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GENERAL AND SYSTEMIC PATHOLOGY Associate Professor Dr. Alexey Podcheko Spring 2015 How to download slides of Pathology course lectures? http://www.sjsm.org/moodle/ TEXTBOOKS You will need for the course: • BASIC PATHOLOGY – ROBBINS 9th Edition • Rubin's Pathology: Clinicopathologic Foundations of Medicine 6th Edition • Illustrated Q&A Review Of Rubin's Pathology, 2nd Ed (!) • Robbins and Cotran Review of Pathology, 3rd Edition (!) PATHOLOGY • GENERAL PATHOLOGY DEALS WITH BASIC CONCEPT OF VARIOUS DISEASE PROCESSES IN THE BODY, LIKE THE CAUSES AND MECHANISMS OF DISEASE AND THE ASSOCIATED ALTERATIONS IN THE STRUCTURE AND THE FUNCTION • SYSTEMIC PATHOLOGY DEALS WITH THE DISEASE PROCESS AFFECTING VARIOUS SYSTEMS AND SPECIFIC ORGANS IN THE BODY ATTENDANCE POLICY • Students must attend at least 80% of lectures. Attendance will be monitored through Moodle • Student must read/review appropriate textbook chapter and download the lecture slides before the lecture (Link is above) • Any student falling short of 80% attendance please refer to the Attendance policy of SJSM Anguilla campus Organization of Course ~12 weeks ~ 60 Lectures/Seminars (5 times/week) EVALUATIONS: MCQs Quizzes: During lectures for attendance (usually 2 questions) 50 question quiz will be administered during lab session one time per block Laboratory Classes • Learning will be based on clinical cases – Problem Based Learning, discussion and review of clinical vignettes, (MCQs from various test banks) • Review of pathology slides: real and virtual GRADING • Grading for course will be provided based on the following schedule: Final course score and grade will be calculated based on the following formula: Final course score=(A+B+C+D)/4 Curving • Note: Curving will be performed only if average score for MCQ exam in the group is below 70. Curving will be done only for MCQ exams. • Aim of curving is to reach average score 70 in the tested population. • No curving for quizzes, labs and poster presentations! Final Tips on how to successfully pass the Pathology Course: • 1. Read the Robbin’s or Rubin’s chapter and download slides before the lecture • 2. During lectures make notes! • 3. Do your best on the quizzes • 4. Do not miss labs • 5. Review your notes and all MCQs from Robbins and Rubin’s Review textbook chapters before exam! • 6. Do not leave reading of textbooks on the day before exam • 7. Final tip: answers for all exam questions can be founded in the lecture slides Administration Course Director – Dr. Alexey Podcheko MD, Ph.D, Email: [email protected] Course Facilitator: Dr. Amitabha Ray, MD, Ph.D Email: [email protected] Dr. Meghnad Bhowmick MBBS, MSc Email: [email protected] My background: 1. 1989-1995 – MD (General Practitioner) from Smolensk State School of Medicine, Russia 2. 1995-1998 – Residency at Departments of Pathology and Clinical Endocrinology of Smolensk State Medical School 3. 1998-2000- Assistant Professor at Department of Clinical Endocrinology 4. 2000-2005 - Ph.D. in Molecular Biology at Nagasaki University, School of Medicine, (Japan) 5. 2005-2010 – Postdoctoral Research Associate at Department of Laboratory Medicine and Pathobiology, University of Toronto, School of Medicine 6. 2010- Associate Professor at Department of Basic Sciences SJSM Research Projects: Ionizing Radiation and Thyroid Cancer -To clarify the mechanisms of radiationinduced thyroid carcinogenesis -To develop novel diagnostic techniques and gene/molecular-targeted therapy for thyroid cancer -To analyze genomic instability in multistep process of radiation carcinogenesis -To analyze radiation-induced cellular and molecular response -To identify the molecular mechanisms of cellular senescence and stress response -To clarify the mechanisms of UV or ionizing radiation-induced DNA damage repair May the tree thrive. Frederick Banting joined by Charles Best in office, 1924 My research in Diabetes area •Role of immunomodulators (thymic extracts) on protection against experimental Type I Diabetes •Identification of novel genes involved in beta-cell growth and survival •Cloning and characterization of novel positive regulator of betacell growth - Plekstrin Homology Interacting Protein 1 (PHIP1) My research/publications: OBJECTIVES of the Course WHAT IS PATHOLOGY? Pathos - Pathos is a Greek term for deep emotion, passion, or suffering. Logos - The Greek word logos traditionally meaning word, thought, principle, speech or study Three Definitions of Pathology: 1. Pathology is the study of diseases. 