BIOCHEMISTRY OF GIT

INTRODUCTION
Secretions of Alimentary System
 Saliva
 Gastric juice
 Pancreatic juice
 Bile
 Succus entericus
Total Secretions per Day
 About seven (07) litres
 98 % of which is reabsorbed
 02 % appears in faeces
The Composition of the Digestive Juices
 Water & electrolytes
 Digestive enzymes
 Mucus
Mechanism of Secretion
 Active
 Passive
Control of Secretion
 Nervous Control (e.g. Saliva)
 Both Nervous (vagal) & Hormonal Control (e.g. Gastric, Pancreatic & Biliary
secretions)
 SALIVA

Salivary Glands

Parotid Sublingual
Submandibular

Serous Mucous
Watery Mixed Viscous
Moderately
viscous

Gland Percentage of total saliva

Parotid Gland 20 %
Submandibular Gland 70 %
Sublingual Gland 05 %
Other minor Glands 05 %
Properties of saliva
 Viscous, colourless and opalescent liquid
 Specific Gravity: 1.002-1.012
 pH: 6.2-7.4 (approaching 8 during active secretion)
Composition of saliva
Total secretion of saliva per day is 1500 ml
 Water: 99.5 %
 Solids: 0.5 % (Inorganic/electrolytes & organic constituents)
Inorganic constituents
 K+, HCO3-, Na+, Cl-,
 Mg++, Ca++, SO4--, PO4---
 Thiocyanate (SCN-)
 Iodine
Organic constituents
1. Digestive enzymes
 Ptyalin/salivary α-amylase
 Lingual lipase
2. Mucin
3. Other organic substances
 Antibacterial Substances (IgA, Lysozymes & Lactoferrin)
 Proline rich proteins
 Urea
 Blood Group antigens
Variation in the ionic composition of saliva
When salivary flow is rapid (Isotonic)
Concentration of Na+, K+, Cl- & HCO3- are close to that of plasma (in acini)
When salivary flow is slow (Hypotonic)
Excretory and Intercalated ducts modify composition of saliva by extracting Na+& Cl- and
adding K+ & HCO3- (ducts are relatively impermeable to water and saliva becomes
hypotonic)
Functions of saliva
1. Lubricant Function
 The water in saliva wets the dry food, and combined with slippery properties of
mucin, saliva facilitates swallowing of food
 By wetting the mouth, it facilitates speech
2. Solvent Function
 For any substance to stimulate the taste buds it must be in solution form, hence
saliva serves as a solvent for the molecules that stimulate the taste buds
3. Role of Bicarbonate, Chloride ion and Thiocyanate (SCN-)
 Saliva is rich in Bicarbonate which neutralizes acids in food as well as acids
produced by bacteria in mouth, thereby helping to prevent dental caries
 Chloride ions are required for activation of Ptyalin
 Thiocyanate (SCN-) has a bacteriostatic action
4. Digestive function:
Ptyalin / Salivary α-amylase
Optimum pH = 6.6-6.8
Ptyalin can digest most of the ingested starch into disaccharides & oligosaccharides
before they reach small intestine. The activity of this enzyme continues in the
stomach until acidity of the gastric juice terminates it.
Lingual lipase
Optimum pH = 3.0-6.0
It begins the digestion of fat, especially milk fat in the stomach
5. Role in Oral Hygiene:
The flow of Saliva itself helps wash away the pathogenic bacteria as well as the food
particles that provide their metabolic support. Moreover, saliva contains several
factors that destroy bacteria e.g.
 IgA: Secretory immunoglobulin provides immune protection against viruses and
bacteria entering the body through mouth
 Lysozymes: An enzyme that lyses or destroys certain bacteria by damaging their
cell walls
 Lactoferrin: An iron binding protein that has a bacteriostatic function
6. Other functions:
 Dryness of mouth during dehydration gives a sensation of thirst which is an
important stimulus for adequate water intake
 Proline rich Proteins protect tooth enamel and bind toxic tannins.
 Saliva also act as a vehicle for excretion of certain drugs e.g. ethanol and
morphine
 Urea is also excreted in saliva
Clinical Module
Xerostomia: Deficient/ Diminished Salivation
Causes
 Sjӧgren’s Syndrome (autoimmune disorder)
 Radiotherapy
Clinical Features
 Difficulty in chewing and swallowing
 Difficulty in speaking
 Rampant increase in dental caries
Management
 Sipping water frequently
 Using sugar free gums and hard candies
Sjögren's syndrome, also known as "Sicca syndrome", is a systemic autoimmune disease in
which immune cells attack and destroy the exocrine glands that produce tears and saliva
Sjögren's syndrome can exist as
 primary Sjögren's syndrome
 Secondary Sjögren's syndrome that may develop years after the onset of an
associated rheumatic disorder, such as rheumatoid arthritis, systemic lupus
erythematosus, scleroderma and primary biliary cirrhosis etc.
Signs and Symptoms
The hallmark symptom of Sjögren's syndrome is a generalized dryness, typically including
 xerostomia (dry mouth)
 rheumatoid arthritis
 keratoconjunctivitis sicca (dry eyes)
In addition, Sjögren's syndrome may cause dryness of
 skin
 nose
 Female genital tract
 GASTRIC JUICE

Oxyntic gland

Pyloric gland

Enterochromaffin-like (ECL)
 Histamine
 Gastric Cell Types and their Secretions
Antrum (Pyloric Glands)
 Mucous Cells secrete mucus
 G Cells secrete gastrin
Body & Fundus (Oxyntic Glands)
 Parietal Cells secrete HCl and Intrinsic Factor
 Chief Cells secrete Pepsinogen and gastric lipase
 Paracrine cells, enterochromaffin-like (ECL), secrete histamine
Properties of Gastric Juice
 Clear, pale yellow fluid
 pH: 1.0-3.2
Composition of Gastric Juice
Total gastric secretion per day is 2500 ml
 Water: 97-99 %
 Solids: 3-1 % (Inorganic & organic constituents)
Inorganic Constituents
 Na+, K+, Mg++, H+
 Cl- , SO4--, PO4---
Organic Constituents
1. Enzymes
 Pepsin
 Lipase
 Rennin
 Gelatinase
2. Other Organic constituents
 Mucus
 Intrinsic factor
Functions of Gastric Juice
Hydrochloric acid (HCl)
 Denaturation of proteins
 Activation of pepsinogen into pepsin
 Provide the optimal pH for pepsin action i.e. 1.6-3.2
 Antiseptic action – destroy swallowed microorganisms
 Stimulates the flow of bile & pancreatic secretion
Mechanism of Gastric Acid (HCl) Secretion
Parietal cells secrete HCl in to the lumen of stomach & concurrently, absorb
HCO3– in to the blood stream as follows:
i. In the parietal cells, CO2 & H2O are converted to H+ & HCO3– catalyzed by carbonic
anhydrase
ii. H+ is secreted in to the lumen of stomach by H +/ K+ pump (H+/ K+ ATPase). Cl –
is
secreted (extruded down its electrochemical gradient) along with H +, thus the
secretion produced by gastric cells is HCl
iii. The HCO3– produced in the cells is absorbed in to the blood stream in the exchange
for Cl- (Cl– - HCO3– exchange)
iv. Eventually this HCO3- will be secreted in pancreatic secretion to neutralize H + in
small intestine
v. Parietal cells contain numerous mitochondria needed to generate the ATP used for
H+/ K+ ATPase
vi. H+/ K+ ATPase unlike Na+/ K+ ATPase is oubain insensitive
vii. The drug omeprazole irreversibly & specifically inhibit H +/ K+ pump (also called
proton pump)

