medina, kristianne medina, sakura cher mejino, carla melgarejo, ivy mendoza alvin mendoza, diana...

Medina, Kristianne

Medina, Sakura Cher

Mejino, Carla

Melgarejo, Ivy

Mendoza Alvin

Mendoza, Diana

Mendoza, Donn Paolo

Upper GI Bleeding due to Peptic Ulcer Disease

Group AMendoza, Gracielle

Mindanao, Ace Malvin

Miranda, Maria Carmela

Molina, Ramon Miguel

Monzon, Jerry West

Morales, Arriane

Musni, Merwen Mitchell

Peptic Ulcer Disease

Definition and Epidemiology

Peptic Ulcer Diseasea chronic, recurrent disorder that is characterized by

an ulcer (defined as mucosal erosions equal to or greater than 0.5 cm) of an area of the gastrointestinal tract.

most common sites of this disease are the duodenum (duodenal ulcer) and the stomach (gastric ulcer).

generally exacerbated by fasting and improved with meals

Harrison’s Principle of Internal Medicine, 17th ed

Peptic Ulcer DiseaseDuodenal Ulcer

Ulcers often occur in the first portion of duodenum

Malignancy rareOccurs 90 mins-3 hrs

after eatingUsually awakens patient

at nightRelieved by food intakeRelieved by antacids

Gastric UlcerDistal to the junction

between antrum and acid secretory mucosa

Occurs later in life than DU

Peak incidence >60 y.o.Males > femalesLess common than DUAggravated by food

intakeRelieved by antacids

Harrison’s Principle of Internal Medicine, 17th ed

Epidemiology

Gastric Ulcer• Tend to occur later in life

– 6th decade as the peak incidence.

• About 75% with gastric ulcers harb or H. pylori.

• There is a higher likelihood to be silent and presenting after complication develops.

Harrison’s Principle of Internal Medicine, 17th ed http://www.doh.gov.ph/faqs/peptic_ulcer

Duodenal Ulcer

• Estimated to occur in 6-15% of the population.

• More than 90% of patients with duodenal ulcers and about 75% with gastric ulcers harbor H. pylori which is responsible for frequent relapses of ulcers.

• Death rates, need for surgery and physician visits decrease by >50% over the past 30 years.

EpidemiologyFrequency

United Statesone-year point prevalence is 1.8%lifetime prevalence is approximately 10% affects approximately 4.5 million people annually.Internationalvariable and determined primarily by association

with the major causes of PUD: H pylori and NSAIDs.

Harrison’s Principle of Internal Medicine, 17th ed

EpidemiologyMortality/Morbidity

decreased by >50% over past 30 years1 death per 100,000 caseshospitalization rate is approximately 30 patients per

100,000 cases.

http://emedicine.medscape.com/article/181753

Harrison’s Principle of Internal Medicine, 17th ed

EpidemiologySex

prevalence has shifted from predominance in males to similar occurrences for both sexes.

lifetime prevalence is approximately 11-14% for men and 8-11% for women.

Ageduodenal ulcer typically affects persons 25-55 years of

age while the peak incidence of gastric ulcer occurs around 55-65 years of age

http://www.doh.gov.ph/faqs/peptic_ulcer

http://emedicine.medscape.com/article/181753

EpidemiologyRisk Factors for PUD

intake of acidic drinks (carbonated drinks, juices,alcohol)

intake of NSAIDSpresence of Helicobacter Pylorismokinggenetic Influencestresshypersecretory states

http://www.doh.gov.ph/faqs/peptic_ulcerhttp://emedicine.medscape.com/article/181753

EpidemiologyRisk Factors for H. pylori infection

- Poor socioeconomic status- Less education on proper sanitation- Birth and residence in developing countries- Domestic crowding- Unsanitary living conditions- Unclean food and water- Exposure to gastric contents of an infected individual

Harrison’s Principle of Internal Medicine, 17th ed

PathoPhysiology

Gastric Bleeding due to

Peptic Ulcer Disease

Peptic ulcers are the most common cause of upper GI bleeding

Aprroximately 50% of cases

an increasing proportion is due to nonsteroidal anti-inflammatory drugs (NSAIDs), with the prevalence of Helicobacter pylori decreasing.

