Practice Essentials

Signs and symptoms

Acute gastrointestinal bleeding is a potentially life-threatening abdominal emergency that remains a common cause of hospitalization. Signs and symptoms of acute upper GI bleeding[1] include the following:

Hematemesis Melena Hematochezia Syncope Presyncope Dyspepsia Epigastric pain Heartburn Diffuse abdominal pain Dysphagia Weight loss Jaundice See Clinical Presentation for more detail.

Diagnosis
Workup includes the following:

Orthostatic blood pressure Complete blood count with differential Hemoglobin level Type and crossmatch blood Basic metabolic profile, blood urea nitrogen, and coagulation profile Calcium level Gastrin level Endoscopy Chest radiography Nasogastric lavage Angiography (if bleeding persists and endoscopy fails to identify a bleeding site) Computed tomography scanning and ultrasonography may be indicated for the evaluation of the following[2] : Liver disease with cirrhosis Cholecystitis with hemorrhage Pancreatitis with pseudocyst and hemorrhage Aortoenteric fistula See Workup for more detail.

Management
Treatment includes the following:

Secure the airway Insert bilateral, 16-gauge (minimum), upper extremity, peripheral intravenous lines

Replace each milliliter of blood loss with 3 mL of crystalloid fluid In patients with severe coexisting medical illnesses, pulmonary artery catheter insertion for monitoring hemodynamic cardiac performance Foley catheter placement for continuous evaluation of urinary output as a guide to renal perfusion Endoscopic hemostatic therapy for bleeding ulcers and varices Surgical repair of perforated viscus For high-risk peptic ulcer patients, high-dose intravenous proton pump inhibitors Indications for surgery in patients with bleeding peptic ulcers include the following: Severe, life-threatening hemorrhage not responsive to resuscitative efforts Failure of medical therapy and endoscopic hemostasis with persistent recurrent bleeding A coexisting reason for surgery (eg, perforation, obstruction, malignancy) Prolonged bleeding, with loss of 50% or more of the patient's blood volume A second hospitalization for peptic ulcer hemorrhage In a randomized study of severe acute upper GI bleeding, the probability of survival at 6 weeks was higher in patients who did not receive transfusions unless their hemoglobin level fell below 7 g/dL, compared with those transfused when the hemoglobin level fell below 9 g/dL (95% vs. 91%), especially in patients with cirrhosis and Child-Pugh class A or B disease. The restrictive transfusion policy was also associated with fewer transfusions (49% vs 86%), further bleeding episodes (10% vs 16%), and adverse events (40% vs 48%). [3, 4] See Treatment and Medication for more detail.

Image library

Ulcer with active bleeding.

Background
Acute gastrointestinal (GI) bleeding is a potentially life-threatening abdominal emergency that remains a common cause of hospitalization. Upper gastrointestinal bleeding (UGIB) is defined as bleeding derived from a source proximal to the ligament of Treitz. The incidence of UGIB is approximately 100 cases per 100,000 population per year.[5] Bleeding from the upper GI tract is approximately 4 times as common as bleeding from the lower GI tract and is a major cause of morbidity and mortality. Mortality rates from UGIB are 6-10% overall.[5] (See Epidemiology, below.) The diagnosis of and therapy for nonvariceal upper gastrointestinal bleeding (UGIB) has evolved since the late 20th century from passive diagnostic esophagogastroduodenoscopy with

medical therapy until surgical intervention was needed to active intervention with endoscopic techniques followed by angiographic and surgical approaches if endoscopic therapy fails.[6] (See Workup and Treatment and Management, below.) Variceal hemorrhage is not discussed in this article because the underlying mechanisms of bleeding are different and require different therapies. The underlying mechanisms of nonvariceal bleeding involve either arterial hemorrhage, such as in ulcer disease and mucosal deep tears, or low-pressure venous hemorrhage, as in telangiectasias and angioectasias. In variceal hemorrhage, the underlying pathophysiology is due to elevated portal pressure transmitted to esophageal and gastric varices and resulting in portal gastropathy. A bleeding ulcer is seen below. (See Etiology, below.) Go to Pediatric Gastrointestinal Bleeding for complete information on this topic.

Ulcer with active bleeding.

In patients with UGIB, comorbid illness, rather than actual bleeding, is the major cause of death. Comorbid illness has been noted in 50.9% of patients, with similar occurrences in males (48.7%) and females (55.4%). One or more comorbid illnesses have been noted in 98.3% of mortalities in UGIB; in 72.3% of patients, comorbid illnesses have been noted as the primary cause of death.[7, 8] (See Epidemiology and Prognosis, below.) Significant comorbidities have become more prevalent as the patient population with UGIB has become progressively older. In a retrospective chart review by Yavorski et al, 73.2% of deaths occurred in patients older than 60 years.[8] (See Epidemiology and Prognosis, below.) Rebleeding or continued bleeding is associated with increased mortality; therefore, differentiating the patient with a low probability of rebleeding and little comorbidity from the patient at high risk for rebleeding with serious comorbidities is imperative. (See Clinical Presentation and Workup, below.)