Blood Parietal cell Gastric lumen

Na+

K+ K+

CO2 + H2O H+/K+ ATPase also

called proton pump
H2CO3
K+
-
HCO3 HCO3- + H+ H+
Cl- HCl
Cl- Cl-
HCO3-/Cl- exchange

Alkaline Tide
The increased secretion of acid after a meal, coupled with increased discharge of HCO3- in
to the blood stream makes the blood pH alkaline & alkaline urine, known as post- prandial
alkaline tide.
Functions of Enzymes
 Pepsin
Pepsins are secreted in their inactive precursors, pepsinogen, which are activated by
gastric HCl & then by pepsin which rapidly activates further molecules of pepsinogen
(autocatalysis)
Pepsin is an endopeptidase specific for peptide bonds formed by aromatic amino acids
(e.g. tyrosine), or dicarboxylic amino acids (e.g. glutamate).
 Gastric lipase
Gastric lipase is of little importance, except in pancreatic insufficiency.
Gastric and lingual lipases initiate lipid digestion by hydrolysing TAGs containing short-
medium, and generally unsaturated long chain fatty acids to form free fatty acids and 1,2-
DAG. The enzymes are destroyed at low pH (optimal pH 3.0-6.0) but are active after
feeding because of the buffering action of dietary proteins in the stomach.
Owing to a retention time of 2-4 hours in stomach, some 30% of dietary TAGs can be
digested in this time, most within the first hour. Milk Fat seems to be a particularly good
substrate.
 Gelatinase
Gelatinase liquefies gelatine
 Rennin (Chymosin, Rennet)
Rennin is a milk-clotting gastric enzyme. It is important in the digestive processes of
infants because it prevents the rapid passage of milk from the stomach. In the presence of
calcium, rennin changes the casein of milk irreversibly to paracasein, which is then acted
upon by pepsin. Rennin is probably absent in adults. It is used in making of cheese
(rennet).
Mucus
The mucus, secreted by neck cells often gastric glands & surface mucosal cells, is made up
of glycoprotein called mucin that forms a flexible gel coating the mucosa. Mucus binds
HCO3- secreted by surface epithelium and non-parietal cells, and together they form a
mucosal barrier that protects gastric mucosa from the damaging effect of gastric acid.
Water & mucus aid mixing of food with enzymes & facilitate its passage in to the
intestines.
As in saliva, 80% of the population secrete their ABO blood group antigens in their gastric
mucus. The ability to secrete these antigens may have a protective role because it has
been found that persons who do not secrete these antigens are more susceptible to
duodenal ulcer.
Intrinsic Factor
Intrinsic factor (IF), produced from the parietal cells, is essential in the absorption of
vitamin B12 (vitamin B12 can be absorbed only when in combination with IF). IF-Vitamin B12
complex binds to special receptors located only in the terminal ileum. This binding triggers
receptor mediated endocytosis of this complex.
Clinical Module
1. Pernicious Anaemia
Vitamin B12 is required for the normal formation of RBCs. In the absence of IF, Vitamin B12
fails to be absorbed, so RBCs production is defective, and pernicious anaemia results.
Causes
Pernicious anaemia is typically caused by an autoimmune attack against the parietal cells.
Treatment
Regular injections of vitamin B12 are recommended, thus bypassing the defective digestive
tract absorptive mechanism.
2. Achlorhydria
In achlorhydria basal gastric acid secretion is low. It is diagnosed when the pH of gastric
secretions fails to fall below 6.5. The digestion process in stomach is affected as pepsin
requires acidic medium for its action. Also, there is failure of acid induced inhibition of G
cells.
Causes: Autoimmune gastritis (pernicious anaemia)
3. Peptic Ulcer
Peptic ulcer (gastric & duodenal ulcers) is related in to break down of barrier that normally
prevents irritation & autodigestion of mucosa by gastric secretion.
Causes
i. Chronic use of NSAIDs (non-steroidal anti-inflammatory drugs) e.g. aspirin,
ibuprofen & indomethacin – prostaglandin E formed by the gastric mucosa
suppresses gastric acid secretion. Consequently, it reduces the risk of peptic
ulcer. The NSAIDs are inhibitors of cyclooxygenase (COX 1 & 2). Aspirin & most
other NSAIDs can cause peptic ulcer by suppressing PGE synthesis & thereby
increasing gastric acid secretion. Selective inhibitors of COX-2 (e.g. celecoxib)
avoid this problem because they prevent prostaglandin synthesis in white blood
cells but not in the stomach
 ii. Chronic infection with bacterium Helicobacter Pylori
 It secretes proteases & phospholipases that causes break down of mucosal
barrier
 It produces ammonia due to urease enzyme
 It secretes adhesins that allow more bacteria to adhere to mucosa
iii. Acid hypersecretory states such as Zollinger Ellison Syndrome
Zollinger–Ellison syndrome is caused by gastrin-secreting gut neuroendocrine
tumors (gastrinomas), which result in hypergastrinemia & acid hypersecretion.
The primary tumor is usually located in the duodenum (45%), the pancreas (25%),
and abdominal lymph nodes (5-15%), and in other locations
Aggravating / precipitating Factors
 Tea/coffee
 Smoking
 Stress
 Steroids
Clinical Features

