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PHYSIOLOGY OF
DIGESTION
 Digestion is a complex of
physical, chemical and
physiological processes, which
break down foodstuffs and
convert them into chemical
compounds capable of being
absorbed by body cells.
Kinds of digestion
Digestion proper
 is carried out by enzymes synthesized by
digestive glands of human
Autolytic digestion
 is performed by enzymes present in
the foodstuffs. For example, breast
milk contains enzymes which cause its
curdling
Symbiontic digestion
 is carried out by enzymes synthesized by symbionts
(microorganisms) present in the digestive tract of a
macroorganism. In this way cellulose is digested in the colon.
This type of digestion is mostly used by herbivores.
Depending on where hydrolysis of
nutrients takes place
Intracellular digestion
 consists in hydrolysis of substances inside cells
by cellular (lysosomal) enzymes. Substances enter
a cell by phagocytosis and pinocytosis.
 intracellular digestion takes place in leukocytes
and in cells of lymphoreticular and histiocytic
system
Extracellular digestion
is subdivided into distant (cavitary) and
contact (parietal, or membrane) digestion.
Distant, or cavitary, digestion occurs in the
cavities of the gastrointestinal tract with the
assistance of enzymes of digestive secretions
at some distance from the place of production
of these enzymes.
Contact, or parietal, digestion (A. Ugolev)
occurs in the glycocalix region of the small
intestine, on the surface of microvilli, with
participation of enzymes fixed on cell
membranes, and ends in absorption (transport
of nutrients across enterocytes into the blood
or lymph).
Functions of Gastrointestinal Tract
 1. Secretory function
 2. Motor function (motility)
 Absorption function (amino acids, glycerol, fatty acids and monosaccharides,
water, salts, medical drugs are absorbed into the blood and lymph)
 4. Incretory, or intrasecretory function consists in release of hormones that
regulate motility, secretion and absorption in the gastrointestinal tract. These
hormones are: gastrin, secretin, cholecystokinin-pancreozymin, motilin, etc.
 5. Excretory function consists in release into the gastrointestinal tract of
metabolites by digestive glands (urea, ammonia, bile pigments), water, heavy
metal salts, medical drugs to be further removed from the body
 6. participation in water-salt metabolism,
 7. local immune reactions,
 8. hematopoiesis,
 9. fibrinolysis
Digestion in Oral Cavity
 Digestion starts in the oral
cavity where food undergoes
mechanical and chemical
processing. Mechanical
processing consists in breakage
of food into smaller pieces,
lubrication of them with saliva
and formation of a bolus of
food. Chemical processing is
done by the enzymes of saliva.
Composition and Properties of Saliva
 Saliva secreted in the mouth is of mixed type with pH in the
range of 6.8-7.4. Salivary glands of an adult human produce 0.5-
2.0 of saliva per day. It contains 99% of water and 1% of a dry
residue consisting of organic and inorganic substances. Inorganic
substances are anions of chlorides, bicarbonates, sulfates,
phosphates; cations of sodium, potassium, calcium, magnesium;
microelements: iron, copper, nickel and others. Organic
substances are mainly proteins. Protein mucous substance mucin
glues individual food particles together to form a bolus of food.
The main salivary enzymes are amylase and maltase which are
active only in the subalkaline environment.
saliva enzymes
 Amylase cleaves polysaccharides (starch, glycogen) to maltose
(disaccharide). Maltase acts on maltose and cleaves it to glucose.
Besides, saliva contains small quantities of other enzymes. They
are: hydrolases, oxyreductases, transferases, proteases,
peptidases, acidic and alkaline phosphatases. Saliva contains
protein substance lysozyme (muramidase) possessing a
bactericidal effect. Food stays in the mouth for only about 15 sec,
and starch does not undergo complete cleavage.
Digestion in Stomach
 The stomach serves as a reservoir of
food. Mechanical processing of food
is provided by motility of the
stomach, chemical processing is
carried out by enzymes of the gastric
juice.
 The stomach serves the following
functions: secretion, motility,
absorption, excretion (of urea, uric
acid, creatinine, heavy metal salts,
iodine, medical substances), incretion
(production of gastrin hormone and
of biogenic amines – histamine),
homeostatic function (regulation of
pH); besides, the stomach
participates in hematopoiesis
(production of the intrinsic factor of
Castle).
Composition and Properties of
Gastric Juice
 The stomach of an adult individual produces 2-2.5 l of
gastric juice per day.
 Gastric juice is acidic with pH in the range of 1.5-1.8. It
contains 99% of water and 1% of the dry residue
consisting of organic and inorganic substances. The main
inorganic component of gastric juice is hydrochloric acid,
which exists in a free or protein-bound form. HCl performs
several functions in the stomach: 1) promotes denaturation
and swelling of proteins preparing them for further
cleavage by pepsins; 2) activates pepsinogens and
converts them into pepsins; 3) creates acidic environment
necessary for action of enzymes of the gastric juice; 4)
supports antibacterial action of gastric juice; 5) provides
normal evacuation of food from the stomach by opening
the pyloric sphincter on the side of the stomach and
closing it on the side of the duodenum; 6) initiates
pancreatic secretion. Besides, gastric juice contains the
following inorganic substances: chlorides, bicarbonates,
sulfates, phosphates, sodium, potassium, calcium,
magnesium and others.
Organic substances of
gastric juice
 Organic substances of gastric juice include
proteolytic enzymes, the most important
being pepsins released in the form of
inactive pepsinogens and activated by
HCL. The optimal pH for proteases is 1.5-
2.0. Proteases cleave proteins into
albumoses and peptones. Gastrixin
hydrolyzes proteins at pH 3.2-3.5. Rennin
(chymosin) causes curdling of milk in the
presence of calcium ions by converting
soluble protein caseinogen into insoluble
casein. Besides, gastric juice contains non-
proteolytic enzymes. Gastric lipase is low-
active and breaks down only emulsified
fats.
 In the stomach hydrolysis of carbohydrates by saliva continues inside the
bolus of food that becomes gradually impregnated with gastric juice but
remains alkaline inside, where salivary enzymes continue their action.
Organic substances include lysozyme that gives gastric juice bactericidal
properties. Gastric mucus containing mucin, protects the mucous
membrane of the stomach against mechanical and chemical factors and
self-digestion. The stomach produces gastromucoprotein, or the intrinsic
factor of Castle which promotes formation of a complex with vitamin B12
required for erythropoiesis. Gastric juice also contains amino acids, urea
and uric acid.
Digestion in Small Intestine
 Composition and Properties of Pancreatic Juice
 The pancreatic juice contains water and a dry portion (0.12%)
represented by inorganic and organic substances. The pancreatic juice
contains Na+, Ca2+, K+, Mg+ cations and Cl-, SO22- and HPO42-
anions. It is especially rich in bicarbonates, which bring its pH up to
7.8-8.5. Enzymes of pancreatic juice are active in subalkaline
environment. These are proteolytic, lipolytic and amylolytic enzymes,
which break down proteins, fats, carbohydrates and nucleic acids.
Alpha-amylase, lipase and nuclease are secreted in the active form,
whereas proteases are secreted in the form of proenzymes. Alpha-
amylase of pancreas cleaves polysaccharides to oligo-, di- and
monosaccharides. Ribo- and deoxyribonucleases cleave nucleic acids.
Pancreatic lipase which is active in the presence of bile acid salts,
cleaves lipids to monoglycerides and fatty acids. Lipids are also
cleaved by phospholipase A and esterase. Hydrolysis of fats is
enhanced in the presence of calcium ions.
