Đang tải... (xem toàn văn)
(BQ) Part 1 book Harrison principles of internal medicine self-Accessment and board review presents the following contents: Practice of medicine, genetics and disease, clinical pharmacology, nutrition, oncology and hematology, infectious diseases, disorders of the cardiovascular system, disorders of the respiratory system, disorders of the kidney and urinary tract.
HARRISON'S 15 TH EDITION P R I N C I P L E S OF INTERNAL MEDICINE SELF-ASSESSMENT AND BOARD REVIEW NOTICE Medicine is an ever-changing science As new research and clinical experience broaden our knowledge, changes in treatment and drug therapy are required The editor and the publisher of this work have checked with sources believed to be reliable in their efforts to provide information that is complete and generally in accord with the standards accepted at the time of publication However, in view of the possibility of human error or changes in medical sciences, neither the editors nor the publisher nor any other party who has been involved in the preparation or publication of this work warrants that the information contained herein is in every respect accurate or complete and they are not responsible for any omissions or for the results obtained from use of such information Readers are encouraged to confirm the information contained herein with other sources For example and in particular, readers are advised to check the product information sheet included in the package of each drug they plan to administer to be certain that the information contained in this book is accurate and that changes have not been made in the recommended dose or in the contraindications for administration This recommendation is of particular importance in connection with new or infrequently used drugs 15 TH HARRISON'S EDITION P R I N C I P L E S OF INTERNAL MEDICINE SELF-ASSESSMENT AND BOARD REVIEW For use with the 15th edition of HARRISON’S PRINCIPLES OF INTERNAL MEDICINE EDITED BY RICHARD M STONE, MD Clinical Director, Adult Leukemia Program Department of Adult Oncology Dana-Farber Cancer Institute Associate Professor of Medicine Harvard Medical School Boston, Massachusetts CONTRIBUTING EDITOR Daniel J DeAngelo, MD, PhD Department of Adult Oncology Dana-Farber Cancer Institute Instructor in Medicine Harvard Medical School Boston, Massachusetts McGraw-Hill MEDICAL PUBLISHING DIVISION New York Milan Chicago New Delhi San Francisco San Juan Lisbon Seoul London Singapore Madrid Sydney Mexico City Toronto abc McGraw-Hill Copyright © 2001 by The McGraw-Hill Companies, Inc All rights reserved Manufactured in the United States of America Except as permitted under the United States Copyright Act of 1976, no part of this publication may be reproduced or distributed in any form or by any means, or stored in a database or retrieval system, without the prior written permission of the publisher 0-07-138678-5 The material in this eBook also appears in the print version of this title: 0-07-137375-6 All trademarks are trademarks of their respective owners Rather than put a trademark symbol after every occurrence of a trademarked name, we use names in an editorial fashion only, and to the benefit of the trademark owner, with no intention of infringement of the trademark Where such designations appear in this book, they have been printed with initial caps McGraw-Hill eBooks are available at special quantity discounts to use as premiums and sales promotions, or for use in corporate training programs For more information, please contact George Hoare, Special Sales, at george_hoare@mcgraw-hill.com or (212) 904-4069 TERMS OF USE This is a copyrighted work and The McGraw-Hill Companies, Inc (“McGraw-Hill”) and its licensors reserve all rights in and to the work Use of this work is subject to these terms Except as permitted under the Copyright Act of 1976 and the right to store and retrieve one copy of the work, you may not decompile, disassemble, reverse engineer, reproduce, modify, create derivative works based upon, transmit, distribute, disseminate, sell, publish or sublicense the work or any part of it without McGraw-Hill’s prior consent You may use the work for your own noncommercial and personal use; any other use of the work is strictly prohibited Your right to use the work may be terminated if you fail to comply with these terms THE WORK IS PROVIDED “AS IS” McGRAW-HILL AND ITS LICENSORS MAKE NO GUARANTEES OR WARRANTIES AS TO THE ACCURACY, ADEQUACY OR COMPLETENESS OF OR RESULTS TO BE OBTAINED FROM USING THE WORK, INCLUDING ANY INFORMATION THAT CAN BE ACCESSED THROUGH THE WORK VIA HYPERLINK OR OTHERWISE, AND EXPRESSLY DISCLAIM ANY WARRANTY, EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO IMPLIED WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE McGraw-Hill and its licensors not warrant or guarantee that the functions contained in the work will meet your requirements or that its operation will be uninterrupted or error free Neither McGraw-Hill nor its licensors shall be liable to you or anyone else for any inaccuracy, error or omission, regardless of cause, in the work or for any damages resulting therefrom McGraw-Hill has no responsibility for the content of any information accessed through the work Under no circumstances shall McGraw-Hill and/or its licensors be liable for any indirect, incidental, special, punitive, consequential or similar damages that result from the use of or inability to use the work, even if any of them has been advised of the possibility of such damages This limitation of liability shall apply to any claim or cause whatsoever whether such claim or cause arises in contract, tort or otherwise DOI: 10.1036/0071386785 Want to learn more? We hope you enjoy this McGraw-Hill eBook! If you’d like more information about this book, its author, or related books and websites, please click here For more informa tion a bout this book, click he re CONTENTS Introduction SECTION I vii PRACTICE OF MEDICINE Questions Answers, Explanations, and References SECTION II GENETICS AND DISEASE Questions Answers, Explanations, and References SECTION III 127 146 DISORDERS OF THE RESPIRATORY SYSTEM Questions Answers, Explanations, and References SECTION IX 79 96 DISORDERS OF THE CARDIOVASCULAR SYSTEM Questions Answers, Explanations, and References SECTION VIII 35 51 INFECTIOUS DISEASES Questions Answers, Explanations, and References SECTION VII 27 30 ONCOLOGY AND HEMATOLOGY Questions Answers, Explanations, and References SECTION VI 21 23 NUTRITION Questions Answers, Explanations, and References SECTION V 13 CLINICAL PHARMACOLOGY Questions Answers, Explanations, and References SECTION IV 171 180 DISORDERS OF THE KIDNEY AND URINARY TRACT Questions Answers, Explanations, and References 197 207 v Copyright 2001 The McGraw-Hill Companies Click Here for Terms of Use vi SECTION X Contents DISORDERS OF THE GASTROINTESTINAL SYSTEM Questions Answers, Explanations, and References SECTION XI DISORDERS OF THE IMMUNE SYSTEM, CONNECTIVE TISSUE, AND JOINTS Questions Answers, Explanations, and References SECTION XII 287 303 NEUROLOGIC DISORDERS Questions Answers, Explanations, and References SECTION XIV 257 267 ENDOCRINE AND METABOLIC DISORDERS Questions Answers, Explanations, and References SECTION XIII 221 235 333 349 ENVIRONMENTAL AND OCCUPATIONAL HAZARDS Questions Answers, Explanations, and References 375 377 Appendix 381 Bibliography 391 INTRODUCTION Harrison’s Principles of Internal Medicine: PreTest SelfAssessment and Review has been designed to provide physicians with a comprehensive, relevant, and convenient instrument for self-evaluation and review within the broad area of internal medicine Although it should be particularly helpful for residents preparing for the American Board of Internal Medicine (ABIM) certification examination and for board-certified internists preparing for recertification, it should also be useful for internists, family practitioners, and other practicing physicians who are simply interested in maintaining a high level of competence in internal medicine Study of this self-assessment and review book should help to (1) identify areas of relative weakness; (2) confirm areas of expertise; (3) assess knowledge of the sciences fundamental to internal medicine; (4) assess clinical judgment and problem-solving skills; and (5) introduce recent developments in general internal medicine This book consists of multiple-choice questions that (1) are representative of the major areas covered in Harrison’s Principles of Internal Medicine, 15th ed., and (2) parallel the format and degree of difficulty of the questions on the examination of the ABIM Questions have been appropriately updated and chosen to reflect important recent developments in internal medicine, such as the increasing contributions of