Secretory Functions of the Alimentary Tract pdf - GIT

The

Effect of Contact of Food with the Epithelium—Function of Enteric Nervous Stimuli.

Tract Glands

Basic Mechanisms of Stimulation of the Alimentary

finally empty into the alimentary tract itself.

lined with secreting glandular cells; these acini feed into a system of ducts that

tract and, in this, differ from all other alimentary glands. They contain millions of

the type shown in Figure 64–2. These glands lie outside the walls of the alimentary

Chapter 70. The salivary glands and the pancreas are compound acinous glands of

sification of food. The liver has a highly specialized structure that is discussed in

salivary glands, pancreas,

Fourth, also associated with the alimentary tract are several complex glands—the

A typical tubular gland can be seen in Figure 64–4, which shows an acid- and

glands.

Third, in the stomach and upper duodenum are large numbers of deep

cells. One of these cells is shown in Figure 64–1.

, are deep and contain specialized secretory

these pits, called

resent invaginations of the epithelium into the submucosa. In the small intestine,

Second, many surface areas of the gastrointestinal tract are lined by

tation of the epithelium: they extrude

because they look like goblets. They function mainly in response to local irri-

First, on the surface of the epithelium in most parts of the gastrointestinal tract are

Several types of glands provide the different types of alimentary tract secretions.

Anatomical Types of Glands

Tract Secretion

General Principles of Alimentary

fore, is to describe the different alimentary secretions, their functions, and reg-

accordance with the types of food present. The purpose of this chapter, there-

proper digestion. Furthermore, in some portions of the gastrointestinal tract,

response to the presence of food in the alimentary tract, and the quantity

to the anus, provide

the ileum. Second, mucous glands, from the mouth

mentary tract, from the mouth to the distal end of

glands subserve two primary functions: First,

Throughout the gastrointestinal tract, secretory

Alimentary Tract

791

Secretory Functions of the

diges-

tive enzymes are secreted in most areas of the ali-

mucus for lubrication and pro-

tection of all parts of the alimentary tract.

Most digestive secretions are formed only in

secreted in each segment of the tract is almost exactly the amount needed for

even the types of enzymes and other constituents of the secretions are varied in

ulation of their production.

billions of single-cell mucous glands called simply mucous cells or sometimes goblet
cells

mucus directly onto the epithelial surface to

act as a lubricant that also protects the surfaces from excoriation and digestion.

pits that rep-

crypts of Lieberkühn

tubular

pepsinogen-secreting gland of the stomach (oxyntic gland).

and liver—that provide secretions for digestion or emul-

acini

mechanical presence of food in a particular segment of the gastrointestinal tract
usually causes the glands of that region and often of adjacent regions to secrete

substrates provided by the nutrients, is then used

3. Energy from the ATP, along with appropriate

adenosine triphosphate (ATP).

mitochondria

2. Many

1. The nutrient material needed for formation of

following principles of secretion, as shown in Figure

are not known, experimental evidence points to the

Basic Mechanism of Secretion

polypeptides or polypeptide derivatives.

Chemically, the gastrointestinal hormones are

where they stimulate secretion. This type of stimula-

absorbed into the blood and carried to the glands,

food in the lumen of the gut. The hormones then are

the secretions. These hormones are liberated from the

stomach and intestine, several different

constrictive reduction of the blood supply.

sometimes significantly so, mainly because of vaso-

causing copious secretion by the glands, superimposed

usually slightly increases secretion. But, second, if

have a dual effect: First, sympathetic stimulation alone

the glands. Therefore, sympathetic stimulation can

of the local glands. But sympathetic stimulation also

pathetic nerves. Secretion in the remainder of the

of the large intestine, innervated by pelvic parasym-

num. It is also true of some glands in the distal portion

glands, pancreas, and Brunner’s glands in the duode-

such as the salivary glands, esophageal glands, gastric

sopharyngeal and vagus parasympathetic nerves)

secretion. This is especially true of the glands in the

wall. The resulting nervous reflexes stimulate both the

(2) chemical irritation, and (3) distention of the gut

of the gut wall. The

In addition, local epithelial stimulation also acti-

cells, results from direct contact stimulation of the

effect, especially the secretion of mucus by mucous

moderate to large quantities of juices. Part of this local

792

Unit XII

Gastrointestinal Physiology

surface glandular cells by the food.

vates the enteric nervous system
types of stimuli that do this are (1) tactile stimulation,

mucous cells on the gut epithelial surface and the deep
glands in the gut wall to increase their secretion.

Autonomic Stimulation of Secretion

Parasympathetic Stimulation.

Stimulation of the

parasympathetic nerves to the alimentary tract almost
invariably increases the rates of alimentary glandular

upper portion of the tract (innervated by the glos-

small intestine and in the first two thirds of the large
intestine occurs mainly in response to local neural and
hormonal stimuli in each segment of the gut.

Sympathetic Stimulation.

Stimulation of the sympa-

thetic nerves going to the gastrointestinal tract causes
a slight to moderate increase in secretion by some

results in constriction of the blood vessels that supply

parasympathetic or hormonal stimulation is already

sympathetic stimulation usually reduces the secretion,

Regulation of Glandular Secretion by Hormones.

In the

gastrointestinal

hormones help regulate the volume and character of

gastrointestinal mucosa in response to the presence of

tion is particularly valuable to increase the output of
gastric juice and pancreatic juice when food enters the
stomach or duodenum.

by Glandular Cells

Secretion of Organic Substances.

Although all the

basic mechanisms by which glandular cells function

64–1.

the secretion must first diffuse or be actively
transported by the blood in the capillaries into the
base of the glandular cell.

located inside the glandular

cell near its base use oxidative energy to form

to synthesize the organic secretory substances;
this synthesis occurs almost entirely in the
endoplasmic reticulum and Golgi complex of the
glandular cell. Ribosomes adherent to the

Zymogen

granules

Ribosomes

Mitochondria

Nerve

fiber

Basement

membrane

Endoplasmic

reticulum

Golgi

apparatus

Secretion

Capillary

enzymes and other secretory substances.

Typical function of a glandular cell for formation and secretion of

Figure 64–1

Primary secretion:
1. Ptyalin
2. Mucus
3. Extracellular fluid

Saliva

active absorption

passive absorption

active secretion

HCO

secretion

Formation and secretion of saliva by a submandibular salivary

Figure 64–2

gland.

serous type of secretion, while the submandibular and

The parotid glands secrete almost entirely the

cating and for surface protective purposes.

-amylase), which is an enzyme for digesting starches,

the average value of 1000 milliliters in Table 64–1.

ranges between 800 and 1500 milliliters, as shown by

glands. Daily secretion of saliva normally

; in addition, there are many very

The principal

Salivary Glands; Characteristics of Saliva.

Secretion of Saliva

water.

secrete saliva, because then it is difficult to swallow solid

lium. A person becomes acutely aware of the lubricat-

In summary, mucus has the ability to allow easy slip-

cally neutralize acids.

of either acids or alkalies; also, mucus often contains

teins of mucus have amphoteric properties, which

, the glycopro-

the gastrointestinal enzymes. And

, mucus is strongly resistant to digestion by

Fourth

can slide along the epithelium with great ease.

has a low resistance for slippage, so that the particles

, mucus

Third

, it has sufficient

over the surfaces.

trointestinal tract, but everywhere it has several im-

electrolytes, and a mixture of several glycoproteins,

Mucus is a thick secretion composed mainly of water,

Gastrointestinal Tract

Importance of Mucus in the

Properties of Mucus, and

Lubricating and Protective

for nerve impulses to regulate secretion. Hormones

theoretical, it does explain how it would be possible

through the membrane to the interior of the cell, thus

signal has arrived, indicating that it is caused by move-

negative than normal. This increase in polarization

ity on the interior and positivity on the exterior.

the cell is between 30 and 40 millivolts, with negativ-

Second, microelectrode studies show that the normal

dular cells are principally on the bases of the cells.

the following findings: First, the nerve endings on glan-

causing flushing of water, electrolytes, and organic

4. The pressure in the cell then initiates minute

pressure inside the cell, causing the cell itself to

force that causes osmosis of water to the interior,

3. Now, the new excess of both negative and

2. The resulting increase in electronegativity induced

transport of chloride ions to the cell interior.

1. Nerve stimulation has a specific effect on the

through the glandular cells in great profusion, washing

The following is a postulated method by which

electrolytes to go along with the organic substances.

Water and Electrolyte Secretion.

open, thus emptying the vesicles to the exterior;

membrane. Then the apical cell membrane breaks

calcium enters the cell. The

, and

membrane permeability to calcium ions

way: The control signal first

surface. This probably occurs in the following

6. These vesicles remain stored until nervous or

are stored in the apical ends of the secretory cells.

