UWorld Review 5/9
A 3-year-old boy is brought to the office with 5 days of productive cough and fever. Examination shows a tachypneic, ill-appearing child with rales over the right lower lung. Chest x-ray reveals right lower lobe pneumonia. The boy is admitted to the hospital for intravenous antibiotics. Review of his medical history shows 4 prior pneumonias, and his weight is at the third percentile. Further testing demonstrates high sweat chloride content, and genetic sequencing shows a mutation in a transmembrane protein. Which of the following best describes the dysfunctional transmembrane protein causing this patient's disease?
ATP-gated - Cystic fibrosis (CF) is an autosomal recessive disorder due to mutations (eg, ΔF508) in the CF transmembrane conductance regulator (CFTR) protein. The channel pore opens after binding of 2 ATP molecules, allowing transport of chloride ions down the electrochemical gradient. The movement of chloride establishes a membrane potential that draws sodium and water across the membrane as well. By encouraging sodium chloride and water transport across epithelial membranes, the CFTR hydrates mucosal surfaces in the airways and bowel. Mutations in the CFTR gene lead to intracellular protein degradation and decreased activity of the proteins that do reach the membrane. This leads to thick mucus on the lining of epithelial cells, which results in clinical manifestations of chronic cough, recurrent pneumonias, and pancreatic damage. The normal CFTR protein also plays a role in the production of hypotonic sweat. In the eccrine gland, sweat is initially isotonic with the plasma, and normally sodium chloride is removed from the ductal lumen by CFTR. In the absence of functional CFTR, patients with CF cannot remove salt from their sweat and therefore have elevated sweat chloride and sodium levels. As early as the 17th century, increased mortality was recognized for children whose foreheads tasted salty. Today, the sweat chloride test is frequently used to screen for CF.
A 64-year-old man dies suddenly while playing tennis. In the preceding months, the patient experienced fatigue and some exertional dyspnea. Autopsy reveals rupture of an unsuspected ascending aortic aneurysm. Heart examination shows a septal thickness of 1.1 cm (normal: ≤1.1), a posterior wall thickness of 1.1 cm (normal: ≤1.1), and an internal left ventricular diameter of 6.8 cm (normal: 3.5-5.9). No focal myocardial scarring is seen. Which of the following is the most likely cause of the cardiac findings seen in this individual?
Aortic regurgitation - This individual's autopsy reveals a dilated left ventricular (LV) cavity with relatively thin ventricular walls, a finding consistent with eccentric hypertrophy. Eccentric hypertrophy results from the addition of myocardial contractile fibers in series in response to chronic volume overload. The adaptation allows the left ventricle to increase stroke volume and maintain cardiac output; however, LV wall stress increases, resulting in eventual decompensation and the development of heart failure. Common causes of eccentric hypertrophy include cardiomyopathy, ischemic heart disease, and chronic aortic or mitral valve regurgitation. In developed countries, aortic root dilation is one of the most common causes of chronic aortic regurgitation. This individual with an ascending aortic aneurysm likely had aortic root dilation with consequent chronic aortic regurgitation, leading to LV volume overload and eccentric hypertrophy.
A 66-year-old man comes to the office for a routine visit. He has a history of hypertension and osteoarthritis. The patient has smoked a pack of cigarettes daily for 40 years and occasionally drinks 1 or 2 glasses of wine but does not use illicit drugs. Blood pressure is 142/82 mm Hg and pulse is 80/min. Cardiopulmonary examination is normal. There is a pulsating, central abdominal mass on physical examination. Which of the following pathologic conditions is the most likely underlying cause of this patient's abnormal findings?
Chronic transmural inflammation - This patient's pulsating, central abdominal mass most likely represents an abdominal aortic aneurysm (AAA), which is a focal dilation of the abdominal aorta that typically occurs below the renal arteries. AAA is associated with several risk factors (eg, age >60, smoking, hypertension, male sex, family history) that lead to oxidative stress, vascular smooth muscle apoptosis, and chronic transmural inflammation of the aorta. Inflammatory cells (particularly macrophages) release matrix metalloproteinases and elastases that degrade extracellular matrix components (eg, elastin, collagen), leading to weakening and progressive expansion of the aortic wall. Furthermore, ischemia of the tunica media may play a role as the infrarenal abdominal aorta has a tenuous vasa vasorum, and atherosclerotic thickening of the intimal layer increases the diffusion distance for oxygen.
A 55-year-old man comes to the emergency department with recurrent episodes of retrosternal chest pain. The episodes occur during physical activity, usually when he climbs stairs or walks uphill. The patient has no known medical problems and does not use tobacco, alcohol, or illicit drugs. He is given a sublingual tablet and reports rapid relief of the pain. This drug most likely improved this patient's symptoms by causing which of the following hemodynamic changes?
Decrease in left ventricular end-diastolic volume - This patient has a classic presentation of chronic stable angina, which is characterized by chest pain that occurs with activity and is relieved with rest or sublingual nitroglycerin. Nitrates exert their effect by direct vascular smooth muscle relaxation that results in: vasodilation of the peripheral veins and arteries, predominantly venodilation, decreased left ventricular wall stress due to reduced preload (decreased left ventricular end-diastolic volume and pressure), modest reduction in afterload due to systemic arterial vasodilation, mild coronary artery dilation and reduction of coronary vasospasm. This results in decreased myocardial oxygen demand, leading to improved exercise tolerance and relief of angina symptoms.
A 39-year-old woman comes to the office due to a nagging cough. Two weeks ago, the patient had a mild upper respiratory illness which resolved spontaneously after several days. Since then, she has had cough that is productive of minimal clear sputum. The patient has had no shortness of breath or chest pain. She took unexpired, leftover dextromethorphan for 2 days. The patient's only other medical condition is major depression, for which she takes sertraline. She does not use tobacco, alcohol, or illicit drugs. Vital signs and physical examination show no abnormalities. Use of dextromethorphan is most concerning for which of the following in this patient?
