Gastrointestinal tract

Physiology

Dr. Suaad M. Ghazi

MBChB, MSc, PhD
 Objectives of
lecture 3
1.Describe the mechanisms of
swallowing.
2.Explain gastric anatomy and
how gastric secretion and
stomach motility are
regulated.
 Swallowing (deglutition)

1. Oral (voluntary) stage.

2. Pharyngeal (involuntary) stage.
3. Esophageal (involuntary) stage.
4. Relaxation of lower esophageal
sphincter.
 Food voluntarily squeezed posteriorly to oropharynx by
pressure of tongue upward and backward against hard palate,
soft palate and back of mouth into the pharynx. From here
swallowing reflux becomes automatic.
Pharyngeal (involuntary) stage of swallowing:
The bolus of food is pushed backward in the mouth
stimulates swallowing receptor areas around the opening of the
pharynx
impulses from these pass to medulla oblongata through the
sensory portions of ( 5th and 9th ) nerves to initiate a series of
automatic pharyngeal muscular contractions by neuronal areas
collectively called swallowing (or deglutition) center distributed
throughout the reticular substance of the medulla and lower
portion of the pons.
The motor impulses from the swallowing center to the pharynx
and upper esophagus that cause swallowing are transmitted by
the ( 5th , 9th , 10th , 12th cranial nerves and few of the superior
cervical nerves )
The swallowing center specifically inhibits the respiratory center
of the medulla during swallowing, halting respiration at any point
in its cycle to allow swallowing to proceed.
 In order:
1. The soft palate is pulled upward closed pos. nares.

2. Approximation of the palatopharyngeal folds

pulled medial ward form sagital slit.
4. Upward movement of larynx stretches opening of
oesophagus. Upper 3 - 4 cm called UES (striated
muscle) relaxes allowing food to move from pos.
pharynx into upper oesophagus. UES between
swallow tonically contracted preventing air from
going into oesophagus.
3. Approximation of vocal cords and pulling the
hyoid bone and larynx upward and anteriorly. Swing
the epiglottis backward to prevent passage of food
into the trachea to keep swallowed material out of the
airways.

5. Larynx is raised and UES is relaxed, superior

constrictor muscle of pharynx contracts. Rapid
peristalses wave downward which propels the food
into oesophagus.
UES
1. Primary peristaltic wave (vagal reflexes)
continuation begins in pharynx to stomach through esophagus.
Reflexes transmitted through vagal afferent from eso. to medulla
and back to eso. through vagal efferent fibers.

2. Secondary peristaltic wave (Enteric reflexes)

initiated from distention of eso. by retained food if the primary
peristaltic wave fails to move all the food that has entered eso.
into the stomach.
 Step 4
Relaxation of lower esophageal
sphincter

As the esophageal peristaltic

wave passes toward the
stomach, the lower esophageal
sphincter relaxes. This relaxation
is vagally mediated.
 The lower esophageal sphincter is not
anatomically separate identifiable muscles.
 The fundus of the stomach and lower
esophageal sphincter extending about 2-5 cm
above its junction with the stomach both relax
during a swallow while the bolus of food is still
higher in the esophagus.
 This phenomenon is called receptive relaxation.
 Receptive relaxation is vagally mediated.
 Nitric oxide is the neurotransmitter thought to
mediate receptive relaxation at the smooth
muscle cell allowing food to pass to the stomach.
Lower Esophageal Sphincter (Gastro esophageal Sphincter)

diaphragm

Prevention of reflux of the gastric contents is achieved by:

