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Basic Principles of Cell Injury and Adaptation

Causes of injury, General principles regarding mechanism of cell injury, Biochemical mechanism, Free radical-induced injury, Reperfusion damage
Cells maintain a narrow range of physiological parameters ("homeostasis") in their immediate environments and intracellular milieus. Under physiological stress or pathological trauma ("injury"), cells can undergo adaptation to the new environment so that they can remain viable. Cells die when their injuries are inflicted in an irreversible manner ("irreversible injury").

Causes of injury

  • Nutritional defects
  • Aging
  • Physical agents
  • Infections
  • Chemical agents
  • Immunological reactions
  • Ischemia and hypoxia
  • Genetic defects

General principles regarding mechanism of cell injury

  • It is not all or nothing when it comes to the cell response to injury
  • Based on the type, status, and genetic makeup of an injured cell, the response to a given stimulus varies
  • The cells in our body are complex interconnected systems with multiple secondary and tertiary effects born from a single injury
  • When cells are injured, their function is lost long before biochemical manifestation and subsequent morphological consequences become apparent

Biochemical mechanism

ATP depletion, oxygen depletion (energy depletion)




Mitochondrial damage (permeability transition)

Loss of calcium homeostasis



Generally, there are five biochemical mechanisms that includes -
  • Defects in plasma membrane permeability
  • Mitochondrial damage
  • Generation of reactive oxygen species and other free radicals
  • Loss of calcium homeostasis
  • Loss of energy

Free radicals

  • Chemical species with just one unpaired electron in the outer orbital of a molecule are free radicals
  • Chemically unstable molecules like free radicals produce chemical damage easily when they interact with other molecules
  • Atoms interacting with free radicals are converted to free radicals in turn; molecules interacting with free radicals also become free radicals

Free radical-induced injury

When free radicals are not neutralized adequately, they can damage cells in three ways:
  • Protein cross linking - As a result of free radicals, proteins are cross-linked via sulfhydryl groups, leading to degradation or loss of activity
  • Lipid peroxidation membrane - Activated oxygen free radicals damage the double bonds in polyunsaturated membrane lipids
  • DNA fragmentation - Atomic and mitochondrial DNA can suffer single strand breaks when free radicals react with thymine

Reperfusion damage

  • It is paradoxical that restoration of blood flow can result in accelerated cellular injury if cells have been reversibly injured by ischemia.
  • Myocardial and cerebrovascular infarctions are significant outcomes of reperfusion damage
  • It is unclear how exactly the mechanisms work, but
  • During flow restoration, compromised cells may be exposed to high calcium concentrations, and
  • In combination with compromised mitochondria and circulating inflammatory cells, reperfusion can result in an increase in free radical production

Chemical injury

  • Mercuric chloride can damage proteins directly when it binds to sulfhydryl groups
  • Conversion of CCl4 to CCl3 results in the generation of toxic metabolites
  • The liver's SER is full of free radicals

Cellular adaption to cell injury

The adaptation of cells can be controlled and/or induced at a number of steps in their regulation, including receptor binding, signal transduction, gene transcription, or protein synthesis.
Adaptive changes manifested most frequently in morphology are
  • Hypertrophy (increase in cell size)
  • Metaplasia (change in cell type)
  • Atrophy (decrease in cell size)
  • Hyperplasia (increase in cell number)
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Ankur Choudhary is India's first professional pharmaceutical blogger, author and founder of Pharmaceutical Guidelines, a widely-read pharmaceutical blog since 2008. Sign-up for the free email updates for your daily dose of pharmaceutical tips.
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