Harrison’s Principles of Internal Medicine 17th ed.

Gastroduodenal Mucosal Defense

Harrison’s Principles of Internal Medicine 17th ed.

Causes of Mucosal DamageCigarette SmokingPsychological StressGenetic PredispositionDiet

Increased intake of:AlcoholCaffeine

Harrison’s Principles of Internal Medicine 17th ed.

H. pylori-induced Peptic Ulcer Disease• Risk-factors of H. pylori infection

– Poor socioeconomic status– Less education

• Mode of Transmission– Oral-oral– Fecal-oral

• Factors Affecting Infection– Bacteria’s motility– Ability to produce urease

Harrison’s Principles of Internal Medicine 17th ed.

Peptic Ulcer Disease(due to Helicobacter pylori)

Bacterial Factors• Structure

S-shaped rod with multiple flagella in one pole

• Adhesins• Porins• Enzymes: Urease,

Protease, Phospholipase

Host Factors• Duration• Location• Inflammatory

Response• Genetics ??

Harrison’s Principles of Internal Medicine 17th ed.

Recruitment of neutrophils, lymphocytes, macrophages & plasma cells

Release of Prostaglandin, Substance P, Histamine

Apoptosis(T cells & IFN gamma)

Inflammatory Response to H. Pylori

ULCER

H. Pylori binds to class II MHC on gastric epithelial cells

Cytokine Production• IL-1 alpha/ Beta• IL-2• IL-6• IL-8• TNF alpha• IFN gamma

Epithelial cell injury

Production of O2 or N2 species(neutrophils)

Harrison’s Principles of Internal Medicine 17th ed.

ULCER

Gastrointestinal bleeding

Clinical Presentation

Upper GI Bleeding due to PUD

Peptic Ulcer DiseaseAbdominal/Epigastric PainCommon to many GI diseasesPoor predictive valueBurning or gnawing discomfortIll-defined aching sensation

Harrison’s Principle of Internal Medicine, 17th ed

Epigastric Pain

Gastric Ulcer Duodenal Ulcer

Precipitated by foodUsually accompanied

by nausea and weight loss

90 minutes to 3 hours after a meal

Frequently relieved by antacids or food

Awakes the patient from sleep (12 midnight to 3am)

Harrison’s Principle of Internal Medicine, 17th ed

Epigastric PainPossible Causes

Acid-induced sensitivity to bile acids and pepsinAltered gastroduodenal motility

Harrison’s Principle of Internal Medicine, 17th ed

Symptoms PUD complicationsUpper GI Bleeding

Tarry stoolsCoffee-ground emesis

Harrison’s Principle of Internal Medicine, 17th ed

PE FindingsPeptic Ulcer DiseaseEpigastric Tenderness

Most frequent finding of Peptic Ulcer

Findings indicative of PUD complications:TachycardiaOrthostasisAnemia

Harrison’s Principle of Internal Medicine, 17th ed

Clinical PresentationOur Patient, O.L.

Vague epigastric discomfort

Dizziness & cold clammy sweats

Weight loss (10 kg) for the past 6 months

Peptic Ulcer Disease

Abdominal/epigastric pain (burning sensation, ill- defined, aching sensation)

Vomiting of undigested food

Nausea

Weight loss (gastric outlet obstruction as complication)

Clinical PresentationOur Patient

Coffee ground vomitusMelena (DRE- marroon

colored stools)

Orthostatic hypotension100/60 when sitting120/80 when supine

Tachycardia (PR- 105/min)

Pale palpebral conjuctiva

Upper GI Bleeding due to Peptic Ulcer Disease

Ground Coffee emesisTarry Stools

(complication)

Orthostasis

Tachycardia

Anemia Epigastric tenderness

Diagnostic Evaluation

Upper GI Bleeding due to PUD

Barium Studycommonly used as 1st test for documenting an

ulcerSingle-Contrast Barium 80% sensitivityDouble-Contrast Barium 90% sensitivityDecreased sensitivity for ulcers < 0.5 cm,

previous scarring, and post-op patients

Source: Harrison’s Principles of Internal Medicine, 17th ed.

