Thursday 30 March 2017

Major causes of upper gastrointestinal bleeding in adultsMajor causes of upper gastrointestinal bleeding in adults


All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Oct 2013. | This topic last updated: Sep 24, 2012.
INTRODUCTION  — Upper gastrointestinal bleeding is a common medical condition that results in high patient morbidity and medical care costs. In a study from one large health maintenance organization in the United States, the annual incidence of hospitalization for acute upper gastrointestinal bleeding was approximately 100 per 100,000 adults; the incidence was twice as common in males as in females and increased with age [ 1 ]. Interestingly, the prognosis of patients with upper gastrointestinal bleeding appears to be improving, whether due to nonvariceal or variceal bleeding [ 2 ].
Upper gastrointestinal bleeding commonly presents with hematemesis (vomiting of blood or coffee-ground like material) and/or melena (black, tarry stools). In a small proportion of cases, upper gastrointestinal bleeding presents as hematochezia. In this situation, bleeding is typically brisk, and if accompanied by hemodynamic instability, represents a medical emergency. Nasogastric tube lavage may be used to confirm this clinical diagnosis, but it is often not necessary and may not be positive, even in the presence of an upper gastrointestinal tract lesion, if bleeding has ceased or arises beyond a closed pylorus. It is important to take a careful history and perform a careful physical examination since this will help localize the source of bleeding and, in turn, shed light on the possible etiology of bleeding. Although helpful, localization of the source of bleeding based upon stool color is not absolute since melena can be seen with proximal lower GI bleeding (especially slow bleeding in some patients), and hematochezia can be seen with massive upper GI bleeding as highlighted above [ 3-5 ]. (See "Approach to resuscitation and diagnosis of acute lower gastrointestinal bleeding in the adult patient" .)
This topic will review the major causes of bleeding from the upper gastrointestinal tract. The most common causes of upper gastrointestinal bleeding are ulcerative disease of the stomach and/or duodenum (often referred to as "peptic ulcer disease") and gastroesophageal varices. The approach to the diagnosis and management of patients with upper gastrointestinal bleeding, as well as other causes of upper gastrointestinal bleeding, such as angiodysplasia, neoplasms, and hemobilia are discussed separately. (See "Approach to acute upper gastrointestinal bleeding in adults" and "Overview of the treatment of bleeding peptic ulcers" and"Uncommon causes of upper gastrointestinal bleeding in adults" and "Mallory-Weiss syndrome" .)
COMMON CAUSES OF UPPER GASTROINTESTINAL BLEEDING  — Upper gastrointestinal bleeding can be classified into several broad categories based upon anatomic and pathophysiologic factors ( table 1 ). Several endoscopic studies have described the most common causes [ 6-9 ]. The reported frequencies of the causes vary, possibly reflecting trends over time or differences in study design, populations, and definitions.
The most common causes of upper gastrointestinal bleeding include the following [ 6 ]:
  • Gastric and/or duodenal ulcers
  • Esophagogastric varices with or without portal hypertensive gastropathy
  • Esophagitis
  • Erosive gastritis/duodenitis
  • Mallory-Weiss syndrome
  • Angiodysplasia
  • Mass lesions (polyps/cancers)
  • Dieulafoy's lesion
Uncommon causes of upper gastrointestinal bleeding include hemobilia, hemosuccus pancreaticus, and aortoenteric fistula. In 11 percent of cases, no upper GI lesion can be identified. (See "Uncommon causes of upper gastrointestinal bleeding in adults" .)
Whereas older studies suggested that peptic ulcer disease was responsible for approximately half of upper gastrointestinal bleeds [ 6 ], more recent studies suggest it is now a less common cause [ 7,8,10 ]:
  • Peptic ulcers were responsible for 21 percent of episodes of upper gastrointestinal bleeding among 7822 patients included in a national, United States database between 1999 and 2001 [ 7 ]. The most common cause was nonspecific mucosal abnormalities (42 percent), while esophageal inflammation and varices accounted for approximately 15 and 12 percent, respectively. Other causes (angiodysplasia, Mallory-Weiss tears, and tumors) each accounted for less than 5 percent of cases. Among ulcer cases, gastric ulcers were more common than duodenal ulcers, representing about 55 percent of all ulcers.
  • A large database study focused on 243,428 upper endoscopies performed between 2000 and 2004 in a practice setting (rather than in tertiary care) [ 8 ]. The most common endoscopic findings in patients with upper gastrointestinal bleeding were an ulcer (33 percent) followed by an erosion (19 percent). Gastric ulcers were more common than duodenal ulcers (55 versus 37 percent). Patients with variceal bleeding were excluded from the analysis.
PEPTIC ULCER DISEASE  — Gastroduodenal ulcer disease remains a common cause of upper gastrointestinal bleeding ( picture 1A-B and picture 2 and picture 3 andmovie 1 ) [ 6 ]. There are four major risk factors for bleeding peptic ulcers [ 11,12 ] (see "Epidemiology and etiology of peptic ulcer disease" and "Unusual causes of peptic ulcer disease" ):
  • Helicobacter pylori infection
  • Nonsteroidal anti-inflammatory drugs (NSAIDs)
  • Physiologic stress
  • Excess gastric acid
Reduction or elimination of these risk factors reduces ulcer recurrence and rebleeding rates [ 13-16 ].
Helicobacter pylori  — Helicobacter pylori is a spiral bacterium that infects the superficial gastric mucosa and appears to be transmitted by the fecal-oral route. The bacterium generally does not invade gastroduodenal tissue. Instead, it renders the underlying mucosa more vulnerable to acid peptic damage by disrupting the mucous layer, liberating enzymes and toxins, and adhering to the gastric epithelium. In addition, the host immune response to H. pylori incites an inflammatory reaction which further perpetuates tissue injury. (See "Pathophysiology of and immune response to Helicobacter pylori infection" .)
