Git class-2

Stomach-Physiology-2
Dr. Sai Sailesh Kumar G
Associate Professor
Department of Physiology
RDGMC

Oxyntic cell
Extensive tubulo vesicular system
Open canalicular system
The apex of the oxyntic cell faces the
lumen of the gastric glands.
In resting sate, more tubules, vesicles and
microvilli rudimentary.
On activation, tubulovesicular membranes
fuse with the cell membrane and microvilli
that project into canaliuculus. (this
ensures increased activity of H+ _ K+ ATP
ase pump

Hydrochloric acid secretion –
perietal cell
Nonsecreting cell Secreting cell

Basic Mechanism of HCl secretion
 On stimulation, parietal cells secretes
160mmol/L of HCL.
 pH of this acid is 0.8
 Oxyntic cells contains intracellular canaliculi.
 HCl is produced at villus like projections
inside these canaliculi and then conducted to
the secretory end of the cell.
 Main driving force for HCl secretion is
hydrogen-potassium pump.

Mechanism of HCl formation
• Step-1:
 In the parietal cell, water dissociates into H+ and OH-.
 The H+ is actively secreted into canaliculi in exchange
with potassium.
 This active process is mediated by H+ _ K+ ATP ase.

• Step-2:
 In the basolateral ( extracellular side) of the
membrane, Na+ _ K+ ATP ase pump transports K+ Into
the cell.
 This K+ tends to leak into the lumen but are recycled
back into the cell by H+ _ K+ ATP ase pump .

• Step-3:
 The basolateral (extracellular side) of the
membrane, Na+ _ K+ ATP ase pump creates low intra
cellular Na+.
 This contributes to reabsorption of sodium from
lumen of the canaliculus.

Thus most of the sodium and potassium
in the canaliculus is reabsorbed into the
cell cytoplasm and hydrogen ions take
their place in the canaliculus.

• Step-4:
 As H+ is pumped out of the cell, OH-
accumulates in the cell. This OH- combines with Co2
and forms HCO3
-
 Co2 is formed with in the cell during metabolism
or entered into the cell from the blood.
 This reaction is catalyzed by carbonic anhydrase.

• Step-5:
 This HCO3
- is transported across the
basolateral membrane into the extra cellular
fluid in exchange with chloride.
 These chloride ions are secreted into the
canaliculus through chloride channels.
 This chloride combines with hydrogen ions and
forms HCl in the canaliculus.

• Step-6:
 This HCl is secreted outward through the
openend of the canaliculus into the lumen of
the gland.
 Water enters into the canaliculus because of
extra ions secreted into the canaluculus.

Final secretion
Final secretion contains water, HCl at
the concentration of about 150-160
mEq/L, potassium at the concentration
of 15 mEq/L and small amounts of
sodium chloride.

Factors that stimulate gastric secretion
Acetyl choline (released by parasympathetic
stimulation)
Gastrin
Histamine
• Note:Ach stimulates secretion of pepsinogen,
HCl and mucous. Gastrin and Histamine
mainly stimulate secretion of HCl and little
effect on pepsinogen and mucous.

Stimulation of acid secretion
Parasympathetics
(Ach)
Gastrin
Histamine
Potentiation of agents

Acetylcholine
Released from vagal cholinergic fibers
Direct action through M3 ( muscarinic)
receptors and Increases intra cellular
calcium.
Calcium activates protein kinases and
increases activity of H+ _ K+ ATP ase pump.
Indirect action through stimulating the
ECL cells and G cells

Gastrin
Acts on gastrin receptors directly and
increases intra cellular calcium which
increases HCl secretion.
Gastrin stimulates ECL cells and
increases HCL secretion indirectly.

Histamine
Acts on H2 receptors
Increases intra cellular CAMP
CAMP stimulates protein kinase and increases
activity of hydrogen-potassium ATP ase pump.
Note: As histamine is stimulated by both
acetylcholine and gastrin, it is considered as
most potent mediator of HCl secretion. So
Patients with peptic ulcer are usually treated
with antagonists of H2 receptors.

Mechanical factors
Accumulation of food in the stomach
causes distention of the stomach.
Mechanical distention of stomach
stimulates G cells and stimulates gastrin
release.

Chemical factors
Products of protein digestion stimulates
HCl secretion.
Hot and spicy foods stimulates HCl
secretion from stomach.

Factors inhibiting HCl secretion
Auto regulation of acid secretion: when
more acid is secreted it itself inhibits
secretion.
This is mediated by inhibition of gastrin
secretion and stimulation of
somatostatin secretion.
Secretin
Gastric inhibitory peptide (GIP)

Phases of gastric juice secretion
Three phases
1. Cephalic phase
2. Gastric phase
3. Intestinal phase

Cephalic phase
 Stimulus: Taste, smell, sight or thought of food
 Signals arise from cerebral cortex or appetite
center in hypothalamus or amygdala
 Transmitted to dorsal motor nucleus of vagus
 Efferent fibers in the vagal nerve to stomach
 Increases HCl secretion

Stimulation of acid secretion
– cephalic phase
 blocked by
vagotomy
 sham feeding
 role of GRP
(bombesin)

Enterogastric Reflex
• CCK
– Initiates enterogastric reflex
• Slows gastric emptying
• Inhibit gastric secretion
• GIP gastric inhibitory peptide
– Inhibit Histamine
• VIP vasoactive Intestinal peptide; somatostatin
– Have moderate inhibitory effects on gastric secretion

Total Gastrectomy
• Removal of whole stomach
• Deficiency of intrinsic factor: Pernicious
anemia
• Protein digestion is normal though pepsin is
absent
• Hyperglycemia is observed due to rapid
absorption of glucose from the intestine.
This increases insulin release so
hypoglycemia after 2 hrs of meal.

