Gi 03: Dyspepsia, H. Pylori, And Nsaids

Front 1

What are the Rome III criteria for dyspepsia?

Back 1

- Post-prandial fullness (after a meal)
- Early satiety
- Epigastric pain or burning

Front 2

What is functional dyspepsia?

Back 2

- Dyspepsia that meets the Rome III criteria (post-prandial fullness, early satiety, and epigastric pain/burning)

* No evidence of structural disease
- Symptoms should be fulfilled for the 3 months with symptom onset at least 6 months before diagnosis

Front 3

What are the types of Functional Dyspepsia?

Back 3

- Post-prandial distress syndrome
- Epigastric pain syndrome

Front 4

What are the criteria for Post-prandial Distress Syndrome (functional dyspepsia)?

Back 4

Must include one or both:
- Bothersome post-prandial fullness, after normal sized meals, several times per week
- Early satiation that prevents finishing a regular meal, several times per week

Supportive:
- Upper abdominal bloating or post-prandial nausea or excessive belching
- Epigastric pain syndrome may co-exist

Front 5

What are the criteria for Epigastric Pain Syndrome (functional dyspepsia)?

Back 5

All of the following:
- Pain or burning localized to abdomen or chest
- Intermittent pain
- Not generalized or localized to other abdominal or chest regions
- Not relieved by defecation or passage of gas
- Not fulfilling criteria for gallbladder or sphincter of Oddi disorders

Supportive:
- Burning quality but w/o retrosternal component
- Pain induced or relieved by ingestion of meal but may occur while fasting

Front 6

What alarm symptoms do you need to look for in patients you are evaluating for dyspepsia?

Back 6

- >55 yo w/ new-onset dyspepsia
- Family hx of upper GI cancer
- Unintended weight loss
- Progressive dysphagia
- Odynophagia (pain swallowing)
- Unexplained iron deficiency anemia
- Persistent vomiting
- Palpable mass or lymphadenopathy
- Jaundice

Front 7

How do you evaluate and manage a patient with dyspepsia w/o GERD or NSAIDs that is >55 yo or has alarm symptoms present?

Back 7

Endoscopy

Front 8

How do you evaluate and manage a patient with dyspepsia w/o GERD or NSAIDs that is <55 yo and has no alarm symptoms?

Back 8

1. Test for H. pylori (if positive, treat)
2. If negative, PPI trial for 8 weeks
3. If H. pylori treatment fails, PPI trial for 8 weeks
4. If fails, reassess diagnosis
5. Consider Endoscopy (if abnormal, biopsies / treatment based on findings)
6. If normal endoscopy, (a) rapid urease test and/or histology for H. pylori; (b) culture sensitivity testing if previously treated for H. pylori --> treat if H. pylori is detected

Front 9

How do you treat Functional Dyspepsia?

Back 9

- Antidepressants (tricyclics, trazodone)
- Prokinetic agents (metoclopramide)
- Fundic relaxant drugs (buspirone)
- Psychological therapy
- Antinociceptive agents (carbamazepine, tramadol, pregabalin)

Front 10

What do you need to do before you consider a diagnosis of functional dyspepsia?

Back 10

Exclude organic causes of dyspepsia (also check for alarm symptoms)

Front 11

What is the initial management for dyspepsia?

Back 11

- Consider upper endoscopy
- H. pylori testing / treatment
- Proton Pump Inhibitor testing for 8 weeks

- Consider adjunctive treatments for refractory cases

Front 12

What kind of bacteria is H. pylori?

Back 12

- G-
- Spiral shaped
- Microaerophilic
- Catalase, oxidase, urease positive
- 2-7 flagella

Front 13

What are the things to know about culture H. pylori?

Back 13

- Slow growing
- Culture on blood agar or Skirrow's media at 37 degrees C for 3-7 days

Front 14

What is the benefit of being Urease positive to H. pylori?

Back 14

Urease hydrolyzes luminal urea to ammonia to neutralize the gastric acid

Front 15

What is the benefit of being Catalase positive to H. pylori?

Back 15

Catalase may protect from oxygen metabolites

Front 16

Where does H. pylori colonize?

Back 16

- Exclusively colonizes gastric type epithelium
- Non-invasive

Front 17

What happens when H. pylori colonizes the stomach?

Back 17

- Stimulates an inflammatory and immune response
- IL-8 activates neutrophils and recruits other inflammatory cells into the mucosa

Front 18

What are the strains of H. pylori?

Back 18

- CagA positive or negative (Cytotoxin-Associated Gene A)
- If CagA positive, can also be VacA positive or negative (Vacuolating Cytotoxin)

Front 19

What is VacA? Benefit to H. pylori?

Back 19

Vacuolating Cytotoxin
- Passive urea transporter that can create a favorable environment for infectivity
- Only expressed in conjunction w/ CagA

Front 20

What is CagA?

