Peptic Ulcer Dz

Front 1

Name the four functions of gastric acid.

Back 1

- facilitates digestion of protein
- facilitates the absorption of iron, B12, and calcium
- prevents enteric infection and bacterial overgrowth (BOG)
- facilitates the absorption of certain drugs such as thyroxin

Front 2

Grossly, the stomach can be divided into two functional areas: the oxyntic gland area or pyloric gland area. What are the anatomic areas that are in each?

Back 2

Oxyntic = parietal, so that is the cardia, fundus and body, or 80% of the stomach

Pyloric gland area = antrum , 20% of the stomach

Front 3

True or False:
In the oxyntic gland, gastrin cells and somatostatin cells are coupled to each other and inhibit release of acid and histamine.

Back 3

FALSE. In oxyntic glands, aka glands with parietal cells (so in the fundus, body, cardia), ENTEROCHROMAFFIN-LIKE CELLS and somatostatin cells are coupled to each other to inhibit release of acid and histamine!

In antral gland, the gastrin and somatostatin cells are coupled together to inhibit gastrin secretion.

Front 4

The enteric nervous system consists of two main complexes: the [ myenteric / submucosal ] plexus, which innervates the circular and longitudinal muscle layers and regulates motility, and the [ myenteric / submucosal ] plexus, which innervates the mucosa and regulates secretion.

Back 4

MYENTERIC PLEXUS = muscle layers

SUBMUCOSAL PLEXUS = mucosa and secretion

Front 5

Where are G cells located and what do they secrete?

Back 5

G cells are located in the antral gland mucosa and secrete gastrin. Gastrin is one of three main stimulators of acid secretion. Other two are histamine and ACh.

Gastrin is a hormone that goes thru circulation to reach the parietal cells located in the upper stomach. Gastrin binds to gastrin receptors which are called CCK2 receptors.

Front 6

The three main stimulators of acid secretion are gastrin, histamine and ACh. Describe how each works (hormone/ neurotransmitter / paracrine pathway) and what receptors they bind to.

Back 6

Gastrin - is a hromone, needs to go thru circulation to reach the parietal cells located in the upper stomach. Gastrin binds to gastrin receptors which are called CCK2 receptors.

Histamine - paracrine pathway. Secreted from ECL cells, which are near the parietal cells and teh histamine binds to H2 receptors on the parietal cell. There is then an increase in cAMP in the parietal cell which eventually leads to acid secretion.

ACh- neurotransmitter secreted by the postgang neuron of enteric system and deposited onto the parietal cell's M3 receptor.

Front 7

________ is an acid secretor inhibitor. Inhibits histamine release indirectly and parietal cell directly.

Back 7

Somatostatin

Front 8

True or False:
H.pylori inhibits antral somatostatin secretion and thus stimulates gastrin adn acid secretion in patients with duodenal ulcer infected with the bacteria.

Back 8

TRUE

Front 9

The final step in acid secretion involves activation of ______________. The pump, located on the canalicular membrane, reabsorbs _____ in exchange for _____. At the same time, membrane channels are activated that allow efflux of ___ and ____. The pump recycles most of the ____ exiting the parietal cell, the net result being the production of HCl.

Back 9

The final step in acid secretion involves activation of H+K+ - ATPase. The pump, located on the canalicular membrane, reabsorbs K+ in exchange for H+. At the same time, membrane channels are activated that allow efflux of K+ and Cl-. The pump recycles most of the K+ exiting the parietal cell, the net result being the production of HCl.

Front 10

Explain how acid secretion occurs with the H+ K+ - ATPase pump.

Back 10

The final step in acid secretion involves activation of H+K+ - ATPase. The pump, located on the canalicular membrane, reabsorbs K+ in exchange for H+. At the same time, membrane channels are activated that allow efflux of K+ and Cl-. The pump recycles most of the K+ exiting the parietal cell, the net result being the production of HCl.

Front 11

True or False:
PPIs work on the secretory cell (not resting parietal cell) so best to take it just prior to a meal.

Back 11

TRUE

Esp best with breakfast b/c new proton pumps are made while we sleep. If really severe, then best before breakfast and before dinner.

Front 12

Which of the following is FALSE regarding proton pump inhibitors?
A. The covalent inhibitors are prodrugs that circulate through the body after intestinal absorption.
B. They are lipophilic
C. They are weak bases
D. They become activated sulfenamide and form ionic bonds with cysteines present in the extracellular loops of a subunit
E. Acid secretion cannot resume until new enzyme is synthesized and inserted into the membrane
F. Rebound acid hypersecretion can occur after stopping long-term (8+ weeks) PPIs

Back 12

The one that is FALSE is:
D. They become activated sulfenamide and form COVALENT DISULFIDE bonds with cysteines present in the extracellular loops of a subunit

Note:
Being lipophilic and membrane permeable, they gain access to all cells. However, being weak bases, they get protonated and trapped in acid spaces iwtha pH less than 4.0, such as secretory canaliculi of actively secreting parietal cells.

Front 13

What is Zolllinger-Ellison Syndrome (ZES)?

Back 13

Gastroc acid hypersecretion due to an autonomous release of gastrin by an endocrine tumor, ex. a gastrinoma. (95% of gastrinomas are in the pancreas or duodenum)

Front 14

How is gastric acid secretion measured in humans?
1. The sum of four 15-min collections during the first hour
2. The sum of four 15 min periods after pentagastrin
3. Twice the sum of the two highest consecutive 15 min periods after pentagastrin

Back 14

1. BAO, basal acid output
2. MAO, maximal acid output
3. PAO, peak acid output

Front 15

Define peptic ulcer dz.

