H pylori question from NBME sample questions

[yoyohomieg5432]

Spoiler alert to those who haven't done the USMLE sample questions yet..

An otherwise healthy 45-year-old man comes to the physician because of a 3-week history of progressive epigastric heartburn and a 4.5-kg (10-lb) weight loss. The pain tends to be more severe at night and occurs 1 to 3 hours after meals during the day. He has had similar episodes with lesser intensity during the past year. Abdominal examination shows tenderness to deep palpation. Test of the stool for occult blood is positive. Endoscopy shows a bleeding 3-cm ulcer in the antrum of the stomach. A photomicrograph of Steiner silver-stained tissue (400x) from a biopsy of the gastric mucosa adjacent to the ulcer is shown.
Which of the following processes is most likely to be involved?
(A) Elaboration of proteases and urease with local tissue destruction
(B) Hyperacidity and gastric ulcer development
(C) Ingestion of preformed toxins in contaminated well water
(D) Spirochete invasion of gastric cells

Why is B not a valid answer? I thought that H pylori infections of the stomach antrum cause destruction of the somatostatin D cells, which leads to low somatostatin, increased gastrin and consequently high acid and ulceration. Am I wrong about that?

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[lymphocyte]

Spoiler alert to those who haven't done the USMLE sample questions yet..

An otherwise healthy 45-year-old man comes to the physician because of a 3-week history of progressive epigastric heartburn and a 4.5-kg (10-lb) weight loss. The pain tends to be more severe at night and occurs 1 to 3 hours after meals during the day. He has had similar episodes with lesser intensity during the past year. Abdominal examination shows tenderness to deep palpation. Test of the stool for occult blood is positive. Endoscopy shows a bleeding 3-cm ulcer in the antrum of the stomach. A photomicrograph of Steiner silver-stained tissue (400x) from a biopsy of the gastric mucosa adjacent to the ulcer is shown.
Which of the following processes is most likely to be involved?
(A) Elaboration of proteases and urease with local tissue destruction
(B) Hyperacidity and gastric ulcer development
(C) Ingestion of preformed toxins in contaminated well water
(D) Spirochete invasion of gastric cells

Why is B not a valid answer? I thought that H pylori infections of the stomach antrum cause destruction of the somatostatin D cells, which leads to low somatostatin, increased gastrin and consequently high acid and ulceration. Am I wrong about that?

Um... no. H. pylori produces proteases and urease, which allow it to decrease the pH of the its local environment by cleaving urea into ammonia, which is toxic to gastric mucosa. The answer is definitely A. Think about it this way: isn't gastrin released into the systemic circulation? If so, why would there be a well-localized lesion? Compare this to Zollinger–Ellison syndrome syndrome, where you have increased gastrin and lesions everywhere.

 

[Burnt Almonds]

Um... no. H. pylori produces proteases and urease, which allow it to decrease the pH of the its local environment by cleaving urea into ammonia, which is toxic to gastric mucosa. The answer is definitely A. Think about it this way: isn't gastrin released into the systemic circulation? If so, why would there be a well-localized lesion? Compare this to Zollinger–Ellison syndrome syndrome, where you have increased gastrin and lesions everywhere.

Where in your explanation does it preclude hyperacidity and gastric ulcer formation? And...doesn't cleaving urea into ammonia cause an increase in pH?

 

[lymphocyte]

Where in your explanation does it preclude hyperacidity and gastric ulcer formation? And...doesn't cleaving urea into ammonia cause an increase in pH?

Exactly. Gastric mucin, a protective PGM, stabilizes around a pH of 4, shielding the gastric mucosa. Raising the pH with ammonia destabilizes the mucin and allows H. pylori to colonize the gastric surface. But ammonia is also toxic to the epithelium. This is explained well in Papa Robbins (the big one) and here's an article that strongly supports (and explains) this hypothesis. It's a pretty neat mechanism.

Celli JP, Turner BS, Afdhal NH, et al. Helicobacter pylori moves through mucus by reducing mucin viscoelasticity. Proc Natl Acad Sci USA. 2009;106(34):14321-6.

http://www.pnas.org/content/106/34/14321

 

[wjs010]

OP's explanation was an exact explanation given in uworld. Seems like A and B could both be right?


