OVERVIEW OF THE

STOMACH
PARTS OF THE STOMACH
Cell Enzyme Action

Mucous Neck Cells Mucus Protective against the

diffusion of ions and
molecules; Lubricate food
movement

Chief (Peptic) Cells Pepsinogen Precursor of Pepsin

Parietal (Oxyntic) Cells Hydrochloric Acid Activates Pepsinogen

Intrinsic Factor For B12 absorption
Enterochromaffin Cells ANP (Atrial Natriuretic Modulates gastric secretion
Peptide) via a vagal-dependent
mechanism

Enterochromaffin-like Cells (ECL) Histamine Inhibits D cells

Cell Enzyme Action

D cells Somatostatin Inhibit acid production

G cells Gastrin Stimulates parietal cells;

Aids in gastric motility

Gr cells Ghrelin Stimulates ECL cells

GASTRODUODENAL MUCOSAL
DEFENSE
PHYSIOLOGY OF GASTRIC
SECRETION
 Cephalic Gastric Intestinal
Phase Phase Phase
Sight, smell and taste of Food enters the Food enters the
food stomach intestine
“The Break in the Stomach”
A disruption of the mucosal integrity of the stomach or duodenum that results to a local
defect or excavation due to active inflammation.
  6-15% (Western population)
 Decreased by 50% over the past
years
 Due to the decreasing frequency of H.
pylori (80%)
 Occurs later in life
 Peak incidence in the 6th decade
 Male preponderance of 50%
 Likely to be silent and presents only
when complications have developed

16th edition:
- Very common in the US
- 4M new cases/year
- Lifetime Prevalence of 12% in men and 10% in women
 Most common risk
factors for PUD

1. Helicobacter pylori
infection

2. NSAIDs
(nonsteroidal anti-
inflammatory drug)
Additional Factors

1. Chronic obstructive lung disease (COPD)

2. Chronic renal insufficiency
3. Current tobacco use
4. Former tobacco use
5. Older age
6. Three or more doctor visits in a year
7. Coronary heart disease
PATHOPHYSIOLOGY
Gastric Ulcer Duodenal Ulcer

Stomach Duodenum
(lesser curvature) (1st part) >95%

Rare More common

Rare malignancy Extremely rare

malignancy
 H. pylori NSAIDs

Inflammation Disruption Cytotoxic Inhibit COX1 Impair

of mucosal to & COX2 platelet
secretions epithelium function
Increased
acid & pepsin
Decreased Decreased Bleeding
Smoking mucus repair
Stress Barrier production mechanism
Genes
Others disruption

Gastric Gastric injury

metaplasia

Antral Gastric
Ulceration
predominant ulcer

Duodenal
ulcer
 4

3
2
 most common complication in PUD
 more often in 60 and older
 mortality rate is 2.5 to 10% in 30 days
 higher incidence in elderly taking NSAIDs
PUD-related bleeding may further complicate into. . .

 Multi-organ failure (24%)

 Pulmonary complications (24%)
 Malignancy (34%)
 second most common ulcer-related complication
 6-7% of PUD patients with a >20% mortality
 higher incidence in patients taking NSAIDs (GU)

• form of perforation
• The ulcer bed tunnels into an adjacent organ
DU = penetration into the pancreas posteriorly causing pancreatitis
GU = penetration into the hepatic lobe; also causes gastrocolic fistulas
 second most common ulcer-related complication
 6-7% of PUD patients with a >20% mortality
 higher incidence in patients taking NSAIDs (GU)

• form of perforation
• The ulcer bed tunnels into an adjacent organ
DU = penetration into the pancreas posteriorly causing pancreatitis
GU = penetration into the hepatic lobe; also causes gastrocolic fistulas
  least common complication
 1-2% of patients
 Usually resolves with healing
 Usually presents a new onset of signs and symptoms
New Causes:
 ulcer-related inflammation
 peripyloric edema and/or scar formation causing mechanical obstruction
 requiring surgery/ endoscopic ballooning
Duodenal Ulcer Gastric Ulcer
Epigastric Pain (Gnawing and Burning sensation)
Hypersecretion of stomach acid (HCl) Normal – hyposecretion of stomach
acid (HCl)
Weight gain Weight Loss
Pain occurs 2-3 hours after a meal; often Pain occurs ½ to 1 hour after a meal;
awakened between 1-2AM rarely occurs at night; may be relieved
by vomiting
Ingestion of food relieves pain Ingestion of food does not help,
sometimes increases pain
Vomiting uncommon Vomiting common
Melena more common Hematemesis more common
Diagnostics
Laboratory and Radiology
Laboratory Tests