Peptic ulcer disease and UGIB

Peptic ulcer disease (PUD) remains the most common cause of UGIB. In a literature review involving more than 10,000 patients with UGIB, PUD was responsible for 27-40% of all bleeding episodes.[9] High-risk patient populations at risk for PUD include those with a history of alcohol abuse, chronic renal failure, and/or nonsteroidal anti-inflammatory drug (NSAID) use.[10] Peptic ulcer disease is strongly associated with Helicobacter pylori infection. The organism causes disruption of the mucous barrier and has a direct inflammatory effect on gastric and

duodenal mucosa, reducing mucosal defenses and increasing back diffusion of acid by loosening tight cellular junctions. (Rates of H pyloriinfection are reportedly lower in patients with complicated ulcer disease than in patients with uncomplicated ulcers. Hosking et al reported a 71% incidence of H pylori infection in patients with bleeding duodenal ulcers; patients with nonbleeding ulcers had an incidence of 93%.) This discrepancy may be due to the decrease in sensitivity of biopsy in patients with ulcer bleeding.[11] Eradication of H pylori been demonstrated to reduce the risk of recurrent ulcers and, thus, recurrent ulcer hemorrhage after the initial episode. In fact, the proportion of UGIB cases caused by peptic ulcer disease has declined,[12] a phenomenon that is believed to be due to the use of proton pump inhibitors (PPIs) and H pylori therapy. Duodenal ulcers are more common than gastric ulcers, but the incidence of bleeding is identical for both. In most cases, the bleeding is caused by the erosion of an artery in the base of the ulcer. In approximately 80% of patients, bleeding from a peptic ulcer stops spontaneously.[9] Initial endoscopic attempts to maintain hemostasis have a high failure rate. Bleeding vessels larger than 1.5 mm in diameter are associated with an increased mortality rate due to the difficulty of producing adequate hemostasis with thermal probes. A minority of patients experience recurrent bleeding after endoscopic therapy, and these cases are usually associated with risk factors for rebleeding. These factors include age older than 60 years, the presence of shock upon admission, coagulopathy, active pulsatile bleeding, and the presence of cardiovascular disease. (The appearance of the ulcer at the time of endoscopy provides important information regarding the risk of rebleeding.) These circumstances are associated with a poorer prognosis and a higher mortality rate.[13] Despite the dangers associated with a bleeding peptic ulcer, a study by Sung et al of 10,428 cases of such bleeding (in 9,375 patients) found that most patient deaths were not caused by it.[14] Of the 577 deaths that occurred in the cohort, almost 80% resulted from other causes, including multiorgan failure, pulmonary conditions, and terminal malignancy. The authors concluded that the management of patients with peptic ulcers should focus not only on hemostasis but also on lowering the risk of multiorgan failure and cardiopulmonary death.

Recurrent bleeding risk in peptic ulcers

Forrest et al were the first to classify the stigmata of hemorrhage from peptic ulcers. Based on these classifications, the risk of recurrent bleeding can be predicted. The ulcers at highest risk for rebleeding are those that involve active arterial bleeding or those with a visible, protuberant, nonbleeding vessel in the base of the ulcer. The study not only correlated the incidence of rebleeding with the stigmata of recent bleeding and the endoscopic appearance of an ulcer, but also determined prognostic information regarding the need for surgery. Mortality was also correlated.[15] In patients with H pylori infection, the rate of recurrent bleeding is extremely low. This is why documenting the presence of H pylori and aggressively treating the infection are important. Patients who are not infected with H pylori may require a subsequent acid-lowering surgical procedure or long-term medical therapy for recurrent ulcer disease and bleeding.

Other causes of UGIB

Other major causes of UGIB are mucosal tears of the esophagus or fundus (Mallory-Weiss tear), erosive gastritis, erosive esophagitis, Dieulafoy lesion, gastric cancer, and ulcerated gastric leiomyoma. Patients with chronic liver disease and portal hypertension are at increased risk for variceal hemorrhage and portal gastropathy in addition to ulcer hemorrhage. Rare causes of UGIB include aortoenteric fistula, gastric antral vascular ectasia, angiectasias, and Osler-Weber-Rendu syndrome. An aortoenteric fistula results from the erosion of the aortic graft into the bowel lumen, usually the third or fourth portion of the duodenum. The result is a direct communication between the aortic graft lumen and the bowel lumen. Most aortoenteric fistulas involve the proximal aortic anastomotic suture line. UGIB can also result from acute stress gastritis, a disease process characterized by diffuse superficial mucosal erosions that appear as discrete areas of erythema.[15] The bleeding is usually mild and self-limiting and rarely progresses to life-threatening hemorrhage. In intensive care unit (ICU) patients, the incidence of clinically significant GI bleeding (eg, hypotension, transfusion) from acute stress gastritis was found to be 1.5%.[16] Stress gastritis and mucosal ulceration are historically associated with (1) head injuries with associated elevations in intracranial pressure and (2) burn injuries. These stress ulcers are called Cushing ulcers and Curling ulcers, respectively. Angiodysplasia of the upper GI tract accounts for 2-4% of bleeding lesions.[9] The condition is also a cause of lower GI bleeding in 6% of cases.[15] The lesion is a vascular malformation that represents an abnormal dilation of mucosal and submucosal vessels. Histologically, angiodysplasias are dilated, thin-walled vascular channels that appear macroscopically as a cluster of cherry spots. When located in the upper GI tract, they most commonly involve the stomach and duodenum. The lesions can be acquired or congenital, as in hereditary hemorrhagic telangiectasia and Rendu-Osler-Weber syndrome. The acquired angiodysplasias are commonly found in patients with chronic renal failure requiring hemodialysis and with aortic valvular disease (especially aortic stenosis). Other diseases, such as cirrhosis and von Willebrand disease, are associated with a higher frequency of angiodysplasias. Most lesions are smaller than 1 cm in diameter and can be multiple in 66% of patients.[9]

Etiology
Ulcer-related UGIB
As previously mentioned, peptic ulcer disease is strongly associated with H pyloriinfection. The organism causes disruption of the mucous barrier and has a direct inflammatory effect on gastric and duodenal mucosa. In cases of ulcer-associated UGIB, as the ulcer burrows deeper into the gastroduodenal mucosa, the process causes weakening and necrosis of the arterial wall, leading to the development of a pseudoaneurysm. The weakened wall ruptures, producing hemorrhage.

