Fundamentals of Pathology 2023 Review PDF

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Www.Medicalstudyzone.com  Www.Medicalstudyzone.com This PDF was created and uploaded by www.medicalstudyzone.com which is one the biggest free resources platform for medical students and healthcare professionals. You can access all medical Video Lectures, Books in PDF Format or kindle Edition, Paid Medical Apps and Softwares, Qbanks, Audio Lectures And Much More Absolutely for Free By visiting our Website https://medicalstudyzone.com all stuff are free with no cost at all. Furthermore You can also request a specific Book In PDF Format OR Medical Video Lectures.  Www.Medicalstudyzone.com PATHOMA.COM Fundamentals of Pathology : Medical Course and Step 1 Review ISBN 978-0-9832246-3-l Printed in the United States of America. Copyright© 2023 by Pathoma LLC. Previous editions copyrighted 2011, 2013, 2014, 2015, 2016, 2017, 2018,2019,2020,21,22 All rights reserved. No part of this publication may be reproduced, distributed, or transmitted in any form, or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without prior permission in writing from the publisher (email: [email protected]). Disclaimer Fundamentals of Pathology aims at providing general principles of pathology and its associated disciplines and is not intended as a working guide to patient care, drug administration or treatment. Medicine is a constantly evolving field and changes in practice regularly occur. It is the responsibility of the treating practitioner, relying on independent expertise and knowledge of the patient, to determine the best treatment and method of application for the patient. Neither the publisher nor the author assume any liability for any injury and/or damage to persons or property arising from or related to the material within this publication. Furthermore, although care has been taken to ensure the accuracy of information present in this publication, the author and publisher make no representations or warranties whatsoever, express or implied, with respect to the completeness, accuracy or currency of the contents of this publication. This publication is not meant to be a substitute for the advice of a physician or other licensed and qualified medical professional. Information presented in this publication may refer to drugs, devices or techniques which are subject to government regulation, and it is the responsibility of the treating practitioner to comply with all applicable laws. This book is printed on acid-free paper. Published by Pathoma LLC. http://www.pathoma.com [email protected] Cover and page design by Olaf Nelson, Chinook Design, Inc. http://www.chinooktype.com  Www.Medicalstudyzone.com CONTENTS Chapter 1. Growth Adaptations, Cellular Injury, and Cell Death 1 Chapter 2. Inflammation, Inflammatory Disorders, and Wound Healing 11 Chapter 3. Principles of Neoplasia 23 Chapter 4. Hemostasis and Related Disorders 31 Chapter 5. Red Blood Cell Disorders 41 Chapter 6. White Blood Cell Disorders 53 Chapter 7. Vascular Pathology 65 Chapter 8. Cardiac Pathology 73 Chapter 9. Respira espiratory ory Tr Tract act Pathology 85 Chapter 10. Gastroin astrointtestinal P Paathology 99 Chapter 11. Exocrine Ex ocrine Pancr Pancreas eas,, Gallbladder Gallbladder,, and Liver Liver P Paathology....... 115 115 Chapter 12. Kidney idney and Urinary Urinary Tract act Pa Pathology 125 Chapter 13. Female Genital System and Gestational Pathology 137 » Chapter 14. Male Genital System Pathology 151 Chapter 15. Endocrine Pathology 159 Chapter 16. Breast Pathology 175 Chapter 17. Central Nervous System Pathology 181 Chapter 18. Musculoskeletal Pathology 195 Chapter 19. Skin Pathology 205 Index................................................................. 213  Www.Medicalstudyzone.com USING THIS BOOK This work is intended as a review for students during their preclinical years and while preparing for examinations, such as the USMLE. To this effect, the organization of this book follows that of most primary texts in the field and parallels the syllabus used in pathophysiology courses in medical schools throughout the United States. Ample space is provided for students to make notes during course study and while viewing the online videos that cover each section of the text (www.pathoma.com). We recommend that students use Fundamentals of Pathology during their medical courses, taking notes in the margin as pertinent topics are