UWorld 4/20 pt 2

A 37-year-old woman is evaluated for progressive shortness of breath and dry cough. The patient has seasonal allergies and takes no medications. There is no significant family history. On physical examination, the lungs are clear to auscultation. Chest imaging studies reveal pulmonary infiltrates and hilar adenopathy. The patient undergoes lung biopsy; the findings are shown below. (granulomas) Which of the following sets of immune cells and cytokines is most likely responsible for the development of this patient's pathologic findings? A. Th1, IL-2, interferon-γ (%) B. Th1, IL-5, IL-10 (%) C. Th2, IL-3, interferon-γ (%) D. Th2, IL-4, IL-5 (%) E. Th2, IL-5, tumor necrosis factor-alpha (%)

A. Th1, IL-2, interferon-γ (%) This patient with dyspnea and dry cough has pulmonary infiltrates and hilar adenopathy; this presentation suggests pulmonary sarcoidosis. The biopsy specimen with multiple, noncaseating granulomas—characterized by a central collection of tightly clustered epithelioid macrophages with abundant pink cytoplasm surrounded by a rim of mononuclear cells—confirms the diagnosis. Multinucleated giant cells, formed by macrophage fusion, are discernable at higher magnification. Sarcoidosis is thought to result from a dysregulated cell-mediated immune response to an unidentified antigen, which causes the formation of granulomas. Cell-mediated immunity is stimulated by production of IL-12 from activated antigen-presenting cells. IL-12 stimulates CD4+ helper T cells to differentiate into the Th1 subtype. Th1 cells then secrete IL-2 and interferon-γ (IFN-γ). IL-2 stimulates the autocrine proliferation of Th1 cells and furthers Th1 recruitment. IFN-γ activates macrophages and promotes granuloma formation. Activated macrophages and T cells also produce tumor necrosis factor-alpha, further assisting in leukocyte recruitment and granuloma maintenance

A 65-year-old man with type 2 diabetes mellitus comes to the office due to decreased sexual performance over the last 6 months. The patient says his libido, muscle strength, and energy level are normal, but his erections are inconsistent, weak, and of inadequate duration for sexual activity. Past medical history is positive for hypertension, but he has no history of coronary artery disease and no suspicious chest pain. Bilateral ankle brachial index testing is within normal limits. The patient is treated with sildenafil, which gives significant improvement in his sexual performance. The intracellular signaling of this drug is most similar to that of which of the following substances? A. 1,25-dihydroxycholecalciferol (%) B. Brain natriuretic peptide (%) C. Gamma-aminobutyric acid (%) D. Insulin (%) E. Interleukin-2 (%) F. Platelet-derived growth factor (%)

B. Brain natriuretic peptide (%) Atrial and brain natriuretic peptides (ANP and BNP) are polypeptide hormones that exert their effect by binding ANP receptors. These transmembrane receptors are linked to a guanylyl cyclase that converts guanosine 5′-triphosphate to cyclic guanosine 3′,5′-monophosphate (cGMP). cGMP then activates a downstream cGMP-dependent protein kinase, leading to relaxation of vascular smooth muscle and subsequent vasodilation. Nitric oxide activates the same cGMP second messenger system by binding a cytosolic guanylyl cyclase. Penile erection is initiated by release of acetylcholine and nitric oxide (NO) from parasympathetic fibers, leading to a rise in intracellular cGMP and vasodilation of the arteries supplying the corpus cavernosum. Sildenafil is a phosphodiesterase-5 inhibitor that decreases degradation of cGMP, enhancing the effect of parasympathetic activation in erectile tissues. Because vasodilatory nitrates (eg, nitroglycerin, isosorbide mononitrate) work by releasing NO, coadministration of sildenafil with nitrates can lead to excessive cGMP-induced vasodilation and severe hypotension.

