World Library  
Flag as Inappropriate
Email this Article

Gastroesophageal reflux disease

Article Id: WHEBN0000196991
Reproduction Date:

Title: Gastroesophageal reflux disease  
Author: World Heritage Encyclopedia
Language: English
Subject: Cough, Peptic ulcer, Achalasia, Discovery and development of proton pump inhibitors, Esophageal pH monitoring
Collection: Medical Conditions Related to Obesity, Stomach Disorders
Publisher: World Heritage Encyclopedia

Gastroesophageal reflux disease

Gastroesophageal reflux disease
X-ray showing radiocontrast agent injected into the stomach entering the esophagus due to severe reflux
Classification and external resources
Specialty Gastroenterology
ICD-10 K21
ICD-9-CM 530.81
OMIM 109350
DiseasesDB 23596
MedlinePlus 000265
eMedicine med/857 ped/1177 radio/300
MeSH D005764

Gastroesophageal reflux disease (GERD), gastro-oesophageal reflux disease (GORD), gastric reflux disease, acid reflux disease, or reflux (in babies and young children) is a chronic symptom of mucosal damage caused by stomach acid coming up from the stomach into the esophagus.[1]

GERD is usually caused by changes in the barrier between the stomach and the esophagus, including abnormal relaxation of the lower esophageal sphincter, which normally holds the top of the stomach closed, impaired expulsion of gastric reflux from the esophagus, or a hiatal hernia. These changes may be permanent or temporary.

Treatment is typically via lifestyle changes and medications such as proton pump inhibitors, H2 receptor blockers or antacids with or without alginic acid.[2] Surgery may be an option in those who do not improve. In the Western world between 10 and 20% of the population is affected.[2]


  • Signs and symptoms 1
    • Adults 1.1
    • Children 1.2
    • Barrett's esophagus 1.3
  • Causes 2
  • Diagnosis 3
    • Endoscopy 3.1
    • Differential diagnosis 3.2
  • Treatment 4
    • Lifestyle 4.1
    • Medications 4.2
    • Surgery 4.3
    • Pregnancy 4.4
    • Infants 4.5
    • Overtreatment 4.6
  • Epidemiology 5
  • History 6
  • Research 7
  • References 8
  • Further reading 9
  • External links 10

Signs and symptoms


The most-common symptoms of GERD in adults are heartburn[3] and regurgitation. Less-common symptoms include pain with swallowing/sore throat, increased salivation (also known as water brash), nausea,[4] chest pain, and coughing.

GERD sometimes causes injury of the esophagus. These injuries may include one or more of the following:

Some people have proposed that symptoms such as sinusitis, recurrent ear infections, and idiopathic pulmonary fibrosis are due to GERD; however, a causative role has not been established.[4]


GERD may be difficult to detect in infants and children, since they cannot describe what they are feeling and indicators must be observed. Symptoms may vary from typical adult symptoms. GERD in children may cause repeated vomiting, effortless spitting up, coughing, and other respiratory problems, such as wheezing. Inconsolable crying, refusing food, crying for food and then pulling off the bottle or breast only to cry for it again, failure to gain adequate weight, bad breath, and belching or burping are also common. Children may have one symptom or many; no single symptom is universal in all children with GERD.

Of the estimated 4 million babies born in the US each year, up to 35% of them may have difficulties with reflux in the first few months of their lives, known as 'spitting up'.[6] One theory for this is the "fourth trimester theory" which notes most animals are born with significant mobility, but humans are relatively helpless at birth, and suggests there may have once been a fourth trimester, but children began to be born earlier, evolutionarily, to accommodate the development of larger heads and brains and allow them to pass through the birth canal and this leaves them with partially undeveloped digestive systems.

Most children will outgrow their reflux by their first birthday. However, a small but significant number of them will not outgrow the condition. This is particularly true when a family history of GERD is present.

Barrett's esophagus

GERD may lead to Barrett's esophagus, a type of intestinal metaplasia,[5] which is in turn a precursor condition for esophageal cancer. The risk of progression from Barrett's to dysplasia is uncertain, but is estimated at about 20% of cases.[7] Due to the risk of chronic heartburn progressing to Barrett's, EGD every five years is recommended for people with chronic heartburn, or who take drugs for chronic GERD.[8]


GERD is caused by a failure of the lower esophageal sphincter. In healthy patients, the "Angle of His"—the angle at which the esophagus enters the stomach—creates a valve that prevents duodenal bile, enzymes, and stomach acid from traveling back into the esophagus where they can cause burning and inflammation of sensitive esophageal tissue.

