1. Peptic Ulcer Disease
Khalayleh Harbi

2. Definition
PUD is a disease of multiple etiology that characteristic of local gastric or duodenal damage and ulceration

3. Epidemiology
The annual incidence in USA 1.8% or new cases per year.
There are 4 million ulcer recurrences yearly.
More than operation for PUD performed yearly.
About 4000 patient die from complication of their PUD yearly

4. Pathogenesis
Disbalance between aggressive factors and defenisive factors cause ulcer
Protective factor (defensive) – mucous bicarbonate secretion ,blood flow, grwoth factors, cell renewal, endogenous prostaglandine
Damaging(aggressive ) factors-HCL secretion, ethanol, smoking, reflux of bile, NSAID, hypoxia, HP

5. cause 1. H.PYLORI infection (most common cause)
2.NSAID (second most common cause)
3.stress
4. incrased pepsin and acid secretion

6. Role of HP
90% of duodenal ulcer and 70% of gastric ulcer are associated with H.Pylori infection
H.Pylori is a gram-negative rod with 6 flagella.

7. HP HP is a chronic infection that found worldwide
Person is infected, usually in childhood.
Developing countries have a higher rate of HP infection.

8. HP infection varies with racial and ethnic group- in USA white tend to have lowest rates of infection, African American rates of infection at each age is doubled those of white.
This difference in prevalence is related to lower socioeconomic status during childhood.

9. Rout of transmission
HP infection in one household member is associated with greater chance of infection in other members.
This mean that infection is transmitted person- to- person route and acquired early in life

10. HP
HP resides in gastric type epithelium within or beneath the mucus layer which is protect it from acid and antibiotic.
It shape and flagella aid it movement within through the mucus layer
HP produce variety of enzymes that help it adapt to hostile environment

11. HP HP most potent producer of urease
Urease an enzyme that split urea into ammonia and bicarbonate creating an alkaline microenvironment in the sitting of acidic gastric milieu
This facilitate DS in laboratory test

12. Mechanism of gastric injury by HP
1. production of toxic product to case local tissue injury
2. induction of local mucosal immune response
3. increased gastrin levels with a resultant increase in acid secretion.

13. 1.Toxic product -local injury
HP locally produce toxic product include:
* breakdown product from urease activity (ammonia).
* cytotoxins : - a mucinase that degrades mucus and glycoprotein's , phospholipases that damage epithelial and mucus cells
* platelet-activating factor-known to cause mucusal injury and thrombosis in microcalcification

14. 2. Local Immune Injury d/t HP
HP known to case local inflammatory reaction in gastric mucusa and to produce chemotactic factors that attract neutrophils and monocytes
Activated monocytes and neutrophils in turn produce a number of proinflamatory cytokines and reactive oxygen metabolites

15. 3.Gastrine and HP
In patient with HP infection basal and stimulated gastrine level are increased secondry to reduction in antral D cells caused by infection with HP.
HP-infected patient with duodenal ulcer did have a marked increase in acid secretion

16. HP and other GI disorder
HP is present in most case of chronic gastritis
HP most gastric cancer patient show evidence of past HP infection.
There is strong association between mucosa-associated lymphoid tissue( MALT) lymphoma and HP infection
Eradication of HP infection cause regression of these MALT lymphoma

17. Gastritis and PUD PUD strongly associated with antral gastritis.
All patient with PUD have histologic evidence of antral gastritis (95%)
The only patient with gastric ulcer and no gastritis those ingesting aspirin or NSAID
25% of patient with NSAID- associated ulcer have evidence of antral gastritis.