Dumping syndrome
• Weakness, dizziness, hypoglycemia after
meal
• Rapid entry of the hypertonic meal into
intestine cause movement of water from
plasma into gut.
• This causes hypovolemia and hypotension.

MUCOSAL BARRIER &
PEPTIC ULCER
37

GASTRIC MUOSAL BARRIER
The gastric mucosal barrier is the property of the
stomach that allows it to contain acid
If the barrier is broken, then the acid diffuses
back into the mucosa and damage the stomach wall
The gastric mucosal barrier is made up of 3
components:
38

GASTRIC MUCOSAL BARRIER
a) Compact epithelial cell lining with tight
junctions
b) Gastric mucus covering (gel like coating)
c) Bicarbonate ions, secreted by the surface
epithelial cells. The bicarbonate ions act to
neutralize harsh acids
39

GASTRIC MUCOSAL BARRIER
• The gastric mucosal barrier is the property of
the stomach that allows it to contain acid.
• The barrier consists of three protective components.
These provide the additional resistance for the
mucosal surface of the stomach. to neutralize harsh
acids.
40

THREE COMPONENTS
 The three components include:
• a) A compact epithelial cell lining. Cells in the epithelium of the
stomach are bound by tight junctions that repel harsh fluids that may
injure the stomach lining.
• b) A special mucus covering, derived from mucus secreted by surface
epithelial cells and Foveolar cells. This insoluble mucus forms a
protective gel-like coating over the entire surface of the gastric mucosa.
The mucus protects the gastric mucosa from auto digestion by
e.g. pepsin and from erosion by acids and other caustic materials that are
ingested.
• c) Bicarbonate ions, secreted by the surface epithelial cells. The
bicarbonate ions act as buffers
41

MUCUS
Mucus is secreted by mucus cells
Present allover the GIT
Acts as a protectant and lubricant of wall of gut
Mucus is a viscous gel which contains mucin,
phospholipids, electrolytes (mainly HCO3) and water
Separates the epithelial cells from acid of stomach
43

CONT’D
 This maintains the Ph of epithelial cells alkaline despite
gastric acid
 Mucus is strongly resistant to digestion by gastric enzymes
 Has buffering properties (neutralize acid)
 Helps in propulsive movement by lubrication
 Easy slippage of food
44

PEPTIC ULCER
Ulcer :- An Ulcer is a discontinuity or break in a
bodily membrane, or breach in the epithelium
Ulcer may occur anywhere in the body
When it occurs in stomach its gastric ulcer
In duodenum its duodenal ulcer
45

CONT’D
Ulcer occurring in either of these two sites is
called peptic ulcer
Its also known as acid peptic disease (APD)
46

PATHO PHYSIOLOGY OF
PEPTIC ULCER
Defect in the mucosal barrier
Hyper secretion of acid
Helicobacter bacterial infection
49

DEFECT IN THE MUCOSAL
BARRIER
If the secretion of mucus is impaired
Or bicarbonate production is impaired
Such damage is caused by drugs like asprin,
NSAID
Chronic stress conditions (stress ulcer)
50

HYPER SECRETION OF
ACID
 Chronic anxiety
 Common in people with busy life style (Type A personality)
 Hurry, worry, curry
 Intake of spicy food – leads to hyper chlorhydria
 Conditions with hyper chlorhydria
(Zollinger Ellison syndrome ) gastrin secreting tumor
51

H.PYLORI INFECTION
Major cause of peptic ulcer
This bacterial infection causes Damage to the
mucosal barrier
Increase in gastrin secretion from G cells
Reduce somatostatin from D cells
Initially causes gastritis which later on leads to peptic
ulcer
52

CONTD …..
 Helicobacter pylori, previously Campylobacter pylori, is a
Gram-negative, micro aerophilic bacterium found in the stomach,
and may be present in other parts of the body, such as the eye.
 It was identified in 1982 by Australian scientists
Barry Marshall and Robin Warren, who found that it was
present in a person with chronic gastritis and gastric ulcers,
conditions not previously believed to have a microbial cause.
 It is also linked to the development of duodenal ulcers and
stomach cancer. However, over 80% of individuals infected with
the bacterium are asymptomatic and it may play an important
role in the natural stomach ecology.
53

CONTD…..
 More than 50% of the world's population harbor H. pylori in
their upper gastrointestinal tract.
 Infection is more prevalent in developing countries, and
incidence is decreasing in Western countries.
 H. pylori's helical shape (from which the genus name is
derived)(Screw like, spiral) is thought to have evolved to penetrate
the mucoid lining of the stomach.
55

