Nighttime Gastric Acid Hypersecretion: Why Reflux Symptoms Often Worsen During Sleep

Nighttime gastric acid hypersecretion (NSRH) is often diagnosed in patients with esophageal diseases such as gastroesophageal reflux disease (GERD) and Barrett's esophagus. Nocturnal GERD symptoms not only disrupt sleep quality and affect daily activities, but also pose a particular danger to patients with erosive esophagitis and Barrett's esophagus due to prolonged exposure of the esophageal mucosa to gastric acid, which can lead to disease progression and even malignant transformation.

NSRH – gastric acid hypersecretion

Esophageal acid clearance is a two-step process involving volume clearance and acid neutralization, whereby most of the acid is removed from the esophagus during primary and secondary peristalsis and neutralized by bicarbonates secreted by the salivary glands and esophageal submucosal glands. Acid clearance is reduced during sleep. Almost no swallowing occurs at night, so primary peristalsis, which is induced by swallowing, is not stimulated. Due to the small amount of content in the esophagus, secondary peristalsis, which contributes to esophageal volume clearance during sleep, is also minimally stimulated. Esophageal acid clearance at night is worse than during the day, not only because of the supine position but also because of the absence of swallowing and the reduced amount of salivary bicarbonates available to neutralize acid. Nighttime acid secretion can be particularly harmful because of prolonged acid contact with the mucosa. Nocturnal GERD symptoms are influenced not only by reduced peristaltic activity but also by impaired lower esophageal sphincter pressure and increased sensitivity of the esophageal mucosa. The presence of pepsin and bile in the refluxate may also play a role, as the esophageal mucosa is believed to be particularly sensitive to these substances. GERD is the most common esophageal disease. Although the prevalence of GERD has been widely studied, there is a lack of data regarding nocturnal GERD symptoms. It is believed that reduced esophageal peristaltic activity at night may predispose patients to proximal acid migration, which can damage the upper respiratory tract. As a result, the risk of developing respiratory conditions such as pharyngitis, laryngitis, chronic bronchitis, bronchial asthma, sinusitis, chronic cough, and hoarseness is increased. When endoscopic signs of GERD are present, treatment is generally more effective than in patients with non-erosive GERD. If GERD is confirmed by endoscopy and there is no response to treatment, it is necessary to determine whether the patient is taking the medication correctly and whether the dosage and duration of treatment are appropriate. Barrett's esophagus is a condition of particular importance because changes in the esophageal mucosa have the potential to progress to adenocarcinoma. By effectively controlling gastric acid hypersecretion, it is possible to halt disease progression and reduce the risk of malignant transformation, making effective 24-hour suppression of gastric acid especially important in this group of patients. Unfortunately, NSRH is diagnosed in up to 50% of patients with scleroderma esophagitis and Barrett's esophagus who take PPIs twice daily. The addition of histamine receptor antagonists at bedtime may help effectively suppress nocturnal gastric acid secretion. In cases of gastric acid hypersecretion, it is important to regulate both basal and stimulated acid secretion continuously throughout the day. The most commonly used medications for treating gastric acid hypersecretion belong to two groups: proton pump inhibitors (PPIs) and H2 receptor antagonists (H2RAs). PPIs are the most effective class of drugs for treating conditions caused by increased gastric acidity, including gastric and duodenal ulcers, GERD, and erosive esophagitis. However, their effect on nocturnal gastric hypersecretion remains questionable. The pharmacological phenomenon of NSRH has been observed during treatment with PPIs such as omeprazole, lansoprazole, rabeprazole, and pantoprazole in both healthy individuals and patients with GERD. The onset of NSRH depends on the timing of PPI administration. When a PPI is administered once daily in the morning before breakfast, NSRH typically occurs early in the evening, around 11 p.m. When a PPI is administered twice daily before breakfast and dinner, NSRH usually occurs 6–7 hours after the last dose, typically between 1 a.m. and 4 a.m. The nocturnal increase in gastric acidity is not fully explained by hypergastrinemia. It is believed that cholinergic stimulation, particularly histamine hypersecretion, plays a greater role. PPIs block only activated proton pumps within the secretory canaliculi, and proton pump activation decreases during periods of rest; therefore, the effect of PPIs on gastric acid hypersecretion is reduced at night. By prescribing H2RAs at bedtime, NSRH can be effectively reduced because these drugs block H2 receptors on gastric parietal cells, thereby inhibiting basal gastric acid secretion. Depending on symptom severity, the extent of esophageal damage, concomitant diseases, medications being taken, and patient age, appropriate antisecretory therapy should be selected. In cases of mild non-erosive reflux disease (NERD), a PPI may be prescribed once daily, 15–30 minutes before breakfast. If symptoms persist at night, ranitidine may be added at bedtime or the PPI dose may be increased to twice daily before breakfast and dinner. Increasing a single PPI dose does not prolong morning suppression of gastric acid secretion compared with a lower dose; therefore, increasing the morning dose solely to reduce NERD symptoms is not considered beneficial. The maximum antisecretory therapy for NERD consists of a PPI twice daily before meals combined with an H2RA at bedtime. All PPIs, except rabeprazole, are metabolized in the liver through the cytochrome P450 system (CYP2C19); therefore, they are not recommended for patients with liver disease. Drug interactions have also been observed when PPIs are taken together with medications metabolized by the P450 system, potentially leading to faster PPI metabolism and reduced therapeutic effectiveness. Clinical studies have shown that PPIs may reduce the effect of clopidogrel, increase the risk of myocardial infarction, increase the risk of bone fractures, and contribute to other adverse effects. In clinical practice, the treatment outcomes of diseases caused by gastric acid hypersecretion have improved significantly since the introduction of PPIs. However, it should not be forgotten that every medication must be prescribed according to appropriate indications and after careful consideration of the balance between benefits and risks. Source: Internistas, No. 5, 2016.