Non-ionic diffusion and the excretion of weak acids and bases

Abstract

1. 1. Biological membranes are more permeable to the unionized fraction of some weak acids and bases than to the ionized component. This differential permeability may result in concentration of the bases in acidic fluids and of the acids in alkaline fluids. No active transport system is involved, and no energy other than that necessary to maintain a hydrogen ion gradient is required. 2. 2. Many weak bases are concentrated into acid gastric juice, and some weak acids are present in less concentration than in plasma. Weak acids are therefore often absorbed from the stomach more rapidly than bases. 3. 3. The excretion of a few weak acids and bases is dependent on urinary pH. The clearance of the bases is higher in acid urine and the clearance of the acids is higher in alkaline urine. 4. 4. The quantitative aspects of the diffusion of weak bases and acids from plasma into gastric juice and urine are discussed in detail. Actual concentration ratios between these fluids and plasma are lower than the theoretical values calculated from a simple system in which it is assumed that there is complete impermeability to the ionized fraction, and that complete equilibrium is reached. It is shown that the three limiting factors of permeability to the ionized fraction, rate limitation of diffusion, and false reference of concentration ratios to arterial rather than to capillary plasma are sufficient to account for this discrepancy. 5. 5. The excretion of ammonia and other weak bases and acids excreted by a diffusion mechanism is discussed in detail. 6. 6. The tubular reabsorption of some weak acids is dependent on systemic acid-base balance and not on urinary pH. The use of carbonic anhydrase inhibitors in differentiation of this type of excretion from a diffusion mechanism is discussed. 7. 7. Present knowledge of the excretion of citric and α-ketoglutaric acids is reviewed.