Drug-drug interaction - Dextromethorphan (DXM) is a popular cough suppressant (antitussive agent) that is readily available over the counter. Its primary mechanism of action is inhibition of the medullary cough center through sigma (σ) receptor activation. Although structurally very closely related to other opioid morphinans (eg, codeine, morphine), DXM has trivial mu (μ) and delta (δ) opioid receptor affinity. Therefore, classic opioid adverse effects (eg, constipation, respiratory depression, analgesia, sedation) are not seen at therapeutic doses. This favorable pharmacologic profile makes DXM a first-choice agent for cough suppression. However, DXM also increases serotonin activity in the CNS by decreasing the rate of presynaptic serotonin reuptake and directly stimulating serotonin receptors. For this reason, DXM abuse can cause serotonin syndrome, manifesting as muscular hypertonia, spasticity (eg, clonus, hyperreflexia), autonomic instability (eg, hyperthermia, hypertension), and encephalopathy. This potentially fatal condition most often occurs in settings of overdose or accidental drug interaction with other serotonergic drugs (eg, selective serotonin reuptake inhibitors, triptans, monoamine oxidase inhibitors).
A 13-year-old girl is undergoing hematologic evaluation. She is found to have a hemoglobin mutation that changes the partial pressure of oxygen at which hemoglobin is 50% saturated to 20 mm Hg. In comparison, normal hemoglobin becomes 50% saturated with oxygen at 26 mm Hg. Which of the following sequelae is this patient most likely to develop as a result of her mutation?
Erythrocytosis - A P50 shift from 26 to 20 mmHG indicates that the affinity for oxygen has increased (left shift). Mutations that cause production of hemoglobin with high oxygen affinity (hemoglobins Chesapeake and Kempsey) reduce the ability of hemoglobin to release oxygen within the peripheral tissues. Low oxygen levels stimulate the kidneys to increase erythropoietin synthesis which results in compensatory erythrocytosis to help maintain oxygen delivery. These patients are often asymptomatic due to this compensation.
A 37-year-old woman is evaluated for exertional shortness of breath. The patient has had progressive dyspnea for the last year and for the last 2 months has been unable to walk half a block without stopping to rest. She also describes lightheadedness during exertion. Medical history is insignificant, and vital signs are within normal limits. BMI is 23 kg/m2. Physical examination reveals a 2/6 holosystolic murmur at the lower sternal border, which increases with inspiration. Further evaluation indicates no evidence of obstructive or interstitial lung disease or venous thromboembolism. Cardiac catheterization results are as follows: Mean pulmonary artery pressure 43 mm Hg (normal: 8-20) Pulmonary capillary wedge pressure 9 mm Hg (normal: 6-12) Pharmacotherapy blocking the effects of which of the following substances is most likely to benefit this patient?
Endothelin - This patient has pulmonary hypertension, which typically presents with progressive dyspnea and fatigue, sometimes with associated chest pain and exertional lightheadedness or syncope. Due to right ventricular enlargement, a holosystolic murmur of functional tricuspid regurgitation is often present. Pulmonary hypertension due to a primary change in the pulmonary arteries, termed pulmonary arterial hypertension (PAH), results from proliferative vasculopathy of the pulmonary arteriolar smooth muscle, which may occur in the setting of hereditary genetic mutation (BMPR2 mutation is most common), connective tissue disease, or HIV infection. Endothelin is a potent vasoconstrictor that also promotes smooth muscle cell proliferation; it is typically found in high concentrations in patients with PAH and it is an important target of therapy for the disease. Endothelin receptor antagonists (eg, bosentan, ambrisentan) inhibit pulmonary arteriolar smooth muscle proliferation and alleviate vasoconstriction to lower pulmonary arterial pressure and improve dyspnea in patients with PAH.
A 53-year-old man comes to the office with progressive exertional dyspnea. He has smoked 2 packs of cigarettes per day for the last 35 years. Physical examination shows increased anteroposterior diameter of his chest. Auscultation reveals decreased breath sounds and scattered wheezes throughout his lungs. Examination of his extremities is unremarkable. Echocardiography reveals moderate dilation of the right ventricle and increased central venous pressure. The absence of peripheral edema in this patient is best explained by which of the following compensatory mechanisms?
Increased tissue lymphatic drainage - This patient has dyspnea, signs of lung hyperinflation, and a heavy smoking history, suggesting chronic obstructive pulmonary disease (COPD). Chronic hypoxia in COPD can lead to pulmonary vasoconstriction, increased pulmonary artery pressure, and right heart failure (ie, cor pulmonale), which is confirmed by this patient's echocardiogram. In turn, right heart failure leads to increased central venous pressure and elevated peripheral capillary hydrostatic pressure, encouraging the development of peripheral edema. Fluid movement across the capillary wall (filtration) into the interstitium is dependent on hydrostatic pressure, oncotic pressure, and capillary permeability. It is tightly balanced by lymphatic drainage, which returns interstitial fluid to the vasculature. Peripheral edema (accumulation of excess fluid in the interstitial space) develops when transcapillary plasma filtration exceeds the resorptive capacity of the lymphatics. Factors that favor development of edema include: Elevated capillary hydrostatic pressure: Higher capillary pressures increase plasma filtration into the interstitium, particularly in dependent tissues. Causes include sodium and water retention (eg, heart failure, renal failure), arteriolar dilation (eg, dihydropyridine calcium channel blockers), and impaired venous return (eg, venous thrombosis). Decreased plasma oncotic pressure: Plasma proteins (eg, albumin) generate oncotic pressure that pulls interstitial fluid back into the capillary bed venules. Edema develops in conditions with decreased albumin levels (eg, nephrotic syndrome, cirrhosis, malnutrition). Lymphatic obstruction: Decreased lymphatic return impairs removal of excess interstitial fluid. Common causes of lymphatic obstruction include filariasis, invasive malignancies, and iatrogenic etiologies (eg, surgical lymph node dissection and radiation therapy). The peripheral lymphatics can significantly increase lymphatic drainage from baseline, allowing compensation for increased capillary fluid filtration that can temporarily delay the development of peripheral edema. However, because the peripheral lymphatics offload fluid to the central venous system (via the thoracic duct), which in heart failure is already volume overloaded, the overall ability to compensate is limited.
A 19-year-old man comes to the office due to frequent episodes of disorientation, palpitations, tremulousness, and excessive sweating over the past 3 months. He says the symptoms resolve quickly after drinking some juice or a carbonated beverage. The patient was diagnosed with type 1 diabetes mellitus at age 12 and takes short- and long-acting insulin. He has had no dose changes in the past 2 years or diabetic complications and follows up with an ophthalmologist frequently. The patient is a college student and reports some stress due to an upcoming midterm examination. He does not use tobacco, alcohol, or illicit drugs. Vital signs and physical examination are within normal limits. Laboratory results show a hemoglobin A1c of 6.8% and no proteinuria. Which of the following factors most likely precipitated this patient's current symptoms?