 Proteolytic enzymes are secreted in the
form of proenzymes – trypsinogen,
chymotrypsinogen, procarboxypeptidases
A and B, proelastases. Under influence of
enterokinase secreted by the duodenal
mucosa, trypsinogen is converted to
trypsin, which then acts on the remaining
trypsinogen and other propeptidases and
convert them into active enzymes. Trypsin,
chymotrypsin, elastase primarily break the
internal peptide bonds of dietary proteins
and turn them into low-molecular peptides
and amino acids. Carboxypeptidases A and
B cleave C-terminal bonds of proteins and
peptides.
Composition and Properties of Intestinal
Juice
 The daily secretion of intestinal juice in an adult
human is 2-3 liters, with pH ranging from 7.2 to 9.0.
The juice contains water and a dry portion
consisting of inorganic and organic substances.
Inorganic substances include high amounts of
bicarbonates, chlorides, sodium, calcium and
potassium phosphates. Organic substances are
proteins, amino acids, mucus. Intestinal juice
contains more than twenty enzymes, which work at
the final stages of digestion of all nutrients. These
enzymes are: enterokinase, peptidases, alkaline
phosphatase, nuclease, lipase, phospholipase,
amylase, lactase, saccharase.
Composition of Bile
 it is first secreted by the liver and then after it
has been concentrated in the gallbladder
 substances secreted in the bile are bile salts,
which account for about one half of the total
solutes also in the bile.Also secreted or excreted
in large concentrations are bilirubin, cholesterol,
lecithin, and the usual electrolytes of plasma. In
the concentrating process in the gallbladder,
water and large portions of the electrolytes
(except calcium ions) are reabsorbed by the
gallbladder mucosa; essentially all other
constituents, especially the bile salts and the
lipid substances cholesterol and lecithin, are not
reabsorbed and, therefore, become highly
concentrated in the gallbladder bile.
 By far the most potent stimulus for causing the
gallbladder contractions is the hormone
cholecystokinin
Function of Bile Salts in Fat Digestion and
Absorption
 The cholesterol is first converted to cholic acid or
chenodeoxycholic acid in about equal quantities. These acids in
turn combine principally with glycine and to a lesser extent with
taurine to form glyco- and tauroconjugated bile acids. The salts of
these acids, mainly sodium salts, are then secreted in the bile.
 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.
 The bile salts help in the absorption of (1) fatty acids,(2)
monoglycerides,(3) cholesterol, and (4) other lipids from the
intestinal tract. They do this by forming very small physical
complexes with these lipids; the complexes are called micelles, and
they are semi-soluble in the chyme because of the electrical
charges of the bile salts.
Cavitary and Parietal
Digestion in Small
Intestine
 The function of cavitary
digestion is hydrolysis of
high-molecular-weight
substances (polymers) to
oligomers. Further hydrolysis
of these substances occurs in
the region adjacent to the
mucosa and directly on the
mucosa (parietal digestion)
Parietal digestion
 Parietal digestion occurs in the mucous
layers of the glycocalix, in the glycocalix
and on the surface of microvilli. The
mucous layers contain mucus produced
by the intestinal mucosa, desquamated
cells of intestinal epithelium and,
besides, many enzymes of pancreatic
and intestinal juices. Nutrients passing
through the mucous layer, become
exposed to these enzymes. Glycocalix
adsorbs enzymes of the digestive juices
from the gut lumen which participate in
the intermediate stages of hydrolysis of
all the main nutrients
Membrane digestion
 Products of hydrolysis settle on the apical membranes of enterocytes
with the built-in digestive enzymes that perform their own
membrane digestion and finally convert these products into
monomers capable of being absorbed. Close proximity of the
intestinal enzymes built into the membrane and of transport systems
providing absorption, creates favorable conditions for coupling
hydrolysis of nutrients with their absorption.
 Membrane digestion is characterized by a progressive decrease in
secretory activity of epitheliocytes from crypts to the apex of the
intestinal villus. The main process at the apex of the villus is
hydrolysis of dipeptides, while the main process at the base of the
villus is hydrolysis of disaccharides
Digestion in Large Intestine
 Processes occurring in the large intestine include further
concentration of the chyme through absorption of water;
formation of fecal masses and their removal from the intestine. In
the large intestine electrolytes, water-soluble vitamins, fatty acids
and carbohydrates are absorbed.
 Secretory Function of Large Intestine
 Glands of the large intestinal mucosa release a small amount of
juice (pH = 8.5-9.0), which consists mainly of mucus, rejected
epithelial cells and a small amount of enzymes (peptidase, lipase,
amylase, alkaline phosphatase, cathepsin, nuclease), which are
much less active here than in the small intestine. Nevertheless, in
case of some disorders in the upper parts of the digestive tract,
the large intestine can compensate for them by a significant
increase in the secretory capacity. Secretion of juice in the large
intestine is controlled by local mechanisms. Mechanical stimulation
of the intestinal mucosa increases secretion 8-10 fold.
Motility of Digestive
Tract
 Motility takes place in all parts of the
digestive tract and includes grinding of
food (breaking the food into smaller
pieces) in the mouth, mixing and
propelling it along the tract, constriction
and relaxation of sphincters, movements
of villi and microvilli of the small intestine
and removal of indigested food residues.
At the oral and aboral ends of the
gastrointestinal tract motility is provided
by voluntary striated muscles, and in
other parts of the gastrointestinal tract –
by smooth muscles
Gastric Motility
 Peristaltic movements are provided by
contractions of circular muscles. They begin on
the large curvature in the cardial pacemaker
region in close vicinity to the esophagus. The
2nd pacemaker is located in the prepyloric part.
Contractions of muscles of the distal part of
the antrum and of pylorus are systolic
contractions providing emptying of the gastric
contents into the duodenum. Tonic contractions
are caused by a change in the muscle tone.
 An empty stomach maintains a certain tone
and performs periodical contractions (“hungry”
motility) alternating with periods of rest. These
contractions are associated with a sensation of
hunger
Emptying of Chyme into Duodenum
 Gastric contents are emptied into the duodenum in squirts (small portions) by
contractions of stomach muscles and by opening of the pyloric sphincter. The
pyloric sphincter opens reflexly in response to stimulation of receptors of the
gastric mucosa by hydrochloric acid (HCl) present in chyme. After entering the
duodenum with the chyme, HCl stimulates chemoreceptors of the duodenal
mucosa that causes a reflex closure of the pyloric sphincter. After neutralization of
the acid in the duodenum by the alkaline duodenal juice, the pyloric sphincter
opens again.
Motility of Small
Intestine
 Rhythmic segmentation is provided by contraction of circular muscles that form transverse
constrictions (isthmuses) dividing the gut (together with the chyme) into small segments which
facilitates better grinding and mixing of the chyme with the digestive juices.
 Pendulum movements result from alternating contractions of circular and longitudinal muscles
of the intestine, which cause shortenings, or dilations, and lengthenings, or constrictions, of the
gut. This causes back-and-forth movement of the chyme in a pendulum-like manner ensuring its
thorough mixing with digestive juices.
 Peristaltic movements result from coordinated contractions of circular and longitudinal muscles.
Contraction of circular muscles of the upper section of the gut squeezes the chyme out into the
lower part, which is simultaneously dilated by contraction of longitudinal muscles. Peristaltic
movements propel the chyme further down the intestine.
Motility of Small Intestine
 All contractions occur with the underlying basal
tone of the intestinal wall. Absence of muscle
tone (atonia) in paresis makes any contractions
of the intestine impossible. Besides, the whole
process of digestion is accompanied by
continuous contractions and relaxations of the
gut villi which provides their continuous coming
into contact with new portions of chyme and
facilitates absorption of nutrients and outflow of
lymph.