The chronic inflammation induced by H. pylori upsets gastric secretory physiology to varying degrees and leads to chronic gastritis that, in most individuals, is asymptomatic and does not progress. In some cases, however, altered gastric secretion coupled with tissue injury leads to peptic ulcer disease, while in other cases, gastritis progresses to atrophy, intestinal metaplasia, and eventually to gastric carcinoma or rarely, due to persistent immune stimulation of gastric lymphoid tissue, gastric lymphoma [ 17-20 ]. (See "Association between Helicobacter pylori infection and gastrointestinal malignancy" .)
H. pylori eradication should be attempted for all patients who are diagnosed with the infection and who have peptic ulcer disease to prevent ulcer recurrence and rebleeding [ 21,22 ]. In one report of 19 published studies, for example, the recurrence rates in cured versus noncured H. pylori infection were 6 versus 67 percent for duodenal ulcers, and 4 versus 59 percent for gastric ulcers [ 22 ]. Various multidrug regimens (usually a combination of antibiotics and an antisecretory agent) have eradication rates in the range of 80 to 90 percent [ 23 ]. (See "Treatment regimens for Helicobacter pylori" .)
Nonsteroidal anti-inflammatory drugs  — NSAIDs, including low-dose aspirin , are a common cause of gastrointestinal ulceration [ 24-29 ]. NSAID-induced injury results from both local effects and systemic prostaglandin inhibition. The majority of these ulcers are asymptomatic and uncomplicated. However, elderly patients with a prior history of bleeding ulcer disease are at increased risk for recurrent ulcer and complications [ 30-32 ]. NSAIDs also have been implicated as an important factor for non-healing ulcers [ 33 ]. (See "NSAIDs (including aspirin): Pathogenesis of gastroduodenal toxicity" .)
Stress  — Stress related ulcers are a common cause of acute upper gastrointestinal bleeding in patients who are hospitalized for life-threatening non-bleeding illnesses [ 34 ]. Patients with these secondary episodes of bleeding have a higher mortality than those admitted to the hospital with primary upper gastrointestinal bleeding [ 35 ]. The risk of stress ulcer-related bleeding is increased in patients with respiratory failure and those with a coagulopathy [ 36 ]. Primary ulcer prophylaxis with antisecretory agents such as H2 receptor antagonists or proton pump inhibitors decreases the risk of stress related mucosal damage and upper gastrointestinal bleeding in high-risk patients [ 37-39 ]. (See "Stress ulcer prophylaxis in the intensive care unit" .)
Gastric acid  — Gastric acid and pepsin are essential cofactors in the pathogenesis of peptic ulcers [ 40 ]. Impairment of mucosal integrity by factors such as H. pylori, NSAIDs, or physiologic stress leads to increased cell membrane permeability to back diffusion of hydrogen ions, resulting in intramural acidosis, cell death, and ulceration [ 40 ]. Rarely, hyperacidity is the sole cause of peptic ulceration, as in patients with the Zollinger-Ellison syndrome. Control of gastric acidity is considered an essential therapeutic maneuver in patients with active upper gastrointestinal bleeding. (See "Clinical manifestations and diagnosis of Zollinger-Ellison syndrome (gastrinoma)" and "Approach to acute upper gastrointestinal bleeding in adults" .)
Treatment  — Treatment of bleeding peptic ulcers typically involves acid suppression, endoscopic therapy, and treatment/removal of risk factors for peptic ulcer disease. The approach to the treatment of bleeding peptic ulcers is discussed in detail elsewhere. (See "Approach to acute upper gastrointestinal bleeding in adults"and "Overview of the treatment of bleeding peptic ulcers" .)
ESOPHAGOGASTRIC VARICES  — Esophagogastric varices develop as a consequence of portal hypertension ( picture 4A-B and picture 5 ). The most common causes of portal hypertension in the United States are viral hepatitis, alcoholic liver disease, and nonalcoholic steatohepatitis (NASH). (See "Prediction of variceal hemorrhage in patients with cirrhosis" and "Diagnostic approach to the patient with cirrhosis" .)
Isolated gastric varices can result from segmental portal hypertension due to obstruction of the splenic vein from pancreatitis, pancreatic carcinoma, or trauma in the left upper quadrant ( picture 5 ). The risk factors for bleeding from gastric varices are similar to the risk factors for bleeding from esophageal varices [ 41 ]. (See"Prediction of variceal hemorrhage in patients with cirrhosis" .)
Diagnosis  — Endoscopy is the diagnostic modality of choice for esophagogastric varices [ 6 ]. If endoscopy is inconclusive and gastric variceal bleeding is suspected, one of the following tests should be considered to confirm the clinical suspicion:
Prognosis  — Variceal bleeding stops spontaneously in over 50 percent of patients, but the mortality rate approaches 70 to 80 percent in those with continued bleeding. Each episode of variceal hemorrhage is associated with a 30 percent risk of mortality [ 42 ]. The risk of rebleeding is high (60 to 70 percent) until gastroesophageal varices are obliterated.
The risk of rebleeding can be substantially reduced by follow-up endoscopic therapy to obliterate residual varices. However, long-term survival depends upon the severity of liver disease and may not be improved following successful variceal obliteration. The administration of a nonselective beta blocker such as propranololcan also decrease the risk of rebleeding. (See "Prevention of recurrent variceal hemorrhage in patients with cirrhosis" .)
The onset of massive upper gastrointestinal bleeding from gastroesophageal varices usually signifies advanced liver disease (Child class B or C), and patients who develop bleeding while being treated with a beta-blocker have a poor prognosis [ 43 ]. Liver transplantation is the only treatment that significantly improves the long-term prognosis in these patients.
