glucagon
c. somatostatin
d. pancreatic polypeptide
2. Exocrine pancreas
- secretes pancreatic juice
- contains microscopic, blind-ended tubules that
are surrounded by polygonal acinar cells and
are organized into lobules (acini) which drain
into intercalated ducts  intralobular ducts 
extralobular ducts  main pancreatic duct
 Both neural and hormonal signals control
pancreatic exocrine secretion
 Innervation:
parasympathetic NS – stimulation
sympathetic NS – inhibition
PANCREATIC JUICE
Components of Pancreatic Juice
1. Aqueous component
 secreted by the epithelial cells of the ducts of
the pancreas.
 nearly isotonic to plasma at all flow rates
 Na+ and K+ - similar to those in plasma
 HCO3- - above those in plasma major
anions
 Cl- - vary reciprocally w/ HCO3-
 serves to buffer HCl-
 HCO3- in the blood is the major source of the
HCO3- secreted into the lumen of the
extralobular duct.
 Stimulated by secretin
UST FMS MEDICAL BOARD REVIEW 2022
GASTROINTESTINAL PHYSIOLOGY
Asst. Prof. ANITA Q. SANGALANG, MD, MHPEd
Department of Physiology
Feedback Loop that Responds to a Fall in
pH in the Duodenum
2. Enzyme component
 secreted by the acinar cells of the pancreas
 for digestion of food.
 Stimulated bv CCK.
 CCK is the product of I cells of the small
intestinal epithelium. Its release is regulated
by:
a. Amino acids, fatty acids
b. Releasing factor - CCK-releasing factor or
peptide (CCK-RP) – secreted by paracrine
cells within the epithelium into the SI
lumen
CCK- Induced Pancreatic Acinar Cell Secretion
GASTROINTESTINAL
DIGESTION AND ABSORPTION
CARBOHYDRATE ASSIMILATION
 The small intestine is critical not only for
absorption of macronutrients into the body but
also for the final stages of digestion into
molecules that are simple enough to be
transported across the intestinal epithelium.
 Phases of Carbohydrate Digestion
1. Luminal - in the lumen of the SI
2. Brush border digestion – surface of
enterocytes
 Molecular Classes of Dietary
Carbohydrates
1. Starch - mixture of both straight-chain
(amylose) and branched-chain
(amylopectin) polymers of glucose.
2. Dietary fiber – consists of carbohydrate
polymers that cannot be digested by human
enzymes. These polymers are digested by
colonic bacteria, allowing salvage of their
caloric value.
14 | PHYSIOLOGY
 GASTROINTESTINAL PHYSIOLOGY
Asst. Prof. ANITA Q. SANGALANG, MD, MHPEd
Department of Physiology

3. Disaccharides against its concentration gradient by coupling its

a. Sucrose - glucose + fructose transport to that of Na+.
b. Lactose – glucose + galactose  GLUT 5 - transport protein through which
fructose is taken across the apical membrane.
DIGESTION OF CARBOHYDRATES  GLUT 2 – transport protein through which
glucose, galactose, and fructose exit the cell via
1. Luminal the basolateral membrane.
a. Salivary amylase
 Starch digestion is initiated in the oral
cavity via salivary amylase.
 Salivary amylase, however, is not
essential for starch digestion (except in
neonates or in patients whom the output
of pancreatic enzymes is impaired by
disease).

b. Pancreatic amylase
 most significant contributor to the
luminal digestion of starch
 Both salivary and pancreatic amylase Absorption of Glucose, Galactose, and Fructose
hydrolyze internal α1,4 bonds in both in the Small Intestine
amylose and amylopectin but not
external bonds nor the α 1,6 bonds that PROTEIN ASSIMILATION
form the branch points in the
amylopectin molecule  Proteins are water soluble polymers that must be
A. D segmentation digested into their smaller constituents before
absorption is possible.
 igestion of starch by amylase is
 Their absorption is more complicated than that of
incomplete and results in glucose
carbohydrates because they contain 20 different
oligomers including dimers (maltose),
amino acids and short oligomers of these amino
trimers (maltotriose), and α limit
acids (dipeptides, tripeptides, and perhaps even
dextrins, the simplest branching structure
tetrapepides) can also be transported by
 to allow absorption of its constituent
enterocytes.
monosaccharides, starch must also
 The liver has substantial ability to interconvert
undergo brush border digestion
various amino acids subject to the body’s needs.
 Essential amino acids – amino acids that cannot
be synthesized by the body either de novo or
2. Brush border digestion
from other amino acids and thus must be obtained
 disaccharides are hydrolyzed to their
from the diet.
component monomers through brush border
digestion
DIGESTION OF PROTEINS
 mediated by a family of membrane-bound,
 Proteins can be hydrolyzed to long peptides simply
heavily glycosylated hydrolytic enzymes
by virtue of the acidic pH that exists in the gastric
synthesized by SI epithelial cells.
lumen.

