Medical Physiology of the GIT:
Mucosa, principles of GIT function, afferent sensory innervation, GI reflexes, motility throughout the GI system, control of stomach emptying, coordination of motility, GI secretions, Gastric events following ingestion of a meal......
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Gastrointestinal physiology
1. GASTROINTESTINAL PHYSIOLOGY
Ingestion of food is controlled by hunger and
appetite. In health the body controls the rate at which
ingested food moves through the GI system, so that
digestion and absorption are optimised. The first
residue from a meal will pass through the GI system
in 7-10 hours, but some may take up to 5 or 6 days to
pass through.
2. Ingested food pass through the mouth, esophagus,
stomach, small intestine, (duodenum, jejunum, and
ileum), and the large intestine (colon) before exiting the
body.
THE GI WALL HAS FOUR LAYERS.
The basic structure of the GIT wall is similar in the
stomach and intestine though with some variations
between different sections of the GIT.
An inner layer—mucosa
a middle layer--- submucosa
An outer layer---muscle
Cover-----------serosa
3. I. THE MUCOSA
The inner lining of the GIT created from;
A. A single layer of epithelial cells
B. Lamina propria, subepithelial connective tissue that
holds the epithelium in place
C. Muscularis mucosa, a thin layer of smooth muscle .
Several modifications have evolved to increase the amount
of surface area that is contained within the lumen.
1st
entire wall is crumpled into folds –the rugae in the
stomach and plicae in the intestine. Intestinal mucosa also
projects into the lumen in small fingerlike extensions-villi
4. Additional surface area is created by tubular
invaginations of the surface that extend down into the
suppository connective tissue. These invaginations are
gastric glands in the stomach and crypts in the
intestine. Some of the deepest invaginations form
secretory submucosal glands that open into the
lumen through ducts
The surface area of each individual cell is increased by
microvilli along apical membrane
5. II. THE SUBMUCOSA
Middle layer composed of connective tissue with
larger blood and lymph vessels. It also contains,
submucosal plexus, (meissner’s) one of the 2 major
nerve networks of the enteric nervous system. The
enteric NS is a unique division of the nervous system
that helps coordinate digestive functions
6. iii. MUSCULATURE
The outer wall of the intestinal tract consists mostly
of 2 layers of smooth muscle, an inner circular layer,
and an outer longitudinal layer. Contraction of the
circular layer decreases the diameter of the lumen ,
and contraction of the longitudinal layer shortens the
tube.
Myenteric plexus (Auerbach’s) which is the second
nerve network of the Enteric NS lies between the two
muscle layers
Iv. THE SEROSA
This is the outer covering of the GIT
7. Principles of GI Function
Neural Control of GI Function
The gut is controlled by its own nervous system the
Enteric nervous system,
Autonomic nervous system (parasympathetic
and sympathetic)
Endocrinal Control of GI Function
Several hormones.
8. ENTERIC NERVOUS SYSTEM
Contains all the neural elements required for complex
integrative function and behaves like a “little brain “ in the
generation and modulation of phasic patterns of neuronal
activity. It programs and regulates all GI functions. The 2
peripheral plexuses of the ENS are
the submucosal (Meissner’s) plexus located within the
submucosa , is more involved with local conditions and
controls local secretion, absorption and local movements
Myenteric (Auerbach’s) plexus located between the circular
and outer longitudinal muscle layer. MOTILITY throughout
the whole gut. Stimulation of the plexus increases the tone
and velocity and intensity of the contractions. Inhibition
helps relax the sphincters
9. The mucosa and epithelium have sensory nerve
endings that feed signals to the both layers of the
enteric plexus as well as sending information back to
the sympathetic pre- vertebral ganglia, the spinal corn
and to the brain stem. Numerous transmitters seem
to be involved, the more important of which are
acetylcholine and norepinephrine. The former excites,
the latter inhibits it.
10. EXTRINSIC NERVES
I. PARASYMPATHETIC FIBERS are supplied by the vagus
nerve and pelvic nerves which are of sacral origin.
Parasympathetic fibers are cholinergic and innervate both
plexuses of the enteric NS. Increased parasympathetic
activity increases smooth muscle activity. Motility and
secretion is increased, there is a reduction in constriction of
sphincters. An increase in parasympathetic activity
promotes digestive and absorptive processes.
The proximal half of the nervous system is innervated from
the cranial parasympathetic nerve fibers via the vagal nerve.
The distal half is innervated via Sacral Parasympathetic
nerves, which gives supply to the sigmoid colon, rectum and
anus, and are important in controlling defecation
11. SYMPATHETIC INNERVATION
The fibers originate in the sympathetic ganglia of T-5 to L-2
and terminate on the enteric nervous plexus, but also a few
nerves terminate in the mucosa it self
SYMPATHETIC FIBERS innervation of the GI is
noradrenergic postganglionic. Increased sympathetic
discharge inhibit acetylcholine secretion from cholinergic
neurons.
Some sympathetic fibers innervate smooth muscle cells
directly and some innervate splanchnic blood vessels and
act to cause vasocostriction, leading to decreased motility
and secretions, increase in constriction of sphincters.
12. Afferent Sensory Innervation
Numerous afferent sensory fibers innervate the gut.
Some have their cell bodies in the enteric plexus, and
some in the spinal cord. As well as sending information
concerning irritation and over distension, they can
also pick up the presence of chemical signals in the gut.
80% of the fibers in the vagus nerve are afferent, and
these send signals all the way to the medulla for
processing
13. Gastrointestinal Reflexes
GI reflexes can be considered;
1. Local
2. Regional
3. Systemic
Local reflexes are processed entirely within the enteric system and
control secretion, local motility, and mixing contractions.
Regional reflexes go to the sympathetic ganglia, and are important for
reflexes at a distant, such as the gastro- colic reflex causing
evacuation of the colon, and messages from the intestine to the
stomach to inhibit emptying, the entero- gastric reflex, or the
colono- ilial reflex that inhibits emptying of the ilial contents into the
colon.
Systemic reflexes are processed in the spinal cord or brainstem and
will control overall activity f the GI system, for example pain reflexes
that will inhibit the entire GI system.
14. Hormone Source Stimulus Stomach
Motility and
Secretion
Pancreas Gall bladder
1. Secretin S cells lining
the duodenum
Acid entering
duodenum
Inhibits Stimulates
fluid secretion
(HCO3
-
)
2. CCK Cells lining the
duodenum
Fat and amino
acids entering
duodenum
Inhibits
emptying
Stimulates
enzyme
secretion
1. Contraction
2. Relaxation
sphincter
(Oddi)
3. Gastrin G cells of
stomach
Antrum
Duodenum
Stomach
distension
Parasymp
Peptides
Stomach acid
inhibits
Stimulates
4. GIP Duodenum Fat, CH0,
amino acids
Inhibits
CCK = Cholecystokonin, GIP = Gastric inhibitory peptide (glucose insulintropic peptide)
Note: In a non-acid producing stomach (e.g, chronic gastritis), the reduced negative feedback increases circulating
gastrin.
All four hormones stimulate insulin release.
15. MOTILITY
In the GIT serves 2 purposes
I. Moving food from mouth to the anus
II.Mechanically mixing food to maximize exposure to
digestive enzymes and the absorptive epithelium.
