Gastrointestinal physiology

109,806 views 176 slides Jun 06, 2014
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About This Presentation

Gastrointestinal physiology


Slide Content

The Digestive
System

Digestive
Process
Figure 23.2

GI Tract
External environment for the digestive process
Regulation of digestion involves:
Mechanical and chemical stimuli – stretch receptors,
osmolarity, and presence of substrate in the lumen
Extrinsic control by CNS centers
Intrinsic control by local centers

Receptors of the GI Tract
Mechano- and chemoreceptors respond to:
Stretch, osmolarity, and pH
Presence of substrate, and end products of digestion
They initiate reflexes that:
Activate or inhibit digestive glands
Mix lumen contents and move them along

Nervous Control of the GI Tract
Intrinsic controls
Nerve plexuses near the GI tract initiate short reflexes
Short reflexes are mediated by local enteric plexuses
(gut brain)
Extrinsic controls
Long reflexes arising within or outside the GI tract
Involve CNS centers and extrinsic autonomic nerves

Nervous
Control
of the GI
Tract
Figure 23.4

Secretions of the Stomach
Chyme: ingested food plus stomach secretions
Mucus: surface and neck mucous cells
Viscous and alkaline
Protects from acidic chyme and enzyme pepsin
Irritation of stomach mucosa causes greater mucus
Intrinsic factor: parietal cells. Binds with vitamin B12 and helps it to
be absorbed. B12 necessary for DNA synthesis
HCl: parietal cells
Kills bacteria
Stops carbohydrate digestion by inactivating salivary amylase
Denatures proteins
Helps convert pepsinogen to pepsin
Pepsinogen: chief cells. Packaged in zymogen granules released by
exocytosis. Pepsin catalyzes breaking of covalent bonds in proteins.
G-cells: secrete the hormone gastrin which stimulates HCl secretion
from parietal cells

Hydrochloric Acid Production
1. CO
2
and Cl
-
diffuse from the
blood into the stomach cell.
2. CO
2
combines with H
2
O
to form H
2
CO
3.
3. H
2
CO
3
dissociates into
bicarbonate (HCO3
-
) and H
+
.
4. H
+
combines with Cl
-
in duct
of gastric gland to form HCl
-
.
5. An ATP pump is necessary to
pump the HCl
-
into the duct
since the concentration of
HCl
-
is about a million times
more concentrated in the
duct than in the cytosol of the
cell.

Regulation of Gastric Secretion
Neural and hormonal mechanisms regulate the
release of gastric juice
Stimulatory and inhibitory events occur in three
phases
Cephalic (reflex) phase: prior to food entry
Gastric phase: once food enters the stomach
Intestinal phase: as partially digested food enters the
duodenum

Release of Gastric Juice
Figure 23.16

Cephalic Phase
The taste or smell of food, tactile
sensations of food in the mouth, or
even thoughts of food stimulate the
medulla oblongata.
Parasympathetic action potentials
are carried by the vagus nerves to the
stomach.
Preganglionic parasympathetic vagus
nerve fibers stimulate postganglionic
neurons in the enteric plexus of the
stomach.
Postganglionic neurons stimulate
secretion by parietal and chief cells
(HCl and pepsin) and stimulate the
secretion of the hormone gastrin.
Gastrin is carried through the
circulation back to the stomach
where it stimulates further secretion
of HCl and pepsin.

Gastric Phase
Distention of the stomach
activates a parasympathetic
reflex. Action potentials are
carried by the vagus nerves to
the medulla oblongata.
Medulla oblongata stimulates
further secretions of the
stomach.
Distention also stimulates
local reflexes that amplify
stomach secretions.

Intestinal Phase
Chyme in the duodenum with a
pH less than 2 or containing lipids
inhibits gastric secretions by three
mechanisms
1.Sensory input to the medulla from
the duodenum inhibits the motor
input from the medulla to the
stomach. Stops secretion of pepsin
and HCl.
2.Local reflexes inhibit gastric
secretion
3.Secretin, gastric inhibitory
polypeptide, and cholecystokinin
produced by the duodenum
inhibit gastric secretions in the
stomach.

Regulation of Gastric Emptying
Gastric emptying is regulated by:
The neural enterogastric reflex
Hormonal (enterogastrone) mechanisms
These mechanisms inhibit gastric secretion and
duodenal filling
Carbohydrate-rich chyme quickly moves through
the duodenum
Fat-laden chyme is digested more slowly causing
food to remain in the stomach longer

Regulation of
Gastric
Emptying
Figure 23.19

Microscopic Anatomy of the Liver
Figure 23.24c, d

Histology of
the Liver
Connective tissue septa branch from
the porta into the interior
Divides liver into lobules
Nerves, vessels and ducts follow the
septa
Lobules: portal triad at each corner
Three vessels: hepatic portal vein,
hepatic artery, bile duct (hepatic duct
in diagram)
Central vein in center of lobule
Central veins unite to form hepatic
veins that exit liver and empty into
inferior vena cava
Hepatic cords: radiate out from
central vein. Composed of
hepatocytes
Hepatic sinusoids: between
cords, lined with endothelial cells
and hepatic phagocytic
(Kupffer) cells
Bile canaliculus: between cells
within cords

Functions of the Liver
Bile production: 600-1000 mL/day. Bile salts (bilirubin), cholesterol,
fats, fat-soluble hormones, lecithin
Neutralizes and dilutes stomach acid
Bile salts emulsify fats. Most are reabsorbed in the ileum.
Secretin (from the duodenum) stimulates bile secretions,
increasing water and bicarbonate ion content of the bile
Storage
Glycogen, fat, vitamins, copper and iron. Hepatic portal blood
comes to liver from small intestine.
Nutrient interconversion
Amino acids to energy producing compounds
Hydroxylation of vitamin D. Vitamin D then travels to kidney
where it is hydroxylated again into its active form
Detoxification
Hepatocytes remove ammonia and convert to urea
Phagocytosis
Kupffer cells phagocytize worn-out and dying red and white blood
cells, some bacteria
Synthesis
Albumins, fibrinogen, globulins, heparin, clotting factors

Composition of Bile
A yellow-green, alkaline solution containing bile
salts, bile pigments, cholesterol, neutral fats,
phospholipids, and electrolytes
Bile salts are cholesterol derivatives that:
Emulsify fat
Facilitate fat and cholesterol absorption
Help solubilize cholesterol
Enterohepatic circulation recycles bile salts
The chief bile pigment is bilirubin, a waste
product of heme