A 22-year-old woman comes to the office due to worsening dyspnea and heart pounding with exercise for the last week. She has no chronic medical conditions but reports aches and pains over the past several weeks. The patient takes ibuprofen as needed but no other medications. Temperature is 37.2 C (99 F), blood pressure is 138/86 mm Hg, and pulse is 90/min. BMI is 18 kg/m2. Physical examination shows an erythematous rash in sun-exposed regions. The lungs are clear to auscultation. A midsystolic click and systolic murmur are heard best at the apex without radiation. There is mild tenderness of joints. Laboratory results are as follows: Hemoglobin 7.8 g/dL Reticulocytes 6% Platelets 205,000/mm3 Leukocytes 11,200/mm3 Creatinine 1.4 mg/dL Which of the following is the most likely cause of this patient's hematologic findings? A. Bone marrow suppression (%) B. Extravascular hemolysis (%) C. Intrinsic factor antibodies (%) D. Thrombotic microangiopathy (%) E. Traumatic intravascular hemolysis (%)

B. Extravascular hemolysis (%) This patient with dyspnea and heart pounding with exercise has symptomatic anemia. Her other findings, including the presence of joint pain, a photosensitive rash, and mild renal insufficiency, raise suspicion for systemic lupus erythematosus (SLE), an autoimmune disease primarily seen in young women. SLE frequently causes anemia due to a combination of factors, including chronic inflammation (anemia of chronic disease), gastrointestinal serositis (iron deficiency from bleeding), and/or autoimmune hemolytic anemia (AIHA). Approximately 10% of patients with SLE develop AIHA due to immune dysregulation, which results in the formation of IgG autoantibodies against the erythrocyte membrane. Erythrocytes coated with IgG are subsequently identified by the Fc-receptor on splenic macrophages and partially or wholly phagocytized, leading to extravascular hemolysis. Laboratory assessment typically reveals elevated reticulocyte count (ie, reticulocytosis) because interstitial fibroblasts in the kidney sense tissue hypoxia and increase the release of erythropoietin; this drives the bone marrow to increase erythrocytosis, leading to the presence of immature red cells in the peripheral blood (normoblasts, reticulocytes). Choice E) Although traumatic intravascular hemolysis can occur with a mechanical heart valve or severe aortic stenosis, it is uncommon in otherwise healthy young individuals. Furthermore, this patient's heart murmur is most consistent with mitral valve prolapse, which is common in patients with SLE but rarely causes traumatic hemolysis.

A 34-year-old woman is evaluated in the emergency department due to 1-day of chest and left shoulder pain. The patient describes the pain as constant and worse in certain positions. A month ago, she was treated for a skin rash and joint pain. Her medical history is otherwise unremarkable. She is a lifetime nonsmoker and does not use alcohol or illicit drugs. Her father has hypertension and had a stroke at age 64. Temperature is 37.5 C (99.5 F), blood pressure is 122/70 mm Hg, and pulse is 97/min and regular. A triphasic, scratchy sound is heard over the left sternal border with the patient sitting up. The lungs are clear on auscultation. ECG shows sinus rhythm with ST-segment elevation in all leads except avR and V1. Which of the following is the most likely diagnosis? A. Eosinophilic myocarditis (%) B. Fibrinous pericarditis (%) C. Hemorrhagic pericarditis (%) D. Nonbacterial endocarditis (%) E. Purulent pericarditis (%)

B. Fibrinous pericarditis (%) This patient with pleuritic-type chest pain radiating to the shoulder and a recent history of skin rash and joint pain likely has acute fibrinous pericarditis due to systemic lupus erythematosus. Fibrinous pericarditis is the most common type of pericarditis and consists of pericardial inflammation with serous fluid and fibrin-containing exudate in the pericardial space. Patients typically have pleuritic (sharp, worse with breathing or movement) anterior chest pain that can radiate to the left shoulder or posteriorly to the bilateral scapulae. Fibrin deposition causes roughening of the visceral and parietal pericardium, often heard as a triphasic friction rub (occurring during atrial systole, ventricular systole, and early ventricular diastole) on cardiac auscultation; however, the rub can be absent if significant pericardial effusion is present. ECG typically shows diffuse ST elevation due to inflammation of the ventricular myocardium. Other causes of fibrinous pericarditis include viral infection, myocardial infarction, uremia, and other rheumatologic disease (eg, rheumatoid arthritis). If acute fibrinous pericarditis goes without treatment, chronic constrictive pericarditis can develop in some patients.

A 12-year-old Caucasian male with history of seizure disorder experiences several stroke-like episodes with residual neurological deficit. He also suffers from muscle weakness. Blood tests show increased serum lactate levels both post-exercise and at rest. This patient's condition is known to be maternally inherited. This patient's sister is also affected by the same disorder, but she displays very few symptoms. Which of the following is the most likely explanation for the variability in clinical presentation between the patient and his sister? A. Genetic imprinting (%) B. Heteroplasmy (%) C. Anticipation (%) D. Low expression variability (%) E. Female sparing (%)

B. Heteroplasmy (%) Mitochondrial diseases affect both male and female offspring with equal frequency (100%), but there are variable degrees of severity. This variability occurs because, during mitosis, mitochondria are randomly distributed between daughter cells. As a result, some cells contain mitochondria with mostly damaged mtDNA, while some contain mostly normal mitochondrial genomes. This mixture of two types of genetic material is called heteroplasmy and is responsible for the clinical variability of mitochondrial diseases.

