Pathology: a. The Study of Disease b. A Clinical Specialty

1. Pathology: a. The Study of Disease b. A Clinical Specialty Why the teaching of concepts and mechanisms of disease is important at the high school level. The basic principles of general pathology. Application of the principles and methods of pathology to the diagnosis, as well as the understanding of disease. • The potential career pathways for pathologists.

2. Biology Pathology • Health Disease • Order Disorder • Symbiosis Parasitism • Homeostasis Host Defense • Growth Neoplasia • Circulation Infarction • Hormones Endocrine Diseases

4. WHY INCLUDE DISEASE PRINCIPLES IN HIGH SCHOOL CURRICULUM? A. IT’S IMPORTANT • Confront disease in their daily lives • Inundated by disease (mis)information (news, entertainment) • New threats to be faced (emerging pathogens, bioterrorism) • Increasing complexity of medical care (informed consumers) IT’S INTERESTING • Focus on themselves & their bodies (as well as frogs and paramecia) Integration of both sides of the force • IT’S REINFORCING • Observation & Classification • Conceptualization & Abstraction, • Explanation & Prediction • Application • (Career choices)

5. GENERAL PATHOLOGYThere are general principles that apply to the various diseases • Finite set of patterns of injury • Similar physiologic and morphologic consequences of different injuries • Small number of reparative processes

6. HOST DEFENSE Injury Protective Response Inflammation Immunity Repair Fibrosis Regeneration Resolution mediators Inflammation is an immediate reaction to damage that limits it directly, helps focus an immune reaction, and sets the stage for subsequent repair.

7. INFLAMMATION & IMMUNITY INFLAMMATION vessels serum factors cells IMMUNE RESPONSE antibodies activated cells cytokines Inflammatory/Immune Cells

8. EFFECTOR FUNCTIONS OF THE IMMUNE SYSTEM Antibody-Mediated • Precipitation • Neutralization • Complement activation • Mask Receptors • Enhance Phagocytosis • Activate leukocytes • ADCC Cytokine-Mediated • Cell destruction • Cell proliferation • Cell movement • Cell differentiation • Cell activation Cell-Mediated Cytotoxic T cells Activated NK Cells Activated Macrophages

9. LYMPHOCYTES LEAVING A BLOOD VESSEL

10. CANCER

11. POSITION TITLE: MALIGNANT CELLJob Description • Survive and proliferate locally • Invade adjacent tissue • Induce supporting stroma and blood supply • Gain access to the circulation a. Cross basement membrane b. Cross endothelium • Leave circulation a. Cross endothelium b. Cross basement membrane • Colonize new location • Survive and proliferate at distant site

12. CANCER OF PANCREAS GROSS PHOTOGRAPH MICROPHOTOGRAPH

15. THE KISS OF DEATH

16. CAUSES OF CANCER • SOME GENERAL CAUSES • Breathing • Drinking • Eating • Working • Sunshine • Sex • Doctors • SOME SPECIFIC CAUSES • Sweeping chimneys • Using aniline dyes • Smoking cigarettes • Building ships in WWII • Renovating old houses • SOME UNDERLYING CAUSES • Loss of negative growth signals • Excessive production of growth factors • Decreased (normal) cell death • Loss of spatial constraints

18. Physical Exam Patient Internist Pathologist Radiologist Surgeon

19. Normal Breast

20. MAMMOGRAM

21. BREAST CANCER • DIAGNOSTIC SURGICAL PROCEDURES • Fine Needle Aspiration (FNA) • Needle Core Biopsy • Excision Biopsy

22. CANCER CELLS BY CYTOLOGY

23. TISSUE EXAMINATION PROCESSING FINAL DIAGNOSIS S-01-10 SLIDE PREPARATION

24. BREAST CARCINOMA- THROUGH MICROSCOPE

25. DETECTION & IDENTIFICATION METHODS • ANTIBODIES AS DETECTION AGENTS • Immunohistochemistry • Immunofluorescence • DNA AS PROBES • In situ hybridization • DNA sequencing • Polymerase Chain Reaction

26. Amplification of signal with biotin

27. IMMUNOHISTOCHEMISTRY

30. FLUORESCENT IN SITU HYBRIDIZATION (FISH)

34. MOLECULAR IDENTIFICATION • Cellular phenotypes • Differentiation stages • Tumor classification • Gene activation & RNA expression • Detection of proteins, nucleotide sequences, mutations • Exogenous pathogens • Altered proteins

36. APPENDIX: INTEGRATION OF PATHOLOGY AND BIOLOGY CURRICULUM • UNIT 1: WHAT IS BIOLOGY? • Module 1: Basic Aspects of Pathology • The relationship between homeostasis and response to damage • Self-protection: inflammation, immunity, & repair • How organisms adapt to functional losses • How we study disease, and what tools are available • The use of biological principles to treat disease • UNIT 2: PRINCIPLES OF ECOLOGY • Module 2: The Ecology of Disease • Distinguishing self from non-self • How populations resist injury by adaptation • How populations resist injury by evolution • Infectious diseases as predators • How do humans experience symbiosis and parasitism

37. INTEGRATION OF PATHOLOGY & BIOLOGY CURRICULUM • UNIT 3: THE LIFE OF CELLS • Module 3: Cellular Pathology • How does the cell maintain a boundary around it, other cells & the outside world? • What happens when these boundaries are breached? • Susceptibility of organelles to damage & disturbances of cellular metabolism • What triggers a cell to divide and how can this stimulus become defective? • What are the consequences of uncontrolled cell proliferation? • How we study disease, and what tools are available? • The use of biological principles to treat disease • UNIT 4: GENETICS • Module 4: The Genetics of Disease • How can diseases be inherited? • Does heredity play a role in diseases that are not inherited? • Do different populations have different risk factors? • The difference between germ cell and somatic cell mutation • What are the principles of genetic engineering?

38. INTEGRATION OF PATHOLOGY & BIOLOGY CURRICULUM • UNIT 5: EVOLUTION • Module : Evolutionary Forces in Disease • The forces driving molecular evolution in animals & pathogens • Information transfer without DNA (prions & retroviruses) • Do disease organisms co-evolve with their hosts and/or evolve to take advantage of new hosts • What are the differences between evolution & genetic engineering? • UNIT 6: DIVERSITY OF LIFE • Module 6: diversity of Disease • What are the different kinds of pathogenic agents (pathogens)? • How do we classify infectious organisms? • Differences in the response to different kinds of pathogens • How do different individuals respond differently to the same or similar pathogens?