18. PUD and NSAID

19. after HP infection NSAID is the most common cause of PUD.
Risk of complication and bleeding in patient taking NSAID is increased with age >60 , patient having prior GI event or use of steroid and anticoagulant

20. Epidemiology of PUD and NSAID
3 million people in USA take daily NSAID
1 in 10patient taking NSAID have an acute ulcer
2%-4% of NSAID user have GI complication each year
More than 3000 death and hospitalization per year are attributed to NSAID induced GI complication

21. NSAID injury NSAID can cause acute gastroduodenal injury or chronic.
Acute injury occur within 2 week of use and range from hyperemia to erosion
Chronic injury occur after month of use and range from erosion to ulceration

22. Characteristic of NSAID ulcer
NSAID ulcer more frequently found in stomach whereas HP- ulcer found in duodenum
Chronic active gastritis always associated with HP and not found in NSAID associated ulcer
When NSAID is stopped the ulcer not recur but HP – associated ulcer recurrence is 50%-80% in 1 year unless the organism is eradicated

23. DU pathophisiology Is a disease of multiple ethiology
Absolute requirement: acid and pepsin secretion in combination of H.Pylori infection or NSAIDs ingestion
Secretor abnormalities such as : bicarbonate secretion, nocturnal acid secretion, daytime acid secretion
DU associated with parietal cell number

24. Pathophysiology of gastric ulcer
GU may occur anywhere in stomach
GU rarely develop before age of 40, peak incidence years
Predispose condition: age>40, sex f:m 2:1, ingestion of barrier breaking drug (aspirin), abnormalities in acid and pepsin secretion, gastric stasis, delayed gastric emptying, coexisting DU, duodenal gastric reflux of bile, infection with HP, smoking, alcohol intake

25. TYPE I of GU Account for 60% of GU
Occur within 1.5cm of the histologic transition zone between the fundic and and antral mucosa (in the lesser curvature near the incisura)
Are not associated with excessive acid secretion
Not associated with DU or prepyloric ,pyloric mucosal abnormalities
Malignancy are major concern

26. TYPE II of GU
About 15%
Are located in the body of stomach in combination with a duodenal ulcer
Associated with excess acid secretion

27. TYPE III of GU About 20% Located in the preylorus
Are associated with excess of acid secretion

28. TYPE IV of GU
ABOUT 10%
Occur hiegh in the lesser curvature near the gasroesophageal junction
Are not associated with excessive acid secretion

29. clinical feature Abdominal midepigastric pain. Pain is well localized
Tolerable and relieve by food in DU and exagerated by food in GU
Pain irradiation to back suggest pentration to pancreas
Other magnifestation: perforation, bleeding, obstruction

30. Perforation
About 5% of the time ulcer perforated into free peritoneal cavity and elicit chemical peritonitis.
The patient recall the exact time of onset of pain.
Pain accompanied by fever, tachycardia, dehydration and ileus.

31. Perforation Examination reveal: tenderness, rigidity and rebound
Diagnosis is established by free air in upright chest X-Ray underneath the diaphragm.
Treatment is operative after fluid resuscitation

32. Bleeding
The most common cause of death with PUD is bleeding in those who have medical problems or are older than 60 years
In DU bleeding usually from GDA
Most case of massive GI bleeding are DU following penetration of ulcer in GDA
Bleeding can manifests as melena or bloody vomiting

33. Obstruction
Active inflamation of duodenum can cause mechanical obstruction and functional gastric outlet obstruction
Delayed gastric emptying lead to nausea and vomiting
Can lead to hypochloremic hypokalemic metabolic alkalosis secondry to loss of gastric juice and H+, CL-, K

34. Zollinger –Ellison Syndrome
ZES clinical triade:
1 .Gastric acid hyper secretion
2. Severe PUD
3. Non-b islet cell tumors
ZES are known to produce gastrin and called gastrinomas

35. ZES
ZES usually localized to the head of pancreas, duodenal wall or regional LN.
½ of ZES are multiple
2/3 of ZES are malignant
¼ of ZES are associated with MEN1

36. ZES Clinically- abdominal pain and PUD in 80% of case.
½ of patient have diarrhea secondary to increase gastric acid secretion (Gastrin stimulation secretion of acid)
Weight loss and steatorrhea occur secondary to decreased duodenal and jeujenal PH and inactivation of lipase
Esophagitis is common

37. When consider ZES
In a ptient with recurrent or intractable PUD despite eradication of H.Pylori.
In patient with multiple or atypically located ulcer.
PUD associated with significant diarrhea
PUD associated with symptom of MEN1: hyperparthyroidism
Patient with other pancreatic endocrine tumors
Large gastric rugae in endoscopy

38. How to diagnose ZES
Elevated serum gastrin > 200 pg/ml, value >1000 is diagnostic
Secretin test: give secretine 2u/kg and measure serum gastrin before and after gastrin administration evrey 5 minute for 30 minute: an increase of serum gastrin of greater than 200pg/ml above basal level is specific for gastrinoma.

