Effect of Aspirin on the Stomach

Recent experiments have shown that salicylic acid or acetylsalicylic acid (aspirin) can breach the mucosal barrier and produce bleeding. This has been demonstrated by labeling red blood cells in the body with radioactive chromium (Cr-51); measurement of the radioactivity in the feces then gives a measurement of the amount of blood that has been lost by breakdown of the mucosal barrier. By this means it has been found that for most persons the bleeding produced by aspirin is trivial; the blood loss after taking two five-grain tablets usually amounts to only something between half a milliliter and two milliliters. Some susceptible people, however, may lose hundreds of milliliters of blood as a reaction to aspirin. Physicians have found that most patients coming to the emergency room with massive bleeding of the upper gastrointestinal tract have taken salicylates within the preceding 24 hours. There have been cases in which habitual users of salicylates have developed profound anemia by losing blood at a rate higher than the body's production of red blood cells.

The effect of a salicylate in producing bleeding can be highly variable in different people or at different times. Why should this be? The present understanding of the stomach mucosal barrier provides the beginning of an explanation. The solubility of a salicylate, such as aspirin, in fat depends on the acidity of the medium in which it is dissolved. In a neutral solution aspirin becomes ionized, the hydrogen being removed from its carboxyl group (COOH) so that the group is left with a negative charge (COO-). In that state the molecule is relatively insoluble in fat; consequently it does not readily penetrate the lipid barrier of the mucosa. In an acid solution, on the other hand, the carboxyl group remains un-ionized and aspirin is then soluble in fat and can diffuse rapidly through the mucosal barrier (see below). Once in the mucosa, the salicylate is immediately ionized and prevented from crossing the barrier in the opposite direction. Thus a steep gradient for diffusion of the salicylate into the mucosa builds up. Salicylate pours into the mucosa at a rate that depends in the first instance on the acidity of the contents of the stomach cavity.

Experiments also show that if alcohol is present in the stomach, the ability of a salicylate to break the mucosal barrier is enhanced, even when the acidity of the stomach contents is low. These results have been found in human volunteers as well as in dogs with the experimental pouch.

Normal stomach lining. Surface of human stomach’s inner lining, which is the glandular mucosa, is seen enlarged some 700 diameters in this scanning micrograph. The view shows the tops of epithelial cells, the gastric pits and characteristic folds of a normal stomach.

Look what aspirin does to your stomach! Damaged epithelial cells on the surface of the inner wall of a human stomach are magnified about 12,000 diameters in this scanning electron micrograph. The tops of some cells have been destroyed, leaving holes in the mucosal barrier.

The penetration of the salicylate into the mucosa has two damaging effects: (1) it breaks the barrier (by killing cells at the mucosal surface), thereby opening the gates for further influx of acid, and (2) it acts as a weapon to destroy the mucosa (by promoting bleeding).

Synergism of aspirin and alcohol in damaging mucosal barrier is shown by increased flow of sodium ions through the broken barrier. Aspirin (red curve) in acid solution causes damage. A 4 percent solution of ethanol added to aspirin (green curve) increases damage. Even greater damage is caused by aspirin and 9 percent ethanol (black).

ASPIRIN AND ALCOHOL WOULD APPEAR TO BE AN UNWISE COMBINATION!