Regulation of
Bile Release
Figure 23.25

Blood and
Bile Flow
Through the
Liver

Pancreas
Pancreas both endocrine and exocrine
Head, body and tail
Endocrine: pancreatic islets. Produce
insulin, glucose, and somatostatin
Exocrine: groups acini (grape-like
cluster) form lobules separated by
septa.
Intercalated ducts lead to
intralobular ducts lead to
interlobular ducts lead to the
pancreatic duct.
Pancreatic duct joins common bile duct
and enters duodenum at the
hepatopancreatic ampulla controlled
by the hepatopancreatic ampullar
sphincter

Pancreatic Secretions: Pancreatic Juice
Aqueous. Produced by columnar epithelium lining smaller ducts. Na
+
, K
+
,
HCO
3
-
, water. Bicarbonate lowers pH inhibiting pepsin and providing
proper pH for enzymes
Enzymatic portion:
Trypsinogen
Chymotrypsinogen
Procarboxypeptidase
Pancreatic amylase
Pancreatic lipases
Deoxyribonucleases and ribonucleases
Interaction of duodenal and pancreatic enzymes.
Enterokinase from the duodenal mucosa and attached to the brush
border activates trypsinogen to trypsin.
Trypsin activates chymotrypsinogen to chymotrypsin
Trypsin activates procarboxypeptidase to carboxypeptidase.
Trypsin, chymotrypsin and carboxypeptidase digest proteins: proteolytic.
Pancreatic amylase continues digestion of starch
Pancreatic lipase digests lipids
Deoxyribonucleases and ribonucleases digest DNA and ribonucleic acid,
respectively

Bicarbonate Ion Production in Pancreas

Regulation of Pancreatic Secretion
Figure 23.28

Secretions of Large Intestine
Mucus provides protection
Parasympathetic stimulation increases rate of goblet cell secretion
Pumps: bacteria produce acid and the following remove
acid from the epithelial cells that line the large intestine
Exchange of bicarbonate ions for chloride ions
Exchange of sodium ions for hydrogen ions
Bacterial actions produce gases (flatus) from particular
kinds of carbohydrates found in legumes and in artificial
sugars like sorbitol
Bacteria produce vitamin K which is then absorbed
Feces consists of water, undigested food (cellulose),
microorganisms, sloughed-off epithelial cells

Digestion, Absorption,
Transport
Digestion
Breakdown of food molecules for absorption into
circulation
Mechanical: breaks large food particles to small
Chemical: breaking of covalent bonds by digestive enzymes
Absorption and transport
Molecules are moved out of digestive tract and into
circulation for distribution throughout body

Carbohydrates: Hydrolyzed into Monosaccharides
Glucose is transported to cells requiring energy; insulin influences
rate of transport

Lipids
Include triglycerides, phospholipids, steroids,
fat-soluble vitamins
Bile salts surround fatty acid and glycerol to
form micelles
Chylomicrons are 90% triglyceride, 5%
cholesterol, 4% phospholipid, 1% protein.
Chylomicrons enter blood stream and travel to
adipose tissue. In blood, triglycerides converted
back into fatty acids and glycerol where they are
transported into the adipose cells, then
converted back into triglycerides.

Transport of Lipids Across Intestinal Epithelium

Fatty Acid
Absorption
Figure 23.36

Lipoproteins
All lipids carried in the blood are done so
in combination with protein to make them
soluble in plasma.
Cholesterol: 15% ingested; 85%
manufactured in liver and intestinal
mucosa
Lipids are lower density than water;
proteins are higher density than water
Chylomicrons: 99% lipid and 1% protein
(extremely low density); enter lymph
VLDL: 92% lipid, 8% protein
Form in which lipids leave the liver
Triglycerides removed from VLDL and
stored in adipose cells. VLDL has been
converted to LDL.
LDL: 75% lipid, 25% protein
Transports cholesterol to cells
Cells have LDL receptors
# of LDL receptors become less once
cell’s lipid/cholesterol needs are met.
HDL: 55% lipid, 45% protein
Transports excess cholesterol from
cells to liver

Transport of LDL into Cells

Proteins
Pepsin breaks proteins into smaller polypeptide
chains
Proteolytic enzymes produce small peptide chains
Dipeptides, tripeptides, amino acids
After absorption, amino acids are are carried through
the hepatic portal vein to the liver.

Amino Acid Transport

Chemical Digestion: Nucleic Acids
Absorption: active transport via membrane carriers
Absorbed in villi and transported to liver via hepatic
portal vein
Enzymes used: pancreatic ribonucleases and
deoxyribonuclease in the small intestines

Electrolyte Absorption
Most ions are actively absorbed along the length of
small intestine
Na
+
is coupled with absorption of glucose and amino acids
Ionic iron is transported into mucosal cells where it binds
to ferritin
Anions passively follow the electrical potential
established by Na
+
K
+
diffuses across the intestinal mucosa in response
to osmotic gradients
Ca
2+
absorption:
Is related to blood levels of ionic calcium
Is regulated by vitamin D and parathyroid hormone (PTH)

Water Absorption
95% of water is absorbed in the small intestines
by osmosis
Water moves in both directions across
intestinal mucosa
Net osmosis occurs whenever a concentration
gradient is established by active transport of
solutes into the mucosal cells
Water uptake is coupled with solute uptake,
and as water moves into mucosal cells,
substances follow along their concentration
gradients

Water and Ions
Water: can move in
either direction
across wall of small
intestine depending
on osmotic gradients
Ions: sodium,
potassium, calcium,
magnesium,
phosphate are
actively transported

Introduction to Introduction to
Gastrointestinal Gastrointestinal
PhysiologyPhysiology

Gastrointestinal System(GIS)Gastrointestinal System(GIS)
The main function of the GIS is to process
ingested food into molecular forms that are
transferred, with salts and water to the body’s
internal environment where the circulatory
system can distribute them to cells.
This system includes the Gastrointestinal Tract
(GI) which is made up of; mouth, pharynx,
oesophagus, stomach, small intestine, large
intestine and accessory organs.
The accessory organs include; salivary glands,
liver, gall bladder and pancreas