 CBC – to evaluate blood loss; patient is likely to be

anemic in the setting of bleeding
 Blood typing – in case patient needs transfusion

 Urinalysis – to rule out possible infection

 Electrolytes, BUN and Creatinine – to assess for

hypoperfusion; to determine needs in fluid
resuscitation
aPTT, PT and INR - for patients with an active
bleed

Liver Function Tests with Amylase and Lipase – to

rule out other causes of the epigastric pain

Tests for detection of H. pylori

 Invasive and
Noninvasive Tests for
Helicobacter pylori
Helicobacter pylori
֎ Curved or spiral-shaped pathogens
֎ Has multiple flagella at one pole and is
actively motile
֎ Grows in 3–6 days when incubated at
37°C in a microaerophilic environment
֎ Oxidase positive, catalase positive, and
is a strong producer of urease

35
36
 Invasive?
Noninvasive?
37
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40
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46
IMAGING STUDIES
 CT SCAN
Sensitivity for Ulcers: 29.6% to 54%,
with an average size of 25 mm for visible ulcers
compared to 16 mm of missed ones
Direct Signs for PUD

1. Focal Discontinuity of
Mucosal Hyperenhancement

2. Luminal Outpouching
INDIRECT SIGNS FOR PUD

1. HALLMARK: MURAL
THICKENING OF THE
AFFECTED PORTION OF THE
STOMACH AND OF THE
PROXIMAL DUODENUM

2. EDEMATOUS
“STRANDING” OF THE
PERIGASTRIC OR
PERIDUODENAL FAT
GASTRIC CA
BARIUM STUDIES
Single-contrast barium = 80% sensitivity
Double-contrast barium = 90% sensitivity
30% false negative; 10% false positive rate
 DUODENAL ULCER
■ WELL-DEMARCATED CRATER
DUODENAL
ULCER
GASTRIC
ULCER
GASTRIC CA
Duodenal Ulcer Hemorrhage
(+) Dilated duodenum filled by
hyperattenuating fluid
Duodenal Ulcer Hemorrhage
• Subtle hyperattenuating
content (proximal duodenum)
• Mucosal enhancement
Treatment
of Peptic
Ulcer
Disease

Acid-Supressing Drugs

Mucosal protective agents

A Summary of Commonly Used Drugs
for Treatment of Acid Peptic Disorders
Acid-Neutralizing/Inhibitory
Drugs
Antacids
– used by patients for symptomatic relief of dyspepsia
– most commonly used agents: mixture of aluminum hydroxide and magnesium hydroxide
(E.g. Mylanta, Maalox, Tums, Gaviscon)
– Side effects:
– hypermagnesemia for Mg-containing preparation
– chronic neurotoxicity for the aluminum preparation

– Calcium carbonate & sodium bicarbonate are potent antacids but with varying levels of
potential problems (hypercalcemia, systemic alkalosis)
Acid-Neutralizing/Inhibitory
Drugs
H2-Receptor Antagonists
– Cimetidine, Ranitidine, Famotidine, Nizatidine
– All will siginificantly inhibit basal and stimulated acid secretion when used at
therapeutic doses
– Often used for treatment of active ulcers (4-6 weeks) in combination with
antibiotics directed at eradicating H. Pylori
Side effects:
– reversible systemic toxicities include pancytopenia, neutropenia, anemia, and
thrombocytopenia
Acid-Neutralizing/Inhibitory
Drugs
Proton Pump (H+,K+-ATPase) Inhibitors (PPIs)
– Omeprazole, Esomeprazole, Lansoprazole, Rabeprazole, and Pantoprazole
– Dexlansoprazole - most recent, dual delayed-release system, aimed at
improving treatment of GERD
– Omeprazole & Lansoprazole - used for the longest time
Acid-Neutralizing/Inhibitory
Drugs
Proton Pump (H+,K+-ATPase) Inhibitors (PPIs)
– Lipophilic compounds; upon entering the parietal cell, they are protonated and
trapped within the acid environment of the tubulovesicular and canalicular
system
– Potently inhibit all phases of gastric acid secretion
– Onset of action is rapid, with a maximum acid inhibitory effect between 2 and 6
h after administration and duration of inhibition lasting up to 72–96 h
Mechanism of Action of PPIs
Acid-Neutralizing/Inhibitory
Drugs Potential Adverse Effects of PPIs
Cytoprotective Agents

Sucralfate
– complex sucrose salt in which the hydroxyl groups have been substituted by
aluminum hydroxide and sulfate
– insoluble in water and becomes a viscous paste within the stomach and duodenum,
binding primarily to sites of active ulceration
– Mechanisms: serving as a physicochemical barrier, promoting a trophic action by
binding growth factors such as EGF, enhancing prostaglandin synthesis, stimulating
mucus and bicarbonate secretion, and enhancing mucosal defense and repair.
– Toxicity: rare; constipation (2-3%)
– Std dosing: 1g qid
Cytoprotective Agents