Treatment  — Primary prophylaxis against variceal hemorrhage is desirable in view of the relatively high rate of bleeding from esophageal varices and the high mortality associated with this complication [ 44 ]. "Pre-primary" prophylaxis, in an attempt to prevent development of varices, is not recommended [ 45 ]. (See "Primary and pre-primary prophylaxis against variceal hemorrhage in patients with cirrhosis" .)
Various treatments are available for acute hemostasis [ 44 ]. Endoscopic band ligation is the standard treatment, with sclerotherapy used in situations where band ligation is not technically feasible. Early transjugular intrahepatic portosystemic shunt (TIPS) placement may be appropriate early in the course for some patients with gastroesophageal bleeding [ 46 ]. If this treatment is considered, it is critical that it be undertaken in collaboration with an experienced hepatologist. (See "Treatment of active variceal hemorrhage" .)
INFORMATION FOR PATIENTS  — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5 th to 6 th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10 th to 12 th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
SUMMARY
  • Upper gastrointestinal bleeding is a common medical condition that results in high patient morbidity and medical care costs, with an annual incidence in the Unites States of approximately 100 per 100,000 adults.
  • The most common causes of upper gastrointestinal bleeding include gastric and/or duodenal ulcers ( picture 6 and picture 2 and movie 1 and image 1 ) and esophagogastric varices ( picture 7A-B and table 1 ), with or without portal hypertensive gastropathy. Other common causes include. Other common causes include (see 'Common causes of upper gastrointestinal bleeding' above):
  • Esophagitis
  • Severe or erosive gastritis/duodenitis
  • Mallory-Weiss syndrome
  • Angiodysplasia
  • Mass lesions (polyps/cancers)
  • Dieulafoy's lesion
  • No lesion identified
  • Uncommon causes of upper gastrointestinal bleeding include hemobilia, hemosuccus pancreaticus, and aortoenteric fistula. (See "Uncommon causes of upper gastrointestinal bleeding in adults" .)
  • Helicobacter pylori infection, nonsteroidal anti-inflammatory drugs, physiologic stress, and excess gastric acid are major risk factors for bleeding peptic ulcers. Reduction or elimination of these risk factors reduces ulcer recurrence and rebleeding rates. (See 'Peptic ulcer disease' above.)
  • Esophagogastric varices develop as a consequence of portal hypertension. The most common causes of portal hypertension in the United States are viral hepatitis, alcoholic liver disease, and nonalcoholic steatohepatitis (NASH). (See 'Esophagogastric varices' above.)
ACKNOWLEDGMENT  — The author and UpToDate would like to thank Drs. Rome Jutabha and Dennis Jensen, who contributed to earlier versions of this topic review.

REFERENCES

  1. Longstreth GF. Epidemiology of hospitalization for acute upper gastrointestinal hemorrhage: a population-based study. Am J Gastroenterol 1995; 90:206.
  2. Crooks C, Card T, West J. Reductions in 28-day mortality following hospital admission for upper gastrointestinal hemorrhage. Gastroenterology 2011; 141:62.
  3. Jensen DM, Machicado GA. Diagnosis and treatment of severe hematochezia. The role of urgent colonoscopy after purge. Gastroenterology 1988; 95:1569.
  4. Zuckerman GR, Trellis DR, Sherman TM, Clouse RE. An objective measure of stool color for differentiating upper from lower gastrointestinal bleeding. Dig Dis Sci 1995; 40:1614.
  5. Wilcox CM, Alexander LN, Cotsonis G. A prospective characterization of upper gastrointestinal hemorrhage presenting with hematochezia. Am J Gastroenterol 1997; 92:231.
  6. Jutabha R, Jensen DM. Management of upper gastrointestinal bleeding in the patient with chronic liver disease. Med Clin North Am 1996; 80:1035.
  7. Boonpongmanee S, Fleischer DE, Pezzullo JC, et al. The frequency of peptic ulcer as a cause of upper-GI bleeding is exaggerated. Gastrointest Endosc 2004; 59:788.
  8. Enestvedt BK, Gralnek IM, Mattek N, et al. An evaluation of endoscopic indications and findings related to nonvariceal upper-GI hemorrhage in a large multicenter consortium. Gastrointest Endosc 2008; 67:422.
  9. Balderas V, Bhore R, Lara LF, et al. The hematocrit level in upper gastrointestinal hemorrhage: safety of endoscopy and outcomes. Am J Med 2011; 124:970.
  10. Loperfido S, Baldo V, Piovesana E, et al. Changing trends in acute upper-GI bleeding: a population-based study. Gastrointest Endosc 2009; 70:212.
  11. Hunt RH, Malfertheiner P, Yeomans ND, et al. Critical issues in the pathophysiology and management of peptic ulcer disease. Eur J Gastroenterol Hepatol 1995; 7:685.
  12. Hallas J, Lauritsen J, Villadsen HD, Gram LF. Nonsteroidal anti-inflammatory drugs and upper gastrointestinal bleeding, identifying high-risk groups by excess risk estimates. Scand J Gastroenterol 1995; 30:438.
  13. Graham DY, Hepps KS, Ramirez FC, et al. Treatment of Helicobacter pylori reduces the rate of rebleeding in peptic ulcer disease. Scand J Gastroenterol 1993; 28:939.
  14. Tytgat GN. Peptic ulcer and Helicobacter pylori: eradication and relapse. Scand J Gastroenterol Suppl 1995; 210:70.
  15. Rokkas T, Karameris A, Mavrogeorgis A, et al. Eradication of Helicobacter pylori reduces the possibility of rebleeding in peptic ulcer disease. Gastrointest Endosc 1995; 41:1.
  16. Bayerdörffer E, Neubauer A, Rudolph B, et al. Regression of primary gastric lymphoma of mucosa-associated lymphoid tissue type after cure of Helicobacter pylori infection. MALT Lymphoma Study Group. Lancet 1995; 345:1591.