molecular biology to the understanding, diagnosis, and treatment of many disorders This edition represents a reorganized version in which the sections correspond to those in the parent textbook Many questions have been revised Except-type questions have been eliminated to reflect the changing ABIM certification examination format New sections in general medicine, pharmacology, nutrition, and genetics have been added Each question is accompanied by an answer, a paragraph-length explanation, and a reference to a specific chapter in Harrison’s In some cases references to more specialized textbooks and current journal articles are also given A list of normal values used in the laboratory studies in this book can be found in the Appendix, followed by a Bibliography listing all the sources used for the questions As in the current edition of Harrison’s, the system of international units (SI) appears first in the text and the traditional units follow in parentheses All color plates referred to in the text are found at the back of the book We have assumed that the time available to the reader is limited; therefore, this book has been designed to be used profitably a chapter at a time By allowing no more than two and a half minutes to answer each question, you can simulate the time constraints of the actual board examinations When you finish answering all the questions in a chapter, spend as much time as necessary verifying answers and carefully reading the accompanying explanations If after reading the explanations for a given chapter, you feel a need for a more extensive and definitive discussion, consult the chapter in Harrison’s or any of the other references listed Based on our testing experience, on most medical examinations, examinees who answer half the questions correctly would score around the 50th or 60th percentile A score of 65 percent would place the examinee above the 80th percentile, whereas a score of 30 percent would rank him or her below the 15th percentile In other words, if you answer fewer than 30 percent of the questions in a chapter correctly, you are relatively weak in that area A score of 50 percent would be approximately average, and 70 percent or higher would probably be honors This book is a teaching device that provides readers with the opportunity to evaluate and update their clinical expertise, their ability to interpret data, and their ability to diagnose and solve clinical problems The editor wishes to acknowledge the efforts of his administrative assistant, Cynthia Curti, whose tireless efforts allowed completion of this complicated project Key individuals at McGraw-Hill Medical Publishing Division, Mariapaz Ramos Englis, Catherine H Saggese, and Martin J Wonsiewicz, Publisher, provided critical support, advice, and understanding during the production of this and previous editions of the PreTest vii Copyright 2001 The McGraw-Hill Companies Click Here for Terms of Use This page intentionally left blank 206 IX DISORDERS OF THE KIDNEY AND URINARY TRACT — QUESTIONS IX-49 (Continued) (A) Decreased renal tubular secretion of furosemide (B) Diminished bioavailability of furosemide (C) Binding of furosemide to albumin in the tubular fluid (D) Decreased proximal reabsorption of sodium (E) Decreased distal reabsorption of sodium IX-50 A 46-year-old man with long-standing diabetes mellitus and ESRD is undergoing hemodialysis He has completed his run of dialysis and you find him somewhat confused, with a blood pressure of 86/42 Which of the following factors most likely contributed to the postdialysis hypotension? (A) (B) (C) (D) (E) Reduced temperature dialysate Concomitant use of antihypertensive therapy Impaired autonomic response Poor dietary intake during dialysis Hyperphosphatemia IX-51 A 46-year-old man has long-standing hypertension, and his current medications include hydrochlorothiazide He presents with right flank pain radiating to his groin Urinalysis reveals 3ϩ hematuria without proteinuria He has had a similar episode previously Routine laboratory analysis reveals a normal serum creatinine of 88 mol/L (1.0 mg/dL), serum calcium of 2.6 mmol/L (10.3 mg/dL), serum uric acid of 268 mol/L (4.5 mg/ dL), and a total urine calcium of 200 mg per 24 h The patient passes a stone, and upon microscopic analysis of the stone it is found to contain calcium The most likely cause of the patient’s recurrent nephrolithiasis is which one of the following? (A) (B) (C) (D) (E) Idiopathic absorptive hypercalciuria A common complication of thiazide diuretic Diathesis Primary hyperparathyroidism Hypocitraturia IX DISORDERS OF THE KIDNEY AND URINARY TRACT ANSWERS IX-1 The answer is E (Chap 47) Up to 150 mg/d of protein may be excreted by a normal person The bulk of normal daily excretion is made up of the Tamm-Horsfall mucoprotein Urine dipsticks may register a trace result in response to as little as 50 mg protein per liter and are definitively positive once the urine protein exceeds 300 mg/L A false negative may occur if the proteinuria is due to immunoglobulins, which are positively charged If proteinuria is suspected or documented, a 24-h urine collection should be undertaken to measure the absolute protein excretion Urine immunoelectrophoresis also may identify the particular immunoglobulin that is produced in excess IX-2 The answer is E (Chap 49) Because of the powerful effect of ADH secretion in the setting of hypertonicity, severe persistent hypernatremia is possible only in patients who cannot respond to thirst by ingesting water A nursing home patient with a fever may lose significant amounts of body fluid, which can result in dangerous levels of hypernatremia Manifestations of hypernatremia include central nervous system dysfunction such as neuromuscular irritability, seizures, obtundation, or coma Calculation of water replacement needs is based on total-body water, since water loss occurs from both intracellular and extracellular sites In this case, a 60-kg woman has a plasma sodium of 160 mmol/L, which one would like to lower to 140 mmol/L Total-body water is roughly 60% of weight (36 L) To reduce the plasma sodium, this volume must be increased to 160/140 times 36 L, or about 41 L Thus, a positive water balance of L (41 Ϫ 36) is needed This deficit is best corrected fairly slowly, with the aim being to replace about half the water deficit in the first day If correction is done in this conservative fashion with close monitoring of electrolytes, progressive central nervous system dysfunction is not likely If the patient had signs of circulatory collapse indicating an associated sodium deficiency, treatment would begin with normal saline to provide intracellular volume In certain situations, such as hyperosmolar diabetic coma, the plasma osmolarity is elevated because of hyperglycemia as well as hypernatremia Therefore, initial treatment should consist of normal saline to ensure circulatory integrity and insulin to lower plasma glucose and partially reduce intracellular osmolarity Finally, half normal saline could be used to slowly replace the remaining water and salt deficits IX-3 The answer is A (Chaps 47, 329) Failure to concentrate urine despite substantial hypertonic dehydration suggests a diagnosis of diabetes insipidus A nephrogenic origin will be postulated if there is no increase in urine concentration after exogenous vasopressin The only useful mode of therapy is a low-salt diet and use of a thiazide or amiloride, a potassium-sparing distal diuretic agent The resultant volume contraction presumably enhances proximal reabsorption and thereby reduces urine flow IX-4 The answer is A (Chap 47 Gennari, N Engl J Med 339:451 – 458, 1998.) This man’s electrolyte pattern is consistent with a hyporeninemic hypoaldosteronism state, or type IV renal tubular acidosis The defect is believed to be due to an insufficiency of both angiotensin- and adrenal mineralocorticoid-secreting capacity Inhibition of the renin-angiotensin system by -adrenergic blockade such as propranolol can cause hyperkalemia; in addition, nonsteroidal anti-inflammatory agents or angiotensin-converting enzyme (ACE) inhibitors may also lead to hyperkalemia The use of carbenicillin, theophyllin, and hy207 208 IX DISORDERS OF THE KIDNEY AND URINARY TRACT — ANSWERS drochlorothiazide promote the loss of potassium through the distal renal tubule Calcium channel blockers such as verapamil have no significant effect on serum potassium concentrations at the usual doses IX-5 The answer is B (Chap 50 Wrenn, Am J Med 91:119, 1991.) A reasonable way to approach the diagnosis of metabolic acidosis is to separate patients into those with an increased anion gap and those with a normal anion gap (hyperchloremic acidosis) A calculation of these unmeasured anions consists of the sum of plasma