Intense exercise - This patient has frequent symptomatic hypoglycemia—disorientation, sweating, and palpitations, which are relieved by intake of glucose—despite no changes to his chronic insulin regimen. Hypoglycemia is often induced in patients with type 1 diabetes by inadvertent overdose of insulin or decreased carbohydrate intake (eg, skipped meal), but can also be triggered by intensive physical activity/exercise. Glucose uptake by skeletal muscle cells is mediated by glucose transporter type 4 (GLUT4). GLUT4 is translocated to cell membranes and transverse tubules (deep invaginations in the cell membrane) in response to insulin. GLUT4 translocation also occurs during muscle contraction by an insulin-independent mechanism, which is mediated by several cellular factors, including AMP-activated kinase, nitric oxide, and calcium-calmodulin-activated protein kinase. In normal individuals, overt hypoglycemia does not occur with exercise because a drop in blood glucose suppresses insulin release from the beta cells, and counterregulatory hormones (eg, glucagon) increase endogenous glucose production via glycogenolysis and gluconeogenesis. However, patients taking exogenous insulin are vulnerable to exercise-induced hypoglycemia because insulin will continue to be released from the injection site despite falling glucose levels.
An 8-year-old male is brought to his pediatrician's office by his mother. The child has had a runny nose, sore throat, cough, and low-grade fever for the past 24 hours. The patient's mother recalls that several of the child's friends have been ill recently with similar symptoms. The mother asks whether the child will need antibiotics for his condition. His pediatrician recommends symptomatic therapy and feels that his illness is most likely of viral etiology. Cytotoxic CD8+ lymphocytes are able to kill virus-infected nasal epithelial cells once sensitized. Cytotoxic CD8+ lymphocyte receptors recognize foreign proteins on the epithelial cell surface. Foreign proteins are presented on the epithelial cell surface by MHC molecules. These MHC molecules comprise which of the following components?
MHC class I heavy chain and B2 microglobulin - Antigens are presented to cytotoxic CD8+ T-lymphocytes in association with MHC class I molecules. MHC class I is present on the surface of all nucleated cells. Each molecule of MHC class I protein consists of a single heavy chain and an associated β2-microglobulin. Heavy chains are highly polymorphic, allowing them to present a large variety of antigens. After penetrating a cell, the virus uncoats and releases its core proteins. Some viral polypeptides are processed in the host cell cytoplasm and combined with MHC class I in the endoplasmic reticulum. The foreign antigen is then presented in association with MHC class I protein on the surface of the infected cell, signaling to CD8+ lymphocytes that the cell needs to be destroyed. The infected cell is ultimately eliminated via apoptosis.
A 23-year-old woman is brought to the emergency department unconscious after a motor vehicle accident. The patient was texting on her cell phone and was not wearing a seatbelt during the incident. She has no known medical problems and takes no medications. Her temperature is 36.7 C (98 F), blood pressure is 155/90 mm Hg, pulse is 62/min, and respirations are 10/min. A linear skull fracture at the junction of the frontal, parietal, temporal, and sphenoid bones is seen on head CT scan. A branch of which of the following arteries is most likely severed in this patient?
Maxillary - This patient has suffered a fracture at the pterion, a region where the frontal, parietal, temporal, and sphenoid bones meet in the skull. The bone is thin in this region, and fractures there risk lacerating the middle meningeal artery and causing an epidural hematoma. Epidural hematomas require prompt treatment as they are under systemic arterial pressure and can expand rapidly, leading to elevated intracranial pressure (can cause Cushing reflex), brain herniation (eg, uncal herniation with oculomotor nerve palsy), and death. The middle meningeal artery is a branch of the maxillary artery (one of the terminal branches of the external carotid artery), which enters the skull at the foramen spinosum and supplies the dura mater and periosteum.
A 24-year-old man comes to the physician with complaints of tinnitus, vertigo, and hearing loss. A contrast-enhanced, T1-weighted image of his brain is shown. The patient's condition is most likely associated with a mutation involving which of the following genes?
NF2 on chromosome 22 - The MRI image above shows bilateral tumors at the cerebellopontine angle. Most intracranial schwannomas are found at the cerebellopontine angle and are attached to CN VIII. Schwannomas at this location are called acoustic neuromas. Tinnitus, vertigo, and hearing loss are the typical symptoms of an acoustic neuroma. Bilateral acoustic neuromas occur in neurofibromatosis (NF) type 2. NF-2 differs from NF-1 in that it causes fewer cutaneous manifestations and presents with central nervous system involvement. Both types of neurofibromatosis are autosomal dominant conditions, although they occur due to mutations on different chromosomes. NF1 tumor suppressor gene codes the protein neurofibromin and is on chromosome 17, which presents with cafe-au-lait spots, multiple neurofibromas, and Lisch nodules. NF2 suppressor gene codes the protein merlin and is on chromosome 22, it typically presents with bilateral acoustic neuromas.
A 32-year-old woman comes to the emergency department requesting medication for severe back pain. She has tried multiple over-the-counter agents and says that nothing has relieved her pain except oxycodone. The patient was seen in a pain clinic a year ago but cannot recall the name of the physician and says that her prescription has run out. Medical history includes a motor vehicle collision 10 years earlier and obesity. Temperature is 37.1 C (98.8 F), blood pressure is 130/80 mm Hg, pulse is 76/min, and respirations are 16/min. Physical examination shows no abnormalities. A recent MRI was normal. The patient says that her pain level is 10 on a scale of 0-10 and becomes frustrated when the physician suggests nonprescription pain medication. Which of the following is the most appropriate next step by the physician?
