Cell Injury and Cell Death

Course Name: Pathology
Year: 1
Class: FFP1
Lecturer: Professor Muna Sabah
Date: 15th October 2025
Email: pathteachcoord@rcsi.ie
Institution: RCSI Royal College of Surgeons in Ireland (Coláiste Ríoga na Máinleá in Éirinn)

Describe cell injury and define necrosis and apoptosis: Understanding the differences, causes, and mechanisms of cell death forms.
Describe the causes, mechanisms, and cellular responses to cell injury: Recognizing how cells react to damage.
Describe cellular adaptation: Learning how cells adjust to stressors.
Describe the mechanisms of injury: Understanding how and why injuries occur.
List the morphological changes of reversible and irreversible injury: Identifying changes in cell structure and function.
Describe the types of necrosis: Understanding different patterns of cell death due to pathological processes.
Describe intracellular accumulation and calcification: Understanding the buildup of substances within cells and abnormal mineral deposits.

Cellular Responses: Stress and noxious stimuli lead to adaptive responses, injury, or cell death.
Cellular Adaptation: Includes processes like atrophy, hypertrophy, hyperplasia, and metaplasia.
Cell Injury: Involves causes, mechanisms, and morphological changes.
Types of Cell Death: Both necrosis and apoptosis as results of injury.
Intracellular Accumulation: Recognition of pathological buildup in cells.
Pathologic Calcification: Abnormal mineral deposits in tissues.
Cellular Aging: Factors contributing to aging at the cellular level.

Adaptive Responses:
- Atrophy: Reduction in cell size or number. Includes causes such as decreased workload, loss of innervation, diminished blood supply, inadequate nutrition, loss of hormonal stimulation, aging, and fetal development.
- Hypertrophy: Increase in cell size. Characterized by gene activation and increased protein synthesis without new cells forming. Physiological examples include skeletal muscle growth from exercise; pathological examples include left ventricular hypertrophy due to hypertension.
- Hyperplasia: Increase in cell number, often occurs with hypertrophy and is typically found in capable dividers. Physiological examples include hormonal stimulation during pregnancy; pathological examples include thyroid hyperplasia due to excess hormones.
- Metaplasia: Reversible change where one cell type is replaced by another, often due to chronic irritation or inflammation (e.g., squamous metaplasia in smokers).

Oxygen Deprivation:
- Hypoxia: Low oxygen delivery to tissue.
- Ischemia: Decreased blood flow leading to reduced oxygen and nutrient supply.
- Shock: General perfusion failure.
Physical Agents: Can be trauma, thermal injury, or radiation exposure.
Chemical Agents: Poisonous substances, environmental pollutants, or drugs.
Infectious Agents: Bacteria, viruses, fungi can induce cell injury.
Immunologic Reactions: Autoimmunity or hypersensitivity can damage tissues.
Genetic Defects: Can lead to cellular malfunction.
Nutritional Deficiencies or Excess: Imbalance can cause cell injury.

Cellular Response: Dependent on injury type, severity, duration, and the cell's nature.
Vulnerable Cell Systems: Mitochondria, cell membranes, synthetic apparatus, cytoskeleton, and genetic apparatus are most susceptible.
Injury Consequences: Include ATP depletion, mitochondrial damage, membrane permeability defects, calcium homeostasis disruption, and DNA/protein damage.

Definition: Extremely unstable molecules with unpaired electrons.
Sources: Normal metabolic processes, radiation, inflammation, and exposure to toxins.
Examples of Free Radicals: O2^− (superoxide), H2O2 (hydrogen peroxide), OH^− (hydroxyl ion).
Consequences of Free Radical Action: Lipid peroxidation, protein alterations, DNA mutation leading to cellular dysfunctional changes.

Reversible Injury: Characterized by cytoplasmic swelling, changes in organelle structure, and nuclear alterations.
Irreversible Injury: Includes extensive plasma membrane damage, mitochondrial changes, and lysosomal damage.

Definitions:
- Necrosis: Unplanned cell death due to pathological conditions, resulting in inflammation.
- Apoptosis: Programmed cell death that is genetically regulated and often does not induce inflammation.

Coagulative Necrosis: Characterized by preservation of cell structure despite cell death, typical in hypoxic conditions.
Liquefactive Necrosis: Transformation of tissue into liquid, often due to bacterial infections; tissue architecture is destroyed.
Caseous Necrosis: Seen in tuberculous infections, presenting a cheesy appearance with granulomatous inflammation.
Fat Necrosis: Occurs when lipases damage fat tissue, leading to saponification.
Fibrinoid Necrosis: Associated with blood vessel wall damage in vasculitis.
Gangrenous Necrosis: Not a distinct type but results from loss of blood supply; includes dry (coagulative) and wet (liquefactive) varieties due to bacterial superinfection.

Definition: Programmed cell death.
Physiologic Roles: Key in embryogenesis, remodeling tissues, and removing harmful or aged cells.
Pathological Roles: Engages in response to infections and cellular damage, especially with cancer.
Mechanism: Involves a cascade of cellular events and activation of caspases that lead to cell shrinking, DNA fragmentation, and the formation of apoptotic bodies.
Morphology: Distinguished by single cell apoptosis without accompanying inflammation, evidenced by chromatin condensation and DNA fragmentation.
Diseases Associated with Apoptosis: Increased apoptosis is seen in neurodegenerative diseases, while disorders of cell survival such as neoplasms arise from dysregulation of apoptotic pathways.

Endogenous Substances: Include normal substances produced at an increased rate or through metabolic inadequacy; examples include lipofuscin accumulation causing pigmentation in aging.
Exogenous Substances: Inability of cells to degrade foreign materials like carbon.

Definition: Abnormal deposition of calcium salts in tissues, which may arise in necrotic areas (dystrophic calcification) or normal tissues in the presence of hypercalcemia (metastatic calcification).
- Dystrophic Calcification: Occurs in necrotic tissue despite normal serum calcium levels, found in areas of injury.
- Metastatic Calcification: Occurs in normal tissues during hypercalcemic conditions and commonly affects organs such as the lungs, kidneys, and blood vessels.

Theories on Aging:
- Wear-and-Tear Theory: Proposes aging is due to cumulative damage at the cellular and molecular levels.
- Intrinsic Cellular Aging: Focuses on predetermined genetic factors that limit replication, emphasized by telomere shortening with each cell division.