UWorld 4/27

This patient with edema, proteinuria, and hypoalbuminemia has nephrotic syndrome. The histopathology demonstrating normal glomeruli on light microscopy (LM) suggests a diagnosis of minimal change disease (MCD). MCD is the most common cause of nephrotic syndrome in children. It is often idiopathic but may be triggered by drugs (eg, nonsteroidal anti-inflammatory drugs [NSAIDs], as in this patient), immunizations, or malignancy (eg, Hodgkin lymphoma). T-cell dysfunction results in the production of a glomerular permeability factor (possibly IL-13), which damages podocytes and decreases the anionic charge of the glomerular basement membrane (GBM), allowing for selective loss of albumin in the urine. Clinical features include acute weight gain, diffuse edema, and "frothy urine" due to heavy proteinuria. Renal biopsy demonstrates normal glomeruli on LM, with no immunoglobulin or complement deposits visible on immunofluorescent microscopy. However, electron microscopy shows diffuse effacement and fusion of podocyte foot process. E. Minimal change disease (%)

15-year-old girl is brought to the clinic for evaluation of swelling around her eyes that developed over the past week. The patient is a cheerleader, and she had been taking ibuprofen daily for the last 3 months for various sprains and aches after practice. She has no chronic medical conditions. Vital signs are normal. On physical examination, there is moderate periorbital edema with bilateral lower extremity pitting edema. Serum creatinine is 0.5 mg/dL and serum albumin is 2.1 g/dL. Urinalysis shows 4+ protein and negative blood. Multiple regions of the kidney are biopsied, and a representative image is shown below: Which of the following is the most likely diagnosis? A. Acute interstitial nephritis (%) B. Crescentic glomerulonephritis (%) C. Focal segmental glomerulosclerosis (%) D. Membranous nephropathy (%) E. Minimal change disease (%) F. Poststreptococcal glomerulonephritis (%)

This patient's vomiting, volume depletion, glucosuria, and ketonuria are consistent with diabetic ketoacidosis (DKA). DKA is treated with an intravenous infusion of regular insulin that begins to lower serum glucose and ketone levels within minutes of administration. Regular insulin has a half-life of 5 minutes when administered intravenously, allowing rapid adjustment of the infusion rate based on glucose levels. Regular insulin can also be used subcutaneously in the subacute and chronic management of diabetes, usually in combination with an intermediate-acting or a long-acting insulin analog to provide bolus and basal coverage. When given subcutaneously, regular insulin can polymerize into hexamers, which slightly delays systemic absorption; it starts working within 30 minutes, peaks in 2-4 hours, and lasts 5-8 hours. Regular insulin and neutral protamine Hagedorn (NPH) are the only human recombinant insulins without any modifications in the amino acid sequence. All other insulin preparations (eg, detemir, glargine, lispro, aspart, glulisine) have structural modifications (eg, amino acid modifications) and are considered insulin analogs. B- regular insulin

A 21-year-old man comes to the emergency department due to several days of dizziness and extreme fatigue. The patient has been drinking a lot of water and urinating more than usual for the past 2 weeks.He developed nausea and vomiting a day ago and has had difficulty keeping food and liquids down since then. The patient has no other medical conditions and takes no medications. Blood pressure is 90/60 mm Hg, pulse is 120/min, and respirations are 20/min. Urinalysis is positive for glucose and ketones. The patient is given intravenous fluids and an intravenous infusion of recombinant human insulin without any amino acid modification. After his condition is stabilized, the insulin infusion is stopped, and the same insulin formulation is administered subcutaneously. Which of the following drug concentration curves is most likely to be obtained after the subcutaneous insulin injection?

This patient has atopic dermatitis, an inflammatory condition characterized by acute exacerbations of dry, pruritic, erythematous patches, papules, and/or vesicles. As in this patient, flexural regions (eg, antecubital and popliteal fossae) are commonly affected in adults. The pathogenesis of atopic dermatitis involves immune dysregulation and genetically mediated skin barrier dysfunction (eg, filaggrin mutation). The epidermal dysfunction increases cutaneous exposure to environmental allergens, which induce a Th2-predominant immune response. Key Th2 cytokines that trigger acute inflammation in atopic dermatitis are IL-4 and IL-13, and mechanisms include the following: Stimulation of plasma cell IgE production, which facilitates allergen sensitization and inflammation Suppressed expression of epidermal barrier components, which enhances Staphylococcus aureus colonization and inflammation Inhibition of Th1-type immune response and antimicrobial peptide production, which facilitate secondary microbial infections that complicate atopic dermatitis A. IL-4 and IL-13 (%)

