DIGESTIVE SYSTEM

[Gastrointestinal tract – G.I.T.]

- Dr. Vivek V. Nalgirkar

Table of contents
 Section 1: Introduction ~ Structural overview, Innervation of digestive tract,
electrical activity
 Section 2: Motor activity in digestive tract ~ Mastication, deglutition, motor
function of stomach, motility of small & large intestines, defecation
 Section 3: Secretions in digestive tract ~ Saliva, Gastric juice, Pancreatic juice,
succus entericus, bile
 Section 4: Regulatory hormones/peptides related to gut
 Section 5: Digestion and absorption of nutrients

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 Section 1
Introduction

Structural overview:

- The digestive system is made up of a long muscular tube – the

alimentary canal or the gastrointestinal tract (G.I. tract), and the
structures associated with it.
- The G.I. tract starts with the oral cavity; and then there are pharynx,
esophagus, stomach, small intestine, large intestine (colon), rectum, and
anal canal, in the given sequence.
- Some other associated structures are: Exocrine glands such as salivary
glands and pancreas, and liver & gall bladder.
 Function of the digestive system is to breakdown the ingested foodstuffs,
so that they are converted into simpler forms and absorbed into the blood,
to be made available to all cells for their energy production. There is also
absorption of water and minerals & vitamins.

~ The wall of the alimentary canal consists of 4 layers:

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[Figure: The layers of the alimentary canal.]

From inside out:

1. Mucous layer: It consists of glands.

2. Submucous layer: It has blood vessels and lymphatics. Between the
submucous layer and the inner circular muscle lies the submucous plexus
(Meissner’s plexus); this nerve plexus is connected to the Auerbach’s plexus
and to the extrinsic autonomic nerves.
3. The muscular layer or muscularis mucosae: Two layers of smooth muscle in
it are – inner circular layer and outer longitudinal layer. Between these two
layers of smooth muscle, there is myenteric plexus (Auerbach’s plexus).
This nerve plexus is under extrinsic autonomic control.

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 4. The serous layer or serosa: The outermost layer; it is a part of the
peritoneum that suspends the organs within the abdomen.

Innervation of G.I.T.

Enteric nervous system (ENS): sometimes called “peripheral brain” or minibrain

due to extensive network of nerve fibers. ENS is considered the enteric division of
the autonomic nervous system.

~ Neuron types in the gut:

Two primary types of neurons in the ENS are: (1) After-hyperpolarization

type (AH), which have multiple long processes, and (2) Synaptic type (S), which
have a single long axon and multiple short dendrites. [AH type mainly present in
the myenteric plexus; S type mainly present in the submucous plexus.]

(A) Intrinsic innervation:

1. Myenteric plexus (Auerbach’s plexus):
 Mainly motor in function.
 Excitatory motor neurons release Ach and substance P; inhibitory
motor neurons release VIP and NO. Quantitatively, NO is the
most important mediator of relaxation of G.I. smooth muscles.
 Controls the peristalsis
2. Submucous plexus (Meissner’s plexus):
 It has many sensory neurons. Regulates glandular, endocrine, and
epithelial cell secretion.
 Secretomotor neurons release Ach and VIP onto gland cells or
epithelial cells. {VIP inhibits motility but stimulates secretion at
some places.}
(B) Extrinsic innervation:
1. Parasympathetic nerves: vagus nerve (from esophagus upto proximal
colon) and pelvic nerves - S2,3,4 (distal colon, rectum and anus). Their
stimulation would increase motility and secretion.

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 2. Sympathetic nerves: arise from T6 – L2 segments; their stimulation would
decrease motility and secretion, and cause contraction of sphincters.

~ Electrical activity in G.I. smooth muscle:

- Except in esophagus and proximal stomach, the smooth muscle of G.I. tract
shows spontaneous waves of electrical activity: the slow waves.

[Fig: The electrical activity in GI smooth muscle. It shows the the slow waves occurring at
a certain frequency, and spikes at the peak of the slow waves.]

- Frequency of slow waves determines the basic electrical rhythm (BER).

- BER is generated by pacemaker cell: the interstitial cell of Cajal.
- Slow waves or BER does not cause muscle contraction. Spike potentials
superimposed on depolarizing portions of slow waves cause contraction.
- Amount of tension developed by smooth muscle is proportional to number
of spikes
- Rate of BER:

Segment of gut Frequency of BER

- Stomach 4/min
- Duodenum 12/min
- Jejunum 9/min
- Ileum 7/min

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 - Cecum 2/min
- Sigmoid colon 6/min
[Note: In the small intestine, the frequency of BER goes decreasing from duodenum to ileum.
This is responsible for the law of gut ~ oral to anal orthograde direction of peristalsis. In the
colon, there is reversal of gradient, with cecum showing the BER of 2/min, and a higher BER
of 6/min in the sigmoid colon. This may be responsible for the occurrence of anti-peristalsis,
from hepatic flexure of colon to cecum.]

Nerve reflexes in the gut:

1. Intrinsic/local reflexes: only the ENS is involved. E.g. peristaltic reflex.

2. Extrinsic reflexes: prevertebral ganglia, spinal cord, or brain is involved.
a. Short reflex – impulses from ENS to prevertebral ganglia and then back
to gut. E.g. intestino-intestinal inhibitory reflex (overdistension of one
part of intestine causes inhibition of the adjacent intestinal segments).
b. Long reflex – impulses from gut to the spinal cord / brain and back to gut
via autonomic nerves. E.g. (i) gastric juice secretion due to stomach
distension; (ii) defecation reflex, (iii) gastroileal reflex, gastrocolic reflex,
and enterogastric reflex (described elsewhere)

Video link ~ There are 6 sphincters in digestive tract; plus, the sphincter of Oddi.

LES is the “Physiological sphincter”

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 Section 2

Motor activity in digestive tract

Learning objectives:

- To learn the movement of foodstuffs along the digestive tract.

 Mastication:
- Mastication (chewing) is the mechanical process; it breaks larger
food particles into smaller pieces.
(i) It makes the swallowing of food easier.
(ii) It allows the mixing of food with the salivary secretions.
(iii) It increases the surface area of the food particles, which helps
in the subsequent digestion of the food in alimentary canal.

 Deglutition (Swallowing)
- It is the process of food movement from the oral cavity into the
stomach.
- It occurs in 3 stages: (1) oral stage, (2) pharyngeal stage, and (3)
esophageal stage.
- Oral stage is voluntary. The other two stages are involuntary.
(1) Oral stage: Once the food is chewed thoroughly, and mixed with
the saliva, it is rolled into a bolus. Movement of the tongue
(upward & backward) then presses this bolus against the hard
palate. The bolus is pushed backward into the pharynx; then the
pharyngeal stage begins. Now on, the process becomes
involuntary (reflex).
(2) Pharyngeal stage: (The events in this stage ensure that the food
particles do not regurgitate from nose or enter the respiratory
tract; the bolus enters esophagus.)

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 As food enters pharynx, a series of events occur to allow the food
to pass through the pharynx.
 Closure of posterior nares: The soft palate is raised upward
to close the posterior nares, so that food does not
regurgitate from the nasal cavity.
 Closure of respiratory passage: The epiglottis swings
backward over the opening of the larynx. Vocal cords of
the larynx are pulled medially to close the laryngeal
opening. These changes will prevent entry of the food
particles into the respiratory passage.
 The palatopharyngeal folds on each side of the pharynx
are pulled medially to approximate each other. These folds
form a sagittal slit through which the food must pass into
the posterior pharynx. This slit performs a selective action.
Large bolus of food will not be able to pass through the
pharynx into the esophagus.
 Opening of the esophagus is pulled up and enlarged. At the
same time, the upper esophageal sphincter (“pharyngo-
esophageal sphincter”) relaxes, thus allowing food to move
easily and freely from the posterior pharynx into the upper
esophagus.
 A wave of contraction begins in the pharynx and spreads
down rapidly. It propels the food into the esophagus.
Nervous control of the pharyngeal stage:
Sensory signals – Pharyngeal stage is reflexly initiated by
stimulation of receptors in pharynx (particularly, near the
tonsillar pillars). The impulses are transmitted through sensory
portions of the V and IX cranial nerves to the medulla
oblongata.
Swallowing center – The areas in the medulla and lower pons
that control swallowing are collectively called the “deglutition
or swallowing center”.

