Date of Award
Doctor of Philosophy
Dr. Frank Andrews
Dr. Alan Mathew, Dr. Kelly Robbins, Dr. Richard Heitmann, Dr. James Blackford
Forty-three horses were necropsied to determine if volatile fatty acids (VFAs)produced from fermentation of carbohydrates (acetic, butyric, propionic, and valeric acids) cause cellular injury which leads to gastric ulceration when exposed to the nonglandular mucosa of the stomach at pH 1.5, 4 and 7. In part I of the study thirty horses were necropsied to determine if acetic, butyric, or propionic acid could cause cellular injury. In part 2 of the study thirteen horses were necropsied to determine if acetic, butyric, propionic or valeric acid could cause cellular injury. In both studies the stomach was removed within one hour of death and dissected along the greater curvature. A 3 cm 2 piece of non-glandular tissue was mounted mucosal side up in an Ussing’s chamber. 60 mM of each VFA (acetic, butyric, propionic, or valeric acid) was combined with normal Ringer's solution and each VFA solution or normal Ringer’s solution was added to the mucosal side of the chamber. Normal Ringer's solution was added to the serosal side of the chamber. The pH of the mucosal solution was changed at 30 minutes to pH 1.5, 4 or 7 and exposed for three hours. The solution on the mucosal side was drained and replaced with normal Ringer's solution at pH 7.0 at the end of three hours. Spontaneous potential difference (PD) across tissue and short-circuit current (Isc) (current necessary to nullify PD = sodium transport across tissue) were measured every 15 minutes throughout the study. Percentage of control short-circuit current (PCIsc), resistance (R), and conductance (G) were calculated. At the end of the experiment, tissues were placed in 10% formalin and stained with hematoxylin and eosin for routine histopathologic examination. In part I of the study, Isc was decreased (P<0.01) and resistance was increased in tissues exposed to a low pH alone, as well as those exposed to acetic acid, butyric acid and propionic acid at an acid pH (1.5, 4.0). Tissues exposed to HCl only and acetic acid recovered to initial Isc values. Tissues exposed to butyric acid and propionic acid solutions did not recover (P<0.01) to initial Isc values. Tissues exposed to pH 1.5 (33%) had the greatest percent (P<0.05) of histopathologic change compared to pH 4.0 (28%) or pH 7.0 (25%). In part II of the study Isc was decreased (P<0.01) and resistance was increased (P<0.01) in tissues exposed to acetic acid, butyric acid and propionic acid compared to normal Ringer's solution at acid pHs (1.5,4.0). However, Isc and tissue resistance both decreased in tissues exposed to valeric acid. Also, valeric acid exposed tissues had lower (P<0.01) conductance values than acetic acid, butyric acid, propionic acid or normal Ringer's solution exposed tissues. Valeric acid (42%), propionic acid (31%) and butyric acid (28%) had the greatest percent (P<0.01) of histologic change. Normal Ringer's solution (26%) and acetic acid (18%) exposed tissues had the least percent (P<0.01) of histologic change. PH alone and volatile fatty acids in the presence of acid pH of the non-glandular mucosa of the stomach causes cellular swelling that may lead to necrosis and ulceration.
Nadeau, Jenifer Ann, "Pathogenesis of Acid Injury in the Non-Glandular Region of the Equine Stomach: Implications in Gastric Ulcer Disease. " PhD diss., University of Tennessee, 2001.