Motility of Large Intestine
 Motility of the large intestine functions to
accumulate the chyme and to periodically remove
it from the intestine. Besides, motility of the colon
provides absorption of water. In the colon the
following kinds of contractions occur: peristaltic,
antiperistaltic, propulsive, pendulum contractions,
rhythmic segmentation. The outer layer of muscles
is arranged in strips and maintains a constant tone.
Contractions of separate portions of the circular
muscular layer form folds and swellings (haustra).
Haustration waves slowly sweep along the colon.
Three to four times a day a strong propulsive
peristalsis (mass movement) occurs that propels
the chyme in the distal direction
Absorption
 Absorption is transport of digested substances from the cavity of
the gastrointestinal tract into the blood, lymph and extracellular
space.
 In the mouth absorption is insignificant, since the food does not
stay long there, although some substances, e.g., potassium
cyanide, some medical drugs (essential oils, validol, nitroglycerin,
etc.) are absorbed directly from the mouth and very rapidly enter
the circulation, bypassing the intestine and the liver. This
peculiarity is used for introduction of medical drugs. In the
stomach some amino acids, a small amount of glucose, water
with dissolved mineral salts and alcohol are absorbed.
Absorption
 Products of hydrolysis of proteins, lipids and carbohydrates are primarily absorbed in the small
intestine. Proteins are absorbed in the form of amino acids, carbohydrates – in the form of
monosaccharides, fats – in the form of glycerol and fatty acids. Water-insoluble fatty acids are
absorbed with assistance of watersoluble salts of bile acids.
 Absorption from the large intestine is insignificant: glucose, amino acids, chlorides, mineral
salts, fatty acids and fat-soluble vitamins A, D, E, K are absorbed in small quantities, but water
is absorbed very intensively which is important for formation of feces.
 From the rectum, like from the mouth, substances are directly absorbed into the blood
Absorption
 Absorption depends on the area of the absorbing surface, which is
especially large in the small intestine due to existence of folds, villi
and microvilli. Thus, 1 mm2 of intestinal mucosa contains 30-40 villi,
and each enterocyte carries 17004000 microvilli. A villus is a
microorgan containing muscular contractile elements, blood and
lymph microvessels and a nerve ending. Microvilli are covered with a
layer of glycocalyx 0.1 µm thick formed by mucopolysaccharide fibers
interconnected with calcium cross-bridges. This molecular network is
negatively charged and hydrophilic which permits passage of low-
molecular-weight substances to the microvillus membrane, but holds
back high-molecular-weight substances and xenobiotics. Glycocalyx,
together with the mucus covering the intestinal epithelium, adsorbs
from the gut lumen hydrolytic enzymes necessary for cavitary
hydrolysis of nutrients that are then transported to the microvillus
membrane
 An important part in absorption is played by
contractions of microvilli; in an empty gut the rate of
contractions is low, but in the presence of chyme the
rate of contractions increases to 6 per minute.
Contractions of microvilli are controlled by intramural
nervous system (submucosal, or Meissner’s,
plexuses). Substances extracted from food, glucose,
peptides, some amino acids enhance contractions of
microvilli. Acidic contents of the stomach promote
production of a special hormone in the small intestine
– villikinin, which being present in blood, stimulates
contractions of villi.
Mechanisms of Absorption
 Micromolecules (products of hydrolysis of nutrients,
electrolytes, medical drugs) are absorbed by several
transport mechanisms: 1. passive transport including
diffusion, filtration and osmosis; 2. facilitated diffusion; 3.
active transport.
 Diffusion of substances occurs down their concentration
gradient in the small intestine, blood or lymph. Water,
ascorbic acid, pyridoxin, riboflavin and many medical drugs
are transported across the intestinal mucosa by diffusion.
Filtration is based on the hydrostatic pressure gradient.
Thus, an increase in the intraintestinal pressure up to 8-10
mm Hg twice increases absorption of NaCl solution from
the small intestine
 Water and electrolytes are absorbed down
their osmotic gradients.
 Facilitated diffusion also occurs down the
concentration gradient, but with
participation of special membrane
transporters. This mechanism consumes
no energy and takes less time than simple
diffusion. By facilitated diffusion fructose is
transported.
 Active transport occurs against the
electromechanical gradient even with low
concentration of the given substance in
the gut lumen. The process uses
transporters and consumes energy. The
transporter is mostly Na+ that
participates in absorption of glucose,
galactose, free amino acids, bile acid salts,
bilirubin, some di- and tripeptides.
 Some high-molecular-weight substances are
transported by endocytosis (pinocytosis and
phagocytosis). In this mechanism the membrane of
enterocyte surrounds the absorbed substance with
formation of a vesicle, which is immersed into the
cytoplasm and then moves to the basal surface of the
cell where the contained substance is released from
the vesicle. This mechanism is used for transport of
proteins, immunoglobulins, vitamins and enzymes of
breast milk in newborns.
 Some substances, e.g., water, electrolytes, antibodies
and allergens can pass across the intercellular space.
This kind of transport is called persorption.
Methods to Study Functions of
Gastrointestinal Tract
 Secretory activity is studied by exteriorizing the ducts of glands
outside onto the skin, and by using a fistula method. A fistula is
an artificial communication between the cavity of an organ and
the external environment.
 In 1842 V. Basov first conducted an operation with insertion of a
fistula into the stomach. However, this method did not permit to
obtain pure gastric juice. In 1889 I. Pavlov and E. Shumova-
Simakova developed a method of “fictitious feeding” with
insertion of a fistula with simultaneous transection of the
esophagus (esophagotomy). When the dog was eating, the food
dropped out of the transected esophagus, and the stomach
secreted pure gastric juice which was collected through the
fistula.
Methods to Study Functions of
Gastrointestinal Tract
 Intubation methods (gastric intubation, duodenal
intubation) allow evaluation of the quantity and
composition of secretion both in a fasting stomach and
after stimulation of digestive glands with food or other
agents (histamine, pentagastrin for evaluation of
gastric secretion and magnesia sulphate for
investigation of bile secretion).
 Nowadays, there is a wide use of endoscopic methods
to study the activity of the stomach and intestine.
These methods allow not only “to see” the mucous
membrane, but also to take biopsy material. Tubeless
methods permit to determine concentration in blood
and excretion with urine of substances released from
medical drugs under action of digestive secretions
Methods to Study Functions of
Gastrointestinal Tract
 Motility is also investigated using masticaciography (a
graphic record of chewing motions of the lower jaw) and
electogastrography (record of biocurrents produced by
contractions of the stomach and picked up from the anterior
abdominal wall)
 In clinical practice a wide use is made of X-ray methods of
examination using contrast substances, methods of
radioisotope (radionuclide) scanning, ultrasound scanning of
the liver and the gallbladder.
 Hydrolysis and absorption are evaluated in clinical practice
by biochemical methods
General Principles of Control of Digestive Process
 There are three basic mechanisms of regulation of the
digestive apparatus: reflex, humoral and local. These
mechanisms have different significance in different parts of
the gastrointestinal tract.
 Digestive processes are controlled by sympathetic,
parasympathetic and metasympathetic (enteric) nervous
systems. Enteric innervation is represented by nervous
plexuses, of which the most important for regulation of
digestive functions are myenteric plexuses (Auerbach’s
plexuses) and submucosal plexuses (Meissner’s plexuses).
They participate in realization of local reflexes terminating
on the intramural ganglia. Sympathetic preganglionic
neurons release acetylcholine, enkephalin, neurotensin;
sympathetic postsynaptic neurons release norepinephrine,
acetylcholine, vasoactive intestinal polypeptides (VIPs)
 Parasympathetic preganglionic
neurons release acetylcholine and
enkephalin; postganglionic
parasympathetic neurons release
acetylcholine, enkephalin, VIPs.