• Epigastric pain

• Nausea, vomiting

• Retrosternal burning
Treatment

• Antacids/sucralfate

• H2 receptor antagonist -- cimetidine

• Proton pump inhibitor --- Omeprazole

 PANCREATIC JUICE

Pancreas is a mixed gland that contains both exocrine and endocrine portions.
Exocrine portion (predominant) consists of secretory cells that form sacs known as acini.
Acini connect to ducts that eventually empty into the duodenum.
Endocrine portion (smaller) consists of Islets of Langerhans, which are dispersed
throughout the pancreas.
Properties of Pancreatic Juice
It is a watery, highly alkaline fluid with pH 7.5 - 8.3
Composition of Pancreatic Juice
Total secretion per day is 1500 ml
 Water: 98.5 %
 Solids: 1.5 % (2/3rd electrolytes, 1/3rd proteins)
Electrolytes (meq/l)
 Na+ 142.0; K+ 4.8; Ca++ 6.0
 HCO3- 100; Cl- 81.0; HPO4- 1.0
 Small amounts of zinc and sulphate
Organic constituents
a. Enzymes for digestion of proteins
Trypsin, Chymotrypsin, Elastase, and Carboxypeptidase
b. Enzymes for digestion of carbohydrates
Pancreatic amylase
 c. Enzymes for digestion of lipids
Lipase, Cholesteryl ester hydrolase and Phospholipase A2
d. Enzymes for digestion of nucleic acids
Ribonucleases and deoxyribonucleases
Activation of pancreatic enzymes
Pancreatic enzymes are secreted as inactive precursors i.e. trypsinogen,
chymotrypsinogen, proelastase, procarboxypeptidase & prophospholipase A2.
 Trypsinogen is activated to trypsin by enterokinase (enteropeptidase) secreted
by the mucosa of the duodenum and upper intestine. Trypsin in turn activates
not only trypsinogen (autocatalysis), but also all the other proteases.
 Lipase is activated by bile salts, colipase & phospholipids.
Functions of Pancreatic Juice
1. Enzymes
a. Enzymes for digestion of proteins
Trypsin
Trypsin is an endopeptidase. It attacks proteins and polypeptides released from the
stomach to produce polypeptides, peptides or both. Trypsin is specific for peptide bonds of
basic amino acids.
Chymotrypsin
Chymotrypsin is an endopeptidase. It attacks proteins and polypeptides released from the
stomach to produce polypeptides, peptides or both. Chymotrypsin is specific for peptide
bonds containing uncharged amino acid residues such as aromatic amino acid
Elastase
Elastase is an endopeptidase. It attacks proteins and polypeptides released from the
stomach to produce polypeptides, peptides or both. Elastase, in spite of its name, has
rather broad specificity in attacking bonds next to small amino acid residues such as
glycine, alanine and serine.
Carboxypeptidase
Carboxypeptidase is an exopeptidase. The further attack on the polypeptides produced by
the action of endopeptidases is carried on by carboxypeptidase which attacks the carboxyl
terminal peptide bond, liberating single amino acids.
 Carboxypeptidase A: Ala, Ile, Leu, Val
 Carboxypeptidase B: Arg, Lys
 b. Enzymes for digestion of carbohydrates
Pancreatic Amylase
It attacks starch and glycogen. It is similar in action to salivary amylase, hydrolyzing starch
and glycogen to maltose, maltotriose (3 glucose residues linked by α 1 - 4 bonds) and a
mixture of branched oligosaccharides (α-limit dextrins), non-branched oligosaccharides and
some glucose.
c. Enzymes for digestion of lipids
Pancreatic Lipase
The pancreatic lipase acts at the oil-water interface of the finely emulsified lipid droplets
formed by mechanical agitation in the gut in the presence of the products of lingual &
gastric lipase activity, bile salts, colipase, phospholipids & phospholipase A 2.
Colipase binds to the bile salt-covered triacylglycerol interface. Thus it anchors the lipase
to its triacylglycerol substrate. Colipase is secreted as the zymogen, procolipase, which is
activated by trypsin.
Pancreatic lipase is virtually specific for the hydrolysis of primary ester linkage, i.e., at
position 1 & 3 of TAGs. The end products of triacylglycerol digestion by pancreatic lipase
are 2-monoacylglycerol & fatty acids. This is because of the difficulty of hydrolysis of the
secondary ester linkage in the triacylglycerol by pancreatic lipase.
Cholesteryl ester hydrolase (cholesterol esterase)
It catalyzes the hydrolysis of the cholesteryl esters, which are thus absorbed from the
intestine in the non esterified free form.
Phospholipase A2
It is secreted as proenzyme which is activated by trypsin & Ca 2+. It hydrolyzes the ester
bond in the 2 position of glycerophosholipids of both biliary and dietary origin to form
lysophospholipids, which, being detergents, aid emulsification and digestion of lipids.
d. Enzymes for digestion of nucleic acids
Ribonuclease and Deoxyribonuclease
These are responsible for the digestion of the dietary nucleic acids and convert them into
nucleotides.
2. Importance of the high bicarbonate content
The bicarbonate concentration of the pancreatic juice is much higher than that of plasma.
The bicarbonate is very important for neutralizing the acid chyme from the stomach, and
providing the right pH for the action of pancreatic enzymes.
Clinical Module
Cystic Fibrosis (CF)
 An autosomal recessive disorder of chloride transport affecting exocrine glandular
secretion with respiratory & GIT being most affected
 Serious genetic disease among whites in north America (1:2500 individuals)
 Diagnostic hallmark is high amount of NaCl in sweat
 Gene involved is cystic fibrosis transmembrane conductance regulator (CFTR), it is
the protein involved in transmembrane transport of chloride.
Some of the Mechanisms Involved in the Causation of CF

Mutations in the gene encoding CFTR

Alterations in the structure and function of CFTR protein

Decreased secretion of chloride from epithelial cells,

absorption of Na+ is also affected, and is excessive,
leading secondarily to increased uptake of water

Increased viscosity of mucus in the airway

Impaired mucociliary clearance, bacterial colonization

and recurrent infections

Clinical features
 Chronic or recurrent cough, sputum production, haemoptysis, dyspnoea
 Recurrent respiratory infections, thick viscous respiratory secretions (chronic
lung disease)
 Recurrent pancreatitis
 Thick viscous pancreatic secretions leading to pancreatic malabsorption
(fats, proteins & polysaccharides)
 Steatorrhea – fatty, bulky stools
 Diarrhoea, abdominal pain
Diagnosis
i. Quantitative pilocarpine iontopheresis sweat test (Cl- concentration is increased
i.e., > 60meq/l on two separate days)
ii. Bronchiectasis & scarring on chest radiographs
iii. Faecal fat content is increased
 BILE

 Bile is synthesized by hepatocytes & cells lining the bile canaliculi.