Factors that can contribute to GERD:

  • Hiatal hernia, which increases the likelihood of GERD due to mechanical and motility factors.[9][10]
  • Obesity: increasing body mass index is associated with more severe GERD.[11] In a large series of 2000 patients with symptomatic reflux disease, it has been shown that 13% of changes in esophageal acid exposure is attributable to changes in body mass index.[12]
  • Zollinger-Ellison syndrome, which can be present with increased gastric acidity due to gastrin production.
  • A high blood calcium level, which can increase gastrin production, leading to increased acidity.
  • Scleroderma and systemic sclerosis, which can feature esophageal dysmotility.
  • The use of medicines such as prednisolone.
  • Visceroptosis or Glénard syndrome, in which the stomach has sunk in the abdomen upsetting the motility and acid secretion of the stomach.

GERD has been linked to a variety of respiratory and laryngeal complaints such as laryngitis, chronic cough, pulmonary fibrosis, earache, and asthma, even when not clinically apparent. These atypical manifestations of GERD are commonly referred to as laryngopharyngeal reflux (LPR) or as extraesophageal reflux disease (EERD).

Factors that have been linked with GERD, but not conclusively:

In 1999, a review of existing studies found that, on average, 40% of GERD patients also had H. pylori infection.[15] The eradication of H. pylori can lead to an increase in acid secretion,[16] leading to the question of whether H. pylori-infected GERD patients are any different than non-infected GERD patients. A double-blind study, reported in 2004, found no clinically significant difference between these two types of patients with regard to the subjective or objective measures of disease severity.[17]


Endoscopic image of peptic stricture, or narrowing of the esophagus near the junction with the stomach: This is a complication of chronic gastroesophageal reflux disease and can be a cause of dysphagia or difficulty swallowing.

The diagnosis of GERD is usually made when typical symptoms are present.[18] Reflux can be present in people without symptoms and the diagnosis requires both symptoms or complications and reflux of stomach content.[19]

Other investigations may include esophagogastroduodenoscopy (EGD). Barium swallow X-rays should not be used for diagnosis.[18] Esophageal manometry is not recommended for use in diagnosis being recommended only prior to surgery.[18] Ambulatory esophageal pH monitoring may be useful in those who do not improve after PPIs and is not needed in those in whom Barrett's esophagus is seen.[18] Investigations for H. pylori is not usually needed.[18]

The current gold standard for diagnosis of GERD is esophageal pH monitoring. It is the most objective test to diagnose the reflux disease and allows monitoring GERD patients in their response to medical or surgical treatment. One practice for diagnosis of GERD is a short-term treatment with proton-pump inhibitors, with improvement in symptoms suggesting a positive diagnosis. Short-term treatment with proton-pump inhibitors may help predict abnormal 24-hr pH monitoring results among patients with symptoms suggestive of GERD.[20]


Endoscopy, the looking down into the stomach with a fibre-optic scope, is not routinely needed if the case is typical and responds to treatment.[18] It is recommended when people either do not respond well to treatment or have alarm symptoms, including dysphagia, anemia, blood in the stool (detected chemically), wheezing, weight loss, or voice changes.[18] Some physicians advocate either once-in-a-lifetime or 5- to 10-yearly endoscopy for people with longstanding GERD, to evaluate the possible presence of dysplasia or Barrett's esophagus.[21]

Biopsies performed during gastroscopy may show:

  • Edema and basal hyperplasia (nonspecific inflammatory changes)
  • Lymphocytic inflammation (nonspecific)
  • Neutrophilic inflammation (usually due to reflux or Helicobacter gastritis)
  • Eosinophilic inflammation (usually due to reflux): The presence of intraepithelial eosinophils may suggest a diagnosis of eosinophilic esophagitis (EE) if eosinophils are present in high enough numbers. Less than 20 eosinophils per high-power microscopic field in the distal esophagus, in the presence of other histologic features of GERD, is more consistent with GERD than EE.[22]
  • Goblet cell intestinal metaplasia or Barrett's esophagus
  • Elongation of the papillae
  • Thinning of the squamous cell layer
  • Dysplasia
  • Carcinoma

Reflux changes may not be erosive in nature, leading to "nonerosive reflux disease".