39. Diagnosis of PUD

40. History and physical examination.
Laboratory to R/O other condition: CBC, Liver chimistry, cre, elecgtrolytes, amylase
Serum Gastrin in refractory ulcer
Chest- X-ray- to rule out perforation
Endoscopy or contrast radiography
H.pylori testing

41. H.Pylori testing
Serology- HP ilicites a local as a systemic immunoglonulin G mediated immune response that can measured by ELISA
Serology is test of choice when endoscopy is not indicated
Sensitivity 90%
Limitation: the test remain high for year or more thus cannot used to assess eradication

42. Urease breath test Carbon- labeled urea breath test
Based in ability of HP to hydrolyze urea to ammonia and bicarbonate
Patient ingest 14C or 13C Isotope after carbone ingestion urea metabolized to ammonia and bicarbonate if HP present

43. Urease breath test
The bicarbonate is excreted in the breath as labeled carbon dioxide
Negative result occur if the test done early after treatment , , 4 weak.
Is the method of choice to documment erradication,
Test not expensive

44. Rapid urease assay
The urease catalize urea to ammonia and bicarbonate creating an alkaline environment
This environment can measured by PH indicator
Endoscopy is performed and gastric mucosal biopsied to perform the test
Sensitivity 90%, specificity 98%.

45. Diagnosis of HP by histology
Endoscopy performed and biopsy obtained
Diagnosis is by visualization of HP by hematoxyline and eosin stain
Sensitivity is 90%, specificity is 99%
HP can cultured – diagnosis required 3-5 days and expensive, sensitivity 80%, specificity is 99%

46. Upper GI radiography
The barium is demonstrated within the ulcer crater which is round or oval and may or may not surrounded by edema
With single contrast 50% of ulcer may be missed
With double contrast 80-90% of ulcer carter can be detected
Can asses the depth and penetration
Limitation- cannot r/o malignancy

48. Endoscopy The most reliable method of diagnosis
Ability to diagnose malignancy
Benign ulcer have smooth ulcer base
Malignant ulcer associated with mass and protrude into the lumen or have fold surrounding the ulcer carter
Biopsy can performed with endoscopy .

49. Treatment
Medical management

50. The goals of treatment 1.symptom need to be relieved
2.The ulcer need to be healed
3. Recurrence must be prevented
The antisecretory agent achieve the first 2 goals
With NSAIDs related ulcer discontinuation of NSAIDs achieve the 3 goal
Eradication of HP achieve the 3 goal

51. Antacids
Antacids reduce the gastric acidity by reacting with HCL forming a salt and water
If taking on an empty stomach the antacids are emptied rapidly and have only transient effect ( for this take just after meal)
Can result in 80% healing at 1 month
Magnesium antacids – the best buffers but can cause significant diarrhea
Aluminum antacis can bind phosporus and result in hypophospatemia and constipation

52. H2-receptor antagonist
Structurally similar to histamine
Undergo hepatic metabolism and excreted by kidney
Half-life hours
The most potent is famotidine
Less potent is cimetidine.
Result in DU healing 70-80% after 4 weak and 80-90% after 8 weak
Continuous IV infusion can produce more effect than intermittent administration

53. Proton Pump Inhibitor Are the most potent antisecretory agent
Bond to the catalytic alfa subunit of the proton pump and negate all types of acid secretion
Inhibition is more potent than H2 antagonist and more prolonged and irreversible
Produce more rapid healing of ulcer, healing rate 85% at 4 weeks , and 95% at 8 weeks
PPI require an acidic environment within gastric lumen to become activated