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 Motor signals – from the swallowing center to the pharynx
and upper esophagus are transmitted via V, IX, X, and XII
cranial nerves; they execute the changes mentioned above.
 Deglutition apnea: The respiratory center that controls breathing is
situated in the medulla. During the pharyngeal stage of swallowing,
the impulses from the swallowing center cause a temporary
inhibition of the respiratory center. Respiration is interrupted, to
allow swallowing to proceed. It is called “deglutition apnea”.
(3) Esophageal stage: Esophagus conducts food from the pharynx
into the stomach. The movement of food occurs by virtue of two
types of peristalsis exhibited by esophagus.
(a) Primary peristalsis – It is just the continuation of the
peristaltic wave that begins in the pharynx (during
pharyngeal stage) and spreads into the esophagus.
(b) Secondary peristalsis – If all the food was not moved
into the stomach during primary peristalsis, another
wave of contraction will clear it from the esophagus.

The motor impulses for this stage are transmitted via the IX
and X cranial nerves. The reflex activity is co-ordinated at
the brain-stem swallowing center.

- The lower esophageal sphincter (LES): [The “Physiological”

sphincter] Also known as the “gastro-esophageal sphincter”;
situated at the lower end of the esophagus (3 cm above the juncture
with the stomach). It is not an anatomical entity; the esophageal
circular muscle functions as sphincter at this region. When a
peristaltic swallowing wave passes down the esophagus, there is
‘receptive relaxation’ of the LES, so that the swallowed food passes
easily into the stomach.
[The relaxation of LES is mediated by the X nerve (vagus) and the
chemical transmitter ‘vasoactive intestinal polypeptide’ (VIP).]
 Applied physiology:

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 - Dysphagia: difficulty in swallowing. It may occur from a
variety of disorders (such as carcinoma of esophagus.)
- Achalasia: A condition in which there is excessive tone of the
LES and it does not relax during swallowing; food accumulates
in the esophagus.

Motor functions of stomach

(storage, mixing, and slow emptying)

[Fig: It shows the functional anatomy of stomach. The 3 regions of stomach ~ fundus, body,
and pylorus. The two sphincters ~ Lower esophageal sphincter (LES) at the junction of
esophagus and stomach, and pyloric sphincter at the junction of stomach and 1st part of

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duodenum. The two curvatures ~ lesser & greater curvature.]

 Anatomical regions of the stomach are fundus, body, antrum, and pylorus.
 Two functional divisions of the stomach: proximal reservoir (fundus and
proximal 1/3rd of the body) and distal antral pump (distal 2/3rd of the body,
antrum, pylorus). The proximal stomach can maintain “tonic contraction”;
distal stomach shows “phasic contractions” and propulsive activity. Reason
for these phasic contractions:- A pacemaker complex located near the
midregion of the body; it initiates the electrical and phasic contractile
activity.
 Motor functions of stomach:
(i) Storage:
Large quantities of food can be stored in the stomach until the food
can be passed on and processed in the duodenum.
Receptive relaxation: Without a rise in intragastric pressure, stomach
can accommodate about 1.5 L of volume; due to receptive relaxation.
It is initiated by the act of swallowing food; it occurs in the proximal
body region. Distension of stomach by food initiates a “vago-vagal
reflex” that causes this relaxation.
(ii) Mixing:
Weak peristaltic constrictions, called ‘mixing waves’, begin in the
midportion of the stomach and move toward the antrum. As the I

constrictor waves progress toward the antrum, they become more

intense.

Major mixing activity in the pyloric antrum is called “retropulsion”.

The forceful contractions of the antral pump dig deeply into the food
contents. Yet the opening of the pyloric sphincter is small; only a few
mL of the food contents are expelled into the duodenum. Most of
the antral food contents are squeezed backward (‘retro’). Another
constrictor wave again causes the food contents to move toward the
sphincter. Thus, back and forth movement of the food contents
cause a thorough breakdown and mixing of food with the gastric

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 juice. Breakdown of ingested food, and mixing of it with gastric juice,
converts it into a semisolid paste – the chyme.

(iii) Emptying of the stomach:

Pumping action of the pyloric pump slowly empties the chyme into
the duodenum.
Water (or, liquids) and solids in food travel differently through
stomach. Water moves quickly, along the lesser curvature, to reach
small intestine in no time. Solids are stored in stomach, mixed with
gastric juice, and slowly emptied into 1st part of duodenum.
Normal gastric emptying time for solids: 4 to 6 hours. Most of the
ingested food is emptied from the stomach into the duodenum by
this time. Gastric emptying time is longest for fats (6-8 hours).

Video link ~ After eating fat-rich food, we don’t feel hungry for a longer duration; why?

 Factors influencing gastric emptying:

1. Weak gastric factors that promote gastric emptying –
 Gastrin (increases stomach contractility, although constricts
pyloric sphincter, hence a weak factor), a hormone secreted by
the pyloric G-cells.
2. Strong duodenal factors that inhibit gastric emptying (emptying time
will be prolonged) –
(There are osmoreceptors and chemoreceptors in the duodenal
mucosa; they respond to physical properties and chemical
composition of the duodenal contents and evoke enterogastric
reflexes which are inhibitory. Arising from the duodenal wall
(‘entero’), the impulses reach the stomach (‘gastric’) and inhibit
gastric contractions and constrict pyloric sphincter – thus inhibit
gastric emptying.)

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 I. Hypertonic contents reaching duodenum:

Video link ~ Why is it necessary to normalize the tonicity of the contents

before they reach duodenum? DUMPING SYNDROME

II. Acidic chyme (pH < 3.5) in duodenum

- In duodenum, pancreatic enzymes will be acting on the
foodstuffs; these enzymes can be active in alkaline pH only.
Hence, if acidic chyme from stomach starts reaching
duodenum in large amounts, further gastric emptying has to
be prevented.

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III. Irritation of duodenal mucosa
- It will evoke enterogastric reflexes; further gastric emptying
will be inhibited.
Video link ~ Why does the irritation of duodenum prevent further gastric emptying; a
protective mechanism

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 IV. Fat/protein breakdown products in duodenum
- fat is the most potent inhibitor of gastric emptying.

Applied Physiology:

1. Dumping syndrome: (Rapid gastric emptying)

- If the gastric contents are rapidly emptied into duodenum, it
may result in “dumping syndrome” (as if, the contents are
hurriedly “dumped” into duodenum).
- It occurs after gastric surgeries (in which some part of the
stomach is removed).
- It has two components – (a) Early dumping syndrome:
Hypertonic contents reach duodenum —> pull water into
duodenum —> diarrhea and decrease in blood volume

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 (b) Late dumping syndrome: Excess glucose reaches
duodenum and gets absorbed into blood —> secretion of
insulin —> insulin pushes blood glucose into cells —->
hypoglycemia.

- Decreased blood volume, decreased BP, and hypoglycemia

may cause dizziness, weakness, and fainting.
2. Slowed gastric emptying:
- Diabetic gastroparesis results in delayed gastric emptying.
Long standing DM may result in autonomic neuropathy. With
involvement of the vagus nerve, gastric motility may be lost
(gastroparesis).

 Vomiting: (also called emesis)

- It is a reflex that causes anti-peristlasis; gastric contents are expelled out
through mouth.
- It generally occurs due to irritation of stomach or intestines
- Sequence of events:
(i) Closure of glottis and of nasopharynx so that the vomitus does not
enter the trachea or nose (this is similar to the event in deglutition)
(ii) Contraction of pylorus; anti-peristalsis in stomach
(iii) Rise in intra-abdominal pressure: Contraction of abdominal muscles
and diaphragm creates a propulsive force; gastric contents are pushed
into esophagus and then ejected out through mouth (anti-peristalsis
in esophagus helps the process)

Vomiting reflex is integrated in the medullary center, located ventral to NTS. It may be
stimulated by afferents (nerve signals) coming from the gut or pharynx, or may be
stimulated directly by raised intracranial pressure, circulating drugs & toxins.

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  Hunger contractions – (“Hunger pangs”)
When the stomach has been empty for several hours, rhythmic peristaltic
contractions occur in the body of the stomach.
They are greatly increased by a low blood sugar.
When strong hunger contractions occur in the stomach, the person
sometimes experiences mild pain in the pit of the stomach, called “hunger
pangs”.

~ From the pyloric sphincter, chyme enters small intestine. The 3 parts of the small intestine are
– duodenum, jejunum, and ileum. Ileum empties its contents into the large intestine (colon); it
begins with cecum and ascending colon, transverse colon, descending colon. Then there is
sigmoid colon that leads to rectum, and finally the anal canal.

 Movements of the small intestine:

[Movements of the small intestine show two patterns: 1. In the fed state, that is
after the food is ingested. They are aimed at slow propulsion of food and its
digestion and absorption. 2. In the interdigestive period – When there is no
food/chyme in the intestine.]

(A) Motor activity in the fed state:

(1) Segmentation contractions –
- They cause mixing of intestinal contents.
- A section of small intestine contracts, sending the intestinal contents
(chyme) in both forward and backward directions. That section of
small intestine then relaxes, and the contents move back into the
segment.
- This back-and-forth movement caused by segmentation
contractions is designed to cause mixing, without any net forward
movement of the chyme.

