UWorld Review 5/24

An 18-year-old man comes to the emergency department with sudden-onset right-sided chest pain and dyspnea. The patient was at home watching a football game on television when his symptoms abruptly started. He now has pain with deep breaths. He has no other medical problems and takes no medications. The patient has smoked a pack of cigarettes daily for the past 2 years. His respirations are 24/min. Physical examination shows a thin, tall patient in acute distress. The right side of the chest is hyperresonant to percussion and lacks audible breath sounds. His chest x-ray is shown. Which of the following conditions most likely led to this patient's presentation?

Apical sub pleural blebs - This young male patient with sudden-onset unilateral chest pain, dyspnea, and absent breath sounds on examination likely has primary spontaneous pneumothorax (PSP). PSP is nontraumatic and is found in patients without preexisting pulmonary disease (eg, cystic fibrosis). It occurs when a large change in the alveolar or intrapleural pressure results in a break in the visceral pleura and subsequent trapping of air between the parietal and visceral spaces. The superficial alveoli in the apices experience greater pressure changes (due to the weight of the lungs pulling down on the apical tissue), predisposing them to the formation of subpleural blebs. The blebs then can spontaneously rupture through the visceral pleura, frequently while the patient is at rest. Tall, thin males around the age of 20 are most commonly affected. Although the most important risk factor is smoking, taller individuals also appear to be at higher risk due to more negative intrapleural pressure in the lung apices.

A 62-year-old, obese woman is brought to the hospital due to acute-onset chest pain and shortness of breath. Medical history includes hyperlipidemia, diet-controlled type 2 diabetes mellitus, and peripheral artery disease. Two years ago, she had an ischemic stroke but had no residual neurologic deficits. The patient is a current smoker with a 30-pack-year history. After initial evaluation, she is taken to the cardiac catheterization laboratory where she has a cardiac arrest due to ventricular arrhythmia and cannot be resuscitated. Autopsy reveals thrombotic occlusion of the left anterior descending artery. In addition, it shows 95% atherosclerotic narrowing of the proximal right renal artery but no significant stenosis of the left renal artery. Compared with the right kidney, this patient's left kidney is more likely to demonstrate which of the following findings?

Arteriolar wall thickening - This patient's autopsy findings are consistent with severe, unilateral renal artery stenosis (RAS), a condition that occurs most commonly in older individuals due to atherosclerosis. Hypoperfusion of the stenotic (right) kidney stimulates renin release by juxtaglomerular apparatus cells. Renin converts angiotensinogen to angiotensin I, which is then converted by angiotensin-converting enzyme to angiotensin II, a potent vasoconstrictor that causes systemic hypertension. Unilateral RAS causes morphologic changes that markedly differ in the stenotic (right) kidney and the nonstenotic (left) kidney. Narrowing of the renal artery in the stenotic (right) kidney leads to hypoperfusion and renal parenchymal ischemia, which manifests as diffuse cortical thinning, tubular atrophy, interstitial fibrosis, and small crowded glomeruli. Juxtaglomerular apparatus enlargement can also occur due to chronic stimulation and increased renin release. In contrast, the contralateral, nonstenotic (left) kidney is exposed to high blood pressure and therefore demonstrates typical signs of hypertensive nephrosclerosis, which is characterized by arteriolar wall thickening due to hyaline arteriolosclerosis (hyalinization of the arterioles due to extravasation of plasma proteins) and hyperplastic arteriolosclerosis (concentric smooth muscle cell proliferation in response to pressure ["onion-skinning"]).

A 64-year-old man comes to the emergency department due to flank discomfort and red urine. He has a history of hypertension and type 2 diabetes mellitus. Three months ago, the patient had an ischemic stroke and now has mild, residual, right-sided weakness. Serum creatinine is 0.9 mg/dL, and serum lactate dehydrogenase is elevated. Urine microscopy shows many red blood cells. The findings of a CT scan of the abdomen with contrast are shown. Which of the following is the most likely cause of this patient's symptoms?

Atrial fibrillation - This patient with flank pain, hematuria, and a wedge-shaped kidney lesion on CT scan likely has a renal infarction, which results from interruption of the normal blood supply to the kidney. The lack of collaterals between segmental renal arteries ("end-organ" blood supply) means that any interruption of blood flow can lead to coagulative infarcts. Common laboratory findings include elevated lactate dehydrogenase (reflecting cell necrosis), mild leukocytosis, and hematuria. Serum creatinine is usually normal due to compensation by the unaffected kidney. Macroscopically, renal infarcts appear as pale wedges, with the base (widest part) at the renal cortex and the apex pointing to the medulla. The most common cause of renal infarction is systemic thromboembolism from the left atrium or ventricle. Thromboembolism is a common complication of atrial fibrillation because the irregular contractions lead to sluggish, uneven flow in the left atrium and facilitate clot formation. Emboli from atrial fibrillation, which can be paroxysmal (thereby going undiagnosed), may have also caused this patient's recent stroke. The brain and kidneys are more likely than other organs to suffer embolic infarctions because they are perfused at a higher rate.

A 38-year-old woman comes to the emergency department due to severe headache. An hour ago, she experienced a sudden, explosive headache followed by a brief loss of consciousness. Since regaining consciousness spontaneously, she has had persistent global headache and nausea. Head movement or bright light worsens the pain. Temperature is 37.2 C (99 F), blood pressure is 142/90 mm Hg, and pulse is 98/min. The patient is somnolent but easily rouses to voice. She is well oriented to time, place, and person. There is increased resistance to neck flexion, which elicits pain. The pupils are equal and reactive to light. Deep tendon reflexes and sensory examination are normal. Brain imaging would most likely reveal which of the following?

Blood layering the cerebral sulci - This patient with a sudden-onset, explosive headache (ie, thunderclap headache), brief loss of consciousness, and signs of meningeal irritation (eg, neck stiffness, pain) likely has a subarachnoid hemorrhage (SAH). SAH usually results from the spontaneous rupture of a saccular (berry) aneurysm. These aneurysms most commonly develop at branch points of the anterior, middle, or posterior cerebral arteries in patients with a genetic predisposition (eg, family history, autosomal dominant polycystic kidney disease, Ehlers-Danlos syndrome). Blood empties into the subarachnoid space and pools in the cerebral sulci and basal cisterns, which is the diagnostic finding of SAH on CT scan. Blood in direct contact with the pia mater triggers severe headache and meningeal irritation. Nausea, photophobia, and transient loss of consciousness are also common. Many patients appear neurologically intact at presentation; however, progressively deteriorating mental status (eg, somnolence) is typical. In addition, SAH commonly triggers delayed cerebral vasospasm (eg, 4 days after initial bleeding) resulting in stroke with focal neurologic deficits.

A 36-year-old woman, gravida 2 para 1, at 30 weeks gestation comes to the office for a prenatal visit. The patient has noticed some ankle swelling at the end of the day that is relieved with elevating her legs, but she has no other concerns. The pregnancy has been uncomplicated, and her only medications are a prenatal vitamin and iron supplement. The patient has no chronic medical conditions. She does not use tobacco or alcohol. Blood pressure is 118/78 mm Hg and pulse is 72/min. BMI is 30 kg/m2. Fetal heart tones are normal. There is trace bilateral pedal edema to the shins. Physical examination is otherwise unremarkable. Urinalysis shows no protein. Compared to a nonpregnant state, which of the following cardiac changes are most likely to be found in this patient?