A 24-year-old woman comes to the office with a pruritic rash on her arms and legs; it has been present on and off for most of her life. Examination of the posterior left leg reveals erythematous patches and papules, as shown in the exhibit. A similar rash is present on the right leg and bilateral antecubital fossae. Which of the following cytokines primarily initiated her current exacerbation? A. IL-4 and IL-13 (%) B. IL-8 and C3b (%) C. IL-12 and IFN-gamma (%) D. IL-17 and IL-23 (%) E. TNF-alpha and IL-1 (%)

A 34-year-old man comes to the hospital due to several hours of difficulty swallowing, dry mouth, and blurred vision. The patient has a history of major depression. Examination shows mydriasis and poorly reactive pupils. Electrodiagnostic studies reveal normal nerve conduction velocity but decreased compound muscle action potential (CMAP). Rapid, repetitive nerve stimulation leads to facilitation of CMAP. Further review of this patient's medical history would most likely reveal which of the following? A. Consumption of home-canned food (%) B. Diarrheal disease after eating undercooked poultry (%) C. Episodic diplopia and ptosis (%) D. Occupational exposure to insecticides (%) E. Recent consumption of puffer fish (%) F. Tricyclic antidepressant overdose (%)

A. Consumption of home-canned food (%) The combination of nicotinic (eg, diplopia, dysphagia) and muscarinic blockade (eg, dry mouth) is strongly suggestive of food poisoning with Clostridium botulinum toxin, a highly potent preformed neurotoxin. The toxin inhibits acetylcholine release from presynaptic nerve terminals at the neuromuscular junction (NMJ), thereby preventing muscular contraction. This effect can be seen on electromyography as a decrease in the compound muscle action potential (CMAP, or electrical response of the muscle) following stimulation of a motor nerve. High-rate, repetitive nerve stimulation improves the deficit as the rapid depolarization rate increases calcium concentration in the presynaptic nerve terminal, helping mobilize additional acetylcholine vesicles. The anaerobic environment within canned foods contaminated by C botulinum spores allows for germination and growth of the organism. The toxin (produced by vegetative bacteria) is not actively secreted, remaining intracellular until autolysis causes its release into food. The toxin is readily destroyed by heat; however, if food containing the toxin is not cooked properly, the classic diplopia, dysphagia, and dysphonia ("3 Ds") can develop within 12-36 hours of consumption Choice F) Anticholinergic toxicity is one of the manifestations of tricyclic antidepressant overdose. However, this produces muscarinic (not nicotinic) blockade with no effect on the NMJ (ie, no alterations in CMAP).

A n 18-year-old man is admitted to the hospital with cough, fever, and hypoxemia. Despite multiple intravenous antibiotics and frequent chest physiotherapy, the patient decompensates and is transferred to the intensive care unit for mechanical ventilation. Sputum cultures grow >100,000 colony-forming units of a non-lactose-fermenting gram-negative rod. After several days, the patient dies of overwhelming pneumonia complicated by respiratory failure. Since age 1, he had been hospitalized for recurrent episodes of multi-lobar pneumonia, sinusitis, and poor growth. On autopsy, both vas deferens are absent. Which of the following findings is also likely to be present on autopsy? A. Distension and obstruction of pancreatic ducts (%) B. Lobar sequestration (%) C. Lymphocytic infiltrate of pancreatic islet cells (%) D. Nodular lymphoid hyperplasia in the intestine (%) E. Situs inversus (%)

A. Distension and obstruction of pancreatic ducts (%) Cystic fibrosis transmembrane conductance regulator (CFTR) normally allows for transport of chloride into gastrointestinal and respiratory lumens, followed by sodium and water, leading to thin mucus. In cystic fibrosis (CF), the dysfunctional or absent CFTR gene leads to decreased water within the lumen, resulting in thick, dehydrated, and viscous mucus within organs. This patient's recurrent sinopulmonary infections and congenital absence of the vas deferens are consistent with CF. Pneumonia due to a non-lactose-fermenting, gram-negative rod (Pseudomonas aeruginosa or Burkholderia cepacia) is very common. The most common gastrointestinal manifestation of CF is pancreatic insufficiency (PI). Pancreatic duct obstruction and distension due to viscous mucus and subsequent inflammation develop in utero, eventually leading to fibrosis. PI is present from birth in most patients with CF. The loss of pancreatic tissue prevents these patients from developing pancreatitis. PI results in inability to absorb fats and fat-soluble vitamins (ADEK), leading to steatorrhea and failure to thrive. Patients with PI require pancreatic enzyme supplementation.