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 - Pendular movements: They are similar to the segmentation
contractions; but individual segments formed are large, about 20 cm
in length. It helps the liquid chyme to move to-and-fro (like the
pendulum of a wall clock.)
(2) Peristalsis –
- These are propulsive movements in the intestines. A ring of
contraction moves in the aboral direction, propelling the chyme
forward.
- Mechanism: When any segment of the gut is distended (by chyme),
the segment behind it will contract and the segment ahead of it
will relax. Thus, propulsive movements will always occur in the
caudad or analward direction.
 Frequency of contractions is highest in the duodenum. The frequency
gradually declines caudally; it is least in the ileum.
 Law of the gut: Analward orthograde direction of the peristalsis. {Peristalsis
always occurs in one direction – oral to anal.}
 Peristalsis is co-ordinated by the enteric nervous system (ENS).

[Fig: Peristaltic wave. The part behind the bolus of food contracts, and the segment
ahead of it relaxes.]

(B) Motor activity in the interdigestive (or fasting) period:

The migrating motor complexes (MMCs) –
Once the food has been digested and absorbed, and intestines are
almost empty, these motor complexes occur in the GIT. A ring of

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 contraction appears at one point in the digestive tract, and then it
sweeps over the entire length of intestine. Then, another ring of
contraction appears at some next point. These contractions are hence
called “migrating” motor complexes.
Function: Any remaining food particles, debris, sloughed enterocytes, or
biliary secretion are cleared from the intestine. Hence, it is known as the
“housekeeper of the GIT”.
Total duration of an MMC, at one point, is about 90 minutes. It then
migrates to next point.
At any one point, an MMC has 3 phases:
(i) Phase I: Quiescent phase: (70 minutes)
Only electrical activity (slow waves) in this phase; no contractions
(ii) Phase II: (15 minutes)
Irregular contractions
(iii) Phase III: Activity front: (5-10 minutes)
Each slow wave/spike is followed by contraction

The complex then ‘migrates’ and the cycle is repeated elsewhere.

The hormone motilin strenthens MMC contractions.

Video link ~ Erythromycin, the macrolid antibiotic, can be used as a prokinetic

drug.

~ Regulation of the intestinal motility: (neural & hormonal)

- Enteric nervous system co-ordinates the peristaltic contractions.

- Effect of the extrinsic nerves:
1. Parasymppathetic stimulation increases the smooth muscle
contractility in the intestines; the peristaltic activity will increase.
2. Sympathetic stimulation decreases the peristaltic contractions.

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 - Hormonal influence: Gastrin, CCK, insulin, serotonin enhance
intestinal motility. Secretin and glucagon hormones inhibit small
intestinal motility.

[*Gastro-ileal reflex: When food enters stomach, it may initiate contractions in

ileum. With opening of ileo-cecal valve, the contents are pushed into colon. This
may be responsible for urge for defecation after eating foodstuffs.]

 Applied Physiology:
o Paralytic ileus: (also called adymanic ileus)
- There is functional motor paralysis of the digestive tract
- Intestine fails to transmit peristaltic waves
- It is sometimes also referrred to as pseudo-obstruction; there is no
real obstruction in intestines (it is a “functional” obstruction).
- It may occur due to surgery (post operative ileus), or peritonitis.
- Due to failure of activity (motility), there is stasis in the intestine and
accumulation of gas and fluid.

~ Movements of the large intestine (colon):

 By the time chyme enters the colon, the digestion and absorption of the
nutrients in the foodstuffs has already occurred (in the small intestine). The
principal functions of the colon are: (i) absorption of water and electrolytes
from the chyme to form solid feces, and (ii) storage of fecal matter until it
can be expelled.
 Colon is roughly divided into two segments – 1. Proximal colon: It includes
the cecum, ascending colon, and proximal half of transverse colon. 2. Distal
colon: Distal half of the transverse colon, descending colon, and sigmoid
colon. Sigmoid colon eventually leads to rectum and anal canal.
 Proximal colon is the absorptive colon. Absorption of water and
electrolytes from the chyme converts it into a solid fecal matter. Distal
colon is the storage colon. Fecal material is stored temporarily until it can

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 be excreted. Because intense colon movements are not required for these
functions, the movements of the colon are normally very sluggish.
(I) Mixing movements: Large circular constrictions occur in the large
intestine; about 2.5 cm of the circular muscle contracts. The
longitudinal muscle of the colon is aggregated into 3 longitudinal
strips, called the teniae coli. There are combined contractions of the
circular and longitudinal strips of muscle. This causes the
unstimulated portion of the colon to bulge outward into baglike sacs
called “haustrations”.
(II) Propulsive movements – “Mass movements”: They are the
modified type of peristalsis. From the beginning of transverse colon
to the sigmoid, the “mass movements” take over the propulsive role.
They occur 1 to 3 times per day. They cause colonic contents to move
distally for long distances.

[* Gastrocolic reflex: After meals, as the stomach is distended, there is initiation

of mass movements in the colon. They are initiated by the ANS. Commonly
occurring in children, they initiate defecation reflex soon after eating.]

~ Defecation: {Excretion of the feces out from the rectum through the anal canal
to the exterior.}

 When a mass movement forces feces into the rectum, the desire for
defecation is normally initiated. Once the rectum is filled to about 25% of
its capacity, there is an urge to defecate.
 The two anal sphincters are – (i) the internal anal sphincter, and (ii) the
external anal sphincter. The external sphincter is composed of striated
voluntary muscle, and it is controlled by nerve fibers in the pudendal nerve.
It exerts voluntary, conscious control over the process of defecation. As
long as the external sphincter is constricted, defecation if not possible. And,
when defecation is desired, the external sphincter will be relaxed, under
voluntary control, so as to allow passage of fecal material to the exterior.

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 Man being the social animal, time and place for defecation is chosen
appropriately. Until then, the process will be voluntarily withheld.
 Defecation reflex: When feces enter the rectum, distension of the rectal
wall initiates afferent signals that spread through the myenteric plexus to
initiate peristaltic waves in the descending colon, sigmoid, and rectum.
Fecal material forced toward the anus. Internal anal sphincter is relaxed as
the peristaltic wave approaches downward. If the external anal sphincter is
also consciously, voluntarily relaxed at the same time, defecation occurs.
 The pelvic parasympathetic nerves carry nerve fibers that send impulses
for the contractions of the sigmoid and rectum, for the process of
defecation.
 The effects associated with defecation, which force the fecal contents
downward, are – closure of the glottis, and contraction of the abdominal
wall muscles.
orthocolic reflex

—
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 Section 3

Secretions in digestive tract

Learning objectives:

- To learn the compositions of various digestive juices

- To learn regulation of secretions in the digestive tract
- To correlate the disorders associated with various secretions in gut

SECRETIONS OF THE G.I.TRACT

Salivary secretion:

- Saliva is the fluid secreted into the oral cavity.

- The principal glands of salivation: the parotid, submandibular, and
sublingual glands. In addition, there are many small buccal glands.
 Formation and composition of saliva:
- Daily secretion: 800-1500mL/day; 99.5% is water, rest is solids.
- pH of resting salivary secretions is around 6.0.
- Saliva is hypotonic to plasma. (Water relatively greater in proportion
to solutes.)

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 [Figure: The primary salivary secretion is rich in Na+ & water. As it flows through the
salivary duct, “ductular modification” causes Na + to be reabsorbed and K+ to be secreted.
However, Na+ reabsorption is excess over K+ secretion; and the duct is impermeable to
water. Hence, the final secretion, with less of Na+ and relatively more water, is hypotonic.
HCO3- is present in the primary secretion as well. Increased rate of secretion will therefore
increase the pH of saliva correspondingly.]