Phases of Protein Assimilation

1ST PHASE
 occurs in the gastric lumen, mediated by pepsin.
 pepsinogen - in acidic pH, is autocatalytically
cleaved to pepsin.
 pepsin cleaves proteins at sites of neutral amino
acids, with preference for aromatic or large
aliphatic side chains.
 pepsin is not capable of digesting protein fully
into a form that can be absorbed by the intestines
 yields a mixture of intact protein, large peptides
and a limited number of free amino acids.
ABSORPTION OF CARBOHYDRATES
2ND PHASE
 occurs in the lumen of the small intestine,
 Water soluble monosaccharides resulting from
mediated by proteases of pancreatic juice.
digestion must be transported across the plasma
 these enzymes are secreted in the inactive forms.
membrane.
Their activation is delayed until they are in the
 Sodium/glucose transporter 1 (SGLT 1) – a
lumen by virtue of the localized presence of an
symporter that takes up glucose and galactose
UST FMS MEDICAL BOARD REVIEW 2022 15 | PHYSIOLOGY

activating enzyme, enterokinase, only on the
brush border of small intestinal epithelial cells.
Activation of Pancreatic Proteases
 Enterokinase – cleaves trypsinogen to yield active
trypsin
 Trypsin - cleaves all the other protease precursors
secreted by the pancreas
 Chymotrypsin & Elastase – are also
endopeptidases, similar mechanism of action as
trypsin but cleave at sites of neutral amino acids.
 Carboxypeptidase A / B – are ectopeptidases.
They act on the peptides that result from
endopeptidase activity. They cleave single amino
acids from the end of a peptide chain of neutral
(carboxypeptidase A) or basic (carboxypeptidase
B) amino acids situated at the C-terminal.
 The products that result after digestion of a
protein meal by gastric and pancreatic secretions
include neutral and basic amino acids, as well as
short peptides that have acidic amino acids at
their C-terminal and thus are resistant to
carboxypeptidase A or B.
3RD PHASE
 takes place at the brush border.
 mature enterocytes express a variety of
peptidases on their brush borders including both
aminopeptidases and carboxypeptidase that
generate products suitable for uptake across the
apical membrane.
 SI can take up not only single amino acids but
also peptides.
 peptides that are taken up into the enterocytes in
their intact form are then subjected to a final
stage of digestion in the cytosol of the
enterocyte to liberate their constituent amino
acids for use in the cell or elsewhere in the body.
ABSORPTION OF PROTEINS
 Peptide transporter 1 (PepT1) – primary
transporter responsible for uptake of products of
protein digestion. It is a proton-coupled
symporter that carries peptides in conjunction
with proteins.
 Peptides taken up into enterocytes are then
immediately hydrolyzed by a series of cytosolic
peptidases into their constituent amino acids.
 Amino acids not required by the enterocyte are in
turn exported across the basolateral membrane
and enter blood capillaries to be transported to
the liver via the portal system.
UST FMS MEDICAL BOARD REVIEW 2022
GASTROINTESTINAL PHYSIOLOGY
Asst. Prof. ANITA Q. SANGALANG, MD, MHPEd
Department of Physiology
Porta
l
Uptake of Peptides and Amino Acids
by Enterocytes
LIPID ASSIMILATION
Forms of Lipids
1. Dietary:
a. triglycerides – predominant form of lipid in
the human diet. Majority of these have long-
chain fatty acids (carbon chains > 12
carbons) esterifed to the glycerol backbone.
b. phospholipids
c. cholesterol
2. Lipids from bile – exceeds cholesterol from diet
3. Fat-soluble vitamins A, D, E, K
EMULSIFICATION AND SOLUBILIZATION OF
LIPIDS
 When a fatty meal is ingested, the lipid becomes
liquefied at body temperature and floats on the
surface of the gastric contents.
 an early stage in the assimilation of lipids is
emulsification. The mixing action of the
stomach churns the dietary lipid into a
suspension of fine droplets, which vastly
increases the surface area of the lipid phase.
DIGESTION OF LIPIDS
 It begins in the stomach via the action of gastric
lipase.
 Gastric lipase is released in large quantities from
gastric chief cells. It adsorbs to the surface of fat
droplets dispersed in the gastric contents and
hydrolyzes component triglycerides to
diglycerides and free fatty acids (FFAs).
 Little lipid assimilation takes place in the stomach
because of acidic pH
 Majority of lipolysis occurs in the small intestines.
 Pancreatic lipolytic enzymes:
1. Pancreatic lipase -
 capable of hydrolyzing both 1 and 2
positions of triglyceride to yield large
quantities of FFAs and monoglycerides.
 lipase activity is sustained by a cofactor,
colipase, which is a bridging molecule that
binds to both bile acids and to lipase. It
anchors lipase to the oil droplet even in
the presence of bile acids
2. Phospholipase A2 - hydrolyzes phospholipids
secreted as an inactive pro-form that is
activated only when it reaches the small
intestines.
16 | PHYSIOLOGY
 GASTROINTESTINAL PHYSIOLOGY
Asst. Prof. ANITA Q. SANGALANG, MD, MHPEd
Department of Physiology

