UWorld 4/20

This patient has a biventricular pacemaker, a device that requires 2 or 3 leads. If 3 leads are used, the first 2 are placed in the right atrium and right ventricle. The third lead is used to pace the left ventricle. Right atrial and ventricular leads are easy to place as they only need to traverse the left subclavian vein and superior vena cava to reach these cardiac chambers. In contrast, the lead that paces the left ventricle is more difficult to position. The preferred transvenous approach involves passing the left ventricular pacing lead from the right atrium into the coronary sinus, which resides in the atrioventricular groove on the posterior aspect of the heart. It is then advanced into one of the lateral venous tributaries in order to optimize left ventricular pacing. B. Atrioventricular groove (%)

A 65-year-old man with a history of coronary artery disease comes to the physician complaining of progressive exertional shortness of breath, fatigue, and lower extremity swelling. His medical history is significant for a myocardial infarction 5 years ago and an electronic pacemaker implanted 2 years ago. His chest x-ray is shown below. A segment of one of the leads is highlighted (arrow). The highlighted segment most likely lies within which of the following structures? A. Anterior interventricular sulcus (%) B. Atrioventricular groove (%) C. Pulmonary artery (%) D. Right atrium (%) E. Right ventricle (%)

A 35-year-old man comes to the physician because of a 2-week history of nasal congestion. He has used a topical decongestant every few hours since his symptoms began. He experienced relief for almost 1 week, but then his nasal congestion returned. The patient has a history of allergic rhinitis and has had episodes of rhinorrhea in the past, but none of them lasted longer than a few days. He denies fever, throat pain, headaches, cough, and lymph node enlargement. Aside from his allergic rhinitis, the patient has no other medical problems. Physical examination shows nasal mucosa that appears edematous and red with a few areas of punctate bleeding. The remainder of the examination reveals no abnormalities. Which of the following is the most appropriate next step in the management of this patient? A. Stop the decongestant (%) B. Switch to ephedrine (%) C. Add oral corticosteroids (%) D. Add antihistamines (%) E. Start antibiotics (%)

A. Stop the decongestant (%) Vasoconstriction by α-adrenergic agonists is prominent in the vessels of the nasal mucosa, making these medications effective decongestants. Phenylephrine, xylometazoline, and oxymetazoline are used as topical preparations for the treatment of allergic rhinitis and common cold associated congestion and rhinitis. These medications, however, are characterized by rapidly declining effect after a few days of use. This phenomenon is called tachyphylaxis. It occurs because of decreased production of endogenous norepinephrine from the nerve terminals due to a negative feedback mechanism, resulting in relative vasodilation (ie, removal of normal vasoconstrictive tone) and subsequent edema and congestion. This leads to exacerbation of the nasal congestion symptoms. Rebound rhinorrhea (ie, rhinitis medicamentosa) is described as nasal congestion without cough, sneezing, or postnasal drip. Rhinorrhea may or may not be present (note the paradox in naming). Rebound rhinorrhea is associated with the use of topical decongestants for > 3 days. The use of adrenergic agonists should be stopped to allow the restoration of normal norepinephrine feedback pathways. Another medication associated with the phenomenon of tachyphylaxis is nitroglycerine. The decrease in its effect is explained by the diminished release of NO from the target cells. Drug-free intervals of 8-10 hours should be maintained during the use of nitroglycerine to prevent tachyphylaxis.

A 1-week-old boy is brought to the emergency department due to recurrent vomiting and poor feeding. The infant was born at term via spontaneous vaginal delivery with no complications. Temperature is 36.7 C (98 F), blood pressure is 58/30 mm Hg, pulse is 180/min, and respirations are 40/min. On examination, the patient is tired appearing with a sunken anterior fontanelle and dry mucous membranes. The remainder of the examination is unremarkable. Laboratory results are as follows: Serum chemistry Sodium 122 mEq/L Potassium 5.7 mEq/L Blood urea nitrogen 25 mg/dL Creatinine 0.6 mg/dL Which of the following additional laboratory findings are most likely to be seen in this patient? Cortisol Aldosterone Serum ACTH 17-hydroxyprogesterone A. ↓ ↓ ↑ ↑ (%) B. ↓ ↑ ↑ ↓ (%) C. ↓ ↓ ↑ ↓ (%) D. ↓ ↓ ↓ ↑ (%) E. ↑ ↓ ↑ ↑ (%)

A. ↓ ↓ ↑ ↑ (%) This infant is dehydrated (ie, sunken fontanelle, dry mucous membranes) with hypotension, hyponatremia, and hyperkalemia. These findings are consistent with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Patients with 21-hydroxylase deficiency cannot convert 17-hydroxyprogesterone (17-OHP) into 11-deoxycortisol, which results in elevated 17-OHP and decreased aldosterone and cortisol production. Corticosteroid precursors accumulate and are diverted toward excess adrenal androgen biosynthesis. Low cortisol levels (ie, loss of negative feedback) also trigger increased ACTH production by the anterior pituitary, which further stimulates the formation of adrenal androgens (Choice D). Although affected girls are usually identified at birth due to ambiguous genitalia (virilization) from excess androgens, boys have normal genitalia and typically are identified at age 1-2 weeks with vomiting, hypotension, hyponatremia, and hyperkalemia due to lack of sufficient mineralocorticoids (salt wasting). Cortisol deficiency causes hypoglycemia and further impairs the ability to maintain blood pressure

