Mechanisms of acid injury in porcine gastroesophageal mucosa.

OBJECTIVE

To identify the cause and mechanisms of injury in gastroesophageal ulcer disease in market weight swine.

DESIGN

Comparison of mechanisms of injury caused by HCI with those caused by short chain fatty acids (SCFA) in gastric mucosa.

ANIMALS

Pigs weighing 30 to 40 kg.

PROCEDURE

Gastric tissues were studied in Ussing chambers; short-circuit current (lsc) and electrical resistance (R) were recorded in response to treatment, and tissues were examined histologically.

RESULTS

60 mM mucosal acetate abruptly ( < or = 75 minutes) and irreversibly abolished lsc at pH < or = 4.5, whereas R decreased more slowly. These data were associated with cell swelling and vesicle formation in mid-zonal layers, followed by sloughing of the outer barrier, erosion into deeper zones, and finally, ulceration. Mucosal HCl at pH > 1.5 was ineffective; however, at pH 1.5, HCl induced an abrupt decrease in R, followed by a slow decrease in lsc, an effect opposite to that caused by SCFA. Serosal addition of HCl rapidly abolished lsc suggesting a barrier to free H+ diffusion from the mucosal solution.

CONCLUSIONS

Undissociated SCFA rapidly penetrate the outer barrier and acidify underlying viable tissue. Cellular acidification inhibits Na pumping and osmoregulation, resulting in cell swelling and necrosis. In contrast, HCl induces and increase in outer barrier permeability before accessing the transporting cells, a much longer process ( > or = 5 hours) requiring a lower pH. These studies suggest that microbial production of SCFA may be important in the pathogenesis of porcine gastric ulcers.