Cell Injury and Cell Death Overview

Cell Injury and Cell Death

• Cell injury occurs due to biochemical and morphologic changes
• Causes include exogenous factors (e.g., trauma, heat, chemicals, bacterial toxins, radiation, drug toxicity) and endogenous factors (e.g., genetic defects, nutritional deficiency, hypoxia, anoxia)
• Cell injury can result in reversible damage or irreversible disruption of normal cell function
• Hypoxia is a decrease in the supply of oxygen, while anoxia is a complete block in oxygen supply
• Causes of hypoxia and anoxia include low oxygen concentration in air, anemia, ischemia, thrombosis/embolism, rupture of an aneurysm, and cyanide poisoning
•  Injury to cells results in ATP depletion, mitochondrial damage, calcium changes, and oxygen-derived free radical formation
• ATP depletion leads to detachment of ribosomes, increase in anaerobic glycolysis, lactic acid accumulation, decreased activity of cellular enzymes, reduced activity of plasma membrane sodium pumps, and lysosomal membrane damage
• Mitochondrial damage causes swelling of the inner mitochondrial membrane, alterations in membrane permeability, and changes in transmembrane potential
• Calcium increases lead to loss of homeostasis, activating ATPases, proteases, phosphatases, and endonucleases
• Reactive oxygen species (ROS) formation leads to reactions with inorganic and organic materials, lipid peroxidation, protein modifications, and DNA damage
• Cell injuries are categorized as reversible or irreversible

Types of Cell Injury

• Reversible cell injury: A form of cell injury where cells can recover to their original state if the environmental changes within the range of homeostasis. Changes in this type include cell swelling, impaired cellular regulation and loss of microvilli structure
• Causes of reversible injury include exposure to low concentrations of toxins or brief hypoxia/anoxia
• Irreversible injury: Results in permanent damage and a loss of function. Leads to cell death through necrosis or apoptosis
• Causes of irreversible injury include heavy doses of toxins, anoxia, severe or prolonged hypoxia, and other overwhelming injuries that the cell cannot recover from

Necrosis

• Stages of necrosis include pyknosis (irreversible chromatin condensation), karyorrhexis (destructive fragmentation of the nucleus or nucleus burst), and karyolysis (complete dissolution of chromatin by endonucleases)
• Cytoplasmic changes in necrosis include swelling of organelles (especially mitochondria and rough ER), and rupture of the plasma membrane leading to spillage of cytoplasmic contents
• Types of necrosis include coagulative, liquefactive, caseous, and gangrene
• Coagulative necrosis: The most common type; tissue retains its form, architecture, and cell shape but becomes firm
• Liquefactive necrosis: Tissues become liquified through enzymatic action
• Caseous necrosis: Tissue appears soft and white, proteinaceous mass
• Gangrene: Coagulative necrosis- dry gangrene or liquefactive superimposed with infection - wet gangrene

Apoptosis

• Apoptosis is a form of programmed cell death, which is energy-dependent
• Intrinsic mitochondrial pathway and extrinsic or death receptor pathway are two pathways for apoptosis
• Mitochondrial pathway involves mitochondrial damage, cytochrome C release, activation of caspases, and apoptotic death
• Extrinsic pathway involves cell surface death receptors (e.g., Fas receptor), granzyme B, perforin, activation of caspases, and apoptosis
• Apoptosis is characterized by mitochondrial function loss, DNA fragmentation, decrease in cell volume and cell shrinkage, and membrane blebbing, and formation of apoptotic bodies

Anoikis

• Anoikis is a specific form of apoptotic process that occurs in cells when integrin-mediated interactions are disrupted, or loss of adhesion to the extracellular matrix
• Preventing the spreading of mutated tumor cells

This quiz covers the mechanisms of cell injury and death, highlighting biochemical and morphological changes. It explores various causes of cell injury, distinguishing between exogenous and endogenous factors, and discusses the implications of hypoxia and anoxia. Understand the consequences of ATP depletion and mitochondrial damage on cellular function.