Cell Growth and Death Mechanisms

Cell Growth/Proliferation, Necrosis/Apoptosis, Tissue Injury

• The stability of a structure is directly related to the security of its foundation (Blake Higginbotham quote)
• The lecture outlines cell growth/proliferation, cell injury/death (reversible/irreversible), cell injury mechanisms, and morphological features of cell death (necrosis/apoptosis).

Lecture Outline

• Cell Growth/Proliferation
• Cell Injury/Death
  • Reversible injury
  • Irreversible injury
  • Mechanisms of cell injury
  • Mechanisms and morphological features of cell death
    • Necrosis
    • Apoptosis

Lecture Objectives

• Define and use relevant terms (pyknosis, karyorrhexis, karyolysis, ischemia, infarct) correctly.
• Describe the morphological and biochemical features of apoptosis.
• List examples of apoptosis in physiological and pathological conditions.
• Describe the morphological and biochemical features of necrosis.
• Compare necrosis and apoptosis in terms of critical features, common situations of occurrence, and mechanisms of development.
• Compare the types of necrosis (coagulative, caseous, fat, liquefactive, and gangrenous) by gross and microscopic features, common sites/tissues involved, and common causes/mechanisms
• Provide examples for each type

Cell Cycle

• The cell cycle includes the phases: M phase (mitosis), S phase (DNA replication), G1/G2 phases
• Control/regulatory systems regulate DNA replication, mitosis, and cytokinesis.
• Checkpoints occur in G1 and G2 to decide if a cell proceeds to the next phase.

Cell Growth/ Proliferation: Cellular Requirements

• Cellular requirements for growth and proliferation include nutrients and chemical signals from other cells.
• Signal molecules are either soluble proteins, proteins bound to the surface of other cells, or proteins bound to the extracellular matrix (ECM).
• Signal molecules stimulate or inhibit cellular function.

Cell Signaling

• Endocrine: Hormones secreted into the bloodstream are distributed throughout the body.

• Paracrine: Paracrine signals are released into the extracellular fluid and affect nearby cells.

• Synaptic: Neuronal signals are transmitted electrically along a nerve axon; this causes neurotransmitter release to adjacent target cells

• Contact-dependent: A cell-surface-bound signal molecule binds to a receptor protein on an adjacent cell.

Cell Growth/Proliferation: Signal Molecules Categories

• Stimulatory signal molecules are classified into three major categories:
  • Survival factors: Suppress apoptosis
  • Mitogens: Stimulate cell division
  • Growth factors: Stimulate cell growth

Cell Injury/Cell Death - Reversible vs. Irreversible

• Cell death is the consequence of cell injury.
• Reversible vs. irreversible injury
  • Stress
  • Injurious stimulus
  • Adaptive response
  • Ability/Inability to adapt
  • Reversible cell injury vs. cell death (e.g., necrosis, apoptosis)

Reversible Cell Injury

• Hallmarks: Decreased oxidative phosphorylation (ATP formation), Na+/K+ ATPase pump abnormalities, membrane alterations, changes in intracellular ion concentration, cellular swelling, alterations in intracellular organelles, defects in protein synthesis, cytoskeletal damage, DNA damage.

• Light microscopic features: Cellular swelling due to energy-dependent ion pump failure, fatty change, abnormal processing of fatty acids.

• Ultrastructural features: Plasma membrane blebbing, loss of microvilli, mitochondrial swelling, dilation of ER, detachment of polysomes, myelin figures, nuclear alterations.

Irreversible Cell Injury

• Cell can no longer adapt, resulting in cell death.
• Characterized by severe mitochondrial damage and loss of membrane integrity.

Cell Injury/Cell Death: Two Types

• Necrosis:
  • Unregulated cell death, leakage of lysosomal enzymes into cytoplasm, inflammatory reaction, and a pathological process.
• Apoptosis:
  • Programmed cell death, nuclear dissolution, no inflammatory reaction, and serves many normal cellular functions.

Necrosis: Morphologic Changes

• Increased eosinophilia, glassy appearance, vacuolated appearance, myelin figures, dilated mitochondria with amorphous densities
• Nuclear changes:
  • Karyolysis (fading/loss of basophilia)
  • Pyknosis (nuclear shrinking; increased basophilia)
  • Karyorrhexis (nuclear fragmentation)

Patterns of Tissue Necrosis

• Coagulative necrosis: Preservation of tissue architecture for a few days; blocked proteolysis of dead cells. Seen in ischemia due to vessel obstruction (e.g., infarcts).
• Liquefactive necrosis: Tissue converted to a liquid viscous mass; common in bacterial infections (abscesses) and brain infarcts.
• Caseous necrosis: Area of necrosis appears white, friable, and cheese-like; a characteristic feature of tuberculous infection.
• Fibrinoid necrosis: Deposition of immune complexes, blood vessels, pink amorphous area of necrosis.
• Fat necrosis: Focal area of fat destruction, common in acute pancreatitis, formation of calcium soaps.
• Gangrenous necrosis: Often coagulative, involving multiple tissue planes and necrosis of a limb due to blood supply loss.

Cell Injury: Causes

• Oxygen deprivation: Hypoxia (deficiency of oxygen), ischemia (reduced blood flow), inadequate blood oxygenation, decreased oxygen-carrying capacity, decreased blood volume.
• Physical agents: Mechanical trauma, extremes of temperature (burns, deep cold), radiation, electric shock.
• Chemical agents and drugs: Normal ions in high concentrations, poisons, pollutants, insecticides, herbicides, alcohol, therapeutic drugs.
• Infectious agents
• Immunologic reactions: Autoimmune reactions, reactions to microbes.
• Genetic defects: Defects in functional proteins, accumulation of misfolded proteins, DNA damage
• Nutritional imbalances: Protein-calorie deficiencies, vitamin deficiencies, nutritional excess

Mechanisms of Cell Injury

• Cellular response depends on injury type, duration, and severity.
• Consequences depend on injured cell type, state, and adaptability
• Key cellular components frequently damaged include mitochondria, cell membranes, proteins synthesis/packaging, and DNA
• Key mechanisms include decrease in ATP, mitochondrial damage, loss of calcium homeostasis, oxygen-derived free radicals (oxidative stress), defects in membrane permeability, and abnormal proteins.

This quiz focuses on cell growth, proliferation, and the mechanisms of cell injury and death, including necrosis and apoptosis. It covers definitions and characteristics of these processes, ensuring an understanding of their comparative aspects and implications in health and disease.