3. Cholesterol esterases – break down esters of

cholesterol and fat-soluble vitamins and
triglycerides.
 this enzyme requires bile acids for activity
and is related to an enzyme produced in
breast milk that plays an important role in
lipolysis in neonates.
 as lipolysis proceeds, the products are abstracted
from the lipid droplet, first into a lamellar or
membrane phase and subsequently into mixed
micelles composed of lipolytic products and bile
acids.
 the amphiphatic (both having a hydrophobic and
hydrophilic face) bile acids serve to shield the
hydrophobic regions of lipolytic products from
water while presenting their own hydrophilic faces
to the aqueous environment.
 Micelles increase the solubility of lipid in the Fat Absorption Across Walls of Small Intestine
intestinal contents. They increase the rate at
which molecules such as fatty acids can diffuse to WATER AND ELECTROLYTE
the absorptive epithelial surface. SECRETION AND ABSORPTION

ABSORPTION OF LIPIDS  The fluidity of intestinal contents, especially in the

 The products of fat digestion are capable of small intestine, is important in allowing the meal
crossing cell membrane readily because of their to be propelled along the length of the intestine
lipophilicity. and to permit digested nutrients to diffuse to thie
 Unlike monosaccharides and amino acids, which site of absorption.
leave the enterocyte in molecular form and enter
the portal circulation, the products of lipolysis are
reesterified in the endoplasmic reticulum (ER) of SECRETION OF WATER & ELECTROLYTES
enterocyte to form triglycerides, phospholipids,  Dietary fluid intake ~ 2 Liters/day
and cholesterol esters.  Total amount of fluid secreted by the GI tract and
 Concurrently, the enterocyte synthesizes a series its accessory organs = 8 L/day
of proteins known as apolipoproteins in the rough  Saliva - 1500 ml.day
ER. These proteins are then combined with the re-  Gastric secretions - 2500 ml.day
synthesized lipids to form chylomicrons  Bile - 500 ml.day
 chylomicrons consist of a lipid core (predominantly  Pancreatic juices - 1500 ml/day
triglyceride, much less cholesterol, phospholipid,  Intetsinal secretions - 1000 ml/day
and fat-soluble vitamins) coated by  Total amount of fluid for absorption by the SI ~9
apolipoproteins. L/day (99%)
 chylomicrons are then exported from the  Total amount of fluid passed onto the LI ~ 2 L
enterocyte through exocytosis then taken up into  Total amount of fluid lost in the feces = 100 - 200
the lymphatics and bloodstream. ml/day

ABSORPTION OF WATER & ELECTROLYTES

 During the postprandial period, absorption of fluid
is promoted in the small intestines predominantly
via the osmotic effects of nutrient absorption.
 an osmotic gradient is established across the
intestinal epithelium that simultaneously drives
the movement of water across the tight junctions.
 in the period between meals, when nutrients are
absent, fluid absorption can still occur via the
coupled uptake of Na+ and Cl- mediated by Na+
H+ antiporter and Cl-HCO3- antiporter.

