When you have
toxic levels of ammonia, it’s called hyperammonemia (high ammonia levels in
blood). People with hyperammonemia may
experience loss of appetite, vomiting, migraine, mood swings, irritability,
seizures and/or disorientation progressing to coma and death. Most of these symptoms and pathology are due
to effects on the brain. First, the brain
will swel (cerebral edema) and raised intracranial pressure, which indicates an
issue with osmotic homeostasis.
There has been many investigations to figure out exactly what is
going on and try to treat hyperammonemia
before it becomes lethal. Here are some
possible reasons:
When [ammonia] rises, Gln is formed at
the expense of a-ketoglutarate (KG) and ATP to attempt to remove the
ammonia. The deficiency of KG and the
acute use of ATP to make Gln in the Gln synthetase reaction causes a depletion of energy. The brain does not have any glycogen stores!
Second, and particularly
in the glial cells (astrocytes), the buildup of Gln
causes a disruption of the osmotic pressure. When [Gln] increases,
water comes into the cells due to osmosis and they swell.
Third,
there are additional thoughts that ammonia induces NMDA(N-methyl D-Aspartate)
receptors, which cause increased production of superoxide anions (ROS) which damage
the astrocytes. Ammonia has been reported to interfere with
the Na/K pump on glial cells limiting the ability of the pump to transport of
potassium into the brain’s glial cells.
Potassium accumulation outside of neurons causes perturbations of the
normal ability of neurons to communicate (action potentials).