Peptic Ulcer Disease.Ppt.Fmdrl

1. Peptic Ulcer Disease
Ramona Carter-Burdine M.D.
UTMB Galveston, Tx

2. Learning Objectives
On completion of this lecture participants will be
able to:
•Recognize the typical clinical presentation and
risk factors for peptic ulcer disease
•Understand pathophysiology of PUD focusing on
H. pylori
•Describe an appropriate diagnostic plan based
on individual risk factors
•Prescribe an appropriate therapeutic regimen

3. Disease Prevalence
•Lifetime Prevalence = 10% of Americans
develop PUD
•10% of ER patients with abdominal pain
diagnosed with PUD
•Prevalence decreasing over last 30yrs
•Male-to-female ratio of gastritis = 1:1
•Male-to-female ratio of PUD = 2:1

4. Definition
• Peptic ulcer disease (PUD) = Mucosal
defect in the gastrointestinal tract (gastric
or duodenal) exposed to acid and pepsin
secretion
•Gastritis is the precursor to PUD and it is
clinically difficult to differentiate the two

5. Differentiating gastric from peptic
ulcer disease
•Duodenal ulcers - age 25-75 years.
•Gastric ulcer - age 55-65 years
•Pain awakening patient from sleep
between 12-3 a.m. present in 2/3
duodenal ulcer patients and 1/3 gastric
ulcer patients

6. Case Presentation
Mr. Jones is a 45 year old male who
presents to your clinic with epigastric
abdominal pain x 2 weeks.
What is your initial differential diagnosis at
this point given the limited information?

7. Initial Differential Diagnosis
More Common:
•Gastroesophageal reflux
disease
•Nonulcer dyspepsia/
Gastritis
•Ulcer disease
•Gastroenteritis
•Biliary colic or
cholecystitis
•Pancreatitis
• Irritable bowel disease
Less Common:
•Mesenteric Ischemia
•Stomach/Pancreas/
Hepatobiliary cancers
•Atypical manifestion
CAD/angina
•Posterior Wall AMI
•Aortic Aneurysm
•Inflammatory Bowel Dz

8. Mr. Jones HPI
•Mr. Jones is a 45 year old male who presents to
your clinic with epigastric abdominal pain x 2
weeks. He describes it as a burning pain which
is non-radiating and is worse after he eats. He
has frequent belching with bloating sensation but
denies nausea, vomiting, diarrhea, constipation,
or weight loss. He has tried rolaids which do
help a little.

•Which symptoms support the possible diagnosis
of PUD?

9. Signs and Symptoms of PUD
•Epigastric pain is most common symptom
•Pain described as gnawing or burning
•May radiate to the back (consider penetration)
•Occurs 1-3 hours after meals or at night
•Relieved by food, antacids (duodenal), or
vomiting (gastric)
•Dyspepsia including belching/ bloating
•Hematemesis or melena with GI bleeding

10. Clinical Pearls
•NSAID-induced gastritis or ulcers are
frequently “silent”
•Dyspeptic sx’s are non-specific –
approx 20-25% of patients with sx’s will
have peptic ulcer on further workup

11. Mr Jones History
PMH: HTN stable, Osteoarthritis in knees, treated
for an ulcer 3 years ago
Meds: Hydrochlorothiazide, ibuprofen prn
Soc HX: Married, employed as bank manager,
smokes 1ppd x 20years, drinks 2 beers per day,
and 2-4 cups coffee per day
What risk factors can you identify for PUD?

