title: Mechanisms of acid injury in porcine gastroesophageal mucosa.
abstract: OBJECTIVE
  To identify the cause and mechanisms of injury in gastroesophageal ulcer disease in market weight swine.
  
  
  METHODS
  Comparison of mechanisms of injury caused by HCI with those caused by short chain fatty acids (SCFA) in gastric mucosa.
  
  
  METHODS
  Pigs weighing 30 to 40 kg.
  
  
  METHODS
  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.
authors.affiliation: Department of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh 27606, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Argenzio
authors.forename: J
authors.initials: J
authors.lastname: Eisemann
mesh_terms: D000085:Acetates / Q000633:toxicity; D000704:Analysis of Variance; D000818:Animals; D004594:Electrophysiology; D004935:Esophageal Diseases / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D004947:Esophagus / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D005230:Fatty Acids, Nonesterified / Q000633:toxicity*; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D006851:Hydrochloric Acid / Q000633:toxicity*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009092:Mucous Membrane / Q000473:pathology / Q000502:physiology; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D013552:Swine; D014456:Ulcer / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*
chemical_list: D000085:Acetates; D005230:Fatty Acids, Nonesterified; D006851:Hydrochloric Acid