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1. CELLULAR RESPONSE

2. OUTLINE Definition of Pathology General Divisions of Pathology Four Aspects of Disease Process Overview: Cellular Responses to Stress and Noxious Stimuli Adaptations of Cellular Growth and Differentiation Morphological Alterations in Cell Injury Quality Control and Quality Assurance

3. DEFINITION OF PATHOLOGY Study of diseases by scientific methods. Study (logos) of diseases (pathos) Study of the structural, biochemical, and functional changes in cells, tissues, and organs that underlie the disease. Serves as a bridge between basic sciences and clinical medicine; scientific foundation for all of medicine Explains the whys and wherefores of the signs and symptoms via microbiologic, immunologic, and morphological techniques.

4. GENERAL DIVISION OF PATHOLOGY a) General Pathology – concerned with the reaction of cells and tissues to abnormal stimuli and inherited defects. b) Systemic Pathology – examines the alterations in specialized organs and tissues that are responsible for disorders that involves organs.

5. FOUR ASPECTS OF DISEASE PROCESS Etiology - Most of the common afflictions are multifactorial and arise from the effects of various external triggers on a genetically susceptible individual. Pathogenesis - Refers to the sequence of events in the response of cells or tissues to the etiologic agent, from the initial stimulus to the ultimate expression of the disease.

6. FOUR ASPECTS OF DISEASE PROCESS Molecular and Morphological Changes - Structural alterations in cells or tissues that are either characteristic of a disease or diagnostic of an etiologic process. Clinical Manifestations – functional consequences of these changes.

7. OVERVIEW: CELLULAR RESPONSES TO STRESS AND NOXIOUS STIMULI Homeostasis – equilibrium of the microenvironment of the cell. Adaptations – are reversible functional and structural responses to more severe physiologic stresses and some pathologic stimuli, during which new but altered steady states are achieved, allowing the cell to survive and continue to function

8. ADAPTATIONS OF CELLULAR GROWTH AND DIFFERENTIATION Hypertrophy- Refers to an increase in the size of cells, resulting in an increase in the size of the organ. Hyperplasia - Increase in the number of cells in an organ or tissue, usually resulting in increased mass of the organ or tissue. Atrophy - is reduced size of an organ or tissue resulting from a decrease in cell size and number. Metaplasia - Reversible change in which one differentiated cell type (epithelial or mesenchymal) is replaced by another cell type.

9. MORPHOLOGICAL ALTERATIONS IN CELL INJURY Cellular Swelling – appears whenever cells are incapable of maintaining ionic and fluid homeostasis and is the result of failure of energy-dependent ion pumps in the plasma membrane. Fatty Change – occurs in hypoxic injury and various forms of toxic or metabolic injury. Necrosis- Morphologic appearance of necrosis is the result of denaturation of intracellular proteins and enzymatic digestion of the lethally injured cell.

10. 3 PATTERNS OF NUCLEAR CHANGES a) Karyolysis - fading of basophilia of the chromatin reflecting loss of DNA because of enzymatic degradation by endonucleases. b) Pyknosis - characterized by nuclear shrinkage and increased basophilia; chromatin condenses into a solid, shrunken basophilic mass. c) Karyorrhexis – fragmentation of the pyknotic nucleus.

11. OUTLINE Definition and General Features of Inflammation Acute Inflammation Chronic Inflammation Systemic Effects of Inflammation Tissue Repair

12. INFLAMMATION Protective response involving host cells, blood vessels, and proteins and other mediators Initiates the process of repair Diluting, destroying, or otherwise neutralizing harmful agents Innate immunity

13. ACUTE VS CHRONIC INFLAMMATION ACUTE CHRONIC ONSET FAST SLOW CELLULAR INFILTRATE MAINLY NEUTROPHIL MONO/MACRO AMD LYMPHOCYTES TISSUE INURY USUALLY MILD AND SELF LIMITED OFTEN SEVERE AND PROGRESSIVE LOCAL AND SYSTEMIC SIGN PROMINENT LESS PROMINENT MAY BE SUBTLE

14. CARDINAL SIGNS OF INFLMMATION a. Calor (heat) b. Rubor (redness) c. Tumor (swelling) d. Dolor (pain) e. Functio Laesa (loss of function) • described by Rudolf Virchow (“father of modern pathology.”)