A 45-year-old man is referred to an endocrinologist for newly diagnosed diabetes mellitus. A week ago, his primary care physician noted an elevated fasting serum glucose level. The endocrinologist discusses the different treatment options available, including oral and injectable medications. He recommends treatment with a medication that alters glucose metabolism within the liver by increasing the concentration of fructose 2,6-bisphosphate within hepatocytes. Which of the following conversions will be inhibited by high intracellular concentrations of this metabolite? A. Acetyl CoA → fatty acids (%) B. Alanine → glucose (%) C. Fructose-6-phosphate → fructose-1,6-bisphosphate (%) D. Glucose → glycogen (%) E. NAD+ → NADH (%)

B. Alanine → glucose (%) Fructose 2,6-bisphosphate helps control the balance between gluconeogenesis and glycolysis through inverse regulation of phosphofructokinase-1 (PFK-1) and fructose 1,6-bisphosphatase. Fructose 2,6-bisphosphate activates PFK-1, the main regulatory enzyme involved in glycolysis, which converts fructose 6-phosphate to fructose 1,6-bisphosphate. The opposite reaction (fructose 1,6-bisphosphate to fructose-6-phosphate) occurs in gluconeogenesis and is catalyzed by the enzyme fructose-1,6-bisphosphatase (inhibited by fructose 2,6-bisphosphate). The interconversion of fructose-6-phosphate and fructose 2,6-bisphosphate is achieved by a bifunctional enzyme complex composed of PFK-2 (increases fructose 2,6-bisphosphate levels) and fructose 2,6-bisphosphosphatase (decreases fructose 2,6-bisphosphate levels). Insulin causes activation of PFK-2, leading to increased fructose 2,6-bisphosphate levels and augmented glycolysis. High concentrations of fructose 2,6-bisphosphate also inhibit gluconeogenesis, leading to decreased conversion of alanine and other gluconeogenic substrates to glucose

A 45-year-old man comes to clinic due to frequent episodes of palpitations accompanied by dizziness, fatigue, and shortness of breath. Prolonged ECG monitoring identifies episodes of atrial fibrillation associated with a rapid ventricular response rate. A radiofrequency ablation procedure is planned. The access site is the right femoral vein. The ablation catheter is advanced to the left atrium where radiofrequency energy is used to eliminate an ectopic focus of abnormal electrical activity. During the procedure, the catheter most likely passes through which of the following structures? A. Aortic valve (%) B. Interatrial septum (%) C. Interventricular septum (%) D. Pulmonic valve (%) E. Tricuspid valve (%)

B. Interatrial septum (%) A venous catheter traveling from the femoral vein to the heart passes through the iliac vein and inferior vena cava to reach the right atrium. Once in the right atrium, structures within the right side of the heart and the pulmonary arteries are readily accessible. However, because the pulmonary capillaries are far too small to pass through, the left side of the heart must be accessed by traversing the interatrial septum. The interatrial septum is traversed at the site of the foramen ovale, which in adults is typically covered by a thin membrane of fibrous tissue that can be easily punctured. Entry into the left atrium allows for direct measurement of left atrial pressure (rather than an estimate via pulmonary capillary wedge pressure) and for access to arrhythmogenic foci that may be located on the left atrial myocardium or the pulmonary veins. Following the procedure, the small atrial septal defect created by the catheter typically closes spontaneously.

A 10-year-old boy who recently immigrated from overseas with his family is brought to the office due to exertional dyspnea and fatigability. The boy tires easily when walking and cannot keep up with his peers at the playground. According to his parents, he was diagnosed with congenital heart disease in infancy, but corrective surgery was unavailable. They cannot recall the details of his diagnosis. He takes a daily multivitamin and no medications. Pulse oximetry of the right hand shows 99% on room air. Physical examination reveals no murmurs. There is bilateral cyanosis and clubbing of the toes. The fingers are normal. All extremity pulses are full and equal. Which of the following is the most likely diagnosis? A. Atrial septal defect (%) B. Patent ductus arteriosus (%) C. Tetralogy of Fallot (%) D. Transposition of the great arteries (%) E. Ventricular septal defect (%)

B. Patent ductus arteriosus (%) This patient with cyanosis and clubbing of the feet but normal peripheral pulses most likely has a large patent ductus arteriosus (PDA). A PDA initially results in a left-to-right shunt with increased pulmonary blood flow. Over time, this can lead to increased pulmonary vascular resistance (PVR) due to progressive vascular remodeling. If the shunt is not corrected, PVR can eventually exceed systemic resistance and cause reversal of the shunt to right-to-left blood flow (ie, Eisenmenger syndrome), resulting in arterial hypoxemia, cyanosis, and eventually clubbing. Differential clubbing and cyanosis in the lower extremities occurs when there is a significant decrease in postductal oxygen saturation (the arteries perfusing the head and upper extremities arise proximal to the ductus). In patients with a PDA and Eisenmenger syndrome, the upper extremities are supplied by oxygenated blood from the left ventricle, but deoxygenated blood flows right-to-left across the PDA and supplies the descending aorta, resulting in lower body hypoxemia and cyanosis of the toes. The right-to-left shunting in Eisenmenger syndrome does not typically cause a murmur, but some patients may develop a murmur of tricuspid regurgitation due to progressive right ventricular enlargement.