[1] The tonic contraction of LES.
[2] Subdiaphragmatic oblique entrance of esophagus to the stomach
(valve-like mechanism).
Disorders of swallowing:
Esophageal reflux: Reflux of stomach acid to the esophagus
causes esophageal pain (heartburn) and may lead to esophagitis.
• Intragastric pressure is usually greater than atmospheric
pressure.
• The pressure gradient between the lumens of the stomach and
esophagus would tend to facilitate the reflux of food from the
stomach into the esophagus.
• (LES) normally prevents this and mediates the unidirectional
transfer of food.
• Largest pressure gradient from stomach to esophagus would
occur during inspiration.
• An increase in intra-abdominal pressure will increase both
intragastric pressure and the closing pressure for the LES by
approximately the same amount. Therefore, the closing pressure of
the LES will always exceed intragastric pressure by 30-40 mmHg.
Gastroesophageal reflux initiates a cycle of
increased esophageal acid exposure
 The esophagitis results in chronic injury to the
distal esophagus affecting the peristaltic function
and causing frequent ineffective peristalsis which
prolongs the acid contact secondary to reflux.
The esophagitis may also cause chronic
decreases in LES pressure, resulting in a
damaging cycle of events that combine to
perpetuate the reflux injury.
Causes that increase intraabdominal pressure :
 Ingestion of a very large meal.
 Production of intestinal gas by bacterial metabolism.
 Pregnancy.
 An abdominal mass such as a tumor.
 Straining (contraction of abdominal muscles) against a
closed glottis.
 Etc.
Latter maneuver increases intraabdominal pressure
relative to atmospheric pressure, and just as it facilitates
defecation, it will also facilitate gastro-esophageal reflux if
the LES is not contracted.
Esophageal reflux may occur :
[A] If the intragastric pressure rises high enough to force the
lower esophageal sphincter open.
[B] If the lower esophageal sphincter is unable to maintain its
normal tone.
[C] If the lower esophageal sphincter is forced through the
diaphragm and into the thoracic cavity as in hiatus hernia.
In this situation (The same may occur during pregnancy) :
 Intra-abdominal pressure no longer contributes to the
closing pressure of the LES.
 Negative intrathoracic pressure would reduce the closing
pressure.
In either case, the low intrathoracic pressure compared to
the high intra-abdominal pressure, causes LES to expand,
allowing reflux to occur.
Belching (eructation): Following a
heavy meal or the ingestion of large
amounts of gas (e.g., from
carbonated beverages), the gas
bubble that is usually in the fundus of
the stomach is displaced to the
cardia. When lower esophageal
sphincter relaxes during the
swallowing process, gas enters the
esophagus and is regurgitated.
Dysphagia: Difficulty in swallowing. Persons with
dysphagia usually report choking, coughing, or an
abnormal sensation of food sticking in the back of
the throat or upper chest when they swallow. If
swallowing is painful, it is referred to as
odynophagia. Dysphagia can result from altered
nerve function or from disorders such as:
 Narrowing of the esophagus.
 Lesions of the central nervous system (CNS), such
as a stroke, often involve the cranial nerves that
control swallowing.
 Strictures and cancer of the esophagus and
strictures resulting from scarring can reduce the size
of the esophageal lumen and make swallowing
difficult.
Achalasia: It is a neuromuscular disorder
of the lower two-thirds of the esophagus
that leads to absence of peristalsis and
failure of the lower esophageal sphincter to
relax. Food accumulates above this
sphincter, taking hours to enter the
stomach and dilating the esophagus.
 Regions of the stomach