16. Most of the intestinal tract is composed of single unit
muscle whose cells are electrically connected by gap
junctions
Certain intestinal muscle cells act as pacemaker and exhibit
spontaneous depolarization which is similar to pacemaker
of the heart. These generate slow wave potentials at a rate
of 8-11 per minute. When the slow wave reaches threshold, it
fires a battery of AP’s that spread through gap junctions to
adjacent muscle cells. The longitudinal layer of muscle
conducts these action potentials along the length of the GI
tract, creating a wave of contractions.
17. Smooth muscle is unique in that it can contract even
without a significant change in membrane potential.
This occurs when a chemical ligand such as hormones
or drugs combine with membrane receiptors that either
open Ca++ channels in the muscle cell membrane, or
cause release of Ca++ from the SR. This type of
contraction is termed pharmacomechanical coupling.
18. SMOOTH MUSCLE
CHARACTERISTICS
Smooth, also called involuntary or un-striated muscle
is usually found in the walls of the hollow organs, and
have many unique characteristics. Contraction of
these cells is due an influx of Ca++ ions. In the gut
three types of contraction are seen;
Tonic sustained contractions such as occur in
sphincters
Peristaltic contractions
Segmental contractions
By a variety of these contractions, food and chyme is
moved through the bowel.
19. TONIC, SUSTAINED CNTRACTION
These type of contractions occur in rings or bands of
muscles- sphincters that separate different sections of
the digestive system.
There are several sphincters , upper and lower esophageal
sphincters which close off the 2 ends of esophagus
-the pyloric sphincter located between the stomach and
the small intestine.
-the sphincter of oddi- which controls the flow of bile and
pancreatic juices into the small intestine
20. -ileocecal sphincter found between the small intestine
and the large intestines.
-internal and external anal sphincters
The upper esophageal and the external anal sphincter
are composed of skeletal muscle, and the remaining 5
are smooth muscles
All sphincters are tonically contracted . When they
relax material is able to pass from one segment of the
GI to another
21. PERISTALTIC CONTRACTIONS
These are progressive waves of contractions that move
from one section of the intestinal tract to another.
-this movement is responsible for the rapid forward
propulsion of material through the tract.
The forward movement of material with peristaltic
contraction occurs at a speed of between 2 and
25 cm/sec
22. In the peristaltic Reflex, peristaltic waves are triggered
in isolated segment of the intestine by distention of the
wall. This reflex is mediated strictly through the enteric
NS- peristalsis is also subject to external control by
hormones, paracrines and ANS
23. SEGMENTAL CONTRACTION
These are mixing contraction that knead material back
and forth without propelling it forward at a very fast
rate . In this segment contraction alternative segments
of intestine contract and relax, propelling material
short distances in both directions.
Segmental contractions – churn the intestines
contracts back and forth mixing them and keeping
them in contact with absorptive epithelium.
24. MECHANICS OF CONTRACTION
Smooth or un-striated muscle cells contract by
altering their shape. They contain numerous actin-
myosin bundles. Some of the strands attach to the cell,
they are all anchored to the dense bodies in the
cytoplasm of the cell. On activation the actin strands
slide over the myosin causing shortening of the actin-
myosin bundle.
25. MOTILITY THROUGHOUT THE GI
SYSTEM
The passage of food through the gut, its conversion to
chyme, and finally feces is all under involuntary
control. Only the first part –ingestion and swallowing,
and the last part – defecation are under voluntary
control.
26. MASTICATION
Chewing is extremely important part of the digestive
progress especially for fruits and vegetables as these
have indigestible cellulose coats which must be
physically broken down . Also digestive enzymes only
work on the surfaces of food particles, so the smaller
particle, the more efficient the digestive process
27. SWALLOWING
Swallowing is coordinated by the swallowing or
deglutition center located in the lower pons. Impulses
are carried by the Trigeminal, Glossopharangeal, and
Vagus nerves.
STAGES has 3 stages
The 1st
stage-Oral/buccal voluntary
2nd
stage-pharyngeal
3rd
stage Eosophageal involuntary
28. SWALLOWING
I. The tongue pushes a bolus of food against the soft palate
triggering the swallowing reflex.
II. The soft palate is pulled upwards preventing reflux of
food into the nasal cavities
The vocal cords are strongly approximated
The larynx is pulled upwards, closing the epiglottis,
preventing food entering the trachea. The esophageal
sphincter relaxes.
The muscular wall of the pharynx contracts beginning
superiorly, pushing the food into the esophagus
III.Peristaltic waves assisted by gravity push the food down
the esophagus.
29. ESOPHAGUS
Food is carried down the esophagus by peristaltic
contractions. If these are insufficient to move all the
food, stronger secondary peristaltic waves develop.
These are initiated by both the myenteric plexus and
centrally
The muscle at the lower end of the esophagus thickens
and is called the lower esophageal sphincter. This is
usually tonically contracted, but relaxes when the
peristaltic wave reaches it, allowing passage of food
into the stomach.
30. STOMACH
Food entering the stomach passes into the fundus of
the stomach where it is stored. Weak peritaltic waves
known as mixing waves originate in the upper stomach
and pass down to the antrum. These waves become
stronger as they approach the antrum, and as they
push the food against a closed pylorus they also act as
mixing waves. Food in the antrum of the stomach is
also thoroughly mixed with segmental contractions.
The mixed fluid contents are called chyme, and
amounts of this are pushed through the pylorus into
the duodenum with the stronger peristaltic
contractions.
31. Control of stomach emptying
T he rate of emptying of the stomach is controlled by
various factors originating in the duodenum and stomach,
of which the duodenal factors are the most important.
Gastric factors include increased volume of food in the
stomach and stretching of the stomach wall. The hormone
Gastrin also appears to promote stomach emptying
Duodenal factors serve mainly to inhibit entering , thereby
ensuring that the intestine is not overwhelmed by sudden
influx of acidic chyme. They include nervous reflexes and
hormones. The nerve reflexes are transmitted both by the
enteric nervous system and through extrinsic nerves via the
pre-vertebral sympathetic ganglia.
32. Control of Stomach Emptying
cont..
Factors that inhibit emptying include
Distention of the duodenum
The degree of acidity of the duodenal chyme
The osmolarity of the chyme
Irritation of the duodenum
The reflexes are particularly sensitive to acidity and irritation which
cause rapid inhibition of the stomach emptying
Hormones that inhibit emptying include cholecystokinin, secretin,
Gastric Inhibitory Peptide (GIP) Secretin is secreted in response
to acidity in the duodenum, Cholecytokinin and GIP response to
the presence of fats in the chyme
All these factors ensure that the rate of stomach emptying is limited
to what the small intestine can process.
33. SMALL BOWEL
In the small intestine mixing with segmental
contractions continues and the food is slowly passed
through the intestine , finally passing through the ileo-
caecal sphincter to the large intestine, to a large extent
the separation of segmental contractions from
peristaltic contractions is artificial as both serve to
move chyme forward and both add to mixing. Chyme
moves down the small intestine at a rate about 1
cm/min, so will reach the ileocaecal junction in 3-5
hours. It often stays there till the next meal the
gastroileal reflex intensifies peristalsis in the distal
ileum forcing chyme through the ileocaecal valve.
34. Small Bowel cont.
Intensity of peristalsis is controlled by both neuronal
reflexes and hormones. Neuronal factors include
distension of the intestine wall, but also distension of
the stomach will also cause increased small intestine
peristalsis. Both of these reflexes are mediated by the
mesenteric plexus.
Hormonal factors increasing peristalsis include
gastrin, CCK, insulin, motulin and serotonin.
Glucagon and secretin inhibit peristalsis.
