A 74-year-old woman comes to the emergency department due to 2 days of left leg pain and numbness. She has a history of atrial fibrillation and hypertension. Her left lower limb is pale and cold to palpation below the knee. Arterial Doppler ultrasound shows an occluding thrombus, and a left femoral embolectomy is performed. Post-procedure dorsalis pedis and posterior tibial pulses become palpable. Several hours later, the patient begins to experience severe left calf pain. On repeat examination, the left calf is swollen, tense, and tender, and the pain worsens with dorsiflexion of the left foot. The distal pulses are also absent. The physician suspects injury of the reperfused muscles in part due to overproduction of reactive oxygen species. Which of the following enzymes is most likely to help neutralize these toxic molecules?

Question

A 74-year-old woman comes to the emergency department due to 2 days of left leg pain and numbness.  She has a history of atrial fibrillation and hypertension.  Her left lower limb is pale and cold to palpation below the knee.  Arterial Doppler ultrasound shows an occluding thrombus, and a left femoral embolectomy is performed.  Post-procedure dorsalis pedis and posterior tibial pulses become palpable.  Several hours later, the patient begins to experience severe left calf pain.  On repeat examination, the left calf is swollen, tense, and tender, and the pain worsens with dorsiflexion of the left foot.  The distal pulses are also absent.  The physician suspects injury of the reperfused muscles in part due to overproduction of reactive oxygen species.  Which of the following enzymes is most likely to help neutralize these toxic molecules?

Quizplus · Accepted Answer

11ec160b_39f3_e81c_9249_6faa3d710f7e_MD0001_00 The vignette describes acute compartment syndrome secondary to reperfusion injury. Restoration of arterial blood flow to an affected limb floods ischemic tissue with oxygen. Molecular oxygen reacts with xanthine oxidase, NADPH oxidase, and nitric oxide synthase to form reactive oxygen species (ROS) such as superoxide, hydroxyl radicals, and singlet oxygen. ROS disrupt cellular functions leading to DNA mutations, protein synthesis disruption, and membrane lipid peroxidation. Antioxidant enzymes, such as superoxide dismutase, glutathione peroxidase, and catalase, convert ROS to oxygen and water, neutralizing their capacity for cellular damage. ROS generated during cellular respiration are typically neutralized by antioxidants before they become problematic. However, in the postischemic state, the production of ROS exceeds the neutralizing capabilities of antioxidant enzymes (high oxidative stress), leading to increased cell injury and death. (Choice A) Cytochrome oxidase is the final component of the electron transport chain and functions to convert molecular oxygen to water while establishing the proton gradient necessary for synthesis of ATP. (Choice B) Cytochrome P450 enzymes metabolize endogenous toxins as well as drugs. They are capable of producing reactive oxygen species, which can contribute to the hepatotoxicity seen with certain drugs. (Choice C) Myeloperoxidase is found in neutrophils and converts hydrogen peroxide to hypochlorous acid, a bactericidal compound that also causes oxidative damage to host cells. (Choice D) NADPH oxidase catalyzes the reduction of molecular oxygen to superoxide free radicals, aiding in bacterial destruction by phagocytic cells. Deficiency leads to chronic granulomatous disease in which those affected are unable to destroy catalase-positive organisms. Educational objective: As an antioxidant, superoxide dismutase neutralizes reactive oxygen species, preventing cell injury. In a pathologic state such as post-ischemic reperfusion, oxidative stress is high and reactive oxygen species production exceeds the neutralizing capability of antioxidants, leading to increased cell damage and death. __________ References: Reperfusion injury and reactive oxygen species: The evolution of a concept. (http://www.ncbi.nlm.nih.gov/pubmed/26484802)

A 74-Year-Old Woman Comes to the Emergency Department Due to 2