, which

cytoplasm in the form of

added to, concentrated, and discharged into the

5. In the Golgi complex, the materials are modified,

the tubules of the endoplasmic reticulum, passing

4. The secretory materials are transported through

Secretory Functions of the Alimentary Tract

Chapter 64

793

reticulum are specifically responsible for
formation of the proteins that are secreted.

in about 20 minutes all the way to the vesicles of
the Golgi complex.

secretory vesicles

hormonal control signals cause the cells to
extrude the vesicular contents through the cells’

increases the cell

calcium in turn causes

many of the vesicles to fuse with the apical cell

this process is called exocytosis.

A second necessity for

glandular secretion is secretion of sufficient water and

nervous stimulation causes water and salts to pass

the organic substances through the secretory border of
the cells at the same time:

basal portion of the cell membrane to cause active

inside the cell by excess negatively charged
chloride ions then causes positive ions such as
sodium ions also to move through the cell
membrane to the interior of the cell.

positive ions inside the cell creates an osmotic

thereby increasing cell volume and hydrostatic

swell.

openings of the secretory border of the cell,

materials out of the secretory end of the glandular
cell.

In support of these secretory processes have been

electrical potential across the membrane at the base of

Parasympathetic stimulation increases this polariza-
tion voltage to values some 10 and 20 millivolts more

voltage lasts for 1 second or longer after the nerve

ment of negative ions (presumably chloride ions)

leading to secretion.

Although this mechanism for secretion is still partly

acting on the cell membrane are believed also to cause
similar secretory results to those caused by nervous
stimulation.

which themselves are composed of large polysaccha-
rides bound with much smaller quantities of protein.
Mucus is slightly different in different parts of the gas-

portant characteristics that make it both an excellent
lubricant and a protectant for the wall of the gut. First,
mucus has adherent qualities that make it adhere tightly
to the food or other particles and to spread as a thin film

Second

body that

it coats the wall of the gut and prevents actual contact
of most food particles with the mucosa.

mucus causes fecal particles to adhere to one another
to form the feces that are expelled during a bowel move-
ment. Fifth

sixth

means that they are capable of buffering small amounts

moderate quantities of bicarbonate ions which specifi-

page of food along the gastrointestinal tract and to
prevent excoriative or chemical damage to the epithe-

ing qualities of mucus when the salivary glands fail to

food even when it is eaten along with large amounts of

glands of salivation are the parotid, submandibular,
and sublingual glands
small buccal

Saliva contains two major types of protein secretion:

(1) a serous secretion that contains ptyalin (an
a
and (2) mucus secretion that contains mucin for lubri-

sublingual glands secrete both serous secretion and

(e.g., a pebble), cause marked salivation, whereas

the basal rate of secretion. Also, certain tactile stimuli,

stimuli, especially the sour taste (caused by acids),

other areas of the mouth and pharynx. Many taste

The salivatory nuclei are located approximately at

ways for regulating salivation, demonstrating that the

Figure 64–3 shows the parasympathetic nervous path-

erwise infected, and caries of the teeth can become

salivation, oral tissues often become ulcerated and oth-

ing some that cause dental caries. In the absence of

protein antibodies that can destroy oral bacteria, includ-

, saliva often contains significant amounts of

Third

cles, thus helping further to remove the bacterial meta-

in turn become bactericidal, and (c) digest food parti-

cyanate ions in entering the bacteria where these ions

that (a) attack the bacteria, (b) aid the thio-

bacteria. One of these is

, saliva contains several factors that destroy

, the flow of saliva itself helps wash away patho-

in several ways.

caries. Saliva helps prevent the deteriorative processes

oral tissues. The mouth is loaded with pathogenic bac-

sleep, secretion becomes very little. This secretion plays

the mucous type, is secreted each minute; but during

ditions, about 0.5 milliliter of saliva, almost entirely of

rises only to one half or two thirds that of plasma, and

are being secreted, the sodium chloride concentration

reduced. Therefore, when copious quantities of saliva

increase as much as 20-fold. This acinar secretion

, the salivary ionic con-

ions is 50 to 70 mEq/L, about two to three times that

as in plasma; and the concentration of bicarbonate

potassium ions is about 30 mEq/L, seven times as great

trations in plasma. Conversely, the concentration of

L each, about one seventh to one tenth their concen-

, the concentrations of sodium

The net result of these transport processes is that

active secretory process.

chloride ions, but it may also result partly from an

epithelium into the lumen of the duct. This is at least

level, matching the ductal decrease in sodium ion

to be reabsorbed passively. Therefore, the chloride ion

in the salivary ducts; this in turn causes chloride ions

sodium reabsorption over potassium secretion, and

tration becomes increased. However, there is excess

greatly reduced, whereas the potassium ion concen-

secreted in exchange for the sodium. Therefore, the

First,

primary secretion flows through the ducts, two major

from those of typical extracellular fluid. As the

second, the salivary ducts. The acini secrete a

operation: the first stage involves the acini, and the

. Salivary secretion is a two-stage

gland, a typical compound gland that contains

Figure 64–2 shows secretion by the submandibular

plasma. One can understand these special concentra-

Conversely, the concentrations of both sodium and

large quantities of potassium and bicarbonate ions.

has a pH between 6.0 and 7.0, a favorable range for

mucus. The buccal glands secrete only mucus. Saliva

794

Unit XII

Gastrointestinal Physiology

the digestive action of ptyalin.

Secretion of Ions in Saliva.

Saliva contains especially

chloride ions are several times less in saliva than in

tions of ions in the saliva from the following descrip-
tion of the mechanism for secretion of saliva.

acini

and salivary ducts

primary

secretion that contains ptyalin and/or mucin in a solu-
tion of ions in concentrations not greatly different

active transport processes take place that markedly
modify the ionic composition of the fluid in the saliva.

sodium ions are actively reabsorbed from all

the salivary ducts and potassium ions are actively

sodium ion concentration of the saliva becomes

this creates electrical negativity of about

-70 millivolts

concentration in the salivary fluid falls to a very low

concentration.

Second, bicarbonate ions are secreted by the ductal

partly caused by passive exchange of bicarbonate for

under resting conditions
and chloride ions in the saliva are only about 15 mEq/

of plasma.

During maximal salivation

centrations change considerably because the rate of
formation of primary secretion by the acini can

then flows through the ducts so rapidly that the ductal
reconditioning of the secretion is considerably

the potassium concentration rises to only four times
that of plasma.

Function of Saliva for Oral Hygiene.

Under basal awake con-

an exceedingly important role for maintaining healthy

teria that can easily destroy tissues and cause dental

First

genic bacteria as well as food particles that provide their
metabolic support.

Second

thiocyanate ions and another

is several proteolytic enzymes—most important,
lysozyme—

bolic support.

rampant.

Nervous Regulation of Salivary
Secretion

salivary glands are controlled mainly by parasympa-
thetic nervous signals all the way from the superior and
inferior salivatory nuclei in the brain stem.

the juncture of the medulla and pons and are excited
by both taste and tactile stimuli from the tongue and

elicit copious secretion of saliva—often 8 to 20 times

such as the presence of smooth objects in the mouth

rough objects cause less salivation and occasionally
even inhibit salivation.

Salivation can also be stimulated or inhibited by

nervous signals arriving in the salivatory nuclei from

Table 64–1

Brunner’s gland secretion

200

8.0–8.9

Small intestine secretion

1800

7.5–8.0

Bile

1000

7.8

Pancreatic secretion

1000

8.0–8.3

Gastric secretion

1500

1.0–3.5

Saliva

1000

6.0–7.0

Daily Volume (ml)

Daily Secretion of Intestinal Juices

Large intestinal secretion

200

7.5–8.0

Total

6700

) cells, which secrete large quantities of

chief

, which secrete mainly

neck cells

64–4. It is composed of three types of cells: (1)

A typical stomach oxyntic gland is shown in Figure

Secretions from the Oxyntic (Gastric) Glands

proximal 80 per cent of the stomach. The pyloric

of the body and fundus of the stomach, constituting the

The oxyntic glands are located on the inside surfaces

pyloric mucosa from the stomach acid. They also

. The pyloric

, and

hydrochloric acid

. The oxyntic

pyloric glands

oxyntic glands

surface of the stomach, the stomach mucosa has two

Characteristics of the Gastric

Gastric Secretion

occur at the gastric end of the esophagus.

Despite this protection, a peptic ulcer at times can still

from the stomach back into the lower esophagus.

food, whereas the compound glands located near the

The mucus

compound mucous glands.

extent in the initial portion of the esophagus, there

. At the gastric end and to a lesser

The main body of the esophagus is lined with many

acter and principally provide lubrication for swallowing.