35. Ileocaecal valve
T he prime function of the ileoceacal valve is to prevent
reflux of fecal contents into the small intestines. The
valve protrudes into the caecum, thus increased ceacal
pressure will cause occlusion. Furthermore, the muscle
is thickened for a few centimeters from the distal end of
the ileum, and this acts as a functional sphincter.
Increased pressure or irritation in the distal ileum will
cause relaxation, increased caecal pressure or irritation
will cause constriction.
36. LARGE BOWEL and DEFECATION
The principle function of the large intestine is to
remove water and electrolytes from the chyme, and to
store the resultant faeces until it can be eliminated.
In the colon the longitudinal muscle coat is condensed
into three narrow bands called taenia coli.
Thus mixing movements of the circular muscle coat , so
called haustrations predominate . These will also
slowly move the contents towards the rectum.
37. Much of the movement comes from haustrations, but
is the third type of contraction called mass movement
which sends substantial amounts of material forward.
These typically occur 2-3 times a day, usually after a
meal- the so called gastrocolic reflex, and last for
about 20 minutes. They are responsible for the final
formation of the faeces and the filling of the rectum.
Filling of the rectum is a signal for the relaxation of the
Internal anal sphincter. However the External anal
sphincter is under voluntary control.
38. Although the myenteric defecation signal only weakly
relaxes the Internal anal sphincter, the stronger signal
comes from parasympathetic reflexes synapsing in the
sacral cord .These can be inhibited centrally, and when
time to defecate is convenient, the inhibition is
released, and the external anal sphincter, under
voluntary control is relaxed.
The sequence of defecation is often initiated
voluntarily; the epiglotis is closed a deep breath, and
contraction of the abdominal muscles increase intra-
abdominal pressure.
39. Coordination of motility
All these actions are coordinated, and are under
control of hormones, and the autonomic nervous
system as well as the enteric nervous system, the result
is that in health food products and chyme are moved
forward at the optimal rate to allow for efficient
digestion and absorption.
40. GASTROINTESTINAL SECRETIONS
Secretions in the GI tract
About 9 L of fluid pass through the GI system each
day, and only about 2 L are ingested, the rest represent
secretions from the system itself. About 3.5 L is
secreted from the exocrine glands, the salivary glands,
the pancreas and the liver, and other half is secreted by
the epithelial cells of the digestive tract it self. Nearly
all this fluid is absorbed, so the pellets of feces only
contain a significant amount of fluid in diarrhea.
41. To put this in perspective a 70 kg man has 42 L of
fluid, so the secretions represent about a sixth of the
body’s volume. The circulation contains about 3.5
liters, so these secretions represent twice the body’s
circulating volume! Failure of absorption of the
intestinal secretions can thus lead to rapid dehydration
and electrolyte imbalance.
The secretions consist of digestive enzymes, mucous
and substantial amounts of fluid and ions.
43. Types of glands
Several different types of gland and are found in the GIT
Single cell mucous glands and goblet cells.
Pit glands. Invaginations of the epithelia into the
submucosa. In the Small intestine these are called Crypts
of Lieberkuhn
Deep tubular glands. These are found in the stomach – the
gastric glands, and the upper duodenum-Brunners
glands.
Complex glands, the salivary glands, the pancreas, and the
liver. The salivary glands and the pancreas are compound
acinous glands.
44. Mechanisms of stimulation
Stimulation occurs due to local effects; autonomic
stimulation; and hormones
Local effects
The mechanical presence of food causes stimulation
not only locally but also adjacent regions. This may
either be a direct effect, or via the enteric nervous
system.
45. Autonomic Stimulation
Stimulation of parasympathetic nerves serve to
increase secretion. Stimulation of sympathetic nerves
may increase some secretions, but usually diminish
blood flow, which will usually decrease overall
secretion
Hormones
Several different hormones affect secretions
46. Digestive Enzymes
Digestive enzyme are secreted by glandular cells which
will store the enzyme in secretory vesicles until they
are released. These cells are characterised by a robust
rough endoplasmic reticulum and numerous
mitochondria. Passage of materials from the
ribosomes, through the endoplasmic reticulum and
Golgi body to the secretory vesicles takes about 20
minutes.
47. Water and Electrolyte secretions
Glandular secretions must also secrete water
and electrolytes to go along with the organic substances.
In its resting state the membrane resting potential is about
-30 -40 mV.
Neural stimulation causes an influx of -ve chloride ions
decreasing resting potential by 10-20 mV
Sodium ions follow down the electrical gradient. Cell
contents become hyper osmotic
Water follows. Intracellular pressure increases.
Increased pressure opens ports on the apical side of cell
flushing water and electrolytes
48. Mucus Secreting Cells
Mucous is viscous secretion used for protection and
lubrication. It consists mainly of Glycoproteins. It is
made by mucous cells in the stomach and Goblet
cells in the small intestine. Up to 25% of the intestinal
epithelial cells are goblet cells. In the mouth about 70%
of the mucous is secreted by the minor salivary glands.
49. Mucous has the following properties:
Adherent properties, it sticks well to surfaces
Enough body to prevent contact of most food particles
with tissue.
Lubricates well- has a low resistance to slippage
Strongly resistant to digestive enzymes
Neutralizing properties..As well as a buffer like effect,
mucous can also contain large quantities of
bicarbonate.
50. Electrolytes and Fluids
A large portion of the 7 liters is composed of water and ions.
The ionic composition varies from region to region.
The acini of the salivary glands secrete a sodium and
chloride rich secretion, this is then turned to a potassium,
bicarbonate rich secretion as it travels down the lumen and
ducts of the glands.
The oxyntic cells of the stomach secrete hydrochloric acid
The mucous cells of the stomach secrete mucous rich in
bicarbonates
The pancreatic ducts and ductules secrete a solution
rich in bicarbonate
The Crypts of Liberkuhn of the intestine secrete a solution
almost indistinguishable from intestinal fluid
51. MOUTH
The salivary glands consist of the Parotid,
submandibular, and sublingual as well as numerous
smaller buccal glands secreting both serous and
mucoid secretions. The parotid secretions are mainly
serous, the buccal glands mucus, and the sublingual
and submandibular are a mixture of the two. The acini
secrete proteins and a fluid similar in consistency to
interstitial fluid, and the ducts exchange the sodium for
potassium and bicarbonate for chloride leaving saliva
rich in potassium and bicarbonate.
The saliva secrete between 800- 1500 mls a day.
52. The sodium ions are actively reabsorbed, and the
potassium ions are actively secreted at the luminal side
of the cell with an excess of sodium reabsorption
causing a – 70m V gradient. This causes passive
reabsorption of chloride ions. Bicarbonate ions are
both passively exchanged, and actively secreted in
exchange for chloride.
The saliva contains enzyme ptyalin, an amylase for
breaking down carbohydrates as well as lipase.
53. Anti bacterial action of Saliva
The mouth contains numerous bacteria, and an
important function of saliva is oral hygiene. The saliva
contains thiocyanate, a potent antibacterial. The lipase
in saliva will also breakdown bacteria cell walls and
facilitates the passage of thiocyanate into bacteria.
The enzyme lipase is not very important for the
digestion of food, most of fat digestion occurs with the
pancreatic enzymes, but is important in its
antibacterial and oral hygiene role
54. Regulation of Salivary Secretion.
Salivation is controlled via the parasympathetic system
from the salivary nuclei in the brain stem. Factors that
induce salivation include;
Taste stimuli, especially sour taste
Higher centers especially appetite anticipation, smells
and visual clues
In response to signals from the stomach and upper GI
tract, particularly irritating stimuli.
