NBME CBSE REAL EXAM 600 QUESTIONS AND ANSWERS LATEST (usmle step 1) MEDICAL EXAMINATION comprehensive practice exam test GRADED A+ (

NBME CBSE REAL EXAM 600 QUESTIONS AND ANSWERS LATEST (usmle step 1) MEDICAL EXAMINATION comprehensive practice exam test GRADED A+ (Exam Section 1: Item 1 of 50 National Board of Medical Examiners Comprehensive Basic Science Self-Assessment 1. A75-year-old man has decreased exercise tolerance and occasional syncopal episodes related to exertion. Left-heart catheterization discloses this pressure tracing (Ao -aorta; LV -left ventricle; LA - left atrium). The most frequently encountered mechanism underlying this disorder is which of the following? ЕCG A) Amyloid deposition 150- B) Calcification C) Cystic medial necrosis D) Pericardial effusion 100- O E) Septal hypertrophy Ao 50- LV LA Time Time- Correct Answer: B. The pressure tracing demonstrates a large pressure gradient between the left ventricle and aorta during systole, which is consistent with the diagnosis of aortic stenosis. In the setting of aortic stenosis, the left ventricle must generate higher pressures in order to overcome the opening resistance of the stenotic valve. This increased pressure is not fully transmitted across the stenotic valve to the aorta, which causes a delay in the aortic peak pressure. In a normal aortic valve, the pressure tracing in the left ventricle and aorta follow a similar curve during systole while the valve is open. Calcification of the valve is a pathologic consequence of mechanical stresses on the heart valves, and results from repetitive microtrauma from the opening and closing of valve leaflets with associated chronic inflammation. Many people will develop some degree of valve stenosis because of chronic inflammation with resultant calcification and fibrosis over time, with the aortic valve most commonly affected. Early-onset aortic stenosis can occur in the setting of bicuspid aortic valve or chronic rheumatic heart disease. Patients may report fatigue, shortness of breath, cough, diminished exercise tolerance, or syncope with exertion. Physical examination findings include a crescendo-decrescendo systolic murmur best heard at the upper right sternal border, and pulsus parvus et tardus (weak and delayed) may be noted on examination of peripheral pulses. As a result of the chronic increased afterload from a fixed obstruction by the valve, left ventricular hypertrophy, and resultant diastolic dysfunction can occur. Incorrect Answers: A, C, D, and E. Amyloid deposition (Choice A) occurs in cardiac amyloidosis, which is an infiltrative cardiomyopathy caused by the deposition of amyloid protein throughout the extracellular space of the heart. It does not directly cause aortic stenosis. Cystic medial necrosis (Choice C) is a disorder of the large arteries (particularly the aorta) which is associated with connective tissue diseases such as Marfan syndrome, Ehlers-Danlos syndrome, and annuloaortic ectasia. It is characterized by basophilic ground substance deposition in the tunica media with cyst-like lesions. It increases the risk for dissection, aneurysm, or rupture of the aorta, but it is not associated with aortic stenosis. Pericardial effusion (Choice D) refers to the presence of an abnormal amount of fluid in the pericardium. If severe enough, it can potentially progress to cardiac tamponade with compression of the cardiac chambers and obstructive shock. It typically causes the equalization of pressures amongst the four heart chambers. Septal hypertrophy (Choice E) is present in hypertrophic cardiomyopathy. If there is severe hypertrophy, the cardiac pressure tracing is like that seen in aortic stenosis with a large pressure gradient between the left ventricle and the aorta. This is because of left ventricular outflow tract obstruction from the septal hypertrophy. However, aortic stenosis is a far more common disorder, especially in older adults. Educational Objective: Aortic stenosis can be identified on a cardiac pressure tracing by the presence of a large pressure gradient between the left ventricle and the aorta. It is most commonly caused by age-related fibrosis and calcification. Pressure (mm Hg) 2. New reagents are being designed to treat graft-versus-host disease in HLA-unrelated bone marrow transplant recipients. Reagents should be designed that selectively deplete which of the following donor cells? A) B lymphocytes O B) Dendritic cells C) Macrophages D) Neutrophils E) T lymphocytes Correct Answer: E. T lymphocytes, which are responsible for the immune attack against the recipient, should be the target of agents used to treat graft-versus-host disease (GVHD) in HLA-unrelated bone marrow transplant recipients. Prior to grafting of allogeneic stem cells in a bone marrow transplant, recipient native marrow must be completely ablated. It is then replaced with donor marrow, which recolonizes the marrow cavity. Successful transplantation results in reconstitution of the immune system with the donor's immune cells. GVHD occurs when the donor's immune system recognizes the host's tissues as foreign and mounts an immune response against them. Manifestations of acute GVHD include rash, ranging from maculopapular to blistering, diarrhea, abdominal pain, and hepatitis with hyperbilirubinemia. Diagnosis should be suspected in patients with any of these symptoms and a recent bone marrow transplant. Medications that are used in the treatment of GVHD act either by directly inhibiting the production of T lymphocytes or by suppressing the normal function of these cells. Examples include mycophenolate mofetil, which inhibits the synthesis of nucleotides needed for lymphocyte proliferation; etanercept, a TNF-alpha receptor inhibitor; pentostatin, a purine analog that inhibits Ť lymphocyte proliferation; sirolimus, which inhibits mTOR to suppress T lymphocyte proliferation; and anti-thymocyte