This presentation is ment for undergraduate medical student to revise PUD

1. Peptic Ulcer Disease
Dr. Shatdal Chaudhary
Assistant Professor (Internal Medicine)
B.P. Koirala Institute of Health Sciences,
Dharan

2.  An ulcer is defined as disruption of the
mucosal integrity leading to a local defect or
excavation due to active inflammation
 Erosion: Damage within the mucosal layer
 Ulcers are defined as breaks in the mucosal
surface >5 mm in size, with depth to the
submucosa.
 The term 'peptic ulcer' refers to an ulcer in the
lower oesophagus, stomach or duodenum, in
the jejunum after surgical anastomosis to the
stomach or, rarely, in the ileum adjacent to a

4. Gastroduodenal Mucosal Defense
• 3-level barrier preepithelial, epithelial, and
subepithelial elements
• Mucus-bicarbonate layer serves as a
physicochemical barrier
• Surface epithelial cells provides defense
 mucus production,
 epithelial cell ionic transporters that maintain
intracellular pH and HCO3 production
 intracellular tight junctions

5. Gastroduodenal Mucosal Defense
Role of Prostaglandins
 Gastric mucosa contains abundant levels of
PG
 Play central role in epithelial defense/repair
 Regulate release of mucosal HCO3 & mucus
 Inhibit parietal cell secretion
 Maintain mucosal blood flow
 Epithelial cell restitution.

6. Synthesis of PGE2 & prostacyclin (PGI2)

7. Duodenal Ulcers
 duodenal sites are 4x as common as gastric sites
 most common in middle age
 peak 30-50 years
 Male to female ratio—5:1
 Genetic link: 3x more common in 1st degree relatives
 more common in patients with blood group O
 associated with increased serum pepsinogen
 H. pylori infection common
 up to 95%
 smoking is twice as common

8. Gastric Ulcers
 common in late middle age
 incidence increases with age
 Male to female ratio—2:1
 More common in patients with blood group A
 Use of NSAIDs - associated with a three- to four-fold
increase in risk of gastric ulcer
 Less related to H. pylori than duodenal ulcers – about
70%
 10 - 20% of patients with a gastric ulcer have a
concomitant duodenal ulcer

9. H. Pylori
HISTORY
1982- Waren and Marshall described first-named
“campylobacter pyloridis”
1985: Association with peptic ulcer
1989: Named as ‘helicobacter ‘(helico-curved; bacter-staff)

10. Pathophysiology
• H. pylori inf. is virtually always associated with
chronic active gastritis.
• But only 10–15% develop frank PUD.

11. Interplay between bacterial and host
factors

12. Pathophysiology
Tolerance of the acid conditions (pH 1-2)
1. Urease: urea -> CO2 + NH3,
then NH3 + H+ -> NH4+, which
provides buffering.
2. Residence in mucus and on
the epithelial cells.
3. Capacity to create an ionic
gradient at a low pH.
4. Release of factors that
decrease acid secretion by
parietal cells during early
infection.

13. • H. pylori is able to fight off the stomach acid that does reach it
with the enzyme urease.
• Urease converts urea into bicarbonate and ammonia, which
are strong bases.
• These acid neutralizing chemicals
around the H. pylori protect if from
the acid in the stomach.

14. Natural history of H. pylori infection

15. Etiology
• AThe most important contributing factors are
H pylori, NSAIDs, acid, and pepsin.
• Additional aggressive factors include smoking,
ethanol, bile acids, aspirin, steroids, and
stress.
• Important protective factors are mucus,
bicarbonate, mucosal blood flow,
prostaglandins, hydrophobic layer, and
epithelial renewal.
– Increased risk when older than 50 d/t decrease
protection

16. Causes of Ulcers Not Caused by Hp and
NSAIDs
Infection Miscellaneous
Cytomegalovirus,
Herpes simplex virus Basophilia in myeloproliferative disease
Helicobacter heilmanni Duodenal obstruction (e.g., annular
pancreas)
Drug/Toxin Infiltrating disease
Bisphosphonates Ischemia
Glucocorticoids (when combined
with NSAIDs)
Radiation therapy
Chemotherapy Sarcoidosis
Potassium chloride Crohn's disease
Mycophenolate mofetil Idiopathic hypersecretory state

17. Clinical Features : DU
 Abdominal pain
 Typical pain pattern in DU occurs 90 min to 3 h
after meal and is relieved by antacids or food.
 Awakes the patient from sleep : the most
discriminating symptom( 2/3rd of DU pt.)
 Unfortunately, this symptom also present in
1/3rd of patients with NUD.

18. Clinical Features: GU
 Pain pattern in GU may be different
 Precipitated by food.
 While vomiting relieves it.
 Nausea and weight loss occur more commonly
in GU patients.

19. Clinical features
 Mechanism of pain in ulcer is unknown.
 Possible explanations include
 acid-induced activation of chemical receptors
in the duodenum
 enhanced duodenal sensitivity to bile acids
and pepsin, or
 altered gastroduodenal motility

20. On Examination
 Epigastric tenderness
 Guaic-positive stool resulting from occult blood loss
 Succussion splash resulting from scaring or edema
due to partial or complete gastric outlet obstruction
 A succussion splash describes the sound obtained by
shaking an individual who has free fluid and air or gas in a
hollow organ or body cavity.
 Usually elicited to confirm intestinal or pyloric obstruction.
 Done by gently shaking the abdomen by holding either
side of the pelvis. A positive test occurs when a splashing
noise is heard, either with or without a stethoscope. It is
not valid if the pt has eaten or drunk fluid within the last
three hours.

