Introduction to Pathology

Pathology

• The study of disease (pathos) and suffering (logos).
• Focuses on changes in cells, tissues, and organs caused by disease.
• Involves laboratory examination of body tissue.
• Bridges basic sciences with clinical medicine.
• Utilizes various techniques (morphologic, molecular, microbiologic, immunologic).
• Pathologist: Physician who interprets and diagnoses disease-related changes.

Introduction to Pathology

• General Pathology: Studies cellular and tissue responses to abnormal stimuli.
  • Examples: cell injury, inflammation, repair, hemodynamic disorders, genetic disorders, immune system diseases, infectious diseases, and environmental diseases.
• Systemic Pathology: Examines alterations in specific organs and tissues in a diseased state.
  • Aspects include etiology, pathogenesis, and disease classification.
• Etiology (Cause):
  • Genetic: Mutations (congenital or acquired).
  • Acquired: Infectious, nutritional, chemical factors.
• Pathogenesis (Mechanism): The sequence of events from initial stimulus to disease manifestation.

Classification of Pathology

• Anatomical/ Surgical Pathology:
  • Gross and microscopic examination of tissues for diagnosis.
  • Includes: histopathology, cytopathology, autopsy, and subspecialties (like neuropathology).
• Clinical Pathology:
  • Involves hematology, microbiology, immunology, serology, and biochemistry.

Diagnosis in Anatomical Pathology

• Biopsies: Tissue samples for diagnosis.
  • Excisional: Removal of the entire tissue.
  • Incisional: Removal of a portion of the tissue.
• Smears: Cell samples for diagnosis.
  • Exfoliative: Obtaining cells naturally shed (e.g., Pap smear for cervical cancer screening).
  • Fine Needle Aspiration (FNA): Sampling cells using a needle (e.g., breast or thyroid).

Biopsy Types

• Fine Needle Aspiration (FNA):
  • Advantages: Easy to obtain, can be guided by ultrasound or CT, useful for peripheral adenopathy.
  • Limitations: Only obtains a few cells, limited use for certain diagnoses.
• Core Biopsy (Larger Needle):
  • Advantages: More tissue for confident diagnosis, can be used for flow cytometry (confirming lymphoma diagnosis).
  • Limitations: May not identify all lymphomas/ leukemias.
• Excisional Biopsy:
  • Advantages: Most tissue for diagnosis.
  • Limitations: More invasive, time-consuming to arrange.
• EBUS/TANA:
  • Advantages: Necessary for lung lesions inaccessible by other methods.
  • Limitations: Same limitations as FNA.

Stages of Tissue Processing

• Preservation and Processing of Tissues:
  • Specimen Identification and Labeling:
    • Each specimen receives a unique number for identification.
  • Gross Examination:
    • Initial visual inspection of the specimen.
  • Fixation:
    • Preserves the specimen using 10% formaldehyde (formalin).
  • Dehydration:
    • Removal of water using increasing concentrations of alcohol.
  • Clearing:
    • Replacement of alcohol with xylene or toluene.
  • Impregnation:
    • Infiltration of the specimen with molten paraffin.
  • Embedding:
    • Encasing the specimen in solidified paraffin.
  • Section Cutting:
    • Thin slices of embedded tissue are made.
  • Staining:
    • Staining the slices for visualization.
      • Hematoxylin-Eosin (H&E) Staining:
        • Stains nuclei blue and cytoplasm/extracellular components red.
  • Mounting:
    • Preparing the stained slices for microscopic examination.

Cellular Responses to Stress

• Basic Principles:
  • Organ: A differentiated structure (heart, liver, kidney) composed of cells and tissues.
  • Homeostasis: The normal physiological state that maintains a stable internal environment.
  • Stress on an organ can lead to cellular responses (adaptation, injury, death).
• Cellular Responses:
  • Adaptation: Reversible changes in cell size, number, and function in response to stress.
  • Injury: Reversible or irreversible damage to cells.
  • Apoptosis: Programmed cell death.
  • Intracellular Accumulation: Buildup of substances within cells.
  • Calcification: Deposition of calcium salts in tissues.
  • Cellular Aging: Changes associated with the aging process.
• Factors Determining Cellular Response:
  • Nature and Severity of Stress:
    • Fast, severe, or prolonged stress leads to cell injury.
    • Less severe stress leads to cellular adaptation.
  • Involved Cell: Cell types vary in their ability to adapt or respond to stress.

Growth Adaptations

• Adaptation: A new steady state achieved by cells in response to stress, preserving viability and function.
• Growth Adaptations:
  • Hypertrophy: Increase in cell size leading to increased organ size.
    • Mechanism: Increased production of cellular proteins and organelles.
    • Causes: Increased functional demand (workload), hormonal stimulation, growth factor stimulation.
    • Limitations: Hypertrophy has limits, excessive stress can lead to cell injury.
  • Hyperplasia: Increase in cell number leading to increased organ size.
    • Mechanism: Production of new cells from stem cells.
    • Types:
      • Physiological: Normal growth due to hormones or compensation.
      • Pathological: Excessive hormone stimulation.
    • Examples:
      • Physiological: Uterine enlargement during pregnancy (hormonal), compensatory hyperplasia after liver resection (growth factors).
      • Pathological: Endometrial hyperplasia (excessive estrogen), prostate hyperplasia (androgen).
    • Note: Pathological hyperplasia can increase cancer risk.
  • Atrophy: Decrease in cell size and number leading to decreased organ size.
    • Mechanism:
      • Decreased protein synthesis and increased protein degradation.
      • Reduced metabolic activity.
      • Ubiquitin-proteasome pathway: Degradation of cellular components.
      • Autophagy (self-eating) to find protein sources.
    • Causes: Decreased workload, loss of innervation, diminished blood supply, inadequate nutrition, loss of endocrine stimulation, aging.
    • Types:
      • Physiological: Embryonic development, involuting gravid uterus.
      • Pathological: Disuse atrophy, denervation atrophy, inadequate nutrition, loss of endocrine stimulation, aging.
  • Metaplasia: A change in cell type due to stress.
    • Mechanism: Reversible replacement of one differentiated cell type with another.
    • Example: Squamous metaplasia in the respiratory tract of smokers.