covered. When exam time comes around, these notes will likely be invaluable. For examination preparation, we suggest students read the material first, then listen to the online lecture, and then reread the material to develop a solid grasp of each topic. One should not become disheartened if they are not able to retain all the information contained herein. This deceptively slim volume covers a tremendous amount of material, and repetition will be a key aid as you progress in your studies. An effort has been made to emphasize concepts and principles over random facts, the forest rather than the trees. Attention to the same by the student will provide a deeper, more meaningful understanding of human disease. We must always remind ourselves that ultimately our goal is to learn, to share, and to serve. Fundamentals of Pathology was developed with this goal in mind. Husain A. Sattar, MD Chicago, Illinois ACKNOWLEDGMENTS This work would not have been possible without the support and encouragement of those around me. To begin with, I would like to acknowledge Shaykh Zulfiqar Ahmad, whose clear vision has guided me to horizons I would never have known. My family is to be acknowledged for their limitless sacrifice, in particular the constant encouragement and support of my wife Amina, who has proved through the years to be the wind under my wings. Thomas Krausz, MD and Ali ya Husain, MD (both Professors of Pathology at the University of Chicago) deserve particular mention for their valuable advice and guiding vision, both in the development of this book as well as my career. Special thanks to the multiple reviewers at medical centers throughout the country for their critical comments, in particular Mir Basharath Alikhan, MD (Pathology resident, University of Chicago) and Joshua T.B. Williams (Class of 2013, Pritzker School of Medicine, University of Chicago) for their extensive review. Olaf Nelson (Chinook Design, Inc.) is to be commended for his excellent layout and design. Finally, I would be remiss without acknowledging my students, who give meaning to what I do.  Www.Medicalstudyzone.com TO MY PARENTS AND EACH OF MY TEACHERS - YOUR SACRIFICE FORMS THE FOUNDATION UPON WHICH OUR WORK IS BUILT Www.Medicalstudyzone.com  Www.Medicalstudyzone.com Growth GrowthAdaptations, Adaptations,Cellular Cellular Injury, Injury,and CellDeath andCell Death 11 GROWTH ADAPTATIONS I. BASIC PRINCIPLES A. An organ is in homeostasis with the physiologic stress placed on it. B. An increase, decrease, or change in stress on an organ can result in growth adaptations. IL HYPERPLASIA AND HYPERTROPHY A. An increase in stress leads to an increase in organ size. 1. Occurs via an increase in the size (hypertrophy) and/or the number (hyperplasia) of cells B. Hypertrophy involves gene activation, protein synthesis, and production of organelles. C. Hyperplasia involves the production of new cells from stem cells. D. Hyperplasia and hypertrophy generally occur together (e.g., uterus during pregnancy). 1. Permanent tissues (e.g., cardiac muscle, skeletal muscle, and nerve), however, cannot make new cells and undergo hypertrophy only. 2. For example, cardiac myocytes undergo hypertrophy, not hyperplasia, in response to systemic hypertension (Fig. 1.1). E. Pathologic hyperplasia (e.g., endometrial hyperplasia) can progress to dysplasia and, eventually, cancer. 1. A notable exception is benign prostatic hyperplasia (BPH), which does not increase the risk for prostate cancer. III. ATROPHY A. A decrease in stress (e.g., decreased hormonal stimulation, disuse, or decreased nutrients/blood supply) leads to a decrease in organ size (atrophy). 1. Occurs via a decrease in the size and number of cells B. Decrease in cell number occurs via apoptosis. C. Decrease in cell size occurs via ubiquitin-proteosome degradation of the cytoskeleton and autophagy of cellular components. 1. In ubiquitin-proteosome degradation, intermediate filaments of the cytoskeleton are "tagged" with ubiquitin and destroyed by proteosomes. 2. Autophagy of cellular components involves generation of autophagic vacuoles. These vacuoles fuse with lysosomes whose hydrolytic enzymes breakdown cellular components. IV. METAPLASIA A. A change in stress on an organ leads to a change in cell type (metaplasia). 