cell injury
Reversible vs Irreversible Cell Injury
Definition: Reversible (sublethal) injury is recoverable after removal of the insult; Irreversible injury leads to cell death regardless of intervention.
Determinants: extent of injury, rate of insult, and energy availability/membrane integrity.
Core mechanisms: membrane damage and energy depletion; disruption of ion pumps and osmotic balance.
Morphology and Functional Changes in Reversible Injury
Cell swelling (hydropic change) and vacuolar degeneration due to water influx from impaired membranes/pumps.
Impaired cellular functions due to altered intracellular environment; reduced metabolic activity.
Surface changes: loss or shortening of microvilli/cilia; detachment from basement membrane in epithelia.
Membrane blebbing and minor membrane damage.
Organelle swelling: mitochondria, endoplasmic reticulum; ribosomes detach from ER; lysosome swelling.
Cytoplasmic changes on light microscopy: loss of blue ribosomal staining; cytoplasm shifts toward pink due to reduced ribosome content.
Reversibility: if insult is removed, cells can recover and return to normal.
Hepatic Lipidosis (Fatty Change) as a Reversible Injury Example
Liver is richly lipogenic/metabolically active and shows visible lipid accumulation during injury.
Mechanism: excess lipid mobilization or overwhelmed processing leads to lipid droplet accumulation in hepatocytes.
Histology: vacuolated hepatocytes with clear nuclei; pale lobular pattern; in severe cases large fat vacuoles push the nucleus to the side.
Specificity: reversible lipidosis occurs in hepatocytes due to their lipid metabolism role; other epithelial cells do not typically show hepatic lipidosis.
Reversibility: with time and removal of insult, lipid content can be cleared and function can recover.
Transition to Irreversible Injury
Key changes: pronounced breakdown of membranes; mitochondria severely damaged; nucleus fragments; ER and ribosomes disassemble; lysosomes rupture.
Mitochondrial damage: severe swelling and loss of ATP production.
Calcium: massive influx of Ca^{2+} activates damaging pathways (phospholipases, etc.) and promotes membrane and cytoskeletal damage; mitochondria may calcify.
Consequences: leakage of lysosomal enzymes; proteolysis and further cellular destruction; pink cytoplasm due to loss of ribosomes and degradation of content.
Driving factors: combination of membrane failure and ATP depletion; calcium influx accelerates lethal injury.
Energy, Ischemia, and the Cascade
Ischemia reduces ATP production: ; pumps fail.
Ionic disturbance: Na^{+}/K^{+} pump failure → Na^{+} and water influx; K^{+} efflux.
Calcium influx: contributes to damage and activates destructive enzymes.
pH changes: anaerobic glycolysis lowers pH; metabolic disruption worsens injury.
Protein synthesis: ribosome detachment reduces protein synthesis; hepatocytes show lipid accumulation when lipid processing fails.
Transition marker: sustained energy failure and membrane breakdown mark irreversible injury.
Summary of Key Concepts
Reversible injury is recoverable; irreversible injury culminates in cell death.
Primary drivers are membrane integrity loss and energy depletion; calcium influx is a critical tipping point.
Hepatic lipidosis illustrates reversible injury in hepatocytes; lipid droplets distort cytology but can be reversible.
Ischemia links to decreased ATP, pump failure, ionic shifts, pH drop, and eventual membrane breakdown.