Gastrointestinal Physiology

By Kedir Endris (Msc)

Assistant professor of Physiology
 Objectives
• Describe the functional significance of the gastrointestinal
system
• Describe the special features of the enteric nervous system
and the splanchnic circulation.
• List the major gastrointestinal secretions, their
components, and the stimuli that regulate their production.
• Identify the major hormones, other peptides, and key
neurotransmitters of the gastrointestinal system
• Explain types of motility in the GIT
• Describe the role of oral cavity, stomach, small intestine
and large intestine in the digestive process
Gastrointestinal system (GIS), Structure
Introduction: Gastrointestinal system (GIS), Structure
 Introduction
• Digestion: breakdown of food into simple chemical
subs. that can be absorbed and used as nutrients by the
body.
• Food broken into smaller particles to be absorbed into
blood and distributed to various parts of the body
• Digestive system is responsible for these functions.
• Digestive process is accomplished by mechanical and
enzymatic breakdown of food into simpler chemical cpd.
• A normal young healthy adult consumes about 1 kg of
solid diet and 1 to 2 liter of liquid diet every day.
• All these food materials are subjected to digestive
process, before being absorbed into blood and
distributed to the tissues of the body.
• Digestive system plays the major role in the digestion
and absorption of food substances
 Functions of the Digestive System
The digestive system performs six basic
processes:
1. Ingestion: taking food into mouth.
2. Secretion: release of water, acid,
buffers, and enzymes into lumen of GI
tract.
3. Mixing and propulsion: churning and
movement of food through GI tract.
4. Digestion: mechanical and chemical
breakdown of food.
5. Absorption: passage of digested
products from GI tract into blood
and lymph.
6. Defecation: elimination of feces from
GI tract
 Role of GI-system in homeostasis
• Body cells require nutrients to obtain energy and
function optimally.

• The food has to be crushed into smaller units and be

available for utilization by cells.

• The main role of the GI-system to digest, propel,

absorb, and eliminate unwanted residues out of the
body.

• The GIT serves as one of the homeostatic organs in

maintaining the day-to-day balance of food intake
and excretion, thereby sustaining life.
June 10, 2023 8
 GIS and Fluid balance
A. Secretion:
- GI secretions include saliva,
gastric juice, pancreatic juice,
bile.
~ 7 Liters of fluid is secreted
(added) from different
organs into the tract
~ 2 Liters of fluid is drunk daily
~ 9 Liters of fluid added into the
Gut daily.
B. Absorption:
~ 8.5 Lit is absorbed by the SI
~ 400 ml is absorbed by the LI
C. Excretion: only ~ 100 ml of
fluid is excreted feces
June 10, 2023 9
 GIT & microbial defense
• The openness of GIT favors the entrance and thus
harboring of microorganisms (bacteria) in its luminal
surfaces.
• However, the GI-system can protect itself from such
hazards by some defense mechanisms found in:

a. Mouth: Saliva contains lysozymes etc

b. Stomach: HCl acid, Pepsin etc both have
bactericidal effects
c. Small intestine (e.g., Payer's patches): Immuno-
competent lymph tissues
d. Macrophages: Located in SI walls attacks
bacteria (e.g., by phagocytosis)
June 10, 2023 10
 GIT & it’s role in defense

June 10, 2023 11

The basic principles of function in the entire alimentary trac
• The alimentary tract provides the body with a
continual supply of water, electrolytes, vitamins,
and nutrients.
• To achieve this requires:-
• 1) Movement of food through the alimentary tract
• 2) Secretion of digestive juices and digestion of the
food
• 3) Absorption of water, various electrolytes,
vitamins, and digestive products;
• 4) Circulation of blood through the gastrointestinal
organs to carry away the absorbed substances
 Cont…
• 5) Control of all these functions by local, nervous,
and hormonal systems.

• Each part is adapted to its specific functions:

 some to simple passage of food, such as the esophagus
 others to temporary storage of food, such as the stomach
 And others to digestion and absorption, such as the
small intestine.
Physio- anatomy of GIT
 Structures of Digestive System
• Digestive system is made up of GI tract or
alimentary canal and accessory organs.
• GI tract is a tubular structure extending from
mouth to anus with a length of 5-10m
• It opens to the external environment on both ends.
• GI tract is formed by two types of organs:
1. Primary digestive organs.
2. Accessory digestive organs.
• The primary digestive organs are the organs where
actual digestion takes place. Those are
- Mouth, Pharynx, Esophagus, Stomach, SI, and LI
• That make up the alimentary canal
 Cont…
2. Accessory Digestive Organs
• Are organs which help primary digestive organs in the
process of digestion.
• Accessory digestive organs are:
- Teeth, Tongue, Salivary glands, Exocrine part of pancreas,
Liver, Gallbladder
• Teeth aids mechanical breakdown of food
• Tongue assists chewing and swallowing
• Salivary glands secrete saliva for digestion and lubrication
• The pancreas produces hydrolytic enzymes for the digestion
of our daily foodstuff and bicarbonate for the neutralization
of our gastric contents
• The liver secretes bile, stored in the gallbladder and delivered
to the duodenum for fat digestion and absorption
Functional structures, Different Organs & Accessories of the GI-System
Physiologic Anatomy of the Gastrointestinal Wall
• The wall of the GI tract from the
lower esophagus to the anal canal has
the same basic, four-layered
arrangement of tissues.
• The following layers from outer
surface inward:
1) The serosa
2) A longitudinal smooth muscle
layer
3) A circular smooth muscle layer
4) The submucosa
5) The mucosa.
Histology of the GIT
 MUCUS LAYER
• Mucus layer is the inner most layer of GI tract
• It is also called gastrointestinal mucus membrane.
• It faces the cavity of GI tract.
• It consists of an epithelium, the lamina propria, and
the muscularis mucosae.
• The epithelium: it contains exocrine gland cells,
which secrete mucus and digestive enzymes into the
lumen, and
• Endocrine cells release GI hormones into the blood
• Lamina propria: it contains small blood vessels, nerve
fibers, and lymphatic cells/tissues.
• A thin muscle layer called muscularis mucosae is also
found
• The activity of its muscle is responsible for controlling
mucosal blood flow and GI secretion.
 SUBMUCUS LAYER
• Submucus layer is also present in all parts of GI tract,
except the mouth and pharynx.
• It contains loose collagen fibers, elastic fibers, reticular
fibers and few cells of connective tissue.
• Blood vessels, lymphatic vessels and nerve plexus
(submucosal nerve plexus) are present in this layer.
• Muscularis externa is a thick muscle and its
contraction contributes to major gut motility.
• This muscle layer typically consists of two substantial
layers of smooth muscle cells
• An inner circular layer and an outer longitudinal layer.
• The myenteric nerve plexus, is also located between
the circular and longitudinal smooth muscle layers
 Cont…
A. The circular layer (inner luminal side)
• Thicker layer and more powerful in exerting
contractile forces on the contents of the lumen.
• Their contractions decrease the diameter of the
lumen and increase the length.
• Innervated by both excitatory and inhibitory
musculo-motor neurons.
• More gap junctions are found in the circular than in
the longitudinal muscle layer.
• At some regions, the circular SM thicken and forms
a sphincter that prevents backflow of food content
 Cont…
B. The outer longitudinal layer
• When it contracts, it decreases the length of the tract
and cause shortening and lengthening of the tract.
• The effect of both contractions help mix and propel the
chyme in aboral direction.
• Innervated mainly by excitatory musculomotor neurons
• Muscular layer in lips, cheeks and wall of pharynx
contain skeletal muscle fibers
• The esophagus has both skeletal and smooth muscle
fibers.
• Wall of the stomach and intestine is formed from SM
fibers.
• The external anal sphincter is formed by skeletal muscle
 Function of the Serosa
4. Serosa
– Is an outermost layer consisting of connective tissues.

– It protects the underlying tissues and supplies blood

vessels, lymph and nerves to the gut wall.

– Its squamous epithelial cells secrete serous fluid that

helps in moistening & lubricating the tubes outer
surface.

– This helps the abdominal cavity to slide freely against

one another, there by decreasing friction.
June 10, 2023 24
The four major gut layers from inside outward, i.e. mucosa, submucosa,
muscularis externa and serosa
 GI Smooth Muscle Functions as a Syncytium
• The individual smooth muscle fibers are 200 to 500 micrometers
in length and 2 to 10 micrometers in diameter
• In the longitudinal muscle layer
- The bundles extend longitudinally down the intestinal tract
• In the circular muscle layer
- They extend around the gut.
• The muscle fibers are electrically connected with one another
through gap junctions
• Each bundle of smooth muscle fibers is partly separated from the
next by loose connective tissue.
• Each muscle layer functions as a syncytium
- When an action potential is elicited anywhere within the
muscle mass, it generally travels in all directions in the muscle.
 Cont…
• Smooth muscles of the stomach and intestine contract
spontaneously
• Contract spontaneously in the absence of neural or endocrine
influence and contract in response to stretch.
• There are no structured neuromuscular junctions.
• Neurotransmitters travel by diffusion to influence large
numbers of muscle fibers simultaneously.
• The smooth muscle of the esophagus and gallbladder is more
like multiunit-type smooth muscle.
• These muscles do not contract spontaneously
• Contraction is by nervous input at structured junctions to
relatively small groups of muscle fibers.
 Electrical Activity of GI Smooth Muscle
• The GI tract is excited by continual slow, intrinsic electrical activity
-This activity has two basic types of electrical waves:-
1) slow waves and 2) spikes
• Most GI contractions occur rhythmically determined mainly by the
frequency of so-called "slow waves"
• Electrical slow waves are always present and responsible for
triggering action potentials in some regions.
• These waves are not action potentials rather they are slow,
undulating changes in the resting membrane potential.
• Electrical slow-wave frequencies differ in the stomach, small
intestine, and colon.
• Their intensity usually varies between 5 and 15 millivolts, and their
frequency ranges in different parts of GIT from 3 to 12 per minute
• About 3 in the body of the stomach,12 in the duodenum, 8 or 9 in
the terminal ileum and 2 to 13 in the colon.
 Cont..
• Therefore, the rhythm of contraction of the stomach is usually
about 3/min. the duodenum about 12/min, the ileum 8 to
9/minute and 2 to 13 waves/min in the colon.
• The maximum contractile frequency of the muscle does not
exceed the frequency of the slow waves.
• It may occur at a lower frequency because all slow waves may
not trigger contractions.
• Electrical slow waves may occur with or without action
potentials in the small intestine.
• The slow waves appear to be caused by complex interactions
among the smooth muscle cells and specialized cells, called the
interstitial cells of Cajal (ICCs)
• ICCs generate the electrical slow waves in the stomach, small
and LI
• That are believed to act as electrical pacemakers for smooth
muscle cells.
 Cont…
• Electrical slow waves trigger action potentials and action
potentials trigger contractions.
• Electrical slow waves in the small intestine are always present.
• Action potentials are not always associated with a slow wave.
• The slow waves usually do not by themselves cause muscle
contraction in most parts of the gastrointestinal tract, except in
the stomach.
• Instead, they mainly excite the appearance of intermittent
spike potentials
 The spike potentials
• Are true action potentials occur automatically when the
RMP becomes more positive than about -40 millivolts
• The normal RMP of the gut is between -50 and -60 mV
• The higher the slow wave potential rises, the greater the
frequency of the spike potentials, ranging between 1 and 10
spikes per second.
• In GI the channels responsible for the action potentials
formation is calcium-sodium channels.
• They allow especially large numbers of calcium ions to
enter along with smaller numbers of sodium ions.
• Also, the movement of large amounts of calcium ions plays
a special role in causing the intestinal muscle fibers to
contract.
 Role of Ca 2+ ion in excitation
- Ca2+ is important than Na+-ion in the generation of AP (excitation)
during smooth muscle contraction. This is because,
- SM has increased voltage gated ca2+ channels that remain open for
longer periods
-Ca2+ directly combines with Calmoduline and activates the filaments to
cause contraction of the smooth muscles.
- The slow waves do not cause calcium ions to enter the smooth muscle
fiber (only sodium ions).
• Some gastrointestinal tract exhibits tonic contraction
• Tonic contraction is continuous, not associated with the basic electrical
rhythm of the slow waves but often lasting several minutes or even hrs.
• Caused by continuous repetitive spike potentials, by hormones or other
factors that bring about continuous partial depolarization without
causing action potentials and continuous entry of calcium ions
June 10, 2023 32
 Changes in Voltage of the Resting Membrane Potential
• In the GIT-SM, the RMP is not constant, but variable between -50 and -
60 milli volts.
• When the potential becomes less negative depolarization of the
membrane
- The muscle fibers become more excitable.
• When the potential becomes more negative hyperpolarization
- The fibers become less excitable.
• Factors that depolarize the membrane:-
1) Stretching of the muscle
2) Stimulation by acetylcholine released from parasympathetic nerves
3) Stimulation by several specific gastrointestinal hormones.
• Factors hyperpolarize the membrane
1) The effect of norepinephrine or epinephrine on the fiber membrane
2) Stimulation of the sympathetic nerves that secrete mainly NE at
their endings
Neural and Hormonal Regulators of
Gastrointestinal Function
Neural and Hormonal Regulators of GI Function
• The GI tract has its own endocrine system and its local
nervous system, i.e. enteric nervous system (ENS).
• Although its functions can be modulated by the central
nervous system and autonomous nervous system
• The gut can work on its own and independently from
the CNS and ANS.
• This is because numerous regulatory systems are
intrinsic and “hard-wired”,
• There are three principal control mechanisms involved
in the regulation of GI function
• Namely endocrine, paracrine, and neurocrine pathways,
depending on the methods by which the regulators are
delivered to their target sites.
 NERVE SUPPLY TO GIT TRACT
• GI tract has two types of nerve supply:
I. Intrinsic nerve supply
II. Extrinsic nerve supply.
INTRINSIC NERVE SUPPLY
• Intrinsic nerves to GI tract form the Enteric Nervous System
• Consists of nerve cells and fibers which originate and located
in the intestinal wall itself.
• This system supplies the smooth muscles of GIT except upper
esophagus and external anal sphincter which contain striated
muscl
• This system controls most of the gastrointestinal functions
like secretion and motility.
• The enteric nervous system is composed mainly of two
plexuses.
1. Myenteric plexus ( Auerbach plexus)
2. Submucosal plexus (Meissner plexus)
 Myenteric plexus
• Auerbach’s plexus is present in b/n the circular and
longitudinal muscle fibers GIT.
• Stimulation of myenteric plexus causes increase in
- Tone of the gut wall,
- Intensity of rhythmical contractions of gut wall
- Rate of contraction and velocity of contraction
• Generally this plexus regulate the GI tract motility
• Some nerve fibers of this plexus accelerate the movemen
by secreting the excitatory NTs (Ach, Serotonin and
Substance P)
• Others fibers of this plexus inhibit the GI mobility by
secreting inhibitory Nts (VIP, neurotensin and encephali
 Meissner Nerve Plexus
• Also called submucosal nerve plexus
• It is located in b/n the muscular layer & submucosal
layer of GI tract.
• It regulate the secretory functions of GI tract
• It also cause constriction of blood vessels of GI tract

• The ENS plexus contain nerve cell bodies, processes

of nerve cells and receptors.
• The receptor in the GI tract are stretch and chemo
receptors
• Enteric nervous system is controlled by extrinsic
nerves
 Cont…
• The plexuses of the ENS consist of motor neurons,
interneurons, and sensory neurons
• Because the motor neurons of the myenteric plexus
supply the longitudinal and circular smooth muscle
layers of the muscularis.
• This plexus mostly controls GI motility particularly the
frequency and strength of contraction of the muscularis.
• The motor neurons of the submucosal plexus supply the
secretory cells of the mucosal epithelium
• Which control the secretions of the organs of the GI
• The interneurons of the ENS interconnect the neurons
of the myenteric and submucosal plexuses.
• The sensory neurons of the ENS supply the mucosal
epithelium.
• Some of these sensory neurons function as
chemoreceptors
• Receptors that are activated by the presence of certain
chemicals in food located in the lumen of a GI organ.
• Other sensory neurons function as stretch receptors,
receptors that are activated when food distends the wall of
a GI organ.
• The ENS consists of
sensory neurons,
interneurons, and
motor neurons.

