Ammonia is generated in the intestines from different sources:

• diet

• deamination of glutamine (skeletal muscle has glutaminase)

• breakdown of urea in the colon

Majority of the NH3 goes to the liver and metabolized to urea (urea cycle); small amount goes to the kidney and excreted as urea and some of the NH3 is taken up by skeletal muscle and converted to glutamine (acting as a buffer). When there is liver failure and/or portal-systemic shunts cause a rise in NH3 over coming the kidney and skeletal muscle role causing an accumulation of NH3 in the brain. NH3 affects astrocytes, specifically, by impairing the mitochondria and the glutamate-glutamine patheays between astrocytes and neurons.

Because skeletal muscle plays an important role in NH3 removal (buffer system), thus, malnutrition may further compound neuropsychiatric status.