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Melissa BrownMaurissa HarrisScarlett SassoThomas L. BurphyMary PenningtonTaslima Jaby LaVon Edwards

Peptic UlcerBlock 2 - C.C.B.S.

Dr. Dusic

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Introduction Etiology Signs and Symptoms Differential Diagnosis Diagnosis Pathophysiology Proton Pump Treatment/Medication conclusion

OUTLINE

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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?

Introduction

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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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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

Etiology

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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

Signs and Symptoms

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Differential Diagnoses Acute Cholangitis Acute Coronary Syndrome Acute / Chronic Gastritis Cholecystitis Cholecystitis and Biliary Colic in Emergency Medicine Diverticulitis Pancreatitis Gastric Cancer Esophagitis Gallstones (Cholelithiasis) Gastroesophageal Reflux Disease Inflammatory Bowel Disease Viral Hepatitis

Diagnosis PH or HP? 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. Blood4. Stool monoclonal antigen tests:

1. Enzyme immunoassay2. Immunochromatography3. Antibody tests

 

Types Of Examinations

• 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.

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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

Pathophysiology

Discovery of Helicobacter pylori• “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.stmPublished: 2005/10/04 10:39:09 GMT© BBC MMVII

H. pylori

• 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

H. pylori

• 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

Differentiating between H. pylori and NSAID

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

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Proton Pump

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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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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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.

▪ 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. pyloriIf 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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Treatment

▪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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 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. Thanks.

Conclusion

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%20(PUD)_files/frame.htm http://www.cdc.gov/ulcer/history.htm http://www.drugdigest.org/DD/Comparison/NewComparison/0,10621,550540-21,00.htm Fendrick M, Forsch R etal. Peptic Ulcer Disease Guidleines for Clinical Care. University of

Michigan Health System May 2005 American Gastroenterological Association medical position statement: evaluation of

dyspepsia. Gastroenterology 1998;114:579-81. Krogfelt K, Lehours P, Mégraud F. Diagnosis of Helicobacter pylori Infection. Helicobacter

2005 10:s1 5 Meurer L, Bower D. Management of Helicobacter pylori Infection. American Family Physician

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The role of endoscopy in dyspepsia. Gastrointestinal Endoscopy Vol 54, No. 6, 2001 pp 815-817

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

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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 known to be effective. Oxford: Cortecs Limited and Health Technology Evaluation Association.

Pounder, R. (1994). Peptic ulceration. Medicine International, 22:6, 225-30. Rodney, W.M. (2005, Summer). H. Pylori eradication options for peptic ulcer.

Nurse Practitioners Prescribing Reference,12(2), 150. Uphold, C. R. & Graham, M. V. (2003). Clinical Guidelines in Family Practice (4th

ed.). Gainesville, FL: Barmarrae Books, Inc.

References