Etiology and Clinical Presentation of Gastroparesis

  • Laura A. PaceEmail author


Gastroparesis is a clinical syndrome characterized by delayed emptying of solid food from the stomach in the absence of a mechanical obstruction, which results in symptoms of nausea, early satiety, postprandial fullness, gastroesophageal reflux, abdominal pain, and often vomiting. Gastroparesis represents a disorder of neuromuscular dysfunction and is typically described to encompass three broad categories: diabetic, postsurgical, and idiopathic. The neuromuscular dysfunction of gastroparesis arises from derangements in extrinsic neuronal control, dysfunction of the elaborate interconnections of intrinsic nerves and interstitial cells of Cajal (ICC), dysfunction of smooth muscle, or some combination thereof. While gastroparesis is most commonly thought to be secondary to diabetes, idiopathic gastroparesis is in fact the most common etiology of gastroparesis and includes individuals with underlying immune, neurologic, or metabolic disorders. Furthermore, gastroparesis disproportionality affects females 4:1 and, based on a recent study, may be dramatically underrecognized in clinical practice (Jung et al., Gastroenterology 136:1225–1233, 2009).


Gastroparesis Gastrointestinal dysmotility Neuromuscular dysfunction Neuroimmune Autoimmune gastrointestinal dysmotility Dysautonomia Ehlers-Danlos Syndrome 


