5. The Stomach
Stomach consists of 3 parts viz. Fundus, Body
and Antrum. Stomach is the part of the GIT,
which produces Hydrochloric acid.
Functions of HCl are
1.Destroying the bacteria present in the food
2.Chemical breakdown of food
3.Activation of digestive enzyme
pepsin
6. The Stomach
FUNDUS: Food enters the upper section of the
stomach, called the FUNDUS.
Contains rugae folds to help with expansion when food
enters stomach, which the main function of the fundus.
BODY: It is the middle part of the stomach, which
follows after fundus. Food remains here for some
time, mixes with gastric juices and then forwarded to
the antrum.
The body of the stomach consists of majority of
secreting cells.
7. The Stomach
ANTRUM: The lower region of the stomach is called as
ANTRUM.
Grinds up swallowed food and regurgitates the
hydrochloric acid that is produced by the fundic and
body parietal cells.
8. Anatomy of Stomach
Stomach contain 5 types of Cells
Name of the Cell Function
Parietal Cell To Secrets HCL
G Cell To Secrets Gastrin
Chief Cell To Secrets Pepsin
Mast Cell To Secrets
Histamine
Mucus cell To Secrets Mucin
9. Acid Secretion
Acid secretion in the stomach is a continuous
process. Acid secretion is increased at the sight
or smell of food, at the meal times and during
stress.
10. Acid Secretion
There are 3 phases of acid secretion
1. Basal acid secretion: This secretion is devoid
of any stimulation and is governed by circadian
system of the body
2. Gastrin stimulated acid secretion: In this
phase, secretion is initiated by the presence of
food in stomach, sight, smell or even thought
of food.
11. Acid Secretion
3. Histamine stimulated acid secretion: Mast cells
secrete histamine. Stress and tensions
influence secretion of histamine. This secretion
is controlled by vagal stimulation.
Vagal stimulation also releases acetylcholine.
These in turn stimulate histamine (H2) and
muscarinic receptors respectively present on
the parietal cells leading to increased gastric
acid secretion.
13. Role of HCL
Strongly acidic fluid - Kills many microbes in food
Stimulates the secretion of hormones that promote the flow of
bile and pancreatic juice.
It is required for digestion of Proteins.
Chemical breakdown of food.
Create an environment for absorption of Nutrients, Vitamin
B12 and calcium.
14. Altered acid physiology & consequences
A mismatch between aggressive forces (mainly acid
and pepsin) and defensive forces (mucosal integrity) is
responsible for various acid related disorders. This
mismatch can occur because of
Increased acid secretion, and/or
Decreased mucosal defenses like-
1. Mucus
2. Mucosal blood flow
3. Bicarbonate
4. Cell renewal
5. Endogenous prostaglandins
15. Gastric Acid Pathogenesis
Gastric acid plays a pivotal role in the pathogenesis of various acid
related disorders or acid-peptic disorders, including
Reflux Esophagistis
Non-erosive reflux disease
Gastro Esophageal Reflux Disease
Non-cardiac chest pain
NSAID Induced gastritis
Peptic Ulcers
Functional Dyspepsia
pathologic gastrointestinal hypersecretory conditions
16. Reflux Esophagistis
Reflux esophagitis is better known as “heartburn.”
It is often felt behind the breastbone as a burning
chest discomfort, feeling of food coming back into the
mouth as an acid or bitter taste.
It mostly happens after meals and last a couple of
minutes to a couple of hours. It may not be relieved by
rest nor be caused by exercise, and may become worse
if you lie flat or bend over.
17. Symptoms
Bad taste in the mouth
Loss of tooth enamel
Chronic sore throat
Hoarseness
Choking
Cough or wheezing
18. Complications of Reflux Esophagistis
If RE is not treated, the inflamed area may bleed
slowly. Too much blood loss may cause low blood
count.
Damage to the lower esophagus may also cause scars to
form. Too much scarring causes the lower end of the
esophagus to narrow, making it harder and harder to
swallow.
