var killers_step1 = new Array( //1 "A newborn presents with severe acidosis, vomiting, hypotonia, and neurologic deficits. Serum analysis reveals elevated levels of lactate and alanine. These observations suggest a deficiency in which of the following enzymes?$$Alanine aminotransferase%%Glutamate dehydrogenase^^Lactate dehydrogenase&&Pyruvate carboxylase##Pyruvate dehydrogenase", //2 "A group of patients with lung cancer is matched to a group of patients without lung cancer. Their smoking habits over the course of their lives is compared. Based on this information, researchers compute the rate of lung cancer in patients who smoke versus those who never smoked. This is an example of $$case-control study%%cohort study^^cross-sectional study&&longitudinal study##randomized control study", //3 "
A pharmacologist is examining a new drug with potential sedative properties. He begins by analyzing the pharmacokinetic properties of the drug. Studies of the drug\'s rate of elimination yield the above data. Which of the following drugs has similar kinetics to the drug being studied?$$Carbamazepine%%Cimetidine^^Ethanol&&Ketoconazole##Phenobarbital", //4 "A 46-year-old woman presents to her doctor complaining of weakness and fatigue. On physical examination, her physician notices a 10-pound weight gain since her last visit 6 months ago. Her blood pressure is 160/100 mmHg. Blood tests reveal serum Na+ 155 mEq/L, K+ 2.8 mEq/L, and a decreased serum renin. Which of the following is the most likely diagnosis?$$Cushing\'s syndrome%%Diabetes mellitus^^Pheochromocytoma&&Primary aldosteronism##Secondary aldosteronism", //5 "A 38-year-old woman complains of cold, painful fingertips, as well as difficulty swallowing and indigestion. Physical examination is remarkable for a thickened, shiny epidermis over the entire body, with restriction of movement of the extremities, particularly the fingers, which appear claw-like. Which of the following autoantibodies is likely to be found in this patient\'s serum?$$Anti-DNA topoisomerase I (anti-Scl-70)%%Anti-double-stranded DNA (ds DNA)^^Anti-IgG&&Anti-Sm##Anti-SS-A", //6 "A 26-year-old woman and her 29-year-old husband have been trying to have a child for the last 3 years. During this time the woman has had 5 spontaneous abortions. The karyotypes of the mother, father, and the most recently aborted fetus all contained 46 chromosomes, and all pairs were normal except for the pairs shown below.



The event that led to the child\'s abnormal karyotype was:$$adjacent I segregation%%adjacent II segregation^^alternate segregation&&a recombination event within a paracentric inversion##a recombination event within a pericentric inversion", //7 "A 70-year-old woman undergoes a gastrectomy for Zollinger-Ellison syndrome. Her doctor informs her that she will need to take intramuscular vitamin B12 shots for the rest of her life. Absence of which of the following cell types is responsible for this vitamin replacement requirement?$$Chief cells%%G cells^^Goblet cells&&Mucous neck cells##Parietal cells", //8 "A patient presents with right lower quadrant pain, fever, and diarrhea. Physical examination reveals diffuse abdominal tenderness; laboratory examination reveals a moderate leukocytosis, leading to a presumptive diagnosis of acute appendicitis. Surgical exploration of the abdomen reveals mesenteric adenitis, but the appendix is normal. Which of the following organisms is most likely responsible for these signs and symptoms?$$Clostridium difficile%%Enterohemorrhagic E. coli^^Enteroinvasive E. coli&&Enteropathogenic E. coli##Yersinia enterocolitica", //9 "
Mean arterial blood pressure (MAP) and heart rate (HR) measurements were recorded during the intravenous administration of two different drugs. Select the most likely drugs given at the indicated points.$$ X, Acetylcholine Y,phentolamine%%X, epinephrine Y,hexamethonium^^X, isoproterenol Y, propranolol&&X, metaproterenol Y, propranolol##X, norepinephrine Y, hexamethonium", //10 "A 21-year-old man is competing in a weight-lifting competition. He lifts 325 lbs over his head and holds it there for 5 seconds. Suddenly, his arms give way and he drops the weights to the floor. Which of the following receptors is responsible for this sudden muscle relaxation?$$Free nerve ending%%Golgi tendon organ^^Merkel\'s disk&&Muscle spindle##Pacinian corpuscle", //11 "A normal volunteer consents to an intravenous infusion of p-aminohippuric acid (PAH). After a short time, the plasma PAH is 0.02 mg/ml, the concentration of PAH in urine is 13 mg/ml and the urine flow is 1.0 ml/min. What is the effective renal plasma flow?$$0.26 ml/min%%26 ml/min^^65 ml/min&&260 ml/min##650 ml/min", //12 "A 4-day-old male is brought to the pediatric clinic because of breathing difficulties and poor feeding. He coughs, chokes, and spits up milk very soon after beginning to suckle. Physical exam and radiographs reveal the presence of the most common type of tracheoesophageal fistula. The baby\'s defect likely resulted from:$$failure of the buccopharyngeal membrane to rupture%%failure of the tracheoesophageal ridges to fuse^^incomplete formation of the septum secundum&&incomplete recanalization of the larynx##patent thyroglossal duct", //13 "A 4-month-old blue-eyed, fair-skinned child who appeared normal at birth is brought to the pediatrician because of the development of scaly skin lesions and seizures. On physical examination, the infant appears to be mentally retarded, and a musty odor is noted. Which of the following defects is responsible for this child\'s illness?$$Deficiency of alpha-ketoacid decarboxylase%%Deficiency of hexosaminidase A^^Deficiency of homogentisate oxidase&&Deficiency of hypoxanthine-guanine phosphoribosyltransferase##Deficiency of phenylalanine hydroxylase", //14 "
A 31-year-old stockbroker drives to a high-altitude mountain resort to do some rock-climbing. Later that day, he experiences headache, fatigue, dizziness, and nausea. Which point on the graph above best corresponds to the relationship between plasma bicarbonate, pH, and PCO2 in this patient?$$Point A%%Point B^^Point C&&Point D##Point E", //15 "A 13-year-old male presents to the emergency room with a deep skin abrasion on his knee. He states that it has not stopped bleeding since it happened during recess approximately 20-30 minutes ago. Physical examination reveals a well-developed, well-nourished adolescent. There are multiple purpura over his legs and arms, and a few scattered petechiae on his chest and gums. His bleeding time is 22 minutes, platelets = 300,000/mm3, hemoglobin = 11g/dL. A trial of cryoprecipitate transfusion does not improve his bleeding time. A normal platelet transfusion does improve bleeding time. Which of the following is the correct diagnosis?$$Bernard-Soulier syndrome%%Henoch-Schönlein purpura^^Idiopathic thrombocytopenic purpura&&Thrombotic thrombocytopenic purpura##Von Willebrand\'s disease", //16 "An 88-year-old male complaining of abdominal pain enters the emergency room with his wife. A mini-mental status exam reveals pronounced forgetfulness and confusion. The patient is discovered to have acute appendicitis requiring immediate surgery. He is unable to understand the situation and cannot provide informed consent. Which of the following further actions must the physician take?$$Do not perform surgery%%Have another doctor confirm the necessity of surgery^^Obtain a court order to perform surgery&&Obtain consent from his wife to perform surgery##Try to persuade the patient to consent to surgery", //17 "A 42-year-old obese woman experiences episodic abdominal pain. She notes that the pain increases after the ingestion of a fatty meal. The action of which of the following hormones is responsible for the postprandial intensification of her symptoms?$$Cholecystokinin%%Gastrin^^Pepsin&&Secretin##Somatostatin", //18 "Which of the pharyngeal pouches develops into the palatine tonsil?$$First%%Second^^Third&&Fourth##Fifth", //19 "A worried mother complains to her pediatrician that both she and her 6-year-old son\'s teacher have noticed that the child has become inattentive. She states that her son frequently stops what he is doing and \"stares blankly into space\" before resuming his activities. Electroencephalography reveals a 3/second spike and slow wave pattern of discharges. Which of the following agents would most effectively treat this child\'s disorder?$$Carbamazepine%%Diazepam^^Ethosuximide&&Methylphenidate##Phenytoin", //20 "
In the family shown above, individuals affected with profound deafness are represented by a shaded symbol. The phenotypes of individuals in the fourth generation can best be explained by: $$autosomal dominant inheritance%%locus heterogeneity^^mitochondrial inheritance&&multifactorial inheritance##X-linked dominant inheritance", //21 "
At which point on the diagram above would the length of the myocardial sarcomere be approximately 2 mm with maximal actin-myosin cross bridging?$$A%%B^^C&&D##E", //22 "Absence of which of the following enzymes would impair the rate-limiting step of glycogenolysis?$$alpha-1,4-glucan transferase%%Glycogen phosphorylase^^Glycogen synthase&&Phosphoglucomutase##UDP-glucose pyrophosphorylase", //23 "A 34-year-old female is brought to her family physician by her brother. He states that the patient\'s husband had run away with another woman the previous day. After discovering this, the patient arrived at her brother\'s home in a \"dazed state,\" was unable to function appropriately the remainder of the evening, and slept fitfully all night. Early in the morning she began to talk to people who were not present, and debated whether or not to kill her children and herself. He denies anything like this ever happening before. Which of the following is the most likely diagnosis?$$Bipolar disorder%%Brief psychotic disorder^^Schizoaffective disorder&&Schizophrenic disorder##Schizophreniform disorder", //24 "A 34-year-old woman presents with abdominal pain and reports changes in her bowel habits. On pelvic examination a mass is palpated on her right ovary. Laparoscopic surgery is performed and the mass is removed. The gross appearance of the tumor is shown below. What type of tumor is it?