Cardiac output: ↑ Preload: ↑ Afterload: ↓ During pregnancy, the increased metabolic demand required for fetal growth and development leads to multiple physiologic maternal adaptations, particularly cardiovascular changes. These changes both benefit the fetus and protect the patient against the risks of delivery (eg, hemorrhage). The driving force behind maternal hemodynamic changes is a significant decrease in systemic vascular resistance (SVR) due to both increased release of peripheral vasodilators (eg, nitric oxide, prostacyclin) and formation of a high-flow, low-resistance uteroplacental circuit (increases blood flow to the placenta and fetus). There is also significantly increased blood volume. These changes have the following effects on cardiac preload and afterload: Both increased blood volume and decreased SVR (which allows blood to return to the heart more quickly and easily) contribute to increased cardiac venous return (ie, increased preload). The marked reduction in SVR leads to decreased blood pressure (ie, reduced afterload). Both the increased preload and decreased afterload facilitate an increase in stroke volume, which is the primary cause of increased cardiac output (ie, stroke volume x heart rate) in early pregnancy. As the pregnancy progresses, the stroke volume decreases but maternal heart rate gradually increases, contributing to an overall increase in cardiac output of up to 30%-50% during pregnancy.

A 13-year-old boy is brought to the clinic by his parents due to a change in behavior. His special education teacher reported that for the last several weeks he has frequently taken off his shoes to scratch his feet during class. The patient has a history of learning disability but is otherwise healthy. Examination shows erythema and excoriations between the toes of both feet. Microscopy of skin scrapings from the rash is shown in the exhibit. Which of the following antimicrobial drugs is likely to be the most effective against the pathogen causing this patient's condition?

Clotrimazole - This patient has a pruritic, erythematous rash affecting the feet. Microscopy of skin scrapings shows branching hyphae, confirming the diagnosis of tinea pedis (athlete's foot). Tinea pedis is a superficial infection of the epidermis caused by dermatophytes, especially Trichophyton rubrum and similar species. The organisms are widespread and are often acquired following exposure to public places while barefoot (eg, athletic facilities, swimming pools). They can also spread from other areas (eg, groin [tinea cruris], body [tinea corporis]) on the same patient via autoinoculation. Tinea pedis most commonly occurs between the toes (interdigital pattern) but in chronic cases can cause a hyperkeratotic rash extending up the sides of the feet (moccasin pattern). Tinea pedis is treated with a variety of topical antifungals, including azoles (eg, miconazole, clotrimazole), allylamines (eg, terbinafine), and tolnaftate. However, nystatin (primarily used for Candida infections) is not effective against dermatophytes.

A 30-year-old primigravid woman at 35 weeks gestation comes to the emergency department due to fever, nausea, vomiting, watery diarrhea, and myalgias that began one day ago. She has no contractions, vaginal bleeding, or leakage of fluid. Temperature is 39.3 C (102.7 F), blood pressure is 90/60 mm Hg, and pulse is 126/min. The abdomen is soft, and the uterus is nontender. Fetal heart rate is 180/min on Doppler ultrasound. The remainder of the physical examination is normal. Blood cultures grow gram-positive rods. Which of the following is the major virulence factor of the organism responsible for this patient's clinical presentation?

Cytotoxin that creates pores in phagosomes - This pregnant woman has febrile gastroenteritis (eg, fever, vomiting, diarrhea) and gram-positive rods in her bloodstream, raising strong suspicion for Listeria monocytogenes infection. L monocytogenes is a motile, facultatively intracellular organism with several unique adaptations that allow it to evade the host immune response, including the following: Listeriolysin O: This major virulence factor generates pores in phagosome membranes, which allows phagocytosed L monocytogenes to escape into the cytoplasm of monocytes and avoid lysosomal destruction. Actin-based transcellular spread: The organism hijacks the actin-based cellular motility mechanism of host cells, which allows it to spread to adjacent cells without reentering the extracellular space. This significantly reduces exposure of L monocytogenes to antibodies and phagocytic cells. Because of these adaptations, antibody- and phagocyte-mediated destruction of the pathogen is impaired; therefore, infections are controlled primarily by the cytotoxic T-cell response. Most L monocytogenes infections occur in pregnant women in the third trimester. Although antibiotics are curative, L monocytogenes quickly invades the placenta and may cause fetal death, premature birth, and neonatal infection.

A 20-year-old man suddenly collapses while walking on a college campus. He is found to be unresponsive and pulseless by a bystander. Despite efforts by emergency medical personnel, the man is unable to be resuscitated. His friends say he appeared fatigued and described palpitations and dyspnea with exertion in the weeks leading up to the event. He had no known medical history and did not use tobacco, alcohol, or illicit drugs. The man's 3 younger siblings are healthy. His parents confirm a history of "early heart disease" in a paternal grandfather and request an autopsy and genetic testing for further evaluation. Genetic studies reveal a defect in a TTN gene exon resulting in a truncated titin protein. Autopsy findings are most likely to show which of the following phenotypes?

Dilated cardiomyopathy - Dilated cardiomyopathy (DCM) occurs due to a direct insult to the myocardium that leads to a decrease in contractile function of one or both ventricles with a consequent increase in ventricular cavity size. It can result from a variety of causes, including viral infection, chemical toxicity (eg, doxorubicin, alcohol, cocaine), and infiltrative disease (late manifestation). Patients typically have symptoms of decompensated heart failure (eg, fatigue, dyspnea, orthopnea). In addition, the left ventricular structural changes place these patients at risk for sudden cardiac death due to ventricular arrhythmia. Patients are classified as having idiopathic DCM when no apparent cause of DCM is identified on routine clinical evaluation. A large percentage of these patients likely have a familial (inherited) cause. Familial DCM can result from a variety of genetic mutations affecting either sarcomere (ie, the contractile apparatus) or nonsarcomere proteins. Truncating mutations (usually nonsense mutations) affecting the TTN gene, which encodes for the sarcomere protein titin, are the most common cause of familial DCM. Titin is an elastic protein that anchors the beta-myosin heavy chain to the Z-discs and likely contributes to passive myocardial tension; absence of complete titin proteins leads to myocardial dysfunction. TTN gene mutations follow autosomal dominant inheritance; however, they have incomplete penetrance, leading to delayed or absent clinical manifestations in some family members.

A 65-year-old man comes to the emergency department due to sudden-onset headache. The patient has had no recent falls or head trauma. Medical history includes hypertension and lung adenocarcinoma with abdominal metastasis. Initial noncontrast CT scan of the head reveals a small temporal lobe hemorrhage. Over the next 24 hours, the patient becomes progressively obtunded and develops generalized tonic-clonic seizures. Blood pressure is 190/96 mm Hg, pulse is 38/min, and respirations are 10/min with brief episodes of apnea. A repeat noncontrast CT scan of the head reveals acute hemorrhage expansion with brain herniation. Which of the following findings is most likely to be observed on this patient's repeat neurologic examination?