Barium StudyDU appears as a well demarcated craterA benign GU appears as a discrete crater with

radiating mucosal folds from the ulcer marginMalignant ulcers are often associated with > 3

cm ulcers or those associated with a mass

Source: Harrison’s Principles of Internal Medicine, 17th ed.

Barium Study

A double-contrast radiograph showing a normal stomach

Normal duodenum

Barium Study

Normal duodenum

Barium Study of a benign duodenal ulcer

Barium Study

Normal duodenum Benign Gastric Ulcer

Radiographic Signs of a Benign Gastric Ulcer

•Ulcer Crater•Hampton Line•Ulcer mound•Ulcer Collar

Collection of barium on dependent surface which usually projects beyond anticipated wall of stomach

Collection of barium on dependent surface which usually projects beyond anticipated wall of stomach

1-2 mm thin straight line at neck of ulcer view which represents the thin rim of undermined gastric mucosa

1-2 mm thin straight line at neck of ulcer view which represents the thin rim of undermined gastric mucosa

Smooth, sharply delineated tissue mass surrounding a benign ulcerSmooth, sharply delineated tissue mass surrounding a benign ulcerRadiolucent rim seen in necks of

deep ulcers, representing thicker rim of edematous gastric wall

Radiolucent rim seen in necks of deep ulcers, representing thicker rim of edematous gastric wall

Benign vs Malignant?

ShapeShape

Round, oval, linearIrregular

PenetrationPenetration

Beyond the contour of the stomach

Projects to the lumen

Mucosal FoldsMucosal Folds

Symmetric, radiate to edge of crater

Irregular arrangement, nodular, fused, clumped

Ulcer MoundUlcer Mound

Smooth symmetrical mound of edema with

central crater

Irregular, asymmetric mound of edema with

eccentric crater

EndoscopyMost sensitive and

specific approach Permits direct

visualization of the mucosa

Facilitates photographic documentation of a mucosal defect and tissue biopsy to rule out malignancy or H. pylori

Helpful in identifying lesions too small to detect radiography

For evaluation of atypical radiographic abnormalities

Determines if an ulcer is a source of blood loss

Source: Harrison’s Principles of Internal Medicine, 17th ed.

Esophagogastroduodenoscopy Examination of the lining of the

esophagus, stomach, and upper duodenum.

Performed by passing a flexible endoscope through the mouth

Best method for examining the upper gastrointestinal mucosa

Sensitivity and specificity in diagnosing gastric and duodenal ulcers and cancers

More than 90% Intravenous conscious sedation or

topical pharyngeal anesthesia needed

•Harrison’s Principles of Internal Medicine 17th edition•Bailie, J. (1992). Gastrointestinal Endoscopy, Basic Principles and Practice

•American Family Physician Web site at www.aafp.org/afp

Endoscopy

Normal architecture of the gastric folds Benign duodenal ulcer

www.gastrointestinalatlas.com

Endoscopy

Normal architecture of the gastric foldsBenign gastric ulcer

www.gastrointestinalatlas.com

Endoscopy

www.gastrointestinalatlas.com

Laboratory Tests

Laboratory TestsTests for detection of Helicobacter pylori

Harrison’s Principles of Internal Medicine, 17th ed.Helicobacter pylori and Peptic Ulcer – RA Moore

Invasive (Endoscopy / Biopsy required)