$$Choriocarcinoma%%Dysgerminoma^^Fibroma&&Granulosa-theca cell##Teratoma", //25 "A 55-year-old woman is receiving chemotherapy for non-Hodgkin\'s lymphoma. Several days after a treatment, she notes that she has blood in her urine. Which of the following antineoplastic drugs is most likely responsible for this side effect?$$Bleomycin%%Cisplatin^^Cyclophosphamide&&Doxorubicin##Plicamycin" ); var answers_step1 = new Array('E','A','C','D','A','B','E','E','E','B','E', 'B', 'E', 'B', 'A', 'D', 'A', 'B', 'C', 'B', 'B', 'B', 'B', 'E', 'C'); var description_step1 = new Array( //1 "The correct answer is E. Pyruvate dehydrogenase (PDH) catalyzes the irreversible conversion of pyruvate to acetyl-CoA. If PDH is absent, pyruvate will be used in other pathways instead. Pyruvate will be converted to alanine via alanine aminotransferase (choice A) and to lactate via lactate dehydrogenase (choice C).

Glutamate dehydrogenase (choice B) is involved in oxidative deamination, releasing ammonium ion for urea synthesis. Deficiency of this enzyme would not cause the symptoms described.

Pyruvate carboxylase (choice D) is a gluconeogenic enzyme that catalyzes the conversion of pyruvate to oxaloacetate. Deficiency of this enzyme would not cause the symptoms described.", //2 "The correct answer is A. Case-control studies are retrospective and are as described in the question stem. Case-control studies allow researchers to compute an odds ratio.

In cohort studies (choice B), subjects are assembled on the basis of some common experience (such as attending medical school) and are then monitored for a specified amount of time at regular intervals (e.g., taking USMLE Steps 1, 2, and 3; see also longitudinal studies below) until they develop the outcome of interest (they become practicing physicians) or the follow-up time ends. The cohort study minimizes many of the biases evident in case-control designs and is the definitive observational clinical study. Cohort studies allow researchers to compute a relative risk.

Cross-sectional studies (choice C) usually have more modest goals than those of case-control and cohort studies. A variable or group of variables is measured in a sample of a larger population to get an idea of the distribution and interrelationships of those variables in that population.

Longitudinal studies (choice D) identify individual subjects and follow them over a given period of time. For example, the study of cholesterol-lowering drugs on cardiovascular events requires that the same subject is observed over a significant period of time (e.g., 10 years).