 The hepatocytes secrete cholesterol, bile pigments & synthesize & secrete bile
salts, but as the bile passes through the ducts, water & bicarbonate are secreted
in to it by the ducts under the action of secretin. The ductal secretion gives
volume to the bile. Hepatic secretion of bile is termed choleresis
 The hepatic bile is yellow-green or golden brown watery liquid, which becomes
highly concentrated, viscous & less alkaline as it is stored in the gall bladder
 Composition of Bile
Total secretion per day is 500 ml

Organic constituents of bile

1. Bile acids
Bile acids are synthesized from cholesterol. These are:
Primary bile acids are cholic acid & chenodeoxycholic acid. They are conjugated in the
liver with either taurine or glycine e.g., taurocholic acid or glycocholic acid. In the
alkaline pH of bile, bile acids are converted to sodium & potassium salts.
Secondary bile acids are formed from primary bile acids by bacteria in colon i.e., cholic
acid is converted to deoxycholic acid & chenodeoxycholic acid to lithocholic acid.
2. Bile salts
Bile salts are sodium & potassium salts of bile acids. Bile salts are amphipathic molecules.
In the aqueous solution bile salts orient themselves around lipid droplets & keep the lipids
droplets dispersed (emulsification)
3. Cholesterol
Cholesterol is insoluble in water but is made water soluble through the formation of
aggregates known as micelles. The micelles consist of cholesterol, phospholipids (lecithin)
& bile salts.
4. Bile pigments
The bile pigments, bilirubin (mainly) & biliverdin, which give colour to bile & faeces, are
excretory products of haemoglobin. Liver conjugates bilirubin with glucuronic acid before
secretion in to bile.
Biosynthesis and degradation of bile acids
Background
The ring structure of cholesterol cannot be metabolized to CO 2 and H2O in humans. Rather,
the intact sterol nucleus is eliminated from the body by conversion to bile acids and bile
salts, which are excreted in the feces, and by secretion of cholesterol into the bile, which
transports it to the intestine for elimination. Some of the cholesterol in the intestine is
modified by bacteria before excretion. The primary compounds made are the isomers
coprostanol and cholestanol, which are reduced derivatives of cholesterol. Together with
cholesterol, these compounds make up the bulk of neutral fecal sterols.
Synthesis of primary bile acids
The primary bile acids are synthesized in the liver from cholesterol. These are cholic acid
(found in the largest amount) and chenodeoxycholic acid. The 7α-hydroxylation of
cholesterol is the first and principal regulatory step in the biosynthesis of bile acids. This
reaction is catalyzed by cholesterol 7 α -hydroxylase, a microsomal cytochrome P450
enzyme (a typical monooxygenase) that requires oxygen and NADPH. Subsequent
hydroxylation steps are also catalyzed by monooxygenases. The pathway of bile acid
biosynthesis divides early into one subpathway leading to cholyl-CoA, characterized by an
extra α-OH group on position 12, and another pathway leading to chenodeoxycholyl-CoA.
Conjugation of primary bile acids
Conjugation takes place in liver peroxisomes. The primary bile acids are conjugated to a
molecule of either glycine or taurine (derived from cystiene) by an amide bond between
the carboxyl group of the bile acid and the amino group of the added compound. Addition
of glycine or taurine results in the presence of a carboxyl group with a lower pKa (from
glycine) or a sulfonate group (from taurine), both of which are fully ionized (negatively
charged) at physiologic pH. Conjugated bile acids are more effective detergents than
primary bile acids because of their enhanced amphipathic nature. The ratio of the glycine
to the taurine conjugates is normally 3:1. The conjugated primary bile acids enter the bile.
Synthesis of bile salts
Conjugated primary bile acids are readily converted to their sodium and potassium salts in
the alkaline bile (pH 7.6-8.4), and are termed bile salts.
Formation of secondary bile acids
Primary bile acids are further metabolized in the intestine by the activity of the intestinal
bacteria. Deconjugation and 7α-dehydroxylation occur, producing the secondary bile acids,
deoxycholic acid, and lithocholic acid.
Enterohepatic Circulation of bile acids
The primary and secondary bile acids are absorbed almost exclusively in the ileum, and
98% to 99% is returned to the liver via the portal circulation. This is known as the
enterohepatic circulation. However, lithocholic acid, because of its insolubility, is not
reabsorbed to any significant extent. Only a small fraction of the bile salts escapes
absorption and is therefore eliminated in the feces. Nonetheless, this represents a major
pathway for the elimination of cholesterol. Each day the pool of bile acids (about 3-5 g) is
cycled through the intestine 6 to 10 times and an amount of bile acid equivalent to that
lost in the feces is synthesized from cholesterol, so that a pool of bile acids of constant
size is maintained.

Biosynthesis and degradation of bile acids

Functions of Bile
Emulsification
Bile salts act like detergents in that they lower surface tension of fats in chyme entering
intestines. This disperses fats in to fine particles, so that the surface area for contact with
pancreatic lipase is greatly increased. This process, known as emulsification, is essential
for the digestion & absorption of fats as well as the absorption of fat soluble vitamins A, D,
E & K.
Neutralization of acid
Bile has a normal pH above 7, and therefore assists pancreatic juice in neutralizing acid
chyme.
Excretion
Many substances are removed from the body through bile e.g., cholesterol, bile pigments,
bile acids, drugs, iodine, toxins, Cu, Zn, & Hg.
Clinical Module
Gallstones / Cholelithiasis:
Causes
The actual solubility of cholesterol in bile depends on the relative proportions of
1. Bile salts
2. Cholesterol
3. Phospholipids (lecithin)
The ratio of bile acids, phosphatidylcholine (lecithin) and cholesterol in canalicular bile is
approximately 10:3:1. When there is an abnormality in the relative proportions of the
three components of the micelle, cholesterol precipitates in the gall bladder, forming gall
stones. Solubility also depends on water content of bile.
Clinical Features
 Biliary colic – right upper quadrant pain
 Nausea, vomiting
 Fever
 Distension, flatulence
Treatment
 Cholecystectomy
 Oral administration of chenodeoxycholic acid for patients who are unable to
undergo surgery. It works by dissolving the cholesterol that makes gallstones and
inhibiting production of cholesterol in the liver and absorption in the intestines,
which helps to decrease the formation of gallstones.
 INTESTINAL SECRETIONS
Succus entericus
Succus means “juice”; entericus means “of the intestine”. Succus entericus is secreted by
the glands of Bruner & Lieberkühn.

