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Pathology • US:MLEStep ·1 Pathology Lecture Notes. 2006-2007 Edition 'USMLE is a joint program of the Federation of State Medical Boards of the United States, Inc. and the National Board of Medical Examiners. ,~r-.,,·, " j. ;1 ',-: ~.'. ~" " " ©2006 Kaplan, Inc, - ":~ All tights r~seryed" No part <;>fthisbook may be reproduced in any form, by photostat, midofiliri, xe1=ographyor ariy othermeans, or incorporated into any information retrieval system, electronic or mechanical, without the written permission of Kaplan, Inc. Not for resale. Author John Barone, M.D. Anatomic and Clinical Pathologist Beverly Hills, CA Contributors Director of Curriculum ." Earl J. Brown, M.D. Sonia Reichert, M.D. Associate Professor Department of Pathology Editorial Director James H. Quillen College of Medicine Kathlyn McGreevy East Tennessee State University Chief of Hematopathology Pathology and Laboratory Medicine Service Production Artist/Manager James H. Quillen Veterans Affairs Medical Center Michael Wolff Mountain Home, TN Medical Illustrators William DePond, M.D. Christine Schaar Associate Professor, University of Missouri/Kansas City Lisa DiPetto Vice Chairman, Department of Pathology Truman Medical Center Kansas City, MO Production Editor William Ng Pier Luigi Di Patre, M.D., Ph.D. Neuropathologist Cover Design Institute of Neuropathology Joanna Myllo University Hospital of Zurich Zurich, Switzerland Cover Art Elissa Levy,M.D. Christine Schaar Kaplan Medical Michael S. Manley, M.D. Department of Neurosciences University of California, San Diego Director, Medical Curriculum Kaplan Medical Nancy Standler, M.D., Ph.D. Department of Pathology W O. Moss Regional Medical Center Louisiana State University ,I • ~1 '" j , Contents Preface vii Chapter 1: Fundamentals of Pathology 1 Chapter 2: Cellular Injury and Adaptation 5 Chapter 3: Inflammation ················· 17 Chapter 4: Wound Healing and Repair 27 Chapter 5: Circulatory Pathology 31 Chapter 6: Genetic Disorders 47 Chapter 7: Immunopathology ············ 63 Chapter 8: Amyloidosis 73 Chapter 9: The Fundamentals of Neoplasia Tl Chapter 10: Environment and Lifestyle-Related Pathology . .. 89 Chapter 11: Vascular Pathology. .. 99 Chapter 12: Cardiac Pathology. .. 113 Chapter 13: Respiratory System Pathology 127 Chapter 14: Renal Pathology 143 Chapter 15: Gastrointestinal Tract Pathology 157 Chapter 16: Pancreatic Pathology . .. 175 Chapter 17: Gallbladder and Biliary Tract Pathology 183 mvulcaUP~~. '. v Chapter 18: Liver Pathology 187 Chapter 19: Red Blood Cell Pathology 199 Chapter 20: White Blood Cell Pathology. 213 Chapter 21: Myeloid Neoplasms 225 Chapter 22: Female Genital Pathology 231 Chapter 23: Breast Pathology 241 Chapter 24: Male Pathology 247 Chapter 25: Endocrine Pathology 255 Chapter 26: Bone Pathology 267 Chapter 27: Joint Pathology 281 Chapter 28: Skeletal Muscle and Peripheral Nerve Pathology 289 Chapter 29: Central Nervous System Pathology 295 Chapter 30: Skin Pathology 317 Index 327 UP~'!I. I vi mvulC8 Preface These seven volumes of Lecture Notes represent a yearlong effort on the part of the Kaplan Medical faculty to update our curriculum to reflect the most-likely-to-be-tested material on the current USMLE Step 1 exam. Please note that these are Lecture Notes, not review books. The Notes were designed to be accompanied by faculty lectures-live, on video, or on the web. Reading these Notes without accessing the accompanying lectures is not an effective way to review for the USMLE. To maximize the effectiveness of these Notes, annotate them as you listen to lectures. To facilitate this process, we've created wide, blank margins. While these margins are occasionally punctuated by faculty high-yield "margin notes;' they are, for the most part, left blank for your notations. Many students find that previewing the Notes prior to the lecture is a very effective way to prepare for class. This allows you to anticipate the areas where you'll need to pay particular attention. It also affords you the opportunity to map out how the information is going to be presented and what sort of study aids (charts, diagrams, etc.) you might want to add. This strategy works regardless of whether you're attending a live lecture or watching one on video or the web. Finally, we want to hear what you think. What do you like about the notes? What do you think could be improved? Please share your feedback by [email protected]. Thank you for joining Kaplan Medical, and best of luck on your Step 1 exam! Kaplan Medical meClical vii ~I I ! I I Fundamentals of Pathology A. DEFINITIONS OF PAT"OLOGY 1. Literal translation: "the study of suffering (pathos)" 2. The study of the essential nature of disease, disease processes, and the structural and functional changes in organs and tissues that cause or are caused by disease 3. The study of the gross and microscopic patterns of disease B. OVERVIEW OF PATHOLOGY 1. Etiology (cause) a. Genetic b. Acquired 2. Pathogenesis: sequence and patterns of cellular injury that lead to disease 3. Morphologic changes of the disease process a. Gross changes b. Microscopic changes 