lower oesophageal sphincter

Pyloric Fundus
sphincter “Pacemaker
Duodenum zone”
- peristaltic
contractions
Body
(corpus)
“acid-secreting”
Antrum
“muscular pump”
 The stomach
a. the fundus.
b. the body.
c. the antrum.
Physiologically the fundus functions mainly as part
of the body.
stomach mucosa is a simple columnar epithelium
composed entirely of mucous cells.
They produce a cloudy, protective two-layer coat of
alkaline mucus in which the surface layer consists of
viscous, insoluble mucus that traps a layer of
bicarbonate-rich fluid beneath it.
Tubular gastric glands produce the stomach
secretion called gastric juice.
 The functions of the stomach
1. Storage of food
♦ Is mediated by the process of receptive relaxation of the stomach.
♦ When food enters the stomach a vago-vagal reflex greatly reduces
the tone in the muscular wall of the body of the stomach.
♦ Nitric oxide is the neurotransmitter thought to mediate receptive
relaxation at the smooth muscle cell.
♦ The wall can bulge progressively outward accommodating greater
and greater quantities of food up to a limit of about 1 liter.
♦ Stomach accommodation depends exclusively upon an intact
vago-vagal reflex.
♦ If vagal innervation is interrupted, then intra-gastric pressure
increases. This is a potential cause of vomiting due to the inability of
the proximal stomach smooth muscle to undergo receptive
relaxation.
2. Mixing of this food with gastric
secretions
♦ When the stomach is filled, weak
peristaltic and segmentation (mixing)
contractions move toward the antrum along
the stomach wall>
♦ Propelling and mixing food with gastric
juice until it forms a semifluid mixture
called chyme.
♦ This is due to distension of the stomach
which elicit vago-vagal reflex.
3. Emptying
♦ Slow emptying of chyme from the stomach
into the small intestine at a rate suitable for
proper digestion and absorption by the small
intestine.
♦ The degree of constriction of the pyloric
sphincter and the intensity of antral peristaltic
wave (mediated by myenteric reflexes) can be
varied according to signals both, from the
stomach and from duodenum.
♦ The antral peristaltic waves provide a
pumping action and are frequently called the
pyloric pump.
 The stomach is a poor absorptive area
of the GIT.
 Because it lacks the typical villus type
of absorptive membrane, and also
because the junctions between the
epithelial cells are tight junctions.
 Only a few highly lipid-soluble
substances, such as alcohol and some
drugs like aspirin can be absorbed in
small quantities.
 Regulation of gastric emptying (pyloric pump)
 Gastric emptying is a key control point in the GIT
to ensure the orderly delivery of nutrients in a form
that can be digested and to give appropriate signals
of fullness (satiety).
 Gastroparesis (“weak stomach”) is a common
complication of poorly controlled diabetes mellitus
and significantly slows gastric emptying.
 The rate at which the stomach empties is regulated
by signals both from the stomach and duodenum.
 Gastric emptying takes about 3 hours and very
closely regulated so that nutrient absorption is
maximized and H+ in the duodenum has time to be
neutralized.
 Gastric secretion
 Gastric secretions aid in the breakdown
of food into small particles and continue
the process of digestion which had begun
by the salivary enzymes.
 About 2 L / day of gastric secretions are
produced.
 The stomach mucosa contains two main
types of gastric glands:
[A] Gastric glands
[B] Pyloric glands
 THE MUCOSA OF GASTRIC GLAND

Major cell types Functions

 surface epithelial mucus, HCO3 -

-

 chief (peptic or zymogen) pepsinogen -

BODY  Parietal (oxyntic) HCl, intrinsic factor -
(oxyntic
 enterochromaffin-like histamine -
gland)
(ECL)

 surface epithelial - mucus, HCO3-

 chief (zymogen) - pepsinogen
ANTRUM
(pyloric  G-cells - gastrin
gland)  D-cells - somatostatin
[A] Gastric glands
 Are located in the fundus and the body of the
stomach.
 They contain these types of secretory cells:
1. Mucus secreting cells which secretes mucus.
2. Parietal (oxyntic) cells which secrete intrinsic
factor and HCl.
3. Peptic (chief) cells which secrete pepsinogen, the
precursor for the proteolytic enzyme pepsin.
4. Enteroendocrine cells (or enterochromaffin-like
cells, ECL cell) release a variety of chemical
messengers directly into the interstitial fluid of the
mucosa of the stomach. Some of these are histamine,
serotonin, and somatostatin.
[B] Pyloric glands
 Are located in the antral and pyloric
regions of the stomach. They contain:
G cells and some mucous cells, G
cells are responsible for the release of
the hormone gastrin.
D cells, which release somatostatin, a
hormone that inhibits the release of
gastrin.
Oxyntic glands secrete:
1. mucus from mucus
secreting cells
2. intrinsic factor and HCl
from parietal cells
3. pepsinogen from peptic
cells
4. ECL
Mucus and endocrine
cells throughout mucosa
secrete mucus,
bicarbonate, histamine
and other hormones
 Gastric HCl secretion
HCl is secreted into the parietal cell canaliculi by the
following steps:
[1] CO2 diffuses from blood to inside the parietal cells.
[2] Within the parietal cells, carbonic acid is formed. The
formation of H2CO3 from CO2 is catalyzed by the enzyme
carbonic anhydrase.
[3] HCO3- diffuses back into the plasma in exchange for
Cl-, thus providing Cl- for the initial step in the secretory
process.
As HCO3- is added to the venous blood, the pH of the
blood drained from the stomach increases (alkaline tide).
The active transport process is begun by the transport of
Cl- ion into the canaliculi that open to the lumen of the
stomach.
[4] The H+ that is supplied by the
dissociation of carbonic acid into H+
and HCO3- within the parietal cells is
exchanged for K+ by the H+-K+-
ATPase pump (proton pump).
[5] Chloride ions diffuse with the
charged H+.
[6] Water enters the canaliculi down
the osmotic gradient created by the
movement of HCl into the canaliculi.
Mechanism of gastric HCl secretion:
Mechanism of gastric HCl secretion:

