Peptic Ulcer

Chaohui Yu

ych623@sina.com 13957161659

Suggested readings

消化性溃疡 , 内科学第二版 , 人民卫生出版社 ,434-445

Acid peptic disease, Cecil medcine,24th edition,886-895

Peptic ulcer disease, Lancet, 2009; 374: 1449-1461

Helicobacter pylori infection, N Engl J Med,2010;363;1597-1604

The self-digestion of GI mucosa caused by gastric acid and pepsin The rate is 10% in population

Why does the ulcer happen?- normal defense

Acid, pepsine

epithelial cell

submucosa

mucus layer

Bicarbonate

Defensive barrier of gastric and duodenal mucosa

mucus barrier physical defense chemical counteraction

mucosal barrier quick refreshment of

epithelial cellabundant circulation of

blood nutrition factor: PGE1,EGF intercellular tight junctionabundant submucosal

blood vesselHCO3

- counteracts H+

Balance in attack and defence

Acid, pepsine

Mucosal damage

Pathogenesy of PU

•Acid and Pepsine •Helicobacter pylori •NSAIDs •Motility disturbance •Stress •Systemic inflammatory disorders•Ischemia•Hypergastrinemic Syndromes•Hyperhistaminic Syndromes•Anastomotic or marginal Ulceration•Alcohol•Tobacco

Pathogenesy of PU—Acid & Pepsine

0

20

40

60

80

100

Maximum activity of enzyme(%)

1 2 3 4Gastric fluid pH

42

Pepsine rely on Acid

 no acid,no ulcer

 parietal cell mass

 parietal sensibility

feedback suppression vagal tone

 Biology bostrychoid,have flegalla, microamount

requirement of oxygen  urase: urea NH3Vac A, Cag A

 Evidence-based medicine

high positive rate of HP in PUthe eradication of Hp

facilitate the healing of PU the eradication of Hp

degrades the recurrence of PU

Pathogenesy of PU

—Helicobacter Pylori

2005 年 10 月

The colonization factor of HPbostrychoid,have flegallauraseespecial adherence factor

Invasive factorurase ammoniacal toxicityVac A, Cag A and phosphatidase A1 chemotact and activate inflammatory cellantigen imitate

Two theory: hypothesis of leaking roof gastrin-link hypothesisD cell & somatostatin

Pathogenesy of PU—Helicobacter Pylori

IL-8

Proteolyticenzymes

O2 radicals

Infection withInfection with H. pylori H. pylori results in anresults in anacute inflammatory reactionacute inflammatory reaction

Epithelial cell

Polymorph

1995 2000

H. pylori-positive gastroduodenal ulcers

13%

87%

33%

67%

H. pylori-negative gastroduodenal ulcers

Juhasz, Gut 2001; 49: A64.

Increasing proportion of H. pylori-negative ulcers 1995–2000

Increasing proportion of H. pylori-negative ulcers 1995–2000

Pathogenesy of PU— non-steroidal anti-inflammatory drugs, NSAID

Arachidonic acid

cycloxygenase

X

prostaglandin

Maintain the function of kidney and platelet

guard gastric and duodenal mucosa

Inflammation 、 pain

antiinflammatory analgesia gastrointestinal damagenephrotoxicity

Cox1

Cox2

The synergistic affection of Hp and

NSAID

Bicarbonate

PROTECTIVE FACTORS

Prostaglandins

Mucosal bloodsupply

Surface epithelial

cells

Mucus layer

AGGRESSIVE FACTORS

Acid + pepsin H. pylori

Seager & Hawkey, BMJ 2001; 323: 1236–9.

++Bicarbonate

Prostaglandins

Mucosal bloodsupply

Surface epithelialcells

Mucus layer

AGGRESSIVE FACTORS

Acid + pepsin H. pyloriNSAIDs

PROTECTIVE FACTORS

Pathogenesis of NSAID-induced ulcersPathogenesis of NSAID-induced ulcers

Seager & Hawkey, BMJ 2001; 323: 1236–9.