Differential diagnosis

Other causes of chest pain such as heart disease should be ruled out before making the diagnosis.[18] Another kind of acid reflux, which causes respiratory and laryngeal signs and symptoms, is called laryngopharyngeal reflux (LPR) or "extraesophageal reflux disease" (EERD). Unlike GERD, LPR rarely produces heartburn, and is sometimes called silent reflux.


The treatments for GERD include lifestyle modifications, medications, and possibly surgery. Initial treatment is frequently with a proton-pump inhibitor such as omeprazole.[18]


Certain foods and lifestyle are considered to promote gastroesophageal reflux, but most dietary interventions have little supporting evidence.[23] Avoidance of specific foods and of eating before lying down should only be recommended to those in which they are associated with the symptoms.[19] Foods that have been implicated include coffee, alcohol, chocolate, fatty foods, acidic foods, and spicy foods.[19] Weight loss and elevating the head of the bed are generally useful.[24] Moderate exercise improves symptoms; however in those with GERD vigorous exercise may worsen them.[23] Stopping smoking and not drinking alcohol do not appear to result in significant improvement in symptoms.[24]


The primary medications used for GERD are proton-pump inhibitors, H2 receptor blockers and antacids with or without alginic acid.[2]

Proton-pump inhibitors (PPIs), such as omeprazole, are the most effective, followed by H2 receptor blockers, such as ranitidine.[19] If a once daily PPI is only partially effective they may be used twice a day.[19] They should be taken one half to one hour before a meal.[18] There is no significant difference between agents in this class.[18] When these medications are used long term, the lowest effective dose should be taken.[19] They may also be taken only when symptoms occur in those with frequent problems.[18] H2 receptor blockers lead to roughly a 40% improvement.[25]

The evidence for antacids is weaker with a benefit of about 10% (NNT=13) while a combination of an antacid and alginic acid (such as Gaviscon) may improve symptoms 60% (NNT=4).[25] Metoclopramide (a prokinetic) is not recommended either alone or in combination with other treatments due to concerns around adverse effects.[2][19] The benefit of the prokinetic mosapride is modest.[2]

Sucralfate has a similar effectiveness to H2 receptor blockers; however, sucralfate needs to be taken multiple times a day, thus limiting its use.[2] Baclofen, an agonist of the GABAB receptor, while effective, has similar issues of needing frequent dosing in addition to greater adverse effects compared to other medications.[2]


The standard surgical treatment for severe GERD is the Nissen fundoplication. In this procedure, the upper part of the stomach is wrapped around the lower esophageal sphincter to strengthen the sphincter and prevent acid reflux and to repair a hiatal hernia.[26] It is only recommended in those who do not improve with PPIs.[18] Benefits are equal to medical treatment in those with chronic symptoms.[18] In addition, in the short and medium term, laparoscopic fundoplication improves quality of life compared to medical management.[27] When comparing different fundoplication techniques, partial posterior fundoplication surgery is more effective than partial anterior fundoplication surgery.[28]

In 2012 the FDA approved a device called the LINX, which consists of a series of metal beads with magnetic cores that are placed surgically around the lower esophageal sphincter, for those with severe symptoms that do not respond to other treatments. Improvement of GERD symptoms are similar to those of the Nissen fundoplication, although there is no data regarding long-term effects. Compared to Nissen fundoplication procedures, the procedure has shown a reduction in complications such as gas bloat syndrome that commonly occur.[29] Adverse responses include difficulty swallowing, chest pain, vomiting, and nausea. Contraindications that would advise against use of the device are patients who are or may be allergic to titanium, stainless steel, nickel, or ferrous iron materials. A warning advises that the device should not be used by patients who could be exposed to, or undergo, magnetic resonance imaging (MRI) because of serious injury to the patient and damage to the device.[30]


In pregnancy, dietary modifications and lifestyle changes may be attempted, but often have little effect. Calcium-based antacids are recommended if these changes are not effective. Aluminum- and magnesium-based antacids are also safe, as is ranitidine[31] and PPIs.[18]


Infants may see relief with changes in feeding techniques, such as smaller, more frequent feedings, changes in position during feedings, or more frequent burping during feedings.[32] They may also be treated with medicines such as ranitidine or proton pump inhibitors.[33] Proton pump inhibitors however have not been found to be effective in this population and there is a lack of evidence for safety.[34]


The use of acid suppression therapy is a common response to GERD symptoms and many patients get more of this kind of treatment than their individual case merits.[35] The overuse of this treatment is a problem because of the side effects and costs which the patient will have from undergoing unnecessary therapy, and patients should not take more treatment than they need.[35]