The flow through the vessel varies with the fourth power of the radius; thus, small increases in vessel size can mean much larger amounts of blood flow and bleeding, with more severe hypotension and more complications, especially in older patients. Visible vessels usually range from 0.3-1.8 mm. Exsanguinating hemorrhage has been reported from larger vessels. The larger vessels are located deeper in the gastric and duodenal submucosa and serosa. Larger branches of the left gastric artery are found high on the lesser curvature, while the pancreatoduodenal artery and its major branches are located posteroinferiorly in the duodenal bulb.

Vomiting-related UGIB
During vomiting, the lower esophagus and upper stomach are forcibly inverted. Vomiting attributable to any cause can lead to a mucosal tear of the lower esophagus or upper stomach. The depth of the tear determines the severity of the bleeding. Rarely, vomiting can result in esophageal rupture (Boerhaave syndrome), leading to bleeding, mediastinal air entry, left pleural effusion (salivary amylase can be present) or left pulmonary infiltrate, and subcutaneous emphysema.

Mallory-Weiss tears in UGIB

Mallory-Weiss tears account for 15% of acute upper GI hemorrhage.[9] Kenneth Mallory and Soma Weiss first described the syndrome in 1929.[17] The massive UGIB results from a tear in the mucosa of the gastric cardia. This linear mucosal laceration is the result of forceful vomiting, retching, coughing, or straining. These actions create a rapid increase in the gradient between intragastric and intrathoracic pressures, leading to a gastric mucosal tear from the forceful distention of the gastroesophageal junction.[18] In 80-90% of cases, this is a single, 1.75- to 2.5-cm mucosal tear along the lesser curve of the stomach just distal to the gastroesophageal junction.[17] Go to Mallory-Weiss Tear for complete information on this topic.

Acute stress gastritis in UGIB

Acute stress gastritis results from predisposing clinical conditions that have the potential to alter local mucosal protective barriers, such as mucus, bicarbonate, blood flow, and prostaglandin synthesis. Any disease process that disrupts the balance of these factors results in diffuse gastric mucosal erosions. This is most commonly observed in patients who have undergone episodes of shock, multiple trauma, acute respiratory distress syndrome, systemic respiratory distress syndrome, acute renal failure, and sepsis. The principal mechanisms involved are decreased splanchnic mucosal blood flow and altered gastric luminal acidity.

Dieulafoy lesions in UGIB

The Dieulafoy lesion, first described in 1896, is a vascular malformation of the proximal stomach, usually within 6 cm of the gastroesophageal junction along the lesser curvature of the stomach. However, it can occur anywhere along the GI tract. This lesion accounts for 2-5% of acute UGIB episodes.[19]

Endoscopically, the lesion appears as a large submucosal vessel that has become ulcerated. Because of the large size of the vessel, bleeding can be massive and brisk. The vessel rupture usually occurs in the setting of chronic gastritis, which may induce necrosis of the vessel wall. Alcohol consumption is reportedly associated with the Dieulafoy lesion. In a review of 149 cases, the Dieulafoy lesion mostly occurred in men and mostly in those in their third to tenth decade.[20]

NSAIDs in UGIB
NSAIDs cause gastric and duodenal ulcers by inhibiting cyclooxygenase, which causes decreased mucosal prostaglandin synthesis and results in impaired mucosal defenses. Daily NSAID use causes an estimated 40-fold increase in gastric ulcer creation and an 8-fold increase in duodenal ulcer creation.[15] Long-term NSAID use is associated with a 20% incidence in the development of mucosal ulceration.[21] Medical therapy includes avoiding the ulcerogenic drug and beginning a histamine2 (H2)receptor antagonist or a proton pump inhibitor that provides mucosal protection.

Epidemiology
Annually, approximately 100,000 patients are admitted to US hospitals for therapy for UGIB. UGIB is a common occurrence throughout the world. In France, a report concludes that the mortality from UGIB has decreased from about 11% to 7%; however, a similar report from Greece finds no decrease in mortality. In a nationwide study from Spain, UGIB was 6 times more common than lower GI bleeding.[22] The incidence of UGIB is 2-fold greater in males than in females, in all age groups; however, the death rate is similar in both sexes.[8] The population with UGIB has become progressively older, with a concurrent increase in significant comorbidities that increase mortality. Mortality increases with older age (>60 y) in males and females.[21]