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[Burnt Almonds]

Exactly. Gastric mucin, a protective PGM, stabilizes around a pH of 4, shielding the gastric mucosa. Raising the pH destabilizes the mucin and allows H. pylori to colonize the gastric surface. But ammonia is also toxic to the epithelium. This is explained well in Papa Robbins (the big one) and here's an article that strongly supports (and explains) this hypothesis. It's a pretty neat mechanism.

Celli JP, Turner BS, Afdhal NH, et al. Helicobacter pylori moves through mucus by reducing mucin viscoelasticity. Proc Natl Acad Sci USA. 2009;106(34):14321-6.

http://www.pnas.org/content/106/34/14321

Yes, so urease helps to raise pH leading to destabilization of the mucin. Great. What about that H. pylori reduces antral somatostatin and increases gastrin release to cause hyperacidity (a mechanism of GERD).

 

[lymphocyte]

Once you see silver stain and a single ulcer you automatically think of H. pylori. The main pathogenicity of H. pylori for causing ulceration is as explained above. Auto-click.

Sure maybe antral somatostatin plays a role, but if you look at PubMed, all of those articles are from the 1990s.

I don't know what to say about UWorld. It's simply outdated here. Papa Robbins is always the Bible.

Yet another way to think about it is that, if you were correct, adequate acid control with a PPI or antihistamine would be enough to prevent ulceration. Nope.

And we're not talking about GERD or gastritis, we're talking about PUD. A localized ulceration. You could honestly answer this question knowing that H. pylori is not a spirochete, doesn't dump performed toxin in well water, and the guy had a single ulcer.

 

[zhopv10]

Lymphocyte is correct the mechanism for the gastric ulcers is local damage of the mucosa and inflammation. The acid levels as mentioned here are actually lowered right near the bacteria due to urease. However with damaged mucosa and inflammation you can get irritation with the acid around and just mainly the big itself. Now the key point is that is for GASTRIC ulcers. Now most commonly you actually get duodenal ulcers with h pylori infections. These are indeed caused by the decreased somatostatin leading to increased gastric leading to increased acid. This acid goes on to the duodenum and cannot be fully neutralized by bicarb.


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[zhopv10]

I should also mentioned, as lymphocyte said, gastric levels on the larger scale are rarely increased. This is a local process as compared to zollinger. You still get the increase acid (increase to normal). But it is more patchy, enough to irritate the duodenal tissue over time though. Hope they helps.

*also I do not think this is a mechanism of GERD. PUD and GERD are totally different diseases. GERD largely derives from increased laxity of the LES. Allowing acid to irritate the mucosa. PUD is, as discussed, in the stomach/duodenum (or jejunum even potentially with Zollinger Ellison if you want to get all fancy haha)


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[wjs010]

Another classic description of ZES from uworld is that it is usually found in the DISTAL duodenum( unlike the usual ulcers on the proximal part), and instead of secretin lowering gastric levels, secretin actually stimulates gastric in ZES. And it is resistant to PPI


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[Burnt Almonds]

I should also mentioned, as lymphocyte said, gastric levels on the larger scale are rarely increased. This is a local process as compared to zollinger. You still get the increase acid (increase to normal). But it is more patchy, enough to irritate the duodenal tissue over time though. Hope they helps.

*also I do not think this is a mechanism of GERD. PUD and GERD are totally different diseases. GERD largely derives from increased laxity of the LES. Allowing acid to irritate the mucosa. PUD is, as discussed, in the stomach/duodenum (or jejunum even potentially with Zollinger Ellison if you want to get all fancy haha)


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Obviously LES tone is a huge part of it but then why would we treat GERD with PPIs? Last time I checked PPIs don't increase LES tone.

 

[zhopv10]

Obviously LES tone is a huge part of it but then why would we treat GERD with PPIs? Last time I checked PPIs don't increase LES tone.

Because we can't treat LES tone really so we at least reduce the acid content, thus reducing the irritation and chance of the irritation going on to bad complications (ulcer, stricture, barrets etc). So you don't necessarily have increased acid someone can have normal acid and you are lowering it. Hence why these can affect the absorption of a variety of drugs, increase the risk of aspiration pneumonia a little bit etc. Now plausibly if someone already had or develops GERD and they have an H pylori infection sure it could make things worse worse since it increases acid. But it is not like it is causing the GERD, it is simply affecting an already present pathology.


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[yoyohomieg5432]

so if i summarize what i gather from this thread: gastric ulcers are due to direct damage from H pylori onto the t issue from the bug itself.. then local acid can get in and cause t he ulcer?

whereas in duodenal ulcers, that is more somatostatin mediated?