Organ Exocrine
secretions
Digestion AbsorptionBulk transport/
Function
Mouth and
Pharynx
Salivary glands
Salt and
water
Mucus
Amylase
Chewing breaks
down food
particles
Amylase partially
digests
polysaccharides
No Moistens and lubricates
food particles
Oesophagus Mucus No No Moves food to stomach
by peristaltic waves
Provides lubrication
Stomach HCl
Pepsins
Mucus
Solubilises food
particles, kills
microbes,
activates
pepsinogens to
pepsin
Pepsins break
down protein
No Store food particles
Regulate rate at which
contents are emptied
into the small intestine
Pancreas Enzymes
Bicarbonate
Carbohydrates
Fats
Proteins and
Nucleic acids
No Neutralize HCl
entering the small
intestine

Organ Exocrine
secretions
Digestion Absorption Bulk transport/
Function
Liver Bile Salts
Bicarbonate
Organic
waste
products
and trace
metals
Solubilizes water
insoluble fats
No Neutralizes HCl entering
the small intestine
Elimination of feces
Gall Bladder No No No Stores and concentrates
bile between meals
Small
Intestine
Enzymes
Salt and
water
Mucus
Hydrolytic
enzymes break
down
carbohydrates,
fats and proteins
into
monosaccharides
, fatty acids,
amino acids
Monosaccharides,
fatty acids, amino
acids, vitamins,
minerals, water
Maintain fluidity of
luminal contents
Lubrication
Large IntestineMucus No Salt, water Storage and concentration
of undigested matter
Mixing and propulsion of
contents
Defecation
Lubrication

Structure of the GI Tract WallStructure of the GI Tract Wall
The wall of the gastrointestinal tract has the same
general structure from mid-oesophagus to the
anus.
The wall comprises:
- mucosa,
-submucosa,
-muscularis externa
- serosa.

Walls of the GI Tract
In the small intestine finger like projections called villi
which extend from the luminal surface. The centre of
each villus is occupied both by lacteal (single blind-
ended lymphatic vessel) and a capillary network.
The surface of each villus is covered with a layer of
epithelial cells whose surface membrane form
projections called microvilli

Epithelial Function
The increased surface area of the wall in the small
intestine by villi and microvill allow for mass
absorption.
The invaginatons in the wall form exocrine glands
and allow passage of substances.
They also have a paracrine function which refers to
the ability of the endocrine cells within the epithelial
layer to release hormones and bind to the receptors of
nearby cells to affect their function.

Epithelia Lifetime
17 Billion epithelial cells are replaced each day.
The entire epithelium of the small intestine is
replaced approximately every five days.
The rapid cell turnover makes the lining of the
intestinal tract suseptible to damage by agents that
inhibit cell division (e.g. anticancer drugs)

Digestion & Absorption ObjectivesDigestion & Absorption Objectives
Describe the process involved in the breakdown and absorption of
ingested carbohydrates.
Describe fat absorption, resynthesis of triglycerides and
phospholipids, the formation of chylomicrons and the absorption
into the lacteals.
Describe the absorptive mechanisms involved in protein
absorption.
 Describe the absorption mechanisms for the different water- and
fat soluble vitamins, noting the special role of intrinsic factor in the
absorption of vitamin B 12.
Describe the epithelial processes involved in the active absorption
of water and minerals.

Digestion and Absorption Digestion and Absorption
Overview of the four basic
digestive processes:
Digestion: dissolving and
breaking down process of food
into small molecules.
Absorption: the process
whereby molecules produced
from digestion moves from the GI
tract across a layer of epithelial
cells and enters the blood.
Secretion: The release of
substances that aid in digestion.
( HCL acid, bile and digestive
enzymes)
Motility: Contraction of the GI
tract .

Digestion and Absorption Digestion and Absorption
Carbohydrates:

Digestion and Absorption Digestion and Absorption
Carbohydrates

Digestion and AbsorptionDigestion and Absorption
Glucose & Galactose
enter epithelial cells via
sodium-linked
secondary active
transport across the
epithelial membrane.
Fructose enters by
facilitated diffusion.
 These monosaccharides
exit via the Basolateral
Membrane by facilitated
diffusion transporters
and then diffuse into the
capillaries.

Digestion and AbsorptionDigestion and Absorption
Proteins
 Proteins need to be broken down into smaller molecules (amino
acids, dipeptides & tripeptides) before they can be absorbed
by the small intestine.
 Proteases involved in this process are :
-Pepsin: secreted as pepsinogen into the stomach
-Trypsin: secreted as trypsinogen into small intestine.
-Chymotrypsin: secreted as chymotrypsinogen, into small
intestine.
-Carboxypeptidase: secreted as procarboxypeptidase into
small intestine.
-Aminopeptidase (brush border enzyme) is also used.

Digestion and AbsorptionDigestion and Absorption

Digestion and AbsorptionDigestion and Absorption

Digestion and AbsorptionDigestion and Absorption
Free Amino acids enter absorptive
epithelial cells via sodium-linked
secondary active transport across
the apical membrane.
Others are transported via
facilitated diffusion into cells.
Dipeptides and Tripeptides are
actively transported across the
apical membrane and then broken
down to amino acids within the cell.
Amino acids from the cell enter
the capillaries via facilitated
diffusion across the basolateral
membrane.

Digestion and AbsorptionDigestion and Absorption
Fats
 Fats are ingested in the form of Triglycerides.
Fat digestion occurs almost entirely in the small intestine
whereby lipase splits bonds linking fatty acids to the first and
third carbon atoms of glycerol. Two fatty acids and a
monoglyceride are produced.

Ingested fats aggregate into large lipid droplets in the upper
portion of the stomach. (insolubility in water).
Emulsification: breakdown of large lipid droplets into smaller
droplets resulting in an increased rate of digestion.

Digestion and AbsorptionDigestion and Absorption
Fats

Digestion and AbsorptionDigestion and Absorption
 ‘Mechanical disruption of fat
globlets’ (contractions of stomach and
small intestine) & ‘ An emulsifying
agent’ (Phospholipids in food and
secreted bile salts) is needed for the
emulsification of fat.
 Non polar regions on phospholipids
and bile salts associate with the non
polar interior of the lipid droplets.
Repulsion of other lipid droplets occurs
preventing reaggregation.
Although accessibility to lipase is
impaired, colipase (secreted from
pancreas) binds lipase onto the
surface of the lipid droplet.