33-year old primigravida comes to the office to discuss results of prenatal testing. The patient is at 12 weeks gestation based on her last menstrual period. She has been taking prenatal vitamins inconsistently due to pregnancy-related nausea. Maternal alpha-fetoprotein level is reduced, and an ultrasound reveals increased nuchal translucency. Chorionic villous sampling shows a fetal karyotype of 47, XX, +21. The fetus is at greatest risk of developing which of the following conditions? A. Duodenal atresia (%) B. Holoprosencephaly (%) C. Myelomeningocele (%) D. Nephroblastoma (%) E. Omphalocele (%) F. Pyloric stenosis (%)

A. Duodenal atresia (%) Duodenal atresia, the failure of recanalization of the duodenum in early gestation, is the most common gastrointestinal abnormality associated with Down syndrome. Infants present during the first few days of life with bilious emesis and the classic "double-bubble" sign, which represents the dilated stomach and proximal duodenum. Patients with Down syndrome are also at risk for imperforate anus, Hirschsprung disease, tracheoesophageal fistula, and celiac disease. (Choice B) Holoprosencephaly, a severe developmental defect of the forebrain (prosencephalon), is associated with trisomy 13 (Patau syndrome). Additional features include microcephaly, microphthalmia, cleft lip/palate, and intellectual disability. (Choices C and E) Markedly elevated AFP levels are associated with open neural tube and ventral wall defects (omphalocele, gastroschisis). Myelomeningocele is associated with trisomy 18, and omphalocele is associated with trisomies 13 and 18. Educational objective:Down syndrome (trisomy 21) is associated with decreased maternal serum alpha-fetoprotein and increased nuchal translucency. Duodenal atresia is the most common gastrointestinal complication in these patients

A 67-year-old man comes to the office due to increased fatigue and weight gain over the past 6 months. He has hypertension controlled with a calcium channel blocker. Two years ago, the patient's physical examination was unremarkable, and his blood tests, including a lipid panel, were normal. Blood pressure is 135/98 mm Hg, and pulse is 62/min. BMI is 28 kg/m2. On physical examination, the thyroid appears to be mildly enlarged and is irregular and firm in consistency. Laboratory studies reveal elevated TSH, low free thyroxine (T4), high total and LDL cholesterol, and mildly elevated triglyceride levels. Which of the following is the most likely underlying mechanism for the elevated cholesterol in this patient? A. Activation of transcription factor peroxisome proliferator-activated receptor alpha (%) B. Decreased LDL receptor gene expression (%) C. Increased lipoprotein lipase gene expression (%) D. Induction of HMG-CoA reductase (%) E. Upregulation of LDL receptor degradation (%)

B. Decreased LDL receptor gene expression (%) This patient has primary hypothyroidism presenting with fatigue, weight gain, and goiter, along with elevated TSH and low free thyroxine (T4) levels. Hypothyroidism can cause a number of adverse effects on serum lipids, including elevating total cholesterol, LDL cholesterol, and triglyceride levels. Hypothyroidism causes decreased LDL receptor expression, leading to decreased clearance of LDL with resultant increased blood LDL levels. Hypothyroidism may also decrease LDL receptor activity and biliary excretion of cholesterol. Hypertriglyceridemia can occur in hypothyroidism due to decreased expression of lipoprotein lipase (Choice C). Along with effects on blood pressure (eg, hypertension due to increased peripheral vascular resistance), the adverse effects of hypothyroidism on lipid levels can increase the risk of coronary atherosclerosis

A 71-year-old man comes to the emergency department due to several episodes of bright red blood per rectum. His recent colonoscopy revealed numerous colonic diverticula. Laboratory studies on admission are notable for a hemoglobin of 8.2 g/dL with an unremarkable coagulation profile. An abdominal angiogram shows active bleeding from the sigmoid colon. Catheter embolization is planned via the femoral artery. During the procedure, the arterial catheter is most likely to proceed in which of the following orders? A. External iliac, common iliac, abdominal aorta, celiac (%) B. External iliac, common iliac, abdominal aorta, inferior mesenteric (%) C. External iliac, common iliac, abdominal aorta, superior mesenteric (%) D. External iliac, internal iliac, internal pudendal (%) E. External iliac, internal iliac, middle rectal (%)

