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A newborn boy is assessed in the newborn nursery due to central cyanosis that does not respond to oxygen therapy. The patient was born to a G1P1 mother at 39 weeks gestation. The mother had diabetes that was managed with exercise and insulin during the pregnancy. The mother has never been vaccinated and did not follow routine prenatal care. The newborn's temperature is 99.5°F (37.5°C), blood pressure is 70/30 mmHg, pulse is 160/min, respirations are 27/min, and oxygen saturation is 80% on room air. The initial workup of the patient includes a chest radiograph seen in Figure A as well as lab values as seen below. Hemoglobin: 14 g/dL Hematocrit: 42% Leukocyte count: 6,500/mm^3 with normal differential Platelet count: 197,000/mm^3 Serum: Na+: 139 mEq/L Cl-: 101 mEq/L K+: 4.3 mEq/L HCO3-: 24 mEq/L BUN: 12 mg/dL Glucose: 99 mg/dL Creatinine: 0.5 mg/dL Ca2+: 10.0 mg/dL AST: 12 U/L ALT: 10 U/L An electrocardiogram is obtained as seen in Figure B. Which of the following is the most likely diagnosis?
Tetralogy of Fallot
Total anomalous pulmonary venous return
Transposition of the great vessels
Tricuspid valve atresia
Truncus arteriosus
C
Transposition of the great vessels
This patient is presenting with right axis deviation on ECG and an "egg on a string" heart on chest radiograph suggesting a diagnosis of transposition of the great vessels. Transposition of the great vessels occurs when the spiral septum that divides the truncus arteriosus into the aorta and pulmonary artery fails to spiral and connect the right ventricle to the pulmonary artery and the left ventricle to the aorta. Patients will present with central cyanosis and must have another cardiac defect/shunt in order to remain viable (such as an atrial septal defect, ventricular septal defect, or patent ductus arteriosus). Chest radiograph will reveal an "egg on a string" heart and ECG will reveal right axis deviation. The diagnosis is confirmed with echocardiography and treated surgically. Cohen et al. review the treatment of patients with transposition of the great vessels. They discuss how multiple surgical procedures have been performed in an attempt to address this congenital abnormality. They recommend using MRI to characterize the success of these procedures. Figure A is a chest radiograph demonstrating an elongated cardiac shadow (red circle). This classic "egg on a string" appearance of the heart is seen in transposition of the great vessels. Figure B is an ECG demonstrating right axis deviation as revealed by being down in lead I (red circle) and up in aVF. Right axis deviation is classically seen in transposition of the great vessels. Incorrect Answers: Answer A: Tetralogy of Fallot presents with a boot-shaped heart on a chest radiograph and classic "Tet spells" where patients will squat thus improving shunting and cardiac performance. Treatment is with surgical correction of the abnormal spiral septum. Answer B: Total anomalous pulmonary venous return occurs when pulmonary veins drain into the right heart circulation. It presents with cyanosis that does not correct with oxygenation but does not present with an "egg on a string" heart on a chest radiograph. Treatment is with surgical reconfiguration of pulmonary venous return. Answer D: Tricuspid valve atresia occurs when the tricuspid valve never forms and thus there is no connection between the right atrium and right ventricle. Patients will present with cyanosis and poor feeding/poor growth. Treatment is with surgical creation of a connection between these chambers. Answer E: Truncus arteriosus occurs secondary to failure of the spiral septum to divide the aorta and pulmonary artery. It presents with poor feeding, diaphoresis, tachypnea, and cyanosis. Treatment is with surgical separation of these arterial chambers. Bullet Summary: Transposition of the great vessels presents with central cyanosis, an "egg on a string" appearance on a chest radiograph, and right axis deviation on ECG.
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A 55-year-old man presents to the emergency department with nausea and vomiting for the past week. He decided to come in when his symptoms worsened. He feels that his symptoms are exacerbated with large fatty meals and when he drinks alcohol. His wife recently returned from a cruise with symptoms of vomiting and diarrhea. The patient has a medical history of poorly managed diabetes, constipation, anxiety, dyslipidemia, and hypertension. His temperature is 99.5°F (37.5°C), blood pressure is 197/128 mmHg, pulse is 100/min, respirations are 17/min, and oxygen saturation is 95% on room air. Physical exam reveals a systolic murmur heard loudest along the left upper sternal border. Abdominal exam reveals an obese, tympanitic and distended abdomen with a 3 cm scar in the right lower quadrant. Vascular exam reveals weak pulses in the lower extremities. Which of the following is the most likely underlying etiology of this patient's symptoms?
