Upper gastrointestinal bleeding (UGIB) is an important medical problem for patients and the medical system. The causes of UGIB are varied and their accurate identification guides appropriate management. The major cause of UGIB is peptic ulcer disease, for which Helicobacter pylori and nonsteroidal antiinflammatory drug use are major risk factors. Lesser causes include Dieulafoy lesion, gastric antral vascular ectasia, hemobilia, aortoenteric fistulas, and upper gastrointestinal tumors. Awareness of causes and management of UGIB should allow physicians to treat their patients more effectively.
Upper gastrointestinal bleeding (UGIB) remains a common and major medical problem, resulting in significant morbidity and mortality. An estimated 300,000 to 350,000 hospital admissions for UGIB occur annually in the United States, with an overall mortality of approximately 7% to 10%. UGIB commonly presents with hematemesis or melena. In comparison, hematochezia is usually a sign of a lower gastrointestinal source. Although helpful, the distinctions based on stool color are not absolute because melena can be seen with proximal lower gastrointestinal bleeding, and hematochezia can be seen with massive UGIB ( Table 1 ).
| Cause | Incidence (%) |
|---|---|
| Peptic ulcer disease | 55 |
| Esophagogastric varices | 14 |
| Arteriovenous malformations | 6 |
| Mallory-Weiss tears | 5 |
| Tumors and erosions | 4, each |
| Dieulafoy lesion | 1 |
| Other | 11 |
Duodenal and gastric ulcers
Five per cent of gastric ulcers are malignant, whereas duodenal ulcers are rarely malignant. Gastric ulcers are characterized at the time of esophagogastroduodenoscopy (EGD) as likely being benign if they have a round margin, smooth border, antral or prepyloric location, small size, radiating folds, and lack of an associated mass. It is recommended that gastric ulcers are followed with repeat EGD to confirm healing, to exclude a nonhealing malignant ulcer.
About 50% of gastric ulcers are associated with Helicobacter pylori infection, whereas up to 80% of duodenal ulcers are caused by this infection. Duodenal ulcers develop in about 15% of patients who have H pylori infection. There is a virulent strain of H pylori , containing the cagA gene, which has been strongly associated with duodenal ulcers. The chronic inflammation induced by H pylori upsets the normal physiology of gastric secretion to varying degrees and leads to chronic gastritis, which, in most individuals, is asymptomatic and does not progress. In some cases, altered gastric secretion coupled with tissue injury leads to peptic ulcer disease (PUD), whereas, in other cases, gastritis progresses to atrophy, intestinal metaplasia, and eventually gastric carcinoma. Rarely, because of persistent immune simulation of gastric lymphoid tissue, this chronic inflammation induced by H pylori can lead to gastric lymphoma. Eradication promotes ulcer healing, which facilitates prevention of recurrence of ulcers.
Nonsteroidal antiinflammatory drugs (NSAIDs) make up the most important cause of PUD after infection with H pylori . Although NSAIDs may cause duodenal ulcers, they more commonly produce ulcerations in the antrum. In the elderly, NSAIDs are an especially common cause of PUD. In about 50% of patients, NSAID-induced ulcers are painless because of the analgesic properties of NSAIDs, which mask ulcer pain, in addition to the early discontinuation of NSAID therapy (before developing PUD) in patients who experience abdominal pain. NSAID-induced ulcers often lack inflammation beyond the margin of the ulcer, in contrast with H pylori –related ulcers, which usually occur in a field of chronic active gastritis.
Zollinger-Ellison syndrome (also known as gastrinoma) should be included in the differential diagnosis whenever ulcers are multiple, refractory to conventional therapy, located in otherwise unusual places (eg, the esophagus or the second portion of the duodenum), associated with thick gastric folds, an acidic diarrhea, or with gastric hypersecretion and hyperchloryhydria.
Endoscopic therapies include injection, ablation, and mechanical therapy. All 3 therapies are effective as monotherapies, but combined therapies increase efficacy.
Gastritis
Causes of acute hemorrhagic gastritis include infection (eg, cytomegalovirus or syphilis), aspirin or NSAID use, radiation, and toxic ingestion. Erosive gastritis in patients experiencing severe physiologic stress from critical diseases is referred to as stress-related mucosal disease (SRMD). This disease occurs especially in those suffering from overwhelming sepsis or respiratory failure requiring mechanical ventilation, as well as patients in intensive care units with multiple medical problems. Gastric mucosal ischemia and acid-mediated injury is the pathophysiologic mechanism. Patients with SRMD usually only experience mild bleeding. EGD usually shows multiple superficial ulcers with surrounding erythema.
Lesion healing depends on treatment of the underlying disease that caused the SRMD. Although proton pump inhibitors have an established role in treating SRMD, their role in preventing SRMD is not well validated.