Dilated pupil - This patient developed a spontaneous intracerebral hemorrhage with subsequent clinical deterioration due to ongoing bleeding and hemorrhage expansion. Expanding space-occupying lesions (eg, hemorrhage, hematoma) increase intracranial pressure, which can manifest with headache, vomiting, impaired consciousness, and ultimately Cushing triad (eg, hypertension, bradycardia, irregular respirations) when brain herniation is imminent. Herniation can occur in different portions of the brain depending on the location of the initial lesion. Lesions in the temporal lobe tend to cause transtentorial herniation of the uncus, which can compress the ipsilateral oculomotor nerve (CN III) as it exits the midbrain at the same level. Patients often develop ipsilateral CN III palsy with a fixed dilated pupil due to preganglionic parasympathetic nerve fiber damage. If intracranial pressure continues to increase, the herniation can progress to involve the uncus bilaterally, ultimately causing downward displacement of the brainstem (ie, central herniation). This results in brainstem hemorrhages (ie, from rupture of paramedian basilar artery branches), continued clinical deterioration from damage to medullary cardiac and respiratory centers, abnormal posturing, and ultimately death.

A 34-year-old woman is hospitalized due to abdominal pain and fever. She has had increasing dull pain in the right upper quadrant, malaise, and anorexia for the past 2 weeks. The patient has no prior medical conditions. She drinks alcohol occasionally but does not use tobacco or recreational drugs. She lives in the northeastern United States and traveled to East Africa 2 months ago. Physical examination shows right upper quadrant tenderness. Ultrasonography reveals a 3-cm right liver lobe abscess. Serology for Entamoeba histolytica is positive. Treatment with metronidazole is started, and paromomycin will be added. Which of the following is the most likely reason for the use of paromomycin in this patient?

Eradication of pathogens in the intestinal lumen - Entamoeba histolytica is a protozoan endemic to resource-limited regions (eg, East Africa) where sanitation is poor. Transmission primarily occurs via the fecal-oral route due to the ingestion of infectious cysts in contaminated food and water. Ingested cysts travel to the distal small intestine, where they release trophozoites that migrate to the colon. The trophozoites multiply in the colon and mature to cysts that are released in stool and subsequently transmitted to other persons. The vast majority of infected individuals are asymptomatic. However, in a minority of cases, the trophozoites invade the colon mucosa, leading to colitis (eg, bloody stools). Rarely, trophozoites enter the bloodstream and travel to extraintestinal sites, particularly the liver. The most common extraintestinal finding is a single liver abscess in the right hepatic lobe; patients usually develop fever, right upper quadrant pain, and malaise. E histolytica serology is positive in nearly all cases. Empiric treatment requires a 2-phase approach: A tissue agent (eg, metronidazole) is administered first to kill trophozoites, and then an intraluminal agent (eg, paromomycin) is given to eliminate intraintestinal cysts to prevent reinfection.

A 7-year-old girl is brought to the office due to a diffuse rash. The father says she developed a lace-like, erythematous rash this morning on her stomach, back, and extremities. Two days ago, the girl developed red, flushed cheeks. She also had congestion, headache, and a low-grade fever for 3 days earlier this week. Last week, her younger brother had similar symptoms that resolved spontaneously. The infectious agent most likely responsible for this patient's disease replicates in progenitors of which of the following cell lines?

Erythrocytes - Erythema infectiosum, or fifth disease, is a benign childhood illness caused by parvovirus B19, a single-stranded DNA virus. After a 1-2 week incubation period, a nonspecific prodrome (eg, malaise, congestion, headache, fever) is followed by an erythematous rash on the cheeks. This "slapped-cheek" rash, as shown in the image above, usually spares the nasolabial folds and develops after the initial symptoms have resolved. A lacy, reticular rash then follows, spreading over the trunk and extremities. The rash may result from immune complex deposition, the timing of which coincides with increasing levels of serum virus-specific IgM and IgG. Parvovirus B19 replicates in erythrocyte precursors in the bone marrow. These cells express blood group P antigen (also known as globoside), which is the cellular receptor for parvovirus B19. Viral replication in the nucleus leads to cell lysis (ie, decreased reticulocytes and red blood cells). Acute and chronic sequelae of parvovirus B19 infection can occur in specific populations (eg, chronic anemia in immunosuppressed patients, aplastic crisis in those with underlying hematologic abnormalities such as sickle cell disease).

A 34-year-old man is being evaluated for acute hematuria and oliguria. He has no chronic medical conditions and takes no medications on a regular basis. Blood pressure is 170/100 mm Hg. Blood urea nitrogen is 38 mg/dL and serum creatinine is 4.5 mg/dL. The patient undergoes a kidney biopsy and the following microscopic changes are seen after silver staining to highlight the glomerular tuft. The area marked with an arrow is likely to have abnormal deposition of which of the following substances?

Fibrin - This patient with acute renal failure and hematuria has a glomerular crescent, defined as >2 layers of proliferating cells within Bowman's space. Glomerular crescent formation occurs in response to immune or inflammatory-mediated injury to glomerular capillaries. Disruption of the glomerular basement membrane allows gaps to form within the capillary, resulting in an influx of coagulation factors (eg, fibrinogen) and inflammatory cells (eg, lymphocytes, macrophages) into Bowman's space. Initiation of the coagulation cascade promotes the deposition of large quantities of fibrin, while inflammatory cells proliferate and release growth factors and inflammatory cytokines that recruit fibroblasts and stimulate parietal cell proliferation. This eventually results in progressive glomerular hypercellularity, fibrosis, and irreversible renal injury. Crescent formation is diagnostic of rapidly progressive glomerulonephritis (RPGN), a syndrome of severe renal injury that can occur in a number of disease processes (eg, anti-glomerular basement antibody [Goodpasture] disease, granulomatosis with polyangiitis). Like other nephritic syndromes, it typically presents with hematuria, hypertension, and progressive renal failure; however, renal decompensation and progression to end-stage renal disease occur particularly quickly (weeks to months) in RPGN.

Rats exposed to high concentrations of carbon tetrachloride suffer rapid and extensive liver damage. Light microscopic examination of affected liver specimens shows fatty change and hepatocyte necrosis. These changes are the result of:

Free radical injury - Carbon tetrachloride (CCl4) causes free radical injury. Like many other toxic substances, CCl4 is oxidized by the P450 oxidase system in the liver. The result is the formation of the free radical CCl3, which reacts with structural lipids of cell membranes. The result is lipid degradation and hydrogen peroxide (H2O2) formation. This process is called lipid peroxidation. The peroxides go on to form new radicals, continuing the vicious circle of lipid degradation. Carbon tetrachloride cell injury develops rapidly and leads to swelling of the endoplasmic reticulum, destruction of mitochondria, and increased permeability of cell membranes. These processes culminate in hepatocyte necrosis.

A 32-year-old man comes to the clinic due to several months of fatigue and weight loss. The patient has no significant medical history. He drinks 1 or 2 alcoholic beverages daily and has used intravenous recreational drugs in the past. He is sexually active with his girlfriend. The patient has a maternal aunt with hypothyroidism, but his family history is otherwise unremarkable. Temperature is 36.7 C (98 F), blood pressure is 110/70 mm Hg, pulse is 65/min, and respirations are 18/min. Physical examination is normal. A liver biopsy is obtained, and light microscopy reveals large hepatocytes filled with finely granular, homogeneous, pale pink cytoplasm. Which of the following is the most likely diagnosis?