A 35-year-old woman, gravida 2 para 1, comes to the office for prenatal evaluation. The patient says she had been using condoms for birth control and unintentionally became pregnant. Her last menstrual period was 2 months ago, and home pregnancy tests are positive. She has not been taking prenatal vitamins. The patient has a healthy, 5-year-old daughter who was born after an uneventful pregnancy. She has a history of rheumatoid arthritis, and her joint symptoms are controlled with methotrexate therapy. The patient has no other medical conditions and takes no other medications. She does not use tobacco, alcohol, or illicit drugs. Vital signs are within normal limits, and physical examination shows no abnormalities. Serum β-hCG is elevated, and transvaginal ultrasonography shows a normal gestational sac and embryo. This patient's unborn child is at the greatest risk for which of the following congenital defects? A. Branchial arch anomalies (%) B. Neural tube defects (%) C. Renal dysplasia (%) D. Sacral agenesis (%) E. Skeletal lesions (%) F. Thyroid hypoplasia (%)

B. Neural tube defects (%)

A 68-year-old woman comes to the emergency department due to pain in the left upper arm after a fall from standing height. Medical history is significant for hypothyroidism and hypertension. Physical examination shows bruising of the shoulder. Left arm movement is limited due to pain. Plain radiographs reveal a nondisplaced left humerus fracture at the anatomical neck. This patient is at greatest risk for which of the following complications? A. Biceps tendon rupture (%) B. Brachial artery tear (%) C. Humeral head necrosis (%) D. Median nerve injury (%) E. Radial nerve palsy (%)

C. Humeral head necrosis (%) This patient suffered a fracture of the proximal humerus at the anatomical neck. Humeral neck fractures commonly occur in falls; risk factors include age >65 and osteoporosis. They often occur as isolated injuries but may also be associated with glenohumeral dislocation. The proximal humerus and glenohumeral joint receive their blood supply via the anterior and posterior circumflex humeral arteries, which are branches of the axillary artery that form an anastomosis encircling the neck of the humerus in the quadrangular space. This anastomosis gives rise to intraosseous arteries that travel back to the humeral head; humeral neck fractures can disrupt this retrograde blood flow, leading to avascular necrosis (osteonecrosis) of the humeral head. Osteonecrosis presents insidiously with shoulder pain, decreased range of motion, and flattening of the humeral head on x-ray

A 34-year-old missionary in southern Asia is traveling to a remote village and becomes stranded when his bus breaks down. He has no access to water for 36 hours, during which his urine osmolality reaches 1100 mOsm/L. Urine concentration depends primarily on the serum level of vasopressin, which is regulated by the neurohypophysis in response to plasma osmolality and blood volume. Which of the following nephron segments responds to vasopressin by increasing absorption of a specific solute that is important for generating a high medullary concentration gradient? A. Cortical segment of the collecting duct (%) B. Early distal tubule (%) C. Medullary segment of the collecting duct (%) D. Proximal tubule (%) E. Thin ascending limb of the loop of Henle (%)

C. Medullary segment of the collecting duct (%) Vasopressin, or antidiuretic hormone (ADH), is the primary physiologic inhibitor of free water excretion. This hormone acts on 2 major receptors, V1 and V2. Stimulation of the V1 receptor causes vasoconstriction and increased prostaglandin release; stimulation of the V2 receptor results in an antidiuretic response. ADH is secreted in response to plasma hyperosmolality and, to a lesser extent, depletion of the effective circulating volume. Water deprivation initially increases plasma osmolality, resulting in increased ADH secretion. This causes the kidney to produce concentrated urine, which helps to counteract the rise in plasma osmolality by reducing urinary free water excretion. The medullary portion of the collecting duct is of particular importance in the production of maximally concentrated urine as the medullary interstitium is the region of highest osmolarity in the kidney. In the setting of high serum ADH levels, a large osmotic gradient drives the absorption of free water into the hypertonic medullary interstitium. As water leaves the tubular fluid, urea concentration greatly increases. ADH also increases the number of passive urea transporters in the inner medullary collecting duct, allowing a substantial fraction of the highly concentrated urea to diffuse down its concentration gradient into the medullary interstitium. When ADH levels are high, this urea resorption contributes up to 50% of total osmolarity of the medulla, further increasing the water-absorbing capacity of the nephron. (Choice A) ADH also increases water absorption in the cortical segment of the collecting duct, reducing the amount of free water delivered to the medullary collecting duct. This prevents excess water from being absorbed into the medullary interstitium, which would otherwise dilute the osmotic gradient and reduce the maximum achievable urine concentration.