Properties
It is a thin, colourless / straw coloured fluid
Composition
Total secretion per day is about 1000 ml
 Water – 98-99%
Inorganic Constituents
 Electrolytes – HCO3-
Organic constituents
 Mucus
 Enzymes
Functions of Succus Entericus
Mucus
The only true exocrine secretion from the intestines is highly viscid alkaline mucus from
the Brunner’s gland of the duodenum. It serves as a lubricant & protects the walls of small
intestine from gastric acid. Mucus is also secreted by the crypts of Lieberkühn.
Enzymes
Intestinal secretion is almost devoid of digestive enzymes. The small intestine does
synthesize digestive enzymes, but they are attached to the luminal surface of the
intestinal mucosal cells instead of being secreted directly into the lumen. These are called
as brush border enzymes. The catalytic domains of these enzymes protrude into the
intestinal lumen. Their concentration is highest in the proximal jejunum. The only enzyme
secreted by the small intestine is enterokinase.
1. Enterokinase (enteropeptidase)
It activates trypsinogen which in turn activates all other proteases.
2. Brush Border Enzymes
i. Aminopeptidase: It is an exopeptidase that attacks peptide bonds next to amino
terminal amino acids of polypeptides and oligopeptides.
ii. Dipeptidases: These are of various specificities. Some of the dipeptidases may be
within the intestinal epithelial cells. These enzymes complete the digestion of
dipeptides to free amino acids.
iii. Specific disaccharidases and oligosaccharidases
 Maltase (α-glucosidase): It removes single glucose residue from α (1-4) linked
oligosaccharides and disaccharides starting from the non-reducing ends.
 Sucrase-Isomaltase complex: It is found as the proenzyme on one polypeptide
chain but as active enzymes on separate polypeptides and hydrolyzes sucrose and
1-6 bonds in α-limit dextrins.
 Lactase (β glycosidase): It removes galactose from lactose, but also attacks
cellobiose and other β glycosides. It also has a second catalytic site that splits
glycosylceramide.
 Trehalase: It hydrolyzes disaccharide trehalose
iv. Phosphatase: It removes phosphate from certain organic phosphates e.g. hexose
phosphates and nucleotides.
v. Polynucleotidases: These enzymes split nucleic acids into nucleotides.
vi. Nucleosidases: These enzymes catalyse the phosphorolysis of nucleosides to give the
free nitrogen base plus a pentose phosphate.
vii. Phospholipase: It attacks phospholipids to produce glycerol, fatty acids, phosphoric
acid and bases such as choline.
Clinical Module:
Hereditary deficiencies of the individual disaccharidases have been reported in infants &
children with disaccharide intolerance. Alterations in disaccharide degradation can also be
caused by a variety of intestinal diseases, malnutrition, or drugs that injure the mucosa of
the small intestine.
For example, brush border enzymes are rapidly lost in normal individuals with severe
diarrhoea, causing a temporary acquired enzyme deficiency.
Biochemical Explanation of the Symptoms associated with Disaccharidase Deficiency
Relative disaccharides (maltose, lactose, sucrose) are passed undigested in to the large
intestine. As a consequence of the presence of these osmotically active materials, water is
drawn from the mucosa in to the large intestine, causing osmotic diarrhoea. This is
reinforced by the bacterial fermentation of the remaining carbohydrates to 2 & 3 carbon
compounds, which are also osmotically active. Bacterial action also produces large volume
of CO2 & H2 gas, causing abdominal cramps & flatulence.
 DIGESTION AND ABSORPTION
OVERVIEW
The final result of the action of the digestive enzymes is to convert the foodstuff of the
diet to the forms that can be absorbed. These end products of digestion are:
 Carbohydrates: monosaccharides (principally glucose)
 Proteins: amino acids
 Lipids (TAGs): fatty acids, glycerol, & monoacylglycerol
 Nucleic acids: nucleosides, nitrogen bases, & pentoses
Site of Absorption of Nutrients
Stomach: There is little absorption from the stomach.
 Short & medium chain fatty acids
 Ethanol

Small intestine: About 90% of the ingested foodstuff is absorbed in the small intestine, and
water is absorbed at the same time.

Jejunum

 Monosaccharides, some disaccharides

 Monoacylglycerols, fatty acids, glycerol, cholesterol
 Amino acids, peptides
 Vitamins, folate
 Electrolytes, iron, calcium, water
Ileum
 Bile acids
 Vitamin B12
 Electrolytes, water

Large intestine
 Water
 Electrolytes

There are two pathways for the transport of materials absorbed by the intestines
 The hepatic portal system, which leads directly to the liver, transporting water-
soluble nutrients
 Lymphatic vessels, which lead to the blood by way of the thoracic duct & transport
lipid-soluble nutrients
 DIGESTION & ABSORPTION OF CARBOHYDRATES
Dietary carbohydrates include starch (glycogen from animal), sucrose, lactose, maltose,
glucose, fructose & cellulose.
Starch constitute major portion of dietary carbohydrates. It consists of two types of
polysaccharides i.e.
i. Amylose – straight chain polymer of glucose with α 1→4 linkage
ii. Amylopectin – branched chain polymer of glucose with α 1→6 linkage at
branched points
Digestion:
Digestion of carbohydrates occurs in the oral cavity & small intestines. Amylases catalyze
the hydrolysis of starch (plant) & glycogen (animal).
Salivary Amylase
The digestion of starch begins by salivary amylase which is terminated by acidity of gastric
juice. It acts randomly on the interior α 1→4 glycosidic bonds of amylose, giving rise to
maltose & maltotriose. The action of amylase on amylopectin yields in addition α-limit
dextrins which contain α 1→6 linkage.
Pancreatic Amylase
The chyme is neutralized by HCO 3- of pancreatic juice so that pancreatic amylase
continues the above action.

Intestinal brush border enzymes

The final breakdown of carbohydrates to monosaccharides occurs by the intestinal brush
border enzymes as shown in table. Human lack β (1→4) endoglucosidase, therefore, they
are unable to digest cellulose.
 Polysaccharides

Enzyme Sugar Product s

Lactase Lactose Galactose

(β-galactosidase) Glucose

Sucrase Sucrose Fructose

Glucose

Isomaltase Isomaltose, α-dextrin Glucose

Maltase Maltose Glucose

Maltotriose

Trehalase Trehalose Glucose

Absorption:
The products of carbohydrate digestion are monosaccharides chiefly as hexose (glucose,
fructose, mannose, & galactose) and as pentose sugars (ribose). Different sugars have
different mechanisms of absorption.
Absorption of Glucose & Galactose
Glucose & galactose are absorbed by sodium-dependent process (secondary active sodium-
glucose co-transport). They are carried by the same transport protein, sodium-glucose
transporter (SGLT-1), & compete with each other for intestinal absorption. Once inside the
cell, glucose leaves the cell by facilitated diffusion to enter the blood & sodium by Na +-K+
ATPase pump. Insulin has no effect on glucose absorption from the gut.
The active transport of glucose is inhibited by ouabain (a cardiac glycoside), an inhibitor of
the sodium pump, and by phlorhizin, a known inhibitor of glucose reabsorption in the
kidney tubule. The maximal rate of glucose absorption from the intestine is about 120 g/h.
Absorption of Fructose
Fructose is absorbed by means of facilitated diffusion. Fructose uptake requires a sodium-
independent monosaccharide transporter (GLUT-5) for its absorption.
All three monosaccharides are transported from intestinal mucosal cells in to the portal
circulation by yet another transporter, GLUT-2.