The esophageal secretions are entirely mucous in char-

Esophageal Secretion

vasodilator.

an alpha2-globulin, to form

acts as an enzyme to split one of the blood proteins,

secreted by the activated salivary cells, which in turn

nutrition as needed by the secreting cells. Part of this

vessels, thus providing increased salivatory gland

addition, salivation itself directly dilates the blood

salivation also moderately dilate the blood vessels. In

The parasympathetic nerve signals that induce copious

glands.

thetic stimulation. The sympathetic nerves originate

a slight amount, much less so than does parasympa-

by diluting or neutralizing the irritant substances.

abnormality. The saliva, when swallowed, helps to

parasympathetic centers of the anterior hypothalamus,

regulates these effects, is located in proximity to the

of the brain, which partially

or eaten. The

instance, when a person smells or eats favorite foods,

higher centers of the central nervous system. For

Secretory Functions of the Alimentary Tract

Chapter 64

795

salivation is greater than when disliked food is smelled

appetite area

and it functions to a great extent in response to signals
from the taste and smell areas of the cerebral cortex
or amygdala.

Salivation also occurs in response to reflexes origi-

nating in the stomach and upper small intestines—par-
ticularly when irritating foods are swallowed or when
a person is nauseated because of some gastrointestinal

remove the irritating factor in the gastrointestinal tract

Sympathetic stimulation can also increase salivation

from the superior cervical ganglia and travel along the
surfaces of the blood vessel walls to the salivary

A secondary factor that also affects salivary secre-

tion is the blood supply to the glands because secretion
always requires adequate nutrients from the blood.

additional vasodilator effect is caused by kallikrein

bradykinin, a strong

simple mucous glands

are also many
secreted by the compound glands in the upper esopha-
gus prevents mucosal excoriation by newly entering

esophagogastric junction protect the esophageal wall
from digestion by acidic gastric juices that often reflux

Secretions

In addition to mucus-secreting cells that line the entire

important types of tubular glands:

(also

called gastric glands) and
(acid-forming) glands secrete

pepsinogen, intrinsic factor

mucus

glands secrete mainly mucus for protection of the

secrete the hormone gastrin.

glands are located in the antral portion of the stomach,
the distal 20 per cent of the stomach.

mucous

mucus; (2) peptic

(or

Superior and inferior
salivatory nuclei

Submandibular gland

Submandibular

ganglion

Sublingual gland

Chorda
tympani

Otic ganglion

Taste and
tactile stimuli

Tongue

Glossopharyngeal

nerve

Parotid
gland

Tractus

solitarius

Facial
nerve

Parasympathetic nervous regulation of salivary secretion.

Figure 64–3

Surface
epithelium

Mucous neck
cells

Oxyntic
(or parietal)
cells

Peptic
(or chief)
cells

Oxyntic gland from the body of the stomach.

Figure 64–4

concentration of about 150 to 160 mEq/L,

contains water, hydrochloric acid at a

Thus, the final secretion from the canaliculus

because of extra ions secreted into the canaliculus.

3. Water passes into the canaliculus by osmosis

of hydrochloric acid in the canaliculus. The

place in the canaliculus, giving a strong solution

the cell cytoplasm, and hydrogen ions take their

reabsorbed by a separate sodium pump. Thus,

ATPase. In addition, the sodium ions are actively

canaliculus in exchange for potassium ions: this

in the cell cytoplasm. The

hydroxyl ions

2. Water becomes dissociated into

canaliculus.

effect, mainly potassium chloride and much

cell cytoplasm into the canaliculus. Thus, in

millivolts in the canaliculus, which in turn causes

cytoplasm of the parietal cell. These two effects

the canaliculus, and sodium ions are actively

cytoplasm of the parietal cell into the lumen of

1. Chloride ion is actively transported from the

One of these, shown in Figure 64–6, consists of the

The hydrochloric acid is formed at

Figure 64–5 shows schematically the functional

energy per liter of gastric juice.

blood. To concentrate the hydrogen ions this tre-

its extreme acidity. At this pH, the hydrogen ion con-

fluids. The pH of this acid is about 0.8, demonstrating

per liter, which is almost exactly isotonic with the body

stimulated, the parietal cells secrete an acid solution

When

special mechanisms, as follows.

. Secretion

hydrochloric acid

, which

oxyntic

; and (3)

796

Unit XII

Gastrointestinal Physiology

pepsinogen

parietal (or

) cells

secrete

and intrinsic factor

of hydrochloric acid by the parietal cells involves

Basic Mechanism of Hydrochloric Acid Secretion.

that contains about 160 millimoles of hydrochloric acid

centration is about 3 million times that of the arterial

mendous amount requires more than 1500 calories of

structure of a parietal cell (also called oxyntic cell),

demonstrating that it contains large branching intra-
cellular canaliculi.
the villus-like projections inside these canaliculi and is
then conducted through the canaliculi to the secretory
end of the cell.

Different suggestions for the chemical mechanism

of hydrochloric acid formation have been offered.

following steps:

transported out of the canaliculus into the

together create a negative potential of

-40 to -70

diffusion of positively charged potassium ions
and a small number of sodium ions from the

smaller amounts of sodium chloride enter the

hydrogen ions

and
hydrogen ions are then actively secreted into the

active exchange process is catalyzed by H

most of the potassium and sodium ions that had
diffused into the canaliculus are reabsorbed into

hydrochloric acid is then secreted outward
through the open end of the canaliculus into the
lumen of the gland.

Mucous

neck cells

Oxyntic

(parietal)

cell

Canaliculi

Secretion

Figure 64–5

Schematic anatomy of the canaliculi in a parietal (oxyntic) cell.

Parietal cell

Lumen of canaliculus

Extracellular fluid

(Osmosis)

HCO

Cl–

(3 mEq/L)

Cl–

(155 mEq/L)

(15 mEq/L)

(173 mEq/L)

represent free diffusion and

tion of hydrochloric acid. (The

Postulated mechanism for secre-

Figure 64–6

points labeled “P” indicate active
pumps, and the dashed lines

osmosis.)

these are important, the smaller is more abundant.

G-17, which contains 17 amino acids. Although both of

which contains 34 amino acids, and a smaller form,

tide secreted in two forms: a large form called G-34,

distal end of the stomach. Gastrin is a large polypep-

pyloric glands

These cells are located in the

, also called

wall. Let us discuss first the gastrin mechanism for

(2) In addition, the ECL cells can be stimulated by

, which is formed almost

different ways: (1) Probably the most potent mecha-

tamine secreted by the ECL cells. In turn, the ECL

contact with the parietal cells of the glands. The rate

The ECL cells lie in the deep recesses of the oxyntic

enterochromaf-

Furthermore, the parietal cells operate in close associ-

tinuous control by both endocrine and nervous signals.

low as 0.8. However, secretion of this acid is under con-

secreted by these cells can be very great, with pH as

noted earlier in the chapter, the acidity of the fluid

are the only cells that secrete hydrochloric acid. As

, located deep

The

Stimulation of Gastric Acid Secretion

ties of this thick, alkaline, viscid mucus.

stomach secretion. Even the slightest contact with

not directly exposed to the highly acidic, proteolytic

. Therefore, the

mucus often more than 1 millimeter thick, thus

They secrete large quantities of a very

mucous cells called simply “surface mucous cells.”

The entire surface of the stomach mucosa between

shortly.

key role in controlling gastric secretion, as we discuss

from digestion by the gastric enzymes. The pyloric

food movement, as well as to protect the stomach wall

of pepsinogen, as discussed earlier, and an especially

the oxyntic glands. These cells secrete a small amount

no parietal cells. Instead, they contain mostly mucous

The pyloric glands are structurally similar to the

ulation of the bone marrow. This is discussed in detail

achlorhydria

occurs in chronic gastritis, the person develops not only

cells of the stomach are destroyed, which frequently

hydrochloric acid. When the acid-producing parietal

in the ileum, is

The substance

Secretion of Intrinsic Factor.

protein digestion in the stomach; this is discussed

time. Hydrochloric acid is as necessary as pepsin for

a highly acid medium (optimum pH 1.8 to 3.5), but

form a pepsin molecule, having a molecular weight of

having a molecular weight of about 42,500, is split to

In this process, the pepsinogen molecule,

with hydrochloric acid, it is activated to form active

tive activity. However, as soon as it comes in contact

When pepsinogen is first secreted, it has no diges-

functions.