Gastritis
Causes of acute hemorrhagic gastritis include infection (eg, cytomegalovirus or syphilis), aspirin or NSAID use, radiation, and toxic ingestion. Erosive gastritis in patients experiencing severe physiologic stress from critical diseases is referred to as stress-related mucosal disease (SRMD). This disease occurs especially in those suffering from overwhelming sepsis or respiratory failure requiring mechanical ventilation, as well as patients in intensive care units with multiple medical problems. Gastric mucosal ischemia and acid-mediated injury is the pathophysiologic mechanism. Patients with SRMD usually only experience mild bleeding. EGD usually shows multiple superficial ulcers with surrounding erythema.
Lesion healing depends on treatment of the underlying disease that caused the SRMD. Although proton pump inhibitors have an established role in treating SRMD, their role in preventing SRMD is not well validated.
Esophagitis
Potential sources of esophageal bleeding include infections (eg, Candida , herpes simplex, cytomegalovirus, or human immunodeficiency virus), reflux, caustic ingestion, and NSAID-induced or other pill esophagitis. Endoscopic findings in reflux esophagitis include mucosal erythema, hypervascularity, edema, exudation, erosions, bleeding, and ulceration. This finding is usually most severe just proximal to the gastroesophageal junction (GEJ).
Endoscopic therapy for acute esophageal bleeding point sources includes epinephrine injection or ablative therapy. The offending drug should be discontinued with pill esophagitis. In infectious esophagitis, specific antimicrobial therapy is recommended.
Dieulafoy Lesion
A Dieulafoy lesion is a submucosal artery that is congenital, abnormally large, and has the potential to bleed through a small mucosal defect. These lesions account for about 2% of all nonvariceal UGIB (NVUGIB). Patients usually present with acute, severe UGIB, often associated with hypotension or orthostasis. EGD commonly shows a pigmented protuberance (representing the vessel stump), most commonly with minimal surrounding erosion and no ulceration. In three-fourths of cases, the Dieulafoy lesion is located 6 to 10 cm below the GEJ, in the proximal stomach along the lesser curvature, but it can also occur anywhere in the gastrointestinal tract. The lesion typically has a diameter of only 2 to 5 mm. Liver disease has been associated with this lesion. The use of NSAIDs is common, with one theory being that NSAIDs incite bleeding by causing mucosal atrophy and ischemic injury.
Hemostasis can be achieved with epinephrine injection, ablative therapy (including argon plasma coagulation [APC]), or mechanical therapy (including band ligation or endoclips). There has been a recent trend toward mechanical therapy in the treatment of this lesion. It is particularly amenable to mechanical therapy because of the lesion’s focal nature and protuberant shape. There is comparable efficacy between band ligation and endoclips. Documentation of absence of flow following injection therapy via Doppler ultrasound has been used to confirm ablation of a Dieulafoy lesion. Another helpful technique is endoscopic tattooing with India ink injection of the site, which is helpful for locating the lesion for endoscopic retreatment or intraoperative wedge resection.
Mallory-Weiss
A common cause of UGIB is a Mallory-Weiss tear, which is a lesion that occurs at the GEJ. Patients typically present after repeated vomiting, retching, or coughing, with hematemesis, which is often associated with an alcoholic binge, diabetic ketoacidosis, or chemotherapy. At the time of EGD, a tear typically arising from the gastric side of the GEJ is visualized, which is linear and longitudinally arrayed. This lesion can also manifest as a superficial ulcer, erosion, scab, or crevice depending on the stage of evolution and severity. A Mallory-Weiss tear can result in bleeding that is typically mild to moderate, but can rarely be severe. In about 90% of cases, the bleeding spontaneously ceases.
The optimal endoscopic therapy for bleeding Mallory-Weiss tears (injection, ablative, or mechanical) is still being evaluated, and is likely to be influenced by endoscopic preference and technical factors. It is unclear whether combination therapy improves hemostasis.
Gastric Cancer
Gastric ulcers are characterized as likely malignant if they possess an irregular and indurated border, heaped margins, location in the proximal stomach, large size, absence of gastric folds near the ulcer, and an associated mass. Endoscopic appearance, together with performance of at least 7 biopsies from the ulcer margin and base, is 98% sensitive at discerning malignancy. These biopsies do not have to be performed during the index EGD, while the ulcer is actively bleeding, or if it has recently bled, to avoid exacerbating or inducing bleeding.
Only 3% of all cases of severe UGIB are caused by neoplasms of the UGI tract. The most common primary malignancy is adenocarcinoma. The usual presentation can be that of a gastric mass, ulcerated mass, nonhealing ulcer, or stricture. If the stomach seems poorly motile and noncompliant at the time of EGD, linitis plastica should be suspected, which results from diffuse infiltration of adenocarcinoma throughout the gastric wall. Lung cancer, breast cancer, and cutaneous melanoma are common sources of gastric metastases. Patients with malignant UGI tumors that bleed severely have a poor prognosis with a high mortality within 12 months.
Endoscopic hemostasis of gastric malignancies is usually achieved with ablative therapy, epinephrine injection, or both.