Back 20

Cytotoxin-Associated Gene A

Front 21

Which of the following is true about H. pylori? Fix the rest.
a) gram positive
b) catalase +, oxidase +, urease -
c) colonizes gastric and duodenal epithelium
d) non-invasive organism

Back 21

d - non-invasive organism

a - it is G-
b - it is ureas +
c - it only colonizes gastric epithelium

Front 22

How do you spread H. pylori?

Back 22

- Not known, but likely person to person via fecal/oral or oral/oral exposure
- Humans are the only reservoir

Front 23

If you have had an H. pylori infection and it has been cured, what are your chances of being reinfected?

Back 23

Not typical - only 2% / year

Front 24

What are the conditions associated with H. pylori?

Back 24

- Gastric adenocarcinoma
- MALT lymphoma (Mucosa-associated lymphoid tissue)
- Gastritis
- Iron-deficiency anemia w/o bleeding and Vitamin B12 deficiency
- Functional dyspepsia?
- Acid reflux
- Peptic ulcer disease

Front 25

What is the difference between corpus predominant and antrum predominant gastritis associated with H. pylori? How are they affected by treatment?

Back 25

- Corpus predominant: ↓ acid secretion d/t local inflammation and ↑ cytokines, mild worsening w/ treatment

- Antrum predominant: ↑ gastrin level, improves with treatment

Front 26

How does treatment affect corpus predominant gastritis associated with H. pylori?

Back 26

- Treatment helps heal the parietal cells that are damaged by local inflammation and cytokines in this area (corpus)
- Thus once the parietal cells are healthier, they can release more acid which can make the acid reflux symptoms worse

Front 27

How does treatment affect antrum predominant gastritis associated with H. pylori?

Back 27

Treatment improves the acid reflux symptoms

Front 28

How do you diagnose an H. pylori infection?

Back 28

Endoscopic testing:
- Urease testing (90% sensitivity/specificity)
- Histology ± special stains (eg, Giemsa)
- Brush cytology (rarely used, 95% s/s)
- Bacterial culture (not routine)

Non-invasive testing:
- Urea breath testing (90% s/s)
- Serology - IgG (positive for active and past infections)
- Stool antigen (90% s/s)
- 13C-urea blood test (rare)

Front 29

How effective is urease testing by endoscopy for diagnosis of H. pylori? False negatives?

Back 29

- 90% sensitivity and specificity
- False negatives: recent bleeding, PPIs, antibiotics, bismuth-containing compounds, H2 antagonists

(therefore, if you are taking anything to treat H. pylori or had recent bleeding this may be falsely negative)

Front 30

How effective is histology ± special stains (eg, Giemsa) by endoscopy for diagnosis of H. pylori? False negatives?

Back 30

- Sensitivity may be decreased in patients on anti-secretory therapy (but not as much as for urease testing)
- False negative: potential sampling error (biopsy an area not infected, but could be infected else where)

Front 31

How effective is brush cytology by endoscopy for diagnosis of H. pylori?

Back 31

- Rarely used
- 95% sensitivity and specificity

Front 32

How effective is bacterial culture by endoscopy for diagnosis of H. pylori? Benefits?

Back 32

- Not routine
- Potentially useful for antibiotic sensitivity testing

Front 33

How effective is non-invasive urea breath testing for diagnosis of H. pylori? False negatives?

Back 33

- Detect labeled CO2 and ammonia with hydrolysis of urea
- 90% sensitivity and specificity
- False negatives: PPIs, bismuth, and antibiotics
- Useful for initial diagnosis and confirmation of eradication

Front 34

What is the test of choice for confirming eradication of H. pylori?

Back 34

Urea Breath Testing (detect labeled CO2 and ammonia w/ hydrolysis of urea)

Front 35

How effective is non-invasive serology (IgG) for diagnosis of H. pylori? Usefulness?

Back 35

- High sensitivity but variable specificity (76-96%)
- Positive result represents an active infection only about 50% of the time
- Negative test result useful to exclude infection in a low pretest probability situation
- Cure if a positive test converts to a negative after treatment (not common)

Front 36

How effective is non-invasive stool antigen testing for diagnosis of H. pylori? False negatives?

Back 36

- 90% sensitivity and specificity (but not as good as urea breath test)
- Useful for initial diagnosis and documenting successful eradication (may be less accurate for latter)
- Higher false negative result w/ PPI or bismuth

Front 37

What tests can be used to document successful eradication of H. pylori infection?

Back 37

- Serology (IgG) testing
- Stool Antigen testing

Front 38

How effective is non-invasive 13C-urea blood testing for diagnosis of H. pylori? How?

Back 38

- Rarely used
- Serum testing before and after ingestion of a 13C-urea rich meal

Front 39

How do you treat H. pylori gastritis?