Adhesions
Enteric nervous system damage
Impacted stool
Norovirus
Twisting of the bowel
A
Adhesions
This patient is presenting with abdominal pain and a tympanitic abdomen, which are symptoms suggestive of a small bowel obstruction. In developed countries, these typically occur secondary to adhesions. Small bowel obstructions (SBO) typically present with an absence of bowel sounds, bowel movements, and flatus, as well as abdominal distension, nausea, and vomiting. They typically occur secondary to adhesions which entrap the bowel and disrupt its normal peristalsis. Adhesions can occur after abdominal surgery or trauma as part of the normal healing process. The diagnosis of SBO can be confirmed using abdominal imaging such as a CT scan. Treatment often involves observation; however, surgical decompression of the SBO may be needed if there is a closed-loop obstruction or an obstruction that does not resolve on its own. Rami Reddy and Cappell review the evidence regarding the diagnosis and treatment of SBO. They discuss how this disease has a 30% mortality rate if the diagnosis is missed and bowel perforation occurs. They recommend early evaluation and treatment of these patients. Incorrect Answers: Answer B: Enteric nervous system damage describes diabetic gastroparesis which can present similarly to SBO; however, this patient's age and history of surgery points toward SBO as the most likely diagnosis. Treatment is with pro-motility agents. Answer C: Impacted stool describes constipation which could present similarly to SBO; however, this diagnosis is less likely to cause nausea and vomiting unless it is severe. The vomit typically smells like stool. Treatment is with dis-impaction of the colon. Answer D: Norovirus typically causes nausea, vomiting, and diarrhea but does not cause distension and a tympanitic abdomen. Treatment is supportive as the virus self-resolves. Answer E: Twisting of bowel describes a volvulus which presents similarly to SBO; however, it is a more common diagnosis in the elderly and is a less common diagnosis than is SBO in a patient with a history of abdominal surgery. Treatment is with surgical untwisting of the bowel. Bullet Summary: Small bowel obstruction (commonly caused by adhesions) presents with nausea, vomiting, absence of flatus/bowel movements, and a distended/tympanic abdomen.
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A 52-year-old G3P3 woman presents to clinic with a 2-year history of urinary incontinence. She has had frequent, involuntary loss of urine over the last 2 years but presented today because of 10 days of dysuria. She has been treated for 2 urinary tract infections over the past 6 months. She does not endorse any loss of urine with coughing or laughter. She has no chronic medical illnesses and no surgical history. Her temperature is 99.5°F (37.5°C), blood pressure is 120/80 mmHg, pulse is 92/min, and respirations are 15/min. Her BMI is 30 kg/m^2. On pelvic examination, the vagina is dry and atrophic with a 2-cm tender, palpable anterior vaginal mass. The mass does not change with Valsava maneuver. Her postvoid residual volume is 60 mL. Which of the following is the most likely diagnosis?
Overflow incontinence
Pelvic organ prolapse
Stress urinary incontinence
Urethral diverticulum
Vesicovaginal fistula
D
Urethral diverticulum
This patient is presenting with a history of dysuria, incontinence, and recurrent lower urinary tract infections in conjunction with a tender anterior vaginal wall mass. The most likely diagnosis is a urethral diverticulum. A urethral diverticulum is an abnormal, localized outpouching of the urethral mucosa often due to recurrent periurethral gland infection. The outpouching can often collect and store urine, resulting in slow postvoid dribbling and recurrent urinary tract infections. Urethral diverticula can often be associated with expressed purulent or bloody discharge on exam. Initial workup includes urinalysis and transvaginal ultrasound. Diagnosis can be confirmed with a pelvic MRI before referral for surgical excision. Greiman et al. review urethral diverticula and its treatment. They note that surgical repair is challenging. However, it is still recommended to perform surgery in appropriate candidates. Incorrect Answers: Answer A: Overflow incontinence (caused by impaired detrusor activity or bladder outlet obstruction) can also present with involuntary loss of urine due to urinary retention. However, this patient’s normal postvoid residual volume (< 150 mL) makes this an unlikely diagnosis. Patients will often present with a constant dribbling of urine and a sensation of incomplete voiding. Answer B: Pelvic organ prolapse occurs due to weakened pelvic support and increased intraabdominal pressure and can be exacerbated by increasing parity. While it can also present with incontinence, physical exam often reveals a bulging mass that increases with Valsava maneuver - a finding that is absent in this patient. Answer C: Stress urinary incontinence is caused by urethral hypermobility leading to urinary leakage from increased intraabdominal pressure. This patient’s urinary loss is unrelated to coughing or laughing, and stress incontinence would not explain the anterior vaginal mass. On exam, urine may be released with coughing. Answer E: Vesicovaginal fistula is an abnormal tract between the vagina and bladder that presents with constant leakage of urine due to the direct draining of urine from the bladder to the vagina. This patient’s incontinence is intermittent and not constant, and a vesicovaginal fistula would not explain the anterior vaginal mass. Bullet Summary: A urethral diverticulum presents with dysuria, intermittent urinary incontinence, and a tender anterior vaginal wall mass that may cause recurrent urinary tract infections.