Gastric antral vascular ectasia
Gastric antral vascular ectasia (GAVE) commonly presents with iron deficiency anemia, sometimes as an incidental finding, and occasionally causes acute UGIB. It usually occurs in women and in the elderly. The patient may have a long history of chronic gastrointestinal bleeding, and, because of delayed diagnosis, also may have a history of multiple prior blood transfusions. GAVE is associated with scleroderma, chronic renal disease, and, possibly, chronic liver disease, but is not associated with portal hypertension without liver disease. EGD can show parallel folds that originate from the pylorus and extend into the proximal antrum. The tops of the gastric folds usually contain red linear streaks ( Fig. 1 ). Watermelon stomach is a pseudonym of this entity, because the linear streaks resemble the stripes of a watermelon rind. GAVE can be distinguished from ordinary antral gastritis by its blanching on pressure, fold location, and sharp demarcation. Biopsies can be safely performed in patients with GAVE with only minimally increased and minor bleeding, because the intravascular pressure is low. Biopsy characteristically shows dilated, tortuous mucosal capillaries often occluded by bland fibrin thrombi and dilated submucosal veins with no inflammatory infiltration.
APC therapy could become the therapy of choice owing to the diffuse nature and superficial lesion location. Transjugular intrahepatic portosystemic shunt (TIPS), which is designed to decompress the portal system, does not reduce bleeding, highlighting the uncertain relationship of portal hypertension to GAVE. UGIB was decreased in one report with combination estrogen/progesterone therapy, although there was persistence of ectatic vessels.
Lymphomas
Five per cent of gastric tumors are caused by gastric lymphomas. Extranodal marginal zone B cell lymphomas (extranodal MZL), also known as mucosa-associated lymphoid tissue (MALT) lymphomas, are early B cell lymphomas. They rarely cause acute UGIB, but commonly cause chronic occult gastrointestinal bleeding. Possible findings at the time of EGD include a gastric ulcer, polypoid mass, or thickened gastric folds. Innocuous-appearing gastric nodularity is another possible presentation. In contrast with gastric adenocarcinomas, gastric lymphomas, including extranodal MZL, can extend from the stomach across the pylorus into the duodenum.
Extranodal MZL is distinguished pathologically by an infiltrate of lymphocytes and plasma cells that express standard B cell antigens. Diagnosis of lymphoma is accomplished via immunophenotyping, which can differentiate extranodal MZL from other lymphomas.
There is a strong association between chronic H pylori infection and extranodal MZL. Proliferation of B lymphocytes is stimulated by chronic H pylori infection, which can result in genetic mutations, particularly translocation of chromosome 11:18, which can lead to unregulated proliferation of B cells that have been transformed. Importance is placed on early diagnosis because early lymphoma often responds to treatment of H pylori . Complete histologic regression has been noted in 50% to 80% of extranodal MZL after treatment of H pylori .
Angiodysplasia
Approximately 2% to 5% of acute UGIB are caused by angiodysplasia. Most commonly, UGI angiodysplasia can be seen in the stomach, rarely in the esophagus, and sometimes in the duodenum. Often, angiodysplasia are multiple, and tend to be clustered. Angiodysplasia are made up of dilated, tortuous, and thin-walled vessels lined by endothelium, histologically, with no or little smooth muscle, and no inflammation, fibrosis, or atherosclerosis. The elderly are more likely to have angiodysplasia. Risk factors for bleeding angiodysplasia include chronic renal failure, aortic stenosis, and CREST (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) syndrome. Loss of large amounts of von Willebrand factor from high shear forces across a stenotic aortic valve is believed to be cause of the association between bleeding angiodysplasia and aortic stenosis.
A mutation in the ENG (endoligin) gene (type I) or the ACVRL1 gene (type II) results in a rare genetic vascular disorder known as hereditary hemorrhagic telangiectasia, which is characterized by multiple orocutaneous and mucosal telangiectasias. These telangiectasias are especially common in the gastrointestinal tract and the nose. Clinically significant gastrointestinal bleeding can arise in one-fourth of affected patients, and typically begins during middle age. The clinical triad of telangiectasia, recurrent epistaxis, and a compatible family history can make the diagnosis straightforward in these patients.
At the time of EGD, angiodysplasia may appear as dense, macular, and reticular networks of vessels (vascular tuft) ( Fig. 2 ). Typically, these vessels are 2 to 8 mm wide and are intensely red because of the erythrocyte high oxygen content within vessels supplied by arteries without intervening capillaries. At EGD, angiodysplasia may not be as prominent in patients who have profound anemia or hypotension, and may be obscured by meperidine administration.
Related posts:
Pathology of Diseases that Cause Upper Gastrointestinal Tract Bleeding
Epidemiology and Demographics of Upper Gastrointestinal Bleeding: Prevalence, Incidence, and Mortality
Epidemiology and Role of Nonsteroidal Antiinflammatory Drugs in Causing Gastrointestinal Bleeding
Radiologic Techniques and Effectiveness of Angiography to Diagnose and Treat Acute Upper Gastrointestinal Bleeding
Management of Nonvariceal Upper Gastrointestinal Bleeding
New Diagnostic Imaging Technologies in Nonvariceal Upper Gastrointestinal Bleeding
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