Current understanding of pathophysiology of GERD.
Current understanding of Pathophysiology of GERD
I DewaNyomanWibawa
Gastroentero-hepatologyDiv,
Dept.of Internal Medicine, UdayanaUniv./
SanglahGeneralHospital, Denpasar, Bali.
According to the Montreal International Consensus Group,
gastroesophageal reflux disease (GERD) is defined as a condition that develops
when the reflux of stomach contents causes troublesome reflux-associated
symptoms.1Gastroesophageal reflux is the reflux of gastric contents other than air
into or through the esophagus.Gastroesophageal reflux results from several factors
that lead to symptoms or injury of the mucosa of the esophagus or the airway by
reflux of corrosive material from the stomach.2
GERD is a common disorder, affecting almost half of the US population,
with varying severity. Forty percent of the US population experiences reflux
symptoms about once per month, 20% complain of symptoms once per week, and
7–10% report daily symptoms (essential) GERD affects 10–20% of western
populations. It is less common in Asian and African countries.3
GERD is believed to be caused by the effect of refluxed gastric acid on
esophageal epithelial cells. Several factors have been proposed as important in the
pathophysiology of GERD. They include dysfunction of the lower esophageal
sphincter (LES), hiatal hernia, esophageal dysmotility, impaired esophageal
defense mechanisms, gastric acid hypersecretion, duodeno-gastroesophageal
reflux, esophageal hypersensitivity, delayed gastric emptying and genetic factors
(tiberiu). Risk factors of GERD are advancing age (>65 years), obesity, genetic
factors (essential), cigarette smoking, alcohol, coffee, obesity, high fat diet, food
products such as chocolate, peppermint, and citrus juices; as well as a slew of
medications (narcotics, calcium channel blockers etc).4
The etiology of GERD is multifactorial. Aberrant transient lower
esophageal sphincter relaxations (TLESRs) are the major pathophysiologic factor
in GERD. TLESR is defined as the relaxation of the lower esophageal sphincter in
response to gastric distension. In healthy persons, TLESRs occur in the absence of
a swallow, last 10–30 seconds, and result in physiologic gastroesophageal reflux.
TLESRs are regulated by the neurotransmitter γ-aminobutyric acid (GABA)
acting on GABA type B receptors located in the peripheral nervous system as well
as in the brainstem. In many cases, GERD is thought to be caused by an increased
number of or prolonged TLESRs.3,4
Increased gastric acid production as well as delayed gastric emptying with
distention may trigger TLESRs. Poor esophageal clearance due to defects in
primary or secondary esophageal peristalsis allows prolonged exposure of the
esophageal mucosa to acid.3,4
Dietary factors such as acidic foods, caffeine, alcohol, peppermint, and
chocolate may reduce LES tone or increase gastric acid production. Medications
such as calcium channel blockers, hormones (e.g., progesterone, cholecystokinin,
secretin), and barbiturates can decrease LES tone, thereby predisposing to
gastroesophageal reflux. Smoking has also been associated with a predisposition
to gastroesophageal reflux.3,4
Figure 1. Pathophysiology of GERD.5
A hiatal hernia usually occurs when there is a defect in the
diaphragmatichiatus that allows the proximal stomach to herniate above
thediaphragm and into the thorax. It is unclear how this predisposes
togastroesophageal reflux; however, it is thought that the barrier functionof the
LES to prevent the reflux of gastric contents into theesophagus is disrupted. Large
hiatal hernias also lead to increasedacid dwell times in the distal esophagus. 3,4
The association of GERD and Helicobacter pylori (H. pylori) is very
controversial. While some argue that the infection might play a role in the
prevention of GERD by altering the nature of the refluxate (gastritis leading to
achlorhydria), others find no link between the infection and esophageal diseases
Prevalence studies seem to suggest that H. pylori infection is inversely associated
with reflux esophagitis in some populations. Eradication studies also suggest that
H. pylori infection is protective with respect to GERD.6
References
1. Vakil N, van Zanten SV, Kahrilas P, et al. The Montreal definition and
classification of gastroesophageal reflux disease: a global evidence-based
consensus. Am J Gastroenterol. 2006;101(8):1900-1920.
2.
Murray JA. Gastroesophageal reflux disease. In: Hauser SC, ed. Mayo
Clinical Gastroenterology and Hepatology Board Review. 4th ed. New York:
Oxford University Press, Inc. 2011. pp: 3-17.
3.
Christie J. Gastroesophageal reflux disease. In: Sitaraman SV, Friedman LS,
eds. Essentials of Gastroenterology. 1st ed. West Sussex: John Wiley & Sons,
Ltd. 2012. pp: 3-16.
4.
Hershcovici T, Fass R. Gastroesophageal reflux disease. In: Hawkey CJ,
Bosch J, Richter JE, et al. Textbook of Clinical Gastroenterology and
Hepatology. 2nd ed. West Sussex: Blackwell Publishing Ltd. 2012. pp:177193.
5.
Weinstein WM, Hawkey CJ, Bosch J. Gastroesophageal reflux disease. In:
Weinstein WM, Hawkey CJ, Bosch J, eds. Clinical Gastroenterology and
Hepatology. 1st ed.New York: Elsevier Mosby. 2005.p157-166.
6.
Herbella FA, Patti MG. Gastroesophageal reflux disease: from
pathophysiology to treatment. World J Gastroenterol 2010;16(30):3745-49.