 Saliva is secreted from the blood into the acinus of the salivary gland.
Primary salivary secretion is isotonic to plasma; it is rich in Na +. However, as
it flows through the ducts, it gets modified. Na + and Cl- are reabsorbed, and
K+ and HCO3- are added by the ducts. The final saliva reaching mouth is
hypotonic since Na+ was removed from it but water is not reabsorbed
(ducts are impermeable to water). It is rich in K+ and HCO3-, and has low
Na+ and Cl-.
 If the salivary flow is rapid, there is less time for ductular modification.
Then, it will be rich in Na+ and Cl-; and K+ and HCO3- will be low.
 Enzymes in saliva:
(i) Ptyalin (an -amylase) – for carbohydrate digestion; inactivated in
stomach (acidic pH);

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 (ii) Lingual lipase – can digest up to 30% of dietary triglycerides; active
in stomach.
 Saliva also contains:
- lysozyme (proteolytic enzyme that attacks bacteria),
- thiocyanate ions (which can kill bacteria in the presence of
lysozyme),
- mucin (lubricating material; makes the food slippery)
- antibodies (immunoglobulins; they can destroy oral bacteria)
- blood group antigens (in some people, called “secretors”, blood
group antigens are secreted in the saliva)
- kallikrein (an enzyme that acts on the globulins of local interstitial
fluid to produce ‘bradykinin’ which is a powerful vasodilator)
 Functions of saliva:
1. Digestive function –
(a) Carbohydrate digestion:
The -amylase (ptyalin) present in the saliva initiates starch digestion
in the mouth. Big polysaccharide molecules are broken down into
maltose and triose.
[Note: As the food mixed with saliva is swallowed and enters
stomach, the starch digestion stops. Stomach pH is acidic (around 2
to 3); at this pH the amylase enzyme cannot remain active.]
(b) Fat digestion:
The lingual lipase present in saliva initiates digestion of triglycerides
(TGs) in the ingested food. [Lingual lipase continues to act in the
stomach pH.]
2. Lubrication –
Mucin in the saliva helps in the lubrication of the ingested foodstuffs.
This facilitates the swallowing of food.
3. Helps in speech –
Saliva lubricates oral cavity. This facilitates articulation of organs of
mouth (tongue, lips, and palate) involved in speech. Speaking becomes
easier.
4. Appreciation of taste –

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 Saliva acts as a solvent for many substances. When such substances
dissolve in mouth and come in contact with the ‘taste buds’ (of tongue),
it produces the sensation of taste.
5. Defense mechanisms/oral hygiene –
- Flow of saliva helps to wash out bacteria of mouth.
- Lysozyme, thiocyanate ions, and IgA antibodies (immunoglobulins)
present in saliva can attack and kill bacteria that cause dental caries.
6. Regulation of water content/osmolarity of the body fluids – (an
indirect function)
When body water content is decreased (or plasma becomes hypertonic),
saliva dries up. Water loss via saliva is minimized. In addition to the
stimulation of the thirst center, it is an indication to drink fluids; the
water content will normalize.
7. Temperature regulation – (not important in humans)
(In some animals) a mechanism of “panting” helps reduce body
temperature when it is increased. Heavy breathing by a dog causes
evaporation of saliva from the tongue, reducing the temperature in the
oral region. Then, heat from the other parts of the body is carried via
blood to the oral region and lost from there, thus reducing body
temperature.
 Regulation of salivary secretion:
[All other digestive tract secretions are regulated by neural and hormonal
mechanisms. Salivary secretion is regulated only by neural mechanism.]
o Salivary secretion is regulated by parasympathetic and sympathetic
nervous systems.
o Saliva production is unique in that it is increased by both
parasympathetic and sympathetic activity. {Generally, these two
systems have opposite effects on the effector organs.} However,
parasympathetic regulation is more important.
o Parasympathetic stimulation (impulses carried by VII & IX cranial
nerves) – increases salivary secretion by increasing transport
processes in the acinar cells of the salivary glands and cells lining

27
 their ducts. Acetyl choline is the transmitter released by the
parasympathetic nerves.
o Parasympathetic nerve signals arise from the superior and inferior
salivatory nuclei in the brain stem. They are stimulated by taste
stimuli from tongue, especially the sour taste. Smell and sight of food
also stimulate nerve signals.
o Parasympathetic nerve signals increase salivary secretion by another
(indirect) mechanism. These signals cause vasodilatation near the
salivary glands. Increased blood flow increases the salivary secretion.
[Partly, the vasodilator effect is due to kallikrein secreted by the
activated salivary cells. It acts as an enzyme that forms bradykinin in
blood. Bradykinin is a strong vasodilator.]
o Fear, dehydration, sleep inhibit parasympathetic signals, and thus
reduce salivary secretion.
o Sympathetic stimulation can also increase salivation, but only to a
lesser extent. Sympathetic nerves arise from the superior cervical
ganglion and reach the salivary glands.
 Salivary reflexes:
Reflex salivary secretion occurs with two types of reflexes ~ (1)
unconditioned reflex, and (2) conditioned reflex.
It was demonstrated by the Russian physiologist Pavlov. Pavlov’s
experiment on dog was aimed to prove the effects of training or
“conditioning”.
Unconditioned reflexes are inborn reflexes. {When the dog was presented
with some food, there was reflex salivation. Or, if a sour or acidic food is
placed on the tongue of a person, there is reflex salivation. This type of
“unconditioned” reflex is present naturally since birth; no training
required.}
Conditioned reflexes are not inborn; they are acquired after training
(“conditioning”). With previous experience of sour or acidic taste, when the
person only sees the same food, there is reflex salivation. This occurs due
to the process of learning or training. {In the dog’s experiment – a bell is
rung first and then food is presented. This is repeated several times. The

28
 dog “learns” that every time the bell is rung, food is served. Then, reflex
salivation occurs only on ringing of bell.}

~ Applied physiology –

 Sialorrhea: excessive salivation; it may occur in a variety of disorders, e.g.

Parkinsonism, irritation of esophagus due to Ca-esophagus, etc.
 Sialolith: thick salivary secretion may dry up in the ducts; forming a stony
plug in the ducts or the acini of the salivary glands.

Gastric juice:

Gastric juice has acidic pH. Enzyme present in the gastric juice can be active at
acidic pH only.

- Daily volume: 1500 mL.

- pH: 1.0 to 3.5
- 99.5% is water; 0.5% solids (inorganic & organic constituents)
Major constituents are mentioned below:

 The stomach consists of 2 types of glands – (1) gastric glands, and (2)
pyloric glands.
1. The gastric glands has the following cell types (with their secretions
mentioned:
a. Mucus secreting cells – mucus
b. Parietal/oxyntic cells – (i) HCl, (ii) intrinsic factor of Castle
c. Peptic/chief cells – pepsinogen
2. The pyloric gland has following cell types (and secretions):
a. Mucous cells – mucus
b. “G” cells – gastrin

29
 c. Enterochromaffin-like (ECL) cells – histamine
3. Gastric juice also contains these enzymes – rennin, gastric lipase.

 Functions of the gastric juice:

1. Solubilize the foodstuffs:
The ingested food enters the stomach, mixed with the gastric juice and
its solidity is reduced. Eventually the stomach contractions and gastric
juice action convert the food into a semisolid paste called “chyme”.
This action helps in further digestion in the small intestine and
absorption of nutrients from it.
2. Protective function:
HCl acts as an antiseptic. It can kill bacteria (if bacteria are ingested with
food).
3. Optimum pH:
HCl present in the gastric juice provides the optimum pH for the action
of the enzyme pepsin. Pepsin can act only at the acidic pH (around 2.0).
4. Protection against autodigestion of stomach:
 Mucous neck cells secrete mucus. A thick layer of mucus spreads
over the stomach wall. It creates a physical barrier and protects
the stomach wall from the action of HCl. (HCl secreted by the
stomach may attack and destroy the stomach wall itself. This
possible “autodigestion” is prevented by mucus layer.)
 HCO3- is secreted by the surface epithelial cells of the stomach.
These bicarbonate ions present in the mucus layer strengthen the
mucus barrier further. Bicarbonate neutralizes the acidity.
 Small amounts of prostaglandins (PGs) are also secreted in the
mucus layer. These PGs have “cytoprotective action”; they
prevent the possible damage to the gastric cells by the acidic
juice.
5. Activation of the enzyme pepsin:
HCl is necessary for the conversion of pepsinogen to pepsin. {Pepsin is
the proteolytic enzyme in the gastric juice. It is secreted as a precursor –
pepsinogen. It is then converted into the active form – pepsin.

30
6. Protein digestion:
 Pepsinogen is a precursor; it is secreted by the peptic or chief cells of
the stomach. PEPSINOGEN → PEPSIN. Pepsin then initiates digestion
of proteins in the ingested food.
 Pepsin digests proteins up to the stage of peptones.
Importance: These partially digested proteins, when they enter the
small intestine, provoke the secretions of further G.I. hormones.
 Of the total protein digestion, 10-20% occurs in the stomach by the
action of pepsin.
 The unique action of pepsin is digestion of meat collagen (or meat
protein).
7. Coagulation of milk protein: (not important in humans)
Rennin is an enzyme generally present in infants and children. It
coagulates caseinogen of milk.
8. Fat digestion: (not important)
Gastric lipase present in the gastric juice is a tributyrase. It digests
butterfat.
9. Absorption of vit. B12:
Intrinsic factor (I.F.) of Castle, secreted by the parietal cells, combines
with vitamin B12 ingested in the diet. This combination is necessary for
the absorption of B12. Vitamin B12 is absorbed from the ileum (terminal
small intestine).
{Vit. B12 is necessary for the erythropoiesis. It forms an intermediate
which is essential for the nuclear DNA synthesis in RBC precursors.
Deficiency of I.F. will cause deficiency of B 12. This will lead to deficient
nucleus formation in the RBC precursors. Cell division will be hampered.
RBCs released into the circulation will be large and immature –
“megaloblasts”; and the resultant condition is ‘megaloblastic anemia’.}
10. Excretory function:
Toxins, heavy metals, and certain alkaloids (e.g. morphine) are excreted
through the gastric juice.