Clinical Module:
1. Lactose Intolerance
In most human beings, lactase activity begins to fall after weaning, & is almost completely
lost by late adolescence, leading to lactose intolerance. The mechanism by which this age
dependent loss of the enzyme occurs is not clear, but it is determined genetically &
represents the reduction in the amount of enzyme protein rather than the modified
inactive enzyme.
More than three quarters of the world’s adults are lactose intolerant. It is particularly
manifested in certain races e.g. most of the African or Asian descent are lactase-deficient
than the individuals of northern European origin.
Causes
There are three types of lactase deficiency:
1. Inherited lactase deficiency
In congenital deficiency of lactase, which is relatively rare, symptoms of intolerance
develop very soon after birth. There is failure to thrive when fed on breast milk or normal
infant formula.
 2. Primary low-lactase activity
This is relatively common syndrome. It is presumed that there is a gradual decline in
activity of lactase in susceptible individuals owing to reduction in expression of the
enzyme – this is not due to lack of lactase mRNA rather a failure in translation appears to
be a likely cause.
3. Secondary low-lactase activity
It is due to intestinal diseases that destroy microvilli e.g.
 Diarrhoea- tropical & non-tropical (celiac) sprue, gastroenteritis
 Drugs that injure the mucosa of the small intestine
 Malnutrition – kwashiorkor
Biochemical explanation of the symptoms associated with lactase deficiency
Lactose is passed undigested in to the large intestine. As a consequence of the presence of
this osmotically active material, water is drawn from the mucosa in to the large intestine,
causing osmotic diarrhoea. This is reinforced by the bacterial fermentation of the
remaining carbohydrates to 2 & 3 carbon compounds, which are also osmotically active.
Bacterial action also produces large volume of CO 2 & H2 gas, causing abdominal cramps &
flatulence.
Clinical features
 Diarrhoea
 Abdominal cramps
 Abdominal distension/flatulence
Diagnosis
 H2 breath test – measurement of H2 gas in the breath
 Oral tolerance test with the lactose
Treatment
 Reduce consumption of milk
 Intake of yogurt & cheese
 Use of lactase treated products e.g. live-culture yogurt (provides β-galactosidase)
 Lactase pills prior to eating
2. Sucrase Deficiency:
There is an inherited deficiency of the disaccharidases sucrase & isomaltase. These two
deficiencies coexist, because sucrase & isomaltase occur together as a complex enzyme.
Symptoms occur in early childhood & are the same as those in lactase deficiency.
 DIGESTION AND ABSORPTION OF PROTEINS
Digestion:
Digestion of proteins takes place in the stomach & small intestine. Few bonds are
accessible to the proteolytic enzymes that catalyze hydrolysis of peptide bonds without
prior denaturation of dietary proteins. Dietary proteins are denatured by heat in cooking &
by the action of gastric acid. Denaturation allows the polypeptide chain to unfold, making
it more accessible to the action of proteases. Proteolytic digestive enzymes are produced
by three different organs i.e. stomach, pancreas and small intestine.
There are two main classes of proteolytic digestive enzymes.
 Endopeptidases
 Exopeptidases
Endopeptidases
These hydrolyze peptide bonds between specific amino acids throughout the molecule.
They are the first enzymes to act, yielding large peptide fragments. Pepsin, trypsin,
chymotrypsin & elastase are endopeptidases.
 Pepsin (gastric enzyme)
Pepsin is stable & active at acidic pH. It is specific for peptide bonds formed by
hydrophobic & aromatic amino acids (Phe, Trp, Tyr, Leu).
 Trypsin (pancreatic enzymes)
Trypsin is specific for peptide bonds of basic amino acids (Arg, Lys).
 Chymotrypsin (pancreatic enzymes)
Chymotrypsin is specific for peptide bonds containing uncharged amino acid residues such
as aromatic amino acid (Phe, Trp, Tyr, Met, Leu)
 Elastase (pancreatic enzymes)
Elastase, in spite of its name, has rather broad specificity in attacking bonds next to small
amino acid residues such (Gly, Ala, Ser).
Exopeptidases
These catalyze the hydrolysis of peptide bonds, one at a time, from the ends of peptides.
These are:
 Carboxypeptidases (A & B), secreted in the pancreatic juice, release amino acids
from the carboxyl terminal.
 Carboxypeptidase A: specific for Vai, Leu, Ile, Ala
 Carboxypeptidase B: specific for Arg & Lys
 Aminopeptidases, brush border enzyme, release amino acids from the amino
terminal. There are two types of aminopeptidases, Aminopeptidase A and N.
The products of exopeptidases are free amino acids, dipeptides & tripeptides.
Dipeptides & tripeptides are further acted upon by intestinal brush border enzymes
dipeptidases & tripeptidases
Dipeptidases & Tripeptidases
These are the brush border enzymes that catalyze the hydrolysis of dipeptides &
tripeptides which are not substrates for amino & carboxypeptidases.
Absorption:
The end product of endopeptidases & exopeptidases is a mixture of free amino acids,
dipeptides, tripeptides & oligopeptides, all of which are absorbed.
Free amino acids are absorbed by sodium dependent active transport (secondary active
transport). There are several different transporters, with specificity for the nature of
amino acid side chain.
Dipeptides & tripeptides enter the brush border of intestinal mucosal cells, where they are
hydrolyzed to free amino acids, which are then transported in to portal vein.
Relatively large peptides may be absorbed intact, either by uptake in to mucosal epithelial
cells (transcellular) or by passing between epithelial cells (paracellular).
Absorption of intact peptides that stimulate antibody responses, cause allergic reactions
and celiac disease is an allergic reaction to wheat gluten (see celiac disease).
Clinical Module:
Hartnup Disease:
There is decrease in the transport of neutral amino acids (monoamino monocarboxylic
acid)
Cause
It is a genetic defect in the sodium coupled transporter that normally mediates absorption
of neutral amino acids from the lumen of small intestine & the proximal tubule of kidney.
Clinical Features
 Impaired intestinal absorption & renal reabsorption of tryptophan limits the
tryptophan availability for niacin biosynthesis & accounts for pellagra like signs &
symptoms (rash, cerebellar ataxia – irregular & jerky muscular movements)
 Neutral amino aciduria (alanine, serine, threonine, valine, leucine, isoleucine,
phenylalanine, tyrosine, tryptophan, glutamine, asparagine)
 Increased excretion of indole derivatives arising from intestinal bacterial
degradation of unabsorbed tryptophan
Treatment
 Regular supplements of niacin
 DIGESTION AND ABSORPTION OF LIPIDS
The major lipids in diet are triacylglycerols (90%) &, to lesser extent, phospholipids,
cholesterol & cholesteryl esters. Fat soluble vitamins (A, D, E & K) are also absorbed
dissolved in lipid micelles.
Digestion:
Digestion by Lingual & Gastric Lipases
Both enzymes are relatively acid-stable. They act mainly on TAGs containing short- &
medium chains (less than 12 C – milk fat)
Digestion by Pancreatic Enzymes
Fat digestion occurs mainly in the small intestine through the action of pancreatic lipase.
Before lipids can be digested by pancreatic enzymes they must be broken down by bile
salts in to small droplets (less than 1 µm), a process known as emulsification.
Emulsification: Emulsification is accomplished by two complementary mechanisms
i. Mechanical mixing due to peristalsis
ii. Use of detergent properties of bile salts
Bile salts interact with the lipid particles & the aqueous duodenal contents, thereby
stabilizing the particles as they become smaller, & preventing them from coalescing.
Emulsification increases the surface area of the hydrophobic lipid droplets so that
enzymes, which work at the interface, can act efficiently.
Following pancreatic enzymes take part in lipid digestion:
 Pancreatic lipase:
The pancreatic lipase acts at the oil-water interface of the finely emulsified lipid droplets
through colipase. Colipase binds to the bile salt-covered triacylglycerol interface. Thus it
anchors the lipase to its triacylglycerol substrate. Colipase is secreted as the zymogen,
procolipase, which is activated by trypsin.
Pancreatic lipase is virtually specific for the hydrolysis of primary ester linkage, i.e., at
position 1 & 3 of TAGs. The end products of triacylglycerol digestion by pancreatic lipase
are 2-monoacylglycerol & fatty acids. This is because of the difficulty of hydrolysis of the
secondary ester linkage in the triacylglycerol by pancreatic lipase.
 Cholesterol esterase:
Most dietary cholesterol is present in free form, with 10-15% present in the esterified
form. These are hydrolyzed by cholesterol esterase in to free cholesterol & a free fatty
acid.
  Phospholipase A2
It is secreted as proenzyme which is activated by trypsin & Ca 2+. It hydrolyzes the ester
bond in the 2 position of glycerophosholipids of both biliary and dietary origin to form
lysophospholipids, which, being detergents, aid emulsification and digestion of lipids.
Absorption:
Free fatty acids, free cholesterol, & 2-monoacylglycerol are the primary products of lipid
digestion. The emulsified products of fat digestion must also become water soluble before
they can be absorbed – achieved by micelle formation.
Micelle Formation
Emulsified products of lipid digestion with bile salts, together with phospholipids &
cholesterol from bile, & fat soluble vitamins, form mixed micelles.
Micelles are disc-shaped clusters of amphipathic lipids that coalesce with their
hydrophobic groups on the inside & their hydrophilic groups on the outside. Micelles are
therefore soluble in the aqueous environment of intestinal lumen.
Micelles facilitates the transport of the products of lipids digestion and fat soluble vitamins
through the unstirred water layer to the brush border membrane, from there they diffuse
into the intestinal epithelial cells, leaving the bile salts in the lumen. Bile salts pass on to
the ileum & enter the enterohepatic circulation.
Short and medium chain length fatty acids do not require the assistance of mixed micelles
for absorption.