B. External iliac, common iliac, abdominal aorta, inferior mesenteric (%)

A 17-year-old boy is brought to the clinic due to poor vision at night. The patient developed mild difficulty seeing at night about 4 months ago, and it has slowly worsened. Visual field examination shows visual loss in the midperiphery. External eye examination reveals normal tear formation. Funduscopic examination shows bilateral optic disc pallor, attenuation of retinal vessels, and areas of dark discoloration in the retina. Which of the following is the most likely mechanism of this patient's visual impairment? A. Biallelic inactivation of RB1 gene (%) B. Genetic progressive retinal dystrophy (%) C. Increased intracranial pressure (%) D. Poor aqueous outflow due to narrow angle (%) E. Retinal artery occlusion (%)

B. Genetic progressive retinal dystrophy (%) This patient has poor night vision, visual field loss, and funduscopic changes (eg, pigment accumulation, optic disc pallor, retinal vessel attenuation) consistent with retinitis pigmentosa, a genetic disease characterized by progressive dystrophy of the retinal pigmented epithelium and photoreceptors (eg, rods, cones). Rods, which are highly metabolically active and most prevalent in the periphery, are affected first, leading to the initial manifestations of progressive night blindness and loss of peripheral vision. Early funduscopic changes include retinal vessel attenuation (ie, narrow vessels likely due to alterations in retinal metabolic demand) and a waxy, pale optic disc (due to optic nerve atrophy and gliosis). In advanced disease, loss of cones (most prevalent in the central retina) causes decreased central visual acuity. Degeneration of retinal pigmented epithelial cells releases pigment, which deposits in a characteristic bone-spicule pattern over the course of the disease.

A 45-year-old woman diagnosed with Crohn disease 3 years ago comes to the office due to recurrent right upper quadrant abdominal pain. The pain is graded 5/10 in intensity, is characterized as dull, and occasionally radiates to the right shoulder. It typically occurs after eating fatty meals and is associated with nausea. The patient has no fever, vomiting, melena, or hematochezia. She currently takes infliximab for Crohn disease and atorvastatin for hyperlipidemia. Vital signs and abdominal examination are normal. Abdominal ultrasonography reveals multiple mobile calculi within the gallbladder. Which of the following processes is most likely responsible for the development of gallstones in this patient? A. Gallbladder hypomobility (%) B. Increased bile acid wasting (%) C. Increased intestinal oxalate absorption (%) D. Medication side effect (%) E. Red blood cell destruction (%)

B. Increased bile acid wasting (%) This patient with Crohn disease most likely developed gallstones due to inflammation of the terminal ileum causing decreased bile acid reabsorption. Bile acids are produced in the liver and excreted with bile into the duodenum. There, they emulsify fat droplets to form water-soluble micelles that allow pancreatic lipase to efficiently hydrolyze triglycerides into fatty acids and monoglycerides. In the jejunum, these micelles come in close contact with the gut epithelium, which facilitates the passive absorption of fatty acids, monoglycerides, and cholesterol across the brush border into enterocytes. However, bile acids are ionized molecules that cannot passively cross the intestinal wall. The bile acids eventually reach the terminal ileum, where specialized transport proteins allow them to be reabsorbed. The terminal ileum is a typical location of activity in Crohn disease. When the mucosa of the terminal ileum is inflamed, bile acids are lost in the feces. As a result, a lesser amount of bile acid is present in the bile, so the ratio of cholesterol/bile acids increases. Supersaturation of the bile with cholesterol then leads to formation of gallstones

An 85-year-old man is transferred to the hospital from a nursing home due to fever and confusion. On arrival, the patient is admitted directly to the intensive care unit with a presumptive diagnosis of septic shock. Antibiotic therapy is initiated. The patient is unable to provide any history, but his caretakers state that he has had nonspecific symptoms, including fever, for the past few days. The patient has a history of cardiovascular disease, diverticulitis, and dementia. Blood pressure is 60/40 mm Hg despite aggressive intravenous hydration. Intravenous norepinephrine is administered in response to the patient's hypotension. Which of the following cellular changes is most likely to occur in direct response to the medication? A. cAMP decrease in bronchial smooth muscle cells (%) B. cAMP increase in cardiac muscle cells (%) C. cAMP increase in vascular smooth muscle cells (%) D. DAG decrease in vascular smooth muscle cells (%) E. IP3 increase in cardiac muscle cells (%)