Back 39

- Antibiotics (eg, amoxicillin and clarithromycin)
- Acid suppression w/ PPIs
- Treat for 10-14 days

Front 40

What is the pathogenesis of NSAID gastroduodenal toxicity?

Back 40

- COX-1 constitutively expressed to produce prostaglandins but NSAIDs inhibit COX-1
- Prostaglandins are cytoprotective

Front 41

What are the cytoprotective effects of prostaglandins?

Back 41

- Stimulates mucin, bicarbonate, and phospholipid secretion
- Increases mucosal blood flow and O2 delivery
- Enhances epithelial cell proliferation
- Increases epithelial cell migration

Front 42

What are the cytoprotective effects of NO through NO Synthase?

Back 42

- Mediates gastric mucin release
- Stimulation of alkaline fluid
- Maintenance of epithelial barrier
- Increases mucosal blood flow

Front 43

What are the general repair mechanisms for gastroduodenal toxicity?

Back 43

- Restitution: rapid migration of new epithelial cells from progenitor cells

- Proliferation: less rapid regeneration of new epithelial cells from progenitor cells

- Prostaglandins and NO important in both

Front 44

What is the term for rapid migration of new epithelial cells from progenitor cells to repair the gastroduodenal epithelium?

Back 44

Restitution

Front 45

What is the term for less rapid regeneration of new epithelial cells from progenitor cells to repair the gastroduodenal epithelium?

Back 45

Proliferation

Front 46

What contributes to the pathogenesis of gastroduodenal toxicity by NSAIDs?
a) ↑ COX-1 activity
b) ↓ COX-2 activity
c) ↑ NOS activity
d) ↓ Phospholipid secretion

Back 46

d) ↓ phospholipid secretion

(COX-1 is the main enzyme affecting the GI, so ↓ COX-1 would also have been correct; ↓ NOS activity would also mediate the gastroduodenal toxicity)

Front 47

How does NSAID use relate to H. pylori?

Back 47

- They are independent and synergistic risk factors for PUD
- ↓ Risk of PUD w/ H. pylori eradication before starting NSAIDs

Front 48

What are the risk factors for PUD with NSAID use?

Back 48

- Duration of therapy (most commonly complications occur in first 3 months)
- Higher dose
- Age
- Hx of gastroduodenal toxicity to NSAIDs
- Hx of PUD
- Glucocorticoids, anticoagulation, clopidogrel, bisophosphonates, SSRIs

Front 49

Are dyspepsia and GI toxicity from NSAIDs related?

Back 49

No

Front 50

How long does it take to recover COX-1 activity after aspirin is stopped?

Back 50

5-8 days (remember aspirin is an irreversible acetylator of COX-1)

Front 51

How does NSAID use affect the stomach vs the duodenum?

Back 51

Stomach
- Interference of NSAIDs w/ restitution and proliferation in stomach
- Ulcer formation less dependent on gastric acid than the COX-1 mediated prostaglandin production

Duodenum
- Ulcer formation w/ NSAIDS highly dependent on stomach acid

Front 52

How do PPIs and H2 blockers help the stomach vs the duodenum in NSAID GI toxicity?

Back 52

H2 blockers and PPIs are more effective in preventing injury in the duodenum than in the stomach

Front 53

How can NSAIDs affect the distal small intestine and colon?

Back 53

- High local concentration of NSAID necessary which could be exacerbated by enteric-coated, sustained-release, or slow-release NSAIDs
- Localized mucosal injury → inflammation and ulceration → fibrosis and stricture
- NSAIDs inhibit prostaglandins, alter blood flow, and increase small intestinal permeability

Front 54

What is the clinical presentation of NSAID related GI toxicity to the stomach and duodenum?

Back 54

- Edema, erythema, subepithelial hemorrhage
- Erosions (mucosal break w/o visible depth)
- Ulcers (mucosal breaks w/ visible depth)

Front 55

Which is deeper an erosion or an ulcer?

Back 55

Ulcer

Front 56

What is the clinical presentation of NSAID related GI toxicity to the distal small intestine and colon?

Back 56

- Iron deficiency anemia
- Overt bleeding from ulcers (picture)
- Hypoalbuminemia
- Malabsorption from enteropathy
- Bowel obstruction from strictures (eg, diaphragm)
- Diarrhea from colitis
- Acute abdomen from perforation

Front 57

How do you treat NSAID related GI toxicity to the stomach and duodenum?

Back 57

- Stop NSAID
- Start PPI >> H2 antagonist (4 weeks for duodenal ulcers and 8 weeks for gastric ulcers b/c more effective in duodenum)
- Assess H. pylori status and treat if positive

Front 58

How do you treat NSAID related GI toxicity to the distal small intestine and colon?

Back 58

- Stop NSAID
- Dilation for strictures
- Surgery