Hepatitis B infection -Hepatitis B infection, one of the most common causes of hepatic injury in the United States, is frequently transmitted sexually or via percutaneous inoculation (eg, intravenous drug use). A distinct histopathologic manifestation of chronic infection is the accumulation of hepatitis B surface antigen within infected hepatocytes. This results in the appearance of a finely granular, homogeneous, pale eosinophilic cytoplasm (ground-glass hepatocytes). Other nonspecific morphologic changes include hepatocyte necrosis, apoptosis, steatosis, and mononuclear portal inflammation (lymphocytes, macrophages). Acidophil (Councilman) bodies, deeply eosinophilic globules that represent shrunken apoptotic hepatocytes, can be seen in a variety of liver diseases.

A 44-year-old man with a history of intravenous drug use came to the emergency department due to fever and chills. Multiple blood culture sets were positive for Staphylococcus aureus, and the patient was diagnosed with infective endocarditis. He was successfully treated with a long course of antibiotics. Six months later, he returns to the clinic for a follow-up evaluation. The patient has no symptoms and reports good exercise tolerance. He is afebrile, blood pressure is 140/62 mm Hg, pulse is 82/min, and respirations are 16/min. Chest auscultation reveals a decrescendo diastolic murmur over the third intercostal space along the left sternal border. Echocardiogram shows severe aortic regurgitation, likely as a sequela to the prior infection. Which of the following changes is most responsible for maintaining cardiac output in the setting of this valvular abnormality? A. Concentric left ventricular hypertrophy (22%) B.Decrease in left ventricular preload (2%) C.Increase in aortic elasticity (1%) D.Increase in left ventricular afterload (4%) E.Increase in left ventricular stroke volume (56%) F.Sustained increase in heart rate (13%)

Increase in left ventricular stroke volume - This patient has developed chronic aortic regurgitation (AR) as a consequence of infective endocarditis. Incomplete closure of the aortic valve during diastole allows a portion of left ventricular stroke volume to leak back into the left ventricle; in severe AR this regurgitant flow volume may be up to 50% of total forward stroke volume. Left ventricular dilation caused by the increase in left ventricular end-diastolic volume (LVEDV) (volume overload) triggers eccentric hypertrophy, which involves ventricular wall lengthening due to the addition of myocardial contractile fibrils organized in series. This compensatory response causes an increase in stroke volume that is able to maintain cardiac output, and allows for a relatively long asymptomatic period (eg, several years) in most patients with chronic AR. However, the compensatory eccentric hypertrophy in chronic AR is overall maladaptive. Over time, progressive left ventricular dilation leads to overwhelming wall stress with decreased stroke volume and eventual left ventricular failure.

A 72-year-old man comes to the office due to progressive shortness of breath. Over the past year, the patient has been unable to perform many of his usual outdoor activities, including afternoon walks and working in the yard. During the last several weeks, he has frequently become easily fatigued and short of breath, and at night he needs several pillows to sleep comfortably. He has also had ankle swelling. The patient has had no chest pain, syncope, abdominal pain, or cough. He is a lifetime nonsmoker. Bibasilar crackles are heard on physical examination. Echocardiography reveals no valvular disease and a nondilated left ventricle with an ejection fraction of 55%. Which of the following is most strongly associated with this patient's current condition?

Increased left ventricular afterload -This patient has clinical signs and symptoms of decompensated heart failure (eg, dyspnea, fatigue, orthopnea, lower extremity edema, bibasilar crackles); however, echocardiography shows a preserved left ventricular (LV) ejection fraction (>50%) without chamber dilation. Heart failure with preserved ejection fraction (HFpEF) develops due to diastolic dysfunction, which frequently occurs in the setting of prolonged systemic hypertension (ie, increased afterload). Over time, increased pressure load causes the left ventricle to undergo concentric hypertrophy with the addition of myocardial contractile fibers in parallel to increase contractile strength. The thickened LV walls become stiff and less compliant, leading to impaired diastolic relaxation and increased LV end-diastolic pressure (point 1). Gradually, the elevated pressure transmits back to the pulmonary veins and capillaries, resulting in pulmonary edema. There is also an eventual decline in LV end-diastolic volume (also indicated at point 1) leading to reduced cardiac output and further decompensation (stroke volume decreases despite preserved ejection fraction).

A 24-year-old man is evaluated for recurrent episodes of abdominal pain and bloody diarrhea. The patient has also had low-grade fevers and fatigue. Physical examination reveals left lower quadrant tenderness. CT scan of the abdomen shows thickening of the distal colon and rectum. During one of the laboratory tests, the patient's anticoagulated blood is placed in an upright, thin glass tube and left undisturbed. His red blood cells form a stack and settle to the bottom at a fast rate of 50 mm/hr. Serum levels of which of the following substances is most closely associated with this observed finding?

Interleukin 6 - This patient who has recurrent abdominal pain and bloody diarrhea with CT evidence of bowel wall thickening in the distal colon and rectum likely has ulcerative colitis. Chronic inflammatory conditions are characterized by the persistent stimulation of neutrophils and macrophages, leading to long-term elevation of circulating pro-inflammatory cytokines such as IL-1, IL-6, tumor necrosis factor-alpha, and interferon-gamma. The liver responds to these circulating cytokines (particularly IL-6) by generating acute phase reactants, proteins that modulate and influence the inflammatory response and play some role in innate immunity. Testing for acute phase reactants can help diagnose and track conditions associated with inflammation, including infections, autoimmune diseases, and malignancies. The test described in this case is the erythrocyte sedimentation rate (ESR), which begins by placing whole blood in a narrow vertical tube. Erythrocytes settle at the bottom of the tube over time due to gravity as their density is greater than plasma. ESR is a measure of the length of plasma on top of the erythrocyte sediment layer at 1 hour. The presence of acute phase reactants, particularly fibrinogen and globulins, causes erythrocytes to overcome their zeta potential (negative charge that separates them) and form a stacked, rouleaux formation, which settles to the bottom of the tube more quickly and increases ESR.

A 24-year-old, previously healthy woman comes to the emergency department due to hematemesis. The patient was binge drinking when she became very nauseated and began vomiting repeatedly. She reports vomiting approximately a cupful of bright red blood during the most recent episode. Blood pressure is 136/78 mm Hg and pulse is 96/min. Physical examination shows mild epigastric tenderness. Endoscopy reveals a longitudinal mucosal laceration in the distal esophagus with active bleeding. Endoscopic treatment is performed, but the bleeding recurs. Angiography with transarterial embolization of the bleeding vessel is planned. A distal branch of which of the following blood vessels is most likely to be embolized during this patient's procedure?

Left gastric artery - This patient has a mucosal laceration of the distal esophagus (Mallory-Weiss tear). It typically occurs during episodes of severe retching, which can raise intraabdominal pressure high enough to tear the superficial layers of the distal esophagus. Mallory-Weiss tears cause hematemesis, which is often self-limited, although severe bleeding may require endoscopy and/or angiography. Arterial embolization in this patient should target branches of the left gastric artery, which arises from the celiac trunk and provides the primary arterial supply to the distal esophagus. Branches of the left inferior phrenic artery may also perfuse the distal esophagus but are a minor contributor. More proximal segments of the esophagus are served by other primary arteries. The proximal esophagus receives arterial blood from branches of the inferior thyroid artery, whereas the midesophagus is supplied by branches of the thoracic aorta.

