Cell Injury and Death in Pathology

Cell Injury and Death

•  The images show normal and hyperplastic thyroid follicles.

Causes of Cell Injury

•  Trauma
•  Physical agents (e.g., heat, cold)
•  Chemical agents
•  Drugs
•  Infectious agents (bacterial, viral, fungal, mycobacterial, parasites)
•  Immunologic/autoimmune
•  Genetic factors
•  Nutritional factors
•  Vascular factors
•  Neoplasia
•  Environmental factors (e.g., silica)
•  Metabolic factors (e.g., endocrine)
•  Iatrogenic factors

Cellular Responses to Stress and Stimuli

•  Cells adapt to stress or increased demand, either functionally or structurally.
•  Cells adapt up to a certain point; if the stress becomes too great or injurious, the cells will sustain injury.
•  Reversible cell injury can be reversed if the stimulus is removed.
•  Irreversible cell injury cannot be reversed; it can progress to cell death.

Types of Cellular Adaptation: Hyperplasia and Hypertrophy

•  Hyperplasia: cells respond to increased demand by increasing the number of cells.
•  Hypertrophy: cells respond to increased demand by increasing the size of the cells, but not the number.

Hyperplasia and Hypertrophy

• Cells capable of undergoing mitosis respond with hyperplasia.
• Cells incapable of mitosis respond with hypertrophy alone.

Two Types of Hyperplasia

•  Physiological hyperplasia: includes hormonal (e.g., uterus during pregnancy) and compensatory (liver regeneration) hyperplasia.
•  Pathological hyperplasia: results from excessive hormonal stimulation, although the process is still controlled.

Hypertrophy

• Hypertrophy refers to an increase in the size of cells.

Two Types of Hypertrophy

• Physiological hypertrophy: results from increased functional demand or hormonal stimulation. (e.g., pregnant uterus).
• Pathological hypertrophy: results from increased functional demand resulting in structural changes (e.g., left ventricular hypertrophy from hypertension.)

Left Ventricular Hypertrophy

•  Left ventricular thickness greater than 1 cm.
•  Secondary to hypertension in patients

Types of Cellular Adaptation: Atrophy

• Atrophy: reduction in the size of cells or tissues through shrinkage of cell size.
• Physiological atrophy: common during normal development.
• Pathological atrophy: depends on the underlying cause, can be local or generalized.

Common Causes of Atrophy

• Decreased workload
• Loss of innervation (denervation atrophy)
• Diminished blood supply
• Inadequate nutrition
• Loss of endocrine stimulation
• Aging (senile atrophy)
• Pressure

Types of Cellular Adaptation: Metaplasia

•  Metaplasia: is reversible change in which one adult cell type is replaced by another adult cell type.
• Examples: columnar to squamous metaplasia (e.g., bronchial epithelium in response to cigarette smoke), squamous to columnar metaplasia (e.g., esophagus epithelium in response to acidic gastric contents).

Manifestations of Adaptation or Sub-lethal Cell Injury: Intracellular Accumulations.

• Intracellular accumulations, often linked with metaplasia, can be normal or abnormal.
  • Can be endogenous (originating within the body) or exogenous (originating outside the body).

Pathologic Calcification

•  Dystrophic calcification: Calcium deposits on previously injured tissue.
•  Metastatic calcification: Calcium deposits in originally healthy tissue in patients with hypercalcemia.

Cell Injury

•  Cell injury occurs when a cell is no longer able to adapt, or when it is exposed to inherently damaging agents.

Reversible Cell Injury

• Reversible cell injury is reversible if the damaging stimulus is removed.
• Hallmarks of reversible injury include reduced oxidative phosphorylation, ATP depletion, and cellular swelling caused by changes in ion concentrations and water influx.

Two Major Microscopic Changes in Reversible Cell Injury

• Cellular swelling
• Fatty change

Kidney with Reversible Injury: Diffuse Cellular Swelling

• Pale, swollen cortex

Cellular Swelling and Fatty Change

•  Microscopic images showing these changes.

Causes of Cell Injury (continued)

•  Hypoxia (due to ischemia, cardiorespiratory failure, severe blood loss, anemia, or carbon monoxide poisoning)
•  Physical agents
•  Chemical agents and drugs
•  Infectious agents
•  Immunologic reactions
•  Genetic derangements
•  Nutritional imbalances
•  Vascular factors
•  Neoplasia
•  Environmental factors (e.g., silica)
•  Metabolic factors (e.g., endocrine)
•  Iatrogenic factors (caused by treatment/medical intervention)

Basic Cellular and Molecular Factors in Irreversible Cell Injury and Death

•  Mitochondrial damage
•  Increased calcium (Ca2+) entry
•  Reactive oxygen species (ROS)
•  Membrane damage
•  Protein misfolding/DNA damage
•  A common underlying process leading to cell death is hypoxia.

Two Types of Cell Death: Necrosis and Apoptosis

• Necrosis:
  • Severe plasma membrane damage
  • Plasma membrane dysfunction and eventual rupture
  • Internal organelle membrane dysfunction and rupture
  • Lysosomal enzymes digest the cell.
  • Extracellular injurious enzymes elicit an acute inflammatory response
  • Always pathological
• Apoptosis:
  • Cell DNA and/or proteins damaged beyond repair.
  • Genetic program for cell destruction
  • Nuclear dissolutions
  • Cell fragmentation
  • Rapid removal of cellular debris without an acute inflammatory response.
  • Not necessarily associated with cell injury, may occur during development.

Morphologic Changes with Necrosis: Coagulative Necrosis - Kidney

•  Microscopic images of kidney showing coagulative necrosis.

Patterns of Tissue Necrosis

• When large numbers of cells undergo necrosis, the whole tissue or organ is described as necrotic
• Several morphologically distinct patterns of necrosis give clues about the underlying cause.

Coagulative Necrosis

• The basic architecture of the tissue is preserved for a few days.
• The injury denatures structural and enzymatic proteins.
• Eosinophilic, anucleate cells persist.
• Ischemia leads to coagulative necrosis; a localized area is an infarct.

Liquefactive Necrosis

• Digestion of cells results in a liquid, viscous mass (pus).
• Common in bacterial and fungal infections, or ischemic brain damage.

“Dry” Gangrenous Necrosis

• commonly applied to limbs/bowel that lose blood supply and undergo coagulative necrosis.

Caseous Necrosis

•  Encountered most often with tuberculosis infection.
•  Friable white “cheese-like” area of necrosis.
•  Contains foci of inflammation (granulomas).

Fat Necrosis

•  Focal areas of fat destruction.
•  Common location: inflamed pancreas (pancreatitis).
•  Pancreatic enzymes leak from injured cells.
•  Trauma to the breast is another example.

Fat Necrosis with Dystrophic Calcification

•  Imaging (e.g., ultrasound or X-ray) demonstrating fat necrosis and dystrophic calcification in the breast. 

Fibrinoid Necrosis

•  Usually seen in immune reactions involving blood vessels.

This quiz explores the concepts of cell injury and death, outlining various causes such as physical, chemical, and environmental factors. It also discusses cellular responses to stress, adaptation mechanisms like hyperplasia and hypertrophy, and the differences between reversible and irreversible cell injury. Test your understanding of these crucial topics in pathology!