I DewaNyomanWibawa
Gastroentero-hepatologyDiv,
Dept.of Internal Medicine, UdayanaUniv./
SanglahGeneralHospital, Denpasar, Bali.
According to the Montreal International Consensus Group,
gastroesophageal reflux disease (GERD) is defined as a condition that develops
when the reflux of stomach contents causes troublesome reflux-associated
symptoms.1Gastroesophageal reflux is the reflux of gastric contents other than air
into or through the esophagus.Gastroesophageal reflux results from several factors
that lead to symptoms or injury of the mucosa of the esophagus or the airway by
reflux of corrosive material from the stomach.2
GERD is a common disorder, affecting almost half of the US population,
with varying severity. Forty percent of the US population experiences reflux
symptoms about once per month, 20% complain of symptoms once per week, and
7–10% report daily symptoms (essential) GERD affects 10–20% of western
populations. It is less common in Asian and African countries.3
GERD is believed to be caused by the effect of refluxed gastric acid on
esophageal epithelial cells. Several factors have been proposed as important in the
pathophysiology of GERD. They include dysfunction of the lower esophageal
sphincter (LES), hiatal hernia, esophageal dysmotility, impaired esophageal
defense mechanisms, gastric acid hypersecretion, duodeno-gastroesophageal
reflux, esophageal hypersensitivity, delayed gastric emptying and genetic factors
(tiberiu). Risk factors of GERD are advancing age (>65 years), obesity, genetic
factors (essential), cigarette smoking, alcohol, coffee, obesity, high fat diet, food
products such as chocolate, peppermint, and citrus juices; as well as a slew of
medications (narcotics, calcium channel blockers etc).4
The etiology of GERD is multifactorial. Aberrant transient lower
esophageal sphincter relaxations (TLESRs) are the major pathophysiologic factor
in GERD. TLESR is defined as the relaxation of the lower esophageal sphincter in
response to gastric distension. In healthy persons, TLESRs occur in the absence of
a swallow, last 10–30 seconds, and result in physiologic gastroesophageal reflux.
TLESRs are regulated by the neurotransmitter γ-aminobutyric acid (GABA)
acting on GABA type B receptors located in the peripheral nervous system as well
as in the brainstem. In many cases, GERD is thought to be caused by an increased
number of or prolonged TLESRs.3,4
Increased gastric acid production as well as delayed gastric emptying with
distention may trigger TLESRs. Poor esophageal clearance due to defects in
primary or secondary esophageal peristalsis allows prolonged exposure of the
esophageal mucosa to acid.3,4
Dietary factors such as acidic foods, caffeine, alcohol, peppermint, and
chocolate may reduce LES tone or increase gastric acid production. Medications
such as calcium channel blockers, hormones (e.g., progesterone, cholecystokinin,
secretin), and barbiturates can decrease LES tone, thereby predisposing to
gastroesophageal reflux. Smoking has also been associated with a predisposition
to gastroesophageal reflux.3,4
Figure 1. Pathophysiology of GERD.5
A hiatal hernia usually occurs when there is a defect in the
diaphragmatichiatus that allows the proximal stomach to herniate above
thediaphragm and into the thorax. It is unclear how this predisposes
togastroesophageal reflux; however, it is thought that the barrier functionof the
LES to prevent the reflux of gastric contents into theesophagus is disrupted. Large
hiatal hernias also lead to increasedacid dwell times in the distal esophagus. 3,4
The association of GERD and Helicobacter pylori (H. pylori) is very
controversial. While some argue that the infection might play a role in the
prevention of GERD by altering the nature of the refluxate (gastritis leading to
achlorhydria), others find no link between the infection and esophageal diseases
Prevalence studies seem to suggest that H. pylori infection is inversely associated
with reflux esophagitis in some populations. Eradication studies also suggest that
H. pylori infection is protective with respect to GERD.6
References
1. Vakil N, van Zanten SV, Kahrilas P, et al. The Montreal definition and
classification of gastroesophageal reflux disease: a global evidence-based
consensus. Am J Gastroenterol. 2006;101(8):1900-1920.
2.
Murray JA. Gastroesophageal reflux disease. In: Hauser SC, ed. Mayo
Clinical Gastroenterology and Hepatology Board Review. 4th ed. New York:
Oxford University Press, Inc. 2011. pp: 3-17.
3.
Christie J. Gastroesophageal reflux disease. In: Sitaraman SV, Friedman LS,
eds. Essentials of Gastroenterology. 1st ed. West Sussex: John Wiley & Sons,
Ltd. 2012. pp: 3-16.
4.
Hershcovici T, Fass R. Gastroesophageal reflux disease. In: Hawkey CJ,
Bosch J, Richter JE, et al. Textbook of Clinical Gastroenterology and
Hepatology. 2nd ed. West Sussex: Blackwell Publishing Ltd. 2012. pp:177193.
5.
Weinstein WM, Hawkey CJ, Bosch J. Gastroesophageal reflux disease. In:
Weinstein WM, Hawkey CJ, Bosch J, eds. Clinical Gastroenterology and
Hepatology. 1st ed.New York: Elsevier Mosby. 2005.p157-166.
6.
Herbella FA, Patti MG. Gastroesophageal reflux disease: from
pathophysiology to treatment. World J Gastroenterol 2010;16(30):3745-49.