1. PEPTIC ULCER DISEASE Lykhatska G.V.

2. Peptic ulcer disease -
Is recurrent disease, the main feature of which is the formation of defects (ulcers) of the stomach mucosa and / or duodenal mucosa, which penetrates to mucosal layer, submucosa and deeper, unlike erosion

3. Definition
Ulcers may range in size from several millimeters to several centimeters.
Ulcers are delineated from erosions by the depth of penetration; erosions are more superficial and do not involve the muscularis mucosae.

4. SPREAD UD
Prevalence of peptic ulcer disease among adults in different countries is 5 to 15% (average 10.7%). Duodenal ulcers are 4 times more common than gastric ulcers, the ratio of people male and female 4: 1.

5. ETIOLOGY of peptic ulcer disease
1. Helicobacter pylori
2. NSAIDS
3. Heredity
4. Smoking
5. Association with other diseases or known factors

6. Zollinger-Ellison syndrome
Clinical manifestation hypergastrinaemia caused gastrynoma: gastrin-producing tumor (1 or more) of the pancreas, colon, duodenum , peripancreatic lymph nodes, G-cells of the gastric mucosa (triangle gastrin)
Spread 2.1 cases /
60-80% of cases - benign
1% of gastroduodenal ulcers
Gastrin> 100ph/ml (N), ph/ml

7. Helicobacter pylori
It is the most important factor in peptic ulcer disease.
It causes 90-96% of duodenal ulcers and 70-80% of gastric ulcers.

8. Etiology: Helicobacter pylori infection.
Hyperacidity - eg. zollinger ellison.
Drugs - anti-inflammatory (NSAIDs) & Corticostroids.
Cigarette smoking, Alcohol,
Rapid gastric emptying
Personality and stress

9. Helicobacter pylori: Most common infection in the world (20%)
10% of men, 4% women develop PUD *
Positive in % of PUD patients.
H.pylori related disorders:
Chronic gastritis – 90%
Peptic ulcer disease – %
Gastric carcinoma – 70%
Gastric lymphoma
Reflux Oesophagitis.
Non ulcer dyspepsia

11. Peptic Ulcer Morphology:
90% ulcers in first portion of duodenum or lesser curvature of stomach(4:1).
80 to 90% cases single ulcer. Round Small ulcers with sharply punched out edges*
Small <2cm, clean base*.
Microscopy: 4 zones.
Superficial necrotic layer.
Inflammatory cells zone.
Granulation tissue zone
Collagenous scar layer.

12. NSAIDS
Aspirin and other non steroidal anti inflammatory agents damage the gastric mucosal barrier and are an important etiologic factor in 30% cases of gastric ulcer.

13. Heredity
Peptic ulcer tends to run in families. Two specific factors identified are:
•Larger Parietal cell mass
With increased gastric acid output in patients with duodenal ulcer perhaps represents an inborn characteristic of the individual.
•Blood group and blood group antigen
Those with blood group О and those unable to secrete their blood group antigen into the saliva and gastric juice are more predisposed to peptic ulceration.

14. Smoking Smoking is an important risk factor.
It also decreases the rate of healing and increases the risk of recurrence.
Tobacco exerts its effects by stimulating acid secretion and impairing mucosal defenses by means of decreased blood flow and reduced prostaglandin synthesis.

15. Association with other diseases or known factors
Higher incidence in patients with COPD, corpulmonale, cirrhosis, chronic renal failure.
Steroids in high doses, severe burns
Alcohol and dietary factors do not appear to cause peptic ulcer

16. Pathogenesis: Helicobacter pylori infection
Colonization of gastric mucous
Urease ammonia neutralization of acid  Rebound acid production.
Protease – Mucous break down.
Weak mucosal resistance
Acid & Pepsin digestion of mucosa
Chronic Ulceration

17. PATHOGENESIS An ulcer forms when there is an imbalance between
- aggressive factors
(e.g. acid and pepsin)
- and defense factors.

18. Classification IV. Association with Helicibacter pylori:
I. Phase of disease:
-Acute
-Uncomplete remission
-Remission
II. Course of disease:
-mild
-moderate
- severe.
III. Localization:
-stomach
-duodenum
-stomach + duodenum
-gastroeneroanostomosis
IV. Association with Helicibacter pylori:
- H. pylori – associated
- H. pylori – not associated
V. Complications
-Hemorrhage
-Perforation
-Penetration
-Pyloristenosis
-Malignancy

19. Example of diagnosis Peptic ulcer disease, acute phase, mild course,
active ulcer of duodenum,
H. pylori – associated.