A 43-year-old man comes to the office due to occasional chest discomfort over the last 6 weeks. He thinks he is most likely experiencing musculoskeletal pain but is concerned due to family history of heart disease. The patient has no medical conditions and does not use tobacco. He leads an active lifestyle and exercises every day. He undergoes treadmill exercise stress testing. Baseline blood pressure is 122/75 mm Hg and pulse is 54/min. After 10 minutes of exercise, his blood pressure is 155/80 mm Hg and pulse is 150/min. He has no chest pain and ECG shows no abnormalities. Compared to pretest conditions, which of the following is the single most important limiting factor for left ventricular myocardial blood supply during the test? A. Contraction force (%) B. Coronary vasoconstriction (%) C. Diastolic aortic pressure (%) D. Duration of diastole (%) E. Intraventricular pressure (%) F. Systolic ventricular wall stress (%)

D. Duration of diastole (%) Myocardial perfusion is provided by the right and left coronary arteries arising directly from the aortic root. In contrast to most other vascular beds in the body, left ventricular myocardial perfusion occurs mainly during diastole. During ventricular systole, intraventricular pressure and wall stress in the left ventricle exceed the aortic perfusion pressure (eg, 120 mm Hg), preventing effective coronary perfusion. Wall tension is highest in the subendocardial region, making this area of the myocardium particularly susceptible to ischemia. Relaxation of the left ventricle during diastole decreases intraventricular pressure to about 10 mm Hg (which is much lower than aortic diastolic pressure [~80 mm Hg]), providing a driving force that allows for adequate perfusion. Increased heart rate shortens the time of ventricular relaxation (duration of diastole); therefore, the time available for maximal coronary blood flow decreases and consequently becomes the major limiting factor for coronary blood supply to the myocardium

A 68-year-old woman comes to the office due to a month-long history of worsening fatigue, shortness of breath, and dry cough. The patient has symptoms that worsen with exertion and when lying flat. She has had no chest pain, palpitations, or lightheadedness. The patient has a history of hypertension and breast cancer that is in remission after surgery and doxorubicin-based chemotherapy 15 years ago. She does not use tobacco, alcohol, or illicit drugs. Blood pressure is 110/62 mm Hg and pulse is 94/min. Physical examination shows crackles at the lung bases and bilateral pedal edema. Which of the following sets of findings are most likely present in this patient? Right Atrial Pressure Left Ventricular End-Diastolic Pressure A. Decreased Decreased (%) B. Decreased Increased (%) C. Increased Decreased (%) D. Increased Increased (%) E. Increased No change (%) F. No change Increased (%)

D. Increased Increased (%) This patient with fatigue, dyspnea on exertion, orthopnea, cough, and lower extremity swelling is in acute decompensated heart failure. Anthracycline chemotherapeutic agents (eg, doxorubicin) are a common cause of dilated cardiomyopathy and can precipitate symptomatic heart failure that presents years after exposure. Dilated cardiomyopathy results from a direct insult to cardiomyocytes that impairs their contractile function. There is an increase in left ventricular volume that is initially compensated for by the Frank-Starling mechanism and later by eccentric hypertrophy to maintain cardiac output. However, overwhelming wall stress eventually leads to marked impairment in myocardial contractile function, reduced cardiac output, and symptomatic decompensated heart failure. The elevated left ventricular end-diastolic pressure (LVEDP) is transmitted backward to the pulmonary veins and capillaries, leading to pulmonary edema (evidenced by crackles on lung auscultation)

A 45-year-old man comes to the office for an annual medical visit. The patient has had prediabetes for the last 2 years. He feels well and takes no medications but has gained weight since his last visit a year ago. The patient has a strong family history of type 2 diabetes mellitus. Blood pressure is 124/78 mm Hg and BMI is 32 kg/m2. Laboratory results show a fasting blood glucose of 157 mg/dL and serum creatinine of 0.7 mg/dL. Hemoglobin A1c is 7.4%. Urine assay shows no detectable albuminuria. Which of the following renal changes is most likely present in this patient at this time? A. Decreased peritubular capillary oncotic pressure (%) B. Decreased intraglomerular capillary pressure (%) C. Glomerular atrophy (%) D. Increased glomerular filtration rate (%) E. Increased oncotic pressure in Bowman's space (%)

