Gastric Secretion, Peptic Ulcer Disease, and H. Pylori Flashcards
What do mucus cells secrete
mucus, pepsingoen II
parietal cell secretion
HCl, IF
Chief Cell secretion
Pepsinogen I
D Cell
Somatostatin
G cell secretion
Gastrin
Mast Cell secretion
Histamine
Enterochromaffin cell secretion
histamine
what cells are located in the crypts of the villi of the stromach?
Chief cells mainly, some ECL cells and some parietal cells.
role of somatostatin
negative regulates the parietal cells (that secrete HCl), prevents acid from being released. somatostatin irs realeased from the D cells.
fundus function
storage
the body of the stomach has ___ galnds, which contain
oxyntic glands, which contain parietal cells, mucus cells, ECL cells, and chief cells.
the antrum of the stomach has ___ glands, which contain
pyloric glands, which contain mucus cells, G cells (gastrin) and D cells (somatostatin)
Food, amino acids, and vagus nerve stimulation stimulates ___ cells to produce _____, which signals ECL cells to produce ____< which ___ acid production via proton pump
Food, amino acids, and vagus nerve stimulation stimulates G cells to produce gastrin, which signals ECL cells to produce histamine< which INCREASES acid production via proton pump
prostaglandins and somatostatin ____ acid production
decrease
PPIs act on what part of the mechanism of acid secretion
at the end stage. it inhibits the proton pump which usually pumps H+ into the lumen from HCl (of the parietla cells)
H2 blockers act on what part of the mechanism
they block histamine that was released from the ECL cells that were activated by acetylcholine (from vaus nerve), food, AA etc. H2 blockers prevent parietla cells from releasing HCl
3 phases of gastric acid secretion
cephalic phase
gastric phase
intestinal phase
outline the processes of the cephalic phase
effective stimuli including conditioned reflexes, smell, taste chewing swallowing, hypoglycemia.
the cephalic phase is mediated by the ___ nerve. outline
by the vagus nerve. Ach acts on the G cell via Gastrin releasing peptide to stimulate gastrin release. this acts on the parietal cells. Ach also can act directly on the parietla cell to induce acid secretion.
mechanisms that stimulate the gastric acid secretion during the gastric phase of digestion
- distention, stimulates the vagus nerve which releases Ach onto parietal cells and G cells to promote H+ release
- Amino acids– peptides can stimulate G cells to release gastrin which influence parietal cells to promote H+ release
when is gastrin release inhibited during gastric phase
if the pH is low enough. gastrin stops getting released to stop parietal release of HCl.
Outline the processes of the intestinal phase
protein digestion products in the duodenum stimulate acid secretion.
this is likely via intestinal G clels and gastrin release
IV administrationi can also induce acid secretion.
part of the intestinal phase may be due to absorbed AAs,
somatostatin released when pH is below three, this slows down acid production. When chyme gets released to intestines, parietal cells also get inhibited.
SEE SLIDE 12 of this lecture for a good pic!
Reasons to order Serum Gastrin in PUD
multiple ulcers ulcers in unusual locations, associated with severe esophagitis, resistant to therapy with frequent recurrences, awaiting surgery - extensive family history for pUF - post operative ulcer recurrence -basal hyperchloryhydria unexplained diarrhea or steatorrhea -hypercalcemia -family history of pancreatic islet, pituitary or parathryoid tumor -prominent gastric or duodenal folds.
DDx for hypergastrinemia (lots of gastrin)
Decreased acid production reasons: (there’s not enough acid so theres lots of G cells trying to stimulate more acid)
- H2 blocker or PPI
- H. Pylori
- Atrophic corporal gastritis
- Renal failure
- Vagotomy
Normal/Increased Acid Production (inappropriate hypergastrinemia)
- ZES
- Retained antrum syndrome
- antral G cell hyperplasia
- gastric outlet obstruction
DDx for hypergastrinemia (lots of gastrin)
Decreased acid production reasons: (there’s not enough acid so theres lots of G cells trying to stimulate more acid)
- H2 blocker or PPI *if you stop PPI then hypergastrinemia should resolve if it’s “normal” hypergastrinemia causes
- H. Pylori
- Atrophic corporal gastritis
- Renal failure
- Vagotomy
Normal/Increased Acid Production (inappropriate hypergastrinemia)
- ZES
- Retained antrum syndrome
- antral G cell hyperplasia
- gastric outlet obstruction
(for in depth reasoning see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4527266/)
secretory diarrhea and etiology
excessive secretion of electrolytes featuring watery diarrhea, persists with fasting. there is an absense of osmotic gap in fecal water
etiologies - carcinoid syndrome zollinger ellison VIP-secreting pancreatic adnomas -medullary carcinoma of thyroid -villous ademoa of rectum -microscopic colitis - cholerrheic diarrhea
what is secretin
a hormone produced by S cells in the duodenum
The major physiological actions of secretin are stimulation of pancreatic fluid and bicarbonate secretion. S cells in the small intestine emit secretin. Gastric acid stimulates secretin release, allowing movement into the duodenal lumen. Secretin causes an increase in pancreatic and biliary bicarbonate secretion and a decrease in gastric H+ secretion. Secretin stimulates the secretion of bicarbonate-rich pancreatic fluid.[11] Secretin enters the intestinal lumen and stimulates bicarbonate secretion, ultimately neutralizing gastric H+, which plays an essential role in fat digestion by creating a more neutral (pH 6 to 8) environment. H+ and fatty acids in the duodenum regulate secretin release.
Secretin Stimulation test should be done when
- gastrin is <1000pg/mL
- if its actually gastric acid hypersecretion
- pts are given excess secretin. Usually, secretin should inhibit gastrin and prevent H+ from being further released.