Salivation can also occur as a prelude to vomiting.
55. Esophagus
Esophageal secretions are entirely mucous in
character, and assist passage of food as well as
protecting the lower end of the esophagus from
gastric reflux.
56. Stomach
The adult stomach secretes about 1500 ml in a normal day
consisting of hydrochloric acid, bicarbonate rich mucous,
and the digestive hormone precursor pepsinogen.
Pepsinogen is activated to pepsin by the acidity of the stomach.
G cells also secrete the hormone gastrin.
The gastric pits of the stomach open on to branching glands;
pyloric glands in the antral part of the stomach; gastric or
oxyntic glands in the fundus and body of the stomach.
The parietal or oxyntic cells secrete hydrochloric acid; the peptic
or chief cells secrete pepsinogen; the mucous cells secrete a
bicarbonate rich mucous; and the G cells secrete the hormone
Gastrin.
57. Hydrochloric Acid secretion
The oxyntic or parietal cell contains a large number of
intracellular canaliculi. The pH of the secreted acid is
0.8, and has hydrogen ion concentration of about 3
million times that of arterial blood. To achieve this
level of concentration requires a lot of energy, about
1500 calories per liter of secretion
58. Mechanism of Hcl Secretion
Carbon dioxide and water enter the cell and combine
to form carbonic acid under the influence of enzyme
carbonic anhydrase.
Bicarbonate is actively excreted at the basal side of the
cell and is exchanged for chlorine.
Potassium is exchanged for hydrogen ions at the apical
side of the cell.
Chlorine ions are also actively secreted.
59. The chief cells also secrete intrinsic factor, a substance
essential for the absorption of vitamin B12 in the small
intestine. In chronic gastritis, this may not be secreted,
and the medical condition pernicious anemia will
develop.
Bicarbonate Rich Mucous Secretion
Mucous secretion rich in alkaline bicarbonate protects
the stomach from the acid of the gastric juice.
60. Mechanism of mucous
secretion
Carbon dioxide and water enter the cell and combine to
form carbonic acid under the influence of the enzyme
carbonic anhydrase.
Hydrogen ions are actively secreted on the basal side of
the cell in exchange for sodium.
Bicarbonate ions are actively secreted on the apical or
lumen side of the cell in exchange for chlorine.
61. Secretion and activation of Pepsinogen
Pepsinogen is secreted by the peptic or chief cells of
the gland
When first secreted pepsinogen is inactive, but contact
with acid converts it to the active form pepsin by
splitting pepsinogen molecule. Pepsin functions best
between 1.8 and 3.8
62. Stimulation of Gastric Acid
secretion
The oxyntic cells function in close association with
histamine producing cells called enterochromaffin
cells (ECL),which secrete histamine. These cells
release histamine in direct contact with the oxyntic
glands and promote the secretion of Hcl.
The activation of this complex is under hormonal
(gastrin) and nervous control.
stimulating action
63. Gastrin, secreted by the G cells in the antrum of the
stomach in response to the presence of proteins is the
most potent stimulator of the Histamine /Acid
complex.
The gastrin is not only carried by the blood directly
into the lumens of gastric pits as a direct stimulating
action.
The Histamine/Hcl complex is also activated by
acetylcholine released by the vagus nerve.
Other substances also control Acid secreted, mainly
through their action on Gastrin production
64. Inhibition of Gastric Acid secretion
Factors which slow stomach emptying, which was
discussed when considering motility will also reduce
gastrin production and hence Acid secretion
Regulation of pepsinogen Secretion
Pepsinogen secretion occurs in response to two
signals;
Acetylcholine release from the vagus nerve
Stimulation of peptic cell secretion in response to acid
in the stomach, probably not directly but through the
enteric nervous system.
65. Gastric Events Following
Ingestion of a meal
Digestion is traditionally divided into three phases;
Cephalic Phase
Gastric
Intestinal
66. The Cephalic Phase
Secretion of gastric juice is a continuous process.
Secretion of gastric juice by the stimuli arising from
head region is called cephalic phase.
This phase of gastric secretion is under nervous
control.
During this phase, the gastric secretion occurs without
the presence of food in the stomach.
The gastric juice secreted during this phase is called
appetite juice.
The quantity of the juice is less but it is rich in
enzymes and hydrochloric acid.
67. Cephalic phase is regulated by the nervous
mechanisms which operate through reflex action. Two
types of reflexes occur;
Unconditioned
Conditioned
68. Unconditioned Reflex
Unconditioned reflex is the inborn reflex. When food is
placed in the mouth, it induces salivary secretion.
Simultaneously, gastric secretion also occurs.
Stages of the reflex action
i. The presence of food in the mouth stimulates the
taste buds and other receptors in the mouth
ii. The sensory ( afferent) impulses from mouth pass
via afferent nerve fibers of glossopharyngeal and facial
nerves to the appetite center present in the amygdala of
the hypothalamus.
69. iii. From here, the efferent impulses pass through
dorsal nucleus of the vagus and vagal efferent nerve
fibers to the wall of the stomach
iv. Acetylcholine is secreted at the vagal efferent nerve
endings and stimulates gastric glands to increase the
secretion.
70. Conditioned Reflex
Conditioned reflex is the reflex response acquired by
previous experience. Presence of food in the mouth is
not necessary to elicit this reflex. By this reflex, the
sight , smell, hearing or thought of food which induce
salivary secretion induce gastric secretion also.
Stages of reflex action;
i. Impulses from the special sensory organs (eye, ear,
and nose) pass through afferent fibers of neural circuits
to the cerebral cortex
ii. Thinking of food stimulates the cerebral cortex
(Integrating center) directly
71. iii. From cerebal cortex the impulses pass through
dorsal nucleus of vagus and vagal effents and reach
stomach wall.
iv. The vagal nerve endings secrete acetylcholine. It
stimulates the gastric glands to increase its secretion.
72. The cephalic vagal reflex then causes the stomach to
begin acid secretion.
The parasympathetic neurons innervate;
Parietal Cells, which release gastric acid
Enterochromaffin cells, which release histamine
that triggers gastric acid release
G cells, which release hormone Gastrin.
Gastrin in turn promotes acid release, both directly
and indirectly through histamine release.
73. By the time food reaches the stomach, the lumen has
become acidified. When acid being secreted, mucosal
bicarbonate secretion increases to protect the mucosa
from autodigestion.
74. Gastric Phase
The secretion of gastric juice when the food enters the
stomach is called gastric phase. It is under both
nervous and hormonal control. The gastric juice
secreted during this phase is rich in pepsinogen and
hydrochloric acid.
The mechanisms involved in this phase are;
1 Nervous mechanism through local myenteric reflex
and vagovagal reflex
2 Hormonal mechanism through gastrin.
75. The stimuli, which initiate these mechanisms are;
1 Distention of the stomach
2 Mechanical stimulation of gastric mucosa by bulk of
food
3 Chemical stimulation of gastric mucosa by food
contents
76. 1. Nervous Mechanism
Local myenteric reflex
Local myenteric reflex is the reflex secretion of gastric
juice which is elicited by stimulation of myenteric nerve
plexus in stomach wall. After entering stomach, the
food particles stimulate the local nerve plexus present
in the wall of the stomach. These nerve fibers release
additional acetylcholine, which further stimulate the
gastric glands to secrete a large quantity of gastric
juice. Simultaneously, acetylcholine stimulates G cells
to secrete gastrin
77. Vagovagal reflex( both afferent and efferent impuses
pass through vagus)
Vagovagal reflex is the reflex in which entrance of food
in the stomach causes secretion of gastric juice.
