Endogenous Ammonia Production

Evidence suggests that the highest airway NH3 concentrations occur in the oral cavity,78 the only segment of the respiratory system that is normally colonized by bacteria, and that the remainder of the airway, including the nasal passages, have significantly lower levels. Diffusion of NH3 from the bloodstream into the airway lumen is probably the primary source of NH3 for the entire airway except the oral cavity.78 Blood ammonium concentration, [NH4+]B, is normally the consequence of protein deamination during dietary protein digestion,86 though deamination of AMP in muscle tissue during strenuous exercise can significantly increase [NH4+]g.86-88 Ureolysis by gastrointestinal bacteria can also contribute to [NH4+]b.86 It is theorized that airstream NH, concentration, [NH3)^ is in equi­librium with [NH4+]B throughout most of the respiratory tract,78 though this has not been demonstrated. Airway mucus may impede diffusion of blood ammo­nia into the airway lumen because of its net negative charge.83 The effect this Donnan exclusion phenomenon may exert on airway NH3 diffusion has not been demonstrated, since [NH4+]B has not yet been correlated with [NH3j4 in hu­mans.

Bacterial catabolism of oral food residue is probably responsible for a higher [NH3|a in the oral cavity than in the rest of the respiratory tract.78 Am­monia, the by-product of oral bacterial protein catabolism and subsequent ure­olysis, desorbs from the fluid lining the oral cavity to the airstream.89’90 Saliva, gingival crevicular fluids, and dental plaque supply urea to oral bacteria 90 and may themselves be sites of bacterial NH3 production, based on the presence of urease in each of these materials.89»91 Consequently, oral cavity [NH3] A is con­trolled by factors that influence bacterial protein catabolism and ureolysis. Such factors may include the pH of the surface lining fluid, bacterial nutrient sources (food residue on teeth or on buccal surfaces), saliva production, saliva pH, and the effects of oral surface temperature on bacterial metabolism and wall blood flow. The role of teeth, as structures that facilitate bacterial colonization and food entrapment, in augmenting fNH3]/4 is unknown.

The significance of pH is particularly interesting since pH may either aug­ment or diminish NH3 production. The possible mechanisms by which pH af­fects NH3 production are: (a) inhibition of bacterial metabolism, (b) pH-dependent changes in urea metabolic pathways, (c) pH-dependent bacterial utilization of glucose and urea as energy sources, and (d) increased bacterial uti­
lization of NH3 in amino acid synthesis. Ureolysis appears to be very sensitive to pH; N’H, production increases as salivary pH is reduced from 7.0 to 6.092 but decreases significantly when pH is lowered to approximately pH 2.5.93 A sali­vary pH of 2.5, however, only temporarily depresses NH3 production93 since NH3 diffusing from the bloodstream may neutralize acids responsible for re duced oral cavity pH and slowly increase oral pH. Ureolysis may increase rap­idly at some pH threshold, perhaps near pH 5.5,94 because of the steady supply of salivary urea.90 Oral pH continues to increase as NH3 is generated,94 with peak NH3 production thought to occur near an oral pH of 6.0.92 Salivary HC03 may act to buffer increases in oral pH and thus maintain NH3 produc­tion rates.95 Therefore, an increase in salivary flow will not only increase the availability of urea to oral bacteria but also help maintain oral conditions ad­vantageous for NH3 production. Theories regarding in vivo regulation of oral NH3 production are speculative since the bulk of data was obtained from in vitro studies of salivary sediments and dental plaque samples; greater knowl­edge of in vivo interaction between oral cavity NH3 production, pH, and saliva is needed.

Fasting combined with poor oral hygiene results in an elevated dental plaque pH ( -7.6),96 suggestive of active ureolysis. Whether fasting or poor oral hygiene is responsible for the higher pH is unclear. Carbohydrates in the mouth lower dental plaque pH,96 while glucose, in particular, buffers oral pH97 thereby inhibiting NH3 production.92 The formation of NH3 appears to be inhibited by glucose for two other reasons: (a) it is preferentially used for bacterial energy production in place of proteins and peptides, and (b) its pres­ence favors acid-producing bacteria that scavenge NH3.92 Oral food residues with a high protein content should serve as a rich substrate for oral NH 5 pro­duction through bacterial deamination.