Pathology of Atrophy and Metaplasia

Atrophy

• Reduced size of cell, tissue, or organ due to loss of cell substance
• Two types: physiologic and pathologic
• Physiologic atrophy occurs during normal development, such as the involution of the gravid uterus.
• Pathologic atrophy can be caused by:
  • Decreased workload (disuse atrophy)
  • Loss of innervation (denervation atrophy)
  • Diminished blood supply
  • Inadequate nutrition
  • Loss of endocrine stimulation (loss of estrogen)
• Mechanisms of atrophy:
  • Decreased protein synthesis and increased protein degradation
  • Degradation of cellular protein caused by the ubiquitin-proteasome pathway
  • Increased autophagy

Metaplasia

• Reversible change in which one differentiated cell type is replaced by another cell type
• The new epithelium is better suited to dealing with the current stress or irritation
• Persistence of factors causing metaplasia may lead to progression into malignant transformation
• Most common epithelial metaplasia is columnar to squamous, often seen in the respiratory tract of smokers
• Mechanism: reprogramming of stem cells to differentiate along a new pathway.

Cell Injury

• Stress (if severe, prolonged or damaging) leads to injury
• Cell injury can be reversible or irreversible
• Irreversible cell injury results in cell death, which can be necrosis or apoptosis

Mechanisms of Cell Injury

• Depletion of ATP: caused by reduced oxygen and nutrient supply, mitochondrial damage, or toxins
• Mitochondrial damage: sensitive to hypoxia, chemical toxins, and radiation; can lead to necrosis or apoptosis
• Influx of calcium: increased intracellular calcium can induce apoptosis
• Accumulation of oxygen-derived free radicals (oxidative stress)
• Defects in membrane permeability: increased permeability leads to loss of osmotic balance, influx of fluids, and loss of cellular contents
• Damage to DNA and proteins: can trigger apoptosis if repair mechanisms fail

Cellular Responses and Adaptations to Stress

• Cells adapt to surrounding stimuli or changes to survive
• Cellular responses include adaptation, injury, intracellular accumulation, and calcification
• Adaptation: reversible changes in size, number, phenotype, metabolic activity, or function in response to changes in the environment
• Adaption can be physiologic or pathologic

Hypertrophy

• An increase in cell size resulting in an increase in the size of the organ
• Occurs in nondividing cells (cardiac myocytes, skeletal muscles)
• Can coexist with hyperplasia in dividing cells (skin, GI tract cells)
• Caused by increased functional demand (workload) or hormonal stimulation
• Mechanism: increased production of cellular structural proteins and organelles
• Example: left ventricle hypertrophy in the heart

Hyperplasia

• An increase in the number of cells resulting in an increased mass of the organ or tissue
• Takes place in cells capable of dividing
• Mechanism: growth factor-driven proliferation of mature cells, or increased output of new cells from tissue stem cells
• Types:
  • Physiologic: hormonal (e.g., female breast during puberty and lactation) or compensatory (e.g., partial liver resection)
  • Pathologic: excessive hormone stimulation (e.g., endometrial hyperplasia), or infections (e.g., skin warts)
• Pathologic hyperplasia can be a fertile soil for development of malignancy.

Explore the concepts of atrophy and metaplasia in this quiz. Learn about the mechanisms and causes behind these physiological changes, including the types of atrophy and their implications. Test your understanding of cellular adaptations and their significance in pathology.