Human Biochemistry, Volume 1 - Murray R. 1993

Metabolism of Proteins and Amino Acids
Catabolism of Amino Acid Nitrogen
Ammonia Production

In addition to the ammonia produced in Tissues, significant amounts are generated by intestinal Bacteria from dietary protein and urea contained in fluids secreted into the gastrointestinal tract. From the intestine, ammonia enters the Blood of the portal Venous system (which is characterized by an elevated ammonia content). Under normal conditions, the Liver rapidly extracts ammonia from the portal blood, so the blood leaving the liver (like all blood in the systemic Circulation) is virtually free of ammonia. This is highly crucial, as even small amounts of ammonia are toxic to the Central Nervous system. Symptoms of ammonia poisoning include characteristic tremors, slurred speech, blurred Vision, and, in severe cases, coma and death. These symptoms resemble those characteristic of hepatic coma syndrome, which develops when ammonia concentrations rise in the blood and, presumably, the Brain. Ammonia toxicity appears to be a major etiological factor in hepatic coma. Therefore, Treatment focuses, in particular, on lowering blood ammonia levels.

In severe liver dysfunction, as well as when collateral pathways develop between the portal venous system and the general circulation (which frequently occurs in liver cirrhosis), portal blood may bypass the liver. Consequently, blood ammonia levels in the systemic circulation can rise to toxic thresholds. Surgical Procedures involving portal system shunting (such as Eck's fistula or other shunt types connecting the portal system and the INFERIOR VENA CAVA) can also precipitate ammonia toxicity, especially following high-protein meals or gastrointestinal hemorrhages that expose blood Proteins to the action of colonic bacteria.

¹ At physiological pH values, ammonia is present almost exclusively as the NH⁺₄ ion.

The ammonia content in the renal Veins exceeds that in the renal Arteries, indicating that the Kidneys produce ammonia and release it into the bloodstream. However, the urinary Excretion of ammonia produced in renal tubular Cells reflects a vital aspect of renal Ammonia METABOLISM. Ammonia generation in the renal tubules serves as a crucial mechanism for regulating acid-base balance and conserving cations. It increases dramatically during metabolic acidosis and decreases during alkalosis. This ammonia is derived not from urea, but from intracellular Amino Acids, particularly glutamine. The liberation of ammonia is catalyzed by renal glutaminase (Fig. 30.7).