Other neurotransmitters in the
stomach and intestine are
substance P, gastrin, somatostatin,
cholecystokinin. Motility and
secretion of the gastrointestinal
tract are stimulated by cholinergic
neurons and inhibited by
adrenergic neurons.
Main Effects of
Gastrointestinal Hormones
 APUD cells – amine precursor uptake and decarboxylation
cells. A class of cells that produce hormones (insulin, ACTC,
glucagon and thyroxin) and amines (dopamine, serotonin
and histamine).
 Gastrin - (G-cells) - Increases secretion of HCl and
pepsinogen in stomach, and of pancreatic juice. Stimulates
motility of stomach, of small and large intestine and of
gallbladder
 Gastron - (G-cells) - Inhibits secretion of gastric juice
 Bulbogastron - (G-cells) - Inhibits secretion and motility of
stomach
 Secretin – (S-cells) - Increases secretion of bicarbonates by
pancreas, inhibits secretion of HCl in stomach, increases
production of bile and secretion in small intestine. Inhibits
motility of stomach, increases motility of intestine and
contraction of pyloric sphincter
 Cholecystokinin –pancreozymin - (I-cells) - Increases motility
of gallbladder and secretion of enzymes by pancreas; inhibits
secretion of HCl in stomach and motility of stomach;
increases secretion of pepsinogen, stimulates motility of
small and large intestine, relaxes Oddi’s sphincter.
Suppresses appetite
Main Effects of Gastrointestinal Hormones
 Gastoinhibitory peptide (GIP) – (K-cells) - Increases glucose-dependent
release of insulin by pancreas. Decreases secretion (of HCl and
pepsinogen) and motility of stomach through release of gastrin.
Stimulates secretion of intestinal juice, suppresses absorption of
electrolytes in small intestine
 Somatostatin - (D-cells) - Inhibits production of secretin, gastric
inhibitory peptide, motilin, gastrin, insulin and glucagon
 Pancreatic peptide (PP) - (PP-cells) - Decreases secretion of enzymes
and of bicarbonates by pancreas, increases proliferation of small
intestine, pancreas, liver and motility of stomach. Participates in
metabolism of carbohydrates and lipids of the mucous membrane
 Substance P - (EC1-cells) - Increases motility of intestine, salivation;
inhibits release of insulin and absorption of Na
 Villikinin - (EC1-cells) - Inhibits secretion of enzymes by pancreas
Secretion of gastric
juice
 passes three phases: reflex (cephalic), gastric and
intestinal phases
 Reflex (cephalic) phase is based on conditioned
and unconditioned reflexes. Conditioned reflex-
based secretion of gastric juice is elicited by
stimulation of olfactory, visual, auditory
receptors (odor, sight of food, sounds associated
with cooking, talks about food). Synthesis of
afferent visual, auditory and olfactory stimuli in
the thalamus, hypothalamus, limbic system and
cerebral cortex increases excitability of neurons
of the bulbar digestive center. This activates
gastric glands, which secrete juice which was
called “priming” (initiating) juice by I. Pavlov
 Unconditioned reflex-based gastric secretion starts at
the moment of entry of food into the mouth, and is
induced by stimulation of receptors of the mouth,
pharynx and esophagus. Impulses from these receptors
travel through the afferent fibers of glossal (V cranial
nerve), glossopharyngeal (IX cranial nerve) and superior
laryngeal nerve (X nerve) to the center of gastric
secretion in the medulla oblongata. From this center
impulses go through efferent fibers of the vagus to
gastric glands with the result of increase in secretion.
The juice secreted in the first phase, possesses high
proteolytic activity and is very important for digestion
because it prepares the stomach for receiving food.
Secretion of gastric juice is inhibited by stimulation of
efferent sympathetic fibers going from the centers of
the spinal cord.
Gastric phase
 Gastric phase of secretion begins at the moment of
entry of food into the stomach. This phase is
mediated by the vagus nerve, enteric nervous system
and humoral factors (Fig.2). Gastric secretion in this
phase is induced by stimulation of receptors of the
gastric mucosa by food. Impulses proceed via afferent
fibers of the vagus to the medulla oblongata and then
to secretory cells via efferent branches of the vagus.
The vagus nerve influences gastric secretion in several
ways: by direct contact with the principal, parietal and
accessory cells of gastric glands (excitation of M-
cholinoreceptors by acetylcholine), through the
enteric nervous system and through humoral factors
since the vagus fibers innervate G-cells of pyloric part
of the stomach which produce gastrin. Gastrin
increases activity of principal cells, but primarily of
parietal cells.
Intestinal phase
 Intestinal phase of secretion starts with emptying of chyme
from the stomach into the intestine. The chyme acts on chemo-,
osmo-, mechanoreceptors of the intestine and reflexly changes
intensity of gastric secretion. Depending on the extent of
hydrolysis of food substances, the stomach receives signals that
increase or, on the contrary, inhibit gastric secretion. Secretion
is stimulated by local and central reflexes realized through the
vagus nerve, enteric nervous system and humoral factors
(release of gastrin by G-cells of the duodenum).
 This phase is characterized by a prolonged latent period and by
long duration. Acidity of gastric juice in this period is low.
Gastric secretion is inhibited by release of secretin and CCK-PS,
which suppress secretion of HCl, but enhance secretion of
pepsinogen. Secretion of HCl is also inhibited by glucagon,
gastric inhibitory peptide (GIP), vasoactive intestinal
polypeptide (VIP), neurotensin, somatostatin, serotonin,
bulbogastron, products of hydrolysis of fats.
Modern Concept of Mechanisms of Hunger
and Satiety
 A demand for nutrients is manifested by sensation of hunger
and is a motivation for search for and intake of food. A complex
of neurons that determine food-seeking behavior and control
digestive functions in animals and humans make up the feeding
center. These neurons can be found in the cerebral cortex, limbic
system, reticular formation, hypothalamus, and form the network
called feeding center. Stimulation of these nuclei in animals
causes hyperphagia (intensive eating of food). Destruction of
these nuclei causes aphagia (rejection of food).
 The center of satiety is located in the ventromedial nuclei of the
hypothalamus. Stimulation of these neurons leads to aphagia,
their destruction leads to hyperphagia. Feeding and satiety
centers operate reciprocally meaning that activation of one
center causes inhibition of the other. Excitation or inhibition of
these nuclei is determined by concentration of nutrients in
blood and by signals received from different receptors.
Theories of Hunger
 Glucostatic theory – sensation of hunger is associated with
decrease in blood glucose level.
 Aminoacidostatic theory – sensation of hunger is associated
with reduction in the concentration of amino acids in blood.
 Lipostatic theory – sensation of hunger is associated with
stimulation of neurons of the feeding center by lack of fatty
acids and triglycerides in blood.
 Metabolic theory – neurons of the feeding center are
stimulated by products of metabolic Krebs’ cycle.
 Thermostatic theory – sensation of hunger is provoked by
decrease in the blood temperature.
 Local theory – sensation of hunger is induced by impulses
coming from mechanoreceptors of the stomach in “hungry”
contractions.
Modern Theory
 A modern theory of the origin of hunger rests not on one, but rather on a
complex of mechanisms underlying the phenomenon of hunger. Satiety
results from stimulation of the neurons of the satiety center. There are
distinguished primary, or sensory, satiety, and secondary, or metabolic,
satiety. Sensory satiety is associated with inhibition of the lateral
hypothalamic nuclei by impulses arriving from receptors of the mouth and
stomach stimulated by food. At the same time impulses from these
receptors stimulate neurons of the ventromedial hypothalamic nuclei
which causes mobilization of nutrients from storages into the blood.
