Hyperammonemia
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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
- Caused by several inborn errors of metabolism
- Characterized by reduced activity of urea cycle enzymes
- 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]
- 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
- Valproic acid
- Barbiturates
- ETOH intoxication|ETOH]]
- Diuretics
- ASA
- Glycine toxicity
Altered mental status
Diffuse brain dysfunction
- Hypoxic encephalopathy
- Acute toxic-metabolic encephalopathy (Delirium)
- Hypoglycemia
- Hyperosmolar state (e.g., hyperglycemia)
- Electrolyte Abnormalities (hypernatremia or hyponatremia, hypercalcemia)
- Organ system failure
- Hepatic Encephalopathy
- Uremia/Renal Failure
- Endocrine (Addison's disease, Cushing syndrome, hypothyroidism, myxedema coma, thyroid storm)
- Hypoxia
- CO2 narcosis
- Hypertensive Encephalopathy
- Toxins
- TTP / Thrombotic thrombocytopenic purpura
- Alcohol withdrawal
- Drug reactions (NMS, Serotonin Syndrome)
- Environmental causes
- Deficiency state
- Wernicke encephalopathy
- Subacute Combined Degeneration of Spinal Cord (B12 deficiency)
- Vitamin D Deficiency
- Zinc Deficiency
- Sepsis
- Osmotic demyelination syndrome (central pontine myelinolysis)
- Limbic encephalitis
Primary CNS disease or trauma
- Direct CNS trauma
- Diffuse axonal injury
- Subdural/epidural hematoma
- Vascular disease
- SAH
- Stroke
- Hemispheric, brainstem
- CNS infections
- Neoplasms
- Paraneoplastic Limbic encephalitis
- Malignant Meningitis
- Pancreatic Insulinoma
- Seizures
- Nonconvulsive status epilepticus
- Postictal state
- Dementia
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
- Lactulose 20g PO or (300mL in 700cc H2O retention enema x30min)
- 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
- ↑ Ferenci, P. Hepatic encephalopathy in adults: Clinical manifestations and diagnosis. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2020
- ↑ 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.