The document discusses ammonia toxicity and the role of the liver in filtering and converting ammonia into urea for excretion. It highlights the consequences of impaired liver function, which can lead to high ammonia levels in the blood and potentially fatal outcomes. The document also covers both acquired and inherited forms of hyperammonemia, emphasizing the significance of the urea cycle in preventing toxicity.

1. AMMONIA TOXICITY
Eric Mbindo Njunju
Bsc; Msc

2. • Breakdown of amino acids and nucleic acids

3. Liver
• Filters ammonia out of blood
• Renders it inert
• Converts to urea
• Eliminated in urine
Importance of a Healthy Liver

4. • Normal <50µmol/L
• 100µmol/L- disturbance in consciousness
• 200µmol/L -coma and convulsions
• Tremors, slurring speech, blurring vision

5. • Liver converts ammonia into urea- urine
• Impaired liver function- excessive
concentrations of ammonia in blood
(ammonia toxicity)-fatal

6. • In CNS the brain’s defense is severely
challenged
– Short circuit of transport of K+ into brain cells
– Cells absorb excessive amounts of K+ and cl-

7. • Reductive amination of α-ketoglutarate- limits
Krebs cycle- reduction in levels of ATP and
NADH

8. • Acquired hyperammonemia-formation of
collateral circulation- liver cirrhosis, hepatitis,
biliary obstruction- detoxification of ammonia
severely impaired

9. • Inherited hyperammonemia-genetic
deficiencies of any of the 5 enzymes of the
urea cycle
• Prevalence 1 in 30,000 live births
• Inability to synthesize urea- mental
retardation

10. UREA CYCLE

11. • Converts highly toxic ammonia to urea for
excretion
• 1st metabolic cycle to be discovered