Digestion and AbsorptionDigestion and Absorption
Micelles: similar in structure to
emulsion droplets & comprise clusters of
bile salts, fatty acids, monoglycerides &
phospholipids. (Polar ends oriented
toward micelle surface; nonpolar
portions form micelle’s core).
Micelles continuously breakdown &
reform which increases absorption.
Broken-down micelles release its
contents (fatty acids and
monoglycerides) which diffuse into
epithelial cells.
Fatty acids and monoglycerides enter the
intestinal lumen and triglycerides are
released into the interstitial fluid.
Re-synthesis of triglycerides occurs on
the smooth E.R. within epithelial cells.

Digestion and AbsorptionDigestion and Absorption
 Chylomicrons: extracellular fat
droplets
containing triglycerides and other
lipids (phospholipids, cholesterol &
fat-soluble vitamins)
which have been absorbed in the
absorption process.
Chylomicrons released from
epithelial cells enter lacteals and then
into the lymph.
A basement membrane(extracellular
glycoprotein layer) prevents entry of
chylomicrons into the capillaries.

Digestion and AbsorptionDigestion and Absorption

Digestion and AbsorptionDigestion and Absorption
Water & Minerals:
Small amounts of water are absorbed in the stomach in spite of the
absence of solute absorbing mechanisms.
Significant absorption takes places in the epithelial membranes of the
small intestine.
A water concentration difference is required for net water diffusion and
this is established via active absorption of solutes.( active transport of
sodium across epithelium)
Water moves by osmosis across the epithelium.
Iron absorption
Increased iron deposition leads to hemochromatosis.

Mouth
Food enters the digestive
tract through the mouth.
As food enters the mouth,
breakdown begins:
Mechanical breakdown by
chewing (teeth) and actions
of the tongue.
Chemical breakdown of
starch by production of
salivary amylase from the
salivary glands.

SalivaSaliva
Salivary amylase
hydrolyzes internal α1-4
bonds within starch.
A second digestive
enzyme, lingual lipase,
is produced by lingual
serous glands on the
tongue and in the back
of the mouth.
This enzyme hydrolyzes
dietary triacylglycerols
(triglycerides) in the
stomach.
Mucus secretions found in
saliva contain
glycoproteins.
Mucus lubricates food and
coats and protects the oral
mucosa.

The secretion of saliva is controlled by
both sympathetic and parasympathetic
neurons.
There is no hormonal regulation of
salivary secretion.
In the absence of ingested material, a low
rate of salivary secretion keeps the mouth
moist.

In the presence of food, salivary secretion
increases markedly.

This reflex response is initiated by
chemoreceptors (acidic fruit juices are a
particularly strong stimulus) and pressure
receptors in the walls of the mouth and on
the tongue.
Increased secretion of saliva is
accomplished by a large increase in
blood flow to the salivary glands,
which is mediated by both neural
activity and paracrine/autocrine
agents released by the active cells in
the salivary gland.
 The volume of saliva secreted per
gram of tissue is the largest
secretion of any of the body’s
exocrine glands.

SwallowingSwallowing
Swallowing is a complex reflex initiated when
pressure receptors in the walls of the pharynx are
stimulated by food or drink forced into the rear of
the mouth by the tongue.
These receptors send afferent impulses to the
swallowing center in the brainstem medulla
oblongata.
This center then elicits swallowing via efferent
fibers to the muscles in the pharynx and esophagus
as well as to the respiratory muscles.

Swallowing is an example of a reflex in which multiple
responses occur in a temporal sequence determined by
the pattern of synaptic connections between neurons in a
brain coordinating center.
Since both skeletal and smooth muscles are involved, the
swallowing center must direct efferent activity in both
somatic nerves (to skeletal muscle) and autonomic nerves
(to smooth muscle).
Simultaneously, afferent fibers from receptors in the
esophageal wall send information to the swallowing
center that can alter the efferent activity.

PharynxPharynx
Swallowing moves ingested material (bolus) from the mouth into the pharynx.
The pharynx is 14-16cm long.
As the ingested material (bolus) moves into the pharynx, the soft palate elevates
and lodges against the back wall of the pharynx.
This prevents food from entering the nasal cavity.
Impulses from the swallowing center inhibit respiration, raise the larynx, and
close the glottis (the area around the vocal cords and the space between them).
This keeps food from moving into the trachea.
As the tongue forces the food farther back into the pharynx, the food tilts a flap
of tissue, the epiglottis, backward to cover the closed glottis, thereby preventing
food from entering the trachea.

PharynxPharynx
The pharynx is
divided into three
sections:
the nasopharynx
the oropharynx
the laryngopharynx

How the Esophagus Works….How the Esophagus Works….
As a person swallows, food moves
from the mouth to the throat,
also called the pharynx (1).
The upper esophageal sphincter
opens (2) so that food can enter
the esophagus,
where waves of muscular
contractions, called peristalsis,
propel the food downward (3).
The food then passes through the
lower esophageal sphincter (4)
and moves into the stomach (5).

“Food goin’ down d wrong
hole”
http://kidshealth.org/kid/watch/er/choking.html

Once in the esophagus, the
food is moved toward the
stomach by a progressive wave
of muscle contractions that
proceeds along the esophagus,
compressing the lumen and
forcing the food ahead of it.

Such waves of contraction in
the muscle layers surrounding
a tube are known as peristaltic
waves.
One esophageal peristaltic
wave takes about 9 s to reach
the stomach.

Upper Esophageal
Sphincter
Lower Esophageal
Sphincter
The esophageal phase of
swallowing begins with
relaxation of the upper
esophageal sphincter.
Immediately after the food
has passed, the sphincter
closes, the glottis opens, and
breathing resumes.
The lower esophageal
sphincter opens and remains
relaxed throughout the
period of swallowing,
allowing the arriving food to
enter the stomach.
After the food has passed,
the sphincter closes,
resealing the junction
between the esophagus and
the stomach.

The ability of the lower esophageal sphincter to
maintain a barrier between the stomach and the
esophagus when swallowing is not taking place is
aided by the fact that the last portion of the
esophagus lies below the diaphragm, and is subject
to the same abdominal pressures as is the stomach.
This prevents the formation of a pressure gradient
between the stomach and esophagus that could
force the stomach’s contents into the esophagus.

Heartburn
Some people have
less efficient lower
esophageal
sphincters, resulting
in repeated episodes
of refluxed
gastric contents into
the esophagus
(gastro-esophageal
reflux), heartburn,
and in extreme cases,
ulceration, scarring,
obstruction, or
perforation of the
lower esophagus.