Obtain confirmation of the patient's prescription history - Back pain accompanied by a request for opioid medication is a relatively common occurrence in the emergency department that requires differentiating inadequate pain management from drug-seeking behavior. This patient exhibits many features concerning for drug-seeking behavior, including requesting a specific medication by name, running out of medication, and claiming pain out of proportion to the physical examination. Reporting lost or stolen medication and obtaining multiple opioid prescriptions from different providers are other red flags indicating misuse or diversion. The best initial approach is to clarify the patient's medication history to determine which drugs have been prescribed, by whom, and at what frequency. State-based, online, prescription drug-monitoring programs are increasingly used in emergency departments to check for undisclosed prescriptions, clarify prescription patterns, and identify patients who obtain prescriptions from multiple providers. By identifying potential opioid misuse, physicians can make more informed decisions regarding pain prescriptions.
A 55-year-old man comes to the emergency department with fever and chills. He has a history of acute myeloid leukemia for which he is receiving chemotherapy. His temperature is 38.3 C (101 F), blood pressure is 90/50 mm Hg, pulse is 124/min, and respirations are 22/min. Physical examination is notable for multiple skin patches with necrotic centers and occasional ulcerations, as shown in the image below. Laboratory results are as follows: Complete blood count Platelets 240,000/mm3 Leukocytes 800/mm3 Neutrophils 60% Serum chemistry Creatinine 0.9 mg/dL Coagulation studies Prothrombin time 12 sec Activated partial thromboplastin time 33 sec Blood cultures are drawn. Which of the following organisms is most likely responsible for this patient's symptoms?
Pseudomonas aeruginosa - This immunosuppressed patient has febrile neutropenia (absolute neutrophil count [ANC] of 0.60 × 800 = 480/mm3, likely in the setting of chemotherapy) and sepsis. With neutropenia (typically ANC <500/mm3), there is increased susceptibility to infections with gram-negative organisms such as Pseudomonas aeruginosa. The dermatologic lesions in this patient are consistent with ecthyma gangrenosum (EG), which is strongly associated with P aeruginosa bacteremia. Perivascular bacterial invasion of arteries and veins in the dermis and subcutaneous tissue, with subsequent release of exotoxins destructive to human tissue, leads to characteristic skin patches exhibiting necrosis and ulceration as a result of insufficient blood flow. P aeruginosa virulence factors that may contribute to EG include exotoxin A (protein synthesis inhibition), elastase (degrades elastin - important for blood vessel destruction), phospholipase C (degrades cellular membranes), and pyocyanin (generates reactive oxygen species). Although gram-negative sepsis is sometimes associated with disseminated intravascular coagulation (DIC) and resultant purpuric skin lesions, DIC is unlikely given the normal platelet count and coagulation times (prothrombin and activated thromboplastin times).
A 16-year-old boy is evaluated for progressive gait instability, dysmetria, and dysarthria for the past several years. The patient enjoys basketball but can no longer play due to his worsening symptoms. He is worried because his brother developed similar symptoms and died at age 21. Physical examination of the lower extremities reveals bilateral motor weakness and loss of deep tendon reflexes, joint position, and vibration sense. MRI of the brain and spine shows degeneration of the posterior columns and spinocerebellar tracts. Which of the following conditions has neurologic manifestations that most closely resemble this patient's disease?
Vitamin E deficiency - This patient has progressive ataxia, dysmetria, and dysarthria. With a family history of similar symptoms, the most likely diagnosis is Friedreich ataxia (FA), the most common hereditary form of ataxia. This degenerative condition is due to an autosomal recessive mutation in the frataxin gene, which leads to degeneration of the posterior columns and spinocerebellar tracts; affected patients usually have symptom onset in adolescence and a shortened life span. A condition that can mimic FA is vitamin E deficiency. Vitamin E is a lipid-soluble, antioxidant vitamin that is widely available in the diet; deficiency is rare and typically occurs in patients with fat malabsorption (eg, cystic fibrosis) or abetalipoproteinemia. Neurologic dysfunction in vitamin E deficiency occurs due to free radical damage to neuronal cell membranes. Shared features of FA and vitamin E deficiency include: ataxia due to degeneration of spinocerebellar tracts, loss of position and vibration sense due to degeneration of the dorsal columns, and weakness and loss of deep tendon reflexes due to peripheral nerve degeneration. Patients with suspected FA but without a frataxin mutation should undergo vitamin E testing. Unlike FA, individuals with vitamin E deficiency often have additional hemolytic anemia due to free radical damage of erythrocyte membranes. Vitamin B12 deficiency may also present similarly to FA due to subacute combined degeneration of the dorsal and lateral spinal columns.
A 43-year-old man comes to the office after a recent hospitalization for Pneumocystis pneumonia. The patient is taking trimethoprim-sulfamethoxazole and says that his pulmonary symptoms are better. He has a history of HIV and was on highly active antiretroviral therapy until self-discontinuing treatment 2 years ago. On physical examination, the patient appears to be in no acute distress. BMI is 20 kg/m2. A few crackles are heard at the lung bases. His most recent CD4 count is 122/mm3. After discussing medical compliance and the need to resume antiretroviral therapy, HIV genotyping assay is performed. Additional testing for HLA-B*57:01 yields positive results. Which of the following medications is contraindicated in this patient due to the risk of a potentially fatal hypersensitivity reaction?
Abacavir - Abacavir is a nucleoside reverse transcriptase inhibitor (NRTI) used in the treatment of HIV/AIDS. Allergic responses can occur with many HIV/AIDS medications. Abacavir hypersensitivity reaction (AHR) is an allergic reaction that develops in 2%-8% of patients and is strongly associated with the HLA-B*57:01 allele of the human leukocyte antigen (HLA) system. AHR occurs due to direct binding of abacavir to a segment on the HLA-B*57:01 molecule, which alters the presentation of self-peptides to the immune system and results in a delayed hypersensitivity reaction (type IV). Manifestations are mediated by a cytotoxic T-cell response and typically include fever, malaise, gastrointestinal symptoms, and a delayed rash. Abacavir discontinuation results in rapid improvement. A negative test for the HLA-B*57:01 allele has almost a 100% negative predictive value for AHR. Therefore, genetic testing is usually done prior to administering the medication.
A 25-year-old man comes to the emergency department due to chest heaviness and palpitations for the last 3 hours. Over the past year, he has had similar episodes that resolved with deep breathing, but none lasted as long as this one. The patient has no chronic medical conditions and takes no medications. He does not use tobacco, alcohol, caffeine, or illicit drugs. Blood pressure is 100/70 mm Hg, and pulse is 160/min and regular. The neck is supple, the thyroid is normal, and there is no lymphadenopathy. The lungs are clear to auscultation. ECG is shown in the exhibit. Which of the following is the most likely cause of this patient's symptoms?