  17. Nakamura S, Yao T, Aoyagi K, et al. Helicobacter pylori and primary gastric lymphoma. A histopathologic and immunohistochemical analysis of 237 patients. Cancer 1997; 79:3.
  18. Parsonnet J, Hansen S, Rodriguez L, et al. Helicobacter pylori infection and gastric lymphoma. N Engl J Med 1994; 330:1267.
  19. Pajares JM. H. pylori infection: its role in chronic gastritis, carcinoma and peptic ulcer. Hepatogastroenterology 1995; 42:827.
  20. Shibata T, Imoto I, Ohuchi Y, et al. Helicobacter pylori infection in patients with gastric carcinoma in biopsy and surgical resection specimens. Cancer 1996; 77:1044.
  21. Soll AH. Consensus conference. Medical treatment of peptic ulcer disease. Practice guidelines. Practice Parameters Committee of the American College of Gastroenterology. JAMA 1996; 275:622.
  22. Hopkins RJ, Girardi LS, Turney EA. Relationship between Helicobacter pylori eradication and reduced duodenal and gastric ulcer recurrence: a review. Gastroenterology 1996; 110:1244.
  23. Walsh JH, Peterson WL. The treatment of Helicobacter pylori infection in the management of peptic ulcer disease. N Engl J Med 1995; 333:984.
  24. Scheiman JM. NSAID-induced peptic ulcer disease: a critical review of pathogenesis and management. Dig Dis 1994; 12:210.
  25. Bretagne JF, Raoul JL. Management of nonsteroidal anti-inflammatory drug-induced upper gastrointestinal bleeding and perforation. Dig Dis 1995; 13 Suppl 1:89.
  26. Bjorkman DJ, Kimmey MB. Nonsteroidal anti-inflammatory drugs and gastrointestinal disease: pathophysiology, treatment and prevention. Dig Dis 1995; 13:119.
  27. Lanas A, Perez-Aisa MA, Feu F, et al. A nationwide study of mortality associated with hospital admission due to severe gastrointestinal events and those associated with nonsteroidal antiinflammatory drug use. Am J Gastroenterol 2005; 100:1685.
  28. Lanas A, Wu P, Medin J, Mills EJ. Low doses of acetylsalicylic acid increase risk of gastrointestinal bleeding in a meta-analysis. Clin Gastroenterol Hepatol 2011; 9:762.
  29. De Berardis G, Lucisano G, D'Ettorre A, et al. Association of aspirin use with major bleeding in patients with and without diabetes. JAMA 2012; 307:2286.
  30. Hansen JM, Hallas J, Lauritsen JM, Bytzer P. Non-steroidal anti-inflammatory drugs and ulcer complications: a risk factor analysis for clinical decision-making. Scand J Gastroenterol 1996; 31:126.
  31. Koch M, Dezi A, Ferrario F, Capurso I. Prevention of nonsteroidal anti-inflammatory drug-induced gastrointestinal mucosal injury. A meta-analysis of randomized controlled clinical trials. Arch Intern Med 1996; 156:2321.
  32. Smalley WE, Ray WA, Daugherty JR, Griffin MR. Nonsteroidal anti-inflammatory drugs and the incidence of hospitalizations for peptic ulcer disease in elderly persons. Am J Epidemiol 1995; 141:539.
  33. Lanas AI, Remacha B, Esteva F, Sáinz R. Risk factors associated with refractory peptic ulcers. Gastroenterology 1995; 109:1124.
  34. Navab F, Steingrub J. Stress ulcer: is routine prophylaxis necessary? Am J Gastroenterol 1995; 90:708.
  35. Zimmerman J, Meroz Y, Siguencia J, et al. Upper gastrointestinal hemorrhage. Comparison of the causes and prognosis in primary and secondary bleeders. Scand J Gastroenterol 1994; 29:795.
  36. Cook DJ, Fuller HD, Guyatt GH, et al. Risk factors for gastrointestinal bleeding in critically ill patients. Canadian Critical Care Trials Group. N Engl J Med 1994; 330:377.
  37. Kuusela AL, Ruuska T, Karikoski R, et al. A randomized, controlled study of prophylactic ranitidine in preventing stress-induced gastric mucosal lesions in neonatal intensive care unit patients. Crit Care Med 1997; 25:346.
  38. Cook DJ, Reeve BK, Guyatt GH, et al. Stress ulcer prophylaxis in critically ill patients. Resolving discordant meta-analyses. JAMA 1996; 275:308.
  39. Balaban DH, Duckworth CW, Peura DA. Nasogastric omeprazole: effects on gastric pH in critically Ill patients. Am J Gastroenterol 1997; 92:79.
  40. Peterson WL. The role of acid in upper gastrointestinal haemorrhage due to ulcer and stress-related mucosal damage. Aliment Pharmacol Ther 1995; 9 Suppl 1:43.
  41. Kim T, Shijo H, Kokawa H, et al. Risk factors for hemorrhage from gastric fundal varices. Hepatology 1997; 25:307.
  42. Smith JL, Graham DY. Variceal hemorrhage: a critical evaluation of survival analysis. Gastroenterology 1982; 82:968.
  43. de Souza AR, La Mura V, Reverter E, et al. Patients whose first episode of bleeding occurs while taking a β-blocker have high long-term risks of rebleeding and death. Clin Gastroenterol Hepatol 2012; 10:670.
  44. Garcia-Tsao G, Sanyal AJ, Grace ND, et al. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology 2007; 46:922.
  45. Groszmann RJ, Garcia-Tsao G, Bosch J, et al. Beta-blockers to prevent gastroesophageal varices in patients with cirrhosis. N Engl J Med 2005; 353:2254.
  46. García-Pagán JC, Caca K, Bureau C, et al. Early use of TIPS in patients with cirrhosis and variceal bleeding. N Engl J Med 2010; 362:2370.