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A 7-year-old boy is brought to the emergency department by his parents for worsening symptoms of previously diagnosed acute sinusitis. Initially, the pediatrician prescribed decongestants and sent the patient home. Since then, the patient has developed a nasal discharge with worsening pain. The patient has a medical history of asthma which is well-controlled with albuterol. His temperature is 99.5°F (37.5°C), blood pressure is 90/48 mmHg, pulse is 124/min, respirations are 17/min, and oxygen saturation is 98% on room air. The cardiopulmonary exam is within normal limits. Inspection of the patient's nose reveals a unilateral purulent discharge mixed with blood. The rest of the patient's exam is within normal limits. Which of the following is the most likely diagnosis?
Bleeding and infected vessel of Kiesselbach plexus
Foreign body obstruction
Nasopharyngeal carcinoma
Septal perforation
Sinusitis with bacterial superinfection
B
Foreign body obstruction
This patient presents with unilateral bloody/purulent discharge from the nose suggesting a diagnosis of a nasal foreign body. The most common cause of unilateral nasal symptoms in a pediatric patient is a nasal foreign body. Nasal foreign bodies tend to be unilateral (though bilateral symptoms are plausible) and present with a purulent and bloody discharge. The treatment of choice is to remove the object which may be done in the emergency department or operating room depending on how deep the object is. Visualization of the object should be attempted when possible in order to allow for safe retrieval. Krulewitz and Fix review the evidence regarding the diagnosis and treatment of patients with epistaxis. They discuss how foreign body insertion is a major risk factor for the development of epistaxis. They recommend assessment of airway and breathing in the setting of severe epistaxis. Incorrect Answers: Answer A: A bleeding and infected vessel of the Kiesselbach plexus could suggest a complicated case of epistaxis. The persistent, unilateral symptoms in this patient point toward a different diagnosis. A high index of suspicion for foreign bodies should be suspected in children. Answer C: Nasopharyngeal carcinoma tends to occur in young male patients and can be associated with infectious mononucleosis. Epistaxis can be a symptom and the mass can be visualized. This disease tends to present in older patients and is far less common than foreign bodies. Treatment is with surgical resection. Answer D: Septal perforation can occur secondary to repeat cocaine use but would not present with unilateral nasal discharge in a pediatric patient. It would be highly unlikely in a pediatric patient with no history of drug use. Treatment is with cessation of the offending agent. Answer E: Sinusitis with bacterial superinfection would typically present with systemic symptoms as well as bilateral symptoms. Though this diagnosis is possible, it is less likely than a foreign body. Treatment is with systemic antibiotic therapy. Bullet Summary: A nasal foreign body presents with unilateral bloody/purulent nasal discharge.
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A 23-year-old man presents to the emergency department. He was brought in by police for shouting on a subway. The patient claims that little people were trying to kill him and he was acting within his rights to defend himself. The patient has a medical history of marijuana and IV drug use as well as multiple suicide attempts. He is currently homeless. While in the ED, the patient is combative and refuses a physical exam. He is given IM haloperidol and diphenhydramine. The patient is transferred to the inpatient psychiatric unit and is continued on haloperidol throughout the next week. Though he is no longer aggressive, he is seen making "armor" out of paper plates and plastic silverware to defend himself. His temperature is 98.6°F (37°C), blood pressure is 115/71 mmHg, pulse is 72/min, and respirations are 12/min. The patient's treatment history is significant for failure to obtain symptom control with risperidone, haloperidol, and ziprasidone. Which of the following is the most appropriate next step in management?