It involves both afferent and efferent vagal fibers.
Presence of food in the stomach stimulates the sensory
(afferent) nerve endings of vagus which generates the
sensory impulses.
The sensory impulses are transmitted to the brainstem
via the sensory fibers of vagus.
Brain stem in turn sends efferent impules through the
motor (efferent ) fibers of the vagus back to the
stomach and cause secretion of gastric juice.
78. 2. Hormonal Mechanism-
Gastrin
Gastrin is released when food enters the stomach. The
mechanism involved in the release of gastrin may be
the local nervous reflex or vagovagal reflex.
The nerve endings release the neurotransmitter called
gastrin releasing peptide which stimulates the G cells
to secrete gastrin.
Gastrin stimulates the secretion of Hcl and pepsinogen
by the gastric glands
79. Intestinal Phase
As chyme enters the small intestine, the intestinal
phase begins. Some reflexes from this phase feed back
to regulate gastric function, serving as a means by
which the intestine influences the delivery of chyme
from the stomach. Presence of acidic chyme in the
duodenum inhibits gastric motility and secretion.
These reflexes are mediated through the enteric
nervous system and through various hormones.
80. Initial stage of intestinal phase
The chyme entering the intestine stimulates the
duodenal mucosa to release gastrin which is
transported to the stomach by the blood.
There (in the stomach) it increases gastric secretion.
81. Later stage of intestinal phase
When food enters the intestine, after the initial stage
of increase in secretion of gastric juice, there is
decrease or complete stoppage of secretion of gastric
juice.
The gastric secretion is inhibited by 2 factors:
1. Enterogastric reflex
2. GI hormones
82. 1. Enterogastric reflex
It is the reflex that inhibits the secretory motor
activities of the stomach due to the distention or
chemical or osmotic irritation of intestinal mucosa.
It is mediated by myenteric nerve plexus of the enteric
plexus and vagus.
2. GI hormones
Presence of chyme in the intestine stimulates the
secretion of many GI hormones from the intestinal
mucosa and other structures.
84. The net result of all three phases of gastric function is
the digestion of proteins in the stomach by pepsin, the
formation of chyme by the action of acid and churning,
and the controlled entry of chyme into the small
intestine so that further digestion and absorption can
take place.
85. FUNCTIONS OF STOMACH
1. Mechanical function
i, Storage Function
Food is stored in the stomach for a long period 3-4hrs
and emptied into the small intestine slowly.
The maximum capacity of the stomach is up to 1.5
liters.
This slow emptying of the stomach provides enough
time for proper digestion and absorption of food
substances in the small intestine.
ii. Formation of chyme
The peritaltic movements of stomach mix gastric juice
and convert it into semisolid material known an
87. Small Intestine
The upper small intestine secretes the hormones
cholecystokinin and secretin, mucous, intestinal
digestive juices, and possibly enzymes. The small
intestine secretes 1800mL daily. The pH7.5 to 8.0
88. Hormone Secretion
Cholecystokinin( CCK) is secreted in response to fats
and peptides in upper small intestines particularly the
duodenum. Actions of CCK include;
Secretion of Pancreatic Enzymes
Contraction of Gallbladder
Relaxation of the sphincter of Oddi
Increased tension in the pyloric sphincter, inhibiting
stomach emptying.
89. Secretin is released in response to the presence of Acid
in the duodenum. Actions of secretin include;
Secretion of copious amounts of bicarbonate rich
fluid by the biliary and gall bladder ducts
Secretion of alkaline rich mucous by the Brunners
glands
Increased tension in the pyloric sphincter, inhibiting
stomach emptying.
90. Brunner’s Glands
The first few centimeters of the duodenum, between
the stomach and the ampulla of Vater, which contain
numerous compound mucous glands called Brunner’s
Glands. These secrete an alkaline rich mucous –pH
between 8.0 and 8.9- in response to various stimuli;
Local irritation and the presence of acid
Vagal stimulation
Gastrointestinal hormones especially secretin
91. Peptic ulcers
Gastric and duodenal ulcers are due mainly to the
breakdown of the protective barrier of alkaline mucous.
The following factors have been identified as causes;
Non Steroidal Anti- inflammatory Drugs
The bacteria Heliobacter Pylori.
Excess acid secretion which can over whelm the
defenses. This can occur particularly in Zollinger-
Ellison syndrome, caused by benign gastrin secreting
tumors which may develop in the stomach or
duodenum
92. It is of interest that Brunner Cell secretion is inhibited
by sympathetic stimulation, thus this may be a
connection between the hyper personality and their
disposition to duodenal ulcers. Less mucous may be
secreted making the duodenum more vulnerable to
stomach acid and stomach pepsin.
93. Crypts of Lieberkuhn
These are located over the entire surface of the small
intestine adjacent to the villi. They secrete a copious
solution almost identical to interstitial fluid.
Mucous cells
The villi are covered with goblet cells. About a quarter
to a half of the villi cells are mucous producing
94. Enzyme secretion
Small intestine secretions that are free of cellular
debris contains almost no enzymes! Thus the enzymes
are either secluded within the cell or possibly they are
attached to the brush border. In any case they are not
flushed down the lumen and they remain local.
Regulation of the small intestine secretions
Secretions are produced almost entirely from local
enteric nervous reflexes in response to local stimuli.
95. Pancreas
The pancreas is a large endocrine and exocrine gland
situated retroperitonealy beneath the stomach. The
microscopic structure of the pancreas is similar to the
salivary glands, the acini secretes enzymes, and the
ductules and ducts secrete large quantities of a
bicarbonate rich juice. These travel down the
pancreatic duct to the second part of the duodenum
where it exits via the Ampulla of Vater protected by
the Sphincter of Oddi.
96. Enzymes secreted by the acini include proteolytic
enzymes, amylases and lipases. The proteolytic
enzymes are all secreted in an inactive form to
prevent auto-digestion.
GROUP ENZYMES SUBSTRATES
Carbohydrates and starch Amylase Starch
Fats Lipase and Colipase
Phospholipase cholesterol
esterase
Trigycerides
Phospholipids
Hydrolysis of Cholesterol
esters
Proteins and Peptides Trypsin (Trypsinogen)
Chymotrypsin
(Chymotrypsinogen)
Carboxypolypeptidase
Peptides
Peptides
Peptides
97. Amylase breaks down carbohydrates (except
Cellulose) to di-saccharides and some tri-saccharides.
Proteolytic enzymes are secreted in the inactive
form to prevent auto digestion, they are converted to
the active form in the small intestine. Trypsin is
activated by enterokinase, secreted by the intestinal
mucosa;
Trypsin then activates Chymotrypsinogen
Lipase converts fats to fatty acids and monoglycerides
Phospholipase splits fatty acids from phospholipids
Cholesterol esterase hydrolyses cholesterol esters.
98. Inhibition and Activation of Enzymes
The cells that secrete proteolytic enzymes also secrete
another substance called trypsin inhibitor. This
prevents any trypsin that may form in the cells or ducts
from becoming active, or activating the other enzymes.
If however the pancreas becomes damaged or the
pancreatic ducts become blocked then the action of
trypsin inhibitor can be overwhelmed, and the very
serious condition acute pancreatitis can develop.
This can also occur if there is registration of intestinal
contents through the Ampulla of Vater.