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Oct 2013. | This topic last updated: Sep 24, 2012.
INTRODUCTION  — Upper gastrointestinal bleeding is a common medical condition that results in high patient morbidity and medical care costs. In a study from one large health maintenance organization in the United States, the annual incidence of hospitalization for acute upper gastrointestinal bleeding was approximately 100 per 100,000 adults; the incidence was twice as common in males as in females and increased with age [ 1 ]. Interestingly, the prognosis of patients with upper gastrointestinal bleeding appears to be improving, whether due to nonvariceal or variceal bleeding [ 2 ].
Upper gastrointestinal bleeding commonly presents with hematemesis (vomiting of blood or coffee-ground like material) and/or melena (black, tarry stools). In a small proportion of cases, upper gastrointestinal bleeding presents as hematochezia. In this situation, bleeding is typically brisk, and if accompanied by hemodynamic instability, represents a medical emergency. Nasogastric tube lavage may be used to confirm this clinical diagnosis, but it is often not necessary and may not be positive, even in the presence of an upper gastrointestinal tract lesion, if bleeding has ceased or arises beyond a closed pylorus. It is important to take a careful history and perform a careful physical examination since this will help localize the source of bleeding and, in turn, shed light on the possible etiology of bleeding. Although helpful, localization of the source of bleeding based upon stool color is not absolute since melena can be seen with proximal lower GI bleeding (especially slow bleeding in some patients), and hematochezia can be seen with massive upper GI bleeding as highlighted above [ 3-5 ]. (See "Approach to resuscitation and diagnosis of acute lower gastrointestinal bleeding in the adult patient" .)
This topic will review the major causes of bleeding from the upper gastrointestinal tract. The most common causes of upper gastrointestinal bleeding are ulcerative disease of the stomach and/or duodenum (often referred to as "peptic ulcer disease") and gastroesophageal varices. The approach to the diagnosis and management of patients with upper gastrointestinal bleeding, as well as other causes of upper gastrointestinal bleeding, such as angiodysplasia, neoplasms, and hemobilia are discussed separately. (See "Approach to acute upper gastrointestinal bleeding in adults" and "Overview of the treatment of bleeding peptic ulcers" and"Uncommon causes of upper gastrointestinal bleeding in adults" and "Mallory-Weiss syndrome" .)
COMMON CAUSES OF UPPER GASTROINTESTINAL BLEEDING  — Upper gastrointestinal bleeding can be classified into several broad categories based upon anatomic and pathophysiologic factors ( table 1 ). Several endoscopic studies have described the most common causes [ 6-9 ]. The reported frequencies of the causes vary, possibly reflecting trends over time or differences in study design, populations, and definitions.
The most common causes of upper gastrointestinal bleeding include the following [ 6 ]:
  • Gastric and/or duodenal ulcers
  • Esophagogastric varices with or without portal hypertensive gastropathy
  • Esophagitis
  • Erosive gastritis/duodenitis
  • Mallory-Weiss syndrome
  • Angiodysplasia
  • Mass lesions (polyps/cancers)
  • Dieulafoy's lesion
Uncommon causes of upper gastrointestinal bleeding include hemobilia, hemosuccus pancreaticus, and aortoenteric fistula. In 11 percent of cases, no upper GI lesion can be identified. (See "Uncommon causes of upper gastrointestinal bleeding in adults" .)
Whereas older studies suggested that peptic ulcer disease was responsible for approximately half of upper gastrointestinal bleeds [ 6 ], more recent studies suggest it is now a less common cause [ 7,8,10 ]:
  • Peptic ulcers were responsible for 21 percent of episodes of upper gastrointestinal bleeding among 7822 patients included in a national, United States database between 1999 and 2001 [ 7 ]. The most common cause was nonspecific mucosal abnormalities (42 percent), while esophageal inflammation and varices accounted for approximately 15 and 12 percent, respectively. Other causes (angiodysplasia, Mallory-Weiss tears, and tumors) each accounted for less than 5 percent of cases. Among ulcer cases, gastric ulcers were more common than duodenal ulcers, representing about 55 percent of all ulcers.
  • A large database study focused on 243,428 upper endoscopies performed between 2000 and 2004 in a practice setting (rather than in tertiary care) [ 8 ]. The most common endoscopic findings in patients with upper gastrointestinal bleeding were an ulcer (33 percent) followed by an erosion (19 percent). Gastric ulcers were more common than duodenal ulcers (55 versus 37 percent). Patients with variceal bleeding were excluded from the analysis.
PEPTIC ULCER DISEASE  — Gastroduodenal ulcer disease remains a common cause of upper gastrointestinal bleeding ( picture 1A-B and picture 2 and picture 3 andmovie 1 ) [ 6 ]. There are four major risk factors for bleeding peptic ulcers [ 11,12 ] (see "Epidemiology and etiology of peptic ulcer disease" and "Unusual causes of peptic ulcer disease" ):
  • Helicobacter pylori infection
  • Nonsteroidal anti-inflammatory drugs (NSAIDs)
  • Physiologic stress
  • Excess gastric acid
Reduction or elimination of these risk factors reduces ulcer recurrence and rebleeding rates [ 13-16 ].
Helicobacter pylori  — Helicobacter pylori is a spiral bacterium that infects the superficial gastric mucosa and appears to be transmitted by the fecal-oral route. The bacterium generally does not invade gastroduodenal tissue. Instead, it renders the underlying mucosa more vulnerable to acid peptic damage by disrupting the mucous layer, liberating enzymes and toxins, and adhering to the gastric epithelium. In addition, the host immune response to H. pylori incites an inflammatory reaction which further perpetuates tissue injury. (See "Pathophysiology of and immune response to Helicobacter pylori infection" .)