Back 15

A benign ulcerative lesion of the stomach (gastric ulcer) or duodenum (duodenal ulcer) that EXTENDS THRU THE MUSCULARIS MUCOSA.

Front 16

What condition is described?

Imbalance between aggressive (ex. acid, pepsin, H.pylori, NSAIDs) and defensive (ex. epithelial cell integrity, mucus, bicarbonate, mucosal blood flow) factors. These disorders can be completely healed and remission maintained with antisecretory therapy.

Back 16

Peptic ulcer dz!

Front 17

What is the treatment for peptic ulcer dz?

Back 17

Antisecretory drugs (H2, PPIs)
Eliminate inciting factor (H.pylori, NSAIDs)
Surgery (highly selective vagotomy)

Front 18

How can you detect the presence of Helicobacter pylori with regards to peptic ulcer dz?

Back 18

Histologic stains, rapid urease test (urease activity metabolizes urea to NH3 and CO2), urea breath test, serology, culture.

Front 19

Which of the following is FALSE about Helicobacter pylori?
A. is a spiral shaped gram negative bacterium with 4-6 unipolar flagella
B. rapid urease test can detect its presence
C. associated dzs include peptic ulcer dz
D. patients with low grade MALT lymphoma should NOT be tested for H.pylori

Back 19

D. patients with low grade MALT lymphoma should NOT be tested for H.pylori

YES THEY SHOULD, in addition to patients with proven peptic ulcer dz!

Front 20

What are four conditions/diseases associated with Helicobacter pylori?

Back 20

DU and GU (50-70%)
Chronic active superficial gastritis (100%)
MALT lymphoma (marginal zone B-cell lymphoma)
Gastric cancer

Front 21

True or False:
There is sufficient data to recommend anti-H.pylori therapy in patients with non-ulcer dyspepsia or patients with abdominal complaints but no documented ulcer.

Back 21

FALSE.

INSUFFICIENT DATA.

Front 22

Group the following into their appropriate suggested 14 day anti-H.pylori treatment regimens.

Amoxicillin BID
Bismuth QID
Clarithromycin 500 mg BID
Clarithromycin 500 mg BID
Lansoprazole BID
Metronidazole 250 mg QID
Metronidazole 500 mg BID
Omeprazole BID
Tetracycline QID

Back 22

1. Bismuth QID, Tetracycline QID, Metronidazole 250 mg QID
2. Metronidazole 500 mg BID, Omeprazole BID, Clarithromycin 500 mg BID
3. Amoxicillin BID, Clarithromycin 500 mg BID, Lansoprazole BID

Front 23

Which of the following is TRUE of helicobacter pylori?

A. Eradication is enhanced by regimen of antibitioics and cyclosporine.
B. Patient must be off PPI for one month to prevent false negative rapid urease test, HP histology, and breath test.
C. Serology may take up to 2 years to convert to negative after eradication

Back 23

C. Serology may take up to 2 years to convert to negative after eradication

The others would be true if...
A. Eradication is enhanced by regimen of antibitioics and PPI, not cyclosporine!
B. Patient must be off PPI for TWO WEEKS (not one month) to prevent false negative rapid urease test, HP histology, and breath test.

Front 24

GERD can occur after H.pylori is eradicated! This occurs in ____% of patients.

Back 24

33%!

Front 25

NSAIDs inhibit which enzyme?

Back 25

COX enzyme!

Front 26

How do you prevent an NSAID-induced ulcer?

Back 26

D/C NSAID (change it, decrease dose)
Take misoprostol
Take a PPI
Take a COX-2 selective NSAID like Celecoxib

Front 27

Who should receive prophylaxis (PPI) versus an NSAID-Induced Ulcer? (4)

Back 27

1. Age > 65
2. History of Peptic Ulcer Dz and/or Upper GI bleeding
3. Concomitant steroids/ anticoagulants
4. Major co-morbid conditions

Front 28

20% of patients with multiple endocrine neoplasia type 1 (MEN-1) have this condition.

A. H.pylori bacterial overgrowth
B. Peptic Ulcer Dizease
C. Zenker's Syndrome
D. Zollinger-Ellison Syndrome (ZES)

Back 28

D. Zollinger-Ellison Syndrome (ZES)

This is gastric acid hypersecretion due to an autonomous release of gastrin by an endocrine tumor, ie. a gastrinoma. Usually that gastrinoma is in the pancreas or duodenum.

Clinical features are: pain only (25%), diarrhea only (20%), pain and diarrhea (50%), dysphagia/heartburn (30%)

Front 29

What are the clinical features of Zollinger-Ellison Syndrome (ZES) and how is it diagnosed?

Back 29

Clinical features: pain only (25%), diarrhea only (20%), pain AND diarrhea (50%), dysphagia/heartburn (30%).

Diagnosed by:
Elevated fasting gastrin (>1k pg/mL) and gastric pH < 2.5
OR Elevated fasting gastrin (<1k pg.mL) and gastric pH <2.5 and positive secretin test (+/- gastric analysis)

Front 30

How does one manage Zollinger-ELlison Syndrome?

Back 30

Control acid hypersecrtion with PPIs, localize the tumor (if no liver mets, evaluate MEN-1 status), if no MEN, exploratory laparotomy