D. Increased glomerular filtration rate (%) This patient has type 2 diabetes mellitus, confirmed by elevated blood glucose and hemoglobin A1c. Diabetic nephropathy can occur with any form of diabetes mellitus and is the most common cause of end-stage renal disease in the United States. One of the earliest derangements that contributes to the pathogenesis of diabetic nephropathy is an increase in the filtered glucose load. This increases sodium resorption in the proximal tubule by the sodium glucose cotransporter, leading to decreased sodium and fluid delivery to the macula densa and subsequent activation of the tubuloglomerular autoregulation system. Subsequent dilation of the afferent arterioles and constriction of the efferent arterioles increases intraglomerular capillary pressure, resulting in an increased glomerular filtration rate (hyperfiltration) and glomerular hypertrophy (Choices B and C). Although the increased filtration rate appropriately counteracts the excessive sodium reabsorption and prevents fluid retention, over a prolonged period, chronically elevated intraglomerular capillary pressures contribute to glomerular structural changes. These include basement membrane thickening, mesangial expansion, and broadening of the podocyte foot processes, which result in the loss of small amounts of albumin in the urine (30-300 mg/day, or moderately increased albuminuria). Albuminuria is the earliest clinical sign of diabetic nephropathy and typically occurs before any appreciable rise in serum creatinine. Later in the disease process, there is widespread glomerulosclerosis and a decline in glomerular filtration. TLDR increased sodium delivery to PCT = increased sodium glucose uptake= less sodium delived to macula densa= increased RAAS

A 56-year-old previously healthy man comes to the office due to decreased hearing in both ears. He reports difficulty understanding conversations in crowded rooms. His wife adds that they often argue about the volume of the television set. The patient cannot remember precisely when he first noticed hearing loss but says it has been present at least 6 months and is getting worse. For the past 12 years, he has worked in a factory where he has to shout to communicate with coworkers and has seldom worn hearing protection. An audiogram is obtained as shown in the image below. (hearing loss at high frequencies >1000 Hz) Which of the following is most likely abnormal in this patient? A. Auditory nerve (%) B. Cochlear cupula (%) C. Middle ear ossicles (%) D. Organ of Corti (%) E. Round window (%) F. Tympanic membrane (%)

D. Organ of Corti (%) This patient has high-frequency hearing loss due to chronic noise exposure. Transduction of mechanical sound waves into nerve impulses occurs in the organ of Corti through the following steps: Sound reaches the middle ear by vibrating the tympanic membrane. The vibration is transferred to the oval window by the ossicles. Vibration of the oval window causes vibration of the basilar membrane, which in turn causes bending of the hair cell cilia against the tectorial membrane. Hair cell bending causes oscillating hyperpolarization and depolarization of the auditory nerve, thereby creating nerve impulses from sound. Noise-induced hearing loss results from trauma to the stereociliated hair cells of the organ of Corti. The acoustic reflex normally dampens the effects of loud noise by causing the stapedius and tensor tympani muscles to contract, which lessens the responsiveness of the ossicles to sound. However, prolonged noise exposure can cause distortion or fracture of the stereocilia due to shearing forces against the tectorial membrane. High-frequency hearing is lost first, regardless of the frequency of the sound causing the damage.

A 17-year-old boy who was recently diagnosed with type 1 diabetes mellitus is found unresponsive at home. His family reports that the patient did not feel good last night and skipped dinner, but he still took his usual dose of insulin. Paramedics find that his fingerstick blood glucose is 32 mg/dL and immediately administer intramuscular glucagon. Glucagon binds to a transmembrane receptor in hepatocytes, which promotes binding of intracellular GTP to a specific receptor-associated protein. This leads to further downstream signaling and rapid metabolic changes within hepatocytes, including a rapid decrease in intracellular glycogen stores and release of glucose into the blood. Which of the following is the most likely mediator responsible for these effects? A. cGMP-dependent protein kinase (18%) B. Janus tyrosine kinase (6%) C. Phosphodiesterase (3%) D. Protein kinase A (61%) E. Tyrosine-specific protein kinase (10%)