Products of Fat Digestion by Lipase are held in

Solution in the Micellar State

UST FMS MEDICAL BOARD REVIEW 2022 17 | PHYSIOLOGY

 GASTROINTESTINAL PHYSIOLOGY
Asst. Prof. ANITA Q. SANGALANG, MD, MHPEd
Department of Physiology

Lumen Lumen Blood

Blood

Mechanism of HCO3- Secretion in

Mechanism of NaCl Absorption
in the Small Intestine
SECRETION OF WATER & ELECTROLYTES
 Secretion of water and electrolyte is regulated in
response to signals derived from the
 luminal contents , and/or
 deformation of the mucosa or intestinal distention
 Secretagogues: Ach, VIP, prostaglandins,
serotonin
 Secretion makes sure that the intestinal contents
are appropriately fluid while digestion and
absorption are still ongoing and may be important
to lubricate the passage of food particles along the
length of the intestine.
 The majority of the intestinal secretory flow of
fluid into the lumen is driven by the active
secretion of Cl- ions.
Lumen Blood
the Duodenum
Changes that represent the intestinal phase of
the response to meal
1. increased pancreatic secretion
2. increased gallbladder contraction
3. relaxation of the sphincter Oddi
4. regulation of gastric emptying
5. inhibition of gastric acid secretion
6. interruption of the migrating myoelectric
complex (MMC)
HEPATOBILIARY PHYSIOLOGY
LIVER
Structural Features of the Liver
 largest organ of the body
 2% total body weight
 Hepatocyte – major cell type
 Hepatic lobule
 functional unit of liver; human liver contains
50,000-100,000 individual lobules
 composed of hepatocytes arranged in plates
that radiate from the central vein like spokes in
a wheel.

Mechanism of Cl- Secretion

Small Intestine and Colon

 Some segments of intestine may engage in

additional secretory mechanisms such as secretion
of HCO3- ions
 This local HCO3- protects the epithelium,
particularly in the most proximal portions of the
duodenum immediately downstream from the Hepatic Lobule
pylorus, from the damage caused by acid and
pepsin. Hepatic / Portal Triad
 consists of (HaPv Bday)
1. Hepatic artery
2. Hepatic portal vein
3. Bile duct
UST FMS MEDICAL BOARD REVIEW 2022 18 | PHYSIOLOGY

Hepatic Sinusoids
 capillaries that are surrounded by hepatocytes
supplied by branches of both portal vein and
hepatic artery. Nutrients and other substances
present are taken up by hepatocytes
Features of Hepatic Sinusoids
1. Low resistance cavities
 blood flow through liver can increase
considerably without concomitant increase in
pressure.
 during fasting, many sinusoids are collapsed.
During postprandial period more sinusoids
are recruited allowing absorbed nutrients to
be transported to liver.
2. Endothelial cells- with specialized openings -
fenestrations - allowing passage of molecules
as big as albumin; lack basement membrane –
allow access of albumin-bound substances to
hepatocytes that will eventually take them up
3. Kupffer cells (or reticuloendothelial cells)
 resident macrophages that line the sinusoids.
 involved in the liver's response to infection,
toxins, ischemia, resection and other
stresses.
 able to phagocytize bacteria and other
foreign matter in the hepatic sinus blood.
4. Space of Disse (perisinusoidal spaces)
 thin layer of loose connective tissues beneath
sinusoidal endothelium and separating
endothelium from hepatocytes
 provides little resistance to movement of
large molecules like albumin.
5. Stellate cells
 serves as storage sites for retinoids
 source of key growth factors for hepatocytes
 site of synthesis of excessive collagen during
disease states  hepatic fibrosis  cirrhosis
Hepatic Sinusoids
Hepatic Vascular and Lymph System
Hepatic portal vein – drains into liver from small
intestine
Hepatic arteries – bring oxygenated blood to liver
from descending aorta.
Central veins – drain the lobules and merge to form
the hepatic veins into vena cava
1. High blood flow and low vascular resistance
UST FMS MEDICAL BOARD REVIEW 2022
GASTROINTESTINAL PHYSIOLOGY
Asst. Prof. ANITA Q. SANGALANG, MD, MHPEd
Department of Physiology
 1050 mL of blood that flows from portal vein
into liver sinusoids/minute + 300 mL of blood
that flows into sinusoids from the hepatic
artery each minute = 1350 mL/min or 27%
resting cardiac output
 resistance to blood flow through the hepatic
sinusoids low (9 mmHg)
2. Blood reservoir
 liver is a large expandable venous organ
 Its normal blood volume including that in
hepatic veins and sinuses is 450 mL or 10%
total blood volume.
 can expand to 0.5-1 L especially in cardiac
failure with peripheral congestion
3. High lymph flow
 Very permeable pores in hepatic sinusoids
and high permeability of liver sinusoid
epithelial cells allows passage of fluid and
proteins into space of Disse.
 Half of all lymph formed in body under resting
conditions arises in the liver.
4. Regeneration
 Hepatic growth factor (HGF) – secreted by
mesenchyme cells in the liver after partial
hepatectomy; promotes hepatic cell division
and growth
 Transforming growth factor-β – cytokine
secreted by hepatic cells; potent inhibitor of
liver cell proliferation;
 main terminator of liver regeneration after
liver has returned to its original size.
Zones of the Liver
1. Zone 1
 Periportal Zone
 consists of hepatocytes lying closest to
hepatic triad
 greatest supply of 02 and nutrients
 most active in detoxification functions
 more sensitive to oxidative injury
2. Zone 2 – Intermediate Zone
3. Zone 3
 Pericentral Zone
 most active in bile synthesis
 more sensitive to ischemia
Zones of the Liver
19 | PHYSIOLOGY