1. Most commonly involves change of one type of surface epithelium (squamous, columnar, or urothelial) to another 2. Metaplastic cells are better able to handle the new stress. B. Barrett esophagus is a classic example. pathoma.com 1  Www.Medicalstudyzone.com 2 FUNDAMENTALS OF PATHOLOGY 1. Esophagus is normally lined by nonkeratinizing squamous epithelium (suited to handle friction of a food bolus). 2. Acid reflux from the stomach causes metaplasia to nonciliated, mucin-producing columnar cells (better able to handle the stress of acid, Fig. 1.2). C. Metaplasia occurs via reprogramming of stem cells, which then produce the new cell type. 1. Metaplasia is reversible, in theory, with removal of the driving stressor. 2. For example, treatment of gastroesophageal reflux may reverse Barrett esophagus. D. Under persistent stress, metaplasia can progress to dysplasia and eventually result in cancer. 1. For example, Barrett esophagus may progress to adenocarcinoma of the esophagus. 2. A notable exception is apocrine metaplasia of breast, which carries no increased risk for cancer. E. Vitamin A deficiency can also result in metaplasia. 1. Vitamin A is necessary for differentiation of specialized epithelial surfaces such as the conjunctiva covering the eye. 2. In vitamin A deficiency, the thin squamous lining of the conjunctiva undergoes metaplasia into stratified keratinizing squamous epithelium. This change is called keratomalacia (Fig. 1.3). F. Mesenchymal (connective) tissues can also undergo metaplasia. 1. A classic example is myositis ossificans in which connective tissue within muscle changes to bone during healing after trauma (Fig. 1.4). V. DYSPLASIA A. Disordered cellular growth B. Most often refers to proliferation of precancerous cells 1. For example, cervical intraepithelial neoplasia (CIN) represents dysplasia and is a precursor to cervical cancer. C. Often arises from longstanding pathologic hyperplasia (e.g., endometrial hyperplasia) or metaplasia (e.g., Barrett esophagus) D. Dysplasia is reversible, in theory, with alleviation of inciting stress. 1. If stress persists, dysplasia progresses to carcinoma (irreversible). VI. APLASIA AND HYPOPLASIA A. Aplasia is failure of cell production during embryogenesis (e.g., unilateral renal agenesis). B. Hypoplasia is a decrease in cell production during embryogenesis, resulting in a relatively small organ (e.g., streak ovary in Turner syndrome). Fig. 1.1 Left ventricular hypertrophy. (Courtesy of Fig.1.2 Barrett esophagus. Aliya Husain, MD)  Www.Medicalstudyzone.com Growth Adaptations, Cellular Injury, and Cell Death 3 CELLULAR INJURY I. BASIC PRINCIPLES A. Cellular injury occurs when a stress exceeds the cell's ability to adapt. B. The likelihood of injury depends on the type of stress, its severity, and the type of cell affected. 1. Neurons are highly susceptible to ischemic injury; whereas, skeletal muscle is relatively more resistant. 2. Slowly developing ischemia (e.g., renal artery atherosclerosis) results in atrophy; whereas, acute ischemia (e.g., renal artery embolus) results in injury. C. Common causes of cellular injury include inflammation, nutritional deficiency or excess, hypoxia, trauma, and genetic mutations. II. HYPOXIA A. Low oxygen delivery to tissue; important cause of cellular injury 1. Oxygen is the final electron acceptor in the electron transport chain of oxidative phosphorylation. 2. Decreased oxygen impairs oxidative phosphorylation, resulting in decreased ATP production. 3. Lack of ATP (essential energy source) leads to cellular injury. B. Causes of hypoxia include ischemia, hypoxemia, and decreased O2-carrying capacity of blood. C. Ischemia is decreased blood flow through an organ. Arises with 1. Decreased arterial perfusion (e.g., atherosclerosis) 2. Decreased venous drainage (e.g., Budd-Chiari syndrome) 3. Shock - generalized hypotension resulting in poor tissue perfusion D. Hypoxemia is a low partial pressure of oxygen in the blood (Pao2 < 60 mm Hg, Sao2 < 90%). Arises with 1. High altitude - Decreased barometric pressure results in decreased PAo2 2. Hypoventilation - Increased PAco2 results in decreased PAo2 3. Diffusion defect - PAo2 not able to push as much O2 into the blood due to a thicker diffusion barrier (e.g., interstitial pulmonary fibrosis) 4. V/Q mismatch - Blood bypasses oxygenated lung (circulation problem, e.g., right- to-left shunt), or oxygenated air cannot reach blood (ventilation problem, e.g., atelectasis). E. Decreased O2-carrying capacity arises with hemoglobin (Hb) loss or dysfunction. Examples include 1. Anemia (decrease in RBC mass)-Pao2 normal; Sao2 normal 2. Carbon monoxide poisoning Fig. 1.3 Keratomalacia. (Courtesy of Fig.1.4 Myositis Ossificans. (Reprinted with motherchildnutrition.org) permission from orthopaedia.com)  Www.Medicalstudyzone.com 4 FUNDAMENTALS OF PATHOLOGY i. CO binds hemoglobin more avidly than oxygen-Pao2 normal; Sao2 decreased ii. Exposures include smoke from fires and exhaust from cars or gas heaters. iii. Classic finding is cherry-red appearance of skin. iv. Early sign of exposure is headache; significant exposure leads to coma and death. 