138b/139b - Pathology of Gastric Disorders, PUD, H. Pylori

Question 1

Do benign gastric ulcers occur in pernicious anemia?

Answer 1

No!

• Pernicious anemia is often caused by autoimmune destruction of parietal cells
  
  • ​=> decreased gastric acid
• Any ulcer that forms in the setting of pernicious anemia should be considered for malignancy

Question 2

Which stimulants of parietal cell gastric acid secretion act through the IP3/Ca2+ pathway?

Answer 2

• ACh
  
  • Released when we think about food (cephalic phase) or secondary to antral distention (gastric phase)
• Gastrin

Question 3

Which part of the stomach is affected by H. pylori gastritis?

Answer 3

Antrum

Question 4

Describe the pathophysiology of diarrhea in patinets with Zollinger-Ellison syndrome

Answer 4

ZE = gastrin-secreting tumor

• Increased HCl secretion
• HCL spills into duodenum
  
  • Denatures pancreatic enzymes
    
    • Maldigestion of fat and protein
    • Diarrhea
  • Directly damages the small intestinal epithelium
    
    • Secretory diarrhea

Question 5

What is the treatment for Zollinger-Ellison Syndrome?

Answer 5

High dose PPI

• Resect tumor if you can, but they can be hard to find!

Question 6

Describe the pathophysiology of chronic autoimmune gastritis

Answer 6

• Antibodies against parietal cells and intrinsic factor
  
  • -> Destruction of parietal cells
• -> Hypochlorhydria, high serum gastrin

Question 7

How does H. pylori cause an increase in gastric acid release?

Answer 7

H. Pylori preferentially destroys D cells

• D cells normally secrete somatostatin
  
  • Normally inhibits gastrin secretion from G cells
  • Results in decreased gastric acid release
• No D cells = no brakes on gastrin secretion
  
  • Lots of gatrin -> lots of gastric acid

Question 8

Describe the pathophysiology of H. pylori infection in the gastric epithelium

(Starting with ingestion of H. pylori)

Answer 8

• Ingestion of H. pylori
• H. pylori lodges into the mucus using adhesins
  
  • Protected from acid by urease (Urea -> CO2 + NH3)
  • NH3 is converted to NH4+ in the acidic stomach; NH4+ cloud protcts H. pylori
• H. pylori multiplies
• Immune response
  
  • Cytokine release
  • Damage to mucosa
  • H. pylori internalizes in the epithelium

Question 9

Describe the pathophysiology of a Curling ulcer

Answer 9

Severe burns/trauma -> hypovolemia -> ischemia

Question 10

What is the eradication rate for H. pylori after antibiotic treatment?

Answer 10

~75% and decreasing due to abx resistance

Question 11

What is the most common cause of benign peptic ulcer disease?

Answer 11

H. pylori

Question 12

What are the two subtypes of gastric adenocarcinoma?

How do you tell them apart?

Answer 12

• Intestinal
  
  • Ulcer with raised borders
  • Composed of glands
• Diffuse
  
  • Diffusely thickened gastric wall
  • Signet ring cells are present

Question 13

List two hypertrophic gastropaties

How do you tell them apart histologically?

Answer 13

• Menetrier disease (excess TGF-alpha)
  
  • Foveolar hyperplasia
• Zollinger-Ellison syndrome (gastrin-secreting tumor)
  
  • Parietal cell hyperplasia

Endoscopically, both will have enlarged folds

Question 14

H. pylori typically colonizes in gastric epithelium

How, then, does it caue duodenal ulcers?

Answer 14

• H. pylori colonization in the stomach results in increased post-prandial gastrin release, resulting in increased gastric acid
  
  • Due to destruction of D cells (no brakes on gastrin release)
• Gastric acid spills into the duodenum
• -> Gastric metaplasia
• -> H. pylori colonizes in the gastric metaplasia in the duodenum

Question 15

What is the effect of somatostatin on gastric acid secretion?

Answer 15

Somatostatin inhibits gastric acid secretion

• Inhibits gastrin secretion from G cells, histamine secretion from HCL cells

Question 16

Describe the pathophysiology of a Cushing ulcer

Answer 16

• Increased intracranial pressure
• -> Vagal stimulation
• -> Acid production
• -> Ulcer formation

Question 17

Which of the following mechanisms plays an important role in the development of a gastric ulcer in a 32 year old patient with rheumatoid arthritis taking ibuprofen 800 mg three times daily for one month?

1. Reduction in blood flow to the gastric mucosa
2. Ion trapping and low pKa of ibuprofen
3. Excessive production of acid induced by ibuprofen
4. Concomitant infection with H.pylori
5. Autoimmune damage to the gastric epithelium

Answer 17

a. Reduction in blood flow to the gastric mucosa

• Ibuprofen is a nonselective COX inhibitor
• -> Decreased prostaglandins production
• -> Decreased blood flow

Ishcemic damage = nidus for ulcer

Question 18

Which protein is elevated in Menetrier disease?

What endoscopic changes will occur?

Histologic changes?

Clinical signs?

Answer 18

TGF-alpha

• Prominent gastric folds
• Diffuse, foveolar hyperplasia
• Weight loss, diarrhea, peripheral edema, hypoproteinemia

Question 19

Are NSAIDs more likely to cause gastric ulcers or duodenal ulcers?

Answer 19

Gastric ulcers

• But, H. pylori is the most ocmmon cause of both gastric and duodenal ulcers

Question 20

What percent of patinets infected with H. pylori develop clinical disease?

Should patinets without clinical disease be treated?

Answer 20

1-10%

• Many people are affected asymptomatically!!
• Treat asymptomatic infections if the backround prevalence of H. pylori is >20%

Question 21

What are the possible sequelae of untreated H. pylori infection?