a) View from outside (c) diagram from cross section d) diagram of a rod shaped micelle
In Intestinal Mucosal Cells

• 1-monoacylglycerols are hydrolyzed to fatty acids & glycerol by an intestinal lipase

• 2-monoacylglycerols are reconverted to triacylglycerols via the monoacylglycerol

pathway (figure given below).

• Glycerol released in the intestinal lumen is not reutilized but passes into the portal
vein; glycerol released within the epithelium can be reutilized for TAG synthesis

• Long- chain fatty acids are esterified to yield TAG

• Short- & medium-chain triacylglycerols can be absorbed & are then hydrolyzed by
the glycerol ester hydrolase directly in to the hepatic portal vein as free fatty acids.

• The absorbed lysophospholipids together with much of the absorbed cholesterol, are
also reacylated with acyl-CoA to regenerate phospholipids & cholesteryl esters

• Unesterified cholesterol & other sterols are actively transported out of the mucosal
cells into the lumen
The great majority of absorbed lipids, including triacylglycerols, phospholipids, cholesteryl
esters, cholesterol, & fat soluble vitamins generate chylomicrons (form a milky fluid, the
chyle) that are collected by lymphatic vessels & passed to the systemic blood via the
thoracic duct.
Clinical Module:
Malabsorption
Causes
i. Pancreatic enzymes deficiency
 Chronic pancreatitis
 Cystic fibrosis (already discussed)
ii. Bile salt deficiency
 Biliary obstruction
 Hepatic disease
iii. Intestinal
 Celiac disease
 Tropical sprue
Clinical Features
i. Due to retention of non-absorbed nutrients
 Diarrhoea
 Flatulence
 Steatorrhea
 Abdominal discomfort & distension
ii. Due to decreased absorption of nutrients
 Anaemia (iron, folate, vitamin B12 deficiency)
 Glossitis, angualar stomatitis (iron deficiency)
 Osteomalacia, Rickets, osteoporosis (calcium & vitamin D deficiency)
 Oedema (Hypoalbuminemia)
 Bleeding tendency (Vitamin K deficiency)
 Weight loss, growth failure in children
Intestinal Malabsorption Syndrome:
Malabsorption may be caused by a reduction of the absorptive area because of flattened
intestinal villi (villous atrophy) e.g.
 Celiac Disease
 Tropical sprue
Celiac Disease:
Synonyms: Celiac sprue, nontropical sprue, gluten-induced (or sensitive) enteropathy,
idiopathic steatorrhea
Caused by
Celiac disease is caused by sensitivity to protein α-gliadin present in gluten. Gluten is a
storage protein that is present in certain grains such as wheat, rye and barley but not in
oats, corn & rice. α-gliadin is one of the digestive product of gluten. Gliadin produces an
immune & inflammatory response in some people, which can lead to reduced intestinal
mucosal surface, reduced digestive/absorptive capacity, & diarrhoea.
Characterized by
 Malabsorption – a specific lesion of the small intestinal mucosa. As a result the
absorptive surface is markedly reduced resulting in severe maldigestion &
malabsorption. The mucosal lesion consists of
 Flattening of the mucosal surface
 Absence of villi
 Disappearance of the microvilli
 An improvement is seen when gluten containing foods are withdrawn from the diet
Clinical features
*Those of classic malabsorption syndrome (given above)
Clinical symptoms became evident at one year of age with failure to thrive
Diagnosis
 Small intestinal mucosal biopsy
 Antibodies to α-gliadin may be detected in plasma
Treatment
Gluten containing foods should be withdrawn from the diet
Tropical sprue:
Tropical sprue is a chronic acquired disorder
Caused by
 There may be a bacterial cause which responds to broad spectrum antibiotics
(tetracycline) & folic acid
 Occurs only among people who visit or reside in certain tropical areas
Characterized by
 Abnormalities of small bowel structure & function that become progressively more
severe & lead to nutritional deficiency
 Villous atrophy does not respond to gluten free diet
NOTE: In pancreatic steatorrhea, absorptive capacity is normal but fat cannot be digested because
there is deficiency of digestive enzymes whereas, in intestinal malabsorption, fat digestion is normal
but absorption of products of digestion is impaired
 DIGESTION OF DIETARY NUCLEIC ACIDS
Ribonucleases and deoxyribonucleases, secreted by the pancreas, hydrolyze dietary RNA
and DNA primarily to oligonucleotides. Oligonucleotides are further hydrolyzed by
pancreatic phosphodiesterases, producing a mixture of 3'- and 5'-mononucleotides. In the
intestinal mucosal cells, a family of nucleotidases removes the phosphate groups
hydrolytically, releasing nucleosides that are further degraded to free bases. Dietary
purine bases are not used to any appreciable extent for the synthesis of tissue nucleic
acids. Instead, they are generally converted to uric acid in intestinal mucosal cells.
Most of the uric acid enters the blood, and is eventually excreted in the urine. A summary
of this pathway is shown in Figure.
 NORMAL FLORA OF THE INTESTINAL TRACT
At birth intestine is sterile but organisms are soon introduced with food.
In breast fed children:
The intestine contains large number of lactic acid streptococci &lactobacilli (gram +ve)
In bottle fed children:
A more mixed flora exists in the bowel & the lactobacilli are less prominent
In adults:
As food habits develop towards the adult pattern, the bowel flora changes
Stomach
The normal pH of stomach markedly protects against infections. Administration of
cimetidine for peptic ulcer leads to a great increase in microbial flora of the stomach
In upper intestine
Lactobacillli & streptococci and yeast (particularly candida albicans)
In the terminal ileum
The flora is same as in intestine but more in number
In the colon
More than 90% bacterial flora consists of anaerobes e.g.
 Bacteroids species especially B fragilis
 Anaerobic lactobacilli e.g., bifidobacteria
Only 1- 4 % are facultative anaerobes e.g.
 Coliform bacteria - E.coli (gram -ve)
 Enterococci -
 Small number of pseudomonas, lactobacilli, candidae & others
Role of bacterial flora:
Intestinal bacteria are important in
 synthesis of vitamin K
 Conversion of bile pigments & bile acids (primary bile acids to secondary bile acids)
 Absorption of nutrients & breakdown products
 antagonism to microbial pathogens
 Production of ammonia from nitrogenous substrates which is absorbed in portal
circulation where it is rapidly removed by liver. In severe liver impairment this
contributes to ammonia intoxication & hepatic coma

