Clinical Correlation in Basic Science - SJSM

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3.  Case 3
 A 43 year old man presents to the physician’s clinic with complaints
of epigastric pain. After a thorough workup, the patient is diagnosed
with peptic ulcer disease. He is started on medication that that
inhibits the “proton pump” of the stomach
 What is the “Proton pump” that is referred to above?
 What type of cell membrane transport would this medication be
blocking?
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4.  According to the Center for Disease and Control, CDC,
 Peptic ulcer disease (PUD) affects more than 6 million people in the
United States each year. This is not only of clinical concern but
public health concern that accounts for a major source of large
economic cost to the healthcare system.

 PUD and its complications risks are significantly increased if one is
Infection with Helicobacter pylori.

 Its is good news to know that there are appropriate antimicrobial
drug regimens to eradicate the infection and cure ulcers as such
early detection and treatment is crucial.
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5. Peptic ulcer disease (PUD), also known as a peptic ulcer or stomach ulcer,
is a break in the lining of the stomach, first part of the small intestine, or
occasionally the lower esophagus. An ulcer in the stomach is known as a
gastric ulcer while that in the first part of the intestines is known as a
duodenal ulcer.
The most common symptoms are waking at night with upper abdominal
pain or upper abdominal pain that improves with eating. The pain is often
described as a burning or dull ache. Other symptoms include belching,
vomiting, weight loss, or poor appetite. About a third of older people have
no symptoms. Complications may include bleeding, perforation, and
blockage of the stomach. Bleeding occurs in as many as 15% of people.
Common causes include the bacteria, Helicobacter pylori and non-steroidal
anti-inflammatory drugs (NSAIDs). Other less common causes include
tobacco smoking, stress due to serious illness, Behcet disease, Zollinger-
Ellison syndrome, Crohn disease and liver cirrhosis, among others 5

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10.  Pain felt anywhere from your navel up to your breastbone
 Pain worse when your stomach is empty
 Flare at night
 Temporarily relieved by eating
 Disappear and then return for a few days or weeks
 Less often, ulcers may cause severe signs or symptoms such as:
 The vomiting of blood — which may appear red or black
 Dark blood in stools or stools that are black or tarry
 Nausea or vomiting
 Unexplained weight loss
 Appetite changes 10

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12. Tests for Helicobacter Pylori
1. History and physical examination
2. Urea breath test (Carbon 13): When the breath test is carried out you
would be asked to eat or drink something containing radioactive H.
Pylori, this substance would break down in your stomach. You would
then be asked to exhale in to a bag which is sealed. If found infected
with H. Pyolri your breath sample will contain radioactive carbon which
will be in the form of carbon dioxide.
3. Blood
4. Stool monoclonal antigen tests:
1. Enzyme immunoassay
2. Immunochromatography
3. Antibody tests

13. • Endoscopy: To examine your upper digestive
system.
• Endoscopy is when your doctor passes a
narrow hollow tube down your throat and into
your oesophagus, stomach and small
intestine, which is equipped with a lens called
an endoscope. This will enable your doctor to
look for ulcers.
• If an ulcer is detected a biopsy (small tissue
samples) may be extracted to examine in a
lab, this can also be used to identify if H.
Pylori is present in your stomach lining.
• Endoscopy is more likely to be recommended
in patients who have signs of bleeding, older
55+ or have had some sort weight loss or
problems with eating and swallowing.
• X-ray : To examine upper digestive
system.
• Sometimes called a barium swallow or
upper gastrointestinal series.
• The series of X-rays will create images
of the esophagus, stomach and small
intestine.
• During the X-ray, the patient is asked
to swallow a white liquid which
contains barium which will coat the
digestive tract and make an ulcer
more visible.

14.  Peptic ulcers result from an imbalance between factors
 Aggressive factors such as gastric juice, including hydrochloric acid,
pepsin, and bile salts refluxed from the duodenum, H pylori, and NSAIDs
 The mucosal defenses comprise a mucus bicarbonate layer secreted by
surface mucus cells forming a viscous gel over the gastric mucosa
 The integrity of tight junctions
 Break in the epithelial lining is rapidly filled by adjacent epithelial and
mucosal stromal cells migrating and flattening to fill the gap
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15. • “Two Australian physicians won the 2005 Nobel Prize in
Medicine or Physiology for showing - at least partly by
accident -- that many ulcers are the result of a bacterial
infection.”
“Robin Warren
and Barry
Marshall's work
on ulcers was
pioneering”Story from BBC NEWS:
http://news.bbc.co.uk/go/pr/fr/-
/2/hi/asia-pacific/4307826.stm
Published: 2005/10/04 10:39:09 GMT
© BBC MMVII

16. • Curvelinear, gram (-) rod
with flagella
• H pylori is most common
cause of PUD
• Transmission route fecal-
oral
• Secretes urease →convert
urea to ammonia
• Produces alkaline
environment enabling
survival in stomach

17. • Higher prevalence in Low SES
• In US more common in Hispanics/Blacks
• Estimated 60% of Americans older than 60 H pylori (+)
• Almost all duodenal and 2/3 gastric ulcer pt’s infected with
HP
• Asymptomatic in approx 70% of those who are H pylori (+)
• Considered class 1 carcinogen → gastric cancer