A randomized controlled trial (choice E) is considered the most rigorous and powerful approach to answering a clinical question in which two treatments, strategies, or therapies are compared or when one therapy is compared to placebo. In this type of study, subjects are assigned treatments on a randomized basis.", //3 "The correct answer is C. The graph presented is classic for zero-order elimination; the graph is a straight line using standard graphical coordinates. Note that the plasma concentration of the drug diminishes linearly with time. Zero-order elimination means that the rate of elimination is constant and is independent of the drug plasma concentration. Another way of saying this is that a constant amount of drug is cleared per unit time. There are very few drugs that exhibit zero-order elimination; examples include alcohol, phenytoin and aspirin (at high concentrations).

The vast majority of drugs exhibit first-order elimination kinetics. First-order elimination means that a constant fraction of the drug is cleared per unit time. Thus, elimination is proportional to the drug plasma concentration. This can be graphically depicted in several different ways. Using standard graphical coordinates, an exponential decrease in the concentration of the drug is seen. If a semi-logarithmic scale is used, the graph will appear as a straight line, similar to the graph in this question.", //4 "The correct answer is D. Primary aldosteronism (Conn\'s syndrome) is a condition of hyperaldosteronism originating in the adrenal gland. The causes include an aldosterone-secreting adrenocortical adenoma, hyperplasia of the zona glomerulosa, and very rarely, an adrenal carcinoma. It is characterized by hypertension secondary to sodium retention, hypokalemia, and a decreased serum renin due to a negative feedback of increased blood pressure on renin secretion.

Cushing\'s syndrome (choice A) is the result of increased glucocorticoid production, particularly cortisol. Physical signs typically include \"moon facies,\" truncal obesity, \"buffalo hump,\" and purple abdominal striae.

Diabetes mellitus (choice B) is a condition of inadequate insulin production that presents with hyperglycemia and ketoacidosis.

Pheochromocytoma (choice C) is a rare tumor of chromaffin cells occurring most commonly in the adrenal medulla. The tumor secretes epinephrine and norepinephrine, resulting in secondary hypertension.

Secondary aldosteronism (choice E) results from an activation of the renin-angiotensin system caused by renal ischemia, edema, and renal tumors. In contrast to primary aldosteronism, secondary aldosteronism is associated with increased serum renin.", //5 "The correct answer is A. This patient is suffering from systemic sclerosis, also called scleroderma. Antibodies to topoisomerase I (anti-Scl-70) occur in up to 70% of patients with diffuse systemic sclerosis, but only rarely in other disorders. Systemic sclerosis is characterized initially by excessive fibrosis and edema of the skin, especially the hands and fingers, producing sclerodactyly (characteristic changes in the fingers, which resemble claws). Raynaud\'s phenomenon is common. The diffuse type of systemic sclerosis generally spreads to include visceral organs such as the esophagus (producing dysphagia), the lungs (producing pulmonary fibrosis), the heart (leading to heart failure or arrhythmia), and the kidneys (renal failure causes 50% of scleroderma deaths). Females are affected more than males (3:1 ratio). A more restricted variant of systemic sclerosis with a somewhat more benign course is CREST syndrome (Calcinosis, Raynaud\'s syndrome, Esophageal dysmotility, Sclerodactyly, and Telangiectasia), characterized by the presence of anti-centromere antibodies (although 10% of CREST patients will have anti-topoisomerase antibody as well).

Anti-ds DNA (choice B) is characteristic of systemic lupus erythematosus, but is not common in patients with systemic sclerosis.

Rheumatoid factor is an autoantibody directed against IgG (choice C). It is found in patients with rheumatoid arthritis.

Anti-Sm (Smith antigen; choice D) is also characteristic of SLE rather than systemic sclerosis.

Anti-SS-A (choice E) is typically seen in Sjögren\'s syndrome (although it may also be seen in SLE).", //6 "The correct answer is B. The couple is experiencing infertility and a high rate of spontaneous abortions because the father has a reciprocal translocation between chromosome 7 and chromosome 12. His karyotype is 46, XY, t(7;12) (12qter ® 12q23::7p13 ® 7qter; 12pter ® 12q23::7p13 ® 7pter). During meiosis I, the four chromosomes involved in the translocation will pair together in a structure called a quadrivalent, which is pictured below.



There are three ways that the quadrivalent can separate during meiosis I. They are called adjacent I, adjacent II, and alternate segregation. Adjacent II segregation occurs only when the breakpoint of the translocation is so close to the centromere of a chromosome that the cell cannot distinguish between the centromeres. In this specific case, the fetus received a normal chromosome 7 and a normal chromosome 12 from his mother. From his father, the fetus received a normal chromosome 7 and a chromosome composed of 12qter ® 12q23::7p13 ® 7qter. This gives the fetus a total of three copies of the material from 7p13 ® 7qter, and only one copy of material from 12pter ® 12q23. Note that the zygote has three copies of the centromere of chromosome 7, the hallmark of adjacent II segregation. Since the zygote is unbalanced, it aborts.

Adjacent I segregation (choice A) produces cells that contain different centromeres, but have duplication and deletions that lead to spontaneous abortion. In this case, the products of adjacent I segregation would be 12qter ® 12q23::7p13 ® 7qter and the normal chromosome 12, or 12pter ® 12q23::7p13 ® 7pter and the normal chromosome 7.

Alternate segregation (choice C) yields the only outcomes that produce viable progeny. Two products are produced. One contains a normal chromosome 7 and a normal chromosome 12, and the second product contains the balanced translocation. This cell has all the information it needs; it is just arranged in a unique order. In this case, 12qter®12q23::7p13®7qter and 12pter®12q23::7p13®7pter.

A recombination event within a paracentric inversion (choice D) leads to the formation of an acentric fragment and a dicentric bridge. This cell will not complete meiosis.

A recombination event within a pericentric inversion (choice E) leads to chromatids that are duplicated for material on one of the arms and deleted for material on the other arm.", //7 "The correct answer is E. The parietal cells of the stomach produce intrinsic factor, a glycoprotein that binds vitamin B12 in the lumen of the stomach and facilitates its absorption in the terminal ileum. Patients without a stomach and those with pernicious anemia (autoimmune destruction of parietal cells) will require B12 replacement therapy. Recall that B12 deficiency will lead to megaloblastic anemia and the USMLE-favorite picture of a blood smear with hypersegmented neutrophils. Note that parietal cells also synthesize and secrete HCl.