bicarbonate and chloride minus the plasma sodium concentration (the normal value is to 16 mmol/L) Reasons for increased acid production include diabetic ketoacidosis, alcoholic ketoacidosis (as in this patient), starvation, lactic acidosis caused by circulatory failure, certain drugs and toxins, and poisoning resulting from salicylates, ethylene glycol, or methanol Finally, renal failure increases the anion gap because sulfate, phosphate, and organic acid ions are not excreted normally Normal anion gap acidosis is due to renal tubular dysfunction or colonic losses Since the ratio of -hydroxybutyrate to acetoacetate is high in alcoholic ketoacidosis, ketonemia can be missed by the routinely employed nitroprusside (Acetest) reagent, which detects acetoacetate but not -hydroxybutyrate Patients suffering from alcoholic ketoacidosis well on infusions of glucose and saline Neither insulin nor alkali is required in these situations unless the acidosis is extreme (bicarbonate Ͻ6 to mmol/L) IX-6 The answer is D (Chap 270) Development of advancing peripheral neuropathy is an indication for dialysis Delaying dialysis could allow the development of irreversible motor deficits, such as foot drop Prompt institution of dialysis, by contrast, usually prevents the progression of uremic peripheral neuropathy and may ameliorate early sensory defects No pharmacologic agent would be of significant benefit in the clinical situation described IX-7 The answer is A (Chap 270 Ifudu, N Engl J Med 339:1054 – 1062, 1998.) Renal osteodystrophy is a common complication of chronic renal disease, and the most common complication secondary to impaired renal production of 1,25(OH)2 D3 This leads to a decreased calcium absorption within the gut as well as impaired renal phosphate excretion The resulting hyperphosphatemia causes a secondary hyperparathyroidism Hyperparathyroidism is subsequently worsened by hypocalcemia, which is present because of the hyperphosphatemia and the decreased enzymatic conversion of 25-hydroxyvitamin D to 1,25(OH)2D3 Finally 1,25(OH)2D3 deficiency worsens hyperparathyroidism as the former is a direct inhibitor of parathyroid hormone secretion into the bone The resultant decreased serum calcium concentration leads to secondary hyperparathyroidism In addition, other causes of renal osteodystrophy include chronic metabolic acidosis, due to dissolution of bone buffers and decalcification, and the long-term administration of aluminum-containing antacids There is no significant loss of vitamin D or calcium associated with currently employed dialysis techniques, and the treatment of renal osteodystrophy often employs calcitriol IX-8 The answer is A (Chap 50) To offer optimal management to patients with acute renal failure, it is helpful to distinguish prerenal azotemia (generally managed with volume replacement or amelioration of cardiac dysfunction) from intrinsic renal dysfunction Sodium reabsorption, which is quite avid in prerenal azotemia, is impaired in intrinsic renal disease However, creatinine is reabsorbed less efficiently than sodium in both conditions Therefore, the fractional excretion of sodium is very helpful in distinguishing between these two etiologies of renal failure The fractional excretion of sodium is calculated by multiplying the urine sodium by the plasma creatinine, dividing this by the plasma sodium times the urine creatinine, and multiplying by 100 In this case the result is approximately 1.4, which suggests that impaired reabsorption of sodium is ongoing and that intrinsic renal failure is occurring Only about 15% of patients receiving nephrotoxins such as aminoglycosides or radiocontrast agents have renal failure associated with a fractional excretion of sodium of Ͻ1% and so an elevated value in this case points in the direction IX DISORDERS OF THE KIDNEY AND URINARY TRACT — ANSWERS 209 of nephrotoxic injury The other causes of acute renal failure listed here are all associated with prerenal azotemia and therefore with a more avid reabsorption of sodium than that described IX-9 The answer is D (Chap 274) One of the more common forms of asymptomatic urinary abnormalities is Berger’s disease, which may be a cause of recurrent hematuria of glomerular origin Such episodes of macroscopic hematuria and may be associated with minor flulike illnesses or vigorous exercise Skin rash, arthritis, and abdominal pain usually are absent, which tends to distinguish this entity from Henoch-Schoănlein purpura Occasionally patients develop a nephrotic or nephritic syndrome Serum IgA levels are increased in about 50% of all cases, though serum complement is normal Renal biopsy in these situations may reveal a spectrum of changes, though diffuse mesangial proliferation or focal and segmental proliferative glomerulonephritis is most common The essential feature of Berger’s disease is the finding of diffuse mesangial deposition of IgA on immunofluorescence microscopy IgG, C3, and properdin, but not C1q or C4, also may be found on this study Although the disease progresses slowly, about 50% of patients develop endstage renal failure within 25 years of the original presentation Men with hypertension and proteinemia (Ͼ1 g/d) are most likely to progress Except for a recent report suggesting that omega-3 fatty acids may play a role, specific therapy has not been useful However, glucocorticoids or antibiotics may reduce the frequency of episodic gross hematuria IgA deposition in the kidney and recurrent renal failure may occur in about 35% of those who receive a renal allograft Fortunately, such recurrent pathologic findings usually are not associated with loss of renal function IX-10 The answer is B (Chap 274) The characteristic pattern of focal (not all glomeruli) and segmental (not the entire glomerulus) glomerular scarring is shown The history and laboratory features are also consistent with this lesion: some associated hypertension, diminution in creatinine clearance, and a relatively inactive urine sediment The “nephropathy of obesity” may be associated with this lesion secondary to hyperfiltration; this condition may be more likely in obese patients with hypoxemia, obstructive sleep apnea, and rightsided heart failure Hypertensive nephrosclerosis exhibits more prominent vascular changes and patchy, ischemic, totally sclerosed glomeruli In addition, nephrosclerosis seldom is associated with nephrotic-range proteinuria Minimal-change disease usually is associated with symptomatic edema and normal-appearing glomeruli as demonstrated by light microscopy This patient’s presentation is consistent with that of membranous nephropathy, but the biopsy is not With membranous glomerular nephritis all glomeruli are uniformly involved with subepithelial dense deposits There are no features of crescentic glomerulonephritis present IX-11 The answer is D (Chap 274) Persons who have solid tumors and develop nephrotic syndrome usually have membranous glomerulopathy Diagnosis of the nephrotic syndrome may precede recognition of the primary tumor In several cases, tumor antigens have been discovered in the glomerular deposits; the nephrotic syndrome may remit after effective tumor therapy Patients with Hodgkin’s disease may develop nephrotic syndrome on the basis of minimal-change disease (diffuse epithelial foot process effacement on ultrastructural examination) IX-12 The answer is A (Chaps 277, 279) Cystine crystals appear as flat hexagonal plates and are found in association with cystine stones, which are caused by a hereditary deficiency in tubular cystine transport Struvite stones result from chronic urinary tract infection with Proteus spp These bacteria degrade urea to carbon dioxide and ammonia, which alkalinizes the urine, thereby favoring the formation of the insoluble triple salt MgNH4PO4 Struvite crystals can appear in the urine as rectangular prisms Patients with proteinuria resulting from albuminuria exhibit a sediment characteristic of the nephrotic syndrome with oval fat bodies Patients with intestinal malabsorption with concomitant steatorrhea, as in the case of a jejunoileal bypass done for obesity, may hyperabsorb oxalate 210 IX DISORDERS OF THE KIDNEY AND URINARY TRACT — ANSWERS and form calcium oxalate renal stones Calcium oxalate crystals appear bipyramidal or as biconcave ovals The sediment depicted here displays flat, square plates, which represent one of the several forms uric acid crystals manifest Hyperuricemia may accompany rapid cell turnover (as occurs in the rapid lysis of lymphomas with large tumor burdens after chemotherapy) In such settings aggressive hydration, the use of allopurinol, and urinary alkalinization may provide effective prophylaxis against uric acid nephropathy IX-13 The answer is E (Chap 277) A number of drugs may elicit an acute interstitial