In some cases, a person with GERD symptoms can manage them by taking over-the-counter drugs and making lifestyle changes.[36] This is often safer and less expensive than taking prescription drugs.[36] Some guidelines recommend trying to treat symptoms with an H2 antagonist before using a proton-pump inhibitor because of cost and safety concerns.[36]


In Western populations GERD affects approximately 10% to 20% of the population and 0.4% newly develop the condition.[2] For instance, an estimated 3.4 million to 6.8 million Canadians are GERD sufferers. The prevalence rate of GERD in developed nations is also tightly linked with age, with adults aged 60 to 70 being the most commonly affected.[37] In the United States 20% of people have symptoms in a given week and 7% every day.[2] No data support sex predominance with regard to GERD.


An obsolete treatment is vagotomy ("highly selective vagotomy"), the surgical removal of vagus nerve branches that innervate the stomach lining. This treatment has been largely replaced by medication.


A number of endoscopic devices have been tested to treat chronic heartburn. One system, Endocinch, puts stitches in the lower esophogeal sphincter (LES) to create small pleats to help strengthen the muscle. However, long-term results were disappointing, and the device is no longer sold by Bard.[38] Another, the Stretta procedure, uses electrodes to apply radio-frequency energy to the LES. The long-term outcomes of both procedures compared to a Nissen fundoplication are still being determined.

The NDO Surgical Plicator creates a plication, or fold, of tissue near the gastroesophageal junction, and fixates the plication with a suture-based implant. The company ceased operations in mid-2008, and the device is no longer on the market.

Another treatment, transoral incisionless fundoplication, which uses a device called Esophyx, may be effective.[39]