99. Secretion of Bicarbonate ions
Copious quantities of Bicarbonate ion rich solutions
are secreted by the ducts and ductules of the pancreas
in response to the hormone Secretin.
100. Like gastric secretions, pancreatic secretions can be
divided into three phases;
Cephalic
Gastric
Intestinal
101. Cephalic Phase
The cephalic phase occurs when we think about or
anticipate food. It is mediated by the vagus nerve. It
causes secretion of about 20% of the enzymes, but as
this secretion is not accompanied by fluid secretions,
the enzymes are not flushed out and tend to remain in
the ducts .
102. Gastric phase
This phase occurs when the food enters the stomach,
and again is mediated by neural stimuli. This accounts
for another 5-10%, and again in the absence of serous
flow these secretions tend to remain in the ducts
103. Intestinal phase
This phase occurs when food enters the small intestine
and both serous pancreatic secretion becomes copious
due to the hormone secretin.
104. Regulation of pancreatic
Secretion
These basic stimuli control pancreatic secretion;
Nerves and Hormones
1. Acetylcholine from the parasympathetic nerves of
the vagus and the cholinergic nerves of the enteric
nervous system
2. Cholecystokinin secreted in the duodenum and the
upper small intestine
3. Secretin, also secreted in the duodenum and upper
jejunum
105. Acetylcholine and Cholecystokinin cause secretion of
digestive enzymes, but these tend to remain in the
gland, as there are no secretions to flow them out.
Secretin causes copious secretions of sodium
bicarbonate rich fluids which wash the enzymes into
the small intestines, and also neutralize the Hcl from
the stomach.
Pancreatic enzymes work best between a pHof 7-8.
Sodium bicarbonate has a pH of about 8
106. Biliary System
About 1500 ml of bile daily. The bile is secreted
continuously by the hepatocytes of the liver, and if not
immediately required for digestion are stored in the gall
bladder. In the GB the bile is concentrated up to 15
times. Initially bile fluid has about the same electrolyte
concentration of interstitial fluid, but during
concentration large quantities of electrolytes( but not
Ca++ ions) are reabsorbed.
107. In the presence of fats in the duodenum, CCK is
secreted which causes strong contractions of the gall
bladder and relaxation of the Sphincter of Oddi,
propelling the bile into the small intestine. Vagal
stimulation can have a similary but secondary effect.
Bile contains bile salts, an emulsifying agent necessary
for the digestion and absorption of fats, as well as
bilirubin, cholesterol and fatty acids
108. Composition of Human Hepatic
Duct Bile
Water 97%
Bile Salts 0.7%
Bile Pigments 0.2%
Cholesterol 0.07%
Inorganic Salts 0.7%
Fatty Acids 0.15%
Fat 0.1%
Lecithin 0.1%
109. Bile is continuously secreted by the hepatocytes. The
fluid part of the secretion, a watery substance rich in
sodium and bicarbonate is added by the ducts of the
biliary system, and this secretion is stimulated by
secretin.
110. Bile Salts
Bile salts are the sodium and potassium salts of bile
acids., which are conjugated with glycine or taurine
Formation of Bile Salts
Bile salts are formed from bile acids. There are two
primary bile acids in human, cholic acid and
chenodeoxycholic acid which are formed in the liver
and enter the intestine through bile. Due to the
bacterial action in the intestine the primary bile salts
are conjugated into secondary bile acids.
111. Cholic acid – deoxycholic acid
Chenodeoxycholic acid----- lithocholic acid
Secondary bile acids from the intestine are transported
back to the liver through enterohepatic circulation. In
the liver secondary bile acids are conjugated with
glycine or taurin and form conjugated bile acids
namely glycocholic acid and taurocholic acids. These
bile acids combine with sodium or potassium to form
the salts, sodium or potassium glycocholate and
sodium or potassium taurocholate
112. Recycling of bile salts
Enterohepatic circulation of
bile salts
Bile salts are recycled by the GI System. About 95% of
bile salts are reabsorbed from the terminal ileum and
returned to the liver via the portal system. In addition,
some salts are produced by bacterial action in the large
intestine, and these too are returned to the liver.5% of
the bile salts enter large intestines and they are
converted into deoxycholate and lithocholate which is
excreted in feces.
113. Recycling of bile salts
Enterohepatic circulation of
bile salts.cont….
About 0.2 gm per day of bile salts are manufactured by
the liver, and the total pool of salts is about 3.5gm, so
recycling occurs 6-8 times per day or about twice per
meal. If compromised, and mal absorption of fat
soluble vitamins can occur
114. Functions of bile salts
They are the following:
1. Emulsification of Fats
This is the process by which the fat globules are broken
down into minute droplets and made in the form of
milky emulsion. Fats are made into an emulsion in the
small intestine by action of bile salts. Emulsification
increases the surface area of these lipids making them
much easier to digest. Un emulsified fat usually passes
through the intestines and then it is eliminated in feces.
115. BILE SALTS Contnd..
The lipolytic enzymes of the GI tract can not digest
the fats directly because the fats are insoluble in water
due to the surface tension. The bile salts emulsify the
fat by reducing the surface tension of the fats due to
their detergent action. Because of the reduction in
surface tension, the lipid granules are broken into
minute particles which can be easily digested by
lipolytic enzymes. The emulsification of fats by bile
salts needs the presence of lecithin from bile.
116. 2.Absorption of fats
Bile salts help in the absorption of digested fats from
the intestine into blood. The bile salts combine with
fats and make complexes of called micelles. The fats in
the form of micelles can be absorbed easily
117. 3. Choleretic Action
Bile salts stimulate the secretion of bile from liver. This
action is called choleretic action.
118. 4. Cholagogue Action
Cholagogue is an agent, which increases the release of
bile from GB into the intestine by contraction of the
GB. Bile salts act as cholagogues indirectly by
stimulating the secretion of hormone CCK. This
hormone causes contraction of GB resulting in release
of bile
119. 5.Laxative
Laxative is an agent which induces defecation. Bile
salts act as laxatives by stimulating peristaltic
movements of the intestine.
120. 6. Preventing of Gallstone
Formation
Bile salts prevent the formation of gall stones by
keeping the cholesterol and lecithin in solution. In the
absence of bile salts, cholesterol precipitates along with
lethicin and forms gallstone.
121. Bile pigments
These are the excretory products in the bile. Bilirubin
and biliverdin are the two bile pigments and bilirubin is
the major bile pigment in humans.
The bile pigments are formed during the breakdown of
hemoglobin, which is released from the destroyed RBCs
in the reticuloendothelial system.
122. Formation and excretion of
bile pigments
Stages of formation and circulation of bile pigments
1. The senile erythrocytes are destroyed in
reticuloendothelial system and the hemoglobin is
released from hem.
2. The hemoglobin is broken into globin and heme
3. Heme is split into iron and pigment biliverdin
4. The iron goes to iron pool and is reused
5. The first formed pigment biliverdin is reduced to
bilirubin
123. Formation and excretion of
bile pigments contnd
6. The bilirubin is released into blood from
reticuloendothelial cells.
7. In the blood, the bilirubin is transported by the
plasma protein, albumin. The bilirubin circulating in
the blood is called free bilirubin.
8. Within few hours after entering the circulation, the
free bilirubin is taken up by the liver cells.