20. The most important cause of ulcer disease :
А. Smoking
В. Alcohol abuse
C. Imbalance between aggressive factors and defence factors
D. Increasing of acidity of gastric juice
E. Stress

21. The most important cause of ulcer disease :
C. Imbalance between aggressive factors and defence factors *

22. COMPARISION OF DUODENAL AND GASTRIC ULCERS
Duodenal ulcer
It usually occurs in the first part of duodenum, 50% are on the anterior wall.
More common 4 times than gastric ulcer.
More common in male at age years
Risk factors: H Pylori, smoking, NSAIDS, COPD, cirrhosis, chronic renal failure
Gastric ulcer
Most common cause NSAID use, other are bile reflux and H Pylori.
Gastric ulcer may be malignant
Less common than duodenal ulcer

23. CLINICAL AND INSTRUMENTAL SYNDROMES
Pain syndrome
Dyspeptic syndrome: nausea
- vomiting
- heartburn
- eructation
- constipation
Asthenic syndrome
Syndrome of endoscopic changes
Syndrome of roentgenographical changes

24. CLINICAL FEATURES
PAIN
Site:
Epigastrium
Mendel’s symptom “+”

25. Character:
Burning in character
Radiation:
Pain is localised and patient is able to point it with his one finger "pointing sign". If pain is radiating to the back in inter scapular region and not responding to antacids or other anti-ulcer drug, suggests posterior penetration of ulcer into the pancreas.
Time of pain:
Soon after eating within minutes in gastric ulcer while 2-3 hours after eating in duodenal ulcer that frequently awakens the patient at night.
Relation with food:
Patient with gastric ulcer are afraid to eat because it causes pain due to release of acid in response to food. Patients with duodenal ulcer feel pain in empty stomach and get relief after taking food which causes partial neutralization of acid. Then in response to food there is increased acid secretion which causes pain after 2-3 hours. Acid induced pain is believed due to acid stimulation of chemical receptors.

26. Aggravating factors:
Smoking
Excessive intake of coffee and tea
Alcohol
Eating precipitates pain in gastric ulcer while missing a meal in duodenal ulcer.
Relieving factors:
Antacids and milk
Vomiting relieves pain in gastric ulcer
Intake of food relieves pain in duodenal ulcer

27. A few weeks in gastric ulcer A month or two in duodenal ulcer
Periodicity:
Pain comes and goes in a 2-3 month cycle in gastric ulcer
In duodenal ulcer episode occurs with 4-6 month cycle, often worse in spring and autumn.
Relapse occurs move frequently in smokers than in non smokers.
Duration of attack:
A few weeks in gastric ulcer
A month or two in duodenal ulcer

28. VOMITING
Vomiting relieves pain of gastric ulcer and some patients force themselves to vomit after eating to relieve symptoms.
It is uncommon in duodenal ulcer.

29. Endoscopy:
Endoscopy is the procedure of choice for diagnosis of peptic ulcer
All patients with gastric ulcer require biopsy initially and the follow up endoscopy and biopsy after 6 weeks of starting therapy, to confirm that the ulcer has healed.

30. PEPTIC ULCER DISEASE

31. PLAN of INVESTIGATIONS
Total blood count
Biochemical analysis
Urinanalysis, Diastase of urine
Coprogram
Hidden blood in feces
ECG
Endoscopy+biopsy+ Histology
Diagnosis of HP infection
X-ray
USD
pH-metry

32. ENDOSCOPY

33. Gastric ulcer (posterior wall)

34. Gastric ulcer (angle of stomach)

35. Duodenal ulcer (anterior wall of duodenal bulb)

36. Duodenal ulcer (posterior wall of duodenal bulb)

37. Duodenal ulcer (middle part, anterior wall, 9-12 mm)

38. Duodenal ulcer

39. GASTRIC CANCER (endoscopy)

40. Barium meal (double contrast technique)
Barium meal is less commonly used now.
It also reveals gastric and duodenal ulcers.

41. Upper GI series in which double contrast (barium and air) is used, showing rounded collection of barium in an ulcer (arrow) in the duodenal bulb of a patient presenting with dyspepsia (uncomplicated duodenal ulcer)

42. - Histology
- Cytology
- rapid urease test
Culture
- carbon urea breath test
blood antibody test
Stool antigen test

43. Histology
H. pylori can be detected histologically on biopsy of gastric mucosa obtained at endoscopy and stained with haematoxylin and eosin.

44. Rapid urease activity test
H. pylori produces urease that is required for gastric colonization by H. pylori and that may protect it from the effects of gastric acid.
This urease producing activity of the organism is utilized for diagnosis by placing the biopsy specimen in urea and assessing ammonia release that changes the color of the solution.