The absence of physiologic suppression by secretin implies neoplastic autonomy of gastrin releasing sites. While an augmented gastrin response to secretin is commonly seen in patients with gastrinoma, from a physiologic standpoint, a lack of suppression constitutes a positive secretin suppression test.
When should you diagnose gastrinoma following the secretin stimulation test?
1) if gastrin is over 1000 pg/ML and theres lots of HCl with a pH <2
2) or if gastrin rises >200pg/mL following secretin indusion in setting of increased HCl. Gastrin usually should be decreased if secretin is infused
which vitamin are pts with ZES deficient in? What symptoms are associated with ZES
high levels of HCl and high levels of gastrin. steatorrhea resulting in ugly poops. heart burn, abdominal pain and weight loss are all associated. 1% of PUD
they are defiicnet in B12. there is also an inactivation of pancreativ enzymes
ZES causes ulcer disease, increased HCl, and non beta islet cell tumors of the pancreas, plus gastrinoma tumors. most tumors are located in the pancreas and duodenum. What are the best methods of localizing gastrinomas and metastases
CT MRI SRS Indium somatoreceptor scintigraphy **THE BEST ONE SRS with CT Gallium-enhanced PET combined Gallium PET and CT Endoscopic ultrasound
Treatment of ZES
- Acid suppression via PPI
- Surgery on gastrinoma
- Octreotide (somatostatin analogue)– reduces acid secretion too
- chemotherapy (not really the standard of care though)
Too much acid causes: (4 main)
- PUD
- esophagitis
- maldigestion/malabsorption
- enteropathy (other GI diseases)
List of PUD symptoms
abdominal pain
- worsens with food (gastric ulcers)
- improves with food (duodenal ulcers)
- worse in the middle of the night
- relieved by taking antacid meds
bloating nausea -- hematemesis or coffee ground emesis weight loss melena fatigue or no symptoms at all
aggressive factors for ulcers(what makes ulcers worse/causes them in the first place)
acid, pepsin nsaids alcohol bile h.pylori
vast majority of ulcers due to nsaids or H pylori
protective factors against tumors
gastric blood flow (removes H+, provides energy to mucosa for better repair)
- proper epithelial cell barrier function
- epithelial cell extrusion of acid/buffering bicarbonate
- mucus
IN DETAIL:
- unstired layer of mucus and bicarbonate
- surface epithelial cells with fast turnover
- cell renewal
- alkaline tide - acid shifts away to dif areas of the stomach to prevent erosion in one spot
- microcirculation– maintained by continuous generation of prostaglandins that prevent plately and leukocyte aggregation
- sensory nerves
- prostaglandins (PGE2 and PGIs) maintain and enhance all mucosal defensive mechanisms working synergistically with nitric oxide
Is H. Pylor gram neg or positive
gram negative curved rod with flagella/ difficult to cultures.
typical time of acquisition of H pylori
usually in childhood, especially in developing countries with poor sanitation or overcrowding or contaminated drinking water.
explain the statistical relationship with Hpylori and PUD
- in HP + pts it is 10-20%, whereas life time prevalence of PUD in general is 5-10%
- ulcer recurrence following healing is 90% if H pylori is not truly eradicated.
- H.pylori increases risk of NSAID for pain relied related to PUD too
H.Pylori associated diseases
acute/chronic gastritis, gastric atrophy, gastric cancer, duodenal ulcer, gastric ulcer, MALT lymphoma
non endoscopic tests for H pylori
serological tests
urea breath test
fecal antigen test
pros and cons for serological test
widelt available, least expensive compared to other tests.
cons: positive result may reflect previous rather than current infection
pros and cons of urea breath test for h pylori
high negative and positive predictive values,
cons: false negative results possible in the presense of PPIs or with recent use of antibiotics
pros and cons of fecal antigen test for h pylori
useful before and after treatment, its also reliable
cons: may be distasteful to the patient. and fase negative results
endoscopic tests for H pylori
usease-bsaed tests– but also influenced by PPIs or recent antibiotic (false negative)
histological assessment– sensitive but requires trained personell
cultures.– takes a long time
what type of enzyme does Hpylori make?
urease. for a CLOtest(urea breath test), you give labelled urea, and if theres lots of urease (lots of Hpylori), it breaks down to NH4 and labelled CO2.
who to test for Hpylori
- PUD
- previous PUD
- lowgrade gastric MALT lymphoma
- history of endoscopic resection of early gastric cancer
- initiating chronic treatment with an NSAID
- unexplained iron deficiency anemia despite appropriate evaluation
- pateints with ITP
- patients with uninvestigated dyspepsia under than 60 years without alarm features
- patients taking long term low dose ASA= chronic NSAID use might indicate a chronic problem
First line H Pylori Treatment
- PAMC: CLarithromycin, Amoxilicilin, Metronidazole
- PBMT: PPI, Bismuth subsalicylate, Metronidazole, Tetracycline
second line of H pylory treatment
PBMT
- PAL: PPI, amoxicillin, levoflocaxin
- PAR: PPI, amoxicilin, rifabutin
Overall treatment protocol of HPylori when combining first and second line treatment
PAMC, PAL, PBMT, PAR
or
PBMT, PAL, PBMT (optimized), PAR
drug therapies for acid suppression
PPIs H2RA Misoprostol Bismuth Antacids Sucralate* old Anticholinergics*
different antacids
Mg hydroxides
Ca2+ hydroxides – can cause diarrhea
Aluminum– can cause constipation
are biopsies necessary all the time to diagnose H pylori
not all the time because you can do serum Hpyl or fecal antigen or urease breath test
BUT if they’re on PPI, then it would create false negatives on urease or fecal antigen tests. Therefore, endoscopy is required if on previous PPIs because the HPyl cells might not be sensitive
usually if you have an endoscopy they should just take the biopsy anyway.