31
Mechanism of HCl secretion:

- HCl is secreted by the parietal cell located in the stomach wall. Parietal cell
shows a canaliculus where H+ ions are secreted actively.

[Figure: It shows the secretion of HCl by a parietal cell. The transporters shown in the figure ~
Cl-/HCO3- exchanger and H+/K+- ATPase or proton pump. Refer to text for details.]

- CO2 from blood enters the parietal cell. There, it combines with water to
form H2CO3. {CO2 + H2O → H2CO3.} This reaction is catalyzed by the enzyme
carbonic anhydrase. H2CO3 then splits into H+ and HCO3-.
- H+ is then secreted into the parietal cell canaliculus by an active transporter
(ATPase) or pump. The H+-K+-ATPase is the active transporter(also called
“proton pump”) which actively secretes the H+ ions against their
concentration gradient.

32
- HCO3- is transported into blood and Cl- from blood is transported from
blood into the parietal cell by a transporter called chloride-bicarbonate
exchanger (Cl-/HCO 3- exchanger).
- Chloride ions diffuse from the parietal cell into the lumen of the stomach,
combine with the H+ ions and form HCl.
[Also note: H+ is pumped against a concentration gradient that is about 1
million-fold: pH 7 in the parietal cell cytosol to about pH 1 in the lumen of
gastric gland.
As H+ is secreted in the lumen of stomach, HCO 3- (alkali) is added to blood.
This bicarbonate will be excreted in urine (“alkaline tide”).]

 Regulation of gastric secretion:

[Gastric juice secretion is stimulated by two systems - Neural and hormonal
(or chemical). Neural – vagus nerve; chemical – histamine and gastrin.]
Stimulators of the secretion -
1. Vagus nerve: (neural regulation)
- Stimulation of the vagus nerve causes release of the transmitter
acetyl choline (Ach). Ach acts via muscarinic receptors on the
parietal cell to increase gastric secretion.
2. Histamine: (paracrine regulation)
- Enterochromaffin-like [ECL] cells are located within the stomach
wall. These cells secrete histamine. Histamine then reaches the
parietal cells. Acting via the H2-receptors it stimulates gastric acid
secretion.
3. Gastrin: (endocrine regulation)
- G-cells are located at the pylorus of the stomach. These cells secrete
the hormone gastrin.
- Gastrin is carried via blood stream to the parietal cells. It stimulates
the gastric secretion.
 Note: Histamine is the most important stimulus for the gastric acid
secretion. The other two regulators (gastrin & vagus) stimulate gastric acid
secretion independently to a lesser extent. These two additionally also

33
 stimulate histamine action on the parietal cell, to increase gastric secretion.
Thus, histamine plays a pivotal role in regulation of gastric acid secretion.

Inhibition of the gastric secretion –

Negative feedback mechanisms inhibit the H+ secretion by parietal cells.

 When antral pH falls below 3.0, further gastric secretion will be inhibited
by inhibition of gastrin release. {Reason - When food is mixed with
gastric juice, pH of the gastric contents should increase. If the chyme
leaving the stomach and entering duodenum is too acidic (too low pH),
the pancreatic enzymes coming in duodenum will be ineffective. Hence,
further gastric H+ secretion is inhibited if the antral pH falls below 3.0.}
 Somatostatin – It is a hormone secreted by the -cells of pancreas. It
acts directly on the parietal cells, to reduce gastric acid secretion. It also
acts indirectly – by inhibiting histamine & gastrin release.
 Gastric acid secretion is also inhibited by CCK, secretin, VIP, GIP. PGE 2
inhibits secretion by blocking histamine action.

o Phases of gastric acid secretion: (as per the location of food)

[There is a basal acid secretion; it occurs during the interdigestive or fasting
period. It is about 10% of the total stimulated acid secretion.]
1. Cephalic phase: (“cephal”= head. Food stimulus in head; that is,
thought, sight and smell of food – initiate secretion in stomach)
 Initiated by thought, sight, smell of food
 About 20% of the total acid secretion
 Mediated by vagus.
2. Gastric phase: (food in stomach)
 Once the food is eaten and it reaches stomach, gastric juice
secretion occurs.
 Initiated partly by gastric distension and partly by protein
breakdown products
 70% of the total acid secretion

34
  Mediated partly by vagus and partly by gastrin.
3. Intestinal phase: (food in small intestine)
 When food proceeds from stomach to intestine, still some
secretion of gastric juice occurs in stomach.
 Initiated by protein breakdown products and distension of
duodenum
 10% of the total acid secretion
 Mediated by gastrin and entero-oxyntin (postulated); inhibited by
peptide YY, neurotensin.

~ Applied Physiology –

1. Peptic ulcer disease:

- Ulcer is breach (break) in the continuity of an epithelium. When it
occurs in the stomach or duodenum, it is called peptic ulcer.
- Peptic ulcer may occur due to an imbalance between the aggressive
factors (HCl, pepsin, etc.) and defensive factors (mucus, HCO3-, PGs).
- There may be hyperacidity; and the acid breaks the mucus barrier
and causes injury to the stomach mucosa.
- Some factors responsible for hyperacidity and peptic ulceration are
“hurry, worry, and curry”.
- Non-steroidal anti-inflammatory drugs (NSAIDs; e.g. aspirin) are
particulatly known as ‘ulcerogenic’ drugs. They increase the acid
secretion and also break the mucosal defense.
2. Zollinger-Ellison syndrome:
- Gastrinoma, or a gastrin-secreting tumor of the pancreas may lead
to excessive gastrin release. This results in hyperacidity and peptic
ulceration.
3. Drug treatment for peptic ulcer disease:
- Antacids: To neutralize the already formed acid
- Suppressors of gastric acid secretion: (1) H2-receptor blockers – E.g.
cimetidine, ranitidine. (2) Proton pump inhibitors: e.g., omeprazole

35
 Pancreatic juice:

(Exocrine pancreas)

Pancreas is a mixed gland. (98% exocrine; 2% endocrine)

It has endocrine secretions – insulin, glucagon, somatostatin hormones.

The exocrine part of the pancreas is discussed here.

The exocrine pancreas secretes a juice in the second part of duodenum. It

contains enzymes for digestion of most of the types of nutrients in the food.

 Composition of pancreatic juice:

- Volume: 1500 mL/day.
- pH: (alkaline) 8-8.3
- It is isotonic to plasma.
-

- 98% water; 2% solids

Two major constituents of pancreatic juice are:
(a) Enzymes and (b) inorganic substances (ions)
a. Enzymes:
 Protein-digesting enzymes –
- Trypsinogen
- Chymotrypsinogen
- Procarboxypeptidase
- Proelastase
- Nuclease & ribonuclease
 Fat-digesting enzymes –
- Lipase
- Colipase
- Phospholiase A & B
 Carbohydrate-digesting enzyme –
- Amylase
b. Inorganic constituents:

36
  Most important is the HCO3-. It makes the pH of the juice
- -
--

alkaline
-
which is necessary for the action of pancreatic
enzymes.
>

 Cations – Na+, K+, Ca++, and others

 Anions – bicarbonate, chloride, and others
 Following points should be noted –
 Two types of pancreatic juice secretion occur, according to the need
(and stimulus).
- Bicarbonate-rich pancreatic secretion: When large amount of
acidic chyme enters duodenum, the acid needs to be
neutralized and the duodenal environment should be made
alkaline. Reason: Pancreatic enzymes can function in alkaline
pH only. Hence, when acidic contents of stomach enter
duodenum, a bicarbonate-rich pancreatic juice is secreted.
(low on enzymes; high on alkali/bicarbonate)
- Enzyme-rich pancreatic secretion: When nutrients of the
ingested food enter duodenum, digestion of these nutrients
needs to be initiated. Hence, enzyme-rich pancreatic juice will
be secreted in the duodenum.
 If the enzymes secreted by pancreas (particularly the proteolytic
enzymes) are in active form within the pancreas, they may digest
the pancreas itself – “autodigestion of pancreas”. To prevent this,
when enzymes are secreted by the pancreatic acini, they are in
inactive (precursor) forms. They enter the pancreatic duct, reach
duodenum and then are activated in the lumen of duodenum.
 First enzyme to be activated is the trypsin. It is secreted as
trypsinogen by pancreas. On reaching duodenum, it is converted
into trypsin (active form) by the enzyme enterokinase. Enterokinase
is an enzyme secreted by the duodenal lining cells.
 Trypsin then activates the other proteolytic enzymes in duodenum.

