Cellular Injury II: Classification

Cellular injury is any process that disrupts a cell’s ability to maintain homeostasis, leading to structural or functional changes. It is broadly classified based on etiology (cause) and mechanism of damage.

Classification by Etiology

Cellular injury may result from several causes. Hypoxic injury happens due to reduced oxygen delivery, most commonly from inadequate blood supply, such as arterial obstruction; for example, coronary artery thrombosis can cause myocardial infarction. Chemical injury arises from toxic substances such as heavy metals, industrial chemicals, or drugs like acetaminophen, which may damage cells directly or through their harmful metabolites. Physical injury includes trauma, extreme temperatures, electrical shock, or radiation, all of which can directly disrupt cellular structure. Infectious injury is caused by bacteria, viruses, fungi, or parasites that either directly damage cells or trigger inflammatory responses. Immunologic injury results from abnormal immune responses, including hypersensitivity reactions and autoimmune diseases such as lupus. Additionally, genetic and metabolic causes, such as inherited mutations or conditions like diabetes, can impair normal cellular function.

Classification by Mechanism

Cell injury also happens through key mechanisms. ATP depletion, often due to mitochondrial dysfunction, leads to failure of energy-dependent processes. Oxidative stress leads to the accumulation of reactive oxygen species, which damage lipids, proteins, and DNA. Calcium influx activates destructive enzymes, while membrane damage results in leakage of cellular contents. Mitochondrial damage further reduces ATP and may trigger cell death pathways. Finally, protein misfolding and DNA damage impair cellular repair mechanisms and can lead to apoptosis or necrosis if unresolved.