14-year-old boy is brought to the clinic by his mother due to changes in vision. For the last few weeks, the patient has been squinting when trying to read the interactive whiteboard in class and has had to sit closer to the front of the room. He has also developed headaches. The patient has no chronic medical conditions and takes no medications. Temperature is 37.2 C (99 F), blood pressure is 116/76 mm Hg, and pulse is 70/min. Examination of the eyes shows equal and reactive pupils. Extraocular muscles are intact, and visual field testing reveals no defects. Visual acuity shows 20/70 in both eyes. His ability to read close text is normal. Which of the following is the most likely cause of this patient's symptoms? A. Chronically increased intraocular pressure (%) B. Disturbance in development of the visual cortex (%) C. Increased anterior-posterior diameter of the eyes (%) D. Loss of accommodating power of the lens (%) E. Refracted image focused posterior to the retina (%)

C. Increased anterior-posterior diameter of the eyes (%) This patient with decreased visual acuity and an otherwise normal ophthalmic examination likely has simple myopia (nearsightedness), a refractive error caused by an increased anterior-posterior diameter of the eye. The risk is greatest for those with a positive family history or those of East Asian descent. During the adolescent growth spurt, the axial length of the globe also grows rapidly, making the incidence of new-onset myopia highest in this age group. As the anterior-posterior diameter increases, the focal point of a refracted image lies anterior to the retina. For images to be seen clearly, they must be projected directly onto the retina; therefore, the image displacement in myopia causes blurred vision of long-distance objects and decreased visual acuity on examination. Vision of nearby objects is unaffected and appears clear in myopic patients. The remainder of the examination, including extraocular movements, peripheral field testing, and funduscopic examination, is normal. Management is with prescription glasses with a diverging (concave) lens, which refocuses the refracted image onto the retina. The degree of myopia usually stabilizes by early adulthood.

3-year-old girl is brought to the emergency department due to worsening fever and lethargy. Her parents report that she has had recurrent upper respiratory illness and recently had been irritable and pulling at her ears. She has also been eating poorly and vomiting, and has progressively become more lethargic. The patient has no chronic medical conditions and has received all recommended vaccinations. While being evaluated in the emergency department, she has a generalized tonic-clonic seizure. CT scan of the head shows a solitary 2-cm, ring-enhancing lesion in the left lateral temporal lobe. The pathogen responsible for this patient's current condition most likely gained access to the brain from which of the following structures? A. Ethmoid air cells (%) B. Frontal sinus (%) C. Mastoid air cells (%) D. Maxillary sinus (%) E. Nose and upper lips (%) F. Peritonsillar space (%)

C. Mastoid air cells (%) A single brain abscess is usually caused by direct spread of a contiguous infection. Temporal lobe abscess is usually a result of otitis media that has spread to the mastoid air cells, while frontal lobe abscess is usually due to ethmoid or frontal sinusitis. Multiple brain abscesses typically indicate hematogenous dissemination of a distant infection (eg, endocarditis, empyema). Brain abscess is a contained area of liquefactive necrosis with a surrounding inflammatory capsule and marked vasogenic edema. It usually appears on imaging as a ring-enhancing lesion and often presents with headache, fever, and/or focal neurologic findings (eg, seizure). Most cases are bacterial in origin (eg, viridans streptococcus, Staphylococcus aureus) and stem from an underlying adjacent or distant infection. The number and location of lesions helps differentiate the likely underlying source, as follows: Single abscess is usually due to the direct invasion of a contiguous infection. This patient who was pulling at her ears likely had otitis media that spread to the mastoid air cells and then invaded the adjacent temporal lobe leading to temporal lobe abscess. In contrast, frontal lobe abscess is generally due to direct spread of ethmoid or frontal sinusitis (Choices A and B) Multiple abscesses usually arise due to hematogenous dissemination of a distant infection, most commonly the heart (eg, endocarditis) or lungs (eg, abscess, empyema)

A 29-year-old man comes to the office due to progressive headaches, fatigue, and visual disturbances for the past 6 weeks. He was diagnosed with sarcoidosis a year ago after having a dry cough and hypercalcemia. The patient's condition was treated with oral glucocorticoid therapy, which was discontinued after 6 months due to improvement in symptoms. Physical examination reveals bitemporal defects on visual field testing but is otherwise normal. Laboratory studies again show mild hypercalcemia, but the remainder of the values, including complete blood count, serum glucose, creatinine, and electrolytes, are within normal reference ranges. MRI of the brain reveals a soft tissue mass involving the hypothalamus and pituitary stalk. Which of the following pituitary hormones is most likely elevated in this patient? A. ACTH (%) B. Growth hormone (%) C. Prolactin (%) D. Thyrotropin (%) E. Vasopressin (%)