45. Culture
Obtained biopsies can be cultured on special medium and sensitivities to antibiotics can be ascertained.

46. Noninvasive method
carbon urea breath test : Breathing tests with labelled 13C (the "gold standard") and 14C carbon atoms "Helik" - test
Serum (immunological) methods: determination of serum IgG, IgA; rapid tests using capillary blood from immunoprecipitation reactions
Molecular biological methods based on PCR (material for research: saliva, plaque, urine, feces)
Stool test - definition of Hp antigen in stool

47. Urea breath test with I3C
This is a quick and easy way of detecting the presence of H. pylori by urease production with release of labelled CO2 detected on a mass spectrometer.
This test indicates active infection but is expensive.

48. Screening - method
For the more commonly used screening methods based on the detection of specific anti-helicobacter antibodies Ig classes A i G in serum, capillary blood subjects. The most studied following serological methods:
1. Enzymatic analysis.
2. Rapid tests based on immunoprecipitation or immunocytochemistry using as test material capillary blood of patients with color enhancement of the reaction products.

49. Control eradication
Urease test (preference not invasive: 13C urea breath, Helik test)
Stool test (antigen, PCR DNA)
Urea biopsy - less appropriate
All tests perform 4-6 weeks after eradication.

50. COMPLICATIONS Hemorrhage Perforation Penetration Pylorostenosis
Malignancy

51. Peptic ulcer bleeding - clinical signs
Vomiting unmodified blood with clots, as coffee grounds
Symptoms of hypovolemia, anemia
Termination of pain
Most (80%) gastroduodenal ulcer bleeding stopped independently
Mortality 5-10%, re-bleeding increases the risk of mortality is 10 times

52. Perforation Free perforation usually presents as an acute abdomen.
Ulcers that perforate the peritoneal cavity are usually located in the anterior wall of the duodenum or, less commonly, in the stomach.
The patient experiences sudden, intense, steady epigastric pain that spreads rapidly throughout the abdomen, often becoming prominent in the right lower quadrant and at times referred to one or both shoulders.
The patient usually lies still because even deep breathing can worsen the pain.
Palpation of the abdomen is painful, rebound tenderness is prominent, abdominal muscles are rigid (boardlike), and bowel sounds are diminished or absent.

53. PERFORATION Diagnosis is confirmed if an upright or a lateral decubitus x-ray of the abdomen shows free air under the diaphragm or in the peritoneal cavity, but the diagnosis is not excluded if no air is seen.

54. Clinical periods flow perforated ulcer
F1 - shock period (up to 6 hours. Since perforation)
F2 - between mental well-being (6-12h. Since perforation)
F3 - during peritonitis (more than 12 hours.)

55. Penetration - penetration ulcers contiguous organ tissues which are its bottom (30-35% of all complications).
the head of the pancreas
liver
gall bladder
omentulum
liver, duodenum ligament

56. The clinical picture is diverse and depends on the organ in which ulcers penetrates.
It is noted more aggressive course of disease with steady, frequent attacks of abdominal pain that does not diminish with eating after vomiting, with irradiation
Conservative treatment is ineffective

57. Gastric outlet obstruction
This may be caused by scarring, spasm, or inflammation associated with an ulcer.
Symptoms include recurrent large volume vomiting, occurring more frequently at the end of the day and often as late as 6 h after the last meal.
Persistent bloating or fullness after eating and loss of appetite also suggest gastric outlet obstruction.
Prolonged vomiting may cause weight loss, dehydration, and alkalosis.

58. Pyloroduodenal stenosis - severity level
I - the stage of formation
II - compensated stenosis
III - subcompensated stenosis
IV - decompensated stenosis
                        (Yu.M.Pantsyrev, A.A.Hrinberh, 1979)

59. Differential Diagnosis of Peptic Ulcer Disease
Presentation
Diagnosis
Suspected uncomplicated
ulcer
Nonulcer dyspepsia, gastroesophageal reflux, biliary colic, pancreatic disease, angina pectoris, gastric cancer
Bleeding ulcer
Varices, Mallory-Weiss tear, esophagitis, vascular lesion (angiodysplasia)
Perforated ulcer
Appendicitis, pancreatitis, cholecystitis,
spontaneous bacterial peritonitis, bowel
ischemia or infarction, diverticulitis
Penetrating ulcer
Pancreatitis, muscle strain, herniated vertebral disk, ureteral stone