The lower
esophageal sphincter
not only undergoes
brief periods of
relaxation during a
swallow but also in
the absence of a
swallow.
During these periods
of relaxation, small
amounts of the acid
contents from the
stomach are
normally refluxed
into the esophagus.

Multiple mechanisms,
including neural and
hormonal, regulate
gastroesophageal
sphincter pressure.
The musculature of the
gastroesophageal
sphincter has a tonic
pressure.
It is normally higher than
the intragastric pressure
(the pressure within the
stomach).
This high tonic pressure at
the gastroesophageal
sphincter keeps the
sphincter closed.
Keeping this sphincter
closed is important.
It prevents
gastroesophageal reflux:
the movement of
substances from the
stomach back into the
esophagus.

The StomachThe Stomach
The stomach is a typically J shaped enlargement
of the GI tract.
It connects the oesophagus to the duodenum
(the first part of the small intestine).

Anatomy of the StomachAnatomy of the Stomach
The stomach has four (4)
main regions:
The cardia
The fundus
The body
The pyloric region
The pyloric antrum
The pyloric canal
The phyloricsphinter

Histology of the StomachHistology of the Stomach
The stomach wall is composed of the same four(4) basic
layers as the rest of the GI tract, with certain
modifications.
The surface of the mucosa is a layer of simple columnar
epithelial cells called mucous surface cells.
The epithelial cells extend down into the lamina propia,
where they form columns of secretory cells called gastric
glands that line many narrow channels called gastric
pits.
Secretions from the gastric glands flow into each gastric
pit and into the lumen of the stomach.

Gastric pits contain four (4) major secretory cells:
Chief cells
Pepsinogen
Activation of pepsinogen by low pH to form pepsin
Once pepsin is formed, it can act on pepsinogen to produce more pepsin
Pepsin is a protease for protein digestion
Parietal cells
HCl
Kills microbes in food
Denatures protains
Converts pepsinogen to pepsin
Intrincis factors
Needed for absorption of vitamin B12
G-cells (enteroendocrine cell)
Secretes gastrin hormone
Gastrin activates gastric juice secretion and gastric smooth muscle “churning”
Gastrin activates gastroileal reflex which moves chyme from ileum to colon
Mucus cells
Protective role of mucus against acid and digestive enzymes

The submucosa layer of the stomach is composed of
areolar connective tissue.
The muscularis has three (3) (rather than two) layers of
smooth muscle:
An outer longitudinal layer
A middle circular layer
An inner oblique layer (limited to the body of the
stomach).
The serosa (simple squamous mesothelium and areolar
connective tissue) covering the stomach is part of the
viseral peritoneum.

Functions of the StomachFunctions of the Stomach
Storage
Because of its accordionlike folds (called rugae), the wall of the
stomach can expand to store two to four liters of material.
Temporary storage is important because you eat considerably
faster than you can digest food and absorb its nutrients.
Mixing
The stomach mixes the food with water and gastric juice to
produce a creamy medium called chyme.
Controlled release
Movement of chyme into the small intestine is regulated by
a sphincter at the end of the stomach, the pyloric sphincter.

Physical breakdown
Three layers of smooth muscles (rather than the usual two) in
the muscularis externa churn the contents of the stomach,
physically breaking food down into smaller particles. In
addition, HCl denatures (or unfolds) proteins and loosens the
cementing substances between cells (of the food). The HCl also
kills most bacteria that may accompany the food.
Chemical breakdown
Proteins are chemically broken down by the enzyme pepsin.
Chief cells, as well as other stomach cells, are protected from
self-digestion because chief cells produce and secrete an inactive
form of pepsin, pepsinogen. Pepsinogen is converted to pepsin
by the HCl produced by the parietal cells. Only after pepsinogen
is secreted into the stomach cavity can protein digestion begin.
Once protein digestion begins, the stomach is protected by the
layer of mucus secreted by the mucous cells.

Hydrochloric Acid Production

HCl is produced in the parietal cells through a complex
series of reactions.
Carbon dioxide diffuses into the parietal cell and the
enzyme carbonic anhydrase catalyzes a reaction between
the carbon dioxde and water to form carbonic acid.
Carbonic acid dissociates into bicarbonate ion and
hydrogen ion and the bicarbonate ion is transported back
into the bloodstream.
An ion exchange molecule in the plasma membrane
exchange bicarbonate going out for chloride coming in.

Proton pumps powered by H+/K+ ATPases is used to
transport the potassium and hydrogen ions.
The hydrogen ions are actively transported into the duct
of the gastric gland and the negatively charged chloride
ions diffuse with the positively charged hydrogen ions.
Potassium ions are counter transported into the parietal
cells in exchange for hydrogen ions. The potassiun ions
leak back into the lumen via potassium channels.
The net result is production of HCl in the parietal cells
and its secretion into the duct of the gastric gland.

Four (4) chemical messengers regulate acid secretion:
GastrinGastrin
released from G-cell
stimulates acid secretion
Acetylcholine (Ach)Acetylcholine (Ach)
released from the plexus neurons
stimulates acid secretion
HistamineHistamine
released from ECL cells
stimulates acid secretion
potentiates the response to gastrin and Ach.
Somatostatin Somatostatin –
released from endocrine cells in the gastric wall
Acts on parietal cells to inhibit acid secretion
Inhibits release of gastrin and histamine
Parietal cell membranes contain receptors for all 4 of these molecules. Not
only do these chemical messengers act directly on the parietal cells, they also
influence each other’s secretion.
Pepsinogen secretion parallels acid secretion, i.e. most of the factors stimulate
or inhibit acid secretion exert the same effect on pepsinogen secretion.

Three Phases of Gastric SecretionThree Phases of Gastric Secretion
Regulation of stomach secretion is divided into three (3)
phases:
•Cephalic
•Gastric
•Intestinal

Cephalic phase:Cephalic phase:
Taste, sight, tactile sensation of
or thought of food in the mouth
sends nervous impulse to the
medulla oblongata.
These impulses cause
parasympathetic neurons via the
vagus nerves to stimulate
secretion of HCl, pepsinogen and
mucus in the stomach.
The parasympathetic stimulation
also results in secretion of
gastrin from the lower part of
the stomach.
Gastrin travels through the
bloodstream and further
stimulated HCl and pepsinogen
secretion in the upper and
middle part of the stomach.