Metabolic Satiety
 Metabolic, or true, satiety occurs in 1.5-2 hours after
intake of food when products of hydrolysis of
nutrients have been absorbed into the blood.
Hormones of the gastrointestinal tract also play a role
in initiation of sensations of hunger and satiety.
 Cholecystokinin, somatostatin, bombesin and other
products reduce consumption of food. Pentagastrin,
oxytocin and other substances stimulate sensation of
hunger.
PHYSIOLOGY OF DIGESTION.digistive system

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PHYSIOLOGY OF DIGESTION.digistive system

  • 2.  Digestion is a complex of physical, chemical and physiological processes, which break down foodstuffs and convert them into chemical compounds capable of being absorbed by body cells.
  • 3. Kinds of digestion Digestion proper  is carried out by enzymes synthesized by digestive glands of human Autolytic digestion  is performed by enzymes present in the foodstuffs. For example, breast milk contains enzymes which cause its curdling Symbiontic digestion  is carried out by enzymes synthesized by symbionts (microorganisms) present in the digestive tract of a macroorganism. In this way cellulose is digested in the colon. This type of digestion is mostly used by herbivores.
  • 4. Depending on where hydrolysis of nutrients takes place Intracellular digestion  consists in hydrolysis of substances inside cells by cellular (lysosomal) enzymes. Substances enter a cell by phagocytosis and pinocytosis.  intracellular digestion takes place in leukocytes and in cells of lymphoreticular and histiocytic system Extracellular digestion is subdivided into distant (cavitary) and contact (parietal, or membrane) digestion. Distant, or cavitary, digestion occurs in the cavities of the gastrointestinal tract with the assistance of enzymes of digestive secretions at some distance from the place of production of these enzymes. Contact, or parietal, digestion (A. Ugolev) occurs in the glycocalix region of the small intestine, on the surface of microvilli, with participation of enzymes fixed on cell membranes, and ends in absorption (transport of nutrients across enterocytes into the blood or lymph).
  • 5. Functions of Gastrointestinal Tract  1. Secretory function  2. Motor function (motility)  Absorption function (amino acids, glycerol, fatty acids and monosaccharides, water, salts, medical drugs are absorbed into the blood and lymph)  4. Incretory, or intrasecretory function consists in release of hormones that regulate motility, secretion and absorption in the gastrointestinal tract. These hormones are: gastrin, secretin, cholecystokinin-pancreozymin, motilin, etc.  5. Excretory function consists in release into the gastrointestinal tract of metabolites by digestive glands (urea, ammonia, bile pigments), water, heavy metal salts, medical drugs to be further removed from the body  6. participation in water-salt metabolism,  7. local immune reactions,  8. hematopoiesis,  9. fibrinolysis
  • 6. Digestion in Oral Cavity  Digestion starts in the oral cavity where food undergoes mechanical and chemical processing. Mechanical processing consists in breakage of food into smaller pieces, lubrication of them with saliva and formation of a bolus of food. Chemical processing is done by the enzymes of saliva.
  • 7. Composition and Properties of Saliva  Saliva secreted in the mouth is of mixed type with pH in the range of 6.8-7.4. Salivary glands of an adult human produce 0.5- 2.0 of saliva per day. It contains 99% of water and 1% of a dry residue consisting of organic and inorganic substances. Inorganic substances are anions of chlorides, bicarbonates, sulfates, phosphates; cations of sodium, potassium, calcium, magnesium; microelements: iron, copper, nickel and others. Organic substances are mainly proteins. Protein mucous substance mucin glues individual food particles together to form a bolus of food. The main salivary enzymes are amylase and maltase which are active only in the subalkaline environment.
  • 8. saliva enzymes  Amylase cleaves polysaccharides (starch, glycogen) to maltose (disaccharide). Maltase acts on maltose and cleaves it to glucose. Besides, saliva contains small quantities of other enzymes. They are: hydrolases, oxyreductases, transferases, proteases, peptidases, acidic and alkaline phosphatases. Saliva contains protein substance lysozyme (muramidase) possessing a bactericidal effect. Food stays in the mouth for only about 15 sec, and starch does not undergo complete cleavage.
  • 9. Digestion in Stomach  The stomach serves as a reservoir of food. Mechanical processing of food is provided by motility of the stomach, chemical processing is carried out by enzymes of the gastric juice.  The stomach serves the following functions: secretion, motility, absorption, excretion (of urea, uric acid, creatinine, heavy metal salts, iodine, medical substances), incretion (production of gastrin hormone and of biogenic amines – histamine), homeostatic function (regulation of pH); besides, the stomach participates in hematopoiesis (production of the intrinsic factor of Castle).
  • 10. Composition and Properties of Gastric Juice  The stomach of an adult individual produces 2-2.5 l of gastric juice per day.  Gastric juice is acidic with pH in the range of 1.5-1.8. It contains 99% of water and 1% of the dry residue consisting of organic and inorganic substances. The main inorganic component of gastric juice is hydrochloric acid, which exists in a free or protein-bound form. HCl performs several functions in the stomach: 1) promotes denaturation and swelling of proteins preparing them for further cleavage by pepsins; 2) activates pepsinogens and converts them into pepsins; 3) creates acidic environment necessary for action of enzymes of the gastric juice; 4) supports antibacterial action of gastric juice; 5) provides normal evacuation of food from the stomach by opening the pyloric sphincter on the side of the stomach and closing it on the side of the duodenum; 6) initiates pancreatic secretion. Besides, gastric juice contains the following inorganic substances: chlorides, bicarbonates, sulfates, phosphates, sodium, potassium, calcium, magnesium and others.
  • 11. Organic substances of gastric juice  Organic substances of gastric juice include proteolytic enzymes, the most important being pepsins released in the form of inactive pepsinogens and activated by HCL. The optimal pH for proteases is 1.5- 2.0. Proteases cleave proteins into albumoses and peptones. Gastrixin hydrolyzes proteins at pH 3.2-3.5. Rennin (chymosin) causes curdling of milk in the presence of calcium ions by converting soluble protein caseinogen into insoluble casein. Besides, gastric juice contains non- proteolytic enzymes. Gastric lipase is low- active and breaks down only emulsified fats.
  • 12.  In the stomach hydrolysis of carbohydrates by saliva continues inside the bolus of food that becomes gradually impregnated with gastric juice but remains alkaline inside, where salivary enzymes continue their action. Organic substances include lysozyme that gives gastric juice bactericidal properties. Gastric mucus containing mucin, protects the mucous membrane of the stomach against mechanical and chemical factors and self-digestion. The stomach produces gastromucoprotein, or the intrinsic factor of Castle which promotes formation of a complex with vitamin B12 required for erythropoiesis. Gastric juice also contains amino acids, urea and uric acid.
  • 13. Digestion in Small Intestine  Composition and Properties of Pancreatic Juice  The pancreatic juice contains water and a dry portion (0.12%) represented by inorganic and organic substances. The pancreatic juice contains Na+, Ca2+, K+, Mg+ cations and Cl-, SO22- and HPO42- anions. It is especially rich in bicarbonates, which bring its pH up to 7.8-8.5. Enzymes of pancreatic juice are active in subalkaline environment. These are proteolytic, lipolytic and amylolytic enzymes, which break down proteins, fats, carbohydrates and nucleic acids. Alpha-amylase, lipase and nuclease are secreted in the active form, whereas proteases are secreted in the form of proenzymes. Alpha- amylase of pancreas cleaves polysaccharides to oligo-, di- and monosaccharides. Ribo- and deoxyribonucleases cleave nucleic acids. Pancreatic lipase which is active in the presence of bile acid salts, cleaves lipids to monoglycerides and fatty acids. Lipids are also cleaved by phospholipase A and esterase. Hydrolysis of fats is enhanced in the presence of calcium ions.
