Transcript Peptic Ulcer Disease

Peptic Ulcer Disease
Khalayleh Harbi
Definition
• PUD is a disease of multiple etiology that
characteristic of local gastric or duodenal
damage and ulceration
Epidemiology
• The annual incidence in USA 1.8% or 500.000
new cases per year.
• There are 4 million ulcer recurrences yearly.
• More than 15.000 operation for PUD
performed yearly.
• About 4000 patient die from complication of
their PUD yearly
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
cause
• 1. H.PYLORI infection (most common cause)
• 2.NSAID (second most common cause)
• 3.stress
• 4. incrased pepsin and acid secretion
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.
HP
• HP is a chronic infection that found worldwide
• Person is infected, usually in childhood.
• Developing countries have a higher rate of HP
infection.
• 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.
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
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
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
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.
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
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
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
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 mucosaassociated lymphoid tissue( MALT) lymphoma
and HP infection
• Eradication of HP infection cause regression of
these MALT lymphoma
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.
PUD and NSAID
• 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
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 25000
hospitalization per year are attributed to
NSAID induced GI complication
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
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
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
Pathophysiology of gastric ulcer
• GU may occur anywhere in stomach
• GU rarely develop before age of 40, peak
incidence 55-60 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
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
TYPE II of GU
• About 15%
• Are located in the body of stomach in
combination with a duodenal ulcer
• Associated with excess acid secretion
TYPE III of GU
• About 20%
• Located in the preylorus
• Are associated with excess of acid secretion
TYPE IV of GU
• ABOUT 10%
• Occur hiegh in the lesser curvature near the
gasroesophageal junction
• Are not associated with excessive acid
secretion
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
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.
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
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
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
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
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
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
•
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
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.
Diagnosis of PUD
• 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
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
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
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
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%.
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%
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
Endoscopy
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•
•
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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 .
Treatment
Medical management
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
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
H2-receptor antagonist
• Structurally similar to histamine
• Undergo hepatic metabolism and excreted by
kidney
• Half-life 1.5-3 hours
• The most potent is famotidine
• Less potent is cimetidine.
• Result in DU healing 70-80% after 4 weak and 8090% after 8 weak
• Continuous IV infusion can produce more effect
than intermittent administration
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
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
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
Surgical Procedure for PUD
Indication for operation
• 1.intractability (failure of ulcer healing after 812 weeks of therapy)
• 2.hemorrhage
• 3.perforation
• 4.obstruction
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%
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
heineke-mikulicz
Finney, jaboulay pyloroplasty
Highly Selective Vagotomy
(Parietal Cell Vagotyomy)
• Divide only the vagus nerve supplying the acidproducing 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
• 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
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
Subtotal Gastrectomy
• Rarely used today for treatment of PUD
• Are preserved for malignancy
Laparoscopy
• All previous procedure can performed
laparoscopicaly
• Also omentopexy for perforation can
performed laparoscopicaly.
• Taylor procedure- parietal cell
vagotomy+posterior truncal
vagotomy+seromyotomy
Surgical Treatment
Recommendations for
Complications Related to Peptic
Ulcer Disease
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
Gastric Ulcer
• Intractable
• Type I: distal gastrectomy with Billroth I
• Type II or III: distal gastrectomy with truncal vagotomy
Bleeding
• Type I: distal gastrectomy with Billroth I
• 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
Thank you