C. Prolactin (%) This patient with sarcoidosis has a hypothalamic and pituitary stalk mass with mass-effect symptoms (eg, headache, bitemporal visual field defects). In combination with the recurrent hypercalcemia (caused by excessive calcitriol formation by activated macrophages) 6 months after the discontinuation of glucocorticoid therapy, this presentation suggests active sarcoidosis with involvement of the hypothalamus (neurosarcoidosis). Although sarcoidosis classically causes noncaseating granulomas involving the lungs, lymph nodes, and skin, granulomas can form in any tissue. Mass lesions in the hypothalamus or pituitary stalk can disrupt the hypothalamic-pituitary axis by obstructing the hypophyseal portal system. Unlike other pituitary hormones, prolactin release is negatively regulated by dopamine produced in the hypothalamus. Dopamine acts on the dopamine D2 receptors of lactotrophs, the prolactin-producing cells of the pituitary. Disruption of dopaminergic pathways (eg, by an infiltrating sarcoid lesion) in the pituitary stalk leads to loss of inhibition and a subsequent increase in prolactin

A 67-year-old woman comes to the office due to difficulty concentrating. She reports repeatedly reading the same page of material due to an inability to focus. She also describes memory problems, stating that it "takes a while to remember another person's name." The patient's medical history is significant for hypertension and type 2 diabetes mellitus. These are well controlled through diet, exercise, and oral medications. She lives alone and describes her mood as "good." Blood pressure is 127/67 mm Hg and pulse is 65/min. The physician decides to administer a brief cognitive test to assess her difficulty in concentrating. Which of the following elements of cognitive testing would best assess for impaired attention and concentration in this patient? A. Following a brief 3-step command (%) B. Recalling 3 unrelated words after 5 minutes (%) C. Reciting months of the year backwards (%) D. Remembering past events (%) E. Writing a complete sentence (%)

C. Reciting months of the year backwards (%) There are several quick clinical tests to assess attention and concentration in situations where they may be impaired (eg, dementia, delirium, head injury, depression). These include counting down from 100 by intervals of 3 or 7, reciting the months of the year in reverse order, or spelling "world" backwards. Asking a patient to recite the months of the year backwards is often helpful if the patient has a low educational level or is hesitant to perform a task involving math or spelling. Attention and concentration are tested in the Montreal Cognitive Assessment (MoCA), a widely used screening tool for cognitive impairment. The MoCA also measures time/place orientation, executive function, language, visual-spatial ability, and memory registration and recall. Results must be interpreted with consideration of the patient's education level and existing language, motor, and visual impairments. In order to make a diagnosis of dementia, the patient must demonstrate impairment in ≥1 cognitive domains (eg, memory, language, executive function) during testing as well as functional impairment in activities of daily living (eg, bathing, shopping, cooking).

Cytomegalovirus point of entry

Cellular integrins

A state's population for 2016 was estimated at 4,000,000. At the beginning of the same year, the state reported having 20,000 cases of a rare and fatal neurodegenerative condition. At the end of 2016, the state reported 7,000 new cases, as well as 1,000 deaths attributable to this condition. Another 40,000 deaths from all other causes were also reported at the end of the year. What was the cumulative incidence of the disease in 2016? A. 1,000 / 4,000,000 (%) B. 6,000 / 3,980,000 (%) C. 6,000 / 4,000,000 (%) D. 7,000 / 3,980,000 (%) E. 7,000 / 4,000,000 (%) F. 26,000 / 3,959,000 (%) G. 41,000 / 4,000,000 (%)

D. 7,000 / 3,980,000 (%) Cumulative incidence (CI) is calculated as the total number of new cases of a disease (eg, neurodegenerative condition) over a specific period (eg, during 2016) divided by the number of people at risk at the beginning of the period. It does not account for deaths in the period under study because the patients who died were, at some point in the intervening period, still considered part of the baseline population at risk for the disease. In this case, there were 3,980,000 people at risk (ie, 4,000,000 − 20,000 already with the disease) at the beginning of 2016, and 7,000 new cases of the disease occurred over the 1-year period being analyzed. Therefore, the CI is: CI = 7,000 / (4,000,000 − 20,000) = 7,000 / 3,980,000 Unlike incidence rate (which is typically reported as the number of cases per person-year), CI does not incorporate time into the denominator; it is simply the proportion of at-risk individuals who contract the disease over the specified period

A 30-year longitudinal study that follows untreated individuals with no known cardiovascular disease from age 50 to 80 is performed to investigate normal age-related cardiovascular changes. Several parameters are measured annually. Patients age 80 are most likely to show which of the following changes compared to when they were age 50? Systolic blood pressure Diastolic blood pressure Pulse pressure A. Decreased Decreased Decreased (%) B. Decreased Decreased Unchanged (%) C. Unchanged Decreased Increased (%) D. Increased Decreased Increased (%) E. Increased Increased Increased (%)