Chlorpromazine
Clozapine
Fluphenazine
Olanzapine
Thioridazine
B
Clozapine
This patient is presenting with symptoms of schizophrenia that are refractory to treatment with both typical and atypical antipsychotics. The most appropriate next step in management is treatment with clozapine. Schizophrenia presents with auditory and/or visual hallucinations among many other findings. The most appropriate initial treatments are with a typical antipsychotic (haloperidol) or an atypical antipsychotic (risperidone). Once a patient has failed treatment with multiple medications (at least 2) from different classes, the next best step in management is clozapine. This medication is reserved for patients who have sustained treatment failure (because of the side effects of clozapine). These include weight gain, life-threatening agranulocytosis, and aplastic anemia. Regular complete blood count laboratory testing should be drawn while on clozapine to check for this side effect. Patients who develop this complication should immediately stop the medication but the side effect can be irreversible. Khokhar et al. review the evidence regarding the use of clozapine to treat schizophrenia. They discuss how side effects of this medication include agranulocytosis, myocarditis, and seizures. They recommend using this medication with care and monitoring for the development of these complications. Incorrect Answers: Answer A: Chlorpromazine is a typical antipsychotic that is likely to fail given that haloperidol did not work for him. Important side effects of this medication include hypotension and sedation due to anticholinergic properties. This medication also has an idiosyncratic complication of corneal deposits. Answer C: Fluphenazine is another typical anti-psychotic that is a strong D2 antagonist like haloperidol. If haloperidol failed, it is unlikely that another typical antipsychotic would work with such a similar mechanism of action. This medication has a high association with extrapyramidal side effects such as dystonia, akathisia, and tardive dyskinesia. Answer D: Olanzapine is another atypical antipsychotic. Switching to another atypical antipsychotic is a viable option. Given that this patient has already failed another atypical antipsychotic and that his symptoms remain, the best therapy at this point would be clozapine. Side effects include weight gain and dyslipidemia. Answer E: Thioridazine is a low-potency anti-psychotic that would likely not work if more potent drugs such as haloperidol or risperidone have already failed. Important side effects to be aware of include hypotension and sedation due to anticholinergic properties. This medication also has an idiosyncratic complication of retinal deposits. Bullet Summary: Clozapine is the treatment of choice in patients who have failed therapy with multiple different classes of antipsychotics and who have severe symptoms.
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A 37-year-old machinist presents to his primary care physician with eye problems. He has felt a mass in his eye that has persisted for the past month. The patient has a medical history of blepharitis treated with eye cleansing and squamous cell carcinoma of the skin treated with Mohs surgery. His temperature is 99.5°F (37.5°C), blood pressure is 157/102 mmHg, pulse is 90/min, respirations are 17/min, and oxygen saturation is 98% on room air. Physical exam is notable for a firm and rubbery nodule palpable inside the patient's left eyelid. Physical exam does not elicit any pain. Which of the following is the most likely diagnosis?
Chalazion
Foreign body
Hordeolum
Ingrown eyelash follicle
Meibomian cell carcinoma
A
Chalazion
This patient presenting with a painless firm and rubbery nodule has symptoms that are suggestive of a chalazion. Chalazion presents with a hard and painless eyelid nodule. This pathology occurs secondary to granulomatous inflammation of the Meibomian gland. The lesion can be treated with simple excision; however, recurrent lesions are concerning for Meibomian cell carcinoma. The most important differential diagnosis to consider in these patients is a hordeolum which presents with a firm and painful lid nodule (in contrast to painless). Treatment is with warm compresses followed by incision and curettage in refractory cases. Li et al. review the evidence regarding the diagnosis and treatment of chalazion. They discuss how gland loss is a possible sequelae from this disorder. They recommend using warm compresses for symptomatic relief. Incorrect Answers: Answer B: Foreign body is a possible diagnosis given this patient's occupation as a machinist; however, this would typically present with pain over the patient's cornea with a sudden onset of symptoms. Treatment is with removal of the foreign body. Answer C: Hordeolum presents with a hard and painful lid nodule in contrast to a hard and painless lid nodule. Treatment is with warm compresses and possible debridement in refractory cases. Answer D: Ingrown eyelash follicle could present with a firm lid nodule; however, it would be located near the margin of the eyelid and would likely be inflamed and tender. Treatment is with warm compresses and possible debridement in refractory cases. Answer E: Meibomian cell carcinoma is a possible diagnosis but is epidemiologically less common than a chalazion. This diagnosis would be more likely if the lesion was recurrent despite excision. Treatment is with wide excision of the lesion. Bullet Summary: Chalazion presents with a firm and painless eyelid nodule.