SIGNS & SYMPTOMS OF H.
PYLORI INFECTION
 Up to 85% of people infected with H. pylori never experience symptoms
or complications.
 Acute infection may appear as an acute gastritis with abdominal
pain (stomach ache) or nausea.
 Where this develops into chronic gastritis, the symptoms, if present, are
often those of non-ulcer dyspepsia:
• stomach pains
• Nausea
• Bloating
• Belching
• sometimes vomiting or black stool.
56

 Individuals infected with H. pylori have a 10 to 20% lifetime risk of
developing peptic ulcers and a 1 to 2% risk of acquiring stomach cancer.
 Inflammation of the pyloric antrum is more likely to lead to duodenal ulcers,
while inflammation of the corpus (body of the stomach) is more likely to lead
to gastric ulcers and gastric carcinoma.
 H. pylori has also been associated with colorectal polyps and colorectal cancer.
57

ADAPTATION TO THE STOMACH’S
ACIDIC ENVIRONMENT
 To avoid the acidic environment of the interior of the stomach
(lumen), H. pylori uses its flagella to burrow into the mucus lining of the
stomach to reach the epithelial cells underneath, where the pH is more
neutral.
 H. pylori is able to sense the pH gradient in the mucus and move
towards the less acidic region (chemotaxis).
58

CONTD…..
 H. pylori is found in the mucus, on the inner surface of the epithelium,
and occasionally inside the epithelial cells themselves.
 It adheres to the epithelial cells by producing adhesions, which bind to
lipids and carbohydrates in the epithelial cell membrane.
59

CONTD…..
 In addition to using chemotaxis to avoid areas of low pH, H.
pylori also neutralizes the acid in its environment by producing large
amounts of urease, which breaks down the urea present in the stomach
to carbon dioxide and ammonia.
 The ammonia, which is basic, then neutralizes stomach acid.
60

SYMPTOMS OF PEPTIC ULCER
Upper abdominal pain
Pain usually by empty stomach relieved by
food or antacid
Vomiting
Blood vomiting and perforation in severe
cases
61

FACTORS THAT STIMULATE ACID
SECRETION
Acetylcholine
Gastrin
Histamine
63

TREATMENT
 Anti histamines
 Anticholinergic drugs
 Proton pump blockers
 Sucralfate
 Gastrin blockers
 Antacids
65

• Drugs that neutralize existing acid
Antacids
• Drugs that suppress acid formation
H2 receptor antagonists
PPI
Antimuscarinic agents
• Drugs for Mucosal protection
Prostaglandins Sucralfate
Carbenoxolone colloidal bismuth
• Miscellaneous

2/1/2020 67
histamine
H+
H +
HCl
H+
Cl-
AXIDAXIDAXID
Proton Pump
H+
H+
parietal cell
parietal cell membrane
H2 receptor
gastrin
H2-receptor antagonist
H +
acetylcholine
HOW H2-RECEPTOR
ANTAGONISTS WORK
Figure 1-4 H2 Receptor Antagonist Mechanism of Action

H2 Receptor Antagonists
Cimetidine Famotidine
Ranitidine
• Structures share homology with histamine
• Different potency but all significantly inhibit
basal and stimulated acid secretion
• Similar ulcer healing rates
• Often used for active ulcers (4 - 6 wks) in
combination with antibitiotics for H.Pylori

Proton Pump Inhibitors
Omeprazole Lanzoprazole
Pantoprazole
• Substituted benzimidazole derivatives that
covalently bind and IRREVERSIBLY inhibit
H+,K+, ATPase
• Most potent acid inhibitors

2/1/2020 70
histamine
H+
HCl
H+
H +
Cl-
Proton Pump
H+
H+
parietal cell
parietal cell membrane
H2 receptor
gastrin
Proton pump inhibitors
H +
acetylcholine
HOW PROTON PUMP
INHIBITORS WORK
Figure 1-5 Proton Pump Inhibitor Mechanism of Action

Antacids
• Calcium bicarbonate
• Sodium bicarbonate
• Aluminum hydroxide
• Magnesium hydroxide
Rarely used as a primary therapeutic agent
but for symptomatic relief only
Mostly used in combination

H. Pylori Eradication Therapy
Treatment Efficacy
H2-blockers alone No effect
Omeprazolealone No effect
Bismuth+amoxycillin 44%
Bismuth+metronidazole 55%
Omeprazole+amoxycillin 58%
Bismuth+metronidazole+amoxycilli
n
73%
Bismuth+metronidazole+tetracycli
ne
94%

NON SPECIFIC TREATMENT
Avoid stress
Adequate sleep
Regulation of diet
Avoid spicy foods, alcohol
Withdrawal of drugs like aspirin, NSAIDS
73

SURGICAL TREATMENT
Vagotomy
Gastrectomy
74

FACTORS THAT CAN
DAMAGE THE BARRIER
Bacterial Infection by Helicobacter pylori
-Alcohol
-Aspirin
-NSAID
75

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