4. Clinical significance a. Know the signs and symptoms of each disease b. Disease course c. Prognosis C. METHODS USED IN PATHOLOGY 1. Gross examination of organs a. Gross examination of organs on the exam has two major components i. Determining what organ are you looking at! ii. Determining what's wrong (the pathology)! b. Useful gross features i. Size ii. Shape iii. Consistency iv. Color 2. Microscopic examination of tissue a. Light microscopy i. Hematoxylin and Eosin (H&E) - Gold Standard Stain UP~~. I maulC8 1 ,. USMLE Step 1: Pathology Table 1-1. Structures Stained by Hematoxylin and Eosin - , Hematoxylin Eosin Stains blue to purple Stains pink to red . I I Nuclei Cytoplasm I Nucleoli . Collagen I Bacteria Fibrin I ! ! Calcium RBCs I Many others Thyroid colloid Many others L___ ...__ ......... _----_. b. Other histochemical stains (chemical reactions) i. Prussian blue ll. Congo red :";t iii. Acid fast (Ziel-Neelson, Fite) IV. Periodic acid-Schiff (PAS) v. Gram stain VI. Trichrome vii. Reticulin c. Immunohistochemical (antibody) stains , -, I. Cytokeratin ll. Vimentin Ill. Desmin IV. Prostate specific antigen (PSA) v. Many others 3. Ancillary techniques a. Immunofluorescence microscopy (rFM) is typically used for: I. Renal diseases n, Autoimmune diseases b. Transmission electron microscopy (EM) is typically used for: I. Renal disease ll. Neoplasms ui, Infections IV. Genetic disorders 4. Molecular techniques a. Protein electrophoresis b. Southern and Western blots c. Polymerase chain reaction (PCR) 2 ~~iliCaI • Fundamentals of Pathology !i I Chapter Summary Pathology is the study of disease and concerns itself with the etiology, pathogenesis, morphologic changes, and clinical significance of different diseases. Gross examination of organs involves identifying pathologic lesions by evaluating abnormalities of size, shape, consistency, and color. Tissue sections stained with hematoxylin and eosin are used for routine light microscopic examination. Additional techniques that are used to clarifydiagnoses in particular settings include histochemical stains, immunohistochemical stains, immunofluorescence microscopy, transmission electron microscopy, and molecular techniques. Review Questions 1. A 27-year-old homeless man comes to the clinic because of a 3-week history of a fever, weight loss, night sweats,shortness of breath, and a cough with blood-tinged sputum. He says that a few of his acquaintances have similar symptoms. His temperature is 38.2°C (l00.8°P), blood pressure is 120/80mm Hg, pulse is 70/rnin, and respirations are 20/min. Crackles are heard over the upper lobes on auscultation. A chest x-ray shows upper lobe infiltrates and a .l-cm cavity in the left upper lobe. Three sputum samples are taken and sent to pathology for microscopic evaluation. Which of the following is the most appro- priate histochemical stain to use for these specimens? A. Acid-fast B. Congo red C. Periodic acid-Schiff D. Prussian blue E. Trichrome 2. A 48-year-old man comes to the physician because of an "odd discoloration" of his skin. He recently began to notice that he looks suntanned, even though it is the middle of the winter. A full work-up for this abnormal skin pigmentation shows diabetes mellitus and increased levelsof serum ferritin and transferrin saturation. He is admitted to the hospital for a liver biopsy. The biopsy is sent to pathology for microscopic evaluation. In addition to hematoxylin and eosin (H&E), which of the following is the most appropriate histo- chemical stain to use for this specimen? A. Acid-fast B. Congo red C. Gram stain D. Periodic acid-Schiff E. Prussian blue Answers 1. Answer: A. 2. Answer: E. mvulC8UP~~. I' 3 I: I ! Cellular Injury and Adaptation A. CAUSES OF CELLULAR INJURY Note 1. Hypoxia Overview of the 8edron Transport Chain a. Most common cause of injury b. Definition: lack of oxygen leads to the inability of the cell to synthesize sufficient ATP by aerobic oxidation c. Major causes of hypoxia I. Ischemia: loss of blood supply 7-~ NADH NAD Most common cause of hypoxia Decreased arterial flow or decrease venous outflow e.g., atherosclerosis, thrombus, thromboembolus ii. Cardiopulmonary failure iii. Decreased oxygen-carrying capacity of the blood (example: anemia) 2. Infections a. Viruses, bacteria, parasites, and fungi (and probably prions) b. Mechanism of injury I. Direct infection of cells O2 H20 u. Production of toxins ill. Host inflammatory response \ 3. Immunologic reactions Delivered by Hemoglobin a. Hypersensitivity reactions b. Autoimmune diseases 4. Congenital disorders a. Inborn errors of metabolism (i.e., inherited disorders [see Section VI for a more detailed discussion of specific genetic disorders]) 5. Chemical injury Note a. Drugs b. Poisons (cyanide, arsenic, mercury, etc.) Genetic defects involving enzymes are most often c. Pollution inherited in a recessive d. Occupational exposure (CCI , asbestosis, carbon monoxide, etc.) 4 manner, whereas those e. Social/lifestyle choices (alcohol, cigarette smoking, intravenous drug abuse involving structural proteins [IVDAJ, etc.) are most often inherited in a 6. Physical forms of injury dominant fashion.