• Some sensory signals

travel centrally from
the ENS.

• Both the PsNS and

the SNS divisions of
the ANS modulate
the ENS.
 EXTRINSIC NERVE SUPPLY
• Extrinsic nerves that control the enteric nervous system are from
autonomic nervous system.
• Both sympathetic and parasympathetic divisions innervate the GI
tract
 Sympathetic Nerve Fibers
• The sympathetic fibers to the GIT originate in the spinal cord
between segments T5 and L-2.
• The preganglionic fibers terminate in the celiac and mesenteric
ganglia.
• The post ganglion fibers terminated in the Enteric nerve plex.
• Sympathetic nerves innervate blood vessels, mucosa, and
muscularis of the gut and suppress gut activity when stimulated
• Sympathetic nerve endings secrete nor epinephrine.
• NE acts directly on sphincteric muscles (lower esophageal
sphincter [LES] and internal anal sphincter) to increase
tension and keep the sphincter closed.
• In general, stimulation of SNS inhibits the movement and
decrease the secretion of of GIT.
• Strong stimulation of sympathetic system can totally block
GIT motility.
Sympathetic and parasympathetic innervation o f GI
 Parasympathetic innervations to the gut
• Parasympathetic innervations to the gut is divided into cranial and
sacral division.
• The cranial parasympathetic are transmitted almost entirely in the
vagus nerves
• Providing extensive innervations to the esophagus, stomach, small
intestine and first half of the large intestine
• Preganglionic nerve fibers to lower part of large intestine arise from the
2nd -4th of spinal cord and pass through pelvic nerve.
• All these preganglionic parasympathetic fibers synapse with the
postganglionic nerve cells in the myenteric and submucosal plexus
• PsN fibers accelerate the movements and secretion of GIT except the
sphincters to which it inhibits.
• The NTs secreted by the parasympathetic nerve fibers is Ach
• However other NTs such as VIP released from parasympathetic nerve
endings causes relaxation of the lower esophageal, pyloric, and internal
anal sphincters.
• Stimulation of PNS causes a general increase in activity of the entire
enteric NS, enhancing GI function.
46
Neural control of the gut wall
 (Cont…) Neural innervations of the Gut
a. Parasympathetic : is cholinergic
(Ach)
- Excitatory and causes constrictions of
the gut.
- However, at the sphincters, PNS is
dilatatory in action

b. Sympathetic fibers
- are adrenergic and inhibitory in
action.
It causes dilatation of the alimentary
tract.
- at sphincters, it causes constriction

June 10, 2023 48

 GIT reflexes
1. Reflexes that occur entirely within the ENS. These include reflexes that
control GI-secretion, peristalsis, mixing contractions, local inhibitory
effects.
2. Reflexes that arise from the gut go to the sympathetic ganglia and then
back to the GI-tract.
• Examples:
a) The gastro-colic reflex: signals send from the stomach to cause
evacuation of the colon.
b) The entero-gastric reflexes: signals from the colon and small intestine
to inhibit stomach motility and secretion.
c) The colono-ileal reflex: reflexes from the colon to inhibit emptying
of ileal contents into the colon.
3. Reflexes from the gut to the spinal cord or brain stem and then back to
GIT: Example: defecation reflex
- Vagovagal reflex controls contractions of gastrointestinal muscle layers in
response to food stimuli.
- It is GI reflex circuits in which afferent and efferent fibers of the vagus
nerve coordinate response to gut stimuli.
50
 Reflexes of the GIT cont..
Different GIT reflexes
1. Short localized reflexes (intrinsic)
- occurs within the Enteric NS and at
Ganglionic regions (Pre-vertbral ganglion)
- cause tonic contractions, secretions etc
e.g., gastro-colic, entero-gastric, gastroileal, etc

2. Long reflexes (both extrinsic and intrinsic )

- effected mainly by CNS and parasympathetic
(vagus) nerves
e.g., Defecation reflex

June 10, 2023 51

Nervous Control of the GI Tract

52 Figure 23.4
 Hormonal control of GI function
• The gastrointestinal hormones are released into the
portal circulation and exert physiological actions on
target cells
• Cells responding to a GI hormone express specific
receptors for the hormone.
• Hormones released from the GI tract have effects
on cells located in other regions of the GI tract
• Also on glandular structures associated with the GI
tract, such as the pancreas.
• GI hormones have effects on other tissues that have
no direct role in digestion and absorption, including
endocrine cells in liver and brain
 Hormonal control of GI function
• The hormones that control the gastrointestinal system are
secreted mainly by endocrine cells
• The effect of these hormone act together with regulation
by both the nervous and endocrine systems
• To coordinate the activity of different region of digestive
system and secretion of pancreatic juice.
• These hormone-secreting cells are called -endocrinocytes
• Several dozen substances are currently being investigated
as possible gastrointestinal hormones, but only four have
met all the criteria for true hormone
 Gastrin
 Cholecystokinin
Secretin
June 10, 2023 Gastric inhibitory polypeptide (GIP) & VIP 54
 Gastrin
• Gastrin is secreted by the “G” cells of the antrum of the stomach
• In fetus, the islets of Langerhans also secrete this hormone
Stimulants for secretion of gastrin are:
i. Presence of food in the stomach.
ii. Stimulation of local nervous plexus in stomach and small
intestine.
iii. Vagovagal reflex during the gastric phase of gastric
secretion:
Actions of gastrin
• i. Stimulates gastric glands to secrete gastric juice with more pepsin
and hydrochloric acid.
• ii. Accelerates gastric motility.
• iii. Promotes growth of gastric mucosa.
• iv. Stimulates secretion of pancreatic juice, which is rich in enzymes
• v. Stimulates islets of Langerhans in pancreas to release pancreatic
hormones.
 Functional Phases of Gastric Secretion

1. Cephalic Phase of Gastric 2. Gastric Phase of Gastric

Secretion (approx. 30% of Secretion (approx 60% of
total) total)
(initiated by brain) (initiated by gastric events)

vagus vagus
nerve nerve

FOOD

HCl HCl

Distension
Peptides

circulation circulation
G
G
gastrin
gastrin
56
June 10, 2023 57
 Secretin
• It was the first ever hormone discovered.
• It is secreted by the S-cells of duodenum, jejunum and ileum.
• Secretin is first produced in an inactive form prosecretin
• It is converted into secretin by the acidity of chyme
• The acid chyme entering the duodenum from stomach
stimulate the release of prosecretin
• Secretin stimulates exocrine pancreatic secretion.
• It acts on the cells of pancreatic duct and causes secretion of
large amount of watery juice with bicarbonate ion.
• Other function of Secretin:
i. Inhibits secretion of gastric juice
ii. Inhibits motility of stomach
iii. Causes constriction of pyloric sphincter
iv. Increases the potency of action of cholecystokinin on
pancreatic secretion.
Response to Acidity

Regulation by Secretin
liver
+
HCO3

+
gall
bladder
- HCl
motility
NaCl
+ H2O
HCl
+ HCl
HCl + NaHCO3 NaCl + CO2 + H2O 59
 Cholecystokinin (CCK)
• CCK is secreted by I cells in mucosa of duodenum and jejunum
• Stimulant for the release of this hormone is the presence of
digestive product of fat and proteins (FA, peptides and AA) in
the upper part of small intestine.
Major actions of CCK
i. Contracts gallbladder to release bile
ii. It activates the pancreatic acinar cells and causes secretion
of pancreatic juice with large amount of enzymes.
Other actions of CCK
• i. Accelerates the activity of secretin to produce alkaline
pancreatic juice
• ii. Increases the secretion of enterokinase.
• iii. Inhibits the gastric motility.
• iv. Increases the motility of intestine.
• v. Augments contraction of pyloric sphincter.
• vi. Plays an important role in satiety by suppressing hunger.
Cont…

Fig 15

61
 MOTILIN
• It is secreted by Mo cells, which are present in stomach and
intestine.
• Motilin is secreted when the chyme from stomach enters the
duodenum.
Actions of motilin
• i. Accelerates gastric emptying
• ii. Increases the mixing and propulsive movements of small
intestine
• iii. Increases the peristalsis in colon
• Motilin is released cyclically and stimulates waves of
gastrointestinal motility called interdigestive myoelectric
complexes
• That move through the stomach and small intestine every 90
minutes in a fasted person.
• Motilin secretion is inhibited after ingestion by mechanisms
that are not fully understood
 Gastric inhibitory peptide [GIP]
• It is secreted by K cells in duodenum and in jejunum.
• It is also secreted in antrum of stomach.
• GIP secreted mainly in response to fatty acids and amino
acids but to a lesser extent in carbohydrate.
Actions of Gastric inhibitory peptide (GIP)
• i. Stimulates the beta cells in the pancreas to release insulin.
• It causes insulin secretion, whenever chyme with glucose
enters the small intestine.
• Hence it is called glucose dependent insulinotropic hormone.
• ii. Inhibits the secretion of gastric juice.
• iii. Inhibits gastric motility.
• Recent studies reveal that GIP does not show significant
action on gastric secretion.
 Ghrelin
• Ghrelin is a recently discovered hormone.
• It is synthesized by epithelial cells in the fundus of
stomach.
• It is also produced in smaller amounts in hypothalamus,
pituitary, kidney and placenta.
• Secretion of ghrelin increases during fasting and decreas
when stomach is full.
Actions of Ghrelin:
• i. Promotes the secretion of growth hormone (GH) by
stimulating somatotropes in anterior pituitary.
• ii. Induces appetite and food intake by acting via feeding
center in hypothalamus.
• iii. Stimulates gastric emptying.
VASOACTIVE INTESTINAL POLYPEPTIDE
• VIP is secreted in the stomach and small intestine.
• A small amount of this hormone is also secreted in LI.
• Stimulant for Secretion VIP is the presence of acid
chyme in the stomach and intestine
Actions of VIP
• i. Dilates splanchnic blood vessels.
• ii. Inhibits hydrochloric acid secretion in gastric juice.
• iii. Stimulates secretion of succus entericus (IJ) with
large amounts of electrolytes and water.
• iv. Relaxes smooth muscles of intestine.
• v. Augments action of acetylcholine on salivary glands.
• vi. Stimulates insulin secretion
GI Hormone Actions, Stimuli for Secretion, and Site of Secretion
FUNCTIONAL MOVEMENTS IN THE GIT
 Motility
• Motility in the gastrointestinal tract serves two purposes
1. Moving food from the mouth to the anus
2. Mechanically mixing food to break it into small particles.