Even so, all the pepsinogens perform the same

the peptic and mucous cells of the gastric glands.

are later secreted into the canaliculus.

diffuse out of the cell cytoplasm into the

step 2) to form bicarbonate ions. These then

the blood, combines under the influence of

4. Finally, carbon dioxide, either formed during

L, and a small amount of sodium chloride.

potassium chloride at a concentration of 15 mEq/

Secretory Functions of the Alimentary Tract

Chapter 64

797

metabolism in the cell or entering the cell from

carbonic anhydrase with the hydroxyl ions (from

extracellular fluid in exchange for chloride ions
that enter the cell from the extracellular fluid and

Secretion and Activation of Pepsinogen.

Several slightly

different types of pepsinogen are secreted by

pepsin.

about 35,000.

Pepsin functions as an active proteolytic enzyme in

above a pH of about 5 it has almost no proteolytic
activity and becomes completely inactivated in a short

further in Chapter 65.

intrinsic factor,

essential for absorption of vitamin B

secreted by the parietal cells along with the secretion of

(lack of stomach acid secretion) but often

also pernicious anemia because of failure of maturation
of the red blood cells in the absence of vitamin B

stim-

in Chapter 32.

Pyloric Glands—Secretion of Mucus
and Gastrin

oxyntic glands but contain few peptic cells and almost

cells that are identical with the mucous neck cells of

large amount of thin mucus that helps to lubricate

glands also secrete the hormone gastrin, which plays a

Surface Mucous Cells

glands has a continuous layer of a special type of

viscid mucus

that coats the stomach mucosa with a gel layer of

providing a major shell of protection for the stomach
wall as well as contributing to lubrication of food
transport.

Another characteristic of this mucus is that it is alka-

line

normal underlying stomach wall is

food or any irritation of the mucosa directly stimulates
the surface mucous cells to secrete additional quanti-

Parietal Cells of the Oxyntic Glands Are the Only Cells That
Secrete Hydrochloric Acid.

parietal cells

in the oxyntic glands of the main body of the stomach,

ation with another type of cell called
fin-like cells (ECL cells), the primary function of which
is to secrete histamine.

glands and therefore release histamine in direct

of formation and secretion of hydrochloric acid by the
parietal cells is directly related to the amount of his-

cells can be stimulated to secrete histamine in several

nism for stimulating histamine secretion is by the hor-
monal substance gastrin
entirely in the antral portion of the stomach mucosa
in response to proteins in the foods being digested.

(a) acetylcholine released from stomach vagal nerve
endings and (b) probably also by hormonal substances
secreted by the enteric nervous system of the stomach

control of the ECL cells and their subsequent control
of parietal cell secretion of hydrochloric acid.

Stimulation of Acid Secretion by Gastrin.

Gastrin is itself a

hormone secreted by gastrin cells

G cells.

in the

influences.

other times. This inhibition results from at least two

secretion, it paradoxically inhibits gastric secretion at

Intestinal Factors

Inhibition of Gastric Secretion

small amounts of gastric juice, probably partly because

denum, will continue to cause stomach secretion of

portion of the small intestine, particularly in the duo-

The presence of food in the upper

about 1500 milliliters.

remains in the stomach. The gastric phase of secretion

and (3) the gastrin mechanism, all of which in turn cause

brain and back to the stomach, (2) local enteric reflexes,

Once food enters the stomach, it excites

thence through the vagus nerves to the stomach. This

of the amygdala and hypothalamus. They are trans-

the more intense is the stimulation. Neurogenic signals

thought, or taste of food, and the greater the appetite,

while it is being eaten. It results from the sight, smell,

occurs even before food enters the stomach, especially

The cephalic phase of gastric secretion

intestinal phase.

, a

shown in Figure 64–7): a

Gastric secretion is said to occur in three “phases” (as

also decreased, even though the peptic cells may

normal amounts of acid, secretion of pepsinogen is

stomach. In people who have lost the ability to secrete

that causes protein digestion, is

nervous signals to the peptic cells. Therefore, the rate

stomach. The acid probably does not stimulate the

, and (2) stimulation

acetylcholine

types of signals: (1) stimulation of the

lation of acid secretion; it occurs in response to two

Regulation of Pepsinogen Secretion

The histamine

directly into the deep oxyntic glands.

body of the stomach, causing release of

transports the gastrin rapidly to the ECL cells in the

stomach. The vigorous mixing of the gastric juices

gastrin cells in the pyloric glands

reach the antral end of the stomach, some of the pro-

When meats or other protein-containing foods

798

Unit XII

Gastrointestinal Physiology

teins from these foods have a special stimulatory effect
on the

to cause

release of gastrin into the digestive juices of the

histamine

then acts quickly to stimulate gastric hydrochloric acid
secretion.

Regulation of pepsinogen secretion by the peptic cells
in the oxyntic glands is much less complex than regu-

peptic cells by

released from the vagus nerves or from

the gastric enteric nervous plexus
of peptic cell secretion in response to acid in the

peptic cells directly but instead elicits additional
enteric nervous reflexes that support the original

of secretion of pepsinogen, the precursor of the
enzyme pepsin
strongly influenced by the amount of acid in the

otherwise appear to be normal.

Phases of Gastric Secretion

cephalic phase

gastric phase,

and an

Cephalic Phase.

that cause the cephalic phase of gastric secretion origi-
nate in the cerebral cortex and in the appetite centers

mitted through the dorsal motor nuclei of the vagi and

phase of secretion normally accounts for about 20 per
cent of the gastric secretion associated with eating a
meal.

Gastric Phase.

(1) long vagovagal reflexes from the stomach to the

secretion of gastric juice during several hours while food

accounts for about 70 per cent of the total gastric secre-
tion associated with eating a meal and therefore
accounts for most of the total daily gastric secretion of

Intestinal Phase.

of small amounts of gastrin released by the duodenal
mucosa.

by Other Post-Stomach

Although intestinal chyme slightly stimulates gastric
secretion during the early intestinal phase of stomach

Vagal center
of medulla

Cephalic phase via vagus

Parasympathetics excite
pepsin and acid production

Intestinal phase:
1. Nervous mechanisms
2. Hormonal mechanisms

Circulatory system

Afferent

fibers

Vagus

trunk

Secretory

fiber

Small bowel

Gastrin

Food

Local nerve

plexus

Gastric phase:
1. Local nervous
secretory reflexes
2. Vagal reflexes
3. Gastrin-histamine
stimulation

Phases of gastric secretion and their regulation.

Figure 64–7

secreted into the intestinal tract. Trypsinogen is

cally. They become activated only after they are

, which are all inactive enzymati-

boxypolypeptidase

, and

chymotrypsinogen

When first synthesized in the pancreatic cells, the

phospholipids.

phospholipase,

, which causes hydrolysis of cholesterol esters;

cholesterol

into fatty acids and monoglycerides; (2)

, which is capable of hydrolyzing neutral fat

The main enzymes for fat digestion are (1)

to form mostly disaccharides and a few trisaccharides.

gen, and most other carbohydrates (except cellulose)

, which hydrolyzes starches, glyco-

The pancreatic enzyme for digesting carbohydrates

some proteins all the way to the amino acid state.

individual amino acids, thus completing digestion of

not cause release of individual amino acids. However,

Trypsin and chymotrypsin split whole and partially

. By far the most abundant of these

boxypolypeptidase

, and

chymotrypsin

The most important of the pancreatic enzymes for

ties of bicarbonate ions, which play an important role

carbohydrates, and fats. It also contains large quanti-

digesting all of the three major types of food: proteins,

creas. These are discussed in detail in Chapter 78.)

juice. Instead, insulin is secreted directly into the

, but this is not secreted by the same

the types of food in the chyme. (The pancreas also

tions of the small intestine, and the characteristics of

, surrounded by the

papilla of Vater

ducts leading from the acini. The combined product of

, and large volumes of sodium bicarbonate

to that of the salivary glands shown in Figure 64–2. The

stomach (illustrated in Figure 64–10), is a large com-

The pancreas, which lies parallel to and beneath the

Pancreatic Secretion

the natural gastrin. This synthetic product is called

alanine, has all the same physiologic properties as

A synthetic gastrin, composed of the terminal four

eight amino acids. All the amino acids in the secretin

the activity for cholecystokinin resides in the terminal

gastrin resides in the terminal four amino acids, and

ular chains are the same. The functional activity of

amino acids in the gastrin and cholecystokinin molec-

respectively, of 2000, 4200, and 3400. The terminal five

polypeptides with approximate molecular weights,

, and

cholecystokinin

Chemical Composition of Gastrin and

ment of peptic ulcers, as discussed in Chapter 66.