globulin, which directly targets T lymphocytes. Incorrect Answers: A, B, C, and D. B lymphocyte depletion (Choice A) is the result of several medications that target CD20, a surface marker found on B lymphocytes. The most used monoclonal antibody targeting this site is rituximab. It is currently used as a primary component of chemotherapy regimens to treat a variety of B-cell lymphomas. It is also used to treat vasculitis such as granulomatosis with polyangiitis, microscopic polyangiitis, neurologic disorders such as myasthenia gravis and autoimmune encephalitis, and refractory immune thrombocytopenia. It is well tolerated, but patients must be tested for hepatitis B prior to treatment, as reactivation of hepatitis B is a known side effect. Dendritic cell depletion (Choice B) occurs indirectly through targeted medications against the inflammatory cytokines produced by dendritic cells. One example of this is anakinra, an IL-1 receptor antagonist. It is used for the treatment of gout, rheumatoid arthritis, and neonatal-onset multisystem inflammatory disease (NOMID). Macrophage cell depletion (Choice C) occurs indirectly through inhibiting the release of inflammatory cytokines such as TNF-a and through the inhibition of antigen presentation and activation of T lymphocytes, thereby dampening the overall immune response. Examples of anti-TNF-a therapies include infliximab, adalimumab, and eculizumab. Medications that target antigen presentation include abatacept. These medications have broad use, often to treat autoimmune diseases such as rheumatoid and psoriatic arthritis. Neutrophil depletion (Choice D) is exceedingly common and is typical of many medications. Neutrophil suppression is typified by neutropenia and can be seen for example with the use of methimazole, clozapine, and dapsone, among others. Some nonsteroidal anti-inflammatory drugs also impair neutrophil function without causing neutropenia. Educational Objective: Acute GVHD may occur in HLA-unrelated bone marrow transplant recipients as a result of donor T lymphocytes recognizing and targeting recipient cells of the gastrointestinal tract, skin, and liver. Treatment is with medications that directly or indirectly prevent T lymphocyte proliferation, activation, and function. I3D 3. A9-year-old boy has had alopecia and hypocalcemia since birth. His serum 1,25-dihydroxycholecalciferol concentration is within the reference range, serum 24,25-dihydroxycholecalciferol is undetectable. Serum parathyroid hormone concentration is above the upper limit of the laboratory assay and needs to be reassayed at a dilution. The results are pending. Which of the following is the most likely cause of his condition? O A) Loss-of-function mutation in the calcium-sensing receptor B) Multiple endocrine neoplasia type I C) Mutations inactivating the vitamin D 24-hydroxylase gene D) Mutations inactivating the vitamin D receptor Correct Answer: D. Vitamin D plays a role in serum calcium and phosphate homeostasis by promoting the intestinal absorption of calcium and phosphate. Parathyroid hormone (PTH) also has a role in calcium and phosphate regulation by stimulating osteoclastic bone reabsorption and distal convoluted tubular calcium reabsorption and phosphate excretion in the kidney. Vitamin D deficiency can be caused by malabsorption in the intestinal tract, malnutrition or insufficient dietary intake, and decreased sun exposure. Decreased concentration of vitamin D results in decreased intestinal calcium absorption and hypocalcemia, sensed by the parathyroid gland via calcium-sensing receptors, which leads to an increase in secretion of PTH to normalize serum calcium concentration. Increased PTH causes bone resorption, liberating calcium and phosphorus, otherwise stored in bone. In this patient, 1,25-dihydroxycholecalciferol, the active form of vitamin D, is within reference range. However, the vitamin D receptor must also exist and function appropriately for the hormone to exert its effect. Vitamin D binds a nuclear receptor, exerting its effect by gene transcription. In this case, a normal concentration of Vitamin D with persistent hypocalcemia suggests an inactivating mutation in the receptor itself, or a mutation in a regulatory sequence that prevents transcription of the genes coding for the receptor. In turn, the patient experiences persistent hypocalcemia despite normal vitamin D concentration, as the receptor mutation prevents the action of vitamin D in promoting the intestinal absorption of calcium. Incorrect Answers: A, B, and C. Loss-of-function mutation in the calcium-sensing receptor (Choice A) in the parathyroid gland would prevent the parathyroid gland from sensing low concentrations of calcium and reacting by secreting PTH. This would cause hypoparathyroidism, not hyperparathyroidism as seen in the patient. Multiple endocrine neoplasia type I (Choice B) is characterized by often functional pituitary, pancreatic, and parathyroid tumors. Pituitary tumors may secrete prolactin or growth hormone, pancreatic tumors may secrete insulin, glucagon, or vasoactive intestinal peptide, and parathyroid adenomas may secrete PTH. A functionally active parathyroid adenoma would cause an increase in PTH, and because of the role of PTH in calcium reabsorption and bone resorption, hypercalcemia would result. Mutations inactivating the vitamin D 24-hydroxylase gene (Choice C) would result in decreased concentration of 24,25-dihydroxycholecalciferol, an inactive metabolite. Vitamin D would persist in its active form as a result, which may indirectly result in hypercalcemia. Educational Objective: Vitamin D plays a role in serum calcium and phosphate homeostasis by promoting the intestinal absorption of calcium and phosphate. Vitamin D deficiency typically leads to decreased intestinal calcium absorption, hypocalcemia, increased PTH secretion, and increased PTH-mediated bone resorption.