Gastric Phase:Gastric Phase:
Food has entered and
distended the stomach. The
pH of the stomach is also
altered because protein has
entered the stomach and
buffered some of the stomach
acid causing a low pH.
This distention activated a
parasympathetic reflex via the
medulla oblongate, and also
has a direct stimulatory effect
on the gastric glands. The
result is the continued
secretion of HCl and
pepsinogen.
Negative feedback control of
acid secretion is done by
somatostatin. As the contents
of the gastric lumen become
more acidic, the stimuli that
promote acid secretion
decrease.

Intestinal phaseIntestinal phase
Chyme has entered the duodenum so
gastric secretion is no longer needed.
When the chyme contains lipids from
the digestion of fats or contains enough
HCl to bring its pH to below 2, gastric
secretion is inhibited.
The lipid and hydrogen ions inhibit
gastric secretion by three simultaneous
actions.
They cause impulses to go to the
medulla oblongata to decrease
parasympathetic stimulation of
gastric glands
They set up local reflexes, via
neurons in the wall of the gut,
that decrease gastric secretion.
They cause the release of three
local hormones collectively called
enterogastrones (secretin, CCK
inhibitory peptides) which travel
via the circulation to the gastric
glands and inhibit their secretion.

Gastric MotilityGastric Motility

After food enters the stomach, gentle, rippling, peristaltic
movements called mixing waves pass over the stomach
every 15-25 seconds.
These waves macerate food, mix it with gastric juice and
reduce it to a soupy liquid called chyme.
As digestion proceeds, more vigorous mixing waves begin
at the body of the stomach and intensify as they reach the
pylorus.
As food reaches the pylorus, each mixing wave forces
several milliliters of chyme into the duodenum through
the pyloric sphincter.
Most chyme is forced back into the body of the stomach
where mixing continues.

The next wave pushes the chyme forward again and forces a little
more into the duodenum.
These forward and backward movement of gastric contents are
responsible for most mixing in the stomach.
The rhythm of gastric waves are generated by pacemaker cells in
the longitudinal smooth muscle layer.
These smooth muscle cells undergo spontaneous depolarization-
repolarization cycles (slow waves) known as basic electrical
rhythm of the stomach.
These slow waves are conducted through gap junctions along the
stomach’s longitudinal muscle layer and also induce similar slow
waves in overlying circular muscle layer.

Slow wave oscillations in the membrane potential of
gastric smooth muscle fibers trigger bursts of action
potentials when threshold potential is reached at the
wave peak.
Membrane depolariztion bring the slow wave closer
to threshold. Increasing the action potential
frequency and thus the force of smooth muscle
contraction.

Regulation of Gastric EmptyingRegulation of Gastric Emptying
Stimulation of gastric emptying:
Gastric emptying, the periodic release of chyme from the stomach into
the duodenum, is regulated by both neural and hormonal reflexes, as
follows:
1.Stimuli (distention of the stomach, presence of partially digested
proteins, alcohol and caffeine) initiate gastric emptying.
2.These stimuli increase the secretion of gastrin and generate
parasympathetic impulses in the vagus (X) nerves.
3.Gastrin and nerve impulses stimulate contraction of the lower
oesophagus sphincter, increase motility of the stomach and relax the
pyloric sphincter.
4.The net effect of these actions is gastric emptying.

Inhibition of Gastric emptying
Inhibition of Gastric emptying is controlled by the enterogastric
reflex and CCK.
1.Stimuli (distention of the duodenum and the presence of fatty
acids, partially digested proteins and glucose) in the duodenal
chyme initiate gastric emptying.
2.These stimuli the enterogastric reflex: Nerve impulses propagate
from the duodenum to the medulla oblongata, where they inhibit
parasympathetic stimulation and stimulate sympathetic activity in
the stomach. The same stimuli also increase secretion of CCK.
3.Increased sympathetic impulses and CCK both decrease gastric
motility.
4.The net effect if these actions is inhibition of gastric emptying.

PANCREATIC SECRETIONS

 The proteolytic enzymes are secreted in inactive
forms (zymogens) and then activated in the
duodenum by other enzymes.
Activation is acquired in steps and is catalyzed by
enterokinase. This is embedded in the luminal
plasma membrane of the intestinal epithelial cells.
Proteolytic enzymes splits off a peptide from
pancreatic trypsinogen thus forming the active
enzyme trypsin

When activated trypsin which is also a proteolytic
enzyem similarly splits off peptide fragments and in so
doing activates the other pancreatic zymogens (this is
in addition to its role in protein digestion).
Note bicarbonates function is to neutralize acid
entering the deodenum from the stomach.
Also CCK responsible for the secretion of enzymes,
(inclusive of those for fat, and protein digestion).
CCK’s release is dependent on the levels/presence of
fatty acids and amino acids in the duodenum

Glucagon, Insulin and Blood Glucose
Regulation
The islets of Langerhans (clusters of emdocrine cells)
secrets these two peptide hormones.
Insulin
 Secreted by beta cells of islets of Langerhans within
the pancreas when blood glucose level.
Stimulates the uptake of glucose from the blood
stream and does this by increasing the transport of
glucose from the blood to muscle cells and
adipocytes. Also a net uptake of glucose by the liver.

Insulin secretion and subsequently signaling leads to
the movement of a glucose transport protein GLUT 4
from the intracellular vesicles to the cell membrane.
(*)
Once in the cell membrane the GLUT4 protein allows
more glucose to enter the cell thus lowering the blood
glucose level.
Note insulin secretion is not only dependent on blood
glucose levels. Secretion is also dependent on:
Elevated amino acid concentration
Hormonal controls
The autonomic neurons to the islets of Langerhans

 Glucagon
Secreted by the alpha cells of Langerhans within the
pancreas at low blood glucose levels also by neural
and hormonal inputs to these islets.
Stimulates the release of glucose to the blood stream.
It binds to specific receptors to set off a chain of
events which makes glucose available i.e.
Increased glycogenolysis (glycogen break down
Increased gluconeogenesis
Increases in the synthesis of ketones

BILE SECRETION AND LIVER
FUCTION
Bile is secreted by liver cells into a number of small
ducts (the bile canaliculi which converge to form the
common hepatic duct.
Note bile salts and lecithin are synthesized in the liver
and helps to solubilize fat in the small intestine
Where as cholesterol, bile pigments and trace metals
are extracted from the blood by the liver and excreted
via the bile.
Bicarbonate ions neutralize acid in the duodenum

When fatty meals are being digested most of the bile salts
entering the intestinal tract via bile are absorbed by
specific sodium-coupled transporters in the ileum.
Absorbed bile salts are returned via the portal vein to the
liver where they are secreted once again.
Bile salts uptake from portal blood into hepatocytes is
driven by secondary active transport coupled to sodium
Cholesterol homeostasis in the blood and the process by
which cholesterol –lowering drugs work is maintained by
the secretion of bile followed by the excretion of
cholesterol in feces.