tion excites secretion at the onset of a meal. This

acidic) to 50 milliliters or more per hour, in very much

Unfortunately, emotional stimuli frequently increase

nonoxyntic type, composed mainly of

no digestion is occurring anywhere in the gut. The secre-

hour during the “interdigestive period,” when little or

The

that they reduce gastric secretion, as was discussed in

already filled or already overactive. In fact, the entero-

The functional purpose of inhibitory gastric secretion

, and

secretin opposes stomach secretion. Three other

for control of pancreatic secretion. However,

, which is especially important

causes release of several intestinal hormones. One

products, hyperosmotic or hypo-osmotic fluids, or

2. The presence of acid, fat, protein breakdown

This is part of the complex mechanism discussed in

breakdown products, or by irritation of the mucosa.

in the upper intestine, by the presence of protein

distending the small bowel, by the presence of acid

stomach secretion. This reflex can be initiated by

extrinsic sympathetic and vagus nerves, that inhibits

, transmitted through

1. The presence of food in the small intestine initiates

Secretory Functions of the Alimentary Tract

Chapter 64

799

a reverse enterogastric reflex
the myenteric nervous system as well as through

Chapter 63 for slowing stomach emptying when the
intestines are already filled.

any irritating factor in the upper small intestine

of these is secretin

hormones—gastric inhibitory peptide, vasoactive
intestinal polypeptide

somatostatin—also have

slight to moderate effects in inhibiting gastric
secretion.

by intestinal factors is presumably to slow passage of
chyme from the stomach when the small intestine is

gastric inhibitory reflexes plus inhibitory hormones
usually also reduce stomach motility at the same time

Chapter 63.

Gastric Secretion During the Interdigestive Period.

stomach secretes a few milliliters of gastric juice each

tion that does occur usually is almost entirely of the

mucus but little

pepsin and almost no acid.

interdigestive gastric secretion (highly peptic and

the same way that the cephalic phase of gastric secre-

increase of secretion in response to emotional stimuli is
believed to be one of the causative factors in develop-

Other Gastrointestinal Hormones

Gastrin,

secretin are all large

molecule are essential.

amino acids of natural gastrin plus the amino acid

pentagastrin.

pound gland with most of its internal structure similar

pancreatic digestive enzymes are secreted by pancre-
atic acini
solution are secreted by the small ductules and larger

enzymes and sodium bicarbonate then flows through
a long pancreatic duct that normally joins the hepatic
duct immediately before it empties into the duodenum
through the

sphinc-

ter of Oddi.

Pancreatic juice is secreted most abundantly in

response to the presence of chyme in the upper por-

the pancreatic juice are determined to some extent by

secretes insulin
pancreatic tissue that secretes intestinal pancreatic

blood—not into the intestine—by the islets of Langer-
hans that occur in islet patches throughout the pan-

Pancreatic Digestive Enzymes

Pancreatic secretion contains multiple enzymes for

in neutralizing the acidity of the chyme emptied from
the stomach into the duodenum.

digesting proteins are trypsin,

car-

is trypsin.

digested proteins into peptides of various sizes but do

carboxypolypeptidase does split some peptides into

is pancreatic amylase

pancre-

atic lipase

esterase
and (3)

which splits fatty acids from

proteolytic digestive enzymes are in the inactive
forms trypsinogen,

procar-

cholecystokinin, stimulate the acinar cells of the

The first two of these stimuli, acetylcholine and

, which is also secreted by the duodenal

, which is secreted by the

, which is released from the

Acetylcholine

Three basic stimuli are important in causing pancre-

Basic Stimuli That Cause Pancreatic Secretion

of water also into the pancreatic duct, thus

3. The overall movement of sodium and bicarbonate

neutrality for the secreted bicarbonate ions.

luminal border

This supplies the sodium ions (Na

cell by a secondary active transport process.

sodium ions through the blood border

exchanged for

2. The hydrogen ions formed by dissociation of

luminal border

). Then the bicarbonate ions

). The carbonic acid in turn

carbonic anhydrase, combines with water to form

cell from the blood and, under the influence of

1. Carbon dioxide diffuses to the interior of the

ductules and ducts are shown in Figure 64–8. They are

The basic steps in the cellular mechanism for secret-

ate ions in the plasma. This provides a large quantity

145 mEq/L, a value about five times that of bicarbon-

to secrete copious quantities of pancreatic juice, the

lead from the acini. When the pancreas is stimulated

juice, bicarbonate ions and water, are secreted mainly

secreted entirely by the acini of the pancreatic glands,

Secretion of Bicarbonate Ions

time of pancreatic insufficiency.

even if not lethal, it usually leads to a subsequent life-

. This sometimes is

entire pancreas within a few hours, giving rise to the

whelmed, in which case the pancreatic secretions

tions, the effect of trypsin inhibitor is often over-

damaged areas of the pancreas. Under these condi-

when a duct becomes blocked, large quantities of pan-

When the pancreas becomes severely damaged or

enzymes, trypsin inhibitor prevents activation of the

the acini and ducts of the pancreas. And, because it is

cytoplasm of the glandular cells, and it prevents acti-

. This substance is formed in the

digest the pancreas itself. Fortunately, the same cells

Secretion of Trypsin Inhibitor Prevents Digestion of the

in a similar manner.

motrypsin, and procarboxypolypeptidase is activated

in contact with the mucosa. Also, trypsinogen can be

, which is

800

Unit XII

Gastrointestinal Physiology

activated by an enzyme called enterokinase
secreted by the intestinal mucosa when chyme comes

autocatalytically activated by trypsin that has already
been formed from previously secreted trypsinogen.
Chymotrypsinogen is activated by trypsin to form chy-

Pancreas Itself.

It is important that the proteolytic

enzymes of the pancreatic juice not become activated
until after they have been secreted into the intestine
because the trypsin and the other enzymes would

that secrete proteolytic enzymes into the acini of the
pancreas secrete simultaneously another substance
called trypsin inhibitor

vation of trypsin both inside the secretory cells and in

trypsin that activates the other pancreatic proteolytic

others as well.

creatic secretion sometimes become pooled in the

rapidly become activated and can literally digest the

condition called acute pancreatitis
lethal because of accompanying circulatory shock;

Although the enzymes of the pancreatic juice are

the other two important components of pancreatic

by the epithelial cells of the ductules and ducts that

bicarbonate ion concentration can rise to as high as

of alkali in the pancreatic juice that serves to neutral-
ize the hydrochloric acid emptied into the duodenum
from the stomach.

ing sodium bicarbonate solution into the pancreatic

the following:

carbonic acid (H

dissociates into bicarbonate ions and hydrogen

ions (HCO

and H

are actively transported in association with
sodium ions (Na

) through the

the cell into the lumen of the duct.

carbonic acid inside the cell are

of the

) that are

transported through the

into the

pancreatic duct lumen to provide electrical

ions from the blood into the duct lumen creates
an osmotic pressure gradient that causes osmosis

forming an almost completely isosmotic
bicarbonate solution.

Regulation of Pancreatic Secretion

atic secretion:
1.

parasympathetic vagus nerve endings and from
other cholinergic nerves in the enteric nervous
system

2. Cholecystokinin

duodenal and upper jejunal mucosa when food
enters the small intestine

3. Secretin

and jejunal mucosa when highly acid food enters
the small intestine

Blood

Lumen

Ductule cells

(Active

transport)

(Active
transport)

(Carbonic anhydrase)

HCO

O H

creatic ductules and ducts.

Secretion of isosmotic sodium bicarbonate solution by the pan-

Figure 64–8

num) stimulated by cholecystokinin.

response to soap (a fat), and (3) intense digestive

denum, stimulated by secretin, (2) a dual effect in

Figure 64–9, which demonstrates (1) intense sodium

effects of secretin and cholecystokinin are shown in

The differences between the pancreatic stimulatory

ulation but even more pronounced, accounting for 70

cells. This effect is similar to that caused by vagal stim-

Cholecystokinin, like secretin, passes by way of the

long-chain fatty acids

num and upper jejunum. This release of cholecys-

, in the mucosa of the duode-

group of cells, the

taining 33 amino acids, to be released from yet another

, a polypeptide con-

cholecystokinin

second hormone,

The presence

Its Contribution to Control of Diges-

tion averages 8.0.