Functions of the Liver
1. Metabolic
2. Detoxification
3. Excretion of protein-bound lipid-soluble waste
products
A. Metabolic Functions
1. Carbohydrate Metabolism
a. Storage of large amount of glycogen
b. Conversion of galactose and fructose to
glucose
c. Gluconeogenesis
d. Formation of many chemical compounds from
intermediate products of carbohydrate
metabolism
2. Fat Metabolism
a. Oxidation of fatty acids to supply energy for
other body functions
b. Synthesis of large quantities of cholesterol,
phospholipids, and most lipoproteins
c. Synthesis of fat from proteins and
carbohydrates
3. Protein Metabolism
a. Deamination of amino acids
b. Formation of urea for removal of ammonia
from the body fluids
c. Formation of plasma proteins
d. Interconversion of the various amino acids and
synthesis of other compounds from amino
acids
4. Other metabolic functions:
a. Storage of vitamins
i. Vitamin A stores can prevent
deficiency for 10 months
ii. Vitamin D stores can prevent
deficiency for 3-4 months
iii. Vitamin B12 stores can prevent
deficiency for at least 1 year
b. Stores iron as ferritin – hepatocytes contain
apoferritin capable of combining reversibly with
iron. The apoferritin-ferritin system of the liver
act as blood iron buffer.
c. Forms blood substrates used in coagulation
 Vitamin K - required by the metabolic
processes of liver for formation of clotting
factors: prothrombin, Factors VII, IX, and X.
B. Detoxification
First Pass Metabolism
 This is a process where absorbed substances
in intestines are metabolized by liver before
making it to systemic circulation. Little or
none of absorbed substances make it to the
systemic circulation.
 Liver limit entry of toxic substances into the
bloodstream.
 It has unusual blood supply. Majority of blood
draining into liver is venous in nature via
portal vein from the intestines. Thus, liver
absorbs not only nutrients but potentially
harmful absorbed molecules ex: drugs and
toxins
UST FMS MEDICAL BOARD REVIEW 2022
GASTROINTESTINAL PHYSIOLOGY
Asst. Prof. ANITA Q. SANGALANG, MD, MHPEd
Department of Physiology
Levels of Detoxification
1. Physical - involves the Kupffer cells, which are
phagocytic cells
2. Biochemical
 Hepatocytes are endowed with a broad array
of enzymes that metabolize and modify both
endogenous and exogenous toxins so that the
products are more soluble and less
susceptible to reuptake by the intestines.
Metabolic reactions:
a. Phase I reactions
 oxidation, hydroxylation, other reactions
catalyzed by cytochrome p450 enzymes
b. Phase II reactions
 conjugate the resulting products with
another molecule such as glucoronic acid,
sulfate, amino acids, or glutathione to
promote their excretion.
C. Excretion
 Small water-soluble catabolites are excreted
by the kidneys.
 Larger water-soluble catabolites and
molecules bound to plasma proteins (lipophilic
metabolites, xenobiotics, steroid homones,
and heavy metals) cannot be filtered by the
process of glomerular filtration.
 These substances are taken up by basolateral
membrane transporters that will metabolize
them at the level of microsomes and in the
cytosol.
 These substances ultimately exported through
bile across the canalicular of hepatocytes via a
different transporters. They are then excreted
into the intestine and into the feces.
BILIARY SYSTEM
BILE
 excretory fluid of the liver important in lipid
digestion
 micellar solution with major solutes
Composition of Bile
1. bile acids
2. phosphatidylcholine
3. cholesterol
* In ratios of 10:3:1, respectively
Bile Acid
 Bile acids are produced by hepatocytes as end
products of cholesterol metabolism.
 Cholesterol 7 -hydroxylase – catalyzes the rate-
limiting step of bile acid synthesis.
A. Primary Bile Acids
1. Chenodeoxycholic acid -a dihydroxy bile acid
2. Cholic acid - trihydroxy bile acid
The primary bile acids are acted upon by colonic
bacteria to yield secondary bile acids.
20 | PHYSIOLOGY

