SALIVARY SECRETION

Saliva contains two major types of protein secretion: (1) a serous secretion that contains ptyalin (α-amylase), which
is an enzyme for digesting starches, and (2) mucus secretion that contains mucin for lubricating and for surface
protective purposes.

Composition of Saliva

1. Mucus

Mucus is an aqueous mixture of proteoglycans and glycoproteins. Salivary mucins are O-glycosylated and consist of
peptides with many oligosaccharides linked covalently to the hydroxyamino acid serine or threonine.

The physiological functions of mucin are related to its high viscosity.

2. Electrolytes

The principal inorganic constituents of saliva are sodium, potassium, chloride, and bicarbonate, which, with the
exception of bicarbonate, originate directly from the plasma. Rates of salivary flow vary depending on stimulation,
and there are wide variations in electrolyte concentration. Saliva is formed by a process that initially requires
uptake of sodium and other electrolytes from the interstitium of the terminal structural unit of the salivary gland,
the acinus or end piece. Water flows passively. This primary or precursor fluid has a sodium concentration similar
to plasma, and the potassium concentration is similar to or slightly higher than plasma. As the primary fluid passes
from the acinus along the duct system, the concentration of sodium, potassium, and other electrolytes changes.

3. Amylase

Salivary amylase splits the α1, 4-glucosidic bonds of various polysaccharides. 

C. Functions of Saliva

Saliva continuously bathes the oral cavity, which protects the surface epithelium. Ingested food is moistened and
lubricated by saliva, thereby facilitating mastication and swallowing. 

Regulation of Salivary Secretion

Salivation is controlled via the parasympathetic system from the salivary nuclei in the brain stem. Factors that
induce salivation include:

 Taste stimuli, especially sour taste

 Higher centers especially appetite anticipation, smells and visual clues

 In response to signals from the stomach and upper GI tract, particularly irritating stimuli. Salivation can
also occur as a prelude to vomiting.
SECRETION IN STOMACH

The adult stomach secretes about 1500 cc in a normal day consisting of hydrochloric acid, bicarbonate rich
mucous, and the digestive hormone precursor pepsinogen. Pepsinogen is activated to its active form pepsin by the
acidity of the stomach. G cells also secrete the hormone gastrin.

The gastric pits of the stomach open on to branching glands: pyloric glands in the antral part of the
stomach; gastric or oxyntic (acid forming) glands in the fundus and body of the stomach. A schematic diagram of
an oxyntic gland is shown here (see also anatomy).

The parietal or oxyntic cells secrete hydrochloric acid; the peptic or chief cells secrete pepsinogen; the mucous
cells secrete a bicarbonate rich mucous; and the G cells (found only in the antral glands) secrete the hormone
Gastrin.

Hydrochloric Acid secretion

The oxyntic or parietal cell contains a large number of intracellular canaliculi shown schematically here:
The pH of the secreted acid is about 0.8, and has a hydrogen ion concentration of about 3 million times that of
arterial blood. To achieve this level of concentration requires a lot of energy, about 1500 calories per liter of
secretion. The mechanism of hydrogen ion formation is illustrated schematically here.

 Carbon dioxide and water enter the cell and combine to form carbonic acid under the influence of the
enzyme carbonic anhydrase.

 Bicarbonate is actively excreted at the basal side of the cell and is exchanged for chlorine.

 Potassium is exchanged for hydrogen ions at the apical side of the cell

 Chlorine ions (not shown in diag.) are also actively secreted.

Clinical Note: Intrinsic factor and Pernicious anemia

Bicarbonate Rich Mucous Secretion

Mucous secretion rich in alkaline bicarbonate protects the stomach from the Hydrochloric acid of the gastric juice.

Bicarbonate ions are generated by the mechanism illustrated below:

 Carbon dioxide and water enter the cell and combine to form carbonic acid under the influence of the
enzyme carbonic anhydrase.

 Hydrogen ions are actively secreted on the basal side of the cell in exchange for sodium.