B. cAMP increase in cardiac muscle cells (%) Stimulation of adrenoreceptors leads to a change in concentration of a second messenger (eg, cAMP), which mediates the effects on the target organ. Norepinephrine, an adrenergic agonist, is the preferred pharmacologic treatment for septic shock as it predominately stimulates a1, a2, and B1 receptors, with little influence on B2 receptors. This leads to the following clinical effects: Stimulation of α1 adrenoreceptors leads to vasoconstriction in the skin and viscera, resulting in increased systolic and diastolic blood pressure with decreased renal and hepatic blood flow. α1-mediated vasoconstriction occurs via the IP3-second messenger pathway. Stimulation of β1 adrenoreceptors within the heart increases cAMP concentrations through Gs-mediated receptor coupling, which leads to increased cardiac contractility, conduction, and heart rate. However, the direct effect of norepinephrine on heart rate is counteracted by an indirect, baroreceptor-mediated reflex bradycardia that occurs following the increase in peripheral resistance. The combined result of these effects is often an unchanged or even decreased heart rate. Stimulation of α2 adrenoreceptors causes a decrease in cAMP in pancreatic β cells and in the intestines, resulting in decreased insulin secretion and reduced intestinal motility. Central α2 adrenoreceptors are not stimulated by intravenous administration of norepinephrine as the molecule does not cross the blood-brain barrier.

24-year-old woman participates in a study of changes in blood pressure during aerobic exercise. She is healthy and takes no medications. During the study she is asked to run on a treadmill at incrementally increasing speed until her heart rate reaches 90% of her expected maximum heart rate. Compared to at rest, which of the following changes in blood pressure are expected during this time? Systolic blood pressure Diastolic blood pressure Pulse pressure A. Decreased Decreased Unchanged (%) B. Unchanged Increased Decreased (%) C. Increased Unchanged Increased (%) D. Increased Increased Unchanged (%) E. Increased Increased Increased (%)

C. Increased Unchanged Increased (%) During aerobic exercise, there is vasoconstriction of splanchnic arterioles and a larger degree of vasodilation of skeletal muscle arterioles, which shunts blood to exercising muscle and leads to overall reduced SVR. In addition, venoconstriction of capacitance veins mobilizes stored blood to increase venous return (ie, increased preload), and myocardial contractility is also increased. Both the increased preload and increased myocardial contractility increase stroke volume, which in combination with increased heart rate, markedly increases cardiac output. The reduced SVR during aerobic exercise facilitates decreased DBP but it is somewhat offset by mobilization of a higher percentage of blood volume from the venous to the arterial circulation (due to venoconstriction and increased heart rate), resulting in slightly decreased or unchanged DBP. The increased stroke volume leads to increased PP, and consequently increased SBP

A 35-year-old man comes to the office due to a painful tongue sore. For the past 2 weeks he has had a fever and has experienced myalgias and arthralgias. He has no known medical problems. The patient works as a driver for a local delivery service. He had unprotected sex with a stranger approximately 1 month ago. Physical examination shows a rash over his trunk and cervical lymphadenopathy. An ulcer is located on the median sulcus of the tongue and is 2 cm anterior to the foramen cecum. Blood is drawn for an HIV test. The pain sensation from his ulcer is most likely carried by which of the following nerves? A. Chorda tympani (%) B. Glossopharyngeal nerve (%) C. Mandibular division of the trigeminal nerve (%) D. Maxillary division of the trigeminal nerve (%) E. Vagus nerve (%)

C. Mandibular division of the trigeminal nerve (%)

A 54-year-old man comes to the emergency department after vomiting blood. He has also had melena, fatigue, and lethargy over the last 24 hours. The patient emigrated from sub-Saharan Africa 20 years ago and occasionally returns to visit friends and family. Temperature is 37.5 C (99.5 F), blood pressure is 90/60 mm Hg, and pulse is 115/min. Abdominal palpation reveals an enlarged liver and a spleen tip below the level of the umbilicus. Laboratory results are as follows: Complete blood count Hemoglobin 5.2 g/dL Platelets 75,000/mm3 Leukocytes 8,000/mm3 Neutrophils 79% Eosinophils 15% Lymphocytes 6% Upper endoscopy reveals bleeding esophageal varices. Which of the following is the most likely underlying cause of this patient's symptoms? A. Cysticercosis (%) B. Hookworm infection (%) C. Malaria (%) D. Schistosomiasis (%) E. Toxoplasmosis (%)