Chief cells (choice A) are responsible for secreting pepsinogen, the precursor to pepsin.

G cells (choice B) are gastrin-secreting cells. Gastrin stimulates secretion of acid by the parietal cells found in the body and fundus of the stomach. Zollinger-Ellison syndrome is caused by a pancreatic or duodenal tumor that secretes gastrin (a gastrinoma). It is characterized by the development of severe peptic ulcer disease.

Goblet cells (choice C) are part of the mucosa of the small intestine, not the stomach. They produce glycoproteins (mucins) that protect and lubricate the lining of the intestine.

Mucous neck cells (choice D) are mucus-secreting cells located in the necks of the gastric glands.", //8 "The correct answer is E. Many patients with Yersinia enterocolitica infection present with symptoms suggesting appendicitis (although constipation, rather than diarrhea, is common in appendicitis). Surgical exploration of the abdomen reveals mesenteric adenitis (involvement of the lymph nodes located in the mesentery), along with a normal appendix. Mesenteric adenitis is the tip-off that the patient has a Yersinia enterocolitica infection, and culture of the involved lymph nodes or of the stool are generally diagnostic.Following antibiotic use (e.g., clindamycin, ampicillin, or a third-generation cephalosporin), Clostridium difficile (choice A) may cause bloody diarrhea due to pseudomembranous colitis.

Enterohemorrhagic Escherichia coli (choice B) is the causative organism to suspect in a patient who develops severe, hemorrhagic, traveler\'s diarrhea with bleeding manifestations, hematuria, oliguria, and a microangiopathic hemolytic anemia. This bacteria produces verocytotoxin, which is responsible for the symptoms.

Enteroinvasive E. coli (EIEC; choice C), causes fever, pain, diarrhea, and dysentery, usually following ingestion of contaminated cheese or water.

Enteropathogenic E. coli (EPEC; choice D), causes a watery diarrhea in infants and toddlers secondary to ingestion of contaminated food or water.

Enterotoxigenic E. coli (ETEC; choice E) causes traveler\'s diarrhea, a watery diarrhea due to ingestion of contaminated food or water. (Mnemonic: Traveler\'s diarrhea = ETEC = Toxigenic E. coli).", //9 "The correct answer is E. There are several strategies that are useful in solving drug tracing problems. First, always look at blood pressure first and heart rate second. Blood pressure changes will be the direct result of the administered drug; heart rate changes may be a direct effect or they may result from a baroreceptor reflex. Second, assume that when an agonist effect is gone, so is the agonist; however, assume that an antagonist stays on board for the entire trace. Third, begin by eliminating as many options as possible by examining the initial agonist effect.

The only two agonists that would be expected to raise blood pressure to this degree are norepinephrine (alpha-1, alpha-2, and beta-1 agonist) and phenylephrine (alpha-1 agonist). Thus, choices A, B, C, and D can be eliminated immediately.

Drug Y lowers blood pressure and raises heart rate. Hexamethonium (ganglionic blocker) would lower blood pressure and increase heart rate by blocking the predominant tone of the arterioles (sympathetic) and the heart (parasympathetic). Phentolamine (alpha antagonist) would lower blood pressure by blocking arteriolar alpha-1 receptors. The increase in heart rate would be a baroreceptor reflex.

The second administration of Drug X causes an increase in both blood pressure and heart rate. Only the combination of norepinephrine (NE) and hexamethonium could do this. NE would still increase blood pressure by stimulating end organ receptors; however, the baroreceptor reflex would be blocked by hexamethonium. NE\\'s ability to increase heart rate by stimulating cardiac beta-1 receptors is now revealed.

(Choice A) Acetylcholine would cause a decrease in blood pressure by stimulating non-innervated muscarinic receptors present on arterioles. Heart rate would increase because of a baroreceptor reflex. Phentolamine would cause a decrease in blood pressure and an increase in heart rate (baroreceptor reflex). It should have no effect on a subsequent ACh administration.

(Choice B) Epinephrine would cause a small increase in mean blood pressure, but not enough to elicit a baroreceptor reflex. So, an increase in heart rate would be seen as a result of beta-1 stimulation of the heart. Hexamethonium would cause a decrease in blood pressure and an increase in heart rate. Hexamethonium should not affect a subsequent epinephrine administration because a baroreceptor reflex was not initially produced.

(Choice C) Isoproterenol (beta-1 and beta-2 agonist) would cause a decrease in blood pressure (by stimulating arteriolar beta-2 receptors) and an increase in heart rate (a combination of cardiac beta-1 receptor stimulation and baroreceptor reflex). Propranolol (beta-1 and beta-2 antagonist) would decrease blood pressure and heart rate. It would completely block a subsequent administration of isoproterenol.

(Choice D) Metaproterenol (beta-2 agonist) would decrease blood pressure (by stimulating arteriolar beta-2 receptors) and increase heart rate (baroreceptor reflex). Propranolol (beta-1 and beta-2 antagonist) would decrease blood pressure and heart rate. It would completely block a subsequent administration of metaproterenol.

(Choice F) Phenylephrine would increase blood pressure and decrease heart rate (baroreceptor reflex). Phentolamine would decrease blood pressure and increase heart rate (baroreceptor reflex). Phentolamine would completely block a subsequent administration of phenylephrine.", //10 "The correct answer is B. Normally, stretching of muscle results in a reflex contraction: the harder the stretch, the stronger the contraction. At a certain point, when the tension becomes too great, the contracting muscle suddenly relaxes. The reflex that underlies this sudden muscle relaxation is called the Golgi tendon organ reflex, also known as the inverse stretch reflex or autogenic inhibition. The Golgi tendon organ (GTO) is an extensive arborization of nerve endings (encapsulated by a connective tissue sheath and located near the muscle attachment) that is connected in series with the extrafusal skeletal muscle fibers. As a result, GTOs respond to muscle tension rather than muscle length. Increased tension leads to stimulation of Ib afferents, which inhibit the homonymous muscle via spinal interneurons.