• Motility is determined by the properties of the tract’s smooth

muscle and
• Modified by chemical input from nerves, hormones, and
paracrine signals
• Two types of movements occur in the gastrointestinal tract:
1) Propulsive movements
2) Mixing movements
 Functional Types of Movements in the Gastrointestinal Tract
Propulsive Movements-Peristalsis
• The basic propulsive movement of the gastrointestinal tract is peristalsis
• Peristalsis is responsible for propelling food down the GI tract
• A contractile ring appears around the gut and then moves forward
• Stimulation at any point in the gut can cause a contractile ring to
appear in the circular muscle and this ring then spreads along the gut
tube.
• Peristalsis also occurs in the bile ducts, glandular ducts, ureters, and
many other smooth muscle tubes of the body.
• The usual stimulus for intestinal peristalsis is distention of the gut.
• Other stimuli that can initiate peristalsis include chemical or physical
irritation of the epithelial lining in the gut.
• Also, strong parasympathetic nervous signals to the gut will elicit strong
peristalsis.
• Directional movement of peristaltic waves Cont…
toward the anus
• The law of the gut” movement always
occurs from mouth- to- anus unless
pathological
• A peristalitic motion consists of a progressive
wave of strong contraction preceded by
relaxation.
• This phenomena of relaxation where the
muscular walls ahead of the ring relaxes is
called receptive relaxation.
• Peristalsis produces audible sounds (bowel
sounds).
• Peristalsis occurs only weakly or not at all in
any portion of the GIT that has congenital
absence of the myenteric plexus.
 Cont…
Mixing:
• occurs due to local contractions
taking place in small segments.
•
• It chops, shakes, and thereby
mixes food with digestive juices.
•
• Provides increase in surface
area for mixing of digestive
juices with the chyme (stomach,
small and large intestine).
 Blood Supply to Digestive System
• The blood vessels of the GI-system are part of a more extensive system
called the splanchnic circulation.
• Includes blood flow through the GIT plus through the spleen, pancreas
and the liver.
• All of the blood that flows through the gut, spleen and pancreas then
passes into the liver by way of the portal vein.
• The nonfat, water-soluble nutrients absorbed from the gut (such as
carbohydrates and proteins) are transported in the portal venous blood
to the same liver sinusoids
• Leaves the liver by way of the hepatic veins that empty into the inferior
vena cava of the general circulation.
• The advantage is the reticuloendothelial cells in the liver remove bacteria
and other particles entering the blood from the GIT & preventing
pathogens
72
 Blood Supply to Digestive System
• The hepatic cells, absorb and store temporarily from 50% to 75% of
the nutrients.
• Almost all of the fats absorbed from the intestinal tract are not carried in
the portal blood
• Instead absorbed into the intestinal lymphatics and then conducted to
the systemic circulating blood by way of the thoracic duct, bypassing
the liver
ANATOMY OF THE GASTROINTESTINAL BLOOD SUPPLY
• The superior mesenteric and inferior mesenteric arteries supply
blood to the wall of small and large intestine.
• The celiac artery supplies blood to the stomach.
• Big arteries are branched and re-branched to encircle and penetrate
deep into the mucosal, villi, layers of the gut wall.
• the blood flow in each area of the GIT is directly related to the level of
local activity.
• Blood flow to the GIT is increased by 100% during meal time.
73
 Factors that control Blood flow to GIT
1. Metabolic & Vasoactive substances
2. Countercurrent
3. Neural
vasoactive substance
• The release of vasodilator GI hormones during
digestive processes.
• These include CCk, VIP, gastrin, secretin, bradykinin
nitric oxide.
• Local factors affecting blood flow to the gut
– Decreased O2 concentration.
– Increased metabolic products
– Increased Metabolic demand
 (Cont…) blood flow of the GIT
Metabolism:
• Blood flow to the gut generally increases by more than 8-fold after a
meal.
• This is because motor, secretory, and digestive activities increase during
eating.
• Increased metabolic activity, on the other hand, enhances O2-utilisation
by tissues.
• The by-product of metabolism releases Vasoactive agents.
• Vasoactive agents have the effect of dilating blood vessels and increase
blood flow to the GI-tract during rest.
Countercurrent mechanism and flow:
• GIT-blood flow shows a characteristics of countercurrent mechanism,
• Where blood is simply shunted from the arteries to the veins in the villus
(artery & vein are situated very near) .
• Effect: O2 is shunted to venous blood and the villus tip may become
ischemic.
June 10, 2023 75
 (Cont…GIT) Blood flow
Blood flow and neural control of the Gut:
A. Sympathetic
- Cause intense vasoconstriction and thus reduces blood
flow to splanchnic bed.
- The vasoconstriction is important during exercise stress
and during blood loss (hemorrhage) to shunt blood to
skeletal muscles
and to the general circulation, respectively
B. Parasympathetic
- Generally, increases blood flow to the gut because of its
vasodilatatory effect.

June 10, 2023 76

Blood Supply to GIT (cont’d)

77
 The Mouth
The mouth (oral cavity)
- Is responsible for mechanical digestio
of solid food by mastication.
- Mastication helps mix food with
saliva.

Parts of the oral cavity:

- The cheeks, the lips
- The tongue
- The hard and soft palate
- The teeth
- Saliva is released into the oral cavity
June 10, 2023 78
 The Mouth in digestion
• The mouth (oral cavity) is responsible for mechanical digestion of
solid food by mastication.
• In the oral cavity begins mastication of food that involves breaking
and mixing of food with saliva.
• Its functions include ingestion, taste and other sensory responses to
food.
• Mastication (chewing), chemical digestion, swallowing, speech, and
respiration.
• The teeth are admirably designed for chewing
• Most of the muscles of chewing are innervated by the motor branch
of the fifth cranial nerve
• The chewing process is controlled by nuclei in the brain stem.
• Chewing is important for digestion of all foods especially for most
fruits and raw vegetables.
• Aids the digestion of food by increasing surface area for enzymatic
reaction
• Grinding
June 10, 2023 the food prevents excoriation of the gastrointestinal 79tract
 The mouth is enclosed by
a. The Cheeks:

• Cheeks are lateral walls that include skin, elastic skeletal

muscles, and subcutaneous fats.
• The cheeks can hold relatively greater volume of food because
of its elasticity.
• The cheeks and lips retain food and push it between the teeth
for chewing.

b. Lips:
• It has unusually tall dermal papillae, which allow blood
capillaries and nerve endings to come closer to the epidermal
surface
• This area is redder and more sensitive than the cutaneous
area.
• Helps keep food between the upper and lower teeth.
• These muscles also assist in speech.
June 10, 2023 80
 Teeth:
• Grinds into smaller peaces;
• Increases surface area for digestive enzymes react more effectively.
• Incisors (cutting), Canines (tearing), Premolars & Molars
(crushing and grinding, respectively).
• There are two sets of teeth:
1. Primary/deciduous
2. Permanent
• Primary – 20 deciduous teeth that erupt at intervals between 6
and 24 months
• Permanent – enlarge and develop causing the root of deciduous
teeth to be resorbed and fall out between the ages of 6 and 12
years
• All but the third molars have erupted by the end of adolescence
• Usually there are 32 permanent teeth
June 10, 2023 81
June 10, 2023 82
 Dental Formula: Permanent Teeth

• A shorthand way of indicating the number and relative

position of teeth
• Written as ratio of upper to lower teeth

• Deciduous: 2I (incisors), 1C (canine), 2M (molars) = 20

• Permanent: 2I, 1C, 2PM (premolars), 3M =32

2I 1C 2PM 3M X 2 =(32 teeth)

2I 1C 2PM 3M

83
 (Cont.) Mouth or oral cavity
d. Tongue: connected to the flour of the mouth.
• Is a thick mass of voluntary skeletal muscle that shows a high
degree of movement in every angle.
• Mucous membranes are important for lubrication.
• The papillae are projections of the tongue and contain test buds.
• The tongue mixes food with saliva and pushes food towards the
pharynx.
e. Palate: (the hard & soft palate):
• The palate, separating the oral cavity from the nasal cavity
• Makes it possible to breathe while chewing food.
• The uvula helps to retain food in the mouth until one is ready to
swallow.
• During swallowing, it moves upwards & closes the nasal cavity to
prevent food from entering.
June 10, 2023 84
 Types of Salivary glands and their secretions
- Salivary glands are a heterogeneous group of
exocrine glands that produce two types of protein
secretion
- The serous cells and contains amylase an enzyme
that breaks down starch
- The mucous cells and contains mucin for
lubrication and protection.
Three major pairs of salivary glands are:-
a. Parotid 25%:
- Secrete mainly serous rich in water and
electrolytes and contain ptyline.
b. Submandibular 70%:
- Produce both serous and mucous fluid.
c. Sublingual ~5%:
- Secrete mainly thick mucous with little serous
fluid
- All of which empty saliva into the mouth via
June 10, 2023 secretory ducts 85
 Salivary secretion cont…
• Salivon is the functional unit of the salivary gland
• The salivon consists of the acinus, the intercalated duct, the
striated duct, and the excretory (collecting) duct.
• Serous cells secrete digestive enzymes, and mucous cells secrete
mucin.
• Serous cells contain rough endoplasmic reticulum (RER), which
reflects active protein synthesis, and numerous zymogen granules.
• Salivary amylase is synthesized and stored in the zymogen
granules and secreted by the serous acinar cells
• The mucous acinar cells store numerous mucin droplets.
• In the resting state salivary secretion is low amounting to about 30
mL/h.
• The most potent stimuli for salivary secretion are acidic-tasting
substances such as citric acid and the smell of food and chewing.
Mechanisms of salivary secretion
A. Clusters of cells called acini secrete
electrolytes, enzymes, proteins etc
- The electrolyte composition of the primary
secretion produced by the acinar cells and
intercalated ducts resembles that of plasma
(isotonic)
B. The primary secretion are modified by
active absorption of (Na+) and passive
absorption of (Cl-) ions. K+ and
HCO3- are secreted into the lumen as
they pass through the ducts
- samples from the striated & excretory
(collecting) ducts are hypotonic relative
to plasma
• The electrolyte composition of saliva
depends on the rate of secretion.
• At low secretion rates, the ductal
epithelium has more time to modify
and reduce the osmolality of the
primary secretion.
• The epithelial lining of the duct is not
June 10, 2023
permeable to water
 (Cont…), Constituents of saliva
Constituents of saliva • Salivary gland is heterogeneous
A. H2O (99.5%): group of exocrine glands
B. Electrolytes ( 0.5%): • Saliva contains 2-types protein
Na+, Cl-, K+, HCO3- secretions
Mg, Iodine, etc.
C. Other organic
substances include: 1. Serous secretion:
Enzymes (amylase), – Secretion that contains mainly
the enzyme alpha-amylase
lingual lipases, (begins digestion of starch to
Lysozymes, disaccharides)
thiocyanate,
Glycoproteins, 2. Mucous secretion:
(albumin, globulin), – Secretion that contains a
IgA, mucus, etc) protein mucin that helps for
lubrication and surface
(Total secretion = protection.
about 1-1.5 L/day)

June 10, 2023 88

Composition of saliva
 (Cont…) Saliva, functions
a. Digestion:
- CHO-digestion begins in saliva .
- The enzyme ptyalin breaks starch- to-maltose.
- Lingual lipase begins fat digestion in the mouth.
b. Protection:
- Has anti-microbial actions (contains Lysozyme & thiocyanate that kills
microbes).
c. Speech:
- Clear & fluent articulation is possible in the presence of saliva.
d. Secretes HCO3- :
- Good to maintains the pH to neutral range (6-to-7), the neutral pH is good
for ptyline action.
e. Lubrication:
- Muncin found in saliva facilitates moistening and swallowing of
food.
f. Water intake
- Saliva plays an important role in water intake
- low salivary secretion urges a person to drink
June 10, 2023 90
 (Cont.) Salivary secretion
Reflex control of salivation: (Nervous control)
- Sight, smell, and test or thinking of food  Receptors in
oral cavity or smell  Sensory fibers from the tongue to the
nuclei in brain stem (MO), so called Salivatory nuclei 
Parasympathetic fibers act on salivary glands to increase
copious salivary secretion.

* Salivation can also be controlled by higher centers like

hypothalamus which has nerve connections with salivatory
nuclei in the Medulla oblongata (MO)

* Higher centers like appetite area in the hypothalamus are

also involved in reflex control.

June 10, 2023 92

 (Cont…) Reflex secretion of saliva
Salivary innervations are: mainly
autonomic
A. Parasympathetic fibers: causes copious
secretion of saliva (Cholinergic).
- Cranial nerve IX to the parotid glands.
- Cranial nerve VII to the submandibular
and sublingual glands.
- increases saliva secretion which is rich in
electrolytes and salivary amylase.
B. Sympathetics: Causes small and
insignificant secretion which is viscious
(Adrenergic).
- Increases mucus secretion, making the
saliva much more viscous

- Interrupting sympathetic fibers do not

greatly affect salivary secretions, but
June 10, 2023
parasympathetic denarvation causes 93
atrophy of the gland.
 Reflex secretion of the saliva
June 10, 2023 96
 (Cont…) Phases of Salivary secretions

3-phases of salivary secretions include

1. Cephalic (brain) phase: triggered by thought, smell, or
sight of food

2. Oral phase: triggered by food that stimulate touch & test

receptors in the mouth

3. Gastric phase: triggered by substances which stimulate

the gastric mucosa (acids or sour tastes) in the stomach.

June 10, 2023 97

 MASTICATION
• Mastication or chewing is the first mechanical process
in the GIT.
• By which food are cut into small particles and crushed
into a soft bolus.
Significances of mastication
• Breakdown of foodstuffs into smaller particles
• Mixing of saliva with food substance thoroughly
• Lubrication and moistening of dry food by saliva so
that the bolus can be swallowed easily
• Appreciation of taste of the food
• Action of mastication is mostly a reflex process carried
out voluntarily
• The center of mastication is situated in medulla and
cerebral cortex.
 Deglutition
• Swallowing is the process by which food moves from
mouth into stomach.
• Deglutition has three stages
1. Oral stage
• When food moves from mouth to pharynx
• Oral stage of swallowing is a voluntary stage
2. pharyngeal stage
• Pharyngeal stage is involuntary stage
• The bolus is pushed from pharynx into the esophagus
• Pharynx is a common passage for food and air
• Swallowing apnea is the arrest of breathing during
pharyngeal stage of deglutition for 1-2 sec.
 Pharyngeal phase cont…
• The swallowing center specifically inhibits the respiratory center of the
medulla during this time
Pharyngeal Stage of Swallowing
- a. The soft palate is pulled upward and closes the nasopharynx.
- b. The vocal cords are pulled together and narrow.
- c. The epiglottis moves upward and covers the larynx
- d. This so called “primary peristalsis” in the pharynx starts
and pushes the bolus downward through the upper
esophageal sphincter.
Reflex pathways:
• This reflex inhibits respiration and entrance of food into the trachea.
• Simulation of tactile receptors in the pharynx > Sensory impulses
carry impulses to > swallowing center found in MO and lower pons >
Reflex motor impulses reach back to the pharynx and upper
esophagus through different cranial nerves causing swallowing
reaction.
 3. Esophageal stage
• It is also involuntary stage.
• In this stage food move from esophagus into stomach
• The movement food in the esophagus form peristaltic waves.
• Peristalsis means a wave of contraction followed by relaxation of
muscle fibers in aboral dirction of GI
• When bolus reaches the esophagus the peristaltic wave are
initiated
• There are two types of peristaltic contraction are produced in
esophagus.
• The primary and secondary
• When the bolus reach esophagus primary peristalsis start
• Pressure developed during primary peristaltic contractions is
important to propel the bolus.
• If the primary peristaltic contractions are unable to propel the
bolus into the stomach, the secondary peristaltic appear and push
the bolus into stomach.
• Secondary peristaltic contractions are induced by the distention
of upper esophagus by the bolus.
 DEGLUTITION REFLEX
• The beginning of swallowing is a voluntary act
• Later it becomes involuntary and is carried out by a reflex action called
deglutition reflex.
• It occurs during the pharyngeal and esophageal stages.
• When the bolus enters the oropharyngeal region, the receptors present in
this region are stimulated
• Deglutition center is at the floor of the fourth ventricle in medulla
oblongata of brain