Some patients with severe scarring may have trouble
swallowing.
19. Complications of Reflux Esophagistis
Barrett esophagus: sometimes called Barrett syndrome
or columnar epithelium lined lower oesophagus
(CELLO), refers to an abnormal change in the cells of the
lower portion of esophagus.
When the normal squamous epithelium lining of the
esophagus is replaced by goblet cells (cells usually found
lower in the gastrointestinal tract), Barrett's esophagus is
diagnosed.
A small number of people with Barrett’s esophagus
develop a rare but often deadly type of cancer of the
esophagus.
20. Gastro Esophageal Reflux Disease
Gastro Esophageal Reflux Disease is the result of the
reflux of gastric contents into the esophagus such an
extent that it overcomes the mucosal defense and
causes injury to the esophageal mucosa
21. Factors causing reflux and contribution to GERD
LES Related Disorder
1. A mechanical defect in LES
2. Inappropriate transient relaxation of LES
3. Hiatal hernia (also provides a reservoir for acid)
Type of food
1. Fatty and/or spicy food eating habit
2. Coffee, citrus or tomato juices
22. Factors causing reflux and contribute to GERD
Increased Gastric Pressure
1. Delayed gastric emptying
2. Obesity
3. Pregnancy
Others
1. Certain medications
2. Smoking
Sometimes if pylorus is impaired, bile and other
duodenal contents reflux from duodenum to
stomach and to esophagus adding aggravation
GERD.
23. GERD Symptoms
Intermittent substernal burning of pain (heartburn) is
characteristic of GERD. Other symptoms include
1. Angina-like chest pain
2. Laryngitis
3. Hoarseness
4. Chronic cough
5. Bronchitis
6. Aspiration pneumonia
24. Non-erosive reflux disease
NERD is defined as the presence of classic GERD
symptoms in the absence of esophageal mucosal
injury.
25. Symptoms
persistent heartburn
acid regurgitation
Nausea
Hoarseness in the morning or trouble swallowing
May feel like food is stuck in the throat
Bad breath
Persistent dry cough
but they do not have visible esophageal injury.
26. Non-cardiac chest pain
When acid from the stomach flows up into the
esophagus, it can cause a burning sensation in the
chest that's often mistaken for angina or a heart attack
Because the pain is similar to heart pain (called
angina), patients present to emergency rooms
concerned about a heart attack and commonly
undergo cardiac tests). After these cardiac tests fail to
show evidence of heart disease, the patients receive
the diagnosis of NCCP.
27. Symptoms
Non-cardiac chest pain typically is felt behind the
breast bone (sternum) and is described as
oppressive, squeezing or pressure-like. It may radiate
to the neck, left arm or the back (the spine). It may be
precipitated by food intake.
Heartburn
Fluid regurgitation
Bitter or sour taste
30. Peptic Ulcer
The two major risk factors known to impair
mucosal defenses and lead to peptic ulcers are
bacterium Helicobacter pylori (H. pylori) and the
frequent use of NSAIDs.
Gastric acid, further, contributes to formation of
ulcers once mucosal defenses are impaired. But
acid usually does not cause ulcers independently.
31. Helicobacter pylori
The risk of PUD is up to seven times higher in
patients with H. pylori infection than in general
population.
More than 70% of patients with gastric ulcers and
more than 90% of patients with duodenal ulcers are
infected with H. pylori.
H. pylori is thought to damage the gastric mucosa.
32. Symptoms of PU
Main symptom is dull aching or gnawing epigastric pain or
burning 1 to 3 hours after eating as per the location of
ulcer.
It is often relieved by eating or by antacids. Pain may
worsen in night because of increased acid secretion and
lack of food material in stomach to dilute the acid.
The nighttime paid normally interferes with sleep. Nausea,
vomiting and bloating are the other symptoms.
33. Complications of PU
Bleeding ulcers
Perforation into the peritoneal cavity
Penetration into adjacent organs
Gastric/intestinal passage obstruction
34. NSAIDs Induced gastritis
Non Steroidal Anti-inflammatory Drugs NSAIDs
damage the GI mucosa by dual mechanism.
