Cellular Injury I: Introduction

Cellular injury occurs when a cell cannot maintain homeostasis or adapt to stressors such as hypoxia, toxins, or trauma. Depending on severity and duration, injury may be reversible, allowing recovery, or irreversible, leading to cell death.

General Mechanisms of Cell Injury

Although causes vary, most cellular injuries arise from a few key mechanisms that disrupt essential functions and often amplify one another. Cell survival depends on the extent and balance of these disturbances.

ATP depletion from reduced mitochondrial function limits energy for vital processes, causing cell swelling, impaired protein synthesis, defective membrane transport, and altered lipid metabolism.

Reactive oxygen species (ROS)—such as superoxide, hydrogen peroxide, and hydroxyl radicals—are generated during hypoxia and reoxygenation. These free radicals damage cellular membranes, proteins, mitochondria, and DNA, worsening dysfunction.

Calcium influx occurs when ischemia or toxins disrupt membrane integrity, raising cytosolic calcium levels. This activates enzymes like phospholipases, proteases, and endonucleases, which degrade cellular structures.

Mitochondrial damage, driven by ROS and calcium overload, further reduces ATP production and triggers cell death pathways, including apoptosis and necrosis.

Membrane damage is an early feature of injury. Increased permeability and lysosomal membrane rupture release enzymes, causing self-digestion and structural breakdown.

Protein misfolding and DNA damage activate stress responses, and if severe, can lead to programmed cell death.