• Stages of deglutition. A. Preparatory stage; B. Oral stage; C. Pharyngeal stage; D. Esophageal stage.
 (Cont…) Swallowing reflex, Esophagus
1. Voluntary phase:–
- The bolus is pushed by tongue
towards the pharynx
2. Pharyngeal phase:
- Cause of primary peristalsis.
- The musculature of the
pharyngeal wall and upper 1/3 of the
esophagus is striated muscle.
- Therefore, the peristaltic waves in
these regions are controlled by
skeletal nerve impulses from the
glossopharyngeal and vagus nerves
3. Esophageal phase (involuntary)
- Distention of the esophageal walls
causes the so called “secondary
peristalsis” (10 sec)
- In the lower 2/3 of the esophagus,
the musculature is smooth muscle
- Controlled by the vagus nerves
acting through connections with
myenteric nervous system.
June 10, 2023 103
 Esophageal Secretion
• Esophageal secretions are entirely mucous and mainly
provide lubrication for swallowing.
• The main body of the esophagus is lined with many
simple mucous glands.
• At the gastric end and in the initial portion of the
esophagus, contain many compound mucous glands
• The mucus in the upper esophagus prevents mucosal
excoriation by newly entering food
• Whereas the mucus near the esophagogastric junction
protect the esophageal wall from digestion by acidic
gastric juices
• Despite this protection, a peptic ulcer at times can still
occur at the gastric end of the esophagus.
 Esophageal abnormality

• Esophageal abnormality
• Dysphagia means difficulty in swallowing due to:
• Mechanical obstruction of esophagus due to tumor,
strictures,
• Decreased movement of esophagus due to
neurological disorders such as parkinsonism
• Muscular disorders leading to difficulty in
swallowing during oral stage or esophageal stage.
 Esophageal achalasia
• Esophageal achalasia or achalasia cardia
• It is a neuromuscular disease characterized by accumulation
of food in the esophagus
• It is due to the failure of lower esophageal (cardiac) sphincter
to relax during swallowing.
• The accumulated food cause dilatation of esophagus.
• Features of esophageal achalasia are dysphagia, chest pain,
weight loss, cough.
Gastroesophageal Reflux Disease (GERD)
• GERD is a disorder characterized by regurgitation of acidic
gastric content through esophagus.
• The regurgitated gastric content flows into pharynx or
mouth.
• Regurgitation is due to the weakness or incompetence of
lower esophageal sphincter.
Functional structure of the stomach
 FUNCTIONAL ANATOMY OF STOMACH
• Stomach is a hollow organ situated just below the
diaphragm on the left side in the abdominal cavity.
• Volume of empty stomach is 50 ml.
• Under normal conditions, it can expand to accommodate
1 L to 1.5 L of solids and liquids.
• However, it is capable of expanding still further up to 4
„ PARTS OF STOMACH
• In humans, stomach has four parts:
• 1. Cardiac region
• 2. Fundus
• 3. Body or corpus
• 4. Pyloric region
 1. Cardiac Region
• Cardiac region is the upper part of the stomach where esophagus
opens.
• The opening is guarded by a sphincter called cardiac sphincter
• Which opens only towards stomach.
2. Fundus
• Fundus is a small dome shaped structure.
• It is elevated above the level of esophageal opening.
3. Body or Corpus
• Body is the largest part of stomach forming about 75% to 80% of
the whole stomach.
• It extends from just below the fundus up to the pyloric region
4. Pyloric Region
• Pyloric region has two parts, antrum and pyloric canal
• The body of stomach ends in antrum.
• Antrum is continued as the narrow canal, pyloric canal .
• The opening of pyloric canal is guarded by pyloric sphincter
 Functional parts of stomach
• Functionally, the stomach is divided into

• A proximal gastric reservoir and distal antral pump

•
• Differences in motility between the two compartments
•
• The proximal stomach are adapted for maintaining
continuous contractile tone (tonic contraction)

• In contrast, the muscles of the antral pump contract

phasically (propels the gastric contents toward the
gastroduodenal junction)
 Cont..

- Gastric Motility
- A pacemaker in the antral pump generates
gastric action potentials that evoke ring-like
contractions as they propagate to the
gastroduodenal junction.
 Function
1. Storage (1-1.5 Liter) for 3-4hrs

2. Formation of Chyme
Peristaltic movements of stomach
mix the bolus with gastric juice and
convert it into the semisolid
material known as chyme

3. Secretion of intrinsic factor and

other enzymes

4. Protein digestion

5. Has antiseptic actions (HCl) etc

June 10, 2023 112
 STRUCTURE OF STOMACH WALL
• The stomach wall consists of four distinct layers from inside
to outside:
• Gastric mucosa, submucosa, muscularis externa, and serosa.
• The mucosa layer consists of epithelium that houses the
secretory glands.
• The submucosa consists of fibrous connective tissue that
separates the mucosa from the muscularis externa.
• The muscularis externa contains three layers of smooth
muscle instead of two.
• These three layers of smooth muscle fibers, namely inner
oblique, middle circular and outer longitudinal
• The serosa is the outer layer of the stomach consisting of
connective tissue and is continuous with the peritoneum.
 Stomach walls cont…
- 4-layers + 1 oblique muscle (is essential in mixing of the
chyme)
- Under resting conditions the mucosa of the stomach is
thrown into many folds called rugae
- Rugae, Increases surface area as the stomach fills with
chyme.
- The rugae disappear when the stomach is distended after
meals.
- Throughout the inner mucus layer, small depressions called
gastric pits are present.
- Folds have tube like depressions called gastric pits that
contain different gastric glands.
- Glands of the stomach open into these pits
- The secretions are released into the base of the gastric pit.
114
 Stomach walls cont…
- Microscopic Anatomy of the Stomach
• Muscularis
– Allows the stomach to churn, mix, and pump food
physically
– Breaks down food into smaller fragments
• Epithelial lining
– Goblet cells that produce a coat of alkaline mucus
• The mucous surface layer traps a bicarbonate-rich
fluid beneath it
• Gastric pits
– contain gastric glands that secrete gastric juice, mucus,
and gastrin
115
 STRUCTURE OF STOMACH WALL
• The epithelium of the stomach’s mucosa contains two main
types of glands: pyloric and oxyntic
• The pyloric glands secrete gastrin and mucus for protection
(20%)
• The oxyntic glands are located on the inside surfaces of the
body and fundus of the stomach occupies 80%
• The oxyntic glands (gastric glands) secrete mainly
hydrochloric acid and pepsinogen.
• The oxyntic glands contain parietal (oxyntic) cells, chief
cells, mucous neck cells, and some endocrine cells
Secretions From the Gastric (Oxyntic) Glands
• It is composed of three main types
of cells:
• 1) Mucous neck cells, which secrete
mainly mucus
• 2) Peptic (or chief) cells, which
secrete pepsinogen
• 3) Parietal (or oxyntic) cells, which
secrete HCL and intrinsic factor.
• Oxyntic glands also contain some
additional cells types, including the
enterochromaffin-like (ECL) cells
that secrete histamine
The digestive juices of the stomach are secreted by gastric glands

6/10/2023 10:18 PM GIP K.E.(Msc) 118

 Basic Mechanism of Hydrochloric Acid Secretion
• When stimulated, the parietal cells secrete an acid solution that
contains about 160 mmol/L of Hcl.
• Which is nearly isotonic with the body fluids.
• The pH of this acid is about 0.8 extreme acidity.
• The H+ concentration is about 3 million times greater that of
the arterial blood.
• To concentrate the H+ requires more than 1500 calories of
energy/L of gastric juice.
• At the same time that H+ is secreted, HCO3− diffuses into
the blood
• So that gastric venous blood has a higher pH than arterial
blood when the stomach is secreting acid
• The Hcl is formed at the villus like projections inside these
canaliculi
• Then conducted through the canaliculi to the secretory end of
the cell.
 HCl secretion by Parietal cells
1. H+ ions that result from the dissociation of H20 in the cytoplasm of the
parietal cells are continuously pumped (actively) through the membrane of
the gland (canaliculi) into the gland lumen (pit).

2. Within the cell cytoplasm (intracellular), CO2 and OH- combine to

produce bicarbonate ions HCO3-.

3. Cl- ions are transported from the blood into the parietal cell and finally into
the lumen (pit) of the gland by facilitated diffusion.

4. HCO3- in exchange to Cl- is transported in reverse direction (from the

cytoplasm into the blood, charge balance).
-The blood coming from the stomach during active acid secretion
contains much HCO 3−, a phenomenon called the alkaline tide.

5. Finally, H+ and Cl- ions combine in the lumen of the gland (pit) and
produce HCl that is collected and stored in the pit until used for different
physiological functions. 121
 cont…
• The basic factors that stimulate gastric secretion are
• Acetylcholine, Gastrin, and Histamine.
• Ach released by parasympathetic stimulation secretion of
• Pepsinogen by peptic cells
• Hydrochloric acid by parietal cells
• Mucus by mucous cells.
• Both gastrin and histamine strongly stimulate acid secretion by parietal
cells but have little effect on the other cells.
Secretion and Activation of Pepsinogen
• Pepsinogen are secreted by the peptic and mucous cells of the gastric
glands
• When pepsinogen is first secreted, it has no digestive activity
• As it comes in contact with Hcl it is activated to form active pepsin.
• Pepsin functions as an active proteolytic enzyme in a highly acidic
medium (optimum pH, 1.8–3.5)
• Pepsin is important for protein digestion in the stomach
 Secretion of Intrinsic Factor by Parietal Cells.
• The substance IF is essential for vitamin B12 absorption in
the ileum,
• It is secreted by the parietal cells along with the secretion of
Hcl.
• When the parietal cells are destroyed, a person develop
achlorhydria (lack of stomach acid secretion) and pernicious
anemia (PA)
• PA because of failure of red blood cell maturation in the
absence of vitamin B12
PYLORIC GLANDS SECRETE MUCUS AND GASTRIN
• These cells secrete a small amount of pepsinogen and large
amount of thin mucus
• That helps to lubricate food movement and to protect the
stomach wall from digestion by the gastric enzymes.
• The glands also secrete the hormone gastrin
• Which plays a key role in controlling gastric secretion
 SURFACE MUCOUS CELLS
• The entire surface of the stomach mucosa has a special
type of mucous cells “surface mucous cells.”
• They secrete large quantities of viscid mucus that coats
the stomach mucosa with a gel layer of mucus 1mm thick
• It provide a major shell of protection for the stomach wall
and lubrication of food transport.
• Another characteristic of this mucus is that it is alkaline.
• Therefore, the normal underlying stomach wall is not
directly exposed to the highly acidic secretion.
 PROPERTIES AND COMPOSITION OF GASTRIC JUICE
• Gastric juice is a mixture of secretions from different
gastric glands
PROPERTIES OF GASTRIC JUICE
• Volume : 1200 mL/day to 1500 mL/day.
• Reaction : Gastric juice is highly acidic with a pH of 0.9
to 1.2.
• Acidity of gastric juice is due to the presence of Hcl
• Specific gravity : 1.002 to 1.004
COMPOSITION OF GASTRIC JUICE
• Gastric juice contains 99.5% of water and 0.5% solids.
• Solids are organic and inorganic substances
Composition of gastric juice
 FUNCTIONS OF GASTRIC JUICE
1. DIGESTIVE FUNCTION
• Gastric juice acts mainly on proteins.
• Proteolytic enzymes of the gastric juice is pepsin
• Gastric juice also contains some other enzymes like
gastric lipase and gastric amylase.
• Pepsin converts proteins into proteoses, peptones and
polypeptides
• Gastric lipase is a weak lipolytic enzyme when
compared to pancreatic lipase.
• It hydrolyzes butter fat into fatty acids and glycerols.
• Gastric amylase: Degrades starch but its action is
insignificant
 2. HEMOPOIETIC FUNCTION
• Intrinsic factor secreted by parietal cells of gastric glands plays
an important role in erythropoiesis.
• IF is necessary for the absorption of vitamin B12
• Vitamin B12 is an important maturation factor during
erythropoiesis
3. PROTECTIVE FUNCTION
• Mucus is a mucoprotein, secreted by mucus neck cells and
surface mucus cells
• Protects the stomach wall from irritation or mechanical injury
• Prevents the digestive action of pepsin on the wall of the
stomach (gastric mucosa)
• Protects the gastric mucosa from hydrochloric acid
4. FUNCTIONS OF HYDROCHLORIC ACID
• Hydrochloric acid is present in the gastric juice:
• i. Activates pepsinogen into pepsin
• ii. Kills some of the bacteria entering the stomach along
with food substances.
• iii. Provides acid medium, which is necessary for the
action of hormones

Phases of Gastric Secretion

• Gastric secretion is said to occur in three “phases” a
cephalic phase, a gastric phase, and an intestinal phase.
 Phases of gastric juice secretion cont..
- Gastric secretion resulting from the ingestion of food can be
divided into three phases:
A. Cephalic B. Gastric C. Intestinal phases

The cephalic (neural):

- Afferent impulses from taste, smell, sight, or thought of food are
carried to MO that causes reflex stimulation of the stomach to
secrete gastric juices.
2-ways of increasing gastric secretion:
a. The transmitter (Ach) released from Vagal nerve acts on
parietal and chief cells to secrete (HCl + intrinsic factor) &
pepsinogen, respectively.
b. Mechanical stimulation + protein foods directly stimulates G-
cells to release the hormone gastrin and indirectly HCl
- The cephalic phase probably accounts for about 40% of total acid
June 10, 2023 132
secretion.
 (Cont…) Regulation of gastric secretion
2. The gastric phase
- When food distends the stomach, mechanoreceptors and chemoreceptor
are activated by products of food.
- Sensory information from the receptors pass to the brain stem (MO).
- Reflex Vagal stimulation on the stomach causes increased gastric
secretions through Ach .