nephritis The classic offender is methicillin, although ampicillin, penicillin, cephalothin, thiazides, furosemide, and nonsteroidal anti-inflammatory drugs also have been associated with this problem Hematuria, fever, and skin rash may occur within to weeks of exposure to the drug Urinalysis reveals protein, pyuria, and eosinophiluria Ultrasonography discloses enlarged kidneys A biopsy (usually not necessary, since withdrawal of the offending drug leads to complete resolution) will reveal normal glomeruli but infiltration of the interstitium with polymorphonuclear leukocytes, lymphocytes, plasma cells, and eosinophils IX-14 The answer is D (Chap 275) A variety of diseases involve both pulmonary and renal (and often dermal) microvasculature and may present with either prominent pulmonary or renal manifestations When a firm diagnosis cannot be made serologically or by biopsy of skin or lesions of the upper respiratory tract, renal biopsy may be necessary In the case described in this question, the serologic findings, though not specific, are typical of Wegener’s granulomatosis, a diagnosis established by the renal biopsy report Granulomas are an uncommon microscopic finding in polyarteritis as well as in lupus nephritis and Henoch-Schoănlein purpura, though a spectrum of pathologic abnormalities may be seen in the latter two conditions Antineutrophil antibodies in the serum are highly suggestive of Wegener’s granulomatosis and other systemic vasculitides The renal biopsy in Goodpasture’s syndrome usually reveals linear immunoglobulin deposits IX-15 The answer is D (Chap 277 Bennett, DeBroe, N Engl J Med 320:1269 – 1271, 1989 DeBroe, Elseviers, N Engl J Med 338:446 – 452, 1998.) Patients with damage to renal papillae may be unable to excrete maximally concentrated urine owing to chronic tubular damage Moreover, the necrosed papillae can lead to the gradual development of renal failure Renal papillary necrosis has been classically associated with long-term analgesic abuse This is most commonly manifested by chronic use of acetaminophen or phenacetin In addition to analgesic abuse, renal papillary necrosis can also be caused by sickle cell anemia, diabetic nephropathy, or acute obstructive uropathy It is not associated with the presence of early-stage prostate cancer in the absence of prostatic hypertrophy In addition, patients can present with renal papillary necrosis after multiple episodes of pyelonephritis, but this is uncommon after a single uncomplicated episode Aspirin can potentiate the deleterious effects of chronic analgesic abuse by inhibiting the production of renal vasodilatory prostaglandins Ingestion of lead, such as that caused by lead leaching out from an unusual distilling apparatus, can lead to a nephropathy manifested by tubular atrophy and fibrosis of small renal arteries IX-16 The answer is E (Chap 275) The pathophysiology of nephrotoxic involvement by SLE is thought to be immune complex deposition Renal disease in SLE can range from mild abnormalities of the urinalysis to a fulminant inflammatory process that leads to progressive renal failure Renal biopsy findings in patients with SLE who have worsening renal function can range from minimal glomerular lesions to diffuse proliferative lupus glomerulonephritis and membranous lupus glomerulonephritis Patients with membranous lupus glomerulonephritis may be managed conservatively with therapy directed toward extrarenal manifestations By contrast, those with more extensive or proliferative glomerular lesions require a more aggressive approach using glucocorticoids (with or without another immunosuppressive agent, such as azathioprine or cyclophosphamide) However, little is gained by using immunosuppressant therapy in patients with advanced renal failure IX DISORDERS OF THE KIDNEY AND URINARY TRACT — ANSWERS 211 characterized by obliterative sclerosing lesions of the glomeruli If such patients have other indications for dialysis, such as systemic symptoms and hyperkalemia, they are best managed with dialysis followed by renal transplantation Measurement of serologic evidence of disease (e.g., double-stranded DNA autoantibodies or a decrease in serum complement components) may be helpful Patients with end-stage lupus nephritis can be managed successfully with hemodialysis Moreover, patients with SLE who have undergone renal allografting rarely experience recurrence of disease in the new kidney IX-17 The answer is B (Chap 272) In the first week after renal transplantation the differential diagnosis of graft dysfunction includes early rejection, hypovolemia, cyclosporine intoxication, acute tubular necrosis, urinary obstruction, and renal artery thrombosis Cyclosporine can mask many of the classic signs of rejection, such as fever and graft tenderness; renal biopsy often is needed to make the diagnosis However, renal ultrasonography should precede any manipulation to rule out mechanical outflow obstruction, as it should in any patient with acute deterioration of renal function IX-18 The answer is D (Chap 94) The most important differential diagnosis in the case presented is between a renal cell carcinoma and a benign cystic lesion Urinalysis may be normal in the presence of renal cell carcinoma, and urinary cytology is unfortunately of little value in the diagnosis of this lesion Ultrasonography will reveal whether the lesion is cystic If the lesion fulfills the criteria for a simple cyst (lack of internal echoes, smooth borders, through transmission) and the patient does not have hematuria, the cyst can be considered benign with a diagnostic accuracy of 97% If greater assurance is required or if there are changes on follow-up radiologic studies, needle aspiration should be carried out If the ultrasound appearance is not consistent with a simple cyst, contrast-enhanced CT scanning, the optimal test for the diagnosis and staging of renal cell carcinoma, should be performed IX-19 The answer is D (Chap 274 Hricik, Chung-Park, N Engl J Med 339:888 – 899, 1998.) The syndrome described is typical of rapidly progressive glomerulonephritis (GN) with rapid onset of acute renal failure in the setting of glomerular disease (manifested by red blood cell casts and proteinuria) The patient’s vomiting is consistent with the development of azotemia over a short time period Renal biopsy is highly recommended early in the course of such a disease to define the nature and severity of the glomerular lesion for both prognostic and therapeutic purposes The hallmark pathologic lesion associated with this clinical scenario is crescentic glomerulonephritis, the manifestation of extracapillary endothelial proliferation Such a finding on renal biopsy carries an ominous prognosis, especially if crescents are present in 70% of glomeruli or if glomerular filtration rate (GFR) is Ͻ5 mL/min Spontaneous resolution rarely occurs except in cases associated with an infectious cause, such as endocarditis and streptococcal disease Though controlled trials are lacking, it appears that high-dose methylprednisolone given parenterally (“pulse steroids”) can stave off the need for hemodialysis in some patients Plasmapheresis may benefit some patients, especially those who have antiglomerular basement antibodies IX-20 The answer is B (Chaps 94, 222, 280) Carcinoma of the bladder typically affects older men Transitional cell carcinoma is the most common histologic subtype and is associated with a more favorable prognosis than is adenocarcinoma or squamous carcinoma Squamous carcinomas occur more frequently in Egypt and are associated with S haematobium and not S mansoni, which typically causes an infection of the intestines or biliary tract Risk factors for carcinoma of the bladder include exposure to the aromatic amines, which result from cigarette smoke or products of the dye, rubber, and chemical industries, but it is not associated with positive family history or a prior diagnosis of renal carcinoma Chronic bladder irritation, such as that produced by the metabolites of cyclophosphamide or ifosfamide as well as by recurrent bladder stones or infections, also leads to a higher incidence of carcinoma of the bladder 212 IX DISORDERS OF THE KIDNEY AND URINARY TRACT — ANSWERS IX-21 The answer is C (Chaps 49, 276 Narins, Am J Med 72:496, 1982.) The evaluation of patients with hypokalemia should first include a consideration of redistribution of body potassium into cells as occurs in alkalosis, 2 -agonist excess with refeeding syndrome and/ or insulin therapy, vitamin B12 therapy, patients with pernicious anemia, and periodic paralysis In periodic paralysis serum bicarbonate is normal If the patient is hypertensive and plasma renin is elevated, renovascular hypertension or a renin-secreting tumor (including Wilms’) must be considered and