2. Pathology is the study of essential nature of disease, disease process, 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 History All diseases are the results of visible cell abnormalities Rudolph Virchow 1821-1902 The Father of Modern Pathology All diseases are the results of visible cell abnormalities Who is Pathologist? Physician who specializes in the diagnosis and management of human disease by laboratory methods Pathologist: • Diagnostician • Teacher • Scientific Researcher Pathology Anatomic Pathology Specialty: Microscopic analysis of tissue changes. Pathologist plays a central role in the diagnosis of surgically removed tissues Clinical Pathology Specialty: •Hematology •Microbiology •Immunology •Clinical Chemistry •Blood Bank (Transfusion Medicine) •Laboratory Data Management •Molecular Pathology Anatomic Pathology: Surgical Pathology Analysis of Biopsies and Surgical Specimens Surgically Removed Tissue Frozen Section/ Gross and Microscopic Evaluation Diagnosis and Prognostic Information A Case Study in Lung Cancer Patient: 46 year-old man Heavy smoker Complains of: Weakness Chronic cough Chest pain •Physical and Lab Findings: Elevated Blood Pressure Elevated Serum Calcium A Case Study in Lung Cancer CT imaging reveals mass in right lung Patient taken to surgery Mass biopsied and sent for frozen section Microscopic evaluation yields: - Precise diagnosis - Extent of disease - Information needed to determine course of action Anatomic Pathology: Cytopathology A Case Study in Thyroid Cancer Patient with thyroid mass receives a tracer dose of radioactive iodine, which reveals a “cold” nodule Pathologist performs fine- needle aspiration (FNA) Surgeon and oncologist determine course of action based on pathologist’s FNA diagnosis Mass removed during surgery Anatomic Pathology: Autopsy Autopsy provides insight into disease processes and the influence of therapy on disease: Reveals cause of death May detect previously undiagnosed genetic disorders – information that may benefit living family members Provides feedback to physicians involved in patient care: 1. Accuracy of diagnoses 2. Effectiveness of treatment Clinical Pathology Clinical pathology specialty laboratories include: Hematology Microbiology Immunology Clinical Chemistry Toxicology Transfusion Medicine Pathologists serve as consultants to other physicians by: recommending appropriate tests interpreting test results Cytology Dermatopathology Molecular Pathology •DNA sequencing to identify infectious agents •Molecular identification of chromosomal rearrangements •Genetic alterations •Prenatal screening for hemoglobin disorders and metabolic diseases •Genetic susceptibility to cancer Forensic Hematopathology The Pathologist as a Consultant •Interprets laboratory results •Advises physicians on appropriate diagnostic tests •Contributes to medical and surgical patient management decisions •Serves on hospital committees (e.g. quality assurance, blood utilization, infection control) •Updates physicians about laboratory medicine in Continuing Medical Education programs The Pathologist in Research Investigates the causes and mechanisms of diseases by: •Tracing new diseases to their origins •Improving diagnostic approaches to diseases •Identifying the genetic basis for patient response to treatments •Identifying new pathogenic bacteria and other infectious agents •Identifying genes involved in specific cancers What Kinds of People Go Into Pathology? Lectures: ACADEMIC CONTENT Major Themes disease - major categories emphasis on the following: • etiology • pathogenesis (as a variation of normal physiology) • structural alterations • clinical manifestations in patient and correlation with diagnosis and treatment What kind of questions will be asked on USMLE? • ETIOLOGY - cause • PATHOGENESIS – sequence of changes which leads to disease • MORPHOLOGY - gross and microscopic changes • CLINICAL EXPRESSION – disease presentation, clinical symptoms and prognosis, progression of disease SOME EXAMPLES: Cell Pathology -5 LECTURES ON CELL INJURY AND CELL DEATH INCLUDING FOLLOWING TOPICS: • • • • • • • • CELL INJURY NECROSIS APOPTOSIS SENESCENCE INTRACELLULAR ACCUMULATIONS CELL GROWTH AND DIFFERNTIATION REVIEW OF MATERIAL FOR EXAM EXAM (USMLE TYPE) Today’s Topic a) Definitions b ) Techniques in the Pathology Methods Used in Pathology 1. Gross examination of organs: a. What organ are you looking at b. What is wrong How to determine if there is something wrong with the organ: a. b. c. d. e. Size Shape Consistency Color But the most important – read history!!!! Autopsy: Main Techniques 1. En Masse (Le Tulle) Organs are removed as a single bulky aggregate 2. En Bloc (Ghon/Zenker) 3. Virchow’s 4. Rokitansky (in situ) Pulmonary emphysema Normal Lung -Note the dilation of airspaces. -This pattern is most characteristic for the centrilobular pattern of emphysema, Most often associated with