9. In the liver, it is conjugated with glucuronic acid to
form conjugated bilirubin
10. Conjugated bilirubin is then excreted into intestine
through bile
124. Fate of conjugated bilirubin
Stages of excretion of conjugated bilirubin
1. In the intestine 50% of the conjugated bilirubin is
converted to urobilinogen by intestinal bacteria. First
the conjugated bilirubin is deconjugated into free
bilirubin which is later reduced into urobilinogen.
2. Remaining 50% of the conjugated bilirubin from the
intestine is absorbed into blood and enters the liver
through portal vein( enterohepatic circulation). From
liver, it is re excreted in bile.
125. Fate of conjugated bilirubin
contnd.
3. Most of the urobilinogen from the intestine enters
the liver via enterohepatic circulation. Later it is re-
excreted through bile.
4. About 5% of the urobolinogen is excreted by kidney
through urine. In urine , due to the exposure to air, the
urobilinogen is converted into urobilin by oxidation.
5. Some of the urobilinogen is excreted in feces as
stercobilinogen. In feces, stercobilinogen is oxidized to
stercobilin
126. Functions of Bile
1. Digestive
2. Absorbtive
3. Excretory
Bile pigments, Heavy metals copper and iron, bacteria
like typhoid bacteria, toxins, cholesterol, lecithin and
alkaline phosphatase
4. Laxative
5. Antiseptic action
Bile inhibits the growth of certain bacteria in the
lumen of intestine by its natural detergent action
127. Functions of Bile contnd
6. Choleretic action
7. Maintenance of pH in GI tract
As bile is highly alkaline, it neutralizes acid chyme
which enters the intestine from the stomach.
8. Prevention of gall stone formation
9. Lubricates
Mucin in bile acts as lubricant
10. Cholagogue action
128. Regulation of Bile Secretion
Bile secretion is a continuous process though the
amount may be less during fasting. It increases three
hours after meals. The secretion of bile from the liver
and release of bile from the gallbladder are influenced
by some chemical factors which are categorized into
three groups:
1. Choleretics
2.Cholagogue
3. Hydrocholeretic agents
129. 1. Choleretics
Substances, which increase the secretion of bile
in the liver, are known as choleretics. The
effective choleretic agents are :
1. Acetycholine
2. Secretin
3. Cholecystokinin
4. Acid chyme in intestine
5. Bile salts
130. Cholagogues
Cholagogue is an agent, which increases the release of bile
from gallbladder into the intestine. It does not influence
the secretion of bile in the liver. The release of bile into
intestine is achieved by causing contraction of gallbladder.
The common cholagogues are;
1. Bile salts
2. Calcium
3. Fatty acids
4. Amino acids
5. Inorganic acids
All these substances stimulate the secretion of
cholecytokinin, which in turn causes contraction of
gallbladder and flow of bile into intestine.
131. Hydrocholeretic Agents
Hydrocholeretic agent is a
substance which causes
secretion of bile from liver with
large amount of water and less
amount of solids. Hydrochloric
acid is a hydrocholeretic agent.
132. JAUNDICE OR ICTERUS
Jaundice or icterus is the condition characterized by yellow coloration
of the skin, mucous membrane and deeper tissues due to the
increased bilirubin level in the blood. The word jaundice is derived
from the French word “jaune” meaning yellow.
The normal serum bilirubin level 0.5-1.5 mg/dL. Jaundice occurs when
biliburin level exceeds 2mg/dL.
TYPES OF JAUNDICE
Jaundice is classified into three types:
1. Prehepatic or hemolytic jaundice
2. Hepatic or hepatocellular jaundice
3. Posthepatic or obstructive jaundice
133. 1.Prehepatic or hemolytic Jaundice.
Hemolytic jaundice is the type of jaundice that occurs
because of excessive destruction of RBCs resulting in
increased blood level of free (unconjugated) biliburin.
In this condition the function of the liver is normal.
But the quantity of biliburin increases enomously.
The liver cells cannot excrete that much biliburin
rapidly. So, it accumulates in the blood resulting in
jaundice.
Formation of urobilinogen also increases resulting in
the excretion of more amount to urobilinogen in
urine.
134. CAUSES
Any condition that causes hemolytic anemia can lead to
hemolytic jaundice. The common causes of hemolytic
jaundice are:
1. Liver failure
2. Renal disorder
3. Hypersplenism
4. Burns
5. Infections such as malaria
6.Hemoglobin abnormalities such as sickle cell anemia or
thalassemia
7. Drugs or chemical substances causing red cell damage
8. Autoimmune diseases
135. 2. Hepatic or Hepatocellular or Cholestatic
Jaundice
This is the type of jaundice that occurs due to the
damage of hepatic cells. Because of the damage, the
conjugated biribulin from liver cannot be excreted
and it returns to blood.
Causes
1. Infection (infective jaundice) by virus resulting in
hepatitis (viral hepatitis)
2.Alcoholic Hepatitis
3. Cirrhosis of liver
4.Exposure to toxic materials
136. 3. Posthepatic or Obstructive or Extrahepatic
Jaundice
This type of jaundice occurs because of the
obstruction of bile flow at any level of the biliary
system. The bile cannot be excreted into small
intestine. So, bile salts and bile pigments enter the
circulation. The blood contains more amount of
conjugated bilirubin
137. COLONIC SECRETIONS
The chief function of the large intestine is absorption
of fluids and formation of feces. About 1-2 liters of fluid
enter the large intestine, and these are mainly
absorbed, only about 200ml being egested daily. The
large intestine secretes about 200ml of fluid a day,
mainly in the form of mucous.
138. Diarrhea
The large intestine can produce large quantities of
water and electrolytes in response to irritation, such as
occurs in infections. This can lead to dehydration, but
also has the beneficial effect of flushing out the
irritants.
139. Digestion and Absorption
Overview
Digestion of food breaks the large molecules into
smaller molecules suitable for absorbing in the small
intestine. This takes place either both in the lumen of
the canal in the chyme and at the epithelial junction of
the cells of the small intestine.
The surface area for absorption is greatly increased by
the christal folds and the villi of the small intestine ,
and the microvilli of the epithelial cells themselves,
which form the brush border.
140. Digestion and Absorption
overview contnd
Small intestinal enzymes are anchored in the apical
margin of the epithelial cell, in the brush border. This
prevents them from being washed down stream with
the chyme.
The enterocyte is specialized for absorption of food
stuffs, it is divided into an apical or luminal surface
where the final digestion and absorption takes place,
and a basal/lateral surface where the products of
digestion are passed into the interstitial fluid. The
transport mechanisms at these two surfaces are quite
different.
141. Digestion and absorption
overview contnd
The apical surface is characterized by numerous
microvilli which greatly increase the surface area
available for absorption. Adjacent to this is an
unstirred layer of mucous that the products of
digestion must penetrate before being absorbed.
The junctions between the cells is very tight, and no
leakage takes place. At the walls of the base of the cells
there is a space continuous with the interstitial space.
142. The enzymes of the small intestine consist of several
peptidases; several enzymes for splitting disaccharides
into monosaccharides and a lipase. These enzymes
operate while the substrates are being absorbed
through the epitheium.
143. Carbohydrate Digestion
Carbohydrates are digested by salivary and pancreatic
enzymes (α-amylases) and by numerous
oligosaccharidases of the small intestinal wall.
TABLES…
144. Carbohydrate Digestion
contnd
The amylase of the salivary gland (Ptyalin) is
inactivated by stomach acid, but when food enters the
stomach it is first stored in the fundus of the stomach
and not mixed with acid, so ptyalin can carry on acting
until mixing with stomach acid takes place, which can
be sometime. By some estimates up to a third of the
carbohydrates are reduced to polysaccharides by the
time chyme leaves the stomach. The other two thirds
are digested by pancreatic amylase.
