General and Systemic Pathology: Disease Processes

• Pathology is the study of disease
• It bridges basic science and clinical medicine
• It explains the "why" behind illnesses, from mechanisms to signs and symptoms

General Pathology

• General pathology focuses on the basic reactions of cells and tissues to abnormal stimuli
• It underlies all diseases

Systemic Pathology

• Systemic pathology examines the specific responses of particular organs and tissues to defined insults

Four Aspects of a Disease Process

• Etiology: The cause of the disease.
• Pathogenesis: The mechanisms of its development.
• Morphologic changes: The structural alterations induced in cells and organs.
• Clinical manifestations: The functional consequences of the morphologic changes.

Etiology

• Divided into genetic and acquired (infectious, nutritional, chemical, physical)
• Most diseases are multifactorial, arising from the interaction of several genetic traits and environmental influences

Pathogenesis

• Describes the sequence of events from initial stimulus to the ultimate expression of the disease

Morphologic Changes

• These are the structural alterations in cells or tissues that are characteristic of a disease or diagnostic of an etiologic process

Clinical Manifestations

• These are the signs and symptoms of disease

Pathology's Role

• Pathology is the scientific foundation for clinical medicine
• It is essential for understanding disease, making diagnoses, and planning treatment

Adaptations, Cell Injury, and Cell Death

• Cells adapt to changes in their environment
• If the adaptive capability is exceeded or if the external changes are intrinsically harmful, cell injury develops

Cellular Adaptations

• Cells adapt to changes in their environment by undergoing adaptations.
• Adaptations include: Hypertrophy, Hyperplasia, Atrophy, Metaplasia

Hypertrophy

• An increase in cell size, leading to an increase in the size of the organ
• Occurs when cells cannot divide
• Caused by increased functional demand or hormonal stimulation
• Examples include:
  • Enlargement of skeletal muscle with weight training
  • Uterine enlargement during pregnancy

Hyperplasia

• An increase in cell number
• Can only occur in tissues with cells capable of dividing
• Often occurs together with hypertrophy
• Caused by increased functional demand or hormonal stimulation
• Examples include:
  • Proliferation of glandular epithelium of the breast at puberty and during pregnancy
  • Compensatory hyperplasia of the liver after partial resection

Atrophy

• A decrease in cell size and number, leading to a decrease in the size of the organ
• Caused by decreased functional demand, loss of innervation, diminished blood supply, inadequate nutrition, loss of endocrine stimulation, and aging
• Examples include:
  • Muscle atrophy after immobilization
  • Brain atrophy in elderly individuals

Metaplasia

• A reversible change in which one adult cell type is replaced by another adult cell type
• Occurs in response to chronic irritation
• Allows cells to better withstand the adverse environment
• May lead to reduced function or increased propensity for malignant transformation
• Examples include:
  • Replacement of columnar epithelium with squamous epithelium in the trachea and bronchi of smokers
  • Replacement of squamous epithelium with columnar epithelium in the esophagus in Barrett esophagus

Cell Injury

• Occurs when cells are unable to adapt to changes in their environment
• Reversible injury: Cell can recover if the damaging stimulus is removed
• Irreversible injury: Cell death occurs

Causes of Cell Injury

• Oxygen deprivation (hypoxia, ischemia)
• Physical agents (trauma, heat, cold, radiation)
• Chemical agents and drugs
• Infectious agents
• Immunologic reactions
• Genetic derangements
• Nutritional imbalances

Mechanisms of Cell Injury

• ATP depletion
• Mitochondrial damage
• Influx of calcium
• Accumulation of free radicals
• Damage to DNA and proteins
• Membrane damage

Reversible Cell Injury

• Cellular swelling
• Fatty change
• Plasma membrane alterations
• Mitochondrial changes
• Dilation of the endoplasmic reticulum
• Nuclear alterations

Irreversible Cell Injury and Cell Death

• Necrosis
• Apoptosis

Necrosis

• Cell death due to external injury; always pathologic
• Results from the degradation of cells by enzymes
• Induces inflammation
• Morphologic changes include:
  • Increased eosinophilia
  • Cell swelling
  • Plasma membrane rupture
  • Nuclear changes (karyolysis, pyknosis, karyorrhexis)

Apoptosis

• Programmed cell death; can be physiologic or pathologic
• Results from an internally programmed series of events
• Minimizes inflammation
• Morphologic changes include:
  • Cell shrinkage
  • Chromatin condensation
  • Formation of cytoplasmic blebs and apoptotic bodies
  • Phagocytosis of apoptotic bodies by macrophages

