Acid, Ulcers, and H. pylori Flashcards
What does low pH in the stomach induce?
Somatostatin release by D cells, which provides negative feedback to histamine and gastrin secretion.
Two different second messenger systems involved in acid secretion by parietal cells?
Gastrin -> PLC -> etc etc. -> Ca++ influx -> more K+/H+ ATPase activity.
Histamine -> cAMP -> more K+/H+ ATPase activity.
Which cells secrete mucus and bicarb in the stomach? What drives them to do this?
The surface epithelial cells (i.e. not the ones down in the pits).
Prostaglandins drive this (the ones made by COX-1).
Is it just the acid that can damage the gastric mucosa if protective mechanism fail?
Nope, it’s pepsin too -> autodigestion.
What are 3 main “aggressive factors” in ulcer formation?
Acid. (hypersecretion syndromes, esp ZES)
NSAIDS.
H. pylori.
What are the “other” aggressive factors in ulcer formation that may contribute to poor healing?
Steroids, smoking, EtOH, bile, etc.
Does pain with food vs. fasting really distinguish a gastric from a duodenal ulcer?
No.
It’s commonly said that gastric ulcers hurt while eating, duodenal ulcers hurt when fasting…
Changing trends in ulcer prevalence?
Uncomplicated ulcers going down (PPIs, Tx of H. pylori).
Bleeding ulcers account for a greater proportion of those seen.
What is Zollinger-Ellison Syndrome?
An islet cell tumor that secretes gastrin and isn’t inhibited by somatostatin -> very high acid levels in stomach -> ulcers.
Why does giving a stomatostatin analogue (e.g. octreotide) work for ZES?
Because you’re giving it systemically.
The somatostatin made by D cells acts in a paracrine fashion, and apparently doesn’t reach the islet cell tumors of ZES.
Diagnostic hallmark of ZES?
Inappropriate hypergastrinemia:
High acid, high gastrin.
When is appropriate for gastrin to be high?
Any time acid is low in the stomach, such as when the patient is on PPIs.
(you have to take patients off of PPIs to really diagnose ZES, which can be risky)
How can H. pylori cause both appropriate and inappropriate hypergastrinemia?
Appropriate: H. pylori can induce pangastritis that reduces acid production.
Inappropriate: inflammation can H. pylori in the antrum can cause G cell hyperplasia.
What genetic syndrome is associated with ZES?
MEN-1
(Recall the 3 P’s: Parathyroid, Pituitary, and Pancreas - ZES is from the pancreas part)
(encodes Menin)
When measuring basal acid output (BAO), is it the concentration that matters?
No. It’s total amount of acid (protons) made per hour.
In idiopathic peptic ulcer disease…
the acid is high (esp. while fasting), and we don’t know why
4 possible causes for hypersecretion in peptic ulcer disease?
Increased sensitivity of parietal cells to secretogogues.
Hypergastrinemia (basal and/or meal-based).
Insufficient inhibition (eg. by somatostatin).
Decreased bicarb secretion.
What does H. pylori notably make? What does it do the epithelium?
Urease -> makes a cloud of ammonia around it that neutralizes pH.
It adheres to the epithelium, induces inflammation that reduces its integrity (which may help it get nutrients).
How is H. pylori spread?
person-to-person by the fecal-oral route
What kind of immune response does H. pylori evoke?
Antibodies are detectable in the serum.
Inflammation in the mucosa (gastritis).
Does H. pylori invade the mucosa?
No.
How does H. pylori change acid secretion dynamics in patients?
Infected patients have more gastrin-mediated acid secretion during meals.
How does H. pylori cause hypergastrinemia?
By inhibiting somatostatin release.
How is H. pylori thought to cause duodenal ulcers?
Hypergastrinemia -> acid -> metaplasia of the duodenal bulb to be more gastric.
H. pylori can then colonize the duodenal bulb -> inducing local loss of integrity of mucosa.
Loss of integrity + high acid -> duodenal ulcer.
