The purpose of this study is to determine the mechanism of hyperchloremic metabolic acidosis in urinary intestinal diversions. With the new forms of urinary diversions, the incidence of this disorder has been reported to range between 60 and 100%. This acidosis when chronic results in numerous metabolic abnormalities including altered growth and development, osteomalacia, altered sensorium, impaired drug metabolism and altered hepatic metabolism. Moreover, the effect of chronic exposure of intestinal mucosa to urine on its transport processes is unknown. Alterations in the transport processes would likely significantly effect the systemic acidosis over time. By defining the mechanism of the acidosis and the alterations which gut transport processes undergo over time specific therapy may be developed to prevent it. The experiments outlined in this proposal employ membrane vesicles composed of either brush boarder or basolateral membranes to define the transport of protons across the cell and to define the mechanism of ammonium transport. Preliminary studies in our laboratory strongly implicate ammonium as the primary proton source for the acidosis. Specific techniques to measure ionized ammonia movement have been defined utilizing the methodology of fluorescent quenching of acridine orange and quantitative measurement. The Na/H, C1/HCO3, and Na/K/2C1 transporters will be defined both in normal ileal and colon mucosa and that which has been chronically exposed to urine. These determinations will define the role of NH4 and the activity of the transporters most likely responsible for proton addition to the systemic circulation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK046825-02
Application #
2146080
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1993-09-30
Project End
1997-08-31
Budget Start
1994-09-01
Budget End
1995-08-31
Support Year
2
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
Stampfer, D S; McDougal, W S (1997) Inhibition of the sodium/hydrogen antiport by ammonium ion. J Urol 157:362-5
McDougal, W S; Stampfer, D S; Kirley, S et al. (1995) Intestinal ammonium transport by ammonium and hydrogen exchange. J Am Coll Surg 181:241-8