Free nerve endings (choice A) are unmyelinated, unencapsulated nerve endings that penetrate the epidermis. These types of receptors respond to pain and temperature.

Merkel\'s disks (choice C) are comprised of specialized tactile epidermal cells and their associated nerve endings. They are located in the basal layer of the epithelium and are slowly adapting receptors that respond to touch and pressure.

Muscle spindles (choice D) are spindle-shaped bundles of muscle fibers (intrafusal fibers) that are encapsulated by connective tissue. Muscle spindles are arranged in parallel with extrafusal skeletal muscle fibers, so they sense the length of the muscle. They are innervated by Group Ia and II sensory afferent neurons.

Pacinian corpuscles (choice E) are unmyelinated nerve endings surrounded by thin, concentric layers of epithelioid fibroblasts. In transverse section, this receptor resembles a sliced onion. They are found primarily in the deep layer of the dermis, loose connective tissue, male and female genitalia, mesentery, and visceral ligaments. They are rapidly adapting receptors that respond to touch and pressure.", //11 "The correct answer is E. Approximately 90% of a small dose of PAH is cleared by the kidney in a single pass. If it were 100%, then the amount of PAH in urine (concentration ´ urine flow rate) divided by the amount of PAH in plasma would exactly equal the renal plasma flow. Because the extraction ratio (arterial-venous PAH concentration divided by arterial concentration) is 0.9 (90%) instead of 100%, physiologists speak of the quantity UPAHV/PPAH as the effective renal plasma flow (ERPF). So, in this patient, we have (13 mg/ml ´ 1.0 ml/min)/0.02 mg/ml = 650 ml/min.

0.26 ml/min (choice A) can be obtained by multiplying 13 by 0.02 and dividing by 1. This value is far too low to be a normal ERPF, which is typically around 625 ml/min.

26 ml/min (choice B) is 100 times (13 ´ 0.02)/1. This value is far too low to be a normal ERPF, which is typically around 625 ml/min.

65 ml/min (choice C) might indicate that you set the ratio up correctly, but dropped a power of 10 in your calculations. This value is far too low to be a normal ERPF, which is typically around 625 ml/min.

260 ml/min (choice D) is 1000 times (13 ´ 0.02)/1, and is still too low to be a normal ERPF.

Timesaving note: If you remembered that the ERPF is approximately 625 ml/min, you do not really need to calculate anything in this question. Choice E is the only reasonable answer.", //12 "The correct answer is B. The tracheoesophageal ridges are two longitudinal ridges that separate the respiratory diverticulum from the foregut. Eventually, they fuse to form a septum separating the esophagus (dorsal) from the trachea (ventral) and lung buds, maintaining a communication only rostrally at the pharynx. Incomplete formation of the tracheoesophageal septum (by fusion of ridges) results in the most common type of tracheoesophageal fistula, whereby the proximal part of the esophagus ends as a blind sac (esophageal atresia), while the distal part is connected to the trachea by a narrow canal just above the bifurcation. This defect occurs in approximately 1 of every 2500 births.

The buccopharyngeal membrane is a bilaminar membrane (ectoderm externally, endoderm internally) separating the stomodeum (mouth) from the pharynx. The membrane ruptures at about 4 weeks. The buccopharyngeal membrane is not involved in formation of the esophagus and trachea and so failure to rupture (choice A) would not lead to tracheoesophageal fistula.

The septum secundum is a membrane that forms on the right side of the developing interatrial wall of the heart. It is not associated with formation of the esophagus and trachea and so failure to close would not lead to tracheoesophageal fistula. Failure of formation of the septum secundum (choice C) leads to a patent foramen ovale, a relatively common atrial septal defect.

Incomplete recanalization of the larynx (choice D) is relatively rare and results in a membrane (laryngeal web) that may partially obstruct the airway. Though there may be difficulty breathing, there should be little problem with swallowing and keeping milk down.

The thyroid gland forms from a primordium associated with development of the tongue that eventually descends into the neck. For a short time, it remains connected to the tongue by a narrow canal called the thyroglossal duct. The duct normally closes, but occasionally, it remains patent (choice E) or develops cysts, which are usually asymptomatic unless they become infected. They do not interfere with breathing or feeding and do not involve the trachea or esophagus.", //13 "The correct answer is E. Phenylketonuria occurs in approximately 1:10000 births. Seemingly normal at birth, these infants later develop seizures, eczematous lesions, and mental retardation. The musty odor is extremely characteristic; if a child is described on the USMLE as smelling musty or having musty-smelling urine, he/she will almost certainly have PKU. PKU results from a defect in phenylalanine hydroxylase, the enzyme responsible for converting phenylalanine to tyrosine. Without this enzyme, phenylalanine is converted to phenylpyruvate, a phenylketone that spills into the urine. (If you did not recall the exact enzyme deficiency, a clue might be to note that the prefix \"phenyl\" in choice E is the same as in phenylketonuria.) Phenylalanine accumulation and its consequences lead to brain damage and mental retardation. The primary treatment for PKU is a diet low in phenylalanine (note that patients with PKU must avoid products with aspartame/Nutrasweet®, as it contains Phe).

Deficiency of alpha-keto acid decarboxylase (choice A), an enzyme involved in the catabolism of branched-chain amino acids (isoleucine, leucine, valine), results in maple syrup urine disease. Without this decarboxylase, the alpha-keto acids spill into the urine, giving it a characterisitc sweet smell.

Hexosaminidase A deficiency (choice B) results in Tay-Sachs disease. Cerebral accumulation of gangliosides results in mental retardation. Cherry red spots on retinal examination are characteristic.

Deficiency of homogentisate oxidase (choice C), an enzyme involved in tyrosine metabolism, results in alkaptonuria. In this disease, there is an accumulation of homogentisate derivatives that polymerize into melanin-like pigments. Classically, these patients will have brownish connective tissue and their urine will turn dark upon standing.