B. Secondary Bile Acids
1. ursodeoxycholic acid
2. deoxycholic acid
3. lithocholic acid – formed from bacterial enzymes
acting on chenodeoxycholic acid; relatively
cytotoxic
 Both primary and secondary bile acids can be
conjugated with either glycine or taurine.
 Conjugated bile acids are retained in the
intestinal lumen until they are actively
absorbed in the terminal ileum.
 Conjugated bile acids that escape this uptake are
deconjugated by bacterial enzymes in the colon,
then passively reabsorbed across the colonic
epithelium because they are no longer charged.
Regulation of Bile Acid Syntesis
 Bile acid synthesis can be up- or down
regulated, depending on the body’s
requirements
 If bile acid levels are reduced in the blood
flowing to the liver, synthesis can be
increased up to 10-fold.
 feeding of bile acids suppresses the new
synthesis of bile acids by hepatocytes
Pathway of Bile
Bile from hepatocytes  cannaliculus  biliary
ductules bile ducts  right and left hepatic duct 
common hepatic duct  cystic duct  gallbladder 
common bile duct  duodenum
Pathway of Bile
ENTEROHEPATIC CIRCULATION
 Actively reabsorbed conjugated bile acids
travel the portal blood back to the hepatocyte,
where they are efficiently taken up by
basolateral transporters that may be Na+
dependent or independent
 Bile acids that are deconjugated in the colon
also return to the hepatocytes, where they are
reconjugated to be secreted into bile.
 A pool of circulating primary and secondary bile
acids, and daily synthesis is then equal only to the
UST FMS MEDICAL BOARD REVIEW 2022
GASTROINTESTINAL PHYSIOLOGY
Asst. Prof. ANITA Q. SANGALANG, MD, MHPEd
Department of Physiology
minor fraction ( 10%/day or 200-400 mg) that
escapes uptake and lost in stool.
Role of the Gallbladder
 Gallbladder - a muscular sac lined with high
resistance epithelial cells
 In the postprandial period, bile enters the ducts
and is conveyed toward the SI.
 In the period between meals, bile outflow is
blocked by constriction of the sphincter of Oddi,
and bile is redirected to the gallbladder.
Enterohepatic Circulation
BILE CONCENTRATION IN THE GALLBLADDER
(STANDING OSMOTIC GRADIENT
MECHANISM)
 During gallbladder storage, bile becomes
concentrated because Na+ ions are actively
absorbed in exchange for protons and bile acids
as the major anions are too large to exit across
the gallbladder epithelial tight junction.
 Actively absorbed Na+ are pumped into the lateral
interstitial spaces. Cl- follows through basolateral
Cl- channels.
 The resultant hyperosmotic interstitial space
induces osmotic flow of water from the gallbladder
lumen through the chalangiocyte or through the
lateral intercellular spaces.
 Hydrostatic pressure in the intercellular spaces
elevates forcing fluid to the capillaries.
 Although concentration of bile acids can rise more
than 10-fold, bile remains isotonic because a
single micelle acts as only one osmotically active
particle.
 Any additional bile acid monomers are
immediately incorporated into existing mixed
micelles reducing the risk that cholesterol will
precipitate from bile.
21 | PHYSIOLOGY
 GASTROINTESTINAL PHYSIOLOGY
Asst. Prof. ANITA Q. SANGALANG, MD, MHPEd
Department of Physiology