12. Common Risk Factors for Gastric
Mucosal Disruption
•H.pylori
•NSAIDs/ASA (even at low dose)
•Coffee/Caffeine
•Ethanol
•Tobacco
•Severe physiologic stress (Burns, CNS
trauma, Surgery, Severe medical illness)
•Steroids

13. Pathophysiology
PUD is a result of
acid/pepsin
production imbalance
with protective
mechanisms such as
mucous production

14. NSAIDs
•Approximately 15% of patients on long-term
NSAID develop PUD
•NSAIDs/ASA - ↓prostaglandin (PG) by
inhibiting the cyclooxygenase (COX) enzymes

•Three isoenzymes COX-1, COX-2, COX-3
•COX-1 → PG production in gastric mucosa
•COX-2 specific NSAIDs reduce GI side effects –
cardiovascular side effects have limited use

15. Individual NSAID Risk
High Risk
•Piroxicam/Feldene®
•Ketorolac/Toradol®
•Indomethacin/
Indocin®
Lower Risk
•COX-2 specific -
Celebrex®
•Ibuprofen (< 1500mg/d)
•Relatively selective COX-2
nabumetone/Relafen®
etodolac/Lodine®
meloxicam/Mobic®

16. History of Ulcer Treatment
•Early 20
th
Century – ulcers believed to be
caused by stress and dietary factors
•1982 - Dr’s Warren and Marshall identify
link between H. pylori and ulcers - medical
community is slow to accept
•1994 - NIH concludes a strong association
between H. pylori and ulcer disease -
recommends antibiotic treatment

17. History of Ulcer Treatment Cont’d
•1995 - 75 percent of patients treated with
antisecretory medications- only 5 percent
receive antibiotic therapy
•1996- FDA approves first antibiotic for treatment
of ulcer disease
•1997 - CDC launches national education
campaign to inform health care providers about
link between H. pylori and ulcers
http://www.cdc.gov/ulcer/history.htm

18. Discovery of Helicobacter pylori
•“Two Australian physicians won the 2005
Nobel Prize in Medicine or Physiology for
showing - at least partly by accident -- that
many ulcers are the result of a bacterial
infection.”
“Robin Warren
and Barry
Marshall's work
on ulcers was
pioneering”
Story from BBC NEWS:
http://news.bbc.co.uk/go/pr/fr/-/2/hi/
asia-pacific/4307826.stm
Published: 2005/10/04 10:39:09
GMT
© BBC MMVII

19. H. pylori
•Curvelinear, gram (-) rod
with flagella
•H pylori is most common
cause of PUD
•Transmission route fecal-
oral
•Secretes urease →convert
urea to ammonia
•Produces alkaline
environment enabling
survival in stomach.

20. H. pylori
•Higher prevalence in Low SES
•In US more common in Hispanics/Blacks
•Estimated 60% of Americans older than 60 H
pylori (+)
•Almost all duodenal and 2/3 gastric ulcer pt’s
infected with HP
•Asymptomatic in approx 70% of those who are H
pylori (+)
•Considered class 1 carcinogen → gastric cancer

21. Differentiating between H. pylori
and NSAID-induced ulcer
Ulcers associated with
H. pylori

•more often in
duodenum
•often superficial
•less severe GI
bleeding
Ulcers associated with
NSAIDs
•more often in
stomach
•often deep
•more severe GI
bleeding
•sometimes
asymptomatic

22. Other Disease Conditions
Associated with PUD
•Hypersecretory states: Gastrinoma
(Zollinger-Ellison syndrome) or multiple
endocrine neoplasia (MEN-I)
•Diseases assoc. with increased risk of
PUD: cirrhosis, chronic pulmonary
disease, renal failure

23. Mr. Jones Physical Exam
•VS: BP 137/82, HR 85, afeb, RR 14
•HEENT: conjunctiva pink, OP MMM
•Heart: RRR no M/R/G
•ABD: Soft, NABS, mild-moderate
epigastric TTP, no HSM or masses, no
acute abd signs
•Skin: no pallor
•Rectal: stool brown, heme (-), no masses
What are typical PE findings in PUD?