Prognosis
As previously mentioned, age older than 60 years is an independent marker for a poor outcome in upper gastrointestinal bleeding (UGIB),[23] with the mortality rate ranging from 12-25% in this group of patients. The American Society for Gastrointestinal Endoscopy (ASGE) grouped patients with UGIB according to age and correlated age category to risk of mortality. The ASGE found a mortality rate of 3.3% for patients aged 21-31 years, a rate of 10.1% for those aged 41-50 years, and a rate of 14.4% for those aged 71-80 years.[23] Tthe following risk factors are associated with increased mortality, recurrent bleeding, the need for endoscopic hemostasis, or surgery[24, 13] :

Age older than 60 years Severe comorbidity Active bleeding (eg, witnessed hematemesis, red blood per nasogastric tube, fresh blood per rectum) Hypotension

Red blood cell transfusion greater than or equal to 6 units Inpatient at time of bleed Severe coagulopathy Patients who present in hemorrhagic shock have a mortality rate of up to 30%. Peptic ulcer disease refers to painful sores or ulcers in the lining of the stomach or first part of the small intestine, called the duodenum. What Causes Ulcers? No single cause has been found for ulcers. However, it is now clear that an ulcer is the end result of an imbalance between digestive fluids in the stomach and duodenum. Ulcers can be caused by:

Infection with a type of bacteria called Helicobacter pylori (H. pylori) Use of painkillers called nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, naproxen (Aleve, Anaprox, Naprosyn, and others), ibuprofen (Motrin, Advil, Midol, and others), and many others available by prescription. Even safety-coated aspirin and aspirin in powered form can frequently cause ulcers. Excess acid production from gastrinomas, tumors of the acid producing cells of the stomach that increases acid output (seen in Zollinger-Ellison syndrome).

What Are the Symptoms of an Ulcer? An ulcer may or may not have symptoms. When symptoms occur, they may include:

A gnawing or burning pain in the middle or upper stomach between meals or at night Bloating Heartburn Nausea or vomiting In severe cases, symptoms can include:

Dark or black stool (due to bleeding) Vomiting blood (that can look like "coffee-grounds") Weight loss Severe pain in the mid to upper abdomen How Serious Is an Ulcer? Though ulcers often heal on their own, you shouldn't ignore their warning signs. If not properly treated, ulcers can lead to serious health problems, including:

Bleeding Perforation (a hole through the wall of the stomach)

Gastric outlet obstruction from swelling or scarring that blocks the passageway leading from the stomach to the small intestine. Taking NSAIDs can cause any of the above symptoms without warning. The risk is especially concerning for the elderly and for those with a prior history of having peptic ulcer disease. Who Is More Likely to Get Ulcers? You may be more likely to develop ulcers if you:

Are infected with the H. pylori bacterium Take NSAIDs such as aspirin, ibuprofen, or naproxen Have a family history of ulcers Have another illness such as liver, kidney, or lung disease Drink alcohol regularly Are 50 years old or older

How Are Ulcers Diagnosed? Your doctor may be able to determine if you have an ulcer just by talking with you about your symptoms. However, to confirm the diagnosis one of several tests should be taken. First, your doctor may ask you to take an acid-blocking medication, such as those used to treat heartburn, for a short period of time to see if symptoms improve. If needed, your doctor may recommend a procedure called an upper endoscopy. It involves inserting a small, lighted tube (endoscope) through the throat and into the stomach to look for abnormalities. This procedure is usually given if you are having severe symptoms of ulcers. Doctors will frequently treat for ulcers without confirming the diagnosis using endoscopy. If the cause is not likely to be from NSAIDs, then it is very likely to be from H. pylori. Many doctors will now test for and treat H. pylori, in addition to giving medications to reduce the symptoms. How Are Ulcers Treated? If not properly treated, ulcers can lead to serious health problems. There are several ways in which ulcers can be treated, including making changes to ones lifestyle, limiting dairy, taking medication, and/or undergoing surgery. Lifestyle Changes to Treat an Ulcer To treat an ulcer, first eliminate substances that can be causing the ulcers. If you smoke or drink alcohol, stop. If the ulcer is believed to be caused by the use of NSAIDs, they need to be stopped. Ulcer Medications

Ulcer medications can include:

Proton pump inhibitors (PPI). Proton pump medications reduce acid levels and allow the ulcer to heal. They include Prilosec, Prevacid, Aciphex, Protonix, Zegerid, Dexilant, and Nexium. Antibiotics. If you have H. pylori infection, then antibiotics are used. There are multiple combinations of antibiotics that are taken for one to two weeks along with a PPI. Pepto-Bismol is also part of some treatment regimens. Upper endoscopy . Some bleeding ulcers can be treated through an endoscope. Surgery. Sometimes an operation is needed if the ulcer has created a hole in the wall of the stomach or if there is serious bleeding that can't be controlled with an endoscope. Will Drinking Milk Help Cure an Ulcer? No. In fact, milk can make an ulcer worse. Milk provides brief relief of ulcer pain because it coats the stomach lining. But milk can also stimulate the stomach to produce more acid and digestive juices, which can aggravate ulcers. How Can I Prevent Ulcers? To reduce the risk of developing ulcers:

Don't smoke. Avoid alcohol. Don't overuse aspirin and/or NSAIDs. If you have symptoms of an ulcer, contact your health care provider.