Test Sensitivity Specificity Cost Comments

Rapid urease

90 – 95 98 – 100 +++

False negative with recent use of PPIs, antibiotics, or bismuth compounds

Histology 80 – 90 > 95 ++++

Requires pathology processing and staining; provides histologic information

Culture 60 – 95 100 ++++

Time-consuming, expensive, dependent on experience; allows determination of antibiotic susceptibility

Laboratory TestsTests for detection of Helicobacter pylori

Harrison’s Principles of Internal Medicine, 17th ed.Helicobacter pylori and Peptic Ulcer – RA Moore

Non-Invasive

Test Sensitivity

Specificity

Cost Comments

Serology 85 - 98 90 – 100+

Not useful for early follow-up

Urea breath test

95 - 100 98 – 100 ++useful for early follow-up; false negative with recent therapy

Stool antigen

90 > 90 not established for eradication but promising

Invasive TestsBiopsy Urease Test

one large or two small biopsy specimens are placed into a gel test solution containing urea, a pH color reagent and a bacteriostatic agentIf H pylori is present, bacterial urease converts urea to ammonia

Invasive Tests (Based on Endoscopy Biopsy)

Urea

color change often occurs within minutes but can require up to 24 hours

Ammonia

↑ pHUrease

Urea

Sensitivity Specificity

90 – 95 98 – 100 Biopsy Urease Test

endoscopic diagnostic test of choice

Invasive TestsHistologic Examination

the criterion standard to establish a diagnosis of H pylori infection

Usually performed when the rapid urease test is negative and a high suspicion for H. pylori persists

Invasive Tests (Based on Endoscopy Biopsy)

Histologic Examinationpermitting optimal visualization of H. pyloriyields additional information:

degree and pattern of inflammation

atrophy

metaplasia

dysplasia

detected with hematoxylin & eosin (H&E) stain of gastric tissue, but special stains like a modified Giemsa, Brown-Hopps or silver stain increases the sensitivity

Sensitivity Specificity

80 – 90 > 95

Invasive TestsMicrobiologic Culture

Sensitivity can be limited by prior therapy and contamination with other mucosal bacteria

Culture primarily is used in research studies and is not available routinely for clinical use.

Invasive Tests (Based on Endoscopy Biopsy)

Microbiologic Cultureculture homogenized biopsy on a variety of specialized agar plates at elevated temperatures for at least seven daysthe identity of H. pylori can be confirmed by its typical appearance on Gram’s stain and its positive reactions in oxidase, catalase, and urease testsantibiotic sensitivities can be determined

most specific but may be insensitive because of difficulty with H. pylori

isolation

Sensitivity Specificity

60 – 90 100

Noninvasive Tests13C or 14C Urea Breath Test

the patient drinks a solution containing urea labeled with either the nonradioactive isotope 13C or a minute dose of the radioactive isotope 14C. 13С/12С isotope ratio change which can be detected by mass spectrometry or radioactive counting

13C

13CO2

13CO2

13C-urea

Sensitivity Specificity

95 – 100 98 – 100

Noninvasive TestsStool AntigenTest

simple assay that is dependent on the detection of H. pylori antigens in stoolmore convenient and less expensive than the urea breath test but has been slightly less accurate

Serologymeasuring specific IgG levels in serum by enzyme-linked immunosorbent assay (ELISA) or immunoblot

Sensitivity Specificity

90 >90

Sensitivity Specificity

>80 >90

Noninvasive TestsSerology

USTH: ImmunoComb® Based on a solid phase enzyme immunoassay principle plastic comb  with 12 teeth, sensitized at different spots with

reactive materials and an  internal control

testtest control

control

HRP Sensitivity

Specificity

96 100

Treatment

Upper GI bleeding due to PUD

GoalsControl upper GI bleedingProvide symptom reliefPromote ulcer healingPrevent recurrence and other complications

Peptic Ulcer Bleeding

Sung, J(2006).Current Management of Peptic Ulcer Bleeding. Journal on Nature Clinical Practice of Gastroenterology and Hepatology. Ret. http://www.medscape.com/viewarticle/521189

Common medical emergency; 300,000 hospital admissions in the US.