The chronic inflammation induced by H. pylori upsets gastric secretory physiology to varying degrees and leads to chronic gastritis that, in most individuals, is asymptomatic and does not progress. In some cases, however, altered gastric secretion coupled with tissue injury leads to peptic ulcer disease, while in other cases, gastritis progresses to atrophy, intestinal metaplasia, and eventually to gastric carcinoma or rarely, due to persistent immune stimulation of gastric lymphoid tissue, gastric lymphoma [ 17-20 ]. (See "Association between Helicobacter pylori infection and gastrointestinal malignancy" .)
H. pylori eradication should be attempted for all patients who are diagnosed with the infection and who have peptic ulcer disease to prevent ulcer recurrence and rebleeding [ 21,22 ]. In one report of 19 published studies, for example, the recurrence rates in cured versus noncured H. pylori infection were 6 versus 67 percent for duodenal ulcers, and 4 versus 59 percent for gastric ulcers [ 22 ]. Various multidrug regimens (usually a combination of antibiotics and an antisecretory agent) have eradication rates in the range of 80 to 90 percent [ 23 ]. (See "Treatment regimens for Helicobacter pylori" .)
Nonsteroidal anti-inflammatory drugs  — NSAIDs, including low-dose aspirin , are a common cause of gastrointestinal ulceration [ 24-29 ]. NSAID-induced injury results from both local effects and systemic prostaglandin inhibition. The majority of these ulcers are asymptomatic and uncomplicated. However, elderly patients with a prior history of bleeding ulcer disease are at increased risk for recurrent ulcer and complications [ 30-32 ]. NSAIDs also have been implicated as an important factor for non-healing ulcers [ 33 ]. (See "NSAIDs (including aspirin): Pathogenesis of gastroduodenal toxicity" .)
Stress  — Stress related ulcers are a common cause of acute upper gastrointestinal bleeding in patients who are hospitalized for life-threatening non-bleeding illnesses [ 34 ]. Patients with these secondary episodes of bleeding have a higher mortality than those admitted to the hospital with primary upper gastrointestinal bleeding [ 35 ]. The risk of stress ulcer-related bleeding is increased in patients with respiratory failure and those with a coagulopathy [ 36 ]. Primary ulcer prophylaxis with antisecretory agents such as H2 receptor antagonists or proton pump inhibitors decreases the risk of stress related mucosal damage and upper gastrointestinal bleeding in high-risk patients [ 37-39 ]. (See "Stress ulcer prophylaxis in the intensive care unit" .)
Gastric acid  — Gastric acid and pepsin are essential cofactors in the pathogenesis of peptic ulcers [ 40 ]. Impairment of mucosal integrity by factors such as H. pylori, NSAIDs, or physiologic stress leads to increased cell membrane permeability to back diffusion of hydrogen ions, resulting in intramural acidosis, cell death, and ulceration [ 40 ]. Rarely, hyperacidity is the sole cause of peptic ulceration, as in patients with the Zollinger-Ellison syndrome. Control of gastric acidity is considered an essential therapeutic maneuver in patients with active upper gastrointestinal bleeding. (See "Clinical manifestations and diagnosis of Zollinger-Ellison syndrome (gastrinoma)" and "Approach to acute upper gastrointestinal bleeding in adults" .)
Treatment  — Treatment of bleeding peptic ulcers typically involves acid suppression, endoscopic therapy, and treatment/removal of risk factors for peptic ulcer disease. The approach to the treatment of bleeding peptic ulcers is discussed in detail elsewhere. (See "Approach to acute upper gastrointestinal bleeding in adults"and "Overview of the treatment of bleeding peptic ulcers" .)
ESOPHAGOGASTRIC VARICES  — Esophagogastric varices develop as a consequence of portal hypertension ( picture 4A-B and picture 5 ). The most common causes of portal hypertension in the United States are viral hepatitis, alcoholic liver disease, and nonalcoholic steatohepatitis (NASH). (See "Prediction of variceal hemorrhage in patients with cirrhosis" and "Diagnostic approach to the patient with cirrhosis" .)
Isolated gastric varices can result from segmental portal hypertension due to obstruction of the splenic vein from pancreatitis, pancreatic carcinoma, or trauma in the left upper quadrant ( picture 5 ). The risk factors for bleeding from gastric varices are similar to the risk factors for bleeding from esophageal varices [ 41 ]. (See"Prediction of variceal hemorrhage in patients with cirrhosis" .)
Diagnosis  — Endoscopy is the diagnostic modality of choice for esophagogastric varices [ 6 ]. If endoscopy is inconclusive and gastric variceal bleeding is suspected, one of the following tests should be considered to confirm the clinical suspicion:
Prognosis  — Variceal bleeding stops spontaneously in over 50 percent of patients, but the mortality rate approaches 70 to 80 percent in those with continued bleeding. Each episode of variceal hemorrhage is associated with a 30 percent risk of mortality [ 42 ]. The risk of rebleeding is high (60 to 70 percent) until gastroesophageal varices are obliterated.
The risk of rebleeding can be substantially reduced by follow-up endoscopic therapy to obliterate residual varices. However, long-term survival depends upon the severity of liver disease and may not be improved following successful variceal obliteration. The administration of a nonselective beta blocker such as propranololcan also decrease the risk of rebleeding. (See "Prevention of recurrent variceal hemorrhage in patients with cirrhosis" .)
The onset of massive upper gastrointestinal bleeding from gastroesophageal varices usually signifies advanced liver disease (Child class B or C), and patients who develop bleeding while being treated with a beta-blocker have a poor prognosis [ 43 ]. Liver transplantation is the only treatment that significantly improves the long-term prognosis in these patients.
Treatment  — Primary prophylaxis against variceal hemorrhage is desirable in view of the relatively high rate of bleeding from esophageal varices and the high mortality associated with this complication [ 44 ]. "Pre-primary" prophylaxis, in an attempt to prevent development of varices, is not recommended [ 45 ]. (See "Primary and pre-primary prophylaxis against variceal hemorrhage in patients with cirrhosis" .)
