Cell Injury and Death

Cell Injury and Death

• Cell injury can be reversible or irreversible, and may lead to cell death
• Cells can adapt to stress, recover, or die in response to injury
• Causes of cell injury include:
  • Infectious pathogens producing toxins
  • Hypoxia and ischemia
  • Toxins and medications
  • Environmental insults (e.g. radiation, trauma)
  • Genetic abnormalities
  • Immune reactions
  • Aging
• Reversible cell injury is characterized by:
  • Functional and structural changes
  • No permanent damage
  • Can be corrected if the injurious agent is removed
  • Examples: swelling of endoplasmic reticulum and mitochondria, breakdown of plasma membrane

Mechanisms of Cell Injury and Death

• Reversible cell injury can progress to irreversible injury and cell death
• Irreversible cell injury is characterized by:
  • Permanent damage
  • Unable to be corrected
  • Leads to cell death
  • Examples: breakdown of nucleus, leakage of contents
• Two major pathways of cell death:
  • Necrosis: unprogrammed cell death, characterized by:
    • Inflammation
    • Cellular fragments
    • Phagocytosis of apoptotic cells
  • Apoptosis: programmed cell death, characterized by:
    • Condensation of chromatin
    • Membrane blebs
    • Apoptotic bodies
    • Phagocytosis of apoptotic cells

Cellular Adaptations to Stress

• Cells can adapt to stress through:
  • Changes in cellular function
  • Changes in cellular structure
  • Increased production of certain proteins
  • Activation of cellular defenses
  • Changes in gene expression

Pathologic Accumulations in Cells

• Fatty change: accumulation of triglycerides in cells
• Eosinophilia: accumulation of eosinophilic proteins in cells

Endoplasmic Reticulum (ER) Stress

• ER stress: disruption of ER function
• Causes: hypoxia, toxins, genetic abnormalities
• Results: accumulation of misfolded proteins, activation of cellular defenses### Cell Injury and Cell Death

Reversible Cell Injury

• Characterized by a sequence of events that can lead to necrosis or apoptosis
• Cell injury can be caused by various factors, including ischemia, toxins, and physical injury
• The injury can be reversible if the cell is able to repair itself

Necrosis

• A pathologic process that results in cell death
• Characterized by cellular swelling, disruption of plasma membrane, and leakage of cellular contents
• Can cause local inflammation and release of enzymes that break down cellular components
• Examples of necrosis include:
  • Coagulative necrosis (e.g., heart attack, stroke)
  • Liquifactive necrosis (e.g., bacterial infections)
  • Caseous necrosis (e.g., tuberculosis)
  • Fat necrosis (e.g., acute pancreatitis)
  • Fibrinoid necrosis (e.g., immune reactions)

Apoptosis

• A regulated process of cell death
• Characterized by cell shrinkage, fragmentation of DNA, and formation of apoptotic bodies
• Apoptotic cells are typically engulfed by macrophages and removed
• Examples of apoptosis include:
  • Physiologic apoptosis (e.g., embryonic development, tissue remodeling)
  • Pathologic apoptosis (e.g., cancer, neurodegenerative diseases)

Key Features of Necrosis and Apoptosis

• Necrosis:
  • Involves cellular swelling and disruption of plasma membrane
  • Results in leakage of cellular contents and local inflammation
  • Can be caused by various factors, including ischemia, toxins, and physical injury
• Apoptosis:
  • Involves cell shrinkage and fragmentation of DNA
  • Results in formation of apoptotic bodies and removal by macrophages
  • Can be a physiologic or pathologic process

Table 1.1: Features of Necrosis and Apoptosis

• Necrosis:
  • Enlarged cell size
  • Pyknosis → karyorrhexis → karyolysis
  • Disrupted plasma membrane
  • Enzymatic digestion of cellular contents
  • Frequent inflammation
• Apoptosis:
  • Reduced cell size
  • Fragmentation of DNA into nucleosome-sized fragments
  • Intact plasma membrane
  • Intact cellular contents
  • No inflammation### Cell Injury and Cell Death
• Cell injury can lead to cell death, which is a complex process involving various mechanisms and pathways.
• There are two main types of cell death: necrosis and apoptosis.

Necrosis

• Necrosis is a form of cell death characterized by cell swelling, rupture, and inflammation.
• It is a passive process, meaning it is not programmed or controlled by the cell.
• Necrosis can be caused by various factors, including:
  • Ischemia (lack of blood flow)
  • Infections (bacterial, viral, or fungal)
  • Toxins (chemicals, heavy metals, etc.)
  • Physical damage (trauma, burns, etc.)
• There are several types of necrosis, including:
  • Coagulative necrosis (characterized by protein denaturation and cell shrinkage)
  • Liquefactive necrosis (characterized by cell lysis and tissue dissolution)
  • Fibrinoid necrosis (characterized by fibrin deposition and inflammation)
  • Caseous necrosis (characterized by cheesy, yellow-white debris)
  • Fat necrosis (characterized by calcium soap formation and fat saponification)

Apoptosis

• Apoptosis is a form of programmed cell death, meaning it is a controlled and regulated process.
• It is a critical mechanism for eliminating unwanted or damaged cells, and is essential for development, tissue homeostasis, and immune response.
• Apoptosis is characterized by:
  • Cell shrinkage
  • Nuclear fragmentation
  • Chromatin condensation
  • Membrane blebbing
  • Formation of apoptotic bodies
• Apoptosis can be triggered by various factors, including:
  • DNA damage
  • Growth factor withdrawal
  • Hormonal changes
  • Infections
  • Immune responses
• There are two main pathways of apoptosis:
  • Intrinsic pathway (mitochondrial pathway)
  • Extrinsic pathway (death receptor pathway)

Physiologic and Pathologic Conditions Associated with Apoptosis

• Physiologic conditions:
  • Embryogenesis
  • Turnover of proliferative tissues
  • Involution of hormone-dependent tissues
  • Decline of leukocyte numbers
• Pathologic conditions:
  • DNA damage
  • Accumulation of misfolded proteins
  • Infections
  • Immune responses
  • Cancer
  • Neurodegenerative diseases

This quiz covers the basics of cell injury, its causes, and related topics like oxidative stress and cell death.