Pathology Lecture 1 PDF

PATHOLOGIC BASIS OF CLINICAL MEDICINE Block: Foundations Block Director: James Proffitt, PhD Session Date: Monday, July 29, 2024 Time: 3:00 – 4:00 pm Instructor: Deborah Fuchs, MD Department: Pathology Email: [email protected]...

PATHOLOGIC BASIS OF CLINICAL MEDICINE Block: Foundations Block Director: James Proffitt, PhD Session Date: Monday, July 29, 2024 Time: 3:00 – 4:00 pm Instructor: Deborah Fuchs, MD Department: Pathology Email: [email protected] INSTRUCTIONAL METHODS Primary Method: IM10: Independent Learning ☐ Flipped Session ☐ Clinical Correlation Resource Types: RE18: Written or Visual Media (or Digital Equivalent) INSTRUCTIONS Please read lecture objectives, notes and watch pre-recorded video. READINGS N/A LEARNING OBJECTIVES: 1. Understand the role of pathology in prevention, diagnosis, treatment, and management of disease. 2. Describe the basic mechanisms of disease 3. Describe the three basic competencies in pathology 4. Describe the approach used in the diagnosis of neoplasms and other pathologies, including the use of tumor markers. CURRICULAR CONNECTIONS Below are the competencies, educational program objectives (EPOs), disciplines and threads that most accurately describe the connection of this session to the curriculum. Related Related Competency\EPO Disciplines Threads COs LOs CO-01 LO #1-4 MK-05: The altered structure and Pathology N/A function (pathology & pathophysiology) of the body/organs in disease CONTEXT: Pathology is a diagnostic specialty in medicine that bridges basic science and clinical medicine, so an understanding of pathological processes will be vitally important to your practice of medicine, regardless of the specialty you choose. Pathology is built on underlying Block: Foundations | FUCHS [1 of 6] PATHOLOGIC BASIS OF CLINICAL MEDICINE foundational principles including chemistry, biochemistry, cell biology, anatomy, genetics and physiology. In this block, general pathology topics will be covered, including cell injury, inflammation and repair, immune disorders, thromboembolism, mutations, neoplasia, and infection. These core principles will be applicable as you progress through specific organ systems in subsequent blocks. This session will demonstrate these core principles of general pathology through the use of clinical cases. In addition, the medical specialty of pathology will be introduced. OVERVIEW Pathology is a medical specialty that involves the study and diagnosis of disease through examination/analysis of a wide variety of patient specimens, including organs removed during surgery, tissue biopsies, blood, sputum, feces, other body fluids (urine, peritoneal fluid, synovial fluid, pleural fluid, cerebrospinal fluid) and even the entire body during post-mortem examination (autopsy). Through examination of these specimens, the pathologist provides pivotal information for prevention, diagnosis, treatment and management of disease. Basic Competencies in Pathology: 1) Understand core principles of disease mechanisms/processes (general pathology) such as cell injury, inflammation, tissue repair, vascular damage and response, mutations, neoplasia, and infection. a. Cell Injury, cell death and adaptations – cells encounter many stresses due to changes in their internal and external environments. If an injury exceeds the cells ability to adapt, the cell will die. Causes of cellular injury are many, including: i. Hypoxia (lack of oxygen) ii. Pathogens (viruses, bacteria, parasites, fungi, prions) iii. Immunologic dysfunction (hypersensitivity, autoimmune) iv. Inherited mutations v. Chemical injury (drugs, poisons, occupational exposures, alcohol, tobacco, etc) vi. Physical injury (trauma, burns, frostbite) vii. Nutritional or vitamin imbalance Cellular responses to injury include adaptation (hypertrophy, atrophy, hyperplasia, metaplasia), reversible injury, and irreversible injury and cell death (necrosis, apoptosis). b. Inflammation and repair – Inflammation is a reaction of tissue to an injurious agent (pathogens, damaged tissue) which facilitates entry of inflammatory cells, plasma proteins and fluid to the site of injury. Block: Foundations | FUCHS [2 of 6] PATHOLOGIC BASIS OF CLINICAL MEDICINE Inflammation involves vascular responses, migration and activation of leukocytes and systemic reaction. Acute inflammation is an immediate response (minutes to days) to infection (to eliminate pathogen) or injury (to clear dead cells). The key players of which are vascular changes, chemical mediators, and neutrophils. Chronic inflammation is a delayed response to persistent infection (most common cause), infection with certain organisms (viruses, mycobacteria, parasites, fungi), autoimmune disease, foreign material (sutures), and some cancers. Repair of damaged tissues is initiated when inflammation begins. This process involves hemostasis (coagulation, platelets), inflammatory cells, regeneration of cells (if possible), fibrosis, and remodeling. c. Hemodynamic disorders, thromboembolism and shock – the health of tissues depends on circulation of blood, which delivers oxygen and nutrients and removes waste. This exchange typically occurs in the capillary beds, where there is little net movement of water and electrolytes into the tissues. When this balance is lost and fluid accumulates in the tissues, we call this edema. Blood vessels may be damaged during trauma; hemostasis, or blood clotting, is the process that prevents excessive bleeding after injury to a vessel. If hemostasis is inadequate, excessive bleeding or hemorrhage may ensue. If hemorrhage is massive and rapid, it may lead to hypotension and shock. On the other hand, if clotting is excessive (pathologic thrombosis) or a portion of a blood clot migrates (embolism), a blood vessel may be occluded, impairing delivery to the tissue (ischemia, infarction). d. Diseases of the immune system – defects in the immune system (immunodeficiency diseases) can lead to increased susceptibility to infections. The immune system can also cause tissue injury and disease through immune reactions that cause injury (hypersensitivity reactions). In