37
 Trypsinogen Enterokinase Trypsin

chymotrypsinogen chymotrypsin

 Once trypsin is formed, it acts on chymotrypsinogen to form

chymotrypsin. Trypsin also converts procarboxypeptidase into
carboxypeptidase. The action of proteolytic enzymes is inhibited by
“trypsin inhibitor” in the pancreatic juice.

~ Functions of pancreatic juice:

1. Neutralization of acidic contents coming from stomach:

Bicarbonate ions present in pancreatic juice neutralize the acidic contents
reaching duodenum. This action is necessary since enzymes in pancreatic
juice cannot be active in acidic pH.
2. Digestion of proteins:
Proteolytic enzymes (trypsin, chymotrypsin) of the pancreatic juice are
“endopeptidases”. (Endopeptidases are the enzymes that digest proteins
by hydrolyzing interior peptide bonds.) They act on proteins/polypeptides
in the diet; digest them up to dipeptide and tripeptide stage.
Carboxypeptidases are exopeptidases, the enzymes that hydrolyze one
amino acid at a time by breaking the terminal peptide bond. They act on

38
 polypeptides and split off terminal amino acids. Free amino acids thus
formed are the end products of protein digestion.
3. Digestion of carbohydrates:
Pancreatic amylase is similar to the salivary amylase, but much more
potent. It acts on boiled as well as unboiled starch (salivary amylase acts on
boiled starch only).
Starches and polysaccharides are hydrolyzed at 1,4-linkages to ultimately
form maltose and -dextrins.
Polysaccharides → disaccharides.
4. Digestion of fats:
The main lipolytic enzyme is pancreatic lipase.
Pancreatic lipase acts on dietary triglycerides (TGs) and forms fatty acids
and monoglycerides.
Colipase in the pancreatic lipase helps the activity of the pancreatic lipase,
by fixing of the lipase with the TG molecule.
Phospholipases hydrolyze the phospholipids into smaller molecules.
 Regulation of pancreatic secretion:
{Neural & hormonal regulation; neural via the vagus (X nerve;
parasympathetic). However, neural regulation is less important. Pancreatic
secretion is mainly regulated by G.I. hormones.}
1. Neural regulation:
Stimulation of vagus nerve increases pancreatic secretion. It is a
parasympathetic nerve, and its action is mediated via the Ach. However,
it is not an important mode of regulation of the pancreatic secretion.
2. Hormonal regulation: (CCK & secretin; Stimulate the secretion)
A. Cholecystokinin (CCK) – (enzyme-rich pancreatic secretion)
 This hormone was previously called cholecystokinin-
pancreozymin (CCK-PZ).
 “I” cells in the duodenal mucosa secrete this hormone. It then,
via bloodstream, reaches the pancreatic acinar cells. It
stimulates pancreatic secretion.
 It should be noted that, CCK secretion is induced by amino
-

"
I acids and fatty acids reaching duodenum. CCK then stimulates

39
 the pancreatic juice which is rich in enzymes. These enzymes
will in turn cause further digestion of the nutrients.
 The other important action of CCK is that it causes gall bladder
contractions and increases bile flow into the duodenum. (chole
= bile, cyst = sac/bladder, kinin = movement/contraction) This
bile then helps in the digestion & absorption of fats.
B. Secretin – (bicarbonate-rich pancreatic secretion)
 “S” cells in the duodenal mucosa secrete the hormone
secretin.
 If chyme released into the duodenum is more acidic, it acts as
a stimulus for the secretin release.
 Secretin reaches the pancreas via blood stream, and stimulates
pancreatic juice secretion which is watery and rich in HCO3-.
Bicarbonate ions then neutralize the acid.
 Secretin action is important because pancreatic enzymes
cannot function in the acidic pH.
{All the actions of secretin are aimed at achieving this one goal
– to maintain alkaline environment in the small intestine.
Secretin inhibits gastric emptying in duodenum and induces
bicarbonate-rich secretion from pancreas.}
 Phases of pancreatic secretion -
(Cephalic, gastric, intestinal. Just like gastric juice; but proportions
differ.)
3 phases of pancreatic secretion:
 Cephalic phase: Sight, smell, taste of food induces this secretion. This
phase is mediated by vagus nerve. (10-15% secretion)
 Gastric phase: This phase begins when the food reaches stomach.
About 10% secretion occurs in this phase. Distension of stomach
elicits vago-vagal reflexes that cause this secretion.
 Intestinal phase: Major secretion in this phase, as the food moves
into the duodenum. (Obviously, because pancreatic juice is meant to
cause digestion of food when it reaches small intestine.)About 75%

40
 secretion of pancreatic juice occurs in this phase. This phase is
hormonally-regulated; that is, by CCK & secretin.

~ Applied physiology:

1. Steatorrhea –
When there is deficiency of the pancreatic enzymes, fat digestion does not
occur. Unabsorbed fats then appear in feces; fecal fat content increases –
“steatorrhea”. More than 10 gms of fat excretion in stools = steatorrhea.
2. Autodigestion of pancreas and pancreatitis –
Pancreatic enzymes may get activated within the pancreas. They cause
autodigestion and damage to the pancreas. Resultant inflammation of the
gland is termed pancreatitis.

Secretions of intestines

Small intestine: {‘succus entericus’}

Secretion of the small intestine is called “succus entericus”. The digestive

enzymes present in it are present intracellularly, within the cells lining small
intestine. With desquamation, the cells are shed off and the enzymes released
into the intestinal lumen.

Composition of succus entericus:

- Quantity: 1-2 L/day

- pH: 6.3 to 9.0
- 98.5% water, 1.5% solids.
- Inorganic constituents: salts of Na+, K+, Ca++
- Enzymes:
(a) For carbohydrate digestion – sucrase, maltase, lactase
(b) For protein digestion – aminopeptidase, and other
peptidases.
(c) For fat digestion – small amounts of intestinal lipase

41
  There are compound mucous glands, called “Brunner’s glands”,
located in the first few centimeters of duodenum. These glands
secrete large amounts of alkaline mucus. The function – This mucus
protects the duodenal wall from digestion by highly acidic gastric
juice.
 Located over the entire surface of small intestine are small pits called
“crypts of Lieberkuhn”. The intestinal villi and these crypts are lined
by – (i) goblet cells, which secrete mucus that lubricates and protects
intestinal surfaces, and (ii) enterocyts – secreting large quantities of
water and electrolytes in the crypts. Intestinal villi then reabsorb this
water & electrolytes, along with end products of digestion.

In the mucous membrane of

Villi the small intestine, there are
finger-like projections called
intestinal villi. Villi are
composed of two types of cells
– goblet cells which secrete
mucus, and enterocytes which
help in absorption. Crypts of
Lieberkuhn are small pits
located in between the
Crypt intestinal villi.

 Functions of succus entericus:

(i) Disaccharidases – (sucrase, maltase, lactase)
Pancreatic enzymes digest the dietary polysaccharides & starches
upto the disaccharide stage (sucrose, maltose, lactose). Then, the

42
 disaccharidases in succus entericus digest them further to form
monosaccharides (so that these monosaccharides can then be
absorbed).

sucrase
Sucrose glucose + fructose
lactase
Lactose glucose + galactose
maltase
Maltose glucose + glucose
(ii) Peptidases –
Once pancreatic peptidases have digested the proteins and
polypeptides in diet, further action of the peptidases in succus
entericus will digest them so as to form tri- and dipeptides and single
amino acids. These can then be absorbed from small intestine.
(iii) Intestinal lipase –
It causes further digestion of fats (after the action of pancreatic
lipases); free fatty acids and glycerol will be formed. These fat
digestion products will then be absorbed.
 Regulation of intestinal secretion:
- Local stimulus: Chyme in the intestine increases the secretion
of small intestine.
- Hormonal regulation: Secretin & CCK increase small intestinal
secretion.

Applied Physiology:

 Lactose intolerance:
- Inability to digest lactose (milk and milk products)
- Occurs due to deficiency of lactase
- After eating milk products, there is gas production, bloating,
and diarrhea.
- Unabsorbed lactose reaches colon; breakdown of lactose by
colonic bacteria results in production of hydrogen gas. This
hydrogen can then be absorbed into blood stream, and then,

43
 upon reaching lungs, will be exhaled out. Thus, a breath test
for hydrogen can be used to diagnose lactose intolerance.

Secretions of large intestine (colon):

{The proximal colon includes ascending colon and first part of transverse colon.
Distal colon includes later part of transverse colon, descending colon, and sigmoid
colon. The proximal colon is also called “absorptive colon”. It has a capacity to
absorb large amount of water (and electrolytes). When un-digested and un-
absorbed fraction of food reaches colon, most of water & electrolytes are
absorbed from the proximal colon. The remaining portion will be the fecal
material to be excreted.