Bismuth-Containing Preparations
– Colloidal bismuth subcitrate (CBS) and bismuth subsalicylate (BSS, Pepto-
Bismol) are the most widely used
– Mechanism: unclear
– Adverse effects with short-term use: black stools, constipation, darkening of the
tongue.
– Adverse effects with long-term use with high doses: neurotoxicity
– These compounds are commonly used as one of the agents in an anti-H. pylori
regimen
Cytoprotective Agents

Prostaglandin Analogues
– In view of their central role in maintaining mucosal integrity and repair, stable
prostaglandin analogues were developed for the treatment of PUD
– Mechanism: enhancement of mucosal defense and repair
– Toxicity: most common diarrhea (10-30%); uterine bleeding and contractions;
misoprostol is contraindicated in women who may be pregnant
– Std dosing: 200 μg qid
Cytoprotective Agents

Miscellaneous Drugs
– anticholinergic agents and tricyclic antidepressants
– but in light of their toxicity and the development of potent antisecretory agents,
these are rarely, if ever, used today
Physician’s goal
o provide relief of symptoms (pain or dyspepsia)
o promote ulcer healing
o prevent ulcer recurrence and complications
Maastricht IV/Florence Consensus Report on
H. pylori treatment considerations:
ofirst-degree relatives with gastric CA
oprevious gastric neoplasm treated
oa risk of gastritis or severe atrophy
ogastric acid inhibition for >1 year
ostrong environmental risk factors for gastric CA
oH. pylori–positive patients with a fear of gastric CA
 Choice of regimen will be
influenced by:
 Efficacy
 Patient tolerance
 Existing antibiotic resistance
 Prior antibiotic use
 Cost of the drugs
 85-90% - aim for initial eradication rates
 PPI + amoxicillin

Dual Therapy PPI + clarithromycin

ranitidine bismuth citrate [Tritec]

+
clarithromycin

eradication rates of <80–85%.

 FIRST TRIPLE REGIMEN
BISMUTH METRONIDAZOLE TETRACYCLINE

PPA /H2 BLOCKER

ANTIBIOTICS /BISTHMUTH
ANTIBIOTICS
COMPUND

ACID early symptom relief and

SUPPRESSION
enhances bacterial eradication
 PREPACKAGED FORMULATION
REGIMENS

PREVPAC HELIDAC
Lansoprazole BSS
Clarithromycin Tetracycline
Amoxicillin Metronidazole
Twice per day for Four times per day
14 days (with an antisecretory
agent)for 14 days
 Bismuth - black stools, constipation, or darkening of the tongue
Amoxicillin - pseudomembranous colitis ( <1–2% ); lead to
antibiotic-associated diarrhea, nausea, vomiting, skin rash, and
allergic reaction
Tetracycline - rashes and, very rarely, hepatotoxicity and
anaphylaxis

 Probiotics - ameliorate some of the antibiotic side effects

 Most common cause for
treatment failure in compliant
patients!
Clarithromycin
excluded in patients with
prior macrolide usage.

An approach to antibiotic
selection for H. pylori
therapy has been
recommended in the ACG
clinical guidelines.
 NEW APPROACHES TO TREATMENT

5 days of amoxicillin + PPI

5 days of PPI + TINIDAZOLE and CLARITHROMCIN/ LEVOFLOXACIN

 5 DAYS OF CONCOMITANT THERAPY

PPI TWICE DAILY TINIDAZOLE 500

MG TWICE DAILY
AMOXICILLIN 1 G LEVOFLOXACIN 500
TWICE DAILY MG TWICE DAILY
 NON–ANTIBIOTIC-MEDIATED APPROACHES

N-acetylcysteine mucolytic agent

PROBIOTICS inhibit H. pylori

 SUCCESSFUL
H.PYLORI ERADICATION

REINFECTION
AFTER THERAPY COMPLETED
FOR 6MONTHS

RECRUDESCENCE
THERAPY FOR NSAID-
RELATED MUCOSAL
INJURY
Medical intervention for NSAID-related
Mucosal Injury

Treatment of
the active Primary
ulcer prevention of
future injury
Recommendations for Treatment of
NSAID-Related Mucosal Injury
Clinical Setting Recommendation

Active Ulcer

NSAID •H2 receptor antagonist

Discontinued or PPI

NSAID •PPI
Continued
Recommendations for Treatment of
NSAID-Related Mucosal Injury
Clinical Setting Recommendation