Bile pigments are substances formed from the heme
portion of hemoglobin when digestion of old or damaged
erythrocytes occurs in the spleen and liver.
Bile components are secreted by two different cells, they
are:
Hepatocytes which secrets bile salts and pigments, lecithin.
Epithelial cells which secrets most of the bicarbonate rich salt
solutions
Secretion of the salt solution by the bile ducts is
stimulated by secretin in response in response to acidity in
the duodenum.
Note the secretion of bile salts is controlled by the
concentration of bile salts within the blood

The liver is always secreting bile however, greater
secretion occurs at meal times (during and just after).
The sphincter of oddi is a ring of smooth muscles
surrounding the common bile duct at the point at
which it enters the duodenum. When closed the
diluted bile secreted by the liver is shunted into the
gallbladder. It is at this point the organic components
of bile (water and sodium chloride) are absorbed into
the blood

The Small Intestine

Secretion
Intestinal epithelium secretes mineral ions such as,
sodium, chloride and bicarbonate ions into the lumen
and water follows by osmosis.
Chloride is the primary ion that determines the
magnitude of fluid secretion.
Various hormonal ,paracine signals as well as toxins
and bacterial toxins can increase the frequency of these
channels and fluid secretion.
Water movement into the lumen occurs when the
stomach is hypertonic, this then causes osmotic
movement of water.

Absorption
All fluid secreted by the small intestine is absorbed
back into the blood.
Large volumes of fluid which includes, salivary, gastric,
hepatic, pancreatic secretions and ingested water is
simultaneously absorbed from lumen into the blood.
There is a large net absorption of water from small
intestine.
Absorption is achieved by transport of ions mostly
sodium from lumen into the blood with water followed
by osmosis.

Motility
Stationary concentration and relaxation of intestinal
segments occurs during the digestion of a meal.
Each contracting segment is a few cm long and the
digestion last for a few seconds.
Chyme in the lumen is forced up and down the
intestine.
Segmentation- the rhythmical contraction and
relaxation of the intestine.
Mixes the chyme in lumen and bringing it into
contact with intestinal wall.

Segmentation movement
-initiated by electrical activity by
pacemaker cells with circular smooth
muscle layer.
-intestinal basic electrical rhythm
produces oscillations in the smooth
muscle membrane potential. If
threshold is reached action potentials
are triggered that increase muscle
contraction.
-the frequency of segmentation is set
by the frequency of the intestinal basic
rhythm
-unlike the stomach that has a single
rhythm 3 mins/sec intestinal rhythm
varies along the length of the
intestine.
-each successive region have a
slightly lower frequency than the
above

Motility
Produces a slow migration of the intestinal contents
toward the large intestine.
Segmentation intensity can be altered by hormones:
Enteric nervous system and autonomic nerves.
Parasympathetic activity increases the force of
contraction.
Sympathetic stimulation decreases it.

Migrating myoelectric complex
Begins in the lower portion of stomach.
Repeated waves of peristaltic activity.
Moves any undigested material remaining in the small
intestine into the large intestine that is long enough to
grow and multiply excessively.
Rise in plasma concentration of intestinal hormone
MOTILIN initiates MMC.
Motilin stimulates MMCs via both the enteric and
autonomic nervous system.

Motility
Contractile activity in certain regions of the small
intestine can be altered by reflexes.
Eg, segmentation intensity in the ileum increases
during periods of gastric emptiness (gastroileal reflex)
Intestino intestinal reflex lead to complte cessastion of
motility.

Large Intestine
6.5CM in diameter, 1.5m long
First portion Cecum
Cecum forms a blind ended pounch that extends to
appendix
COLON: 3 SEGMENTS
Ascending
Transverse
Descending (forms sigmoid colon)
Function –is to store and concentrate faecal material
before defecation.

Large intestine
Chyme enters the cecum through the ilocecal
sphincter.
Sphincter relaxes each time the terminal portion of
the ileum contracts.
Chyme enters the large intestine.
The primary absorptive process in the intestine is
active transport of Na+ from lumen to blood. Also
osmotic absorption of water.
There is a net movement of K+ from blood into the
large intestine lumen. Stimulated by cAMP

Motility &Defecation
Contraction of circular smooth muscle produce
segmentation motion.
Slower than small intestine
Following a meal a wave contraction known as mass
movement spreads over transverse segment of intestine
to rectum
Unlike a peristaltic wave in the small intestine, the
smooth muscle in the intestine remains contracted for
some time after mass mov’t
Parasympathetic input increases segmental
contractions whereas sympathetic input decreases
colonic contractions

PATHOPHYSIOLOGY OF THE
GASTROINTESTINAL TRACT
Peptic Ulcer Disease, Vomiting
and Gallstones, Lactose
Intolerance, IBD, Constipation and
Diarrhoea

DEFINITION
Peptic Ulcer Disease (PUD)= These are areas of tissue
degradation that can be caused by increased acid and
pepsin or impaired mucosal defenses such as
decreased bicarbonate secretions.
Ulcers are normally found in the stomach (gastric),
duodenum (duodenal) and oesophagus (oesophagal).

Common Risk Factors for Gastric
Mucosal Disruption
Associated with Helicobacter pylori.
Alcohol
NSAID- Induced gastritis or ulcers are frequently
“silent”.
Corticosteroids
Tobacco
Coffee/ Caffeine

Clinical Manifestation
Pain (epigastic burning)
Nausea, vomiting or bloating
Weight Loss
Upper Gastrointestinal haemorrhaging or blood in
the stomach

Diagnostic Methods
Abdominal X-ray
Blood Count
Endoscopy and biopsy of ulcer
H pylori testing

Therapy
In mild disease, treat with bismuth or misoprostal
For H pylori give antibiotics

Vomiting
Vomiting is the forceful expulsion of the contents of
the stomach and upper intestinal tract through the
mouth.
It is a complex co-ordination by a region in the
brainstem, the medulla oblongata.