An 18-year-old man comes to the clinic for a routine physical. The patient has no medical conditions and takes no medications. He does not use tobacco, alcohol, or recreational drugs. He plays on his high school football team. Review of systems is unremarkable. Blood pressure is 120/76 mm Hg, pulse is 68/min, and respirations are 15/min. BMI is 28 kg/m2. Blood pressures in the upper and lower extremities are equal. There is no jugular venous distension. Carotid upstrokes are brisk. A grade 2/6 midsystolic murmur is present along the left sternal border. The murmur decreases in intensity with handgrip and passive leg elevation. Lung sounds are normal without crackles or wheezes. Echocardiography is most likely to demonstrate which of the following findings?

Left ventricular mass: increased Left ventricular cavity size: small Left ventricular ejection fraction: preserved Left ventricular relaxation: impaired This patient with a systolic murmur along the left sternal border that decreases in intensity with maneuvers that increase left ventricular (LV) blood volume likely has hypertrophic cardiomyopathy (HCM). HCM typically involves hypertrophy of the interventricular septum that can partially obstruct LV outflow and cause a murmur. Increases in LV blood volume, caused by maneuvers that increase preload (eg, passive leg elevation) or afterload (eg, handgrip), alleviate LV outflow obstruction and decrease the intensity of the murmur. Characteristic findings in HCM include increased LV muscle mass and a small LV cavity. Because LV contractility is typically intact and outflow obstruction is dynamic and commonly present only with exercise, there is usually preserved ejection fraction (EF) at rest (ie, carotid pulses are full). Diastolic dysfunction is typically present due to impaired relaxation of the hypertrophied LV wall. Affected patients can be asymptomatic or may have exertional symptoms, depending on the level of phenotypic expression and degree of LV outflow tract obstruction.

A 56-year-old man dies in the hospital due to aspiration-related complications. The patient was admitted 5 days ago with right-sided weakness, sensory loss, and difficulty with speech and swallowing. CT scan revealed an area of hypodensity in the left frontoparietal region. Autopsy examination is performed, and a section of loose, spongy tissue from the abnormal brain area is obtained. Histologic findings after staining for lipids are shown below. The cells most intensely stained in this patient's brain specimen represent which of the following cell types?

Microglial cells - This patient developed acute-onset neurologic defects (eg, hemiparesis, dysphagia, dysarthria) secondary to an ischemic stroke, which was confirmed by CT scan and autopsy findings. An ischemic infarct results from regional hypoperfusion (eg, thrombosis, embolism) or a global decline in cerebral blood flow. Characteristic CT findings are evident 6-12 hours after the onset of ischemic injury and include hypoattenuation of the tissue and loss of grey-white matter differentiation within the affected region. Microscopically, neurons in the necrotic area display signs of irreversible damage during the first 24 hours after injury (red neurons). Neutrophils initially move into the area in the first 1-2 days, followed by microglia (derived from yolk-sac monocytes) 3-7 days after the onset of ischemia. As the neurons disintegrate, their fragments are phagocytized by microglia, and myelin breakdown products accumulate in the cytoplasm of microglia as foamy lipids. Infiltration of the brain tissue by microglia (arrow) is seen on light microscopy in the photo and is consistent with the expected histology findings 5 days post-infarction.

A 68-year-old man comes to the office due to fatigue, weight loss, and constipation. He has refused to undergo screening colonoscopy for several years because "nobody in my family had colon cancers." Past medical history is notable for emphysema and stable angina. The patient has smoked a pack of cigarettes daily for 50 years and drinks alcohol occasionally. Physical examination is unremarkable. He is referred for colonoscopy, which reveals a circumferential mass encircling the sigmoid colon. Pathology is positive for adenocarcinoma. CT scan of the chest, abdomen, and pelvis is negative for signs of metastasis. Serum carcinoembryonic antigen assay is ordered. The results of this assay would be most useful for which of the following aspects of this patient's care?

Monitoring for residual disease - Carcinoembryonic antigen (CEA) is a glycoprotein involved in cell adhesion. It is produced in the embryonic pancreas, liver, and intestine and is also detected in minute amounts in the serum of healthy adults. CEA levels are increased in most patients with colon cancer. Elevated preoperative CEA levels are associated with a worse prognosis, and failure to normalize following surgery suggests residual disease. During long-term follow-up, rising CEA levels are a sensitive indicator of colorectal cancer recurrence. However, CEA has low sensitivity and specificity for initial screening and diagnosis of colon cancer. CEA levels are elevated in pancreatic, gastric, and breast malignancies along with other nonmalignant diseases (eg, inflammatory bowel disease, chronic obstructive pulmonary disease, cirrhosis, pancreatitis). CEA levels are also higher in smokers than nonsmokers.

A 28-year-old woman comes to the office due to several months of progressive abdominal pain and intermittent diarrhea. She denies fever or chills but has lost weight due to poor appetite. The patient works for an organization that installs wood pellet cookstoves in rural villages in Central Africa and has spent much time in the region over the last 5 years. Temperature is 37.8 C (100 F), blood pressure is 126/72, and pulse is 86. BMI is 19 kg/m2. Physical examination is normal. Laboratory results are as follows: Complete blood count Hemoglobin 9.5 g/dL Platelets 195,000/mm3 Leukocytes 8,800/mm3 Neutrophils 54% Eosinophils 14% Lymphocytes 32% An intestinal biopsy sample is shown in the exhibit. Which of the following is the most appropriate treatment for this patient?

Praziquantel - This patient's travel history, chronic intestinal symptoms, eosinophilia, and biopsy findings suggest schistosomiasis, a parasitic blood fluke infection primarily seen in rural parts of sub-Saharan Africa and East Asia. Exposure occurs when humans swim or bathe in freshwater that contains contaminated snails (the intermediate host). Cercariae from the snails penetrate human skin and migrate to the liver, where they mature into adult worms. Adult worms then travel through the portal circulation to the mesenteric venules (S mansoni and S japonicum) or the venous plexus of the bladder (S haematobium). Adult worms release eggs through host tissue to be excreted in feces or urine. Although most patients are asymptomatic, eggs can trigger a significant granulomatous inflammatory response, leading to manifestations in the gastrointestinal tract (eg, diarrhea, weight loss, anorexia, anemia), bladder (eg, terminal hematuria), or periportal system (eg, portal hypertension, splenomegaly). Eosinophilia is common early in the disease course as eosinophils release granules that are toxic to adult worms. Diagnostic confirmation requires the identification of round/oval eggs with a characteristic terminal (S. haematobium) or lateral (S. mansoni) spine on stool/urinary testing or tissue biopsy. Treatment with praziquantel, which alters parasite digestion and calcium transport, is generally curative.

A 63-year-old man comes to the office for follow-up of hypertension. At his last appointment, he revealed that he had increased his intake of 12-oz cans of beer from 3 to 6 cans daily due to stress at work. The physician advised him to seek help for his alcohol use because it could be causing his elevated blood pressure and has many negative health risks. The patient now tells the physician, "I thought about what you said. I know my alcohol use has gotten out of hand and is affecting my health. My wife and daughter also say that I need to quit. I have made an appointment with a counselor to talk about my options." Which of the following best describes this patient's stage of behavioral change?