Near total deficiency of hypoxanthine-guanine phosphoribosyltransferase (choice D), an enzyme involved in the purine salvage pathway, results in Lesch-Nyhan syndrome. This syndrome is characterized by impaired purine salvage and increased de novo purine synthesis and catabolism, leading to hyperuricemia. Children with Lesch-Nyhan syndrome are mentally retarded and classically exhibit self-mutilating behavior.", //14 "The correct answer is B. Acute mountain sickness is caused by hypoxemia and alkalosis due to exposure to high altitude. Hyperventilation occurs in response to the hypoxemia, which helps bring the oxygen saturation back toward normal, but \"blows off\" excessive amounts of CO2, producing acute respiratory alkalosis.

(Choice A) is respiratory acidosis with renal compensation or metabolic alkalosis with respiratory compensation.

(Choice C) is uncompensated respiratory acidosis.

(Choice D) is either metabolic acidosis with respiratory compensation or respiratory alkalosis with renal compensation.

(Choice E) represents normal values.

(Choice F) represents metabolic acidosis.

(Choice G) represents metabolic alkalosis.

(Choice H) represents partially compensated chronic respiratory acidosis.", //15 "The correct answer is A. Bernard-Soulier syndrome is an autosomal recessive disease of platelet adhesion which causes prolonged bleeding times in the presence of normal platelet counts. These patients\' platelets cannot bind to subendothelial collagen properly because of a deficiency or dysfunction of the glycoprotein Ib-IX complex. Clinically the patients have impaired hemostasis and recurrent severe mucosal hemorrhage. The only treatment for an acute episode is a transfusion of normal platelets. This patient has a slightly decreased hemoglobin due to blood loss.

Henoch- Schönlein purpura (choice B) is a self-limited autoimmune vasculitis that affects children and young adults, usually following an upper respiratory infection. Affected individuals develop purpuric rashes on the extensor surfaces of their arms, legs, and buttocks. They also have abdominal pain and hematuria from glomerulonephritis. Despite the tendency toward hemorrhage, the bleeding times and platelet count would be normal.

Idiopathic thrombocytopenic purpura (choice C) causes an increase in the bleeding time, but as the name implies, platelet counts are decreased.. There is bleeding from small vessels, especially of the skin, gastrointestinal tract and genitourinary tract. Purpura and petechiae frequently develop. It is considered a self-limited autoimmune disorder, typically affecting children after a recent viral infection.

Thrombotic thrombocytopenic purpura (choice D) is characterized by an increased bleeding time, but a decreased platelet count. It is a rare disorder of unknown etiology, thought to be initiated by endothelial injury, which releases certain procoagulant materials into the circulation, causing platelet aggregation. It causes purpura, fever, renal failure, microangiopathic hemolytic anemia and microthrombi, generally in young women. In this disorder, platelet transfusion is actually contraindicated, as it can precipitate thrombosis.

Von Willebrand\'s disease (choice E) causes increased bleeding times with normal platelet counts. It is the most common inherited bleeding disorder, caused by a defect in von Willebrand factor, which aids the binding of platelets to collagen. Even though the platelets themselves are normal, binding is impaired, thus a platelet transfusion would not correct the problem. Cryoprecipitate, a plasma fraction rich in von Willebrand factor, would help in the case of von Willebrand\'s disease, but would not help with Bernard-Soulier syndrome.", //16 "The correct answer is D. In cases in which an emergency exists, the patient is incompetent to give consent, and the withholding of treatment would be potentially life-threatening, the physician must seek out close relatives of the patient to supply consent. The physician should proceed with treatment, assuming the patient would want the treatment had he or she understood the situation.

Not performing surgery (choice A) could cost the patient\'s life.

Having another doctor confirm the necessity of surgery (choice B) is favorable (if done immediately) but not mandatory and does not change the patient\'s consent status.

Obtaining a court order (choice C) is not necessary with the patient\'s wife immediately accessible.

Trying to persuade the patient to consent to surgery (choice E) would not only waste time and prove futile but might agitate the patient as well.", //17 "The correct answer is A. This woman has a risk profile (female, fat, forties) and symptomatology consistent with gallstones (cholelithiasis). As would be expected, contraction of the gallbladder following a fatty meal often exacerbates the pain caused by gallstones. Cholecystokinin (CCK), the release of which is stimulated by dietary fat, is the hormone responsible for stimulation of gallbladder contraction. It is produced in I cells of the duodenum and jejunum. In addition to gallbladder contraction, CCK also stimulates pancreatic enzyme secretion and decreases the rate of gastric emptying.

Gastrin (choice B) is produced by the G cells of the antrum and duodenum. Gastrin stimulates the secretion of HCl from the parietal cells and pepsinogen from the chief cells of the stomach. Gastrin secretion is stimulated by gastric distention, digestive products (e.g., amino acids), and vagal discharge.

Pepsin (choice C) is a protease produced by the chief cells of the stomach (as pepsinogen). It is involved in the digestion of proteins. Pepsinogen release is stimulated by vagal stimulation, gastrin, local acid production, secretin, CCK, and histamine.

Secretin (choice D) is produced by the S cells of the duodenum. It is secreted primarily in response to acidification of the duodenal mucosa. Secretin stimulates the secretion of bicarbonate-containing fluid from the pancreas and biliary ducts. This neutralization allows pancreatic enzymes to function. Secretin also inhibits gastric acid production and gastric emptying.

Somatostatin (choice E) is produced by the D cells of the pancreatic islets and in the gastric and intestinal mucosa. Somatostatin is an inhibitory hormone-it inhibits the secretion of most gastrointestinal hormones, gallbladder contraction, gastric acid and pepsinogen secretion, pancreatic and small intestinal fluid secretion, and both glucagon and insulin release.", //18 "The correct answer is B. The epithelial lining of the second pharyngeal pouch buds into the mesenchyme to form the palatine tonsil. Part of the pouch remains in the adult as the tonsillar fossa.

It is important to review the other choices since pharyngeal pouch derivatives are typically tested on the USMLE Step 1:

The first pharyngeal pouch (choice A) develops into the middle ear cavity and eustachian tube.

The third pharyngeal pouch (choice C) develops into the thymus and the inferior parathyroid glands.

The fourth pharyngeal pouch (choice D) gives rise to the superior parathyroid glands. Recall that abnormal development of the 3rd and 4th pouches leads to DiGeorge syndrome and results in hypocalcemia as well as abnormal cellular immunity and consequent susceptibility to viral and fungal illnesses.