145. Carbohydrate Digestion
Contnd
Carbohydrates are taken in mainly in the form of plant
carbohydrate (amylose) and animal carbohydrate
(glycogen) together with some sugars, mainly
disaccharides.
Both the parotid and pancreatic amylases hydrolyse
the 1:4 link, but not the terminal 1:4 links or the 1:6
links. This breaks amylose down into disaccharides,
and glycose with its 1:6 linkages into polysaccharides.
The net result of these actions are numerous
disaccharides and polysaccharides. These are broken
down into monosaccharides by enzymes attached to
the enterocytes of the small intestine.
146. Carbohydrate Absorption
Glucose is transported from the lumen into the cell by
a sodium linked co-transporter or symport (SGLT) and
is thus highly dependent on the concentration of
sodium in the lumen. Galactose uses the same
mechanism.
Fructose uses a different mechanism, a facilitated
carrier and is sodium independent.
Glucose is carried across the baso-lateral membrane by
a facilitated carrier
Sugars are absorbed in the capillaries and carried to
the liver.
147. Protein Digestion
Protein and polypeptides are digested by hydrolysis of
the C-N bond.
Proteolytic enzymes are all secreted in an inactive
form, to prevent auto-digestion, and are activated in
the lumen of the gut: by HCl in the case of the stomach
pepsinogen; by the enteropeptidase and trypin in the
case of the pancreatic enzymes.
148. Protein Digestion contnnd
The enzymes are divided into endo and exo-
peptidases. The endopeptidases cleave the polypeptide
at the interior peptide bonds, the exopeptidases
cleave the terminal amino acid. Exopeptidases are
further subclassified into amino peptidases which
cleave off the terminal amino acid at the amine end of
the chain, and carboxypeptidases which cleave off
the terminal amino acid at the carboxyl end of the
chain.
149. Protein Digestion contnnd
Stomach pepsin cleaves interior bond of amino acids,
and is particularly important for its ability to digest
collagen. This is a major constituent of connective
tissue of meat. In the absence of stomach pepsin,
digestion in the small intestine proceeds with difficult.
Stomach pepsin digests about 20% of the proteins, the
rest is digested by pancreatic and small intestine
enzymes.
TABLE…..
150. Protein Absorption
Several different transport systems transport amino
acids into the enterocyte, each dealing with different
groups of amino acids. Most of these are sodium
dependent co- transporters. Di-peptides and tri-
peptides are transported by a H+ ion dependent co –
transporter. In the cell the poly- peptides may be
reduced to amino acids, or they may be carried across
the cell intact.
They are transported across the baso-lateral border by
both co-transporters and facilitated transporters.
151. Protein Absorption cont..
Some large peptides or proteins can be carried across
the cell by transcytosis., this is particularly true in
small children, and is a mechanism whereby the
immunoglobulins in the mother’s milk can be
transferred to the child.
The enterocytes that do this are probably situated in
the Crypts of Lieberkuhn, in infants the openings to the
pits are much larger than in older children and adults
This mechanism also operates , but a lesser extent in
adults.
152. Fats and Cholesterol Digestion
Fats are digested by lipases which hydrolyze the
glycerol- fatty acid bonds. Of particular importance in
fat digestion and absorption are bile salts which
emulsify the fats allowing for their solution as micelles
in chyme, and increasing the surface area on which the
pancreatic lipases can operate. Lipases are found in the
mouth; stomach and the pancreas. Lingual lipase is
inactivated by the acid of the stomach, it has an effect
on the bolus in the fundus of the stomach before it is
mixed with acid, as much as 30% of the fats are
digested by this lipase.
153. Fats and Cholesterol Digestion
Cont…
Gastric lipase is of little importance in humans.
Pancreatic lipase accounts for the majority of fat
digestion, and operates in conjunction with the bile
salts
Bile salts have hydrophobic and hydrophilic side. These
will attach to fat globules, emulsifying them to form
micelles. Micelles are small and because they have
hydrophilic side externally, they effectively allow the
fats to acts like water soluble particles. This allows
them to penetrate the unstirred layer adjacent to the
small intestine epithelium, and to be absorbed.
154. Fat and Cholesterol digestion
cont…
In the absence of bile salts very few fatty acids make it
through this layer and much of the fat will pass
through the gut unabsorbed causing steatorrhea(fatty
stool)
155. Fats and Cholesterol
Absorption
The micelles enable the fatty acids and the cholesterol
to cross the unstirred layer and come in contact with
the brush border, where they easily cross the fat-
soluble cell membrane. A smaller free fatty acids
transfuse across the cell and out at the baso-lateral
border, passing into the capillaries. However most fatty
acids enter the smooth endoplasmic reticulum where
they are repackaged into cholemicrons. These are
carried out of the cell by exocytosis. The cholemicrons
do not enter the capillaries, but pass instead into the
lymphatic system where they carried to the thoracic
duct. The thoracic duct empties into the superior
156. Nucleic Acids
RNA and DNA are broken down by pancreatic enzymes
in the intestinal mucosa. The nucleic bases are
absorbed by active transport, the pentoses are
absorbed with the other sugars.
157. Vitamins and Minerals
Vitamins
The fat soluble vitamins A, D, and E are absorbed in
the upper small intestine. The factors that cause
malabsorption of fat can affect absorption of these
vitamins. Vitamin B12 is absorbed in the ileum and
requires to be bound to Intrinsic factor, a protein
secreted in the stomach, to be absorbed. If intrinsic
factor is missing then Vitamin B12 is not absorbed and
pernicious anemia results.
158. Vitamins and minerals cont…
Of the water soluble vitamins, transport of folate and
B12 across the apical membrane are Na+ independent,
but the other water soluble vitamins are absorbed by
Na+ co- transporters.
Calcium
Between 30 and 80% of the bodies calcium intake is
absorbed. The rate of absorption is dependent on Ca++
needs.
159. Iron
Almost all iron absorption occurs in the ferrous (Fe2+
)
form in the duodenum. The ferric (Fe3+
) form is
converted to ferrous by an enzyme ferric reductase. A
protein transporter designated DMTI is responsible for
the absorption at the apical surface of the enterocyte.
Heme molecules are transported by the HT protein
transporter. At the basal lateral part of the enterocyte
Ferrous ions are transported into the interstitial fluid
by a transporter called ferroportin (FP)
In the plasma the ferrous form is reconverted back to
the ferric form, and bound to an iron transporting
protein Transferrin(TF)
160. Water and Electrolytes
The small intestine is presented with 9 liters, 2
extrinsic, and 7 intrinsic, of fluid a day for
reabsorption. In health all but 200ml of fluid leave the
small intestine and enter the colon.
In the small intestine water is absorbed via the osmotic
effects of nutrient absorption. The osmotic gradient is
established across the intestinal epithelium that
simultaneously drives the movement of water across
tight junctions. The mechanism for nutrient driven
Na+ and water
161. Water and Electrolytes
The junctions between epithelial cells in the large
intestine are much tighter than in the small intestine,
and this precludes leakage of sodium into the lumen.
Most of the fluid and electrolytes are absorbed in the
descending colon.
Although proteins and sugars have usually all been
absorbed by the time fluid reaches the large intestine,
the colon is capable for absorbing these substrates.
Some hard to digest substances, such as beans, can be
digested by colonic bacteria, and these bacteria can
digest small amounts of cellulose.