Hyperammonemia is a condition characterized by elevated levels of ammonia in the blood. Ammonia is normally produced and excreted by the liver through the urea cycle. Primary hyperammonemia is caused by deficiencies in urea cycle enzymes, while secondary hyperammonemia can be caused by other metabolic disorders or liver/kidney dysfunction. Symptoms range from lethargy and vomiting in neonates to intellectual impairment and seizures later in life. Treatment focuses on reducing ammonia levels through dietary changes, medications to increase nitrogen excretion, and in severe cases dialysis or liver transplantation.

1. Hyperammonemia
• By:
• Twana
• Rebin
• Rozhgar
• Zana

2. Hyperammonemia:
• is a metabolic condition characterized by
elevated levels of ammonia in the blood.

3. Background
Ammonia is a normal constituent of all body
fluids. At physiologic pH, it exists mainly
as ammonium ion. Reference serum levels
are less than 35 µmol/L. Excess ammonia
is excreted as urea, which is synthesized
in the liver through the urea cycle.

4. Background
• Sources of ammonia include bacterial
hydrolysis of urea and other nitrogenous
compounds in the intestine, the purine-
nucleotide cycle and amino acid
transamination in skeletal muscle, and
other metabolic processes in the kidneys
and liver

5. Background
• Increased entry of ammonia to the brain is
a primary cause of neurological disorders
associated with hyperammonemia, such
as congenital deficiencies of urea cycle
enzymes, hepatic encephalopathies, Reye
syndrome, several other metabolic
disorders, and some toxic
encephalopathies

6. Types of Hyperammonemia
• Primary Hperammonemia
• This type of Hyperammonemia is caused
due to different inborn metabolic
complications that get obvious by the
reduced level of Enzymes present in the
Urea cycle of a human being.

7. Types of Hyperammonemia
• Secondary Hyperammonemia
• caused by inborn errors of
intermediary metabolism characterised by
reduced activity in enzymes that are not
part of the urea cycle or dysfunction of
cells that make major contributions to
metabolism

8. Pathophysiology
• Acute ammonia intoxication leads to
increased extracellular concentration of
glutamate in the brain and results in
activation of the N -methyl D-aspartate
(NMDA) receptor.
• Activation of this receptor mediates ATP
depletion and ammonia toxicity

9. Pathophysiology
• High levels of ammonia induce other
metabolic changes that are not mediated
by activation of the NMDA receptor and
thus are not involved directly in ammonia-
induced ATP depletion or neurotoxicity.

10. Pathophysiology
• Chronic hyperammonemia is associated
with an increase in inhibitory
neurotransmission as a consequence of 2
factors. The first is downregulation of
glutamate receptors secondary to
excessive extrasynaptic accumulation of
glutamate

11. Signs and symptoms
• Signs and symptoms of early-onset
hyperammonemia (neonates) may include
the following:
• Lethargy
• Irritability
• Poor feeding
• Vomiting
• Seizures
• Hyperventilation, grunting respiration

12. Signs and symptoms of early-onset
hyperammonemia (neonates) may include
the following:

13. • symptoms of late-onset hyperammonemia
(later in life) may include the following:
• Intermittent ataxia
• Intellectual impairment
• Failure to thrive
• Gait abnormality
• Behavior disturbances
• Epilepsy
• Recurrent Reye syndrome
• Protein avoidance
• Rarely, episodic headaches and cyclic
vomiting

14. • symptoms of late-onset hyperammonemia
(later in life) may include the following:

15. Causes:
• Enzyme defects in urea cycle

16. Causes:
• Organic acidemias
• Congenital lactic acidosis
• Fatty acid oxidation defects
• Dibasic amino acid transport defects
• Transient hyperammonemia of the
newborn
• Drugs

17. Causes:
• Reye syndrome:is an acquired disorder
usually occurring after a viral infection
• Drugs
• Liver disease
• Renal disease
Liver Failure

18. causes:

19. Diagnosis
• Lab tests
• Arterial blood gas analysis
• Serum amino acid levels
• Urinary orotic acid levels
• Urinary ketone tests
• Plasma and urinary organic acid levels
• Enzyme assays
• DNA mutation analysis: Method of choice
to confirm the diagnosis of urea cycle
disorders

20. Diagnosis
• Imaging studies
• Neuroimaging: CT or MRI of the brain
• MR spectroscopy

21. Managment:
• The therapeutic aims in patients with
hyperammonemia are to correct the
biochemical abnormalities and ensure
adequate nutritional intake. Treatment
involves compounds that increase the
removal of nitrogen waste
• also Medications used in the treatment of
hyperammonemia

22. • Other treatments
• Cessation of protein and/or nitrogen intake
• Hemodialysis
• Supportive care with parenteral intake of
calories

23. Surgery:
• Surgical intervention for patients with
hyperammonemia include liver
transplantation for correction of the
metabolic error and/or liver cell
transplantation as an alternative or bridge
to liver transplantation

24. •Thank you