  1. 1.
    Rey E, Choung RS, Schleck CD, Zinsmeister AR, Talley NJ, Locke GR. Prevalence of hidden gastroparesis in the community: the gastroparesis “iceberg”. J Neurogastroenterol Motil. Korean Society of Neurogastroenterology and Motility. 2012;18(1):34–42.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Jung H-K, Choung RS, Locke GR, Schleck CD, Zinsmeister AR, Szarka LA, et al. The incidence, prevalence, and outcomes of patients with gastroparesis in Olmsted County, Minnesota, from 1996 to 2006. Gastroenterology. 2009;136(4):1225–33.CrossRefGoogle Scholar
  3. 3.
    Camilleri M, Chedid V, Ford AC, Haruma K, Horowitz M, Jones KL, et al. Gastroparesis. Nat Rev Dis Primers. Nature Publishing Group. 2018;4(1):41.PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    Grover M, Farrugia G, Lurken MS, Bernard CE, Faussone-Pellegrini MS, Smyrk TC, et al. Cellular changes in diabetic and idiopathic gastroparesis. Gastroenterology. 2011;140(5):1575–8.CrossRefGoogle Scholar
  5. 5.
    Faussone-Pellegrini MS, Cortesini C. The muscle coat of the lower esophageal sphincter in patients with achalasia and hypertensive sphincter. An electron microscopic study. J Submicrosc Cytol. 1985;17(4):673–85.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Grover M, Bernard CE, Pasricha PJ, Lurken MS, Faussone-Pellegrini MS, Smyrk TC, et al. Clinical-histological associations in gastroparesis: results from the Gastroparesis Clinical Research Consortium. Neurogastroenterol Motil. John Wiley & Sons, Ltd (10.1111). 2012;24(6):531–9, e249.PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Grover M, Gibbons SJ, Nair AA, Bernard CE, Zubair AS, Eisenman ST, et al. Transcriptomic signatures reveal immune dysregulation in human diabetic and idiopathic gastroparesis. BMC Med Genomics. BioMed Central. 2018;11(1):62.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Choi KM, Gibbons SJ, Nguyen TV, Stoltz GJ, Lurken MS, Ordog T, et al. Heme oxygenase-1 protects interstitial cells of Cajal from oxidative stress and reverses diabetic gastroparesis. Gastroenterology. 2008;135(6):2055–64, 2064.e1–2.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Allanore Y, Borderie D, Hilliquin P, Hernvann A, Levacher M, Lemaréchal H, et al. Low levels of nitric oxide (NO) in systemic sclerosis: inducible NO synthase production is decreased in cultured peripheral blood monocyte/macrophage cells. Rheumatology (Oxford). Oxford University Press. 2001;40(10):1089–96.CrossRefGoogle Scholar
  10. 10.
    Ravella K, Al-Hendy A, Sharan C, Hale AB, Channon KM, Srinivasan S, et al. Chronic estrogen deficiency causes gastroparesis by altering neuronal nitric oxide synthase function. Dig Dis Sci. Springer US. 2013;58(6):1507–15.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Fikree A, Grahame R, Aktar R, Farmer AD, Hakim AJ, Morris JK, et al. A prospective evaluation of undiagnosed joint hypermobility syndrome in patients with gastrointestinal symptoms. Clin Gastroenterol Hepatol. 2014;12(10):1680–7.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Schvarcz E, Palmér M, Aman J, Horowitz M, Stridsberg M, Berne C. Physiological hyperglycemia slows gastric emptying in normal subjects and patients with insulin-dependent diabetes mellitus. Gastroenterology. 1997;113(1):60–6.PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Vijayvargiya P, Camilleri M. Gastroparesis. In: Lacy BE, DiBaise JK, Pimentel M, Ford AC, editors. Essential medical disorders of the stomach and small intestine. A clinical casebook. Cham: Springer; 2019. p. 23–50.CrossRefGoogle Scholar
  14. 14.
    Boronikolos GC, Menge BA, Schenker N, Breuer TGK, Otte J-M, Heckermann S, et al. Upper gastrointestinal motility and symptoms in individuals with diabetes, prediabetes and normal glucose tolerance. Diabetologia. Springer Berlin Heidelberg. 2015;58(6):1175–82.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Camilleri M. Functional dyspepsia and gastroparesis. Dig Dis. Karger Publishers. 2016;34(5):491–9.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Dale RC, Nosadini M. Infection-triggered autoimmunity: The case of herpes simplex virus type 1 and anti-NMDAR antibodies. Neurol Neuroimmunol Neuroinflamm. Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. 2018;5(4):e471.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Kalkan Ç, Soydal Ç, Özkan E, Maden A, Soykan I, et al. Clin Auton Res. Springer Berlin Heidelberg. 2016;26(3):189–96.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Ashat M, Lewis A, Liaquat H, Stocker A, McElmurray L, Vedanarayanan V, et al. Intravenous immunoglobulin in drug and device refractory patients with the symptoms of gastroparesis-an open-label study. Neurogastroenterol Motil. John Wiley & Sons, Ltd (10.1111). 2018;30(3).Google Scholar
  19. 19.
    Flanagan EP, Saito YA, Lennon VA, McKeon A, Fealey RD, Szarka LA, et al. Immunotherapy trial as diagnostic test in evaluating patients with presumed autoimmune gastrointestinal dysmotility. Neurogastroenterol Motil. John Wiley & Sons, Ltd (10.1111). 2014;26(9):1285–97.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Patcharatrakul T, Gonlachanvit S. Technique of Functional and Motility Test: How to Perform Antroduodenal Manometry. J Neurogastroenterol Motil. Korean Society of Neurogastroenterology and Motility. 2013;19(3):395–404.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Malagelada C, Karunaratne TB, Accarino A, Cogliandro RF, Landolfi S, Gori A, et al. Comparison between small bowel manometric patterns and full-thickness biopsy histopathology in severe intestinal dysmotility. Neurogastroenterol Motil. John Wiley & Sons, Ltd (10.1111). 2018;30(3):e13219.CrossRefGoogle Scholar
  22. 22.
    Zarate N, Farmer AD, Grahame R, Mohammed SD, Knowles CH, Scott SM, et al. Unexplained gastrointestinal symptoms and joint hypermobility: is connective tissue the missing link? Neurogastroenterol Motil. John Wiley & Sons, Ltd (10.1111). 2010;22(3):252–78.PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Fikree A, Chelimsky G, Collins H, Kovacic K, Aziz Q. Gastrointestinal involvement in the Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017;175(1):181–7.PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Yang H, Xu D, Li M, Yao Y, Jin M, Zeng X, et al. Gastrointestinal manifestations on impaired quality of life in systemic sclerosis. J Dig Dis. John Wiley & Sons, Ltd (10.1111). 2019;20(5):256–61.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Kovacic K, Chelimsky TC, Sood MR, Simpson P, Nugent M, Chelimsky G. Joint hypermobility: a common association with complex functional gastrointestinal disorders. J Pediatr. 2014;165(5):973–8.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Moshiree B, Potter M, Talley NJ. Epidemiology and pathophysiology of gastroparesis. Gastrointest Endosc Clin N Am. 2019;29(1):1–14.PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    Ghebremariam YT, LePendu P, Lee JC, Erlanson DA, Slaviero A, Shah NH, et al. Unexpected effect of proton pump inhibitors: elevation of the cardiovascular risk factor asymmetric dimethylarginine. Circulation. 2013;128(8):845–53.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Ortiz V, García-Campos M, Sáez-González E, delPozo P, Garrigues V. A concise review of opioid-induced esophageal dysfunction: is this a new clinical entity? Dis Esophagus. 2018;31(5):424.CrossRefGoogle Scholar