A peptic ulcer, also known as peptic ulcer disease (PUD),[1] is the most common ulcer of an area of the gastrointestinal tract that is usually acidic and thus extremely painful. It is defined as mucosal erosions equal to or greater than 0.5 cm. As many as 7090% of such ulcers are associated withHelicobacter pylori, a rod-shaped bacterium that lives in the acidic environment of the stomach; however, only 40% of those cases go to a doctor. Ulcers can also be caused or worsened by drugs such as aspirin, ibuprofen, and other NSAIDs.[2] Four times as many peptic ulcers arise in the duodenumthe first part of the small intestine, just after the stomachas in the stomach itself. About 4% of gastric ulcers are caused by a malignant tumor, so multiple biopsies are needed to exclude cancer. Duodenal ulcers are generally benign.

Classification
By Region/Location

Duodenum (called duodenal ulcer) Esophagus (called esophageal ulcer)

Stomach (called gastric ulcer) Meckel's diverticulum (called Meckel's diverticulum ulcer; is very tender with palpation)

Modified Johnson Classification of peptic ulcers:

Type I: Ulcer along the body of the stomach, most often along the lesser curve at incisura angularis along the locus minoris resistantiae. Type II: Ulcer in the body in combination with duodenal ulcers. Associated with acid oversecretion. Type III: In the pyloric channel within 3 cm of pylorus. Associated with acid oversecretion. Type IV: Proximal gastroesophageal ulcer Type V: Can occur throughout the stomach. Associated with chronic NSAID use (such as aspirin).

[edit]Signs

and symptoms

Symptoms of a peptic ulcer can be

abdominal pain, classically epigastric strongly correlated to mealtimes. In case of duodenal ulcers the pain appears about three hours after taking a meal; bloating and abdominal fullness; waterbrash (rush of saliva after an episode of regurgitation to dilute the acid in esophagus although this is more associated with gastroesophageal reflux disease); nausea, and copious vomiting; loss of appetite and weight loss; hematemesis (vomiting of blood); this can occur due to bleeding directly from a gastric ulcer, or from damage to the esophagus from severe/continuing vomiting. melena (tarry, foul-smelling feces due to oxidized iron from hemoglobin); rarely, an ulcer can lead to a gastric or duodenal perforation, which leads to acute peritonitis. This is extremely painful and requires immediate surgery.

A history of heartburn, gastroesophageal reflux disease (GERD) and use of certain forms of medication can raise the suspicion for peptic ulcer. Medicines associated with peptic ulcer includeNSAID (non-steroid anti-inflammatory drugs) that inhibit cyclooxygenase, and most glucocorticoids (e.g. dexamethasone and prednisolone). In patients over 45 with more than two weeks of the above symptoms, the odds for peptic ulceration are high enough to warrant rapid investigation by esophagogastroduodenoscopy. The timing of the symptoms in relation to the meal may differentiate between gastric and duodenal ulcers: A gastric ulcer would give epigastric pain during the meal, as gastric acid production is increased as food enters the stomach. Symptoms of duodenal ulcers would

initially be relieved by a meal, as the pyloric sphincter closes to concentrate the stomach contents, therefore acid is not reaching the duodenum. Duodenal ulcer pain would manifest mostly 23 hours after the meal, when the stomach begins to release digested food and acid into the duodenum. Also, the symptoms of peptic ulcers may vary with the location of the ulcer and the patient's age. Furthermore, typical ulcers tend to heal and recur and as a result the pain may occur for few days and weeks and then wane or disappear.[3] Usually, children and the elderly do not develop any symptoms unless complications have arisen. Burning or gnawing feeling in the stomach area lasting between 30 minutes and 3 hours commonly accompanies ulcers. This pain can be misinterpreted as hunger, indigestion or heartburn. Pain is usually caused by the ulcer but it may be aggravated by the stomach acid when it comes into contact with the ulcerated area. The pain caused by peptic ulcers can be felt anywhere from the navel up to the sternum, it may last from few minutes to several hours and it may be worse when the stomach is empty. Also, sometimes the pain may flare at night and it can commonly be temporarily relieved by eating foods that buffer stomach acid or by taking anti-acid medication.[4] However, peptic ulcer disease symptoms may be different for every sufferer.[5] [edit]Complications

Gastrointestinal bleeding is the most common complication. Sudden large bleeding can be life-threatening.[6] It occurs when the ulcer erodes one of the blood vessels, such as the gastroduodenal artery.

Perforation (a hole in the wall) often leads to catastrophic consequences. Erosion of the gastro-intestinal wall by the ulcer leads to spillage of stomach or intestinal content into the abdominal cavity. Perforation at the anterior surface of the stomach leads to acute peritonitis, initially chemical and later bacterial peritonitis. The first sign is often sudden intense abdominal pain. Posterior wall perforation leads to bleeding due to involvement of gastroduodenal artery that lies posterior to the 1st part of duodenum. perforation and Penetration are when the ulcer continues into adjacent organs such as the liver and pancreas.[3] Gastric outlet obstruction is the narrowing of pyloric canal by scarring and swelling of gastric antrum and doudenum due to peptic ulcers. Patient often presents with severe vomiting without bile. Cancer is included in the differential diagnosis (elucidated by biopsy), Helicobacter pylori as the etiological factor making it 3 to 6 times more likely to develop stomach cancer from the ulcer.[3]