3. Methemoglobinemia i. Iron in heme is oxidized to Fe3+, which cannot bind oxygen-Pao2 normal; Sao2 decreased ii. Seen with oxidant stress (e.g., sulfa and nitrate drugs) or in newborns iii. Classic finding is cyanosis with chocolate-colored blood. iv. Treatment is intravenous methylene blue, which helps reduce Fe2+ back to Fe2+state. III. REVERSIBLE AND IRREVERSIBLE CELLULAR INJURY A. Hypoxia impairs oxidative phosphorylation resulting in decreased ATP. B. Low ATP disrupts key cellular functions including 1. Na+-K+pump, resulting in sodium and water buildup in the cell 2. Ca 2+pump, resulting in Ca2+ buildup in the cytosol of the cell 3. Aerobic glycolysis, resulting in a switch to anaerobic glycolysis. Lactic acid buildup results in low pH, which denatures proteins and precipitates DNA. C. The initial phase of injury is reversible. The hallmark of reversible injury is cellular swelling. 1. Cytosol swelling results in loss of microvilli and membrane blebbing. 2. Swelling of the rough endoplasmic reticulum (RER) results in dissociation of ribosomes and decreased protein synthesis. D. Eventually, the damage becomes irreversible. The hallmark of irreversible injury is membrane damage. 1. Plasma membrane damage results in i. Cytosolic enzymes leaking into the serum (e.g., cardiac troponin) ii. Additional calcium entering into the cell 2. Mitochondrial membrane damage results in i. Loss of the electron transport chain (inner mitochondrial membrane) ii. Cytochrome c leaking into cytosol (activates apoptosis) 3. Lysosome membrane damage results in hydrolytic enzymes leaking into the cytosol, which, in turn, are activated by the high intracellular calcium. E. The end result of irreversible injury is cell death. Fig. 1.5 Coagulative necrosis of kidney. A, Gross appearance. B, Microscopic appearance. C, Normal kidney histology for comparison. (A, Courtesy of Aliya Husain, MD)  Www.Medicalstudyzone.com Growth Adaptations, Cellular Injury, and Cell Death 5 CELL DEATH I. BASIC PRINCIPLES A. The morphologic hallmark of cell death is loss of the nucleus, which occurs via nuclear condensation (pyknosis), fragmentation (karyorrhexis), and dissolution (karyolysis). B. The two mechanisms of cell death are necrosis and apoptosis. II. NECROSIS A. Death of large groups of cells followed by acute inflammation B. Due to some underlying pathologic process; never physiologic C. Divided into several types based on gross features III. GROSS PATTERNS OF NECROSIS A. Coagulative necrosis 1. Necrotic tissue that remains firm (Fig. 1.5A); cell shape and organ structure are preserved by coagulation of proteins, but the nucleus disappears (Fig. 1.5B). 2. Characteristic of ischemic infarction of any organ except the brain 3. Area of infarcted tissue is often wedge-shaped (pointing to focus of vascular occlusion) and pale. 4. Red infarction arises if blood re-enters a loosely organized tissue (e.g., pulmonary or testicular infarction, Fig. 1.6). B. Liquefactive necrosis 1. Necrotic tissue that becomes liquefied; enzymatic lysis of cells and protein results in liquefaction. 2. Characteristic of i. Brain infarction - Proteolytic enzymes from microglial cells liquefy the brain. ii. Abscess - Proteolytic enzymes from neutrophils liquefy tissue. iii. Pancreatitis - Proteolytic enzymes from pancreas liquefy parenchyma. C. Gangrenous necrosis 1. Coagulative necrosis that resembles mummified tissue (dry gangrene, Fig. 1.7) 2. Characteristic of ischemia of lower limb and GI tract 3. If superimposed infection of dead tissues occurs, then liquefactive necrosis ensues (wet gangrene). D. Caseous necrosis 1. Soft and friable necrotic tissue with "cottage cheese-like" appearance (Fig. 1.8) 2. Combination of coagulative and liquefactive necrosis 3. Characteristic of granulomatous inflammation due to tuberculous or fungal infection Fig. 1.6 Hemorrhagic infarction of testicle. Fig. 1.7 Dry