54. Sucralafate
Structurally related to heparin but not have anticoagulant effect
Aluminum salt of sulfated sucrose disassociates under acidic condition to sucrose polymerizes and bind protein in ulcer crater to produce a kind of protective coating that can last for 6 hours
DU healing after 4-6 weeks of treatment : 1g *4/day
Effect is compared to cimetidine

55. Treatment of HP
Very important, recurrence without eradication is 72%, after eradication is 2%.
Use antibiotic:
Moxypen 1gr*2 + clarythromycin 0.5 gr*2 for 14 days
Or Moxypen 1gr*2 for 10 days followed by clarythromycin 0.5*2 or metronidasole 0.5*3 for 5 days

56. Surgical Procedure for PUD

57. Indication for operation
1.intractability (failure of ulcer healing after 8-12 weeks of therapy)
2.hemorrhage
3.perforation
4.obstruction

58. The goals of operation Prevent of gastric acid secretion Achieved by:
1.anterctomy- removal of the gastrin-secretion portion of stomach
2.vagotomy alone decrease the acid secretion by 50%
3.Combination of vagotomy and anterectomy decrease acid secretion by 85%

59. Truncal vagotomy
Division of RT and LT vagus nervus above the hepatic and celiac branches just above the GEJ
Most commonly used for DU .
Performe drainage procedure mandatory
drainage operation: heineke-mikulicz, Finney, jaboulay pyloroplasty
Side effects- bile reflux after gastroduodenostomy, diarrhea after pyloroplasty

61. heineke-mikulicz

62. Finney, jaboulay pyloroplasty

63. Highly Selective Vagotomy (Parietal Cell Vagotyomy)
Divide only the vagus nerve supplying the acid-producing portion of stomach within the corpus and fundus
Preserve the vagal innervation of antrum , thus no need for drainage procedure
The nerve of latarjet devided and crows feet innervation of fundus and body devided until point 7 cm proximal to pylorus and to point 5 cm proximal to GEJ.
Tow or three branchs to antrum and pylorus preserved

64. The criminal nerve of Grassi represent a very proximal branch of the posterior trunk of vagus and great attention is take to avoid missing of them, because is cited predisposition for ulcer recurrence
Recurrence rate 10-15% and usually patient responsive to medical therapy
This not procedure of choice for pylorus ulcer but for duodenal ulcer
Postvagotomy syndrome is rare

66. Truncal Vagotomy and Antrectomy
Indication- gastric ulcer and benign gastric tumours
Contraindication- cirrhosis, previous operation on duodenum
Recurrence rate 0-2%
Postagstrectomy and postvagotomy syndrome occur in 20% .
Reconstruction of GI tract done by biloroth 1 or 2 or Roux-En-Y

69. Subtotal Gastrectomy Rarely used today for treatment of PUD
Are preserved for malignancy

70. Laparoscopy All previous procedure can performed laparoscopicaly
Also omentopexy for perforation can performed laparoscopicaly.
Taylor procedure- parietal cell vagotomy+posterior truncal vagotomy+seromyotomy

71. Surgical Treatment Recommendations for Complications Related to Peptic Ulcer Disease

72. Duodenal Ulcer Intractable: parietal cell vagotomy
Bleeding: truncal vagotomy with pyloroplasty and oversewing of bleeding vessel
Perforation: patch closure with treatment of H. pylori with or without parietal cell vagotomy
Obstruction: rule out malignancy and parietal cell vagotomy with gastrojejunostomy

73. Gastric Ulcer Intractable Type I: distal gastrectomy with Billroth I
Type II or III: distal gastrectomy with truncal vagotomy Bleeding
Type II or III: distal gastrectomy with truncal vagotomy Perforated
Type I, stable: distal gastrectomy with Billroth I
Type I, unstable: biopsy, patch, and treatment for H. pylori
Type II or III: patch closure with treatment of H. pylori
Obstruction:
rule out malignancy and antrectomy with vagotomy
Type IV: depends on ulcer size, distance from the gastroesophageal junction, and degree of surrounding inflammation.
Giant gastric ulcers: distal gastrectomy, with vagotomy reserved for type II and III gastric ulcers

74. Thank you