CC March 2016 Hyperammonemia

echoecho's version from 2016-05-16 19:15


Question Answer
What 3 sequelae can come about by acute elevation in ammonia levels?1) cerebral edema 2) intracranial hypertension 3) seizures
List 2 causes of ammonia increasing suddenly?1) urea cycle dysfunction (occurring with medications like valproic acid (Depakote) 2) secondary to hereditary disorders of amino acid metabolism
Chronic hyperammonemia due to liver disease may progress to what?acute toxicity with added hepatic stress such as increased alcohol intake or a protein-rich diet
What is the pathophysiology of hyperammonemia?1) the liver, through the urea cycle, metabolizes ammonia 2) in the brain, metabolism of ammonia by astrocytes produces glutamine 3) when excess amounts of glutamine develop rapidly in the brain, intracellular hyperosmolarity can result, leading to cerebral edema and astrocyte death (apoptosis) 4) astrocyte death can promote inflammatory processes and activation of the N-methyl-D-aspartate (NMDA) receptor pathways, which further contributes to cerebral vascular deregulation, intracranial hypertension, and possible seizure activity
What is the goal of initial management of hyperammonemia-induced intracranial HTN?reduce cerebral edema and improve cerebral vascular blood flow regulation
Treatment of hyperammonemia?1) hypotheramia and hyperosmolar (mannitol) diuresis to attempt to restore normal neurologic function 2) may require supportive care (aireway protection, electrolyte monitoring 3) hemodynamic support until neurologic function is restored
*** What 2 therapies may be added to help reduce ammonia levels, but they do not immediately reverse intracranial HTN?1) hemodialysis 2) sodium benzoate therapy
Chronic hyperammonemia, most often associated with chronic liver disease and impaied hepatic clearance of ammonia, amy present with what symptoms?lethargy, altered mental status, coma
Chronic stimulation of the NMDA (N-methy-D-aspartate) recepotor systme leads to what?down-regulation of the NMDA receptors resulting in these neurological symptoms
What 2 medications may help to reduce chronic ammonia levels and help reduce symptoms?1) Lactulose (Enulose) and 2) Rifaximin (Xifaxan)
How does Lactulose work?through 2 mechanisms = 1) conversion of ammonia (NH3) to the less absorable ammonium (NH4+) in the gut AND 2) increased bowel transient time (reducing absorption of ammonia formed by intestinal gut flora)
How does Rifaximin work?it is a poorly absorbed oral antibiotic, which reduces ammonia-producing gut flora
Acute hyperammonemia may progres to chronic hyperammonemia. List the factors contributing to this progresion?1) deteriorating hepatic function 2) underlying urea cycle dysfunction 3) increased protein intake or spontaneous 4) surgical portacaval shunting in severe cirrhosis
In the above case, what may be necessary to improve neurologic function?1) medication adjustment 2) reduction in protein ingestion
*** SUMMARY = Acute elevations in serum ammonia levels can be associated with what?severe neurological sequelae including cerebral edema, coma, and seizures
*** SUMMARY = List the causes of hyperammonemia?1) deterioration of chronic hyperammonenmia of liver disease 2) certain medications 3) hereditary disorders of amino acid metabolism
*** SUMMARY = List the emergent therapy to resolve cerebral edema and intracranial HTN?1) hypothermia 2) mannitol-induced diuresis FOLLOWED by: 3) sodium benzoate and hemodialysis to reduce ammonia levels