Predominant among the elderly80-85% UGI bleeding stops spontaneously 15-20% continues or develops into recurrent

bleeding

Endoscopic Therapy

Sung, J(2006).Current Management of Peptic Ulcer Bleeding. Journal on Nature Clinical Practice of Gastroenterology and Hepatology. Ret. http://www.medscape.com/viewarticle/521189

Injection TherapyInjection with diluted epinephrine (1:10,000)Tamponade effect

Thermal devicesheater probe, monopolar and bipolar

electrocoagulationMechanical devices

Hemoclips

Pharmacologic Mgt for Bleeding PUD

Antisecretory AgentsProton Pump InhibitorsH2 receptor antagonists

Antisecretory AgentsProton Pump Inhibitors

Irreversibly inhibit gastric parietal cell proton pump H+/K+-ATPase.

Inhibit both fasting and meal stimulated secretion Blocks the final common pathway of acid secretion

Omeprazole 20 mg bid 4-8 weeks or IV Omeprazole

Sung, J(2006).Current Management of Peptic Ulcer Bleeding. Journal on Nature Clinical Practice of Gastroenterology and Hepatology. Ret. http://www.medscape.com/viewarticle/521189

Lau et ala high-dose omeprazole infusion (80 mg intravenous

bolus followed by 8 mg per hour for 72 h) or an equivalent of placebo

rate of recurrent bleeding at day 30 was 21.7% and 5.8%, respectively, for those assigned to placebo and omeprazole infusion .reduction in the need for re-treatment and blood transfusiontrend towards fewer surgeries and deaths among those

assigned to omeprazole infusion

Proton Pump Inhibitors for H. Pylori-induced PUD

Mechanisms:Direct antimicrobial properties(minor)Raising intragastric pH

Lowering minimal inhibitory concentrations of antibiotics against H.Pylori

Antisecretory AgentsProton Pump InhibitorsAdverse effects:

Subnormal B12 levels with prolonged therapyIncreased gastric bacterial concentrationIncreases chronic inflammation of gastric bodySmall benign gastric fundic gland polyps

Antisecretory AgentsH2 receptor antagonist

Competitive inhibitors of the action of Histamine at H2 receptors in the parietal cells.

Antisecretory Agents

H2 receptor antagonistsCimetidineFamotidine 20 mg BIDRanitidine 150 mg tab BID

Algorithm on Treatment of UGI Bleeding

Treatment Regimen for H.Pylori Triple Therapy Quadruple Therapy

Omeprazole (20 mg bid)

Omeprazole (20 mg bid)

Omeprazole (20 mg bid)

Clarithromycin (500 mg bid)

Clarithromycin (500 mg bid)

Bismuth Subcitrate (2 tab qid)

Amoxicillin (1 g bid)

Metronidazole (500 mg bid)

Metronidazole (250 mg tid)Tetracycline (500 mg qid)

Other Drugs used for PUD

AntacidsAluminum Hydroxide

Magnesium Hydroxde

Sodium BicarbonateMechanisms:

Reduction of intragastric acidity Stimulation of mucosal prostaglandin production

Promote mucosal defense

Mucosal Protective AgentsBismuth Subcitrate

Selective binding to an ulcer, coating and protecting from acid and pepsin

Inhibition of pepsin activity; stimulation of mucus production; increase PG synthesis

Mucosal Protective AgentsSucralfate

Forms a viscous, tenacious paste that binds to the ulcer or erosion forming a PHYSICAL BARRIER

1 g qid ; 1 hour before meals

Prostaglandin AnalogsMisoprostol

prostaglandin E1 analogue which acts as natural prostaglandin in the body

Only indicated for prevention of NSAID induced gastric ulcers in high risk patients.

causes spontaneous abortion

Side effectsdiarrhea and crampy abdominal pain