D. Increased Decreased Increased (%) Diastolic blood pressure is the baseline hydrostatic pressure in the arterial system and is directly related to systemic vascular resistance (SVR) and arterial blood volume. Pulse pressure is the amount that arterial pressure increases above diastolic pressure during left ventricular contraction; it is directly related to stroke volume and inversely related to aortic compliance. Systolic blood pressure is the summation of diastolic pressure and pulse pressure. Age-related stiffening of the aorta is the primary driver of characteristic blood pressure changes that occur in those age >65. The reduced aortic compliance in the setting of unchanged stroke volume leads to increased pulse pressure. Reduced compliance also causes less blood volume to be retained in the arterial system (ie, blood is effectively displaced to the more compliant venous compartment), resulting in slightly decreased diastolic pressure. The increase in pulse pressure is greater than the decrease in diastolic pressure, resulting in increased systolic pressure and the characteristic isolated systolic hypertension commonly seen in the elderly population

A 2-year-old, previously healthy boy is brought to the emergency department due to a 4-day history of poor feeding, diarrhea, and abdominal pain. The patient has had 5-7 bowel movements every day for the past 4 days. Temperature is 36.8 C (98.2 F) and blood pressure is 65/42 mm Hg. On physical examination, the patient is lethargic. Mucous membranes are dry, and the eyes are sunken. The lungs are clear to auscultation. No murmurs are heard. Abdominal examination shows distension and tenderness; bowel sounds are hyperactive throughout. Which of the following changes is most likely present in this patient? A. Extravasation of fluid from systemic capillaries (%) B. Increased arteriolar capacitance (%) C. Increased central venous pressure (%) D. Increased ventilatory rate (%) E. Relaxation of venous smooth muscle (%)

D. Increased ventilatory rate (%) This patient has had several days of poor oral intake and diarrhea and now has signs of hypovolemia (eg, dry mucous membranes, sunken eyes) and shock (eg, lethargy, severe hypotension). With shock, there is poor organ and tissue perfusion that leads to tissue hypoxia with increased anaerobic metabolism and consequent lactic acidosis. In response to the reduction in pH caused by metabolic acidosis there is increased ventilation to increase CO2 exhalation (ie, compensatory respiratory alkalosis). Severe diarrhea causes loss of bicarbonate in the stool, further contributing to metabolic acidosis and a compensatory increase in ventilation in this patient.

An 8-year-old girl is brought to the office by her mother due to chronic pruritus affecting her ankles. The mother states that the patient is always scratching herself. She scratches through the night, affecting her ability to sleep. Her sister has similar, but less severe, symptoms. The patient also has intermittent asthma. The rash is shown in the exhibit. (eczema) First-line therapy for this patient's condition works by which of the following mechanisms of action? A. Blockade of leukotriene receptors in inflamed tissue (%) B. Increasing the number of resident dendritic cells (%) C. Induction of keratinocyte apoptosis (%) D. Inhibition of phospholipase A2 activity in cell membranes (%) E. Reduction of serum IgE levels (%)

D. Inhibition of phospholipase A2 activity in cell membranes (%) This patient has pruritic lichenified patches on the bilateral volar ankles, findings consistent with atopic dermatitis. Atopic dermatitis is an inflammatory condition caused by genetically mediated epidermal barrier dysfunction and immune dysregulation favoring a Th2-skewed response. Patients typically have a family history and comorbid atopic conditions (eg, asthma, allergic rhinitis), as in this patient. First-line therapy is topical corticosteroids. Corticosteroids bind to cytoplasmic receptors and translocate to the nucleus, where they act primarily by inhibiting transcription of genes encoding inflammatory mediators. Specific mechanisms include the following: ↓ Local tissue production of proinflammatory prostaglandins and leukotrienes through the inhibition of phospholipase A2 ↓ Synthesis of proinflammatory cytokines (eg, IL-4, IL-13) ↑ Production of anti-inflammatory mediators In addition, corticosteroids act on nonimmune cells and can cause impaired wound healing due to reduced fibroblast growth. They also reduce epithelial proliferation and type I collagen synthesis in the dermis, which can lead to skin atrophy with chronic use.

A 1-day-old infant in the newborn nursery is found to have a harsh, holosystolic murmur on physical examination. The neonate was born at 39 weeks gestation to a 36-year-old woman who opted to defer prenatal screening. Review of medical records shows no family history of genetic or chromosomal disorders. The infant's vital signs are appropriate for his age. The rest of the physical examination shows a flat facial profile, protruding tongue, and small ears. Which of the following most likely occurred prior to conception? A. Chromosomal deletion (%) B. Chromosomal translocation (%) C. Gene inactivation (%) D. Meiotic nondisjunction (%) E. Trinucleotide repeat expansion (%)

