PBL: Hepatic encephalopathy

Demonstrate knowledge of the pathogenesis of hepatic encephalopathy.
The pathogenesis of hepatic encephalopathy is not entirely clear. It may involve a number pathologic processes and may be intensified by the cumulative effects. The primary pathophysiology is understood to be an accumulation of unmetabolized ammnonia (NH3). Other mechanisms include production of false neurotransmitters, activation of central gamma-aminobutyric acid-benzodiazepine receptors, altered cerebral metabolism, and altered Na+/K+ ATPase activity. Zinc deficiency and manganese accumulation may contribute since they impede urea cycle enzymes necessary for ammonia clearance.

Summary:

 * Not entirely clear
 * Compound effects of multiple insults likely
 * Accumulation of NH3
 * Inherited errors of urea cycle
 * Acute (Hepatitis) or chronic (cirrhosis, hepatitis) liver disease
 * Portosytemic venous shunting – spontaneous or iatrogenic (sugery)
 * False neurotransmitters, perhaps related to bacteria
 * Activation of GABA receptors (hyperpolarization and AP dying-out)

List 5 potential causes of altered mental status in a patient with known liver failure.

 * 1) Cerebral edema (more common in acute liver failure)
 * 2) Toxicities: alcohol, psychoactive drugs, salicylates, or heavy metals
 * 3) Hypoglycemia
 * 4) Hypoxia
 * 5) Azotemia
 * 6) Bleeds: subarachnoid, subdural, or intracerebral hemorrhage can also be especially problematic in patients with liver disease.

List 7 potential precipitating causes of hepatic encephalopathy.

 * 1) Excess dietary protein
 * 2) Constipation (anorexia and fluid restriction)
 * 3) GI hemorrhage
 * 4) Infection (bacterial peritonitis)
 * 5) Azotemia
 * 6) Hypokalemia
 * 7) Systemic Alkalosis

List 5 treatments for hepatic encephalopathy

 * 1) Dietary Protein Restriction/Vegetable-protein diet –-> prevent generation of NH3
 * 2) Carbohydrate enemas/oral lactulose –-> get rid of excess NH3
 * 3) Oral antibiotics --> get rid of gut bacteria that produce NH3
 * 4) Ornithine aspartate/sodium benzoate/phenylacetate –-> increase NH3 breakdown
 * 5) Liver transplant with end-stage cirrhosis, especially with medically-refractory encephalopathy with dementia, spastic paraparesis, cerebellar degeneration, and extrapyramidal (basal ganglion) disorders.