Distal colon is also called “storage colon”. It stores the fecal material temporarily,
until defecation process can be initiated. With the defecation process, fecal
matter will be moved through the sigmoid colon, rectum, and finally the anal
canal.}

 Cells lining colon do not secrete enzymes; digestion and absorption of

nutrients has already occurred in the small intestine (i.e., before reaching
colon).
 The cells secrete mucus which protects the walls of colon.
 K+ is actively secreted in the colon. In diarrhea, K+ secretion by colon is
increased. The resultant loss of potassium in feces may lead to
‘hypokalemia’. (hypokalemia = decreased K+ in blood)
 HCO3- is also secreted into the colon.
{K+ & HCO3- are absorbed from the colon as well as secreted. However,
secretion > absorption. Hence, there is net secretion of K+ and HCO 3- into
the colon.}
 Infection/irritation of a segment of colon → there would be copious
secretion containing water & electrolytes by the colon. The resultant
‘diarrhea’ will cause loss of water and electrolytes from the body.

————————————————————————————————————

44
 Liver

(Although liver performs many functions, two functions are closely related to digestive
Physiology ~ (1) Synthesis of bile that contains bile salts, involved in digestion and
absorption of dietary fats, and (2) Metabolism of all nutrients – Dietary nutrients are
absorbed from digestive tract and are presented to liver; they are further metabolized by
liver and eventually presented to cells for the sake of energy production.)

- It is the largest organ in the body; it receives greatest fraction of cardiac output
(25%-27%). Blood from all over the body comes to liver via hepatic artery
(systemic circulation), and blood from the digestive tract comes to liver via portal
vein (portal circulation). Hepatic lobule is the functional unit of the liver.
- Apart from the hepatic parenchymal cells, there are Kupffer cells in liver. These
are macrophages; they have phagocytic function.

Functions of the liver:

1. Secretion of bile: Bile contains bile acids and bile pigments (bilirubin). Bile acids
are crucial for digestion & absorption of fats (discussed elsewhere). Bilirubin,
excreted into bile, is eventually excreted out of body in the form stercobilin (feces)
and urobilinogen (urine).
2. Metabolism of nutrients:
(i) Carbohydrate metabolism:
Stores glucose in the form of glycogen,
Gluconeogenesis (forms glucose from non-carbohydrate sources)
(ii) Protein metabolism:
Synthesis of plasma proteins
Deamination of amino acids
(iii) Fat metabolism:
Oxidation of fatty acids; synthesis of cholesterol
3. Storage function: Storage of vitamins (particularly, vitamins A, D, and B12),
Storage of iron (in the form of ferritin)
4. Excretory function:
Many drugs and toxins are detoxified or excreted by the liver.
Many hormones are modified and/or excreted by the liver.

45
 Liver and gall bladder: (Bile)

 Bile is secreted by the liver cells. It is first drained into the two hepatic
ducts which join to form ‘common hepatic duct’. This bile is diverted to gall
bladder. Gall bladder stores this bile. When foodstuffs (particularly the fats)
arrive in the duodenum, gall bladder contractions move the stored bile.
This bile travels via the common bile duct to ultimately reach 2nd part of
duodenum. Common bile duct and pancreatic duct join together at their
final portions, to form a single duct that discharges pancreatic juice and bile
into the duodenum.
 Bile formation occurs in 3 steps: (1) Hepatocytes actively secrete bile into
the bile canaliculi; (2) Intrahepatic and extrahepatic bile ducts transport this
bile and also add HCO3--rich fluid to it; and (3) As bile is diverted to gall
bladder for storage, water and electrolytes are removed iso-osmotically
from it by the gall bladder epithelium; the bile is concentrated 5 to 20
times.

 Composition of bile:
- Daily secretion: about 1000 mL.
- Colour: yellowish green
- Reaction: alkaline; pH ~ 7-7.6
- Bile salts: sodium taurocholate & sodium glycocholate
- Bile pigments: bilirubin & biliverdin
- Cholesterol and phospholipids
- Inorganic salts: chlorides, carbonates, and phosphates of Na +,
K+, Ca++.
parameter Liver bile Gall bladder bile
pH 7.5 6.0
Cholesterol (g/liter) 1-3.2 6.3
Phospholipids (g/liter) 1.4-8.1 34

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 Bile acids (g/liter) 3-45 32
++
Ca (mM) 1.2-3.2 15
-
HCO3 (mM) 12-55 19
+
K (mM) 2.7-6.7 14
{Note that: Gall bladder stores, concentrates, and acidifies the bile.}

 Biliary secretion has two principal functions: (1) elimination of many

endogenous and exogenous waste products from the body (e.g. bilirubin,
cholesterol, etc), and (2) help in digestion and absorption of lipids from the
intestine.
 Functions of bile:
1. Digestion of fats –
- Emulsification of fats in the diet:-
- Dietary fats are insoluble in water. They cannot be acted upon
by the enzymes in the watery pancreatic juice. Bile salts
produce a detergent-like action on the fats. They reduce the
surface tension; fats are converted to emulsion. This aids the
action of enzymes in the aqueous pancreatic juice.
- Fats are chopped down to smaller droplets. This increases the
surface area on which the pancreatic lipase can act.
- Bile salts have a solvent action; fats are made more soluble.
2. Absorption of fats – (“micelle formation”)
- Bile salt molecules are amphipathic ; they have both
hydrophilic & hydrophobic portions. {see the diagram given
below.}
- Some 20-40 bile salt molecules come together to form a
micelle.
- Bile salt molecules are oriented on the outside of the micelle.
They are oriented with their hydrophilic (water soluble)
portions facing outward, and their hydrophobic (lipid soluble)
portions facing inward.

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 - The fat digestion products accumulate at the central portion of
a micelle (where fat soluble portions of bile salt molecules are
oriented).
- Since water soluble portions are facing outward, they are
dissolved in the watery (aqueous) solution of the intestinal
lumen. Thus, a micelle moves through the aqueous solution of
the intestinal lumen and takes the fat digestion products away
from the site of their digestion to the site of absorption. These
products will be delivered to their absorption site and then
micelle returns to the site of digestion. It again collects some
more fat digestion products and moves them toward their site
of absorption. This is called “ferrying function” of the bile salt
micelle.

Bile salt molecule

micelle
hydrophilic

Fat digestion hydrophobic

products

3. Absorption of fat soluble vitamins (A, D, E, and K) is also facilitated by

the bile salts.
4. Excretion –

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 Metals, toxins, bile pigments, and cholesterol are excreted through bile.
5. Laxative action –
The bile salts act as a mild laxative. They stimulate peristalsis of
intestines.
6. Choleretic action –
The bile secreted by liver reaches the duodenum; a fraction of the bile
salts is absorbed from ileum. It reaches back to liver and causes
secretion of more bile. This is called the ‘choleretic action’ of bile salts.
{The substances that increase bile secretion by liver cells are called
choleretics.}
7. Suitable pH –
The bile helps to maintain a suitable pH in duodenum.

Enterohepatic circulation of bile:

Bile secreted by liver flows into the duodenum. Bile salts reach ileum and
are absorbed from terminal ileum. The bile salts which are absorbed from
ileum, via portal circulation, again reach the liver. They are again secreted
into the bile.
90-95% bile salts are absorbed and re-cycled in this manner.
It occurs 6-8 times per day (or twice in response to each meal).
5-10% enter colon every time, and are eventually excreted.
 Cholagogues: Substances that increase bile flow by causing gall bladder
contraction. E.g. CCK
 Choleretics: Substances that Increase bile flow from hepatocytes and from
the ducts. E.g. bile salts, also vagus & secretin. {Secretin stimulates a
bicarbonate-rich fluid secretion from the epithelial cells of the bile ducts.}

Gall bladder (functions)-

It is sac present underneath the liver. The capacity of the gall bladder is about 50
mL.

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Bile synthesized by liver is flown to gall bladder where it is stored. When fats in
the diet reach duodenum, gall bladder contractions empty the bile into the
duodenum where it aids in digestion and absorption of fats.

Gall bladder emptying is stimulated by the hormone CCK.

1. Storage of bile:
Until it is required for digestion of fats, bile is stored in gall bladder.
2. Concentration of bile:
Gall bladder epithelium absorbs water from the bile. Bile is concentrated up
to 5 times (compared to the bile that was secreted by liver.)

Applied Physiology:

 Gall stones:
- Cholesterol in bile is kept solubilized by bile salts and lecithin.
If cholesterol concentration in bile increases to a level that it
can not be kept solubilized, there is ‘cholesterol
supersaturation’ in bile. There is formation of cholesterol
crystals, which become gall stones. 90% of gall stones are of
this type.
- 10% of gall stones are calcium bilirubinate stones.

