A 16-year-old girl is brought to the emergency department because of progressively increasing nausea, vomiting and right upper quadrant pain. She was initially seen in the emergency department 24 hours ago for nausea and vomiting but was discharged when her examination and laboratory studies were unremarkable. At today's visit, the patient reveals, "I am so upset. My boyfriend broke up with me and I have been taking a lot of pain medication to relieve my pain." Temperature is 37.1 C (98.8 F), blood pressure is 108/70 mm Hg, pulse is 102/min, and respirations are 16/min. Pulse oximetry is 98% on room air. On examination, scleral icterus and marked right upper quadrant tenderness are present. Pupils are normal in size and reactive to light. Neurologic examination shows no abnormalities. Laboratory results are as follows: Which of the following is the most likely underlying mechanism of drug toxicity in this patient?

Question

A 16-year-old girl is brought to the emergency department because of progressively increasing nausea, vomiting and right upper quadrant pain.  She was initially seen in the emergency department 24 hours ago for nausea and vomiting but was discharged when her examination and laboratory studies were unremarkable.  At today's visit, the patient reveals, "I am so upset.  My boyfriend broke up with me and I have been taking a lot of pain medication to relieve my pain."  Temperature is 37.1 C (98.8 F), blood pressure is 108/70 mm Hg, pulse is 102/min, and respirations are 16/min.  Pulse oximetry is 98% on room air.  On examination, scleral icterus and marked right upper quadrant tenderness are present.  Pupils are normal in size and reactive to light.  Neurologic examination shows no abnormalities.  Laboratory results are as follows:  Which of the following is the most likely underlying mechanism of drug toxicity in this patient?

Quizplus · Accepted Answer

11ec160b_3c25_6e6f_9249_4bbeefbd41b1_MD0001_00 This patient who took large quantities of a pain medication initially had nausea and vomiting and has now developed scleral icterus, right upper quadrant pain, and markedly elevated aminotransferases. These findings are consistent with an overdose of acetaminophen, a commonly used analgesic. When taken at appropriate doses, acetaminophen produces small amounts of the toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI), which is conjugated with glutathione in the liver and excreted. At supratherapeutic doses, glutathione becomes saturated, allowing excessive amounts of NAPQI to form adducts with hepatic proteins that disrupt hepatocyte mitochondrial function and cause oxidative injury. Because acetaminophen-induced liver injury primarily affects hepatocytes (ie, hepatocellular liver injury), laboratory findings show markedly elevated aminotransferases with levels sometimes >1,000 U/L. Mild elevations of bilirubin and alkaline phosphatase can be seen but may be normal. Liver biopsy shows centrilobular hepatic necrosis, a common finding in ischemic or toxic liver injury. (Choice A) Certain drugs (eg, carbamazepine, phenytoin) can trigger a robust CD4⁺ and CD8⁺ T-cell response against hepatic proteins, leading to drug reaction with eosinophilia and systemic symptoms (DRESS). Although hepatocellular liver injury can occur, fever, lymphadenopathy, and skin manifestations (eg, facial edema, coalescing erythema) would be expected. (Choice B) Drug-mediated (eg, ceftriaxone) cholestatic liver injury typically causes biliary duct damage or interrupts the flow of bile. These patients have markedly elevated levels of alkaline phosphatase (and sometimes bilirubin), and aminotransferase levels are typically normal. (Choice D) Microvesicular steatohepatitis, or small droplets of intracytoplasmic lipids within hepatocytes, is caused by drugs that disrupt fatty acid beta-oxidation. Ibuprofen and aspirin are commonly used analgesics that can rarely lead to this condition; however, marked aminotransferase elevations are not seen in ibuprofen toxicity, and aspirin toxicity is usually seen in young children with a recent viral infection (ie, Reye syndrome). (Choice E) Chronic alcohol consumption can generate reactive oxygen species (ROS), which activate stellate cells and cause cirrhosis. Although NAPQI does create ROS, stellate cell activation does not occur, and this patient's acute liver injury after analgesic ingestion makes this diagnosis unlikely. Educational objective: Excessive acetaminophen use causes toxicity through its metabolite N-acetyl-p-benzoquinone imine, which disrupts hepatocyte mitochondrial function and induces oxidative injury throughout the liver. The resulting hepatocellular liver injury markedly elevates aminotransferase, with levels sometimes exceeding 1,000 U/L.

A 16-Year-Old Girl Is Brought to the Emergency Department Because