Different mechanisms of gastric release include:

a. Local reflex: stretch causes the enteric nerves to increase gastric acid
secretion
b. Mechanical distention directly stimulates G-cells in the antrum to increase
HCl release
c. Presence of amino acids, dipeptides, alcohol, coffee stimulate histamine
(H-cells), parietal and G-cells that release HCl and other gastric juices in
the stomach.
d. Alcohol and caffeine stimulate gastric acid secretion through mechanisms
that are not well understood.
- The
Junegastric
10, 2023 phase accounts for about 50% of total gastric acid secretion. 133
 • Cephalic and
gastric phases
controlling acid
secretion by the
stomach.

June 10, 2023 134

 (Cont…) Gastric secretion, intestinal phase
3. The intestinal phase
- This stage begins when chyme reaches the duodenum.
- This phase is mostly inhibitory to gastric juice secretion.
- When fatty chyme, amino acids etc. reach the duodenum, they cause
secretion of hormones like Secretin, CCK, GIP that reflexly
inhibit gastric secretion in the stomach.
- In small cases, however, this phase causes secretion of gastric juice
because of the presence of G-cells in the duodenum.
- G- cells release gastrin that stimulates gastric secretion reflexly.????
- The intestinal phase accounts for only about 10% of the total
gastric acid secretion.

June 10, 2023 135

 Phases of gastric juice secretion in the stomach
Cephalic, gastric, and intestinal phases.

June 10, 2023 137

June 10, 2023 138
 (Cont…) Protection of the stomach wall from acids
The following effects protect the stomach wall from acidic attacks (i.e
pH<3)
a. Production of thick mucous
b. HCO3- secretion (bicarbonate ) is secreted by underlying
mucous cells) that usually buffers the acid that diffuses from
the lumen into the luminal wall.

June 10, 2023 139

 Gastric enzymes
• The enzymes that secreted in the stomach are referred to as gastric
enzymes and include:-
• Pepsinogens, pepsins, gastric amylase, gastric lipase, and intrinsic
factor.
• Pepsin is the main gastric enzyme that cleaves proteins into smaller
peptides.
• The optimal pH for pepsin activity is 1.8 to 3.5
• The chief cells of the oxyntic glands release inactive pepsinogen.
• Acid in the gastric lumen activates pepsinogen to form the active
enzyme pepsin.
• Pepsin also catalyzes its own formation from pepsinogen.
• Gastric amylase degrades starch but otherwise appears to be of minor
significance.
• Gastric lipase acts almost exclusively on butterfat.
• The intrinsic factor is necessary for the absorption of vitamin B12 in
the terminal ileum
6/10/2023 10:18 PM GIP K.E.(Msc) 141
Gastric secretion is under neural and hormonal control
 Gastric secretion is under neural and hormonal control
• Vagus nerve stimulation is the neural effector
• Histamine and gastrin are the hormonal
effectors
• Parietal cells possess special histamine
receptors whose stimulation results in
increased acid secretion.
• Omeprazole inhibits the H+/K+-ATPase.
• The source of H+ is mostly the dissociation
of water
• Carbon dioxide and water form carbonic
acid in a reaction catalyzed by carbonic
anhydrase.
• Acetazolamide inhibits carbonic anhydrase.
• Cimetidine an H2 blocker reduce acid
secretion
• Ranitidine, a longer-acting H 2-receptor
antagonist with fewer side effects has largely 143
 Gastric hormones which inhibit Acid secretion
• The inhibition of gastric acid secretion is physiologically important for two
reasons.
• First, the secretion of acid is important only during the digestion of food.
• Second, excess acid can damage the gastric and the duodenal mucosal surfaces,
causing ulcerative conditions
• Gastric luminal pH is a sensitive regulator of acid secretion.
• Proteins in food provide buffering in the lumen consequently the gastric luminal
pH is usually above 3 after a meal.
• If the stomach is empty, the pH of the gastric lumen will fall below 3
• The D cells in the antrum secrete somatostatin which inhibits the release of gastrin
and gastric acid secretion.
• Secretin inhibits the release of gastrin
• Acid, fatty acids, and hyperosmolar solutions in the duodenum stimulate the release
of enterogastrones which inhibit gastric acid secretion.
• Gastric inhibitory peptide produced by the small intestinal inhibits parietal cell acid
 (cont…) Stomach secretions

The following are general factors that decrease gastric

secretion:
1. Low pH: Decreases gastric motility

2. Enterogastric reflex : Deceases Vagal output of the

stomach and thus decreases motility of the stomach

3. CCK: stimulated by fat diet in the duodenum

decreases stomach motility reflexly.

June 10, 2023 145

 MOVEMENTS OF STOMACH
• Activities of stomach increase during gastric digestion and when the
stomach is empty
• Types of movements in stomach
1. Hunger contractions
2. Receptive relaxation
3. Peristalsis
• Hunger contractions are the movements of empty stomach.
• These contractions are related to the sensations of hunger.
• Hunger contractions are the peristaltic waves superimposed over the
contractions of gastric smooth muscle as a whole
• Peristaltic contractions of empty stomach involve the entire stomach.
• This type of peristaltic waves is different from the digestive
peristaltic contractions
• Hunger pangs usually do not begin until 12 to 24 hours after the last
ingestion of food.
 2. RECEPTIVE RELAXATION
• Receptive relaxation is the relaxation of the upper portion
of the stomach
• When bolus enters the stomach from esophagus.
• It involves the fundus and upper part of the body of
stomach.
• Its significance is to accommodate the food easily,
• Without much increase in pressure inside the stomach.
• This process is called accommodation of stomach
 PERISTALSIS
• When food enters the stomach, the peristaltic contraction
appears with a frequency of 3 per minute.
• It starts from the lower part of the body of stomach, passes
through the pylorus till the pyloric sphincter.
• Peristalsis ends with the constriction of pyloric sphincter.
• Some of the waves disappear before reaching the sphincter.
• Each peristaltic wave takes about one minute to travel from
the point of origin to the point of ending.
• This type of peristaltic contraction is called digestive
peristalsis
• Because it is responsible for the grinding of food particles and
mixing them with gastric juice for digestive activities.
 Gastric emptying
• Gastric emptying is the process by which the chyme
from stomach is emptied into intestine
• Partly digested food in stomach becomes the chyme.
• Chyme is the semisolid mass of partially digested food
that is formed in the stomach.
• Acid chyme is emptied from stomach into the intestine
with the help of peristaltic contractions.
• It takes about 3 to 4 hours for emptying of the chyme.
• This slow emptying is necessary to facilitate the final
digestion and absorption of food from small intestine.
• Gastric emptying is influenced by various factors of
the gastric content and food.
 Factors Affecting Gastric Emptying
Volume of gastric content
• Gastric emptying is directly proportional to the volume.
• If the content of stomach is more, a large amount is emptied
into the intestine rapidly
Consistency of gastric content
• Emptying of the stomach depends upon consistency (degree
of density) of the contents.
• Liquids like water leave the stomach rapidly.
• Solids leave the stomach only after being converted into fluid
or semifluid.
• Undigested solid particles are not easily emptied.
Chemical composition
• Carbohydrates are emptied faster than the proteins.
• Proteins are emptied faster than the fats.
• The fats are emptied very slowly.
 Factors Affecting Gastric cont…
pH of the gastric content
• Gastric emptying is directly proportional to pH of
the chyme.
Osmolar concentration of gastric content
• Gastric content which is isotonic to blood, leaves
the stomach rapidly than the hypotonic or
hypertonic content.
 REGULATION OF GASTRIC EMPTYING
• Gastric emptying is regulated by nervous and hormonal factor
Nervous factor
• Nervous factor which regulates the emptying of stomach is the
enterogastric reflex.
• Enterogastric reflex is the reflex that inhibits gastric emptying
• It is elicited by the presence of chyme in the duodenum
• Which prevents further emptying of stomach.
• Factors which initiate enterogastric reflex
1. Duodenal distension
2. Irritation of the duodenal mucosa
3. Acidity of the chyme
4. Osmolality of the chyme
5. Breakdown products of proteins and fats.
 Hormonal Factors
• When an acid chyme enters the duodenum, the
duodenal mucosa releases some hormones
• The hormone enter the stomach through blood and
inhibit the motility of stomach.
• Hormones inhibiting gastric motility and emptying
• 1. Vasoactive intestinal peptide (VIP)
• 2. Gastric inhibitory peptide (GIP)
• 3. Secretin
• 4. Cholecystokinin
• 5. Somatostatin
• 6. Peptide YY
 MMC (Migrating Motility Complex)
 MMC waves are strong contractile activity that starts at a fasting
state by pacemaker cells in the stomach. It stops in the small intestine
(ileum).
 MMC occurs every 70 -to-90 min in humans during fasting state
and is sometimes painful.
Importance MMC:
 MMC cleans or sweeps small intestinal contents into the cecum.
That is, it removes bacteria’s and debris away from the small
intestine and drops it in the Cecum.
 Bacterial overgrowth in the small intestine is associated with an
absence of the MMC.
 Moreover, feces or bacteria from the cecum do not get access to
enter back into the SI during rest. It is thus called “the housekeeper
of the Small intestine”
158
 (Cont…) Gastric emptying
Physiological advantage of delaying stomacheal contents
1. It gives ample time for nutrients (e.g., like fat) to remain
longer in the stomach and be digested by gastric juices.
2. The delay prevents acids (HCl) not to be damped into the
duodenum at higher rates to cause duodenal ulcers.
3. The delay also gives time for pancreatic secretions to reach
duodenum and neutralize the acid.
• Rough estimates of transit times in healthy humans following
ingestion of a standard meal.
• Variability among individuals can exist.
Time
• A. 50% of stomach contents emptied 2.5 to 3 hr
• B. Total emptying of the stomach 4 to 5 hr
• C. 50% emptying of the SI 2.5 to 3 hr
• D. Transit through the colon 30 to 40 hr
June 10, 2023 163
 (Cont…) Absorption from the stomach

• The stomach is a poor absorptive area of the

gastrointestinal tract
• Because it lacks the typical villus type of absorptive
membrane
• Also because the junctions between the epithelial cells are
tight junctions.
• Only a few highly lipid-soluble substances, such as alcohol
and some drugs like aspirin, can be absorbed in small
quantities
• Organic nutrients (glucose, amino acids, and FFA etc. are
not usually absorbed from the stomach.