Preparation - The transtheoretical model of behavioral change describes 5 stages that many people progress through when making significant behavioral change. It begins with initial denial of the problem (precontemplation), moving through admitting the problem and the need to change (contemplation), committing to change and planning a change strategy (preparation), and taking concrete steps to implement change (action). Finally, behavioral change requires efforts for long-term maintenance. This patient has acknowledged his drinking problem and is developing plans for behavioral change. Characteristic features of the preparation stage include the following: The individual is no longer simply considering change but has made a commitment to change. The individual is weighing specific options to effect change. The individual may be seeking supportive resources to assist change. In the preparation stage, the individual may take initial, preliminary steps to effect behavioral change (eg, contacting a substance abuse counselor) but has not yet taken concrete action with a demonstrable change in the subject behavior.

A 62-year-old man comes to the emergency department due to a 2-week history of worsening shortness of breath. The patient reports feeling dyspneic while lying flat and has been sleeping upright in his recliner. Temperature is 36.7 C (98.1 F), blood pressure is 110/70 mm Hg, pulse is 88/min, and respirations are 20/min. On physical examination, jugular venous distension is present. Heart sounds are normal. Decreased breath sounds and dullness to percussion can be heard at the bilateral bases. Pitting edema is present in the bilateral lower extremities. Chest x-ray shows cardiomegaly and bilateral pleural effusions. Serum protein is 6 g/dL and serum lactate dehydrogenase (LDH) is 60 U/L. Which of the following sets of pleural fluid findings is most likely to be seen in this patient?

Protein (g/dL): 2 LDL (U/L): 30 Glucose (mg/dL): 90 Total nucleated cell count (per mm3): 500 This patient with dyspnea, orthopnea, jugular venous distension, and lower extremity swelling likely has an acute heart failure exacerbation. Heart failure commonly leads to pleural effusion due to poor forward blood flow from the left ventricle and a subsequent increase in pulmonary venous and pulmonary capillary hydrostatic pressure. Pleural effusions that result from such pressure changes are typically transudative, whereas those that result from an inflammatory increase in vascular membrane permeability are typically exudative. Because transudative and exudative pleural effusions have differing underlying causes, they also tend to differ in chemical makeup. The Light criteria are used to differentiate the 2 types via analysis of the total protein and lactate dehydrogenase (LDH) levels. Exudative effusions have a high pleural fluid/serum ratio of these proteins due to increased capillary permeability, while transudative effusions are associated with a low pleural fluid/serum ratio. Glucose levels and leukocyte counts can suggest the degree of inflammation in a pleural effusion. Because leukocytes metabolize glucose, highly inflammatory effusions typically have low glucose levels. Transudative effusions are not inflammatory and almost always have low nucleated cell counts and normal (or high) glucose levels.

A 22-year-old woman comes to the office due to worsening cough. The patient has been coughing every day for the past several months, but over the last 4 weeks, the cough has worsened, with increased amounts of thick sputum and shortness of breath. Streaks of blood have been present in the sputum on several occasions. The patient also has a history of chronic sinusitis and repeated hospitalizations for airway infections. She takes pancreatic enzyme supplements for chronic diarrhea. She does not use tobacco, alcohol, or illicit drugs. Physical examination reveals nasal polyps, a barrel-shaped chest, bilateral coarse lung crackles, and digital clubbing. Chest x-ray shows hyperinflated lungs and dilated, thickened airways. Sputum culture from this patient is most likely to yield which of the following organisms?

Pseudomonas aeruginosa - Cystic fibrosis (CF) is a progressive, fatal illness characterized by the development of thick, viscous, clogging secretions in a multitude of organs. Young adults with CF typically have several manifestations of the disorder, including pancreatic insufficiency (eg, diarrhea), chronic sinusitis, nasal polyps, and chronic bronchitis (eg, long-standing productive cough, hyperinflated lungs, barrel chest). However, persistent lower respiratory tract infection is the major source of morbidity and death. Early in the course of the disease, thick airway secretions obstruct mucociliary clearance and lead to the colonization of the lower respiratory tract with pathogenic bacteria. Although Haemophilus influenzae and Staphylococcus aureus are seen in children with CF, Pseudomonas aeruginosa is the major pathogen in adults. This organism forms a biofilm and switches to a mucoid phenotype to prevent its full elimination (even with antibiotics). Neutrophils respond by releasing elastase, myeloperoxidase, and reactive oxygen species, but these compounds are insufficient to clear the infection and progressively destroy the walls of the airway, leading to bronchiectasis and respiratory decline.

A 14-year-old boy comes to the office with his mother due to progressive anterior knee pain affecting the left leg for the past 2 months. The pain started as a mild ache toward the end of a hiking trip. The patient reports no fever, night sweats, or trauma to the knee. On physical examination, he has a normal gait. The hips, knees, and ankles have full range of motion. An area of mild swelling tender to palpation is located about 3 cm below the inferior border of the patella. An x-ray of the left knee is shown in the exhibit. Overuse of which of the following muscles most likely contributed to this patient's condition?

Quadriceps femoris - This patient has Osgood-Schlatter disease (OSD), a common cause of knee pain in adolescents due to overuse of the quadriceps muscle group (ie, rectus femoris, vastus intermedius, vastus lateralis, vastus medialis). The quadriceps is located in the anterior thigh and is responsible for knee extension. Its tendon initially inserts at the superior pole of the patella. The tendon envelops the patella and continues as the patellar ligament, which then inserts at the tibial tubercle. As a result, contraction of the quadriceps (eg, hiking, running) creates traction on the tibial tubercle. In skeletally immature children, the tibial tubercle forms as a secondary ossification center (apophysis) of the tibia, and the cartilaginous nature of the developing tibial tuberosity makes it more prone to injury compared to fully ossified bone in adults. Repetitive quadriceps contraction results in chronic avulsion/fragmentation of the tubercle, with corresponding tenderness and swelling, as seen in this patient.

A 57-year-old man comes to the office accompanied by his wife due to low mood and sleep disturbances for the past 2 months. The patient has also had a loss of interest in his hobbies, concentration difficulties that are affecting his work, and low energy. The patient has no suicidal thoughts. Psychiatric history is significant for a period of depression in his 20s treated with psychotherapy. Medical history is noncontributory. Vital signs and physical examination are within normal limits. The patient has a depressed affect with restricted range and soft speech. Treatment options are discussed, including psychotherapy and antidepressant medications. The patient responds that he is willing to consider psychotherapy but does not believe medication is necessary. His wife says, "I don't think he understands how serious this is—he's in danger of losing his job. I'll make sure he takes the medication." Which of the following is the most appropriate next step in management of this patient?

Recognize the wife's concerns and request to speak with the patient in private about his option for treatment - Family members can provide useful information about a patient's condition and act as a source of support for the patient. However, when it comes to obtaining valid informed consent, the patient's autonomy (ie, the right to make a decision without undue influence) should be the primary concern. In this case, the patient's wife is providing important input into her husband's condition, which is helpful. However, her values and preferences regarding medication do not necessarily reflect those of her husband. The physician should express appreciation for the wife's input and gently ask her to leave the room, explaining the importance of speaking with the patient confidentially. Speaking confidentially will allow the patient to ask questions or express concerns that he may not be comfortable relaying with his wife present and enable a discussion of the risks, benefits, and alternate treatments without coercion. It is also more likely to engage the patient in creating a treatment plan with which he is comfortable.