gangrene. Fig. 1.8 Caseous necrosis of lung. (Courtesy ofYale (Courtesy of humpath.com) Rosen, MD)  Www.Medicalstudyzone.com 6 FUNDAMENTALS OF PATHOLOGY E. Fat necrosis 1. Necrotic adipose tissue with chalky-white appearance due to deposition of calcium (Fig. 1.9) 2. Characteristic of trauma to fat (e.g., breast) and pancreatitis-mediated damage of peripancreatic fat 3. Fatty acids released by trauma (e.g., to breast) or lipase (e.g., pancreatitis) join with calcium via a process called saponification. i. Saponification is an example of dystrophic calcification in which calcium deposits on dead tissues. In dystrophic calcification, the necrotic tissue acts as a nidus for calcification in the setting of normal serum calcium and phosphate. ii. Metastatic calcification, as opposed to dystrophic calcification, occurs when high serum calcium or phosphate levels lead to calcium deposition in normal tissues (e.g., hyperparathyroidism leading to nephrocalcinosis). F. Fibrinoid necrosis 1. Necrotic damage to blood vessel wall 2. Leaking of proteins (including fibrin) into vessel wall results in bright pink staining of the wall microscopically (Fig. 1.10). 3. Characteristic of malignant hypertension and vasculitis IV.APOPTOSIS A. Energy (ATP)-dependent, genetically programmed cell death involving single cells or small groups of cells. Examples include 1. Endometrial shedding during menstrual cycle 2. Removal of cells during embryogenesis 3. CD8 + T cell-mediated killing of virally infected cells B. Morphology 1. Dying cell shrinks, leading cytoplasm to become more eosinophilic (pink, Fig. l.ll). 2. Nucleus condenses and fragments in an organized manner. 3. Apoptotic bodies fall from the cell and are removed by macrophages; apoptosis is not followed by inflammation. C. Apoptosis is mediated by caspases that activate proteases and endonucleases. 1. Proteases break down the cytoskeleton. 2. Endonucleases break down DNA. D. Caspases are activated by multiple pathways. 1. Intrinsic mitochondrial pathway i. Cellular injury, DNA damage, or decreased hormonal stimulation leads to inactivation of Bcl2. ii. Lack of Bcl2 allows cytochrome c to leak from the inner mitochondrial matrix into the cytoplasm and activate caspases. Fig. 1.9 Fat necrosis of peri-pancreatic adipose Fig. 1.10 Fibrinoid necrosis of vessel. Fig.1.11 Apoptosis. tissue. (Courtesy of humpath.com)  Www.Medicalstudyzone.com Growth Adaptations, Cellular Injury, and Cell Death 7 2. Extrinsic receptor-ligand pathway i. FAS ligand binds FAS death receptor (CD95) on the target cell, activating caspases (e.g., negative selection of thymocytes in thymus). ii. Tumor necrosis factor (TNF) binds TNF receptor on the target cell, activating caspases. 3. Cytotoxic CD8+ T cell-mediated pathway i. Perforins secreted by CD8 + T cell create pores in membrane of target cell. ii. Granzyme from CD8 + T cell enters pores and activates caspases. iii. CD8 + T-cell killing of virally infected cells is an example. FREE RADICAL INJURY I. BASIC PRINCIPLES A. Free radicals are chemical species with an unpaired electron in their outer orbit. B. Physiologic generation of free radicals occurs during oxidative phosphorylation. 1. Cytochrome c oxidase (complex IV) transfers electrons to oxygen. 2. Partial reduction of O2 yields superoxide (O2ꜙ), hydrogen peroxide (H2O2 ), and hydroxyl radicals (˙OH ). C. Pathologic generation of free radicals arises with 1. Ionizing radiation - water hydrolyzed to hydroxyl free radical 2. Inflammation - NADPH oxidase generates superoxide ions during oxygen- dependent killing by neutrophils. 3. Metals (e.g., copper and iron)-Fe 2+ generates hydroxyl free radicals (Fenton reaction). 4. Drugs and chemicals - P450 system of liver metabolizes drugs (e.g., acetaminophen), generating free radicals. D. Free radicals cause cellular injury via peroxidation of lipids and oxidation of DNA and proteins; DNA damage is implicated in aging and oncogenesis. E. Elimination of free radicals occurs via multiple mechanisms. 1. Antioxidants (e.g., glutathione and vitamins A , C, and E) 2. Enzymes I) Superoxide dismutase (in mitochondria) - Superoxide (O2ꜙ) → H2O2 II) Glutathione peroxidase (in mitochondria) - 2GSH + free radical → GS-SG and H2O III) Catalase (in peroxisomes) - H 2O2 → O2ꜙ and H2O 3. Metal carrier proteins (e.g., transferrin and ceruloplasmin) II. EXAMPLES OF FREE RADICAL INJURY A. Carbon tetrachloride (CCl4) 1. Organic solvent used in the dry cleaning industry 2. Converted to CCl3 free radical by P450 system of hepatocytes 3. Results in cell injury with swelling of RER; consequently, ribosomes detach, impairing protein synthesis. 