Recent views on the pathogenesis of gastro-oesophageal reflux disease.

The pathogenesis of GORD depends on a mix of factors which vary amongst individual patients. The central issue in the pathogenesis of gastro-oesophageal reflux is understanding of the mechanisms that lead to reflux, since the effects of all other factors depend on this event. Consequently, new information and views about the mechanisms of gastro-oesophageal reflux have been presented in detail. This information suggests that defective lower oesophageal sphincter motility is the most important abnormality that underlies pathological gastro-oesophageal reflux. Two major forms of LOS dysfunction have been identified as responsible for pathological gastro-oesophageal reflux in the horizontal position: (1) an excessively frequent rate of occurrence of transient LOS relaxations; and (2) defective basal LOS tone. Both of these dysfunctions appear to arise from abnormal neural control of the LOS, probably by the central nervous system. The effect of these LOS dysfunctions on gastro-oesophageal competence is probably significantly influenced by non-sphincteric factors, the most important of these apparently being hiatus hernia. Though there is currently poor understanding about the ways in which hiatus hernia impairs gastro-oesophageal competence, measurement techniques have now advanced sufficiently to allow significant accrual of knowledge in this field. Once reflux has occurred, the efficiency of oesophageal acid clearance plays a major role in determining the impact of reflux on the oesophageal mucosa. Recent studies have shown that oesophageal acid clearance depends on both effective volume clearance and neutralization by saliva of residual acid in the oesophageal lumen. The efficiency of oesophageal volume clearance of both stimulated and real reflux has not been studied formally in GORD patients, but the high incidence of peristaltic dysfunction in reflux disease suggests that volume clearance will be defective in some patients. The limited information available about salivation in GORD patients suggests that salivary secretion is no different from that of age-matched controls, but that there is an age-dependent loss of the salivary response to oesophageal acidification. This impairment of salivary response may produce an age-dependent decline of the efficiency of oesophageal acid clearance. Unusually aggressive refluxate and impaired mucosal resistance to injury have been proposed as significant variables which contribute to pathogenesis of reflux disease. The evidence for these factors is circumstantial and scanty. Their importance has probably been overestimated.(ABSTRACT TRUNCATED AT 400 WORDS)