appropriate imaging studies must be carried out If plasma renin levels are low, mineralocorticoid effect may be high, due either to endogenous hormone (glucocorticoid overproduction or aldosterone overproduction as in Conn’s syndrome) or to exogenous agents (licorice or steroids) In a normotensive patient a high serum bicarbonate excludes renal tubular acidosis High urine chloride excretion makes gastrointestinal losses less likely and implies primary renal potassium loss as might be seen in diuretic abuse (ruled out by the urine screen) or Bartter’s syndrome In Bartter’s syndrome, hyperplasia of the granular cells of the juxtaglomerular apparatus leads to high renin levels and secondary aldosterone elevations Such hyperplasia appears to be secondary to chronic volume depletion caused by a hereditary (autosomal recessive) defect that interferes with salt reabsorption in the thick ascending loop of Henle Chronic potassium depletion, which frequently initially presents in childhood, leads to polyuria and weakness IX-22 The answer is D (Chap 275 Hricik, Chung-Park, N Engl J Med 339:888 – 899, 1998.) Cryoglobulinemia with renal involvement is associated with hypocomplementemia in the majority of cases In addition it has been well recognized that hepatitis C is often associated with cryoglobulinemia Diffuse proliferative lupus nephritis (WHO class IV) is the most aggressive form of the disease and is also associated with hypocomplementemia Early in the course of postinfectious glomerulonephritis, immune complex deposition is in full force and serum complements are low Henoch-Schoănlein purpura, the systemic manifestation of IgA nephropathy, is not associated with hypocomplementemia Other causes of hypocomplementemic glomerulonephritis are glomerulonephritis associated with bacterial endocarditis or other chronic infections as well as membranoproliferative glomerulonephritis IX-23 The answer is E (Chap 269) Years before dialysis was routinely available, it was well established that protein restriction (prescribed or self-imposed) could alleviate some of the symptoms of uremia; unfortunately, prolonged protein restriction led to the development of malnutrition and its associated complications In the setting of chronic renal failure, a number of clinical studies have suggested that modest protein restriction may slow the rate of progression of renal failure, particularly in patients with glomerular disease and daily protein excretion rates Ͼ1 g/d There are insufficient data in the setting of acute renal failure to adequately assess the importance of protein intake However, in view of the hypercatabolism that accompanies many cases of acute renal failure, most practitioners provide adequate protein to patients (e.g., Ն1.0 to 1.2 g protein per kg per day) and provide dialysis if uremia ensues There are no set laboratory “cutoffs” (BUN Ͼ100) that indicate the need for dialysis IX-24 The answer is D (Chap 50 Adrogue, Madias, N Engl J Med 338:26 – 34, 1998.) Ingestion of ethylene glycol can produce severe, high-anion-gap metabolic acidosis, caused by the accumulation of toxic metabolites Furthermore, the degree of acidosis is disproportionate to the degree of renal insufficiency Ethylene glycol intoxication often requires a large amount of alkali to correct the severe acidemia Additional measures include gastric lavage, oral charcoal, and intravenous or oral ethanol Ethanol has a higher affinity for alcohol dehydrogenase and will therefore inhibit the generation of toxic metabolites from the ethylene glycol In severe cases hemodyalisis is required In addition, forced diuresis can prevent acute renal failure in some patients with ethylene glycol intoxication IX-25 The answer is B (Chap 50 Adrogue, Madias, N Engl J Med 338:26 – 34, 1998.) This represents a respiratory alkalosis with a combined metabolic acidosis This is typical of salicylate toxicity Salicylate intoxication can result in respiratory alkalosis, mixed res- IX DISORDERS OF THE KIDNEY AND URINARY TRACT — ANSWERS 213 piratory alkalosis and metabolic acidosis, or, less commonly, a simple metabolic acidosis Respiratory alkalosis is caused by direct stimulation of the respiratory center by salicylate The accumulation of lactic acid and ketoacids leads to the concomitant metabolic acidosis The severity of the neurologic manifestations largely depends on the concentration of salicylate in the central nervous system Therapy is directed at limiting further drug absorption by administering activated charcoal and promoting the exit of salicylate from the central nervous system This can be accomplished by alkalinizing the serum, typically by the addition of intravenous fluids with sodium bicarbonate with the goal of raising the serum pH to between 7.45 and 7.50 Increasing the GFR will also enhance salicylate excretion Hemodialysis is reserved for severe cases, especially those involving fulminant renal failure IX-26 The answer is B (Chap 49 Beck, N Engl J Med 301:528 – 530, 1979.) Hyponatremia can be broadly categorized as hypovolemic, euvolemic, or hypervolemic Hepatic cirrhosis in this case is unlikely because of the absence of edema Gastrointestinal fluid loss is unlikely because of normal blood pressure without orthostasis Furthermore, depending on whether the fluid loss is upper (vomiting with resultant alkalosis) or lower (diarrhea with resultant acidosis), it often is accompanied by a disturbance in acid-base balance Addison’s disease is possible, although it often is associated with orthostasis, some degree of hypotension, and hyperkalemia (due to aldosterone deficiency) The uric acid can be very helpful in the differential diagnosis of hyponatremia It is typically elevated in patients with congestive heart failure and renal failure, two other important causes of hyponatremia, and tends to be quite low in patients with SIADH IX-27 The answer is C (Chap 271) Mycobacterial peritonitis and fungal peritonitis are relatively rare but important problems, particularly in patients who receive repeated courses of antibacterial therapy for suspected or documented bacterial peritonitis Dialysis disequilibrium is a syndrome characterized by headache, confusion, and occasionally seizures; it is seen in association with the excessively rapid correction of uremia with dialysis (usually hemodialysis) It is thought to be related to cerebral edema caused by the rapid removal of extracellular solute (urea) with resultant osmotic transfer of water into the cells Peritoneal carcinomatosis (from ovarian or widespread gastrointestinal carcinoma) is possible in this case, although there is no history of cancer IX-28 The answer is E (Chap 50) Hypokalemia impairs the renal excretion of ammonium, which thereby results in hyperammonemia in cases of hepatic failure The use of loop diuretics promotes kaliuresis and therefore may lead to hyperammonemia The alternative choices typically improve hyperammonemia in selected cases IX-29 The answer is E (Chap 277) Nephrocalcinosis is an uncommon cause of interstitial renal disease associated with a variety of metabolic disorders The routine (with or after a meal) use of calcium-based phosphate binders rarely results in hypercalcemia, although injudicious use may lead to complications Crohn’s disease and other abnormalities of ileal fat absorption may cause nephrocalcinosis because of excessive absorption of dietary oxalate and calcium oxalate nephrolithiasis IX-30 The answer is E (Chap 274 Orth, Ritz, N Engl J Med 338:1202 – 1211, 1998.) The patient has nephritic-range proteinuria as documented by a 24-h urine collection of Ͼ3.5g/ 1.73 m2 Such patients typically have hypoalbuminemia, peripheral edema, and hyperlipidemia as well as lipiduria It is thought that the hypoalbuminemia is further compounded by increased renal catabolism The physiology of the edema formation in nephrotic syndrome is less well understood; it is thought that the presence of hypoalbuminemia results in decreased intravascular oncotic pressure leading to leakage of extracellular fluid from blood into the interstitial fluid As a result, the intravascular volume falls, thereby stimulating activation of the renin-angiotensin-aldosterone axis and consequently increasing the release of vasopressin (antidiuretic hormone) In addition, there is suppression of the re- 214 IX DISORDERS OF THE KIDNEY AND URINARY TRACT — ANSWERS lease of atrial natriuretic peptide, and this suppression contributes to the primary renal salt and water retention that contributes to the formation of edema Patients with nephroticrange proteinuria often have elevated serum lipid levels as a consequence of increased hepatic lipoprotein synthesis Both LDL-cholesterol and total cholesterol are increased in the majority of patients, and, though not proven