A couple comes to the clinic for preconception counseling. They are offered genetic screening because they are of Ashkenazi Jewish descent. Test results show that both are carriers for a lysosomal enzyme deficiency disorder that results in decreased metabolic degradation of a phospholipid substrate to ceramide, which leads to a buildup of the phospholipid. They are counseled about the chance that their offspring will be affected by this disorder. The couple wants to know the clinical features of an affected child. Which of the following findings would be most consistent with this condition?

Retinal opacification and splenomegaly - Niemann-Pick disease is an autosomal recessive lysosomal storage disorder. It is caused by a deficiency of sphingomyelinase, the enzyme responsible for metabolizing sphingomyelin (a phospholipid) to ceramide. Excess sphingomyelin results in cells that appear enlarged, foamy, and vacuolated on electron microscopy. These lipid-laden foam cells accumulate in the liver (hepatomegaly), spleen (splenomegaly), and CNS (hypotonia, neurodegeneration). After a period of normal development, affected infants do not attain new skills and regress from previously acquired milestones (eg, sitting with support, head control, social smile). Accumulation of sphingomyelin in the retinal ganglion cells also leads to retinal opacification, which gives the appearance of a cherry-red macula. Disease is progressive, and death usually occurs by age 3. Niemann-Pick disease, like several other rare genetic disorders (eg, Tay-Sachs disease, Gaucher disease, Bloom syndrome), is more common in the Ashkenazi Jewish population than in the general population. The increased risk for rare and often life-threatening genetic mutations is attributed to the founder effect, or the loss of genetic variability within a group that historically conceived within their own community. An Ashkenazi Jewish couple should be offered genetic counseling and testing before they conceive a child.

A 42-year-old man comes to the office due to hematuria, fatigue, and nasal congestion for the last few weeks. He has no chronic medical conditions. Blood pressure is 160/96 mm Hg. Physical examination shows edema around the ankles, hands, and face. Laboratory results reveal blood urea nitrogen of 40 mg/dL and serum creatinine of 3.8 mg/dL. Urinalysis shows moderate proteinuria and a large amount of red blood cells (RBCs) with RBC casts. A kidney biopsy is performed. Light microscopy reveals cellular proliferation, focal necrosis, and crescent formation of most of the glomeruli. On immunofluorescent microscopy, there are no immunoglobulin or complement deposits. Which of the following additional findings is most likely to be present in this patient?

Serum antineutrophil cytoplasmic antibodies - Crescent formation on light microscopy is diagnostic of rapidly progressive (crescentic) glomerulonephritis (RPGN). This is a syndrome of severe glomerular injury that rapidly progresses to renal failure within weeks to months of onset. RPGN can be caused by several different diseases and is classified based on immunologic findings: Antiglomerular basement membrane (anti-GBM) RPGN: Linear GBM deposits of IgG and C3 are found on immunofluorescence. In some patients, anti-GBM antibodies cross-react with pulmonary alveolar basement membranes, producing pulmonary hemorrhages (Goodpasture syndrome). Immune-complex RPGN: There is a "lumpy-bumpy" granular pattern of staining for both antibodies (eg, IgG, IgA) and complement on immunofluorescence microscopy. This can be a complication of poststreptococcal glomerulonephritis, systemic lupus erythematosus, IgA nephropathy, or Henoch-Schönlein purpura. Pauci-immune RPGN: There are no immunoglobulin or complement deposits on the basement membrane, as with this patient. Most patients have elevated serum titers of antineutrophil cytoplasmic antibodies (ANCA). This condition is often associated with vasculitides (eg, granulomatosis with polyangiitis, microscopic polyangiitis) but can also be idiopathic.

A 56-year-old male with history of polycystic kidney disease presented to the emergency room because of sudden onset severe headache. He has never had this type of headache in the past. Examination shows some nuchal rigidity. Neurologic examination is within normal limits. Which of the following is the most likely diagnosis?

Subarachnoid hemorrhage - Although the major pathologic process in Autosomal Dominant Polycystic Kidney Disease (ADPKD) is in the kidneys, it is a systemic disorder. Cysts and other anomalies are noted in different organs. Intracranial berry aneurysms arise in the circle of Willis, and when these aneurysms rupture they cause subarachnoid hemorrhage (SAH). The clinical presentation described in this question is suggestive of SAH. Patients complain of a severe headache ("the worst headache of their life"); neck stiffness is usually present or develops in the next 24 hours as blood in the subarachnoid space acts as a meningeal irritant. Papilledema and pupillary dilation may be noted, but there are no focal neurologic findings. CT scan of the brain without contrast is the most commonly used initial imaging study for diagnosing SAH and should be done during the first 24 hours from the onset of symptoms. This is positive in up to 90% of patients. If the CT scan does not show SAH, but the clinical suspicion remains high, a lumbar puncture needs to be performed to evaluate the cerebrospinal fluid for the presence of xanthochromia (blood in the CSF). Thus, presence of the xanthochromia in a clinical scenario suggestive of SAH is the most sensitive test for diagnosing SAH.

A 46-year-old man comes to the emergency department with chest pain that began 30 minutes ago. The patient describes the pain as a tight, squeezing sensation that radiates to the left arm. He also has increased sweating and nausea. ECG shows multi-lead ST-segment elevation, and cardiac troponin levels are high. The patient has a history of alcohol and cocaine abuse, but no history of cardiac disease. He undergoes emergency cardiac catheterization and is recovering appropriately in the postanesthetic care unit. The physician is approached by a distraught woman who says she is the patient's wife and asks about his condition. She says, "I am so worried; please tell me if my husband is okay." Which of the following is the most appropriate course of action?

Tell the woman that the patient is stable, but that further details will have to wait until the patient can give permission -While this patient is undergoing emergency treatment for acute myocardial infarction, a woman who claims to be his wife arrives at the hospital and asks about his medical condition. The Health Insurance Portability and Accountability Act (HIPAA) is designed to protect patient privacy. This requires the patient's explicit consent (or lack of objection when given the opportunity) to share medical information with others, including family and friends. When the patient is incapacitated or is not present, basic information can be shared if, in the physician's professional judgment, doing so is in the patient's best interest. In this case, there is no way of knowing for sure whether informing this woman (whether she is his wife or not) is in the patient's best interest. However, the woman is distressed, and leaving her to worry for an extended period while the patient is recovering could cause the patient emotional harm if she is indeed family. The best approach to protect the patient's privacy is to explain that he is stable, but that further information (including general diagnostic and treatment information) cannot be shared until he is asked for and provides consent.

A 17-year-old girl is brought to the hospital due to abdominal pain, nausea, and vomiting. She began having periumbilical pain and nausea several hours ago and initially attributed her symptoms to some "bad food" she ate at a potluck lunch earlier in the day. However, her pain progressively worsened and became localized to the right lower quadrant. Temperature is 101 F (38.3 C), blood pressure is 124/78 mm Hg, pulse is 92/min, and respirations are 14/min. On examination, the patient has right lower quadrant tenderness with guarding. Laboratory evaluation shows leukocytosis. Surgical intervention is planned. During surgery, which of the following landmarks is most helpful in identifying the diseased organ?

Teniae coli - This patient most likely has appendicitis, which is usually treated by removing the appendix. During the procedure, the teniae coli can be used as a surgical landmark. The teniae coli begin as a continuous layer of longitudinal muscle that surrounds the rectum just below the serosa. At the rectosigmoid junction, this layer condenses to form 3 distinct longitudinal bands that travel on the outside of the entire colon before converging at the root of the vermiform appendix. The teniae coli have a similar function as the outer layer of the muscularis externa in other portions of the digestive tract. If the appendix cannot be identified by palpation during an appendectomy, it can be located by following the teniae coli to its origin at the cecal base.