24. Physical Exam Findings
In uncomplicated PUD exam findings few
and non-specific:
•Epigastric tenderness - usually mild.
•Bowel sounds - normal.
•Rectal exam may show melena/guaiac+
stool from occult blood loss
•Signs of peritonitis with perforation

25. If Mr. Jones Hemoccult is Positive
What PE findings do you want to specifically
document if Mr. Jones is Heme (+)
indicating a possible active GI bleed?
•Look for signs of volume depletion:
tachycardia, hypotension, orthostatics,
skin turgor, MM appearance
•Look for signs of anemia: conjunctiva or
skin pallor, new heart murmur

26. Lab Studies to Evaluate PUD
•CBC - evaluate acute/chronic blood loss
•H. Pylori
- Serologic antibody test for HP – does not
determine if active HP infection
- Fecal antigen test tests for active HP
- Urea breath test tests for active HP

27. Principles in Selecting
H. pylori Test
Based on the following:
• Probability of previously eradicated infection
• Probability of current active infection
• Need to document active infection
• Need for rapid result
• Patient preferences
• Cost (both of test and possible unnecessary
treatment)

28. H. Pylori Serology Antibody Test
•Office based serology tests faster but less
accurate than lab based ELISA tests
•Sensitivity and specificity of approx 90%
•Not useful for evaluating eradication -
antibody levels can persist for a long time,
need serial titers to evaluate

29. When is a Serology Test Useful?
Not useful in
•Populations with low
disease prevalence
•Elderly populations to
detect active disease
Useful in
•Patients who never
received H. pylori
treatment
•Symptomatic patients
not using NSAIDs- if
negative serology –
unlikely PUD

30. H. Pylori Stool Antigen (HpSa) Test
•Useful in initial diagnosis + confirmation of
eradication
•Sensitivity of 91% and a specificity of 92%*
•Test requires collection of stool sample- size of
an acorn
•Performed in lab or newer POCT available
•Requires little preparation, however patients
may not be compliant with collecting sample
*Gisbert JP, Pajares JM. Stool antigen test for the diagnosis of Helicobacter
pylori infection: a systematic review. Helicobacter 2004;9(4):347-68

31. Urea Breath Test
•Useful for initial diagnosis + confirmation of eradication
•Sensitivity and specificity over 90%*
•Urease activity is present in the stomach in those
infected with H pylori
•Ingest urea labeled with radioactive carbon
•Hydrolysis of urea → labeled carbon dioxide (CO2)
•Rapidly absorbed into bloodstream and within a few
minutes, appears in breath
*Gatta L, Vakil N, Ricci C, et al. A rapid, low-dose, 13C-urea tablet for the detection of Helicobacter
pylori infection before and after treatment. Aliment Pharmacol Ther 2003;17(6):793-8

32. Breath Test Compared to HpSa
•Requires more patient preparation
•More expensive
•Number of drugs can adversely affect accuracy
•Antibiotics and bismuth → stop for 4 weeks
•Proton pump inhibitors → stop for 7 days
•Patients need to fast for at least 6 hours.
•Breath test cannot be used in pregnant women

33. Imaging Studies
•Chest x-ray if perforation is suspected to
detect free abdominal air
•Upper gastrointestinal series
–Performed by experienced radiologist is close
to diagnostic accuracy of endoscopy
–Not as sensitive as endoscopy in diagnosis of
small ulcers (<0.5 cm)
–Unable to obtain biopsy to rule out
malignancy

34. Endoscopy
Endoscopy indicated in following high risk patients:
•>50 years old with new-onset dyspepsia
•Dyspepsia with dysphasia and/or weight loss
•Evidence of GI bleeding
•Failed appropriate trial of empiric therapy
•Using NSAIDs or other high risk meds
•Signs of UGI tract obstruction (early satiety,
vomiting)
•Ethnic background assoc. with increased risk
UGI malignancies
Excerpts from Guidelines prepared by The Standards of Practice Committee of the American Society
for Gastrointestinal Endoscopy

35. Rapid Urease Test and
Histopathology
Gastric mucosal biopsy obtained during
endoscopy:
–Rapid urease tests (CLOtest, Hpfast,
Pyloritek) bacterial urease converts urea
substrate in kit to ammonia → changes pH
producing color change.
–Histopathology often considered gold
standard for diagnosis

36. Mr. Jones Prior Ulcer History
On further questioning Mr. Jones states he had
similar abdominal pain three years ago and was
told by his physician at that time that it was most
likely due to an ulcer. He took “the purple pill” for
a month and his symptoms resolved. He had no
definitive diagnostic tests done at that time.
What would you do at this time?