D. Meiotic nondisjunction (%) During normal meiosis, homologous chromosomes separate to pass on individual chromatids to daughter cells. In meiotic nondisjunction, the chromosomes fail to separate, allowing one or more daughter cells to pass on with an extra copy of a chromosome. Increasing maternal age, particularly age >35, is associated with an elevated risk of nondisjunction that is likely due to cumulative oxidative stress, depletion of available mature oocytes, and shortening of oocyte telomeres. From highest to lowest prevalence, the most common consequences of maternal nondisjunction are trisomies 21 (Down syndrome), 18 (Edwards syndrome), and 13 (Patau syndrome). Less than 5% of Down syndrome cases are caused by a Robertsonian translocation (Choice B), which results from a break near the centromeres of 2 chromosomes (eg, chromosomes 14 and 21) and subsequent transfer of genetic material between these chromosomes. This translocation results in 46 chromosomes in the fetus with 3 effective copies of chromosome 21. Classic features of Down syndrome include a flat facial profile, epicanthal folds, upslanting palpebral fissures, protruding tongue, and small ears. Congenital heart defects (eg, complete atrioventricular defect, ventricular or atrial septal defect) are seen in 50% of patients

A 28-year-old woman, gravida 1, para 0, goes into labor at 38 weeks gestation. During the second stage, as the patient is pushing, the fetus develops a nonreassuring fetal heart rate. A midline episiotomy is performed to expedite delivery. A vertical, midline incision is made at the posterior vaginal opening through the vaginal and subvaginal mucosa. Which of the following structures is most likely involved in this incision? A. External anal sphincter (%) B. Ischiocavernosus muscle (%) C. Levator ani muscle (%) D. Perineal body (%) E. Rectal mucosa (%) F. Transverse perineal muscle (%)

D. Perineal body (%)

A 35-year-old primigravid woman comes to the clinic during the second trimester. The patient reports that she has had some tiredness, which she attributes to pregnancy. She takes 1 nap during the day. She has no chest pain, cough, or lower extremity swelling. As a child, the patient was told that she has a murmur but does not know any details and says that she has felt well until recently. On physical examination, a 3/6 midsystolic murmur is heard at the left upper sternal border and S2 is widely split. Which of the following is the most likely diagnosis? A. Benign flow murmur (%) B. Bicuspid aortic valve (%) C. Hypertrophic cardiomyopathy (%) D. Pulmonic stenosis (%) E. Ventricular septal defect (%)

D. Pulmonic stenosis (%) This patient likely has pulmonic valve stenosis (PS), which most commonly occurs as an isolated congenital defect and rarely occurs as an acquired defect (eg, rheumatic fever, carcinoid syndrome). Severe PS is typically diagnosed early in life due to development of right-sided heart failure, but patients with relatively mild PS often do not present with symptoms (eg, dyspnea, fatigue) until adulthood. The physiologic changes of pregnancy (eg, increased plasma volume) can unmask underlying PS. Cardiac auscultation in PS reveals a pulmonic ejection click followed by a harsh crescendo-decrescendo systolic murmur best heard at the left upper sternal border. The stenosis causes the pulmonic valve to close later than usual as it takes longer for the right ventricle to push blood through the narrowed valve. This results in widened splitting of the aortic and pulmonic components of S2. Inspiration draws additional blood into the right side of heart, which increases the intensity of the murmur and further widens the splitting of S2. Pulmonary hypertension is another cause of widened splitting of S2 because more time is required for the right ventricle to overcome pulmonary arterial pressure (ie, the pulmonic valve opens later and closes later)

A 56-year-old man with type 2 diabetes mellitus, hypertension, and hyperlipidemia comes to the office due to elevated blood glucose levels. The patient's current medications include metformin, lisinopril, and simvastatin. Blood pressure is 150/90 mm Hg and pulse is 88/min. BMI is 37 kg/m2. Physical examination is unremarkable. Laboratory studies show a fasting glucose level of 156 mg/dL, serum creatinine of 1.1 mg/dL, hemoglobin A1c of 8.1%, and urine albumin-creatinine ratio of 200 mg/g (normal: <30). Treatment with empagliflozin is initiated. Which of the following effects is most likely to be seen with this new treatment? A. Decrease in gastrointestinal absorption of glucose (%) B. Increase in body weight (%) C. Increase in endogenous insulin production (%) D. Reduction in glomerular hyperfiltration (%) E. Suppression of glucagon secretion (%)

D. Reduction in glomerular hyperfiltration (%) This patient has incipient diabetic nephropathy with moderately increased albuminuria (ie, 30-300 mg/g). Although patients with more advanced diabetic kidney disease typically have reduced glomerular filtration (rising serum creatinine), in earlier stages, filtration is normal to increased and serum creatinine may be normal. In the kidneys, filtered glucose is normally reabsorbed with sodium by sodium-glucose cotransporter 2 (SGLT2) in the proximal tubule. In patients with diabetes, the excess filtered glucose load causes increased reabsorption of sodium by SGLT2. This results in decreased sodium delivery to the macula densa, stimulating renin secretion by the juxtaglomerular apparatus and, ultimately, increasing angiotensin II levels. Angiotensin II induces relative vasoconstriction in the renal efferent arterioles, increasing hydrostatic pressure in the glomerular capillaries and causing hyperfiltration. SGLT2 inhibitors (eg, empagliflozin) decrease the reabsorption of glucose and sodium in the proximal tubule, causing urine glucose wasting and lowering blood glucose. They also increase sodium delivery to the macula densa, which leads to decreased renin secretion, lower glomerular pressures, reduced hyperfiltration, and delayed progression of nephropathy.