a history of smoking. -The damage to the lung from smoking is in part the result of accentuation of neutrophil proteases, which over time destroy alveolar walls. Which X-ray is normal? Emphysema Normal Methods Used in Pathology 2. Light Microscopy using various staining techniques: a.Hematoxylin and Eosin Hematoxylin Eosin Stains blue to purple Stains pink to red Nuclei Cytoplasm Nicleoli Collagen Bacteria Fibrin Calcium RBC Thyroid colloid Other cell proteins Structures stained by Hematoxylin/Eosin Normal thyroid gland is composed of follicles lined by cuboidal epithelium and filled with pink colloid Medullary carcinoma of thyroid. These neoplasms are derived from the thyroid "C" cells and, therefore, have endocrine features such as secretion of calcitonin. Structures stained by Hematoxylin/Eosin Which image represent normal lung? Emphisema !!! Normal lung tissue What are other high yield stains for USMLE? • • • • • • • Prussian blue stain Congo Red stain Acid Fast (Ziel-Neelson, Fite) Periodic Acid-Schiff (PAS) Gram stain Trichrome Reticulin Prussian blue reaction –staining for Iron • Prussian blue stain involves the treatment of sections with acid solutions of ferrocyanides. Any ferric ion (+3) present in the tissue combines with the ferrocyanide and results in the formation of a bright blue pigment called Prussian blue, or ferric ferrocyanide. • This is one of the most sensitive histochemical tests and will demonstrate even single granules of iron in blood cells. • Small amounts of ferric iron are found normally in the spleen and bone marrow. Excessive amounts are present in hemochromatosis and hemosiderosis. Prussian blue reaction –staining for Iron Acute intra-alveolar hemorrhage and hemosiderin-laden macrophages, reflecting previous hemorrhage Hemochromatosis in cardiac muscle Congo Red stain Amyloid in vessel wall is stained Amyloid in vessel wall is apple green (Green+yellow) when red (normal light microscopy) viewed with fully polarized light amyloid birefringence !!! Acid Fast stain Mycobacterium avium infection in a patient with AIDS, showing massive infection with acid-fast organisms. PAS stain Periodic acid-Schiff (PAS) is a staining method used to detect glycogen in tissues. The reaction of periodic acid selectively oxidizes the glucose residues, creates aldehydes that react with the Schiff reagent and creates a purple-magenta color. Lupus nephritis “wire loop” lesions PAS positive megakaryocytes. disease marrow( glucocerebrosidase) mature Gauchers' lack of Gram stain Boxcar-shaped gram-positive Clostridium perfringens in gangrenous tissue Gram-negative Pseudomonas aeruginosa bacteria (pink-red rods). Trichrome (Mason) stain Detection of collagen, (to differentiate between collagen and smooth muscle in tumors, outline collagen deposits in diseases such as cirrhosis or various types of fibrosis) Non-Alcoholic Steatohepatitis (NASH), showing perivenular fibrosis and perisinusoidal fibrosis (blue fibers) Variable myocyte hypertrophy and interstitial fibrosis (collagen is highlighted as blue) • Reticulin stain The reticulin stain is useful in parenchymal organs such as • A reticulin stain occasionally helps to highlight the growth liver and spleen to outline the architecture pattern of neoplasms. Normal Liver ImmunoHystoChemistry (IHC) Immunoperoxydase Immunofluorescent Anti-cytokeratin Abs Most frequently used for diagnostic of cancers Most frequently used for diagnostic of renal and skin diseases (autoimmune origin) Most frequently mentioned in USMLE immunohistostainings Antibodies Cytokeratin Origin of Positively stained cells Epithelial Cells Vimentin Mesenchymal cells Desmin Muscle cells Prostate Specific Antigen (PSA) Prostate epithelium Transmission Electron Microscopy • • • • Renal diseases Neoplasms Infections Genetic Disorders Crescentic glomerulonephritis. Transmission Electron Microscopy • • • • Renal diseases Neoplasms Infections Genetic Disorders pulmonary adenocarcinoma mesothelioma Transmission Electron Microscopy • • • • Renal diseases Neoplasms Infections Genetic Disorders A B C D Adenovirus Epstein-Barr virus Rotavirus Paramyxovirus Transmission Electron Microscopy • • • • Renal diseases Neoplasms Infections Genetic Disorders Ganglion cells in Tay-Sachs disease Molecular Biology Techniques • Protein Electrophoresis/Western Blotting • Protein Electrophoresis/Western Blotting Density of band Staining of gel with special dye Molecular Biology Techniques • PCR (diagnosis of various infections, mutations) • Microarray (analysis of expression of all known genes expressed in particular tissue, e.g tracing origin of secondary tumor, risk assessment of premalignant lesions, prediction of drug resistance) • Whole genome sequencing