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A 67-year-old man presents to the emergency department 1 hour after sudden-onset weakness and double vision. His medical history is significant for hyperlipidemia and poorly controlled hypertension. His current medications include atorvastatin and amlodipine. His temperature is 98.6°F (37.0°C), blood pressure is 175/95 mmHg, pulse is 90/min, respirations are 16/min. On cranial nerve exam, his left pupil is 6 mm in diameter compared to 3 mm on the right. His left eye is displaced laterally and downward and he also has left-sided ptosis. Strength is 2/5 in the right upper and right lower extremities and 5/5 in the left upper and left lower extremities. He has marked right-sided dysdiadochokinesia. Sensation is intact throughout. Which of the following regions of his brain is most likely affected?
Lateral medulla
Lateral pons
Medial pons
Midbrain
Posterior limb of internal capsule
D
Midbrain
This patient with a history of poorly controlled hypertension, acute onset of left-sided oculomotor nerve palsy (mydriasis, ptosis, and “down and out” pupil), right-sided paresis, and right-sided dysdiadochokinesia most likely has a lacunar stroke of the left midbrain. Important structures in the midbrain often affected by stroke include the oculomotor nucleus, substantia nigra, corticospinal tract, red nucleus, and superior cerebellar peduncle. Occlusions to branches of the basilar artery lead to infarctions of various parts of the midbrain. Midbrain lesions almost always manifest with an ipsilateral oculomotor palsy (ptosis from the levator palpebrae muscle; mydriasis from loss of parasympathetic inflow; abduction and excyclotorsion of the globe from the superior rectus, medial rectus, inferior rectus, and inferior obliques). There may also be contralateral ataxia (cerebellar peduncle after decussation and red nucleus), contralateral hemiparesis (corticospinal tract before decussation at the medulla), and parkinsonian tremor (substantia nigra). Sciacca et al. review the anatomy and clinical signs of strokes of the midbrain, pons, and medulla. They discuss how a stroke of the midbrain will present with oculomotor palsy and paresis. They recommend being vigilant for symptoms of strokes to allow for early diagnosis. Incorrect Answers: Answer A: Lateral medullary syndrome (Wallenberg syndrome) is usually due to a stroke of the posterior inferior cerebellar artery. This presents with ipsilateral ataxia, loss of pain and temperature sensation in the face, dysarthria, and Horner syndrome, as well as contralateral loss of pain and temperature sensation in the body. In this patient with intact sensorium and without dysarthria, lateral medullary syndrome is less likely. Answer B: Lateral pontine syndrome can be caused by interruption of blood supply by the anterior inferior cerebellar artery. It presents with ipsilateral limb and gait ataxia, ipsilateral Horner syndrome, ipsilateral facial hemianesthesia, ipsilateral facial paralysis, nystagmus and vertigo, and contralateral loss of pain and temperature in the body. In this patient with intact sensorium and without facial paralysis, vertigo, and oculomotor palsy, midbrain stroke is more likely than a pontine stroke. Answer C: Medial pontine syndrome can be due to occlusion of the paramedian branches of the basilar artery and disrupts the abducens nerve, the dorsal column-medial lemniscus, and the corticospinal tract. This results in contralateral spastic hemiparesis, ipsilateral lateral rectus paralysis (eye turned down and in), and contralateral loss of vibration and stereognosis. In this patient with ptosis, and an eye turned down and out, oculomotor palsy and a midbrain stroke are more likely than a pontine stroke. Answer E: Strokes of the posterior limb of the internal capsule lead to contralateral hemiparesis. Strokes of the internal capsule would not be expected to lead to oculomotor nerve palsy or dysdiadochokinesia. The constellation of ataxia, hemiparesis, and cranial nerve palsy is more suggestive of a brainstem pathology than of a lacunar stroke in the internal capsule. Bullet Summary: Midbrain strokes commonly present with ipsilateral oculomotor nerve palsy and contralateral hemiparesis/hemiplegia, contralateral hemiataxia, and/or contralateral tremor.