D. Protein kinase A (61%)

A 29-year-old woman comes to the office for treatment of anxiety that has worsened over the past year. She finds herself worrying all the time and fears that she may not complete her graduate studies in time to meet requirements for her degree. The patient is also worried about her son's health and anxiously obsesses about him all the time. She says, "My anxiety just comes out of the blue; one way or another, I'm anxious all the time." The patient has no history of medical problems. Physical examination is unremarkable; complete blood count, chemistry panel, and TSH and B12 levels are normal. An anxiety disorder is diagnosed and fluoxetine is prescribed. The patient's anxiety begins to improve over the next 4-6 weeks. The physician explains that the medication inhibits the reuptake of a neurotransmitter released by a specific set of neurons. These neurons are most likely part of which of the following structures? A. Caudate nucleus (%) B. Locus ceruleus (%) C. Nucleus basalis of Meynert (%) D. Raphe nuclei (%) E. Red nucleus (%) F. Substantia nigra (%)

D. Raphe nuclei (%) In the central nervous system (CNS), serotonergic (serotonin-releasing) neurons are primarily found in the raphe nuclei of the brainstem. The raphe nuclei are located in the midbrain, pons, and medulla, and axons from these cell bodies project widely throughout the CNS to synapse on structures such as the cerebral cortex, thalamus, hypothalamus, cerebellum, hippocampus, and spinal cord. These neurons play a role in the sleep-wake cycle, anxiety, mood, psychosis, sexuality, eating behavior, and impulsivity. Medications that target serotonin neurons are widely used in psychiatric disorders. Serotonergic antidepressants are the primary pharmacotherapy for most depressive and anxiety disorders. Antidepressants such as selective serotonin reuptake inhibitors (SSRIs [eg, fluoxetine]), serotonin-norepinephrine reuptake inhibitors, and tricyclic antidepressants work by prolonging the amount of time that serotonin spends in the synaptic clefts of these neurons before being taken up by presynaptic neurons. (Choice A) The caudate nucleus and putamen form the striatum, which functions in motor activities. In Huntington disease, there is loss of cholinergic and GABA-releasing neurons in the striatum. (Choice B) The locus ceruleus houses norepinephrine-secreting neurons that participate in activation of the "fight or flight" response to physical and emotional stressors. It is located in the dorsal pons. These neurons are implicated in some anxiety symptoms, but they are not serotonergic and not affected by SSRIs. (Choice C) The nucleus basalis of Meynert houses the cell bodies of cholinergic neurons. In Alzheimer disease, these neurons secrete decreased amounts of acetylcholine. (Choice E) The red nucleus is located in the anterior midbrain. Its neurons participate in motor coordination of the upper extremities. (Choice F) The substantia nigra contains dopaminergic neurons. In Parkinson disease, these neurons are depleted.

A 34-year-old man comes to the office with his girlfriend for follow-up of type 1 diabetes mellitus. He was diagnosed 15 years ago and is currently treated with a combination of basal and rapid-acting insulin injections. The patient has been experiencing intermittent episodes of hypoglycemia with a blood glucose of 35-54 mg/dL. Two weeks ago, he was taken to the emergency department after passing out due to low glucose levels. The patient is prescribed an injectable medication to be administered at home by a caregiver when hypoglycemia is associated with impaired consciousness. This medication rapidly improves hypoglycemia by which of the following mechanisms? A. Decreasing uptake of glucose by fat and muscles (%) B. Decreasing uptake of glucose by the liver (%) C. Increasing gastrointestinal absorption of glucose (%) D. Increasing gluconeogenesis (%) E. Increasing glycogenolysis (%)

E. Increasing glycogenolysis (%) Hypoglycemia initially manifests with neurogenic (autonomic) symptoms, including anxiety, tremor, and sweating. However, as hypoglycemia worsens patients may develop life-threatening neuroglycopenic symptoms, including confusion, loss of consciousness, and seizures. Mild to moderate hypoglycemia is usually self-treated with oral fast-acting carbohydrates (eg, glucose tablets, fruit juices). However, when hypoglycemia becomes severe enough to induce unconsciousness, parenteral treatment is necessary. In a medical setting, severe hypoglycemia is usually treated with an infusion of glucose, but this requires intravenous access. In a nonmedical setting, severe hypoglycemia can be treated with emergency glucagon kits, which are produced in intranasal and subcutaneous/intramuscular formulations and can be administered by a caregiver or informed bystander. Glucagon rapidly corrects hypoglycemia by increasing hepatic glycogenolysis; the free glucose residues are then released into the blood, causing a return to consciousness within 10-15 minutes of administration. Subsequently, glucagon induces gluconeogenesis and suppresses hepatic glucose uptake, which provide a delayed but somewhat more sustained effect