June 10, 2023 164

Release of Gastric Juice

165
 THE PANCREAS
Pancreas Location:
• Lies deep to the greater curvature of the stomach
• The head is encircled by the duodenum and the tail abuts
the spleen
• Divided into: Head, body and tail
• Connected to the duodenum via the pancreatic duct (duct
of Wirsung) and accessory duct (duct of Santorini).
• Pancreas contains two types of secretory glands:
1. Endocrine cells (islets of Langerhans) secrete hormones like
insulin, glucagon, and somatostatin.
2. Exocrine cells (acinar cells): secrete a mixture of fluid rich
in NaHCO3 and digestive enzymes called pancreatic juice.
- its internal structure is similar to that of the salivary glands
• Pancreas is supplied by both sympathetic and parasympathetic166
fibers.
 Properties & composition of Juice
PROPERTIES OF PANCREATIC JUICE
• Volume : 500 to 800 mL/day
• Reaction : Highly alkaline with a pH of 8 to 8.3
• Specific gravity : 1.010 to 1.018
COMPOSITION OF PANCREATIC JUICE
• It contains 99.5% of water and 0.5% of solids.
• The solids are the organic and inorganic substances.
• Bicarbonate content is very high in pancreatic juice.
• It is about 110 to 150 mEq/ L, against the plasma level of
24 mEq/L.
• Highly alkaline, protects the intestinal mucosa from acid
chyme by neutralizing it
• It provide the required pH (7 to 9) for the activation of
pancreatic enzymes
 FUNCTIONS OF PANCREATIC JUICE
• Pancreatic juice has digestive functions and neutralizing
action.
• Pancreatic juice plays an important role in the digestion of
proteins, lipids and carbohydrate.
DIGESTION OF PROTEINS
• Major proteolytic enzymes of pancreatic juice are trypsin,
chymotrypsin, and carboxypolypeptidase.
• By far the most abundant of these is trypsin.
• Other proteolytic enzymes are nuclease, elastase and
collagenase
 Trypsin
• It is secreted as inactive trypsinogen
• Which is converted into active trypsin by enterokinase.
• Enterokinase (enteropeptidase) is secreted by the brush-
bordered cells of duodenal mucus membrane.
• Once formed, trypsin itself activates trypsinogen by
means of autocatalytic or autoactive action
• Trypsinogen is activated only in the small intestine.
• Otherwise it may hydrolyze the pancreatic tissue proteins,
resulting in pancreatic damage.
• But its activation in the pancreas is prevented by an
inhibitor protein called trypsin inhibitor.
 Actions of trypsin
Digestion of proteins:
• Converts proteins into proteoses and polypeptides
Curdling of milk:
• It converts caseinogen in the milk into casein
Blood clotting:
• It accelerates blood clotting
It activates the other enzymes of pancreatic juice
• Chymotrypsinogen into chymotrypsin
• Procarboxypeptidases into carboxypeptidases
• Proelastase into elastase
• Procolipase into colipase
• Trypsin also activates collagenase, phospholipase A
and phospholipase B
 Actions of Chymotrypsin
Digestion of proteins:
• Chymotrypsin converts proteins into polypeptides
Digestion of milk:
• Chymotrypsin digests caseinogen faster than
trypsin.
Carboxypeptidases
• It is derived from the procarboxypeptidase
• It split the polypeptides and other proteins into AA
• Elastase: digests the elastic fibers.
• Nucleases: are responsible for the digestion of
nucleic acids into mononucleotides.
• Collagenase: digests collagen.
 DIGESTION OF LIPIDS
• Lipolytic enzymes present in pancreatic juice are:
• Pancreatic lipase, Cholesterol ester hydrolase, phospholipase,
and colipase
Pancreatic lipase
• Pancreatic lipase is a powerful lipolytic enzyme.
• It digests triglycerides (neutral fat) into monoglycerides and
fatty acid
• Activity of pancreatic lipase is accelerated in the presence of
bile.
• Optimum pH required for activity of this enzyme is 7 to 9.
• Digestion of fat by pancreatic lipase requires two more factors:
i. Bile salts
• Which are responsible for the emulsification of fat, prior to
their digestion
 cont…
ii. Colipase
• Which is a coenzyme necessary for the pancreatic lipase to
digest the dietary lipids.
• Colipase facilitates digestive action of pancreatic lipase on fats
• About 80% of the fat is digested by pancreatic lipase.
Cholesterol esterase
• It converts cholesterol ester into free cholesterol and
fatty acid by hydrolysis.
Phospholipase
• A digests phospholipids
Pancreatic amylase
• The pancreatic amylase converts starch and glycogen
into dextrin and maltose.
Digestive enzymes of pancreatic juice
 Formation bicarbonate by the pancreas
• Carbon dioxide diffuses to the interior of the cell from the blood
• CO2 + H2O-CA---H2CO3.
• H2CO3 --- HCO3- and H+
• Then the bicarbonate ions are actively transported in association with
sodium ions (Na+) through the luminal border of the cell into the
lumen of the duct.
• The H+ formed by dissociation H2CO3 inside the cell are exchanged
for Na+through the blood border of the cell by a secondary active
transport process.
• This supplies the Na+ that are transported through the luminal border
into the pancreatic duct lumen to provide electrical neutrality for the
secreted bicarbonate ions.
• The overall movement of sodium and bicarbonate ions from the
blood into the duct lumen creates an osmotic pressure gradient.
• The pancreas secretes about 1 L-1.5L a day of HCO3−rich fluid.
• The osmolality of pancreatic fluid is equal to that of plasma at all
secretion rates.
 Regulation of Pancreatic Secretion
• Three basic stimuli are important in causing pancreatic secretion:
• Acetylcholine, which is released from the parasympathetic nerve endings
and from other cholinergic nerves in the ENS
• Release of Ach simulate pancreatic secretion.
• Stimulation of the sympathetic nerves neither stimulates nor inhibits
pancreatic secretion
• Cholecystokinin, which is secreted by the duodenal and upper jejunal
mucosa when food enters the small intestine.
• CCK stimulates a marked increase in enzyme secretion.
• Secretin which is also secreted by the duodenal and jejunal mucosa when
highly acidic food enters the small intestine
• Stimulate water solution of NaHCO 3rich secretion.
• The small intestine produces both hormones and the pancreas has
receptors for them. 179
 Regulation of Pancreatic Secretions
• Secretin
– acidity in intestine
causes increased
sodium bicarbonate
release
• GIP
– fatty acids & sugar
causes increased
insulin release
• CCK
– fats and proteins
cause increased
digestive enzyme
release
180
 Phases of Pancreatic Secretion
• Pancreatic secretion occurs in three phases:
• The cephalic phase, gastric phase, and intestinal phase.
1. CEPHALIC PHASE 20%
• Is regulated by nervous mechanism through reflex action.
. Unconditioned reflex and Conditioned reflex.
• Unconditioned reflex is the inborn reflex.
• When food is placed in the mouth it induce pancreatic secretion.
• The vagal efferent nerve endings secrete acetylcholine, which
stimulates pancreatic secretion.
• Conditioned reflex is the reflex response acquired by previous
experience
• The sight, smell, hearing or thought of food, which induce
pancreatic secretion
• - Stimulant: Smell, odor, or taste of food acting on receptors
send sensory impulses to the brain (MO) > Vagus nerves stimulate
the pancreatic acinar cells to secrete digestive enzymes.
 2. GASTRIC PHASE
• Secretion of pancreatic juice when food enters the stomach is known
as gastric phase (5-10%).
• This phase of pancreatic secretion is under hormonal control
(Gastrin)
• Here again gastrin hormone stimulate pancreatic enzyme secretion
• However the volume produced is in small quantity.
• Stomacheal distention also contribute
3. Intestinal phase duodenum ( ~ 80%)
• When the chyme enters the intestine activate the secretion.
• Fat food & acid (HCl) reaching the duodenum evoke CCK and
secretin secretion.
• Secretin stimulates large quantities of pancreatic juice production
rich in bicarbonate.
• CCK stimulates the secretion of pancreatic which is rich in enzyme
and low in volume
Schematic diagram showing the regulation of pancreatic secretion
June 10, 2023 185
 Regulation of pancreatic secretion

June 10, 2023 186

 Digestive disorder, Pancreatitis
a. Absence of the enzyme enterokinase:
– In the absence of enterokinase, tripsin is not formed to
activate other proenzyme from the pancreases.
– Dietary proteins, thus, remain undigested. This causes
protein deficiency in the body.

b. Acute pancreatitis:
– Duct blockage produces logging of the secretions in
pancreatic tissues.
– This in turn causes activation of proenzyme causing
digestion of the pancreatic tissues within a few hours
leading to lethal conditions.
June 10, 2023 187
 LIVER AND GALLBLADDER
Liver
• weighs 3 lbs.
• Located below
diaphragm
• right lobe is larger
• gallbladder on right lobe
• causes the right kidney
to be lower than the left
• Gallbladder has
fundus, body, neck

188
 FUNCTIONAL ANATOMY OF LIVER
• Liver is a dual organ having both secretory and excretory
functions.
• It is the largest gland in the body, weighing about 1.5 kg in
man.
• It is located in the upper and right side of the abdominal cavity
immediately beneath diaphragm
• Liver is made up of many lobes called hepatic lobes
• Hepatic lobule is the structural and functional unit of liver.
• Liver receives maximum blood supply of about 1,500 ml/min.
• It receives blood from two sources, namely the hepatic artery
and portal vein
• Hepatic artery arises directly from aorta and supplies
oxygenated blood to liver
 Cont….
• Portal vein is formed by superior mesenteric and splenic vein.
• It brings deoxygenated blood from stomach, intestine, spleen
and pancreas.
• Portal blood is rich in monosaccharides and amino acids.
• It also contains bile salts, bilirubin, urobilinogen and GI
hormones.
• However, the oxygen content is less in portal blood
• Flow of blood from intestine to liver through portal vein is
known as enterohepatic circulation.
• The blood from hepatic artery mixes with blood from portal
vein in hepatic sinusoids.
• Hepatic cells obtain oxygen and nutrients from the sinusoid
 HEPATIC VEIN
• Substances synthesized by hepatic cells, waste products
and carbon dioxide are discharged into sinusoids.
• Sinusoids drain them into central vein of the lobule which
ultimately form hepatic veins (right and left) which open
into inferior vena cava
• Approximately 75% of hepatic blood flow is delivered by
the hepatic portal vein and 25% is from the hepatic
artery.
• Sinusoids are wide, permeable capillaries containing a
mixture of blood from the hepatic artery and the portal
vein.
• Kupifer cells are macrophages interspersed between
endothelial cells
 Enterohepatic circulation
Blood flow through the liver
 Functions of the liver
- The digestive functions of the liver relate to the secretion of
bile
- But the liver has many other integrative functions.
I. Secretory functions
• Liver cells act as an exocrine gland and continuously secrete bile,
(important for digestion and absorption of fats.)
II. Metabolic functions
• Liver is the principal site where the metabolism of carbohydrates,
lipids and proteins takes place.
• Liver is also involved in the metabolism of vitamins and minerals
to certain extent
1. Role in carbohydrate metabolism includes:
• (i) Liver acts as a glucostat in three ways:
-Glycogenesis, i.e. glycogen is formed from glucose and stored in liver.
- Glycogenolysis, i.e. breaking down of liver glycogen to glucose.
- Glucogenesis, i.e. formation of glucose from noncarbohydrate
sources, such as non-nitrogenous residues of amino acids.
•
Cont…
(ii) Liver is the main site of alcohol metabolism for which contain the
enzyme alcohol dehydrogenase.
• (iii) The interconversion of three monosaccharides, such as glucose,
galactose and fructose, also occurs in liver.
2. Role in fat metabolism.
• Both degradation and synthesis of fats take place in the liver.
• Degradation of fat. The enzyme lipoprotein lipase which hydrolyses
triglycerides, cholesterol and phospholipids into fatty acids.
• β-oxidation, i.e. a process which oxidizes the fatty acids into acetoacetic
acid.
Synthesis of fat also takes place in liver.
- Liver synthesizes triglycerides from carbohydrates.
- Cholesterol and phospholipids are synthesized from unused FFA
- Saturated fatty acids are synthesized from the active acetate via Krebs’
cycle.
- Lipoproteins, such as HDL, LDL, VLDL and chylomicrons are also
synthesized in liver.
 Cont…
3. Role in protein metabolism.
- Liver brings about deamination of amino acids
- This is essential for energy production, and their conversion into
carbohydrates or fats.
- Liver is the main site of urea formation.
- Liver is the main site for formation of all non-essential amino acids by
the transamination of ketoacids.
- Albumin is solely resynthesized in liver and also to some extent α-
and β-globulins.

III. Detoxicating and protective functions

 Kupffer cells efficiently remove bacteria and other foreign bodies
from the portal circulation.
 Liver detoxifies certain drugs by either oxidation, hydrolysis,
reduction or conjugation and excretes out through bile
 Cont…
IV. Storage functions
• Liver stores glucose (in the form of glycogen), vitamin B12 and vit A.
• Acts as a blood iron buffer and iron storage medium.
• It stores 60% of excess of iron mainly in the form of ferritin and partly as
haemosiderin
VI. Synthesis functions
• Plasma proteins, especially albumin and α- and β-globulins.
• Coagulation factors. the conversion of pre-prothrombin to active
prothrombin in the presence of Vitamin K.
• It also produces other clotting factors, such as fibrinogen (I), factors V, VII,
IX and X.
• Enzymes, such as alkaline phosphatase, serum glutamic oxaloacetic
transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), serum
isocitrate dehydrogenase.
• Urea. Liver removes ammonia from the body to synthesize urea.
• Cholesterol. It is synthesized from the active acetate
VII. Miscellaneous functions
Cont…
• Reservoir of blood. Liver acts as a reservoir of blood and it stores
about 650 mL of blood.
• Erythropoiesis. Liver is an important site of erythropoiesis in the
fetal life.
• Hormone metabolism. Liver causes:
– Inactivation of some hormones, such as insulin, glucagon and
vasopressin.
– Reduction and conjugation of adrenal and gonadal steroid
hormones,
such as cortisol, aldosterone, estrogen and testosterone.
• Destruction of RBCs also occurs in the liver.
• Thermal regulation. Liver also helps in thermoregulation, as it
produces a large amount of heat.
 PROPERTIES AND COMPOSITION OF BILE
PROPERTIES OF BILE
• Volume : 800 to 1,200 mL/day
• Reaction : Alkaline
• pH : 8 to 8.6
• Color : Golden yellow or green.
• COMPOSITION OF BILE
• Bile contains 97.6% of water and 2.4% of solids.
• Solids include organic and inorganic substances.
 SECRETION OF BILE
• Bile is secreted by hepatocytes.
• The initial bile secreted by hepatocytes contains large quantity of
bile acids, bile pigments, cholesterol, lecithin and FA.
• From hepatocytes, bile is released into canaliculi.
• From here, it passes through hepatic ducts
• From hepatic duct, bile is diverted either directly into the intestine or
into the gallbladder.
• Sodium, bicarbonate and water are added to bile when it passes
through the ducts.
• These substances are secreted by the epithelial cells of the ducts.
• Most of the bile from liver enters the gallbladder, where it is stored
• In the GB bill undergoes many changes
• Volume is decreased b/c of absorption of water and electrolytes
• Concentration of bile salts, bile pigments, cholesterol, fatty acids and
lecithin is increased because of absorption of water and electrolytes
• The pH is decreased slightly and Mucin is added to bile
 BILE SALTS
• Bile salts are the sodium and potassium salts of bile acids, which are
conjugated with glycine or taurine
• Bile salts are formed from bile acids.
• There are two primary bile acids in human cholic acid and
chenodeoxycholic acid
• Which are formed in liver and enter the intestine through bile.
• Due to the bacterial action in the intestine, the primary bile acids are
converted into secondary bile acids
• Secondary bile acids from intestine are transported back to liver
through enterohepatic circulation.
• Enterohepatic circulation is the transport of substances from small
intestine to liver through portal vein.
• About 90% to 95% of bile salts from intestine are transported to
liver through enterohepatic circulation.
• Remaining 5% to 10% of the bile salts enter large intestine.
Formation of bile salts
 Functions of bile salt
• Emulsification of fat: breaking of large fat drops into smaller
droplets b/c of their power of lowering surface tension
• Acceleration of action of pancreatic lipase occurs in the presence of
bile salts due to binding of colipase for the lipase
• Colipase displaces some bile salts, allowing lipase access to fats
inside the bile salt coating.
• Micelle formation: the bile salt combine with the products of
hydrolysis of triglyceride to form micelle
• Absorption of fat soluble vitamins (A,D,E and K)
• Choleretic action: they stimulate liver to secret bile and then make
more bile salts available for fat digestion
• Cholesterol is kept in soluble form in the GB bile to prevent
formation of gall stone
• Intestinal motility is stimulated by the bile salt which help
defecation
 Recycling mechanisms for bile salt.
• Approximately 95% of the bile salts
secreted are reabsorbed in the terminal
ileum and recycled by four
mechanisms: entero-hepatic circulation
• 1) passive diffusion along the small
intestine
• 2) carrier-mediated active absorption in
the terminal ileum (the most important
absorption route)
• 3) deconjugation to primary bile acids
before being absorbed
• 4) conversion of primary bile acids to
secondary bile acids
• About 500 mg of bile acids is lost daily.
• The loss of bile acid in feces is an
efficient way to excrete cholesterol.
 Bile Pigments (Bilirubin)
2. Bile pigments (Bilirubin):
Bilirubin formation
- Bilirubin arises from breakdown of
old red blood cells after the removal
of Fe2- and the protein globins from
the hemoglobin moiety.
- After some intermediate stages
bilirubin is finally formed.
- Free Bilirubin is transported in the
blood bound to albumin, otherwise
free bilirubin is toxic.
- Bilirubin is taken by the liver in its
free form and conjugated with
glucuronic acid to form a non-toxic
water soluble bilirubin glucuronide
that is finally secreted to the bile
canaliculi and excreted
June 10, 2023 207
 (Cont…) Bilirubin in the Small intestine
- In the intestine, bacterial actions change bilirubin into
stercobilin and urobilinogen.
- They are further oxidized and excreted in feces or urine as
stercobilin and urobilin.
• Normal bilirubin content in plasma is 0.5 to 1.5 mg/dL.
• When it exceeds 1mg/dL, the condition is called
hyperbilirubinemia.
• When it exceeds 2 mg/dL, jaundice occurs.
• It is, yellow coloration of the sclera's, skin etc occurs.
• 3- types of jaundice:
• A. Prehepatic jaundice : Increased Hemolysis of RBC
• B. Intrahepatic jaundice: Liver disease
• C. Posthepatic jaundice: Blockage or obstruction of the bile
ducts.
June 10, 2023 208
 FUNCTIONS OF BILE
1. Digestive function: Bile salts help in the digestion of fats by
emulsifying fat drops
2. Absorptive functions. Bile salts help in the absorption of fats (by
micelle formation) and fat-soluble vitamins
3. Excretory function. Bile pigments are the major excretory products of
the bile.
The other substances excreted in bile are heavy metals, some toxins,
some bacteria (e.g. typhoid bacteria), cholesterol, lecithin and alkaline
phosphatase.
4. Laxative action. Bile salts increase the gastrointestinal motility and act
as a laxative.
5. Protective action. Bile is a natural detergent. So, it inhibits the
growth of certain bacteria in the lumen of intestine.
 Cont…
6. Choleretic action, i.e. bile salts stimulate the liver to secrete bile.
7. Maintenance of pH. Being highly alkaline, the bile juice
neutralizes the gastric HCI present in the small intestine.
8. Prevention of gall stone formation.Bile salts keep the
cholesterol and lecithin in solution and prevent the formation of
gall stones.
9. Lubricating function. The mucin secreted by the gall bladder
mucosa into the bile lubricates the chyme in the intestine.
10. Cholagogue function. an agent, which increases the release of
bile from gall bladder into the intestine.
- The bile salts stimulate the secretion of hormone CCK, which
has got cholagogue action.
 Regulation of bile secretion
• The intestinal mucosa secretes CCK when fatty acids or amino
acids are present in the lumen-CCK causes contraction of the
gallbladder-causes increased pressure in the bile ducts-the
sphincter of Oddi relaxes (another effect of CCK) -bile is
delivered into the lumen.
• Bile contributes to the neutralization of acid in the duodenum by
HCO3− secretion from bile ducts when secretin stimulate.
• Gastrin stimulates bile secretion directly by affecting the liver
and
• Indirectly by stimulating increased acid production that results in
increased secretin release.
• Steroid hormones (e.g., estrogen and some androgens) are
inhibitors of bile secretion.
• Parasympathetic stimulation contract the gallbladder and relaxa
the sphincter of Oddi as well as increased bile formation.
• Stimulation of the sympathetic nervous system reduced bile
secretion and relaxation of the gallbladder.
Regulation of Bile Secretion