D. Schistosomiasis (%) Esophageal varices and splenomegaly are signs of portal hypertension, which usually indicates underlying hepatic fibrosis. Although chronic viral hepatitis and alcohol abuse are the leading causes of hepatic fibrosis in the United States, this patient's immigration/travel history and eosinophilia raise suspicion for hepatosplenic schistosomiasis, a parasitic blood fluke infection seen primarily in rural parts of sub-Saharan Africa and East Asia. Exposure to Schistosoma occurs when humans swim in freshwater contaminated by infected snails (the intermediate host). Cercariae penetrate human skin and migrate to the liver, where they mature to adult worms. Adult worms then spread through the portal circulation to the mesenteric venules or venous plexus of the bladder. Here, they release eggs into host tissue that are excreted in the feces or urine. Although many patients with schistosomiasis are asymptomatic, chronic exposure to Schistosoma eggs can activate hepatic stellate cells, leading to collagen deposition in periportal spaces and progressive periportal fibrosis. Occlusion of periportal veins eventually blocks venous outflow from abdominal organs, leading to congestive splenomegaly and gastroesophageal varices. Patients frequently have anemia from intestinal/variceal bleeding, thrombocytopenia from splenic trapping of platelets, and eosinophilia in response to adult worms.

A 64-year-old man is evaluated for a 1-month history of worsening fatigue and low back pain exacerbated by movement. He has no prior medical history and takes no medications. Vital signs are normal. Physical examination shows mucosal pallor and bony tenderness. Radiographs reveal lytic bone lesions. Laboratory studies show that hemoglobin is 8.8 g/dL, serum creatinine is 3.0 g/dL, and serum calcium is 10.8 g/dL. Urine dipstick is negative for protein, but quantitative measurement reveals elevated 24-hour urinary protein excretion. Urine electrophoresis is most likely to detect which of the following? A. Gamma heavy chains (%) B. Immunoglobulin A (%) C. Immunoglobulin G (%) D. Immunoglobulin M (%) E. Lambda light chains (%)

E. Lambda light chains (%) Multiple myeloma (MM) is a lymphoproliferative malignancy characterized by monoclonal plasma cell proliferation and production of monoclonal paraproteins (eg, immunoglobulins, chain fragments). MM should be suspected in elderly patients who have any combination of osteolytic lesions, hypercalcemia, anemia, or acute kidney injury (such as this patient). Other common symptoms include weight loss, constipation (due to hypercalcemia), fatigue, and recurrent infection. Kidney disease in MM is largely due to light chain cast nephropathy (myeloma kidney). Intact immunoglobulins (eg, IgA, IgG, IgM) are too large to pass through the glomerulus, but a small amount of free light chains (eg, kappa, lambda) are freely filtered and resorbed in the proximal tubules. However in MM, the excessive quantities of free light chains exceed the resorptive capacity of the kidney. The filtered light chains then combine with Tamm-Horsfall proteins to form obstructive casts that cause tubular rupture and kidney injury. Monoclonal paraproteins are not detected by urine dipstick (which detects only albumin), but quantitative protein concentrations (spot or 24-hour turbidimetric assay) will be elevated. Urine protein electrophoresis, immunofixation, or free light chain immunoassays can be used for diagnosis.

A 84-year-old woman is sent to the hospital from a nursing home due to 3 days of fever, abdominal pain, and progressive lethargy. The patient has a history of recurrent hospitalizations with multiple antibiotic courses for urinary tract infection, infected decubitus ulcer, and pneumonia. Her temperature is 38.2 C (101 F), blood pressure is 100/60 mm Hg, and pulse is 110/min. She has mild suprapubic and right costovertebral angle tenderness. Urine and blood cultures are obtained, and the patient is started on intravenous fluids and empiric ceftriaxone. Her urine culture shows extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli. Which of the following features is most likely to be found in this organism? A. DNA gyrase with altered A subunit (%) B. Outer membrane with novel porin structure (%) C. Penicillin-binding protein with reduced antibiotic affinity (%) D. Peptidoglycan cell wall with amino acid modification (%) E. Plasmid with drug resistance gene (%) F. Ribosome with methylated 16S rRNA (%)