  • 14.  Proteolytic enzymes are secreted in the form of proenzymes – trypsinogen, chymotrypsinogen, procarboxypeptidases A and B, proelastases. Under influence of enterokinase secreted by the duodenal mucosa, trypsinogen is converted to trypsin, which then acts on the remaining trypsinogen and other propeptidases and convert them into active enzymes. Trypsin, chymotrypsin, elastase primarily break the internal peptide bonds of dietary proteins and turn them into low-molecular peptides and amino acids. Carboxypeptidases A and B cleave C-terminal bonds of proteins and peptides.
  • 15. Composition and Properties of Intestinal Juice  The daily secretion of intestinal juice in an adult human is 2-3 liters, with pH ranging from 7.2 to 9.0. The juice contains water and a dry portion consisting of inorganic and organic substances. Inorganic substances include high amounts of bicarbonates, chlorides, sodium, calcium and potassium phosphates. Organic substances are proteins, amino acids, mucus. Intestinal juice contains more than twenty enzymes, which work at the final stages of digestion of all nutrients. These enzymes are: enterokinase, peptidases, alkaline phosphatase, nuclease, lipase, phospholipase, amylase, lactase, saccharase.
  • 16. Composition of Bile  it is first secreted by the liver and then after it has been concentrated in the gallbladder  substances secreted in the bile are bile salts, which account for about one half of the total solutes also in the bile.Also secreted or excreted in large concentrations are bilirubin, cholesterol, lecithin, and the usual electrolytes of plasma. In the concentrating process in the gallbladder, water and large portions of the electrolytes (except calcium ions) are reabsorbed by the gallbladder mucosa; essentially all other constituents, especially the bile salts and the lipid substances cholesterol and lecithin, are not reabsorbed and, therefore, become highly concentrated in the gallbladder bile.  By far the most potent stimulus for causing the gallbladder contractions is the hormone cholecystokinin
  • 17. Function of Bile Salts in Fat Digestion and Absorption  The cholesterol is first converted to cholic acid or chenodeoxycholic acid in about equal quantities. These acids in turn combine principally with glycine and to a lesser extent with taurine to form glyco- and tauroconjugated bile acids. The salts of these acids, mainly sodium salts, are then secreted in the bile.  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.  The bile salts help in the absorption of (1) fatty acids,(2) monoglycerides,(3) cholesterol, and (4) other lipids from the intestinal tract. They do this by forming very small physical complexes with these lipids; the complexes are called micelles, and they are semi-soluble in the chyme because of the electrical charges of the bile salts.
  • 18. Cavitary and Parietal Digestion in Small Intestine  The function of cavitary digestion is hydrolysis of high-molecular-weight substances (polymers) to oligomers. Further hydrolysis of these substances occurs in the region adjacent to the mucosa and directly on the mucosa (parietal digestion)
  • 19. Parietal digestion  Parietal digestion occurs in the mucous layers of the glycocalix, in the glycocalix and on the surface of microvilli. The mucous layers contain mucus produced by the intestinal mucosa, desquamated cells of intestinal epithelium and, besides, many enzymes of pancreatic and intestinal juices. Nutrients passing through the mucous layer, become exposed to these enzymes. Glycocalix adsorbs enzymes of the digestive juices from the gut lumen which participate in the intermediate stages of hydrolysis of all the main nutrients
  • 20. Membrane digestion  Products of hydrolysis settle on the apical membranes of enterocytes with the built-in digestive enzymes that perform their own membrane digestion and finally convert these products into monomers capable of being absorbed. Close proximity of the intestinal enzymes built into the membrane and of transport systems providing absorption, creates favorable conditions for coupling hydrolysis of nutrients with their absorption.  Membrane digestion is characterized by a progressive decrease in secretory activity of epitheliocytes from crypts to the apex of the intestinal villus. The main process at the apex of the villus is hydrolysis of dipeptides, while the main process at the base of the villus is hydrolysis of disaccharides
  • 21. Digestion in Large Intestine  Processes occurring in the large intestine include further concentration of the chyme through absorption of water; formation of fecal masses and their removal from the intestine. In the large intestine electrolytes, water-soluble vitamins, fatty acids and carbohydrates are absorbed.  Secretory Function of Large Intestine  Glands of the large intestinal mucosa release a small amount of juice (pH = 8.5-9.0), which consists mainly of mucus, rejected epithelial cells and a small amount of enzymes (peptidase, lipase, amylase, alkaline phosphatase, cathepsin, nuclease), which are much less active here than in the small intestine. Nevertheless, in case of some disorders in the upper parts of the digestive tract, the large intestine can compensate for them by a significant increase in the secretory capacity. Secretion of juice in the large intestine is controlled by local mechanisms. Mechanical stimulation of the intestinal mucosa increases secretion 8-10 fold.
  • 22. Motility of Digestive Tract  Motility takes place in all parts of the digestive tract and includes grinding of food (breaking the food into smaller pieces) in the mouth, mixing and propelling it along the tract, constriction and relaxation of sphincters, movements of villi and microvilli of the small intestine and removal of indigested food residues. At the oral and aboral ends of the gastrointestinal tract motility is provided by voluntary striated muscles, and in other parts of the gastrointestinal tract – by smooth muscles
  • 23. Gastric Motility  Peristaltic movements are provided by contractions of circular muscles. They begin on the large curvature in the cardial pacemaker region in close vicinity to the esophagus. The 2nd pacemaker is located in the prepyloric part. Contractions of muscles of the distal part of the antrum and of pylorus are systolic contractions providing emptying of the gastric contents into the duodenum. Tonic contractions are caused by a change in the muscle tone.  An empty stomach maintains a certain tone and performs periodical contractions (“hungry” motility) alternating with periods of rest. These contractions are associated with a sensation of hunger
  • 24. Emptying of Chyme into Duodenum  Gastric contents are emptied into the duodenum in squirts (small portions) by contractions of stomach muscles and by opening of the pyloric sphincter. The pyloric sphincter opens reflexly in response to stimulation of receptors of the gastric mucosa by hydrochloric acid (HCl) present in chyme. After entering the duodenum with the chyme, HCl stimulates chemoreceptors of the duodenal mucosa that causes a reflex closure of the pyloric sphincter. After neutralization of the acid in the duodenum by the alkaline duodenal juice, the pyloric sphincter opens again.
  • 25. Motility of Small Intestine  Rhythmic segmentation is provided by contraction of circular muscles that form transverse constrictions (isthmuses) dividing the gut (together with the chyme) into small segments which facilitates better grinding and mixing of the chyme with the digestive juices.  Pendulum movements result from alternating contractions of circular and longitudinal muscles of the intestine, which cause shortenings, or dilations, and lengthenings, or constrictions, of the gut. This causes back-and-forth movement of the chyme in a pendulum-like manner ensuring its thorough mixing with digestive juices.  Peristaltic movements result from coordinated contractions of circular and longitudinal muscles. Contraction of circular muscles of the upper section of the gut squeezes the chyme out into the lower part, which is simultaneously dilated by contraction of longitudinal muscles. Peristaltic movements propel the chyme further down the intestine.
  • 26. Motility of Small Intestine  All contractions occur with the underlying basal tone of the intestinal wall. Absence of muscle tone (atonia) in paresis makes any contractions of the intestine impossible. Besides, the whole process of digestion is accompanied by continuous contractions and relaxations of the gut villi which provides their continuous coming into contact with new portions of chyme and facilitates absorption of nutrients and outflow of lymph.
