Cell Injury - Mechanisms and Implications

Introduction

When the cells' ability to adapt to stress exceeds due to an increased amount of external or internal stress, it results in a series of events resulting in cell injury. Initially, cell injury can be revered (reversible), but it can also progress to permanent damage, which is also referred to as irreversible cell injury. The response of the cell to exogenous (external) or endogenous (internal) stimuli may vary depending on the type of cell and type of tissue involved (host factors). The cell response also depends on the extent and type of cell injury. This article further discusses the causes, types, and mechanisms of cell injury.

What Are the Principle Adaptive Responses of Cells?

The principle adaptive mechanism of the cell involves:

• Hypertrophy (compensatory increase in the volume of an organ due to increased cell components).

• Atrophy (decrease in the size of a tissue or organ).

• Hyperplasia (enlargement of tissue or organ due to increased organic tissue).

• Metaplasia (conversion of one cell into another type of cell).

What Are the Causes of Cell Injury?

Different causes of cell injury are:

• Genetic Causes: Any mutation or alteration in genes can result in cell injury, such as congenital abnormalities.

• Acquired Causes: A few acquired reasons are-

  • Hypoxia (reduced oxygen content in tissue resulting in cell injury).

  • Ischemia (lack of blood supply to tissues and organs).

  • Physical agents such as excessive exposure to heat resulting in coagulation necrosis, mechanical trauma, extremes of temperature (burns and deep cold), sudden changes in atmospheric pressure, radiation, and electric shock.

  • Chemical agents such as drugs, microbial agents (such as bacteria and fungal infections), immunological substances (such as hypersensitivity fractions and autoimmune diseases), and drug poisoning.

  • Nutritional derangements such as vitamin deficiency and excessive intake of health supplements.

  • Psychological factors such as drug addiction, alcoholism, and smoking.

What Are the Types of Cell Injury?

Cell injury can be classified into two types:

• Reversible Cell Injury (Degeneration): The stress is mild to moderate. The injured cell may recover in case of mild stress, allowing it to recover and resume normal function once the stressor is removed.

• Irreversible Cell Injury: Severe, persistent, and continuous injury can result in permanent cell damage. Such type of injury is referred to as irreversible cell injury, contributing to tissue dysfunction and progression of disease.

What Are the Different Mechanisms of Cell Injury?

Cell injury can occur due to various mechanisms, which can broadly be categorized into two main types:

• Mechanism of Reversible Cell Injury: Reversible cell injury refers to cellular damage that can be recovered if the damaging stimulus is removed promptly. The mechanisms involved in reversible cell injury include:

  • Hydropic Degeneration (Cell Swelling): In the case of microscopic examination, the cytoplasm shows the presence of vacuoles. In extreme cases, the cell gets filled with fluid and ruptures, resulting in cell death.

  • Cell Membrane Damage: Disruption of the plasma membrane integrity, which can lead to leakage of cellular contents and influx of damaging substances.

  • Mitochondrial Dysfunction: Impaired oxidative phosphorylation and ATP production can occur, leading to reduced energy levels within the cell.

  • Glycogen Depletion: Reduced glycogen stores can occur due to increased energy demand or decreased energy production.

  • Reversible Protein Denaturation: Proteins may undergo reversible changes in their structure due to stress but can regain their normal conformation once the stress is removed.

• Mechanism of Irreversible Cell Injury: Irreversible cell injury leads to cell death if the damaging stimulus persists. The mechanisms involved in irreversible cell injury include-

  • Severe Cell Membrane Damage: Excess disturbance of the plasma membrane integrity, leading to loss of cellular contents and influx of damaging substances.

  • Mitochondrial Permeability Transition: Loss of integrity of the mitochondrial membrane, resulting in the release of pro-apoptotic factors and further energy depletion.

  • Lysosomal Rupture: Release of lysosomal enzymes into the cytoplasm, resulting in cellular digestion and death of cells (necrosis).

  • DNA (Deoxyribonucleic Acid) Damage: Severe and irreparable damage to DNA can trigger programmed cell death (apoptosis) pathways or necrosis.

  • Severe ATP (Energy) Depletion: Prolonged and severe depletion of ATP or energy levels can result in irreversible cellular dysfunction and death.

What Are the Histopathological Findings of Cell Injury?

The histopathological characteristics of cell injury are:

• Reversible Cell Injury: The pathological feature of reversible cell injury involves nuclear-chromatin clumping, ribosomal detachments, fatty change, and decreased protein synthesis.

• Irreversible Cell Injury: The pathological characteristics of irreversible cell injury under light microscopy show increased cytoplasmic eosinophilia, large amorphous densities in mitochondria, shrinkage of the nucleus, and nuclear chromatin changes.

What Is the General Mechanism of Cell Injury?

Cell injury is started at the molecular level. The general mechanism of cell injury involves:

• Depletion of ATP (Adenosine triphosphate).

• Permeability of cell membrane.

• Disruption of biochemical pathways such as pathways of protein synthesis.

• Damage to DNA.

What Are the Clinical Implications of Cell Injury on Human Health?

The proper understanding of the mechanisms and consequences of cell injury has significant implications for human health and disease. It helps to provide insights into the pathogenesis of various diseases, guiding the development of diagnostic tools, prognostic markers, and therapeutic interventions. By targeting key pathways involved in cell injury, researchers and clinicians can develop novel treatment strategies aimed at preventing or mitigating cellular and tissue damage, thereby improving patient outcomes and enhancing the overall quality of life of the individuals.

Conclusion

Cell injury is a complex phenomenon with various underlying mechanisms and consequences. Upon encountering injurious stimuli, cells undergo a series of structural and functional alterations that can ultimately lead to cell dysfunction or death. This process can manifest in different ways depending on the type, intensity, and duration of the insult, as well as the resilience of the affected cells. From the observed morphological and biochemical changes, it is evident that cell injury disrupts homeostasis and impairs cellular functions, jeopardizing tissue integrity and organ function. Furthermore, the repercussions of cell injury extend beyond the affected cells, influencing neighboring cells and triggering inflammatory responses that can exacerbate tissue damage. In conclusion, understanding the mechanisms and consequences of cell injury is crucial for elucidating disease pathogenesis and developing therapeutic interventions aimed at preserving cellular viability and tissue function.