[edit]Cause

A major causative factor (60% of gastric and up to 90% of duodenal ulcers) is chronic inflammation due to Helicobacter pylori that colonizes the antral mucosa.[7] The immune system is unable to clear the infection, despite the appearance of antibodies. Thus, the bacterium can cause a chronic active gastritis (type B gastritis), resulting in a defect in the regulation of gastrin production by that part of the stomach, and gastrin secretion can either be increased, or as in most cases, decreased, resulting in hypo- or achlorhydria. Gastrin stimulates the production of gastric acid by parietal cells. In H. pylori colonization responses to increased gastrin, the increase in acid can contribute to the erosion of the mucosa and therefore ulcer formation. Studies in the varying occurrence of ulcers in third world countries despite high H. pylori colonization rates suggest dietary factors play a role in the pathogenesis of the disease.[8] Another major cause is the use of NSAIDs. The gastric mucosa protects itself from gastric acid with a layer of mucus, the secretion of which is stimulated by certain prostaglandins. NSAIDs block the function of cyclooxygenase 1 (cox-1), which is essential for the production of these prostaglandins. COX-2 selective anti-inflammatories (such as celecoxib or the since withdrawnrofecoxib) preferentially inhibit cox-2, which is less essential in the gastric mucosa, and roughly halve the risk of NSAID-related gastric ulceration. The incidence of duodenal ulcers has dropped significantly during the last 30 years, while the incidence of gastric ulcers has shown a small increase, mainly caused by the widespread use of NSAIDs. The drop in incidence is considered to be a cohort-phenomenon independent of the progress in treatment of the disease. The cohort-phenomenon is probably explained by improved standards of living which has lowered the incidence of H. pylori infections.[9] Although some studies have found correlations between smoking and ulcer formation,[10] others have been more specific in exploring the risks involved and have found that smoking by itself may not be much of a risk factor unless associated with H. pylori infection.[11][12][13][nb 1] Some suggested risk factors such as diet, and spice consumption, were hypothesized as ulcerogens (helping cause ulcers) until late in the 20th century, but have been shown to be of relatively minor importance in the development of peptic ulcers.[14] Caffeine and coffee, also commonly thought to cause or exacerbate ulcers, have not been found to affect ulcers to any significant extent.[15][16] Similarly, while studies have found that alcohol consumption increases risk when associated with H. pylori infection, it does not seem to independently increase risk, and even when coupled with H. pylori infection, the increase is modest in comparison to the primary risk factor.[11][17][nb 2] Gastrinomas (Zollinger Ellison syndrome), rare gastrin-secreting tumors, also cause multiple and difficult-to-heal ulcers. [edit]Diagnosis

Endoscopic image of gastric ulcer, biopsy proven to be gastric cancer.

The diagnosis is mainly established based on the characteristic symptoms. Stomach pain is usually the first signal of a peptic ulcer. In some cases, doctors may treat ulcers without diagnosing them with specific tests and observe whether the symptoms resolve, thus indicating that their primary diagnosis was accurate. Confirmation of the diagnosis is made with the help of tests such as endoscopies or barium contrast x-rays. The tests are typically ordered if the symptoms do not resolve after a few weeks of treatment, or when they first appear in a person who is over age 45 or who has other symptoms such asweight loss, because stomach cancer can cause similar symptoms. Also, when severe ulcers resist treatment, particularly if a person has several ulcers or the ulcers are in unusual places, a doctor may suspect an underlying condition that causes the stomach to overproduce acid.[3] An esophagogastroduodenoscopy (EGD), a form of endoscopy, also known as a gastroscopy, is carried out on patients in whom a peptic ulcer is suspected. By direct visual identification, the location and severity of an ulcer can be described. Moreover, if no ulcer is present, EGD can often provide an alternative diagnosis. One of the reasons that blood tests are not reliable for accurate peptic ulcer diagnosis on their own is their inability to differentiate between past exposure to the bacteria and current infection. Additionally, a false negative result is possible with a blood test if the patient has recently been taking certain drugs, such as antibiotics or proton pump inhibitors.[18] The diagnosis of Helicobacter pylori can be made by:

Urea breath test (noninvasive and does not require EGD); Direct culture from an EGD biopsy specimen; this is difficult to do, and can be expensive. Most labs are not set up to perform H. pylori cultures; Direct detection of urease activity in a biopsy specimen by rapid urease test;

Measurement of antibody levels in blood (does not require EGD). It is still somewhat controversial whether a positive antibody without EGD is enough to warrant eradication therapy; Stool antigen test; Histological examination and staining of an EGD biopsy.

The breath test uses radioactive carbon atom to detect H. pylori.[19] To perform this exam the patient will be asked to drink a tasteless liquid which contains the carbon as part of the substance that the bacteria breaks down. After an hour, the patient will be asked to blow into a bag that is sealed. If the patient is infected with H. pylori, the breath sample will contain radioactive carbon dioxide. This test provides the advantage of being able to monitor the response to treatment used to kill the bacteria. The possibility of other causes of ulcers, notably malignancy (gastric cancer) needs to be kept in mind. This is especially true in ulcers of the greater (large) curvature of the stomach; most are also a consequence of chronic H. pylori infection. If a peptic ulcer perforates, air will leak from the inside of the gastrointestinal tract (which always contains some air) to the peritoneal cavity (which normally never contains air). This leads to "free gas" within the peritoneal cavity. If the patient stands erect, as when having a chest X-ray, the gas will float to a position underneath the diaphragm. Therefore, gas in the peritoneal cavity, shown on an erect chest X-ray or supine lateral abdominal X-ray, is an omen of perforated peptic ulcer disease. [edit]Macroscopic

appearance

A benign gastric ulcer (from the antrum) of a gastrectomy specimen.