The fifth pharyngeal pouch (choice E) gives rise to the C cells of the thyroid gland. These cells secrete calcitonin-a hormone that lowers serum calcium.", //19 "The correct answer is C. The child is suffering from absence (petit mal) seizures. The age of onset is typically from 3 to 7 years; seizures may continue into adolescence, but generally subside before adulthood. These seizures have been known to occur up to 100 times a day. Ethosuximide is indicated for this type (but no other type) of seizure. Other drugs used in the treatment of absence seizures are valproic acid, clonazepam, and a new agent, lamotrigine.

Carbamazepine (choice A) is used in the treatment of tonic-clonic (grand mal) and partial (focal) seizures.

Diazepam (choice B) has long been the drug of choice for status epilepticus. Recently, lorazepam (a shorter acting benzodiazepine) has also been accepted as a drug for this condition. Intravenous phenytoin is used if prolonged therapy is required. Phenobarbital has also been used, especially in children. If the status epilepticus is very severe and does not respond to these measures, general anesthesia may be used.

Methylphenidate (Ritalin; choice D) is a stimulant used to treat children with attention deficit disorder. This child has no history of hyperactivity, and the underlying cause of his \"inattentiveness\" is his seizure disorder.

Phenytoin (choice E) is effective in all seizure types except for the one in this question (absence). Note that phenytoin has some idiosyncratic, test-worthy side effects, including hirsutism and gingival hyperplasia.", //20 "The correct answer is B. Locus heterogeneity is the situation in which the same phenotype is caused by defects in different genes. It is commonly seen in syndromes resulting from failures in a complex pathway, such as hearing. In this example, locus heterogeneity is indicated because of complementation. In generations I through III, deafness appears to be due to a single autosomal recessive trait. In generation IV, deaf parents produce normal hearing children, suggesting that the parents have defects in different genes. The children are heterozygous at both loci, and so have normal hearing (complementation).

Autosomal dominant inheritance (choice A), would require multiple assumptions. In generation IV, the parents produce six normal children, although at best they are both heterozygous for the trait. The probability of that event, given that they are both heterozygous, is (1/4)6. Even more troublesome is the mating between II-1 and II-2, in which normal parents produce affected children. While it is possible to invoke the possibility that the gene is an autosomal dominant with incomplete penetrance, no data about this frequency is given, and this hypothesis still requires many more assumptions than the correct answer. Penetrance is the frequency at which the phenotype is expressed in a person who carries a particular genotype. It can complicate pedigree analysis.

Mitochondrial inheritance (choice C), would show a completely different pattern. Genetic information is transmitted to progeny on nuclear chromosomes as well as on mitochondrial chromosomes. Since mitochondria are inherited only from the mother, if affected she will give the trait to all of her progeny. A male with the trait will never transmit it to his progeny.

Multifactorial inheritance (choice D) is a nonmendelian inheritance pattern that depends upon the incremental contributions of multiple loci to a single phenotype, as well as upon contributions from environmental factors. Characteristics that exhibit a broad range of values, like height or eye color, are inherited in this manner.

X-linked dominant inheritance (choice E) affects either sex, but which of the children are affected depends upon the sex of the affected parent. If the male parent is affected, he will produce only affected daughters and normal sons, because he gives his X chromosome to all of his daughters and none of his sons. If the female parent is affected, she contributes an X chromosome to both daughters and sons, hence both can be affected. However, since she is almost always heterozygous for the trait, the probability is 50% that her children will receive a normal X chromosome. Remember that human females randomly inactivate one of their X chromosomes (Lyon hypothesis). Due to this inactivation, a female who is heterozygous for an X-linked dominant will tend to be both more mildly and more variably affected then a male with the same trait.", //21 "The correct answer is B. The diagram of ventricular pressure in millimeters mercury (mmHg) against diastolic volume in milliliters (mL) is drawn as two curves: an intraventricular diastolic pressure curve (lower curve) and an intraventricular systolic pressure curve (upper curve). Point B is the diastolic volume at which initial stretch leads to maximal systolic contraction. This corresponds to the muscle length at which the sarcomeres are closest to their most effective length, Lmax, which is about 2.2 mm. As cardiac muscle is stretched, its ability to contract (after electrical stimulation) increases up to the muscle length corresponding to Lmax, after which it begins to decrease. Lmax represents the length at which potential cross-bridging between actin and myosin in each sarcomere is at a maximum. When applied to the entire heart, rather than a strip of isolated muscle, this length-tension relationship is responsible for the Frank-Starling law: increased end-diastolic volume increases force of systolic contraction (up to Lmax), after which peak systolic pressure begins to decrease.

Choices A, D, and E all correspond to minimum sarcomere length.

Choice C corresponds to an end diastolic pressure so high that no ejection is possible; end diastolic pressure and peak systolic pressure are the same.", //22 "The correct answer is B. The key to excelling in biochemistry on the USMLE is to master the most clinically important elements of metabolic pathways: rate-limiting steps, irreversible steps, steps involving enzymes affected by genetic diseases, etc. In this case, glycogen phosphorylase is the enzyme involved in the rate-limiting step of glycogenolysis:


Note that this enzyme is activated in response to the binding of glucagon to liver cell receptors or the binding of epinephrine to muscle receptors, via signal transduction.

a-1,4-glucan transferase (choice A) is a debranching enzyme that removes three or four glucose units from a branch point and transfers them to the end of another chain. In this reaction, one alpha-1,4 bond is cleaved and another is formed. The elongated chain then becomes a substrate for glycogen phosphorylase.

Glycogen synthase (choice C) is the enzyme involved in the rate-limiting step of glycogen synthesis:


Note that this enzyme is inactivated in response to the binding of glucagon to liver cell receptors or the binding of epinephrine to muscle receptors, via signal transduction.

Phosphoglucomutase (choice D) is a key enzyme in glycogen synthesis that reversibly converts glucose-6-phosphate to glucose-1-phosphate.