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A 55-year-old man with a history of polysubstance abuse is found down in his home acutely obtunded. Emergency medical services administered naloxone which immediately woke the patient up and improved his oxygen saturation from 40% to 90%. However, they noted subsequently that the patient demonstrated increased work of breathing and had crackles and wheezing on pulmonary exam. The patient arrives alert and oriented claiming he feels short of breath. He denies any chest pain or other symptoms aside from shortness of breath. He has a history of cocaine-induced cardiomyopathy and myocardial infarction from cocaine use 2 years ago. The patient has a 40 pack-year smoking history. His temperature is 96.0°F (35.6°C), blood pressure is 120/68 mmHg, pulse is 102/min, respirations are 26/min, and oxygen saturation is 88% on room air. Physical exam reveals increased work of breathing, pulmonary crackles, and wheezing. A chest radiograph is performed as seen in Figure A. Which of the following is the most likely etiology of this patient's current symptoms?
Atypical pneumonia
Chronic obstructive pulmonary disease
Community acquired pneumonia
Medication administration
Poor cardiac function
D
Medication administration
This patient is presenting after administration of naloxone with respiratory distress, wheezing, crackles, and pulmonary edema on chest radiography, suggesting acute pulmonary edema. Given the presence of symptoms immediately following naloxone administration, the cause of the pulmonary edema is likely the naloxone (medication-induced) that was administered. Opioid use disorder is a common problem in the United States and can lead to overdose, which is life-threatening if not treated. Patients with symptoms of opioid intoxication including miosis, bradypnea, and altered mental status should be empirically given naloxone, as it may be life-saving and is relatively benign. Naloxone should only be given for patients with unstable vitals or who are failing to ventilate/oxygenate or protect their airway. Naloxone commonly precipitates withdrawal and may cause nausea, vomiting, diarrhea, and pain. It is possible for naloxone to cause pulmonary edema (via a poorly elucidated mechanism). Pulmonary edema presents with wheezing, tachypnea, and pulmonary crackles. The most important intervention when treating pulmonary edema is to address the underlying cause and start the patient on positive pressure ventilation. Diuretics may be administered if the patient is volume overloaded. An echogardiogram can rule out poor cardiac function as the underlying etiology as well. Lassen et al. review naloxone use and pulmonary edema. They note that naloxone administration can cause non-cardiogenic pulmonary edema and that the mechanism is not well elucidated. They recommend that naloxone should only be used at the lowest dose possible to stabilize the patient. Figure A is a chest radiograph demonstrating "fluffy" interstitial infiltrates throughout both lung fields suggestive of pulmonary edema. Incorrect Answers: Answer A: Atypical pneumonia may present with a dry cough, fever, hypoxia, and increased interstitial markings on chest radiograph. These patients are usually well appearing, and the opacities are not as "fluffy" as pulmonary edema. A common cause is Mycoplasma pneumoniae. Answer B: Chronic obstructive pulmonary disease (COPD) presents with a flattened diaphragm and increased number of visible ribs on chest radiography as a result of air accumulation in the chest. Pneumonia may be present on chest radiograph and is a common cause of COPD flares. A COPD flare may present with wheezing, poor air movement, hypoxia, and hypercarbia. Answer C: Community-acquired pneumonia presents with a fever, cough, hypoxia, and a lobar consolidation on chest radiograph. This infiltrate is usually confined to one lobe and is thus often called "lobar pneumonia." Streptococcus pneumoniae is the most common cause. Answer E: Poor cardiac function can cause pulmonary edema via increased hydrostatic pressure backing up into the lungs causing fluid leakage. Though the appearance of pulmonary edema would be the same, naloxone causes non-cardiogenic pulmonary edema. In this patient with a previous myocardial infarction, a low ejection fraction may plausibly be contributing to this patient's pulmonary edema; however, the association of symptoms with naloxone administration makes this a less likely etiology for this case. Bullet Summary: Naloxone can cause non-cardiogenic pulmonary edema.