1. They cause direct irritation to GI mucosa.
2. They inhibit prostaglandin synthesis leading to
reduced mucosal integrity & mucosal defense.
The acid then contributes to formation of ulcers. Use
of NSAIDs increases the risk of PUD upto 20 fold.
35. pathologic gastrointestinal hypersecretory
conditions
Gastric acid secretion is largely control by
cholinergic, histaminergic and
peptidinergic(especially gastrin) pathways. Disorders
in a number of these pathways can lead to gastric acid
hypersecretion.
Classification of gastric acid hypersecretory state
associated with hypergastrinemia
associated with hyperhistaminemia
unknown etiology
36. Zollinger-Ellison Syndrome
ZES is a clinical syndrome characterized primarily by
refractory peptic ulcer disease which is due to ectopic
release of gastrin by gastrinoma resulting in gastric
acid hypersecretion.
Complications of Zollinger-Ellison Syndrome
A person who has Zollinger-Ellison syndrome may
have only one gastrinoma or may have several
In some ZES patient gastrinomas may be malignant
(cancerous)
37. Symptoms
Burning pain in the abdomen
Nausea
Diarrhea
Vomiting
Bleeding from the stomach
Weakness
Fatigue
38. Pharmacotherapy for Acid Suppression
Different medications are available to inhibit the acids.
ANTACIDS
Histamine H2-Receptor Antagonists
Proton Pump Inhibitors
39. Limitation of Antacids
Antacids relieve the symptoms but cannot healing in
recommended dosage
Have short duration of action (about 2 hours) and need frequent
dosing
Antacids are ineffective for eradication H. pylori
Rebound acid secretion phenomenon may be problematic
Adverse effects (constipation with aluminum salts and diarrhea
with magnesium salts)
Drug interactions
Hampered absorption of other drugs because of change in pH
40. Limitations of H2-Receptor Antagonists
Controls mainly histamine related acid secretions and has
very low efficacy in gastrin related secretions
Recurrence rate is high in patients with H. pylori infection
Healing is delayed in smokers and recurrence rate is high
May interact with other medications
Though generally well tolerated, H2-Receptor
Antagonists can cause headache and other side4 effects
like confusion, diarrhea & gynecomastia (with
cimetidine).
41. Proton Pump Inhibitors
Proton Pump inhibitors were introduced in late 1980s.
Proton Pump inhibitors bind to the Proton Pump on
parietal cell and inhibit the acid secretion regardless of
whether it is stimulated by histamine, acetylcholine or
gastrin.
Proton Pump Inhibitors also have in vitro antimicrobial
activity against H. pylori though they cannot eradicate
H. pylori when used alone.
43. Comparison of all PPI
All PPIs are effective in healing and maintenance of
ARD but they differ in their ability to control
symptoms rapidly and consistently
Rabeprazole is different from other PPI because of
more rapid rate of activation, Rabeprazole results in a
faster onset of action and faster symptoms control
than other PPIs
44. Comparison of all PPI
Pharmacokinetic Profiles
Pharmacodynamic
Parameter
Lansoprazole Omeprazole Rabeprazole
At a pH of 1.2 2 2.8 1.3
At a pH of 5.1 90 84 7.2
At 10min 66% 47% 100%
At 45 Min 100% 83% 100%
Activation Time(min)
% Inhibition of the H+/K+-ATPase
45. Comparison of all PPI
Food does not affect degree of absorption
Rabeprazole, involving both cytochrome P450
mediated reaction in the liver and nonenzymatic
reactions, appears to confer an advantage over other
PPIs
47. Rabe… 20
Dosage and Administration
20 OD for 4 to 8 weeks
And in complicated ARD up to 40 mg for 4 to 8 weeks
48. Rabe…20
USPs
The latest and potent PPI
Maximum speed of onset of action
Maximum acid control
Maximum gastroprotection
Greater and faster symptom relief
Safe and convenient