conclusively, this state of hyperlipidemia may accelerate atherosclerosis as well as the progression of further renal disease Patients often present with a hypercoagulable state due to increased urinary loss of antithrombin III as well as altered levels or activity of proteins C and S There is also impaired fibrinolysis As a consequence of these alterations, patients can develop spontaneous peripheral arterial or venous thrombosis, renal vein thrombosis, and pulmonary embolism Although IgA GN is the most common glomerulopathy, it only occasionally causes nephrotic syndrome The most common cause of nephrotic syndrome in adults is membranous GN which represents approximately 40% of all cases The most common cause of nephritic syndrome in children is minimal-change glomerulopathy Membranous GN can be linked to neoplasms — either carcinoma, sarcoma, lymphoma, or more rarely leukemia This possibility should be specifically considered in older patients who present with new-onset nephrotic syndrome Other metabolic abnormalities include hypocalcemia and secondary hyperparathyroidism as a consequence of vitamin D deficiency due to enhanced urinary excretion of cholecalciferol-binding protein In addition, loss of thyroxin-binding globulin often results in depressed thyroxin levels There is also an increased susceptibility to infection, which may affect low levels of IgG urinary loss as well as increased catabolism IX-31 The answer is D (Chap 50) The key element is the anion gap, calculated as (Na ϩ K) Ϫ Cl (normal to 12) The anion gap is 32 in this case Causes of high-aniongap acidosis include diabetic or alcoholic ketoacidosis, renal failure, and the excessive ingestion of salicylates, methanol, ethanol, or ethylene glycol The clues here are the negative Acetest (making alcoholic and/or diabetic ketoacidosis less likely) and the presence of calcium oxylate crystals (oxylate is a by-product of ethylene glycol) Hemodialysis should be provided in these cases of toxic ingestion, since the products are water-soluble and can quickly cause damage to the CNS if not promptly removed IX-32 The answer is D (Chap 269) Cholesterol embolization (also known as atheroembolic renal disease) is characterized by pyuria, progressive renal failure (usually nonoliguric), and associated organ dysfunction (including bowel, pancreas, and CNS) Hypocomplementemia and eosinophiluria also may be seen The urinalysis is not compatible with acute tubular necrosis because of the absence of granular casts IX-33 The answer is C (Chap 274 Joven et al., N Engl J Med, 323:579 – 584, 1990.) Dyslipidemia is present in the vast majority of patients with nephrotic syndrome and typically is characterized by a relatively selective increase in LDL cholesterol There is evidence of accelerated atherosclerosis in these patients Although there appears to be an increased risk of myositis in patients with renal failure treated with lipid-lowering agents, the risk is relatively low (far below 20%) Combination therapy (e.g., an HMG-CoA reductase inhibitor and a fibric acid derivative) should be used with caution IX-34 The answer is C (Chaps 270, 273 Maschio et al., N Engl J Med 334:939 – 945, 1996.) Evidence continues to accumulate that ACE inhibition can slow the progression of chronic renal insufficiency in a variety of disease states In general, patients with protein excretion rates g/d tend to derive the greatest benefit For reasons that are not entirely clear, patients with ADPKD tend not to benefit from this therapy (and not appear to benefit from a low-protein diet) IX-35 The answer is D (Chap 276 Gabow, N Engl J Med 329:332 – 342, 1993.) Autosomal dominant polycystic kidney disease is one of the most common hereditary disorders Spon- IX DISORDERS OF THE KIDNEY AND URINARY TRACT — ANSWERS 215 taneous mutations occur but account for only 10% or fewer of all cases The majority of cases are linked to a causative gene located on the short arm of chromosome 16, referred to as ADPKD1 A second causative gene (ADPKD2) has not been identified but seems to be at a locus distinct from ADPKD1, which appears to be the cause of the gene in Ն90% of families in the white population A rare syndrome known as autosomal recessive polycystic kidney disease affects between in 10,000 and in 40,000 individuals in the United States, and the causative gene has been localized to chromosome Patients are typically diagnosed during the first year of life, presenting with bilateral abdominal masses Death in the neonatal period is common due to pulmonary hypoplasia The most common complication of polycystic kidney disease is pain secondary to large cystic kidneys; in addition, most patients are hypertensive In addition to the chronic pain, acute pain may represent cystic hemorrhage, infection, or, less commonly, a renal stone Proteinuria occurs in about 1/3 of patients but is typically mild, with Ͻ1 g per 24-h collection The rare patient with nephrotic-range proteinuria often has superimposed glomerular disease Certain endocrine functions of the kidney also appear to be altered Renal secretion seems to be elevated and likely causes a predilection for hypertension Although polycythemia is rare, the hematocrit seems to be better maintained in patients with renal failure due to ADPKD than in patients with other forms of renal disease Extrarenal complications are common and often include hepatic and pancreatic cysts; and cardiac valvular abnormalities are also noted The principal noncystic gastrointestinal manifestation is the development of colonic diverticular disease, which has been reported in as many as 82% of patients with ADPKD The most devastating extrarenal manifestation, however, is the development of intracranial saccular aneurysms, often called berry aneurysms These are generally accepted to be a manifestation of polycystic kidney disease, but occur with an unknown frequency IX-36 The answer is C (Chap 49 Gennari, N Engl J Med 339:451 – 458, 1998.) A wide range of drugs have been implicated in causing hypokalemia as a significant side effect These drugs include the 2 sympathomimetic agonists of many drugs including decongestants, bronchial dilators, and inhibitors of uterine contraction The hypokalemia caused by these drugs is sustained for up to h Intestinal ingestion of excess amounts of pseudoephedrine can cause severe hypokalemia Theophylline and caffeine are not sympathomimetic drugs; however, these agents stimulate the release of sympathetic amines, which may also increase the Naϩ, Kϩ-ATPase activity and thereby lead to hypokalemia Severe hypokalemia is an almost invariable feature of acute theophylline toxicity Although calcium channel blockers increase cellular uptake of potassium in experimental studies, these drugs typically have no effect on serum potassium concentration at the usual doses However, ingestion of large amounts of verapamil can cause hypokalemia The most common cause of drug-induced hypokalemia is diuretic therapy Both thiazide and loop diuretics block chloride-associated sodium reabsorption As a result of the increased delivery of sodium to the collecting tubules, there is a favorable electrochemical gradient leading to increased potassium secretion Amphotericin B causes renal potassium wasting through the inhibition of the secretion of hydrogen ions by the collecting duct In addition, severe magnesium depletion is another manifestation of amphotericin B usage IX-37 The answer is B (Chap 48 Resnick, N Engl J Med 320:1, 1989.) The force for bladder emptying is provided by the detrusor muscle, which is innervated by parasympathetic outflow from the sacral plexus The involuntary control that prevents automatic bladder emptying emanates from sympathetic innervation of the bladder outlet A sacral spinal reflex arc mediates automatic detrusor contraction when the intravesical pressure exceeds 20 cmH2O (a volume of 400 mL) unless it is inhibited by cortical centers via the reticulospinal tracts Diseases leading to damage of inhibitory neural pathways in the brain 216 IX DISORDERS OF THE KIDNEY AND URINARY TRACT — ANSWERS or spinal cord, such as multiple strokes, Alzheimer’s disease, brain tumors, and normalpressure hydrocephalus, create detrusor instability In this situation the bladder will empty automatically before it is filled owing to unchecked operation of the spinal reflex arc By contrast, conditions leading to chronic overflow incontinence caused by obstruction at the bladder neck or a hypotonic bladder caused by autonomic neuropathy can result in hydronephrosis and impaired renal function The most common example of outflow obstruction is benign prostatic hypertrophy Examples of conditions in which autonomic peripheral neuropathy can lead to overflow incontinence include diabetes mellitus, hypothyroidism, uremia, collagen