Abnormal conduction through the atrioventricular node - This patient's ECG reveals a narrow QRS complex tachycardia with a regular rhythm and nonvisible P waves. These findings are consistent with paroxysmal supraventricular tachycardia (PSVT), and episodic cardiac arrhythmia that originates at or above the AV node. The most common type of PSVT is AV nodal reentrant tachycardia (AVNRT) which usually affects young patients with an otherwise normal heart. These patients have 2 distinct AV nodal conduction pathways, a fast pathway and a slow pathway. A reentrant circuit can occur with rapid conduction of impulses to the ventricles. It creates a retrograde P wave but it is often buried in the QRS complex.
A 19-year-old man comes to the emergency department due to intense scrotal pain over the past 6 hours. The pain started shortly after participating in a soccer game; he does not recall any specific trauma. The patient took ibuprofen at home with minimal relief. He is sexually active and has been treated twice in the past for Neisseria gonorrhoeae. Temperature is 36.9 C (98.5 F), blood pressure is 110/86 mm Hg, and pulse is 92/min. On examination, there is no inguinal adenopathy. There is significant discomfort with scrotal examination primarily on the right where a high-riding swollen mass is palpated within the hemiscrotum. The left testicle is palpated lower in the scrotum. Which of the following additional physical examination findings is most likely present in this patient?
Absent elevation of right right testicle while stroking of the ipsilateral thigh - This patient has acute, severe, progressive scrotal pain with a high-riding scrotal mass, findings concerning for testicular torsion. Torsion is caused by twisting of the spermatic cord and its contents, leading to venous congestion, ischemia, and necrosis of the testis if untreated. Classic presentation is an adolescent or young adult male with sudden onset of unilateral scrotal pain, usually with associated nausea and vomiting. Poor testicular perfusion can also cause reactive scrotal edema and discoloration (eg, erythema) on examination. Because the cremaster muscle lies within the spermatic cord, an absent cremasteric reflex (testicular elevation when stroking the ipsilateral inner thigh) is highly suggestive of testicular torsion. The testicle itself is often transverse (due to inadequate fixation of the lower pole of the testis to the tunica vaginalis) and high riding (due to cord shortening with rotation).
A 3-year-old boy is brought to the emergency department due to high fever, vomiting, and lethargy. His symptoms started 1 day ago but rapidly worsened over the last few hours. Physical examination shows hypotension, tachycardia, neck stiffness, and a petechial rash over the trunk and lower extremities. Laboratory results are as follows: Complete blood count Hemoglobin 12.0 g/L Platelets 80,000/mm3 Leukocytes 34,500/mm3 Neutrophils 66% Band forms 20% Lymphocytes 14% Chemistry panel Blood urea nitrogen 30 mg/dL Serum creatinine 1.8 mg/dL Blood glucose 50 mg/dL While being evaluated, the patient develops apnea and asystole. Despite aggressive resuscitation efforts, the patient dies. Autopsy would most likely reveal which of the following?
Adrenal hemorrhage - This patient's rapidly worsening fever, vomiting, altered mental status, and nuchal rigidity are consistent with meningococcal meningitis due to infection with Neisseria meningitidis. Meningococcal infection usually occurs in children and young adults and can present acutely with rapid progression (within hours) to meningococcemia and septic shock. These patients frequently have thrombocytopenia and a petechial rash and are at risk for development of disseminated intravascular coagulation. A serious complication of meningococcemia is bilateral hemorrhagic infarction of the adrenal glands, resulting in acute adrenal insufficiency (Waterhouse-Friderichsen syndrome). Manifestations include hypoglycemia due to cortisol deficiency as well as hyponatremia and hyperkalemia due to aldosterone deficiency. Loss of cortisol and aldosterone also contributes to worsening shock and can result in rapid deterioration and death despite aggressive intervention.
A 72-year-old, previously healthy man is brought to the office by his wife due to unusual movements and behavior during sleep that have occurred with increasing frequency over the past 3 months. She says, "Lately, he's been waking me up in the middle of the night, moaning and thrashing around like he's having a bad dream. Sometimes, he becomes so violent in his sleep that he'll kick and punch me. I can easily wake him up, but he's often confused for a few seconds. Then he usually describes a dream in which he was defending himself from an attack." Physical examination is unremarkable. Neurodegeneration due to accumulation of which of the following is the most likely etiology of this patient's condition?
Alpha-synuclein - This patient's repeated nocturnal episodes of complex motor behaviors that reflect dream enactment are consistent with REM sleep behavior disorder (RBD). RBD is a parasomnia characterized by dream enactment that occurs because the muscle atonia usually accompanying REM sleep is absent or incomplete. When awakened, patients may be transiently confused but very quickly become fully alert. They may not recall their movements during sleep but can frequently remember their dreams. RBD is more likely to occur in men age >50 and is strongly associated with alpha-synuclein neurodegenerative disorders. Alpha-synuclein is a synaptic protein that accumulates in neurodegenerative conditions such as Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. Spontaneous (ie, not associated with medications) RBD is considered a prodromal syndrome of alpha-synuclein neurodegeneration because up to 90% of patients with idiopathic RBD eventually develop one of these conditions.
A 46-year-old woman with confusion and fever is brought to the emergency department. She is disoriented, somnolent, and difficult to rouse. A friend who accompanies the patient says, "She sounded really anxious when I talked to her on the phone so I decided to check in on her. She was just lying on the couch and groaning when I got there. I hope she didn't overdose again—she's tried to before." On physical examination, the patient's skin is flushed, oral mucosa is dry, and pupils are dilated and poorly responsive to light. Which of the following drugs, if taken in overdose, would most likely cause this clinical presentation?
Amitriptyline - This patient exhibits signs and symptoms of anticholinergic toxicity, which results from the inhibition of cholinergic neurotransmission at muscarinic receptors. Classic manifestations include fever, delirium, mucosal and axillary dryness, cutaneous flushing, nonreactive mydriasis, and urinary retention. Tachycardia and decreased bowel sounds are other common signs. Anticholinergic toxicity is associated with numerous over-the-counter (eg, antihistamines, sleep aids, cold preparations) and prescription medications. Tricyclic antidepressants (TCAs) are commonly implicated, particularly ones with strong anticholinergic properties such as amitriptyline. When taken in excess, TCAs can also increase QRS duration, cause arrhythmias, and precipitate seizures.