21. Differential Diagnosis
 Neoplasm of the stomach
 Pancreatitis
 Pancreatic cancer
 Diverticulitis
 Nonulcer dyspepsia (also called functional dyspepsia)
 Cholecystitis
 Gastritis
 GERD
 MI—not to be missed if having chest pain

22. PUD-Related Complications
 Gastrointestinal Bleeding :15%
 Perforation/ Peritonitis : 6–7%
 Gastric Outlet Obstruction:1–2%
 Gastric Carcinoma

23. Diagnostic Evaluation
 Poor predictive value of abdominal pain for the
presence of a gastroduodenal ulcer
 Multiple disease that can mimic this disease
 Most patients with symptoms s/o an ulcer have
NUD;
 Empirical therapy is appropriate for pts who
are otherwise healthy and <45, before
embarking on a diagnostic evaluation .

24. Diagnostic Evaluation Barium studies
• Sensitivity for detecting
a DU
single-contrast Ba meals
80%: double-contrast
90%.
• Sensitivity decreased in
small ulcers (<0.5 cm),
presence of previous
scarring, or in postop
pt.

25. Endoscopy
 Most sensitive and specific .
 Direct visualization of the mucosa,
 Biopsy to rule out malignancy or Hp.
 Identifies lesions too small to detect by Ba
exam, for evaluation of atypical radiographic
abnormalities, or to determine if an ulcer is a
source of blood loss.

26. Tests for Detection of H. pylori
Test Sensitivity/Sp
ecificity, %
Comments
Invasive (Endoscopy/Biopsy Required)
Rapid urease 80–95/95–
100
Simple, false negative with recent use of PPIs,
antibiotics, or bismuth compounds
Histology 80–90/>95 provides histologic information
Culture —/— Time-consuming, expensive ; antibiotic
susceptibility
Non-invasive
Serology >80/>90 Inexpensive, convenient; not useful for early
follow-up
Urea breath
test
>90/>90 Simple, rapid; useful for early follow-up; false
negatives with recent therapy ; exposure to low-
dose radiation with 14C test
Stool antigen >90/>90 Inexpensive, convenient; not established for
eradication but promising

27. Peptic Ulcer Disease: Treatment
Drug Type/Mechanism Examples Dose
Acid-suppressing drugs
Antacids
H2 receptor antagonists Ranitidine
Famotidine
Nizatidine
300 mg hs
40 mg hs
300 mg hs
Proton pump inhibitors Omeprazole
Lansoprazole
Rabeprazole
Pantoprazole
Esomeprazole
20 mg/d
30 mg/d
20 mg/d
40 mg/d
20 mg/d
Mucosal protective agents
Sucralfate Sucralfate 1 g qid
Prostaglandin analogue Misoprostol 200 g qid
Bismuth-containing
compounds
Bismuth subsalicylate (BSS)

28. Regimens for H. pylori eradication
Drug Dose
Triple Therapy
1. Bismuth subsalicylate plus 2 tablets qid
Metronidazole plus 250 mg qid
Tetracyclinea 500 mg qid
2. Ranitidine bismuth citrate plus 400 mg bid
Tetracycline plus 500 mg bid
Clarithromycin or metronidazole 500 mg bid
3. Omeprazole (lansoprazole) plus 20 mg bid (30 mg bid)
Clarithromycin plus 250 or 500 mg bid
Metronidazoleb or 500 mg bid
Amoxicillinc 1 g bid

29. Regimens for H. pylori eradication
Quadruple Therapy
Omeprazole (lansoprazole) 20 mg (30 mg) daily
Bismuth subsalicylate 2 tablets qid
Metronidazole 250 mg qid
Tetracycline 500 mg qid

30. Evaluation/Follow-up/
• H. Pylori Positive: retesting for tx efficacy
• Urea breath test—no sooner than 4 weeks after
therapy to avoid false negative results
• Stool antigen test—an 8 week interval must be allowed
after therapy.
• H. Pylori Negative:
• evaluate symptoms after one month. Patients who are
controlled should cont. 2-4 more weeks.

31. Surgical Therapy
Required for
1. Medically refractory disease: rare
2. Treatment of an ulcer-related complication

32. Specific Operations for Duodenal
Ulcers
1. Vagotomy and drainage (by
pyloroplasty,
gastroduodenostomy, or
gastrojejunostomy),
2. Highly selective vagotomy
(which does not require a
drainage procedure)
3. Vagotomy with antrectomy

33. Zollinger–Ellison Syndrome
Severe peptic ulcer diathesis secondary to
gastric acid hypersecretion due to unregulated
gastrin release from a non- β cell endocrine
tumor (gastrinoma)

34. Zollinger–Ellison Syndrome
 Incidence varies from 0.1 to 1% of individuals
presenting with PUD.
 Males > females,
 Ages 30 and 50 yrs.
 Gastrinomas are classified into sporadic tumors
(more common) and those associated with MEN
type I

35. ZES: Clinical Manifestations
 Peptic ulcer is the most common clinical
manifestation
 Suspicious Ulcers
 in unusual locations (D2 & beyond)
 refractory to standard medical therapy
 recurrence after acid-reducing surgery
 presenting with frank complications
 in the absence of H. pylori or NSAID .

36. ZES: Clinical Manifestations
 Diarrhea, found in up to 50%.
 Gastrinomas can develop in the presence of
MEN I syndrome in ~25% of patients.
 AD disorder involves primarily 3 organs:
parathyroid glands (80–90%), pancreas (40–
80%), and pituitary gland (30–60%).

37. ZES: Treatment
 PPIs are the treatment of choice
 Surgery