Answer 21

• Chronic active gastritis (antrum)
  
  • -> Duoenal ulcer
• Chronic active pangastritis
  
  • -> Gastric ulcer
• Chronic atrophic pangastritis
  
  • -> Cancer

​

Question 22

What causes Zollinger-Ellison syndrome?

Answer 22

Gastrinoma

• Tumor that secretes gastrin
• -> Parietal cells stimulation
  
  • -> HCL secretion
  • -> Parietal cell hyperplasia -> large folds

Question 23

What gastric pathology would you suspect if fasting gastrin levels are >1000 pg/mL?

What test can you use to confirm?

Answer 23

Zollinger-Ellison syndrome

Secretin test
(positive result = increase in gastrin after secretin administration)

Question 24

Which inhibitors of parietal cell gastric acid secretion act through the cAMP pathway?

Answer 24

• Somatostatin
• Prostaglandins

Question 25

What etiologies are implicated in H pylori-negative ulcers?

Answer 25

* Medications * Aspirin, NSAIDs * Zollinger-Ellison syndrome

Question 26

Which stimulant of parietal cell gastric acid secretion act through the cAMP pathway?

Answer 26

* Histamine

Question 27

What are the endoscopic findings of Zolinger-Ellison syndrome?

Answer 27

What medications are implicated in H pylori-negative ulcers? * ZE is caused by a gastrin-secreting tumor * -\> Stimulates parietal cells * -\> hyperplasia

Question 28

List the two most common causes of chronic gastritis

Answer 28

* **H. pylori gastritis** (most common) * **Autoimmune gastritis**

Question 29

Where is the prevalence of H pylori highest?

Answer 29

Places with worse sanitation (underdeveloped countries) Transmitted through fecal-oral route

Question 30

A patient with previously well documented duodenal ulcer and gastrointestinal bleeding was treated for H.pylori infection with 14 days of omeprazole 20 mg BID, amoxicilin 1 gm BID, clarithromycin 500 mg BID. He presents with recurrent epigastric pain 2 months after completion of therapy. What is the best next step?

Answer 30

Urea breath test or stool antigen assay for H. pylori * Need to figure out if H. pylori persists before treating symptoms * Urea breath test and stool antigen are sensitive for active H. pylori infection

Question 31

What genetic mutation is associated with gastric adenocarcinoma?

Answer 31

CDH1 mutation * Tumor suppressor gene * Encodes E-cadherin

Question 32

What gastric pathology is confirmed by a secretin stimulation test? What results would constitute a postiive test?

Answer 32

Zolinger Ellison Syndrome * **Positve result:** gastrin levels **increase** after secretin stimulation Explanation * Normally, secretin stimulates D cells \> G cells * D cells secrete somatostatin, inhibit gastrin release from G cells * **However, it does stimulate G cells a little bit** * In ZE, G cells greatly outnumber D cells. So even though D cells are more strongly stimulated, **there are so many G cells that the G cells response (-\> gastrin release) overwhelms the somatostatin secreted by D cells**

Question 33

How is an active H. pylori infection diagnosed?

Answer 33

Urea breath test OR stool antigen assay But: will only be accurate **\>4 weeks after stopping eradication therapy**

Question 34

What is the most common tumor of the stomach?

Answer 34

Gastric adenocarcinoma

Question 35

Which cancers are associated with H. pylori? (2)

Answer 35

MALT lymphoma Gastric adenocarcinoma (both intestinal and diffuse)

Question 36

Where in the body does H pylori colonize?

Answer 36

Gastric epithelium (stomach) * If gastric epithelium is elsewhere, H. pylori can colonize elsewhere * Barrett's esophagus * Duodenal ulcers * Meckel's diverticulum

Question 37

Describe the pathogenesis of an NSAID-induced ulcer

Answer 37

Usually a **chronic process, after weeks of NSAID use** * Inhibition of **COX1** (when using nonspecific COX inhibitor) for weeks * -\> Depletion of **prostaglandins** * PGEs are important for mucous, HCO3- production, **blood flow** * **-\> Decreased blood flow**, less HCO3- * **-\> Ischemia, necrosis** * **-\> Ulcer** (Single dose of ibuprofen -\> superfiical damage, but usually resolves)

Question 38

What cells types mediate the inflamation caused by H. pylori gastritis?

Answer 38

Neutrophils AND lymphocytes H. pylori gastritis is a **chornic, active gastritis**

Question 39

Describe the typical presentation of Zollinger-Ellison Syndrome (3)

Answer 39

* Intractable or multiple ulcers * Diarrhea * High acid content spilling into duodenum * Denatures pancreatic enzymes * Cannot digest food * Also secretory due to direct mucosal damage * Enlarged gastric folds

Question 40

Which medications are associated with the development of fundic gland polyps?

Answer 40

PPIs * Fundic glands contain **parietal cells, G cells, and D cells** * Inhibited HCL secretion -\> **gastrin** * **​-\>** **G cell hyperplasia** * **-\> Polyp formation**

Question 41

What virulence factor helps H. pylori survive in the acidic gastric environment?

Answer 41

Urease

Question 42

What histologic changes occur in chronic autoimmune gastritis?

Answer 42

* Lymphocyte infiltration * Loss of fundic glands * Extensive metaplasia * Will see **goblet cells** and **pancreatic acinar cells**

Question 43

What is the msot common cause of peptic ulcer disese?

Answer 43

H. pylori gastritis

Question 44

Which cancer is most likely to be cured by antibiotics?

Answer 44

MALT lymphoma * H. pylori plays a role in MALT lymphoma pathogenesis * Antibiotics that kill H. pylori cause regression of MALT lymphoma