15. 2 MAJOR COMPONENTS Vascular Changes Increased blood flow due to vasodilation Activation of endothelial cells Cellular Events Cellular (leukocyte) recruitment: emigration of leukocytes from the circulation to the site of injury Activation of the leukocytes

16. CAUSE OF INFLAMMATION INFECTION TISSUE NECROSIS FOREIGN BODIES IMMUNE REACTIONS

17. OUTCOMES RESOLUTION – REGENRATION AND REPAIR injury is limited and short-lived; no or minimal tissue damage; and when the injured tissue is capable of regenerating then the usual outcome is restoration Chronic Inflammation: if the offending agent is not removed, or it may be present from the onset of injury Scarring: type of repair after substantial tissue destruction; injured tissue is filled in by connective tissue

18. MORPHOLOGIC PATTERNS SEROUS INFLAMMATION - outpouring of a watery, relatively protein-poor fluid Fibrinous inflammation: consequence of more severe injuries, resulting in greater vascular permeability that allows large molecules (e.g. fibrinogen) to pass the endothelial barrier. Suppurative (purulent) inflammation and abscess formation: manifested by the collection of large amounts of purulent exudate or pus ULCERS - local defect or excavation of the surface of an organ or tissue that is produced by necrosis of cells and sloughing (shedding) of necrotic and inflammatory tissue; occur only when tissue necrosis and resultant inflammation exist on or near a surface

19. TISSUE REPAIR Refers to the restoration of tissue architecture & function after an injury By convention, the term repair is often used for parenchymal & connective tissues while healing is for surface epithelia Critical to the survival of an organism

20. REGENERATION • Process where some tissues are able to replace the damaged components & essentially return to a normal state • Occurs by proliferation of residual cells that survive the injury & retain the capacity to proliferate

21. SCAR FORMATION If injured tissues are incapable of competitive restitution, or if the supporting structures of the tissue are severely damaged, repair occurs by the laying down of connective (fibrous) tissue may result in scar formation

22. Quality Control (QC) in Histopathology QC refers to the operational techniques and activities used to fulfill requirements for quality in histopathology. It includes a series of measures and procedures designed to monitor and maintain the accuracy and precision of the diagnostic processes.

23. Key Aspects of QC Pre-analytical Phase: Specimen Collection: Ensuring correct patient identification, proper labeling, and appropriate specimen handling. Fixation: Proper fixation of tissues using formalin or other fixatives to preserve tissue morphology. Processing: Correct dehydration, clearing, and embedding techniques to ensure tissue integrity.

24. Analytical Phase: Sectioning: Precision in cutting thin sections of tissue for mounting on slides. Staining: Consistency in hematoxylin and eosin (H&E) staining, as well as special stains and immunohistochemistry, to ensure reproducibility and accuracy. Microscopy: Routine checking of the quality of slides and the performance of microscopes.

25. Post-analytical Phase: Reporting: Ensuring accurate and timely reporting of histopathological findings. Storage: Proper archiving of slides and blocks for future reference.

26. Quality Assurance (QA) in Histopathology QA is a broader concept that encompasses all the planned and systematic activities implemented within a quality system to provide confidence that the product or service will meet the required quality standards.

27. Key Aspects of QA Standard Operating Procedures (SOPs): Development and adherence to SOPs for all stages of histopathological examination. Training and Competency Assessment: Regular training of staff and assessment of their competency in performing histopathology procedures. Internal Audits: Regular internal audits to check compliance with SOPs and identify areas for improvement. Proficiency Testing: Participation in external quality assessment (EQA) programs to benchmark performance against other laboratories. Corrective Actions: Implementing corrective actions based on audit findings, proficiency testing results, and feedback. Documentation: Maintaining comprehensive records of all QC and QA activities, including equipment maintenance, staff training, and audit results.

28. Implementation Challenges: Human Factors: Variability in human performance can affect the consistency of QC processes. Resource Constraints: Limited resources, including personnel and equipment, can impact the implementation of effective QC and QA measures. Complexity of Cases: Difficult cases may require additional QC measures and expert consultation to ensure diagnostic accuracy.

29. Importance of Continuous Improvement: QC and QA in histopathology are not static processes; they require continuous monitoring, evaluation, and improvement. This ensures that the laboratory can adapt to new challenges, technologies, and standards, maintaining a high level of diagnostic accuracy and patient care. In conclusion, effective QC and QA are essential for the reliability of histopathological diagnoses, impacting patient outcomes significantly.