Fortunately, the pH of the sodium bicarbonate secre-

alkaline or neutral medium, at a pH of 7.0 to 8.0.

tive enzymes, which function optimally in a slightly

prevent development of duodenal ulcers, as is dis-

juice, this is an essential protective mechanism to

blocked. Because the mucosa of the small intestine

neutralized, so that further peptic digestive activity by

ride in the duodenum. In this way, the acid contents

lungs, thus leaving a neutral solution of sodium chlo-

into carbon dioxide and water. The carbon dioxide

Then the carbonic acid immediately dissociates

of sodium bicarbonate. The net result is then the fol-

pH falls to 3.0. This immediately causes copious secre-

below 4.5 to 5.0, and its release increases greatly as the

especially important for two reasons: First, secretin

tration of chloride ion. The secretin mechanism is

bicarbonate ion (up to 145 mEq/L) but a low concen-

absorbed into the blood. The one truly potent con-

release and activation of secretin, which is then

num from the stomach, it causes duodenal mucosal

mucosa of the duodenum and jejunum. When acid

inactive form, prosecretin, in so-called S cells in the

acids (molecular weight about 3400), present in an

Secretin is a polypeptide, containing 27 amino

Neutralization of Acidic Stomach

becomes copious, mainly in response to the hormone

enters the small intestine, pancreatic secretion

meal. But, again, only small amounts reach the duo-

enzyme secretion continues, accounting for another 5

During the gastric phase, the nervous stimulation of

enzymes.

of pancreatic enzymes after a meal. But little of the

in the pancreas. This causes moderate amounts of

of pancreatic secretion, the same nervous signals from

as follows.

. Their characteristics are

, and the

, the

as for gastric secretion: the

Pancreatic secretion occurs in three phases, the same

Phases of Pancreatic Secretion

stimuli, not from one alone.

one another. Thus, pancreatic secretion normally

various stimuli are said to “multiply,” or “potentiate,”

tions caused by each one separately. Therefore, the

ferent stimuli of pancreatic secretion occur at once, the

When all the dif-

basic stimuli, stimulates secretion of large quantities of

the duodenum. Secretin, in contrast to the first two

enzymes. Without the water, most of the enzymes

pancreas, causing production of large quantities of

Secretory Functions of the Alimentary Tract

Chapter 64

801

pancreatic digestive enzymes but relatively small
quantities of water and electrolytes to go with the

remain temporarily stored in the acini and ducts until
more fluid secretion comes along to wash them into

water solution of sodium bicarbonate by the pancre-
atic ductal epithelium.

Multiplicative Effects of Different Stimuli.

total secretion is far greater than the sum of the secre-

results from the combined effects of the multiple basic

cephalic phase

gastric

phase

intestinal phase

Cephalic and Gastric Phases.

During the cephalic phase

the brain that cause secretion in the stomach also
cause acetylcholine release by the vagal nerve endings

enzymes to be secreted into the pancreatic acini,
accounting for about 20 per cent of the total secretion

secretion flows immediately through the pancreatic
ducts into the intestine because only small amounts of
water and electrolytes are secreted along with the

to 10 per cent of pancreatic enzymes secreted after a

denum because of continued lack of significant fluid
secretion.

Intestinal Phase.

After chyme leaves the stomach and

secretin.

Secretin Stimulates Secretion of Copious Quantities of
Bicarbonate Ions—
Chyme.

chyme with pH less than 4.5 to 5.0 enters the duode-

stituent of chyme that causes this secretin release is the
hydrochloric acid from the stomach.

Secretin in turn causes the pancreas to secrete large

quantities of fluid containing a high concentration of

begins to be released from the mucosa of the small
intestine when the pH of the duodenal contents falls

tion of pancreatic juice containing abundant amounts

lowing reaction in the duodenum:

is absorbed into the blood and expired through the

emptied into the duodenum from the stomach become

the gastric juices in the duodenum is immediately

cannot withstand the digestive action of acid gastric

cussed in further detail in Chapter 66.

Bicarbonate ion secretion by the pancreas provides

an appropriate pH for action of the pancreatic diges-

Cholecystokinin—
tive Enzyme Secretion by the Pancreas.

of food in the upper small intestine also causes a

I cells

tokinin results especially from the presence of
proteoses and peptones (products of partial protein
digestion) and

in the chyme

coming from the stomach.

blood to the pancreas but instead of causing sodium
bicarbonate secretion causes mainly secretion of still
much more pancreatic digestive enzymes by the acinar

to 80 per cent of the total secretion of the pancreatic
digestive enzymes after a meal.

bicarbonate secretion in response to acid in the duo-

enzyme secretion (when peptones enter the duode-

HCl NaHCO

NaCl H CO

tion of chloride ions, water, and most other diffusible

epithelium, and this is followed by secondary absorp-

lecithin, and bilirubin.

constituents that contain the bile salts, cholesterol,

bladder mucosa, concentrating the remaining bile

water, sodium, chloride, and most other small elec-

can hold is only 30 to 60 milliliters. Nevertheless, as

duodenum. The maximum volume that the gallbladder

secreted continually by the liver cells, but most of it is

Storing and Concentrating Bile in the Gallbladder.

, which causes

much as an additional 100 per cent. The second secre-

that line the ductules and ducts. This second secretion

of liver secretion is added to the initial bile. This addi-

In its course through the bile ducts, a second portion

, shown in Figure 64

From these the bile either empties directly

ducts,

interlobular septa, where the canaliculi empty into

(2) Next, the bile

that originate between the hepatic cells.

organic constituents. It is secreted into minute

large amounts of bile acids, cholesterol, and other

; this initial secretion contains

the liver, the

Bile is secreted in two stages by the liver: (1) The initial

Physiologic Anatomy of

cholesterol

hemoglobin destruction, and excesses of

, an end product of

These include especially

Second, bile serves as a means for excretion of

the intestinal mucosal membrane.

enzymes secreted in pancreatic juice, and (2) they aid

fat particles of the food into many minute particles,

bile do two things: (1) they help to emulsify the large

that cause fat digestion, but because

and absorption, not because of any enzymes in the bile

First, bile plays an important role in fat digestion

normally between 600 and 1000 ml/day. Bile serves two

Functions of the Biliary Tree

Secretion of Bile by the Liver;

total amount secreted each day is about 1 liter.

factors in the regulation of pancreatic secretion. The

Figure 64

802

Unit XII

Gastrointestinal Physiology

–10 summarizes the more important

One of the many functions of the liver is to secrete bile,

important functions:

bile acids in the

the surface of which can then be attacked by lipase

in absorption of the digested fat end products through

several important waste products from the blood.

bilirubin

Biliary Secretion

portion is secreted by the principal functional cells of

hepatocytes

bile

canaliculi

flows in the canaliculi toward the

ter-

minal bile ducts and then into progressively larger

finally reaching the hepatic duct and common

bile duct.
into the duodenum or is diverted for minutes up to
several hours through the cystic duct into the gall-
bladder

–11.

tional secretion is a watery solution of sodium and
bicarbonate ions secreted by secretory epithelial cells

sometimes increases the total quantity of bile by as

tion is stimulated especially by secretin
release of additional quantities of bicarbonate ions to
supplement the bicarbonate ions in pancreatic secre-
tion (for neutralizing acid that empties into the duo-
denum from the stomach).

Bile is

normally stored in the gallbladder until needed in the

much as 12 hours of bile secretion (usually about 450
milliliters) can be stored in the gallbladder because

trolytes are continually absorbed through the gall-

Most of this gallbladder absorption is caused by

active transport of sodium through the gallbladder

HCI

Soap

Peptone

Water and
NaHCO

Enzymes

Rate of pancreatic secretion

the pancreas, caused by the presence of acid (HCl), fat (soap),

), water, and enzyme secretion by

Figure 64–9

Sodium bicarbonate (NaHCO

or peptone solutions in the duodenum.

Vagal
stimulation
releases
enzymes
into acini

Secretin causes
copious secretion
of pancreatic fluid
and bicarbonate;
cholecystokinin
causes secretion
of enzymes

Acid from stomach
releases secretin from
wall of duodenum;
fats and amino acids
cause release of
cholecystokinin

Common

bile duct

Secretin and
cholecystokinin
absorbed into
blood stream

Regulation of pancreatic secretion.

Figure 64–10

to the cholecystokinin stimulus that itself is initiated

In summary, the gallbladder empties its store of con-

enteric nervous system. They are the same nerves that

In addition to cholecystokinin, the gallbladder is

acinar cells of the pancreas. The stimulus for cholecys-

This is the same cholecystokinin discussed earlier that

cholecystokinin

the gallbladder, but effective emptying also requires

30 minutes after a meal. The mechanism of gallblad-

gastrointestinal tract, the gallbladder begins to empty,

When food begins to be digested in the upper

Emptying of the Gallbladder—Stimulatory Role of Cholecys-

highly concentrated in the gallbladder bile.

lecithin, are not reabsorbed and, therefore, become

mucosa; essentially all other constituents, especially

In the concentrating process in the gallbladder,

, and the usual

cholesterol

about one half of the total solutes also in the bile. Also

, which account for

it has been concentrated in the gallbladder. This table

Table 64

about 5-fold, but it can be concentrated up to a

constituents. Bile is normally concentrated in this way

Secretory Functions of the Alimentary Tract

Chapter 64

803

maximum of 20-fold.