42-year-old previously healthy man comes to the office due to an enlarging mole. The patient has had a mole on his forearm for the past several years, and it has rapidly increased in size over the past 4 months. Physical examination shows an 8-mm raised lesion with variegated pigmentation and ill-defined borders on the right forearm. Excisional biopsy of the lesion is planned. Local anesthesia is administered via an infiltrating injection of lidocaine mixed with epinephrine. Which of the following is the most likely impact of mixing the latter medication with the anesthetic agent? A. Altered neurotransmitter levels of nociceptive fibers (%) B. Decreased pain during subcutaneous infiltration (%) C. Increased anesthesia efficacy by synergistic effect (%) D. Increased anesthesia potency by decreasing tissue pH (%) E. Prolonged duration of action of the anesthetic agent (%)

E. Prolonged duration of action of the anesthetic agent (%) Lidocaine is a local anesthetic that blocks transmission from free nerve endings. It is often mixed with epinephrine, which causes profound vasoconstriction when injected subcutaneously. This results in the following: A decrease in local bleeding, making the procedure easier to complete A prolonged duration of action because more lidocaine remains at the site of injection A decrease in systemic absorption, reducing the potential for serious adverse effects (eg, arrhythmias, seizures)

A new inhaled anesthetic under development by a pharmaceutical company is tested in a series of experiments to determine its pharmacokinetic properties. During one of the experiments, the anesthetic agent is administered at a constant partial pressure while arterial and venous concentrations are monitored. The study results show that the anesthetic has a very large arteriovenous concentration gradient shortly after beginning inhalation. Which of the following best describes the properties of the new anesthetic? A. Fast equilibration with the brain (%) B. Low peripheral tissue solubility (%) C. Low peripheral tissue uptake (%) D. Low potency (%) E. Slow onset of action (%)

E. Slow onset of action (%) Before gas anesthetics can reach the target organ (brain), they must move through a number of compartments (inhaled air → lungs → blood→ brain). The onset of anesthesia occurs when a sufficient quantity of anesthetic is transferred to the brain. The factors shown in the table influence the rate of transfer of anesthetic through the compartments and determine the onset of action. The arteriovenous concentration gradient is the difference between the concentration of a gas anesthetic in arterial and venous blood. The solubility of the anesthetic in the peripheral tissues is a major factor in determining the size of the arteriovenous gradient. If tissue solubility is high, a large amount of anesthetic is taken up from arterial blood, which results in low venous concentration. As a result, saturation of the blood requires further absorption of anesthetic in order to replace that which is absorbed by the peripheral tissues. Because blood saturation takes longer, brain saturation is also delayed and onset of action is slower. In contrast, anesthetic gases with low peripheral tissue solubility have smaller arteriovenous gradients as there is less peripheral tissue uptake (Choices B and C). Less anesthetic is required to replace the amount absorbed by the peripheral tissue and so blood saturation occurs quickly, allowing concentrations in the brain to equilibrate faster (Choice A).

An 82-year-old woman comes to the office due to fatigue, abdominal discomfort, and lower extremity swelling. She also occasionally feels an uncomfortable pulsation in her neck. Six weeks ago, the patient underwent pacemaker implantation due to sick sinus syndrome. Episodes of lightheadedness that she had experienced before the procedure have now resolved. The patient is afebrile, and other vital signs are normal. Physical examination reveals bilateral, lower extremity edema and a tender, pulsatile liver. The lungs are clear on auscultation. The pacemaker implantation site has healed normally. Complete blood count is normal. What is the most likely diagnosis? A. Aortic valve regurgitation (%) B. Constrictive pericarditis (%) C. Infective endocarditis (%) D. Pulmonic valve regurgitation (%) E. Tricuspid valve regurgitation (%)

E. Tricuspid valve regurgitation (%) This patient likely has tricuspid valve regurgitation (TR) due to an adverse effect of her permanent pacemaker. The right ventricular lead of an implantable pacemaker or cardioverter-defibrillator passes through the superior vena cava into the right atrium and then through the tricuspid valve orifice to terminate on the endocardium of the right ventricle. Damage to the tricuspid valve leaflets or inadequate leaflet coaptation can sometimes occur, leading to severe TR in some patients. Severe TR typically presents with right-sided heart failure. Patients can have distended jugular veins, pulsatile and tender hepatomegaly, abdominal distension with ascites, and lower extremity edema. The lungs are clear on auscultation in the absence of concomitant left-sided heart disease. Cardiac examination typically reveals a holosystolic murmur best heard at the left lower sternal border; the murmur intensifies with maneuvers that increase right ventricular preload (eg, deep inspiration, leg raise).