  1. ^ DeVault KR, Castell DO (1999). "Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease. The Practice Parameters Committee of the American College of Gastroenterology".  
  2. ^ a b c d e f g h i Hershcovici T, Fass R (April 2011). "Pharmacological management of GERD: where does it stand now?". Trends in pharmacological sciences 32 (4): 258–64.  
  3. ^ Zajac P, Holbrook A, Super ME, Vogt M (March–April 2013). "An overview: Current clinical guidelines for the evaluation, diagnosis, treatment, and management of dyspepsia". Osteopathic Family Physician 5 (2): 79–85.  
  4. ^ a b c Kahrilas PJ (2008). "Gastroesophageal Reflux Disease".  
  5. ^ a b Wang KK, Sampliner RE (March 2008). "Updated guidelines 2008 for the diagnosis, surveillance and therapy of Barrett's esophagus" (PDF).  
  6. ^ "Spitting Up in Babies". 
  7. ^ and Barrett's Esophagus. Retrieved on 2009-02-01.
  8. ^ "Patient information: Barrett's esophagus (Beyond the Basics)". June 2009. 
  9. ^ Sontag SJ (1999). "Defining GERD". Yale J Biol Med 72 (2–3): 69–80.  
  10. ^ Piesman M, Hwang I, Maydonovitch C, Wong RK (2007). "Nocturnal reflux episodes following the administration of a standardized meal. Does timing matter?".  
  11. ^ Ayazi S; Crookes PF; Peyre CG; et al. (2007). "Objective documentation of the link between gastroesophageal reflux disease and obesity".  
  12. ^ Ayazi S, Hagen JA, Chan LS, DeMeester SR, Lin MW, Ayazi A, Leers JM, Oezcelik A, Banki F, Lipham JC, DeMeester TR, Crookes PF (August 2009). "Obesity and Gastroesophageal Reflux: Quantifying the Association Between Body Mass Index, Esophageal Acid Exposure, and Lower Esophageal Sphincter Status in a Large Series of Patients with Reflux Symptoms". J. Gastrointest. Surg. 13 (8): 1440–7.  
  13. ^ Morse CA, Quan SF, Mays MZ, Green C, Stephen G, Fass R (2004). "Is there a relationship between obstructive sleep apnea and gastroesophageal reflux disease?". Clin. Gastroenterol. Hepatol. 2 (9): 761–8.  
  14. ^ Kasasbeh A, Kasasbeh E, Krishnaswamy G (2007). "Potential mechanisms connecting asthma, esophageal reflux, and obesity/sleep apnea complex—a hypothetical review". Sleep Med Rev 11 (1): 47–58.  
  15. ^ O'Connor HJ (Feb 1999). "Helicobacter pylori and gastro-oesophageal reflux disease-clinical implications and management". Aliment Pharmacol Ther 13 (2): 117–27.  
  16. ^ El-Omar EM, Oien K, El-Nujumi A, Gillen D, Wirz A, Dahill S, Williams C, Ardill JE, McColl KE (1997). "Helicobacter pylori infection and chronic gastric acid hyposecretion". Gastroenterology 113 (1): 15–24.  
  17. ^ Fallone CA, Barkun AN, Mayrand S, Wakil G, Friedman G, Szilagyi A, Wheeler C, Ross D (2004). "There is no difference in the disease severity of gastro-oesophageal reflux disease between patients infected and not infected with Helicobacter pylori". Aliment Pharmacol Ther 20 (7): 761–8.  
  18. ^ a b c d e f g h i j k l m n o Katz PO, Gerson LB, Vela MF (March 2012). "Guidelines for the diagnosis and management of gastroesophageal reflux disease.". The American journal of gastroenterology 108 (3): 308–28.  
  19. ^ a b c d e f g Kahrilas PJ, Shaheen NJ, Vaezi MF, Hiltz SW, Black E, Modlin IM, Johnson SP, Allen J, Brill JV (October 2008). "American Gastroenterological Association Medical Position Statement on the management of gastroesophageal reflux disease". Gastroenterology 135 (4): 1383–1391, 1391.e1–5.  
  20. ^ Numans ME, Lau J, de Wit NJ, Bonis PA (April 2004). "Short-term treatment with proton-pump inhibitors as a test for gastroesophageal reflux disease: a meta-analysis of diagnostic test characteristics" (PDF). Annals of internal medicine 140 (7): 518–27.  
  21. ^ Patient information: Barrett's esophagus 
  22. ^ Mills, S (ed.) 2009.Sternberg's Diagnostic Pathology. 5th Edition. ISBN 978-0-7817-7942-5
  23. ^ a b Festi D, Scaioli E, Baldi F, Vestito A, Pasqui F, Di Biase AR, Colecchia A (Apr 14, 2009). "Body weight, lifestyle, dietary habits and gastroesophageal reflux disease". World journal of gastroenterology : WJG 15 (14): 1690–701.  
  24. ^ a b Kaltenbach T, Crockett S, Gerson LB (2006). "Are lifestyle measures effective in patients with gastroesophageal reflux disease? An evidence-based approach". Arch. Intern. Med. 166 (9): 965–71.  
  25. ^ a b Tran T, Lowry AM, El-Serag HB (2007). "Meta-analysis: the efficacy of over-the-counter gastro-oesophageal reflux disease drugs". Aliment Pharmacol Ther 25 (2): 143–53.  
  26. ^ Abbas AE, Deschamps C, Cassivi SD, Allen MS, Nichols FC, Miller DL, Pairolero PC (2004). "The role of laparoscopic fundoplication in Barrett's esophagus". Annals of Thoracic Surgery 77 (2): 393–6.  
  27. ^ Wileman SM, McCann S, Grant AM, Krukowski ZH, Bruce J (2010). Wileman, Samantha M, ed. "Medical versus surgical management for gastro-oesophageal reflux disease (GORD) in adults". Cochrane database of systematic reviews (Online) 3 (3): CD003243.  
  28. ^ Kurian AA, Bhayani N, Sharata A, Reavis K, Dunst CM, Swanström LL (January 2013). "Partial anterior vs partial posterior fundoplication following transabdominal esophagocardiomyotomy for achalasia of the esophagus: meta-regression of objective postoperative gastroesophageal reflux and dysphagia". JAMA Surg 148 (1): 85–90.  
  29. ^ Badillo, Raul (2014). "Diagnosis and treatment of gastroesophageal reflux disease". World Journal of Gastrointestinal Pharmacology and Therapeutics 5 (3): 105.  
  30. ^ Medical Device Approvals: LINX™ Reflux Management System - P100049, U.S. Food and Drug Administration, U.S. Department of Health and Human Services, Update of 01/17/2014
  31. ^ Mahadevan U, Kane S (July 2006). "American gastroenterological association institute medical position statement on the use of gastrointestinal medications in pregnancy". Gastroenterology 131 (1): 278–82.  
  32. ^ Infant acid reflux. (2013-03-28). Retrieved on 2013-09-27.
  33. ^ Tighe MP, Afzal NA, Bevan A, Beattie RM (2009). "Current pharmacological management of gastro-esophageal reflux in children: an evidence-based systematic review". Paediatr Drugs 11 (3): 185–202.  
  34. ^ van der Pol RJ, Smits MJ, van Wijk MP, Omari TI, Tabbers MM, Benninga MA (May 2011). "Efficacy of proton-pump inhibitors in children with gastroesophageal reflux disease: a systematic review". Pediatrics 127 (5): 925–35.  
  35. ^ a b Here is a plain English explanation, followed by specific studies.
    • Gupta R, Marshall J, Munoz JC, Kottoor R, Jamal MM, Vega KJ (2013). "Decreased acid suppression therapy overuse after education and medication reconciliation". International Journal of Clinical Practice 67 (1): 60–65.  
    • Nardino RJ, Vender RJ, Herbert PN (2000). "Overuse of acid-suppressive therapy in hospitalized patients1". The American Journal of Gastroenterology 95 (11): 3118–3122.  
    • Heidelbaugh JJ, Kim AH, Chang R, Walker PC (2012). "Overutilization of proton-pump inhibitors: What the clinician needs to know". Therapeutic Advances in Gastroenterology 5 (4): 219–232.  
    • Forgacs I, Loganayagam A (2008). "Overprescribing proton pump inhibitors". BMJ 336 (7634): 2–3.  
    • McKay AB, Wall D (2008). "Overprescribing PPIs: An old problem". BMJ 336 (7636): 109.  
  36. ^ a b c
    • Forgacs I, Loganayagam A (2008). "Overprescribing proton pump inhibitors". BMJ 336 (7634): 2–3.  
    • Heidelbaugh JJ, Kim AH, Chang R, Walker PC (2012). "Overutilization of proton-pump inhibitors: What the clinician needs to know". Therapeutic Advances in Gastroenterology 5 (4): 219–232.  
  37. ^ Fedorak RN, Veldhuyzen van Zanten S, Bridges R (July 2010). "Canadian Digestive Health Foundation Public Impact Series: Gastroesophageal reflux disease in Canada: Incidence, prevalence, and direct and indirect economic impact". Canadian Journal of Gastroenterology 24 (7): 431–4.  
  38. ^ Jafri SM, Arora G, Triadafilopoulos G (July 2009). "What is left of the endoscopic antireflux devices?". Current Opinion in Gastroenterology 25 (4): 352–7.  
  39. ^ Testoni PA, Vailati C (August 2012). "Transoral incisionless fundoplication with EsophyX® for treatment of gastro-oesphageal reflux disease". Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 44 (8): 631–5.  