Composition of Bile.

–2 gives the composition of

bile when it is first secreted by the liver and then after

shows that by far the most abundant substances
secreted in the bile are bile salts

secreted or excreted in large concentrations are biliru-
bin,

, lecithin

electrolytes of

plasma.

water and large portions of the electrolytes (except
calcium ions) are reabsorbed by the gallbladder

the bile salts and the lipid substances cholesterol and

tokinin.

especially when fatty foods reach the duodenum about

der emptying is rhythmical contractions of the wall of

simultaneous relaxation of the sphincter of Oddi,
which guards the exit of the common bile duct into the
duodenum.

By far the most potent stimulus for causing the gall-

bladder contractions is the hormone

causes increased secretion of digestive enzymes by the

tokinin entry into the blood from the duodenal
mucosa is mainly the presence of fatty foods in the
duodenum.

stimulated less strongly by acetylcholine-secreting
nerve fibers from both the vagi and the intestinal

promote motility and secretion in other parts of the
upper gastrointestinal tract.

centrated bile into the duodenum mainly in response

Stomach

Acid

Liver

Bile acids via blood
stimulate parenchymal
secretion

Secretin via
blood stream
stimulates
liver ductal
secretion

Bile stored and
concentrated up
to 15 times in
gallbladder

Cholecystokinin via blood stream causes:
1. Gallbladder contraction
2. Relaxation of sphincter of Oddi

Vagal stimulation
causes weak
contraction of
gallbladder

Pancreas

Sphincter of

Oddi

Duodenum

Liver secretion and gallbladder emptying.

Figure 64–11

Table 64–2

100 mEq/L

25 mEq/L

5 mEq/L

23 mEq/L

5 mEq/L

12 mEq/L

145.04 mEq/L

130 mEq/L

Lecithin

0.04 g/dl

0.3 g/dl

Fatty acids

0.12 g/dl

0.3 to 1.2 g/dl

Cholesterol

0.1 g/dl

0.3 to 0.9 g/dl

Bilirubin

0.04 g/dl

0.3 g/dl

Bile salts

1.1 g/dl

6 g/dl

Water

97.5 g/dl

92 g/dl

Liver Bile

Gallbladder Bile

Composition of Bile

28 mEq/L

10 mEq/L

HCO

mucosa, sometimes allowing excessive absorption of

resulting from low-grade chronic infection, may also

ammation of the gallbladder epithelium, often

development of gallstones.

metabolism in the body. For this reason, people on a

by the quantity of fat that the person eats, because liver

12. The

, as shown in Figure 64

cholesterol gallstones

cipitate in the gallbladder, resulting in the formation of

Under abnormal conditions, the cholesterol may pre-

terol, which keeps the cholesterol in solution.

concentrated in the gallbladder, the bile salts and

in more detail in Chapter 65. When the bile becomes

in the form of a colloidal solution, as explained

water, but the bile salts and lecithin in bile combine

day.

bile salts, about 1 to 2 grams of cholesterol are removed

terol in the blood plasma. In the process of secreting the

Liver Secretion of Cholesterol and

ducts.

stomach. Thus, the secretin feedback mechanism for

themselves. The bicarbonate in turn passes into the

by the epithelial cells of the bile ductules and ducts, and

a meal. This increase in secretion is almost entirely

pancreatic secretion increases bile secretion, sometimes

bile secretion, the hormone

This demonstrates that the daily rate of liver bile salt

duction of bile salts 6- to 10-fold, which increases the

reabsorbed from the ileum, the liver increases its pro-

several hundred milliliters per day.

greater the rate of bile secretion. Indeed, ingestion of

culation (usually a total of only about 2.5 grams), the

The quantity of bile secreted by the liver each day is

salts.

continually by the liver cells. This recirculation of the

carried out in the feces. The small quantities of bile salts

recirculated into the bile, so that on the average these

In this way, about 94 per cent of all the bile salts are

resecreted into the bile.

to the liver. On reaching the liver, on

ileum. They then enter the portal blood and pass back

small intestine, about one half of this by

nutrient loss.

the ingested fats are lost into the feces, and the person

of bile salts in the intestinal tract, up to 40 per cent of

described in detail in Chapter 65.Without the presence

they are then absorbed into the blood, as will be

in this form to the intestinal mucosa, where

charges of the bile salts. The intestinal lipids are

, and they are

lipids; the complexes are called

(4) other lipids from the intestinal tract. They do this

(1) fatty acids, (2) monoglycerides, (3) cholesterol, and

fying function, bile salts help in the absorption of

Second, and even more important than the emulsi-

salts.

to break the fat globules into minute sizes. This is

cles in the food. This decreases the surface tension of

First, they have a detergent action on the fat parti-

The bile salts have two important actions in the

sodium salts, are then secreted in the bile.

. The salts of these acids, mainly

in about equal quantities. These

nodeoxycholic acid

che-

cholic acid

liver cells during the course of fat metabolism. The

cholesterol

daily. The precursor of the bile salts is

The liver cells synthesize about 6 grams of

Function of Bile Salts in Fat Digestion

bladder, and its ultimate release from the bladder to

marizes the secretion of bile, its storage in the gall-

empties completely in about 1 hour. Figure 64

quantities of fat are present, the gallbladder normally

the gallbladder empties poorly, but when signi

mainly by fatty foods. When fat is not in the food,

804

Unit XII

Gastrointestinal Physiology

ficant

–11 sum-

the duodenum.

and Absorption

bile salts

which is either present in the diet or synthesized in the

cholesterol is first converted to

acids in turn combine principally with glycine and to a
lesser extent with taurine to form glyco- and tauro-
conjugated bile acids

intestinal tract:

the particles and allows agitation in the intestinal tract

called the emulsifying or detergent function of bile

by forming very small physical complexes with these

micelles

semi-soluble in the chyme because of the electrical

“ferried”

often develops a metabolic deficit because of this

Enterohepatic Circulation of Bile Salts.

About 94 per cent of

the bile salts are reabsorbed into the blood from the

diffusion

through the mucosa in the early portions of the small
intestine and the remainder by an active transport
process through the intestinal mucosa in the distal

first passage

through the venous sinusoids these salts are absorbed
almost entirely back into the hepatic cells and then are

salts make the entire circuit some 17 times before being

lost into the feces are replaced by new amounts formed

bile salts is called the enterohepatic circulation of bile

highly dependent on the availability of bile salts—the
greater the quantity of bile salts in the enterohepatic cir-

supplemental bile salts can increase bile secretion by

If a bile fistula empties the bile salts to the exterior

for several days to several weeks so that they cannot be

rate of bile secretion most of the way back to normal.

secretion is actively controlled by the availability (or
lack of availability) of bile salts in the enterohepatic
circulation.

Role of Secretin in Helping to Control Bile Secretion.

In addi-

tion to the strong stimulating effect of bile acids to cause

secretin that also stimulates

more than doubling its secretion for several hours after

secretion of a sodium bicarbonate-rich watery solution

not increased secretion by the liver parenchymal cells

small intestine and joins the bicarbonate from the pan-
creas in neutralizing the hydrochloric acid from the

neutralizing duodenal acid operates not only through its
effects on pancreatic secretion but also to a lesser extent
through its effect on secretion by the liver ductules and

Gallstone Formation

Bile salts are formed in the hepatic cells from choles-

from the blood plasma and secreted into the bile each

Cholesterol is almost completely insoluble in pure

physically with the cholesterol to form ultramicroscopic
micelles

lecithin become concentrated along with the choles-

–

amount of cholesterol in the bile is determined partly

cells synthesize cholesterol as one of the products of fat

high-fat diet over a period of years are prone to the

Infl

change the absorptive characteristics of the gallbladder

water and bile salts but leaving behind the cholesterol

ions together cause osmotic movement of water.

uid. Finally, all these

crypts and (2) active secretion of bicarbonate ions. The

processes: (1) active secretion of chloride ions into the

The exact

Mechanism of Secretion of the Watery Fluid.

chyme when it comes in contact with the villi. Thus, the

secretions also are rapidly reabsorbed by the villi. This

a slightly alkaline pH in the range of 7.5 to 8.0. The

cytes of the crypts at a rate of about 1800 ml/day. These

The intestinal secretions are formed by the entero-

cent villi, reabsorb the water and electrolytes along

water and electrolytes and, over the surfaces of adja-

, which, in the crypts, secrete large quantities of

intestinal surfaces, and (2) a large number of

types of cells: (1) a moderate number of

the intestinal villi. The surfaces of both the crypts and

13. These crypts lie between

is illustrated in Figure 64

, one of which

Juices by the Crypts of Lieberk

Secretion of Intestinal Digestive

ulcers in about 50 per cent of ulcer patients.

ulation; therefore, such stimulation in very excitable

of bicarbonate ions, which add to the bicarbonate ions

stomach. In addition, the mucus contains a large excess

The function of the mucus secreted by Brunner

(3) gastrointestinal hormones, especially

concurrently with increase in stomach secretion; and

stimuli on the duodenal mucosa; (2) vagal stimulation,

the duodenum. These glands secrete large amounts of

Vater where pancreatic secretion and bile empty into

rst few centimeters of the duodenum, mainly

, is located in the wall of the

An extensive array of compound mucous glands,

Glands in the Duodenum

Secretions of the

gallstones.

amed mucosa, but then progressing to large

Then the cholesterol begins to precipitate,

in the bladder in progressively greater concentrations.