  • 27. Motility of Large Intestine  Motility of the large intestine functions to accumulate the chyme and to periodically remove it from the intestine. Besides, motility of the colon provides absorption of water. In the colon the following kinds of contractions occur: peristaltic, antiperistaltic, propulsive, pendulum contractions, rhythmic segmentation. The outer layer of muscles is arranged in strips and maintains a constant tone. Contractions of separate portions of the circular muscular layer form folds and swellings (haustra). Haustration waves slowly sweep along the colon. Three to four times a day a strong propulsive peristalsis (mass movement) occurs that propels the chyme in the distal direction
  • 28. Absorption  Absorption is transport of digested substances from the cavity of the gastrointestinal tract into the blood, lymph and extracellular space.  In the mouth absorption is insignificant, since the food does not stay long there, although some substances, e.g., potassium cyanide, some medical drugs (essential oils, validol, nitroglycerin, etc.) are absorbed directly from the mouth and very rapidly enter the circulation, bypassing the intestine and the liver. This peculiarity is used for introduction of medical drugs. In the stomach some amino acids, a small amount of glucose, water with dissolved mineral salts and alcohol are absorbed.
  • 29. Absorption  Products of hydrolysis of proteins, lipids and carbohydrates are primarily absorbed in the small intestine. Proteins are absorbed in the form of amino acids, carbohydrates – in the form of monosaccharides, fats – in the form of glycerol and fatty acids. Water-insoluble fatty acids are absorbed with assistance of watersoluble salts of bile acids.  Absorption from the large intestine is insignificant: glucose, amino acids, chlorides, mineral salts, fatty acids and fat-soluble vitamins A, D, E, K are absorbed in small quantities, but water is absorbed very intensively which is important for formation of feces.  From the rectum, like from the mouth, substances are directly absorbed into the blood
  • 30. Absorption  Absorption depends on the area of the absorbing surface, which is especially large in the small intestine due to existence of folds, villi and microvilli. Thus, 1 mm2 of intestinal mucosa contains 30-40 villi, and each enterocyte carries 17004000 microvilli. A villus is a microorgan containing muscular contractile elements, blood and lymph microvessels and a nerve ending. Microvilli are covered with a layer of glycocalyx 0.1 µm thick formed by mucopolysaccharide fibers interconnected with calcium cross-bridges. This molecular network is negatively charged and hydrophilic which permits passage of low- molecular-weight substances to the microvillus membrane, but holds back high-molecular-weight substances and xenobiotics. Glycocalyx, together with the mucus covering the intestinal epithelium, adsorbs from the gut lumen hydrolytic enzymes necessary for cavitary hydrolysis of nutrients that are then transported to the microvillus membrane
  • 31.  An important part in absorption is played by contractions of microvilli; in an empty gut the rate of contractions is low, but in the presence of chyme the rate of contractions increases to 6 per minute. Contractions of microvilli are controlled by intramural nervous system (submucosal, or Meissner’s, plexuses). Substances extracted from food, glucose, peptides, some amino acids enhance contractions of microvilli. Acidic contents of the stomach promote production of a special hormone in the small intestine – villikinin, which being present in blood, stimulates contractions of villi.
  • 32. Mechanisms of Absorption  Micromolecules (products of hydrolysis of nutrients, electrolytes, medical drugs) are absorbed by several transport mechanisms: 1. passive transport including diffusion, filtration and osmosis; 2. facilitated diffusion; 3. active transport.  Diffusion of substances occurs down their concentration gradient in the small intestine, blood or lymph. Water, ascorbic acid, pyridoxin, riboflavin and many medical drugs are transported across the intestinal mucosa by diffusion. Filtration is based on the hydrostatic pressure gradient. Thus, an increase in the intraintestinal pressure up to 8-10 mm Hg twice increases absorption of NaCl solution from the small intestine
  • 33.  Water and electrolytes are absorbed down their osmotic gradients.  Facilitated diffusion also occurs down the concentration gradient, but with participation of special membrane transporters. This mechanism consumes no energy and takes less time than simple diffusion. By facilitated diffusion fructose is transported.  Active transport occurs against the electromechanical gradient even with low concentration of the given substance in the gut lumen. The process uses transporters and consumes energy. The transporter is mostly Na+ that participates in absorption of glucose, galactose, free amino acids, bile acid salts, bilirubin, some di- and tripeptides.
  • 34.  Some high-molecular-weight substances are transported by endocytosis (pinocytosis and phagocytosis). In this mechanism the membrane of enterocyte surrounds the absorbed substance with formation of a vesicle, which is immersed into the cytoplasm and then moves to the basal surface of the cell where the contained substance is released from the vesicle. This mechanism is used for transport of proteins, immunoglobulins, vitamins and enzymes of breast milk in newborns.  Some substances, e.g., water, electrolytes, antibodies and allergens can pass across the intercellular space. This kind of transport is called persorption.
  • 35. Methods to Study Functions of Gastrointestinal Tract  Secretory activity is studied by exteriorizing the ducts of glands outside onto the skin, and by using a fistula method. A fistula is an artificial communication between the cavity of an organ and the external environment.  In 1842 V. Basov first conducted an operation with insertion of a fistula into the stomach. However, this method did not permit to obtain pure gastric juice. In 1889 I. Pavlov and E. Shumova- Simakova developed a method of “fictitious feeding” with insertion of a fistula with simultaneous transection of the esophagus (esophagotomy). When the dog was eating, the food dropped out of the transected esophagus, and the stomach secreted pure gastric juice which was collected through the fistula.
  • 36. Methods to Study Functions of Gastrointestinal Tract  Intubation methods (gastric intubation, duodenal intubation) allow evaluation of the quantity and composition of secretion both in a fasting stomach and after stimulation of digestive glands with food or other agents (histamine, pentagastrin for evaluation of gastric secretion and magnesia sulphate for investigation of bile secretion).  Nowadays, there is a wide use of endoscopic methods to study the activity of the stomach and intestine. These methods allow not only “to see” the mucous membrane, but also to take biopsy material. Tubeless methods permit to determine concentration in blood and excretion with urine of substances released from medical drugs under action of digestive secretions
  • 37. Methods to Study Functions of Gastrointestinal Tract  Motility is also investigated using masticaciography (a graphic record of chewing motions of the lower jaw) and electogastrography (record of biocurrents produced by contractions of the stomach and picked up from the anterior abdominal wall)  In clinical practice a wide use is made of X-ray methods of examination using contrast substances, methods of radioisotope (radionuclide) scanning, ultrasound scanning of the liver and the gallbladder.  Hydrolysis and absorption are evaluated in clinical practice by biochemical methods
  • 38. General Principles of Control of Digestive Process  There are three basic mechanisms of regulation of the digestive apparatus: reflex, humoral and local. These mechanisms have different significance in different parts of the gastrointestinal tract.  Digestive processes are controlled by sympathetic, parasympathetic and metasympathetic (enteric) nervous systems. Enteric innervation is represented by nervous plexuses, of which the most important for regulation of digestive functions are myenteric plexuses (Auerbach’s plexuses) and submucosal plexuses (Meissner’s plexuses). They participate in realization of local reflexes terminating on the intramural ganglia. Sympathetic preganglionic neurons release acetylcholine, enkephalin, neurotensin; sympathetic postsynaptic neurons release norepinephrine, acetylcholine, vasoactive intestinal polypeptides (VIPs)
  • 39.  Parasympathetic preganglionic neurons release acetylcholine and enkephalin; postganglionic parasympathetic neurons release acetylcholine, enkephalin, VIPs. Other neurotransmitters in the stomach and intestine are substance P, gastrin, somatostatin, cholecystokinin. Motility and secretion of the gastrointestinal tract are stimulated by cholinergic neurons and inhibited by adrenergic neurons.