E. Plasmid with drug resistance gene (%) This patient has a urinary tract infection caused by an extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli. ESBL enzymes can inactivate extended-spectrum penicillins and cephalosporins (including third- and fourth-generation cephalosporins) and monobactams (aztreonam). Genes encoding these enzymes are often located on plasmids and therefore can be transferred between organisms and between different species through conjugation. Some have been incorporated into bacterial chromosomes. Carbapenems (eg, imipenem) are the treatment of choice for ESBL-producing organisms (although unfortunately, organisms with carbapenem resistance have emerged).

A 17-year-old boy is referred to a clinic for ongoing muscle weakness. He has noticed difficulty climbing stairs at home over the last several months, and he recently stopped playing basketball due to difficulty lifting the ball over his head. The patient takes no medications and does not know of any family members with muscle weakness. On neurologic examination, he is unable to lift his arms or legs against resistance when fully outstretched. He undergoes a muscle biopsy to evaluate the cause of his proximal muscle weakness. Electron microscopy of the specimen reveals sparse transverse tubules in some of the muscle fibers. Which of the following is the most likely consequence of this patient's biopsy findings? A. Decremental force generation on repeated muscle stimulation (%) B. Impaired ATP production during active muscle contraction (%) C. Impaired relaxation after sustained muscle contraction (%) D. No contraction of the myocyte in response to increased intracellular Ca2+ (%) E. Uncoordinated contraction of myofibrils within affected muscle fibers (%)

E. Uncoordinated contraction of myofibrils within affected muscle fibers (%) Transverse tubules (T-tubules) are invaginations of the muscle cell membrane (sarcolemma) located in close proximity to the terminal cisterns of the sarcoplasmic reticulum. They are found in striated (eg, cardiac, skeletal) muscle and contain voltage-gated L-type calcium channels (dihydropyridine receptors) adjacent to the ryanodine receptors on the terminal cisterns. During muscle contraction, T-tubules allow the depolarization impulse to rapidly propagate through the interior of the muscle fiber. This ensures that calcium release from the sarcoplasmic reticulum occurs uniformly throughout the fiber, allowing for synchronized contraction of myofibrils in each muscle cell. This patient most likely has a form of limb girdle muscular dystrophy due to a mutated sarcolemma protein (eg, caveolin) affecting excitation-contraction coupling. Decreased numbers of functional T-tubules in affected muscle fibers lead to uncoordinated contraction of myofibrils, which manifests as muscle weakness.

ATN timeline

This patient has ischemic acute tubular necrosis (ATN) as a result of hypotension from hemorrhage. The clinical course of ATN may be divided into the initiation, maintenance (oliguric), and recovery phases. The initiation phase corresponds with the original ischemic or toxic insult and lasts approximately 24-36 hours. During this phase, only a slight decrease in urine output is present as renal tubular cell damage begins. During the maintenance phase, tubular damage is fully established, resulting in oliguria, fluid overload, and electrolyte abnormalities (eg, hyperkalemia, metabolic acidosis). This phase usually lasts 1-2 weeks, during which the glomerular filtration rate remains well below normal with a corresponding rise in serum creatinine. Light microscopy shows tubular epithelial necrosis, sloughing of cells with denuded basement membranes, and casts containing degenerating cells and debris. The recovery phase is characterized by the re-epithelization of tubules. The glomerular filtration rate recovers relatively quickly as the tubules clear of casts and debris. However, the tubular cells recover more gradually, resulting in transient polyuria and loss of electrolytes due to impaired tubular resorption and decreased renal concentrating ability. The majority of patients eventually have complete restoration of renal function.

adjustment disorder

an emotional disturbance caused by ongoing stressors within the range of common experience a disorder in which a person's response to a common stressor is maladaptive and occurs within 3 months of the stressor

In addition, there is a characteristic "scooped-out" expiratory pattern consistent with the reduced expiratory flow rates seen in

obstructive lung disease. This hyperinflation and expiratory airflow obstruction occur in chronic obstructive pulmonary disease (COPD)

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

quadriceps!

Cancers of the pelvis, including the prostate, spread to the lumbosacral spine via the

vertebral venous plexus (VVP). The VVP communicates with a number of venous networks, including the prostatic venous plexus, which receives the venous supply from the prostate, penis, and bladde