AGGRESSIVE FACTORS

Acid + pepsin H. pyloriNSAIDs

Bicarbonate

Prostaglandins

Mucosal bloodsupply

Surface epithelialcells

Mucus layer

PROTECTIVE FACTORS

Pathogenesis of NSAID-induced ulcersPathogenesis of NSAID-induced ulcers

Seager & Hawkey, BMJ 2001; 323: 1236–9.

++

AGGRESSIVE FACTORS

Acid + pepsin H. pyloriNSAIDs

Bicarbonate

Mucosal bloodsupply

Surface epithelialcells

Mucus layer

Prostaglandins

PROTECTIVE FACTORS

Pathogenesis of NSAID-induced ulcersPathogenesis of NSAID-induced ulcers

Seager & Hawkey, BMJ 2001; 323: 1236–9.

++

AGGRESSIVE FACTORS

Acid + pepsin H. pyloriNSAIDs

Bicarbonate

Mucosal bloodsupply

Surface epithelialcells

Mucus layer

Prostaglandins

PROTECTIVE FACTORS

Pathogenesis of NSAID-induced ulcersPathogenesis of NSAID-induced ulcers

Seager & Hawkey, BMJ 2001; 323: 1236–9.

++

AGGRESSIVE FACTORS

Acid + pepsin H. pyloriNSAIDs

Bicarbonate

Mucosal bloodsupply

Surface epithelialcells

Mucus layer

Prostaglandins

PROTECTIVE FACTORS

Pathogenesis of NSAID-induced ulcersPathogenesis of NSAID-induced ulcers

Seager & Hawkey, BMJ 2001; 323: 1236–9.

++

AGGRESSIVE FACTORS

Acid + pepsin H. pyloriNSAIDs

Bicarbonate

Mucosal bloodsupply

Surface epithelialcells

Mucus layer

Prostaglandins

PROTECTIVE FACTORS

Pathogenesis of NSAID-induced ulcersPathogenesis of NSAID-induced ulcers

Seager & Hawkey, BMJ 2001; 323: 1236–9.

++

AGGRESSIVE FACTORS

Acid + pepsin H. pyloriNSAIDs

Bicarbonate

Mucosal blood

supply

Surface epithelialcells

Mucus layer

Prostaglandins

PROTECTIVE FACTORS

Pathogenesis of NSAID-induced ulcersPathogenesis of NSAID-induced ulcers

Seager & Hawkey, BMJ 2001; 323: 1236–9.

++

31%

59%

17%

83%

Ulcers not related to NSAID use

NSAID-related ulcers

Juhasz, Gut 2001; 49: A64.

Ulcers related to NSAID use1995–2000

Ulcers related to NSAID use1995–2000

1995 2000

Large GU, which healed in 14Wk after stopping aspirin use

Deep GU unhealed for 5 years with continued aspirin abuse

Large DU, which healed after stopping aspirin

Aspirin correlated ulcer

Location

DU: bulbar zone,antetheca GU:lesser curvature side of sinus ventriculi,gastric corner

Especial denomination

complex ulcer: DU+GU multiple ulcer: ≥twotwo symmetria ulcersenormous ulcer

DU>2cm,GU>3cm

Clinical manifestation—upper GI symptoms

Chronicity 、 periodicity 、 rhythmic

Pain  DU ： pain in hanger/hypnalgia ，

remittence after the meal pain- foodintake-remittence  GU ： pain after the meal

foodintake-pain-remittence  location/property

Other dyspepsia symptoms

Especial type of ulcerSymptomless PU ： 15-35% ， see a doctor after the

appearance of the complications PU in olders ： most of superior positional/enormous ulcer ,often atypical symptoms Complex ulcer ： DU often happens earlier than GU, often atypical symptomsUlcer of pyloric canal ： more gastric acid 、 bad curative effect 、 more complicationsPost bulbar ulcer ： night pain 、 radiating pain 、 more complications ， bad curative effect.