• Misoprostol
Prophylactic • PPI
therapy • Selective COX-2 inhibitor

• Eradication if active ulcer present or

H. pylori infection there is a past history of PUD
 Guide to NSAID Therapy
No/Low NSAID GI
NSAID GI Risk
Risk

Coxib or
No CV Risk Traditional NSAID Traditional NSAID + PPI or Misoprostol
(no aspirin)
Consider non-NSAID therapy

Traditional NSAID + PPI or A gastroprotective agent must be

CV Risk misoprostol if GI risk warrants added if a traditional NSAID is
(consider gastroprotection prescribed
aspirin) Consider non-NSAID therapy Consider non-NSAID therapy
Surgical
Treatment
Ulcer related
complications
a. bleeding
b. perforation
c. obstruction
d. intractability or non healing
Specific Operations for Duodenal Ulcers

Surgical treatment was originally designed to decrease

gastric acid secretion. Procedures commonly
performed:
1. vagotomy and drainage (by pyloroplasty,
gastroduodenostomy, or gastrojejunostomy),
2. highly selective vagotomy
3. vagotomy with antrectomy
 • Vagotomy – ablating cholinergic input to the
Specific stomach to decrease gastric secretion
• Drainage – compensate for the vagotomy-induced
Operations for gastric motility disorder
Duodenal Ulcers • Antrectomy – eliminate additional stimulant for
gastric acid secretion, gastrin
Specific
Operations for
Duodenal Ulcers

• Highly selective
vagotomy
• Also known as: parietal
cell, super selective,
proximal vagotomy
• Only vagal fibers
innervating the portion
of the stomach that
contains parietal cells
are transected
 Specific Operations
for Gastric Ulcers

 Antrectomy (including the ulcer) with a

Billroth I anastomosis – treatment of
choice for antral ulcer
 Vagotomy is peformed ONLY if DU is
present
 Csendes’ procedure – for ulcers near
the esophagogastric junction
 Kelling-Madlener – for fragile patients
with high GU; includes antrectomy,
intraoperative ulcer biopsy and
vagotomy
 Antrectomy and Anastomosis
 Antrectomy – removal of the
stomach antrum
 Anastomosis include:
 Billroth I
(GASTRODUODOSTOMY) – if
adequate length of normal
duodenum is available
 Billroth II
(GASTROJEJUNOSTOMY) – a loop
of proximal jejunum is selected
and brought in an antecolic or
retrocolic fashion towards the
transected stomach
Roux-en-Y

– ESOPHAGOGASTROJEJUNOSTOMY
 end to side surgical anastomosis between the stomach
and distal bowel
SURGICAL
COMPLICATIONS
SURGICAL COMPLICATIONS

Recurrent Afferent Loop Dumping

Ulcerations Syndrome Syndrome

Post Maldigestion
Vagotomy &
Diarrhea Malabsorption
Recurrent Ulcerations
Persistent / Retained
Surreptitious N Recurrent Gastric
SAID use H.Pylori Antrum
Infection

Incomplete Inadequate
Vagotomy Drainage
Afferent Loop Syndromes

Partially
Obstructed
Afferent Loop

Incomplete
Bacteria
Drainage of
Overgrowth
Bile and
Secondary to
Pancreatic
Stasis
Secretions
Dumping Syndrome

Vagotomy
TWO PHASES:
&
EARLY & LATE
Drainage
 EARLY PHASE LATE PHASE
15-30 minutes after a meal 90 min to 3 h after meals

rapid emptying of gastric cont vasomotor symptoms

ents

release of vasoactive GI horm Hypoglycemia due to excessiv

ones e insulin release
Post-Vagotomy Diarrhea

Truncal
Vagotomy

Interruption of
Luminal Fibers Intermittent
supplying the Diarrhea
gut
Bile Reflux Gastropathy

• Common among post–partial gastrectomy patients

• mucosal erythema of the gastric remnant with associated
abdominal pain, early satiety, nausea, and vomiting
• Categorized as bile or alkaline reflux gastropathy /
gastritis
Maldigestion And Malabsorption

SURGICAL PROCEDURE COMPLICATION

Partial Gastrectomy Decreased serum Vit B12

Billroth II Iron-defiency anemia, Fol

Gastrojejunostomy ate-deficiency anemia
Partial Gastrectomy & Osteoporosis
Gastrojejunostomy osteomalacia
Surgeries that bypass Copper deficiency
the Duodenum
THANK YOU!
 Primary prevention of NSAID-induced
ulceration
Avoiding the agent

Using lowest possible dose for shortest period of time possible

Using theoretically less injurious NSAIDs

Using newer topical NSAID preparation

Using concomitant therapy medical therapy to prevent NSAID-

induced ulceration

RBS