212
 (Cont…) Bile secretion

June 10, 2023 213

 (Cont…) Gall bladder and gall stone formation
• Gallbladder (GB) is a
storage sac for bile.
• GB is stimulated by CCK to
contact and release bile.
• Bile emulsifies fat in the
duodenum.
• Gallbladder bile has a different
composition from hepatic bile.
• The principal difference is that
gallbladder bile is more highly
concentrated.
• Cholesterol and other
substances precipitate in
the GB and this effect
June 10, 2023
favors gall-stone formation.214
 Composition of bile

June 10, 2023 215

 Digestive disorder, Gallstone
- The Gallbladder stores bile between meals, concentrates bile
(by reabsorbing water & electrolytes), and
- Releases bile through cystic and common bile duct into the
duodenum.
- During the reabsorption process bile salts, bile pigments, and
cholesterol become increasingly concentrated.
- These substances precipitate and form solid crystals.
- When they become larger they form gallstones.
- Gallstones may then block the flow of bile causing obstructive
jaundice.
- Gallstone accumulation may obstruct bile flow to the
duodenum resulting in jaundice
- Bilirubin a yellowish-green by-product of heme metabolism
increases in plasma giving yellowish pigment.
June 10, 2023 216
 Digestive disorders
Gallstones ( Cholelithiasis)
• Bile stored for too long or too
much water removed, cholesterol
crystallizes
• Blockage of common hepatic or
bile ducts prevent bile into small
intestine, backs up into liver. Bile
pigments enter blood and
circulate, yellowing jaundice

June 10, 2023 Role of Liver in digestion 217

 Formation of Gall stone
• During the reabsorption process bile
salts, bile pigments, and cholesterol
become increasingly concentrated.

• These substances precipitate and

form solid crystals.

• When they become larger they form

gallstones.

June 10, 2023 Role of Liver in digestion 218

 Jaundice
 In the intestine, bacterial
actions change bilirubin
into stercobilin and
urobilinogen.
 They are further oxidized 3- types of jaundice:
and excreted in feces or
1. Prehepatic jaundice : RBC
urine as stercobilin and
2. Intrahepatic jaundice
urobilin.
3. Posthepatic jaundice:
 Excess level of bilirubin in the
obstruction
blood (>18 mg/L) causes
jaundice.
June 10, 2023 Role of Liver in digestion 219
Functional anatomy of small intestine (SI)
• SI is the part of GIT extending b/n the pyloric sphincter
of stomach and ileocecal valve
• It has small diameter, compared to that of the large intest.
• But it is longer than large intestine (6 meter).
• Maximum absorption of digested food products takes place
in small intestine.
Small intestine consists of three portions:
• 1. Proximal part known as duodenum
• 2. Middle part known as jejunum
• 3. Distal part known as ileum.
• Wall of the SI has all the four layers (Mucosa, Submucosa,
Muscularis externa & Serosa).
 Intestinal villi
• Mucous membrane of SI is covered by villi.
• Villi are lined by columnar cells, which are called enterocytes.
• Each enterocyte gives rise to hair-like projections called microvilli.
• Within each villus, there is a lacteal and blood vessels.
• The villous is the functional unit of the intestine
• The villous epithelium consists of enterocytes, goblet cells, and
endocrine cells.
• The three regions of a villous form a functional continuum:
• The crypt. The maturation zone, and the villous tip
• The crypt contains rapidly dividing stem cells that force migration
of cells up the side of a villous.
• Crypt cells are immature and do not express enzymes or membrane
transporters for nutrient absorption.
• Crypt cells are the source of intestinal fluid secretion
 Cont…
• In the maturation zone cells
are beginning to expresses
enzymes and absorptive
membrane transport proteins.
• At the villous tip. enterocytes
are fully differentiated and
undertake the absorption of
nutrients, electrolytes. And
fluid.
• After 3-4 days, the cells are
sloughed off the villous tip as
a defense mechanism
 (Cont…) Small intestine, Villi
- The intestinal secretions are formed by the enterocytes of the crypts
- It secretes 2 to 3 L/d of isotonic alkaline fluid to aid in the digestive
process.
- The secretion of watery fluid is derived mainly from cells in the crypts
of Lieberkühn
- Unlike the gastric pits, the intestinal crypts do not secrete digestive
enzymes, but do secrete mucus, electrolytes, and water
- Cells in the Liberkuhn crypts divide fast (mitosis) and are replaced by
new ones (every 2-5days)
- The epithelial cells contain digestive enzymes like sucrase, maltase,
lactase, and peptidases in the membranes of the microvillus.
- Villi: Are numerous finger like projections that emerge from the
mucous membrane.

Small intestinal Villi

- Glands at the base of Villi (entrecotes): Secrete large watery fluid.
- Epithelial cells of the villus: Also secrete digestive enzymes that break
nutrients before absorption takes place.
June 10, 2023 223
Small intestine, Villi • Mucus: protect and lubricate
The Mucus is secreted by:
a. Brunner's glands located in the duodenum
-secrete thick alkaline mucoid
secretion that serves a protective
role.
- preventing HCl and chyme from
damaging the duodenal mucosa
b. Goblet cells in other parts of the
intestine
- secrete a lot of mucus, which protects
the intestinal mucosa and lubricates the
chyme.
c. Paneth cells:- involved in the host defense
system in the small intestine.
-They are known to produce lysozyme which
destroys bacteria.
June 10, 2023
- They may also produce other enzymes. 224
 COMPOSITION OF SUCCUS ENTERICUS
• Secretion from small intestine is called succus entericus
• Succus entericus contains water (99.5%) and solids (0.5%).
• Solids include organic and inorganic substances
FUNCTIONS OF SUCCUS ENTERICUS
• DIGESTIVE FUNCTION
• Enzymes of succus entericus act on the partially digested food and
convert them into final digestive products
• Enzymes are produced and released into succus entericus by
enterocytes of the villi.
• Proteolytic Enzymes:- is peptidases,
Peptidases convert peptides into amino acids
• Amylolytic Enzymes are Lactase, sucrase and maltase and dextrinase
Lactase, sucrase and maltase convert the disaccharides into two
molecules of monosaccharides
• Dextrinase converts dextrin, maltose and maltriose into glucose.
 Cont…
• Lipolytic Enzyme
• Intestinal lipase acts on triglycerides and converts them into FA
2. PROTECTIVE FUNCTION
• Mucus present in the intestinal wall from the acid chyme
• Defensins secreted by paneth cells of intestinal glands are the
antimicrobial peptides.
3. ACTIVATOR FUNCTION
• Enterokinase present in intestinal juice activates trypsinogen
into trypsin. Trypsin, in turn activates other enzymes.
4. HEMOPOIETIC FUNCTION
• Intrinsic factor in the intestine plays an important role in
erythropoiesis
• It is necessary for the absorption of vitamin B12.
5. HYDROLYTIC PROCESS
 Small intestine, motility
• Motility in the small intestine are of 2-types
1. Segmentation & 2. Peristalsis
1. Segmentation: involves ring like (rhythmical) contraction and relaxation of
the intestine in short distances.
- Segmentation provides a sustained small divisions and mixes the chyme by
bringing it into contact with the intestinal wall.
- Sending the intestinal contents (chyme) in both oral and caudal directions.
- This small ring like contractions help chop, cut and mix the
chyme to a greater degree with intestinal juice.
- Responsible for the proper mixing of chyme with digestive juices
like pancreatic juice, bile juice and intestinal juice.
- Also such motility allows the contents to stay longer and promote increased
absorption of the chyme.
• Segmentation contractions occur about 12 times/min in the duodenum and 8
times/min
June 10, 2023
in the ileum. 228
 (Cont…) Motility, Segmentation in small intestine

June 10, 2023 229

 (Cont…) Small intestine, peristalsis
2. Peristalsis (propulsive) motility
• Pushing the chyme towards the aboral end of intestine
• Peristaltic waves move the chyme to the anal direction (velocity
2 cm/sec)
• Generally, it takes 3-5 hours to pass the chyme from the
pylorus to Ileo-secal valve.
• Nervous reflexes that increases peristalsis includes gastro-
enteric reflex that starts when stomach distends and sends
signals to small intestine
• Hormonal signals that stimulate peristalsis include CCK,
gastrin, serotonin, insulin, motilin
• Secretin and glucagon inhibits SI motility
June 10, 2023 230
 (Cont…) Small intestinal motility, peristalsis

Peristalsis in SI:
Generally the usefulness of peristalsis is 2-fold:
A. To cause progression of chyme to LI
B. To spread out the chyme along intestinal mucosa
- When reaching the Ileosecal sphincter, the chyme is blocked
for several hours until the person eats another meal.
- There after, a gastro-ileal reflex intensifies peristalsis and this
reflex forces the chyme to reach the large intestine.
Peristaltic rush:
• Is a powerful and rapid contraction of the small intestine
caused by irritation of the intestinal walls (e.g, as in diarrhea).
• It sweeps the contents of the intestine into the colon and
relives
June 10, 2023the SI of irritation and excessive distension 231
 (Cont…) Small intestine, Ileosecal valve
• Function of Ileo-secal valve and delay of emptying from small
intestine
- The Ileosecal sphincter prevents backflow of fecal matter from the colon
to small intestine
- When pressure builds in the cecum, the valve protrudes into the lumen
of the cecum and is forcefully closed.
- Reflex control of the Ileosecal sphincter (cause of delay of emptying from
SI).
Cecum distention--- increased contraction of the sphincter ---
ileum peristalsis is inhibited- Delay of emptying is caused
Also irritants in the cecum delay emptying

June 10, 2023 232

Absorption & transport from SI
 DIETARY CARBOHYDRATES
• Major carbohydrates in the human diet are present in following
forms:
1. Polysaccharides. These may be present in following forms:
- Starch is the carbohydrate reserve of plants.
- Glycogen. It is available in non-vegetarian diet and so often
referred to as animal starch.
- Cellulose (plant polysaccharide), which is present in diet in
large amounts. But there is no enzyme in the human
gastrointestinal tract (GIT) to digest it.
2. Oligosaccharides. Based on the number of monosaccharide units
present, oligosaccharides are further subdivided into di, tri, tetra
and penta saccharide.
 Cont..
Disaccharides include:
• Sucrose (glucose + fructose) is also known as table sugar (cane
sugar)
• Lactose (glucose + galactose) is also called milk sugar.
• Maltose (glucose + glucose). It is a product of starch hydrolysis.
Monosaccharides. consumed mostly in human diet are:
• Hexoses such as:
- Glucose (in fruits, vegetables and honey) and
- Fructose in fruits.
• Pentoses: found in nucleic acid and in certain polysaccharides,
such as pentosans of fruits and gums.
• Other carbohydrates, which may be present in the human diet are
alcohol, lactic acid, pyruvic acid pectin, dextrin and minor
quantities of carbohydrate derivatives in the meat.
 DIGESTION OF CARBOHYDRATES
• The digestion of carbohydrates begins in mouth, continues in
stomach? but occurs mainly (almost all) in the small intestine
• Initial starch digestion starts in the mouth by the enzyme α-amylase
(ptyalin) present in the saliva
• It digests cooked starch to maltose
• In the stomach there occurs minimal carbohydrates digestive activity.
• α-amylase activity continues in the stomach till the highly acidic
gastric juice mixes with the food and makes it inactive.
• In the small intestine the carbohydrates are digested by:
• Pancreatic a-amylase is present in the pancreatic juice it converts
starch into oligosaccharides, such as maltose, maltotriose and dextrin

• Brush border enzymes of small intestine (dextrinase, maltase, sucrase

and lactase.)
• Digest the oligosaccharides into monosaccharides
 Cont…
• a limiting
dextrinase
Dextrin Glucose

• Maltase, sucrase and lactase hydrolyse the corresponding

disaccharides into monosaccharides as below:
Maltase
Maltose 2 Glucose
sucrase
Sucrose Glucose + Fructose
lactase
Lactose Glucose + Galactose
• The end products of carbohydrates are monosaccharides, such as
glucose, fructose and galactose
 ABSORPTION OF CARBOHYDRATES
• Carbohydrates are absorbed from the GIT in the form of monosaccharides.
Site of absorption
• Most of the monosaccharides are absorbed from the mucosal surface of
jejunum and upper ileum.
Mechanism of absorption
• Glucose and galactose are absorbed by a common Na+-dependent active
transport system;
• Fructose is absorbed by facilitated diffusion and
• Pentoses are absorbed by simple diffusion.
FATE OF GLUCOSE IN THE BODY
1. Storage as glycogen. About 5% of the total glucose absorbed is stored as
glycogen in the liver and muscles
2. Catabolism to produce energy. About 50–60% of the glucose absorbed is
catabolised in the body tissues to produce energy.
3. Conversion into fat. About 30–40% of glucose is converted into fat and is
stored in the fat depot
 (Cont…) Small intestine, CHO absorption

June 10, 2023 240

Digestion Carbohydrates

241
 Digestion of carbohydrates

June 10, 2023 242

 DIGESTION AND ABSORPTION OF PROTEINS
• The proteins that are digested and absorbed in the GIT come from two
sources: exogenous and endogenous.
1. Exogenous (dietary) proteins
• Sources of dietary proteins with high biological value are meat, fish, eggs,
cheese and other milk products, Soybeans and wheat
• The dietary proteins are made of long chains of amino acids bound
together by peptide linkages.

