Because the brain parenchyma must be in N balance and there must be net inputs of essential amino acids, there must also be a route or routes for N removal. As the brain normally doesn’t produce urea as a means of disposing of NH4+ [364–366], the two main routes for exit to be considered are efflux of NH4+ and efflux of glutamine. Fluxes of NH4+ are easily demonstrated to occur in both directions across the blood–brain barrier and are almost certainly by diffusion across the membranes of NH3 combined with transport either of H+ in the same direction or, more likely, of HCO3− in the opposite direction [4, 359, 367]. Because concentrations of NH4+ in brain, 150–300 µM, and CSF, 100–300 µM, normally exceed those in arterial plasma, 50–250 µM [359], it is likely that there is some net NH4+ efflux. However, an arterio-venous difference in NH4+ concentration and thus its net transport have only been demonstrated in the brain when plasma NH4+ concentration is raised as in hepatic insufficiency [359, 368]. There is then net NH4+ entry, rapid incorporation of the NH4+ into glutamine by reaction with glutamate [359], and efflux of the resultant glutamine. Glutamine efflux is considered further in Sect. 5.5.4.