A 23-year-old woman comes to the emergency department due to 2 hours of fever, chills, headache, and myalgias. Earlier in the day, the patient saw her primary care physician for a genital ulcer. She underwent testing for sexually transmitted infections and was found to have a positive VDRL and fluorescent treponemal antibody absorption test. The remainder of her testing was negative. The patient received an intramuscular injection of benzathine penicillin G, and several hours later her current symptoms began. Temperature is 38 C (100.4 F), blood pressure is 120/70 mm Hg, and pulse is 92/min and regular. Lung sounds are normal. There is an indurated, nontender vulval ulcer and several enlarged inguinal lymph nodes. No other skin rash is present. Which of the following is the most likely cause of this patient's current symptoms?
Drug-induced bacterial cell wall disintegration - This patient with a genital ulcer, inguinal lymphadenopathy, and positive nontreponemal/treponemal testing was treated for primary syphilis with intramuscular benzathine penicillin G. She then developed an acute febrile syndrome (fever, chills, myalgia, headache) a few hours later, raising strong suspicion for the Jarisch-Herxheimer reaction. This systemic inflammatory response occurs within hours of antibiotic initiation for spirochetal infections (eg, syphilis, Lyme disease, leptospirosis). The rapid lysis of spirochetes spills bacterial lipoproteins into the bloodstream and triggers a strong innate immunologic response. Most cases are self-limited and do not require intervention.
A 24-year-old woman comes to the emergency department due to joint pain. A week ago, the patient had a flu-like illness with fever, malaise, and fleeting joint aches in her wrists, ankles, and knees. Over the past 2 days, the joint pain worsened, and she developed new swelling of the right knee. The patient has no chronic medical problems and has had no similar symptoms in the past. She does not use tobacco, alcohol, or injection drugs. She is sexually active, uses an oral contraceptive for birth control, and her last menstrual period was a week ago. Temperature is 38 C (100.4 F). On examination, there is no scleral icterus, facial rash, or oral ulcers but a few scattered painless vesiculopustular lesions are present on the upper extremities. The right knee is warm, swollen, and tender with decreased range of motion. Both ankles and the left wrist are mildly tender to palpation but not swollen or erythematous. Arthrocentesis of the right knee joint yields 20 mL of cloudy fluid with a leukocyte count of 50,000/mm3 (90% neutrophils). Additional evaluation of the joint fluid is most likely to show which of the following?
Gram-negative intracellular diplococci - This patient has purulent arthritis of the knee, oligoarticular joint pain, and a few vesiculopustular lesions on the extremities, raising suspicion for disseminated gonococcal infection (DGI). DGI is one of the most common causes of septic arthritis in young, sexually active individuals. It is due to the spread of Neisseria gonorrhoeae from a (usually asymptomatic) genitourinary infection into the systemic circulation. Patients typically present with either purulent arthritis or the triad of polyarthralgia, dermatitis, and tenosynovitis; however, some overlap in these 2 syndromes can occur (as in this patient). Microscopy of blood, urine, or joint fluid samples will often reveal gram-negative intracellular diplococci.
A 55-year-old man comes to the office due to progressive headaches over the past 2 months. The headaches are throbbing, often associated with nausea, and worsen whenever the patient coughs or bears down during a bowel movement. Medical history is significant for episodic migraine without aura. MRI of the brain with gadolinium reveals a cystic mass, as shown. Which of the following findings is most likely to be seen on physical examination of this patient?
Left dysdiadochokinesia - This patient has an expanding cystic neoplasm (likely a hemangioblastoma) in the left cerebellar hemisphere causing progressive headaches that worsen with Valsalva (maneuver increases intracranial pressure). The cerebellum is the largest structure in the posterior fossa and consists of the vermis at the midline and 2 cerebellar hemispheres. The cerebellar hemispheres are primarily responsible for motor planning and coordination of the ipsilateral extremities via their connections with the lateral descending motor systems (eg, lateral corticospinal tract, rubrospinal tract). Consequently, lesions affecting the left cerebellar hemisphere typically result in left dysdiadochokinesia (impaired rapid alternating movements), limb dysmetria (overshoot/undershoot during targeted movement), and intention tremor (tremor during targeted movement). The cerebellar vermis modulates axial/truncal posture and coordination via connections with the medial descending motor systems (eg, anterior corticospinal, reticulospinal, vestibulospinal, and tectospinal tracts). Lesions to this region result in truncal ataxia (eg, wide-based, unsteady gait). Vertigo and nystagmus may also occur due to disruption of the inferior vermis and the flocculonodular lobe.
A 24-year-old man is brought to the emergency department by police and emergency medical services personnel due to aggressive behavior toward his girlfriend. She reports that he has no history of medical or psychiatric illness and that this behavior is new. During transport, the patient was combative and difficult to restrain. He currently appears agitated, disoriented, and confused and seems to be responding to internal stimuli. Temperature is 37.2 C (99 F), blood pressure is 170/96 mm Hg, pulse is 118/min, and respirations are 20/min. Nystagmus and ataxia are present on initial neurologic examination. The patient does not cooperate with urine toxicology testing. His symptoms begin to resolve after 8 hours in the emergency department. He has very poor recollection of the previous night's events. Which of the following substances is most likely causing the constellation of symptoms seen in this patient?
Phencyclidine - This patient's combative behavior, confusion, poor judgment, memory loss, and hallucinations, accompanied by nystagmus and ataxia on physical examination, are consistent with phencyclidine (PCP) intoxication. PCP is a hallucinogen that works primarily as an N-methyl-D-aspartate glutamate receptor antagonist, as well as a monoamine reuptake inhibitor. PCP was originally developed as an anesthetic, but its use was discontinued due to its adverse effects in humans. Moderate amounts of PCP cause dissociative symptoms, including detachment and withdrawal. At higher doses, it can induce agitation, hallucinations, and violent behavior. Ataxia and nystagmus (both horizontal and vertical) are other distinguishing symptoms of PCP abuse. Hospital urine toxicology screens usually test for PCP.
