Cellular Adaptations Lecture 2

Cellular Adaptations

• Pathology studies the causes and consequences of human disease through etiology, pathogenesis, morphologic changes, and clinical manifestations.
• Cellular adaptations are reversible changes in size, number, and function due to environmental changes, preserving cell viability.

Types of Cellular Adaptations

• Hypertrophy: Increase in cell size due to increased workload, linked to growth factors and mechanical stress.
• Hyperplasia: Increase in cell number in tissues capable of division, often induced by hormones or growth factors.
• Atrophy: Decrease in cell size leading to reduced tissue size, can be physiologic or pathologic.
• Metaplasia: Replacement of one cell type with another, seen in response to chronic irritation.

Hypertrophy

• Induces larger cells without increasing the number of cells in an affected organ.
• Physiologic hypertrophy is a normal response (e.g., uterine growth in pregnancy).
• Pathologic hypertrophy results from disease, like cardiac hypertrophy due to hypertension.
• Mechanism involves protein synthesis and increased myofilament production; eventually may lead to cardiac failure.

Hyperplasia

• Can be physiologic (e.g., breast glandular epithelium during puberty) or compensatory (e.g., liver regeneration).
• Pathologic hyperplasia occurs due to excessive hormonal action, increasing cancer risk (e.g., endometrial hyperplasia).

Atrophy

• Can result from disuse, nutrient deprivation, or loss of stimulation (e.g., muscle atrophy from immobilization).
• Physiologic examples include atrophy of embryonic structures during development.

Metaplasia

• Common transformation of columnar epithelial cells to squamous cells (e.g., Barrett’s esophagus).

Cell Injury

• Occurs when adaptive capacity is exceeded due to external stressors or insults.
• Injury can be reversible or irreversible based on the severity and persistence of the damaging stimulus.

Types and Causes of Cell Injury

• Reversible Cell Injury: Functional and structural changes can be corrected if the harmful stimulus is removed.
• Irreversible Cell Injury: Permanent changes leading to cell death.
• Causes include:
  • Oxygen deprivation (hypoxia, ischemia).
  • Physical agents (trauma, temperature extremes).
  • Chemical agents and drugs.
  • Infectious agents, immunologic reactions, and genetic abnormalities.

Mechanisms of Cell Injury

• ATP depletion, mitochondrial damage, increased membrane permeability, accumulation of damaged DNA and proteins, reactive oxygen species, calcium influx, and endoplasmic reticulum stress.

Features of Reversible Cell Injury

• Characterized by cellular swelling (hydropic change) and fatty changes due to metabolic disruptions.
• Ultrastructural changes include plasma membrane alterations, mitochondrial swelling, and ER dilation.

Irreversible Cell Injury

• Denotes permanent pathological changes leading to cell death, marked by mitochondrial dysfunction and severe membrane disturbances.

Cell Death

• Necrosis: A pathologic process resulting from severe injury, characterized by protein denaturation, cell content leakage, and local inflammation.
• Apoptosis: A programmed form of cell death that is generally less inflammatory.

Necrosis Patterns

• Coagulative Necrosis: Preserved tissue architecture, commonly seen in ischemic injuries.
• Liquefactive Necrosis: Tissue transforms into liquid mass, often in brain infarcts and bacterial infections.
• Gangrenous Necrosis: Typically in limbs with blood supply loss, involving coagulative necrosis across tissue planes.

Morphologic Changes in Necrosis

• Necrotic cells appear eosinophilic on staining, may be glassy or vacuolated, and result in myelin figures leading to potential calcification.