vascular diseases, Guillain-Barre´ syndrome, and exposure to certain toxins (including alcohol) Cholinergic agents such as bethanechol sometimes can aid bladder emptying in those with overflow incontinence IX-38 The answer is E (Chaps 49, 276 Gennari, N Engl J Med 339:451 – 458, 1998.) Mutation of the -hydroxylase gene is a common cause of congenital adrenal hyperplasia This is a hereditary disease often leading to mineralo- or glucocorticoid excess and subsequent hypokalemia with the development of metabolic alkolosis In addition, Liddle’s syndrome can lead to an apparent mineralocorticoid excess syndrome Both Bartter’s and Gitelman’s syndromes are genetic mutations that inactivate or impede the activity of the chloride-associated Naϩ transporter within the loop of Henle (Bartter’s) or the early distal tubule (Gitelman’s) This causes a metabolic alkalosis with hypokalemia The presence of hypertension is not a typical finding with the above two genetic disorders ADPKD often leads to chronic renal insufficiency with the development of hyperkalemia IX-39 The answer is A (Chap 274 Hricik et al., N Engl J Med 339:888 – 899, 1998.) Studies during epidemics of streptococcal disease have shown that the latent period between symptomatic pharyngitis and the appearance of PSGN is to 10 days The latent period after cutaneous infection is more difficult to establish but appears to be longer Persons who receive early antimicrobial therapy for streptococcal infection may develop glomerulonephritis but not mount the immune response to the streptococcal enzymes (e.g., streptolysin O) on which laboratory testing for antecedent streptococcal infection is based Antimicrobial therapy is recommended for persons who have acute glomerulonephritis and continuing streptococcal infection Long-term prophylaxis, however, is unwarranted because affected persons are not markedly predisposed to recurrent episodes of PSGN For unknown reasons, PSGN leads to permanent, progressive renal insufficiency more often in adults than in children IX-40 The answer is E (Chap 274 Hricik, Chung-Park, N Engl J Med 339:888 – 899, 1998.) This patient presents with characteristic symptoms and findings of PSGN PSGN is an acute reversible disease and is characterized by spontaneous recovery in the vast majority of patients The typical urinalysis has a urinary sediment that is nephritic in nature, displaying dysmorphic red blood cells, red cell casts, leukocytes, occasional leukocyte casts, and proteinuria However, fewer than 5% of patients will actually develop nephrotic-range proteinuria The serum creatinine is typically elevated in the range of 88 to 177 mol/L (1 to mg/dL), and compliment levels such as C3 and CH50 are typically depressed in Ͼ90% of cases The vast majority of patients will have transient hypergammaglobulinemia as well as mixed cryoglobulinemia Most patients will present with gross hematuria, headache, and generalized symptoms of anorexia, nausea, vomiting, and malaise Physical examination may reveal hypervolemia, edema, and hypertension The edema probably results from increased sodium retention due to the decrease in the GFR Swelling of the renal capsule can cause occasional flank or back pain Diagnosis is made in Ͼ90% of patients with circulating antibodies against streptococcal enzymes such as antistreptolysin O (ASO), anti-DNAse B, and anti-streptokinase (ASKase) Electron microscopy often reveals the presence of electron-dense immune deposits in the subendothelial, subepithelial, and mesangial areas More extensive immunoglobulin deposition throughout the glomerular capillary wall is associated with a worse prognosis IX DISORDERS OF THE KIDNEY AND URINARY TRACT — ANSWERS 217 IX-41 The answer is B (Chaps 273, 274 Hricik, Chung-Park, N Engl J Med 339:888 – 899, 1998.) The glomerular diseases can be classified according to the presence or absence of proliferative changes In the primary renal disorders, proliferative changes are common in IgA nephropathy, IgM nephropathy, and mesangioproliferative glomerulonephritis as well as in membranoproliferative glomerulonephritis Proliferative changes are not seen in focal segmented glomerulosclerosis, membranous glomerulopathy, minimal-change disease, or thin basement membrane disease Glomerular diseases can also be caused by systemic disease such as lupus nephritis or PSGN, the glomerulonephritis associated with either hepatitis B or C infection All of these are associated with proliferative changes within the glomerular capsule In addition, the glomerular diseases associated with Wegeners granulomatosis, polyarteritis nodosa, or Henoch-Schoănlein purpura are also associated with proliferative changes Diabetes mellitus is a major cause of renal morbidity and mortality Diabetic glomerulosclerosis is associated with morphologic changes that include capillary basement membrane thickening, diffuse diabetic glomerulosclerosis, and nodular glomerulosclerosis The typical lesions in nodular glomerulosclerosis, or Kimmelstiel-Wilson syndrome, take the form of ovoid spherical hyaline deposits within the periphery of the glomeruli Cellular proliferative changes are not typical of diabetic glomerular nephropathy IX-42 The answer is C (Chap 49 Adrogue, Madias, N Engl J Med 342:1493 – 1499, 2000.) This 87-year-old man presents with a hypernatremia caused by pure water depletion, likely due to insensible losses The most appropriate infusion would be replenishment of free water with 5% dextrose The estimated total-body water volume is 50% of his weight, which is 36 L (0.5 ϫ 72) The retention of L of 5% dextrose will reduce the serum sodium concentration by approximately 4.4 mmol/L [(0 Ϫ 164) Ϭ (36ϩ1) ϭ Ϫ4.4 mmol/ L] The goal of treatment is to reduce the serum sodium concentration slowly This can be achieved by lowering the serum sodium by 10 mmol/L over a 24-h period Therefore, 2.3 L of 5% dextrose (10 Ϭ 4.4) is required In addition, 1.5 L is added to compensate for average obligatory water losses over the 24-h period; therefore, approximately 3.8 L will be administered over a 24-h period, which corresponds to a rate of 160 mL/h In addition, the serum glucose concentration will need to be closely monitored and insulin therapy initiated at the first indication of hyperglycemia Hyperglycemia could significantly aggravate the patient’s free water balance Also, close monitoring of the patient’s clinical status and laboratory values will be required during the first to 24 h IX-43 The answer is A (Chap 277) Glycosuria (with a normal blood glucose concentration), proteinuria, and hyperchloremic acidosis constitute evidence of proximal renal tubular dysfunction [type II renal tubular acidosis (RTA)] Frequent nocturia, presumably resulting from an impaired ability to concentrate urine, also suggests renal insufficiency caused by tubulointerstitial disease Multiple myeloma may present in this manner, and similar renal abnormalities may be associated with analgesic abuse and Sjoăgrens syndrome The ndings in this case are not characteristic of primary glomerular diseases, such as diabetic nephropathy, or membranous glomerulonephritis IX-44 The answer is B (Chaps 276, 277, 279) This patient has recurrent renal calculi and nephrocalcinosis and has a normal serum calcium level The serum electrolyte pattern is typical of distal (type I) RTA and not proximal (type II) RTA There is evidence of renal potassium wasting and hyperchloremic metabolic acidosis with the presence of alkaline urine Nephrocalcinosis and distal RTA are consistent with hypervitaminosis D, medullary sponge kidney, hyperparathyroidism, sarcoidosis, or multiple myeloma However, in all these conditions except medullary sponge kidney, there is an increased serum calcium concentration responsible for nephrocalcinosis Intravenous pyelography is abnormal in patients with medullary sponge kidney Intravenous pyelography shows a typical “paintbrush” pattern in the renal papillae, with tiny papillary cysts that contain calcium deposits Although medullary sponge kidney is usually sporadic, some cases have an apparent autosomal dominant inheritance pattern 218 IX DISORDERS OF THE KIDNEY AND URINARY TRACT — ANSWERS IX-45 The answer is B (Chap 272) Living volunteer donors should be healthy, have normal renal arteries, and have the same blood group as the recipient The one exception to the last rule occurs in the case of a type O donor, who can donate to a recipient with any blood group, since no endothelial antigens in the ABO system are present to engender rejection The donor and recipient should be as closely HLA-matched as possible, and the mixed lymphocyte response (MLR) should be absent DNA typing techniques have obviated the need for MLR testing in related donors In the case of cadaveric donor kidneys, there is