H+
+
K+ HCO3-

CI-
 Most of the HCl that is
secreted into the stomach is
neutralized and reabsorbed
within the small intestine.
 If gastric contents are lost
before they enter the small
intestine as in case of vomiting,
sever alkalosis may ensue.
 The pH of the parietal cell
secretion can be as low as 0.8
(or almost 4 million times as
great as the H+ concentration of
plasma).
Parietal cells bear receptors for three potent
stimulators of acid secretion, reflecting a triad of
neural, paracrine and endocrine control:
 Acetylcholine (muscarinic type receptor)
 Gastrin
 Histamine (H2 type receptor)
A variety of substances are capable of reducing
gastric acid secretion including:
 Prostaglandin E2 (PGE2),
 Several peptides hormones, including Secretin,
Gastric inhibitory polypeptide (GIP), Glucagon
and, Somatostatin.
 GIP (glucose-dependent insulinotropic peptide)
released from duodenal and jejunal mucosa in
response to the presence of chyme especially by
hyperosmolarity of glucose in the duodenum and
inhibits gastric gastrin release and stimulate the
release of insulin from pancreas, and inhibit the GI
motility and secretion of acid.
 The amount of insulin secreted is greater when
glucose is administered orally than intravenously.
 It is the only GI hormone released by all three major
foodstuffs (fats, proteins, and carbohydrates).
 PGE2, secretin and somatostatin may be physiologic
regulators. Somatostatin inhibits secretion of gastrin
and histamine, and appears to have a direct inhibitory
effect on the parietal cell.
 The H+-K+-ATPase
pump can be inhibited
by the drug omeprazole.
 Inhibition of pump
activity leads to a
prolonged increase in
gastric pH and the
removal of the
inhibitory effect of low
pH (<3.0) on gastrin
release.
Cimetidin and ranitidine used for
treatment of peptic ulcer. by two
mechanisms:
(1) Histamine released by ECL cells in the
stomach is blocked from binding on
parietal cell H2 receptors, which
stimulate acid secretion.
(2) Therefore, other substances that
promote acid secretion (such as gastrin
and acetylcholine) have a reduced effect
on parietal cells when the H2 receptors
are blocked.
 Mild injury to the mucosal barrier   mucus
secretion and surface desquamation followed by
regeneration.
 A more serious injury  breaks mucosal barrier and
exposes the mucosal surface  ulcer  bleeding.
 Breaks of mucosal barrier and exposure of the
mucosal surface to damage occurs due to highly
concentrated HCl, 10% ethanol, salicylic acid, or
acetylsalicylic acid (aspirin).
 The damaged mucosa liberates histamine   acid
secretion and  capillary permeability and
vasodilatation  edema.
 In addition, the exposure of mucosal capillaries to
the digestive process  bleeding.
 Erosive gastritis can occur as a result of
chronic use of non-steroidal anti-inflammatory
drugs (NSAIDs).
 The mechanism by which NSAIDS cause
gastritis involves the inhibition of prostaglandin
synthesis in the stomach.
 Prostaglandins normally maintain the
physicochemical barrier on the gastroduodenal
mucosal surface by stimulating the secretion of
mucus and bicarbonate.
 Loss of the protective mucus and bicarbonate
barrier renders the gastric mucosa susceptible
to damage by the acidic environment.
Protection of the epithelial lining of the stomach

pH 2 Gastric lumen

Mucus layer
HCO3- HCO3-
pH 7

Mucus

GI-S-19