  • 40. Main Effects of Gastrointestinal Hormones  APUD cells – amine precursor uptake and decarboxylation cells. A class of cells that produce hormones (insulin, ACTC, glucagon and thyroxin) and amines (dopamine, serotonin and histamine).  Gastrin - (G-cells) - Increases secretion of HCl and pepsinogen in stomach, and of pancreatic juice. Stimulates motility of stomach, of small and large intestine and of gallbladder  Gastron - (G-cells) - Inhibits secretion of gastric juice  Bulbogastron - (G-cells) - Inhibits secretion and motility of stomach  Secretin – (S-cells) - Increases secretion of bicarbonates by pancreas, inhibits secretion of HCl in stomach, increases production of bile and secretion in small intestine. Inhibits motility of stomach, increases motility of intestine and contraction of pyloric sphincter  Cholecystokinin –pancreozymin - (I-cells) - Increases motility of gallbladder and secretion of enzymes by pancreas; inhibits secretion of HCl in stomach and motility of stomach; increases secretion of pepsinogen, stimulates motility of small and large intestine, relaxes Oddi’s sphincter. Suppresses appetite
  • 41. Main Effects of Gastrointestinal Hormones  Gastoinhibitory peptide (GIP) – (K-cells) - Increases glucose-dependent release of insulin by pancreas. Decreases secretion (of HCl and pepsinogen) and motility of stomach through release of gastrin. Stimulates secretion of intestinal juice, suppresses absorption of electrolytes in small intestine  Somatostatin - (D-cells) - Inhibits production of secretin, gastric inhibitory peptide, motilin, gastrin, insulin and glucagon  Pancreatic peptide (PP) - (PP-cells) - Decreases secretion of enzymes and of bicarbonates by pancreas, increases proliferation of small intestine, pancreas, liver and motility of stomach. Participates in metabolism of carbohydrates and lipids of the mucous membrane  Substance P - (EC1-cells) - Increases motility of intestine, salivation; inhibits release of insulin and absorption of Na  Villikinin - (EC1-cells) - Inhibits secretion of enzymes by pancreas
  • 42. Secretion of gastric juice  passes three phases: reflex (cephalic), gastric and intestinal phases  Reflex (cephalic) phase is based on conditioned and unconditioned reflexes. Conditioned reflex- based secretion of gastric juice is elicited by stimulation of olfactory, visual, auditory receptors (odor, sight of food, sounds associated with cooking, talks about food). Synthesis of afferent visual, auditory and olfactory stimuli in the thalamus, hypothalamus, limbic system and cerebral cortex increases excitability of neurons of the bulbar digestive center. This activates gastric glands, which secrete juice which was called “priming” (initiating) juice by I. Pavlov
  • 43.  Unconditioned reflex-based gastric secretion starts at the moment of entry of food into the mouth, and is induced by stimulation of receptors of the mouth, pharynx and esophagus. Impulses from these receptors travel through the afferent fibers of glossal (V cranial nerve), glossopharyngeal (IX cranial nerve) and superior laryngeal nerve (X nerve) to the center of gastric secretion in the medulla oblongata. From this center impulses go through efferent fibers of the vagus to gastric glands with the result of increase in secretion. The juice secreted in the first phase, possesses high proteolytic activity and is very important for digestion because it prepares the stomach for receiving food. Secretion of gastric juice is inhibited by stimulation of efferent sympathetic fibers going from the centers of the spinal cord.
  • 44. Gastric phase  Gastric phase of secretion begins at the moment of entry of food into the stomach. This phase is mediated by the vagus nerve, enteric nervous system and humoral factors (Fig.2). Gastric secretion in this phase is induced by stimulation of receptors of the gastric mucosa by food. Impulses proceed via afferent fibers of the vagus to the medulla oblongata and then to secretory cells via efferent branches of the vagus. The vagus nerve influences gastric secretion in several ways: by direct contact with the principal, parietal and accessory cells of gastric glands (excitation of M- cholinoreceptors by acetylcholine), through the enteric nervous system and through humoral factors since the vagus fibers innervate G-cells of pyloric part of the stomach which produce gastrin. Gastrin increases activity of principal cells, but primarily of parietal cells.
  • 45. Intestinal phase  Intestinal phase of secretion starts with emptying of chyme from the stomach into the intestine. The chyme acts on chemo-, osmo-, mechanoreceptors of the intestine and reflexly changes intensity of gastric secretion. Depending on the extent of hydrolysis of food substances, the stomach receives signals that increase or, on the contrary, inhibit gastric secretion. Secretion is stimulated by local and central reflexes realized through the vagus nerve, enteric nervous system and humoral factors (release of gastrin by G-cells of the duodenum).  This phase is characterized by a prolonged latent period and by long duration. Acidity of gastric juice in this period is low. Gastric secretion is inhibited by release of secretin and CCK-PS, which suppress secretion of HCl, but enhance secretion of pepsinogen. Secretion of HCl is also inhibited by glucagon, gastric inhibitory peptide (GIP), vasoactive intestinal polypeptide (VIP), neurotensin, somatostatin, serotonin, bulbogastron, products of hydrolysis of fats.
  • 46. Modern Concept of Mechanisms of Hunger and Satiety  A demand for nutrients is manifested by sensation of hunger and is a motivation for search for and intake of food. A complex of neurons that determine food-seeking behavior and control digestive functions in animals and humans make up the feeding center. These neurons can be found in the cerebral cortex, limbic system, reticular formation, hypothalamus, and form the network called feeding center. Stimulation of these nuclei in animals causes hyperphagia (intensive eating of food). Destruction of these nuclei causes aphagia (rejection of food).  The center of satiety is located in the ventromedial nuclei of the hypothalamus. Stimulation of these neurons leads to aphagia, their destruction leads to hyperphagia. Feeding and satiety centers operate reciprocally meaning that activation of one center causes inhibition of the other. Excitation or inhibition of these nuclei is determined by concentration of nutrients in blood and by signals received from different receptors.
  • 47. Theories of Hunger  Glucostatic theory – sensation of hunger is associated with decrease in blood glucose level.  Aminoacidostatic theory – sensation of hunger is associated with reduction in the concentration of amino acids in blood.  Lipostatic theory – sensation of hunger is associated with stimulation of neurons of the feeding center by lack of fatty acids and triglycerides in blood.  Metabolic theory – neurons of the feeding center are stimulated by products of metabolic Krebs’ cycle.  Thermostatic theory – sensation of hunger is provoked by decrease in the blood temperature.  Local theory – sensation of hunger is induced by impulses coming from mechanoreceptors of the stomach in “hungry” contractions.
  • 48. Modern Theory  A modern theory of the origin of hunger rests not on one, but rather on a complex of mechanisms underlying the phenomenon of hunger. Satiety results from stimulation of the neurons of the satiety center. There are distinguished primary, or sensory, satiety, and secondary, or metabolic, satiety. Sensory satiety is associated with inhibition of the lateral hypothalamic nuclei by impulses arriving from receptors of the mouth and stomach stimulated by food. At the same time impulses from these receptors stimulate neurons of the ventromedial hypothalamic nuclei which causes mobilization of nutrients from storages into the blood.
  • 49. Metabolic Satiety  Metabolic, or true, satiety occurs in 1.5-2 hours after intake of food when products of hydrolysis of nutrients have been absorbed into the blood. Hormones of the gastrointestinal tract also play a role in initiation of sensations of hunger and satiety.  Cholecystokinin, somatostatin, bombesin and other products reduce consumption of food. Pentagastrin, oxytocin and other substances stimulate sensation of hunger.