What is acid reflux?

Esophageal Acid Clearance
The second tier against reflux damage is esophageal acid clearance. Reflux events determine the frequency and extent that gastric contents enter the esophagus, but esophageal acid clearance time determines the duration the mucosa is exposed to acid and probably the severity of acid damage. Esophageal acid clearance involves two related but separate processes: volume clearance, which is the actual removal of the reflux material from the esophagus, and acid clearance, which is the restoration of normal pH in the esophagus after acid exposure through titration with base, rather than true removal of the refluxed material.
Volume Clearance
Esophageal peristalsis operates to clear the acid volume in both the upright and supine positions, but it is inoperative during deep rapid eye movement sleep. Primary peristalsis is elicited by swallowing, which occurs with a frequency of once per minute in awake subjects, regardless of whether reflux occurs. Secondary peristalsis, initiated by esophageal distention from acid reflux, is much less effective in promoting clearance of refluxate, thus offering only an ancillary protective role. Peristaltic dysfunction, that is, failed peristaltic contractions and hypotensive (<30 style="font-style: italic;">Salivary and Esophageal Gland Secretions
Saliva is the second essential factor required for normal esophageal clearance of acid. Saliva has a pH of 6.4 to 7.8 and therefore is a weak base compared with the acidic gastric contents. The high rate of spontaneous swallowing results in saliva production of approximately 0.5 mL per minute. Although saliva is ineffective in neutralizing large volumes of acid (5 to 10 mL), it can neutralize small residual amounts of acid remaining in the esophagus after the volume of refluxed material has been cleared by several peristaltic contractions The importance of swallowed saliva is supported by findings that increased salivation induced by oral lozenges or bethanechol is associated with a significant decrease in acid clearance time. In contrast, suction aspiration of saliva is accompanied by a marked prolongation of esophageal clearance, despite the presence of normal peristaltic contractions. Physiological or pathological compromises of salivation may contribute to GERD. Diminished salivation during sleep explains why nocturnal reflux episodes are associated with markedly prolonged acid clearance times. Similarly, chronic xerostomia is associated with prolonged esophageal acid exposure and esophagitis. Cigarette smoking may promote GER. This was originally attributed to the effects of nicotine on lowering LES pressure, but more recent studies suggest that cigarette smokers have hyposalivation, which may also prolong esophageal acid clearance. Finally, the esophagosalivary reflex may be impaired in patients with reflux esophagitis. This is a vasovagal reflex demonstrated by perfusing acid into the esophagus, thereby stimulating increased salivation. This reflex may explain the symptoms of water brash (copious salivation) observed in some patients with reflux disease. The esophagosalivary reflex is very active in healthy persons, with a doubling or tripling of the salivary flow rate on exposure to acid. However, this reflex is diminished in patients with esophagitis and in those with strictures. In addition to the role of saliva, dilution and neutralization of residual acid are achieved by the aqueous bicarbonate (HCO 3 -)-rich secretions of the esophageal submucosal glands. These glands have been identified in the opossum as well as in the human esophagus. Reflux of acid into the esophageal lumen stimulates these glands and helps to neutralize the acid, even if swallowing does not occur.

Tissue Resistance
Although clearance mechanisms minimize acid contact time with the epithelium, even healthy persons may have their esophagus exposed to acid 1 to 2 hours during the day and sometimes at night. Nevertheless, only a few persons experience symptomatic GER, and even fewer suffer GERD. This is the result of a third tier for esophageal defense, known as tissue resistance. Tissue resistance is not a single factor, but a group of dynamic mucosal structures and functions that interact to minimize mucosal damage from the noxious gastric refluxate. Conceptually, tissue resistance can be subdivided into preepithelial, epithelial, and postepithelial factors.
The preepithelial defense in the esophagus, in contrast to the stomach and duodenum, is poorly developed. There is neither a well-defined mucous layer nor a buffering capacity by the surface cells to secrete HCO 3 - into the unstirred water layer. This results in a lumen-to-surface pH gradient in the esophagus of 1:10, in contrast to the stomach and duodenum, where the gradient can range from 1:1000 to 1:10,000.
The epithelial defenses in the esophagus consist of both structural and functional components. Structural components include the cell membranes and intercellular junctional complexes of the esophageal mucosa. This structure is a 25- to 30-cell-thick, nonkeratinized squamous epithelium functionally divided into a proliferating basal cell layer (stratum basalis), a midzone layer of metabolically active squamous cells (stratum spinosum), and a 5- to 10-cell-thick layer of dead cells (stratum corneum). The esophageal mucosa is a relatively “tight” epithelium with resistance to ionic movement at the intercellular as well as the cellular level as the result of both tight junctions and the matrix of lipid-rich glucoconjugates in the intercellular space. The functional components of tissue resistance include the ability of the esophageal epithelium to buffer and extrude hydrogen ions (H +). Intracellular buffering is accomplished by negatively charged phosphates and proteins, as well as HCO 3 -. When the buffering capacity is exceeded and intracellular pH falls, it has the capacity actively to remove H + from the cells. This is possibly by the action of two transmembrane proteins, one a sodium (Na +)/H + exchanger and the other a Na +-dependent chloride (Cl -)/HCO 3 - exchanger. After reflux-induced cell acidification, these transporters restore the intracellular pH to neutrality by exchanging H + for extracellular Na + or by exchanging Cl - for extracellular HCO 3 -, respectively. Additionally, esophageal cells contain within their membrane a Na +-independent Cl -/HCO 3 - exchanger that extrudes HCO 3 - from the cytoplasm when the intracellular pH is too high. When the epithelial cells are no longer able to maintain intracellular pH, they lose their ability to regulate volume, edema occurs, and balloon cells develop.
The postepithelial defense is provided by the esophageal blood supply. Blood flow delivers oxygen, nutrients, and HCO 3 - and removes H + and carbon dioxide, thereby maintaining normal tissue acid-base balance. Blood flow to the esophageal mucosa increases in response to the stress of lumenal acid. Cellular injury also stimulates cell proliferation, which results in thickening of the basal cell layer of the epithelium. Unlike the stomach, in which superficial mucosal injury is repaired in hours, the esophagus repairs itself more slowly over days to weeks.