Cell Injury and Death

Study Notes

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Cell injury occurs when cells are stressed or exposed to damaging agents, leading to functional and morphological changes.
There are two types of cell death: necrosis and apoptosis, which differ in mechanisms, morphology, and roles in disease and physiology.

Oxygen deprivation (hypoxia)
- Interferes with aerobic oxidative respiration
- Can result from inadequate oxygenation of the blood or reduction in oxygen-carrying capacity
Chemical agents
- Can be toxic or derange the osmotic environment
- Examples: air pollutants, insecticides, CO, asbestos, ethanol
Infectious agents
- Range from submicroscopic viruses to meter-long tapeworms
Immunologic reactions
- Can result in cell and tissue injury
- Examples: autoimmune reactions, allergic reactions
Genetic factors
- Can cause cell injury due to deficiency of functional proteins or accumulation of damaged DNA
- Examples: inborn errors of metabolism, genetic variations (polymorphisms)
Nutritional imbalances
- Can cause cell injury due to protein calorie insufficiency, specific vitamin deficiencies, or disorders of nutrition
- Examples: obesity, type 2 diabetes, atherosclerosis
Physical agents
- Can cause cell injury due to trauma, extreme temperatures, radiation, electric shock, or sudden changes in atmospheric pressure
Aging
- Leads to alterations in replicative and repair abilities of individual cells and tissues
- Results in diminished ability to respond to damage and eventually cell death

Reversible injury
- Characterized by cellular swelling and fatty change
- Morphologic changes lag behind functional changes
Necrosis
- Characterized by changes in the cytoplasm and nuclei of injured cells
- Can result in liquefactive, caseous, or fat necrosis
Patterns of tissue necrosis
- Liquefactive necrosis: transformation of tissue into a liquid viscous mass
- Caseous necrosis: cheese-like appearance of necrotic tissue
- Fat necrosis: focal areas of fat destruction

Depletion of ATP
- Can result from reduced supply of oxygen and nutrients, mitochondrial damage, or toxins
- Leads to widespread effects on cellular systems, including cell swelling, dilation of the ER, and decreased intracellular pH
Mitochondrial damage and dysfunction
- Can result in ATP depletion, failure of energy-dependent cellular functions, and ultimately, necrosis
Influx of calcium
- Can cause damage to cellular components, including membranes, proteins, and DNA
- Can lead to apoptosis
Defects in membrane permeability
- Can result from ischemia, toxins, or physical agents
- Can lead to increased permeability, lipid breakdown, and ultimately, necrosis
Damage to DNA and proteins
- Can result from radiation, oxidative stress, or other forms of cellular injury
- Can trigger apoptosis

Programmed cell death
Characterized by enzymatic degradation of proteins and DNA
Initiated by two major pathways: mitochondrial (intrinsic) and death receptor (extrinsic)
Morphology of apoptotic cells
- Nuclei show chromatin condensation and aggregation
- Cells shrink, form cytoplasmic buds, and fragment into apoptotic bodies

Self-degradation
A survival mechanism in times of nutrient deprivation
Process involves sequestration of intracellular organelles and cytosol, fusion with lysosomes, and digestion of cellular components

Can result from inadequate removal of a normal substance, accumulation of an abnormal endogenous substance, failure to degrade a metabolite, or deposition of an exogenous substance
Examples: fatty change, storage diseases, and accumulation of carbon or silica particles

Result of a progressive decline in the life span and functional capacity of cells
Mechanisms include:
- Accumulation of DNA damage
- Replicative senescence
- Other factors, such as progressive accumulation of metabolic damage and possible roles of growth factors