An 18-year-old man comes to the office due to a mass in his left scrotum. He has no other symptoms. The patient plays basketball regularly but does not recall any recent trauma to the testicle. He is sexually active with 2 partners and does not use condoms. Vital signs are within normal limits. Physical examination shows a left intrascrotal nodule that is difficult to distinguish from the left testis. The mass is nontender, does not change in size upon supine positioning, and does not transilluminate. There is no inguinal lymphadenopathy. Which of the following is the most likely diagnosis? A. Epididymitis (%) B. Hydrocele (%) C. Syphilitic gumma (%) D. Testicular cancer (%) E. Testicular hematoma (%) F. Varicocele (%)

D. Testicular cancer (%) The presence of a painless, solid testicular mass should always be considered testicular cancer until proven otherwise. Most cases present with a nodule or solid swelling in one testicle, which is often initially noticed by a partner or after a minor trauma. Bimanual examination of scrotal contents generally reveals a firm, hard, or fixed nodule within the tunica albuginea (fibrous covering of testes) that is ovoid in shape and painless to palpation. Because light does not penetrate solid tumors, testicular cancer does not transilluminate (unlike fluid-filled hydroceles) (Choice B). Bilateral scrotal ultrasound and serum tumor markers (eg, alpha-fetoprotein, beta human chorionic growth hormone) are usually obtained next to aid diagnosis. Most testicular tumors arise in young men (age 15-35) and are derived from a pluripotent testicular germ cell; these testicular germ cell tumors are generally curable with surgery and (when needed) chemotherapy.

A 17-year-old girl is brought to the emergency department after an episode of syncope. The patient was sitting on the couch watching television when she suddenly passed out. She had no symptoms prior to the event and regained consciousness spontaneously after approximately 2 minutes. Her family noticed a brief twitching while the patient was unconscious, but she had no tongue biting or bowel or bladder incontinence. The patient is taking an antimicrobial agent for a recent infection but has no other chronic medical conditions. Her uncle died suddenly 2 years ago. A detailed evaluation reveals a decrease-in-function mutation in the KCNH2 gene, which codes for a voltage-gated potassium channel that is active during the repolarization phase of cardiomyocyte action potential. The patient's medication was causing further impairment of the ion channel function, leading to the incident of syncope. This patient was most likely taking which of the following medications? A. Acyclovir (%) B. Amoxicillin (%) C. Cephalexin (%) D. Doxycycline (%) E. Erythromycin (%) F. Terbinafine (%)

E. Erythromycin (%)

A 49-year-old man with long-standing hypertension comes to the emergency department with severe shortness of breath. He has not been compliant with outpatient follow-up or his prescribed medications. His blood pressure on arrival is 260/144 mm Hg and pulse is 100/min and regular. Chest examination shows bibasilar crackles. There are no heart murmurs. His serum creatinine level is 1.1 mg/dL. Intravenous furosemide and continuous nitroprusside infusion are started along with noninvasive positive pressure ventilation, and he experiences improvement in his symptoms. The next morning, the patient seems confused and lethargic. The nitroprusside infusion rate is found to be higher than recommended. A medication that acts as a donor of which of the following elements would most likely help reverse this patient's condition? A. Hydrogen (%) B. Phosphorus (%) C. Potassium (%) D. Sodium (%) E. Sulfur (%)

E. Sulfur (%)

A medical student just finished the USMLE Step 1 exam and is anxious about her performance. She is especially unnerved when fellow students talk about the difficulty of the exam and discuss their answers to certain questions. The student decides not to think about the exam until her score arrives because "worrying isn't going to change the result." She is delighted when she receives a very high score several weeks later. Before receiving the result, the student exhibited which of the following defense mechanisms? A. Denial (%) B. Dissociation (%) C. Intellectualization (%) D. Rationalization (%) E. Reaction formation (%) F. Repression (%) G. Suppression (%)

G. Suppression (%) Defense mechanisms are means of protecting oneself from awareness of uncomfortable feelings. They can be classified as immature or mature. Immature defense mechanisms (eg, denial, acting out, regression, splitting) are maladaptive and generally seen in children and in psychopathologic states. Mature defense mechanisms (eg, altruism, sublimation, suppression, humor) are more often used by adults and allow for a healthy, adaptive response to emotional distress. This student is using suppression to alleviate anxiety about her exam results as she is aware of her discomfort but decides not to attend to it. Suppression is a mature defense mechanism in which an individual intentionally puts aside unpleasant thoughts or feelings to better cope with the present reality. Suppression should not be confused with repression (Choice F), in which unacceptable thoughts or feelings are blocked from entering conscious awareness (eg, an adult who was sexually abused as a child unconsciously buries feelings about the trauma). (Choice A) Denial involves avoiding awareness of an external reality (eg, a student who has failed an exam denies having done so). (Choice B) Dissociation is an immature defense in which a transient disruption to memory, identity, and/or consciousness occurs as a way to cope with a distressing event (eg, this student does not remember taking the exam and feels numb when her peers discuss the questions). (Choice C) Intellectualization is an immature defense mechanism that involves focusing on nonemotional components of a distressing event to make it more tolerable (eg, this student becomes preoccupied with thinking about the passing rates and other statistics of the exam). (Choice D) Rationalization involves making excuses for unacceptable feelings or situations (eg, a student explaining that poor performance on an exam was due to the trickiness of the questions). (Choice E) Reaction formation involves unconsciously transforming an unacceptable thought or feeling into its opposite (eg, a student hiding fears of failing the exam by being overly confident).