  29. 29.
    Leppert W. The impact of opioid analgesics on the gastrointestinal tract function and the current management possibilities. Contemp Oncol (Pozn). Termedia. 2012;16(2):125–31.Google Scholar
  30. 30.
    Eagle DA, Gian V, Lauwers GY, Manivel JC, Moreb JS, Mastin S, et al. Gastroparesis following bone marrow transplantation. Bone Marrow Transplant. Nature Publishing Group. 2001;28(1):59–62.PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Schoonjans R, Van VB, Vandamme W, Van HN, Verdievel H, Vanholder R, et al. Dyspepsia and gastroparesis in chronic renal failure: the role of Helicobacter pylori. Clin Nephrol. 2002;57(3):201–7.PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    De Schoenmakere G, Vanholder R, Rottey S, Duym P, Lameire N. Relationship between gastric emptying and clinical and biochemical factors in chronic haemodialysis patients. Nephrol Dial Transplant. Oxford University Press. 2001;16(9):1850–5.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Verne GN, Soldevia-Pico C, Robinson ME, Spicer KM, Reuben A. Autonomic dysfunction and gastroparesis in cirrhosis. J Clin Gastroenterol. 2004;38(1):72–6.PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Rodriguez L, Irani K, Jiang H, Goldstein AM. Clinical presentation, response to therapy, and outcome of gastroparesis in children. J Pediatr Gastroenterol Nutr. 2012;55(2):185–90.PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Chumpitazi B, Nurko S. Pediatric gastrointestinal motility disorders: challenges and a clinical update. Gastroenterol Hepatol (N Y). 2008;4(2):140–8.Google Scholar
  36. 36.
    Chitkara DK, Nurko S, Shoffner JM, Buie T, Flores A. Abnormalities in gastrointestinal motility are associated with diseases of oxidative phosphorylation in children. Am J Gastroenterol. 2003;98(4):871–7.PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Kim BJ, Kuo B. Gastroparesis and functional dyspepsia: a blurring distinction of pathophysiology and treatment. J Neurogastroenterol Motil. Korean Society of Neurogastroenterology and Motility. 2019;25(1):27–35.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Vijayvargiya P, Jameie-Oskooei S, Camilleri M, Chedid V, Erwin PJ, Murad MH. Association between delayed gastric emptying and upper gastrointestinal symptoms: a systematic review and meta-analysis. Gut. BMJ Publishing Group. 2018;68(5). Scholar
  39. 39.
    NORD. National Organization for Rare Disorders.
  40. 40.
    Revicki DA, Rentz AM, Dubois D, Kahrilas P, Stanghellini V, Talley NJ, et al. Development and validation of a patient-assessed gastroparesis symptom severity measure: the Gastroparesis Cardinal Symptom Index. Aliment Pharmacol Ther. John Wiley & Sons, Ltd (10.1111). 2003;18(1):141–50.PubMedCrossRefPubMedCentralGoogle Scholar
  41. 41.
    Revicki DA, Lavoie S, Speck RM, Puelles J, Kuo B, Camilleri M, et al. The content validity of the ANMS GCSI-DD in patients with idiopathic or diabetic gastroparesis. J Patient Rep Outcomes. SpringerOpen. 2018;2(1):61.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Pasricha PJ, Camilleri M, Hasler WL, Parkman HP. White paper AGA: gastroparesis: clinical and regulatory insights for clinical trials. Clin Gastroenterol Hepatol. W.B. Saunders. 2017;15(8):1184–90.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Talley NJ, Goodsall T, Potter M. Functional dyspepsia. Aust Prescr. NPS MedicineWise. 2017;40(6):209–13.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Aziz I, Palsson OS, Törnblom H, Sperber AD, Whitehead WE, Simrén M. Epidemiology, clinical characteristics, and associations for symptom-based Rome IV functional dyspepsia in adults in the USA, Canada, and the UK: a cross-sectional population-based study. Lancet Gastroenterol Hepatol. 2018;3(4):252–62.PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Evans PR, Bak YT, Shuter B, Hoschl R, Kellow JE. Gastroparesis and small bowel dysmotility in irritable bowel syndrome. Dig Dis Sci. 1997;42(10):2087–93.PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Kuo B, McCallum RW, Koch KL, Sitrin MD, Wo JM, Chey WD, et al. Comparison of gastric emptying of a nondigestible capsule to a radio-labelled meal in healthy and gastroparetic subjects. Aliment Pharmacol Ther. John Wiley & Sons, Ltd (10.1111). 2008;27(2):186–96.PubMedCrossRefPubMedCentralGoogle Scholar
  47. 47.
    Diaz Tartera HO, Webb D-L, Al-Saffar AK, Halim MA, Lindberg G, Sangfelt P, et al. Validation of SmartPill® wireless motility capsule for gastrointestinal transit time: Intra-subject variability, software accuracy and comparison with video capsule endoscopy. Neurogastroenterol Motil. 12 ed. John Wiley & Sons, Ltd (10.1111). 2017;29(10):1–9.PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Cojocaru M, Cojocaru IM, Silosi I, Maedica CV. Gastrointestinal manifestations in systemic autoimmune diseases. Maedica. 2011;6(1):45–51.PubMedPubMedCentralGoogle Scholar
  49. 49.
    Lobrano A, Blanchard K, Abell TL, Minocha A, Boone W, Wyatt-Ashmead J, et al. Postinfectious gastroparesis related to autonomic failure: a case report. Neurogastroenterol Motil. John Wiley & Sons, Ltd (10.1111). 2006;18(2):162–7.PubMedCrossRefPubMedCentralGoogle Scholar
  50. 50.
    Pasha SF, Lunsford TN, Lennon VA. Autoimmune gastrointestinal dysmotility treated successfully with pyridostigmine. Gastroenterology. 2006;131(5):1592–6.PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    Dhamija R, Tan KM, Pittock SJ, Foxx Orenstein A, Benarroch E, Lennon VA. Serologic profiles aiding the diagnosis of autoimmune gastrointestinal dysmotility. Clin Gastroenterol Hepatol. W.B. Saunders. 2008;6(9):988–92.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Department of Internal Medicine, Division of Gastroenterology, Hepatology, & NutritionUniversity of UtahSalt Lake CityUSA

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