Gastric ulcers are most often localized on the lesser curvature of the stomach. The ulcer is a round to oval parietal defect ("hole"), 2 to 4 cm diameter, with a smooth base and perpendicular borders. These borders are not elevated or irregular in the acute form of peptic ulcer, regular but

with elevated borders and inflammatory surrounding in the chronic form. In the ulcerative form of gastric cancer the borders are irregular. Surrounding mucosa may present radial folds, as a consequence of the parietal scarring. [edit]Microscopic

appearance

A gastric peptic ulcer is a mucosal defect which penetrates the muscularis mucosae and lamina propria, produced by acid-pepsin aggression. Ulcer margins are perpendicular and present chronic gastritis. During the active phase, the base of the ulcer shows 4 zones: inflammatory exudate, fibrinoid necrosis, granulation tissue and fibrous tissue. The fibrous base of the ulcer may contain vessels with thickened wall or with thrombosis.[20] [edit]Differential

diagnosis

Gastritis Stomach cancer Gastroesophageal reflux disease Pancreatitis Hepatic congestion Cholecystitis Biliary colic Inferior myocardial infarction Referred pain (pleurisy, pericarditis) Superior mesenteric artery syndrome

[edit]Treatment Younger patients with ulcer-like symptoms are often treated with antacids or H2 antagonists before EGD is undertaken. Bismuth compounds may actually reduce or even clear organisms[citation needed], though the warning labels of some bismuth subsalicylate products indicate that the product should not be used by someone with an ulcer.[21] Patients who are taking nonsteroidal anti-inflammatories (NSAIDs) may also be prescribed a prostaglandin analogue (Misoprostol) in order to help prevent peptic ulcers, which are a sideeffect of the NSAIDs. When H. pylori infection is present, the most effective treatments are combinations of 2 antibiotics (e.g. Clarithromycin, Amoxicillin, Tetracycline, Metronidazole) and 1 proton pump inhibitor (PPI), sometimes together with a bismuth compound. In complicated, treatmentresistant cases, 3 antibiotics (e.g. amoxicillin + clarithromycin + metronidazole) may be used together with a PPI and sometimes with bismuth compound. An effective first-line therapy for

uncomplicated cases would be Amoxicillin + Metronidazole + Pantoprazole (a PPI). In the absence of H. pylori, long-term higher dose PPIs are often used. Treatment of H. pylori usually leads to clearing of infection, relief of symptoms and eventual healing of ulcers. Recurrence of infection can occur and retreatment may be required, if necessary with other antibiotics. Since the widespread use of PPI's in the 1990s, surgical procedures (like "highly selective vagotomy") for uncomplicated peptic ulcers became obsolete. Perforated peptic ulcer is a surgical emergency and requires surgical repair of the perforation. Most bleeding ulcers require endoscopy urgently to stop bleeding with cautery, injection, or clipping. Ranitidine and famotidine, which are both H2 antagonists, provide relief of peptic ulcers, heartburn, indigestion and excess stomach acid and prevention of these symptoms associated with excessive consumption of food and drink. Ranitidine and famotidine are available over the counter at pharmacies, both as brand-name drugs and as generics, and work by decreasing the amount of acid the stomach produces allowing healing of ulcers.[22] Sucralfate, (Carafate) has also been a successful treatment of peptic ulcers.[23] [edit]Epidemiology

Disability-adjusted life year for peptic ulcer disease per 100,000 inhabitants in 2004.[24] no data less than 20 2040 4060 6080 80100 100120 120140 140160 160180 180200 200220 more than 220

The lifetime risk for developing a peptic ulcer is approximately 10%.[25] In Western countries the prevalence of Helicobacter pylori infections roughly matches age (i.e., 20% at age 20, 30% at age 30, 80% at age 80 etc.). Prevalence is higher in third world countries where it is estimated at about 70% of the population, whereas developed countries show a maximum of 40% ratio. Overall, H. pylori infections show a worldwide decrease, more so in developed countries. Transmission is by food, contaminated groundwater, and through human saliva (such as from kissing or sharing food utensils).[26] A minority of cases of H. pylori infection will eventually lead to an ulcer and a larger proportion of people will get non-specific discomfort, abdominal pain or gastritis. Peptic ulcer disease had a tremendous effect on morbidity and mortality until the last decades of the 20th century, when epidemiological trends started to point to an impressive fall in its incidence.[27] The reason that the rates of peptic ulcer disease decreased is thought to be the development of new effective medication and acid suppressants and the discovery of the cause of the condition, H. pylori. In the United States about 4 million people have active peptic ulcers and about 350,000 new cases are diagnosed each year. Four times as many duodenal ulcers as gastric ulcers are diagnosed. Approximately 3,000 deaths per year in the United States are due to duodenal ulcer and 3,000 to gastric ulcer.[28] [edit]Diet as a predisposing Cause While working as a general surgeon at Holdsworthy Hospital, Mysore, India Dr Frank Tovey observed that the incidence of peptic ulcers was higher with staple diets of refined wheat flour and polished rice and much lower where the staple diets were village ground millet and pulses. Subsequently he and others have shown a mix of Phospholipids and phytosterol in these diets will prevent ulcers where rats are exposed to ulcerogenic treatment with NSAIDS. They have also shown that H Pylori has a similar incidence in both populations. The combination of phospholipids and phytosterols may be of value in the prevention and treatment of duodenal ulceration and protection against the ulcerogenic effect of NSAIDs.[29] [edit]History See also: Timeline of peptic ulcer disease and Helicobacter pylori John Lykoudis, a general practitioner in Greece, treated patients for peptic ulcer disease with antibiotics, beginning in 1958, long before it was commonly recognized that bacteria were a dominant cause for the disease.[30] Helicobacter pylori was rediscovered in 1982 by two Australian scientists, Robin Warren and Barry J. Marshall as a causative factor for ulcers.[31] In their original paper, Warren