Two graphs illustrating the transport rate of solutes across the plasma membrane are shown. Which of the following best explains the difference in the shape of the curves?

The presence of a protein transporter - The image above illustrates the difference between the rate of transport of solute across the cell membrane in simple diffusion (line 2) and carrier-mediated transport (line 1). There are two types of diffusion: Simple diffusion - molecules move through a membrane without the help of carrier proteins. Facilitated diffusion - requires carrier proteins. Carrier proteins are typically transmembrane proteins that possess binding sites for the substrate they transport. Binding is followed by movement of the substrate across the cell membrane to the intracellular space, where it is released into the cytoplasm. Because there is a finite number of carrier proteins in the cell membrane, transporter saturation occurs with facilitated diffusion, and can be seen as a flattening of the curve (maximum diffusion speed), even as solute concentration continues to increase. This maximum rate of transport is referred to as the transport maximum (Tm) and is similar in principle to the Vmax in standard enzyme kinetics.

A researcher is studying the structure of different hormone receptors. Receptor proteins are isolated and purified from a homogenized tissue sample. Detailed structural analysis shows that one of the proteins contains a 30-amino acid motif coordinating a zinc molecule, as shown in the image below. A receptor for which of the following hormones was most likely isolated in this experiment?

Thyroid hormone - The zinc-finger structure represents the most commonly identified DNA-binding domain in humans. Zinc-finger motifs are composed of chains of amino acids bound together around a zinc atom via linkages with cysteine (and sometimes histidine) residues. This forms a stable, finger-shaped structure containing 2 antiparallel β- strands and an α-helix. Unique combinations of amino acids as well as the specific histidine and cysteine linkages determine DNA-binding specificity. Many transcription factors use multiple zinc-finger motifs to recognize specific genes and alter their activity. Although most hormones alter transcription regulation to some degree in target cells, only intracellular receptors located in the cytoplasm or nucleus can act directly as transcription factors. These intracellular receptors typically bind lipid-soluble hormones because the ligand has to diffuse across the cell membrane to reach the receptor. Once bound to their ligand, these receptors bind directly to target DNA sequences via zinc fingers to regulate gene expression. Examples include steroid (eg, estrogen, aldosterone, cortisol), thyroid hormone, and fat-soluble vitamin receptors. In contrast, non-lipid-soluble hormones interact with transmembrane receptors found on the cell membrane. These receptors use a signal transduction cascade involving second messengers with subsequent activation of non-receptor-associated transcription factors; they do not contain DNA-binding domains. Examples include the G-protein-coupled receptors that bind ACTH, ADH, epinephrine, and glucagon as well as receptors with intrinsic and associated tyrosine kinase activity (eg, insulin and growth hormone receptors, respectively)

A 42-year-old woman is hospitalized for surgical removal of a mediastinal mass. The patient has had intermittent episodes of double vision, difficulty chewing food, and weakness of the extremities for the past several months. During evaluation she was found to have a circumscribed anterior mediastinal mass. Preoperative nerve conduction studies revealed a decremental response to repetitive motor nerve stimulation. She has no other medical conditions and does not use tobacco, alcohol, or illicit drugs. The patient has no drug allergies. Compared to a healthy individual, which of the following anesthesia-related medications is most likely to have increased potency in this patient?

Vecuronium - This patient has an anterior mediastinal mass and a nerve conduction study consistent with myasthenia gravis (MG), an autoimmune disease caused by autoantibodies against postsynaptic nicotinic acetylcholine receptors of the neuromuscular junction. Antibody-induced degradation leads to fewer functional receptors, which may be insufficient to generate muscle action potentials despite normal acetylcholine release. Weakness (most commonly of the extraocular, bulbar, and proximal muscles) worsens with repetitive nerve stimulation (fatigability) as acetylcholine stores in the presynaptic nerve terminal are depleted. Thymic abnormalities (eg, thymoma, thymic hyperplasia) are common and may appear as an anterior mediastinal mass on imaging. Neuromuscular blocking agents are used to induce skeletal muscle relaxation during surgery by competing with acetylcholine at the postsynaptic membrane. They can be subclassified by their effects: Nondepolarizing agents (eg, vecuronium, rocuronium) are competitive antagonists of nicotinic acetylcholine receptors. Due to the low number of functioning receptors, patients with MG are extremely sensitive to these agents; very small doses can induce paralysis with loss of airway patency. Depolarizing agents (eg, succinylcholine) are competitive agonists of nicotinic acetylcholine receptors; persistent depolarization leads to desensitization of the motor end plate. Due to the low number of functioning receptors, patients with MG are often resistant to these agents; extremely large doses are required to induce muscle relaxation.

An 11-year-old boy is brought to the office for a routine checkup prior to enrollment at summer camp. The patient and his mother report no health concerns. Family history is significant for his father passing away suddenly from a heart condition 2 years ago. The patient is at the 75th and 80th percentiles for height and weight, respectively. Vital signs are normal. Physical examination shows a well-appearing child. The lungs are clear to auscultation. Cardiac auscultation findings at the left lower sternal border are given below. The auscultatory abnormality intensifies with the handgrip exercise. Which of the following is the most likely diagnosis?

Ventricular septal defect - The presentation of a ventricular septal defect (VSD) depends on its size. Large defects result in high-volume shunting of blood across the VSD, leading to a low interventricular pressure gradient and a soft or absent murmur; the large degree of shunting may lead to heart failure in infancy (eg, difficulty feeding, tachypnea, failure to thrive). In contrast, small defects allow only a small amount of blood to flow across the VSD; most patients are asymptomatic and have loud murmurs that are detected incidentally on cardiac auscultation. This patient's harsh holosystolic murmur best heard at the left lower sternal border is indicative of blood flow through a small, hemodynamically insignificant VSD. The handgrip maneuver increases systemic vascular resistance, resulting in increased aortic and left ventricular (LV) pressure that intensifies the murmur.

A scientist is conducting research to discover novel drug targets for antiretroviral agents against HIV. An HIV-positive blood sample is analyzed in the laboratory, and purified CD4 T lymphocytes are extracted. Using molecular tracing techniques, the scientist follows a viral HIV protein that is synthesized in the blood sample's T cells. The protein becomes glycosylated before being proteolytically cleaved into 2 smaller proteins in the Golgi apparatus. Which of the following best describes the function of these 2 newly formed HIV proteins?

Virion attachment to the target cells - The HIV genome contains a set of structural genes (gag, pol, and env) that encode polyproteins. These polyproteins are subsequently cleaved by host or viral proteases into the individual proteins that compose the HIV virus. The only glycosylated HIV polyprotein is gp160, the product of the env gene. gp160 is extensively glycosylated in the rough endoplasmic reticulum and Golgi apparatus. It is then cleaved into the envelope proteins gp120, which mediates viral attachment, and gp41, which mediates viral fusion with the host cell. Glycosylation of these proteins is crucial for: Immune evasion - Glycosylation acts as a shield for the conserved regions of these surface proteins, masking them from immune recognition. Host cell binding Proper protein folding