37. Answer
•H. pylori serology - many patients with
history of “ulcer” have not undergone
eradication therapy
•Test for H. pylori antibody and treat if (+)
•Endoscopy if serology negative or if fails
to improve with treatment

38. Moving on to Treatment
Options……….

39. Over The Counter Remedies
•Aluminum and magnesium hydroxide salt
(Maalox®, Mylanta®) Neutralizes gastric
acidity.
•Aluminum side effect = constipation
•Magnesium side effect = diarrhea
•Magnesium and aluminum mixtures used
to avoid side effects

40. Over the Counter Remedies cont’d
•Calcium Carbonate (Tums®, Rolaids®) –
calcium salt neutralizes acid
•Bismuth subsalicylate (Peptobismol®) –
binds to ulcer base forming a protective
coat, has anti-inflammatory and
bacteriocidal properties

41. H2-Blockers
•Selectively block H2-receptors on parietal
cells reducing acid secretion
•Used primarily in ulcer disease not
associated with H pylori
•Treatment duration is 6-8 wk.

42. Side Effects of
Cimetidine/Tagamet®
•Elderly patients – confusion
•Young males - impotence +/- gynecomastia
•May alter levels of other drug - warfarin,
TCA’s, triamterene, phenytoin, propranolol,
metronidazole, antiarrythmics
•May alter renal function requiring lower
doses

43. Proton Pump Inhibitors
•Decreases gastric acid secretion by
inhibiting the parietal cell H+/K+ ATP
pump
•Relieve pain and heal peptic ulcers more
rapidly than H2 blockers
•Drugs in this class are equally effective
•Four weeks to treat active PUD
•Eight weeks to treat erosive esophagitis

44. Other Pharmacotherapy Agents
•Sucralfate (Carafate®) Binds proteins in
exudates and forms a viscous adhesive that
protects GI lining
•Misoprostol (Cytotec®) Prostaglandin analog-
protects lining of GI tract by replacing depleted
prostaglandin E1. Prevents peptic ulcers in
patients taking NSAIDs

45. H. Pylori Triple Therapy Treatment
•Triple therapy for 14 days is treatment of
choice
•Two forms of triple therapy: PPI–based
and bismuth-based
•PPI based = PPI + 2 antibiotics for 2 wk,
cont PPI for additional 2 weeks.
•Bismuth-based = bismuth subsalicylate
and 2 antibiotics, for 2 weeks with addition
of H2- blocker to optimize ulcer healing.

46. H Pylori Treatment
Cure RateSide Effect Rating
81-92% low-medium Prevpak
80-85% medium-high Helidac + H2 blocker
Combination Products
80-90% medium Amoxicillin + Metronidazole + PPI
80-90% medium-low Amoxicillin + Clarithromycin + PPI
80-90% medium Clarithromycin + Metronidazole + PPI
Three Drug Regimens
http://www.drugdigest.org/DD/Comparison/NewComparison/0,10621,550540-21,00.html

47. H. Pylori Therapy cont’d
•Successful eradication of H. pylori reduces
PUD recurrence rates from 90% to less
than 10% per year.
•Patients no longer require ongoing chronic
acid suppression.
•If symptoms return after treatment of PUD,
then testing for recurrence should be
pursued

48. PUD Complications
•Hemorrhagic shock/peritonitis from a
perforated ulcer
•Symptomatic relief with PPI may mask
symptoms of gastric malignancy
•Gastritis may present as bleeding, more
likely in elderly
•Symptoms of anemia (fatigue, dyspnea)