Causes of Vomiting
Gastric contents get into the respiratory tract
Food poisoning
Overeating
Concussion
Vomiting can be induced by stimulation of the
chemoreceptor zone, vestibular apparatus and the GI tract

Consequences
Intestinal Blockage
Aspiration Pneumonia
Disturbances in acid-base balance
Dehydration
Electrolyte Depletion

Diagnosis
Blood Tests- to check electrolytes and blood cell
count
Urinalysis- to check for dehydration and infection
CT Scan- to check for head injuries
X-ray

Treatment
Most of the time, vomiting go away on their own and
could be managed at home.
If vomiting occurs, fluids are given by the mouth or
through a vein into the bloodstream.

Gallstones
Gallstones are solid particles that form from the bile
in the gallbladder. There are two types of them: 1.
Cholesterol Stones and 2. Pigment Stones.
Gallstones can be any size, from as tiny as a grain of
sand to large as a golf ball.

Problems of Gallstones
Gallstones within the gallbladder often cause no problems. If
they are too large or too many, they cause extreme pain. They
may also cause problems if they move out of the gallbladder.
If there movements lead to blockage of any of the ducts
connecting the gallbladder, liver or pancreas with the intestine,
serious complications may occur.
Blockage of a duct can cause bile or digestive enzymes to be
trapped in the duct.
If these conditions go untreated, they can even cause death.

Gallstone Causes
The stones form when the amount of cholesterol or
bilirubin in the bile is high.
Pigment stones form most often in people with liver
disease or blood disease, who have high levels of
bilirubin.
Poor muscle tone may keep the gallbladder from
emptying completely. The presence of residual bile
may promote the formation of gall stones.

Risk Factors for the Formation of
Gallstones
Female Gender
Being Overweight
Losing a lot of weight quickly on a starvation diet
Taking of certain medications such as birth control
pills or cholesterol lowering drugs.

Treatment
Intake of only clear liquids to give the gallbladder a
rest.
Avoid fatty or greasy meals.
Use of painkillers.
Use of drugs made with bile acids.
Gallstone surgery called Cholecystectomy.

LACTOSE INTOLERANCE
LACTOSE
-milk carbohydrate
-digested by LACTASE, into its components
absorbed by glucose & galactose
active transport

Lactase
Enzyme
Embedded in luminal plasma membranes of intestinal
epithelial cells
Present at birth
Production decreases after 2 yrs
Lactose intolerance- inability to digest lactase.

Increases concentration in small intestine
Decreases osmotic gradient, therefore, water retained
in lumen.
Lactose-containing fluid moves to large intestine
bacteria digests lactose metabolizes
monosaccharides
produces gas & short chain fatty acids

Gas distends colon and produces pain
Short chain fatty acids draws water into intestinal
lumen which leads to diarrhea
Lactose intolerance causes mild discomfort to severe
dehydrating diarrhea
Solution: lactose free products/lactase tablets

INFLAMMATORY BOWEL
DESEASE (IBD)
Crohn’s Disease & Ulcerative Colitis
Chronic inflammation of the bowel

Crohn’s Disease
Occurs anywhere along GI tract (mouth–anus)
Most common at the end of the ileum
Inflammation and thickening of bowel wall
causes narrowing or blockage of lumen and
hence, pain
1
st
symptoms – pain in lower right abdomen &
diarrhea (sometimes fever)
Often mistaken for acute appendicitis
Relief: defecation (temporary)

Colitis
Confined to colon
Caused by disruption of normal mucosa with
bleeding, edema & ulcerations
In an extreme case bowel wall thins and tissue lost, so
holes break bowel wall
Symptoms: diarrhoea , rectal bleeding,
abdominal cramps

IBD con’t
Most common in caucasians (late teens to early 20’s
and > 60)
Caused by environmental and genetic factors
As a result of weak immune system and poor tissue
repair
Responses to normal microorganisms in intestinal
lumen

Treatment
Initially – 5-aminosalicylate drugs
e.g. sulfasalazine antibacterial &
anti-inflammatory
effect
In severe case – glucocorticoids or removal of
diseased bowel
New drug therapy – immunosuppressive medicines
Diet changes aid in healing
(NB: overuse of glucocorticoids may cause bone loss)

CONSTIPATION AND
DIARRHEA
Common Belief: Unless you have a bowel
movement everyday, ‘toxic’ substances from fecal
matter (in large colon) will poison you!
WHAT DO YOU THINK???

Toxic agents after a prolonged period of time – still to
be discovered
HOWEVER, fecal retention for days or weeks may
lead to:-
Headache
Loss of appitite
Nausea
Abdominal distention
These are all symptoms of CONSTIPATION

The longer the fecal matter remains in large intestine,
the more water absorbed, feces become drier and
defecation becomes difficult and painful
Common in the elderly, or anyone with damage to the
enteric nervous system (decreased motility of large
intestine) or emotional stress
Cure –distension from dietary fibre or laxatives

Dietary fibre – cellulose & other complex
polysaccharides
- not digested in small intestine, produces
distension in large intestine, leads to motility
- Bran, Fruits, Veggies
Laxatives – increase frequency/ease of defecation
- fiber is a laxative
- mineral oils (lubricate feces)
- Mg & Al salts (epsom salts) (water retention)
- Caster oil (stimulates intestinal tract)
- causes dependence

Diarrhea
Large, frequent, watery, stools
Causes:
 fluid absorption, fluid secretion
Increased motility caused by distension (not
the other way around!)
Secretory diarrhoea – bacterial, protozoan &
viral diseases (E. coli)
- Cholera and Traveller's
diarrhoea

CHOLERA
-Caused by bacteria
Releases toxin that stimulates cyclic AMP
Opens chloride channels
Increase in chloride ions
Increase water content in lumen
Massive life threatening diarrhoea (dehydration,
decreased blood vol.)

TRAVELLER’S DIARRHEA
-Produced by several species of bacteria, parasites,
viruses
-Produces secretary diarrhoea (same process at
cholera)
Other consequences of severe diarrhoea are
potassium depletion, metabolic acidosis

Treatment
Dehydrating effect can be
balanced by drinking salt-
glucose solution to replace
fluids (by active transport).
Until diarrhoea subsides, a
change is diet can help.
Avoid caffeine, greasy
foods, high fibre foods
and lactose rich foods
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