18. Ulcers associated with
H. pylori
• more often in
duodenum
• often superficial
• less severe GI
bleeding
Ulcers associated with
NSAIDs
• more often in
stomach
• often deep
• more severe GI
bleeding
• sometimes
asymptomatic

19.  No matter what the source of gastric acid secretion stimulation
(histamine, gastrin or acetylcholine) the only way acid gets from parietal
cell to the lumen of the stomach is by the action of the enzyme H+, K+-
ATPase also known as the proton pump.
 This pump is located in the canaliculus (the acid-secreting network of
the parietal cell) and is stimulated to secrete acid by the cyclic
adenosine monophosphate, produced through action of histamine on
the Gs coupled H2 receptor. Ca+2 can also stimulate acid secretion and
intracellular concentrations of this ion are increased when gastrin and
ACh act on their receptors.
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22.  Histamine, Gastrin and Ach have to attach to the parietal cell to make
HCL. The parietal’s cell function is to produce HCL. Before HCL is
produced it must be activated by histamine from neighboring ECL cell. If
an H2 antagonist were to be used, histamine would be unable to
stimulate the proton pump to release HCL…….BUT….
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23.  Gastric and ACh would still be actively working. In order to stop the
secretion of all gastric acid, regardless of the original chemical stimulus,
you must INHIBIT the pump itself because it is the very LAST step in the
acid secretion process.
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24. ▪ Treatment depends on the cause of the ulcer.
▪ Bleeding Peptic Ulcer
Endoscopic therapy determines the healing of the gastric ulcer and rules out gastric
cancer. Endoscopy provides an opportunity to visualize the ulcer, to determine the degree
of active bleeding. Urgent esophagogastroduodenoscopy (EGD) is the treatment of choice in
the setting of a bleeding peptic ulcer for diagnostic.
▪ Antibiotic medications to kill H. pylori
If H. pylori is detected in the GI tract it is recommended proton pump inhibitor (PPI)–based
triple therapy including antibodies and histamine-2 receptor antagonists (H2RAs). PPI triple
therapy is a 14 day regimen.
● Medical Management of NSAID Ulcers
○ The lowest possible dose and duration of the NSAID and co-therapy with a PPI are recommended.
Misoprostol may be prescribed for those who take certain arthritis or pain medicines, it protects the
stomach lining and decreases stomach acid secretion.
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25. ▪ Proton pump inhibitors reduce stomach acid by blocking the action of the parts of cells
that produce acid. By suppressing acid production and maintaining a pH above 6,
pepsin becomes less active. PPIs are lipophilic weak bases that cross the parietal cell membrane
and enter the acidic parietal cell.
Examples of proton pump inhibitors:
● omeprazole (Prilosec)
● pantoprazole Protonix)
● lansoprazole (Prevacid)
▪ Acid blockers , also called histamine (H-2) blockers reduce the amount of stomach acid
released into your digestive tract, which relieves ulcer pain and encourages healing.
Examples of H2RA:
● ranitidine (Zantac)
● cimetidine (Tagamet)
● famotidine ( Pepcid)
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26. Case 3
A 43 year old man presents to the physician’s clinic with complaints of
epigastric pain. After a thorough workup, the patient is diagnosed with peptic
ulcer disease. He is started on medication that that inhibits the “proton pump”
of the stomach
What is the “Proton pump” that is referred to above?
What type of cell membrane transport would this medication be blocking?
Most people diagnosed with a peptic ulcer can be treated successfully. Early
diagnose and accurate assessment must not be underestimated. Aggressive
interventions to eradicate the specific causative agent are of high clinical
significance.
Note: I can add specifics to my conclusion once the power point is complete.
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 http://www.emedicine.com/med/topic1776.htm
 http://www.mcg.edu/som/pathology/GraduateEducation/Evidence%20Base%20Path/hpsa1.ppt
 http://www.acg.gi.org/physicians/guidelines/ManagementofHpylori.pdf
 http://www.cdc.gov/ncidod/dbmd/diseaseinfo/hpylori_t.htm
 http://courses.ahc.umn.edu/pharmacy/5880/LectureSlides/Peptic%20Ulcer%20Disease%20(PU
D)_files/frame.htm
 http://www.cdc.gov/ulcer/history.htm
 http://www.drugdigest.org/DD/Comparison/NewComparison/0,10621,550540-21,00.htm
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817
 Vaira D, Gatta L, Ricci C, et al. Peptic ulcer and Helicobacter pylori: update on testing and
treatment. Postgrad Med 2005;117(6):17-22, 46

28.  13. Fantry, G. T. (2005, May 6). Peptic Ulcer Disease. Retrieved September 4th,
2006, from www.emedicine.com/med/topic1776.htm
 General Practice Notebook (2006). Peptic Ulcer. Retrieved September 10th, 2006,
from www.gpnotebook.co.uk/simplepage.cfm?ID=630849536
 Microbe Wiki (2006, August 16). Heliobacter. Retrieved September 10th, 2006,
from www.microbewiki.kenyon.edu/index.php/Helicobacter
 Moore, R. A. (1995). Helicobacter pylori and peptic ulcer: A systematic review of
effectiveness and an overview of the economic benefits of implementing what is
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 Pounder, R. (1994). Peptic ulceration. Medicine International, 22:6, 225-30.
 Rodney, W.M. (2005, Summer). H. Pylori eradication options for peptic ulcer.
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ed.). Gainesville, FL: Barmarrae Books, Inc. 29