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  • Review Article
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Mechanisms of heartburn

Nature Clinical Practice Gastroenterology & Hepatology volume 5, pages 383–392 (2008)Cite this article

Abstract

Heartburn is a typical symptom of GERD. The spectrum of diseases associated with GERD includes reflux esophagitis, Barrett's esophagus and nonerosive reflux disease (NERD). Although acid reflux is the classic cause of heartburn in patients with erosive esophagitis, the relationship between acid and heartburn is far from clear, especially in patients with NERD. Strong evidence exists that weakly acidic reflux and/or non-acid-related events have a significant role in the generation of heartburn. In addition to the role of nonacidic refluxate components, activation of mechanoreceptors and chemoreceptors, and a possible role for central and peripheral sensitization, has been described. Although patients with erosive esophagitis respond well to acid-suppressive therapy, the same does not hold true for those with NERD. NERD represents a major clinical problem, and its management remains a challenge. Discussion of NERD focuses on the mechanisms that cause chest pain in this subgroup of patients. Improved understanding of the pathogenesis underlying heartburn in patients with GERD, in particular those with NERD, will shape our understanding of this condition. Such understanding will serve as a platform for further research and allow additional therapies to be developed for this increasingly encountered clinical condition.

Key Points

  • Heartburn is a typical symptom of GERD; the spectrum of diseases associated with GERD includes reflux esophagitis, Barrett's esophagus and nonerosive reflux disease (NERD)

  • Several mechanisms are postulated to underlie heartburn: acid reflux, weakly acidic reflux, bile reflux, mechanical stimulation of the esophagus, esophageal hyperalgesia and psychological comorbidity

  • Technological advances—prolonged esophageal pH monitoring, ambulatory multiple-channel intraluminal impedance monitoring, and bilirubin-absorbance monitoring—mean that a precise evaluation of the nature of the refluxate is now possible and that the timing of symptoms reported by patients can be correlated with objective evidence of reflux

  • Expanding knowledge of the pathophysiology of heartburn in patients with GERD, in particular those with NERD, will shape our understanding of heartburn, serve as a platform for further research and allow additional therapeutic options to be developed for this increasingly common clinical entity

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Figure 1: Schematic representation of the mechanisms and pathways involved in the generation of heartburn.
Figure 2: Transmission electron micrographs of rabbit esophageal mucosa.
Figure 3: Presence of esophageal exposure to acid and DGER in GERD subgroups.
Figure 4: A heartburn episode without acid reflux that is associated with a sustained esophageal contraction.

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Authors and Affiliations

  1. D Ang is Associate Consultant Gastroenterologist at Changi General Hospital, Singapore; at the time of writing, she was a Motility Research Fellow at the Center for Gastroenterological Research, Leuven.,

    Daphne Ang

  2. at the time of writing, she was a Motility Research Fellow at the Center for Gastroenterological Research, Leuven.,

    Daphne Ang

  3. D Sifrim is a Professor of Medicine and J Tack is a Professor of Medicine and Head of the Department of Pathophysiology, University of Leuven, Belgium.,

    Daniel Sifrim & Jan Tack

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  1. Daphne Ang
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Correspondence to Jan Tack.

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Ang, D., Sifrim, D. & Tack, J. Mechanisms of heartburn. Nat Rev Gastroenterol Hepatol 5, 383–392 (2008). https://doi.org/10.1038/ncpgasthep1160

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