UDP-glucose pyrophosphorylase (choice E) is another key enzyme in glycogen synthesis:


Note that the linkage formed between UDP and glucose is a high-energy bond that can provide energy to many biosynthetic reactions.", //23 "The correct answer is B. Brief psychotic disorder is a thought disorder of psychotic proportion (e.g., the demonstrated auditory hallucinations). There is often a precipitating event. To make this diagnosis, the patient\'s symptoms must have been present for at least 1 day but not more than 1 month. This duration distinguishes brief psychotic disorder from schizophrenic and schizophreniform disorders.

Bipolar disorder (choice A) is defined by the presence of a manic episode (characterized by an altered, intense mood, with rapid/pressured speech and hyperactivity).

Schizoaffective disorder (choice C) is characterized by elements of both schizophrenia (e.g., psychotic symptoms) and mood disorders (e.g., manic or depressive symptoms).

Schizophrenic disorder (choice D) is a chronic recurrent thought disorder often accompanied by bizarre behaviors. It usually begins in early adulthood. To make this diagnosis, the symptoms must last 6 months or more, which distinguishes it from brief psychotic and schizophreniform disorders.

Schizophreniform disorder (choice E) is a thought disorder of psychotic proportion with a duration between 1 and 6 months. This duration distinguishes the condition from brief psychotic disorder and schizophrenic disorder. Often, the onset of the thought disorder is as a young adult, when the person must leave the protected environment of the home and begin to assume personal responsibility for his or her life. He or she is unable to cope with the world and his/her defenses deteriorate to the point of psychosis. Typically, patients with schizophreniform disorder were unable to maintain interpersonal relationships as adolescents.", //24 "The correct answer is E. The most important clue in this question is the photograph. The presence of skin, teeth, and hair in the tumor should have led you to the diagnosis of dermoid cyst, also known as a mature teratoma. These tumors are a benign type of germ cell tumor. They are lined by stratified squamous epithelium and skin adnexal structures (sebaceous glands with associated secretions and hair follicles). They occur most commonly in women of reproductive age.

Choriocarcinomas (choice A) are a malignant type of germ cell tumor that are often widely metastatic. An important clue to this type of tumor is an elevated level of hCG.

Dysgerminomas (choice B) are also germ cell tumors. They are rare and usually occur in women in their 20s and 30s. They are composed of sheets of large cells with clear cytoplasm and are notable for their high degree of radiosensitivity.

Ovarian fibromas (also called fibroma-thecomas; choice C) are a type of sex cord-stromal tumor. They present with pain and a pelvic mass. Ascites is common and hydrothorax may occur. The triad of ovarian mass, ascites, and hydrothorax is called Meig\'s syndrome and most commonly occurs with fibroma.

Granulosa-theca cell tumors (choice D) are a type of sex cord-stromal tumor that typically occur in post-menopausal women. These tumors contain a variable ratio of granulosa cells (small polygonal cells in sheets or strands) and theca cells (cuboidal/spindle-shaped). The granulosa cells may be filled with acidophilic material known as Call-Exner bodies. These tumors may secrete estrogens and are associated with endometrial and breast cancer.", //25 "The correct answer is C. Step 1 questions related to antineoplastic agents are most likely going to ask you about mechanism of action, cell cycle specificity, or side effects. While bone marrow suppression, nausea, vomiting, ulcers, and alopecia are common side effects, you are probably more likely to be asked about the unique side effects of certain drugs. In this case, cyclophosphamide has the unique side effect of hemorrhagic cystitis, which could cause hematuria. Note that cyclophosphamide is also consistent with the fact that the patient is being treated for non-Hodgkin\'s lymphoma.

All the other answer choices have unique, USMLE-worthy side effects:

Bleomycin (choice A) is notable for its pulmonary toxicity. Note that while bleomycin can be used to treat lymphoma, you are more likely to see it as part of the treatment regimen (with vinblastine and cisplatin) for testicular tumors.

Cisplatin (choice B) is notable for its nephrotoxicity and ototoxicity. It is used in the treatment of testicular and lung cancers. It would not be used in a patient with lymphoma.

Doxorubicin (choice D) is also called adriamycin. It is an antibiotic agent used in the treatment of many cancers, including lymphomas, sarcomas, and many carcinomas. Its unique side effect is its cardiotoxicity.

You might have been tempted by plicamycin (choice E) if you recalled that it can cause a hemorrhagic diathesis. You could have eliminated this answer, however, because plicamycin is not used in the treatment of lymphoma. It is used in the treatment of testicular cancer and cases of hypercalcemia." ); var cate_step1 = new Array( //1 "BIO", //2 "BESCI", //3 "PHARM", //4 "PATH", //5 "IMMU", //6 "BIO", //7 "ANAT", //8 "", //9 "PHARM", //10 "PHYSIO", //11 "PHYSIO", //12 "ANAT", //13 "BIO", //14 "", //15 "PATH", //16 "BESCI", //17 "PHYS", //18 "ANAT", //19 "PHARM", //20 "BIO", //21 "PHYSIO", //22 "BIO", //23 "BESCI", //24 "PATH", //25 "PHARM"); var cateSub_step1 = new Array( //1 "GP", //2 "GP", //3 "GP", //4 "ENDO", //5 "GP", //6 "GP", //7 "GI", //8 "GP", //9 "CV", //10 "MS", //11 "RENAL", //12 "RESP", //13 "GP", //14 "GP", //15 "H/L", //16 "GP", //17 "GI", //18 "GP", //19 "NEURO", //20 "GP", //21 "CV", //22 "GP", //23 "GP", //24 "REPRO", //25 "GP"); //THIS IS AN ARRAY WITH THE BASIC CATEGORIES HELD WITHIN THE APP; THEY DO NOT GET DISTRIBUTED WITH QUESTIONS. var baseCats_step1 = new Array ("BS", "IMM", "BIO", "MICRO", "BIOST", "ANAT", "CELL", "PATH", "BESCI", "PAPHYS", "PHARM", "GROSS", "PHYSIO", "HISTO"); var baseOrgs_step1 = new Array ("GP", "MULTI", "CV", "ENDO", "GI", "HEME/LYMPH", "MUS", "NEURO", "RENAL", "REPRO", "RESP", "S/C", "DIG");