and Marshall contended that most gastric ulcers and gastritis were caused by colonization with this bacterium, not by stress or spicy food as had been assumed before.[32] The H. pylori hypothesis was poorly received,[33] so in an act of self-experimentation Marshall drank a Petri dish containing a culture of organisms extracted from a patient and five days later developed gastritis. His symptoms disappeared after two weeks, but he took antibiotics to kill the remaining bacteria at the urging of his wife, since halitosis is one of the symptoms of infection.[34] This experiment was published in 1984 in the Australian Medical Journal and is among the most cited articles from the journal. In 1997, the Centers for Disease Control and Prevention, with other government agencies, academic institutions, and industry, launched a national education campaign to inform health care providers and consumers about the link between H. pylori and ulcers. This campaign reinforced the news that ulcers are a curable infection, and that health can be greatly improved and money saved by disseminating information about H. pylori.[35] In 2005, the Karolinska Institute in Stockholm awarded the Nobel Prize in Physiology or Medicine to Dr. Marshall and his long-time collaborator Dr. Warren "for their discovery of the bacteriumHelicobacter pylori and its role in gastritis and peptic ulcer disease." Professor Marshall continues research related to H. pylori and runs a molecular biology lab at UWA in Perth, Western Australia. Some believed that mastic gum, a tree resin extract, actively eliminates the H. pylori bacteria.[36] However, multiple subsequent studies have found no effect of using mastic gum on reducing H. pylori levels.[37][38]
Upper gastrointestinal bleeding

is characterized by the sudden onset of bleeding from the GI tract at a site (or sites) proximal to the ligament of Treitz. Most upper GI bleeds are a direct result of peptic ulcer erosion, stress related- mucosal disease, that may evidence as superficial erosive gastric lesion to frank ulcerations, erosive gastritis (secondary to use or abuse of NSAIDs, oral corticosteroids, or alcohol) or esophageal varices (secondary to hepatic failure). In addition to these, Mallory-Weiss tears can cause gastroesophageal bleeding as a result of severe retching and vomiting, but the bleeding tends to be less severe than in other types. Hospitalized critically ill patients are at heightened risk for stress related mucosal disease, particularly if they are intubated and mechanically ventilated and/or evidencing coagulopathies.
Signs and Symptoms Melena and hematemesis Pain Hypovolemic shock Physical Examination Vital signs BP < 90 mm Hg HR > 100 beats/min

RR: tachycardia Temperature: maybe elevated Other Hematemesis Melena Bloody stool with fetid odor Coffee ground gastric aspirate Skin Pale, diaphoretic Cool, clammy Jaundice Cardiovascular Weak, thready pulse Capillary refill > 3 sec Abdominal Maybe tender with guarding Bowel sounds hyperactive or absent Acute Care Patient Management Nursing Diagnosis: Deficient fluid volume related to blood loss from hemorrhage. Outcome Criteria Patient alert and oriented Skin, pink, warm, and dry CVP 2 to 6 mm Hg PAS 15 TO 30 mm Hg PAD 5 to 15 mm Hg BP 90 to 120 mm Hg MAP 70 to 105 mm Hg HR 60 to 100 beats/min Urine output 30 ml/hr Patient Monitoring 1. Obtain pulmonary artery pressure, central venous pressure and blood pressure every 15 minutes during acute episodes to evaluate fluid needs and the patients response to therapy. 2. Monitor fluid volume status. Measure intake and output hourly to evaluate renal perfusion. 3. Measure blood loss if possible. 4. Continuously monitor ECG for dysrythmias and myocardial ischemia. Patient Assessment 1. Assess patient for increases restlessness, apprehension or altered consciousness, which may indicate decreased cerebral perfusion. 2. Assess hydration status. 3. Be alert for recurrence of bleedings. Diagnostic Assessment

1. Review Hgb and Hct levels to determine the effectiveness of treatment or worsening of the patients condition. 2. Review clotting factors and serum calcium levels if multiple transfusions have been give. 3. Review serial BUN levels. 4. Review serial ABGs to evaluate oxygenation and acid-base status. 5. Review the result of endoscopic evaluation. Patient Management 1. Maintain a patent airway. Administer supplemental oxygen as ordered. 2. Administer colloids as ordered to restore intravascular volume. 3. Type and crossmatch for anticipated blood products. 4. Evacuate stomach contents with nasogastric tube and initiate lavages with room temperature water or saline to clear blood clots from the stomach. 5. Continue to monitor the patient closely once stabilized. 6. Vitamin K or fresh-frozen plasma (FFP) may be ordered to correct coagulation deficiencies. 7. Explain all procedures and tests to the patient to help alleviate anxiety and decreased tissue oxygen demands.