Further reading

  • Kahrilas PJ, Shaheen NJ, Vaezi MF, Hiltz SW, Black E, Modlin IM, Johnson SP, Allen J, Brill JV (October 2008). "American Gastroenterological Association Medical Position Statement on the management of gastroesophageal reflux disease".  
  • Lichtenstein DR, Cash BD, Davila R, Baron TH, Adler DG, Anderson MA, Dominitz JA, Gan SI, Harrison ME, Ikenberry SO, Qureshi WA, Rajan E, Shen B, Zuckerman MJ, Fanelli RD, VanGuilder T (August 2007). "Role of endoscopy in the management of GERD".  
  • Hirano I, Richter JE (March 2007). "ACG practice guidelines: esophageal reflux testing" (PDF).  

External links

  • Gastroesophageal reflux disease at DMOZ
This article was sourced from Creative Commons Attribution-ShareAlike License; additional terms may apply. World Heritage Encyclopedia content is assembled from numerous content providers, Open Access Publishing, and in compliance with The Fair Access to Science and Technology Research Act (FASTR), Wikimedia Foundation, Inc., Public Library of Science, The Encyclopedia of Life, Open Book Publishers (OBP), PubMed, U.S. National Library of Medicine, National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health (NIH), U.S. Department of Health & Human Services, and, which sources content from all federal, state, local, tribal, and territorial government publication portals (.gov, .mil, .edu). Funding for and content contributors is made possible from the U.S. Congress, E-Government Act of 2002.
Crowd sourced content that is contributed to World Heritage Encyclopedia is peer reviewed and edited by our editorial staff to ensure quality scholarly research articles.
By using this site, you agree to the Terms of Use and Privacy Policy. World Heritage Encyclopedia™ is a registered trademark of the World Public Library Association, a non-profit organization.

Copyright © World Library Foundation. All rights reserved. eBooks from Project Gutenberg are sponsored by the World Library Foundation,
a 501c(4) Member's Support Non-Profit Organization, and is NOT affiliated with any governmental agency or department.