Barrett’s Oesophagus: Pathophysiology & Clinical Implications

Barrett’s oesophagus is a pre-malignant condition characterised by intestinal metaplasia of the normal stratified squamous epithelium in the oesophagus. 

This transformation occurs as a defensive response to chronic acid exposure, but paradoxically increases the risk of oesophageal adenocarcinoma.

🚨 How Does Barrett’s Oesophagus Develop?

The main driver of Barrett’s oesophagus is chronic gastro-oesophageal reflux disease (GORD). Repeated exposure to gastric acid, pepsin, and bile salts induces cellular changes in the oesophageal lining.

🔹 Initial Oesophageal Injury

•  Prolonged acid exposure leads to chronic inflammation, causing epithelial stress and increased cell turnover.
•  Epithelial damage disrupts tight junctions, making the mucosa more susceptible to injury.
•  Inflammatory cytokines (IL-1β, TNF-α, IL-6) and oxidative stress drive cellular adaptation.

🔹 Metaplastic Transformation

•  The normal stratified squamous epithelium cannot withstand persistent acidic stress, leading to cellular reprogramming.
•  Basal stem cells differentiate into columnar epithelium, resembling intestinal mucosa, complete with goblet cells (hallmark of Barrett’s oesophagus).
•  This adaptive change is mediated by transcription factors such as CDX2, which promotes intestinal-type differentiation.

🔹 Progression Toward Dysplasia & Malignancy

•  Over time, genetic and epigenetic mutations accumulate, increasing the risk of low-grade and high-grade dysplasia.
•  TP53 mutations and chromosomal instability promote oncogenesis.
•  Dysplastic changes create a precursor lesion for oesophageal adenocarcinoma—a major concern in Barrett’s patients.

🩸 Histological Features of Barrett’s Oesophagus

✅ Normal Oesophagus: Stratified squamous epithelium, resilient against mechanical stress but vulnerable to acid.

✅ Barrett’s Oesophagus: Columnar epithelium with goblet cells, resembling intestinal mucosa.

✅ Dysplasia (Pre-Malignant): Architectural disorganisation, nuclear atypia, loss of cellular polarity.

✅ Adenocarcinoma: Invasive tumour formation, often arising from dysplastic Barrett’s segments.

📊 Risk Factors & Disease Progression

🔺 Chronic GORD (>5 years) → Persistent acid exposure

🔺 Obesity → Increased intra-abdominal pressure worsens reflux

🔺 Smoking & Alcohol → Synergistic effects promoting oxidative damage

🔺 Genetic Predisposition → Familial clustering suggests inherited susceptibility

🔺 Male Sex & Age >50 → Higher incidence in older males

🛑 Clinical Implications & Screening Guidelines

🚑 Barrett’s oesophagus is a major risk factor for oesophageal adenocarcinoma, but progression varies.

✔ Patients with long-segment Barrett’s (>3cm metaplasia) have higher malignant potential.

✔ Endoscopic surveillance (± biopsies) recommended every 3-5 years for non-dysplastic Barrett’s.

✔ If dysplasia is detected, interventions like radiofrequency ablation or endoscopic mucosal resection may be necessary.

💡 Key Takeaway

Barrett’s oesophagus starts as an adaptive process, but its progression toward dysplasia and adenocarcinoma makes it a clinically significant condition. Early recognition, surveillance, and intervention are crucial in preventing malignant transformation.