49. Initial Treatment Plan in the
Absence of High Risk Symptoms
Based on current evidence, no single
strategy has been demonstrated to be
more medically effective than any other.
•Empiric therapy with acid suppression
•Empiric H pylori testing and treating
strategy
•Early endoscopy
Excerpts from Guidelines prepared by The Standards of Practice Committee of the American Society
for Gastrointestinal Endoscopy

50. Final Recommendations
•Alarm symptoms = endoscopy.
•No alarm symptoms = medical
management favored approach
•Studies still in progress to evaluate if
medical management versus vs
endoscopy is both medically and cost
effective in long-term
•Lack of response or the recurrence of
symptoms warrants endoscopy

51. Medical Legal Pitfalls
•Failure to consider non-GI cause of epigastric
pain (AMI/AAA)
•Failure to consider GI bleed in absence of
abdominal pain (especially in elderly)
•Lack of follow-up care resulting in failure to
diagnose gastric cancer
•Failure to recommend endoscopy early in high
risk patients
•Failure to obtain a history regarding NSAID use

52. Alternate Scenarios of
Mr. Jones Case
Mr Jones is a 63 yo male presenting with
previously noted epigastric symptoms
and PMH. On physical exam he is noted
to have heme (+) stool.
What evaluation would you do next?

53. Alternate Scenarios to Mr. Jones
Case
Mr Jones is a 63 yo male presenting with
previously noted epigastric symptoms and PMH.
On review of his prior ulcer history he was tested
and had a positive H. pylori serology test. He
was treated with triple therapy (PPI and 2
antibiotics) and symptoms resolved.
What would you do next? Would you recheck H.
pylori serology? Repeat triple therapy?

54. Summary
•H. pylori is the most common cause of PUD and
is a risk factor for gastric cancer
•H Pylori eradication reduces risk of disease
recurrence
•Test-and-Treat strategy is recommended for
patients with undifferentiated dyspepsia
•Intial evaluation with endoscopy is
recommended for those with alarm symptoms or
those failing treatment
•Optimum treatment regimens are 14d multidrug
with antibiotics and acid suppressants

55. References
•http://www.emedicine.com/med/topic1776.htm
•http://www.mcg.edu/som/pathology/GraduateEducation/Evidence%20Base%20Path/hpsa1.ppt

•http://www.acg.gi.org/physicians/guidelines/ManagementofHpylori.pdf
•http://www.cdc.gov/ncidod/dbmd/diseaseinfo/hpylori_t.htm
•http://courses.ahc.umn.edu/pharmacy/5880/LectureSlides/Peptic%20Ulcer%20Disease%20(PUD)_files/frame.htm
•http://www.cdc.gov/ulcer/history.htm
•http://www.drugdigest.org/DD/Comparison/NewComparison/0,10621,550540-21,00.html

56. References cont’d
•Fendrick M, Forsch R etal. Peptic Ulcer Disease Guidleines for Clinical
Care. University of Michigan Health System May 2005
•American Gastroenterological Association medical position statement:
evaluation of dyspepsia. Gastroenterology 1998;114:579-81.
•Krogfelt K, Lehours P, Mégraud F. Diagnosis of Helicobacter pylori
Infection. Helicobacter 2005 10:s1 5
•Meurer L, Bower D. Management of Helicobacter pylori Infection. American
Family Physician Vol 65, No. 7, 2002 pp 1327-1336
•Standards of Practice Committee of the American Society for
Gastrointestinal Endoscopy; The role of endoscopy in dyspepsia.
Gastrointestinal Endoscopy Vol 54, No. 6, 2001 pp 815-817
•Vaira D, Gatta L, Ricci C, et al. Peptic ulcer and Helicobacter pylori: update
on testing and treatment. Postgrad Med 2005;117(6):17-22, 46