Inflammation and Repair

• Inflammation is a protective response intended to eliminate the initial cause of cell injury and remove the damaged tissue
• Repair restores tissue structure and function after injury

Inflammation

• Inflammation is a complex reaction to injurious agents such as microbes and damaged cells
• It involves vascular responses, migration and activation of leukocytes, and systemic reactions

Acute Inflammation

• Rapid onset (minutes to hours)
• Characterized by:
  • Exudation of fluid and plasma proteins (edema)
  • Emigration of leukocytes, predominantly neutrophils

Chronic Inflammation

• Longer duration (days to years)
• Characterized by:
  • Infiltration with mononuclear cells (lymphocytes, macrophages, plasma cells)
  • Tissue destruction
  • Attempts at repair (angiogenesis, fibrosis)

Cardinal Signs of Inflammation

• Heat (calor)
• Redness (rubor)
• Swelling (tumor)
• Pain (dolor)
• Loss of function (functio laesa)

Causes of Inflammation

• Infections
• Tissue necrosis
• Foreign bodies
• Immune reactions

Vascular Changes in Acute Inflammation

• Vasodilation
• Increased vascular permeability
• Endothelial cell activation

Cellular Events in Acute Inflammation

• Leukocyte recruitment
• Leukocyte activation
• Phagocytosis

Outcomes of Acute Inflammation

• Resolution: complete restoration to normal
• Healing by fibrosis: scar formation
• Chronic inflammation

Chronic Inflammation

• May follow acute inflammation or arise de novo
• Characterized by:
  • Persistent inflammation
  • Tissue injury
  • Repair

Causes of Chronic Inflammation

• Persistent infections
• Prolonged exposure to toxic agents
• Autoimmunity

Cells of Chronic Inflammation

• Macrophages
• Lymphocytes
• Plasma cells
• Eosinophils
• Mast cells

Granulomatous Inflammation

• A form of chronic inflammation characterized by granulomas, which are collections of activated macrophages, often with T lymphocytes, and sometimes associated with central necrosis
• Typically occurs in response to:
  • Persistent infections (e.g., tuberculosis)
  • Foreign bodies
  • Autoimmune diseases

Tissue Repair

• Regeneration: Complete restoration of tissue structure and function
• Healing by fibrosis: Scar formation

Tissue Regeneration

• Requires cells capable of proliferation and an intact connective tissue scaffold
• Occurs by proliferation of residual (uninjured) cells and maturation of tissue stem cells

Healing by Fibrosis (Scar Formation)

• Occurs when tissue injury is severe or regeneration is not possible
• Involves:
  • Angiogenesis
  • Formation of granulation tissue
  • Collagen deposition
  • Scar formation

Factors Influencing Tissue Repair

• Infection
• Nutrition
• Glucocorticoids
• Mechanical factors
• Poor perfusion
• Foreign bodies
• Type and extent of injury
• Location of injury

Clinical Pathology

• Clinical pathology involves the laboratory analysis of body fluids and tissues to diagnose and monitor disease
• It encompasses various disciplines, including:
  • Clinical chemistry
  • Hematology
  • Microbiology
  • Immunology
  • Transfusion medicine
  • Molecular diagnostics

Clinical Chemistry

• Analyzes the chemical components of body fluids such as blood, urine, and cerebrospinal fluid.
• Common tests include:
  • Glucose
  • Electrolytes
  • Liver function tests
  • Renal function tests
  • Cardiac markers
  • Lipids

Hematology

• Studies the cellular components of blood, including:
  • Red blood cells
  • White blood cells
  • Platelets
• Common tests include:
  • Complete blood count (CBC)
  • Peripheral blood smear
  • Coagulation studies
  • Bone marrow examination

Microbiology

• Identifies and characterizes microorganisms, such as bacteria, viruses, fungi, and parasites, that cause infectious diseases.
• Common tests include:
  • Cultures
  • Gram stains
  • Molecular tests

Immunology

• Studies the body's immune system and its response to infections, autoimmune diseases, and other conditions.
• Common tests include:
  • Antibody testing
  • Flow cytometry
  • Cytokine assays

Transfusion Medicine

• Deals with the collection, processing, and transfusion of blood and blood products.
  • Includes:
  • Blood typing
  • Antibody screening
  • Crossmatching

Molecular Diagnostics

• Uses molecular techniques, such as PCR and DNA sequencing, to detect and analyze genetic material from pathogens, tumors, and other sources.
• Applications include:
  • Infectious disease diagnosis
  • Cancer diagnosis and monitoring
  • Genetic testing