autoimmune disorders, there is failure of tolerance to self-antigens and the immune system response is directed against self- antigens. e. Neoplasia – new tissue growth that is unregulated, irreversible and monoclonal (neoplastic cells derived from a single cell). Include benign and malignant neoplasms. f. Genetics and Pediatric diseases – genetic abnormalities (mutations, amplifications, deletions, translocations, etc) that affect the structure and function of proteins, disrupt cellular homeostasis and cause disease. Block: Foundations | FUCHS [3 of 6] PATHOLOGIC BASIS OF CLINICAL MEDICINE g. Environmental and nutritional diseases. Environmental diseases are caused by environmental factors. Include exposure to chemical or physical agents in the environment: climate change, tobacco, alcohol, drugs (therapeutic and drugs of abuse), physical agents (mechanical trauma, thermal injury, electrical injury, radiation), and nutritional diseases (malnutrition, vitamin deficiencies, obesity, anorexia nervosa and bulimia). 2) Apply knowledge of disease mechanisms to organ systems and become familiar with the epidemiology, pathologic features (gross and microscopic), and diagnostic techniques of common disorders. In addition, the clinical presentation, natural history of the disease if untreated, and likely outcome when treated, should be known. 3) Apply general and system pathology to diagnostic medicine. When signs and symptoms derived from history and physical examination are insufficient to make a diagnosis, what laboratory or imaging studies are indicated? Demonstrate effective utilization of laboratory testing and imaging studies Pathology Methods for Diagnosis As mentioned above, pathologists examine a wide range of specimens obtained from patients. This examination may include gross and microscopic examination of tissue, review/interpretation of laboratory tests in clinical context, and oversight of clinical laboratory function. Pathology is generally divided into two main areas: clinical and anatomic. Clinical pathology (Laboratory Medicine) covers a wide range of laboratory functions and deals with measurements of chemical constituents in blood and other body fluids (clinical chemistry), analysis of blood cells (hematology) and identification of microorganisms (microbiology). Clinical pathologists oversee and direct all of the divisions of a laboratory. Laboratory tests are conducted by a team of medical laboratory technologists or technicians and the pathologist oversee the functioning of the laboratory and is the key bridge between laboratory operations and clinical practice. Anatomic pathology is the branch of pathology that studies the effect of disease on the gross and microscopic structure of organs and tissues. Anatomic pathology includes surgical pathology, cytopathology (examination of single cells) and autopsy pathology. The majority of pathologists in clinical practice are surgical pathologists and a frequent use of surgical and cytopathology is to identify and manage neoplasms. Block: Foundations | FUCHS [4 of 6] PATHOLOGIC BASIS OF CLINICAL MEDICINE Many pathologists have subspecialty fellowship training (beyond the 4-year pathology residency) in a variety of areas, including cytopathology, dermatopathology, hematopathology, neuropathology, renal pathology, bone and soft tissue pathology, blood bank/transfusion medicine, chemical pathology, medical microbiology, pediatric pathology, forensic pathology, and molecular genetic pathology. Microscopic Examination (histologic and cytologic methods) - Several sampling approaches are available, including 1) excision or biopsy, 2) fine- needle aspiration and 3) cytologic smears (ex: cervical Pap smear). The tissue must be adequate (don’t be stingy!), representative of the lesion and properly handled/preserved. A pathologist evaluates the histologic features to determine the nature of the lesion (benign or malignant), the cell/tissue of origin, and other prognostic features (grade, stage, margins etc.). In some instances, the cell/tissue of origin of a neoplasm is not apparent from routine H&E histology; in these cases, other methods are used to determine the origin of the neoplasm (immunohistochemical stains, flow cytometry, molecular/genetic, see below). Ancillary Techniques: Include electron microscopy, flow cytometry, molecular/genetic testing, and immunofluorescence. Molecular/Genetic Testing – An increasing number of techniques are readily available and being used in routine clinical practice for the diagnosis of tumors, prognosis, therapeutic decisions, and to determine response to treatment. Commonly used techniques include karyotypic analysis, PCR and FISH (Fluorescence in situ hybridization). More recently, next generation sequencing and microarrays have gained wider application and availability. Tumor Markers – Substances produced by tumors (tumor-associated enzymes, hormones, and other tumor markers) can be identified in the blood or other body fluid. These substances are useful in several ways: tumor screening, diagnosis, prognostic indicators and monitoring the outcome of therapy (monitoring for relapse). They are not used for a definitive diagnosis of cancer. See Table 7-12 in Robbins, 9th ed. Examples: 1) Prostate specific antigen – prostate carcinoma, may also be elevated in benign prostate conditions. May be useful in monitoring patients with prostate cancer undergoing therapy – monitor for relapse 2) Carcinoembryonic antigen (CEA) – Elevated in a variety of cancers (nonspecific): carcinomas of the colon, pancreas, lung and stomach. May also be elevated in benign conditions, and therefore, lacks sensitivity for the detection of early cancers. 3) Alpha-fetoprotein – cancers of liver and gonads; also elevated in benign states including pregnancy. 4) Immunoglobulins – plasma cell neoplasms Block: Foundations | FUCHS [5 of 6] PATHOLOGIC BASIS OF CLINICAL MEDICINE The pathologist integrates information from the histology, immunohistochemistry, biochemical assays and molecular studies with the patient’s clinical history and issues a diagnosis. Block: Foundations | FUCHS [6 of 6]