————————————————————————————————————

50
 Section 4

Regulatory hormones/peptides related to gut

Learning objectives:

- Although the primary function of digestive tract is to digest

and absorb nutrients, it also has ENDOCRINE function. This
section deals with the regulatory factors secreted by gut.

 Hormones and peptides regulating the G.I. functions:

HORMONE SECRETED BY PRIMARY MAIN ACTIONS

or PEPTIDE STIMULUS
STOMACH
Histamine Enterochromaffin- Gastrin (Paracrine action)
like (ECL) cell acts via H2-receptor
(stomach) on parietal cell to
increase gastric acid
secretion
Gastrin G cell (pylorus) Protein in Gastric acid
stomach secretion
Somatostatin D cell (pylorus, 1st Pyloric pH < 2.0 Inhibits gastric acid
part of secretion
duodenum)
INTESTINE
Secretin S cells Acidic chyme in ↓ gastric emptying,
(duodenum) duodenum ↑ HCO3--rich
pancreatic juice
secretion
CCK I cells Fat in duodenum ↑ enzyme-rich
(duodenum) pancreatic juice
secretion, ↑ gall

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 bladder contraction,
↓ gastric emptying
G.I.P. Duodenal mucosa CHO, proteins, ↓ gastric motility
fats entering and secretion
duodenum
Bombesin Vagal endings on CCK (via activation Release of gastrin
(G.R.P.) G cells of pylorus of vago-vagal (for HCl secretion)
reflex)
Neurotensin Ileal mucosa Fatty acids ↓ G.I. motility, ↓
acid secretion, ↑
ileal blood flow
Peptide YY Ileal mucosa Fat ↓ meal-stimulated
acid secretion, ↓
gastric motility
V.I.P. Nerves in G.I.T. ↑ intestinal
(Vasoactive secretion of
Intestinal electrolytes &
Polypeptide) water, relaxation of
intestinal smooth
muscle
Motilin EC cells and Mo Secreted in inter- ↑ G.I. motility
cells in stomach, digestive period between meals
intestine & colon
{CCK = Cholecystokinin; G.I.P. = Gastric Inhibitory peptide; G.R.P. = Gastrin
Releasing Peptide.}

Video link ~ GIP , an INCRETIN

Video link ~ Central theme of secretin & CCK

 Secretin was the first hormone to be discovered.

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  Secretin decreases gastric emptying by causing contraction of pyloric
sphincter; CCK delays gastric emptying by decreasing the gastric motility.
 Gastric Inhibitory Peptide (G.I.P.): Role of this hormone in inhibiting the
gastric motility and secretion is not considered physiological. Instead, it
is now called “Glucose-dependent Insulinotropic Polypeptide” (G.I.P.). It
stimulates insulin secretion in response to oral glucose ingestion. Due to
this, insulin secretion in response to oral glucose is greater compared to
I.V. glucose.

 Human analogue of bombesin is “Gastrin Releasing Peptide” (G.R.P.)

Video link ~ Vagal ending on G-cell, do not release Ach; it releases BOMBESIN

 Some other hormones:

1. Ghrelin:
- Secreted by stomach
- Secretion decreased by feeding and increased by fasting
- It is involved in control of food intake and GH secretion
2. Guanylin:
- Binds to guanylyl cyclase; increases intracellular cGMP
- This causes increased activity of cystic fibrosis-regulated Cl-
channel;
- increases secretion of chloride ions into intestinal lumen

Video link ~ Somatostatin: Multiple places of release; variety of actions. A pro-insulin as well
as anti-insulin hormone

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 Section 5

Digestion and absorption of nutrients

Learning objectives:

- The ultimate goal of the GI tract is to break the consumed

foodstuffs down into smaller, simpler forms; those basic units
then are absorbed into blood and are eventually presented to
cells for the sake of energy production.

 Carbohydrate digestion & absorption:

- Initiated by salivary -amylase, acting on starches and
polysaccharides, to form oligosaccharides.
- Further digestion by pancreatic amylase, converts the
oligosaccharides upto disaccharide stage.
- The disaccharides ingested and formed from polysaccharide
digestion are acted upon by brush border (small intestine)
↑
disaccharidases – sucrase, lactase, and maltase. They will be
converted into monosaccharides. A key principle is – Intestine
can absorb only monosaccharides and not larger
carbohydrates.
- Colonic bacteria can break down some of the oligosaccharides.

Absorption of monosaccharides: Glucose and other

monosaccharides are absorbed by secondary active transport (co-
transport) with Na+. The transporter in the small intestinal wall is
SGLT 1 (sodium-glucose transporter) transports 2 Na+: 1 glucose.
Fructose absorption occurs by facilitated diffusion – the carrier
protein is GLUT 5 (glucose transporter).

Absorption of the carbohydrate digestion products occurs from

upper small intestine (mainly jejunum).

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Video link ~ Glucose absorption; transporters involved. Glucose-galactose malabsorption

 Protein digestion & absorption:

- Protein digestion is initiated by pepsin in stomach; 10-20%
of the total digestion occurs by pepsin action.
- Pancreatic proteases: trypsin, chymotrypsin, elastase are
endopeptidases (act at interior peptide bonds in the
proteins). The carboxypeptidases of pancreas are
exopeptidases.
- Brush border of small intestine secretes proteases:
aminopeptidase (an exopeptidase) & carboxypeptidase;
and dipeptidases. They cause further digestion of proteins
to form single amino acids, di- and tripeptides.
- Amino acids are absorbed from duodenum and jejunum by
Na+ co-transport (an example of secondary active
transport).
- Approx. 50% of the digested protein comes from ingested
food, 25% from proteins in digestive juices, and 25% from
desquamated mucosal cells.

 Fat digestion & absorption:

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 Video link ~ Why fat digestion & absorption is a complex process, different from other
nutrients?

- Lingual lipase can digest as much as 30% of dietary TGs.

However, most fat digestion begins in duodenum.
- Pancreatic lipase is the most important enzyme for
digestion of dietary lipids. Colipase facilitates activity of
lipase. Bile salts may inactivate the pancreatic lipase; this is
prevented by colipase.
- Bile salts, lecithin, and monoglycerides have detergent
action; it will cause emulsification of fats. This then
facilitates the action of pancreatic lipase on fats.
- Bile salt aggregates called micelles remove the fat digestion
products from the site of digestion. If they are not moved
away, further fat digestion will be blocked.
- Fatty acids containing less than 10-12 carbon atoms are
absorbed directly into portal venous blood.
- Fatty acids containing more than 10-12 carbon atoms are
re-synthesized into TGs as they enter mucosal cells. They
are then absorbed in the lymphatics, in the form of
chylomicrons. Thus TGs are transported to liver and
adipose tissue within the chylomicrons.

 Other nutrients and water:

- Highest fraction of water absorption occurs in jejunum
(5500 ml/day); colon absorbs 1300 ml/day.
- Net rate of Na+ absorption is highest in jejunum.
- Cl- is absorbed in the jejunum, ileum, and colon. HCO 3- is
absorbed in jejunum; secreted in duodenum, ileum, and
colon.

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 - Net absorption of K+ occurs in jejunum and ileum. In colon,
it may be secreted or absorbed. Normally, in the colon, net
secretion of K+ occurs.
- Ca++ is absorbed from all segments of the small intestine;
predominantly from the proximal small intestine.
- Mg++ is absorbed from all segments of the small intestine;
greatest fraction is absorbed from ileum.
- Phosphate is absorbed all along the small intestine. Highest
capacity for absorption (per cm of length of G.I. tract) is in
duodenum. However, due to transit time and length,
largest portion is absorbed from jejunum.
- Fat-soluble vitamins are absorbed in the lymphatics of
upper small intestine. Vitamin B12 is absorbed in terminal
ileum. Apart from B12 and folic acid, all other water soluble
vitamins are absorbed as Na+ co-transport.
- Iron (Fe++) is absorbed from duodenum.

 Colonic microflora: (its contribution in nutrition)

- There are commensals (“friendly microbes”) in intestine and colon. This
gut microflora is important for the overall health of an individual.
- The friendly micro-organisms in gut prevent invasion by pathogenic
microbes. When a person is taking antibiotics (e.g., ampicillin), this
ecosystem is disrupted, resulting in antibiotic-induced diarrhea.
- Role in nutrition:-
1. Complex carbohydrates often remain undigested. As they reach
colon, they are salvaged by the colonic microflora; i.e., they are
converted into short chain fatty acids (SCFAs), which are then
absorbed and used for energy metabolism.
2. Vitamin B12, folic acid, vitamin K are some other nutrients that can
be synthesized by the colonic microflora.

57