A 44-year-old man with a history of heavy alcohol consumption comes to the emergency department with a nosebleed after getting into a fight while intoxicated. Continuous local pressure is applied and his bleeding resolves within 30 minutes. A detailed physical examination is performed after the bleeding subsides and shows distended paraumbilical veins, ascites, and a flapping hand tremor on wrist extension. Which of the following laboratory findings would be most indicative of a poor prognosis for this patient?
Prolonged prothrombin time - This patient has clinical findings consistent with alcohol-induced cirrhosis, namely signs of portal hypertension (ascites/caput medusa) and hepatic encephalopathy (asterixis). Alcohol-associated hepatic injury evolves through the stages of steatosis (reversible), hepatitis (reversible), and cirrhosis (irreversible). Laboratory findings in cirrhosis reflect both hepatocellular/biliary injury and loss of hepatic function. Hepatocyte injury causes a release of intracellular enzymes and an increase in serum transaminases; biliary injury is reflected by increases in alkaline phosphatase and gamma-glutamyl transpeptidase (GGT). Although these laboratory studies are indicative of ongoing hepatobiliary injury, they do not provide information on the liver's functional reserve, a key determinant of prognosis in patients with cirrhosis. Serum albumin levels and prothrombin time (PT) are better indicators of the liver's biosynthetic function, and its ability to transport and metabolize organic anions is reflected by the serum bilirubin level. Hypoalbuminemia, elevated bilirubin levels, and prolonged PT are signs of inadequate liver function (eg, liver failure) and indicate a poor prognosis in cirrhotic patients. For this reason, they are included in multiple scoring systems used to assess the severity of liver failure and need for transplantation. Transaminase elevations do not reflect liver function and do not predict outcomes; these enzymes can be transiently elevated by a number of self-limited processes.
A 17-year-old boy who was recently diagnosed with type 1 diabetes mellitus is found unresponsive at home. His family reports that the patient did not feel good last night and skipped dinner, but he still took his usual dose of insulin. Paramedics find that his fingerstick blood glucose is 32 mg/dL and immediately administer intramuscular glucagon. Glucagon binds to a transmembrane receptor in hepatocytes, which promotes binding of intracellular GTP to a specific receptor-associated protein. This leads to further downstream signaling and rapid metabolic changes within hepatocytes, including a rapid decrease in intracellular glycogen stores and release of glucose into the blood. Which of the following is the most likely mediator responsible for these effects?
Protein kinase A - Glucagon exerts its effects through G protein-coupled receptors using the adenylate cyclase second messenger system. G protein is a heterotrimer consisting of alpha, beta, and gamma subunits associated with the intracellular domain of these transmembrane receptors. The alpha subunit of the inactivated G protein is bound to GDP. On receptor activation, the alpha subunit undergoes a conformational change, which releases GDP and binds GTP. GTP binding allows the alpha subunit to dissociate from the remainder of the G protein complex. There are multiple subtypes of alpha G proteins, each with different secondary effects. A specific alpha subunit known as Gs (present in glucagon, TSH, and PTH receptor complexes) activates adenylate cyclase when released from the G protein complex. Adenylate cyclase converts ATP to cAMP, which activates protein kinase A. Protein kinase A phosphorylates specific serine/threonine residues in various enzymes, leading to their activation or deactivation. Protein kinase A also phosphorylates proteins that bind to the regulatory regions of genes on DNA.
A group of researchers is developing new drugs for osteoporosis. They are testing a new drug, Substance X, that exhibits the following metabolic effects when given via an infusion in varying doses. Both serum Ca and urine phosphate increase with increased amount of substance X. Which of the following most closely resembles the metabolic effects of substance X?
Recombinant parathyroid hormone - This investigational drug causes a dose-dependent increase in serum calcium and urine phosphate excretion, which resembles the activity of parathyroid hormone (PTH). PTH receptors are located on osteoblasts (not osteoclasts), and activation causes osteoblasts to increase production of receptor activator of nuclear factor kappa-B ligand (RANK-L) and monocyte colony-stimulating factor. These factors stimulate osteoclastic precursors to differentiate into bone-resorbing osteoclasts. PTH also decreases the release of osteoprotegerin (OPG), a decoy receptor for RANK-L; therefore, lower levels of OPG allow for more interaction between RANK-L and the osteoclastic receptor, increasing bone resorption and releasing calcium and phosphate into circulation. In the kidney, PTH decreases tubular reabsorption of phosphorus while increasing reabsorption of calcium. Therefore, the combined effects are increased serum calcium and urine phosphate levels. Chronically high levels of PTH (ie, hyperparathyroidism) increase the risk of osteoporosis. However, intermittent administration of recombinant PTH analogs induces a greater increase in osteoblast activity in proportion to osteoclast activity and a net increase in new bone formation. Teriparatide is a recombinant PTH analog used to treat osteoporosis.
A 21-year-old man comes to the office with impaired balance, tremor, and difficulty speaking. His symptoms have developed slowly over the last several months. The patient is found to have elevated serum transaminases. Viral hepatitis serologies are negative. He does not use tobacco, alcohol, or illicit drugs. He has a sibling who was diagnosed at a young age with a progressive neurologic disease. Which of the following diagnostic studies would be the most helpful for confirming the diagnosis in this patient?
Slit lamp examination - Wilson disease is a rare, autosomal recessive disorder most often identified in individuals age 5-40. A mutation of gene ATP7B hinders intracellular hepatocyte copper transport, causing reduced formation/secretion of ceruloplasmin (the major extracellular copper transport protein) and decreased secretion of copper into the biliary system. Copper is a pro-oxidant and causes hepatocellular injury by producing free radicals. Eventually, copper leaks from injured hepatocytes into the blood to be deposited in various tissues (eg, basal ganglia, cornea). Neurologic involvement can result in movement abnormalities and psychiatric symptoms. Almost all patients with neuropsychiatric disease have Kayser-Fleischer rings (green/brown copper deposits in the Descemet membrane of the cornea), which can be detected on slit lamp examination if not seen on visual inspection. The diagnosis can be confirmed by the presence of low serum ceruloplasmin, increased urinary copper excretion, and elevated hepatic copper content on liver biopsy.