A 49-year-old woman comes to the emergency department with a 2-day history of fever, dysuria, and flank pain. The patient has a history of poorly controlled type 2 diabetes mellitus. Temperature is 38.3 C (101 F), blood pressure is 80/44 mm Hg, pulse is 134/min, and respirations are 34/min. On physical examination, the patient appears lethargic, flushed, and diaphoretic. Neck veins are flat. The lungs are clear on auscultation and heart sounds are normal. There is right-sided costovertebral tenderness. Which of the following hemodynamic parameters are most likely to be present in this patient? Pulmonary capillary wedge pressure (PCWP) Cardiac index (CI) Systemic vascular resistance (SVR) Mixed venous O2 saturation (SvO2) A. ↑ ↓ ↑ ↓ (%) B. ↑ ↑ ↓ ↑ (%) C. ↓ ↓ ↑ ↓ (%) D. ↓ ↓ ↓ ↓ (%) E. ↓ ↑ ↓ ↑ (%)

E. ↓ ↑ ↓ ↑ (37%) This patient with fever, dysuria, flank pain, and right costovertebral angle tenderness likely has pyelonephritis. In addition, her hypotension in the setting of infection suggests septic shock. Septic shock is the most common type of distributive shock; other types include anaphylactic shock and neurogenic shock. The primary disturbance in septic shock is widespread vasodilation leading to decreased systemic vascular resistance (SVR). Increased vascular permeability (third-spacing) and peripheral venous dilation also cause a reduction in central venous pressure and pulmonary capillary wedge pressure (PCWP) (Choice B). Initially, the hypotension and inflammation from sepsis trigger a compensatory increase in sympathetic drive that increases heart rate and myocardial contractility, leading to increased cardiac index (cardiac output per body surface area). The high blood flow rates prevent complete extraction of oxygen by the tissues, resulting in high mixed venous oxygen saturation. As shock progresses, tissue ischemia and accumulation of cytotoxic mediators eventually cause a reduction in cardiac output with end-organ dysfunction.

A 21-year-old man comes to the emergency department due to 1 day of left flank pain and gross hematuria. He reports passage of small blood clots in urine but has had no dysuria or similar symptoms in the past. The patient has no other medical problems and does not take any medications. He does not use tobacco, alcohol, or illicit drugs. His younger sister has sickle cell disease. His temperature is 36.7 C (98 F), blood pressure is 126/70 mm Hg, and pulse is 100/min. Abdominal and genitourinary examination is unremarkable. There is no costovertebral angle tenderness. Which of the following is the most likely cause of this patient's hematuria? A. Acute pyelonephritis (%) B. Amyloidosis (%) C. Fanconi syndrome (%) D. Hemolytic-uremic syndrome (%) E. Hypersensitivity interstitial nephritis (%) F. Ischemic tubular necrosis (%) G. Lead nephropathy (%) H. Papillary necrosis (%) I. Renal artery stenosis (%) J. Urate nephropathy (%)

H. Papillary necrosis (%)

The following mitochondrial syndromes are important:

Leber hereditary optic neuropathy leads to bilateral vision loss. Myoclonic epilepsy with ragged-red fibers: myoclonic seizures and myopathy associated with exercise. Skeletal muscle biopsy shows irregularly shaped muscle fibers (ragged red fibers). Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS). The clinical presentation of MELAS is described in this vignette. (A 12-year-old Caucasian male with history of seizure disorder experiences several stroke-like episodes with residual neurological deficit. He also suffers from muscle weakness. Blood tests show increased serum lactate levels both post-exercise and at rest)

Genetic imprinting is

a selective inactivation of paternal or maternal alleles. This phenomenon explains the differences in clinical presentation between Prader-Willi and Angelman syndromes.

The primary disturbance in septic shock is

widespread vasodilation leading to decreased systemic vascular resistance (SVR). Increased vascular permeability (third-spacing) and peripheral venous dilation also cause a reduction in central venous pressure and pulmonary capillary wedge pressure (PCWP)