a direct relationship between the degree of HLA incompatibility and graft loss For example, there is a projected 10-year graft survival rate of 27% if there are five HLA mismatches but a 52% rate if there is only one mismatch Chronic rejection frequently is due to nephrosclerosis, which often is initially characterized by proliferation of the intima (with eventual fibrosis) in the renal vasculature Prophylaxis against rejection includes the use of cyclosporine, which inhibits production of the immunostimulatory molecule IL-2 by helper-inducer T lymphocytes (CD4ϩ) and the mercaptopurine analogue azathioprine Azathioprine is metabolized by the purine degradative pathway to uric acid via the action of xanthine oxidase Thus, coadministration of the xanthine oxidase inhibitor allopurinol could interfere with drug catabolism and lead to a dangerously toxic effect of a given dose of azathioprine IX-46 The answer is B (Chap 271 Pastan, Bailey, N Engl J Med 338:1428 – 1437, 1998.) Peritonitis is the most common serious complication of peritoneal dialysis Patients typically present with abdominal pain, fever, and a cloudy peritoneal dialysate Persistent or recurrent peritonitis may require the removal of the catheter Further complications include losses of amino acids as well as albumin, which may be as much as to 15 g/d In addition, patients can absorb glucose through the peritoneal dialysate, resulting in hyperglycemia not hypoglycemia The resulting hyperglycemia can cause a hypertriglyceridemia, especially in patients with diabetes mellitus Leakage of the dialysate fluid into the pleural space can also occur and can be diagnosed by analysis of the pleural fluid, which typically has an elevated glucose concentration Rapid fluid shifts are uncommon with peritoneal dialysis, and this approach may be favored for patients with congestive heart failure or unstable angina IX-47 The answer is E (Chaps 275, 317 Jennette, Falk, N Engl J Med 337:1512 – 1523, 1997.) The patient in question has Churg-Strauss syndrome Churg-Strauss syndrome has three phases: allergic rhinitis with asthma and eosinophilia; eosinophilic infiltrative disease such as eosinophilic pneumonia; and systemic small-vessel vasculitis The vasculitic phase usually develops within years of onset of asthma Approximately 70% of patients with Churg-Strauss syndrome have ANCA The antibodies are usually perinuclear and not cytoplasmic, consistent with antimyeloperoxidase (MPO-ANCA) antibodies The cytoplasmic ANCA antiproteinase-3 is typically found in Wegner’s granulomatosis Many patients with Churg-Strauss syndrome develop an eosinophilic pneumonia or evidence of eosinophilic infiltrative disease In addition, patients can develop gastroenteritis, coronary arteritis, and myocarditis, which are the principal causes of morbidity and mortality, resulting in over 50% of deaths In addition, patients often complain of frequent neuropathy IX-48 The answer is C (Chap 49 Adrogue, Madias, N Engl J Med 342:1581 – 1589, 2000.) There is no definitive consensus on the optimal treatment of patients with symptomatic hyponatremia The correction of the hyponatremia should be sufficient to reverse the clinical manifestations associated with it In this situation, the patient is obtunded and confused with significant neurologic compromise Even seizures can be induced by hyponatremia and can be stopped by rapid increases of the serum sodium However, one must be cautious to avoid the catastrophic development of osmotic demyelination In this situation the patient’s total-body water is 34 L (0.5 ϫ 68) The planned treatment should increase the serum sodium by mmol/L per hour, and this is best accomplished with hypertonic saline A liter of 3% saline will increase the serum sodium by 11.4 mmol/L [(513 Ϫ 114) Ϭ IX DISORDERS OF THE KIDNEY AND URINARY TRACT — ANSWERS 219 (34 ϩ 1) ϭ 11.4] A rise of mmol/L over h corresponds to approximately 0.27 L (3 Ϭ 11.4), or approximately 90 mL/h IX-49 The answer is C (Chap 270 Brater, N Engl J Med 339:387 – 395, 1998.) Several mechanisms result in decreased diuretic response in patients with nephrotic syndrome These include diminished nephron response to the diuretics as well as binding of the diuretic to urinary protein However, in most patients with nephrotic syndrome as well as those with cirrhosis, renal tubular secretion of furosemide is normal, unless the patient has significant renal insufficiency In addition, patients with nephrotic syndrome have an increase of both proximal and distal reabsorption of sodium These factors can be overcome by higher doses and more frequent administration of loop diuretics In addition, the addition of a thiazide diuretic may also enhance efficacy If these strategies fail and the patient has severe hypoalbuminemia [Ͻ20 g/L (2g/dL)], a trial of a loop diuretic with albumin can be tried IX-50 The answer is C (Chap 271 Pastan, Bailey, N Engl J Med 338:1428 – 1437, 1998.) Hypotension is the most common acute complication after hemodialysis Numerous factors appear to increase the risk of hypotension, including excessive ultrafiltration with inadequate compensatory vascular filling In addition, patients often have impaired vasoactive or autonomic responses, especially those patients with long-standing diabetes mellitus In addition, patients may also have impaired cardiac reserve, and most patients are on significant hypertensive therapy, which in the setting of increased ultrafiltration may lead to a more rapid precipitation of hypotension Although less common, food ingestion during or shortly after hemodialysis can also lead to hypotension secondary to vascular redistribution The temperature of the dialysate seems also to be important in the regulation of blood pressure Temperatures of 37ЊC may cause heat retention and vasodilation Low temperature dialysates often cause an increase in vascular resistance Hyperkalemia, hypokalemia, or hypocalcemia, but not hyperphosphatemia, are associated with hypotension IX-51 The answer is A (Chap 279 Preminger, Semin Nephrol 12:200 – 216, 1992.) The differential diagnosis of calcium renal calculi is broad and includes idiopathic hypercalciuria Calcareous calculi represent approximately 75% of all renal stones; the remaining 25% of the renal calculi are noncalcareous and are composed of either uric acid struvite or cystine Calcareous calculi are composed of either calcium oxalate or calcium phosphate The causes of calcareous stone formation include hypercalciuria, hyperoxaluria, hyperuricosuria, hypomagnesuria, and hypocitruria The association of hypercalciuria with recurrent calcium nephrolithiasis has long been recognized Of the variety of causes of hypercalciuria, the most common is absorptive hypercalciuria This results in an increase in intestinal calcium absorption and therefore an increased filtered load The exact cause of the hyperabsorption is unknown, and it is thought that this process develops through a vitamin D – independent pathway Most patients with this process have a normal serum calcium level, a normal serum parathyroid level, and a normal fasting 24-h urinary calcium level Primary hyperparathyroidism can be diagnosed from an elevated serum calcium level with an elevated serum parathyroid level In addition, patients typically have elevated fasting 24-h urinary calcium levels Normal serum calcium and a normal 24-h urinary calcium make the diagnosis of primary hyperparathyroidism unlikely Hyperoxaluria is typically secondary to inflammatory bowel disease or dietary overindulgence in oxalaterich foods, but it may also be caused by an excessive amount of vitamin C ingestion This is thought to cause stone formation because of reduced urinary output due to fluid losses from the intestinal tract The resultant hypocitruria caused by hypokalemia as well as metabolic acidosis in addition to low urinary magnesium concentrations may also cause stone formation Hypocitruria is a common finding but remains uncommon as a sole etiologic cause of recurrent nephrolithiasis The use of thiazide diuretics decreases the urinary calcium excretion and therefore decreases the frequency of calcium stone formation This page intentionally left blank ... used drugs 15 TH HARRISON' S EDITION P R I N C I P L E S OF INTERNAL MEDICINE SELF-ASSESSMENT AND BOARD REVIEW For use with the 15 th edition of HARRISON S PRINCIPLES OF INTERNAL MEDICINE EDITED... Isochromosome X II -11 Which of the following is an example of a balanced karyotype? (A) (B) (C) (D) (E) 46, X, i(Xq) 46, X, X, 14 , ϩt (14 ; 21) (p 11; q 11) 46X, Y, Ϫ5, ϩder5 (5 ;11 ) (q 21; q 21) mat 46, X,... general internal medicine This book consists of multiple-choice questions that (1) are representative of the major areas covered in Harrison s Principles of Internal Medicine, 15 th ed., and (2)