A 54-year-old man with a history of hepatitis C infection is brought to the emergency department by his wife after several episodes of vomiting bright red blood. He is admitted to the hospital and the appropriate treatment is initiated. During morning rounds the next day, the patient is disoriented and cannot identify the month or his current location. Physical examination shows significant abdominal distention and gynecomastia. Repetitive flicking motions of the hands are seen when the patient is asked to outstretch his arms and dorsiflex his wrists. Which of the following is most likely contributing to this patient's altered mental status?

Question

A 54-year-old man with a history of hepatitis C infection is brought to the emergency department by his wife after several episodes of vomiting bright red blood.  He is admitted to the hospital and the appropriate treatment is initiated.  During morning rounds the next day, the patient is disoriented and cannot identify the month or his current location.  Physical examination shows significant abdominal distention and gynecomastia.  Repetitive flicking motions of the hands are seen when the patient is asked to outstretch his arms and dorsiflex his wrists.  Which of the following is most likely contributing to this patient's altered mental status?

Quizplus · Accepted Answer

11ec160b_3adf_a7a8_9249_d51043a9e783_MD0001_00 This patient with cirrhosis (hepatitis C infection, abdominal distention, gynecomastia) most likely developed hepatic encephalopathy due to his recent gastrointestinal (GI) bleed. Hepatic encephalopathy refers to a reversible decline in neurologic function that occurs due to failure of the liver to metabolize waste products such as ammonia. Ammonia is normally produced by the GI tract as a result of enterocytic catabolism of glutamine and colonic bacterial catabolism of dietary protein. GI bleeding causes increased nitrogen delivery to the gut in the form of hemoglobin, which is then converted into ammonia and absorbed into the bloodstream. The ammonia then enters the liver through the portal vein and is detoxified to urea. In chronic liver failure, hepatocyte dysfunction and the shunting of blood through portosystemic collaterals impair the liver's detoxification ability. This leads to accumulation of ammonia and other neurotoxins in the circulation, causing altered amino acid transport across the blood-brain barrier, impaired neurotransmitter metabolism, and depressed cerebral glucose metabolism. These and other factors result in increased inhibitory neurotransmission (eg, γ-aminobutyric acid [GABA]) and impaired excitatory neurotransmitter release (eg, glutamate, catecholamines). In patients with hepatic encephalopathy, lowering of blood ammonia levels is typically accomplished with oral administration of a disaccharide (eg, lactulose). Bacterial action on lactulose results in acidification of colonic contents, which then converts absorbable ammonia into nonabsorbable ammonium ions, trapping it in the stool and thereby increasing fecal nitrogen excretion. (Choice A) Accumulation of blood urea nitrogen (BUN) is suggestive of renal failure, heart failure, or dehydration. In healthy patients, GI bleeding can also cause a rapid increase in BUN. However, this patient has cirrhosis, which is associated with decreased BUN because ammonia cannot be efficiently converted to urea by the failing liver. (Choice B) Bacterial meningitis presents with altered mental status, fever, nuchal rigidity, headache, and photophobia. In addition, asterixis (flapping tremor) is specific for metabolic encephalopathies. (Choice C) The altered mental status seen in hepatic encephalopathy is due to increased (not decreased) activity of the GABA neurotransmitter system. This enhanced activity is caused by increased GABA receptor affinity and alterations in neurosteroid synthesis rather than increased GABA production. (Choice E) The middle cerebral artery is the largest cerebral artery and the one most commonly involved in cerebrovascular accidents. This patient's presentation is suggestive of hepatic encephalopathy rather than stroke. Educational objective: Hepatic encephalopathy is caused by increased levels of ammonia and other neurotoxins in the circulation that lead to increased inhibitory neurotransmission and impaired excitatory neurotransmitter release. Hepatic encephalopathy is frequently precipitated by a stressor (eg, gastrointestinal bleeding, infection) that increases blood ammonia levels. __________ References: Ammonia, the GABA neurotransmitter system, and hepatic encephalopathy (http://www.ncbi.nlm.nih.gov/pubmed/12602504) Hepatic encephalopathy: a review of its pathophysiology and treatment (http://www.ncbi.nlm.nih.gov/pubmed/17081480)

A 54-Year-Old Man with a History of Hepatitis C Infection