 Bicarbonate ions are actively secreted on the apical or lumen side of the cell in exchange for chlorine
Secretion and Activation of Pepsinogen

Pepsinogen is secreted by the peptic or chief cells of the gland.

When first secreted pepsinogen is inactive, but contact with acid converts it to the active form pepsin by splitting
the pepsinogen molecule. Pepsin functions best at a pH between 1.8 and 3.5

Stimulation of Gastric Acid secretion

The Oxyntic cells function in close association with histamine producing cells called enterochromaffin-like
cells (ECL) which secrete histamine. These cells release histamine in direct contact with the oxyntic glands and
promote the secretion of HCl. The activation of this complex is under hormonal (Gastrin) and nervous control.

 Gastrin, secreted by the G cells in the antrum of the stomach in response to the presence of protein is the
most potent stimulator of the Histamine/Acid complex. The gastrin is not only carried by the blood
stream, but is also carried directly into the lumens of the gastric pits and has a direct stimulating action.

 The Histamine/HCl complex is also activated by acetylcholine released by the vagus nerve

 Other substances also control Acid secretion, mainly through their action on Gastrin production.

Inhibition of Gastric Acid secretion.

Factors which slow stomach emptying, which was discussed when considering motility will also reduce gastin
production and hence Acid secretion.

Regulation of Pepsinogen Secretion

Pepsinogen secretion occours in response to two signals:

 Acetylcholine release from the vagus nerve

 Stimulation of peptic cell secretion in response to acid in the stomach, probably not directly but through
the enteric nervous system.

BILIARY SECRETION

A. Composition of Bile

The bile is secreted continuously by the hepatocytes of the liver, and if not immediately required for digestion are
stored in the gall bladder.

In the presence of fats in the duodenum, cholecystokinin is secreted which causes strong contractions of the gall
bladder and relaxation of the Sphincter of Oddi, propelling the bile into the small intestine.

Composition of Human Hepatic Duct Bile

1. Water- 97%
2. Bile Salts- 0.7%
3. Bile Pigments- 0.2%
4. Cholesterol- 0.07%
 5. Inorganic Salts- 0.7%
6. Fatty Acids- 0.15%
7. Fat- 0.1%
8. Lecithin- 0.1%

B. Function of Bile Salts in Fat Digestion and Absorption

The bile salts have two important actions in the intestinal tract:

First, they have a detergent action on the fat particles in the food. This decreases the surface tension of the
particles and allows agitation in the intestinal tract to break the fat globules into minute sizes. This is called
the emulsifying or detergent function of bile salts.

Second, and even more important than the emulsifying function, bile salts help in the absorption of (1) fatty acids,
(2) mono-glycerides, (3) cholesterol, and (4) other lipids from the intestinal tract.

PANCREATIC SECRETION

The microscopic structure of the pancreas is similar to the salivary glands, the acini secrete enzymes, and the
ductile and ducts secrete large quantities of a bicarbonate rich juice. These travel down the pancreatic duct to the
second part of the duodenum where it exits.

Enzymes secreted by the acini include proteolytic enzymes, amylases and lipases. The proteolytic enzymes are all
secreted in an inactive form to prevent auto-digestion.

Pancreatic Digestive Enzymes

The following table summarizes the digestive enzymes secreted by the pancreas:

Group Enzymes Substrates

Carbohydrates and Starch Amylase Starch

Phospholipase Phospholipids
cholesterol esterase Hydrolysis of Cholesterol esters

Proteins and Peptides Trypsin (Trypsinogen) Peptides

Chymotrypsin, Carboxy-polypeptidase Peptides

 Amylase breaks down carbohydrates (except cellulose) to di-saccharides and some tri-saccharides.

