Pathophysiology of GORD: The Science Behind Acid Reflux

 

Gastro-oesophageal reflux disease (GORD) occurs due to chronic reflux of gastric contents into the oesophagus, leading to mucosal irritation, inflammation, and potential long-term complications.

 The key defect? Lower oesophageal sphincter (LOS) dysfunction, but several additional mechanisms contribute.

🚨 Core Pathophysiological Mechanisms

🔹 Impaired Lower Oesophageal Sphincter (LOS) Function

• Normally, the LOS remains tonically contracted to prevent acid reflux.
• In GORD, transient LOS relaxations (TLOSRs) occur independently of swallowing, allowing gastric contents to escape.
• Some individuals have a hypotonic LOS, meaning it cannot maintain adequate pressure to prevent reflux.

🔹 Oesophageal Hypersensitivity

• Some patients experience symptoms without significant acid exposure, indicating heightened sensory perception of reflux events.
• Visceral hypersensitivity plays a role, with increased pain perception despite normal pH levels.

🔹 Delayed Gastric Emptying & Increased Intragastric Pressure

• Conditions like gastroparesis and high-fat meals - prolong gastric emptying, increasing gastric volume and pressure, leading to reflux.
• Obesity increases intra-abdominal pressure, compressing the stomach and worsening reflux.

🔹 Defective Oesophageal Clearance Mechanisms

• The oesophagus relies on secondary peristalsis (swallow-induced contractions) to clear acid.
• Impaired peristaltic waves, seen in patients with oesophageal motility disorders, lead to prolonged acid exposure.
• Reduced salivary bicarbonate (from conditions like Sjögren’s syndrome) further worsens acid clearance.

🔹 Weak Mucosal Defence Against Acid Injury

• The oesophageal epithelium lacks thick mucus and bicarbonate found in the stomach, making it highly susceptible to acid damage.
• Chronic reflux results in oesophagitis, causing oedema, hyperplasia, and eventual erosion of mucosal layers.

💢 Long-Term Consequences of Chronic Acid Exposure

📍 Oesophagitis → Persistent inflammation leading to ulceration, bleeding, and fibrosis

📍 Barrett’s Oesophagus → Metaplastic transformation of squamous cells into columnar epithelium (pre-malignant)

📍 Oesophageal Strictures → Fibrotic scarring causing progressive dysphagia

📍 Oesophageal Adenocarcinoma → Increased risk due to chronic mucosal irritation and metaplasia

💡 Why Does This Matter in Clinical Practice?

Understanding GORD pathophysiology guides:

✔ Diagnostic Approaches (pH monitoring, manometry, endoscopy)

✔ Management Strategies (PPIs, lifestyle modifications, prokinetics)

✔ Preventative Measures (weight loss, dietary adjustments, avoiding late-night meals)

💡 Key Takeaway: GORD is more than just acid reflux—it involves neuromuscular dysfunction, impaired clearance, hypersensitivity, and long-term structural damage.