Various treatments are available for acute hemostasis [ 44 ]. Endoscopic band ligation is the standard treatment, with sclerotherapy used in situations where band ligation is not technically feasible. Early transjugular intrahepatic portosystemic shunt (TIPS) placement may be appropriate early in the course for some patients with gastroesophageal bleeding [ 46 ]. If this treatment is considered, it is critical that it be undertaken in collaboration with an experienced hepatologist. (See "Treatment of active variceal hemorrhage" .)
INFORMATION FOR PATIENTS  — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5 th to 6 th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10 th to 12 th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
SUMMARY
  • Upper gastrointestinal bleeding is a common medical condition that results in high patient morbidity and medical care costs, with an annual incidence in the Unites States of approximately 100 per 100,000 adults.
  • The most common causes of upper gastrointestinal bleeding include gastric and/or duodenal ulcers ( picture 6 and picture 2 and movie 1 and image 1 ) and esophagogastric varices ( picture 7A-B and table 1 ), with or without portal hypertensive gastropathy. Other common causes include. Other common causes include (see 'Common causes of upper gastrointestinal bleeding' above):
  • Esophagitis
  • Severe or erosive gastritis/duodenitis
  • Mallory-Weiss syndrome
  • Angiodysplasia
  • Mass lesions (polyps/cancers)
  • Dieulafoy's lesion
  • No lesion identified
  • Uncommon causes of upper gastrointestinal bleeding include hemobilia, hemosuccus pancreaticus, and aortoenteric fistula. (See "Uncommon causes of upper gastrointestinal bleeding in adults" .)
  • Helicobacter pylori infection, nonsteroidal anti-inflammatory drugs, physiologic stress, and excess gastric acid are major risk factors for bleeding peptic ulcers. Reduction or elimination of these risk factors reduces ulcer recurrence and rebleeding rates. (See 'Peptic ulcer disease' above.)
  • Esophagogastric varices develop as a consequence of portal hypertension. The most common causes of portal hypertension in the United States are viral hepatitis, alcoholic liver disease, and nonalcoholic steatohepatitis (NASH). (See 'Esophagogastric varices' above.)
ACKNOWLEDGMENT  — The author and UpToDate would like to thank Drs. Rome Jutabha and Dennis Jensen, who contributed to earlier versions of this topic review.

REFERENCES

  1. Longstreth GF. Epidemiology of hospitalization for acute upper gastrointestinal hemorrhage: a population-based study. Am J Gastroenterol 1995; 90:206.
  2. Crooks C, Card T, West J. Reductions in 28-day mortality following hospital admission for upper gastrointestinal hemorrhage. Gastroenterology 2011; 141:62.
  3. Jensen DM, Machicado GA. Diagnosis and treatment of severe hematochezia. The role of urgent colonoscopy after purge. Gastroenterology 1988; 95:1569.
  4. Zuckerman GR, Trellis DR, Sherman TM, Clouse RE. An objective measure of stool color for differentiating upper from lower gastrointestinal bleeding. Dig Dis Sci 1995; 40:1614.
  5. Wilcox CM, Alexander LN, Cotsonis G. A prospective characterization of upper gastrointestinal hemorrhage presenting with hematochezia. Am J Gastroenterol 1997; 92:231.
  6. Jutabha R, Jensen DM. Management of upper gastrointestinal bleeding in the patient with chronic liver disease. Med Clin North Am 1996; 80:1035.
  7. Boonpongmanee S, Fleischer DE, Pezzullo JC, et al. The frequency of peptic ulcer as a cause of upper-GI bleeding is exaggerated. Gastrointest Endosc 2004; 59:788.
  8. Enestvedt BK, Gralnek IM, Mattek N, et al. An evaluation of endoscopic indications and findings related to nonvariceal upper-GI hemorrhage in a large multicenter consortium. Gastrointest Endosc 2008; 67:422.
  9. Balderas V, Bhore R, Lara LF, et al. The hematocrit level in upper gastrointestinal hemorrhage: safety of endoscopy and outcomes. Am J Med 2011; 124:970.
  10. Loperfido S, Baldo V, Piovesana E, et al. Changing trends in acute upper-GI bleeding: a population-based study. Gastrointest Endosc 2009; 70:212.
  11. Hunt RH, Malfertheiner P, Yeomans ND, et al. Critical issues in the pathophysiology and management of peptic ulcer disease. Eur J Gastroenterol Hepatol 1995; 7:685.
  12. Hallas J, Lauritsen J, Villadsen HD, Gram LF. Nonsteroidal anti-inflammatory drugs and upper gastrointestinal bleeding, identifying high-risk groups by excess risk estimates. Scand J Gastroenterol 1995; 30:438.
  13. Graham DY, Hepps KS, Ramirez FC, et al. Treatment of Helicobacter pylori reduces the rate of rebleeding in peptic ulcer disease. Scand J Gastroenterol 1993; 28:939.
  14. Tytgat GN. Peptic ulcer and Helicobacter pylori: eradication and relapse. Scand J Gastroenterol Suppl 1995; 210:70.
  15. Rokkas T, Karameris A, Mavrogeorgis A, et al. Eradication of Helicobacter pylori reduces the possibility of rebleeding in peptic ulcer disease. Gastrointest Endosc 1995; 41:1.
  16. Bayerdörffer E, Neubauer A, Rudolph B, et al. Regression of primary gastric lymphoma of mucosa-associated lymphoid tissue type after cure of Helicobacter pylori infection. MALT Lymphoma Study Group. Lancet 1995; 345:1591.
  17. Nakamura S, Yao T, Aoyagi K, et al. Helicobacter pylori and primary gastric lymphoma. A histopathologic and immunohistochemical analysis of 237 patients. Cancer 1997; 79:3.