An 8-year-old boy is brought to the emergency department due to 24 hours of fever and chills. Temperature is 38.3 C (101 F). On examination, the patient is lethargic with dry mucous membranes. There are no oropharyngeal lesions, and tympanic membranes are normal. The lungs are clear on auscultation, and heart sounds are normal. The abdomen is soft and nontender. There is no skin rash. Laboratory testing shows a leukocyte count of 24,000/mm3 with 15% bands, 80% neutrophils, and 5% lymphocytes. Peripheral blood smear is shown in the exhibit. Blood cultures are obtained and intravenous fluids and empiric antibiotics are initiated. The patient's blood cultures are most likely to grow which of the following organisms?
Streptococcus pneumoniae - Patients with sickle cell anemia have mutations in the beta-globulin gene that cause hemoglobin to reversibly polymerize when deoxygenated, which leads to the formation of sickled-shaped erythrocytes that clog small capillaries and cause end-organ ischemia. The spleen is particularly vulnerable; repeated microinfarction of splenic vascular beds usually results in functional asplenia within the first 18-36 months of life. Because the spleen produces opsonizing antibodies that are important for clearing encapsulated bacteria from the blood, asplenia is associated with significant risk of fulminant bacterial infections. Streptococcus pneumoniae is the leading pathogen, but Neisseria meningitidis and Haemophilus influenzae are also frequently isolated. Therefore, patients with sickle cell anemia who present with signs/symptoms of infection (eg, fever, chills, leukocytosis) require urgent empiric antibiotic therapy that covers these pathogens. Vaccination (pneumococcal and Haemophilus influenzae type b) is recommended to reduce risk of future infection.
A 60-year-old woman comes to the office due to uncontrollable movements that have worsened. Medical history is significant for hypertension, hyperlipidemia, osteoarthritis, and schizophrenia, and she has been on a stable medication regimen for years. Throughout the interview, she exhibits facial grimacing, lip smacking, and twisting movements of her hands and feet. The patient has lived in a group home for many years and worries that her housemates are avoiding her because her symptoms make her look "strange." On mental status examination, the patient makes poor eye contact and is generally distrustful but has no specific delusions or hallucinations. Which of the following is the most likely diagnosis?
Tardive dyskinesia - This patient has a diagnosis of schizophrenia and has likely been treated with antipsychotic medications for many years. Her abnormal movements are characteristic of tardive dyskinesia (TD), a movement disorder associated with long-term treatment with dopamine antagonist medications (eg, antipsychotics, metoclopramide). Possible mechanisms of TD include development of hypersensitive post-synaptic D2 receptors following prolonged D2 blockade and an imbalance between D1 and D2 receptor-mediated effects. TD typically consists of repetitive, rhythmic, involuntary movements of the tongue, lips, face, trunk, and extremities. Orofacial dyskinesias (eg, facial grimacing, tongue movements, lip smacking and puckering) are most common, but choreoathetoid movements of the trunk and limbs can also occur. Older age and exposure to first-generation antipsychotics increase the risk of developing TD. Treatment typically includes discontinuing the offending agent when feasible.
A 70-year-old white woman is brought to the emergency department due to acute right hip pain after a fall. She was walking in her house when she tripped on a floor rug and fell, landing on her hip. The patient has been unable to bear weight on the right leg since the fall and had to call for emergency transport to the hospital. She has no significant medical history and does not use tobacco, alcohol, or illicit drugs. The patient's only medication is an over-the-counter multivitamin. Family history is notable for a hip fracture in her mother. Blood pressure is 150/90 mm Hg and pulse is 112/min. The patient is in moderate pain and her right leg appears shortened and externally rotated. There is tenderness and swelling of the right hip. Radiographs reveal a right femoral neck fracture. Which of the following changes in bone structure is most likely responsible for this patient's condition?
Trabecular thinning with fewer interconnections - This patient has a fragility fracture (ie, due to low-intensity trauma that would not cause a fracture in normal bone). In light of her white ethnicity and post-menopausal age, this is likely due to osteoporosis. After menopause, declining estrogen levels accelerate the loss of bone mass with a decrease in osteoblastic and an increase in osteoclastic activity. Other common risk factors include low body weight, smoking, heavy alcohol intake, and sedentary lifestyle. The 2 major types of bone are trabecular (also called cancellous or spongy bone) and cortical. Trabecular bone composes only 15% of the skeleton by weight but is metabolically more active due to its large surface area. Initially following menopause, bone loss predominantly affects trabecular bone, especially in the dorsolumbar vertebral bodies. Morphologic characteristics include trabecular thinning and perforation with loss of interconnecting bridges. With continued aging, cortical bone, which composes most of the appendicular skeleton, also becomes involved. The neck of the femur has components of both trabecular and cortical bone, and is a common site of osteoporotic fracture.
A 24-year-old woman comes to the office due to worsening acne. Over the past 3 months, the patient has had frequent breakouts on the shoulders and upper back. She had acne on her face during puberty, which cleared spontaneously after several years, but has never before had symptoms on her trunk. The patient has no other medical conditions, and her only medication is a combination oral contraceptive. She has been training for a half-marathon for the past 4 months and has lost 6.8 kg (15 lb) during this period. She does not use tobacco, alcohol, or illicit drugs, and she relocated from California to Wisconsin for work a year ago. Vital signs are within normal limits. Physical examination shows acneiform eruptions on the shoulders and mid-back. Which of the following is most likely contributing to worsening of this patient's acne?
Use of tight fitting sports clothes - Acne vulgaris is a disorder of the pilosebaceous follicle. Hyperkeratinization and obstruction of the follicle in combination with glandular enlargement and increased sebum production provides an optimal environment for Cutibacterium (Propionibacterium) acnes. This organism metabolizes sebaceous lipids, releasing inflammatory factors that lead to follicular and perifollicular inflammation. Acne is most common in areas with a high concentration of sebaceous follicles, including the face, back, chest, and upper arms. Androgens stimulate production of sebum, and increased androgen levels (eg, puberty, polycystic ovary syndrome) increase the incidence of acne. Obstruction of the glands, such as by oil-based hair products (pomade acne), also promotes acne. In addition, mechanical irritation can promote acne by increasing glandular occlusion and disruption of follicles (acne mechanica). Sports participation, as in this patient, frequently triggers acne due to the use of tight-fitting clothing (eg, sports bras) and protective gear (eg, helmets).