fibrinoid necrosis occurs with

HTN and vasculitis

Caseous necrosis occurs with

Mycobacterial infections Fungal infections (eg, Histoplasma, Cryptococcus, Coccidioides)

What does the kidney combine H+ with in the urine to excrete it?

NH3+ and HPO4- Increased acid buffer excretion: In order to facilitate excretion of much larger amounts of acid, the kidney utilizes acid buffers to trap H+ without markedly lowering urinary pH. The 2 most important acid buffers in urine are hydrogen phosphate (HPO42-) and ammonia (NH3), which combine with secreted H+ to form H2PO4- and NH4+. In chronic acidosis, proximal tubular cells greatly increase production of NH3 to increase acid excretion.

A 35-year-old woman, gravida 1 para 0, comes to the office for an initial prenatal visit. The patient has had no vaginal bleeding or abdominal pain and has not yet felt fetal movement. Menarche occurred at age 13. She sometimes has heavy menstrual bleeding with passage of clots, and other times she skips her menses. The patient's estimated gestational age based on her last menstrual period is 16 weeks. She has type 1 diabetes mellitus that is controlled with insulin. She smokes a pack of cigarettes daily. As part of her prenatal laboratory screening, a second-trimester maternal serum quadruple screen is performed and reveals an elevated alpha-fetoprotein level. Which of the following is the most likely etiology of this patient's abnormal screening result? A. Dating error (%) B. Down syndrome (%) C. Edwards syndrome (%) D. Fetal growth restriction (%) E. Fetal heart defect (%) F. Hydatidiform mole (%)

The maternal serum quadruple screen is used to identify pregnancies at risk for congenital defects or fetal aneuploidy (eg, Down syndrome). It measures the concentration of alpha-fetoprotein (AFP), estriol, β-hCG, and inhibin A in the maternal blood. AFP is a glycoprotein produced in the fetal liver and gastrointestinal tract. Levels are dependent on gestational age and maternal conditions such as diabetes mellitus (typically associated with decreased MSAFP and estriol levels). Therefore, accurate pregnancy dating and complete medical history are required to correctly interpret an AFP level. The most common cause of an abnormal AFP level is inaccurate pregnancy dating (ie, dating error). In patients with irregular menses, dating by a last menstrual period can underestimate the true gestational age. Therefore, these patients require a fetal ultrasound, which can accurately determine gestational age and evaluate for other common causes of elevated MSAFP levels, which include multiple gestation (eg, twin pregnancy), open neural tube defects, and abdominal wall defects

A 65-year-old man comes to the emergency department due to acute-onset, severe right flank pain; nausea; and vomiting for the past hour. His medical conditions include prostate cancer and membranous nephropathy. Blood pressure is 148/60 mm Hg and pulse is 95/min. On physical examination, the patient appears to be in moderate distress due to pain and is diaphoretic. There is right costovertebral angle tenderness. Urinalysis shows hematuria. Contrast-enhanced CT scan reveals a wedge-shaped perfusion defect in the right kidney. The affected renal tissue is most likely to develop which of the following histologic changes over the next several days? A. Caseous necrosis (%) B. Coagulative necrosis (%) C. Fat necrosis (%) D. Fibrinoid necrosis (%) E. Liquefactive necrosis (%) F. Tissue calcification (%)

This patient with multiple risk factors for hypercoagulability (ie, malignancy, membranous nephropathy) has flank pain, hematuria, and a wedge-shaped perfusion defect in the right kidney. This presentation is consistent with a renal infarction, likely from thromboembolic disease. Prolonged ischemia (as seen in infarcted tissue) results in irreversible cellular injury and cellular necrosis. Necrosis is an uncontrolled process of cell death that results in denaturation of cellular proteins and enzymatic digestion of cellular components. Unlike apoptosis, necrosis leads to a loss of membrane integrity and leakage of proinflammatory intracellular material that can injure the surrounding tissue. Necrosis occurs in several distinct morphologic patterns. In most organs, irreversible ischemic injury typically results in coagulative necrosis. Because the digestive enzymes denature before they can significantly disrupt tissue integrity, the cellular architecture is maintained but nuclei are absent. A major exception is tissue within the CNS, in which ischemia (eg, stroke) causes liquefactive necrosis with digestion of cellular constituents and liquefaction of necrotic tissue (Choice E

Educational objective:Left ventricular leads in biventricular pacemakers course through the coronary sinus, which resides in the _____ on the posterior aspect of the heart.

atrioventricular groove

What can H influenza bind to prevent binding by C3b?

factor H- degrades c3b