2. Endogenous proteins
• Are the proteins which reach the intestine through various GI secretions
and those which are present in the desquamated epithelial cells of the
gut.
 DIGESTION OF PROTEINS
• Proteins are digested by the proteolytic enzymes to amino
acids and small polypeptides before they are absorbed.
• Digestion of proteins does not occur in the mouth, as there
are no proteolytic enzymes in the saliva.
• Digestion of proteins, thus begins in the stomach and is
completed in the small intestine.
• Pepsin: is responsible for digesting about 10–15% proteins
entering the GIT
• Pepsin splits proteins into proteoses, peptones and
polypeptides
• It is important to note that the optimum pH for the action
of pepsin is 2.0
• In the SI the proteins are digested by the pancreatic
proteases, brush border peptidase and intracellular peptidase
 Cont…
• Pancreatic proteases digest the proteins and split them into dipeptides,
tripeptides and small polypeptides
• Some of the di and tripeptides are absorbed directly into mucosa of SI
and further digested by the intracellular enzymes into AA.
• Brush border peptidases: include aminopeptidases, dipeptidase,
tripeptidase, nuclease and related enzymes
• These enzymes continue the digestive process begun by the pancreatic
proteases and convert the proteins to small polypeptides and AA
• Intracellular peptidases: are the proteolytic enzymes present in the
cytosol of epithelial cells of SI
• These digest the di and tripeptides into AA which then enter the blood
• Nucleic acid and nucleoproteins are found in the foodstuffs which are
rich in nuclei, such as liver, kidney, pancrease, yeast etc.
• In the stomach: HCL hydrolyses the nucleoproteins, removing proteins
which are digested together with other proteins
 Cont…
• Nucleoproteins

• In the small intestine: the free nucleic acids are digested by the
pancreatic enzymes and brush border enzymes
• Pancreatic enzymes, such as ribonuclease and deoxyribonuclease in the
duodenum digest free nucleic acids into nucleotides and nucleosides
• Brush border enzymes, such as nuclease, nucleotidases and
nucleosidases convert nucleotides and nucleosides into pentoses
(purine and pyrimidine)
• The end product of protein digestion are amino acids (AA)
• Absorption of proteins: Na+- dependent active transport
- simple diffusion and endocytosis
 (Cont…) Small intestine, Protein absorption

June 10, 2023 250

Digestion of Proteins

251
 Digestion of proteins

June 10, 2023 252

 (Cont…) Small intestine, fat absorption

June 10, 2023 253

Digestion of Lipids

254
June 10, 2023 257
 (Cont…) Fat soluble vitamins (A, D, E, K)

• Fat soluble vitamins are mixed with micelles formed by the

bile acids and lipid digestion products.

• These bile acids and lipid digestion products in the small

intestine enhances the absorption of Fat-soluble vitamins.

• In the epithelial cells of the small intestine, the fat soluble

vitamins enter the chylomicrons and leave the intestine with
the lymph. However, a small fraction may be absorbed and
leave the intestine with the portal blood
June 10, 2023 258
Absorption of Fe2+ and Ca2+
(Cont…) Absorption of Na+ ion and H2O by osmosis in
the Small intestine

June 10, 2023 260

Absorption in the Small Intestine

261
Absorption from SI

262
 Large intestine (colon), Function

Function of the large intestine

1. Water absorption
2. Electrolyte absorption; mainly NaCl
3. Mucous & HCO3- Secretion
4. Storage, transport, and evacuation of feces
5. Absorption of some drugs (suppositories)
6. Bacterial fermentation in the colon stimulates
synthesis of some vitamins

June 10, 2023 264

 • After the cecum, the colon
consists of the ascending
and transverse colons,
which are mostly involved
in absorption and secretion.
• The descending and
sigmoid colons are mostly
the site of storage of fecal
matter.
• The sigmoid joins the
muscular rectum, where
storage and stimulation of
defecation induces bowel
movement.
• The anus that has two
sphincters is involved in
control of involuntary and
voluntary evacuation of the
6/10/2023 10:18 PM GIP K.E.(Msc)
ingesta (defecation reflex).
265
 Large intestinal motility
• Like Small intestine motility, LI motility is governed by:

A. Haustral movement (segmentation)

B. Mass movement
Haustral movements
• In the colon, segmentation movements occur in a
large circular constrictions that are powerful enough to
close the diameter to a narrow loop.
• Moreover, the 3-longitudinal muscles “teniae coli”
contract and push the segments into a bag-like portions
called haustrations.
 Emptying at the ileocecal valve
• The ileocecal valve protrudes into the
lumen of the cecum
• When excess pressure builds up in the
cecum it forcefully closed the
ileocecal valve
• Tries to push cecal contents backward
against the valve lips.
• Upstream from the ileocecal valve
has a thickened circular muscle called
the ileocecal sphincter.
• Resistance to emptying at the
ileocecal valve prolongs the stay of
chyme in the ileum and facilitate
absorption .
• only 1500 to 2000 ml of chyme
empty into the cecum each day.
 Motility of the colon
A. Characteristics of Haustral movements:
Move slowly through the colon.
– This slow movement rolls the fecal matter and help
expose the fecal contents to the mucosal surfaces of
the colon.
– Its contact with the mucosal surfaces promotes
efficient absorption of fluid and electrolytes from
the colon.
:
-

6/10/2023 10:18 PM GIP K.E.(Msc) 268

 B. Mass (propulsive) movement
- Produced by slow and continuous Haustral contractions
and supported or modified by peristaltic actions.
- Mass movements occur seldom (~ 1 - 3/d or once after a
breakfast)
- The appearance of mass movements after meals is
facilitated by gastrocolic and duodenocolic reflexes.
- These reflexes result from distention of the stomach and
duodenum
- They occur either not at all or hardly at all when the
extrinsic autonomic nerves to the colon have been removed
- Requiring as many as 8 to 15 hours to move the chyme
from the ileocecal valve through the colon
- When mass movement forces feces into the rectum, the
desire for defecation occurs immediately, including reflex
contraction of the rectum and relaxation of the internal
anal sphincter.
 Absorption & secretion from the colon
- To form solid feces the chyme entering the colon should be
dehydrated.
- This is achieved by water absorption across the colon epithelium.
- The absorption is important in the bodies water economy
- Water absorption occurs by osmosis following the active
absorption of Na+ ion.
- Na+ absorption can also be enhanced in the colon by the
hormone aldosterone.
- K+ is secreted in the large intestine and this creates a major
problem of K+ depletion during severe diarrhea.
- Cl- is absorbed in exchange for HC03- ion released into the lumen.
- The resulting secretion of HC03 ion into the lumen helps in
neutralization of acids generated by microbial fermentation in
thecolon.
- Vitamins and drugs are efficiently absorbed from the large
intestine.
- The metabolism and death of colon bacteria provide a useful
source of several vitamins to the body (Vit.K,Vit. B etc). 270
 Mucus secretion
• The mucosa of the large intestine, like that of the small intestine,
has many crypts of Lieberkühn
• However, unlike the small intestine, there are no villi.
• The epithelial cells secrete almost no digestive enzymes they
contain mucous cells that secrete only mucus.
• This mucus contains moderate amounts of bicarbonate ions
secreted by a few non-mucus-secreting epithelial cells.
• Mucus in the large intestine protects the intestinal wall against
excoriation
• It provides an adherent medium for holding fecal matter
together.
• It protects the intestinal wall from the great amount of bacterial
activity that takes place inside the feces
• The mucus plus the alkalinity of the secretion provides a barrier
to keep acids formed in the feces from attacking the intestinal
wall.
 Colon, defecation reflex
- Mainly, the sacral spinal
cord is involved in this
reflex and the Cholinergic
parasympathetic fibers
are important for they
greatly innervate the
large intestine.
- The reflex: Stimulation of
receptors in the rectum
by feces > Sensory
impulses to the sacral
spinal cord > Motor
reflex through PSN (
pelvic + pudendal
nerves) back to the
colon > Powerful
peristalsis mainly at
descending, sigmoid,
rectum, & anal regions +
relaxation of internal
sphincter > expulsion of
the bowel. 272
 (Cont…) defecation reflex
• Taking deep breath & contraction of abdominal and respiratory
muscles elevate intra-abdominal and intra-thoracic pressures that
help force feces through the relaxed sphincter.
• This maneuver termed the Valsalva maneuver
• In new born babies and people with transected spinal cords,
defecation reflexes cause automatic emptying of the lower
bowel at inconvenient times.
• This is because of lack of conscious control exercised through
voluntary contraction and relaxation of the external anal
sphincter.
• The rectum remains usually empty until filled by feces from
sigmoid colon
• The filling of the rectum reflexly relaxes the internal anal
sphincter, but constricts the external anal sphincter
So, defecation can stay at will
• Persons lucking motor innervations to the external sphincter,
defecate involuntarily, when the rectum is filled. 273
 Cont…
• Other autonomic reflexes that affect bowel activity
• several other important nervous reflexes also can
affect the overall degree of bowel activity.
• They are the peritoneointestinal reflex, renointestinal
reflex, and vesicointestinal reflex.
• The peritoneointestinal reflex results from irritation of
the peritoneum.
• It strongly inhibits the excitatory enteric nerves and
cause intestinal paralysis.
• The renointestinal and vesicointestinal reflexes inhibit
intestinal activity as a result of kidney or bladder
irritation, respectively.
 Composition of the Feces
• The feces normally are about three-fourths water and one-fourth
solid matter
• That is composed of about 30%dead bacteria ,10 to 20%fat, 10
to 20% inorganic matter, 2 to 3% protein, and 30%undigested
roughage from the food and dried constituents of digestive
juices, such as bile pigment and sloughed epithelial cells.
• The brown color of feces is caused by stercobilin and urobilin,
derivatives of bilirubin.
• The odor is caused principally by products of bacterial action
• These products vary from one person to another, depending on
each person's colonic bacterial flora and on the type of food
eaten.
• The actual odoriferous products include indole, skatole,
mercaptans, and hydrogen sulfide
 Digestive disorders, Constipation
Constipation
- Is caused mainly by reduced colonic motility.
- Reduced motility increases storage time in the colon that in turn
increases the degree of water absorption from the large intestine.
- Dried feces are less bulky and, therefore, less likely to initiate
movement.
- Increased fiber content (cellulose, raw vegetable etc.) may improve fecal
bulk and thus can stimulate colonic motility.
Diarrhea
• Is characterized by excessive and frequent discharge of watery feces
induced by increased intestinal motility. Some causes of diarrhea
include:
- Toxins acting on intestinal glands (e.g. cholera) cause secretion of
electrolytes (Na+, Cl-, HCO3) into the lumen; water follows by osmosis.
-Nervous (psychogenic) origin: anxiety increases parasympathetic activity
to the lower bowls that increases motility; absorption time decreases
leading to diarrhea.
6/10/2023 10:18 PM GIP K.E.(Msc) 276
 (Cont…) Digestive disorders, Lactose intolerance
Lactose intolerance
- Is mostly hereditary, caused by deficiency of the enzyme lactase located at the
brush border of the small intestine.
- Lactose (milk sugar) is a disaccharide and should be degraded to galactose and
glucose, in order to be absorbed into the blood.
- The undigested lactose reaches the colon (large intestine) and is acted by
bacteria’s.
- This result is increased gas production, borborgymi (noise), flatulence, and
enhanced motility of the colon.
- Lactose intolerant subjects usually dehydrate for they lose water to the colon
(b/s osmolality increases)
- Infants, who are lactose intolerant, dehydrate and show diarrhea for they do
not utilize lactose.
- Thus formula milk with lactose should be avoided.
Peptic ulcers :
- Normally the stomach and intestinal walls are protected by mucosa against the
eroding actions of HCL.
- Excess acid secretion erodes the wall creating wounds (ulcers). If these wounds
are deep enough, they can reach the vascular layer and cause bleeding
- Increased secretion of gastrin and excessive activity of the Vagus nerve as well as
psychological factors stemming from anxiety and stress are believed to be
involved as causatives and also infected with a bacterium known as
Helicobacter pylori. GIP K.E.(Msc)
 Reading Assignment
Metabolism and Temperature Regulation
Chapter 63-74
Guyton 14th edition or
Chapter 68-70
Page 853-888
Guyton 13th edition

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