  18. Parsonnet J, Hansen S, Rodriguez L, et al. Helicobacter pylori infection and gastric lymphoma. N Engl J Med 1994; 330:1267.
  19. Pajares JM. H. pylori infection: its role in chronic gastritis, carcinoma and peptic ulcer. Hepatogastroenterology 1995; 42:827.
  20. Shibata T, Imoto I, Ohuchi Y, et al. Helicobacter pylori infection in patients with gastric carcinoma in biopsy and surgical resection specimens. Cancer 1996; 77:1044.
  21. Soll AH. Consensus conference. Medical treatment of peptic ulcer disease. Practice guidelines. Practice Parameters Committee of the American College of Gastroenterology. JAMA 1996; 275:622.
  22. Hopkins RJ, Girardi LS, Turney EA. Relationship between Helicobacter pylori eradication and reduced duodenal and gastric ulcer recurrence: a review. Gastroenterology 1996; 110:1244.
  23. Walsh JH, Peterson WL. The treatment of Helicobacter pylori infection in the management of peptic ulcer disease. N Engl J Med 1995; 333:984.
  24. Scheiman JM. NSAID-induced peptic ulcer disease: a critical review of pathogenesis and management. Dig Dis 1994; 12:210.
  25. Bretagne JF, Raoul JL. Management of nonsteroidal anti-inflammatory drug-induced upper gastrointestinal bleeding and perforation. Dig Dis 1995; 13 Suppl 1:89.
  26. Bjorkman DJ, Kimmey MB. Nonsteroidal anti-inflammatory drugs and gastrointestinal disease: pathophysiology, treatment and prevention. Dig Dis 1995; 13:119.
  27. Lanas A, Perez-Aisa MA, Feu F, et al. A nationwide study of mortality associated with hospital admission due to severe gastrointestinal events and those associated with nonsteroidal antiinflammatory drug use. Am J Gastroenterol 2005; 100:1685.
  28. Lanas A, Wu P, Medin J, Mills EJ. Low doses of acetylsalicylic acid increase risk of gastrointestinal bleeding in a meta-analysis. Clin Gastroenterol Hepatol 2011; 9:762.
  29. De Berardis G, Lucisano G, D'Ettorre A, et al. Association of aspirin use with major bleeding in patients with and without diabetes. JAMA 2012; 307:2286.
  30. Hansen JM, Hallas J, Lauritsen JM, Bytzer P. Non-steroidal anti-inflammatory drugs and ulcer complications: a risk factor analysis for clinical decision-making. Scand J Gastroenterol 1996; 31:126.
  31. Koch M, Dezi A, Ferrario F, Capurso I. Prevention of nonsteroidal anti-inflammatory drug-induced gastrointestinal mucosal injury. A meta-analysis of randomized controlled clinical trials. Arch Intern Med 1996; 156:2321.
  32. Smalley WE, Ray WA, Daugherty JR, Griffin MR. Nonsteroidal anti-inflammatory drugs and the incidence of hospitalizations for peptic ulcer disease in elderly persons. Am J Epidemiol 1995; 141:539.
  33. Lanas AI, Remacha B, Esteva F, Sáinz R. Risk factors associated with refractory peptic ulcers. Gastroenterology 1995; 109:1124.
  34. Navab F, Steingrub J. Stress ulcer: is routine prophylaxis necessary? Am J Gastroenterol 1995; 90:708.
  35. Zimmerman J, Meroz Y, Siguencia J, et al. Upper gastrointestinal hemorrhage. Comparison of the causes and prognosis in primary and secondary bleeders. Scand J Gastroenterol 1994; 29:795.
  36. Cook DJ, Fuller HD, Guyatt GH, et al. Risk factors for gastrointestinal bleeding in critically ill patients. Canadian Critical Care Trials Group. N Engl J Med 1994; 330:377.
  37. Kuusela AL, Ruuska T, Karikoski R, et al. A randomized, controlled study of prophylactic ranitidine in preventing stress-induced gastric mucosal lesions in neonatal intensive care unit patients. Crit Care Med 1997; 25:346.
  38. Cook DJ, Reeve BK, Guyatt GH, et al. Stress ulcer prophylaxis in critically ill patients. Resolving discordant meta-analyses. JAMA 1996; 275:308.
  39. Balaban DH, Duckworth CW, Peura DA. Nasogastric omeprazole: effects on gastric pH in critically Ill patients. Am J Gastroenterol 1997; 92:79.
  40. Peterson WL. The role of acid in upper gastrointestinal haemorrhage due to ulcer and stress-related mucosal damage. Aliment Pharmacol Ther 1995; 9 Suppl 1:43.
  41. Kim T, Shijo H, Kokawa H, et al. Risk factors for hemorrhage from gastric fundal varices. Hepatology 1997; 25:307.
  42. Smith JL, Graham DY. Variceal hemorrhage: a critical evaluation of survival analysis. Gastroenterology 1982; 82:968.
  43. de Souza AR, La Mura V, Reverter E, et al. Patients whose first episode of bleeding occurs while taking a β-blocker have high long-term risks of rebleeding and death. Clin Gastroenterol Hepatol 2012; 10:670.
  44. Garcia-Tsao G, Sanyal AJ, Grace ND, et al. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology 2007; 46:922.
  45. Groszmann RJ, Garcia-Tsao G, Bosch J, et al. Beta-blockers to prevent gastroesophageal varices in patients with cirrhosis. N Engl J Med 2005; 353:2254.
  46. García-Pagán JC, Caca K, Bureau C, et al. Early use of TIPS in patients with cirrhosis and variceal bleeding. N Engl J Med 2010; 362:2370.
at

No comments:

Post a Comment

Subscribe to: Post Comments (Atom)

Achlorhydria (abse n ce of gastric acid sec r etion) can be caused by im m u ne destruction to the sto...