By fermentation & putrefaction

The bacteria produce various gases e.g. CO2, methane, hydrogen, nitrogen & H2S as well as
lactic acid, propionic & butyric acid.
 The bacterial decomposition of phosphatidylcholine may produce choline & related
toxic amines e.g., neurine
 Decarboxylation of amino acids by bacteria produces toxic amines (protamines) e.g.
 Lysine – Cadaverine
 Arginine – Agmatine
 Tyrosine – Tyramine
 Histidine – Histamine
 Ornithine – putriscine
Many of these amines are powerful vasopressor substances
 The amino acid tryptophan undergoes a series of reactions to form indole & methyl
indole (skatole), the substances particularly responsible for the odor of feces
 The amino acid cysteine undergoes a series of reactions to form mercaptans such as
ethyl & methyl mercaptans as well as H 2S
 GIT HORMONES

A variety of peptides are synthesized in the enteroendocrine cells of the stomach, small
intestine and colon.

Followings are the examples of GIT hormones:

 Gastrin
 Cholecystokinin (CCK)
 Secretin
 Gastric inhibitory peptide (GIP)
 Vasoactive intestinal polypeptide (VIP)
 Motilin
 Enkephalins
 Substance P
 Neurotensin
 Entero-glucagon

Gastrin

Site of release

 Enteroendocrine G- cells in the antral part of gastric mucosa and duodenal bulb

Secretory or inhibitory Stimuli

 Stimuli that increase gastrin secretion

i. Gastric distension
ii. Chemical factors (secretagogues) e.g. peptides/amino acids , coffee, alcohol
and calcium
iii. Increased vagal discharge via GRP (gastrin releasing peptide)
 Stimuli that inhibit gastrin secretion
i. HCl
ii. Somatostatin
iii. Secretin, GIP, VIP, glucagon, calcitonin

Actions

 Increases gastric secretions primarily HCl and pepsin

 Opens pyloric sphincter (between stomach and small intestines
  Stimulates growth of the gastric mucosa and also the mucosa of small and large
intestines
 Increases histamine release by stimulating ECL cells

Cholecystokinin (CCK)

Site of release

 Endocrine cells known as I cells in the mucosa of the upper small intestine

Secretory stimuli

 Contents of intestinal mucosa with the products of digestion (particularly proteins

and fats)
 CCK releasing peptide and monitor peptide

Actions

 Causes gallbladder contraction

 Stimulates release of pancreatic enzymes
 Augments the action of secretin in producing secretion of an alkaline pancreatic
juice
 Causes relaxation of sphincter of Oddi (flow of bile and pancreatic juice into the
intestinal lumen)
 Increases the synthesis of enterokinase
 Inhibits gastric emptying
 Enhances the motility of small intestine

Secretin

Site of release

 Secreted by S cells in the glands of the mucosa of the upper portion of small
intestine

Secretory stimulus

 Acid chyme
 Products of protein digestion
Actions:

 Stimulates secretions of bicarbonate by the duct cells of the pancreas and biliary
tract
 Augments the action of CCK
 Inhibits gastric acid secretions
 May cause contraction of pyloric sphincter

Gastric inhibitory peptide (GIP)

 In large doses GIP inhibits gastric secretion and motility, so it was named as gastric
inhibitory peptide
 It is now often called glucose-dependent insulinotropic peptide because of its action
of glucose dependent insulin release

Site of release

 Produced by K cells in the mucosa of duodenum and jejunum

Secretory stimulus

 Stimulated by glucose and fat (especially long chain fatty acids)in the duodenum

Actions

 Stimulates insulin secretion

 Increases insulin synthesis
 Regulates glucose and lipid metabolism

Vaso-active intestinal peptide (VIP)

VIP is found in nerves of GIT and thus is not itself a hormone

Site of release

 Widely expressed in the central and peripheral nervous system

Secretory stimulus

 Neural stimulation
 Mechanical stimulation of gut
Actions

 Stimulates intestinal secretion of electrolytes and hence water

 Relaxation of intestinal smooth muscles including sphincters
 Inhibits gastric acid secretion

Motilin

Site of release

 Enterochromaffin cells and Mo cells in the stomach, small intestine and colon

Actions

 It acts on enteric neurons and causes contraction of smooth muscles in the stomach
and intestines in the period between meals

Enkephalins

Substance P

It is found in endocrine and nerve cells in the gastrointestinal tract and may enter in
circulation. It increases the motility the small intestine.

Neurotensin

Entero-glucagon