60. Treatment of PUD ANTIBIOTICS (Clarithromycin, Amoxycillin)
ANTISECRETORY DRUGS:
- PROTON PUMP INHIBITORS
- H2 RECEPTOR ANTAGONISTS
- ANTACIDS (Almagel, Maalox)
GASTROCYTOPROTECTORS
DRUGS, WHICH IMPROVE MOTOR FUNCTION OF STOMACH (Cerucal, Motilium, Eglonil);
SPASMOLYTICS

61. H2 RECEPTOR ANTAGONISTS
These are competitive inhibitors of histamine at H2 receptors on the parietal cells.
They can be given two times or a single night dose.
Although these drugs are generally safe, Cimetidine can cause confusion in elderly and impotence and gynecomastia in male, therefore should be
avoided in young males and elderly.
Drugs
Dosage
Cimetidine
800 mg or
400 mg
Ranitidine
300 mg or
150 mg
Famotidine
40 mg or
20 mg
Nizatidine
300 mg or 150 mg

62. PROTON PUMP INHIBITORS
These drugs are also called H+, K+ ATFase inhibitors.
Compared with H2 receptor antagonists, proton pump inhibitors provide faster pain relief and more rapid ullcer healing.
They are the most powerful inhibitor of gastric secretion yet discovered.
They inhibit over 90% of 24 hour acid secretion while H2 blocker less than 65% in standard dosages.
They are also used in combination therapy for eradication of Helicobacter pylori
Drugs
Dosage
Omeprazole
20 mg
Lansoprazole
30 mg
Pantoprazole
40 mg
Rabeprazole
Esomeprazole

63. ANTACIDS (Almagel, Maalox)
Antacids promote ulcer healing through stimulation of gastric defense mechanism.
Due to availability of other potent anti ulcer drugs they are not used as first line agents in the treatment of acute ulcers.
Because of rapid relief of ulcer symptoms (due to acid neutralization) they are commonly used for symptomatic relief (e.g. epigastric pain and burning).

64. ANTACIDS
They are relatively inexpensive but must be taken five to seven times per day.
The optimal antacid regimen for ulcer healing appears to be 16 to 30 mL of liquid or 2 to 4 tablets 1 and 3 h after each meal and at bed­time.

65. GASTROCYTOPROTECTORS
SUCRALFATE (VENTER)
It forms complex with proteins in the ulcer base and protects it from further digestion.
Sucralfate also stimulates mucus, bicarbonate and prostaglandin production.
The drug is not absorbed from gastrointestinal tract and has no known systemic effects.
Only side effect is constipation.
Dose: Tab. Venter l g 4 times daily one hour before meals and bedtime.

66. GASTROCYTOPROTECTORS
BISMUTH COMPOUNDS (DE-NOL)
Bismuth promotes ulcer healing by forming a bismuth-protein coagulant which protects the ulcer from acid and pepsin digestion.
It also stimulates mucosal bicarbonate and prostaglandin production.
It is also a powerful antimicrobial agent against Helicobacter pylori.
Dose: Tab. De-nol 0,12 g 4 times daily one hour before meals and bedtime.

67. GASTROCYTOPROTECTORS
PROSTAGLANDIN ANALOGUES
Misoprostol (Cytotec) is a prostaglandin analogue that promotes ulcer healing by stimulating mucus and bicarbonate secretion and inhibition of acid secretion.
Abdominal pain and diarrhoea are side effects.
It is less effective than other anti ulcer drugs in the treatment of active ulcer, therefore it is used only as a prophylactic agent to prevent NSAID induced ulcer in patient taking NSAID regularly.
Dose: Tab. Cytotec 0,2 g 4 times daily one hour before meals and bedtime.

68. Type of Ulcer Treatment Prevention Helicobacter pylori–related ulcers
Antibiotics +
antisecretory agents
None needed if H. pylori
eradicated
NSAID-related ulcers
Antisecretory agents (PPI, H2 receptor blockers);
Discontinue NSAID use, if possible
Misoprostol (600–800 mg/day) or proton pump inhibitor along with an NSAID
Ulcers associated with Zollinger-Ellison syndrome
High-dose PPI
PPI
Stress ulcers
H2 receptor blocker or PPI
H2 receptor blocker or PPI;
intragastric sucralfate; or intragastric antacid

69. ERADICATION OF H. PYLORI INFECTION
Triple therapy
Amoxycillin 1000mg twice daily +
Clarithromycin 500mg twice daily +
Proton pump inhibitor
(Lansoprazole 30mg twice daily)
Quadruple therapy
Tetracycline 500mg 4 times daily +
Metronidazole 500mg 4 times daily +
De-nol 120mg 4 times daily +