139. Peptic Ulcer Disease & H Pylori

Question 1

Why does pernicious anemia cause NO BENIGN ULCER FORMATION?

Answer 1

autoimmune disease attacking parietal cells

no acid = no ulcer

Question 2

H Pylori

• prevalence
• transmission
• main habitat
• acquired age
• cancer risk
• evidence for causing ulcers

Answer 2

Prevalence: underdeveloped world (China, Africa, South America)
Transmission: human-human, fecal-oral
Habitat: human stomach, or areas of stomach metaplasia (Barrett’s Esophagus, Duodenal Ulcers, Meckel’s Divert)
Age: acquired <10yrs, presents later

Cancer Risk:
Adenocarcinoma: Diffuse Type - HP plays less role (just genetic mutation accumulation); Intestinal Type - caused by genes, HP, and enviro interaction
MALT Lymphoma: HP stim auto-antigen sensitization = B cell clonal expansion = somatic mutations = MALT lymphoma [TREATED WITH HP ERADICATION]

HP present before PUD and HP eradication heals PUD (and MALT Lymphoma)
not everyone with HP infection has clinical disease, but it is a causal factor

Question 3

HP Pathophysiology

• stages of invasion
• pathogenicity

Answer 3

1. HP ingested
2. Flagellated HP swims thru mucus
3. Adhesins attach to epithelium
4. Multiply
5. Release cytokines (VacA) = damage mucosa (inflammation, chronic gastritis, neutrophil migration)
6. Internalized into epithelium

Urease Producer: breakes urea to NH3, forms NH4+ in stomach acid = less acidic than HCl = protective for HP

Phenotypes: High Virulence: +CagA, +OipA, +VacA cytotoxin (higher risk of ulcer/malignancy)

HP causes increased gastrin release after meals = increased acid secretion

HP affects D cells more than G cells = blocks inhibition allowing further gastrin/HCl release

duodenal ulcer formation: HP gastritis = high gastrin = high acid load in duodenum = gastric metaplasia = HP colonization in duodenum = duodenal ulcer

Question 4

HP Dx and Tx

Answer 4

Dx: Urea Breath Test (radiolabel urea and look for radiolabelled CO2 in exhale - HP increased urease activity)
Stool Antigen - test stool
Need active infection w/o PPI use to use urea breath test and stool antigen test!!!
Serology: does not differentiate past vs. current infection

Tx: eradication = prevention of ulcer recurrence, eradication rates are decreasing due to ABx resistance
PPI + 3-4 ABx for extended period of time (14 days) +/- Bismuth pills
Vaccine: poorly effective

HP negative ulcer rates increasing

Question 5

NSAID Ulcers

• effects of NSAIDs
• mechanism of superficial damage
• mechanism of deep damage
• best way to reduce ulcer risk?

Answer 5

cause: GASTRIC/DUODENAL ULCERS, small bowel erosions, strictures, R side Colonic ulcers

Superficial damage: acute, onset in minutes
Mechanism: topical injury (acute burn), acidic NSAIDs ionize in gastric acid (travel across mucosa + damage epithelium/vessels), mucosa damage permits H+ entry (H+ back diffusion) - causes VD + Capillary leakage
Healing: rapid, by restitution (new cells arise)
Stomach can adapt to prevent this

Deep damage: GASTRIC ULCER
chronic, onset over WEEKS
mechanism: block COX-1 = less PG synthesis = less bicarb production = less mucus production = more damage
healing: slow, by restoring bloodflow, mucus/bicarb production, complicated by bleeds/perforations
RF: Age >65yo, coumadin use, high dose NSAIDs use, CS use, comorbidities (heart disease, high complications), previous GI event/ulcer, HP infection

Reduce ulcer risk with selective COX2 inhibitor + PPI (or nonselective NSAID + PPI)

Question 6

Zollinger-Ellison Syndrome

• what is it
• gross
• assoc
• sx
• detection

Answer 6

Tumor in pancreas = hyperacidity = duodenal ulcers

gross: more gastric folds due to gastrin hypersecretion (high parietal cells/HCl secretion)
assoc: Multiple Endocrine Adenomatosis Type I - (Primary hyperparathyroidism - high Ca, pituitary tumors, enteropancreatic tumors (gastrinomas))
sx: multiple ulcers, enlarged gastric folds, diarrhea (causing weight loss; occurs bc high acid denatures pancreatic enzymes = cannot digest proteins/fats)
detection: ENDOSCOPIC ULTRASOUND - most sensitive gastrinoma imaging

Question 7

Dx of Gastrinoma/ZES

Answer 7

High serum gastrin w/o achlorhydria 2/2 atrophic gastritis (and r/o pernicious anemia) >1000pg/mL w/o PPI use

Secretin Stimulation test: HIGH response of gastrin secretion due to secretin stimulation
rationale: normal: secretin stim D and G cells - D cells block G cells (somatostatin) bc more D cells than G cells
ZES: tumor causes G cells to outnumber D cells (mass effect) - more G cell response with less inhibition

Absolute #ulcers in USA decreasing but #non-HP ulcers RISING!