Difficult curable ulcer

Chronic gastritis/functional dyspepsia

  have symptoms ， but no evidence

Chronic cholecystitis/cholelithiasis   the discrimination is

difficult ， oily food ， BUSCastric carcinoma

   the discrimination is difficult in symptoms,gastroscope and pathologicalexamination are critical

atypical+multiple+morecomplications+diarrhea

Hookworm infection

Differential diagnosis of symptoms

Gastrin adenoma

Diagnosis—the existence of ulcer is true or untrue

X –ray examination Direct sign ： niche sign Indirect sign ： spasmus 、 irritation

tenderness 、 deformation

Gastroscopy ： focus lesions+biopsy +Hp examination

 Active stage (A1,A2)  Healing stage(H1,H2)  Scar stage(S1,S2)

A1

H1

S2

Diagnosis—Hp infection is yes or no?

virulence—need taking gastric mucosa

(RUT): ammineHistological examinationCultivation PCR

Non –virulent examination—not need taking gastric mucosa

Breath testSerology Hp stool antigen

Urase based test: RUT 、 UBT

Diagnose-if have complication

upper GI hemorrhage (UGIH)   the most common complication   the first symptom of hemorrhage by

10%-20% ulcer activity symptom before hemorrhage

perforation    acute perforation ： acute diffuse peritonitis    penetrability perforation ： lesser bursa omentalis subacute perforation

pyloric obstruction ： functionality/parenchymatous obstruction canceration ： warning sings and symptoms

chronic patient history age>45(GU) symptom has changed recently and curative effect badly the appearance of hemorrhage :stool OB (+), anemia emaciation

DAY

14121086420

% 100

80

60

40

20

0

Factitiousness intervention to speed up

ulcer healing

PU cure-purpose

Eliminate cause of a disease 、 relieve symptom 、 heal ulcer 、 prevent recurrence 、 avoid complication

Antacid ： counteract gastric acid obviously rebound Acid-reducing Drugs ： H2RA ， PPI

PU cure—degrade gastric acid

Gastrin Histamin

e Ach

H+

Cimetidine Famotidine Nizatidine Ranitidine

Omeprazole Lansoprazole pantoprazole Rabeprazole

PPI

DU:4-6 Wk GU:6-8 Wk

H2RA

PU cure— Eradication HpProgram

Trigeminy with the core of PPIPPI+(Clarithromycin/amoxicillin )+(furazlidone /metronidazole), Bid, 7-14d

Trigeminy with the core of bismuth  To object: blind medication ,single/ double medication

Re-examination ?  Eradication:after course of treatment to end for 4 weeks,HP Negative Generally do not request re-examination

0

100

Hea

lin

g r

ate

(%)

H. pylori eradicated

H. pylori persisted

Duodenal ulcer

***95

76

**88

73

Gastric ulcer

Treiber & Lambert, Gastroenterol 1998; 93: 1080–4.

**p<0.01***p<0.001

Review of 60 trials; 4329 patientsUlcer healing rate according to post-treatment H. pylori status

Influence of successful eradication of H. pylori on ulcer healing

Influence of successful eradication of H. pylori on ulcer healing

Non-eradicated H. pylori infection

Eradicated H. pylori infection

Hopkins et al., Gastroenterol 1996; 110: 1244–52.

0

20

40

60

80

100

Gas

tric

ulc

er

recu

rren

ce (

%)

Labenz Sung Labenz Karita Seppälä& Borsch et al. & Borsch et al. et al. (n=11) (n=19) (n=18) (n=4) (n=42)

Labenz Sung Labenz Karita Seppälä& Borsch et al. & Borsch et al. et al. (n=16) (n=26) (n=32) (n=26) (n=10)

H. pylori eradication reduces recurrence in gastric ulcer

H. pylori eradication reduces recurrence in gastric ulcer

H. pylori + ve H. pylori – ve

Huang et al., Am J Gastroenterol 1996, 91: 1914.

Pat

ien

ts i

n r

emis

sio

n (

%)

100

00

Months 6 12 18 24

58

***95

40

***96

30

***95

25

***92

***p<0.001

Eradication of H. pylori almost eliminates duodenal ulcer recurrence

Eradication of H. pylori almost eliminates duodenal ulcer recurrence

The treatment of complication

Peptic Ulcer Hemorrhage

THANK YOU