Mechanism of Bile Concentration

in the Gallbladder

 in the ER, bilirubin is conjugated with glucoronic

Comparison Between Bile in the Liver and acid.
in the Gallbladder

Gallbladder
Liver Bile Bile
Water 97.5 g/dl 92 g/dl
Bile salts 1.1 g/dl 6 g/dl
Bilirubin 0.04 g/dl 0.3 g/dl
Cholesterol 0.1 g/dl 0.3 to 0.9 g/dl
Fatty acids 0.12 g/dl 0.3 to 1.2 g/dl
Lecithin 0.04 g/dl 0.3 g/dl
Na+ 145 mEq/L 130 mEq/L
K+ 5 mEq/L 12 mEq/L
Ca++ 5 mEq/L 23 mEq/L
Congugation of Bilirubin
Cl- 100 mEq/L 25 mEq/L
pH 7.5 6.0
 Conjugated bilirubin (CB) excreted into bile drains
into the duodenum and passes unchanged
through the proximal small intestines.

 When CB reaches the distal ileum and colon 

Stimuli to Hepatic Secretion of Bile and
Gallbladder Emptying hydrolyzed to unconjugated CB by bacterial
1. Cholecystokinin via blood stream causes: glucoronides.
a. Gallbladder contraction
b. Relaxation of sphincter of Oddi  Unconjugated bilirubin is reduced by normal gut
2. Secretin via blood stream - stimulates liver ductal bacteria  urobilinogens
secretion
3. Bile acids via blood - stimulate hepatic  ~ 80-90% excreted in feces  stercobilins
parenchymal secretion of bile
4. Vagal stimulation (Ach) – causes weak  ~10% of urobilinogens passively absorbed
contraction of gallbladder enter portal venous blood  reexcreted by the
liver. A small fraction (< 3 mg/dl) escapes hepatic
BILIRUBIN uptake, filters across the renal glomerulus
 a tetrapyrole pigment, is a metabolite of heme excreted in urine  urobilin
 About 70-80% derived from the breakdown of
hemoglobin in senescent RBCs
 Formation of bilirubin occurs in RES primarily in
the spleen and liver.
 Bilirubin formed in the RES is unconjugated (UCB)
and insoluble in water.
 To be transported in blood, UCB must be
solubilized. This is accomplished by its reversible,
noncovalent binding to albumin.

UST FMS MEDICAL BOARD REVIEW 2022 22 | PHYSIOLOGY

 GASTROINTESTINAL PHYSIOLOGY
Asst. Prof. ANITA Q. SANGALANG, MD, MHPEd
Department of Physiology

Urea Cycle (Krebe-Henseleit Cycle)

Fate of Bilirubin in the Large Intestine

_______________________
AMMONIA HANDLING

 Ammonia (NH3) is a small metabolite that arises

from protein catabolism and bacterial activity and REFERENCES
is highly membrane permeant.
 Berne, R., Levy, M., Koeppen, B., Stanton, B.
 It is toxic to the central nervous system. Physiology (Updated Version) , 6th edition, 2010
 Boron, W., Boulpaep, E. Medical Physiology, 1st
Sources of Ammonia edition, 2003
 Guyton, A., Hall, J., Textbook of Medical Physiology,
1. Colon – 50% 12th edition, 2011
2. Kidney – 40%  Ganong, W. Review of Medical Physiology, 23rd
3. Liver deamination of amino acids edition, 2010
4. Metabolic processes in muscles 10% Widmaier, Raff & Strang, Vander’s Human
5. Release of glutamine from senescent RBC’s Physiology, 12th edition.

 The liver eliminates ammonia from the body by

converting it to urea via the urea or Krebe-
Henseleit cycle.

 The liver is the only tissue in the body that can

convert NH3 to urea.

 If the metabolic capacity of the liver is

compromised acutely, coma and death can rapidly
ensue due to accumulation of both ammonia and
other toxins that cannot be cleared by the liver 
hepatic encephalopathy.

UST FMS MEDICAL BOARD REVIEW 2022 23 | PHYSIOLOGY