4. Decreased apolipoproteins lead to fatty change in the liver (Fig. 1.12). B. Reperfusion injury 1. Return of blood to ischemic tissue results in production of O2 -derived free radicals, which further damage tissue. 2. Leads to a continued rise in cardiac enzymes (e.g., troponin) after reperfusion of infarcted myocardial tissue  Www.Medicalstudyzone.com IK * * 8 FUNDAMENTALS OF PATHOLOGY AMYLOIDOSIS I. BASIC PRINCIPLES A. Amyloid is a misfolded protein that deposits in the extracellular space, thereby damaging tissues. B. Multiple proteins can deposit as amyloid. Shared features include 1. β- pleated sheet configuration 2. Congo red staining and apple-green birefringence when viewed microscopically under polarized light (Fig. 1.13) C. Deposition can be systemic or localized. II. SYSTEMIC AMYLOIDOSIS A. Amyloid deposition in multiple organs; divided into primary and secondary amyloidosis B. Primary amyloidosis is systemic deposition of AL amyloid, which is derived from immunoglobulin light chain. 1. Associated with plasma cell dyscrasias (e.g., multiple myeloma) C. Secondary amyloidosis is systemic deposition of AA amyloid, which is derived from serum amyloid-associated protein (SAA). 1. SAA is an acute phase reactant that is increased in chronic inflammatory states, malignancy, and Familial Mediterranean fever (FMF). 2. FMF is due to a dysfunction of neutrophils (autosomal recessive) and occurs in persons of Mediterranean origin. i. Presents with episodes of fever and acute serosal inflammation (can mimic appendicitis, arthritis, or myocardial infarction) ii. High SAA during attacks deposits as AA amyloid in tissues. D. Clinical findings of systemic amyloidosis are diverse since almost any tissue can be involved. Classic findings include 1. Nephrotic syndrome; kidney is the most common organ involved. 2. Restrictive cardiomyopathy or arrhythmia 3. Tongue enlargement, malabsorption, and hepatosplenomegaly E. Diagnosis requires tissue biopsy. Abdominal fat pad and rectum are easily accessible biopsy targets. F. Damaged organs must be transplanted. Amyloid cannot be removed. III. LOCALIZED AMYLOIDOSIS A. Amyloid deposition usually localized to a single organ. B. Senile cardiac amyloidosis 1. Non-mutated serum transthyretin deposits in the heart. 2. Usually asymptomatic; present in 25% of individuals > 80 years of age C. Familial amyloid cardiomyopathy I 'V % I.- r Pi * r 4 »' *r&i* r> » * ' -3ft ; te?. w wk:< £. i. - * V \ VN * * H. w > II B 1 \ At? *i i Fig.1.12 Fatty change of liver. Fig. 1.13 Amyloid. A, Congo red. B, Apple-green birefringence. (Courtesy of Ed Uthman, MD)  Www.Medicalstudyzone.com Growth Adaptations, Cellular Injury, and Cell Death 9 1. Mutated serum transthyretin deposits in the heart leading to restrictive cardiomyopathy. 2. 5% of African Americans carry the mutated gene. D. Non-insulin-dependent diabetes mellitus (type II) 1. Amylin (derived from insulin) deposits in the islets of the pancreas. E. Alzheimer disease 1. Aβ amyloid (derived from β-amyloid precursor protein) deposits in the brain forming amyloid plaques. 2. Gene for β-APP is present on chromosome 21. Most individuals with Down syndrome (trisomy 21) develop Alzheimer disease by the age of 40 (early-onset). F. Dialysis-associated amyloidosis 1. β2-microglobulin deposits in joints. G. Medullary carcinoma of the thyroid 1. Calcitonin (produced by tumor cells) deposits within the tumor ('tumor cells in an amyloid background'). I REMINDER Thank you for choosing Pathoma for your studies. We strive to provide the highest quality educational materials while keeping affordability in mind. A tremendous amount of time and effort has gone into developing these materials, so we appreciate your legitimate use of this program. It speaks to your integrity as a future physician and the high ethical standards that we all set forth for ourselves when taking the Hippocratic oath. Unauthorized use of Patho ma materials is contrary to the ethical standards of a training physician and is a violation of copyright. Pathoma videos are updated on a regular basis and the most current version, as well as a complete list of errata, can be accessed through your account at Pathoma.com. Sincerely, Dr. Sattar, MD Www.Medicalstudyzone.com