Hyperammonemia: Difference between revisions

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*Secondary  
*Secondary  
**Caused by inborn errors of intermediary metabolism (i.e. reduced activity of enzymes that are not part of the urea cycle)
**Caused by inborn errors of intermediary metabolism (i.e. reduced activity of enzymes that are not part of the urea cycle)
***Normally from acute or chronic [[liver failure]]
**Typically from acute or chronic [[liver failure]]


==Clinical Features==
==Clinical Features==
 
*[[AMS]]- ranging from mild apathy to frank coma
* +/- asterexis
*Signs/symptoms of underlying disease or trigger for exacerbation


==Differential Diagnosis==
==Differential Diagnosis==
===Elevated ammonia level<ref>Ferenci, P. Hepatic encephalopathy in adults: Clinical manifestations and diagnosis. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2020</ref>===
*[[Liver failure]]
*[[Inborn errors of metabolism]] with urea cycle defects and organic acidemia
*[[Shock]], severe [[dehydration]]
*[[Renal failure]]
*[[Gastrointestinal bleeding]]
*[[Urinary tract infection]] with a urease-producing organism (i.e. [[proteus mirabilis]]), systemic infection with [[mycoplasma]] hominis or ureasplasma species in [[lung transplant]] patients
*[[Reye syndrome]]
*Any cause of portosystemic shunting of blood
*Ureterosigmoidostomy
*Cigarette smoking
*Transient hyperammonemia in newborns
*Parenteral nutrition
*Medication toxicity, including:
**High dose chemotherapy
**[[valproate OD|Valproic acid]]
**[[Barbiturate toxicity|Barbiturates]]
**[[ETOH intoxication]]|ETOH]]
**[[Diuretics]]
**[[Salicylate toxicity|ASA]]
**Glycine toxicity


{{Template:AMS DDX}}


==Evaluation==
==Evaluation==
===Acquired vs. Congenital===
*Evaluate for suspected underlying etiology as above and/or alternate etiology of presenting symptoms (e.g. workup for other causes of [[AMS]])
*Acquired
*Normal range of ammonia in adult is typically 10-80 mcg/dL or 6-47 μmol/L, <100 in neonate, HOWEVER severity of hepatic encephalopathy is inconsistently correlated to severity of ammonia elevation<ref>Ong JP, Aggarwal A, Krieger D, Easley KA, Karafa MT, Van Lente F, Arroliga AC, Mullen KD. Correlation between ammonia levels and the severity of hepatic encephalopathy. Am J Med. 2003 Feb 15;114(3):188-93. doi: 10.1016/s0002-9343(02)01477-8. PMID: 12637132.</ref>
**Diseases that result in [[liver failure]]
**Value of ammonia level in liver disease more helpful to trend rather than as absolute number
**Medications (e.g. [[valproic acid]] overdose)
**Severe dehydration (from small intestinal bacterial overgrowth)  
**Glycine toxicity (CNS symptoms and nausea)
*Congenital
**Genetic


==Management==
==Management==
*Treat underlying disorder
*Treat underlying disorder
*If [[hepatic encephalopathy]]:
**[[Lactulose]] 20g PO or (300mL in 700cc H2O retention enema x30min)
***In colon degrades into lactic acid: acidic environment traps ammonia
***Also inhibits ammonia production in gut wall
*If secondary to inborn error of metabolism
**[[sodium phenylacetate/sodium benzoate]] (Ammonul) 250mg/kg in D10 over 90min; then 250mg/kg/d infusion
**Arginine 210mg/kg IV/IO in D10 over 90min; then 210mg/kg/d infusion
**+/- [[levocarnitine|carnitine]], 400 mg IV/IO in consultation w/specialist
**May require [[dialysis]] if refractory/severe


==Disposition==
==Disposition==

Revision as of 05:02, 21 April 2021

Background

Pathophysiology

  • Acquired: liver failure results in shunting of blood from the liver to the inferior vena cava, decreased filtration of blood and removal of nitrogen-containing toxins by the liver, and then hyperammonemia.
  • Congenital: Defect in one of the enzymes of the urea cycle, which leads to lower production of urea from ammonia.

Types

  • Primary
  • Secondary
    • Caused by inborn errors of intermediary metabolism (i.e. reduced activity of enzymes that are not part of the urea cycle)
    • Typically from acute or chronic liver failure

Clinical Features

  • AMS- ranging from mild apathy to frank coma
  • +/- asterexis
  • Signs/symptoms of underlying disease or trigger for exacerbation

Differential Diagnosis

Elevated ammonia level[1]

Altered mental status

Diffuse brain dysfunction

Primary CNS disease or trauma

Psychiatric

Evaluation

  • Evaluate for suspected underlying etiology as above and/or alternate etiology of presenting symptoms (e.g. workup for other causes of AMS)
  • Normal range of ammonia in adult is typically 10-80 mcg/dL or 6-47 μmol/L, <100 in neonate, HOWEVER severity of hepatic encephalopathy is inconsistently correlated to severity of ammonia elevation[2]
    • Value of ammonia level in liver disease more helpful to trend rather than as absolute number

Management

  • Treat underlying disorder
  • If hepatic encephalopathy:
    • Lactulose 20g PO or (300mL in 700cc H2O retention enema x30min)
      • In colon degrades into lactic acid: acidic environment traps ammonia
      • Also inhibits ammonia production in gut wall
  • If secondary to inborn error of metabolism
    • sodium phenylacetate/sodium benzoate (Ammonul) 250mg/kg in D10 over 90min; then 250mg/kg/d infusion
    • Arginine 210mg/kg IV/IO in D10 over 90min; then 210mg/kg/d infusion
    • +/- carnitine, 400 mg IV/IO in consultation w/specialist
    • May require dialysis if refractory/severe

Disposition

  • Depends on cause

See Also

External Links

References

  1. ↑ Ferenci, P. Hepatic encephalopathy in adults: Clinical manifestations and diagnosis. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2020
  2. ↑ Ong JP, Aggarwal A, Krieger D, Easley KA, Karafa MT, Van Lente F, Arroliga AC, Mullen KD. Correlation between ammonia levels and the severity of hepatic encephalopathy. Am J Med. 2003 Feb 15;114(3):188-93. doi: 10.1016/s0002-9343(02)01477-8. PMID: 12637132.
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