Secretory Functions of the Alimentary Tract

Chapter 64

805

first forming

many small crystals of cholesterol on the surface of
the infl

Small Intestine

Secretion of Mucus by Brunner’s

called Brunner’s glands
fi
between the pylorus of the stomach and the papilla of

alkaline mucus in response to (1) tactile or irritating

which causes increased Brunner’s glands secretion

secretin.

’s

glands is to protect the duodenal wall from digestion
by the highly acid gastric juice emptying from the

from pancreatic secretion and liver bile in neutralizing
the hydrochloric acid entering the duodenum from the
stomach.

Brunner’s glands are inhibited by sympathetic stim-

persons is likely to leave the duodenal bulb unpro-
tected and is perhaps one of the factors that cause this

area of the gastrointestinal tract to be the site of peptic

ühn

Located over the entire surface of the small intestine
are small pits called crypts of Lieberkühn

–

the villi are covered by an epithelium composed of two

goblet cells,

which secrete mucus that lubricates and protects the

entero-

cytes

with end products of digestion.

secretions are almost pure extracellular fluid and have

flow of fluid from the crypts into the villi supplies a
watery vehicle for absorption of substances from

primary function of the small intestine is to absorb
nutrients and their digestive products into the blood.

mechanism that controls the marked secretion of
watery fluid by the crypts of Lieberkühn is not known.
It is believed to involve at least two active secretory

secretion of both of these ions causes electrical drag
as well of positively charged sodium ions through the
membrane and into the secreted fl

Course followed by bile:
1. During rest
2. During digestion

Liver

Stones

Hepatic duct

Common bile duct
Sphincter of Oddi

Pancreatic duct

Duodenum

Papilla of Vater

Cystic duct

Stones

Gallbladder

Causes of gallstones:
1. Too much absorption of water
from bile
2. Too much absorption of bile
acids from bile
3. Too much cholesterol in bile
4. Inflammation of epithelium

Formation of gallstones.

Figure 64–12

Paneth cell

Epithelial cell

Mucous goblet
cell

between the villi, which secretes almost pure extracellular fluid.

, found in all parts of the small intestine

crypt of Lieberkühn

Figure 64–13

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disease. Curr Gastroenterol Rep 6:151, 2004.

Portincasa P, Di Ciaula A, vanBerge-Henegouwen GP:

bladder function. News Physiol Sci 13:64, 1998.

Marve GM: Nerves and hormones interact to control gall-

between membrane transporters. JOP 2(4 Suppl):203,

Lee MG, Ahn W, Lee JA, Kim JY, et al: Coordination of pan-

tion in secretory cells. Annu Rev Physiol 62:493, 2000.

Kidd JF, Thorn P: Intracellular Ca

Mosby, 2001.

Johnson LR: Gastrointestinal Physiology, 6th ed. St. Louis:

trointestinal tract: a review. J Cell Mol Med 5:327, 2001.

Jass JR, Walsh MD: Altered mucin expression in the gas-

gene regulation. Ann N Y Acad Sci 1014:97, 2004.

Hocker M: Molecular mechanisms of gastrin-dependent

284:G551, 2003.

challenges. Am J Physiol Gastrointest Liver Physiol

ulation of bile acid synthesis: past progress and future

Fuchs M: Bile acid regulation of hepatic physiology: III. Reg-

secretion and mucosal protection. News Physiol Sci 16:23,

Flemstrom G, Isenberg JI: Gastroduodenal mucosal alkaline

ucts. Physiol Rev 76:767,1996.

gene expression, processing, and targeting of active prod-

Dockray GJ, Varro A, Dimaline R: Gastric endocrine cells:

63:119, 2001.

production and biological activities. Annu Rev Physiol

Dockray GJ,Varro A, Dimaline R,Wang T:The gastrins: their

test Liver Physiol 284:G349, 2003.

Bile acids and nuclear receptors. Am J Physiol Gastroin-

Chiang JY: Bile acid regulation of hepatic physiology: III.

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epithelium: molecular basis and regulatory aspects. Annu

Barrett KE, Keely SJ: Chloride secretion by the intestinal

recovery from the disease than might otherwise occur.

washes away irritant factors, which promotes earlier

ties of water and electrolytes. But the diarrhea also

anus. The result is

alkaline mucus. This acts to dilute the irritating factors

, the mucosa secretes extra large quantities of

large intestine becomes intensely irritated, as occurs

Whenever a segment of the

Diarrhea Caused by Excess Secretion of Water and Electrolytes

nally, the mucus plus the alka-

inside the feces, and,

Furthermore, it protects the intestinal wall from the

adherent medium for holding fecal matter together.

wall against excoriation, but in addition, it provides an

often as every 30 minutes; this mucus often contains

caused by emotional disturbances, so much mucus can

During extreme parasympathetic stimulation, often

colon, which was discussed in Chapter 63.

can cause marked increase in mucus secretion. This

distal one half to two thirds of the large intestine, also

cord, which carry

by direct, tactile stimulation of the epithelial cells

The rate of secretion of mucus is regulated principally

mucus-secreting epithelial cells.

This mucus

mucus.

that secrete only mucus. The great preponderance of

enzymes. Instead, they consist mainly of mucous cells

are no villi. The epithelial cells contain almost no

hn; however, unlike the small intestine, there

that of the small intestine, has many crypts of

The mucosa of the large intestine, like

Large Intestine

Secretions of the

stimuli from the chyme in the intestines.

exes,

Regulation of Small Intestine

of an intestinal epithelial cell is about 5 days. This rapid

nally shed into the intestinal secretions. The life cycle

digestive enzymes. As the villus cells age, they are

crypts toward the tips of the villi, thus continually

continually undergo mitosis, and new cells migrate

The epithelial cells deep in the crypts of Lieberk

acids.

monosaccharides, and (3) small amounts of

, and

amino acids, (2) four enzymes

the epithelium. These enzymes are the following:

villi, do contain digestive enzymes that digest speci

terocytes of the mucosa, especially those that cover the

cellular debris, they have almost no enzymes. The en-

When

806

Unit XII

Gastrointestinal Physiology

Digestive Enzymes in the Small Intestinal Secretion.

secretions of the small intestine are collected without

fic

food substances while they are being absorbed through

(1) several peptidases for splitting small peptides into

—sucrase, maltase, iso-

maltase

lactase—for splitting disaccharides into

intestinal

lipase for splitting neutral fats into glycerol and fatty

ühn

along the basement membrane upward out of the

replacing the villus epithelium and also forming new

growth of new cells also allows rapid repair of excori-
ations that occur in the mucosa.

Secretion—Local Stimuli

By far the most important means for regulating small
intestine secretion are local enteric nervous refl
especially reflexes initiated by tactile or irritative

Mucus Secretion.

Lieberkü

secretion in the large intestine is
contains moderate amounts of bicarbonate ions
secreted by a few non–

lining the large intestine and by local nervous reflexes
to the mucous cells in the crypts of Lieberkühn.

Stimulation of the pelvic nerves from the spinal

parasympathetic innervation to the

occurs along with increase in peristaltic motility of the

occasionally be secreted into the large intestine that
the person has a bowel movement of ropy mucus as

little or no fecal material.

Mucus in the large intestine protects the intestinal

great amount of bacterial activity that takes place

linity of the secretion (pH of 8.0 caused by large
amounts of sodium bicarbonate) provides a barrier to
keep acids formed in the feces from attacking the
intestinal wall.

in Response to Irritation.

when bacterial infection becomes rampant during
enteritis
water and electrolytes in addition to the normal viscid

and to cause rapid movement of the feces toward the

diarrhea, with loss of large quanti-

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