 Proteolytic enzymes are secreted in the in active form to prevent auto digestion, they are converted to
the active form in the small intestine. Trypsin is activated by enterokinase, secreted by the intestinal
mucosa;

 Trypsin then activates Chymo-trypsinogen

 Lipase converts fats to fatty acids and mono-glycerides

 Phospholipase splits fatty acids from phospholipids

 Cholesterol esterase hydrolyses cholesterol esters

Inhibition and Activation of Enzymes

The cells that secrete proteolytic enzymes also secrete another substance called trypsin inhibitor. This prevents
any trypsin that may form in the cells or ducts from becoming active, or activating the other enzymes. If however
the pancreas becomes damaged or the pancreatic ducts become blocked then the action of trypsin inhibitor can be
over whelmed, and the very serious condition acute pancreatitis can develop.

Secretion of Bicarbonate ions

Copious quantities of Bicarbonate ion rich solutions are secreted by the ducts the pancreas in response to the
hormone Secretin. The mechanisms are similar to that of the mucous cells of the stomach, except that large
quantities of fluid are also produced.
  Carbon dioxide and water enter the cell and combine to form carbonic acid under the influence of the
enzyme carbonic anhydrase.

 Hydrogen ions are actively secreted on the basal side of the cell in exchange for sodium.

 Bicarbonate ions are actively secreted on the apical or lumen side of the cell in exchange for chlorine

 Sodium and Water ions follow either passively through 'leaky' tight junctions, or through cell by the
mechanism described above in 'Water & Electrolyte secretions'.

Phases of Digestion

Like Gastric secretions, pancreatic secretions can be divided into three phases:

 Cephalic

 Gastric

 Intestinal

The Cephalic phase occurs when we think about or anticipate food. It is mediated by the vagal nerve. It causes
secretion of about 20% of the enzymes, but as this secretion is not accompanied by fluid secretions, the enzymes
are not flushed out and tend to remain in the ducts.

The gastric phase occurs when food enters the stomach, and again is mediated by neural stimuli. This accounts for
another 5-10%, and again in the absence of serous flow these secretions tend to remain in the ducts.

The Intestinal phase occurs when food enters the small intestine and both serous pancreatic secretion becomes
copious due to the hormone secretin.
Regulation of pancreatic Secretion

Three basic stimuli control pancreatic secretion

 Acetylcholine from the parasympathetic nerves of the vagal and the cholinergic nerves of the enteric
nervous system.

 Cholecystokinin secreted in the duodenum and the upper small intestine

 Secretin, also secreted in the duodenum and upper jejunum.

The following diagram summarizes the factors controlling pancreatic secretions.

Acetylcholine and Cholecystokinin cause secretion of digestive enzymes, but these tend to remain in the gland, as
there are no secretions to flow them out.

Secretin causes copious secretions of sodium bicarbonate rich fluids which wash the enzymes into the small
intestine, and also neutralize the Hydrochloric acid from the stomach.

2HCl + Na2CO3 --> 2NaCl + H2CO3 --> H2O + CO2

The carbonic acid (a weak acid) immediately dissociates into Carbon Dioxide and water The Carbon dioxide is
absorbed into the blood stream.

Pancreatic enzymes work best between a pH of 7-8. Sodium Bicarbonate has a pH of about 8.

SMALL INTESTINE

The upper small intestine secretes the hormones Cholecystokinase and secretin, mucous, Intestinal digestive
juices, and possibly enzymes.

Hormone Secretion
Cholecystokinin (CCK) is secreted in response to fats and peptides in the upper small intestines, particularly the
duodenum. Actions of CCK include:

 Secretion of Pancreatic Enzymes

 Contraction of Gallbladder

 Relaxation of the sphincter of Oddi

 increased tension in the pyloric sphincter, inhibiting stomach emptying

Secretin is released in response to the presence of Acid in the duodenum. Actions of Secretin include:

 Secretion of Copious amounts of bicarbonate rich fluid by the biliary and gall bladder ducts

 Secretion of alkaline rich mucous by Brunner’s glands

 increased tension in the pyloric sphincter, inhibiting stomach emptying

Regulation of Small Intestine Secretions

Secretions are produced almost entirely from local enteric nervous reflexes in response to local stimuli.

LARGE INTESTINE

The chief function of the large intestine is absorption of fluids and the formation of faeces. The large intestine
secretes about 200 cc of fluid a day, mainly in the form of mucous.